Title of Invention | OXAZOLIDINONES AND THEIR USE |
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Abstract | SUBSTITUTED OXAZOLIDINONES AND THEIR USE The invetion relates to the field of blood coagulation. Novel oxazolidinone derivatives of the general formula (I) process for their preparation and their use as medicianally active compounds for the prophylaxis and/or treatment of disorders are described. |
Full Text | FORM 2 THE PATENTS ACT 1970 [39 OF 1970] 86 THE PATENTS RULES, 2003 COMPLETE SPECIFICATION [See Section 10; rule 13] "OXAZOLIDINONES AND THEIR USE" BAYER HEALTHCARE AG, a body corporate organized under the laws of Germany of 51368 Leverkusen, Germany, The following specification particularly describes the invention and the manner in which it is to be performed: The present invention relates to the field of blood coagulation. In particular, the present invention relates to novel oxazolidinone derivatives, to processes for their 5 preparation and to their use as active compounds in medicaments. Blood coagulation is a protective mechanism of the organism which helps to "seal" defects in the wall of the blood vessels quickly and reliably. Thus, loss of blood can be avoided or kept to a minimum. Haemostasis after injury of the blood" vessels is 10 effected mainly by the coagulation system in which an enzymatic cascade of complex reactions of plasma proteins is triggered. Numerous blood coagulation factors are involved in this process, each of which factors converts, on activation, the respectively next inactive precursor into its active form. At the end of the cascade comes the conversion of soluble fibrinogen into insoluble fibrin, resulting in the 15 formation of a blood clot. In blood coagulation, traditionally the intrinsic and the extrinsic system, which end in a joint reaction path, are distinguished. Here factor Xa, which is formed from the proenzyme factor X, plays a key role, since it connects the two coagulation paths. The activated serine protease Xa cleaves prothrombin to thrombin. The resulting thrombin, in turn, cleaves fibrinogen to fibrin, a 20 fibrous/gelatinous coagulant. In addition, thrombin is a potent effector of platelet aggregation which likewise contributes significantly to haemostasis. Maintenance of normal haemostasis - between bleeding and thrombosis - is subject to . a complex regulatory mechanism. Uncontrolled activation of the coagulant system or 25 defective inhibition of the activation processes may cause formation of local thrombi or embolisms in vessels (arteries, veins, lymph vessels) or in heart cavities. This may lead to serious disorders, such as myocardial infarct, angina pectoris (including unstable angina), reocclusions and restenoses after angioplasty or aortocoronary bypass, stroke, transitory ischaemic attacks, peripheral arterial occlusive disorders, 30 pulmonary embolisms or deep venous thromboses; hereinbelow, these disorders are collectively also referred to as thromboembolic disorders. In addition, in the case of consumption coagulopathy, hypercoagulability may - systemically - result in disseminated intravascular coagulation. 35 These thromboembolic disorders are the most frequent" cause of morbidity and mortality in most industrialized countries (Pschyrembel, Klinisches Worterbuch [clinical dictionary], 257th edition, 1994, Walter de Gruyter Verlag, page 199 ff., entry "Blutgerinnung" [blood coagulation]; R6rPPP Lexikon Chemie, Version 1.5, 1998, Georg Thieme Verlag Stuttgart, entry "Blutgerinnung"; Lubert Stryer, Biochemie [biochemistry], Spektrum der Wisenschaft Verlagsgesellschaft mbH 5 Heidelberg, 1990, page 259 ff.). The anticoagulants, i.e. substances for inhibiting or preventing blood coagulation, which are known from the prior an have various, often grave disadvantages. Accordingly, in practice, an efficient treatment method or prophylaxis of 10 thromboembolic disorders is very difficult and unsatisfactory. In the therapy and prophylaxis of thromboembolic disorders, use is firstly made of heparin, which is administered parenterally of subcutaneously. Owing to more favourable pharmacokinetic properties, preference is nowadays more and more given 15 to low-molecular-weight heparin; however, even with low-molecular-weight heparin, it is not possible to avoid the known disadvantages described below, which are involved in heparin therapy. Thus, heparin is ineffective when administered orally and has a relatively short half-life. Since heparin inhibits a plurality of factors of the blood coagulation cascade at the same time, the action is nonselective. Moreover, 20 there is a high risk of bleeding; in particular, brain haemorrhages and gastrointestinal bleeding may occur, which may result in thrombopenia, drug-induced alopecia or osteoporosis (Pschyrembel, Klinisches Worterbuch, 257th edition, 1994, Walter de Gruyter Verlag, page 610, entry "Heparin"; Rornpp Lexikon Chemie, Version 1.5, 1998, Georg Thieme Verlag Stuttgart, entry "Heparin"). 25 A second class of anticoagulants are the vitamin K antagonists. These include, for example, 1,3-indanediones, and especially compounds such as warfarin, phenprocoumon, dicumarol and other coumafin derivatives which inhibit the synthesis of various products of certain vitamin K-dependent coagulation factors in 30 the liver in a non-selective manner. Owing to the mechanism of action, however, the onset of the action is very slow (latency to the onset of action 36 to 48 hours). It is possible to administer the compounds orally; however, owing to the high risk of bleeding and the narrow therapeutic index, a time-consuming individual adjustment and monitoring of the patient are required. Moreover, other adverse effects, such as 35 gastrointestinal disturbances, hair loss and skin necroses, have been described (Pschyrembel, Klinisches Worterbuch, 257th edition, 1994, Walter de Gruyter Verlag, 3-3 ax 0 R1 . represents 2-thiophenc which is substituted in the 5-position by a radical from the group consisting of chlorine, bromine, methyl and trifluoromethyl, R2 represents D-A-: where: the radical "A" represents phonylene; the radical "D" represents a saturated 5~ or 6-membered heterocyclic, which is attached to "A" via a nitrogen atom. which has a carbonyl group directly adjacent In the linking nitrogen atom and in which one carbon ring member may be replaced by a heteroatom from the group consisting of S, N and 0; where the group "A" defined above may optionally be mono- or disubstituted in the metaposition with respect to the point of attachment to the oxazolidinone, by a radical fromthe group consisting of fluorine, chlorine, nitro. amino, trilhioroinethyl, methyl andeyano, R3; R4, R5, R6 R.7and R8each represent hydrogen and their pharmaeeuticaily acceptable salts, hydrates. liydrates of sails. except for compounds of the general formula (1) in which the radical R is an unsubstituted 2-thiopbene radical and the radical R" is simultaneously a mono- or polysubstituted phenyl radical and the radicals R~", R4, R5, R6, R7 and R are each simultaneously hydrogen. Preference is given here to compounds of the. general formula (I), in which R represents optionally benzo-fused thiophenc (thienyl) which may optionally be mono- or polysubstituted by a radical from the group consisting of halogen; cyano; nitro; amino; aminomethyl; (C7-C8)-alkyl which for its part may optionally be mono- or polysubstituted bv halogen; (C3-C7)-eyeloalkyl: (C1-C-8)-alkoxy; imidazolinyl; -C(=NH)NH2; carbamoyl; and mono- and di-(C1-C-4)-alkyl-aminocarbonyI, R2 represents one of the groups below: 5 A-, A-M-, D-M-A-, B-M-A-, B-, 10 B-M", B-M"B-, D-M-B-, where: 15 the radical "A" represents ( 20 group consisting of S, N, NO (N-oxide) and O; the radical "D" represents a saturated or partially unsaturated, mono-or bicyclic, optionally benzo-fused 4- to 9-membered heterocycle which contains up to three heteroatoms and/or hetero chain members from the group consisting of S,SO,SO2,N,NO (N-oxide)and G, 25 the radical "M" represents -NH-, -CH2-, -CH2CH2-, -O-, -NH-CH2-, -CH2-NH-, -OCHr, -CH2CK -CONH-, -NHCO-, -COO-, -OOC-, -S-, -S02- or represents a covalent bond; where 30 the groups "A", "B" and "D" defined above may each optionally be mono- or polysubstituted by a radical from the group consisting of halogen; trifluoromethyl; oxo; cyano; nitro; carbamoyl; pyridyl; (Cr C6)-alkanoyl; (C3-C7)-cycloalkanoyl; (C6-C14)-arylcarbonyl; (C5-C10)-heteroarylcarbonyl; (C1-C6)-alkanoyloxymethyloxy; (C1-C4)hydroxy- 35 alkylcarbonyl; -COOR27; -S02R27; -C(NR27R28)=NR29; -CONR28R29; -SO2NR28R29; -OR30; -NR30R31, (CrC6)-alkyl and (C3-C7)-cycloalkyl, where (C1-C6)-aIkyI and (C3-C7)-cycloalkyl for their part may optionally be substituted by a radical from the group consisting of cyano; -OR27; -NR28R29; -CO(NH)v(NR27R28) and -C(NR27R28)=NR29, where: v is either 0 or 1 and 10 R27, R28 and R29 are identical or different and independently of one another each represents hydrogen, (C1-C4)-alkyI1 (C3-C7)- cycloalkyl, (C1-C4)-alkanoyl, carbamoyl, trifluoromethyl, phenyl or pyridyl, 15 and/or R27 and R28 or R27 and R29 together with the nitrogen atom to which they are attached form a saturated or partially unsaturated 5- to 7-membered heterocycle having up to three, preferably up to 20 two, identical or different heteroatoms from the group consisting of N, O and S, and R30 and R31 are identical or different and independently of one another each represents hydrogen, (C1-C4)-alkyl, (C3-C7)-cycloalkyl, 25 (CrC4)alkylsuIphonyI, (C1-C4)-hydroxyaikyl, (CrC4)- aminoalkyl, di-(C 1 -C4)-alkylamino-(C 1 -C4)-alkyl, -CH2C(NR27R2S)=NR29 or -COR33, where 30 .33 R33 represents (CrC6)-alkoxy, (C1-C4)-aIkoxy-(CI-C4)- alkyl, (C1-C4)-aIkoxycarbonyl-(CI-C4)-alkyI, (CrC4> aminoalkyl, (C1-C4)~alkoxycarbonyl, (C1-C4)-alkanoyl- (Ci-C4)-alkyl, (C3-C7)-cycloalkylT (C1-C6)-alkenyl, 35 (Ct-Cg^alkyl, which may optionally be substituted by 7- phenyl or acetyl, (C6-CI4)-aryl, (C5-C10)-heteroaryI, trifluoromethyl, tetrahydrofuranyl or butyrolactone, R3, R4, R5, R6, R7 and R8 are identical or different and each represents hydrogen or represents (C1-C6)-alkyl and their pharmaceutically acceptable salts, hydrates and prodrugs, 1 except for compounds of the general formula (I) in which the radical R is an 10 unsubstituted 2-thiophene radical and the radical R2 is simultaneously a mono- or polysubstituted phenyl radical and the radicals R3, R4; R5, Rs, R7 and R8 are each simultaneously hydrogen. 15 Preference is also given here to compounds of the general formula (I), in which R1 represents thiophene (thienyl), in particular 2-thiophene, which may optionally be mono- or polysubstituted by halogen, preferably chlorine or 20 bromine, by amino, aminomethyl or (C1-C8)-alkyl, preferably methyl, where the (C1-C8)-alkyl radical for its part may optionally be mono- or polysubstituted by halogen, preferably fluorine, R2 represents one of the groups below: 25 A-, A-M-, D-M-A-, B-M-A-, B-, 30 B-M-, B-M-B-, D-M-B-, 35 where: 5 the radical "A" represents (C6-C14)-aryl preferably (C6-C1o)-aryl, in particular phenyl or naphthyl, very particularly preferably phenyl; the radical "B" represents a 5- or 6-membered aromatic heterocycle which contains up to 3 heteroatoms and/or hetero chain members, in 5 particular up to 2 heteroatoms and/or hetero chain members, from the group consisting of S, N, NO (N-oxide) and O; the radical "D" represents a saturated or partially unsaturated 4- to 7- membered heterocycle which contains up to three heteroatoms and/or hetero chain members from the group consisting of S, SO, S02, N, NO 10 (N-oxide) and O; the radical "M" represents -NH-, -CH2-, -CH2CH2-, -0~, -NH-CH2-, -CH2-NH-, -OCH2-, -CH20-, -CONH-, -NHCO-, -COO-, -OOC-, -S-or represents a covalent bond; 15 where the groups "A", "B" and "D" defined above may in each case optionally be mono- or polysubstituted by a radical from the group consisting of halogen; trifluoromethyl; oxo; cyano; nitro; carbamoyl; pyridyl; (C1-C6)-alkanoyl; (C3-C7)-cycloalkanoyl; (C6-C14)- 20 arylcarbonyl; (C5-C1o)-heteroarylcarbonyl; (C1-C6)- alkanoyloxymethyloxy; -COOR27; -S02R27; -C(NR27R28)=NR29; -CONR28R29; -S02NR28R29; -OR30; -NR30R31, (C1C6)-alkyl and (C3- C7)-cycloaIkyl, 25 where (C1-C6)-alkyl and (C3-C7)-cycloalkyl for their part may optionally be substituted by a radical from the group consisting of cyano; -OR27; -NR28R29; -CO(NH)v(NR27R28) and -C(NR27R28)=NR29, 30 where: v is either 0 or 1 and R27, R28 and R29 are identical or different and independently of one 35 another each represents hydrogen, (C1-C4)-alkyl or (C3-C7)- cycloalkyl, 9 and/or R27 and R28 or R27 and R29 together with the nitrogen atom to which they are attached form a saturated or partially unsaturated 5- to 5 7-membered heterocycle having up to three, preferably up to two, identical or different heteroatoms from the group consisting of N, O and S, and R30 and R31 are identical or different and independently of one another 10each represents hydrogen, alkylsulphonyl, aminoalkyl, (Ci-C4)~ alkanoyl, 15 R3, R4, R5, R6, R7 and Rs are identical or different and each represents hydrogen or represents (Ci-C6)-alkyl and their phannaceutically acceptable salts, hydrates and prodrugs, 20 except for compounds of the general formula (I) in which the radical R1 is an unsubstituted 2-thiophene radical and the radical R is simultaneously a mono- or polysubstituted phenyl radical and the radicals R3, R4, R5, R6, R7 and Rs are each simultaneously hydrogen. 25 Particular preference is given here to compounds of the general formula (I), in which - ,;J 30 R1 represents thiophene (thienyl), in particular 2-thiophene, which may optionally be mono- or polysubstituted by halogen, preferably chlorine or bromine, or by (Ci-Cg)-alkyl, preferably methyl, where the (Ci-Cg)-alkyl radical for its part may optionally be mono- or polysubstituted by halogen, preferably fluorine, 35 R2 represents one of the groups below; 10 A-, A-M-, D-M-A-, B-M-A-, 5 B-, B-M-, B-M-B-, D-M-B-, 10 where: the radical "A" represents phenyl or naphthyl, in particular phenyl; the radical "B" represents a 5- or 6-membered aromatic heterocycle which contains up to 2 heteroatoms from the group consisting of S, N, NO (N-oxide) and O; 15 the radical "D" represents a saturated or partially unsaturated 5- or 6- membered heterocycle which contains up to two heteroatoms and/or hetero chain members from the group consisting of S, SO, SO2, N, NO (N-oxide) and O; the radical "M" represents -NH-, -O-, -NH-CH2-, -CH2-NH-, -OCHz-, 20 -CH2O-, -CONH-, -NHCO- or represents a covalent bond; where the groups "A", "B" and "D" defined above may in each case optionally be mono- or polysubstituted by a radical from the group 25 consisting of halogen; trifluoromethyl; oxo; cyano; pyridyl; (C1-C3)- alkanoyl; (C6-Cio)-arylcarbonyI; (C5-C6)-heteroarylcarbonyl; (C1-C3)- alkanoyloxymethyloxy; -C(NR27R28)=NR29; -CONR28R29; -S02NR28R29; -OH; -NR30R31; (C1-C4)-alkyl; and cyclopropyl, cyclopentyl or cyclohexyl, 30 where (C1-C4)-alkyl and cyclopropyl, cyclopentyl or cyclohexyl for their part may optionally be substituted by a radical from the group consisting of cyano; -OH; -OCH3; -NR28R29; -CO(NH)v(NR27R28) and -C(NR27R28)=NR29, 35 where: 1) v is either 0 or 1, preferably 0, and R27, R28 and R29 are identical or different and independently of 5 one another each represents hydrogen, (C1-G4)-alkyl or else cyclopropyl, cyclopentyl or cyclohexyl and/or R27 and R28 or R27 and R29 together with the nitrogen atom to which 10 they are attached may form a saturated or partially unsaturated 5- to 7-membered heterocycle having up to two identical or different heteroatoms from the group consisting of N, O and S, and 15 R30 and R31 are identical or different and independently of one another each represents hydrogen, (Ci-GO-alkyl, cyclopropyl, cyclopentyl, cyclohexyl, (C1-C4)-alkylsulphonyl, (C1-C4)-hydroxyalkyl, (C1-C4)-aminoalkyl, di-(C1-C4)-alkylamino-(C1-C4)-alkyl, (C1C3)-alkanoyl or phenylcarbonyl, 20 25 30 R3, R4, R5, R6, R7 and Rs are identical or different and each represents hydrogen or represents (C1-C6)-alkyl and their pharmaceutically acceptable salts, hydrates and prodrugs, except for compounds of the general formula (I) in which the radical R is an unsubstituted 2-thiophene radical and the radical R2 is simultaneously a mono- or polysubstituted phenyl radical and the radicals R3, R4, R5, R6, R7 and R8 are each simultaneously hydrogen. Particular preference is given here to compounds of the general formula (I), in which R1 represents 2-thiophene which may optionally be substituted in the 5-position by a radical from the group consisting of chlorine, bromine, methyl or trifluOromethyl, 5 R2 represents one of the groups below: A-, A-M-, D-M-A-, B-M-A-, 10 B-, B-M-, B-M-P-, D-M-B-, 15 where: the radical "A" represents phenyl or naphthyl, in particular phenyl; the radical "B" represents a 5- or 6-membered aromatic heterocycle which contains up to 2 heteroatoms from the group consisting of S, N, NO (N-oxide) and O; 20 the radical "D" represents a saturated or partially unsaturated 5- or 6- membered heterocycle which contains a nitrogen atom and optionally a further heteroatom and/or hetero chain member from the group consisting of S, SO, SO2 and O; or contains up to two heteroatoms and/or hetero chain members from the group consisting of S, SO, SOx 25 and O; the radical "M" represents -NH-, -O-, -NH-CH2-, -CH2-NH-, -OCH2-, -CH2O-, -CONH-, -NHCO- or represents a covalent bond; where 30 the groups "A", "B" and "D" defined above may in each case optionally be mono- or polysubstituted by a radical from the group consisting of halogen; trifluoromethyl; oxo; cyano; pyridyl; (C1-C3)-alkanoyl; (C6-C10)-aryIcarbonyl; (C5-C6)-hetefoarylcarbonyl; (C1-C3)-alkanoyloxymethyloxy; -CONR28R29; -S02NR28R29; -OH; -NR30R31; 35 (C1-C4)-alkyl; and cyclopropyl, cyclopentyl or cyclohexyl, may, in particular, represent a group of the following formula: Y-X-(CH2),-X-(CO)n-(CH2)1-(CR9R10)m-(CH3)02- where m is an integer from 0 to 6, preferably from 1 to 3, n is either 0 or 1, p is an integer from 0 to 3, preferably either 0 or 1, o{ is an integer 0 or J, o2 is an integer 0 or 1, R9 and R10 are identical or different and each represents hydrogen; (C1-C4)-alkyl, preferably methyl; (C1-C4)-alkoxy, preferably methoxy; (C3-C7)-cycloalkyl; hydroxyl or fluorine, X and X" are identical or different and each represents O; N-R11 or a covalent bond, where R11 represents H; (C1-C4)-aIkyI, preferably methyl, or (C3-C7)-cycloalkyl, Y represents a 3- to 7-membered saturated or partially unsaturated cyclic hydrocarbon radical which optionally contains 1 to 3 identical or different heteroatoms and/or hetero chain members from the group consisting of N, O, S, SO and $O2, where: this radical Y may optionally be substituted by a 5- or 6-membered aromatic or a 3- to 7-membered saturated or partially unsaturated cyclic hydrocarbon radical which optionally contains up to 3 identical or different heteroatoms from the group consisting of N, O and S and where this radical may for its part optionally be substituted by a radical from the group consisting of cyano; hydroxyl; halogen; (C1-C4)-alkyl; -C(=NR12)NR13R!3"; and-NRI4R!5, where: R12 represents hydrogen, (C1-C4)-alkyl or (C3-C7)-cycloalkyl; R13 and R13 are identical or different and independently of one another each represents hydrogen, (C1-C4)-alkyl or (C3-C7)-cycloalkyl and/or R13 and R13 together with the N atom to which they are attached form a 5- to 7-membered heterocycle which may optionally contain up to 2 further heteroatoms from the group consisting of N, O and S; R14 and R15 are identical or different and independently of one another each represents hydrogen, (C1-C4)-alkyI, (C3-C7)-cyc]oalky) or (C1-C5)-alkanoyl; and/or this radical Y may furthermore optionally be substituted by a radical from the group consisting of oxo; cyano; thiono; halogen; -OR16; =NR16; -NR16R17; -C(=NR18)NRI9R19" and (C1C4)-alkyl, in which (C1-C4)-alkyi for its part may optionally be substituted by a radical from the group consisting of hydroxyl; cyano; -NR16R17 and -C(=NR18)NR19R19", 18 where: R16 and R17 are identical or different and independently of one another each represents hydrogen, (C1-C4)-alkyl, (C3-C7)-cycIoalkyI or (C1-C3)-alkanoyl; R18 represents hydrogen, (C1-C4)-alkyl or (C3-C7)-cycloalkyl; 10 R19 and R19 are identical or different and independently of one another each represents hydrogen, (C1-C4)-aIkyI or (C3- C7)-cycloalkyl and/or 15 R19 and R19 together with the N atom to which they are attached form a 5- to 7-membered heterocycle which may optionally contain up to 2 further heteroatoms from the group consisting of N, 0 and S. 20 Particular preference is given to compounds of the general fonnula (I) in which the radical R2 represents a group of the following fonnula: 25 Y-X"-(CH2)p-X-(CO)n-(CH2)Ol-(CR9Rl0)m-(CH2)o2- where m is an integer from 0 to 3, 30 n is an integer 0 or 1, p is an integer 0 or 1, 35 01 is an integer 0 or 1, 19 — 02 is an integer 0 or 1, R9 and R10 are identical or different and each represents hydrogen; methyl; 5 X and X" are identical or different and each represents O; N-R11 or a covalent bond, where R1" represents H or methyl, 10 y represents a 5- to 7-membered saturated cyclic hydrocarbon radical which optionally contains 1 or 2 identical or different heteroatoms and/or hetero chain members from the group consisting of N, O, S, SO and SO2, in particular cyclohexyl, piperazinyl, morpholinyl, 15 thiomorpholinyl, diazepinyl, pyrrolidinyl and piperidinyl, where: this radical Y may optionally be substituted by a 5- or 6-membered 20 aromatic or a 5- to 7-membered saturated or partially unsaturated cyclic hydrocarbon radical which optionally contains up to 2 identical or different heteroatoms from the group consisting of N, O and S and where this radical for its pan may be substituted by a radical from the 25 group consisting of cyano; hydroxyl; fluorine; chlorine; (C1-C4)-alkyl; -C(=NR12)NR13R13"; and -NR14R15, where: 30 R12 represents hydrogen, methyl, ethyl, cyclopropyl, cyclopentyl or cyclohexyl; R13 and R13 are identical or different and independently of one another each represents hydrogen, methyl, ethyl, cyclopropyl, 35 cyclopentyl or cyclohexyl and/or R13 and R13" together with the N atom to which they are attached form a 5- to 7-membered heterocycle which may optionally contain up to 2 further heteroatoms from the group consisting of N, O 5 and S, in particular piperidinyl, piperazinyl, morpholinyl and thiomorpholinyl; R14and R15 are identical or different and independently of one another each represents hydrogen, methyl, ethyl, cyclopropyl, . 10 cyclopentyl or cyclohexyi or else acetyl; and/or this radical Y may furthermore optionally be substituted by a 15 radical from the group consisting of oxo; cyano; thiono; fluorine; chlorine; -OH; -OCH3; =NR16; -NH2; -N(CH3)2; -C(=NR18)NR19R19" and methyl, in which methyl for its part may optionally be substituted by a 20 radical from the group consisting of hydroxyl; cyano; -NR16R17 and-C(=NRI8)NR19R19", where: 25 R16 and R17 are identical or different and independently of one another each represents hydrogen, methyl, (C3-C7)-cycloalkyl or acetyl; 30 R18 reprsents hydrogen, methyl or (C3-C7)-cycloalkyl; R19 and R19" are identical or different and independently of one another each represents hydrogen, methyl or {C3-C7)-cycloalkyl and/or 35 21 -2*-=—= R19 and R19" together with the N atom to which they are attached form a 5- to 7-membered heterocycle which may optionally contain up to 2 further heteroatoms from the group consisting of N, O and S, in particular 5 piperidinyl, piperazinyl, morpholinyl and thio- morpholinyl. Likewise, in the compounds of the general formula (I), the radical 10 R2 may represent a group of the formula below: Z-(CO)r(CR20R2I)s- where; 15 s is an integer from 1 to 6, t is either 0 or 1, 20 R20 and R21 are identical or different and each represents hydrogen, (C1-C4)- alkyl, (C1-C4)-alkoxy, (C3-C7)-cycIoaIkyl, hydroxyl or fluorine, Z represents a radical which is selected from the group consisting of cyano; -C(NR22R23)=NR24; -CO(NH)uNR22R23; and-NR25R26, 25 where: u is either 0 or 1, preferably 0, and 30 R22, R23 and R24 are identical or different and independently of one another each represents hydrogen, (C1-C4)-alkyI or (C3-C7)-cycloalkyl, preferably hydrogen or methyl, and/or 35 R22 and R23 together with the N atom to which they are attached form a 5- to 7-membered heterocycle which may optionally contain up to 2 further heteroatoms and/or hetero chain members from the group consisting of N, O, S, SO and SO2; R25 and R26 are identical or different and independently of one another 5 each represents hydrogen, (C1-C4)-aIkyl or (C3-C7)-cycloalkyl, preferably hydrogen, methyl or ethyl, where (C1-C4)-alkyl and (C3-C7)-cycloalkyl for their part may optionally be substituted by hydroxy! or (C1-C6)-alkoxy. 10 Furthermore, in the compounds of the general formula (I), the radical R2 may represent one of the following groups: A-, A-M-, 15 D-M-A-, B-M-A-, B-, B-M-, B-M-B-, 20 D-M-B-, where: the radical "A" represents (C6-C14)-aryl, preferably (C6-C10)-aryl, in particular 25 phenyl or naphthyl, very particularly preferably phenyl; the radical "B" represents a 5- or 6-membered aromatic heterocycle which contains up to 3 heteroatoms and/or hetero chain members, in particular up to 2 heteroatoms and/or hetero chain members, from the group consisting of.S,, N, NO (N-oxide) and O; 30 the radical "D" represents a saturated or partially unsaturated 4- to 7- membered heterocycle which contains up to three heteroatoms and/or hetero chain members from the group consisting of S, SO, S02, N, NO (N-oxide) and O; the radical "M" represents -NH-, -CH2-, -CH2CB2-, -0-, -NH-CH2-> 35 -CH2-NH-, -OCH2-, -CH20-, -CONH-, -NHCO-, -COO-, -OOC-, -S- or represents a covalent bond; where the groups "A", "B" and "D" defined above may in each case optionally be mono- or polysubstituted by a radical from the group consisting of halogen; trifluoromethyl; oxo; cyano; nitro; carbamoyl; pyridyl; (C1-C6)-alkanoyI; (C3-C7)-cycloalkanoyI; (C6-C14)-arylcarbonyl; (C5-C1o)-heteroarylcarbonyl; (C1-C6)-alkanoyloxymethyloxy; -COOR27; -S02R27; -C(NR27R28)=NR29; -CONR28R29; -S02NR28R29; -OR30; -NR30R31 (CrC6)-aIkyl and (C3-C7)-cycloalkyl, 10 where (C1-C6)-alkyl and (C3-C7)-cycloalkyl for their part may optionally be substituted by a radical from the group consisting of cyano; -OR ; -NR R ; -CO(NH)v(NR27R2s) and -C(NR27R28)=NR29, 15 where: v is either 0 or 1 and R27, R28 and R29 are identical ov different and independently of one another 20 each represents hydrogen, (C1-C4)-alkyl or (C3-C7)-cycloalkyl and/or R27 and R28 or R27 and R29 together with the nitrogen atom to which they are attached form a saturated or partially unsaturated 5- to 7-membered 25 heterocycle having up to three, preferably up to two, identical or different heteroatoms from the group consisting of N, O and S, and R30 and R31 are identical or different and independently of one another each represents hydrogen, (C1-C4)-aIkyl, (C3-C7)-cycloalkyl, (C1C4)-alkyl- 30 sulphonyl, (C1-C4)-hydroxyaIkyl, (C1C4)-aminoalkyl, di-(C1-C4)- alkylamino-(C1-C4)-alkyl, (C1C4)-aIkanoyl, (C6-C14)-aryIcarbonyI, (C5-C10)-heteroarylcarbonyl, (C1-C4)-alkylaminocarbonyl or -CH2C(NR27R28)=NR29. 35 Preference is also given to compounds of the general formula (I) in which the radical Infi-A ^4-P3-T6it;i!Hi Countries -24- R2 represents one of the groups below: A-, A-M-, D-M-A-, B-M-A-, B-, B-M-, B-M-B-, D-M-B-, 10 where: the radical "A" represents phenyl or naphthyl, in particular phenyl; the radical "B" represents a 5- or 6-membered aromatic heterocycle which contains up to 2 heteroatoms from the group consisting of S, N, NO (N-oxide) 15 and O; the radical "D" represents a saturated or partially unsaturated 5- or 6-membered heterocycle which contains up to two heteroatoms and/or hetero chain members from the group consisting of S, SO, S02l N, NO (N-oxide) and O; 20 the radical "M" represents -NH-, -O-, -NH-CH2-, -CH2-NH-, -OCH2-, -CH20-, -CONH-, -NHCO- or represents a covalent bond; where the groups "A", "B" and "D" defined above may in each case optionally be 25 mono- or polysubstituted by a radical from the group consisting of halogen; trifluoromethyl; oxo; cyano; pyridyl; (C1-C3)-alkanoyl; (C6-C10)-arylcarbonyl; (C5-C6)-heteroarylcarbonyl; (C1-C3)-alkanoyloxymethyloxy; -C(NR27R28)=NR29; -CONR28R29; -S02NR28R29; -OH; -NR30R31; (C1-C4)-alkyl; and cyclopropyl, cyclopentyl or cyclohexyl, 30 where (C1-C4)-alkyI and cyclopropyl, cyclopentyl or cyclohexyl for their part may optionally be substituted by a radical from the group consisting of cyano; OH; -OCH3; -NR28R29; -CO(NH)v(NR27R28) and -C(NR27R28)=NR29, 35 where: v is either 0 or 1, preferably 0, and R27, R28 and R29 are identical or different and independently of one another each represents hydrogen, (C1-C4)-alkyl or else cyclopropyl, 5 cyclopentyl or cyclohexyl and/or R27 and R28 or R27 and R29 together with the nitrogen atom to which they are attached may form a saturated or partially unsaturated 5- to 7- 10 membered heterocycle having up to two identical or different heteroatoms from the group consisting of N, O and S, and R30 and R31 are identical or different and independently of one another each represents, hydrogen, (C1-C4)-alkyl, cyclopropyl, cyclopentyl, 15 cyclohexyl, (C1-C4)-alkyIsulphonyI, (C1-C4)-hydroxyalkyl, (C1-C4)- aminoalkyl, di-(C1-C4)-alkylaminO-(C1-C4)-alkyl, (C1-C3)-alkanoyI or phenylcarbonyl. 20 Likewise, in the compounds of the general formula (I), the radical R2 may represent a group of the following formula: 25 30 R32 represents hydrogen or (C1-C4)-alkyl, preferably hydrogen or methyl, and W represents S, NH or O, preferably S. Moreover, in the compounds of the general formula (I), the radical R2 may be a group of the formula below 26 where (C1-C4)-alkyl and cyclopropyl, cyclopentyl or cyclohexyl for their part may optionally be substituted by a radical from the group consisting of cyano; -OH; -OCH3; -NR28R29;-CO(NH)v(NR27R28) and -C(NR27R28)=NR29, 5 where: v is either 0 or 1, preferably 0, and 10 R27, R28 and R29 are identical or different and independently of one another each represents hydrogen, (C1-C4)-alkyl or else cyclopropyl, cyclopentyl or cyclohexyl and/or 15 R27 and R28 or R27 and R29 together with the nitrogen atom to which they are attached may form a saturated or partially unsaturated 5- to 7-membered heterocycle having up to two identical or different heteroatoms from the group consisting of N, O and S, and 20 R30 and R31 are identical or different and independently of one another each represents hydrogen, (C1-C4)-alkyl, cyclopropyl, cyclopentyl, cyclohexyl, (C1-C4)-alkylsulphonyl, (C1-C4)-hydroxyalkyl, (C1-C4)-aminoalkyl, di-(C1-C4)-aIkylarnino- 25 (C1-C4)-alkyl, (C1-C3)-alkanoyl or phenylcarbonyl, R3, R4, R5, R6, R7 and R8 are identical or different and each represents hydrogen or represents (C1-C4)-alkyl 30 and their pharmaceutically acceptable salts, hydrates and prodrugs, except for compounds of the general formula (I) in which the radical R1 is an unsubstituted 2-thiophene radical and the radical R2 is simultaneously a mono- or polysubstituted phenyl radical and the radicals R3, R4, R5, R6, R7 and R8 are each 35 simultaneously hydrogen. --14- Very particular preference is given here to compounds of the general formula (I), in which 5 R1 represents 2-thiophene which is substituted in the 5-position by a radical from the group consisting of chlorine, bromine, methyl and trifluoromethyl, R2 represents D-A-: 10 where: the radical "A" represents phenylene; the radical "D" represents a saturated 5- or 6-membered heterocycle, which is attached to "A" via a nitrogen atom, which has a carbonyl group directly adjacent to the linking nitrogen 15 atom and in which one carbon ring member may be replaced by a heteroatom from the group consisting of S, N and O; where 20 the group "A" defined above may optionally be mono- or disubstituted in the meta position with respect to the point of attachment to the oxazolidinone, by a radical from the group consisting of fluorine, chlorine, nitro, amino, trifluoromethyl, methyl and cyano, 25 R3, R4, R5, R6, R7 and R8 each represent hydrogen and their pharmaceutically acceptable salts, hydrates and prodrugs. Very particular preference is also given here to the compound having the following 30 formula / NW and to its pharmaceutically acceptable salts, hydrates and prodrugs. In the compounds of the general formula (I) above, the radical 5 R1 may in particular represent optionally benzo-fused thiophene (thienyl) which may optionally be mono- or polysubstituted by a radical from the group consisting of halogen; cyano; nitro; (C1-C8)-alkyl, which for its part may optionally be mono- or polysubstituted by halogen; (C3-C7)-cycIoalkyl; 10 (C1-C8)-alkoxy; imidazolinyl; -C(=NH)NH2; carbamoyl; and mono- and di- (C1-C4)-alkylaminocarbonyI. In the compounds of the general formula (I), the radical 15 R1 may preferably represent thiophene (thienyl), in particular 2-thiophene, which may optionally be mono- or polysubstituted by halogen, preferably chlorine or bromine, or by (C1-C8)-alkyl, preferably methyl, where the (C1-C8)-alkyl radical, preferably the methyl radical, may for its part optionally be mono- or polysubstituted by halogen, preferably fluorine. 20 In the compounds of the general formula (I), the radicals R3, R4, R5, R6, R7 and R8 may be identical or different and may represent, in particualr, hydrogen or (C1-C6)-alkyl, preferably hydrogen or (C1-C4)-alkyl, 25 very particularly preferably hydrogen. The radical R2, i.e. the organic radical, can in particular be selected from the substituent groups listed below: 30 In the compounds of the general formula (I), the radical 6 5 Finally, in the compounds of the general formula (I), the radical R2 may be a group of the formula below 10 To date, oxazolidinones have essentially only been described as antibiotics, and in individual cases also as MAO inhibitors and fibrinogen antagonists (review: Riedl, B., Endermann, R., Exp. Opin. Ther. Patents 1999,9 (5), 625), where a small 5-[acyl- 15 aminomethyl] group (preferably 5-[acetylarninoinethyl]) appears to be essential for the antibacterial activity. Substituted aryl- and heteroarylphenyloxazolidinones in which a mono- or polysubstituted phenyl radical may be attached to the N atom of the oxazolidinone 20 ring and which may have an unsubstituted N-methyl-2-thiophenecarboxamide radical in the 5-position of the oxazolidinone ring, and their use as antibacterial substances, are known from U.S. Patents US-A-5 929 248, US-A-5 801 246, US-A-5 756 732, US-A-5 654 435, US-A-5 654 428 and US-A-5 565 571. 25 In addition, benzamidine-containing oxazolidinones are known as synthetic intermediates in the synthesis of factor Xa inhibitors and/or fibrinogen antagonists (WO-A-99/31092, EP-A-623615). Depending on the substitution pattern, the compounds of the general formula (I) 30 according to the invention may exist in stereoisomeric forms which are either like image and mirror image (enantiomers) or not like image and mirror image 27 (diastereomers). The invention relates both to the enantiomers or diastereomers and to their respective mixtures. The racemic forms, like the diastereomers, can be separated in a known manner into the stereoisomerically uniform components. 5 Furthermore, certain compounds of the general formula (I) can be present in tautomeric forms. This is known to the person skilled in the art, and such compounds are likewise within the scope of the invention. Physiologically acceptable, i.e. pharmaceutically compatible, salts can be salts of the 10 compounds according to the invention with inorganic or organic acids. Preference is given to salts with inorganic acids, such as, for example, hydrochloric acid, hydrobromic acid, phosphoric acid or sulphuric acid, or to salts with organic carboxylic or sulphonic .acids, such as, for example, acetic acid, trifluoroacetic acid, propionic acid, maleic acid, fumaric acid, malic acid, citric acid, tartaric acid, lactic 15 acid, benzoic acid, or methanesulphonic acid, ethanesulphonic acid, benzenesulphonic acid, toluenesulphonic acid or naphthalenedisulphonic acid. Other pharmaceutically compatible salts which may be mentioned are salts with customary bases, such as, for example, alkali metal salts (for example sodium or 20 potassium salts), alkaline earth metal salts (for example calcium or magnesium salts) or ammonium salts, derived from ammonia or organic amines, such as, for example, diethylamine, triethylamine, ethyldiisopropylamine, procaine, dibenzylarnine, N-methylmorpholine, dihydroabietylamine or methylpiperidine. 