Title of Invention	NOVEL INDOLE DERIVATIVES AND THEIR USE AS MEDICAMENTS
Abstract	The general formula (1) the substituents should at least be R denotes a - Hydrogen - straight-chain or branched (C1-C6)-alkylcarbonyl - straight-chain or branched (C1-C6)-alkyloxycarbonyl R1 denotes - 5-,6-, 7-quinolyl - pyrido[2,3-b]pyrazinyl - indazolyl - isothiazolyl - indolyl - isoxazolyl optionally substituted by a (C1-C6) alkyl group or (C1-C6)-alkoxy group R2 denotes benzyl, substituted with halogen R3, R4 denote hydrogen Z1, Z2 denote O, S

Title of Invention

NOVEL INDOLE DERIVATIVES AND THEIR USE AS MEDICAMENTS

Abstract

The general formula (1) the substituents should at least be R denotes a - Hydrogen - straight-chain or branched (C1-C6)-alkylcarbonyl - straight-chain or branched (C1-C6)-alkyloxycarbonyl R1 denotes - 5-,6-, 7-quinolyl - pyrido[2,3-b]pyrazinyl - indazolyl - isothiazolyl - indolyl - isoxazolyl optionally substituted by a (C1-C6) alkyl group or (C1-C6)-alkoxy group R2 denotes benzyl, substituted with halogen R3, R4 denote hydrogen Z1, Z2 denote O, S

Full Text	Novel indole derivatives and their use as medicaments The invention relates to novel indole derivatives of the general formula 1, to their preparation and to their use as medicaments, in particular for treating tumors. This invention has been divided out from the Parent Application No. 51/KOLNP/2003 of 15.01.2003, Entitled: Novel indole derivatives and their use as medicaments. Indol-3-yl derivatives having certain 2-, 3-, 4- and 8- quinoline radicals are described in the German application DE 198 14 838.0. However, indol-3-yl derivatives having 5-, 6- or 7-quinoline substituents are neither described nor suggested in this publication. According to one aspect of the invention, novel indole derivatives of the general formula 1 in which R denotes hydrogen; straight-chain or branched (C1-C6) -alkyl; (C1-C6) -alkyl which is mono- or polysubstituted by aryl, where the aryl radical [lacuna] unsubstituted or mono- to penta-[lacuna] by identical or different substituents from the group consisting of halogen, (C1-C6) -alkyl, (C3-C7) -cycloalkyl, carboxyl, (C1-C6) - alkoxy-carbonyl, preferably tert-butoxycarbonyl, straight-chain or branched (C1-C6) - alkyl, which is substituted by one or more fluorine atoms, preferably trifluoromethyi, hydroxyl, straight- chain or branched (C1-C6)-alkoxy, preferably methoxy or ethoxy; benzyloxy or aryl-(C1-C6)-alkyl, where the aryl radical may be unsubstituted or mono- or pentasubsti tuned by identical or different substituents from the group consisting of (C1-C6)-alkyl, halogen and straight-chain or branched (C1-C6)-alkyl which is substituted by one or more fluorine atoms, preferably trifluoromethyi; straight-chain or branched (C1- C6)-alkoy-(C1-C6)-alkyl [sic], substituted or unsubstituted aryl- (C1-C6) -alkyloxycarbonyl, preferably benzyloxycarbonyl, straight-chain or branched (C1-C6)-alkyloxycarbonyl, straight-chain or branched (C1-C6)-alkylcarbonyl, preferably acetyl, (C2-C6)-alkenyl, preferably allyl, (C2-C6)- alkynyl, preferably ethynyl or propargyl, or straight-chain or branched cyano-(C1-Ce)-alkyl, preferably cyanomethyl; denotes a saturated, unsaturated or aromatic (C2-C14)-heterocycle which contains one or more heteroatoms selected from the group consisting of N, 0 and S and which may be attached to the amide nitrogen directly or via a (C1-C6)-alkyl bridge, where the (C1-C4) -alkyl radical may be unsubstituted or mono- [lacuna] polysubstituted by identical or different substituents from the group consisting of (C1-C6)-alkyl, halogen and oxo (=0) and the 2-, 4-, 5- or 6-pyrimidinyl radical may in each case be unsubstituted or mono- to trisubstituted by identical or different substituents from the group consisting of hydrogen, (C1—C6) -alkyl, halogen, nitro, amino, mono- (C1-C6) -alkylamino, di- (C1-C6) -alkylamino, hydroxyl, (C1-C6)-alkoxy, benzyloxy, carboxyl, (C1-C6)-alkoxycarbonyl, (C1-C6)-alkoxycarbonylamino or (C:~C6)-alkyl which is mono- or polysubstituted by fluorine, preferably trifluoromethyi, (C6-C10 - aryl and (C6-C10) -aryl- (C1-C6) -alkyl, with the proviso that Rl does not represent unsubstituted 2- or 4-pyrimidinyl or a 2-pyrimidinyl radical which is mono- or polysubstituted by methyl; and except for (C1-C6)-alkyl-, halogen-, nitro-, amino- and (C1-C6)-alkylamino-substituted or unsubstituted 2-, 3-, 4- and 8-quinolyl and 2-, 3- and 4-quinolylmethyl in which the ring carbon atoms of the pyridylmethyl moiety are unsubstituted or substituted by (C1-C6)-alkyl, (C1-C6)-alkoxy, nitro, amino and (C1-C6)- alkoxycarbonylamino; R2 denotes hydrogen, (C1-C6 -alkyl, (C1-C6)-alkyl which is mono- or polysubstituted by halogen, (C1- C6)-alkyl which is mono- or polysubstituted by phenyl, where the phenyl radical may be unsubstituted or nono- to pentasubstituted by identical or different substituents from the group consisting of halogen, preferably chlorine, bromine or iodine, (C1-C6) -alkyl, (C3-C7)- cycloalkyl, carboxyl, (C1-C6) -alkoxycarbonyl, (C1- C6)-alkyl which is mono- or polysubstituted by halogen, preferably trifluoromethyl, hydroxyl, (C1-C6)-alkoxy, preferably methoxy or ethoxy, phenyl-(C1-C6)-alkoxy, preferably benzyloxy, nitro, amino, mono-(C1-C6)-alkylamino, di-(C1-C6)- alkylamino, mono- (C2-5) -cycloalkylamino, di-(C3-6)- cycloalkylamino, (C1-C6) -acylamino, phenyl- (C1-C6) - alkylamino, arylcarbonylamino, heteroarylcarbonyl- amino, (C1-C6) -alkylsulfonamido, arylsulfonamido, maleinimido, succinimido, phthalimido, benzyl- oxycarbonylamino (Z-amino), tert-butoxy- carbonylamino (BOC-amino), 9-fluorenylmethoxy- carbonylamino (Fmoc-amino), triphenylmethylamino (Tr-amino) , 2-(4'-pyridyl)-ethoxycarbonylamino (Pyoc-amino) , diphenylmethylsilylamino (DPMS- amino), by -NH-CH2-COOH; -NH-CH (CH3)-COOH; (CH3)2CH-CH2-CH2-CH(NH-)-COOH; H3C-CH2-CH (CH3)- CH(NH-)-COOH; H0H2C-CH(NH-)-C0OH; phenyl-CH2-CH (NH- ) -COOH; (4- imidazolyl)-CH2-CH(NH-)-COOH; HN=C (NH2) -NH- (CH2)3- CH(NH-)-COOH; H2N-(CH2)4-CH(NH-)-COOH; H2N-CO-CH2-CH (NH-) -COOH; HOOC- (CH2) 2-CH (NH-) -COOH; a 2-, 3-, 4-, 5-, 6-, 7- and 8-quinolyl-(C:-C6) - alkyl radical, where the 2-, 3-, 4-, 5,-, [sic] 6-, 7- and 8-quinolyl radical may be unsubstituted or mono- to hexasubstituted by identical or different substituents from the group consisting of halogen, (C1-C4)-alkyl or (C:-C4) -alkoxy; a 2~, 3- and 4-pyridyl-(C:-C6>-alkyl radical, where the 2-, 3- and 4-pyridyl radical may be unsubstituted or mono- to tetrasubstituted by identical or different substituents from the group consisting of halogen, (C1-C4)-alkyl and (C-_-C4)- alkoxy; an arylcarbonyl radical, where the aryl radical may be unsubstituted or mono- to pentasubstituted by identical or different substituents from the group consisting of halogen, (C1-Cs) -alkyl, (C3- C7)-cycloalkyl, carboxyl, cyano, (C1-C6)- alkoxycarbonyl, (C1-C6) -alkyl which is mono- or polysubstituted by fluorine atoms preferably trifluoromethyl, hydroxyl, (C1-C4) -alkoxy preferably methoxy or ethoxy, aryl- (C1-C4) -alkoxy, preferably benzyioxy; R;. and R4 may be attached to the indole carbon atoms C-2, C-4, C-5, C-6 or C-7 and independently of one another denote hydrogen, hydroxyl, (C1-C6)-alkyl, (C3-C7) -cycloalkyl, (d-C6)-alkylcarbonyl, (C:-C5)- alkoxy, halogen, aryl-(C1-C4)-alkoxy, preferably benzyioxy, nitro, amino, mono-(C;-C4)-alkylamino, di- (C1-C4) -alkylarr.ino, (C:-C6) -alkoxycarbonylamino , (C1-C6) -alkoxycarbonylamino- (C1-Ce) -alkyl, cyano, straight-chain or branched cyano- (C1-C6) -alkyl, carboxyl, (C2-C4) -alkoxycarbonyl, (C1-C4) -alkyl which , is .substituted by one or more fluorine atoms, preferably trifluoromethyl group, carboxy- (C:-C6)-alkyl or (C:-C5) -alkoxycarbonyl- lCi-C6) - alkyl; Z: denotes oxygen or sulfur or geminally attached hydrogen and hydroxyl; Zi denotes oxygen or sulfur, their tautomers, stereoisomers, including the diastereomers and enantiomers, and the physiologically acceptable salts thereof, are provided. Thus, for example, the compounds of the general formula (1) according to the invention which have one or more centers of chirality and which are present as racemates can be separated by methods known per se into their optical isomers, i.e. enantiomers or diastereomers. The separation can be carried out by column separation on chiral phases or by recrystallization from an optically active solvent or using an optically active acid or base or by derivatization with an optically active reagent, such as, for example, an optically active alcohol, and subsequent removal of the radical. Furthermore, the indole derivatives of the formula (1) according to the invention can be converted into their salts with inorganic or organic acids, in particular, for pharmaceutical use, into their physiologically acceptable salts. Acids which are suitable for this purpose are, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, fumaric acid, succinic acid, lactic acid, malic acid, eribonic acid, malonic acid, citric acid, acetic acid, tartaric acid, trifluoroacetic acid, methanesulfonic acid, sulfoacetic acid or maleic acid. Moreover, the compounds of the formula (1) according to the invention can, if they contain a sufficiently- acidic group, such as a carboxyl group, be converted, if desired,.into their salts with inorganic or organic bases, in particular, for pharmaceutical use, into their physiologically acceptable salts. Bases which are suitable for this purpose are, for example, sodium hydroxide, potassium hydroxide, calcium hydroxide, lysine, cyclohexylamine, ethanolamine, diethanolamine and triethanolamine. According to a preferred embodiment, indole derivatives of the general formula (1) above are provided in which R, R2, R3, R4, Zl and Z2 have the meanings given above and R: denotes a 2-, 4-, 5- or 6-pyrimidinyl radical or 2-, 4-, 5- or 6-pyrimidinyl-(C:-C4)-alkyl radical, where the {C1-C4) -alkyl radical may be unsubstituted or mono- [lacuna] polysubstituted by identical or different substituents from the group consisting of (C1-Ce) -alkyl, halogen and oxo (=0) and the 2-, 4-, 5- or 6-pyrimidinyl radical may be unsubstituted or mono- to trisubstituted by identical or different substituents from the group consisting of hydrogen, (C1-Cs)-alkyl, halogen, nitro, amino, mono- (C:-C£) -alkylamino, di-(.Ci-Cs) - alkylamino, hydroxyl, (C;-Co)-alkoxy, benzyloxy, carboxyl, (d-C6) -alkoxycarbonyl, (C:-C6)- alkoxycarbonylamino or (C1-Cs) -alkyl which is mono- or polysubstituted by fluorine, preferably trif luoromethyl, (C0-C10)-aryl, or (C—Cio) -aryl- (C1-Ce)-alkyl, with the proviso that Rl does not represent unsubstituted 2- or 4-pyrimidinyl or a 2-pyrimidinyl radical which is mono- or polysubstituted by methyl; a 3-, 4-, 5- or 6-pyridazinyl radical or 3-, 4-, 5- or 6-pyridazinyl-(C1-C4)-alkyl radical, where the (C1-C4)-alkyl radical may be unsubstituted or mono- or polysubstituted by identical or different substituents from the group consisting of (C:-C;)- alkyl, halogen and oxo (=0) and the 3-, 4-, 5- or 6-pyridazinyl radical may . be unsubstituted or mono- to trisubstituted by identical or different substituents from the group consisting of hydrogen, (C1-Cs)-alkyl, halogen, nitro, amino, mono- (C1-C6) -alkylamino, di- (C1-Ce) -alkylamino, hydroxyl, (C1-Ce)-alkoxy, benzyloxy, carboxyl, (C:- Co) -alkoxycarbonyl, (C:-C6) -alkoxycarbonylamino or (C1-Co)-alkyl which is mono- or polysubstituted by fluorine, preferably trifluoromethyl, (C5-C10)-aryl and (C6-Cio) -aryl- (C1-C6) -alkyl; a 2-, 3-, 5- or 6-pyrazinyl radical or 2-, 3-, 5,- [sic] or 6-pyrazinyl-(d-C4)-alkyl radical, where the (C1-C4)-alkyl radical may be unsubstituted or mono- or polysubstituted by identical or different substituents from the group consisting of (C:-C5)- alkyl, halogen and oxo (=0) and the 2-, 3-, 5,- [sic] or 6-pyrazinyl radical may be unsubstituted or mono- to trisubstituted by identical or different substituents from the group consisting of hydrogen, (C1-C6)-alkyl, halogen, nitro, amino, mono- (C1-C6) -alkylamino, di- (C1-C6) -alkylamino, hydroxyl, (C1-Ce)-alkoxy, benzyloxy, carboxyl, (C1- C6) -alkoxycarbonyl, (C1-C0) -alkoxycarbonylamino or (C1-Ce)-alkyl which is mono- or polysubstituted by fluorine, preferably trifluoromethyl, (C6-Cio)-aryl and (C6-C:3) -aryl- (C1-Ce) -alkyl ; a 3-, 4-, 5-, 6-, 7- or 8-cinnolinyl radical or 3-, 4-, 5-, 6-, 7-, or 8-cinnolinyl-(C1-C4)-alkyl radical, where the (C^-C^)-alkyl radical may be unsubstituted or mono- or polysubstituted by identical or different substituents from the group consisting of (Cx-C?)-alkyl, halogen and oxo (=0) and the 3-, 4-, 5-, 6-, 7-, or 8-cinnolinyl radical may be unsubstituted or mono- to pentasubstituted by identical or different substituents from the group consisting of hydrogen, (C1-C6)-alkyl, halogen, nitro, amino, . mono- (C1-C6) -alkylamino, di- (C1-C-) -alkylamino, hydroxyl, (C1-C5) -alkoxy, benzyloxy, carboxyl, (d- C6)-alkoxycarbonyl, (C:-Cf)-alkoxycarbonylamino or (C1-C6)-alkyl which is mono- or polysubstituted by fluorine, preferably trifluoromethyl, (C5-C:o) -aryl and (C6-C10)-aryl-(C1-C6)-alkyl; a 2-, 4-, 5-, 6-, 7- or 8-quinazolinyl radical or 2-, 4-, 5-, 6-, 7- or 8-quinazolinyl-(C1-C4)-alkyl radical, where the (C:-C4)-alkyl radical may be unsubstituted or mono- or polysubstituted by identical or different substituents from the group consisting of hydrogen, (C1-Cs) -alkyl, halogen and oxo (=0) and the or [sic] 2-, 4-, 5-, 6-,, 7- or 8-quinazolinyl radical, may be unsubstituted or mono- to pentasubstituted by identical or different substituents from the group consisting of hydrogen, (CN-Ce)-alkyl, halogen, nitro, amino, mono- (C1-C5) -alkylamino, di- (d-C;) -alkylamino, hydroxyl, (C1-C6)-alkoxy, benzyloxy, carboxyl, (C1- Ce) -alkoxycarbonyl, (C:-C£) -alkoxycarbonylamino or (C1-C6)-alkyl which is mono- or polysubstituted by fluorine, preferably trifluoromethyl, (C6-Ci0)-aryl and (C6-Cio)-aryl- (C1-C«) -alkyl; a 2-, 3-, 5-, 6-, 7- or 8-quinoxalinyl radical or 2-, 3-, 5-, 6-, 7- or 8-quinoxalinyl-(C1-C4)-alkyl radical, where the (C:-C unsubstituted or mono- or polysubstituted by identical or different substituents from the group consisting of (C1-Cs) -alkyl, halogen and oxo (=0) and the or [sic] 2-, 3-, 5-, 6-, 7- or 8- quinoxalinyl radical may be unsubstituted or mono- to pentasubstituted by identical or different substituents from the group consisting of hydrogen, (C-.