25 According to the invention, "hydrates" are forms of the compounds of the general formula (I) above which form a molecule compound (solvate) in the solid or liquid state by hydration with water. In the hydrates, the water molecules are attached through secondary valencies by intermolecular forces, in particular hydrogen bridges. Solid hydrates contain water as so-called crystal water in stoichiometric ratios, where the 30 water molecules do not have to be equivalent with respect to their binding state. Examples of hydrates are sesquihydrates, monohydrates, dihydrates or trihydrates. Equally suitable are the hydrates of salts of the compounds according to the invention. According to the invention, "prodrugs" are forms of the compounds of the general 35 formula (I) above which for their part can be biologically active or inactive, but which can be converted into the corresponding biologically active form (for example metabolically, solvolytically or in another way). Halogen represents fluorine, chlorine, bromine and iodine. Preference is given to 5 chlorine or fluorine. (C1-C8)-Alkvl represents a straight-chain or branched alkyl radical having 1 to S carbon atoms. Examples which may be mentioned are: methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl and n-hexyl. The corresponding alkyl groups with 10 fewer carbon atoms, such as, for example, (C1-C6)-aIkyI and (C1-C4)-alkyl, are derived analogously from this definition. In genera], preference is given to (C1-C4)-alkyl The meaning of the corresponding component of other more complex substituents, such as, for example, alkvlsulphonyl. hvdroxvalkvl. hvdroxyalkvlcarbonvl, alkoxy- 15 alkyl, alkoxvcarbonvl-alkvl alkanoylalkyl, aminoalkvl or alkylaminoalkyl is likewise derived from this definition. (C3-C7)-CvcloaIkvl represents a cyclic alkyl radical having 3 to 7 carbon atoms. Examples which may be mentioned are: cyclopropyl, cyclobutyl, cyclopentyl, 20 cyclohexyl or cycloheptyl. The corresponding cycloalkyl groups having fewer carbon atoms, such as, for example, (C3-C5)-cycloalkyl, are derived analogously from this definition. Preference is given to cyclopropyl, cyclopentyl and cyclohexyl. The meaning of the corresponding component of other more complex substituents, 25 such as, for example, cvcloalkanoyl, is likewise derived from this definition. In the context of the invention, (C2-C6)-alkenvl represents a straight-chain or branched alkenyl radical having 2 to 6 carbon atoms. Preference is given to a straight-chain or branched alkenyl radical having 2 to 4 carbon atoms. Examples which may be 30 mentioned are; vinyl, allyl, isopropenyl and n-but-2-en-l-yI. (C1-C8)-Alkoxv represents a straight-chain or branched alkoxy radical having 1 to 8 carbon atoms. Examples which may be mentioned are: methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, n-pentoxy, n-hexoxy, n-heptoxy and 35 n-octoxy. The corresponding alkoxy groups having fewer carbon atoms, such as, for example, (C1-C6)-alkoxy and (C1-C4)-Alkoxy, are derived analogously from this definition. In general, preference is given to (C1-C4)-alkoxy. The meaning of the corresponding component of other more complex substituents, 5 such as, for example alkoxy-alkyl. alkoxvcaibonvl-alkvl and alkoxycarbonyl. is likewise derived from this definition. Mono- or di-(C1-C4)-alkylaminocarbonvl represents an amino group which is attached via a carbonyl group and which has a straight-chain or branched or two identical or 10 different straight-chain or branched alkyl substitutents having in each case 1 to 4 carbon atoms. Examples which may be mentioned are: methylamino, ethylamino, n-propylamino, isopropylamino, t-butylamino, N,N-dimethylamino, N,.N-diethylamino, N-ethyl-N-methylamino, N-methyl-N-n-propylamino, N-isopropyl-N-n-propylamino and N-t-butyl-N-methylamino. 15 (C1-C6)-Alkanovl represents a straight-chain or branched alkyl radical having 1 to 6 carbon atoms which carries a doubly attached oxygen atom in the 1-position and is attached via the 1-position. Examples which may be mentioned are: formyl, acetyl, propionyl, n-butyryl, i-butyryl, pivaloyl, n-hexanoyl. The corresponding alkanoyl 20 groups with fewer carbon atoms, such as, for example, (C1-C5)-alkanoyl, (C1-C4)-alkanoyl and (C1-C3)-alkanoylr are derived analogously from this definition. In general, preference is given to (C1-C3)-alkanoyl. The meaning of the corresponding component of other more complex substituents, 25 such as, for example, cvcloalkanoyl and alkanovlalkvl. is likewise derived from this definition. (C3-C7)-Cycloalkanovl represents a cycloalkyl radical having 3 to 7 carbon atoms .as, defined above which is attached via a carbonyl group. 30 (C1-C6)-AlkanovloxymethvIoxv represents a straight-chain or branched alkanoyloxymethyioxy radical having 1 to 6 carbon atoms. Examples which may be mentioned are: acetoxymethyloxy, propionoxymethyloxy, n-butyroxymethyloxy, i-butyroxymethyloxy, pivaloyloxymethyloxy, n-hexanoyloxymethyloxy. The 35 corresponding alkanoyloxymethyioxy groups having fewer carbon atoms, such as, for 30 example, (CrC3)-aIkanoyIoxymethyloxy, are derived analogously from this definition, In general, preference is given to (C1-C3)-alkanoyloxymethyloxy. (C6-C14)-Aryl represents an aromatic radical having 6 to 14 carbon atoms. Examples 5 which may be mentioned are: phenyl, naphthyl, phenanthrenyl and anthracenyl. The corresponding aryl groups with fewer carbon atoms, such as, for example, (C6-C1o)-aryl are derived analogously from this definition. In general, preference is given to (C6-C10)-aryl 10 The meaning of the corresponding component of other more complex substituents, such as, for example, arylcarbonyl. is likewise derived from this definition. (C5-C10)-Heteroarvl or a 5- to 10-membered aromatic heterocycle having up to 3 heteroatoms and/or hetero chain members from the group consisting of S. O, N and NO 15 (N-oxide) represents a mono- or bicyclic heteroaromatic which is attached via a carbon ring atom of the heteroaromatic or, if appropriate, via a nitrogen ring atom of the heteroaromatic. Examples which may be mentioned are: pyridyl, pyridyl N-oxide, pyrimidyl, pyridazinyl, pyrazinyl, thienyl, furyl, pyrrolyl, pyrazolyl, imidazolyl, thiazotyl, oxazolyl or isoxazolyl, indolizinyl, indolyl, benzofbjthienyl, benzo[b]fuiyl, 20 indazolyl, quinolyl, isoquinolyl, naphthyridinyl, quinazolinyl. The corresponding heterocycles having a smaller ring size, such as, for example, 5- or 6-membered aromatic heterocycles, are derived analogously from this definition. In general, preference is given to 5- or 6-membered aromatic heterocycles, such as, for example, pyridyl, pyridyl N-oxide, pyrimidyl, pyridazinyl, furyl and thienyl. 25 The meaning of the corresponding component of other more complex substituents, such as, for example, (C5-C10)-heteroarvlcarbonyl is likewise derived from this definition. 30 A 3- to 9-membered saturated or partially unsaturated, mono- or bicyclic, optionally benzo-fused heterocycle having up to 3 heteroatoms and/or hetero chain members from the group consisting of S, SO. SO2, N. NO (N-oxide) and Q represents a heterocycle which may contain one or more double bonds, which may be mono- or bicyclic, to which a benzene ring may be fused to two adjacent carbon ring atoms and 35 which is attached via a carbon ring atom or a mtrogen ring atom. Examples which may be mentioned are: tetrahydrofuryl, pyrrolidinyl, pyrrolinyl, piperidinyl, 1,2- dihydropyridinyl, 1,4-dihydropyridinyl, piperazinyl, morpholinyl, morpholinyl N-oxide, thiomorpholinyl, azepinyl, 1,4-diazepinyl and cyclohexyi. Preference is given to piperidinyl, morpholinyl and pyrrolidinyl. 5 The corresponding cycles having a smaller ring size, such as, for example, 5- to 7- membered cycles, are derived analogously from this definition. The present invention also provides a process for preparing the compounds of the general formula (I) according to the invention where either, according to one process 10 alternative [A] compounds of the general formula (II) O R R8 15 in which the radicals R2, R3, R4, R5, R6 and R7 are each as defined above, 20 are reacted with carboxylic acids of the general formula (HI) HO^.R1 (HI), 25 in which the radical R1 is as defined above, 32- or else with the corresponding carbonyl halides, preferably carbonyl chlorides, or else with the corresponding symmetric or mixed carboxylic anhydrides of the carboxylic acids of the general formula (HI) defined above in inert solvents, if appropriate in the presence of an activating or coupling agent and/or a base, to give compounds of the general formula (I) (D, 10 in which the radicals R\ R2, R3, R4, R5, R6, R7 and R8 are each as defined above, 15 or else according to a process alternative [B] compounds of the general formula (IV) R3 R6 R7 Q 20 in which the radicals R1, R3, R4, R5, R6, R7 and R8 are each as defined above, 25 are converted, using a suitable selective oxidizing agent in an inert solvent, into the corresponding epoxide of the general formula (V) 33 R3 R6 B7 ft in which the radicals R1, R3, R4, R5, R6, R7 and R8 are each as defined above, and, by reaction in an inert solvent, if appropriate in the presence of a catalyst, with an amine of the general formula (VI) 10 R2-NH2 (VI), in which 15 the radical R2 is as defined above, the compounds of the general formula (VII) R4 R3 R6 R7 ft 20 in which 25 the radicals R1, R2, R3, R4, R5, R6, R7 and R8 are each as defined above, are initially prepared and subsequently, in an inert solvent in the presence of phosgene or phosgene equivalents, such as, for example, carbonyldiimidazole (CDI), cyclized to 30 give the compounds of the general formula (I) ~?A~- in which 5 the radicals R1, R2, R3, R4, R5, R6, R7 and R8 are each as defined above, where - both for process alternative [A] and for process alternative [B] - in the case where R2 contains a 3- to 7-membered saturated or partially 10 unsaturated cyclic hydrocarbon radical having one or more identical or different heteroatoms from the group consisting of N and S, an oxidation with a selective oxidizing agent to afford the corresponding sulphone, sulphoxide or N-oxide may follow 15 and/or where - both for process alternative [A] and for process alternative [B] - in the case where the compound prepared in this manner has a cyano group in the molecule, an amidination of this cyano group by customary methods may 20 follow and/or where - both for process alternative [A] and for process alternative [B] - in the 25 case where the compound prepared in this manner has a BOC amino protective group in the molecule, removal of this BOC amino protective group by customary methods may follow and/or 30 where - both for process alternative [A] and for process alternative [B] - in the case where the compound prepared in this manner has an aniline or benzylamine radical in the molecule, a reaction of this amino group with various reagents such as carboxylic acids, carboxylic anhydrides, carbonyl chlorides, isocyanates, sulphonyl chlorides or alkyl halides to give the corresponding derivatives may follow and/or 10 where - both for process alternative [A] and for process alternative [B] - in the case where the compound prepared in this manner has a phenyl ring in the molecule, a reaction with chlorosulphonic iicid and subsequent reaction with amines to give the corresponding sulphonamides may follow. 15 The processes according to the invention can be illustrated in an exemplary manner by the equations below: The oxidation step described above, which is optional, can be illustrated in an 5 exemplary manner by the equation below: Suitable solvents for the processes described above are organic solvents which are 10 inert under the reaction conditions. These include halogenated hydrocarbons, such as dichloromethane, trichloromethane, carbon tetrachloride, 1,2-dichloroethane, trichloroethane, tetrachloroethane, 1,2-dichIoroethyIene or trichloroethylene, ethers, such as diethyl ether, dioxane, tetrahydrofuran, glycol dimethyl ether or diethylene glycol dimethyl ether, alcohols, such as methanol, ethanol, n-propanol, isopropanol, 15 n-butanol or tert-butanol, hydrocarbons, such as benzene, xylene, toluene, hexane or cyclohexane, dimethylformamide, dimethyl sulphoxide, acetonitrile, pyridine, hexa-methylphosphoric triamide or water. It is also possible to use solvent mixtures of the solvents mentioned above. 20 37 Suitable activating or coupling agents for the processes described above are the reagents which are customarily used for this purpose, for example N"-(3-dimemyIaminopropyI)-N-ethylcarbodiimide . HO, N,N"-dicyclohexylcarbo-diimide, 1-hydroxy-lH-benzotriazole • H20 and the like. 5 Suitable bases are the customary inorganic or organic bases. These preferably include alkali metal hydroxides, such as, for example, sodium hydroxide or potassium hydroxide, or alkali metal carbonates, such as sodium carbonate or potassium carbonate, or sodium methoxide or potassium methoxide or sodium ethoxide or 10 potassium ethoxide or potassium-tert-butoxide, or amides, such as sodium amide, lithium bis-(trimethylsilyl)amide or lithium diisopropylamide, or amines, such as triethylamine, diisopropylethylamine, diisopropylamine, 4-N,N-dimethylamino-pyridine or pyridine. 15 The base can be employed here in an amount of from 1 to 5 mol, preferably from 1 to 2 mol, based on 1 mol of the compounds of the general formula (II). The reactions are generally carried out in a temperature range of from -78°C to reflux temperature, preferably in the range from 0°C to reflux temperature. 20 The reactions can be carried out at atmospheric, elevated or reduced pressure (for example in the range from 0.5 to 5 bar). In general, the reactions are carried out at atmospheric pressure, 25 Suitable selective oxidizing agents, both for the preparation of the epoxides and for the optional oxidation to give the sulphone, sulphoxide or N-oxide, are m-chloroperbenzoic acid (MCPBA), sodium metaperiodate, N-methylmorpholine N-oxide (NMO), monoperoxyphthalic acid or osmium tetroxide. 30 With respect to the preparation of the epoxides, the preparation conditions which are customary for this purpose are employed. With respect to more detailed process conditions for the optional oxidation to give the sulphone, sulphoxide or N-oxide, reference is made to the following literature: 35 M. R. Barbachyn et al., J. Med. Chem. 1996,39, 680 and WO-A-97/10223. Furthermore, reference is made to Examples 14 to 16 given in the experimental part. The optional amidation is carried out under customary conditions. For more details, reference is made to Examples 31 to 35 and 140 to 147. 5 The compounds of the general formulae (II), (III), (IV) and (VI) are known per se to the person skilled in the art or can be prepared by customary methods. For oxazolidinones, in particular the 5-(aminomethyl)-2-oxooxazolidines required, cf. WO-A-98/01446; WO-A-93/23384; WO-A-97/03072; J.A.Tucker etal., J.Med, 10 Chem. 1998, 41, 3727; S.J.Brickner etal., J.Med Chem. 1996, 39, 673; W. A. Gregory et al., J. Med. Chem. 1989,32,1673. The compounds of the general formula (I) according to the invention have an unforeseeabte useful pharmacological activity spectrum and are therefore parrkttlarYy 15 suitable for the prophylaxis and/or treatment of disorders. The compounds of the general formula (I) according to the ivnention - including the compounds which are excluded by disclaimer from the chemical product protection - act in particular as anticoagulants and can therefore preferably be 20 employed in medicaments for the prophylaxis and/or therapy of thromboembolic disorders. For the purpose of the present invention, "thromboembolic disorders" include, in particular, serious disorders such as myocardial infarct, angina pectoris (including unstable angina), reocclusions and restenoses after angioplasty or aortocoronary bypass, stroke, transitory ischaemic attacks, peripheral arterial 25 occlusion disorders, pulmonary embolisms or deep venous thromboses. Furthermore, the compounds of the general formula (I) according to the invention - including the compounds which are excluded by disclaimer from the chemical product protection - are also suitable for treating disseminated intravascular 30 coagulation (DIC). Finally, the compounds of the general formula (I) according to the invention - including the compounds which are excluded by disclaimer from the chemical product protection - are also suitable for the prophylaxis and/or treatment of 35 atherosclerosis and arthritis, and additionally also for the prophylaxis and/or treatment of Alzheimer"s disease and cancer. 39 4frA-34^l2i-froreign Lountrfes The compounds of the general formula (I) according to the invention - including the compounds excluded by disclaimer from the chemical product protection - act in particular as selective inhibitors of the blood coagulation factor Xa and do not 5 inhibit, or only inhibit at considerably higher concentrations, other serine proteases as well, such as thrombin, plasmin or trypsin. In the context of the present invention, inhibitors of the blood coagulation factor Xa in which the IC50 values for the factor Xa inhibition are lower by a factor of 100, 10 preferably by a factor of 500, in particular by a factor of 1000, than the IC50 values for the inhibition of other serine proteases, in particular thrombin, plasmin and trypsin, are referred to as being selective", where with a view to the test methods for selectivity, reference is made to the test methods of Examples A-l) a.l) and a.2) described below. 15 The compounds of the general formula (I) according to the invention - including the compounds which are excluded by disclaimer from the chemical product protection -can furthermore be used for preventing coagulation ex vivo, for example for banked blood or biological samples which contain factor Xa, 20 The present invention thus provides oxazolidinones of the formula (I) effecting in particular an unexpected, strong and selective inhibition of factor Xa, and this also applies to the compounds excluded by disclaimer from the chemical product protection, 25 The present invention further provides medicaments and pharmaceutical compositions comprising at least one compound of the general formula (I) according to the invention together with one or more pharmacologically acceptable auxiliaries or excipients, which medicaments and pharmaceutical compositions can be used for 30 the indications mentioned above. Furthermore, the present invention relates to a method for the prophylaxis and/or treatment of disorders of the human or animal body, in particular of the abovementioned disorders, using the compounds of the general formula (I) according 35 to the invention - including the compounds excluded by disclaimer from the chemical product protection. Furthermore, the present invention also includes a method for preventing blood coagulation in vitro, in particular in banked blood or biological samples which contain factor Xa, which method is characterized in that compounds of the general 5 formula (I) - including the compounds excluded by disclaimer from the chemical product protection - are added. All customary administration forms are suitable for administration of the compounds according to the invention. Administration is preferably carried out orally, lingually, 10 sublingually, buccally, rectally or parenterally (i.e. bypassing the intestinal tract, that is intravenously, intraarterially, intracardially, intracutaneously, subcutaneously, transdermally, intraperitoneally or intramuscularly). Particularly suitable are oral and intravenous administration. Very particular preference is given to oral administration, this being a further advantage with respect to the prior-art therapy of thromboembolic 15 disorders. The novel active compounds of the general formula (I) can be converted in a known manner into the customary formulations, such as tablets, sugar-coated tablets, pills, granules, aerosols, syrups, emulsions, suspensions and solutions, using inert non- 20 toxic pharmaceutically suitable excipients or solvents. Here, the therapeutically active compound should in each case be present in a concentration of from about 0.1 to 95% by weight, preferably from 0.5 to 90% by weight, in particular from 1 to 85% by weight, of the total mixture, i.e. in amounts which are sufficient in order to achieve the dosage range indicated. 25 In spite of this, if appropriate, it may be necessary to depart from the amounts mentioned, namely depending on the body weight or on the type of administration route, on the individual response to the medicament, on the manner of its formulation and the time or interval at which administration takes place. Thus, in some cases it 30 may be adequate to manage with less than the abovementioned minimum amount, while in other cases the upper limit mentioned must be exceeded. In the case of the administration of relatively large amounts, it may be advisable to divide these into several individual administrations over the course of the day. 35 The formulations are prepared, for example, by extending the active compounds with solvents and/or excipients, if appropriate using emulsifiers and/or dispersants, it being possible, for example if the diluent used is water, optionally to use organic solvents as auxiliary solvents. In general it has proved advantageous in the case of intravenous administration to 5 administer amounts from approximately 0,001 to 10 mg/kg, preferably approximately 0.01 to 10 mg/kg, in particular approximately 0.1 to 8mg/kg, of body weight to achieve effective results. In general, it has proved advantageous in the case of oral administration to administer 10 amounts from approximately 0.01 to 50 mg/kg, preferably approximately 0-1 to 10 mg/kg, in particular approximately 0.5 to 8 mg/kg, of body weight to achieve effective results. In spite of this, if appropriate, it may be necessary in the case of intravenous or oral 15 administration to depart from the amounts mentioned, namely depending on the body weight or on the type of administration route, on the individual response to the medicament, on the manner of its formulation and the time or interval at which administration takes place. Thus, in some cases it may be adequate to manage with less than the abovementioned mininum amount, while in other cases the upper limit 20 mentioned must be exceeded. In the case of the administration of relatively large amounts, it may be advisable to divide these over the course of the day, namely into several individual doses or as a continuous infusion. Compared to the conventional preparations for treating thromboembolic disorders, 25 the compounds of the general formula (I) according to the invention - including the compounds excluded by disclaimer from the chemical product protection - are distinguished in particular by the fact that a greater therapeutic range is achieved by the selective inhibition of factor Xa, For the patient, this means a lower risk- of bleeding, and for the treating physician, this means that the patient is easier to adjust. 30 Moreover - owing to the mechanism - the onset of action is more rapid. Above all, however, the compounds according to the invention permit an oral administration form, which is a further advantage of the therapy with the compounds according to the invention. 35 The present invention is illustrated by the examples below; however, these examples are not meant to restrict the invention in any way. -"42- " Examples A Evaluation of the physiological activity 5 1. General test methods The particularly advantageous biological properties of the compounds according to the invention can be determined by the following methods. 10 a) Test description (in vitro) a.l) Determination of the factor Xa inhibition The enzymatic activity of human factor Xa (FXa) was measured using the conversion 15 of a chromogenic substrate specific for FXa. Factor Xa cleaves p-nitroaniline from the chromogenic substrate. The determinations were carried out in microtitre plates as follows. The test substances, in various concentrations, were dissolved in DMSO and 20 incubated at 25°C with human FXa (0.5 nmol/l dissolved in 50 mmol/1 of tris buffer [C,C,C-tris(hydroxymethyl)-aminomethane], 150 mmol/1 of NaCI, 0.1% BSA (bovine serum albumin), pH = 8.3) for 10 minutes. Pure DMSO was used as control. The chromogenic substrate (150 /imol/1 of Pefachrome® FXa from Pentapharm) was then added. After an incubation time of 20 minutes at 25°C, the extinction at 405 nm 25 was determined. The extinctions of the test mixtures containing test substance were compared with the control mixtures without test substance, and the IC5o values were calculated from these data. - ^ a.2) Determination of the selectivity 30 To assess selective FXa inhibition, the test substances were examined for their inhibition of other human serine proteases such as thrombin, trypsin and plasmin. To determine the enzymatic activity of thrombin (75 mU/ml), trypsin (500 mU/ml) and plasmin (3.2 nmol/l), these enzymes were dissolved in tris buffer (100 mmol/1, 35 20 mmol/1 CaCl2, pH = 8.0) and incubated with test substance or solvent for 10 minutes. The enzymatic reaction was then started by adding the corresponding removed and the nylon thread with the thrombus was weighed immediately. The weight of the nylon thread on its own had been detennined before the experiment was started. Before the extracorporeal circulation was set up, the test substances were administered to the animals while awake either intravenously via the tail vein or orally using a pharyngeal tube. specific chromogenic substrates (Chromozym Thrombin® from Boehringer Mannheim, Chromozym Trypsin® from Boehringer Mannheim, Chromozym Plasmin® from Boehringer Mannheim) and the extinction at 405 nm was determined after 20 minutes. All determinations were carried out at 37°C. The extinctions of the 5 test mixtures containing test substance were compared with the control samples without test substance, and the IC50 values were calculated from these data. a3) Determination of the anticoagulant action 10 The anticoagulant action of the test substances was determined in vitro in human plasma. To this end, human blood was drawn off in a mixing ratio of sodium citrate/blood of 1/9 using a 0.11 molar sodium citrate solution as receiver. Immediately after the blood had been drawn off, it was mixed thoroughly and centrifuged at about 2000 g for 10 minutes. The supernatant was pipetted off. The 15 prothrombin time (PT, synonyms; thromboplastin time, quick test) was determined in the presence of varying concentrations of test substance or the corresponding solvent using a commercial test kit (Neoplastin® from Boehringer Mannheim). The test compounds were incubated with the plasma at 37°C for 10 minutes. Coagulation was then started by addition of thromboplastin, and the time when coagulation occurred 20 was determined. The concentration of test substance which effected a doubling of the prothrombin time was determined. b) Determination of the antithrombotic activity (in vivo) 25 b.l) Arteriovenous shunt model (rat) Fasting male rats (strain: HSD CPB:WU) having a weight of 200-250 g were anaesthetized using a Rompun/Ketavet solution (12 mg/kg/ 50 mg/kg). Thrombus formation was initiated in an arteriovenous shunt in accordance with the method 30 described by Christopher N. Berry et al., Br. J. Pharmacol. (1994), 113, 1209-1214. To this end, the left jugular vein and the right carotid artery were exposed. The two vessels were connected by an extracorporeal shunt using a polyethylene tube (PE 60) of a length of 10 cm. In the middle, this polyethylene tube was attached to a further polyethylene tube (PE 160) of a length of 3 cm which contained a roughened nylon 35 thread which had been arranged to form a loop, to form a thrombogenic surface. The extracorporeal circulation was maintained for 15 minutes. The shunt was then LfrA-3+i23=Fb15i"gn countries 45- The results are shown in Table 1: Table 1: Antithrombotic activity in the arteriovenous shunt model (rat) after oral or intravenous administration Example ED56 [mg/kfi] p.o. ED50 [mg/kg] i.v. 1 10 17 6 44 3 95 3 114 3 115 3 123 3 162 3 b.2) Arterial thrombosis model (rat) Male fasting rats (strain: HSD CPB: WU) were anaesthetized as described above. On 10 average, the rats had a weight of about 200 g. The left carotid artery was exposed (about 2 cm). The formation of an arterial thrombus was induced by mechanical injury to the blood vessel in accordance with the method described by K. Meng et al., Naunyn-Schmiedeberg"s Arch. Pharmacol. (1977), 301, 115-119. To this end, the exposed carotid artery was clamped from the blood flow, cooled to -12°C in a metal 15 trough for 2 minutes and, to standardize the size of the thrombi, simultaneously compressed using a weight of 200 g. The blood flow was then additionally reduced by a clip which was placed around the carotid artery distally from the injured section of the vessel. The proximal clamp was removed, and the wound was closed and re¬opened after 4 hours to remove the injured section of the vessel. The section ofthe 20 vessel was opened longitudinally and the thrombus was removed from the injured section of the vessel. The moist weight of the thrombi was determined immediately. The test substances were administered to the animals while awake at the beginning of the experiment, either intravenously via the tail vein or orally using a pharyngeal tube. 25 b.3) Venous thrombosis model (rat) Male fasting rats (strain: HSD CPB: WU) were anaesthetized as described above. On average, the rats had. a weight of about 200 g. The left jugular vein was exposed 5 (about 2 cm). The formation of a venous thrombus was induced by mechanical injury to the blood vessel in accordance with the method described by K. Meng et al., Naunyn-Schmiedeberg"s Arch. Pharmacol. (1977), 301, 115-119. To this end, the jugular vein was clamped from the blood flow, cooled to -12°C in a metal trough for 2 minutes and, to standardize the size of the thrombi, simultaneously compressed 10 using a weight of 200 g. The blood flow was re-opened and the wound was closed. After 4 hours, the wound was re-opened to remove the thrombi from the injured sections of the vessel. The moist weight of the thrombi was determined immediately. The test substances were administered to the animals while awake at the beginning of the experiment, either intravenously via the tail vein or orally using a pharyngeal 15 tube. B Preparation Examples Starting materials 5 The preparation of 3-morphoIinone is described in US 5 349 045. The preparation of N-(2,3-epoxypropyI)phthalimide is described in J.-W. Chcm et al. Tetrahedron Lett. 1998,39,8483. 10 The substituted anilines can be obtained by reacting, for example, 4-fluoronitro- benzene, 2,4-difluoronitrobenzene or 4-chloronitrobenzene with the appropriate amines or amides in the presence of a base. This can also be carried out using Pd catalysts, such as Pd(OAc)2/DPPF/NaOt-Bu (Tetrahedron Lett 1999,40,2035) or copper (Kenger, Synthesis 1985.856; Aebischer et a]., Heterocycles 1998,48,2225). 15 Likewise, it is possible to initially convert halogenated aromatics without nitro group into the corresponding amides, followed by nitration in the 4-position (US3279880). I. 4-(4-Morpholin-3-onyl)nitrobenzene NO, rV° 20 O 2 mol (202 g) of morpholin-3-one (E. Pfeil, U. Harder, Angew. Chem. 79,1967, 188) are dissolved in 21 of N-methylpyrrolidone (NMP). Over a period of 2 h, 88 g (2.2 mol) of sodium hydride (60% in paraffin) are then added a little at a time. After-the evolution of hydrogen has ceased, 282 g (2 mol) of 4-fluoronitrobenzene are 25 added dropwise with cooling at room temperature, over a period of 1 h, and the reaction mixture is then stirred overnight. At 12 mbar and 76°C, 1,71 of the liquid volume are then distilled off, the residue is poured into 2 1 of water and this mixture is extracted twice with in each case 11 of ethyl acetate. After washing of the combined organic phases with water, the mixture is dried over sodium sulphate and 30 the solvent is distilled off under reduced pressure. Purification is carried out by silica gel chromatography using hexane/ethyl acetate (1:1) and subsequent crystallization 10 15 from ethyl acetate. This gives 78 g of product as a colourless to brownish solid, in a yield of 17.6% of theory. "H-NMR (300 MHz, CDC13): 3,86 (m, 2 H, CH2CH2), 4.08 (m, 2 H, CH2C#2), 4.49 (s, 2H, CH2CO), 7.61 (d, 2H, 3/=8.95 Hz, CHCH), 8.28 (d, 2H, 37=8.95Hz, CHCtf) MS (r.L%) = 222 (74, M+), 193 (100), 164 (28), 150 (21), 136 (61), 117 (22), 106 (24), 90 (37), 76 (38), 63 (32), 50 (25) The following compounds were synthesized analogously: 3-fluoro-4-(4-morpholin-3-onyl)nitrobenzene 4-(N-piperidonyl)nitrobenzene 3-fluoro-4-(N-piperidonyl)nitrobenzene 4-(N-pyrrolidonyl)nitrobenzene 3-fluoro-4-(N-pyrrolidonyl)nitrobenzene II. 4-(4-Morpholin-3-onyI)aniline In an autoclave, 63 g (0.275 mol) of 4-(4-morpholin-3-onyl)nitrobenzene are 20 dissolved in 200 ml of tetrahydrofuran, admixed with 3.1 g of Pd/C (5%ig) and hydrogenated at 70°C and a hydrogen pressure of 50 bar for 8 h. The catalyst is filtered off, the solvent is then distilled off under reduced pressure and the product is purified by crystallization from ethyl acetate. 20 g of product are obtained as a, colourless to bluish solid, in a yield of 37.6% of theory. 25 Purification can also be carried out by silica gel chromatography using hexane/ethyl acetate. ]H-NMR (300 MHz, CDC13): 3.67 (m, 2 H, CH2CH2), 3.99 (m, 2 H, CH2CH2), 4.27 (s, 2H, CH2CO), 6.68 (d, 2H, 3/=8.71 Hz, CHCH), 7.03 (d, 2 H, 3/=8.71 Hz, 30 CHCH) 10 MS (r.L%) = 192 (100, M+), 163 (48), 133 (26), 119 (76), 106 (49), 92 (38), 67 (27), 65 (45), 52 (22), 28 (22) The following compounds were synthesized analogously: 3-fluoro-4-(4-morpholin-3-onyl)aniIine 4-(N-piperidonyI)aniline 3-fluoro-4-(N-piperidonyl)aniline 4-(N-pyrrolidonyl)aniline 3-fluoro-4-(N-pyrrolidonyl)aniline General method for preparing 4-substituted anilines by reacting l-fluoro-4-nitrobenzenes and l-chloro-4-nitrobenzenes with primary or secondary amines, followed by reduction 15 X = F.CI Equimolar amounts of the fluoronitrobenzene or chloronitrobenzene and the amine are dissolved in dimethyl sulphoxide or acetonitrile (0.1 M to 1 M solution), and the mixture is stirred at 100°C overnight. After cooling to RT, the reaction mixture is 20 diluted with ether and washed with water. The organic phase is dried over MgSO4, filtered and concentrated. If a precipitate forms in the reaction mixture, the precipitate is filtered off and washed with ether or acetonitrile. If the mother liquor also contains product, it is worked up as described using ether and water. The crude products can be purified by silica gel chromatography (dichloromethane/cyclohexane- 25 and dichloromethane/ethanol mixtures). For the subsequent reduction, the nitro compound is dissolved in methanol, ethanol or ethanol/dichloromethane mixtures (0.01 M to 0.5 M solution) admixed with palladium on carbon (10%) and stirred under an atmospheric hydrogen pressure 30 overnight. The mixture is then filtered and concentrated. The crude product can be purified by silica gel chromatography (dichloromethane/ethanol mixtures) or preparative reversed-phase HPLC (acetonitrile/water mixtures). Alternatively, the reducing agent used can also be iron powder. To this end, the nitro compound is dissolved in acetic acid (0.1 M to 0.5 M solution) and, at 90°C, six equivalents of iron powder and water (0.3 to 0.5 times the volume of the acetic acid) 5 are added a little at a time over a period of 10-15 rnin. After a further 30 min at 90°C, the mixture is filtered and the filtrate is concentrated. The residue is worked up by extraction with ethyl acetate and 2N aqueous sodium hydroxide solution. The organic phase is dried over magnesium sulphate, filtered and concentrated. The crude product can be purified by silica gel chromatography (dichloromethane/ethanol mixtures) or 10 preparative reversed-phase HPLC (acetonitrile/water mixtures). The following starting materials were prepared in an analogous manner: III-l. tert-butv1-1-(4-aminophesyl)-L-proIinate 15 MS (ESI): m/z (%) = 304 (M+H+MeCN, 100), 263 (M+H, 20); HPLC (method 4): rt = 2.79 min. III-2. l-(4-aminoDhenvl)"3-piperidinecarboxamide MS (ESI): m/z (%) = 220 (M+H, 100); 20 HPLC (method 4): rt = 0.59 min. 1H-3. l-(4-aminophenvl)-4-piperidincarboxamide MS (ESI): m/z (%) = 220 (M+H, 100); HPLC (method 4)-. rt = 0.57 min. 25 III-4. l-(4-aminophenvl)-4-piperidinone MS (ESI): m/z (%) = 191 (M+H, 100); HPLC (method 4): n = 0.64 min. 30 III-5. l-(4-aminophenvl)-L-prolinamide MS (ESI): m/z (%) = 206 (M+H, 100); HPLC (method 4); rt = 0.72 min. III-6. [1-(4-anninophenvl)-3-piperidinvl]methanol 35 MS (ESI): m/z (%) s 207 (M+H, 100); HPLC (method 4): rt - 0.60 min. III-7. [1-(4-aminophenvl)-2-Diperidinvl1methanol MS (ESI): m/z (%) = 207 (M+H, 100); HPLC (method 4): rt = 0.59 min. 5 III-8. ethvl l-(4-aminophenvl)-2-piperiduiecarboxylate MS (ESI): m/z (%) = 249 (M+H, 35), 175 (100); HPLC (method 4): rt = 2.43 min. 10 III-9, [1-(4-aminophenvI)-2-pvrroIidinynmethanol MS (ESI): m/z (%) = 193 (M+H, 45); HPLC (method 4): rt = 0.79 min. 111-10. 4-(2-methvlhexahvdro-5H-Pvrrolor3.4:d]isoxazol-5-vl)phenviamine 15 starting from 2-methylhexahydro-2H-pyrrolo[3,4-d]isoxazoIe (Ziegler, Carl B., et al.; J. Heterocycl Chem.; 25; 2; 1988; 719-723) MS (ESI): m/z (%) = 220 (M+H, 50), 171 (100); HPLC (method 4): rt = 0.54 min. 20 III-11. 4-(l-pvrrolidinvI)-3-(trifluoromethvl)aniline MS (ESI): m/z (%) = 231 (M-fH, 100); HPLC (method 7): rt = 3.40 min. III-12. 3-chloro-4-(l-pvrrolidinyl)aniIine 25 MS (ESI): m/z (%) = 197 (M+H, 100); HPLC (method 4); rt = 0.78 min. 111,-13. 5-amino-2-(4-morpholinvl)benzamide MS (ESI): m/z (%) = 222 (M+H, 100); 30 HPLC (method 4): rt = 0.77 min. 111-14. 3-methoxv-4-(4-morDholinvI)aniline MS (ESI): m/z (%) = 209 (M+H, 100); HPLC (method 4): rt = 0.67 min. 35 111-15. l-f5-aminO-2-(4-morpholinvl)phenvIlethanone MS (ESI): m/z (%) = 221 (M+H, 100); HPLC (method 4): rt = 0.77 min, General method for preparing 4-substituted anilines by reacting l-fluoro-4- 5 nitrobenzenes with amides, followed by reduction The amide is dissolved in DMF and admixed with 1.5 equivalents of potassium tert-butoxide. The mixture is stirred at RT for 1 h, and 1.2 equivalents of the l-fluoro-4- 10 nitrobenzene are then added a little at a time. The reaction mixture is stirred at RT overnight, diluted with ether or ethyl acetate and washed with sat. aqu. sodium bicarbonate solution. The organic phase is dried over magnesium sulphate, filtered and concentrated. The crude product can be purified by silica gel chromatography (dichloromethane/ethanol mixtures). 15 For the subsequent reduction, the nitro compound is dissolved in ethanol (0.01 M to 0.5 M solution), admixed with palladium on carbon (10%) and stirred under atmospheric hydrogen pressure overnight. The mixture is then filtered and concentrated. The crude product can be purified by silica gel chromatography 20 (dichloromethane/ethanol mixtures) or preparative reversed-phase HPLC (acetonitrile/water mixtures). Alternatively, the reducing agent used can also be iron powder. To this end, the nitro compound is dissolved in acetic acid (0.1 M to 0.5 M solution) and, at 90°C; six 25 equivalents of iron powder and water (0.3 to 0.5 times the volume of the acetic acid) are added a little at a time over a period of 10-15 min. After a further 30 min at 90°C, the mixture is filtered and the filtrate is concentrated. The residue is worked up by extraction with ethyl acetate and 2N aqueous sodium hydroxide solution. The organic phase is dried over magnesium sulphate, filtered and concentrated. The crude product 30 can be purified by silica gel chromatography (dichloromethane/ethanol mixtures) or preparative reversed-phase HPLC (acetonitrile/water mixtures). The following starting materials were prepared in an analogous manner: IV-1, l-[4-amino-2-(trifluoromethyl)phenyl]-2-PvrroIidinone MS (ESI): m/z (%) = 245 (M+H, 100); 5 HPLC (method 4): rt = 2.98 min IV-2. 4-[4-amino-2-(trifluoromethyl)phenvl]-3-morpholinone MS (ESI): m/z (%) = 261 (M+H, 100); HPLC (method 4): it = 2.54 min. 10 IV-3. 4-(4-amino-2-chlorophenyl)"3-morpholinone MS (ESI): m/z (%) = 227 (M+H, 100); HPLC (method 4): rt = 1.96 min. 15 IV-4. 4-(4-amino-2-methylphenvl)-3-morpholinone MS (ESI): m/z (%) = 207 (M+H, 100); HPLC (method 4): rt = 0.71 min. IV-5. 5-amino-2-(3-oxo-4-morpholinvl)benzoilitrile 20 MS (ESI): m/z (%) = 218 (M+H, 100); HPLC (method 4): rt = 1.85 min. IV-6. l-(4-ajnino-2-chlorophenvl)-2-pvrrolidinone MS (ESI): m/z (%) = 211 (M+H, 100); 25 HPLC (method 4): rt = 2,27 min. IV-7. 4-(4-aniino-2.6-dimethvlphenvl)-3-morpholinone starting from 2-fluoro-l,3-dimethyl-5-nitrobenzene (Bartoli et al., J. Org. Cherry 1975,40, 872): 30 MS (ESI): m/z (%) = 221 (M+H, 100); HPLC (method 4): rt = 0.77 min. IV-8. 4-(2,4-diaminophenvI)-3-_morpholinone starting from l-fluoro-2,4-drnitrobenzene: 35 MS (ESI): m/z (%) = 208 (M+H, 100); HPLC (method 4): rt = 0.60 min. IV-9. 4-(4-amino-2-chlorophenyl)-2-methvl-3-morpholinone starting from 2-methyl-3-morpholinone (Pfeil, E.; Harder, U.; Angew. Chem. 1967, 79,188): 5 MS (ESI): m/z (%) = 241 (M+H, 100); HPLC (method 4); rt = 2.27 min. IV-10. 4-(4-amino-2-chloropheny)-6-methvl-3-morphollone starting from 6-methyl-3-morpholinone (EP 350 002): 10 MS (ESI): m/z (%) = 241 (M+H, 100); HPLC (method 4): rt - 2.43 min. Synthesis Examples The Examples 1 to 13,17 to 19 and 36 to 57 below refer to process variant [A]. Example 1 Preparation of 5-chloro-N-{[(5S)-3"(3-fluoro-4-morpholinophenyI)-2-oxo-l,3-oxazolidin-5-yI]methyl}-2-thiophenecarboxamide 10 (5S)-5-(Aminomethyl)-3-(3-fluoro-4-morpholinophenyl)-lt3-oxazolidin-2-one (preparation see S. J. Brickner et al., J. Med. Chem. 1996, 39, 673) (0.45 g, 1.52 mmol), 5-chlorothiophene-2-carboxylic acid (0.25 g, 1.52 mmol) and 15 1-hydroxy-lH-benzotriazole hydrate (HOBT) (0.3 g7 1.3 equivalents) are dissolved in 9.9 ml of DMF. 0.31 g (1.98 mmol, 1.3 equivalents) of N-(3-dimethylaminopropyl)-N-ethylcarbodiimide (EDO) are added, and 0.39 g (0.53 ml, 3,05 mmol, 2 equivalents) of diisopropylethylamine (DIEA) are added dropwise at room temperature. The mixture is stirred at room temperature overnight. 2 g of silica gel 20 are added, and the mixture is evaporated to dryness under reduced pressure. The residue is chromatographed on silica gel using a toluene/ethyl acetate gradient. This gives 0,412 g (61.5% of theory) of the target compound of melting point (m.p.) 197°C. Rf (Si02, toluene/ethyl acetate 1:1) = 0.29 (starting material = 0.0); 25 MS (DCI) 440.2 (M+H), CI pattern; "H-NMR (D6VDMSO, 300 MHz) 2.95 (m, 4H), 3.6 (t, 2H), 3.72 (m, 4H), 3.8 (dd, 1H), 4.12 (t, 1H), 4.75-4.85 (m, 1H), 7.05 (t, 1H), 7.15-7.2 (m, 3H), 7.45 (dd, 1H), 7.68 (d, 1H), 8.95 (t, 1H). LftA-34 122^FefektQ-Countries Example 2 5-Chloro-N-{[(5S)-3-(4-morphoIinophenyl)-2-oxo-13-oxazoIidin-5-yl]methyl}-2-thiophenecarboxamide is obtained analogously from benzyl 4-morpholinophenylcarbamate via the (5S)-5- (aminomethyI)-3-(3-fluorc-4-morpholinophenyl)-l,3-oxazolidin-2-one intermediate (see Example 1). M.p.: 198°C; 10 IC50 value = 43 nM; Rf (Si02, toluene/ethyl acetate 1:1) = 0.24. Example 3 15 5-Chloro-N-({(5S)-3-[3-fluoro-4-(l,4-thiazinan-4-yI)phenyl]-2-oxo-l,3-oxazoIi- din-5-yl}methyl)-2-thiophcnecarboxamide is obtained analogously from (5S)-5-(aminomethyl)-3-[3-fluoro-4-(l,4-thiazinan-4- 20 yl)phenyl]-l,3-oxazolidin-2-one (preparation see M. R. Barbachyn et ah, J, Med. Chem. 1996,39, 680). M.p.: 193°C; Yield: 82%; Rf (Si02, toluene/ethyl acetate 1:1) = 0.47 (starting material =0.0). 25 Example 4 5-Bromo-N-({(5S)-3-[3-fluoro-4-(l,4-thiazinan-4-yl)phenyI]-2-oxo-l,3-oxazolidin-5-yI}methyl)-2-thiophenecarboxamide is obtained analogously from 5-bromothiophene-2-carboxylic acid. M.p.: 200°C. 10 Example 5 15 N-({(5S)-3-[3-Fluoro-4-(l,4-thia2inan-4-yl)phenyl]-2-oxo-13-oxazolidin-5-yl}methyI)-5-methyI-2-thiophenecarboxamide Fv Q S\J*-\J~\ 1 CH. Example 6 5-ChIoro-N-{[(5S)-3-(6-methylthieno[2r3-b]pyrldin-2-yl)-2-oxo-l73-oxazoIidin-5. yl]methyl}-2-thiopheriecarboxarnide is obtained analogously from (5S)-5-(aminomethyl)-3-(6--niethylthieno[213-b]pyridin-2-yl)-l,3-oxazolidin-2-one (preparation see EP-A-785 200). M.p.: 247°C. Example 7 5-Chloro-N-{[(5S)-3-(3-methyl-2-oxo-2,3-dihydro-l,3-benzothiazol-6-yI)-2-oxo-l,3-oxazolidin-5-yI]methyl}-2-thiophenecarboxomide is obtained analogously from 6-[(5S)-5-(aminomethyl)-2-oxo-l,3-oxazoIidin-3-yl]-3-methyl-l,3-benzothiazoI-2(3H)-one (preparation see EP-A-738 726). M.p.:217°C. Example 8 5-Chloro-N.[((5S)-3-{3-fluoro-4-[4-(4-pyridinyl)piperazino]phenyl}-2-oxo-l,3-oxazoIidin-5-yI)methyI]-2-thiophenecarboxamide 5 o is obtained analogously from (5S)-5-(aminomethyl)-3-{3-fluoro-4-[4-(4- pyridinyl)piperazino]phenyl}-l,3-oxazolidin-2-one (preparation analogously to J. A. Tucker et al., J. Med. Chem. 1998, 41, 3727). 10 MS (EST) 516 (M+H),C1 pattern. Example 9 5-Chloro-N-({(5S)-3-[3-fluoro-4-(4-methylpiperazino)phenyI3-2-oxo-l,3-oxazoli- 15 dm-5-yl}methyI)-2-thiophenecarboxamide O is obtained analogously from (5S)-5-(aminomethyl)-3-[3-fluoro-4-(4-methylpiperazino)phenyl]-l73-oxazolidin-2-one. 20 Example 10 5-Chloro-N-({(5S)-3-[3-fluoro-4-(4-tert-butoxycarbonyIpiperazin-l-yI)phenyI]-2-oxo-l^-oxazoIidin-5-yI}methyl)-2-thiophenecarboxamide 5 a o" is obtained analogously from (5S)-5-(aminomethyl)-3-[3-fluoro-4-(4-tert-butoxy- carbonylpiperazin-l-yl)phenyl]-l,3-oxazoIidin-2-one (preparation see WO-A-93/23384, which has already been cited). 10 M.p.: 184°C; Rf(Si02, toluene/ethyl acetate 1:1) = 0.42. Example 11 15 5-Chloro-N-({(5S)-3-[3-fluoro-4-(piperazin-l-yl)phenyl]-2-oxo-l,3-oxazoIidin-5- yl}methyl)-2-thiophenecarboxamide C! O" is obtained by reacting Example 12 with trifluoroacetic acid in methylene chloride. 20 IC5o value = 140 nM; 4H-NMR [d6-DMSO]: 3.01-3.25 (m, SH), 3.5-3.65 (m, 2H), 3.7-3.9 (m, IH), 4.05-4.2 (m, IH), 4.75-4.9 (m, IH), 7.05-7.25 (m, 3H), 7.5 (dd, IH), 7.7 (d, IH), 8.4 (broad s, IH), 9.0 (t, IH). Example 12 5-Chloro-N-[((5S)-3-(2?4-bipyiridinyl-5-yI)-2-oxo-1,3-oxazolidin-5-yI)methyl]-2-thiophenecarboxamide 10 15 is obtained analogously from (5S)-5-aminomethyl-3-(2,4-bipyridinyl-5-yI)-2-oxo-l,3-oxazolidin-2-one (preparation see EP-A-789 026). Rf (Si02, ethyl acetate/ethanol 1:2) = 0.6; MS (ESI) 515 (M+H), C\ pattern. Example 13 5-Chloro-N-{[(5S)-2-oxo-3-(4-piperidinophenyl)-l,3-oxazolidin-5-yl3methyI}-2-thiophenecarboxamide 20 ■-^62- is obtained from 5-(hydroxymethyl)-3-(4-piperidinophenyl)-13-o\azolidin-2-one (preparation see DE 2708236) after mesylation, reaction with potassium phthalimide, hydrazinolysis and reaction with 5-chIorothiophene-2-carboxylic acid. Rf (Si02, ethyl acetate/toluene 1:1) = 0,31; 5 m.p. 205°C. Example 17 S-Chloro-N-({(5S)-2-oxo-3-[4-(2-oxo-l-pyrroIidinyl)phenyl]-l^-oxazolidin-5- 10 yl}methyI)-2-thiophenecarboxamide Analogously to the known synthesis scheme (see S.J Brickner et al., J. Med. Chem. 1996, 39, 673), l-(4-aminophenyl)pytrolidin-2-one (preparation see Reppe et al., 15 Justus Liebigs Ann. Chem.; 596; 1955; 209) gives, after reaction with benzyloxycarbonyl chloride, followed by reaction with i?-glycidyl butyrate, mesylation, reaction with potassium phthalimide, hydrazinolysis in methanol and reaction with 5-chlorothiophene-2-carboxylic acid, finally 5-chloro-N-({(5S)-2-oxo-3-[4-(2-oxo- l-pyrrolidinyl)phenyl]-1,3-oxazolidhv5-yl }methyl)-2-thio- 20 phenecarboxamide. The 5-chloro-N-({(5S)-2-oxo-3-[4-(2-oxo-l-pyrrolidinyI)- phenyl]-l,3-oxazoIidin-5-yl}methyl)-2-thiophenecarboxamide obtained in this manner has an IC50 value of 4 nM (test method for the IC50 value according to Example A-l.a.1 described above) "determination of the inhibition of factor Xa"). M.p.:229°C; v 25 Rf value (SiO2, toluene/ethyl acetate 1:1) = 0.05 (starting material: = 0.0); MS (ESI): 442.0 (21%, M+Na, CI pattern), 420.0 (72%, M+H, CI pattern), 302.3 (12%), 215(52%), 145 (100%); "H-NMR (d6-DMSO, 300 MHz): 2.05 (m,2H), 2.45 (m,2H), 3.6 (t,2H), 3.77-3.85 (m,3H), 4.15(t,lH), 4.75-4.85 (m,lH), 7.2 (d,lH), 7.5 (d,2H), 7,65 (d,2H), 7.69 30 (d,iH),8.96(t,lH). The following compounds were prepared in an analogous manner Example 18 5 yI}methyI)-2-thiophenecarboxamide Analogously to Example 17, 4-pyrroIidin-l-yl-aniIine (Reppe et al., Justus Liebigs Ann. Chem.; 596; 1955; 151) gives the compound 5-chloro-N-({(5S)-2-oxo-3-[4-(l- 10 pyrrolidinyl)phenyl]-l,3-oxazolidin-5-yI}methyI)-2-thiophenecarboxamide. IC5o=40 nM; m.p.: 216°C; Rf value (Si02, toluene/ethyl acetate 1:1) = 0.31 [starting material: = 0.0]. 15 Example 19 5-Chloro-N-({(5S)-2-oxo-3-[4-(diethyIamino)phenyl]-l,3-oxazoIidin-5-yl}methyl)-2-thiophenecarboxamide 20 Analogously, N,N-diethyipheny]-l,4-diamine (US-A-2 811 555; 1955) gives the compound 5-chloro-N-({(5S)-2-oxo-3-[4-(diethylamino)phenyl]-l,3-oxazolidin-5- yl }methyl)-2-thiophenecarboxamide. IC50=270 nM; m.p.: 181°C; 25 Rf value (Si02, toluene/ethyl acetate 1:1) = 0.25 [starting material: = 0.0]. Example 36 5-Chloro-N-({(5S)-3-2-methyI-4-(4-morpholinyI)phenyl]-2-oxo-l,3-oxazoIidin-5- 30 yI}methyI)-2-thiophenecarboxamide starting from 2-methyI-4-(4-morpholinyl)aniIine (J.EXuValle et al. J.Am.Chem.Soc. 1948, 70, 2223): MS (ESI): m/z {%) = 436 ([M+H]+, 100), CI pattern; HPLC (method 1): it (%) = 3.77 (98). 35 IC50: 1-26 fiM Le^i M 172-Foreign CosHtries Example 37 5-Chloro-N-{[(55)-3-(3-chIoro-4-morphoIinophenyI)-2-oxo-l,3-oxazolidin-5-yI]methyI}-2-thiophenecarboxamide 5 starting from 3-chloro-4-(4-morpholinyl)aniline (H.R.Snyder et al J.Pharm.Scl 1977,66,1204): MS (ESI): m/z (%) = 456 ([M+H]+, 100), Cl2 pattern; HPLC (method 2): rt (%) = 4.31 (100). IC50: 33 nM 10 Example 38 5-Chloro-N-({(55)-3-[4-(4-morphoIinylsuIphonyl)phenyl]-2-oxo-l,3-oxazolidin-5-yl}methyl)-2-thiophenecerboxamide 15 starting from 4-(4-morphoIinylsulphony])aniline (Adams et al J.Am.Chem.Soc. 1939,61,2342): MS (ESI): m/z (%) = 486 ([M+H]+, 100), CI pattern; HPLC (method 3): rt (%) - 4.07 (100). IC50: 2 fiM 20 Example 39 S-Chloro-N-({(5S)-3-[4-(l-a2etidinylsulphonyl)phenyl]-2-oxo-l,3-oxazolidin-5-yl}methyl)-2-thiophenecarboxamide 25 starting from 4-(l-azetidinylsulphonyl)aniIine: MS (DCI, NH3): m/z (%) = 473 ([M+NH4]+, 100), CI pattern; HPLC (method 3): rt (%) = 4.10 (100). IC50:0.84pM 30 Example 40 5-Chloro-N-[((S5)-3-{4-[(dimethylainino)suIphonyl]phenyl}-2-oxo-l,3-oxazoIidin-5-yl)methyl]-2-thiophenecarboxamide starting from 4-amino-N,N-dimethyIben2enesulphonamide (I.K.Khanna el al 35 JMed.Chem. 1997,40, 1619): MS (ESI): m/z (%) = 444 ([M-4-H]+ 100), CI pattern; HPLC (method 3): rt (%) = 4.22 (100). IC50:90nM General method for the acylation of 5-(aminomethyl)-3-[4-(2-oxo-l-pyrro- 5 IidinyI)phenyl]-l,3-oxazolidin-2-one with carbonyl chlorides. Under argon and at room temperature, an about 0.1 molar solution of 5- 10 (aminomethyl)-3-[4-(2-oxo-l-pyrroIidinyl)phenyl]-l,3-oxazoIidin-2-one (from Example 45) (1.0 eq.) and absolute pyridine (about 6 eq.) in absolute dichloromethane is added dropwise to the appropriate acid chloride (2.5 eq.). The mixture is stirred at room temperature for about 4 h, and about 5.5 eq of PS- trisamine (Argonaut Technologies) are then added. The suspension is stirred gently 15 for 2h, diluted with dichloromethane/DMF (3:1) and then filtered (the resin is washed with dichloromethane/DMF) and the filtrate is concentrated. If appropriate, the product that is obtained is purified by preparative RP-HPLC. 20 The following compounds were prepared in an analogous manner: Example 41 N-({2-oxo-3-[4-(2-oxo-l-pyrrolidinyi)phenyl]-l,3-oxazoIidin-5-yl}methyl)-2-thiophene-carboxamide 25 LC-MS (method 6): m/z (%) = 386 (M+H, 100); LC-MS;rt(%) = 3.04 (100). IC50: 1.3 fiM General method for preparing acyl derivatives starting from 5-(aminomethyl)-3-[4-(2-oxo-l-pyrroIidinyl)phenyI]-l,3-oxazoIidin*2-one and carboxylic adds 5 The appropriate carboxylic acid (about 2 eq.) and a mixture of absolute dichloromethane/DMF (about 9:1) are added to 2.9 eq. of resin-bonded carbodiimide (PS-carbodnmide, Argonaut Technologies), The mixture is shaken gently at room temperature for about 15 min, 5-(aminomethyl)-3-[4-(2-oxo-l-pyrrolidinyl)phenyl]-l,3-oxazo!idin-2-one (from Example 45) (1.0 eq.) is then added and the mixture is 10 shaken overnight, after which the resin is filtered off (and washed with dichloromethane), and the filtrate is concentrated. If appropriate, the resulting product is purified by preparative RP-HPLC. 15 The following compounds were prepared in an analogous manner Example 42 5-MethyI-N-({2-oxo-3-[4-(2-oxo-l-pyrrolidinyl)phenyl]-l,3-oxazolidin-5-yl}methyl)-2-thiophenecarboxamide 20 LC-MS: m/z (%) = 400 (M+H, 100); LC-MS (method 6): it (%) = 3.23 (100). IC50:0.16/iM 25 Example 43 5-Bromo-N-({2-oxo-3-[4-(2-oxo-l-pyrroIidinyI)phenyl]-lT3-oxazoIidin-5-yl}methyl)-2-thiophenecarboxamide LC-MS : m/z (%) = 466 (M+H, 100); LC-MS (method 5): n (%) = 3.48 (78). Example 44 5 5-Chloro-^V-({(55)-2-oxo-3-[4-(3-oxo-4-morphoIinyI)phenyI]-l^-oxa2olidin-5- yI}methyI)-2-thiophenecarboxainide 10 a) 2-((2R)-2-Hydroxy-3-{[4-(3-oxo-4-morpholinyl)phenyl]amino}propyI)-1h-iso- 15 indole-l,3(2H)-dione: A suspension of 2-[(2S)-2-oxiranylmethyl]-lH-isoindole-l,3(2H)-dione (A. Gutcait et al. Tetrahedron Asym. 1996, 7, 1641) (5.68 g, 27.9 mmol) and 4-(4-aminophenyl)-3-morpholinone (5.37 g, 27.9 mmol) in ethanol/water (9:1, 140 ml) is refluxed for 14 h (the precipitate dissolves, after some time again formation of a precipitate). The precipitate (desired product) is filtered off, washed three times with diethyl ether and dried. The combined mother liquors are concentrated under reduced pressure and, after addition of a second portion of 2-[(2S)-2-oxiranylmethyI]-lH-isoindole- 5 l,3(2H)-dione (2.84 g, 14.0 mmol), suspended in ethanol/water (9:1, 70 ml) and refluxed for 13 h (the precipitate dissolves, after some time again formation of a precipitate). The precipitate (desired product) is filtered off, washed three times with diethyl ether and dried. Total yield: 10.14 g, 92% of theory. MS (ESI): m/z (%) = 418 ([M+Na]+, 84), 396 ([M+H]+, 93); 10 HPLC (method 3): rt (%) = 3.34 (100). b) 2-({(55)-2-Oxo-3-[4-(3-oxo-4-morpholinyI)phenyl]-l,3-oxazolidin-5-yI}me- thyl)-lH-isoindole-1,3(2H)-dione: 15 Under argon and at room temperature, N,N"-carbonyldiimidazole (2.94 g, 18.1 mmol) and dimethylaminopyridine (a catalytic amount) are added to a suspension of the amino alcohol (3.58 g, 9.05 mmol) in tetrahydrofuran (90 ml). The reaction suspension is stirred at 60°C for 12 h (the precipitate dissolves, after some time again formation of a precipitate), admixed with a second portion of N,N"- 20 carbonyldiimidazole (2.94 g, 18.1 mmol) and stirred at 60°C for another 12 h. The precipitate (desired product) is filtered off, washed with tetrahydrofuran and dried. The filtrate is concentrated under reduced pressure and further product is purified by flash chromatography (dichloromethane/methanol mixtures). Total yield: 3.32 g, 87% of theory, 25 MS (ESI): m/z (%) = 422 (EM+H]+ 100); HPLC (method 4): rt (%) = 3.37 (100). c) S-Chloro-N-({(55)-2-oxo-3-[4-(3-oxo-4-morphoIinyI)phenyl]-lr3-oxazolidin-5- yl}methyI)-2-thiophenecarboxamide: 30 At room temperature, methylamine (40% strength in water, 10.2 ml, 0.142 mol) is added dropwise to a suspension of the oxazolidinone (4.45 g, 10.6 mmol) in ethanol (102 ml). The reaction mixture is refluxed for 1 h and concentrated under reduced pressure. The crude product is used without further purification for the next reaction. 35 7/ Under argon and at 0°C, 5-chlorothiophene-2-carbonyI chloride (2.29 g, 12,7 mmol) is added dropwise to a solution of the amine in pyridine (90 ml). Ice-cooling is removed and the reaction mixture is stirred at room temperature for 1 h and admixed with water. Dichloromethane is added and the phases are separated, and the aqueous 5 phase is then extracted with dichloromethane. The combined organic phases are dried (sodium sulphate), filtered and concentrated under reduced pressure. The desired product is purified by flash chromatography (dichloromethane/methanol mixtures). Total yield: 3.92 gt 86% of theory. M.p: 232-233°C; 10 lH NMR (DMSO-d6, 200 MHz): 9.05-8.90 (t, J - 5.8 Hz, 1H), 7.70 (d, J = 4.1 Hz, 1H), 7.56 (d, J = 9.0 Hz, 2H), 7.41 (d, / = 9.0 Hz, 2H), 7.20 (d, J = 4.1 Hz, 1H), 4.93-4.75 (m, 1H), 4.27-4.12 (m, 3H), 4.02-3.91 (m, 2H), 3.91-3.79 (dd, J = 6.1 Hz-9.2 Hz, 1H), 3.76-3.66 (m, 2H), 3.66-3.54 (m, 2H); MS (ESI): m/z (%) = 436 ([M+H]+ 100, CI pattern); 15 HPLC (method 2): rt (%) = 3.60 (100); [a]21D = -38° (c 0.2985, DMSO); ee: 99%. IC50: 0.7 nM The following compounds were prepared in an analogous manner: 20 Example 45 5-MethyI-N-({(55)-2-oxo-3-[4-(3-oxo-4-morphoIinyl)phenyI}-l,3-oxazolidin-5-yI}methyl)-2-thiophenecarboxamide 25 MS (ESI): m/z (%) = 831 ([2M+H]+, 100), 416 ([M+H]+, 66); HPLC (method 3): rt (%) = 3.65 (100). IC50:4.2nM Example 46 30 5-Bromo-N-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-l,3-oxazolidin-5-yl }methyl)-2-thiophenecarboxamide MS (ESI): m/z (%) = 480 ([M+H]+ 100, Br pattern); HPLC (method 3): rt (%) = 3.87 (100). 35 IC50: 0.3 nM Example 47 5-ChIoro-N-{[(5S)-3-(3-isopropyl-2-oxo-2,3-dihydro-l,3-benzoxazoI-6-yl)-2-oxo-l,3-oxazolidin-5-yI]methyI}-2-thiophenecarboxatnide 200 mg (0.61 mmol) of 6-[(5S)-5-(aminomethyl)-2-oxo-lT3-oxazolidin-3-yl]-3-isO" pfopyI-l»3-benzoxa2oI-2(3H)-one hydrochloride (EP 738726) are suspended in 5 ml of tetrahydrofuran and admixed with 0,26 ml (1.83 mmol) of tnethylamine and 10 132 mg (0.73 mmol) of 5-chlorothiophene-2-carboriyl chloride. The reaction mixture is stirred at room temperature overnight and then concentrated- The product is isolated by column chromatography (silica gel, methylene chloride/ethanol = 50/1 to 20/1). This gives 115 mg (43% of theory) of the desired compound. MS (ESI): m/z (%) = 436 (M+H, 100); 15 HPLC (method 4): rt = 3.78 min. The following compounds were prepared in an analogous manner: Example No. Structure M.p. [°Cj IC5o {uM} 48 0 S-^C|Chira" 0 210 0.12 49 O CJwal 234 0.074 50 • Ctwai 195 1.15 51 ° 0 212 1.19 52 O Cm 160 0.19 53 O Cnirai MS (ESI): m/z (%) = 431 (IM+H)+, 100), CI pattern 0.74 / ,/ / / / / 74 Example No. Structure M-P- [°C] 1C50 [uM] 54 O CJiiraJ 4 N O from 5-amino-2-pyrrolidino-benzonitrile (Grell, W., Hurnaus, R.; Griss, G., Sauter, R.; Rupprecht, E. et al; J.MedChem.1998, 41; 5219) 221 0.13 55 0 from 3-(4-amino-phenyl)-oxazoIidin-2-one (Artico, M. et al.; Farmaco Ed.Sci. 1969,24; 179) 256 0.04 56 Q CWnU 218 0.004 51 O Chital 0 i 226 0.58 255 228-230 / / / /" -75- 5 Examples 20 to 30 and 58 to 139 below refer to process variant [B], and Examples 20 and 21 describe the preparation of precursors. Example 20 Preparation of N-aIIyI-5-chIoro-2-thiophenecarboxamide o 10 An ice-cooled solution of 2.63 ml (35 mmol) of allylamine in 14.2 ml of absolute pyridine and 14.2 ml of absolute THF is admixed dropwise with 5-chloro-thiophene-2-carbonyl chloride (7.61 g, 42 mmol). Ice-cooling is removed and the mixture is stirred at room temperature for 3 h and then concentrated under reduced pressure. The residue is admixed with water and the solid is filtered off. The crude product is 15 purified by flash chromatography over silica gel (dichloromethane). Yield: 7.20 g (99% of theory); MS (DCI, NH4): m/z (%) = 219 (M+NH4, 100), 202 (M+H, 32); HPLC (method 1): rt (%) = 3.96 min (98.9). 20 Example 21 Preparation of 5-chloro-N-(2-oxiranylmethyl)-2-thiophenecarboxamide 25 An ice-cooled solution of 2,0 g (9.92 mmol) of N-aIlyI-5-chloro-2- thiophenecarboxamide in 10 ml of dichloromethane is admixed with meta- chloroperbenzoic acid (3.83 g, about 60% strength). The mixture is stirred overnight, during which it is allowed to warm to room temperature, and is then washed with 30 10% sodium hydrogen sulphate solution (three times). The organic phase is washed with saturated sodium bicarbonate solution (twice) and with saturated sodium Le A34 I22^ercrgTreountrics chloride solution, dried over magnesium sulphate and concentrated. The product is purified by silica gel chromatography (cyclohexane/ethyl acetate 1:1). Yield: 837 mg (39% of theory); MS (DCI, NHi): m/z (%) =253 (M+NH4,100), 218 (M+H, 80); 5 HPLC (method 1): rt (%) = 3,69 min (about 80). General method for preparing substituted N-(3-amino-2-hydroxypropyl)-5-chloro-2-thiophenecarboxamide derivatives starting from 5-chloro-iV-{2-oxiranylmethyl)-2-thiophenecarboxamide 10 At room temperature or at temperatures up to 80°C, 5-chloro-N-(2-oxiranyImethyI)-2-thiophenecarboxamide (1.0 eq.) is added a little at a time to a solution of the 15 primary amine or aniline derivative (1.5 to 2.5 eq.) in 1,4-dioxane, 1,4-dioxane/water mixtures or ethanol, ethanol/water mixtures (about 0.3 to 1.0 mol/1). The mixture is stirred for 2 to 6 hours and then concentrated. From the reaction mixture, the product can be isolated by silica gel chromatography (cyclohexane/ethyl acetate mixtures, dichloromethane/methanol mixtures or dichloromethane/methanol/triethylamine 20 mixtures). The following compounds were prepared in an analogous manner Example 22 25 iV-[3-(Benzylamino)-2-hydroxypropyl3-5-chloro-2-thiophenecarboxamide MS (ESI): m/z (%) = 325 (M+H, 100); HPLC (method 1): rt (%) = 3.87 min (97.9). 30 Example 23 5-Chloro-N-[3-(3-cyanoanilino)-2-hydroxypropyl]-2-thiophenecarboxamide MS (ESI): m/z (%) = 336 (M+H, 100); HPLC (method 2); rt (%) = 4.04 min (100). Example 24 5-Chloro-iV-[3-(4-cyanoaniIino)-2-hydroxypropyI]-2-thiophenecarboxamide MS (ESI): m/z (%) - 336 (M+H, 100); 5 HPLC (method 1): rt (%) = 4.12 min (100). Example 25 5-ChIoro-N-{3-[4-(cyanomethyI)anilino]-2-hydroxypropyl}-2- thiophenecarboxamide 10 MS (ESI): m/z (%) = 350 (M+H, 100); HPLC (method 4): rt (%) = 3.60 min (95.4). Example 26 15 5.Chloro-N-{3-[3-(cyanomethyl)anilino]-2-hydroxypropyl}-2- thiophenecarboxamide MS (ESI); m/z (%) = 350 (M+H, 100); HPLC (method 4): rt (%) - 3.76 min (94.2). 20 Example 58 tert-Butyl 4-[(3-{[(S-chloro-2-thienyl)carbonyl]amino}-2-hydroxypropyl)amino]-benzylcarbamate 25 starting from fert-butyl 4-aminobenzylcarbamate {Bioorg. Med. Chem. Lett.", 1997; 1921-1926): MS (ES-pos): m/z (%) = 440 (M+H, 100), (ES-neg): m/z (%) - 438 (M-H, 100); HPLC (method 1): rt (%) = 4.08 (100). 30 Example 59 terf-Butyl 4-[(3-{[(5-chloro-2-thienyl)carbonyl]amino}-2-hydroxypropyl)amino]-phenyl-carbamate 35 starting from N-tert-butyloxycarbonyl-l,4-phenylenediamine: MS (ESI): m/z (%) = 426 (M+H, 45), 370 (100); HPLC (method 1): it (%) = 4.06 (100). Example 60 5 fert-Butyl 2-hydroxy-3-{[4-(2-oxo-l-pyrrolidinyI)phenyI]amino}propyI-carb- amate starting from l-(4-aminophenyl)-2-pyrroiidinone (Justus Liebigs Ann. Chem.\ 1955; 596; 204): 10 MS (DCI, NH3): m/z (%) = 350 (M+H, 100); HPLC (method 1): rt (%) = 3.57 (97). Example 61 15 5-Chloro-N-(3-{[3-fluoro-4-(3-oxo-4-morphoIinyI)phenyI]amino}-2-hydroxypro- pyI)-2-thiophenecarboxamide S00 mg (3.8 mmol) of 4-(4-amino-2-fluorophenyl)-3-morpholinone and 700 mg (3.22 mmol) of 5-chloro-N-(2-oxiranyImethyl)-2-thiophenecarboxamide in 15 ml of 20 ethanol and 1 ml of water are heated under reflux for 6 hours. The mixture is concentrated under reduced pressure and treated with ethyl acetate, precipitated crystals are filtered off with suction and the mother liquor is chromatographed giving 276 mg (17% of theory) of the target compound. Rf (ethyl acetate): 0.25. 25 Example 62 (N-(3-Anilino-2-hydroxypropyI)-5-chloro-2-thiophenecarboxamide starting from aniline: 30 MS (DCI, NH3): m/z (%) = 311 ([M+H]+, 100), CI pattern; HPLC (method 3): rt {%) = 3.79 (100). Example 63 35 5-Chloro-N-(2-hydroxy-3-{[4-(3-oxo-4-morpholinyi)phenyl]amino}propyl)-2- thiophenecarboxamide 79 starting from 4-(4-aminophenyl)-3-morphoIinone: MS (ESI): m/z (%) = 410 ([M+Hf, 50), CI pattern; HPLC (method 3): rt (%) - 3.5S (100). 5 Example 64 N-[3-({4-[AcetyI(cycIopropyl)amino]phenyI}aniino)-2-hydroxypropyl]-5-chIoro-2-thiophenecarboxamide starting from N-(4-aminophenyI)-N-cyclopropylacetamide: 10 MS (ESI): m/z (%) - 408 ([M+H]+, 100), CI pattern; HPLC (method 3): it (%) = 3.77 (100). Example 65 15 N-[3-({4-[Acetyl(methyl)amino]phenyl}amino)-2-hydroxypropyl]-5-chloro-2- thiophenecarboxamide starting from N-(4-aminophenyI)-N-methyIacetamide: MS (ESI): m/z (%) - 382 (M+H, 100); HPLC (method 4): it = 3.31 min. 20 Example 66 5-Chloro-N-(2-hydroxy-3-{[4-(lH-l,2,3-triazol-l-yl)phenyl]amino}propyl)-2-thiophenecarboxamide 25 starting from 4-(lH-l,2,3-triazol-l-yI)aniIine (Bouchet et al.; J.Chem.Soc.Perkin Trans.2; 1974; 449): MS (ESI): m/z (%) = 378 (M+H, 100); HPLC (method 4): rt = 3.55 min. 30 Example 67 tert-butyl l-{4-[(3-{[(5-chIoro-2-thienyl)carbonyl]amino}-2-hydroxypropyi)-amino]phenyI}-L-proIinate MS (ESI): m/z (%) = 480 (M+H, 100); 35 HPLC (method 4): rt = 3.40 min. Example 68 l-{4-[(3-{[(5-ChIoro-2-thienyl)carbonyl}amino}-2-hydroxypropyI)amino]phe-nyl}-4-piperidinecarboxamide 5 MS (ESI): m/z (%) = 437 (M+H, 100); HPLC (method 4): rt = 2.39 min. Example 69 10 l-{4-[(3-{[(5-Chloro-2-tbienyI)carbonyI]amino}-2-hydroxypropyI)-aniino]phe- nyl}-3-piperidinecarboxamide MS (ESI): m/z (%) = 437 (M+H, 100); HPLC (method 4): rt = 2.43 min, 15 Example 70 5-ChIoro-N-(2-hydroxy-3-{[4-(4-oxo-l-piperidinyl)phenyI]amino}propyI)-2-thiophenecarboxamide MS (ESI): m/z (%) = 408 (M+H, 100); 20 HPLC (method 4): rt = 2.43 min. Example 71 l-{4-[(3-{[(5-ChIoro-2-thienyl)carbonyI]amino}-2-hydroxypropyl)amino]phe* 25 nyl}-L-prolinamide MS (ESI): m/z (%) = 423 (M+H, 100); HPLC (method 4): rt = 2.51 min. Example 72 30 5-Chloro-N-[2-hydroxy-3-({4-[3-(hydroxymethyI)-l-piperidinyI]phenyI}- amino)propyl]-2-thiophenecarboxamide MS (ESI): m/z (%) = 424 (M+H, 100); HPLC (method 4): rt - 2.43 min. Example 73 5-Chloro--N-[2-hydroxy-3-({4-[2-(hydroxymethyI)-l-piperidinyI]phenyl}-amino)propyl]-2-thiophenccarboxamide 5 MS (ESI): m/z (%) = 424 (M+H, 100); HPLC (method 4): it = 2.49 min. Example 74 10 Ethyl l-{4-[(3-{[(5-cfaIoro-2-thienyl)carbonyI]aniino}-2-hydroxypropyl)- amino]phenyI}-2-piperidinecarboxyIate MS (ESI): m/z (%) = 466 (M+H, 100); HPLC (method 4): it = 3.02 min. 15 Example 75 5-Chloro-N-[2-hydroxy-3-({4-[2-(hydroxymethyI)-l-pyrrolidinyl]phenyl}amino)-propyl]-2-thiophenecarboxamide MS (ESI): m/z (%) = 410 (M+H, 100); 20 HPLC (method 4): rt = 2.48 min. Example 16 5-Chloro-N-(2-hydroxy-3-{[4-(2-methylhexahydro-5H-pyrrolo[3,4-d]isoxa2ol-5- 25 yI)phenyI]amino}propyl)-2-thiophenecarboxamide MS (ESI): m/z (%) = 437 (M+H, 100). HPLC (method 5): rt = 1.74 min. -1 Example 77 30 5-ChIoro-N-(2-hydroxy-3-{[4-(l-pyrrolidinyI)-3-(trinuoromethyI)phenyI]-arnino}propyI)-2-thiophenecarboxamide MS (ESI): m/z (%) s 448 (M+H, 100); HPLC (method 4): rt = 3.30 min. Example 78 5-ChIoro-N-(2-hydroxy-3-{[4-(2-oxo-l-pyrrolidinyl)-3-(trifluoromethyl)phenyI]-amino}propyl)-2-thiophenecarboxamide 5 MS (ESI): m/z (%) = 462 (M+H, 100); HPLC (method 4): rt = 3.50 mm. Example 79 10 5-Chloro-N-(3-{[3-chloro-4-(3-oxo-4-morpholinyl)phenyl]amino}-2-hydroxy- propyl)-2-thiophenecarboxamide MS (ESI): m/z (%) = 444 (M+H, 100); HPLC (method 4): rt = 3.26 min. 15 Example 80 S-ChIoro-N-(2-hydroxy-3-{[4-(3-oxo-4-morpholinyl)-3.(trifluoromethyl)pfaenyl]-amino}propyl)-2-thiophenecarboxamide MS (ESI): m/z (%) = 478 (M+H, 100); 20 HPLC (method 4): rt - 3.37 min. Example 81 5-Chtoro-N-(2-hydroxy-3-{(3-methyI-4-(3-oxo-4-morphoIinyI)phenyI]amino}- 25 propyl)-2-thiophenecarboxamide MS (ESI): m/z (%) = 424 (M+H, 100); HPLC (method 4): rt - 2.86 min. Example 82 30 5-Chloro-N-(3-{[3-cyano-4-(3-oxo-4-morphoIinyl)phenyl]amino}-2-hydroxypro- pyl)-2-thiophenecarboxamide MS (ESI): m/z (%) = 435 (M+H, 100); HPLC (method 4): it = 3.10 min. 35 Example 83 5-Chloro-N-(3-{[3-chIoro-4-(l-pyrrolidinyI)phenyl]amino}-2-hydroxypropyI)-2-thiophenecarboxamide 5 MS (ESI); m/z (%) = 414 (M+H, 100); HPLC (method 4): rt = 2.49 min. Example 84 10 5-Chloro-N-(3-{[3-chloro-4-(2-oxo-l-pyrrolidinyl)phenyl]amino}-2-hydroxypro- pyI)-2-thiophenecarboxamide MS (ESI): m/z (%) = 428 (M+H, 100); HPLC (method 4): rt = 3.39 min. 15 Example 85 5-Chloro-N-(3-{[3^-dimethyl-4-(3-oxo-4-morpbolinyl)phenyI]aniino}-2-hydro- xypropyl)-2-thiophenecarboxamide MS (ESI): m/z (%) =: 438 (M+H, 100); 20 HPLC (method 4): rt = 2.84 min. Example 86 N-(3-{[3-(Aininocarbonyl)-4-(4-morpholinyl)phenyI]anino}-2-hydroxypropyI)- 25 5-chloro-2-thiophenecarboxamide MS (ESI): m/z (%) = 439 (M+H, 100); HPLC (method 4): rt = 2.32 min. Example S7 30 5-Chloro-N-(2-hydroxy-3-{[3-methoxy-4-(4-morphoIinyl)phenyl]amino}propyl)- 2-thiophenecarboxamide MS (ESI): m/z (%) = 426 (M+H, 100); HPLC (method 4): rt = 2.32 mm. Example 88 N-(3-{[3-Acetyl-4-(4-morphoiinyI)phenyl]amino}-2-hydroxypropyl)-5-chloro-2-thiophenecarboxamide 5 MS (ESI): m/z (%) = 438 (M+H, 100); HPLC (method 4): rt = 2.46 min. Example 89 10 N-(3-{ [3-Amino-4-(3-oxo-4-morpholiny l)phenyl]amino}-2-hydroxy propyl)-5- chloro-2-thiophenecarboxamide MS (ESI): m/z (%) = 425 (M+H, 100); HPLC (method 4): rt = 2,45 min. 15 Example 90 5-Chloro-N-(3-{[3-chloro-4-(2-methyl-3-oxo-4-morphoUnyl)phenyl]amino}-2-hydroxypropyI)-2-thiophenecarboxamide MS (ESI): m/z (%) - 458 (M+H, 100); 20 HPLC (method 4); rt = 3.44 min. Example 91 5-Chloro-N-(3-{[3-chloro-4-(2-methyl-5-oxo-4-morpholinyl)phenyl]amino}-2- 25 hydroxypropyl)-2-thiophenecarboxamide MS (ESI): m/z (%) = 458 (M+H, 100); HPLC (method 4): rt = 3.48 min. Example 91a 30 5-Chloro-N-[2-hydroxy-3-({4-[(3-oxo-4-morphoIinyI)methyI]phenyl}amino)-propyI]-2-thiophenecarboxamide starting from 4-(4-amino-benzyI)-3-morphoIinone (Surrey et al.; J. Amer. Chem. 35 Soc; 77; 1955; 633): MS (ESI): m/z (%) = 424 (M+H, 100); HPLC (method 4): it = 2.66 min. General method for preparing 3-substituted 5-chloro-N-[(2-oxo-l,3-oxazolidin- 5-yl)methyI)-2-thiophenecarboxamide derivatives starting from substituted 5 iV-(3-amino-2-hydroxypropyl)-5-chloro-2-thiophenecarboxamide derivatives At room temperature, carbodiimidazole (1.2 to 1.8 eq.) or a similar phosgene 10 equivalent are added to a solution of the substituted Af-(3-amino-2-hydroxypropyI)-5- chloro-2-thtophenecarboxamide derivative (1.0 eq.) in absolute THF (about 0.1 mol/1). At room temperature or, if appropriate, at elevated temperature (up to 70°C), the mixture is stirred for 2 to 18 h and then concentrated under reduced pressure. The product can be purified by silica gel chromatography 15 (dichloromethane/methanol mixtures or cyclohexane/ethyl acetate mixtures). The following compounds were prepared in an analogous manner. Example 27 20 N-[(3-Benzyl-2-oxo-l,3-oxa2oIidin-5-yI)methyI]-5-choro-2-thiophenecarboxamide MS (DCI, NH4): m/z (%) = 372 (M+Na, 100), 351 (M+H, 45); HPLC (method 1): rt (%) = 4.33 min (100). 25 Example 28 5-Chioro-N-{[3-(3-cyanophenyl)-2-oxo-l,3-oxazolidin-5-yl]methyl}-2-thiophenecarboxamide 30 MS (DCI, NH4): m/z (%) = 362 (M+H, 42), 145 (100); HPLC (method 2): it (%) = 4.13 min (100). ^S6^—-Example 29 tbiophenecarboxamide 5 MS (ESI): m/z (%) = 376 (M+H, 100); HPLC (method 4): it = 4.12 min Example 30 10 5-ChIoro-N-({3-[3-(cyanomethyl)phenyl]-2-oxo-l,3-oxazoIidin-5-yl}inethyl)-2- thiophenecarboxamide MS (ESI): m/z (%) = 376 (M+H, 100); HPLC (method 4): rt = 4.17 min 15 Example 92 tert-Butyl 4-[5-({[(5-chIorO-2-thienyI)carbonyI]amino}methyl)-2-oxo-l,3-oxa-zolidin-3-yl]benzylcarbamate starting from Example 58: 20 MS (ESI): m/z (%) = 488 (M+Na, 23), 349 (100); HPLC (method 1): rt (%) = 4.51 (98.5). Example 93 25 terf-Butyl 4-[5-({[(5-chloro-2-thienyl)carbonyI]amino}methyI)-2-oxo-l,3-oxazoIi- din-3~yl]phenylcarbamate starting from Example 59: MS (ESI): m/z (%) = 493 (M+Na, 70), 452 (M+H, 10), 395 (100); HPLC (method 1): rt (%) = 4.41 (100). 30 Example 94 terf-Butyl 2-oxo-3-[4-(2-oxo.l-pyrrolidinyI)phenyI]-l,3-oxazoHdin-5-yl}methyl-carbamate 35 starting from Example 60: MS (DCI, NH3): m/z (%) = 393 (M+NH4,100); h^ HPLC (method 3); rt (%) = 3.97 (100). Example 95 5 5-Chloro-N-({3-[3-fluoro-4-(3-oxo-4-morphoIinyl)phenyl]-2-oxo-l,3-oxazolidin- 5-yl}methyI)-2-thiophenecarboxamide 10 260 mg (0.608 mmol) of 5-chloro-N-(3-{[3-fluoro-4-(3-oxo-4-morpholinyl)phenyl]- amino}-2hydroxypropyl)-2-thiophenecarboxamide (from Example 61), 197 mg (1.22 mmol) of carbonylimidazole and 7 mg of dimethylaminopyridine in 20 ml of dioxane are boiled under reflux for 5 hours. 20 ml of acetonitrile are then added, and the mixture is stirred in a closed vessel in a microwave oven at 180°C for 30 minutes. 15 The solution is concentrated using a rotary evaporator and chromatographed on an RP-HPLC column. This gives 53 mg (19% of theory) of the target compound. NMR (300 MHz, d6-DMSO): 5= 3.6-3.7 (m,4H), 3.85 (dd,lH), 3.95 (m,2H), 4.2 (m,lH), 4.21 (s,2H), 4.85 (m,lH), 4.18 (s,2H), 7.19 (d,lH,thiophene), 7.35 (dd,1H), 20 7.45 (t,lH), 7.55 (dd,lH), 7.67 (d,lH,thiophene), $.95 (t,lH,CONH). Example 96 5-Chloro-N-[(2-oxo-3.phenyI-l,3-oxazoIidin-5-y!)methyI]-2- 25 thiophenecarboxamide starting from Example 62: MS (ESI): m/z (%) = 359 ([M+Na]+, 71), 337 ([M+H)+, 100), Cl pattern; HPLC (method 3): rt (%) = 4.39 (100). IC50: 2 pM 30 Example 97 5-Chloro-N-({2-oxo-3-[4-(3-oxo-4-morpholmyl)phenyl]-l,3-oxa2olidin-5-yl}-methyI)-2-thiophenecarboxamide 5 starting from Example 63: MS (ESI): m/z (%) = 458 ([M+Na)+, 66), 436 ([M+H]+, 100), CI pattern; HPLC (method 3): rt (%) = 3.89 (100), IC50:1.4nM 10 Example 98 iV-[(3-{4+[Acetyl(cyclopropyl)amino]phenyl}-2-oxo-l,3-oxazolidm-5-yl)methyl]-5-chloro-2-thiophenecarboxamide)+de starting from Example 64: 15 MS (ESI): m/z (%) = 456 ([M+Na]+ ,55), 434 ([M+H]+, 100), CI pattern; HPLC (method 3): rt (%) = 4.05 (100). IC50: 50 nM Example 99 20 N-[(3-{4-[Acetyl(methyl)amino]phenyl}-2-oxo-l3.oxazolidin-5-yl)methyl]-5-chloro-2-thiophenecarboxamide MS (ESI): m/z (%) = 408 (M+H, 30), 449 (M+H+MeCN, 100); HPLC (method 4): rt - 3.66 min. 25 Example 100 S-ChIoro-N-({2-oxo-3-[4-(1H-l,2,3.triazol-l-yl)phenyl]-l,3-oxazoIidin-5-yl}-methyl)-2-thiophenecarboxamide 30 MS (ESI): m/z (%) = 404 (M+H, 45), 445 (M+H+MeCN, 100); HPLC (method 4): rt = 3.77 min. Example 101 35 Tert-butyl l-{4-[S-({[(5-chloro-2-thienyl)carbonyl]amino}methyl)-2-oxo-l-3- oxazoIidin-3-yl]phenyI}-L-prolinate MS (ESI): m/z (%) = 450 (M+H-56,25), 506 (M+H, 100); HPLC (method 4): rt = 5.13 min. Example 102 5 l-{4-[5-({[(5-Chloro-2-thienyl)carbonyl]amino}methyl)-2"Oxo-1,3-oxazolidin"3-yl]phenyI}-4-piperidinecarboxamide MS (ESI): m/z (%) = 463 (M+H, 100); HPLC (method 4): rt = 2.51 rain. 10 Example 103 l-{4-[5-({[(5-Chloro-2-thienyl)carbonyI]amino}methyl)-2-oxo-l,3-oxazolidin-3-yl]phenyl}-3-piperidinecarboxamide 15 MS (ESI): m/z (%) = 463 (M+H, 100); HPLC (method 4): rt = 2.67 min. Example 104 20 5-Chloro-N-({2-oxo-3-[4-(4-oxo-l-piperidinyI)phenyI]-l,3-oxazolidin-5- yI}methyI)-2-thiophenecarboxamide MS (ESI): m/z (%) = 434 (M+H, 40), 452 (M+H+H20, 100), 475 (M+H+MeCN, 60); HPLC (method 4): rt - 3.44 min. 25 Example 105 l-{4-[5-({[(5-Chloro-2-thienyl)carbonyI]amino}methyl)-2-oxo-l-3-oxazolidin-3-yl]phenyl}-L-prolinamide 30 MS (ESI): m/z (%) = 449 (M+H, 100); HPLC (method 4): rt = 3.54 min. Example 106 5-ChIoro-N-[(3-{4-[3-(hydroxymethyI)-l-piperidinyl]phenyI}-2-oxo-l;3-oxazoIi-din-5-yI)methyI]-2-thiophenecarboxamide 5 MS (ESI): m/z (%) = 450 (M+H, 100); HPLC (method 5): rt = 2,53 min. Example 107 10 5-Chloro-N-[(3-{4-[2-(hydroxymethyl)-l-piperidinyI]phenyl}-2-oxo-l?3-oxazoli- din-5-yI)methyl]-2-thiophenecarboxamide MS (ESI): m/z (%) = 450 (M+H, 100); HPLC (method 5): rt = 2.32 mm. 15 Example 108 Ethyl l-{4-[5-({[(5-chloro-2-thienyl)carbonyI]amino}methyl)-2-oxo-13-oxazoli-din-3-yl]phenyl}-2-piperidinecarboxylate MS (ESI): m/z (%) = 492 (M+H, 100); 20 HPLC (method 5): rt = 4.35 min. Example 109 5-Chloro-N.[(3-{4-[2-(hydroxymethyl)-l-pyrrolidmyl]phenyl}-2-oxo-l>3-oxazoli 25 dm-5-yl)methyI]-2-thiophenecarboxamide MS (ESI): m/z (%) = 436 (M+H, 100); HPLC (method 4): rt = 2.98 min. Example 110 30 5.Chloro-N-({2- oxo-3-[4-(l-pyrrolidinyl).3-(trifluoromethyl)phenyl]-l,3-oxazoli- din-5-yl}methyl)-2-thiophenecarboxamide MS (ESI): m/z (%) - 474 (M+H, 100); HPLC (method 4): rt = 4.63 min. Example lit 5-Chloro-N-({3-[4-(2-methylhexahydro-5H-pyrrolo[3,4-d]isoxazol-5-yl)phenyl3-2-oxo-l,3-oxazoIidin-5-yl}methyl)-2-thiophenecarboxamide 5 MS (ESI): m/z (%) = 463 (M+H, 100); HPLC (method 4): rt = 2.56 min. Example 112 10 5-Chloro-N-({2-oxo-3.