-C^)-alkyl, halogen, nitro, amino, mono- (C:-C6) -alkylamino, di- (C:-C6) -alkylamino, hydroxyl, (C:-C6) -alkoxy, benzyloxy, carboxyl, (C:- C6) -alkoxycarbonyl, (C1-C6)-alkoxycarbonylamino or (C1-C5)-alkyl which is mono- or polysubstituted by fluorine, preferably trifluoromethyl, (C6-C10)-aryl and (Co-Cn) -aryl- (C1-C6) -alkyl ; a 1-, 4-, 5-, 6-, 7- or 8-phthalazinyl radical or 1-, 4-, 5-, 6-, 7- or 8-phthalazinyl- (C:-C4) -alkyl radical, where the (C1-C4) -alkyl radical may be unsubstituted or mono- or polysubstituted by identical or different substituents from the group consisting of (C1-Cg) -alkyl, halogen and oxo (=0) and the or [sic] 1-, 4-, 5-, 6-, 7- or 8- phthalazinyl radical may be unsubstituted or mono- to pentasubstituted by identical or different substituents from the group consisting of hydrogen, (C-^-Ce) -alkyl, halogen, nitro, amino, mono- (C1-Co) -alkylamino, di- (C1-Ce) -alkylamino, hydroxyl, (C1-C5) -alkoxy, benzyloxy, carboxyl, (Cx- C6) -alkoxycarbonyl, (CN-Co) -alkoxycarbonylamino or (C1-Cs)-alkyl which is mono- or polysubstituted by fluorine, preferably trifluoromethyl, (Cj-Ci;)-aryl and (C6-C::.) -aryl- (C:-C6) -alkyl; a 2-, 3-, 4-, 5-, 6-, 7- or 8-quinolyl radical or 2-, 3-, 4-, 5-, 6-, 7 or 8-quinolyl- (C1-C4) -alkyl radical, where the (C1-C4)-alkyl radical may be unsubstituted or mono- or polysubstituted by identical or different substituents from the group consisting of (C1-Cs) -alkyl, halogen and oxo (=0) and the 2-, 3-, 4-, 5-, 6-, 7- or 8-quinolyl radical may be unsubstituted or mono- to hexasubstituted by identical or different substituents from the group consisting of hydrogen, (d-C6) -alkyl, preferably methyl, particularly preferably 2-methyl, halogen, nitro, amino, mono- (C1-Cs) -alkylamino, N, N-di- (C1-C6) - alkylamino, hydroxyl, (C1-C6)-alkoxy, (C6-C14)- aryl-(C1-C6)-alkyoxy [sic], preferably benzyloxy, carboxyl, (C1-C6)-alkoxycarbonyl, (C:-C;)- alkoxycarbonylamino or (C:-C-;) -alkyl which is mono- or polysubstituted by halogen, preferably trifluoromethyl, (C6-Ci4)-aryl and (C6-Ci4)-aryl- (C1-C6)-alkyl, except for (C1-C6)-alkyl-, halogen-, nitro-, amino- and (C1-C6)-alkylamino-substituted or unsubstituted 2-, 3-, 4- and 8-quinolyl and 2-, 3- and 4-quinolylmethyl in which the ring carbon atoms of the pyridylmethyl moiety are unsubstituted or substituted by (C1-C6)-alkyl, (C1-C6)-alkoxy, nitro, amino and (C1-C6)- alkoxycarbonylamino; a 1-, 3-, 4-, 5-, 6-, 7- or 8-isoquinolyl radical or 1-, 3-, 4-, 5-, 6-, 7- or 8-isoquinolyl-(C1-CJ - alkyl radical, where the (C1-C4)-alkyl radical may be unsubstituted or mono- or polysubstituted by identical or different substituents from the group consisting of (C1-C6) -alkyl, halogen and oxo (=0) and the 1-, 3-, 4-, 5-, 6-, 7- or 8-isoquinolyl radical may be unsubstituted or mono- to hexasubstituted by identical or different substituents from the group consisting of hydrogen, (C1-C.5)-alkyl, halogen, nitro, amino, mono- (C1-Ce) -alkylamino, di- (C:-Cs) -alkylarr.ino, hydroxyl, (C1-C6) -alkoxy, benzyloxy, carboxyl, (C-- Ce) -alkoxycarbonyl, (C1-Ce) -alkoxycarbonylamino or (C:-C6)-alkyl which is mono- or polysubstituted by fluorine, preferably trifluoromethyl, (Ce-Cio)-aryl and (C6-Cio) -aryl- (C1-Ce) -alkyl; a 2-, 6-, 8- or 9- [9H] -purinyl radical or 2-, 6-, 8- or 9-[9H]-purinyl-(C1-C4)-alkyl radical, where the (C1-C4)-alkyl radical may be unsubstituted or mono- or polysubstituted by identical or different substituents from the group consisting of (C1-C5)- alkyl, halogen and oxo (=0) and the 2-, 6-, 8- or 9-[9H] -purinyl radical may be unsubstituted or mono- to trisubstituted by identical or different substituents from the group consisting of hydrogen, (C—Ce)-alkyl, halogen, nitro, amino, mono- (C-.-Cs) -alkylamino, di- (C:-C.O -alkylamino, hydroxyl, (C-L-Co) -alkoxy, benzyloxy, carboxyl, (C-_- CA)-alkoxycarbonyl, (C1-C6)-alkoxycarbonylamino or (C;-Ce)-alkyl which is mono- or polysubstituted by fluorine, preferably trifiuoromethyl, (C6-Cio) -aryl and (C6-C::)-aryl- (C:-C6) -alkyl; a 2-, 6-, 7- or 8- [1H] -purinyl radical or 2-, 6-, 7- or 8-[7tf]-purinyl-(d-d)-alkyl radical, where the . (C1-C4)-alkyl radical may be unsubstituted or mono- or polysubstituted by identical or different substituents from the group consisting of (C1-C6)- alkyl, halogen and oxo (=0) and the 2-, 6-, 7- or 8-[1H] -purinyl radical may be unsubstituted or mono- to trisubstituted by identical or different substituents from the group consisting of hydrogen, (d~d)-alkyl, halogen, nitro, amino, mono- (C1-C6) -alkylamino, di- (d-d) -alkylamino, hydroxyl, (d-C6) -alkoxy, benzyloxy, carboxyl, (d~ C6)-alkoxycarbonyl, (C1-C6) -alkoxycarbonylamino or (C1-C0) -alkyl which is mono- or polysubstituted by fluorine, preferably trif Iuoromethyl, (d~Cio) -aryl and (C6-Ci0)-aryl- (C1-C6) -alkyl; a 1-, 2-, 3-, 4~, 5-, 6-, 7-, 8- or 9-acridinyl radical or 1-, 2-, 3-, 4-, 5-, 6-, 7-, 8- or 9-acridinyl-(C1-C4)-alkyl radical, where the (d- C6)-alkyl radical may be unsubstituted or mono- or polysubstituted by identical or different substituents from the group consisting of (C1-Cg)- alkyl, halogen and oxo (=0) and the 1-, 2-, 3-, 4-, 5-, 6-, 7-, 8- or 9-acridinyl radical may be unsubstituted or mono- to octasubstituted by identical or different substituents from the group consisting of hydrogen, (C1-C5)-alkyl, halogen, nitro, amino, mono- (C1-Ce) -alkylamino, di-(C:-C6)- alkylamino, hydroxyl, (C1-C6)-alkoxy, benzyloxy, carboxyl, (C1-C6) -alkoxycarbonyl, (C1-C6)- alkoxycarbonylamino or (C-.-Ce) -alkyl which is mono- or polysubstituted by fluorine, preferably trif Iuoromethyl, (C5-C:o) -aryl and (C6-C;;:) -aryl- (C-_-C0) -alkyl; a 1-, 2-, 3-, 4-, 6-, 7-, 8-, 9- or 10-phenanthridinyl radical or 1-, 2-, 3-, 4-, 6-, 7-, 8- or 9- or 10-phenanthridinyl- (C1-C6) -alkyl radical, where the (C:-C6) -alkyl radical may be , unsubstituted or mono- or polysubstiluted by identical or different substituents from the group consisting of hydrogen, (C:-Ci)-alkyl, halogen and oxo (=0) and the 1-, 2-, 3-, 4-, 6-, 7-, 8-, 9- or 10-phenanthridinyl radical may be unsubstituted or mono- to octasubstituted by identical or different substituents from the group consisting of (C1-Cg)- alkyl, halogen, nitro, amino, mono-(C1-Ce) - alkylamino, di- (C1-Cg)-aikylamino, hydroxyl, (Cx- C5)-alkoxy, (C6-C:o)-aryl-(C:-C6)-alkoxy, preferably benzyloxy, carboxyl, (C:-C6)-alkoxycarbonyl, (C1- C6) -alkoxy car bony 1 ami no or (C1-Ce) -alkyl which is mono- or polysubstituted by fluorine, preferably trifluoromethyl, (C6-Ci0)-aryl and (C6-Ci0) -aryl- (C1-C6)-alkyl; a 2-, 3-, 4-, 5,- [sic] or 6-pyridyl radical where the 2-, 3-, 4-, 5,- [sic] or 6-pyridyl radical may be unsubstituted or mono- to tetrasubscituted by identical or different substituents from the group consisting of hydrogen, (C1-Ce)-alkyl, halogen, nitro, amino, mono-(C1-C5)-alkylamino, di-fCi-Ce)- alkylamino, hydroxyl, (C1-Ce)-alkoxy, benzyloxy, carboxyl, (d-C6) -alkoxycarbonyl, (C1-C6)- alkoxycarbonylamino or (C1-Cg)-alkyl which is mono- or polysubstituted by fluorine, preferably trifluoromethyl, (C6-Cio)-aryl and (Cr--C;;)-aryl- (C1-C6)-alkyl, with the proviso that zi# Z;, R2, R3 and R4 have the meaning given above or below, without any limitations, and R represents (C2-C0)- alkenyl, preferably allyl, (C2-C6)-alkynyl, preferably ethynyl or propargyl, (C1-C)-alkoxy- (C1-C6)-alkyl, or straight-chain or branched cyano- (C1-C6) -alkyl, preferably cyanomethyl, cr with the proviso that Z2, R, R-, R3 and R.; have the meanings described above or below, without any limitations, and Zi denotes geminally attached hydrogen and hydroxyl; a 2-, 3-, 4-, 5,- [sic] or 6-pyridyi-(C:-C6)-alkyl radical, where the (C:-C£)-alkyl radical may be unsubstituted or mono- or polysubstituted by identical or different substituents from the group consisting of (C1-C5)-alkyl, halogen and oxo (=0) and the 2-, 3-, 4-, 5,- [sic] or 6-pyridyl radical may be unsubstituted or mono- to tetrasubstituted by identical or different substituents from the group consisting of hydrogen, (C1-C0) -alkyl, halogen, nitro, amino, mono-(C:-Cg)-alkylamino, di- (C:-C6)-alkylamino, hydroxyl, (C:-C;) -alkoxy, benzyloxy, carboxyl, (C1-Cg)-alkoxycarbonyl, (C:- C6)-alkoxycarbonylamino or (C1-C6) -alkyl which is mono- or polysubstituted by fluorine, preferably trifluoromethyl, (C6-C;o)-aryl and (C6-C10) -aryl- (C1-C6)-alkyl; a 2-, 3-, 4,- [sic] or 5-thienyl radical or 2-, 3-, 4,- [sic] or 5-thienyl- (C1-C6) -alkyl radical, where the (C;-C--)-alkyl radical may be unsubstituted or mono- or polysubstituted by identical or different substituents from the group consisting of (C1-Cs) -alkyl, halogen and oxo (=0) and the 2-, 3-, 4,- [sic] or 5-thienyl radical may be unsubstituted or mono- to trisubstituted by identical or different substituents from the group consisting of hydrogen, (C1-Ce)-alkyl, halogen, nitro, amino, mono- (C:-Cf) -alkylamino, di-(C1-Cs)- alkylamino, hydroxyl, (C1-C6)-alkoxy, benzyloxy, carboxyl, (C:-C6)-alkoxycarbonyl, (C1-Cs)- alkoxycarbonylamino or (C;-C6) -alkyl which is mono- or polysubstituted by fluorine, preferably trifluoromethyl, (C5-C1:.) -aryl and (C6-Cio) -aryl- (C:-C5)-alkyl; a 2-, 4-, or 5-thiazolyl radical or 2-, 4-, or 5- thiazolyl-(C1-Cf)-alkyl radical, where the (C1-C3)- aikyl radical may be unsubstituted or mono- or polysubstituted by identical or different substituents from the group consisting of (C1-Ce)- alkyl, halogen and oxo (=0) and the 2-, 4-, or 5- thiazolyl' radical may be unsubstituted or mono- or disubstituted by identical or different substituents from the group consisting of hydrogen, (d-C6) -alkyl, halogen, nitro, amino, mono- (C;-C6) -alkylamino, di- (C:-C6) -alkylamino, hydroxyl, (C1-Cs) -alkoxy, benzyloxy, carboxyl, (C1- C6)-alkoxycarbonyl, (C1-Cs)-alkoxycarbonylamino or (C1-Ce) -alkyl which is mono- or polysubstituted by fluorine, preferably trifluoromethyl, (Ce-Cio)-aryl and (C£-Cio)-aryl-(C1-Ce)-alkyl; a 3-, 4-, or 5-isothiazolyl radical or 3-, 4- or 5-isothiazolyl-(C1-C6)-alkyl radical, where the (C1-Ce)-alkyl radical may be unsubstituted or mono- or polysubstituted by identical or different substituents from the group consisting of (C1-Cg)- alkyl, halogen and oxo (=0) and the 3-, 4- or 5- isothiazolyl radical may be unsubstituted or mono- or disubstituted by identical or different substituents from the group consisting of hydrogen, (C1-Ce)-alkyl, halogen, nitro, amino, mono- (C1-Ce) -alkylamino, di- (C1-Ce) -alkylamino, hydroxyl, (C1-C6)-alkoxy, benzyloxy, carboxyl, (C1- Ce)-alkoxycarbonyl, (C1-C6)-alkoxycarbonylamino or (C:-C6)-alkyl which is mono- or polysubstituted by fluorine, preferably trifluoromethyl, (Cg-Cio)-aryl and (Cf-Cio) -aryl- (Cx-C6) -alkyl; a 2-, 4-, 5-, 6- or 7-benzothiazolyl radical or 2-, 4-, 5-, 6- or 7-benzothiazolyl- (C--Cs) -alkyl radical, where the (C1-C6) -alkyl radical may be unsubstituted or mono- or polysubstituted by identical or different substituents from the group consisting of (C1-Ce) -alkyl, halogen and oxo (=0) and the 2-, 4-, 5-, 6- or 7-benzothiazolyl radical may be unsubstituted or mono- to tetrasubstituted by identical or different substituents from the group consisting of hydrogen, (C^-Ce)-alkyl, halogen, nitro, amino, mono-(C1-Ce)-alkylamino, di- (C:-Co) -alkylamino, hydroxyl, (C1-C6) -alkoxy, benzyloxy, carboxyl, (C1-Ce)-alkoxycarbonyl, (C;- C6> -alkoxycarbonylamino or (d~d) -alkyl which is mono- or. polysubstituted by fluorine, preferably trifluoromethyl, (C6-Cio) -aryl and (d~do) -aryl- (C^Ce)-alkyl;. a 1-, 2-, 4- or 5-imidazolyl radical or 1-, 2-, 4- or 5-imidazolyl-(C1-C6>-alkyl radical, where the (C1-C6)-alkyl radical may be unsubstituted or mono- or polysubstituted by identical or different■ substituents from the group consisting of (d~d)- alkyl, halogen and oxo (=0) and the 1-, 2-, 4- or 5-imidazolyl radical may be unsubstituted or mono- to trisubstituted by identical or different substituents from the group consisting of hydrogen, (d~d)-alkyl, halogen, nitro, amino, mono- (C1-C6) -alkylamino, di- (d~d) -alkylamino, hydroxyl, (d~d)-alkoxy, benzyloxy, carboxyl, (d~ d)-alkoxycarbonyl, (d_d)-alkoxycarbonylamino or (d~d) -alkyl which is mono- or polysubstituted by fluorine, preferably trifluoromethyl, (d-d:)-aryl and (Cs-Cio) -aryl- (C;-C6) -alkyl; a 1-, 3-, 4- or 5-pyrazolyl radical or 1-, 3-, 4- or 5-pyrazolyl-(C1-C6)-alkyl radical, where the (C1-C6)-alkyl radical may be unsubstituted or mono- or polysubstituted by identical or different substituents from the group consisting of (C1-C6)- alkyl, halogen and oxo (=0) and the 1-, 3-, 4- or 5-pyrazolyl radical may be unsubstituted or mono- to trisubstituted by identical or different substituents from the group consisting of hydrogen, (C1-Ce)-alkyl, halogen, nitro, amino, mono- (C1-C6) -alkylamino, di- (d-C6) -alkylamino, hydroxyl, (C1-C6) -alkoxy, benzyloxy, carboxyl, (d- C6) -alkoxycarbonyl, (C1-C6) -alkoxycarbonylamino or (d-d)-alkyl which is mono- or polysubstituted by fluorine, preferably trifluoromethyl, (C^-C—.)-aryl and (C6-Cio) -aryl- (C:-C6) -alkyl; a 1-, 2,- [sic] 3,- [sic] 4,- [sic] or 5-pyrroiyl radical or 1-, 2,- [sic] 3,- [sic] 4,- [sic] or 5-pyrrolyl-(C1-C6)-alkyl radical, where the (d- C6)-alkyl radical may be unsubstituted or mono- or polysubstituted by identical or different substituents from the group consisting of (C1-C6)- alkyl, halogen and oxo (=0) and the 1-, 2,- [sic] 3,- [sic] 4,- [sic] or 5-pyrrolyl radical may be unsubstituted or mono- to tetrasubstituted by identical or different substituents from the group consisting of hydrogen, (C1-Ce)-alkyl, halogen, nitro, amino, mono- (C1-C6> -alkylamino, di-(C1-C6>- alkylamino, hydroxyl, (C:-C6)-alkoxy, benzyloxy, carboxyl, (C1-Ce) -alkoxycarbonyl, (C:-C5)- alkoxycarbonylamino or (C:-Cg)-alkyl which is mono- or polysubstituted by fluorine, preferably trif luoromethyl, (C6-Cio)-aryl and (C6-Cio) -aryl- (d-C6)-alkyl; a 1-, 3-, or 5-[1.2.4]-triazolyl radical or 1-, 3- or 5-[1.2.4]-triazolyl-(C1-Cc)-alkyl radical, where the (C1-C6) -alkyl radical may be unsubstituted or mono- or polysubstituted by identical or different substituents from the group consisting of hydrogen, (C1-Ce) -alkyl, halogen and oxo (=0) and the 1-, 3- or 5-[1.2.4]-triazolyl radical may be unsubstituted or mono- or disubstituted by identical or different substituents from the group consisting of (C:-C6)-alkyl, halogen, nitro, amino, mono- (C1-Ce) -alkylamino, di- (C1-C6) -alkylamino, hydroxyl, (C1-C6)-alkoxy, benzyloxy, carboxyl, (C1- Ce)-alkoxycarbonyl, (C:-C5)-alkoxycarbonylamino or (C1-Cj)-alkyl which is mono- or polysubstituted by fluorine, preferably trifluoromethyl, (Ce-C10)-aryl and (C6-Cio) -aryl- (C1-C6) -alkyl; a 1-, 4- or 5-[l.2.3]-triazolyl radical or 1-, 4- or 5-[1.2.3]-triazolyl-(C1-C6)-alkyl radical, where the (C1-Ce)-alkyl radical may be unsubstituted or mono- or polysubstituted by identical or different substituents from the group consisting of (C;-Ce)- alkyl, halogen and oxo (=0) and the 1-, 4- or 5- [1.2.3]-triazolyl radical may be unsubstituted or mono- or disubstituted by identical or different substituents . from the group consisting of hydrogen, (C:-C£>-alkyl, halogen, nitro, amino, mono- (C1-C6) -alkylamino, di- (C1-C6) -alkylamino, hydroxyl, (C1-Ce) -alkoxy, benzyloxy, carboxyl, (C1- Ce)-alkoxycarbonyl, (C1-Ce)-alkoxycarbonylamino or (C1-Ce)-alkyl which is mono- or polysubstituted by fluorine, preferably trifluoromethyl, (Co-Cio)-aryl and (C6-C10)-aryl-(C1-C6)-alkyl; a 1- or 5-[lH]-tetrazolyl radical or 1- or 5-[ltf]- tetrazolyl-(C1-Ce)-alkyl radical, where the (C1- Ce)-alkyl radical may be unsubstituted or mono- or polysubstituted by identical or different substituents from the group consisting of (C1-Cs)- alkyl, halogen and oxo (=0) and the 1- or 5-[lH]- tetrazolyl radical may be unsubstituted or substituted by hydrogen, (C1-C6> -alkyl, halogen, nitro, amino, mono- (C1-Ce) -alkylamino, di-(C1-Ce)- alkylamino, hydroxyl, (C1-Cg)-alkoxy, benzyloxy, carboxyl, (C:-C6)-alkoxycarbonyl, (Ci.