[4-(2-oxo-l-pyrrolidinyl)-3-(trifiuoromethyl)phenyl]-1,3- oxazoIidm-5-yI}methyI)-2-thiophcnecarboxamide MS (ESI): m/z (%) = 488 (M+H, 100); HPLC (method 4): rt = 3.64 min. 15 Example 113 5-Chloro-N-({3-[3-chIoro-4-(3-oxo-4-morphoIinyl)phenyI]-2-oxo-1,3-oxazolidin-5-yl}methyI)-2-thiophenecarboxamide MS (ESI): m/z (%) = 470 (M+H, 100); 20 HPLC (method 4): rt = 3.41 min. Example 114 5-Chloro-N-({2-oxo-3-[4-(3-oxo-4-morphoIinyl)-3-(trifluoromethyI)phenyI]-l,3- 25 oxazolidin-5-yI}methyl)-2-thiophenecarboxamide MS (ESI): m/z (%) = 504 (M+H, 100); HPLC (method 4): rt = 3.55 min. Example 115 30 5-ChIoro-N-({3-[3-methyI-4-(3-oxo-4-morphoIinyl)phenyl]-2-oxo-lr3-oxazolidin-5-yI}methyl)"2-thiophenecarboxamide MS (ESI): m/z (%) = 450 (M+H, 100); HPLC (method 4): rt = 3.23 min. Example 116 5-ChIoro-N-({3-[3-cyano-4-(3-oxo-4"morpholinyl)phenyl]-2-oxo-lT3-oxazoU HPLC (method 4): rt = 3.27 min. Example 117 10 5-Chloro-N-({3-[3-chIoro-4-(l-pyrroHdinyI)pheayI]-2-oxo"l^-oxazolidin-5- yl}methyl)-2-thiophenecarboxamide MS (ESI): m/2 (%) = 440 (M+H, 100); HPLC (method 4): rt = 3.72 min. 15 Example 118 S-Chloro-N-({3-[3-chloro-4-(2-oxo*l-pyrroHdinyl)phetiyl]-2-oxo-l,3-oxazolidin-5-yI}methyI)-2"thiophenecarboxamide MS (ESI): m/z 20 HPLC (method 4): n = 3.49 min. Example 119 25 zolidin-5-yI}methyl)-2"thiophenecarboxamide MS (ESI): m/z (%) = 464 (M+H, 100); HPLC (method 4): rt = 3.39 min. Example 120 30 N-({3-[3-(Aminocarbonyl)-4-(4-morpholinyI)phenyI]-2-oxo-l,3-oxazoiidin-5-yl}methyI)-5-chIoro-2-thiophenecarboxamide MS (ESI); m/z (%) = 465 (M+H, 100); HPLC (method 4): rt - 3.07 min. Example 121 5-ChIoro-N-({3-[3-methoxy-4-(4-morphoIinyI)phenyl]-2-oxo-lr3-oxazolidin-5-yI}methyI)-2-thiophenecarboxamide 5 MS (ESI): m/z (%) = 452 (M+H, 100); HPLC (method 4): rt = 2.86 min. Example 122 10 N-({3-[3-Acety]-4-(4-morphoIinyl)phenyI]-2-oxo-l,3-oxa2oIidin-5-yI}methyl)-5- chloro-2-thiophenecarboxamide MS (ESI): m/z (%) = 464 (M+H, 100); HPLC (method 4): it = 3.52 min. 15 Example 123 N-({3-[3-Amino-4-(3-oxo-4-morpholinyl)phenyl]-2-oxo-1,3-oxazolidin-5-yI}-methyI)-5-chloro-2-thiophenecarboxamide MS (ESI): m/z (%) - 451 (M+H, 100); 20 HPLC (method 6): rt = 3.16 min. Example 124 5-Chloro-N-({3-[3-chIoro-4-(2-methyl-3-oxo-4-morphoIinyl)phenyl]"2-oxo-l,3- 25 oxazolidin-5-yI}methyl)-2-thiophenecarboxamide MS (ESI): m/z (%) = 484 (M+H, 100); HPLC (method 4): rt = 3.59 min. Example 125 30 5-ChIoro-N-({3-[3-chloro-4-(2-methyl-5-oxo-4-morphoIinyI)phenyl]-2-oxo-ly3-oxazolidin-5-yl}niethyl)-2-thiophenecarboxamide MS (ESI): m/z (%) = 484 (M+H, 100); HPLC (method 4): rt = 3.63 min. Example 125a S-Chloro-N-[(2-oxo-3-{4-[(3-oxo-4-morpholinyl)methyl]phenyl}-l,3-oxazolidin-5-yl)methyl]-2-thiophenecarboxamide 5 MS (ESI): m/z (%) = 450 (M+H, 100); HPLC (method 4): rt - 3.25 min. Via epoxide opening with an amine and subsequent cyclization to give the corresponding oxazolidinone, it was also possible to prepare the following 10 compounds: / / / / Examples 14 to 16 below are working examples for the optional oxidation step. Example 14 5 5-Chloro-N-({(SS)-3-[3-fluoro-4-(l-oxo-lDambda]4,4-thiazinan-4-yl)pheny»]-2- oxo-l^-oxazolidin-5-yI}methyl)-2-tMophenecarboxaniide F O n r~0=S N o 10 At 0°C, 5-chloro-N-({(5S)-3-[3-fluoro-4*Cl,4-thiazinan^-yl)phenyl]-2-oxo-l,3- oxazolidin-5~yl}methyI)-2-thiophenecarboxarnide (0.1 g, 0.22 mmol) from Example 3 in methanol (0.77 ml) is added to a solution of sodium periodate (0,05 g, 0.23 mmol) in water (0.54 ml), and the mixture is stirred at 0°C for 3 h. 1 ml of DMF is then added, and the mixture is stirred at RT for 8 h. After addition of a further 15 50 mg of sodium periodate, the mixture is once more stirred at RT overnight. The mixture is then admixed with 50 ml of water, and the insoluble product is filtered off with suction. Washing with water and drying gives 60 mg (58% of theory) of crystals. M.p.: 257°C; 20 Rf (silica gel, toluene/ethyl acetate 1:1)- 0.54 (starting material = 0.46); IC5o value =1.1pM: MS (DCl) 489 (M+NH4), CI pattern. Example 15 Preparation of5-chloro-N-({{5S)-3"[4-(l,l-dioxO"l[lambda]*,4-thiazinan-4-yl)-3- fluorophenyll^-oxo-l^-oxazolidin-S-ylJmethyD-Z-thiophenecarboxamide 5 F O O 5 -Choro-N -({(5S)-3-[3-fluoro-4-( l ,4-thiazrnan-4-yl)pheyl] -2-oxo-1,3-oxazolidin-5-yl}rnethyl)-2-thiophenecarboxamide from Example 3 (0.1 g, 0.22 mmol) in 3.32 ml 10 of a mixture of 1 part of water and 3 parts of acetone is admixed with 80 mg (0.66 mmol) of N-methylmorpholine N-oxide (NMO) and 0.1 ml of a 2.5% strength solution of osmium tetroxide in 2-methyl-2-propanOl. The mixture is stirred at room temperature overnight, and another 40 mg of NMO are added. The mixture is stirred for a further night and then poured into 50 ml of water and extracted three times with 15 ethyl acetate. The organic phase gives, after drying and concentrating, 23 mg and the aqueous phase, after removal of the insoluble solid by filtration with suction, 19 mg (in total 39% of theory) of the target compound. M.p.: 238°C; Rf (toluene/ethyl acetate 1:1) = 0.14 (starting material = 0.46); 20 1C50 value = 210 nM; MS (DO): 505 (M+NH4), CI pattern. Example 16 25 5-ChIoro-N-{[(5S)-3-(3-fluoro~4-morpholinophenyl)-2-oxo-l,3-oxazoIidin-5- yl]methyl}-2-thiophenecarboxamide N-oxide is obtained by treating 5-chloro-N-{[(5S)-3-(3-fluoro-4-morpholinophenyl)-2-oxo- l,3-oxazoIidin-5-y]]methyl}-2-thiophenecarboxarnide from Example 1 with the magnesium salt of monoperoxyphthalic acid. 30 MS (ESI): 456 (M+H, 21 %, CI pattern), 439 (100%). The Examples 31 to 35 and 140 to 147 below refer to the optional amidination step. General method for preparing amidines and amidine derivatives starting from 5 cyanomethylphenyl-substituted 5-chIoro-N-[(2-oxo-l,3-oxazoIidin-5-yl)methyl]- 2-thiophenecarboxamide derivatives The cyanomethylphenyl-substituted 5-chloro-N-[(2-oxo-l,3-oxazolidin-5-yl)methyl]- 2-thiophenecarboxamide derivative in question (1.0 eq.) is, together with 10 triethylamine (8.0 eq.), stirred at RT in a saturated solution of hydrogen sulphide in pyridine (about 0.05 - 0.1 mol/l) for one to two days. The reaction mixture is diluted with ethyl acetate (EtOAc) and washed with 2 N hydrochloric acid. The organic phase is dried with MgSO4, filtered and concentrated under reduced pressure. 15 The crude product is dissolved in acetone (0.01-0.1 mol/l) and admixed with methyl iodide (40 eq.). The reaction mixture is stirred at room temperature (RT) for 2 to 5 h and then concentrated under reduced pressure. The residue is dissolved in methanol (0.01-0.1 mol/l) and, to prepare the 20 unsubstituted amidines, admixed with ammonium acetate (3 eq.) and ammonium chloride (2 eq.). To prepare the substituted amidine derivatives, primary or secondary amines (l.5 eq.) and acetic acid (2 eq.) are added to the methanolic solution. After 5- 30 h, the solvent is removed under reduced pressure and the residue is purified by chromatography over an RP8 silica gel column (water/acetonitrile 9/1-1/1 + 0.1% 25 trifluoroacetic acid). The following compounds were prepared in an analogous manner: Example 31: 30 N-({3-[4-(2-Amino-2-iminoethyl)phenyl]-2-oxo-l,3-oxazolidin-5-yl}methy1)-5-cbloro-2-thiophenecarboxamide MS (ESI): m/z (%) = 393 (M+H, 100); HPLC (method 4): rt = 2.63 min 35 Le A M W-F^WFV Countries Example 32; 5-Chloro-N-({3-[3-(425-dihydro-lH-imidazol-2-yImethyl)phenyI]-2-oxo-1,3-oxazoIidin-5-yI}methyl)-2-thiophenecarboxamide 5 MS (ESI): m/z (%) - 419 (M+H, 100); HPLC (method 4): rt =2.61 min Example 33: 10 5-Chloro-N-t(3-{3-[2-imino-2-(4-raorpholinyl)ethyl]phenyI}-2-oxo-l,3-oxazoIi- din-5-yI)methyI]-2-thiophenecarboxamide MS (ESI): m/z (%) = 463 (M+H, 100); HPLC (method 4): rt - 2.70 min Example 34: S-Chloro-N-[(3-{3-[2-imino-2-(l-pyrroIidinyl)ethyl]phenyI}-2-oxo-l,3-oxazoIi-din-5-yl)methyl]-2-thiophenecarboxamide 20 MS (ESI): m/z (%) = 447 (M+H, 100); HPLC (method 4): rt = 2.82 min Example 35: 25 N-({3-[3-(2-Amino-2-iminoethyl)phenyl]-2-oxo-l;3-oxazolidin-5-yI}inethyl)-5- chloro-2-thiophenecarboxamide MS (ESI): m/z (%) = 393 (M+H, 100); HPLC (method 4): rt = 2.60 min 30 Example 140 5-Chloro-N-({3-[4-(4,5-dihydro-lH-imidazoI-2-ylmethyl)phenyl]-2-oxo-l,3-oxa-zolidin-5-yI}methyI)-2-thiophenecarboxamide MS (ESI): m/z (%) = 419 (M+H, 100); 35 HPLC (method 4): rt = 2.65 min Example 141 5-Chloro-N-[(3-{4-[2-imino-2-(4-morphoIinyI)ethyl]phenyl}-2-oxo-13-oxazoli. din-5-yI)methyI]-2-thiophenecarboxamide 5 MS (ESI): m/z (%) = 463 (M+H, 100); HPLC (method 4): it = 2,65 min Example 142 10 5-Chloro-N-[(3-{4-[2-imino-2-(l-piperidinyl)ethyl]phenyl}-2-oxo-l,3-oxazolidin- 5-yl)methyl]-2-thiophenecarboxamide MS (ESI): m/z (%) = 461 (M+H, 100); HPLC (method 4): rt = 2,83 min 15 Example 143 5-Chloro.N-[(3-{4-[2-imino-2-(l-pyrrolidinyl)ethyl]phenyI}-2-oxo-l,3-oxazoli-din-5-yl)methyl]-2-thiophenecarboxamide MS (ESI): m/z (%) = 447 (M+H, 100); 20 HPLC (method 4): rt = 2.76 min Example 144 5-Chloro-N-[(3-{4-[2-(cyclopentylamino)-2-iminoethyl]phenyl}-2-oxo-1,3-oxazo- 25 Iidin-5-yl)methyl]-2-thiophenecarboxamide MS (ESI): m/z (%) = 461 (M+H, 100); HPLC (method 4): rt = 2.89 min Example 145 30 5-ChIoro-N.{[3-(4-{2-imino-2.[(2,2,2-trifuoroethyI)amino]ethyl}phenyI)-2-oxo- l,3-oxazoIidin-5-yl]methyl}-2-thiophenecarboxamide MS (ESI): m/z (%) = 475 (M+H, 100); HPLC (method 4): rt = 2,79 min T^ A M 177-Frtn-iyn Cntmtnn Example 146 N-({3-[4-(2-Anilino-2-iminoethyI)phenyl]-2-oxo-l^-oxazoljdin-5-yl}methyl)-5-chloro-2-thiophenecarboxamide 5 MS (ESI): m/z (%) = 469 (M+H, 100); HPLC (method 4): rt = 2.83 min Example 147 10 5-Chloro-N- [(3-{4- [2-itnino-2-(2-py ridiny lamino)ethy l]pheny l}-2-oxo-1,3-oxa- zolidin-5-yl)mcthyl]-2-thiophenecarbox:amide MS (ESI): m/z (%) = 470 (M+H, 100); HPLC (method 4): rt = 2.84 min 15 Examples 148 to 151 below refer to the removal of BOC amino protective groups: General method for removing Boc protective groups (tert-butyloxycarbonyl): 20 Aqueous trifluoroacetic arid (TFA, about 90%) is added dropwise to an ice-cooled solution of a ferr-butyloxycarbonyl-(Boc) protected compound in chloroform or dichloromethane (about 0,1 to 0.3 mol/1). After about 15 min, ice-cooling is removed and the mixture is stirred at room temperature for approximately 2-3 h, and the 25 solution is then concentrated and dried under high vacuum. The residue is taken up in dichloromethane or dichloromethane/methanol and washed with saturated sodium bicarbonate or IN sodium hydroxide solution. The organic phase is washed with saturated sodium chloride solution, dried over a little magnesium sulphate and concentrated. If appropriate, purification is carried out by crystallization from ether 30 or ether/dichloromethane mixtures. The following compounds were prepared in an analogous manner from the corresponding Boc-protected precursors: Example 148 Ar-({3-[4-(Aminotnethyl)phenyI]-2-oxo-l^-oxazoIidin-5-yI}methyI)-5-chIoro-2-thiophene-carboxamide 5 starting from Example 92: MS (ESI): m/z (%) = 349 (M-NH2, 25), 305 (100); HPLC (method I); rt (%) = 3.68 (98). IC50: 22 fiU 10 Example 149 ^-{[S-t^AminophenylJ-I-oxo-l^-oxazolidin-S-ylJmethylJ-S-chloro-l-thiophenecarboxamide starting from Example 93: 15 MS (ESI): m/z (%) ~ 352 (M+H, 25); HPLC (method 1): rt (%) = 3.50 (100). IC50: 2 fiM An alternative enantiomerically pure synthesis of this compound is shown in the 20 scheme below (cf. also Delalande S.A., DE 2836305,1979; Chem.Abstr. 90, 186926): 1.) phthalimide, DEAD/PPh Example 150 5-Chloro-iVK{3-[4^glycyiamino)phenyl]-2-oxo-i^-oxa2oIidm-5-yl}inethyl)-2-thiophenecarboxamide 5 starting from Example 152: MS (ES-pos): m/z (%) = 408 (100); HPLC (method 3): rt (%) = 3.56 (97). IC50: 2 fiM 10 Example 151 5-(Aminomethyl)-3-[4-(2-oxo-l-pyrrolidinyl)ph^nyl]-13-oxazolidin-2-one starting from Example 60; MS (ESI): m/z (%) = 276 (M+H, 100); 15 HPLC (method 3): rt (%) = 2.99 (100). IC5o:2/iM The Examples 152 to 166 below refer to the amino group derivatizatjon of aniline- or benzylamine-substituted oxazolidinones using various reagents: 20 Example 152 5-Chloro-Ar-({3-[4-(N-te/t-butyIoxycarbonyl-glyi:yIamino)pheny]]-2-oxo-l,3-oxazolidm-5-yI}methyI)~2-thiophenecarboxamide 25 At 0°C, 754 mg (2.1 mmol) of JV-{[3-(4-aminophenyI)-2-oxo-l,3-oxazolidin-5- yl]methyI}-5-chloro-2-thiophenecarboxamide (from Example 149) are added to a 30 solution of 751 mg (4.3 mmol) of Boc-glycine, 870 mg (6.4 mmol) of HOBT (1-hydroxy-lH-benzotriazole x H20), 1790 mg (4.7 mmol) of HBTU [0-(benzotriazol-l-yl)-N,N,N",N"-tetramethyIuronium hexafluorophosphate] and 1.41 ml (12.9 mmol) of N-methylmorpholine in 15 ml of DMF/CH2C12 (1:1). The mixture is stirred at room temperature overnight and then diluted with water. The precipitated solid is filtered off and dried. Yield: $94 mg (79.7% of theory); MS (DCI, NH3): m/z (%) = 526 (M+NH4, 100); HPLC (method 3): rt (%) = 4.17 (97). Example 153 N-[(3"{4-[(AcetyIamino)methyI]phenyI}-2-oxo-1,3-oxazolidin-S-yl)methyl]-5-chIoro-2-thiophenecarboxamide 10 1U At O0C, a mixture of 30 mg (0.082 mmol) of N -({3-[4-(aminomethyl)phenyl]-2-oxo- l,3-oxazolidin-5-yl}methyl)-5-chloro-2-rhiophene-carboxamide (from Example 148) in 1.5 ml of absolute THF and 1.0 ml of absolute dichloromethane, and 0.02 ml of 15 absolute pyridine is mixed with acetic anhydride (0.015 ml, 0.164 mmol). The mixture is stirred at room temperature overnight. Addition of ether and crystallization affords the product. Yield: 30 mg (87% of theory), MS (ESI): m/z (%) = 408 (M+H, 18), 305 (85); HPLC (method 1): rt (%) = 3.78 (97). 20 IC50: 0.6 pM Example 154 25 methyl}-5-chIoro-2-thiophenecarboxamide - K At room temperature, 0.19 ml (0.82 mmol) of trimethylsilylisocyanate are added dropwise to a mixture of 30 mg (0.082 mmol) of iV-({3-[4-(aminomethyl)phenyl]-2- oxo-l,3-oxazolidin-5-yl }methyI)-5-chloro-2-thiophene-carboxamide (from Example 148) in 1.0 ml of dichloromethane. The mixture is stirred overnight and, after addition of ether, the product is then obtained by filtration. Yield: 21.1 mg (52% of theory), MS (ESI): m/z (%) = 409 (M+H, 5), 305 (72); HPLC (method 1): rt (%) = 3.67 (83). 10 IC50:1-3/AM General method for acylating Ar-{[3-(4-aminophenyl)-2-oxo-l,3-oxazolidin-S-yl]methyl}-5-chloro-2-thiophenecarboxamJde with carbony) chlorides: ^ _ .. .. -CI tr Under argon, an approximately 0.1 molar solution of N-{[3-(4-aminophenyl)-2-oxo- 15 l,3-oxazolidin-5-y]]methyI}-5-chloro-2-thiophenecarboxamide (from Example 149) (1.0 eq.) in absolute dichloromethane/pyridine (19:1) is added dropwise to the appropriate acid chloride (2.5 eq,). The mixture is stirred overnight and then admixed with about 5 eq. of PS trisamine (Argonaut Technologies) and 2 ml of absolute dichloromethane. The mixture is stirred gently for 1 h and then filtered off, and the 20 filtrate is concentrated. If appropriate, the products are purified by preparative RP- HPLC. The following compounds were prepared in an analogous manner: 25 Example 155 N-({3-[4-(AcetyIamino)phenyl]-2-oxo-1,3-oxazolidin-5--yl}methyl)-5-chloro-2-thiophene-carboxamide LC-MS: m/z (%) = 394 (M+H, 100); LC-MS (method 6): rt (%) = 3.25 (100). IC50: 1.2 pM Example 156 5 5-ChIoro-N-[(2-oxo-3-{4-[(2-thienylcarbonyl)amino]phenyI}-l,3-oxazolidin-5-yl)methyl] -2-thiophenecarboxamide LC-MS: m/z (%) = 462 (M+H, 100); LC-MS (method 6): rt (%) = 3.87 (100). 10 IC50: 1.3 pM Example 157 5-Chloro-N-[(3-{4-[(methoxyacetyl)amino]phenyl}-2-oxo-l,3-oxazolidin-5-yI)- 15 methyI]-2-thiophenecarboxamide LC-MS: m/z (%) = 424 (M+H, 100); LC-MS (method 6): rt (%) = 3.39 (100). IC5o:0.73pM 20 Example 158 N-{4.[5-({[(5-Chloro-2-thienyl)carbonyl]amino}methyI)-2-oxo-l,3oxazolidin-3-yl]phenyl}-3,5-dimethyl-4-isoxazolecarboxamide LC-MS: m/z (%) - 475 (M+H, 100). 25 IC50: 0.46pM Example 159 5-Chloro-Af-{[3-(4-{[(3-chIoropropyl)suIphonyl]amino}phenyl)-2-oxo-1,3- 30 oxazolidin-5-yl]methyl}-2-thiophenecarboxamide O An ice-cooled solution of 26.4 mg (0.15 mmol) of 3-chloro-l-propanesulphonyI chloride and 0.03 ml (0.2 mmol) of triethylamine in 3.5 ml of absolute dichloro- methane is admixed with 35 mg (0.1 mmol) of A^[3-(4-arninophenyI)-2-oxo-l,3- oxazoHdin-5-yl]-niethyl}-5-chloro-2-thiophene-carboxamide (from Example 149). 5 After 30 min, ice-cooling is removed and the mixture is stirred at room temperature overnight, and 150 mg (about 5.5 eq.) of PS-trisamme (Argonaut Technologies) and 0.5 ml of dichloromethane are then added. The suspension is stirred gently for 2 h and filtered (the resin is washed with dichloromethane/methanol), and the filtrate is concentrated. The product is purified by preparative RP-HPLC. Yield: 19.6 mg (40% 10 of theory), LC-MS; m/z (%) - 492 (M+H, 100); LC-MS (method 5): it (%) = 3.82 (91). 15 Example 160 5-Chloro-A^-({3-[4-(l,l-dioxido-2-isothia2oIidinyl)phenyI]-2-oxo-l,3-OxazoIidin-5-yl}methyI)-2-thiophenecarboxamide 20 A mixture of 13.5 mg (0.027 mmol) of 5-chloro-N-{(3-(4-{[(3-chloropropyl)sul-phonyl]amino}phenyl)-2-oxo-l,3-oxazolidin-5-yl]methyl}-2-thiophene-carboxamide (from Example 159) and 7.6 mg (0.055 mmol) of potassium carbonate in 0.2 ml of 25 DMF is heated at 100°C for 2 h. After cooling, the mixture is diluted with, dichloromethane and washed with water. The organic phase is dried and concentrated. The residue is purified by preparative thin-layer chromatography (silica gel, dichloromethane/methanol, 95:5). Yield: 1.8 mg (14.4% of theory), MS (ESI): m/z (%) = 456 (M+H, 15), 412 (100); 30 LC-MS (method 4): it (%) = 3.81 (90). IC50: 0.14 pM Example 161 5-Chloro-N-t((5S)-3-{4-[(5-chloropentanoyi)amino]phenyl}-2-oxo-l,3-oxazoli-din-5-yl)methyl]-2-thiophenecarboxamide CI 0 5 0.5 g (1.29 mmol) of N-{[(5S)-3-(4-aminophenyl)-2-oxo-l,3-oxazoIidin-5- yI]methyl}-5-chloro-2-thiophenecarboxamide (from Example 149) is dissolved in 10 27 ml of tetrahydrofuran and admixed with 0.2 g (1.29 mmol) of 5-chlorovaleryl chloride and 0,395 ml (2.83 mmol) of triethylamine. The mixture is concentrated under reduced pressure and chromatographed over silica gel using a toluene/ethyl acetate=l:l -> ethyl acetate gradient. This gives 315 mg (52% of theory) of a solid. M.p.:211°C. 15 Example 162 5-Chloro-N-({(SS)-2-oxo-3-[4-(2-oxo-l-piperidinyI)phenyl]-l,3-oxazolidin-5.yl}. methyl)-2-thiophenecarboxamide 20 Under inert conditions, 5 ml of DMSO are admixed with 30 mg of NaH (60% in paraffin oil), and the mixture is heated at 75°C for 30 min, until the evolution of gas 25 has ceased, A solution of 290 mg (0.617 mmol) of 5-chloro-N-[((5S)-3-{4-[(5- chloropentanoyl)amino]phenyl}-2-oxo-l,3-oxa2olidin-5-yl)methyl]-2-thiophene-carboxamide (from Example 161) in 5 ml of methylene chloride is then added dropwise, and the mixture is stirred at room temperature overnight. The reaction is terminated and the mixture is poured into 100 ml of water and extracted with ethyl 109 acetate. The evaporated organic phase is chromatographed on an RP-8 column and the product is eluted with acetonitrile/water. This gives 20 mg (7.5% of theory) of the target compound. M,p.: 205°C; NMR (300 MHz, d6-DMSO): 5= 1.85 (m,4H), 2.35 (m,2H), 3.58 (m,4H), 3.85 (m,lH), 4.2 (t,lH), 4.82 (m,lH), 7.18 (d,lH,thiophene), 7.26 (d,2H), 7.5 (d,2H), 2.68 (d,lH,thiophene), 9.0 (t,lH,CONH). IC50: 2.8 nM 10 Example 163 5-ChIoro-N-[((5S)-3-{4-[(3-bromopropionyl)amino]phenyI}-2-oxo-l,3-oxazoli-din-5-yl)methyi}-2-thiophenecarboxamide 15 is obtained in an analogous manner from Example 149. Example 164 20 5-ChIoro-N-({(5S).2-oxo-3-[4-(2-oxo-l-.azetidinyl)phenyI]-1,3-oxazolidin-5-yl}- methyI)-2-thiophenecarboxamide 25 is obtained in an analogous manner by cyclization of the open-chain bromopropionyl compound from Example 163 using NaH/DMSO. MS (ESI): m/z (%) = 406 ([M+H]+, 100), CI pattern. 1C50: 380 nM Example 165 tert-Butyl 4-{4-[5-({[(5-chIoro-2-thienyI)carbonyllainino}methyl)-2-oxo-l,3-oxa-zolidin-3-yI]phenyl}-3,5-dioxo-l-piperazinecarboxylate A solution of 199 mg (0.85 mmol) of Boc-iminodi acetic acid, 300 mg (2.2 mmol) of HOBT, 0.66 ml (6 mmol) of N-methylmorphoIine and 647 mg (1.7 mmol) of HBTU 10 is admixed with 300 mg (0.S5 mmol) of N-[3-(4-aminophenyI)-2-oxo-l,3- oxazolidin-5-yl]-methyl }-5-chloro-2-thiophene-carboxamide in 6 ml of a mixture of DMF and dichloromethane (1:1). The mixture is stirred overnight, diluted with dichloromethane and then washed with water, saturated ammonium chloride solution, saturated sodium bicarbonate solution, water and saturated sodium chloride 15 solution. The organic phase is dried over magnesium sulphate and concentrated. The crude product is purified by silica gel chromatography (dichloromethane/methanol 98:2). Yield: 134 mg (29% of theory); MS (ESI): m/z (%) = 571 (M+Na, 82), 493 (100); HPLC (method 3): rt (%) - 4.39 (90). 20 IC50: 2 pM Example 166 N-[((5S)-3-{4-[(3R)-3-Amino-2-oxo-l-pyrToIidinyI]pheny!}-2-oxo-l,3-oxazolidin- 25 5-yI)methyI]-5-chloro-2-thiophepecarboxamide trifluoroacetate O BOCNH^COOH .g^^Cl s^ EDC, DIEA CH- r/9 L HOBT N2-(tert-Butoxycarbonyl)-Nl-{4-[(5S)-5-({[(5-chloro-2-thienyl)carbonyl]amino} 5 methyl)-2-oxo-l,3-oxazolidin-3-yl]phenyl}-D-methionineamide 429 mg (1.72 mmol) of N-BOC-D-methionine, 605 mg (1.72 mmol) of N^[(5S)-3-(4-aminophen yl)-2-oxo-1,3 -oxazol idin-5-yl]methyl) -5-ch loro-2-thiophenecarbox-amide, and 527 mg (3.44 mmol) of HOBT hydrate are dissolved in 35 ml of DMF 10 and admixed with 660 mg (3-441 mmol) of EDCI hydrochloride and then dropwise with 689 mg (5.334 mmol) of N-ethyl-diisopropylamine. The mixture is stirred at room temperature for two days. The resulting suspension is filtered off with suction and the residue is washed with DMF. The combined filtrates are admixed with a little silica gel, concentrated under reduced pressure and chromatographed over silica gel 15 using a toluene -> T10EA7 gradient. This gives 170 mg (17% of theory) of the target compound of melting point 183°C. Rf (Si02, toluene/ethyl acetate=l:l):0.2. }H-NMR (300 MHz. d6-DMSO): (s,lH,BOC), 1.88-1.95 (m,2H), 2.08 (s,3H,SMe), 2.4-2.5 (m,2H, partially obscurbed by DMSO), 3.6 (m,2H), 3.8 (m,lH), 20 4.15 (m,2H), 4.8 (m7lH), 7.2 (1H, thiophene), 7.42 (d, part of an AB system, 2H), 7.6 (d, part of an AB system, 2H), 7,7 (d, 1H, thiophene), 8.95 (t,lH, CH2NHCO), 9.93 (bs,lH,NH). tert-Butyl (3R)-l.{4-[(5S)-5-({[(5-chIoro-2-thieiiyI)carbonyI]aniino}methyi)-2-oxo-1,3-oxazoIidin-3-yl]pheny l}-2-oxo-3-pyrroIidinylcarbamate 170 mg (0.292 mmol) of N2-(tert-butoxycarbonyl)-Nl-{4-[(S$)-5-({[(5-chloro-2- 5 thienyl)carbony]] amino }methyl)-2-oxo~l ,3-oxazolidin-3-yl]phenyl }-D-methionine- amide are dissolved in 2 ml of DMSO and admixed with 178.5 mg (0.875 mmol) of trimethylsulphonium iodide and 60.4 mg (0.437 mmol) of potassium carbonate, and the mixture is stirred at 80°C for 3.5 hours. The mixture is then concentrated under high vacuum and the residue is washed with ethanol. 99 mg of the target compound 10 remain. }H-NMR (300 MHz, d6*DMSO): 6 =1.4 (s,lH,BOC), 1.88-2.05 (m,lH), 23-2.4 (m,lH), 3.7-3.8 (m,3H), 3.8-3.9 (m,lH), 4.1-4.25 (m,lH), 4.25-4.45 (m,lH), 4.75-4.95 (m,lH), 7.15 (1H, thiophene), 7.25 (d,lH), 7.52 (d, part of an AB system, 2H), 7.65 (d, part of an AB system, 2H), 7.65 (d, 1H, thiophene), 9.0 (broad s,lH). 15 N-[((5S)-3-{4-t(3R)-3-Aminio-2-oxo-l-pyrroIidinyI]phenyl}-2-oxo-l,3-oxazoUdm-5-y l)methyl] -S-chloro-2-thiophenecarboxamide trifluoroacetate 97 mg (0.181 mmol) of tert-butyl (3R)-l-{4-[(5S)-5-({[(5-chloro-2- 20 thienyl)carbonyl]amino}methyl)-2-oxo-l,3-oxazolidin-3-yI]phenyl}-2-oxo-3-pyrroli- dinylcarbamate are suspended in 4 ml of methylene chloride, 1.5 ml of trifluoroacetic acid are added and the mixture is stirred at room temperature for 1 hour. The mixture is then concentrated under reduced pressure and the residue is purified on an RP- HPLC (acetonitrile/water/0.1% TFA gradient). Evaporation of the appropriate 25 fraction gives 29 mg (37% of theory) of the target compound of melting point 241 °C (decomp.). Rf (Si02,EtOH/TEA=17:l) 0.19. ]H-NMR (300 MHz, d6-DMSO): =1.92-2.2 (m,lH), 2.4-2.55 (m,lH, partially. obscured by DMSO peak), 3.55-3.65 (m,2H), 3.75-3.95 (m,3H), 4.1-4.3 (m,2H), 30 4.75-4.9 (m,lH), 7.2 (1H, thiophene), 7.58 (d, part of an AB system, 2H), 7.7 (d, part of an AB system, 2H), 7.68 (d, 1H, thiophene), 8.4 (broad s,3H, NIB), 8.9 (t,lH,NHCO). The Examples 167 to 170 below refer to the introduction of sulphonamide groups in phenyl-substituted oxazolidinones: General method for preparing substituted sulphonamides starting from 5 5-chIoro-N-[(2-oxo-3-phenyI-1,3-oxazolidin-5-yl)methyl]-2- thiophenecarboxamide 10 Under argon and at 5°C, 5-chloro-N-[(2-oxo-"3-phenyl-l,3-oxa2olidin-5-yl)methyl]-2- thiophenecarboxamide (from Example 96) is added to chlorosulphonic acid (12 eq.). The reaction mixture is stirred at room temperature for 2 h and then poured into ice-water. The resulting precipitate is filtered off, washed with water and dried. 15 Under argon and at room temperature, the precipitate is then dissolved in tetrahydrofuran (0.1 mol/1) and admixed with the appropriate amine (3 eq.), triethylamine (1.1 eq.) and dimethylaminopyridine (0.1 eq.). The reaction mixture is stirred for 1-2 h and then concentrated under reduced pressure. The desired product is purified by flash chromatography (dichloromethane/methanol mixtures). . 20 The following compounds were prepared in an analogous manner: Example 167 25 5-Chloro-N-({2-oxo.3-[4- MS (ESI): m/2 (%) = 492 ([M+Na]+, 100), 470 ([M+H]+, 68), CI pattern; 114 10 HPLC (method 3): rt (%) = 4.34 (100). IC50: 0.5 pM Example 168 5-ChIoro-N-[(3-{4-[(4-methyl-1-piperazinyI)sulphonyI]phenyl}-2-oxo-l,3-oxa-zolidin-5-yI)methyI]-2-thiaphenecarboxamide MS (ESI): m/z (%) = 499 ([M+H]+, 100), CI pattern; HPLC (method 2); rt (%) = 3.3 (100). Example 169 5-Chloro-N-({2-oxo-3-[4-(l-piperidinylsuIphonyl)phenyl]-l,3-oxazolidin-5-yI}-methyl)-2-thiophcnecarboxamide 15 MS (ESI): m/z (%) = 484 ([M+H]+, 100), Cl pattern; HPLC (method 2): it {%) = 4.4 (100). Example 170 20 5-Chloro-N-[(3-{4-[(4-hydroxy-l-piperidinyl)sulphonyl]phenyI}-2-oxo-l,3-oxa- zoUdin-5-yl)methyl]»2-thiophenecarboxamide MS (ESI): m/z (%) = 500 ([M+H]+, 100), Cl pattern; HPLC (method 3): rt (%) = 3.9 (100). 25 Example 171 5-Chloro-N-({2-oxo-3-[4-(l-pyrrolidinyl)phenyl]-l,3-oxa2oIidin-5-yl)methyl)-2-thiophenecarboxamide H N H,CT;CH, 30 780 mg (1.54 mmol) of tert-butyl l-{4-[5-({[(5-chIoro-2-thienyl)carbonyl]amino}- methyl)-2-oxo-l,3-oxazohdin-3-yl]phenyl}prolinate are dissolved in 6 ml of dichloromethane and 9 ml of trifluoroacetic acid, and the mixture is stirred at 40°C 5 for two days. The reaction mixture is then concentrated and stirred with ether and 2N aqueous sodium hydroxide solution. The aqueous phase is concentrated and stin-ed with ether and 2N hydrochloric acid. The organic phase of this extraction is dried over MgS04, filtered and concentrated. The crude product is chromatographed over silica gel (CH2Cl2/EtOH/conc. aqu. NH3 sol. = 100/1/0.1 to 20/1/0.1). 10 This gives 280 mg (40% of theory) of the product. MS (ESI): m/z (%) = 406 (M+H, 100); HPLC (method 4): rt = 3.81 min. HPLC parameter and LC-MS parameter for the HPLC and LC-MS data given in the 15 examples above (the unit of the retention time (rt) is minutes): [1] Column; Kromasil C18, L-R temperature: 30°C, flow rate = 0.75 ml min-1, eluent: A = 0-01 M HC104, B = CH3CN, gradient: -> 0.5 min 98%A -> 4.5 min 10%A ->6.5 min 10%A 20 [2] Column: Kromasil C18 60*2, L-R temperature: 30oC, flow rate = 0.75 ml min"-1, eluent: A = 0.01 M H3P04, B = CH3CN, gradient: -> 0.5 min 90%A -> 4,5 min 10%A ->6.5 min 10%A 25 [3] Column: Kromasil C18 60*2, L-R temperature: 30°C, flow rate = 0.75 ml min-1, eluent: A = 0.005 M HC104, B = CH3CN, gradient: -> 0.5 min 98%A -> 4.5 min 10%A ->6.5 min 10%A [4] Column: Symmetry C18 2.1x150 mm, column oven: 50°C, flow rate = 30 0.6 ml min"1, eluent: A = 0.6 g 30% strength HC1/ 1 of water, B = CH3CN, gradient: 0.0 min 90%A -> 4.0 min 10%A ->9 min 10%A /■ / / / 116 / f [5] MHZ-2Q, Instrument Micromass Quattro LCZ Column Symmetry C18, 50 mm x 2.1 mm, 3.5 pm, temperature: 40°C, flow rate = 0.5 ml min-1, eluent A = CH3CN + 0.1% formic acid, eluent B = water + 0.1% formic 5 acid, gradient: 0.0 min 10% A -> 4 min 90% A -> 6 min 90% A [6] MH2-2P, Instrument Micromass Platform LCZ Column Symmetry C18, 50 mm x 2.1 mm, 3.5 pm, temperature: 40°C, flow rate = 0.5 ml min-1, eluent A - CH3CN + 0.1% formic acid, eluent B = water + 0.1% formic 10 acid, gradient: 0.0 min 10% A -> 4 min 90% A -> 6 min 90% A [7] MHZ-7Q, Instrument Micromass Quattro LCZ Column Symmetry C18, 50 mm x 2.1 mm, 3.5 pm, temperature: 40°C, flow rate = 0.5 ml min"1, eluent A = CH3CN + 0,1% formic acid, eluent B = water + 0.1% formic 15 acid, gradient: 0.0 min 5% A -> 1 min 5% A -> 5 min 90% A -> 6 min 90% A General method for preparing oxazolidinones of the general formula B by solid-phase-supported synthesis 20 Reactions with different resin-bonded products were carried out in a set of separated reaction vessels. 5-(Bromomethyl)-3-(4-fluoro-3-nitrophenyl)-l,3-oxazolidin-2-one A (prepared from epibromohydrin and 4-fluoro-3-nitrophenyl isocyanate using LiBr/Bu3PO in xylene 25 analogously to US 4128654, Ex.2) (1.20 g, 3.75 mmol) and ethyldiisopropylamine (DIEA, 1.91 ml, 4.13 mmol) were dissolved in DMSO (70 ml), admixed with a secondary amine (1.1 eq., amine component 1) and reacted at 55°C for 5 h. TentaGel SAM resin (5.00 g, 0,25 mmol/g) was added to this solution, and the mixture was reacted at 75°C for 48 h. The resin was filtered, washed repeatedly with methanol 30 (MeOH), dimethylformamide (DMF), MeOH, dichloromethane (DCM) and diethyl ether and dried. The resin (5.00 g) was suspended in dichloromethane (80 ml), admixed with DIEA (10 eq.) and 5-chlorothiophene-2-carbonyl chloride [prepared by reacting 5-chlorothiophene-2-carboxyIic acid (5 eq,) and l-chloro-l-dimethylamino-2-methylpropene (5 eq.) in DCM (20 ml) at room temperature for 15 minutes] and 35 the mixture was reacted at room temperature for 5 h. The resulting resin was filtered, washed repeatedly with MeOH, DCM and diethyl ether and dried. The resin was then 117 suspended in DMF/water (v/v 9:2, 80 ml), admixed with SnCl2*2H20 (5 eq.) and reacted at room temperture for 18 h. The resin was washed repeatedly with MeOH, DMF, water, MeOH, DCM and diethyl ether and dried. This resin was suspended in DCM, admixed with DIEA (10 eq.) and, at 0°C, with an acid chloride (5 eq. of acid 5 derivative 1), and the mixture was reacted at room temperature overnight. Prior to the reaction, carboxylic acids were converted into the corresponding acid chlorides by reaction with l-dimethylamino-l-chloro-2-methylpropene (1 eq„ based on the carboxylic acid) in DCM at room temperature for 15 min. The resin was washed repeatedly with DMF, water, DMF, MeOH, DCM and diethyl ether and dried. If the 10 acid derivative 1 used was an Fmoc-protected amino acid, the Fmoc protective group was removed in the last reaction step by reaction with piperidine/DMF (v/v, 1/4) at room temperature for 15 minutes, and the resin was washed with DMF, MeOH, DCM and diethyl ether and dried. The products were then removed from the solid phase using trifluoroacetic acid (TFA)/DCM (v/v, 1/1), the resin was filtered off and 15 the reaction solutions were concentrated. The crude products were filtered over silica gel (DCM/MeOH, 9:1) and evaporated, giving a set of products B. 2 TentaGelSAM" "TentaGelSAM oHr° -PA - "1>V_A o .s 5 Compounds which were prepared by solid-phase-supported synthesis: Example 172 N-({3-[3-Amino-4-(l-pyrrolidinyl)phenyl]-2-oxo-l,3-oxazolidin-5-yI}metbyl)-5- 10 chloro-2-thiophenecatboxamide Analogously to the general procedure for preparing the derivatives B, 5 g 15 (1.25 mmol) of TentaGel SAM resin were reacted with pyrrolidine as amine derivative 1. The aniline obtained after reduction with SnCL2*2H20 was, without any further acylarion step, removed from the solid phase and concentrated. The crude product was partitioned between ethyl acetate and NaHC03 solution and the organic phase was salted out using NaCl, decanted and evaporated to dryness. This crude product was purified by vacuum flash chromatography over silica gel (dichloro-methane/ethyl acetate, 3:1- 1:2). ]H-NMR (300 MHz, CX>C13): 1.95 - 2.08, br, 4 H; 3.15-3.30, br, 4 H; 3.65-3.81, m, 2 H; 3.89, ddd, 1H; 4.05, dd, 1 H; 4.81, dddd, 1 H; 6.46, dd, 1 H; 6.72, dd, 1 H; 6.90, 5 dd, 1 H; 6.99, dd, 1 H; 7.03, dd, 1 H; 7.29, d, 1 H, Example 173 N-[(3-{3-(B-Alanylamino)-4-t(3-hydroxypropyl)amino]phenyl}-2-oxo-l,3-oxa- 10 zoIidin-5-y))methyl]-5-chloro-2-thiophenecar boxamide Analogously to the general procedure for preparing the derivatives B, 5 g 15 (1.25 mmol) of TentaGel SAM resin were reacted with azetidine as amine derivative 1 and Fmoc-B-alanine as acid derivative 1. The crude product obtained after the removal was stirred in methanol at room temperature for 48 h and evaporated to dryness. This crude product was purified by reversed phase HPLC using a water/TFA/acetonitrile gradient. 20 "H-NMR (400 MHz, CD3OD): 2.31, tt, 2 H; 3.36, t, 2 H; 3.54, t, 2 H; 3.62, t, 2 H; 3.72, dd, 1 H; 3.79, dd, 1 H; 4.01, dd, 1 H; 4.29, dd, 2 H; 4.43, t, 2 H; 4.85-4,.95, m, 1 H; 7.01, d, 1 H; 4.48 - 7.55, m, 2 H; 7.61, d, 1 H; 7.84, d, 1 H. 25 Example 174 N-({3-[4-(3-Amino-l-pyrrolidinyl)-3-nitrophenyl]-2-oxo-l,3-oxazolidin-5-yl}-methyl)-5-chloro-2-thiophenecarboxamide NO. Q S-/ 10 Analogously to the general procedure for preparing the derivatives B, 130 mg (32.5 p.mol) of TentaGel SAM resin were reacted with tert-butyl 3-pyrrolidinylcarbamate as amine derivative 1. The nitrobenzene derivative obtained after the acylation with 5-chlorothiophenecarboxylic acid was removed from the solid phase and concentrated. This crude product was purified by reversed phase HPLC using a water/TFA/acetonitrile gradient. "H-NMR (400 MHz, CD3OH): 2.07-2.17, m, 1 H; 2.39-2.49, m, 1 H; 3.21-3.40, m, 2 H; 3.45, dd, 1 H; 3.50-3.60, m, 1 H; 3.67, dd, 1 H; 3.76, dd, 1 H; 3.88-4.00, m, 2 H; 4.14 - 4.21, t, 1 H; 4.85 - 4.95, m, 1 H; 7.01, d, 1 H; 7,11, d, 1 H; 7.52, d, 1 H; 7.66, dd, 1 H; 7.93, d, 1 H. 15 Example 175 N-({3-[3-Amino-4-(l-piperidinyI)phenyI]-2-oxo-l,3-oxazolidin-5-yI}methyI>5-chloro-2-thiophenecarboxamide 20 25 Analogously to the general procedure for preparing the derivatives B, 130 mg (32.5 pmol) of TentaGel SAM resin were reacted with piperidine as amine. derivative 1. The aniline obtained after the reduction was, without any further acylation step, removed from the solid phase and concentrated. This crude product was purified by reversed phase HPLC using a water/TFA/acetonitrile gradient. "H-NMR (400 MHz, CD3OH): 1.65-1.75, m, 2 H; 1.84-1.95, m, 4 H; 3.20-3.28, m, 4 H; 3.68, dd, 1 H; 3.73, dd, 1H; 3.90, dd, 1 H; 4.17, dd, 1 H; 4.80-4.90, m, 1 H; 7.00, d, 1 H; 7.05, dd, 1 H; 7.30-7.38, m, 2H; 7.50, d, 1 H. Example 176 N-({3-[3-(Acetylamino)-4-(l-pyrrolidinyI)phenyI]-2-oxo-l^-oxazoIidin-5-y|}-methyl)-5-chlorO"2-thiophenecarboxamide 5 Analogously to the general procedure for preparing the derivatives B, 130 mg (32.5 pmol) of TentaGel SAM resin were reacted pyrrolidine as amine derivative 1 10 and acetyl chloride as acid derivative 1. The crude product was partitioned between ethyl acetate NaHCO3 solution and the organic phase was salted out using NaCl, decanted and evaporated to dryness. This crude product was purified by vacuum flash chromatography over silica gel (dichloromethane/ethyl acetate, 1:1-0:1). "H-NMR (400 MHz, CD3OH): 1.93 - 2.03, br, 4 H; 2.16, s, 3 H; 3.20-3.30, br, 4 H; 15 3.70, d, 2 H; 3.86, dd, 1H; 4.10, dd, 1 H; 4.14, dd, 1 H; 4.80^.90, m, I H; 7.00, d, 1 H; 7.07, d, 1 H; 7.31, dd, 1 H; 7.51, d, 1 H; 7.60, d, 1 H. The following compounds were prepared analogously to the general procedure. WE CLAIM: 1. Oxazolidinones of the general formula (I) in which: R1 represents 2-thiophene which is substituted in the 5-position by a radical from the group consisting of chlorine, bromine, methyl and trifluoromethyl, R2 represents D-A-: where: the radical "A" represents phenylene; the radical "D" represents a saturated 5- or 6-membered heterocycle, which is attached to "A" via a nitrogen atom, which has a carbonyl group directly adjacent to the linking nitrogen atom and in which one carbon ring member may be replaced by a heteroatom from the group consisting of S, N and 0; where the group "A" defined above may optionally be mono- or disubstituted in the meta position with respect to the point of attachment to the oxazolidinone, by a radical from the group consisting of fluorine, chlorine, nitro, amino, trifluoromethyl, methyl and cyano, R3, R4, R5, R6, R7 and R8 each represent hydrogen 137 and their pharmaceuticaliy acceptable salts, hydrates, hydrates of salts of the kind such as herein described. 2. Oxazolidinones as claimed in Claim 1 having the following formula and its pharmaceuticaliy acceptable salts, hydrates, hydrates of salts cf the kind such as herein described. 3. Process for preparing substituted oxazolidinones as claimed in Claim 1, where either according to a process alternative [A] compounds of the general formula (II) R T \ p6 in which the radicals R2, R3, R4, R5, R6 and R 7 are each as defined in Claim 1 are reacted with carboxylic acids of the general formula (III) 138 in which the radical R1 is as defined in Claim 1, or else with the corresponding carbonyl halides, preferably carbonyl chlorides, or else with the corresponding symmetric or mixed carboxylic anhydrides of the carboxylic acids of the general formula (III) defined above in inert solvents of the kind such as herein described, if appropriate in the presence of an activating or coupling agent and/or a base of the kind such as herein described, to give compounds of the general formula (I) (I), in which the radicals R1, R2, R3, R4, R5, R6, R7 and R8 are each as defined in Claim 1, or else according to a process alternative [B] compounds of the general formula (IV) r,5 J.S in which the radicals R1, R3, R«, R5j R6? R7 and RS as defined in Claim 1, are converted, using a suitable selective oxidizing agent of the kind such as herein described in an inert solvent of the kind such as herein described, into the corresponding epoxide of the general formula (V) in which the radicals R1, R3, R4 R5, R6,R7 and R8 are each as defined in Claim 1, and, by reaction in an inert solvent of the kind such as herein described, if appropriate in the presence of a catalyst of the kind such as herein described, with an amine of the general formula (VI) R2-NH2 (VI), in which the radical R2 is as defined in Claim 1, the compounds of the general formula (VII) in which the radicals R1, R2, R3, R4, R5, R6, R7 and R8are each as defined in Claim 1, 140 are initially prepared and, subsequently, in an inert solvent of the kind such as herein described in the presence of phosgene or phosgene equivalents, such as, for example, carbonyldiimidazole (CDI), cyclized to give the compounds of the general formula [\) (I), in which the radicals R1, R2, R3, R4, R5, R6, R7 and R8are each as defined in Claim 1. 4. Medicaments, comprising at least one compound as defined in Claim 1 or 2 in a concentration of from 0.1 to 95% by weight of the total mixture and one or more pharmacologically acceptable auxiliaries or excipients of the kind such as herein described. Dated this 11th day of June, 2002. (RANJNA MEHTA-DUTT) OF REMFRY & SAGAR ATTORNEY FOR THE APPLICANTS 141 FORM 2 THE PATENTS ACT 1970 [39 OF 1970] 86 THE PATENTS RULES, 2003 COMPLETE SPECIFICATION [See Section 10; rule 13] "OXAZOLIDINONES AND THEIR USE" BAYER HEALTHCARE AG, a body corporate organized under the laws of Germany of 51368 Leverkusen, Germany, The following specification particularly describes the invention and the manner in which it is to be performed: The present invention relates to the field of blood coagulation. In particular, the present invention relates to novel oxazolidinone derivatives, to processes for their 5 preparation and to their use as active compounds in medicaments. Blood coagulation is a protective mechanism of the organism which helps to "seal" defects in the wall of the blood vessels quickly and reliably. Thus, loss of blood can be avoided or kept to a minimum. Haemostasis after injury of the blood" vessels is 10 effected mainly by the coagulation system in which an enzymatic cascade of complex reactions of plasma proteins is triggered. Numerous blood coagulation factors are involved in this process, each of which factors converts, on activation, the respectively next inactive precursor into its active form. At the end of the cascade comes the conversion of soluble fibrinogen into insoluble fibrin, resulting in the 15 formation of a blood clot. In blood coagulation, traditionally the intrinsic and the extrinsic system, which end in a joint reaction path, are distinguished. Here factor Xa, which is formed from the proenzyme factor X, plays a key role, since it connects the two coagulation paths. The activated serine protease Xa cleaves prothrombin to thrombin. The resulting thrombin, in turn, cleaves fibrinogen to fibrin, a 20 fibrous/gelatinous coagulant. In addition, thrombin is a potent effector of platelet aggregation which likewise contributes significantly to haemostasis. Maintenance of normal haemostasis - between bleeding and thrombosis - is subject to . a complex regulatory mechanism. Uncontrolled activation of the coagulant system or 25 defective inhibition of the activation processes may cause formation of local thrombi or embolisms in vessels (arteries, veins, lymph vessels) or in heart cavities. This may lead to serious disorders, such as myocardial infarct, angina pectoris (including unstable angina), reocclusions and restenoses after angioplasty or aortocoronary bypass, stroke, transitory ischaemic attacks, peripheral arterial occlusive disorders, 30 pulmonary embolisms or deep venous thromboses; hereinbelow, these disorders are collectively also referred to as thromboembolic disorders. In addition, in the case of consumption coagulopathy, hypercoagulability may - systemically - result in disseminated intravascular coagulation. 35 These thromboembolic disorders are the most frequent" cause of morbidity and mortality in most industrialized countries (Pschyrembel, Klinisches Worterbuch [clinical dictionary], 257th edition, 1994, Walter de Gruyter Verlag, page 199 ff., entry "Blutgerinnung" [blood coagulation]; R6rPPP Lexikon Chemie, Version 1.5, 1998, Georg Thieme Verlag Stuttgart, entry "Blutgerinnung"; Lubert Stryer, Biochemie [biochemistry], Spektrum der Wisenschaft Verlagsgesellschaft mbH 5 Heidelberg, 1990, page 259 ff.). The anticoagulants, i.e. substances for inhibiting or preventing blood coagulation, which are known from the prior an have various, often grave disadvantages. Accordingly, in practice, an efficient treatment method or prophylaxis of 10 thromboembolic disorders is very difficult and unsatisfactory. In the therapy and prophylaxis of thromboembolic disorders, use is firstly made of heparin, which is administered parenterally of subcutaneously. Owing to more favourable pharmacokinetic properties, preference is nowadays more and more given 15 to low-molecular-weight heparin; however, even with low-molecular-weight heparin, it is not possible to avoid the known disadvantages described below, which are involved in heparin therapy. Thus, heparin is ineffective when administered orally and has a relatively short half-life. Since heparin inhibits a plurality of factors of the blood coagulation cascade at the same time, the action is nonselective. Moreover, 20 there is a high risk of bleeding; in particular, brain haemorrhages and gastrointestinal bleeding may occur, which may result in thrombopenia, drug-induced alopecia or osteoporosis (Pschyrembel, Klinisches Worterbuch, 257th edition, 1994, Walter de Gruyter Verlag, page 610, entry "Heparin"; Rornpp Lexikon Chemie, Version 1.5, 1998, Georg Thieme Verlag Stuttgart, entry "Heparin"). 25 A second class of anticoagulants are the vitamin K antagonists. These include, for example, 1,3-indanediones, and especially compounds such as warfarin, phenprocoumon, dicumarol and other coumafin derivatives which inhibit the synthesis of various products of certain vitamin K-dependent coagulation factors in 30 the liver in a non-selective manner. Owing to the mechanism of action, however, the onset of the action is very slow (latency to the onset of action 36 to 48 hours). It is possible to administer the compounds orally; however, owing to the high risk of bleeding and the narrow therapeutic index, a time-consuming individual adjustment and monitoring of the patient are required. Moreover, other adverse effects, such as 35 gastrointestinal disturbances, hair loss and skin necroses, have been described (Pschyrembel, Klinisches Worterbuch, 257th edition, 1994, Walter de Gruyter Verlag, 3-3 ax 0 R1 . represents 2-thiophenc which is substituted in the 5-position by a radical from the group consisting of chlorine, bromine, methyl and trifluoromethyl, R2 represents D-A-: where: the radical "A" represents phonylene; the radical "D" represents a saturated 5~ or 6-membered heterocyclic, which is attached to "A" via a nitrogen atom. which has a carbonyl group directly adjacent In the linking nitrogen atom and in which one carbon ring member may be replaced by a heteroatom from the group consisting of S, N and 0; where the group "A" defined above may optionally be mono- or disubstituted in the metaposition with respect to the point of attachment to the oxazolidinone, by a radical fromthe group consisting of fluorine, chlorine, nitro. amino, trilhioroinethyl, methyl andeyano, R3; R4, R5, R6 R.7and R8each represent hydrogen and their pharmaeeuticaily acceptable salts, hydrates. liydrates of sails. except for compounds of the general formula (1) in which the radical R is an unsubstituted 2-thiopbene radical and the radical R" is simultaneously a mono- or polysubstituted phenyl radical and the radicals R~", R4, R5, R6, R7 and R are each simultaneously hydrogen. Preference is given here to compounds of the. general formula (I), in which R represents optionally benzo-fused thiophenc (thienyl) which may optionally be mono- or polysubstituted by a radical from the group consisting of halogen; cyano; nitro; amino; aminomethyl; (C7-C8)-alkyl which for its part may optionally be mono- or polysubstituted bv halogen; (C3-C7)-eyeloalkyl: (C1-C-8)-alkoxy; imidazolinyl; -C(=NH)NH2; carbamoyl; and mono- and di-(C1-C-4)-alkyl-aminocarbonyI, R2 represents one of the groups below: 5 A-, A-M-, D-M-A-, B-M-A-, B-, 10 B-M", B-M"B-, D-M-B-, where: 15 the radical "A" represents ( 20 group consisting of S, N, NO (N-oxide) and O; the radical "D" represents a saturated or partially unsaturated, mono-or bicyclic, optionally benzo-fused 4- to 9-membered heterocycle which contains up to three heteroatoms and/or hetero chain members from the group consisting of S,SO,SO2,N,NO (N-oxide)and G, 25 the radical "M" represents -NH-, -CH2-, -CH2CH2-, -O-, -NH-CH2-, -CH2-NH-, -OCHr, -CH2CK -CONH-, -NHCO-, -COO-, -OOC-, -S-, -S02- or represents a covalent bond; where 30 the groups "A", "B" and "D" defined above may each optionally be mono- or polysubstituted by a radical from the group consisting of halogen; trifluoromethyl; oxo; cyano; nitro; carbamoyl; pyridyl; (Cr C6)-alkanoyl; (C3-C7)-cycloalkanoyl; (C6-C14)-arylcarbonyl; (C5-C10)-heteroarylcarbonyl; (C1-C6)-alkanoyloxymethyloxy; (C1-C4)hydroxy- 35 alkylcarbonyl; -COOR27; -S02R27; -C(NR27R28)=NR29; -CONR28R29; -SO2NR28R29; -OR30; -NR30R31, (CrC6)-alkyl and (C3-C7)-cycloalkyl, where (C1-C6)-aIkyI and (C3-C7)-cycloalkyl for their part may optionally be substituted by a radical from the group consisting of cyano; -OR27; -NR28R29; -CO(NH)v(NR27R28) and -C(NR27R28)=NR29, where: v is either 0 or 1 and 10 R27, R28 and R29 are identical or different and independently of one another each represents hydrogen, (C1-C4)-alkyI1 (C3-C7)- cycloalkyl, (C1-C4)-alkanoyl, carbamoyl, trifluoromethyl, phenyl or pyridyl, 15 and/or R27 and R28 or R27 and R29 together with the nitrogen atom to which they are attached form a saturated or partially unsaturated 5- to 7-membered heterocycle having up to three, preferably up to 20 two, identical or different heteroatoms from the group consisting of N, O and S, and R30 and R31 are identical or different and independently of one another each represents hydrogen, (C1-C4)-alkyl, (C3-C7)-cycloalkyl, 25 (CrC4)alkylsuIphonyI, (C1-C4)-hydroxyaikyl, (CrC4)- aminoalkyl, di-(C 1 -C4)-alkylamino-(C 1 -C4)-alkyl, -CH2C(NR27R2S)=NR29 or -COR33, where 30 .33 R33 represents (CrC6)-alkoxy, (C1-C4)-aIkoxy-(CI-C4)- alkyl, (C1-C4)-aIkoxycarbonyl-(CI-C4)-alkyI, (CrC4> aminoalkyl, (C1-C4)~alkoxycarbonyl, (C1-C4)-alkanoyl- (Ci-C4)-alkyl, (C3-C7)-cycloalkylT (C1-C6)-alkenyl, 35 (Ct-Cg^alkyl, which may optionally be substituted by 7- phenyl or acetyl, (C6-CI4)-aryl, (C5-C10)-heteroaryI, trifluoromethyl, tetrahydrofuranyl or butyrolactone, R3, R4, R5, R6, R7 and R8 are identical or different and each represents hydrogen or represents (C1-C6)-alkyl and their pharmaceutically acceptable salts, hydrates and prodrugs, 1 except for compounds of the general formula (I) in which the radical R is an 10 unsubstituted 2-thiophene radical and the radical R2 is simultaneously a mono- or polysubstituted phenyl radical and the radicals R3, R4; R5, Rs, R7 and R8 are each simultaneously hydrogen. 15 Preference is also given here to compounds of the general formula (I), in which R1 represents thiophene (thienyl), in particular 2-thiophene, which may optionally be mono- or polysubstituted by halogen, preferably chlorine or 20 bromine, by amino, aminomethyl or (C1-C8)-alkyl, preferably methyl, where the (C1-C8)-alkyl radical for its part may optionally be mono- or polysubstituted by halogen, preferably fluorine, R2 represents one of the groups below: 25 A-, A-M-, D-M-A-, B-M-A-, B-, 30 B-M-, B-M-B-, D-M-B-, 35 where: 5 the radical "A" represents (C6-C14)-aryl preferably (C6-C1o)-aryl, in particular phenyl or naphthyl, very particularly preferably phenyl; the radical "B" represents a 5- or 6-membered aromatic heterocycle which contains up to 3 heteroatoms and/or hetero chain members, in 5 particular up to 2 heteroatoms and/or hetero chain members, from the group consisting of S, N, NO (N-oxide) and O; the radical "D" represents a saturated or partially unsaturated 4- to 7- membered heterocycle which contains up to three heteroatoms and/or hetero chain members from the group consisting of S, SO, S02, N, NO 10 (N-oxide) and O; the radical "M" represents -NH-, -CH2-, -CH2CH2-, -0~, -NH-CH2-, -CH2-NH-, -OCH2-, -CH20-, -CONH-, -NHCO-, -COO-, -OOC-, -S-or represents a covalent bond; 15 where the groups "A", "B" and "D" defined above may in each case optionally be mono- or polysubstituted by a radical from the group consisting of halogen; trifluoromethyl; oxo; cyano; nitro; carbamoyl; pyridyl; (C1-C6)-alkanoyl; (C3-C7)-cycloalkanoyl; (C6-C14)- 20 arylcarbonyl; (C5-C1o)-heteroarylcarbonyl; (C1-C6)- alkanoyloxymethyloxy; -COOR27; -S02R27; -C(NR27R28)=NR29; -CONR28R29; -S02NR28R29; -OR30; -NR30R31, (C1C6)-alkyl and (C3- C7)-cycloaIkyl, 25 where (C1-C6)-alkyl and (C3-C7)-cycloalkyl for their part may optionally be substituted by a radical from the group consisting of cyano; -OR27; -NR28R29; -CO(NH)v(NR27R28) and -C(NR27R28)=NR29, 30 where: v is either 0 or 1 and R27, R28 and R29 are identical or different and independently of one 35 another each represents hydrogen, (C1-C4)-alkyl or (C3-C7)- cycloalkyl, 9 and/or R27 and R28 or R27 and R29 together with the nitrogen atom to which they are attached form a saturated or partially unsaturated 5- to 5 7-membered heterocycle having up to three, preferably up to two, identical or different heteroatoms from the group consisting of N, O and S, and R30 and R31 are identical or different and independently of one another 10each represents hydrogen, alkylsulphonyl, aminoalkyl, (Ci-C4)~ alkanoyl, 15 R3, R4, R5, R6, R7 and Rs are identical or different and each represents hydrogen or represents (Ci-C6)-alkyl and their phannaceutically acceptable salts, hydrates and prodrugs, 20 except for compounds of the general formula (I) in which the radical R1 is an unsubstituted 2-thiophene radical and the radical R is simultaneously a mono- or polysubstituted phenyl radical and the radicals R3, R4, R5, R6, R7 and Rs are each simultaneously hydrogen. 25 Particular preference is given here to compounds of the general formula (I), in which - ,;J 30 R1 represents thiophene (thienyl), in particular 2-thiophene, which may optionally be mono- or polysubstituted by halogen, preferably chlorine or bromine, or by (Ci-Cg)-alkyl, preferably methyl, where the (Ci-Cg)-alkyl radical for its part may optionally be mono- or polysubstituted by halogen, preferably fluorine, 35 R2 represents one of the groups below; 10 A-, A-M-, D-M-A-, B-M-A-, 5 B-, B-M-, B-M-B-, D-M-B-, 10 where: the radical "A" represents phenyl or naphthyl, in particular phenyl; the radical "B" represents a 5- or 6-membered aromatic heterocycle which contains up to 2 heteroatoms from the group consisting of S, N, NO (N-oxide) and O; 15 the radical "D" represents a saturated or partially unsaturated 5- or 6- membered heterocycle which contains up to two heteroatoms and/or hetero chain members from the group consisting of S, SO, SO2, N, NO (N-oxide) and O; the radical "M" represents -NH-, -O-, -NH-CH2-, -CH2-NH-, -OCHz-, 20 -CH2O-, -CONH-, -NHCO- or represents a covalent bond; where the groups "A", "B" and "D" defined above may in each case optionally be mono- or polysubstituted by a radical from the group 25 consisting of halogen; trifluoromethyl; oxo; cyano; pyridyl; (C1-C3)- alkanoyl; (C6-Cio)-arylcarbonyI; (C5-C6)-heteroarylcarbonyl; (C1-C3)- alkanoyloxymethyloxy; -C(NR27R28)=NR29; -CONR28R29; -S02NR28R29; -OH; -NR30R31; (C1-C4)-alkyl; and cyclopropyl, cyclopentyl or cyclohexyl, 30 where (C1-C4)-alkyl and cyclopropyl, cyclopentyl or cyclohexyl for their part may optionally be substituted by a radical from the group consisting of cyano; -OH; -OCH3; -NR28R29; -CO(NH)v(NR27R28) and -C(NR27R28)=NR29, 35 where: 1) v is either 0 or 1, preferably 0, and R27, R28 and R29 are identical or different and independently of 5 one another each represents hydrogen, (C1-G4)-alkyl or else cyclopropyl, cyclopentyl or cyclohexyl and/or R27 and R28 or R27 and R29 together with the nitrogen atom to which 10 they are attached may form a saturated or partially unsaturated 5- to 7-membered heterocycle having up to two identical or different heteroatoms from the group consisting of N, O and S, and 15 R30 and R31 are identical or different and independently of one another each represents hydrogen, (Ci-GO-alkyl, cyclopropyl, cyclopentyl, cyclohexyl, (C1-C4)-alkylsulphonyl, (C1-C4)-hydroxyalkyl, (C1-C4)-aminoalkyl, di-(C1-C4)-alkylamino-(C1-C4)-alkyl, (C1C3)-alkanoyl or phenylcarbonyl, 20 25 30 R3, R4, R5, R6, R7 and Rs are identical or different and each represents hydrogen or represents (C1-C6)-alkyl and their pharmaceutically acceptable salts, hydrates and prodrugs, except for compounds of the general formula (I) in which the radical R is an unsubstituted 2-thiophene radical and the radical R2 is simultaneously a mono- or polysubstituted phenyl radical and the radicals R3, R4, R5, R6, R7 and R8 are each simultaneously hydrogen. Particular preference is given here to compounds of the general formula (I), in which R1 represents 2-thiophene which may optionally be substituted in the 5-position by a radical from the group consisting of chlorine, bromine, methyl or trifluOromethyl, 5 R2 represents one of the groups below: A-, A-M-, D-M-A-, B-M-A-, 10 B-, B-M-, B-M-P-, D-M-B-, 15 where: the radical "A" represents phenyl or naphthyl, in particular phenyl; the radical "B" represents a 5- or 6-membered aromatic heterocycle which contains up to 2 heteroatoms from the group consisting of S, N, NO (N-oxide) and O; 20 the radical "D" represents a saturated or partially unsaturated 5- or 6- membered heterocycle which contains a nitrogen atom and optionally a further heteroatom and/or hetero chain member from the group consisting of S, SO, SO2 and O; or contains up to two heteroatoms and/or hetero chain members from the group consisting of S, SO, SOx 25 and O; the radical "M" represents -NH-, -O-, -NH-CH2-, -CH2-NH-, -OCH2-, -CH2O-, -CONH-, -NHCO- or represents a covalent bond; where 30 the groups "A", "B" and "D" defined above may in each case optionally be mono- or polysubstituted by a radical from the group consisting of halogen; trifluoromethyl; oxo; cyano; pyridyl; (C1-C3)-alkanoyl; (C6-C10)-aryIcarbonyl; (C5-C6)-hetefoarylcarbonyl; (C1-C3)-alkanoyloxymethyloxy; -CONR28R29; -S02NR28R29; -OH; -NR30R31; 35 (C1-C4)-alkyl; and cyclopropyl, cyclopentyl or cyclohexyl, may, in particular, represent a group of the following formula: Y-X-(CH2),-X-(CO)n-(CH2)1-(CR9R10)m-(CH3)02- where m is an integer from 0 to 6, preferably from 1 to 3, n is either 0 or 1, p is an integer from 0 to 3, preferably either 0 or 1, o{ is an integer 0 or J, o2 is an integer 0 or 1, R9 and R10 are identical or different and each represents hydrogen; (C1-C4)-alkyl, preferably methyl; (C1-C4)-alkoxy, preferably methoxy; (C3-C7)-cycloalkyl; hydroxyl or fluorine, X and X" are identical or different and each represents O; N-R11 or a covalent bond, where R11 represents H; (C1-C4)-aIkyI, preferably methyl, or (C3-C7)-cycloalkyl, Y represents a 3- to 7-membered saturated or partially unsaturated cyclic hydrocarbon radical which optionally contains 1 to 3 identical or different heteroatoms and/or hetero chain members from the group consisting of N, O, S, SO and $O2, where: this radical Y may optionally be substituted by a 5- or 6-membered aromatic or a 3- to 7-membered saturated or partially unsaturated cyclic hydrocarbon radical which optionally contains up to 3 identical or different heteroatoms from the group consisting of N, O and S and where this radical may for its part optionally be substituted by a radical from the group consisting of cyano; hydroxyl; halogen; (C1-C4)-alkyl; -C(=NR12)NR13R!3"; and-NRI4R!5, where: R12 represents hydrogen, (C1-C4)-alkyl or (C3-C7)-cycloalkyl; R13 and R13 are identical or different and independently of one another each represents hydrogen, (C1-C4)-alkyl or (C3-C7)-cycloalkyl and/or R13 and R13 together with the N atom to which they are attached form a 5- to 7-membered heterocycle which may optionally contain up to 2 further heteroatoms from the group consisting of N, O and S; R14 and R15 are identical or different and independently of one another each represents hydrogen, (C1-C4)-alkyI, (C3-C7)-cyc]oalky) or (C1-C5)-alkanoyl; and/or this radical Y may furthermore optionally be substituted by a radical from the group consisting of oxo; cyano; thiono; halogen; -OR16; =NR16; -NR16R17; -C(=NR18)NRI9R19" and (C1C4)-alkyl, in which (C1-C4)-alkyi for its part may optionally be substituted by a radical from the group consisting of hydroxyl; cyano; -NR16R17 and -C(=NR18)NR19R19", 18 where: R16 and R17 are identical or different and independently of one another each represents hydrogen, (C1-C4)-alkyl, (C3-C7)-cycIoalkyI or (C1-C3)-alkanoyl; R18 represents hydrogen, (C1-C4)-alkyl or (C3-C7)-cycloalkyl; 10 R19 and R19 are identical or different and independently of one another each represents hydrogen, (C1-C4)-aIkyI or (C3- C7)-cycloalkyl and/or 15 R19 and R19 together with the N atom to which they are attached form a 5- to 7-membered heterocycle which may optionally contain up to 2 further heteroatoms from the group consisting of N, 0 and S. 20 Particular preference is given to compounds of the general fonnula (I) in which the radical R2 represents a group of the following fonnula: 25 Y-X"-(CH2)p-X-(CO)n-(CH2)Ol-(CR9Rl0)m-(CH2)o2- where m is an integer from 0 to 3, 30 n is an integer 0 or 1, p is an integer 0 or 1, 35 01 is an integer 0 or 1, 19 — 02 is an integer 0 or 1, R9 and R10 are identical or different and each represents hydrogen; methyl; 5 X and X" are identical or different and each represents O; N-R11 or a covalent bond, where R1" represents H or methyl, 10 y represents a 5- to 7-membered saturated cyclic hydrocarbon radical which optionally contains 1 or 2 identical or different heteroatoms and/or hetero chain members from the group consisting of N, O, S, SO and SO2, in particular cyclohexyl, piperazinyl, morpholinyl, 15 thiomorpholinyl, diazepinyl, pyrrolidinyl and piperidinyl, where: this radical Y may optionally be substituted by a 5- or 6-membered 20 aromatic or a 5- to 7-membered saturated or partially unsaturated cyclic hydrocarbon radical which optionally contains up to 2 identical or different heteroatoms from the group consisting of N, O and S and where this radical for its pan may be substituted by a radical from the 25 group consisting of cyano; hydroxyl; fluorine; chlorine; (C1-C4)-alkyl; -C(=NR12)NR13R13"; and -NR14R15, where: 30 R12 represents hydrogen, methyl, ethyl, cyclopropyl, cyclopentyl or cyclohexyl; R13 and R13 are identical or different and independently of one another each represents hydrogen, methyl, ethyl, cyclopropyl, 35 cyclopentyl or cyclohexyl and/or R13 and R13" together with the N atom to which they are attached form a 5- to 7-membered heterocycle which may optionally contain up to 2 further heteroatoms from the group consisting of N, O 5 and S, in particular piperidinyl, piperazinyl, morpholinyl and thiomorpholinyl; R14and R15 are identical or different and independently of one another each represents hydrogen, methyl, ethyl, cyclopropyl, . 10 cyclopentyl or cyclohexyi or else acetyl; and/or this radical Y may furthermore optionally be substituted by a 15 radical from the group consisting of oxo; cyano; thiono; fluorine; chlorine; -OH; -OCH3; =NR16; -NH2; -N(CH3)2; -C(=NR18)NR19R19" and methyl, in which methyl for its part may optionally be substituted by a 20 radical from the group consisting of hydroxyl; cyano; -NR16R17 and-C(=NRI8)NR19R19", where: 25 R16 and R17 are identical or different and independently of one another each represents hydrogen, methyl, (C3-C7)-cycloalkyl or acetyl; 30 R18 reprsents hydrogen, methyl or (C3-C7)-cycloalkyl; R19 and R19" are identical or different and independently of one another each represents hydrogen, methyl or {C3-C7)-cycloalkyl and/or 35 21 -2*-=—= R19 and R19" together with the N atom to which they are attached form a 5- to 7-membered heterocycle which may optionally contain up to 2 further heteroatoms from the group consisting of N, O and S, in particular 5 piperidinyl, piperazinyl, morpholinyl and thio- morpholinyl. Likewise, in the compounds of the general formula (I), the radical 10 R2 may represent a group of the formula below: Z-(CO)r(CR20R2I)s- where; 15 s is an integer from 1 to 6, t is either 0 or 1, 20 R20 and R21 are identical or different and each represents hydrogen, (C1-C4)- alkyl, (C1-C4)-alkoxy, (C3-C7)-cycIoaIkyl, hydroxyl or fluorine, Z represents a radical which is selected from the group consisting of cyano; -C(NR22R23)=NR24; -CO(NH)uNR22R23; and-NR25R26, 25 where: u is either 0 or 1, preferably 0, and 30 R22, R23 and R24 are identical or different and independently of one another each represents hydrogen, (C1-C4)-alkyI or (C3-C7)-cycloalkyl, preferably hydrogen or methyl, and/or 35 R22 and R23 together with the N atom to which they are attached form a 5- to 7-membered heterocycle which may optionally contain up to 2 further heteroatoms and/or hetero chain members from the group consisting of N, O, S, SO and SO2; R25 and R26 are identical or different and independently of one another 5 each represents hydrogen, (C1-C4)-aIkyl or (C3-C7)-cycloalkyl, preferably hydrogen, methyl or ethyl, where (C1-C4)-alkyl and (C3-C7)-cycloalkyl for their part may optionally be substituted by hydroxy! or (C1-C6)-alkoxy. 10 Furthermore, in the compounds of the general formula (I), the radical R2 may represent one of the following groups: A-, A-M-, 15 D-M-A-, B-M-A-, B-, B-M-, B-M-B-, 20 D-M-B-, where: the radical "A" represents (C6-C14)-aryl, preferably (C6-C10)-aryl, in particular 25 phenyl or naphthyl, very particularly preferably phenyl; the radical "B" represents a 5- or 6-membered aromatic heterocycle which contains up to 3 heteroatoms and/or hetero chain members, in particular up to 2 heteroatoms and/or hetero chain members, from the group consisting of.S,, N, NO (N-oxide) and O; 30 the radical "D" represents a saturated or partially unsaturated 4- to 7- membered heterocycle which contains up to three heteroatoms and/or hetero chain members from the group consisting of S, SO, S02, N, NO (N-oxide) and O; the radical "M" represents -NH-, -CH2-, -CH2CB2-, -0-, -NH-CH2-> 35 -CH2-NH-, -OCH2-, -CH20-, -CONH-, -NHCO-, -COO-, -OOC-, -S- or represents a covalent bond; where the groups "A", "B" and "D" defined above may in each case optionally be mono- or polysubstituted by a radical from the group consisting of halogen; trifluoromethyl; oxo; cyano; nitro; carbamoyl; pyridyl; (C1-C6)-alkanoyI; (C3-C7)-cycloalkanoyI; (C6-C14)-arylcarbonyl; (C5-C1o)-heteroarylcarbonyl; (C1-C6)-alkanoyloxymethyloxy; -COOR27; -S02R27; -C(NR27R28)=NR29; -CONR28R29; -S02NR28R29; -OR30; -NR30R31 (CrC6)-aIkyl and (C3-C7)-cycloalkyl, 10 where (C1-C6)-alkyl and (C3-C7)-cycloalkyl for their part may optionally be substituted by a radical from the group consisting of cyano; -OR ; -NR R ; -CO(NH)v(NR27R2s) and -C(NR27R28)=NR29, 15 where: v is either 0 or 1 and R27, R28 and R29 are identical ov different and independently of one another 20 each represents hydrogen, (C1-C4)-alkyl or (C3-C7)-cycloalkyl and/or R27 and R28 or R27 and R29 together with the nitrogen atom to which they are attached form a saturated or partially unsaturated 5- to 7-membered 25 heterocycle having up to three, preferably up to two, identical or different heteroatoms from the group consisting of N, O and S, and R30 and R31 are identical or different and independently of one another each represents hydrogen, (C1-C4)-aIkyl, (C3-C7)-cycloalkyl, (C1C4)-alkyl- 30 sulphonyl, (C1-C4)-hydroxyaIkyl, (C1C4)-aminoalkyl, di-(C1-C4)- alkylamino-(C1-C4)-alkyl, (C1C4)-aIkanoyl, (C6-C14)-aryIcarbonyI, (C5-C10)-heteroarylcarbonyl, (C1-C4)-alkylaminocarbonyl or -CH2C(NR27R28)=NR29. 35 Preference is also given to compounds of the general formula (I) in which the radical Infi-A ^4-P3-T6it;i!Hi Countries -24- R2 represents one of the groups below: A-, A-M-, D-M-A-, B-M-A-, B-, B-M-, B-M-B-, D-M-B-, 10 where: the radical "A" represents phenyl or naphthyl, in particular phenyl; the radical "B" represents a 5- or 6-membered aromatic heterocycle which contains up to 2 heteroatoms from the group consisting of S, N, NO (N-oxide) 15 and O; the radical "D" represents a saturated or partially unsaturated 5- or 6-membered heterocycle which contains up to two heteroatoms and/or hetero chain members from the group consisting of S, SO, S02l N, NO (N-oxide) and O; 20 the radical "M" represents -NH-, -O-, -NH-CH2-, -CH2-NH-, -OCH2-, -CH20-, -CONH-, -NHCO- or represents a covalent bond; where the groups "A", "B" and "D" defined above may in each case optionally be 25 mono- or polysubstituted by a radical from the group consisting of halogen; trifluoromethyl; oxo; cyano; pyridyl; (C1-C3)-alkanoyl; (C6-C10)-arylcarbonyl; (C5-C6)-heteroarylcarbonyl; (C1-C3)-alkanoyloxymethyloxy; -C(NR27R28)=NR29; -CONR28R29; -S02NR28R29; -OH; -NR30R31; (C1-C4)-alkyl; and cyclopropyl, cyclopentyl or cyclohexyl, 30 where (C1-C4)-alkyI and cyclopropyl, cyclopentyl or cyclohexyl for their part may optionally be substituted by a radical from the group consisting of cyano; OH; -OCH3; -NR28R29; -CO(NH)v(NR27R28) and -C(NR27R28)=NR29, 35 where: v is either 0 or 1, preferably 0, and R27, R28 and R29 are identical or different and independently of one another each represents hydrogen, (C1-C4)-alkyl or else cyclopropyl, 5 cyclopentyl or cyclohexyl and/or R27 and R28 or R27 and R29 together with the nitrogen atom to which they are attached may form a saturated or partially unsaturated 5- to 7- 10 membered heterocycle having up to two identical or different heteroatoms from the group consisting of N, O and S, and R30 and R31 are identical or different and independently of one another each represents, hydrogen, (C1-C4)-alkyl, cyclopropyl, cyclopentyl, 15 cyclohexyl, (C1-C4)-alkyIsulphonyI, (C1-C4)-hydroxyalkyl, (C1-C4)- aminoalkyl, di-(C1-C4)-alkylaminO-(C1-C4)-alkyl, (C1-C3)-alkanoyI or phenylcarbonyl. 20 Likewise, in the compounds of the general formula (I), the radical R2 may represent a group of the following formula: 25 30 R32 represents hydrogen or (C1-C4)-alkyl, preferably hydrogen or methyl, and W represents S, NH or O, preferably S. Moreover, in the compounds of the general formula (I), the radical R2 may be a group of the formula below 26 where (C1-C4)-alkyl and cyclopropyl, cyclopentyl or cyclohexyl for their part may optionally be substituted by a radical from the group consisting of cyano; -OH; -OCH3; -NR28R29;-CO(NH)v(NR27R28) and -C(NR27R28)=NR29, 5 where: v is either 0 or 1, preferably 0, and 10 R27, R28 and R29 are identical or different and independently of one another each represents hydrogen, (C1-C4)-alkyl or else cyclopropyl, cyclopentyl or cyclohexyl and/or 15 R27 and R28 or R27 and R29 together with the nitrogen atom to which they are attached may form a saturated or partially unsaturated 5- to 7-membered heterocycle having up to two identical or different heteroatoms from the group consisting of N, O and S, and 20 R30 and R31 are identical or different and independently of one another each represents hydrogen, (C1-C4)-alkyl, cyclopropyl, cyclopentyl, cyclohexyl, (C1-C4)-alkylsulphonyl, (C1-C4)-hydroxyalkyl, (C1-C4)-aminoalkyl, di-(C1-C4)-aIkylarnino- 25 (C1-C4)-alkyl, (C1-C3)-alkanoyl or phenylcarbonyl, R3, R4, R5, R6, R7 and R8 are identical or different and each represents hydrogen or represents (C1-C4)-alkyl 30 and their pharmaceutically acceptable salts, hydrates and prodrugs, except for compounds of the general formula (I) in which the radical R1 is an unsubstituted 2-thiophene radical and the radical R2 is simultaneously a mono- or polysubstituted phenyl radical and the radicals R3, R4, R5, R6, R7 and R8 are each 35 simultaneously hydrogen. --14- Very particular preference is given here to compounds of the general formula (I), in which 5 R1 represents 2-thiophene which is substituted in the 5-position by a radical from the group consisting of chlorine, bromine, methyl and trifluoromethyl, R2 represents D-A-: 10 where: the radical "A" represents phenylene; the radical "D" represents a saturated 5- or 6-membered heterocycle, which is attached to "A" via a nitrogen atom, which has a carbonyl group directly adjacent to the linking nitrogen 15 atom and in which one carbon ring member may be replaced by a heteroatom from the group consisting of S, N and O; where 20 the group "A" defined above may optionally be mono- or disubstituted in the meta position with respect to the point of attachment to the oxazolidinone, by a radical from the group consisting of fluorine, chlorine, nitro, amino, trifluoromethyl, methyl and cyano, 25 R3, R4, R5, R6, R7 and R8 each represent hydrogen and their pharmaceutically acceptable salts, hydrates and prodrugs. Very particular preference is also given here to the compound having the following 30 formula / NW and to its pharmaceutically acceptable salts, hydrates and prodrugs. In the compounds of the general formula (I) above, the radical 5 R1 may in particular represent optionally benzo-fused thiophene (thienyl) which may optionally be mono- or polysubstituted by a radical from the group consisting of halogen; cyano; nitro; (C1-C8)-alkyl, which for its part may optionally be mono- or polysubstituted by halogen; (C3-C7)-cycIoalkyl; 10 (C1-C8)-alkoxy; imidazolinyl; -C(=NH)NH2; carbamoyl; and mono- and di- (C1-C4)-alkylaminocarbonyI. In the compounds of the general formula (I), the radical 15 R1 may preferably represent thiophene (thienyl), in particular 2-thiophene, which may optionally be mono- or polysubstituted by halogen, preferably chlorine or bromine, or by (C1-C8)-alkyl, preferably methyl, where the (C1-C8)-alkyl radical, preferably the methyl radical, may for its part optionally be mono- or polysubstituted by halogen, preferably fluorine. 20 In the compounds of the general formula (I), the radicals R3, R4, R5, R6, R7 and R8 may be identical or different and may represent, in particualr, hydrogen or (C1-C6)-alkyl, preferably hydrogen or (C1-C4)-alkyl, 25 very particularly preferably hydrogen. The radical R2, i.e. the organic radical, can in particular be selected from the substituent groups listed below: 30 In the compounds of the general formula (I), the radical 6 5 Finally, in the compounds of the general formula (I), the radical R2 may be a group of the formula below 10 To date, oxazolidinones have essentially only been described as antibiotics, and in individual cases also as MAO inhibitors and fibrinogen antagonists (review: Riedl, B., Endermann, R., Exp. Opin. Ther. Patents 1999,9 (5), 625), where a small 5-[acyl- 15 aminomethyl] group (preferably 5-[acetylarninoinethyl]) appears to be essential for the antibacterial activity. Substituted aryl- and heteroarylphenyloxazolidinones in which a mono- or polysubstituted phenyl radical may be attached to the N atom of the oxazolidinone 20 ring and which may have an unsubstituted N-methyl-2-thiophenecarboxamide radical in the 5-position of the oxazolidinone ring, and their use as antibacterial substances, are known from U.S. Patents US-A-5 929 248, US-A-5 801 246, US-A-5 756 732, US-A-5 654 435, US-A-5 654 428 and US-A-5 565 571. 25 In addition, benzamidine-containing oxazolidinones are known as synthetic intermediates in the synthesis of factor Xa inhibitors and/or fibrinogen antagonists (WO-A-99/31092, EP-A-623615). Depending on the substitution pattern, the compounds of the general formula (I) 30 according to the invention may exist in stereoisomeric forms which are either like image and mirror image (enantiomers) or not like image and mirror image 27 (diastereomers). The invention relates both to the enantiomers or diastereomers and to their respective mixtures. The racemic forms, like the diastereomers, can be separated in a known manner into the stereoisomerically uniform components. 5 Furthermore, certain compounds of the general formula (I) can be present in tautomeric forms. This is known to the person skilled in the art, and such compounds are likewise within the scope of the invention. Physiologically acceptable, i.e. pharmaceutically compatible, salts can be salts of the 10 compounds according to the invention with inorganic or organic acids. Preference is given to salts with inorganic acids, such as, for example, hydrochloric acid, hydrobromic acid, phosphoric acid or sulphuric acid, or to salts with organic carboxylic or sulphonic .acids, such as, for example, acetic acid, trifluoroacetic acid, propionic acid, maleic acid, fumaric acid, malic acid, citric acid, tartaric acid, lactic 15 acid, benzoic acid, or methanesulphonic acid, ethanesulphonic acid, benzenesulphonic acid, toluenesulphonic acid or naphthalenedisulphonic acid. Other pharmaceutically compatible salts which may be mentioned are salts with customary bases, such as, for example, alkali metal salts (for example sodium or 20 potassium salts), alkaline earth metal salts (for example calcium or magnesium salts) or ammonium salts, derived from ammonia or organic amines, such as, for example, diethylamine, triethylamine, ethyldiisopropylamine, procaine, dibenzylarnine, N-methylmorpholine, dihydroabietylamine or methylpiperidine. 25 According to the invention, "hydrates" are forms of the compounds of the general formula (I) above which form a molecule compound (solvate) in the solid or liquid state by hydration with water. In the hydrates, the water molecules are attached through secondary valencies by intermolecular forces, in particular hydrogen bridges. Solid hydrates contain water as so-called crystal water in stoichiometric ratios, where the 30 water molecules do not have to be equivalent with respect to their binding state. Examples of hydrates are sesquihydrates, monohydrates, dihydrates or trihydrates. Equally suitable are the hydrates of salts of the compounds according to the invention. According to the invention, "prodrugs" are forms of the compounds of the general 35 formula (I) above which for their part can be biologically active or inactive, but which can be converted into the corresponding biologically active form (for example metabolically, solvolytically or in another way). Halogen represents fluorine, chlorine, bromine and iodine. Preference is given to 5 chlorine or fluorine. (C1-C8)-Alkvl represents a straight-chain or branched alkyl radical having 1 to S carbon atoms. Examples which may be mentioned are: methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl and n-hexyl. The corresponding alkyl groups with 10 fewer carbon atoms, such as, for example, (C1-C6)-aIkyI and (C1-C4)-alkyl, are derived analogously from this definition. In genera], preference is given to (C1-C4)-alkyl The meaning of the corresponding component of other more complex substituents, such as, for example, alkvlsulphonyl. hvdroxvalkvl. hvdroxyalkvlcarbonvl, alkoxy- 15 alkyl, alkoxvcarbonvl-alkvl alkanoylalkyl, aminoalkvl or alkylaminoalkyl is likewise derived from this definition. (C3-C7)-CvcloaIkvl represents a cyclic alkyl radical having 3 to 7 carbon atoms. Examples which may be mentioned are: cyclopropyl, cyclobutyl, cyclopentyl, 20 cyclohexyl or cycloheptyl. The corresponding cycloalkyl groups having fewer carbon atoms, such as, for example, (C3-C5)-cycloalkyl, are derived analogously from this definition. Preference is given to cyclopropyl, cyclopentyl and cyclohexyl. The meaning of the corresponding component of other more complex substituents, 25 such as, for example, cvcloalkanoyl, is likewise derived from this definition. In the context of the invention, (C2-C6)-alkenvl represents a straight-chain or branched alkenyl radical having 2 to 6 carbon atoms. Preference is given to a straight-chain or branched alkenyl radical having 2 to 4 carbon atoms. Examples which may be 30 mentioned are; vinyl, allyl, isopropenyl and n-but-2-en-l-yI. (C1-C8)-Alkoxv represents a straight-chain or branched alkoxy radical having 1 to 8 carbon atoms. Examples which may be mentioned are: methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, n-pentoxy, n-hexoxy, n-heptoxy and 35 n-octoxy. The corresponding alkoxy groups having fewer carbon atoms, such as, for example, (C1-C6)-alkoxy and (C1-C4)-Alkoxy, are derived analogously from this definition. In general, preference is given to (C1-C4)-alkoxy. The meaning of the corresponding component of other more complex substituents, 5 such as, for example alkoxy-alkyl. alkoxvcaibonvl-alkvl and alkoxycarbonyl. is likewise derived from this definition. Mono- or di-(C1-C4)-alkylaminocarbonvl represents an amino group which is attached via a carbonyl group and which has a straight-chain or branched or two identical or 10 different straight-chain or branched alkyl substitutents having in each case 1 to 4 carbon atoms. Examples which may be mentioned are: methylamino, ethylamino, n-propylamino, isopropylamino, t-butylamino, N,N-dimethylamino, N,.N-diethylamino, N-ethyl-N-methylamino, N-methyl-N-n-propylamino, N-isopropyl-N-n-propylamino and N-t-butyl-N-methylamino. 