-Co)- alkoxycarbonylamino or (C1-C5)-alkyl which is mono- or polysubstituted by fluorine, preferably trif luoromethyl, (C6-Ci0) -aryl and (C6-Cio) -aryl- (C1-Cs)-alkyl; a 2- or 5-[2H] -tetrazolyl radical or 2- or 5-[2H]- tetrazolyl-(C1-Ce)-alkyl radical, where the (C1- Ce)-alkyl radical may be unsubstituted or mono- or polysubstituted by identical or different substituents from the group consisting of (C1-C6>- alkyl, halogen and oxo (=0) and the 2- or 5-[2H]- tetrazolyl radical may be unsubstituted or substituted by hydrogen, (C1-Ce)-alkyl, halogen, nitro, amino, mono- (C1-C6> -alkylamino, di-(C1-C6)- alkylamino, hydroxyl, (C1-C6)-alkoxy, benzyloxy, carboxyl, (C1-Ce) -alkoxycarbonyl, (C1-C6)- alkoxycarbonylamino or (C;-Ce)-alkyl which is mono- or polysubstituted by fluorine, preferably trif luoromethyl, (Cs-Cio)-aryl and (Ce-C—)-aryl- (Cx-Cs) -alkyl; a 2-, 4- or 6-[1.3 .5]-triazinyl radical or 2-, 4- or 6-[1.3.5]-triazinyl-(C1-C6)-alkyl radical, where the (C1-C6) -alkyl radical may be unsubstituted or mono- or polysubstituted by identical or different substituents from the group consisting of hydrogen, (C1-C6)-alkyl, halogen and oxo (=0) and the 2-, 4- or 6-[1.3 . 5]-triazinyl radical may be unsubstituted or mono- or disubstituted by identical or different substituents from the group consisting of hydrogen, (C1-C5)-alkyl, halogen, nitro, amino, mono- (C1-C6) -alkylamino, di-(C1-Cs)- alkylamino, hydroxyl, (C-.-Cs)-alkoxy, benzyloxy, carboxyl, (C1-C6)-alkoxycarbonyl, (C1-C6)- alkoxycarbonylamino or (C1-C5)-alkyl which is mono- or polysubstituted by fluorine, preferably trifluoromethyl, (C6-C10) -aryl and (Ce-Cio) -aryl- (C1-C6>-alkyl; a 2-, 4- or 5-oxazolyl radical or 2-, 4- or 5- oxazolyl-(C1-C6)-alkyl radical, where the (C:-Cs)- alkyl radical may be unsubstituted or mono- or polysubstituted by identical or different substituents from the group consisting of (C1-Ce)- alkyl, halogen and oxo (=0) and the 2-, 4-, or 5- oxazolyl radical may be unsubstituted or mono- or disubstituted by identical or different substituents from the group consisting of hydrogen, (C:~C6)-alkyl, halogen, nitro, amino, mono- (C1-Ce) -alkylamino, di- (C:-Co) -alkylamino, hydroxyl, (C:-C$) -alkoxy, benzyloxy, carboxyl, (C1- Co)-alkoxycarbonyl, (C1-C6)-alkoxycarbonylamino or (C1-Ce)-alkyl which is mono- or polysubstituted by fluorine, preferably trifluoromethyl, (C6-C10)-aryl and (C6-Cio)-aryl-(C1-C6)-alkyl; a 3-, 4- or 5-isoxazolyl radical or 3-, 4- or 5- isoxazolyl-(C:-C5)-alkyl radical, where the (C-:- Ce)-alkyl radical may be unsubstituted or mono- or polysubstituted by identical or different substituents from the group consisting of (C1-C6)- alkyl, halogen and oxo (=0) and the 3-, 4- or 5- isoxazolyl radical may be unsubstituted or mono- or disubstituted by identical or different substituencs from the group consisting of hydrogen, (C:-C6)-alkyl, halogen, nitro, amino, mono- (C1-Cs) -alkylamino, di- (C1-C6) -alkylamino, hydroxyl, (C:-C6)-alkoxy, benzyloxy, carboxyl, {Ci- Ce) -alkoxycarbonyl, (Ci~C6)-alkoxycarbonylamino or (C:-C6)-alkyl which is mono- or polysubstituted by fluorine, preferably trifluoromethyl, (C6-C10)-aryl and (C6-Cio) -aryl- (C1-C6) -alkyl; a 1-, 2-, 3-, 4-, 5-, 6- or 7-indolyl radical or 1-, 2-, 3-, 4-, 5-, 6- or 7-indolyl-(C1-C6)-alkyl radical, where the (C1-C6) -alkyl radical may be unsubstituted or mono- or polysubstituted by identical or different substituents from the group consisting of (C1-C6) -alkyl, halogen and oxo (=0) and the 1-, 2-, 3-, 4-, 5-, 6- or 7-indolyl radical may be unsubstituted or mono- to hexasubstituted by identical or different substituents from the group consisting of hydrogen, (C1-Ce)-alkyl, halogen, nitro, amino, mono- (C1-C6) -alkylamino, di- (C1-C6) -alkylamino, hydroxyl, (C1-Ce)-alkoxy, benzyloxy, carboxyl, (C1- Cs)-alkoxycarbonyl, (C1-C0)-alkoxycarbonylamino or (C:-C6)-alkyl which is mono- or polysubstituted by fluorine, preferably trif luoromethyl, (C6-C10) -aryl and (C6-C10)-aryl-(C1-C6)-alkyl, and also the isomers, in particular tautomers, diastereomers and enantiomers, and the pharmaceutically acceptable salts, in particular acid addition salts, thereof [lacuna]. According to a further embodiment, indole derivatives of the general formula (1) are provided which are characterized in that R, R2, R3, R4, Zl and Z2 have the meanings described above and R: represents quinolyl which is mono- or polysubstituted by straight-chain or branched (C1-Cg-alkyl) or (C1-Cs) -alkoxy. According to a further embodiment, indole derivatives of the general - formula (1) are provided which are characterized in that R, R2, R3, R4, Zl and Z2 have the meanings described above and Ri represents 2-methyl-6- quinolyl. According to a further embodiment, indole derivatives of the general formula (1) are provided which are characterized in that R, R2, R3, R4 Zl and Z2 have the meanings described above and Ri denotes (2-methyl)-6- quinolyl, R2 denotes 4-chlorobenzyl, R3 and R4 each denote hydrogen and Zi and Z2 each denote oxygen. According to a further aspect of the invention, a process for preparing indole derivatives of the general formula (1) according to any of claims 1 to 5 is [lacuna] which is characterized in that an indole precursor of the general formula (2) in which R2, R3 and R4 have the meanings mentioned above is reacted with a compound of the general formula (3) in which Zl and Z2 have the meaning mentioned above and Yl and Y2 independently of one another represent a suitable leaving group, such as halogen, (C1-C6)- alkoxy, -O-tosyl, -O-mesyl or -Nl-imidazole, and then with an amine of the general formula (4) or (5) in which R and Rl have the meanings mentioned above, giving the desired indole derivative of the general formula (1) (with amine 4) or the compound of the general formula (6) (with amine 5) in which Rl, R2, R3, R4, Zl and Z2 have the meanings mentioned above, using, if appropriate, diluents and auxiliaries, where the compound of the general formula (6) may subsequently be reacted with a compound of the general formula (7) in which R has the meaning mentioned above and Y3 represents a suitable electrophilic leaving group, such as halogen, (C1-C6)-alkoxy, -O-tosyl, -O-mesyl or -Nl- imidazole, giving' the desired compound (1) , where R does not denote hydrogen, using, if appropriate, diluents and auxiliaries. Synthesis routes; The compounds of the general formula 1 can be obtained according to Scheme 1 below: Furthermore, the compounds of the general formula 1 can also be obtained by the synthesis route of Scheme 2: Scheme 2 The compounds of the general formula 1 in which R= methyl, benzyl, propargyl or cyanomethyl and Ri, R2, R3 and R4 have the meanings given for the general formula 1 can also be prepared according to the synthesis route of Scheme 3: The starting materials (2), (3) and (4) are either commercially available or can be prepared by procedures known per se. The starting materials (2), (3) and (4) are useful intermediates for preparing the indole derivatives of the formula (I) according to the invention. For the preparation of starting materials and target compounds, reference may be made, for example, to the following standard works of organic synthesis, the content of which is hereby explicitly included into the disclosure of the present application: 1) Houben-Weyl, Volume E 7a (part 1) pp. 290-492/ pp. 571-740 Houben-Weyl, Volume E 7a (part 2) pp. 119-156, pp. 205-686, pp. 157-204 2) Monograph "Heterocyclic Compounds" (Elderfield) , Volume 1, pp. 119-207, pp. 397-616 Volume 3, pp. 1-274 Volume 6, pp. 101-135, pp. 234-323 3) Monograph "Comprehensive Organic Chemistry" (S.D. Barton, W.D. Ollis) Volume 4, pp. 155-204, pp. 205-232, pp. 493-564 The solvents and auxiliaries to be used, if appropriate, and the reaction parameters to be used, such as reaction temperature and reaction time, are known to the person skilled in the art owing to his expert knowledge. The indole derivatives of the general formula (1) according to the invention are suitable as medicaments, in particular as antitumor agents, for treating mammals, in particular man, but also domestic animals such as horses, cattle, dogs, cats, hares, sheep, poultry and the like. According to a further aspect of che invention, a method for