15 (C1-C6)-Alkanovl represents a straight-chain or branched alkyl radical having 1 to 6 carbon atoms which carries a doubly attached oxygen atom in the 1-position and is attached via the 1-position. Examples which may be mentioned are: formyl, acetyl, propionyl, n-butyryl, i-butyryl, pivaloyl, n-hexanoyl. The corresponding alkanoyl 20 groups with fewer carbon atoms, such as, for example, (C1-C5)-alkanoyl, (C1-C4)-alkanoyl and (C1-C3)-alkanoylr are derived analogously from this definition. In general, preference is given to (C1-C3)-alkanoyl. The meaning of the corresponding component of other more complex substituents, 25 such as, for example, cvcloalkanoyl and alkanovlalkvl. is likewise derived from this definition. (C3-C7)-Cycloalkanovl represents a cycloalkyl radical having 3 to 7 carbon atoms .as, defined above which is attached via a carbonyl group. 30 (C1-C6)-AlkanovloxymethvIoxv represents a straight-chain or branched alkanoyloxymethyioxy radical having 1 to 6 carbon atoms. Examples which may be mentioned are: acetoxymethyloxy, propionoxymethyloxy, n-butyroxymethyloxy, i-butyroxymethyloxy, pivaloyloxymethyloxy, n-hexanoyloxymethyloxy. The 35 corresponding alkanoyloxymethyioxy groups having fewer carbon atoms, such as, for 30 example, (CrC3)-aIkanoyIoxymethyloxy, are derived analogously from this definition, In general, preference is given to (C1-C3)-alkanoyloxymethyloxy. (C6-C14)-Aryl represents an aromatic radical having 6 to 14 carbon atoms. Examples 5 which may be mentioned are: phenyl, naphthyl, phenanthrenyl and anthracenyl. The corresponding aryl groups with fewer carbon atoms, such as, for example, (C6-C1o)-aryl are derived analogously from this definition. In general, preference is given to (C6-C10)-aryl 10 The meaning of the corresponding component of other more complex substituents, such as, for example, arylcarbonyl. is likewise derived from this definition. (C5-C10)-Heteroarvl or a 5- to 10-membered aromatic heterocycle having up to 3 heteroatoms and/or hetero chain members from the group consisting of S. O, N and NO 15 (N-oxide) represents a mono- or bicyclic heteroaromatic which is attached via a carbon ring atom of the heteroaromatic or, if appropriate, via a nitrogen ring atom of the heteroaromatic. Examples which may be mentioned are: pyridyl, pyridyl N-oxide, pyrimidyl, pyridazinyl, pyrazinyl, thienyl, furyl, pyrrolyl, pyrazolyl, imidazolyl, thiazotyl, oxazolyl or isoxazolyl, indolizinyl, indolyl, benzofbjthienyl, benzo[b]fuiyl, 20 indazolyl, quinolyl, isoquinolyl, naphthyridinyl, quinazolinyl. The corresponding heterocycles having a smaller ring size, such as, for example, 5- or 6-membered aromatic heterocycles, are derived analogously from this definition. In general, preference is given to 5- or 6-membered aromatic heterocycles, such as, for example, pyridyl, pyridyl N-oxide, pyrimidyl, pyridazinyl, furyl and thienyl. 25 The meaning of the corresponding component of other more complex substituents, such as, for example, (C5-C10)-heteroarvlcarbonyl is likewise derived from this definition. 30 A 3- to 9-membered saturated or partially unsaturated, mono- or bicyclic, optionally benzo-fused heterocycle having up to 3 heteroatoms and/or hetero chain members from the group consisting of S, SO. SO2, N. NO (N-oxide) and Q represents a heterocycle which may contain one or more double bonds, which may be mono- or bicyclic, to which a benzene ring may be fused to two adjacent carbon ring atoms and 35 which is attached via a carbon ring atom or a mtrogen ring atom. Examples which may be mentioned are: tetrahydrofuryl, pyrrolidinyl, pyrrolinyl, piperidinyl, 1,2- dihydropyridinyl, 1,4-dihydropyridinyl, piperazinyl, morpholinyl, morpholinyl N-oxide, thiomorpholinyl, azepinyl, 1,4-diazepinyl and cyclohexyi. Preference is given to piperidinyl, morpholinyl and pyrrolidinyl. 5 The corresponding cycles having a smaller ring size, such as, for example, 5- to 7- membered cycles, are derived analogously from this definition. The present invention also provides a process for preparing the compounds of the general formula (I) according to the invention where either, according to one process 10 alternative [A] compounds of the general formula (II) O R R8 15 in which the radicals R2, R3, R4, R5, R6 and R7 are each as defined above, 20 are reacted with carboxylic acids of the general formula (HI) HO^.R1 (HI), 25 in which the radical R1 is as defined above, 32- or else with the corresponding carbonyl halides, preferably carbonyl chlorides, or else with the corresponding symmetric or mixed carboxylic anhydrides of the carboxylic acids of the general formula (HI) defined above in inert solvents, if appropriate in the presence of an activating or coupling agent and/or a base, to give compounds of the general formula (I) (D, 10 in which the radicals R\ R2, R3, R4, R5, R6, R7 and R8 are each as defined above, 15 or else according to a process alternative [B] compounds of the general formula (IV) R3 R6 R7 Q 20 in which the radicals R1, R3, R4, R5, R6, R7 and R8 are each as defined above, 25 are converted, using a suitable selective oxidizing agent in an inert solvent, into the corresponding epoxide of the general formula (V) 33 R3 R6 B7 ft in which the radicals R1, R3, R4, R5, R6, R7 and R8 are each as defined above, and, by reaction in an inert solvent, if appropriate in the presence of a catalyst, with an amine of the general formula (VI) 10 R2-NH2 (VI), in which 15 the radical R2 is as defined above, the compounds of the general formula (VII) R4 R3 R6 R7 ft 20 in which 25 the radicals R1, R2, R3, R4, R5, R6, R7 and R8 are each as defined above, are initially prepared and subsequently, in an inert solvent in the presence of phosgene or phosgene equivalents, such as, for example, carbonyldiimidazole (CDI), cyclized to 30 give the compounds of the general formula (I) ~?A~- in which 5 the radicals R1, R2, R3, R4, R5, R6, R7 and R8 are each as defined above, where - both for process alternative [A] and for process alternative [B] - in the case where R2 contains a 3- to 7-membered saturated or partially 10 unsaturated cyclic hydrocarbon radical having one or more identical or different heteroatoms from the group consisting of N and S, an oxidation with a selective oxidizing agent to afford the corresponding sulphone, sulphoxide or N-oxide may follow 15 and/or where - both for process alternative [A] and for process alternative [B] - in the case where the compound prepared in this manner has a cyano group in the molecule, an amidination of this cyano group by customary methods may 20 follow and/or where - both for process alternative [A] and for process alternative [B] - in the 25 case where the compound prepared in this manner has a BOC amino protective group in the molecule, removal of this BOC amino protective group by customary methods may follow and/or 30 where - both for process alternative [A] and for process alternative [B] - in the case where the compound prepared in this manner has an aniline or benzylamine radical in the molecule, a reaction of this amino group with various reagents such as carboxylic acids, carboxylic anhydrides, carbonyl chlorides, isocyanates, sulphonyl chlorides or alkyl halides to give the corresponding derivatives may follow and/or 10 where - both for process alternative [A] and for process alternative [B] - in the case where the compound prepared in this manner has a phenyl ring in the molecule, a reaction with chlorosulphonic iicid and subsequent reaction with amines to give the corresponding sulphonamides may follow. 15 The processes according to the invention can be illustrated in an exemplary manner by the equations below: The oxidation step described above, which is optional, can be illustrated in an 5 exemplary manner by the equation below: Suitable solvents for the processes described above are organic solvents which are 10 inert under the reaction conditions. These include halogenated hydrocarbons, such as dichloromethane, trichloromethane, carbon tetrachloride, 1,2-dichloroethane, trichloroethane, tetrachloroethane, 1,2-dichIoroethyIene or trichloroethylene, ethers, such as diethyl ether, dioxane, tetrahydrofuran, glycol dimethyl ether or diethylene glycol dimethyl ether, alcohols, such as methanol, ethanol, n-propanol, isopropanol, 15 n-butanol or tert-butanol, hydrocarbons, such as benzene, xylene, toluene, hexane or cyclohexane, dimethylformamide, dimethyl sulphoxide, acetonitrile, pyridine, hexa-methylphosphoric triamide or water. It is also possible to use solvent mixtures of the solvents mentioned above. 20 37 Suitable activating or coupling agents for the processes described above are the reagents which are customarily used for this purpose, for example N"-(3-dimemyIaminopropyI)-N-ethylcarbodiimide . HO, N,N"-dicyclohexylcarbo-diimide, 1-hydroxy-lH-benzotriazole • H20 and the like. 5 Suitable bases are the customary inorganic or organic bases. These preferably include alkali metal hydroxides, such as, for example, sodium hydroxide or potassium hydroxide, or alkali metal carbonates, such as sodium carbonate or potassium carbonate, or sodium methoxide or potassium methoxide or sodium ethoxide or 10 potassium ethoxide or potassium-tert-butoxide, or amides, such as sodium amide, lithium bis-(trimethylsilyl)amide or lithium diisopropylamide, or amines, such as triethylamine, diisopropylethylamine, diisopropylamine, 4-N,N-dimethylamino-pyridine or pyridine. 15 The base can be employed here in an amount of from 1 to 5 mol, preferably from 1 to 2 mol, based on 1 mol of the compounds of the general formula (II). The reactions are generally carried out in a temperature range of from -78°C to reflux temperature, preferably in the range from 0°C to reflux temperature. 20 The reactions can be carried out at atmospheric, elevated or reduced pressure (for example in the range from 0.5 to 5 bar). In general, the reactions are carried out at atmospheric pressure, 25 Suitable selective oxidizing agents, both for the preparation of the epoxides and for the optional oxidation to give the sulphone, sulphoxide or N-oxide, are m-chloroperbenzoic acid (MCPBA), sodium metaperiodate, N-methylmorpholine N-oxide (NMO), monoperoxyphthalic acid or osmium tetroxide. 30 With respect to the preparation of the epoxides, the preparation conditions which are customary for this purpose are employed. With respect to more detailed process conditions for the optional oxidation to give the sulphone, sulphoxide or N-oxide, reference is made to the following literature: 35 M. R. Barbachyn et al., J. Med. Chem. 1996,39, 680 and WO-A-97/10223. Furthermore, reference is made to Examples 14 to 16 given in the experimental part. The optional amidation is carried out under customary conditions. For more details, reference is made to Examples 31 to 35 and 140 to 147. 5 The compounds of the general formulae (II), (III), (IV) and (VI) are known per se to the person skilled in the art or can be prepared by customary methods. For oxazolidinones, in particular the 5-(aminomethyl)-2-oxooxazolidines required, cf. WO-A-98/01446; WO-A-93/23384; WO-A-97/03072; J.A.Tucker etal., J.Med, 10 Chem. 1998, 41, 3727; S.J.Brickner etal., J.Med Chem. 1996, 39, 673; W. A. Gregory et al., J. Med. Chem. 1989,32,1673. The compounds of the general formula (I) according to the invention have an unforeseeabte useful pharmacological activity spectrum and are therefore parrkttlarYy 15 suitable for the prophylaxis and/or treatment of disorders. The compounds of the general formula (I) according to the ivnention - including the compounds which are excluded by disclaimer from the chemical product protection - act in particular as anticoagulants and can therefore preferably be 20 employed in medicaments for the prophylaxis and/or therapy of thromboembolic disorders. For the purpose of the present invention, "thromboembolic disorders" include, in particular, serious disorders such as myocardial infarct, angina pectoris (including unstable angina), reocclusions and restenoses after angioplasty or aortocoronary bypass, stroke, transitory ischaemic attacks, peripheral arterial 25 occlusion disorders, pulmonary embolisms or deep venous thromboses. Furthermore, the compounds of the general formula (I) according to the invention - including the compounds which are excluded by disclaimer from the chemical product protection - are also suitable for treating disseminated intravascular 30 coagulation (DIC). Finally, the compounds of the general formula (I) according to the invention - including the compounds which are excluded by disclaimer from the chemical product protection - are also suitable for the prophylaxis and/or treatment of 35 atherosclerosis and arthritis, and additionally also for the prophylaxis and/or treatment of Alzheimer"s disease and cancer. 39 4frA-34^l2i-froreign Lountrfes The compounds of the general formula (I) according to the invention - including the compounds excluded by disclaimer from the chemical product protection - act in particular as selective inhibitors of the blood coagulation factor Xa and do not 5 inhibit, or only inhibit at considerably higher concentrations, other serine proteases as well, such as thrombin, plasmin or trypsin. In the context of the present invention, inhibitors of the blood coagulation factor Xa in which the IC50 values for the factor Xa inhibition are lower by a factor of 100, 10 preferably by a factor of 500, in particular by a factor of 1000, than the IC50 values for the inhibition of other serine proteases, in particular thrombin, plasmin and trypsin, are referred to as being selective", where with a view to the test methods for selectivity, reference is made to the test methods of Examples A-l) a.l) and a.2) described below. 15 The compounds of the general formula (I) according to the invention - including the compounds which are excluded by disclaimer from the chemical product protection -can furthermore be used for preventing coagulation ex vivo, for example for banked blood or biological samples which contain factor Xa, 20 The present invention thus provides oxazolidinones of the formula (I) effecting in particular an unexpected, strong and selective inhibition of factor Xa, and this also applies to the compounds excluded by disclaimer from the chemical product protection, 25 The present invention further provides medicaments and pharmaceutical compositions comprising at least one compound of the general formula (I) according to the invention together with one or more pharmacologically acceptable auxiliaries or excipients, which medicaments and pharmaceutical compositions can be used for 30 the indications mentioned above. Furthermore, the present invention relates to a method for the prophylaxis and/or treatment of disorders of the human or animal body, in particular of the abovementioned disorders, using the compounds of the general formula (I) according 35 to the invention - including the compounds excluded by disclaimer from the chemical product protection. Furthermore, the present invention also includes a method for preventing blood coagulation in vitro, in particular in banked blood or biological samples which contain factor Xa, which method is characterized in that compounds of the general 5 formula (I) - including the compounds excluded by disclaimer from the chemical product protection - are added. All customary administration forms are suitable for administration of the compounds according to the invention. Administration is preferably carried out orally, lingually, 10 sublingually, buccally, rectally or parenterally (i.e. bypassing the intestinal tract, that is intravenously, intraarterially, intracardially, intracutaneously, subcutaneously, transdermally, intraperitoneally or intramuscularly). Particularly suitable are oral and intravenous administration. Very particular preference is given to oral administration, this being a further advantage with respect to the prior-art therapy of thromboembolic 15 disorders. The novel active compounds of the general formula (I) can be converted in a known manner into the customary formulations, such as tablets, sugar-coated tablets, pills, granules, aerosols, syrups, emulsions, suspensions and solutions, using inert non- 20 toxic pharmaceutically suitable excipients or solvents. Here, the therapeutically active compound should in each case be present in a concentration of from about 0.1 to 95% by weight, preferably from 0.5 to 90% by weight, in particular from 1 to 85% by weight, of the total mixture, i.e. in amounts which are sufficient in order to achieve the dosage range indicated. 25 In spite of this, if appropriate, it may be necessary to depart from the amounts mentioned, namely depending on the body weight or on the type of administration route, on the individual response to the medicament, on the manner of its formulation and the time or interval at which administration takes place. Thus, in some cases it 30 may be adequate to manage with less than the abovementioned minimum amount, while in other cases the upper limit mentioned must be exceeded. In the case of the administration of relatively large amounts, it may be advisable to divide these into several individual administrations over the course of the day. 35 The formulations are prepared, for example, by extending the active compounds with solvents and/or excipients, if appropriate using emulsifiers and/or dispersants, it being possible, for example if the diluent used is water, optionally to use organic solvents as auxiliary solvents. In general it has proved advantageous in the case of intravenous administration to 5 administer amounts from approximately 0,001 to 10 mg/kg, preferably approximately 0.01 to 10 mg/kg, in particular approximately 0.1 to 8mg/kg, of body weight to achieve effective results. In general, it has proved advantageous in the case of oral administration to administer 10 amounts from approximately 0.01 to 50 mg/kg, preferably approximately 0-1 to 10 mg/kg, in particular approximately 0.5 to 8 mg/kg, of body weight to achieve effective results. In spite of this, if appropriate, it may be necessary in the case of intravenous or oral 15 administration to depart from the amounts mentioned, namely depending on the body weight or on the type of administration route, on the individual response to the medicament, on the manner of its formulation and the time or interval at which administration takes place. Thus, in some cases it may be adequate to manage with less than the abovementioned mininum amount, while in other cases the upper limit 20 mentioned must be exceeded. In the case of the administration of relatively large amounts, it may be advisable to divide these over the course of the day, namely into several individual doses or as a continuous infusion. Compared to the conventional preparations for treating thromboembolic disorders, 25 the compounds of the general formula (I) according to the invention - including the compounds excluded by disclaimer from the chemical product protection - are distinguished in particular by the fact that a greater therapeutic range is achieved by the selective inhibition of factor Xa, For the patient, this means a lower risk- of bleeding, and for the treating physician, this means that the patient is easier to adjust. 30 Moreover - owing to the mechanism - the onset of action is more rapid. Above all, however, the compounds according to the invention permit an oral administration form, which is a further advantage of the therapy with the compounds according to the invention. 35 The present invention is illustrated by the examples below; however, these examples are not meant to restrict the invention in any way. -"42- " Examples A Evaluation of the physiological activity 5 1. General test methods The particularly advantageous biological properties of the compounds according to the invention can be determined by the following methods. 10 a) Test description (in vitro) a.l) Determination of the factor Xa inhibition The enzymatic activity of human factor Xa (FXa) was measured using the conversion 15 of a chromogenic substrate specific for FXa. Factor Xa cleaves p-nitroaniline from the chromogenic substrate. The determinations were carried out in microtitre plates as follows. The test substances, in various concentrations, were dissolved in DMSO and 20 incubated at 25°C with human FXa (0.5 nmol/l dissolved in 50 mmol/1 of tris buffer [C,C,C-tris(hydroxymethyl)-aminomethane], 150 mmol/1 of NaCI, 0.1% BSA (bovine serum albumin), pH = 8.3) for 10 minutes. Pure DMSO was used as control. The chromogenic substrate (150 /imol/1 of Pefachrome® FXa from Pentapharm) was then added. After an incubation time of 20 minutes at 25°C, the extinction at 405 nm 25 was determined. The extinctions of the test mixtures containing test substance were compared with the control mixtures without test substance, and the IC5o values were calculated from these data. - ^ a.2) Determination of the selectivity 30 To assess selective FXa inhibition, the test substances were examined for their inhibition of other human serine proteases such as thrombin, trypsin and plasmin. To determine the enzymatic activity of thrombin (75 mU/ml), trypsin (500 mU/ml) and plasmin (3.2 nmol/l), these enzymes were dissolved in tris buffer (100 mmol/1, 35 20 mmol/1 CaCl2, pH = 8.0) and incubated with test substance or solvent for 10 minutes. The enzymatic reaction was then started by adding the corresponding removed and the nylon thread with the thrombus was weighed immediately. The weight of the nylon thread on its own had been detennined before the experiment was started. Before the extracorporeal circulation was set up, the test substances were administered to the animals while awake either intravenously via the tail vein or orally using a pharyngeal tube. specific chromogenic substrates (Chromozym Thrombin® from Boehringer Mannheim, Chromozym Trypsin® from Boehringer Mannheim, Chromozym Plasmin® from Boehringer Mannheim) and the extinction at 405 nm was determined after 20 minutes. All determinations were carried out at 37°C. The extinctions of the 5 test mixtures containing test substance were compared with the control samples without test substance, and the IC50 values were calculated from these data. a3) Determination of the anticoagulant action 10 The anticoagulant action of the test substances was determined in vitro in human plasma. To this end, human blood was drawn off in a mixing ratio of sodium citrate/blood of 1/9 using a 0.11 molar sodium citrate solution as receiver. Immediately after the blood had been drawn off, it was mixed thoroughly and centrifuged at about 2000 g for 10 minutes. The supernatant was pipetted off. The 15 prothrombin time (PT, synonyms; thromboplastin time, quick test) was determined in the presence of varying concentrations of test substance or the corresponding solvent using a commercial test kit (Neoplastin® from Boehringer Mannheim). The test compounds were incubated with the plasma at 37°C for 10 minutes. Coagulation was then started by addition of thromboplastin, and the time when coagulation occurred 20 was determined. The concentration of test substance which effected a doubling of the prothrombin time was determined. b) Determination of the antithrombotic activity (in vivo) 25 b.l) Arteriovenous shunt model (rat) Fasting male rats (strain: HSD CPB:WU) having a weight of 200-250 g were anaesthetized using a Rompun/Ketavet solution (12 mg/kg/ 50 mg/kg). Thrombus formation was initiated in an arteriovenous shunt in accordance with the method 30 described by Christopher N. Berry et al., Br. J. Pharmacol. (1994), 113, 1209-1214. To this end, the left jugular vein and the right carotid artery were exposed. The two vessels were connected by an extracorporeal shunt using a polyethylene tube (PE 60) of a length of 10 cm. In the middle, this polyethylene tube was attached to a further polyethylene tube (PE 160) of a length of 3 cm which contained a roughened nylon 35 thread which had been arranged to form a loop, to form a thrombogenic surface. The extracorporeal circulation was maintained for 15 minutes. The shunt was then LfrA-3+i23=Fb15i"gn countries 45- The results are shown in Table 1: Table 1: Antithrombotic activity in the arteriovenous shunt model (rat) after oral or intravenous administration Example ED56 [mg/kfi] p.o. ED50 [mg/kg] i.v. 1 10 17 6 44 3 95 3 114 3 115 3 123 3 162 3 b.2) Arterial thrombosis model (rat) Male fasting rats (strain: HSD CPB: WU) were anaesthetized as described above. On 10 average, the rats had a weight of about 200 g. The left carotid artery was exposed (about 2 cm). The formation of an arterial thrombus was induced by mechanical injury to the blood vessel in accordance with the method described by K. Meng et al., Naunyn-Schmiedeberg"s Arch. Pharmacol. (1977), 301, 115-119. To this end, the exposed carotid artery was clamped from the blood flow, cooled to -12°C in a metal 15 trough for 2 minutes and, to standardize the size of the thrombi, simultaneously compressed using a weight of 200 g. The blood flow was then additionally reduced by a clip which was placed around the carotid artery distally from the injured section of the vessel. The proximal clamp was removed, and the wound was closed and re¬opened after 4 hours to remove the injured section of the vessel. The section ofthe 20 vessel was opened longitudinally and the thrombus was removed from the injured section of the vessel. The moist weight of the thrombi was determined immediately. The test substances were administered to the animals while awake at the beginning of the experiment, either intravenously via the tail vein or orally using a pharyngeal tube. 25 b.3) Venous thrombosis model (rat) Male fasting rats (strain: HSD CPB: WU) were anaesthetized as described above. On average, the rats had. a weight of about 200 g. The left jugular vein was exposed 5 (about 2 cm). The formation of a venous thrombus was induced by mechanical injury to the blood vessel in accordance with the method described by K. Meng et al., Naunyn-Schmiedeberg"s Arch. Pharmacol. (1977), 301, 115-119. To this end, the jugular vein was clamped from the blood flow, cooled to -12°C in a metal trough for 2 minutes and, to standardize the size of the thrombi, simultaneously compressed 10 using a weight of 200 g. The blood flow was re-opened and the wound was closed. After 4 hours, the wound was re-opened to remove the thrombi from the injured sections of the vessel. The moist weight of the thrombi was determined immediately. The test substances were administered to the animals while awake at the beginning of the experiment, either intravenously via the tail vein or orally using a pharyngeal 15 tube. B Preparation Examples Starting materials 5 The preparation of 3-morphoIinone is described in US 5 349 045. The preparation of N-(2,3-epoxypropyI)phthalimide is described in J.-W. Chcm et al. Tetrahedron Lett. 1998,39,8483. 10 The substituted anilines can be obtained by reacting, for example, 4-fluoronitro- benzene, 2,4-difluoronitrobenzene or 4-chloronitrobenzene with the appropriate amines or amides in the presence of a base. This can also be carried out using Pd catalysts, such as Pd(OAc)2/DPPF/NaOt-Bu (Tetrahedron Lett 1999,40,2035) or copper (Kenger, Synthesis 1985.856; Aebischer et a]., Heterocycles 1998,48,2225). 15 Likewise, it is possible to initially convert halogenated aromatics without nitro group into the corresponding amides, followed by nitration in the 4-position (US3279880). I. 4-(4-Morpholin-3-onyl)nitrobenzene NO, rV° 20 O 2 mol (202 g) of morpholin-3-one (E. Pfeil, U. Harder, Angew. Chem. 79,1967, 188) are dissolved in 21 of N-methylpyrrolidone (NMP). Over a period of 2 h, 88 g (2.2 mol) of sodium hydride (60% in paraffin) are then added a little at a time. After-the evolution of hydrogen has ceased, 282 g (2 mol) of 4-fluoronitrobenzene are 25 added dropwise with cooling at room temperature, over a period of 1 h, and the reaction mixture is then stirred overnight. At 12 mbar and 76°C, 1,71 of the liquid volume are then distilled off, the residue is poured into 2 1 of water and this mixture is extracted twice with in each case 11 of ethyl acetate. After washing of the combined organic phases with water, the mixture is dried over sodium sulphate and 30 the solvent is distilled off under reduced pressure. Purification is carried out by silica gel chromatography using hexane/ethyl acetate (1:1) and subsequent crystallization 10 15 from ethyl acetate. This gives 78 g of product as a colourless to brownish solid, in a yield of 17.6% of theory. "H-NMR (300 MHz, CDC13): 3,86 (m, 2 H, CH2CH2), 4.08 (m, 2 H, CH2C#2), 4.49 (s, 2H, CH2CO), 7.61 (d, 2H, 3/=8.95 Hz, CHCH), 8.28 (d, 2H, 37=8.95Hz, CHCtf) MS (r.L%) = 222 (74, M+), 193 (100), 164 (28), 150 (21), 136 (61), 117 (22), 106 (24), 90 (37), 76 (38), 63 (32), 50 (25) The following compounds were synthesized analogously: 3-fluoro-4-(4-morpholin-3-onyl)nitrobenzene 4-(N-piperidonyl)nitrobenzene 3-fluoro-4-(N-piperidonyl)nitrobenzene 4-(N-pyrrolidonyl)nitrobenzene 3-fluoro-4-(N-pyrrolidonyl)nitrobenzene II. 4-(4-Morpholin-3-onyI)aniline In an autoclave, 63 g (0.275 mol) of 4-(4-morpholin-3-onyl)nitrobenzene are 20 dissolved in 200 ml of tetrahydrofuran, admixed with 3.1 g of Pd/C (5%ig) and hydrogenated at 70°C and a hydrogen pressure of 50 bar for 8 h. The catalyst is filtered off, the solvent is then distilled off under reduced pressure and the product is purified by crystallization from ethyl acetate. 20 g of product are obtained as a, colourless to bluish solid, in a yield of 37.6% of theory. 25 Purification can also be carried out by silica gel chromatography using hexane/ethyl acetate. ]H-NMR (300 MHz, CDC13): 3.67 (m, 2 H, CH2CH2), 3.99 (m, 2 H, CH2CH2), 4.27 (s, 2H, CH2CO), 6.68 (d, 2H, 3/=8.71 Hz, CHCH), 7.03 (d, 2 H, 3/=8.71 Hz, 30 CHCH) 10 MS (r.L%) = 192 (100, M+), 163 (48), 133 (26), 119 (76), 106 (49), 92 (38), 67 (27), 65 (45), 52 (22), 28 (22) The following compounds were synthesized analogously: 3-fluoro-4-(4-morpholin-3-onyl)aniIine 4-(N-piperidonyI)aniline 3-fluoro-4-(N-piperidonyl)aniline 4-(N-pyrrolidonyl)aniline 3-fluoro-4-(N-pyrrolidonyl)aniline General method for preparing 4-substituted anilines by reacting l-fluoro-4-nitrobenzenes and l-chloro-4-nitrobenzenes with primary or secondary amines, followed by reduction 15 X = F.CI Equimolar amounts of the fluoronitrobenzene or chloronitrobenzene and the amine are dissolved in dimethyl sulphoxide or acetonitrile (0.1 M to 1 M solution), and the mixture is stirred at 100°C overnight. After cooling to RT, the reaction mixture is 20 diluted with ether and washed with water. The organic phase is dried over MgSO4, filtered and concentrated. If a precipitate forms in the reaction mixture, the precipitate is filtered off and washed with ether or acetonitrile. If the mother liquor also contains product, it is worked up as described using ether and water. The crude products can be purified by silica gel chromatography (dichloromethane/cyclohexane- 25 and dichloromethane/ethanol mixtures). For the subsequent reduction, the nitro compound is dissolved in methanol, ethanol or ethanol/dichloromethane mixtures (0.01 M to 0.5 M solution) admixed with palladium on carbon (10%) and stirred under an atmospheric hydrogen pressure 30 overnight. The mixture is then filtered and concentrated. The crude product can be purified by silica gel chromatography (dichloromethane/ethanol mixtures) or preparative reversed-phase HPLC (acetonitrile/water mixtures). Alternatively, the reducing agent used can also be iron powder. To this end, the nitro compound is dissolved in acetic acid (0.1 M to 0.5 M solution) and, at 90°C, six equivalents of iron powder and water (0.3 to 0.5 times the volume of the acetic acid) 5 are added a little at a time over a period of 10-15 rnin. After a further 30 min at 90°C, the mixture is filtered and the filtrate is concentrated. The residue is worked up by extraction with ethyl acetate and 2N aqueous sodium hydroxide solution. The organic phase is dried over magnesium sulphate, filtered and concentrated. The crude product can be purified by silica gel chromatography (dichloromethane/ethanol mixtures) or 10 preparative reversed-phase HPLC (acetonitrile/water mixtures). The following starting materials were prepared in an analogous manner: III-l. tert-butv1-1-(4-aminophesyl)-L-proIinate 15 MS (ESI): m/z (%) = 304 (M+H+MeCN, 100), 263 (M+H, 20); HPLC (method 4): rt = 2.79 min. III-2. l-(4-aminoDhenvl)"3-piperidinecarboxamide MS (ESI): m/z (%) = 220 (M+H, 100); 20 HPLC (method 4): rt = 0.59 min. 1H-3. l-(4-aminophenvl)-4-piperidincarboxamide MS (ESI): m/z (%) = 220 (M+H, 100); HPLC (method 4)-. rt = 0.57 min. 25 III-4. l-(4-aminophenvl)-4-piperidinone MS (ESI): m/z (%) = 191 (M+H, 100); HPLC (method 4): n = 0.64 min. 30 III-5. l-(4-aminophenvl)-L-prolinamide MS (ESI): m/z (%) = 206 (M+H, 100); HPLC (method 4); rt = 0.72 min. III-6. [1-(4-anninophenvl)-3-piperidinvl]methanol 35 MS (ESI): m/z (%) s 207 (M+H, 100); HPLC (method 4): rt - 0.60 min. III-7. [1-(4-aminophenvl)-2-Diperidinvl1methanol MS (ESI): m/z (%) = 207 (M+H, 100); HPLC (method 4): rt = 0.59 min. 5 III-8. ethvl l-(4-aminophenvl)-2-piperiduiecarboxylate MS (ESI): m/z (%) = 249 (M+H, 35), 175 (100); HPLC (method 4): rt = 2.43 min. 10 III-9, [1-(4-aminophenvI)-2-pvrroIidinynmethanol MS (ESI): m/z (%) = 193 (M+H, 45); HPLC (method 4): rt = 0.79 min. 111-10. 4-(2-methvlhexahvdro-5H-Pvrrolor3.4:d]isoxazol-5-vl)phenviamine 15 starting from 2-methylhexahydro-2H-pyrrolo[3,4-d]isoxazoIe (Ziegler, Carl B., et al.; J. Heterocycl Chem.; 25; 2; 1988; 719-723) MS (ESI): m/z (%) = 220 (M+H, 50), 171 (100); HPLC (method 4): rt = 0.54 min. 20 III-11. 4-(l-pvrrolidinvI)-3-(trifluoromethvl)aniline MS (ESI): m/z (%) = 231 (M-fH, 100); HPLC (method 7): rt = 3.40 min. III-12. 3-chloro-4-(l-pvrrolidinyl)aniIine 25 MS (ESI): m/z (%) = 197 (M+H, 100); HPLC (method 4); rt = 0.78 min. 111,-13. 5-amino-2-(4-morpholinvl)benzamide MS (ESI): m/z (%) = 222 (M+H, 100); 30 HPLC (method 4): rt = 0.77 min. 111-14. 3-methoxv-4-(4-morDholinvI)aniline MS (ESI): m/z (%) = 209 (M+H, 100); HPLC (method 4): rt = 0.67 min. 35 111-15. l-f5-aminO-2-(4-morpholinvl)phenvIlethanone MS (ESI): m/z (%) = 221 (M+H, 100); HPLC (method 4): rt = 0.77 min, General method for preparing 4-substituted anilines by reacting l-fluoro-4- 5 nitrobenzenes with amides, followed by reduction The amide is dissolved in DMF and admixed with 1.5 equivalents of potassium tert-butoxide. The mixture is stirred at RT for 1 h, and 1.2 equivalents of the l-fluoro-4- 10 nitrobenzene are then added a little at a time. The reaction mixture is stirred at RT overnight, diluted with ether or ethyl acetate and washed with sat. aqu. sodium bicarbonate solution. The organic phase is dried over magnesium sulphate, filtered and concentrated. The crude product can be purified by silica gel chromatography (dichloromethane/ethanol mixtures). 15 For the subsequent reduction, the nitro compound is dissolved in ethanol (0.01 M to 0.5 M solution), admixed with palladium on carbon (10%) and stirred under atmospheric hydrogen pressure overnight. The mixture is then filtered and concentrated. The crude product can be purified by silica gel chromatography 20 (dichloromethane/ethanol mixtures) or preparative reversed-phase HPLC (acetonitrile/water mixtures). Alternatively, the reducing agent used can also be iron powder. To this end, the nitro compound is dissolved in acetic acid (0.1 M to 0.5 M solution) and, at 90°C; six 25 equivalents of iron powder and water (0.3 to 0.5 times the volume of the acetic acid) are added a little at a time over a period of 10-15 min. After a further 30 min at 90°C, the mixture is filtered and the filtrate is concentrated. The residue is worked up by extraction with ethyl acetate and 2N aqueous sodium hydroxide solution. The organic phase is dried over magnesium sulphate, filtered and concentrated. The crude product 30 can be purified by silica gel chromatography (dichloromethane/ethanol mixtures) or preparative reversed-phase HPLC (acetonitrile/water mixtures). The following starting materials were prepared in an analogous manner: IV-1, l-[4-amino-2-(trifluoromethyl)phenyl]-2-PvrroIidinone MS (ESI): m/z (%) = 245 (M+H, 100); 5 HPLC (method 4): rt = 2.98 min IV-2. 4-[4-amino-2-(trifluoromethyl)phenvl]-3-morpholinone MS (ESI): m/z (%) = 261 (M+H, 100); HPLC (method 4): it = 2.54 min. 10 IV-3. 