controlling tumors in mammals, in particular man, is provided which is characterized in that at least one indole derivative of the general formula (1) is administered to a mammal in an amount effective for the treatment , of the tumor. The therapeutically effective dose of the indole derivative according to the invention in question which is to be administered for the treatment depends inter alia on the nature and the stage of the oncosis, the age and the sex of the patient, the type of administration and the duration of the treatment. Administration can take place orally, rectally, buccally (for example sublingually), parenterally (for example subcutaneously, intra- muscularly, intradermally or intravenously) , topically or transdermally. According to a further aspect of the invention, medicaments for the treatment of tumors, are provided which are characterized in that they comprise, as active ingredient, at least one indole derivative according to any of claims 1 to 5 or a pharmaceutically acceptable salt thereof, if appropriate together with customary pharmaceutically acceptable auxiliaries, additives and carriers. These can be solid, semisolid, liquid or aerosol preparations. Suitable solid preparations are, for example, capsules, powders, granules, tablets. Suitable semisolid preparations are, for example, ointments, creams, gels, pastes, suspensions, oil-in-water and water-in-oil emulsions. Suitable liquid preparations are, for example, sterile aqueous preparations for parenteral administration which are isotonic with the blood of the patient. The invention is to be illustrated in more detail by the example below, without being restricted to the example. Working examples Example 1 (Reaction according to Scheme 1, 1. step): Preparation of 1-(4-chlorobenzyl)indole A solution of 5.86 g (0.05 mol) of indole in 25 ml of DMSO is added to a mixture of 1.32 g of sodium hydroxide (0.055 mol, suspension in mineral oil) in 50 ml of dimethyl sulfoxide. The mixture is heated at 60°C for 1.3 hours and then allowed to cool, and 17.7 g (0.11 mol) of 4-chlorobenzyl chloride are added dropwise. The solution is heated at 60°C, allowed to stand overnight and then poured with stirring into 200 ml of water. The mixture is extracted repeatedly with a total of 75 ml of CH2CI2, the organic phase is dried with anhydrous sodium sulfate and filtered and the filtrate is concentrated under reduced pressure. Yield: 11.5 g (95% of theory) Example 2 (Reaction according to the 2. step of Scheme 1) : Preparation of N-(2~methyl~6-quinolyl)-[1-(4- chlorobenzyl)indole-3-yljglyoxylamide (D-69429) At 0°C and under nitrogen, a solution of 10.2 g (42.2 mmol) of 1-(4-chlorobenzyl) indole in 50 ml of ether is added dropwise to a solution of 5.50 ml of oxalyl chloride in 50 ml of ether. The mixture is heated at reflux for 2 hours and the solvent is then evaporated. 100 ml of tetrahydrofuran were then added to the residue and the solution was cooled to -4°C and treated dropwise with a solution of 15.66 g (99.0 mmol) of 6-amino-2-methylquinoline in 350 ml of THF. The mixture is heated at reflux for 4 hours and allowed to stand at room temperature overnight. The 6-amino-2~ methylquinoline hydrochloride is filtered off with suction, the precipitate is washed with THF, the filtrate is concentrated under reduced pressure and the residue is recrystallized from methyl ethyl ketone/ methylene chloride. Yield: 14.8 g (77.3% of theory) Melting point: 182-185°C Preparation of the hydrochloride: The equivalent amount of hydrochloric acid, dissolved in isopropanol, is added to 0.453 g (1 mmol) of N-(2- methyl-6-quinolyl) - [1-^ (4-chlorobenzyl) indol-3- yl]glyoxylamide in 20 ml of hot ethanol, the mixture is heated at 70-80°C and the solution is, at 40°C and under reduced pressure, evaporated to dryness. Repeated additional evaporation with toluene gave the colorless and crystalline hydrochloride. Yield: 0.49 g (100% of theory) m.p.; 196°C Preparation of the methanesulfonate: A mixture of 0.453 g (1 mmol) of N- (2-methyl-6- quinolyl)-[1-(4-chlorobenzyl)indol-3-yl]glyoxylamide and 0.67 ml of methanesulfonic acid in 15 ml of dichloromethane is heated at 50°C for 30 minutes, the resulting solution is concentrated at 35°C under reduced pressure, the residue is additionally evaporated with methyl tert-butyl ether repeatedly, and the resulting residue is dried at 35°C under reduced pressure. Yield: 0.46 g (84% of theory) m.p'. : > 230°C Example 3 (Reaction according to Scheme 3): Preparation of N-propargyl-N-(2-methyl-6-quinolyl)- [1-(4-chlorobenzyl)indol-3-yl]glyoxylamide At room temperature and under nicrogen, a suspension of 2.32 g (5.13 mmol) of N-(2-methyl-6-quinolyl))-[1-(4- chlorobenzyl)indol-3-yl]glyoxylamide in 20 ml of DMF is added to a suspension of 0.154 g of sodium hydride (5.13 mmol, suspension in mineral oil) in 10 ml of DMF. This resulted in strong foaming, with the mixture turning yellow. A solution of 0.382 g (5.13 mmol) of propargyl chloride in 10 ml of DMF is added dropwise, and the mixture is, under nitrogen gas, stirred at room temperature for 24 hours and allowed to stand at room temperature for 4 days. The dark-brown solution is then poured into 120 ml of ice water and extracted in portions with 250 ml of methylene chloride, and the combined organic phases are dried using anhydrous sodium sulfate. The extract is concentrated under reduced pressure and the residue is purified using a silica gel column (silica gel 60, from Merck AG, Darmstadt, Germany) and the mobile phase methylene chloride/ethanol (97:3, v/v). Yield: 1.98 g (78.6% of theory) Mass spectrum: m/e= 491.9 (M) Biological tests 1. Antiproliferative action in various tumor cell lines In a proliferation test, the antiproliferative activity of the substance D-69429 was examined using established tumor cell lines. In the test used, the cellular dehydrogenation activity is determined, which makes it possible to determine the vitality of the cell and, indirectly, the cell count. The cell lines used are the human cervical carcinoma cell line KB/HeLa (ATCC CCL17), the murine lymphocyte leukaemia L1210 (ATCC CCL-219), the human breast adenocarcinoma line MCF7 (ATCC HTB22) and the ovary adenocarcinoma line SKOV-3 (ATCC HTB77). These are established cell lines which are very well characterized and were obtained from ATCC and cultured. The results shown in Tab. 1 demonstrate the highly potent antiproliferative action of D-69429 in the cell lines SKOV-3, L-1210 and HeLa/KB. Owing to the particularly slow growth of the MCF7 line, the effect of D-69429 in the test period of 48 h is only small (18% inhibition at 3.16 ng/ml; thus stated as >3.16). 2. Method XTT Test for cellular dehydrogenase activity The adherently growing tumor cell lines HeLa/KB, SKOV-3 and MCF7 and the L1210 leukaemia line, which grows in suspension, were cultivated under standard conditions in an incubator with gas inlet at 37°C, 5% C02 and 95% atmospheric humidity. On Test Day 1, the adherent cells are detached using trypsin/EDTA and pelleted by centrifugation. The cell pellet is then resuspended in the RPMI culture medium at the appropriate cell count and transferred to a 96-well microtiter plate. The plates are then cultivated overnight in the incubator with gas inlet. The test substances are made up as stock solutions in DMSO and, on Test Day 2, diluted with culture medium to the corresponding concentrations. The substances in the culture medium are then added to the cells and incubated in the incubator with gas inlet for 45 h. Cells which have not been treated with test substance serve as control. For the XTT assay, 1 mg/ml of XTT (sodium 3'-[l- (phenylaminocarbonyl) -3 , 4-tetrazolium] -bis (4-methoxy-6- nitro)benzenesulfonic acid) is dissolved in RPMI-1640 medium without Phenol Red. Additionally, a 0.3 83 mg/ml solution of PMS (N-methyldibenzopyrazine methyl sulfate) in phosphate-buffered saline (PBS) is prepared. On Test Day 4, 75 ul/well of the XTT-PMS mixture are pipetted onto the cell plates, which by now have been incubated with the test substances for 4 5 h. To this end, the XTT solution is mixed with the PMS solution in a ratio of 50; i (v/v) shortly before use. The cell plates are then incubated in the incubator with gas inlet for a further 3 h, and the optical density (OD490nm) is determined in a photometer. Using the OD490nm obtained, the inhibition in percent relative to the control is calculated. The antiproliferative activity is estimated using regression analysis. Example I Tablet containing 50 mg of active compound Composition: (1) Active compound 50.0 mg (2) Lactose 98.0 mg (3) Maize starch 50.0 mg (4) Polyvinylpyrrolidone 15.0 mg (5) Magnesium stearate 2.0 mg Total: 215.0 mg Preparation: (1), (2) and (3) are mixed and granulated with an aqueous solution of (4). The dried granules are admixed with (5). This mixture is tabletted. Example II Capsule containing 50 mg of active compound Composition: (1) Active compound 50.0 mg (2) Maize starch, dried 58.0 mg (3) Lactose powder 50.0 mg (4) Magnesium stearate 2.0 mg Total: 160.0 mg Preparation: (1) is ground with (3) . This ground material is added with vigorous mixing to the mixture of (2) and (4). This powder mixture is, on a capsule filling machine, filled into hard gelatine capsules size 3. We Claim: 1. The general formula (I) the substituents should at least be R denotes a - hydrogen - straight-chain or branched (C1-C6) -alkylcarbonyl - straight-chain or branched (C1 -C6)-alkyloxycarbonyl Rl denotes - pyrido[2,3-b]pyrazinyl - indazolyl - isothiazolyl - indolyl - isoxazolyl optionally substituted by a (C1-C6) alkyl group or (C1-C6)-alkoxy group R2 denotes benzyl, substituted with halogen R3, R4 denote hydrogen Z1,Z2 denote O,S. 2. Indole derivative as claimed in claim 1 wherein R, R2, R3, R4, Z1 and Z2 have the meanings described above and Rl represents quinolyl which is mono- or polysubstituted by straight-chain or branched (C1- C6-alkyl) or (C1-C6)-alkoxy. 3. Indole derivative as claimed in any of claims 1 to 2, wherein R, R2, R3, R4, Zl and Z2 have the meanings described above and R1 represents 2-methyl-6-quinolyl. 4. Indole derivative as claimed in any of claims 1 to 3, wherein R, R2, R3, R4, Zl and Z2 have the meanings described above and Rl denotes (2-methyl)-6-quinolyl, R2 denotes 4-chlorobenzyl, R3 and R4 each denote hydrogen and Z1 and Z2 each denote oxygen. 5. Indole derivative of the general formula (1) according to any of claims 1 to 4 for use as medicaments. 6. Indole derivatives of the general formula (1) to any of claims 1 to 4 is used for preparing a medicament for treating tumors in mammals. 7. Process for preparing indoles derivatives of the general formula (1) as claimed in any of claims 1 to 4 wherein an indole precursor of the general formula (2) in which R2, R3, and R4 have the meanings mentioned above is reacted with a compound of the general formula (3) in which Z1 and Z2 have the meaning mentioned above and Y1 and Y2 independently of one another represent a suitable leaving group, such as halogen, (C1-C6) -alkoxy, -O-tosyl, -O-mesyl or -N1-imidazole, and then with an amine of the general formula (4) or (5). in which R and R1 have the meanings mentioned above, giving the desired compound of the general formula (1) (with amine 4) or the compound of the general formula (6) (with amine 5) in which R1, R2, R3, R4, Z1 and Z2 have the meanings mentioned above, using, if appropriate, diluents and auxiliaries, where the compound of the general formula (6) may subsequently be reacted with a compound of the general formula (7) in which R has the meaning mentioned above and Y3 represents a suitable electrophilic leaving group, such as halogen, (C1 -C6)-alkoxy, -O-tosyl, -O-mesyl or -N1-imidazole, giving the desired compound (1), where R does not denote hydrogen, using, if appropriate, diluents and auxiliaries. The general formula (1) the substituents should at least be R denotes a - Hydrogen - straight-chain or branched (C1-C6)-alkylcarbonyl - straight-chain or branched (C1-C6)-alkyloxycarbonyl R1 denotes - 5-,6-, 7-quinolyl - pyrido[2,3-b]pyrazinyl - indazolyl - isothiazolyl - indolyl - isoxazolyl optionally substituted by a (C1-C6) alkyl group or (C1-C6)-alkoxy group R2 denotes benzyl, substituted with halogen R3, R4 denote hydrogen Z1, Z2 denote O, S

Full Text

Novel indole derivatives and their use as medicaments
The invention relates to novel indole derivatives of the general formula 1, to their
preparation and to their use as medicaments, in particular for treating tumors.
This invention has been divided out from the Parent Application No. 51/KOLNP/2003 of
15.01.2003, Entitled: Novel indole derivatives and their use as medicaments.
Indol-3-yl derivatives having certain 2-, 3-, 4- and 8- quinoline radicals are described in
the German application DE 198 14 838.0. However, indol-3-yl derivatives having 5-, 6-
or 7-quinoline substituents are neither described nor suggested in this publication.
According to one aspect of the invention, novel indole derivatives of the general formula
1

in which
R denotes hydrogen; straight-chain or branched (C1-C6) -alkyl; (C1-C6) -alkyl which is
mono- or polysubstituted by aryl, where the aryl radical [lacuna] unsubstituted or
mono- to penta-[lacuna] by identical or different substituents from the group
consisting of halogen, (C1-C6) -alkyl, (C3-C7) -cycloalkyl, carboxyl, (C1-C6) -
alkoxy-carbonyl, preferably tert-butoxycarbonyl, straight-chain or branched (C1-C6) -
alkyl, which is substituted by one or more fluorine atoms,

preferably trifluoromethyi, hydroxyl, straight-
chain or branched (C1-C6)-alkoxy, preferably
methoxy or ethoxy; benzyloxy or aryl-(C1-C6)-alkyl,
where the aryl radical may be unsubstituted or
mono- or pentasubsti tuned by identical or
different substituents from the group consisting
of (C1-C6)-alkyl, halogen and straight-chain or
branched (C1-C6)-alkyl which is substituted by one
or more fluorine atoms, preferably
trifluoromethyi; straight-chain or branched (C1-
C6)-alkoy-(C1-C6)-alkyl [sic], substituted or
unsubstituted aryl- (C1-C6) -alkyloxycarbonyl,
preferably benzyloxycarbonyl, straight-chain or
branched (C1-C6)-alkyloxycarbonyl, straight-chain
or branched (C1-C6)-alkylcarbonyl, preferably
acetyl, (C2-C6)-alkenyl, preferably allyl, (C2-C6)-
alkynyl, preferably ethynyl or propargyl, or
straight-chain or branched cyano-(C1-Ce)-alkyl,
preferably cyanomethyl;
denotes a saturated, unsaturated or aromatic
(C2-C14)-heterocycle which contains one or more
heteroatoms selected from the group consisting of
N, 0 and S and which may be attached to the amide
nitrogen directly or via a (C1-C6)-alkyl bridge,
where the (C1-C4) -alkyl radical may be
unsubstituted or mono- [lacuna] polysubstituted by
identical or different substituents from the group
consisting of (C1-C6)-alkyl, halogen and oxo (=0)
and the 2-, 4-, 5- or 6-pyrimidinyl radical may in
each case be unsubstituted or mono- to
trisubstituted by identical or different
substituents from the group consisting of
hydrogen, (C1—C6) -alkyl, halogen, nitro, amino,
mono- (C1-C6) -alkylamino, di- (C1-C6) -alkylamino,
hydroxyl, (C1-C6)-alkoxy, benzyloxy, carboxyl,
(C1-C6)-alkoxycarbonyl, (C1-C6)-alkoxycarbonylamino
or (C:~C6)-alkyl which is mono- or polysubstituted
by fluorine, preferably trifluoromethyi, (C6-C10 -

aryl and (C6-C10) -aryl- (C1-C6) -alkyl, with the
proviso that Rl does not represent unsubstituted