4-(4-amino-2-chlorophenyl)"3-morpholinone MS (ESI): m/z (%) = 227 (M+H, 100); HPLC (method 4): rt = 1.96 min. 15 IV-4. 4-(4-amino-2-methylphenvl)-3-morpholinone MS (ESI): m/z (%) = 207 (M+H, 100); HPLC (method 4): rt = 0.71 min. IV-5. 5-amino-2-(3-oxo-4-morpholinvl)benzoilitrile 20 MS (ESI): m/z (%) = 218 (M+H, 100); HPLC (method 4): rt = 1.85 min. IV-6. l-(4-ajnino-2-chlorophenvl)-2-pvrrolidinone MS (ESI): m/z (%) = 211 (M+H, 100); 25 HPLC (method 4): rt = 2,27 min. IV-7. 4-(4-aniino-2.6-dimethvlphenvl)-3-morpholinone starting from 2-fluoro-l,3-dimethyl-5-nitrobenzene (Bartoli et al., J. Org. Cherry 1975,40, 872): 30 MS (ESI): m/z (%) = 221 (M+H, 100); HPLC (method 4): rt = 0.77 min. IV-8. 4-(2,4-diaminophenvI)-3-_morpholinone starting from l-fluoro-2,4-drnitrobenzene: 35 MS (ESI): m/z (%) = 208 (M+H, 100); HPLC (method 4): rt = 0.60 min. IV-9. 4-(4-amino-2-chlorophenyl)-2-methvl-3-morpholinone starting from 2-methyl-3-morpholinone (Pfeil, E.; Harder, U.; Angew. Chem. 1967, 79,188): 5 MS (ESI): m/z (%) = 241 (M+H, 100); HPLC (method 4); rt = 2.27 min. IV-10. 4-(4-amino-2-chloropheny)-6-methvl-3-morphollone starting from 6-methyl-3-morpholinone (EP 350 002): 10 MS (ESI): m/z (%) = 241 (M+H, 100); HPLC (method 4): rt - 2.43 min. Synthesis Examples The Examples 1 to 13,17 to 19 and 36 to 57 below refer to process variant [A]. Example 1 Preparation of 5-chloro-N-{[(5S)-3"(3-fluoro-4-morpholinophenyI)-2-oxo-l,3-oxazolidin-5-yI]methyl}-2-thiophenecarboxamide 10 (5S)-5-(Aminomethyl)-3-(3-fluoro-4-morpholinophenyl)-lt3-oxazolidin-2-one (preparation see S. J. Brickner et al., J. Med. Chem. 1996, 39, 673) (0.45 g, 1.52 mmol), 5-chlorothiophene-2-carboxylic acid (0.25 g, 1.52 mmol) and 15 1-hydroxy-lH-benzotriazole hydrate (HOBT) (0.3 g7 1.3 equivalents) are dissolved in 9.9 ml of DMF. 0.31 g (1.98 mmol, 1.3 equivalents) of N-(3-dimethylaminopropyl)-N-ethylcarbodiimide (EDO) are added, and 0.39 g (0.53 ml, 3,05 mmol, 2 equivalents) of diisopropylethylamine (DIEA) are added dropwise at room temperature. The mixture is stirred at room temperature overnight. 2 g of silica gel 20 are added, and the mixture is evaporated to dryness under reduced pressure. The residue is chromatographed on silica gel using a toluene/ethyl acetate gradient. This gives 0,412 g (61.5% of theory) of the target compound of melting point (m.p.) 197°C. Rf (Si02, toluene/ethyl acetate 1:1) = 0.29 (starting material = 0.0); 25 MS (DCI) 440.2 (M+H), CI pattern; "H-NMR (D6VDMSO, 300 MHz) 2.95 (m, 4H), 3.6 (t, 2H), 3.72 (m, 4H), 3.8 (dd, 1H), 4.12 (t, 1H), 4.75-4.85 (m, 1H), 7.05 (t, 1H), 7.15-7.2 (m, 3H), 7.45 (dd, 1H), 7.68 (d, 1H), 8.95 (t, 1H). LftA-34 122^FefektQ-Countries Example 2 5-Chloro-N-{[(5S)-3-(4-morphoIinophenyl)-2-oxo-13-oxazoIidin-5-yl]methyl}-2-thiophenecarboxamide is obtained analogously from benzyl 4-morpholinophenylcarbamate via the (5S)-5- (aminomethyI)-3-(3-fluorc-4-morpholinophenyl)-l,3-oxazolidin-2-one intermediate (see Example 1). M.p.: 198°C; 10 IC50 value = 43 nM; Rf (Si02, toluene/ethyl acetate 1:1) = 0.24. Example 3 15 5-Chloro-N-({(5S)-3-[3-fluoro-4-(l,4-thiazinan-4-yI)phenyl]-2-oxo-l,3-oxazoIi- din-5-yl}methyl)-2-thiophcnecarboxamide is obtained analogously from (5S)-5-(aminomethyl)-3-[3-fluoro-4-(l,4-thiazinan-4- 20 yl)phenyl]-l,3-oxazolidin-2-one (preparation see M. R. Barbachyn et ah, J, Med. Chem. 1996,39, 680). M.p.: 193°C; Yield: 82%; Rf (Si02, toluene/ethyl acetate 1:1) = 0.47 (starting material =0.0). 25 Example 4 5-Bromo-N-({(5S)-3-[3-fluoro-4-(l,4-thiazinan-4-yl)phenyI]-2-oxo-l,3-oxazolidin-5-yI}methyl)-2-thiophenecarboxamide is obtained analogously from 5-bromothiophene-2-carboxylic acid. M.p.: 200°C. 10 Example 5 15 N-({(5S)-3-[3-Fluoro-4-(l,4-thia2inan-4-yl)phenyl]-2-oxo-13-oxazolidin-5-yl}methyI)-5-methyI-2-thiophenecarboxamide Fv Q S\J*-\J~\ 1 CH. Example 6 5-ChIoro-N-{[(5S)-3-(6-methylthieno[2r3-b]pyrldin-2-yl)-2-oxo-l73-oxazoIidin-5. yl]methyl}-2-thiopheriecarboxarnide is obtained analogously from (5S)-5-(aminomethyl)-3-(6--niethylthieno[213-b]pyridin-2-yl)-l,3-oxazolidin-2-one (preparation see EP-A-785 200). M.p.: 247°C. Example 7 5-Chloro-N-{[(5S)-3-(3-methyl-2-oxo-2,3-dihydro-l,3-benzothiazol-6-yI)-2-oxo-l,3-oxazolidin-5-yI]methyl}-2-thiophenecarboxomide is obtained analogously from 6-[(5S)-5-(aminomethyl)-2-oxo-l,3-oxazoIidin-3-yl]-3-methyl-l,3-benzothiazoI-2(3H)-one (preparation see EP-A-738 726). M.p.:217°C. Example 8 5-Chloro-N.[((5S)-3-{3-fluoro-4-[4-(4-pyridinyl)piperazino]phenyl}-2-oxo-l,3-oxazoIidin-5-yI)methyI]-2-thiophenecarboxamide 5 o is obtained analogously from (5S)-5-(aminomethyl)-3-{3-fluoro-4-[4-(4- pyridinyl)piperazino]phenyl}-l,3-oxazolidin-2-one (preparation analogously to J. A. Tucker et al., J. Med. Chem. 1998, 41, 3727). 10 MS (EST) 516 (M+H),C1 pattern. Example 9 5-Chloro-N-({(5S)-3-[3-fluoro-4-(4-methylpiperazino)phenyI3-2-oxo-l,3-oxazoli- 15 dm-5-yl}methyI)-2-thiophenecarboxamide O is obtained analogously from (5S)-5-(aminomethyl)-3-[3-fluoro-4-(4-methylpiperazino)phenyl]-l73-oxazolidin-2-one. 20 Example 10 5-Chloro-N-({(5S)-3-[3-fluoro-4-(4-tert-butoxycarbonyIpiperazin-l-yI)phenyI]-2-oxo-l^-oxazoIidin-5-yI}methyl)-2-thiophenecarboxamide 5 a o" is obtained analogously from (5S)-5-(aminomethyl)-3-[3-fluoro-4-(4-tert-butoxy- carbonylpiperazin-l-yl)phenyl]-l,3-oxazoIidin-2-one (preparation see WO-A-93/23384, which has already been cited). 10 M.p.: 184°C; Rf(Si02, toluene/ethyl acetate 1:1) = 0.42. Example 11 15 5-Chloro-N-({(5S)-3-[3-fluoro-4-(piperazin-l-yl)phenyl]-2-oxo-l,3-oxazoIidin-5- yl}methyl)-2-thiophenecarboxamide C! O" is obtained by reacting Example 12 with trifluoroacetic acid in methylene chloride. 20 IC5o value = 140 nM; 4H-NMR [d6-DMSO]: 3.01-3.25 (m, SH), 3.5-3.65 (m, 2H), 3.7-3.9 (m, IH), 4.05-4.2 (m, IH), 4.75-4.9 (m, IH), 7.05-7.25 (m, 3H), 7.5 (dd, IH), 7.7 (d, IH), 8.4 (broad s, IH), 9.0 (t, IH). Example 12 5-Chloro-N-[((5S)-3-(2?4-bipyiridinyl-5-yI)-2-oxo-1,3-oxazolidin-5-yI)methyl]-2-thiophenecarboxamide 10 15 is obtained analogously from (5S)-5-aminomethyl-3-(2,4-bipyridinyl-5-yI)-2-oxo-l,3-oxazolidin-2-one (preparation see EP-A-789 026). Rf (Si02, ethyl acetate/ethanol 1:2) = 0.6; MS (ESI) 515 (M+H), C\ pattern. Example 13 5-Chloro-N-{[(5S)-2-oxo-3-(4-piperidinophenyl)-l,3-oxazolidin-5-yl3methyI}-2-thiophenecarboxamide 20 ■-^62- is obtained from 5-(hydroxymethyl)-3-(4-piperidinophenyl)-13-o\azolidin-2-one (preparation see DE 2708236) after mesylation, reaction with potassium phthalimide, hydrazinolysis and reaction with 5-chIorothiophene-2-carboxylic acid. Rf (Si02, ethyl acetate/toluene 1:1) = 0,31; 5 m.p. 205°C. Example 17 S-Chloro-N-({(5S)-2-oxo-3-[4-(2-oxo-l-pyrroIidinyl)phenyl]-l^-oxazolidin-5- 10 yl}methyI)-2-thiophenecarboxamide Analogously to the known synthesis scheme (see S.J Brickner et al., J. Med. Chem. 1996, 39, 673), l-(4-aminophenyl)pytrolidin-2-one (preparation see Reppe et al., 15 Justus Liebigs Ann. Chem.; 596; 1955; 209) gives, after reaction with benzyloxycarbonyl chloride, followed by reaction with i?-glycidyl butyrate, mesylation, reaction with potassium phthalimide, hydrazinolysis in methanol and reaction with 5-chlorothiophene-2-carboxylic acid, finally 5-chloro-N-({(5S)-2-oxo-3-[4-(2-oxo- l-pyrrolidinyl)phenyl]-1,3-oxazolidhv5-yl }methyl)-2-thio- 20 phenecarboxamide. The 5-chloro-N-({(5S)-2-oxo-3-[4-(2-oxo-l-pyrrolidinyI)- phenyl]-l,3-oxazoIidin-5-yl}methyl)-2-thiophenecarboxamide obtained in this manner has an IC50 value of 4 nM (test method for the IC50 value according to Example A-l.a.1 described above) "determination of the inhibition of factor Xa"). M.p.:229°C; v 25 Rf value (SiO2, toluene/ethyl acetate 1:1) = 0.05 (starting material: = 0.0); MS (ESI): 442.0 (21%, M+Na, CI pattern), 420.0 (72%, M+H, CI pattern), 302.3 (12%), 215(52%), 145 (100%); "H-NMR (d6-DMSO, 300 MHz): 2.05 (m,2H), 2.45 (m,2H), 3.6 (t,2H), 3.77-3.85 (m,3H), 4.15(t,lH), 4.75-4.85 (m,lH), 7.2 (d,lH), 7.5 (d,2H), 7,65 (d,2H), 7.69 30 (d,iH),8.96(t,lH). The following compounds were prepared in an analogous manner Example 18 5 yI}methyI)-2-thiophenecarboxamide Analogously to Example 17, 4-pyrroIidin-l-yl-aniIine (Reppe et al., Justus Liebigs Ann. Chem.; 596; 1955; 151) gives the compound 5-chloro-N-({(5S)-2-oxo-3-[4-(l- 10 pyrrolidinyl)phenyl]-l,3-oxazolidin-5-yI}methyI)-2-thiophenecarboxamide. IC5o=40 nM; m.p.: 216°C; Rf value (Si02, toluene/ethyl acetate 1:1) = 0.31 [starting material: = 0.0]. 15 Example 19 5-Chloro-N-({(5S)-2-oxo-3-[4-(diethyIamino)phenyl]-l,3-oxazoIidin-5-yl}methyl)-2-thiophenecarboxamide 20 Analogously, N,N-diethyipheny]-l,4-diamine (US-A-2 811 555; 1955) gives the compound 5-chloro-N-({(5S)-2-oxo-3-[4-(diethylamino)phenyl]-l,3-oxazolidin-5- yl }methyl)-2-thiophenecarboxamide. IC50=270 nM; m.p.: 181°C; 25 Rf value (Si02, toluene/ethyl acetate 1:1) = 0.25 [starting material: = 0.0]. Example 36 5-Chloro-N-({(5S)-3-2-methyI-4-(4-morpholinyI)phenyl]-2-oxo-l,3-oxazoIidin-5- 30 yI}methyI)-2-thiophenecarboxamide starting from 2-methyI-4-(4-morpholinyl)aniIine (J.EXuValle et al. J.Am.Chem.Soc. 1948, 70, 2223): MS (ESI): m/z {%) = 436 ([M+H]+, 100), CI pattern; HPLC (method 1): it (%) = 3.77 (98). 35 IC50: 1-26 fiM Le^i M 172-Foreign CosHtries Example 37 5-Chloro-N-{[(55)-3-(3-chIoro-4-morphoIinophenyI)-2-oxo-l,3-oxazolidin-5-yI]methyI}-2-thiophenecarboxamide 5 starting from 3-chloro-4-(4-morpholinyl)aniline (H.R.Snyder et al J.Pharm.Scl 1977,66,1204): MS (ESI): m/z (%) = 456 ([M+H]+, 100), Cl2 pattern; HPLC (method 2): rt (%) = 4.31 (100). IC50: 33 nM 10 Example 38 5-Chloro-N-({(55)-3-[4-(4-morphoIinylsuIphonyl)phenyl]-2-oxo-l,3-oxazolidin-5-yl}methyl)-2-thiophenecerboxamide 15 starting from 4-(4-morphoIinylsulphony])aniline (Adams et al J.Am.Chem.Soc. 1939,61,2342): MS (ESI): m/z (%) = 486 ([M+H]+, 100), CI pattern; HPLC (method 3): rt (%) - 4.07 (100). IC50: 2 fiM 20 Example 39 S-Chloro-N-({(5S)-3-[4-(l-a2etidinylsulphonyl)phenyl]-2-oxo-l,3-oxazolidin-5-yl}methyl)-2-thiophenecarboxamide 25 starting from 4-(l-azetidinylsulphonyl)aniIine: MS (DCI, NH3): m/z (%) = 473 ([M+NH4]+, 100), CI pattern; HPLC (method 3): rt (%) = 4.10 (100). IC50:0.84pM 30 Example 40 5-Chloro-N-[((S5)-3-{4-[(dimethylainino)suIphonyl]phenyl}-2-oxo-l,3-oxazoIidin-5-yl)methyl]-2-thiophenecarboxamide starting from 4-amino-N,N-dimethyIben2enesulphonamide (I.K.Khanna el al 35 JMed.Chem. 1997,40, 1619): MS (ESI): m/z (%) = 444 ([M-4-H]+ 100), CI pattern; HPLC (method 3): rt (%) = 4.22 (100). IC50:90nM General method for the acylation of 5-(aminomethyl)-3-[4-(2-oxo-l-pyrro- 5 IidinyI)phenyl]-l,3-oxazolidin-2-one with carbonyl chlorides. Under argon and at room temperature, an about 0.1 molar solution of 5- 10 (aminomethyl)-3-[4-(2-oxo-l-pyrroIidinyl)phenyl]-l,3-oxazoIidin-2-one (from Example 45) (1.0 eq.) and absolute pyridine (about 6 eq.) in absolute dichloromethane is added dropwise to the appropriate acid chloride (2.5 eq.). The mixture is stirred at room temperature for about 4 h, and about 5.5 eq of PS- trisamine (Argonaut Technologies) are then added. The suspension is stirred gently 15 for 2h, diluted with dichloromethane/DMF (3:1) and then filtered (the resin is washed with dichloromethane/DMF) and the filtrate is concentrated. If appropriate, the product that is obtained is purified by preparative RP-HPLC. 20 The following compounds were prepared in an analogous manner: Example 41 N-({2-oxo-3-[4-(2-oxo-l-pyrrolidinyi)phenyl]-l,3-oxazoIidin-5-yl}methyl)-2-thiophene-carboxamide 25 LC-MS (method 6): m/z (%) = 386 (M+H, 100); LC-MS;rt(%) = 3.04 (100). IC50: 1.3 fiM General method for preparing acyl derivatives starting from 5-(aminomethyl)-3-[4-(2-oxo-l-pyrroIidinyl)phenyI]-l,3-oxazoIidin*2-one and carboxylic adds 5 The appropriate carboxylic acid (about 2 eq.) and a mixture of absolute dichloromethane/DMF (about 9:1) are added to 2.9 eq. of resin-bonded carbodiimide (PS-carbodnmide, Argonaut Technologies), The mixture is shaken gently at room temperature for about 15 min, 5-(aminomethyl)-3-[4-(2-oxo-l-pyrrolidinyl)phenyl]-l,3-oxazo!idin-2-one (from Example 45) (1.0 eq.) is then added and the mixture is 10 shaken overnight, after which the resin is filtered off (and washed with dichloromethane), and the filtrate is concentrated. If appropriate, the resulting product is purified by preparative RP-HPLC. 15 The following compounds were prepared in an analogous manner Example 42 5-MethyI-N-({2-oxo-3-[4-(2-oxo-l-pyrrolidinyl)phenyl]-l,3-oxazolidin-5-yl}methyl)-2-thiophenecarboxamide 20 LC-MS: m/z (%) = 400 (M+H, 100); LC-MS (method 6): it (%) = 3.23 (100). IC50:0.16/iM 25 Example 43 5-Bromo-N-({2-oxo-3-[4-(2-oxo-l-pyrroIidinyI)phenyl]-lT3-oxazoIidin-5-yl}methyl)-2-thiophenecarboxamide LC-MS : m/z (%) = 466 (M+H, 100); LC-MS (method 5): n (%) = 3.48 (78). Example 44 5 5-Chloro-^V-({(55)-2-oxo-3-[4-(3-oxo-4-morphoIinyI)phenyI]-l^-oxa2olidin-5- yI}methyI)-2-thiophenecarboxainide 10 a) 2-((2R)-2-Hydroxy-3-{[4-(3-oxo-4-morpholinyl)phenyl]amino}propyI)-1h-iso- 15 indole-l,3(2H)-dione: A suspension of 2-[(2S)-2-oxiranylmethyl]-lH-isoindole-l,3(2H)-dione (A. Gutcait et al. Tetrahedron Asym. 1996, 7, 1641) (5.68 g, 27.9 mmol) and 4-(4-aminophenyl)-3-morpholinone (5.37 g, 27.9 mmol) in ethanol/water (9:1, 140 ml) is refluxed for 14 h (the precipitate dissolves, after some time again formation of a precipitate). The precipitate (desired product) is filtered off, washed three times with diethyl ether and dried. The combined mother liquors are concentrated under reduced pressure and, after addition of a second portion of 2-[(2S)-2-oxiranylmethyI]-lH-isoindole- 5 l,3(2H)-dione (2.84 g, 14.0 mmol), suspended in ethanol/water (9:1, 70 ml) and refluxed for 13 h (the precipitate dissolves, after some time again formation of a precipitate). The precipitate (desired product) is filtered off, washed three times with diethyl ether and dried. Total yield: 10.14 g, 92% of theory. MS (ESI): m/z (%) = 418 ([M+Na]+, 84), 396 ([M+H]+, 93); 10 HPLC (method 3): rt (%) = 3.34 (100). b) 2-({(55)-2-Oxo-3-[4-(3-oxo-4-morpholinyI)phenyl]-l,3-oxazolidin-5-yI}me- thyl)-lH-isoindole-1,3(2H)-dione: 15 Under argon and at room temperature, N,N"-carbonyldiimidazole (2.94 g, 18.1 mmol) and dimethylaminopyridine (a catalytic amount) are added to a suspension of the amino alcohol (3.58 g, 9.05 mmol) in tetrahydrofuran (90 ml). The reaction suspension is stirred at 60°C for 12 h (the precipitate dissolves, after some time again formation of a precipitate), admixed with a second portion of N,N"- 20 carbonyldiimidazole (2.94 g, 18.1 mmol) and stirred at 60°C for another 12 h. The precipitate (desired product) is filtered off, washed with tetrahydrofuran and dried. The filtrate is concentrated under reduced pressure and further product is purified by flash chromatography (dichloromethane/methanol mixtures). Total yield: 3.32 g, 87% of theory, 25 MS (ESI): m/z (%) = 422 (EM+H]+ 100); HPLC (method 4): rt (%) = 3.37 (100). c) S-Chloro-N-({(55)-2-oxo-3-[4-(3-oxo-4-morphoIinyI)phenyl]-lr3-oxazolidin-5- yl}methyI)-2-thiophenecarboxamide: 30 At room temperature, methylamine (40% strength in water, 10.2 ml, 0.142 mol) is added dropwise to a suspension of the oxazolidinone (4.45 g, 10.6 mmol) in ethanol (102 ml). The reaction mixture is refluxed for 1 h and concentrated under reduced pressure. The crude product is used without further purification for the next reaction. 35 7/ Under argon and at 0°C, 5-chlorothiophene-2-carbonyI chloride (2.29 g, 12,7 mmol) is added dropwise to a solution of the amine in pyridine (90 ml). Ice-cooling is removed and the reaction mixture is stirred at room temperature for 1 h and admixed with water. Dichloromethane is added and the phases are separated, and the aqueous 5 phase is then extracted with dichloromethane. The combined organic phases are dried (sodium sulphate), filtered and concentrated under reduced pressure. The desired product is purified by flash chromatography (dichloromethane/methanol mixtures). Total yield: 3.92 gt 86% of theory. M.p: 232-233°C; 10 lH NMR (DMSO-d6, 200 MHz): 9.05-8.90 (t, J - 5.8 Hz, 1H), 7.70 (d, J = 4.1 Hz, 1H), 7.56 (d, J = 9.0 Hz, 2H), 7.41 (d, / = 9.0 Hz, 2H), 7.20 (d, J = 4.1 Hz, 1H), 4.93-4.75 (m, 1H), 4.27-4.12 (m, 3H), 4.02-3.91 (m, 2H), 3.91-3.79 (dd, J = 6.1 Hz-9.2 Hz, 1H), 3.76-3.66 (m, 2H), 3.66-3.54 (m, 2H); MS (ESI): m/z (%) = 436 ([M+H]+ 100, CI pattern); 15 HPLC (method 2): rt (%) = 3.60 (100); [a]21D = -38° (c 0.2985, DMSO); ee: 99%. IC50: 0.7 nM The following compounds were prepared in an analogous manner: 20 Example 45 5-MethyI-N-({(55)-2-oxo-3-[4-(3-oxo-4-morphoIinyl)phenyI}-l,3-oxazolidin-5-yI}methyl)-2-thiophenecarboxamide 25 MS (ESI): m/z (%) = 831 ([2M+H]+, 100), 416 ([M+H]+, 66); HPLC (method 3): rt (%) = 3.65 (100). IC50:4.2nM Example 46 30 5-Bromo-N-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-l,3-oxazolidin-5-yl }methyl)-2-thiophenecarboxamide MS (ESI): m/z (%) = 480 ([M+H]+ 100, Br pattern); HPLC (method 3): rt (%) = 3.87 (100). 35 IC50: 0.3 nM Example 47 5-ChIoro-N-{[(5S)-3-(3-isopropyl-2-oxo-2,3-dihydro-l,3-benzoxazoI-6-yl)-2-oxo-l,3-oxazolidin-5-yI]methyI}-2-thiophenecarboxatnide 200 mg (0.61 mmol) of 6-[(5S)-5-(aminomethyl)-2-oxo-lT3-oxazolidin-3-yl]-3-isO" pfopyI-l»3-benzoxa2oI-2(3H)-one hydrochloride (EP 738726) are suspended in 5 ml of tetrahydrofuran and admixed with 0,26 ml (1.83 mmol) of tnethylamine and 10 132 mg (0.73 mmol) of 5-chlorothiophene-2-carboriyl chloride. The reaction mixture is stirred at room temperature overnight and then concentrated- The product is isolated by column chromatography (silica gel, methylene chloride/ethanol = 50/1 to 20/1). This gives 115 mg (43% of theory) of the desired compound. MS (ESI): m/z (%) = 436 (M+H, 100); 15 HPLC (method 4): rt = 3.78 min. The following compounds were prepared in an analogous manner: Example No. Structure M.p. [°Cj IC5o {uM} 48 0 S-^C|Chira" 0 210 0.12 49 O CJwal 234 0.074 50 • Ctwai 195 1.15 51 ° 0 212 1.19 52 O Cm 160 0.19 53 O Cnirai MS (ESI): m/z (%) = 431 (IM+H)+, 100), CI pattern 0.74 / ,/ / / / / 74 Example No. Structure M-P- [°C] 1C50 [uM] 54 O CJiiraJ 4 N O from 5-amino-2-pyrrolidino-benzonitrile (Grell, W., Hurnaus, R.; Griss, G., Sauter, R.; Rupprecht, E. et al; J.MedChem.1998, 41; 5219) 221 0.13 55 0 from 3-(4-amino-phenyl)-oxazoIidin-2-one (Artico, M. et al.; Farmaco Ed.Sci. 1969,24; 179) 256 0.04 56 Q CWnU 218 0.004 51 O Chital 0 i 226 0.58 255 228-230 / / / /" -75- 5 Examples 20 to 30 and 58 to 139 below refer to process variant [B], and Examples 20 and 21 describe the preparation of precursors. Example 20 Preparation of N-aIIyI-5-chIoro-2-thiophenecarboxamide o 10 An ice-cooled solution of 2.63 ml (35 mmol) of allylamine in 14.2 ml of absolute pyridine and 14.2 ml of absolute THF is admixed dropwise with 5-chloro-thiophene-2-carbonyl chloride (7.61 g, 42 mmol). Ice-cooling is removed and the mixture is stirred at room temperature for 3 h and then concentrated under reduced pressure. The residue is admixed with water and the solid is filtered off. The crude product is 15 purified by flash chromatography over silica gel (dichloromethane). Yield: 7.20 g (99% of theory); MS (DCI, NH4): m/z (%) = 219 (M+NH4, 100), 202 (M+H, 32); HPLC (method 1): rt (%) = 3.96 min (98.9). 20 Example 21 Preparation of 5-chloro-N-(2-oxiranylmethyl)-2-thiophenecarboxamide 25 An ice-cooled solution of 2,0 g (9.92 mmol) of N-aIlyI-5-chloro-2- thiophenecarboxamide in 10 ml of dichloromethane is admixed with meta- chloroperbenzoic acid (3.83 g, about 60% strength). The mixture is stirred overnight, during which it is allowed to warm to room temperature, and is then washed with 30 10% sodium hydrogen sulphate solution (three times). The organic phase is washed with saturated sodium bicarbonate solution (twice) and with saturated sodium Le A34 I22^ercrgTreountrics chloride solution, dried over magnesium sulphate and concentrated. The product is purified by silica gel chromatography (cyclohexane/ethyl acetate 1:1). Yield: 837 mg (39% of theory); MS (DCI, NHi): m/z (%) =253 (M+NH4,100), 218 (M+H, 80); 5 HPLC (method 1): rt (%) = 3,69 min (about 80). General method for preparing substituted N-(3-amino-2-hydroxypropyl)-5-chloro-2-thiophenecarboxamide derivatives starting from 5-chloro-iV-{2-oxiranylmethyl)-2-thiophenecarboxamide 10 At room temperature or at temperatures up to 80°C, 5-chloro-N-(2-oxiranyImethyI)-2-thiophenecarboxamide (1.0 eq.) is added a little at a time to a solution of the 15 primary amine or aniline derivative (1.5 to 2.5 eq.) in 1,4-dioxane, 1,4-dioxane/water mixtures or ethanol, ethanol/water mixtures (about 0.3 to 1.0 mol/1). The mixture is stirred for 2 to 6 hours and then concentrated. From the reaction mixture, the product can be isolated by silica gel chromatography (cyclohexane/ethyl acetate mixtures, dichloromethane/methanol mixtures or dichloromethane/methanol/triethylamine 20 mixtures). The following compounds were prepared in an analogous manner Example 22 25 iV-[3-(Benzylamino)-2-hydroxypropyl3-5-chloro-2-thiophenecarboxamide MS (ESI): m/z (%) = 325 (M+H, 100); HPLC (method 1): rt (%) = 3.87 min (97.9). 30 Example 23 5-Chloro-N-[3-(3-cyanoanilino)-2-hydroxypropyl]-2-thiophenecarboxamide MS (ESI): m/z (%) = 336 (M+H, 100); HPLC (method 2); rt (%) = 4.04 min (100). Example 24 5-Chloro-iV-[3-(4-cyanoaniIino)-2-hydroxypropyI]-2-thiophenecarboxamide MS (ESI): m/z (%) - 336 (M+H, 100); 5 HPLC (method 1): rt (%) = 4.12 min (100). Example 25 5-ChIoro-N-{3-[4-(cyanomethyI)anilino]-2-hydroxypropyl}-2- thiophenecarboxamide 10 MS (ESI): m/z (%) = 350 (M+H, 100); HPLC (method 4): rt (%) = 3.60 min (95.4). Example 26 15 5.Chloro-N-{3-[3-(cyanomethyl)anilino]-2-hydroxypropyl}-2- thiophenecarboxamide MS (ESI); m/z (%) = 350 (M+H, 100); HPLC (method 4): rt (%) - 3.76 min (94.2). 20 Example 58 tert-Butyl 4-[(3-{[(S-chloro-2-thienyl)carbonyl]amino}-2-hydroxypropyl)amino]-benzylcarbamate 25 starting from fert-butyl 4-aminobenzylcarbamate {Bioorg. Med. Chem. Lett.", 1997; 1921-1926): MS (ES-pos): m/z (%) = 440 (M+H, 100), (ES-neg): m/z (%) - 438 (M-H, 100); HPLC (method 1): rt (%) = 4.08 (100). 30 Example 59 terf-Butyl 4-[(3-{[(5-chloro-2-thienyl)carbonyl]amino}-2-hydroxypropyl)amino]-phenyl-carbamate 35 starting from N-tert-butyloxycarbonyl-l,4-phenylenediamine: MS (ESI): m/z (%) = 426 (M+H, 45), 370 (100); HPLC (method 1): it (%) = 4.06 (100). Example 60 5 fert-Butyl 2-hydroxy-3-{[4-(2-oxo-l-pyrrolidinyI)phenyI]amino}propyI-carb- amate starting from l-(4-aminophenyl)-2-pyrroiidinone (Justus Liebigs Ann. Chem.\ 1955; 596; 204): 10 MS (DCI, NH3): m/z (%) = 350 (M+H, 100); HPLC (method 1): rt (%) = 3.57 (97). Example 61 15 5-Chloro-N-(3-{[3-fluoro-4-(3-oxo-4-morphoIinyI)phenyI]amino}-2-hydroxypro- pyI)-2-thiophenecarboxamide S00 mg (3.8 mmol) of 4-(4-amino-2-fluorophenyl)-3-morpholinone and 700 mg (3.22 mmol) of 5-chloro-N-(2-oxiranyImethyl)-2-thiophenecarboxamide in 15 ml of 20 ethanol and 1 ml of water are heated under reflux for 6 hours. The mixture is concentrated under reduced pressure and treated with ethyl acetate, precipitated crystals are filtered off with suction and the mother liquor is chromatographed giving 276 mg (17% of theory) of the target compound. Rf (ethyl acetate): 0.25. 25 Example 62 (N-(3-Anilino-2-hydroxypropyI)-5-chloro-2-thiophenecarboxamide starting from aniline: 30 MS (DCI, NH3): m/z (%) = 311 ([M+H]+, 100), CI pattern; HPLC (method 3): rt {%) = 3.79 (100). Example 63 35 5-Chloro-N-(2-hydroxy-3-{[4-(3-oxo-4-morpholinyi)phenyl]amino}propyl)-2- thiophenecarboxamide 79 starting from 4-(4-aminophenyl)-3-morphoIinone: MS (ESI): m/z (%) = 410 ([M+Hf, 50), CI pattern; HPLC (method 3): rt (%) - 3.5S (100). 5 Example 64 N-[3-({4-[AcetyI(cycIopropyl)amino]phenyI}aniino)-2-hydroxypropyl]-5-chIoro-2-thiophenecarboxamide starting from N-(4-aminophenyI)-N-cyclopropylacetamide: 10 MS (ESI): m/z (%) - 408 ([M+H]+, 100), CI pattern; HPLC (method 3): it (%) = 3.77 (100). Example 65 15 N-[3-({4-[Acetyl(methyl)amino]phenyl}amino)-2-hydroxypropyl]-5-chloro-2- thiophenecarboxamide starting from N-(4-aminophenyI)-N-methyIacetamide: MS (ESI): m/z (%) - 382 (M+H, 100); HPLC (method 4): it = 3.31 min. 20 Example 66 5-Chloro-N-(2-hydroxy-3-{[4-(lH-l,2,3-triazol-l-yl)phenyl]amino}propyl)-2-thiophenecarboxamide 25 starting from 4-(lH-l,2,3-triazol-l-yI)aniIine (Bouchet et al.; J.Chem.Soc.Perkin Trans.2; 1974; 449): MS (ESI): m/z (%) = 378 (M+H, 100); HPLC (method 4): rt = 3.55 min. 30 Example 67 tert-butyl l-{4-[(3-{[(5-chIoro-2-thienyl)carbonyl]amino}-2-hydroxypropyi)-amino]phenyI}-L-proIinate MS (ESI): m/z (%) = 480 (M+H, 100); 35 HPLC (method 4): rt = 3.40 min. Example 68 l-{4-[(3-{[(5-ChIoro-2-thienyl)carbonyl}amino}-2-hydroxypropyI)amino]phe-nyl}-4-piperidinecarboxamide 5 MS (ESI): m/z (%) = 437 (M+H, 100); HPLC (method 4): rt = 2.39 min. Example 69 10 l-{4-[(3-{[(5-Chloro-2-tbienyI)carbonyI]amino}-2-hydroxypropyI)-aniino]phe- nyl}-3-piperidinecarboxamide MS (ESI): m/z (%) = 437 (M+H, 100); HPLC (method 4): rt = 2.43 min, 15 Example 70 5-ChIoro-N-(2-hydroxy-3-{[4-(4-oxo-l-piperidinyl)phenyI]amino}propyI)-2-thiophenecarboxamide MS (ESI): m/z (%) = 408 (M+H, 100); 20 HPLC (method 4): rt = 2.43 min. Example 71 l-{4-[(3-{[(5-ChIoro-2-thienyl)carbonyI]amino}-2-hydroxypropyl)amino]phe* 25 nyl}-L-prolinamide MS (ESI): m/z (%) = 423 (M+H, 100); HPLC (method 4): rt = 2.51 min. Example 72 30 5-Chloro-N-[2-hydroxy-3-({4-[3-(hydroxymethyI)-l-piperidinyI]phenyI}- amino)propyl]-2-thiophenecarboxamide MS (ESI): m/z (%) = 424 (M+H, 100); HPLC (method 4): rt - 2.43 min. Example 73 5-Chloro--N-[2-hydroxy-3-({4-[2-(hydroxymethyI)-l-piperidinyI]phenyl}-amino)propyl]-2-thiophenccarboxamide 5 MS (ESI): m/z (%) = 424 (M+H, 100); HPLC (method 4): it = 2.49 min. Example 74 10 Ethyl l-{4-[(3-{[(5-cfaIoro-2-thienyl)carbonyI]aniino}-2-hydroxypropyl)- amino]phenyI}-2-piperidinecarboxyIate MS (ESI): m/z (%) = 466 (M+H, 100); HPLC (method 4): it = 3.02 min. 15 Example 75 5-Chloro-N-[2-hydroxy-3-({4-[2-(hydroxymethyI)-l-pyrrolidinyl]phenyl}amino)-propyl]-2-thiophenecarboxamide MS (ESI): m/z (%) = 410 (M+H, 100); 20 HPLC (method 4): rt = 2.48 min. Example 16 5-Chloro-N-(2-hydroxy-3-{[4-(2-methylhexahydro-5H-pyrrolo[3,4-d]isoxa2ol-5- 25 yI)phenyI]amino}propyl)-2-thiophenecarboxamide MS (ESI): m/z (%) = 437 (M+H, 100). HPLC (method 5): rt = 1.74 min. -1 Example 77 30 5-ChIoro-N-(2-hydroxy-3-{[4-(l-pyrrolidinyI)-3-(trinuoromethyI)phenyI]-arnino}propyI)-2-thiophenecarboxamide MS (ESI): m/z (%) s 448 (M+H, 100); HPLC (method 4): rt = 3.30 min. Example 78 5-ChIoro-N-(2-hydroxy-3-{[4-(2-oxo-l-pyrrolidinyl)-3-(trifluoromethyl)phenyI]-amino}propyl)-2-thiophenecarboxamide 5 MS (ESI): m/z (%) = 462 (M+H, 100); HPLC (method 4): rt = 3.50 mm. Example 79 10 5-Chloro-N-(3-{[3-chloro-4-(3-oxo-4-morpholinyl)phenyl]amino}-2-hydroxy- propyl)-2-thiophenecarboxamide MS (ESI): m/z (%) = 444 (M+H, 100); HPLC (method 4): rt = 3.26 min. 15 Example 80 S-ChIoro-N-(2-hydroxy-3-{[4-(3-oxo-4-morpholinyl)-3.(trifluoromethyl)pfaenyl]-amino}propyl)-2-thiophenecarboxamide MS (ESI): m/z (%) = 478 (M+H, 100); 20 HPLC (method 4): rt - 3.37 min. Example 81 5-Chtoro-N-(2-hydroxy-3-{(3-methyI-4-(3-oxo-4-morphoIinyI)phenyI]amino}- 25 propyl)-2-thiophenecarboxamide MS (ESI): m/z (%) = 424 (M+H, 100); HPLC (method 4): rt - 2.86 min. Example 82 30 5-Chloro-N-(3-{[3-cyano-4-(3-oxo-4-morphoIinyl)phenyl]amino}-2-hydroxypro- pyl)-2-thiophenecarboxamide MS (ESI): m/z (%) = 435 (M+H, 100); HPLC (method 4): it = 3.10 min. 35 Example 83 5-Chloro-N-(3-{[3-chIoro-4-(l-pyrrolidinyI)phenyl]amino}-2-hydroxypropyI)-2-thiophenecarboxamide 5 MS (ESI); m/z (%) = 414 (M+H, 100); HPLC (method 4): rt = 2.49 min. Example 84 10 5-Chloro-N-(3-{[3-chloro-4-(2-oxo-l-pyrrolidinyl)phenyl]amino}-2-hydroxypro- pyI)-2-thiophenecarboxamide MS (ESI): m/z (%) = 428 (M+H, 100); HPLC (method 4): rt = 3.39 min. 15 Example 85 5-Chloro-N-(3-{[3^-dimethyl-4-(3-oxo-4-morpbolinyl)phenyI]aniino}-2-hydro- xypropyl)-2-thiophenecarboxamide MS (ESI): m/z (%) =: 438 (M+H, 100); 20 HPLC (method 4): rt = 2.84 min. Example 86 N-(3-{[3-(Aininocarbonyl)-4-(4-morpholinyl)phenyI]anino}-2-hydroxypropyI)- 25 5-chloro-2-thiophenecarboxamide MS (ESI): m/z (%) = 439 (M+H, 100); HPLC (method 4): rt = 2.32 min. Example S7 30 5-Chloro-N-(2-hydroxy-3-{[3-methoxy-4-(4-morphoIinyl)phenyl]amino}propyl)- 2-thiophenecarboxamide MS (ESI): m/z (%) = 426 (M+H, 100); HPLC (method 4): rt = 2.32 mm. Example 88 N-(3-{[3-Acetyl-4-(4-morphoiinyI)phenyl]amino}-2-hydroxypropyl)-5-chloro-2-thiophenecarboxamide 5 MS (ESI): m/z (%) = 438 (M+H, 100); HPLC (method 4): rt = 2.46 min. Example 89 10 N-(3-{ [3-Amino-4-(3-oxo-4-morpholiny l)phenyl]amino}-2-hydroxy propyl)-5- chloro-2-thiophenecarboxamide MS (ESI): m/z (%) = 425 (M+H, 100); HPLC (method 4): rt = 2,45 min. 15 Example 90 5-Chloro-N-(3-{[3-chloro-4-(2-methyl-3-oxo-4-morphoUnyl)phenyl]amino}-2-hydroxypropyI)-2-thiophenecarboxamide MS (ESI): m/z (%) - 458 (M+H, 100); 20 HPLC (method 4); rt = 3.44 min. Example 91 5-Chloro-N-(3-{[3-chloro-4-(2-methyl-5-oxo-4-morpholinyl)phenyl]amino}-2- 25 hydroxypropyl)-2-thiophenecarboxamide MS (ESI): m/z (%) = 458 (M+H, 100); HPLC (method 4): rt = 3.48 min. Example 91a 30 5-Chloro-N-[2-hydroxy-3-({4-[(3-oxo-4-morphoIinyI)methyI]phenyl}amino)-propyI]-2-thiophenecarboxamide starting from 4-(4-amino-benzyI)-3-morphoIinone (Surrey et al.; J. Amer. Chem. 35 Soc; 77; 1955; 633): MS (ESI): m/z (%) = 424 (M+H, 100); HPLC (method 4): it = 2.66 min. General method for preparing 3-substituted 5-chloro-N-[(2-oxo-l,3-oxazolidin- 5-yl)methyI)-2-thiophenecarboxamide derivatives starting from substituted 5 iV-(3-amino-2-hydroxypropyl)-5-chloro-2-thiophenecarboxamide derivatives At room temperature, carbodiimidazole (1.2 to 1.8 eq.) or a similar phosgene 10 equivalent are added to a solution of the substituted Af-(3-amino-2-hydroxypropyI)-5- chloro-2-thtophenecarboxamide derivative (1.0 eq.) in absolute THF (about 0.1 mol/1). At room temperature or, if appropriate, at elevated temperature (up to 70°C), the mixture is stirred for 2 to 18 h and then concentrated under reduced pressure. The product can be purified by silica gel chromatography 15 (dichloromethane/methanol mixtures or cyclohexane/ethyl acetate mixtures). The following compounds were prepared in an analogous manner. Example 27 20 N-[(3-Benzyl-2-oxo-l,3-oxa2oIidin-5-yI)methyI]-5-choro-2-thiophenecarboxamide MS (DCI, NH4): m/z (%) = 372 (M+Na, 100), 351 (M+H, 45); HPLC (method 1): rt (%) = 4.33 min (100). 25 Example 28 5-Chioro-N-{[3-(3-cyanophenyl)-2-oxo-l,3-oxazolidin-5-yl]methyl}-2-thiophenecarboxamide 30 MS (DCI, NH4): m/z (%) = 362 (M+H, 42), 145 (100); HPLC (method 2): it (%) = 4.13 min (100). ^S6^—-Example 29 tbiophenecarboxamide 5 MS (ESI): m/z (%) = 376 (M+H, 100); HPLC (method 4): it = 4.12 min Example 30 10 5-ChIoro-N-({3-[3-(cyanomethyl)phenyl]-2-oxo-l,3-oxazoIidin-5-yl}inethyl)-2- thiophenecarboxamide MS (ESI): m/z (%) = 376 (M+H, 100); HPLC (method 4): rt = 4.17 min 15 Example 92 tert-Butyl 4-[5-({[(5-chIorO-2-thienyI)carbonyI]amino}methyl)-2-oxo-l,3-oxa-zolidin-3-yl]benzylcarbamate starting from Example 58: 20 MS (ESI): m/z (%) = 488 (M+Na, 23), 349 (100); HPLC (method 1): rt (%) = 4.51 (98.5). Example 93 25 terf-Butyl 4-[5-({[(5-chloro-2-thienyl)carbonyI]amino}methyI)-2-oxo-l,3-oxazoIi- din-3~yl]phenylcarbamate starting from Example 59: MS (ESI): m/z (%) = 493 (M+Na, 70), 452 (M+H, 10), 395 (100); HPLC (method 1): rt (%) = 4.41 (100). 30 Example 94 terf-Butyl 2-oxo-3-[4-(2-oxo.l-pyrrolidinyI)phenyI]-l,3-oxazoHdin-5-yl}methyl-carbamate 35 starting from Example 60: MS (DCI, NH3): m/z (%) = 393 (M+NH4,100); h^ HPLC (method 3); rt (%) = 3.97 (100). Example 95 5 5-Chloro-N-({3-[3-fluoro-4-(3-oxo-4-morphoIinyl)phenyl]-2-oxo-l,3-oxazolidin- 5-yl}methyI)-2-thiophenecarboxamide 10 260 mg (0.608 mmol) of 5-chloro-N-(3-{[3-fluoro-4-(3-oxo-4-morpholinyl)phenyl]- amino}-2hydroxypropyl)-2-thiophenecarboxamide (from Example 61), 197 mg (1.22 mmol) of carbonylimidazole and 7 mg of dimethylaminopyridine in 20 ml of dioxane are boiled under reflux for 5 hours. 20 ml of acetonitrile are then added, and the mixture is stirred in a closed vessel in a microwave oven at 180°C for 30 minutes. 15 The solution is concentrated using a rotary evaporator and chromatographed on an RP-HPLC column. This gives 53 mg (19% of theory) of the target compound. NMR (300 MHz, d6-DMSO): 5= 3.6-3.7 (m,4H), 3.85 (dd,lH), 3.95 (m,2H), 4.2 (m,lH), 4.21 (s,2H), 4.85 (m,lH), 4.18 (s,2H), 7.19 (d,lH,thiophene), 7.35 (dd,1H), 20 7.45 (t,lH), 7.55 (dd,lH), 7.67 (d,lH,thiophene), $.95 (t,lH,CONH). Example 96 5-Chloro-N-[(2-oxo-3.phenyI-l,3-oxazoIidin-5-y!)methyI]-2- 25 thiophenecarboxamide starting from Example 62: MS (ESI): m/z (%) = 359 ([M+Na]+, 71), 337 ([M+H)+, 100), Cl pattern; HPLC (method 3): rt (%) = 4.39 (100). IC50: 2 pM 30 Example 97 5-Chloro-N-({2-oxo-3-[4-(3-oxo-4-morpholmyl)phenyl]-l,3-oxa2olidin-5-yl}-methyI)-2-thiophenecarboxamide 5 starting from Example 63: MS (ESI): m/z (%) = 458 ([M+Na)+, 66), 436 ([M+H]+, 100), CI pattern; HPLC (method 3): rt (%) = 3.89 (100), IC50:1.4nM 10 Example 98 iV-[(3-{4+[Acetyl(cyclopropyl)amino]phenyl}-2-oxo-l,3-oxazolidm-5-yl)methyl]-5-chloro-2-thiophenecarboxamide)+de starting from Example 64: 15 MS (ESI): m/z (%) = 456 ([M+Na]+ ,55), 434 ([M+H]+, 100), CI pattern; HPLC (method 3): rt (%) = 4.05 (100). IC50: 50 nM Example 99 20 N-[(3-{4-[Acetyl(methyl)amino]phenyl}-2-oxo-l3.oxazolidin-5-yl)methyl]-5-chloro-2-thiophenecarboxamide MS (ESI): m/z (%) = 408 (M+H, 30), 449 (M+H+MeCN, 100); HPLC (method 4): rt - 3.66 min. 25 Example 100 S-ChIoro-N-({2-oxo-3-[4-(1H-l,2,3.triazol-l-yl)phenyl]-l,3-oxazoIidin-5-yl}-methyl)-2-thiophenecarboxamide 30 MS (ESI): m/z (%) = 404 (M+H, 45), 445 (M+H+MeCN, 100); HPLC (method 4): rt = 3.77 min. Example 101 35 Tert-butyl l-{4-[S-({[(5-chloro-2-thienyl)carbonyl]amino}methyl)-2-oxo-l-3- oxazoIidin-3-yl]phenyI}-L-prolinate MS (ESI): m/z (%) = 450 (M+H-56,25), 506 (M+H, 100); HPLC (method 4): rt = 5.13 min. Example 102 5 l-{4-[5-({[(5-Chloro-2-thienyl)carbonyl]amino}methyl)-2"Oxo-1,3-oxazolidin"3-yl]phenyI}-4-piperidinecarboxamide MS (ESI): m/z (%) = 463 (M+H, 100); HPLC (method 4): rt = 2.51 rain. 10 Example 103 l-{4-[5-({[(5-Chloro-2-thienyl)carbonyI]amino}methyl)-2-oxo-l,3-oxazolidin-3-yl]phenyl}-3-piperidinecarboxamide 15 MS (ESI): m/z (%) = 463 (M+H, 100); HPLC (method 4): rt = 2.67 min. Example 104 20 5-Chloro-N-({2-oxo-3-[4-(4-oxo-l-piperidinyI)phenyI]-l,3-oxazolidin-5- yI}methyI)-2-thiophenecarboxamide MS (ESI): m/z (%) = 434 (M+H, 40), 452 (M+H+H20, 100), 475 (M+H+MeCN, 60); HPLC (method 4): rt - 3.44 min. 25 Example 105 l-{4-[5-({[(5-Chloro-2-thienyl)carbonyI]amino}methyl)-2-oxo-l-3-oxazolidin-3-yl]phenyl}-L-prolinamide 30 MS (ESI): m/z (%) = 449 (M+H, 100); HPLC (method 4): rt = 3.54 min. Example 106 5-ChIoro-N-[(3-{4-[3-(hydroxymethyI)-l-piperidinyl]phenyI}-2-oxo-l;3-oxazoIi-din-5-yI)methyI]-2-thiophenecarboxamide 5 MS (ESI): m/z (%) = 450 (M+H, 100); HPLC (method 5): rt = 2,53 min. Example 107 10 5-Chloro-N-[(3-{4-[2-(hydroxymethyl)-l-piperidinyI]phenyl}-2-oxo-l?3-oxazoli- din-5-yI)methyl]-2-thiophenecarboxamide MS (ESI): m/z (%) = 450 (M+H, 100); HPLC (method 5): rt = 2.32 mm. 15 Example 108 Ethyl l-{4-[5-({[(5-chloro-2-thienyl)carbonyI]amino}methyl)-2-oxo-13-oxazoli-din-3-yl]phenyl}-2-piperidinecarboxylate MS (ESI): m/z (%) = 492 (M+H, 100); 20 HPLC (method 5): rt = 4.35 min. Example 109 5-Chloro-N.[(3-{4-[2-(hydroxymethyl)-l-pyrrolidmyl]phenyl}-2-oxo-l>3-oxazoli 25 dm-5-yl)methyI]-2-thiophenecarboxamide MS (ESI): m/z (%) = 436 (M+H, 100); HPLC (method 4): rt = 2.98 min. Example 110 30 5.Chloro-N-({2- oxo-3-[4-(l-pyrrolidinyl).3-(trifluoromethyl)phenyl]-l,3-oxazoli- din-5-yl}methyl)-2-thiophenecarboxamide MS (ESI): m/z (%) - 474 (M+H, 100); HPLC (method 4): rt = 4.63 min. Example lit 5-Chloro-N-({3-[4-(2-methylhexahydro-5H-pyrrolo[3,4-d]isoxazol-5-yl)phenyl3-2-oxo-l,3-oxazoIidin-5-yl}methyl)-2-thiophenecarboxamide 5 MS (ESI): m/z (%) = 463 (M+H, 100); HPLC (method 4): rt = 2.56 min. Example 112 10 5-Chloro-N-({2-oxo-3.[4-(2-oxo-l-pyrrolidinyl)-3-(trifiuoromethyl)phenyl]-1,3- oxazoIidm-5-yI}methyI)-2-thiophcnecarboxamide MS (ESI): m/z (%) = 488 (M+H, 100); HPLC (method 4): rt = 3.64 min. 15 Example 113 5-Chloro-N-({3-[3-chIoro-4-(3-oxo-4-morphoIinyl)phenyI]-2-oxo-1,3-oxazolidin-5-yl}methyI)-2-thiophenecarboxamide MS (ESI): m/z (%) = 470 (M+H, 100); 20 HPLC (method 4): rt = 3.41 min. Example 114 5-Chloro-N-({2-oxo-3-[4-(3-oxo-4-morphoIinyl)-3-(trifluoromethyI)phenyI]-l,3- 25 oxazolidin-5-yI}methyl)-2-thiophenecarboxamide MS (ESI): m/z (%) = 504 (M+H, 100); HPLC (method 4): rt = 3.55 min. Example 115 30 5-ChIoro-N-({3-[3-methyI-4-(3-oxo-4-morphoIinyl)phenyl]-2-oxo-lr3-oxazolidin-5-yI}methyl)"2-thiophenecarboxamide MS (ESI): m/z (%) = 450 (M+H, 100); HPLC (method 4): rt = 3.23 min. Example 116 5-ChIoro-N-({3-[3-cyano-4-(3-oxo-4"morpholinyl)phenyl]-2-oxo-lT3-oxazoU HPLC (method 4): rt = 3.27 min. Example 117 10 5-Chloro-N-({3-[3-chIoro-4-(l-pyrroHdinyI)pheayI]-2-oxo"l^-oxazolidin-5- yl}methyl)-2-thiophenecarboxamide MS (ESI): m/2 (%) = 440 (M+H, 100); HPLC (method 4): rt = 3.72 min. 15 Example 118 S-Chloro-N-({3-[3-chloro-4-(2-oxo*l-pyrroHdinyl)phetiyl]-2-oxo-l,3-oxazolidin-5-yI}methyI)-2"thiophenecarboxamide MS (ESI): m/z 20 HPLC (method 4): n = 3.49 min. Example 119 25 zolidin-5-yI}methyl)-2"thiophenecarboxamide MS (ESI): m/z (%) = 464 (M+H, 100); HPLC (method 4): rt = 3.39 min. Example 120 30 N-({3-[3-(Aminocarbonyl)-4-(4-morpholinyI)phenyI]-2-oxo-l,3-oxazoiidin-5-yl}methyI)-5-chIoro-2-thiophenecarboxamide MS (ESI); m/z (%) = 465 (M+H, 100); HPLC (method 4): rt - 3.07 min. Example 121 5-ChIoro-N-({3-[3-methoxy-4-(4-morphoIinyI)phenyl]-2-oxo-lr3-oxazolidin-5-yI}methyI)-2-thiophenecarboxamide 5 MS (ESI): m/z (%) = 452 (M+H, 100); HPLC (method 4): rt = 2.86 min. Example 122 10 N-({3-[3-Acety]-4-(4-morphoIinyl)phenyI]-2-oxo-l,3-oxa2oIidin-5-yI}methyl)-5- chloro-2-thiophenecarboxamide MS (ESI): m/z (%) = 464 (M+H, 100); HPLC (method 4): it = 3.52 min. 15 Example 123 N-({3-[3-Amino-4-(3-oxo-4-morpholinyl)phenyl]-2-oxo-1,3-oxazolidin-5-yI}-methyI)-5-chloro-2-thiophenecarboxamide MS (ESI): m/z (%) - 451 (M+H, 100); 20 HPLC (method 6): rt = 3.16 min. Example 124 5-Chloro-N-({3-[3-chIoro-4-(2-methyl-3-oxo-4-morphoIinyl)phenyl]"2-oxo-l,3- 25 oxazolidin-5-yI}methyl)-2-thiophenecarboxamide MS (ESI): m/z (%) = 484 (M+H, 100); HPLC (method 4): rt = 3.59 min. Example 125 30 5-ChIoro-N-({3-[3-chloro-4-(2-methyl-5-oxo-4-morphoIinyI)phenyl]-2-oxo-ly3-oxazolidin-5-yl}niethyl)-2-thiophenecarboxamide MS (ESI): m/z (%) = 484 (M+H, 100); HPLC (method 4): rt = 3.63 min. Example 125a S-Chloro-N-[(2-oxo-3-{4-[(3-oxo-4-morpholinyl)methyl]phenyl}-l,3-oxazolidin-5-yl)methyl]-2-thiophenecarboxamide 5 MS (ESI): m/z (%) = 450 (M+H, 100); HPLC (method 4): rt - 3.25 min. Via epoxide opening with an amine and subsequent cyclization to give the corresponding oxazolidinone, it was also possible to prepare the following 10 compounds: / / / / Examples 14 to 16 below are working examples for the optional oxidation step. Example 14 5 5-Chloro-N-({(SS)-3-[3-fluoro-4-(l-oxo-lDambda]4,4-thiazinan-4-yl)pheny»]-2- oxo-l^-oxazolidin-5-yI}methyl)-2-tMophenecarboxaniide F O n r~0=S N o 10 At 0°C, 5-chloro-N-({(5S)-3-[3-fluoro-4*Cl,4-thiazinan^-yl)phenyl]-2-oxo-l,3- oxazolidin-5~yl}methyI)-2-thiophenecarboxarnide (0.1 g, 0.22 mmol) from Example 3 in methanol (0.77 ml) is added to a solution of sodium periodate (0,05 g, 0.23 mmol) in water (0.54 ml), and the mixture is stirred at 0°C for 3 h. 1 ml of DMF is then added, and the mixture is stirred at RT for 8 h. After addition of a further 15 50 mg of sodium periodate, the mixture is once more stirred at RT overnight. The mixture is then admixed with 50 ml of water, and the insoluble product is filtered off with suction. Washing with water and drying gives 60 mg (58% of theory) of crystals. M.p.: 257°C; 20 Rf (silica gel, toluene/ethyl acetate 1:1)- 0.54 (starting material = 0.46); IC5o value =1.1pM: MS (DCl) 489 (M+NH4), CI pattern. Example 15 Preparation of5-chloro-N-({{5S)-3"[4-(l,l-dioxO"l[lambda]*,4-thiazinan-4-yl)-3- fluorophenyll^-oxo-l^-oxazolidin-S-ylJmethyD-Z-thiophenecarboxamide 5 F O O 5 -Choro-N -({(5S)-3-[3-fluoro-4-( l ,4-thiazrnan-4-yl)pheyl] -2-oxo-1,3-oxazolidin-5-yl}rnethyl)-2-thiophenecarboxamide from Example 3 (0.1 g, 0.22 mmol) in 3.32 ml 10 of a mixture of 1 part of water and 3 parts of acetone is admixed with 80 mg (0.66 mmol) of N-methylmorpholine N-oxide (NMO) and 0.1 ml of a 2.5% strength solution of osmium tetroxide in 2-methyl-2-propanOl. The mixture is stirred at room temperature overnight, and another 40 mg of NMO are added. The mixture is stirred for a further night and then poured into 50 ml of water and extracted three times with 15 ethyl acetate. The organic phase gives, after drying and concentrating, 23 mg and the aqueous phase, after removal of the insoluble solid by filtration with suction, 19 mg (in total 39% of theory) of the target compound. M.p.: 238°C; Rf (toluene/ethyl acetate 1:1) = 0.14 (starting material = 0.46); 20 1C50 value = 210 nM; MS (DO): 505 (M+NH4), CI pattern. Example 16 25 5-ChIoro-N-{[(5S)-3-(3-fluoro~4-morpholinophenyl)-2-oxo-l,3-oxazoIidin-5- yl]methyl}-2-thiophenecarboxamide N-oxide is obtained by treating 5-chloro-N-{[(5S)-3-(3-fluoro-4-morpholinophenyl)-2-oxo- l,3-oxazoIidin-5-y]]methyl}-2-thiophenecarboxarnide from Example 1 with the magnesium salt of monoperoxyphthalic acid. 30 MS (ESI): 456 (M+H, 21 %, CI pattern), 439 (100%). The Examples 31 to 35 and 140 to 147 below refer to the optional amidination step. General method for preparing amidines and amidine derivatives starting from 5 cyanomethylphenyl-substituted 5-chIoro-N-[(2-oxo-l,3-oxazoIidin-5-yl)methyl]- 2-thiophenecarboxamide derivatives The cyanomethylphenyl-substituted 5-chloro-N-[(2-oxo-l,3-oxazolidin-5-yl)methyl]- 2-thiophenecarboxamide derivative in question (1.0 eq.) is, together with 10 triethylamine (8.0 eq.), stirred at RT in a saturated solution of hydrogen sulphide in pyridine (about 0.05 - 0.1 mol/l) for one to two days. The reaction mixture is diluted with ethyl acetate (EtOAc) and washed with 2 N hydrochloric acid. The organic phase is dried with MgSO4, filtered and concentrated under reduced pressure. 15 The crude product is dissolved in acetone (0.01-0.1 mol/l) and admixed with methyl iodide (40 eq.). The reaction mixture is stirred at room temperature (RT) for 2 to 5 h and then concentrated under reduced pressure. The residue is dissolved in methanol (0.01-0.1 mol/l) and, to prepare the 20 unsubstituted amidines, admixed with ammonium acetate (3 eq.) and ammonium chloride (2 eq.). To prepare the substituted amidine derivatives, primary or secondary amines (l.5 eq.) and acetic acid (2 eq.) are added to the methanolic solution. After 5- 30 h, the solvent is removed under reduced pressure and the residue is purified by chromatography over an RP8 silica gel column (water/acetonitrile 9/1-1/1 + 0.1% 25 trifluoroacetic acid). The following compounds were prepared in an analogous manner: Example 31: 30 N-({3-[4-(2-Amino-2-iminoethyl)phenyl]-2-oxo-l,3-oxazolidin-5-yl}methy1)-5-cbloro-2-thiophenecarboxamide MS (ESI): m/z (%) = 393 (M+H, 100); HPLC (method 4): rt = 2.63 min 35 Le A M W-F^WFV Countries Example 32; 5-Chloro-N-({3-[3-(425-dihydro-lH-imidazol-2-yImethyl)phenyI]-2-oxo-1,3-oxazoIidin-5-yI}methyl)-2-thiophenecarboxamide 5 MS (ESI): m/z (%) - 419 (M+H, 100); HPLC (method 4): rt =2.61 min Example 33: 10 5-Chloro-N-t(3-{3-[2-imino-2-(4-raorpholinyl)ethyl]phenyI}-2-oxo-l,3-oxazoIi- din-5-yI)methyI]-2-thiophenecarboxamide MS (ESI): m/z (%) = 463 (M+H, 100); HPLC (method 4): rt - 2.70 min Example 34: S-Chloro-N-[(3-{3-[2-imino-2-(l-pyrroIidinyl)ethyl]phenyI}-2-oxo-l,3-oxazoIi-din-5-yl)methyl]-2-thiophenecarboxamide 20 MS (ESI): m/z (%) = 447 (M+H, 100); HPLC (method 4): rt = 2.82 min Example 35: 25 N-({3-[3-(2-Amino-2-iminoethyl)phenyl]-2-oxo-l;3-oxazolidin-5-yI}inethyl)-5- chloro-2-thiophenecarboxamide MS (ESI): m/z (%) = 393 (M+H, 100); HPLC (method 4): rt = 2.60 min 30 Example 140 5-Chloro-N-({3-[4-(4,5-dihydro-lH-imidazoI-2-ylmethyl)phenyl]-2-oxo-l,3-oxa-zolidin-5-yI}methyI)-2-thiophenecarboxamide MS (ESI): m/z (%) = 419 (M+H, 100); 35 HPLC (method 4): rt = 2.65 min Example 141 5-Chloro-N-[(3-{4-[2-imino-2-(4-morphoIinyI)ethyl]phenyl}-2-oxo-13-oxazoli. din-5-yI)methyI]-2-thiophenecarboxamide 5 MS (ESI): m/z (%) = 463 (M+H, 100); HPLC (method 4): it = 2,65 min Example 142 10 5-Chloro-N-[(3-{4-[2-imino-2-(l-piperidinyl)ethyl]phenyl}-2-oxo-l,3-oxazolidin- 5-yl)methyl]-2-thiophenecarboxamide MS (ESI): m/z (%) = 461 (M+H, 100); HPLC (method 4): rt = 2,83 min 15 Example 143 5-Chloro.N-[(3-{4-[2-imino-2-(l-pyrrolidinyl)ethyl]phenyI}-2-oxo-l,3-oxazoli-din-5-yl)methyl]-2-thiophenecarboxamide MS (ESI): m/z (%) = 447 (M+H, 100); 20 HPLC (method 4): rt = 2.76 min Example 144 5-Chloro-N-[(3-{4-[2-(cyclopentylamino)-2-iminoethyl]phenyl}-2-oxo-1,3-oxazo- 25 Iidin-5-yl)methyl]-2-thiophenecarboxamide MS (ESI): m/z (%) = 461 (M+H, 100); HPLC (method 4): rt = 2.89 min Example 145 30 5-ChIoro-N.{[3-(4-{2-imino-2.[(2,2,2-trifuoroethyI)amino]ethyl}phenyI)-2-oxo- l,3-oxazoIidin-5-yl]methyl}-2-thiophenecarboxamide MS (ESI): m/z (%) = 475 (M+H, 100); HPLC (method 4): rt = 2,79 min T^ A M 177-Frtn-iyn Cntmtnn Example 146 N-({3-[4-(2-Anilino-2-iminoethyI)phenyl]-2-oxo-l^-oxazoljdin-5-yl}methyl)-5-chloro-2-thiophenecarboxamide 5 MS (ESI): m/z (%) = 469 (M+H, 100); HPLC (method 4): rt = 2.83 min Example 147 10 5-Chloro-N- [(3-{4- [2-itnino-2-(2-py ridiny lamino)ethy l]pheny l}-2-oxo-1,3-oxa- zolidin-5-yl)mcthyl]-2-thiophenecarbox:amide MS (ESI): m/z (%) = 470 (M+H, 100); HPLC (method 4): rt = 2.84 min 15 Examples 148 to 151 below refer to the removal of BOC amino protective groups: General method for removing Boc protective groups (tert-butyloxycarbonyl): 20 Aqueous trifluoroacetic arid (TFA, about 90%) is added dropwise to an ice-cooled solution of a ferr-butyloxycarbonyl-(Boc) protected compound in chloroform or dichloromethane (about 0,1 to 0.3 mol/1). After about 15 min, ice-cooling is removed and the mixture is stirred at room temperature for approximately 2-3 h, and the 25 solution is then concentrated and dried under high vacuum. The residue is taken up in dichloromethane or dichloromethane/methanol and washed with saturated sodium bicarbonate or IN sodium hydroxide solution. The organic phase is washed with saturated sodium chloride solution, dried over a little magnesium sulphate and concentrated. If appropriate, purification is carried out by crystallization from ether 30 or ether/dichloromethane mixtures. The following compounds were prepared in an analogous manner from the corresponding Boc-protected precursors: Example 148 Ar-({3-[4-(Aminotnethyl)phenyI]-2-oxo-l^-oxazoIidin-5-yI}methyI)-5-chIoro-2-thiophene-carboxamide 5 starting from Example 92: MS (ESI): m/z (%) = 349 (M-NH2, 25), 305 (100); HPLC (method I); rt (%) = 3.68 (98). IC50: 22 fiU 10 Example 149 ^-{[S-t^AminophenylJ-I-oxo-l^-oxazolidin-S-ylJmethylJ-S-chloro-l-thiophenecarboxamide starting from Example 93: 15 MS (ESI): m/z (%) ~ 352 (M+H, 25); HPLC (method 1): rt (%) = 3.50 (100). IC50: 2 fiM An alternative enantiomerically pure synthesis of this compound is shown in the 20 scheme below (cf. also Delalande S.A., DE 2836305,1979; Chem.Abstr. 90, 186926): 1.) phthalimide, DEAD/PPh Example 150 5-Chloro-iVK{3-[4^glycyiamino)phenyl]-2-oxo-i^-oxa2oIidm-5-yl}inethyl)-2-thiophenecarboxamide 5 starting from Example 152: MS (ES-pos): m/z (%) = 408 (100); HPLC (method 3): rt (%) = 3.56 (97). IC50: 2 fiM 10 Example 151 5-(Aminomethyl)-3-[4-(2-oxo-l-pyrrolidinyl)ph^nyl]-13-oxazolidin-2-one starting from Example 60; MS (ESI): m/z (%) = 276 (M+H, 100); 15 HPLC (method 3): rt (%) = 2.99 (100). IC5o:2/iM The Examples 152 to 166 below refer to the amino group derivatizatjon of aniline- or benzylamine-substituted oxazolidinones using various reagents: 20 Example 152 5-Chloro-Ar-({3-[4-(N-te/t-butyIoxycarbonyl-glyi:yIamino)pheny]]-2-oxo-l,3-oxazolidm-5-yI}methyI)~2-thiophenecarboxamide 25 At 0°C, 754 mg (2.1 mmol) of JV-{[3-(4-aminophenyI)-2-oxo-l,3-oxazolidin-5- yl]methyI}-5-chloro-2-thiophenecarboxamide (from Example 149) are added to a 30 solution of 751 mg (4.3 mmol) of Boc-glycine, 870 mg (6.4 mmol) of HOBT (1-hydroxy-lH-benzotriazole x H20), 1790 mg (4.7 mmol) of HBTU [0-(benzotriazol-l-yl)-N,N,N",N"-tetramethyIuronium hexafluorophosphate] and 1.41 ml (12.9 mmol) of N-methylmorpholine in 15 ml of DMF/CH2C12 (1:1). The mixture is stirred at room temperature overnight and then diluted with water. The precipitated solid is filtered off and dried. Yield: $94 mg (79.7% of theory); MS (DCI, NH3): m/z (%) = 526 (M+NH4, 100); HPLC (method 3): rt (%) = 4.17 (97). Example 153 N-[(3"{4-[(AcetyIamino)methyI]phenyI}-2-oxo-1,3-oxazolidin-S-yl)methyl]-5-chIoro-2-thiophenecarboxamide 10 1U At O0C, a mixture of 30 mg (0.082 mmol) of N -({3-[4-(aminomethyl)phenyl]-2-oxo- l,3-oxazolidin-5-yl}methyl)-5-chloro-2-rhiophene-carboxamide (from Example 148) in 1.5 ml of absolute THF and 1.0 ml of absolute dichloromethane, and 0.02 ml of 15 absolute pyridine is mixed with acetic anhydride (0.015 ml, 0.164 mmol). The mixture is stirred at room temperature overnight. Addition of ether and crystallization affords the product. Yield: 30 mg (87% of theory), MS (ESI): m/z (%) = 408 (M+H, 18), 305 (85); HPLC (method 1): rt (%) = 3.78 (97). 20 IC50: 0.6 pM Example 154 25 methyl}-5-chIoro-2-thiophenecarboxamide - K At room temperature, 0.19 ml (0.82 mmol) of trimethylsilylisocyanate are added dropwise to a mixture of 30 mg (0.082 mmol) of iV-({3-[4-(aminomethyl)phenyl]-2- oxo-l,3-oxazolidin-5-yl }methyI)-5-chloro-2-thiophene-carboxamide (from Example 148) in 1.0 ml of dichloromethane. The mixture is stirred overnight and, after addition of ether, the product is then obtained by filtration. Yield: 21.1 mg (52% of theory), MS (ESI): m/z (%) = 409 (M+H, 5), 305 (72); HPLC (method 1): rt (%) = 3.67 (83). 10 IC50:1-3/AM General method for acylating Ar-{[3-(4-aminophenyl)-2-oxo-l,3-oxazolidin-S-yl]methyl}-5-chloro-2-thiophenecarboxamJde with carbony) chlorides: ^ _ .. .. -CI tr Under argon, an approximately 0.1 molar solution of N-{[3-(4-aminophenyl)-2-oxo- 15 l,3-oxazolidin-5-y]]methyI}-5-chloro-2-thiophenecarboxamide (from Example 149) (1.0 eq.) in absolute dichloromethane/pyridine (19:1) is added dropwise to the appropriate acid chloride (2.5 eq,). The mixture is stirred overnight and then admixed with about 5 eq. of PS trisamine (Argonaut Technologies) and 2 ml of absolute dichloromethane. The mixture is stirred gently for 1 h and then filtered off, and the 20 filtrate is concentrated. If appropriate, the products are purified by preparative RP- HPLC. The following compounds were prepared in an analogous manner: 25 Example 155 N-({3-[4-(AcetyIamino)phenyl]-2-oxo-1,3-oxazolidin-5--yl}methyl)-5-chloro-2-thiophene-carboxamide LC-MS: m/z (%) = 394 (M+H, 100); LC-MS (method 6): rt (%) = 3.25 (100). IC50: 1.2 pM Example 156 5 5-ChIoro-N-[(2-oxo-3-{4-[(2-thienylcarbonyl)amino]phenyI}-l,3-oxazolidin-5-yl)methyl] -2-thiophenecarboxamide LC-MS: m/z (%) = 462 (M+H, 100); LC-MS (method 6): rt (%) = 3.87 (100). 10 IC50: 1.3 pM Example 157 5-Chloro-N-[(3-{4-[(methoxyacetyl)amino]phenyl}-2-oxo-l,3-oxazolidin-5-yI)- 15 methyI]-2-thiophenecarboxamide LC-MS: m/z (%) = 424 (M+H, 100); LC-MS (method 6): rt (%) = 3.39 (100). IC5o:0.73pM 20 Example 158 N-{4.[5-({[(5-Chloro-2-thienyl)carbonyl]amino}methyI)-2-oxo-l,3oxazolidin-3-yl]phenyl}-3,5-dimethyl-4-isoxazolecarboxamide LC-MS: m/z (%) - 475 (M+H, 100). 25 IC50: 0.46pM Example 159 5-Chloro-Af-{[3-(4-{[(3-chIoropropyl)suIphonyl]amino}phenyl)-2-oxo-1,3- 30 oxazolidin-5-yl]methyl}-2-thiophenecarboxamide O An ice-cooled solution of 26.4 mg (0.15 mmol) of 3-chloro-l-propanesulphonyI chloride and 0.03 ml (0.2 mmol) of triethylamine in 3.5 ml of absolute dichloro- methane is admixed with 35 mg (0.1 mmol) of A^[3-(4-arninophenyI)-2-oxo-l,3- oxazoHdin-5-yl]-niethyl}-5-chloro-2-thiophene-carboxamide (from Example 149). 5 After 30 min, ice-cooling is removed and the mixture is stirred at room temperature overnight, and 150 mg (about 5.5 eq.) of PS-trisamme (Argonaut Technologies) and 0.5 ml of dichloromethane are then added. The suspension is stirred gently for 2 h and filtered (the resin is washed with dichloromethane/methanol), and the filtrate is concentrated. The product is purified by preparative RP-HPLC. Yield: 19.6 mg (40% 10 of theory), LC-MS; m/z (%) - 492 (M+H, 100); LC-MS (method 5): it (%) = 3.82 (91). 15 Example 160 5-Chloro-A^-({3-[4-(l,l-dioxido-2-isothia2oIidinyl)phenyI]-2-oxo-l,3-OxazoIidin-5-yl}methyI)-2-thiophenecarboxamide 20 A mixture of 13.5 mg (0.027 mmol) of 5-chloro-N-{(3-(4-{[(3-chloropropyl)sul-phonyl]amino}phenyl)-2-oxo-l,3-oxazolidin-5-yl]methyl}-2-thiophene-carboxamide (from Example 159) and 7.6 mg (0.055 mmol) of potassium carbonate in 0.2 ml of 25 DMF is heated at 100°C for 2 h. After cooling, the mixture is diluted with, dichloromethane and washed with water. The organic phase is dried and concentrated. The residue is purified by preparative thin-layer chromatography (silica gel, dichloromethane/methanol, 95:5). Yield: 1.8 mg (14.4% of theory), MS (ESI): m/z (%) = 456 (M+H, 15), 412 (100); 30 LC-MS (method 4): it (%) = 3.81 (90). IC50: 0.14 pM Example 161 5-Chloro-N-t((5S)-3-{4-[(5-chloropentanoyi)amino]phenyl}-2-oxo-l,3-oxazoli-din-5-yl)methyl]-2-thiophenecarboxamide CI 0 5 0.5 g (1.29 mmol) of N-{[(5S)-3-(4-aminophenyl)-2-oxo-l,3-oxazoIidin-5- yI]methyl}-5-chloro-2-thiophenecarboxamide (from Example 149) is dissolved in 10 27 ml of tetrahydrofuran and admixed with 0.2 g (1.29 mmol) of 5-chlorovaleryl chloride and 0,395 ml (2.83 mmol) of triethylamine. The mixture is concentrated under reduced pressure and chromatographed over silica gel using a toluene/ethyl acetate=l:l -> ethyl acetate gradient. This gives 315 mg (52% of theory) of a solid. M.p.:211°C. 15 Example 162 5-Chloro-N-({(SS)-2-oxo-3-[4-(2-oxo-l-piperidinyI)phenyl]-l,3-oxazolidin-5.yl}. methyl)-2-thiophenecarboxamide 20 Under inert conditions, 5 ml of DMSO are admixed with 30 mg of NaH (60% in paraffin oil), and the mixture is heated at 75°C for 30 min, until the evolution of gas 25 has ceased, A solution of 290 mg (0.617 mmol) of 5-chloro-N-[((5S)-3-{4-[(5- chloropentanoyl)amino]phenyl}-2-oxo-l,3-oxa2olidin-5-yl)methyl]-2-thiophene-carboxamide (from Example 161) in 5 ml of methylene chloride is then added dropwise, and the mixture is stirred at room temperature overnight. The reaction is terminated and the mixture is poured into 100 ml of water and extracted with ethyl 109 acetate. The evaporated organic phase is chromatographed on an RP-8 column and the product is eluted with acetonitrile/water. This gives 20 mg (7.5% of theory) of the target compound. M,p.: 205°C; NMR (300 MHz, d6-DMSO): 5= 1.85 (m,4H), 2.35 (m,2H), 3.58 (m,4H), 3.85 (m,lH), 4.2 (t,lH), 4.82 (m,lH), 7.18 (d,lH,thiophene), 7.26 (d,2H), 7.5 (d,2H), 2.68 (d,lH,thiophene), 9.0 (t,lH,CONH). IC50: 2.8 nM 10 Example 163 5-ChIoro-N-[((5S)-3-{4-[(3-bromopropionyl)amino]phenyI}-2-oxo-l,3-oxazoli-din-5-yl)methyi}-2-thiophenecarboxamide 15 is obtained in an analogous manner from Example 149. Example 164 20 5-ChIoro-N-({(5S).2-oxo-3-[4-(2-oxo-l-.azetidinyl)phenyI]-1,3-oxazolidin-5-yl}- methyI)-2-thiophenecarboxamide 25 is obtained in an analogous manner by cyclization of the open-chain bromopropionyl compound from Example 163 using NaH/DMSO. MS (ESI): m/z (%) = 406 ([M+H]+, 100), CI pattern. 1C50: 380 nM Example 165 tert-Butyl 4-{4-[5-({[(5-chIoro-2-thienyI)carbonyllainino}methyl)-2-oxo-l,3-oxa-zolidin-3-yI]phenyl}-3,5-dioxo-l-piperazinecarboxylate A solution of 199 mg (0.85 mmol) of Boc-iminodi acetic acid, 300 mg (2.2 mmol) of HOBT, 0.66 ml (6 mmol) of N-methylmorphoIine and 647 mg (1.7 mmol) of HBTU 10 is admixed with 300 mg (0.S5 mmol) of N-[3-(4-aminophenyI)-2-oxo-l,3- oxazolidin-5-yl]-methyl }-5-chloro-2-thiophene-carboxamide in 6 ml of a mixture of DMF and dichloromethane (1:1). The mixture is stirred overnight, diluted with dichloromethane and then washed with water, saturated ammonium chloride solution, saturated sodium bicarbonate solution, water and saturated sodium chloride 15 solution. The organic phase is dried over magnesium sulphate and concentrated. The crude product is purified by silica gel chromatography (dichloromethane/methanol 98:2). Yield: 134 mg (29% of theory); MS (ESI): m/z (%) = 571 (M+Na, 82), 493 (100); HPLC (method 3): rt (%) - 4.39 (90). 20 IC50: 2 pM Example 166 N-[((5S)-3-{4-[(3R)-3-Amino-2-oxo-l-pyrToIidinyI]pheny!}-2-oxo-l,3-oxazolidin- 25 5-yI)methyI]-5-chloro-2-thiophepecarboxamide trifluoroacetate O BOCNH^COOH .g^^Cl s^ EDC, DIEA CH- r/9 L HOBT N2-(tert-Butoxycarbonyl)-Nl-{4-[(5S)-5-({[(5-chloro-2-thienyl)carbonyl]amino} 5 methyl)-2-oxo-l,3-oxazolidin-3-yl]phenyl}-D-methionineamide 429 mg (1.72 mmol) of N-BOC-D-methionine, 605 mg (1.72 mmol) of N^[(5S)-3-(4-aminophen yl)-2-oxo-1,3 -oxazol idin-5-yl]methyl) -5-ch loro-2-thiophenecarbox-amide, and 527 mg (3.44 mmol) of HOBT hydrate are dissolved in 35 ml of DMF 10 and admixed with 660 mg (3-441 mmol) of EDCI hydrochloride and then dropwise with 689 mg (5.334 mmol) of N-ethyl-diisopropylamine. The mixture is stirred at room temperature for two days. The resulting suspension is filtered off with suction and the residue is washed with DMF. The combined filtrates are admixed with a little silica gel, concentrated under reduced pressure and chromatographed over silica gel 15 using a toluene -> T10EA7 gradient. This gives 170 mg (17% of theory) of the target compound of melting point 183°C. Rf (Si02, toluene/ethyl acetate=l:l):0.2. }H-NMR (300 MHz. d6-DMSO): (s,lH,BOC), 1.88-1.95 (m,2H), 2.08 (s,3H,SMe), 2.4-2.5 (m,2H, partially obscurbed by DMSO), 3.6 (m,2H), 3.8 (m,lH), 20 4.15 (m,2H), 4.8 (m7lH), 7.2 (1H, thiophene), 7.42 (d, part of an AB system, 2H), 7.6 (d, part of an AB system, 2H), 7,7 (d, 1H, thiophene), 8.95 (t,lH, CH2NHCO), 9.93 (bs,lH,NH). tert-Butyl (3R)-l.{4-[(5S)-5-({[(5-chIoro-2-thieiiyI)carbonyI]aniino}methyi)-2-oxo-1,3-oxazoIidin-3-yl]pheny l}-2-oxo-3-pyrroIidinylcarbamate 170 mg (0.292 mmol) of N2-(tert-butoxycarbonyl)-Nl-{4-[(S$)-5-({[(5-chloro-2- 5 thienyl)carbony]] amino }methyl)-2-oxo~l ,3-oxazolidin-3-yl]phenyl }-D-methionine- amide are dissolved in 2 ml of DMSO and admixed with 178.5 mg (0.875 mmol) of trimethylsulphonium iodide and 60.4 mg (0.437 mmol) of potassium carbonate, and the mixture is stirred at 80°C for 3.5 hours. The mixture is then concentrated under high vacuum and the residue is washed with ethanol. 99 mg of the target compound 10 remain. }H-NMR (300 MHz, d6*DMSO): 6 =1.4 (s,lH,BOC), 1.88-2.05 (m,lH), 23-2.4 (m,lH), 3.7-3.8 (m,3H), 3.8-3.9 (m,lH), 4.1-4.25 (m,lH), 4.25-4.45 (m,lH), 4.75-4.95 (m,lH), 7.15 (1H, thiophene), 7.25 (d,lH), 7.52 (d, part of an AB system, 2H), 7.65 (d, part of an AB system, 2H), 7.65 (d, 1H, thiophene), 9.0 (broad s,lH). 15 N-[((5S)-3-{4-t(3R)-3-Aminio-2-oxo-l-pyrroIidinyI]phenyl}-2-oxo-l,3-oxazoUdm-5-y l)methyl] -S-chloro-2-thiophenecarboxamide trifluoroacetate 97 mg (0.181 mmol) of tert-butyl (3R)-l-{4-[(5S)-5-({[(5-chloro-2- 20 thienyl)carbonyl]amino}methyl)-2-oxo-l,3-oxazolidin-3-yI]phenyl}-2-oxo-3-pyrroli- dinylcarbamate are suspended in 4 ml of methylene chloride, 1.5 ml of trifluoroacetic acid are added and the mixture is stirred at room temperature for 1 hour. The mixture is then concentrated under reduced pressure and the residue is purified on an RP- HPLC (acetonitrile/water/0.1% TFA gradient). Evaporation of the appropriate 25 fraction gives 29 mg (37% of theory) of the target compound of melting point 241 °C (decomp.). Rf (Si02,EtOH/TEA=17:l) 0.19. ]H-NMR (300 MHz, d6-DMSO): =1.92-2.2 (m,lH), 2.4-2.55 (m,lH, partially. obscured by DMSO peak), 3.55-3.65 (m,2H), 3.75-3.95 (m,3H), 4.1-4.3 (m,2H), 30 4.75-4.9 (m,lH), 7.2 (1H, thiophene), 7.58 (d, part of an AB system, 2H), 7.7 (d, part of an AB system, 2H), 7.68 (d, 1H, thiophene), 8.4 (broad s,3H, NIB), 8.9 (t,lH,NHCO). The Examples 167 to 170 below refer to the introduction of sulphonamide groups in phenyl-substituted oxazolidinones: General method for preparing substituted sulphonamides starting from 5 5-chIoro-N-[(2-oxo-3-phenyI-1,3-oxazolidin-5-yl)methyl]-2- thiophenecarboxamide 10 Under argon and at 5°C, 5-chloro-N-[(2-oxo-"3-phenyl-l,3-oxa2olidin-5-yl)methyl]-2- thiophenecarboxamide (from Example 96) is added to chlorosulphonic acid (12 eq.). The reaction mixture is stirred at room temperature for 2 h and then poured into ice-water. The resulting precipitate is filtered off, washed with water and dried. 15 Under argon and at room temperature, the precipitate is then dissolved in tetrahydrofuran (0.1 mol/1) and admixed with the appropriate amine (3 eq.), triethylamine (1.1 eq.) and dimethylaminopyridine (0.1 eq.). The reaction mixture is stirred for 1-2 h and then concentrated under reduced pressure. The desired product is purified by flash chromatography (dichloromethane/methanol mixtures). . 20 The following compounds were prepared in an analogous manner: Example 167 25 5-Chloro-N-({2-oxo.3-[4- MS (ESI): m/2 (%) = 492 ([M+Na]+, 100), 470 ([M+H]+, 68), CI pattern; 114 10 HPLC (method 3): rt (%) = 4.34 (100). IC50: 0.5 pM Example 168 5-ChIoro-N-[(3-{4-[(4-methyl-1-piperazinyI)sulphonyI]phenyl}-2-oxo-l,3-oxa-zolidin-5-yI)methyI]-2-thiaphenecarboxamide MS (ESI): m/z (%) = 499 ([M+H]+, 100), CI pattern; HPLC (method 2); rt (%) = 3.3 (100). Example 169 5-Chloro-N-({2-oxo-3-[4-(l-piperidinylsuIphonyl)phenyl]-l,3-oxazolidin-5-yI}-methyl)-2-thiophcnecarboxamide 15 MS (ESI): m/z (%) = 484 ([M+H]+, 100), Cl pattern; HPLC (method 2): it {%) = 4.4 (100). Example 170 20 5-Chloro-N-[(3-{4-[(4-hydroxy-l-piperidinyl)sulphonyl]phenyI}-2-oxo-l,3-oxa- zoUdin-5-yl)methyl]»2-thiophenecarboxamide MS (ESI): m/z (%) = 500 ([M+H]+, 100), Cl pattern; HPLC (method 3): rt (%) = 3.9 (100). 25 Example 171 5-Chloro-N-({2-oxo-3-[4-(l-pyrrolidinyl)phenyl]-l,3-oxa2oIidin-5-yl)methyl)-2-thiophenecarboxamide H N H,CT;CH, 30 780 mg (1.54 mmol) of tert-butyl l-{4-[5-({[(5-chIoro-2-thienyl)carbonyl]amino}- methyl)-2-oxo-l,3-oxazohdin-3-yl]phenyl}prolinate are dissolved in 6 ml of dichloromethane and 9 ml of trifluoroacetic acid, and the mixture is stirred at 40°C 5 for two days. The reaction mixture is then concentrated and stirred with ether and 2N aqueous sodium hydroxide solution. The aqueous phase is concentrated and stin-ed with ether and 2N hydrochloric acid. The organic phase of this extraction is dried over MgS04, filtered and concentrated. The crude product is chromatographed over silica gel (CH2Cl2/EtOH/conc. aqu. NH3 sol. = 100/1/0.1 to 20/1/0.1). 10 This gives 280 mg (40% of theory) of the product. MS (ESI): m/z (%) = 406 (M+H, 100); HPLC (method 4): rt = 3.81 min. HPLC parameter and LC-MS parameter for the HPLC and LC-MS data given in the 15 examples above (the unit of the retention time (rt) is minutes): [1] Column; Kromasil C18, L-R temperature: 30°C, flow rate = 0.75 ml min-1, eluent: A = 0-01 M HC104, B = CH3CN, gradient: -> 0.5 min 98%A -> 4.5 min 10%A ->6.5 min 10%A 20 [2] Column: Kromasil C18 60*2, L-R temperature: 30oC, flow rate = 0.75 ml min"-1, eluent: A = 0.01 M H3P04, B = CH3CN, gradient: -> 0.5 min 90%A -> 4,5 min 10%A ->6.5 min 10%A 25 [3] Column: Kromasil C18 60*2, L-R temperature: 30°C, flow rate = 0.75 ml min-1, eluent: A = 0.005 M HC104, B = CH3CN, gradient: -> 0.5 min 98%A -> 4.5 min 10%A ->6.5 min 10%A [4] Column: Symmetry C18 2.1x150 mm, column oven: 50°C, flow rate = 30 0.6 ml min"1, eluent: A = 0.6 g 30% strength HC1/ 1 of water, B = CH3CN, gradient: 0.0 min 90%A -> 4.0 min 10%A ->9 min 10%A /■ / / / 116 / f [5] MHZ-2Q, Instrument Micromass Quattro LCZ Column Symmetry C18, 50 mm x 2.1 mm, 3.5 pm, temperature: 40°C, flow rate = 0.5 ml min-1, eluent A = CH3CN + 0.1% formic acid, eluent B = water + 0.1% formic 5 acid, gradient: 0.0 min 10% A -> 4 min 90% A -> 6 min 90% A [6] MH2-2P, Instrument Micromass Platform LCZ Column Symmetry C18, 50 mm x 2.1 mm, 3.5 pm, temperature: 40°C, flow rate = 0.5 ml min-1, eluent A - CH3CN + 0.1% formic acid, eluent B = water + 0.1% formic 10 acid, gradient: 0.0 min 10% A -> 4 min 90% A -> 6 min 90% A [7] MHZ-7Q, Instrument Micromass Quattro LCZ Column Symmetry C18, 50 mm x 2.1 mm, 3.5 pm, temperature: 40°C, flow rate = 0.5 ml min"1, eluent A = CH3CN + 0,1% formic acid, eluent B = water + 0.1% formic 15 acid, gradient: 0.0 min 5% A -> 1 min 5% A -> 5 min 90% A -> 6 min 90% A General method for preparing oxazolidinones of the general formula B by solid-phase-supported synthesis 20 Reactions with different resin-bonded products were carried out in a set of separated reaction vessels. 5-(Bromomethyl)-3-(4-fluoro-3-nitrophenyl)-l,3-oxazolidin-2-one A (prepared from epibromohydrin and 4-fluoro-3-nitrophenyl isocyanate using LiBr/Bu3PO in xylene 25 analogously to US 4128654, Ex.2) (1.20 g, 3.75 mmol) and ethyldiisopropylamine (DIEA, 1.91 ml, 4.13 mmol) were dissolved in DMSO (70 ml), admixed with a secondary amine (1.1 eq., amine component 1) and reacted at 55°C for 5 h. TentaGel SAM resin (5.00 g, 0,25 mmol/g) was added to this solution, and the mixture was reacted at 75°C for 48 h. The resin was filtered, washed repeatedly with methanol 30 (MeOH), dimethylformamide (DMF), MeOH, dichloromethane (DCM) and diethyl ether and dried. The resin (5.00 g) was suspended in dichloromethane (80 ml), admixed with DIEA (10 eq.) and 5-chlorothiophene-2-carbonyl chloride [prepared by reacting 5-chlorothiophene-2-carboxyIic acid (5 eq,) and l-chloro-l-dimethylamino-2-methylpropene (5 eq.) in DCM (20 ml) at room temperature for 15 minutes] and 35 the mixture was reacted at room temperature for 5 h. The resulting resin was filtered, washed repeatedly with MeOH, DCM and diethyl ether and dried. The resin was then 117 suspended in DMF/water (v/v 9:2, 80 ml), admixed with SnCl2*2H20 (5 eq.) and reacted at room temperture for 18 h. The resin was washed repeatedly with MeOH, DMF, water, MeOH, DCM and diethyl ether and dried. This resin was suspended in DCM, admixed with DIEA (10 eq.) and, at 0°C, with an acid chloride (5 eq. of acid 5 derivative 1), and the mixture was reacted at room temperature overnight. Prior to the reaction, carboxylic acids were converted into the corresponding acid chlorides by reaction with l-dimethylamino-l-chloro-2-methylpropene (1 eq„ based on the carboxylic acid) in DCM at room temperature for 15 min. The resin was washed repeatedly with DMF, water, DMF, MeOH, DCM and diethyl ether and dried. If the 10 acid derivative 1 used was an Fmoc-protected amino acid, the Fmoc protective group was removed in the last reaction step by reaction with piperidine/DMF (v/v, 1/4) at room temperature for 15 minutes, and the resin was washed with DMF, MeOH, DCM and diethyl ether and dried. The products were then removed from the solid phase using trifluoroacetic acid (TFA)/DCM (v/v, 1/1), the resin was filtered off and 15 the reaction solutions were concentrated. The crude products were filtered over silica gel (DCM/MeOH, 9:1) and evaporated, giving a set of products B. 2 TentaGelSAM" "TentaGelSAM oHr° -PA - "1>V_A o .s 5 Compounds which were prepared by solid-phase-supported synthesis: Example 172 N-({3-[3-Amino-4-(l-pyrrolidinyl)phenyl]-2-oxo-l,3-oxazolidin-5-yI}metbyl)-5- 10 chloro-2-thiophenecatboxamide Analogously to the general procedure for preparing the derivatives B, 5 g 15 (1.25 mmol) of TentaGel SAM resin were reacted with pyrrolidine as amine derivative 1. The aniline obtained after reduction with SnCL2*2H20 was, without any further acylarion step, removed from the solid phase and concentrated. The crude product was partitioned between ethyl acetate and NaHC03 solution and the organic phase was salted out using NaCl, decanted and evaporated to dryness. This crude product was purified by vacuum flash chromatography over silica gel (dichloro-methane/ethyl acetate, 3:1- 1:2). ]H-NMR (300 MHz, CX>C13): 1.95 - 2.08, br, 4 H; 3.15-3.30, br, 4 H; 3.65-3.81, m, 2 H; 3.89, ddd, 1H; 4.05, dd, 1 H; 4.81, dddd, 1 H; 6.46, dd, 1 H; 6.72, dd, 1 H; 6.90, 5 dd, 1 H; 6.99, dd, 1 H; 7.03, dd, 1 H; 7.29, d, 1 H, Example 173 N-[(3-{3-(B-Alanylamino)-4-t(3-hydroxypropyl)amino]phenyl}-2-oxo-l,3-oxa- 10 zoIidin-5-y))methyl]-5-chloro-2-thiophenecar boxamide Analogously to the general procedure for preparing the derivatives B, 5 g 15 (1.25 mmol) of TentaGel SAM resin were reacted with azetidine as amine derivative 1 and Fmoc-B-alanine as acid derivative 1. The crude product obtained after the removal was stirred in methanol at room temperature for 48 h and evaporated to dryness. This crude product was purified by reversed phase HPLC using a water/TFA/acetonitrile gradient. 20 "H-NMR (400 MHz, CD3OD): 2.31, tt, 2 H; 3.36, t, 2 H; 3.54, t, 2 H; 3.62, t, 2 H; 3.72, dd, 1 H; 3.79, dd, 1 H; 4.01, dd, 1 H; 4.29, dd, 2 H; 4.43, t, 2 H; 4.85-4,.95, m, 1 H; 7.01, d, 1 H; 4.48 - 7.55, m, 2 H; 7.61, d, 1 H; 7.84, d, 1 H. 25 Example 174 N-({3-[4-(3-Amino-l-pyrrolidinyl)-3-nitrophenyl]-2-oxo-l,3-oxazolidin-5-yl}-methyl)-5-chloro-2-thiophenecarboxamide NO. Q S-/ 10 Analogously to the general procedure for preparing the derivatives B, 130 mg (32.5 p.mol) of TentaGel SAM resin were reacted with tert-butyl 3-pyrrolidinylcarbamate as amine derivative 1. The nitrobenzene derivative obtained after the acylation with 5-chlorothiophenecarboxylic acid was removed from the solid phase and concentrated. This crude product was purified by reversed phase HPLC using a water/TFA/acetonitrile gradient. "H-NMR (400 MHz, CD3OH): 2.07-2.17, m, 1 H; 2.39-2.49, m, 1 H; 3.21-3.40, m, 2 H; 3.45, dd, 1 H; 3.50-3.60, m, 1 H; 3.67, dd, 1 H; 3.76, dd, 1 H; 3.88-4.00, m, 2 H; 4.14 - 4.21, t, 1 H; 4.85 - 4.95, m, 1 H; 7.01, d, 1 H; 7,11, d, 1 H; 7.52, d, 1 H; 7.66, dd, 1 H; 7.93, d, 1 H. 15 Example 175 N-({3-[3-Amino-4-(l-piperidinyI)phenyI]-2-oxo-l,3-oxazolidin-5-yI}methyI>5-chloro-2-thiophenecarboxamide 20 25 Analogously to the general procedure for preparing the derivatives B, 130 mg (32.5 pmol) of TentaGel SAM resin were reacted with piperidine as amine. derivative 1. The aniline obtained after the reduction was, without any further acylation step, removed from the solid phase and concentrated. This crude product was purified by reversed phase HPLC using a water/TFA/acetonitrile gradient. "H-NMR (400 MHz, CD3OH): 1.65-1.75, m, 2 H; 1.84-1.95, m, 4 H; 3.20-3.28, m, 4 H; 3.68, dd, 1 H; 3.73, dd, 1H; 3.90, dd, 1 H; 4.17, dd, 1 H; 4.80-4.90, m, 1 H; 7.00, d, 1 H; 7.05, dd, 1 H; 7.30-7.38, m, 2H; 7.50, d, 1 H. Example 176 N-({3-[3-(Acetylamino)-4-(l-pyrrolidinyI)phenyI]-2-oxo-l^-oxazoIidin-5-y|}-methyl)-5-chlorO"2-thiophenecarboxamide 5 Analogously to the general procedure for preparing the derivatives B, 130 mg (32.5 pmol) of TentaGel SAM resin were reacted pyrrolidine as amine derivative 1 10 and acetyl chloride as acid derivative 1. The crude product was partitioned between ethyl acetate NaHCO3 solution and the organic phase was salted out using NaCl, decanted and evaporated to dryness. This crude product was purified by vacuum flash chromatography over silica gel (dichloromethane/ethyl acetate, 1:1-0:1). "H-NMR (400 MHz, CD3OH): 1.93 - 2.03, br, 4 H; 2.16, s, 3 H; 3.20-3.30, br, 4 H; 15 3.70, d, 2 H; 3.86, dd, 1H; 4.10, dd, 1 H; 4.14, dd, 1 H; 4.80^.90, m, I H; 7.00, d, 1 H; 7.07, d, 1 H; 7.31, dd, 1 H; 7.51, d, 1 H; 7.60, d, 1 H. The following compounds were prepared analogously to the general procedure. WE CLAIM: 1. Oxazolidinones of the general formula (I) in which: R1 represents 2-thiophene which is substituted in the 5-position by a radical from the group consisting of chlorine, bromine, methyl and trifluoromethyl, R2 represents D-A-: where: the radical "A" represents phenylene; the radical "D" represents a saturated 5- or 6-membered heterocycle, which is attached to "A" via a nitrogen atom, which has a carbonyl group directly adjacent to the linking nitrogen atom and in which one carbon ring member may be replaced by a heteroatom from the group consisting of S, N and 0; where the group "A" defined above may optionally be mono- or disubstituted in the meta position with respect to the point of attachment to the oxazolidinone, by a radical from the group consisting of fluorine, chlorine, nitro, amino, trifluoromethyl, methyl and cyano, R3, R4, R5, R6, R7 and R8 each represent hydrogen 137 and their pharmaceuticaliy acceptable salts, hydrates, hydrates of salts of the kind such as herein described. 2. Oxazolidinones as claimed in Claim 1 having the following formula and its pharmaceuticaliy acceptable salts, hydrates, hydrates of salts cf the kind such as herein described. 3. Process for preparing substituted oxazolidinones as claimed in Claim 1, where either according to a process alternative [A] compounds of the general formula (II) R T \ p6 in which the radicals R2, R3, R4, R5, R6 and R 7 are each as defined in Claim 1 are reacted with carboxylic acids of the general formula (III) 138 in which the radical R1 is as defined in Claim 1, or else with the corresponding carbonyl halides, preferably carbonyl chlorides, or else with the corresponding symmetric or mixed carboxylic anhydrides of the carboxylic acids of the general formula (III) defined above in inert solvents of the kind such as herein described, if appropriate in the presence of an activating or coupling agent and/or a base of the kind such as herein described, to give compounds of the general formula (I) (I), in which the radicals R1, R2, R3, R4, R5, R6, R7 and R8 are each as defined in Claim 1, or else according to a process alternative [B] compounds of the general formula (IV) r,5 J.S in which the radicals R1, R3, R«, R5j R6? R7 and RS as defined in Claim 1, are converted, using a suitable selective oxidizing agent of the kind such as herein described in an inert solvent of the kind such as herein described, into the corresponding epoxide of the general formula (V) in which the radicals R1, R3, R4 R5, R6,R7 and R8 are each as defined in Claim 1, and, by reaction in an inert solvent of the kind such as herein described, if appropriate in the presence of a catalyst of the kind such as herein described, with an amine of the general formula (VI) R2-NH2 (VI), in which the radical R2 is as defined in Claim 1, the compounds of the general formula (VII) in which the radicals R1, R2, R3, R4, R5, R6, R7 and R8are each as defined in Claim 1, 140 are initially prepared and, subsequently, in an inert solvent of the kind such as herein described in the presence of phosgene or phosgene equivalents, such as, for example, carbonyldiimidazole (CDI), cyclized to give the compounds of the general formula [\) (I), in which the radicals R1, R2, R3, R4, R5, R6, R7 and R8are each as defined in Claim 1. 4. Medicaments, comprising at least one compound as defined in Claim 1 or 2 in a concentration of from 0.1 to 95% by weight of the total mixture and one or more pharmacologically acceptable auxiliaries or excipients of the kind such as herein described. Dated this 11th day of June, 2002. (RANJNA MEHTA-DUTT) OF REMFRY & SAGAR ATTORNEY FOR THE APPLICANTS 141 |
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IN-PCT-2002-00763-MUM-OTHER DOCUMENT(19-7-2011).pdf
in-pct-2002-00763-mum-petition under rule 137(13-8-2007).pdf
in-pct-2002-00763-mum-petition under rule 138(13-8-2007).pdf
in-pct-2002-00763-mum-power of attorney(13-8-2007).pdf
in-pct-2002-00763-mum-power of attorney(23-7-2004).pdf
IN-PCT-2002-00763-MUM-POWER OF ATTORNEY(30-9-2011).pdf
Patent Number | 211300 | |||||||||||||||||||||
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Indian Patent Application Number | IN/PCT/2002/00763/MUM | |||||||||||||||||||||
PG Journal Number | 45/2007 | |||||||||||||||||||||
Publication Date | 09-Nov-2007 | |||||||||||||||||||||
Grant Date | 24-Oct-2007 | |||||||||||||||||||||
Date of Filing | 11-Jun-2002 | |||||||||||||||||||||
Name of Patentee | BAYER HEALTHCARE AG | |||||||||||||||||||||
Applicant Address | D-51368 LEVERKUSEN, GERMANY | |||||||||||||||||||||
Inventors:
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PCT International Classification Number | C07D413/14 | |||||||||||||||||||||
PCT International Application Number | PCT/EP00/12492 | |||||||||||||||||||||
PCT International Filing date | 2000-12-11 | |||||||||||||||||||||
PCT Conventions:
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