2- or 4-pyrimidinyl or a 2-pyrimidinyl radical
which is mono- or polysubstituted by methyl; and
except for (C1-C6)-alkyl-, halogen-, nitro-,
amino- and (C1-C6)-alkylamino-substituted or
unsubstituted 2-, 3-, 4- and 8-quinolyl and 2-, 3-
and 4-quinolylmethyl in which the ring carbon
atoms of the pyridylmethyl moiety are
unsubstituted or substituted by (C1-C6)-alkyl,
(C1-C6)-alkoxy, nitro, amino and (C1-C6)-
alkoxycarbonylamino;
R2 denotes hydrogen, (C1-C6 -alkyl, (C1-C6)-alkyl
which is mono- or polysubstituted by halogen, (C1-
C6)-alkyl which is mono- or polysubstituted by
phenyl, where the phenyl radical may be
unsubstituted or nono- to pentasubstituted by
identical or different substituents from the group
consisting of halogen, preferably chlorine,
bromine or iodine, (C1-C6) -alkyl, (C3-C7)-
cycloalkyl, carboxyl, (C1-C6) -alkoxycarbonyl, (C1-
C6)-alkyl which is mono- or polysubstituted by
halogen, preferably trifluoromethyl, hydroxyl,
(C1-C6)-alkoxy, preferably methoxy or ethoxy,
phenyl-(C1-C6)-alkoxy, preferably benzyloxy, nitro,
amino, mono-(C1-C6)-alkylamino, di-(C1-C6)-
alkylamino, mono- (C2-5) -cycloalkylamino, di-(C3-6)-
cycloalkylamino, (C1-C6) -acylamino, phenyl- (C1-C6) -
alkylamino, arylcarbonylamino, heteroarylcarbonyl-
amino, (C1-C6) -alkylsulfonamido, arylsulfonamido,
maleinimido, succinimido, phthalimido, benzyl-
oxycarbonylamino (Z-amino), tert-butoxy-
carbonylamino (BOC-amino), 9-fluorenylmethoxy-
carbonylamino (Fmoc-amino), triphenylmethylamino
(Tr-amino) , 2-(4'-pyridyl)-ethoxycarbonylamino
(Pyoc-amino) , diphenylmethylsilylamino (DPMS-
amino), by -NH-CH2-COOH; -NH-CH (CH3)-COOH;

(CH3)2CH-CH2-CH2-CH(NH-)-COOH; H3C-CH2-CH (CH3)-
CH(NH-)-COOH;
H0H2C-CH(NH-)-C0OH; phenyl-CH2-CH (NH- ) -COOH; (4-
imidazolyl)-CH2-CH(NH-)-COOH; HN=C (NH2) -NH- (CH2)3-
CH(NH-)-COOH; H2N-(CH2)4-CH(NH-)-COOH;
H2N-CO-CH2-CH (NH-) -COOH; HOOC- (CH2) 2-CH (NH-) -COOH;
a 2-, 3-, 4-, 5-, 6-, 7- and 8-quinolyl-(C:-C6) -
alkyl radical, where the 2-, 3-, 4-, 5,-, [sic]
6-, 7- and 8-quinolyl radical may be unsubstituted
or mono- to hexasubstituted by identical or
different substituents from the group consisting
of halogen, (C1-C4)-alkyl or (C:-C4) -alkoxy;
a 2~, 3- and 4-pyridyl-(C:-C6>-alkyl radical, where
the 2-, 3- and 4-pyridyl radical may be
unsubstituted or mono- to tetrasubstituted by
identical or different substituents from the group
consisting of halogen, (C1-C4)-alkyl and (C-_-C4)-
alkoxy;
an arylcarbonyl radical, where the aryl radical
may be unsubstituted or mono- to pentasubstituted
by identical or different substituents from the
group consisting of halogen, (C1-Cs) -alkyl, (C3-
C7)-cycloalkyl, carboxyl, cyano, (C1-C6)-
alkoxycarbonyl, (C1-C6) -alkyl which is mono- or
polysubstituted by fluorine atoms preferably
trifluoromethyl, hydroxyl, (C1-C4) -alkoxy
preferably methoxy or ethoxy, aryl- (C1-C4) -alkoxy,
preferably benzyioxy;
R;. and R4 may be attached to the indole carbon atoms
C-2, C-4, C-5, C-6 or C-7 and independently of one
another denote hydrogen, hydroxyl, (C1-C6)-alkyl,
(C3-C7) -cycloalkyl, (d-C6)-alkylcarbonyl, (C:-C5)-
alkoxy, halogen, aryl-(C1-C4)-alkoxy, preferably
benzyioxy, nitro, amino, mono-(C;-C4)-alkylamino,
di- (C1-C4) -alkylarr.ino, (C:-C6) -alkoxycarbonylamino ,
(C1-C6) -alkoxycarbonylamino- (C1-Ce) -alkyl, cyano,
straight-chain or branched cyano- (C1-C6) -alkyl,
carboxyl, (C2-C4) -alkoxycarbonyl, (C1-C4) -alkyl

which , is .substituted by one or more fluorine
atoms, preferably trifluoromethyl group, carboxy-
(C:-C6)-alkyl or (C:-C5) -alkoxycarbonyl- lCi-C6) -
alkyl;
Z: denotes oxygen or sulfur or geminally attached
hydrogen and hydroxyl;
Zi denotes oxygen or sulfur,
their tautomers, stereoisomers, including the
diastereomers and enantiomers, and the
physiologically acceptable salts thereof, are
provided.
Thus, for example, the compounds of the general formula
(1) according to the invention which have one or more
centers of chirality and which are present as racemates
can be separated by methods known per se into their
optical isomers, i.e. enantiomers or diastereomers. The
separation can be carried out by column separation on
chiral phases or by recrystallization from an optically
active solvent or using an optically active acid or
base or by derivatization with an optically active
reagent, such as, for example, an optically active
alcohol, and subsequent removal of the radical.
Furthermore, the indole derivatives of the formula (1)
according to the invention can be converted into their
salts with inorganic or organic acids, in particular,
for pharmaceutical use, into their physiologically
acceptable salts. Acids which are suitable for this
purpose are, for example, hydrochloric acid,
hydrobromic acid, sulfuric acid, phosphoric acid,
fumaric acid, succinic acid, lactic acid, malic acid,
eribonic acid, malonic acid, citric acid, acetic acid,
tartaric acid, trifluoroacetic acid, methanesulfonic
acid, sulfoacetic acid or maleic acid.

Moreover, the compounds of the formula (1) according to
the invention can, if they contain a sufficiently-
acidic group, such as a carboxyl group, be converted,
if desired,.into their salts with inorganic or organic
bases, in particular, for pharmaceutical use, into
their physiologically acceptable salts. Bases which are
suitable for this purpose are, for example, sodium
hydroxide, potassium hydroxide, calcium hydroxide,
lysine, cyclohexylamine, ethanolamine, diethanolamine
and triethanolamine.
According to a preferred embodiment, indole derivatives
of the general formula (1) above are provided in which
R, R2, R3, R4, Zl and Z2 have the meanings given above
and
R: denotes a 2-, 4-, 5- or 6-pyrimidinyl radical or
2-, 4-, 5- or 6-pyrimidinyl-(C:-C4)-alkyl radical,
where the {C1-C4) -alkyl radical may be
unsubstituted or mono- [lacuna] polysubstituted by
identical or different substituents from the group
consisting of (C1-Ce) -alkyl, halogen and oxo (=0)
and the 2-, 4-, 5- or 6-pyrimidinyl radical may be
unsubstituted or mono- to trisubstituted by
identical or different substituents from the group
consisting of hydrogen, (C1-Cs)-alkyl, halogen,
nitro, amino, mono- (C:-C£) -alkylamino, di-(.Ci-Cs) -
alkylamino, hydroxyl, (C;-Co)-alkoxy, benzyloxy,
carboxyl, (d-C6) -alkoxycarbonyl, (C:-C6)-
alkoxycarbonylamino or (C1-Cs) -alkyl which is mono-
or polysubstituted by fluorine, preferably
trif luoromethyl, (C0-C10)-aryl, or (C—Cio) -aryl-
(C1-Ce)-alkyl, with the proviso that Rl does not
represent unsubstituted 2- or 4-pyrimidinyl or a
2-pyrimidinyl radical which is mono- or
polysubstituted by methyl;
a 3-, 4-, 5- or 6-pyridazinyl radical or 3-, 4-,
5- or 6-pyridazinyl-(C1-C4)-alkyl radical, where
the (C1-C4)-alkyl radical may be unsubstituted or

mono- or polysubstituted by identical or different
substituents from the group consisting of (C:-C;)-
alkyl, halogen and oxo (=0) and the 3-, 4-, 5- or
6-pyridazinyl radical may . be unsubstituted or
mono- to trisubstituted by identical or different
substituents from the group consisting of
hydrogen, (C1-Cs)-alkyl, halogen, nitro, amino,
mono- (C1-C6) -alkylamino, di- (C1-Ce) -alkylamino,
hydroxyl, (C1-Ce)-alkoxy, benzyloxy, carboxyl, (C:-
Co) -alkoxycarbonyl, (C:-C6) -alkoxycarbonylamino or
(C1-Co)-alkyl which is mono- or polysubstituted by
fluorine, preferably trifluoromethyl, (C5-C10)-aryl
and (C6-Cio) -aryl- (C1-C6) -alkyl;
a 2-, 3-, 5- or 6-pyrazinyl radical or 2-, 3-, 5,-
[sic] or 6-pyrazinyl-(d-C4)-alkyl radical, where
the (C1-C4)-alkyl radical may be unsubstituted or
mono- or polysubstituted by identical or different
substituents from the group consisting of (C:-C5)-
alkyl, halogen and oxo (=0) and the 2-, 3-, 5,-
[sic] or 6-pyrazinyl radical may be unsubstituted
or mono- to trisubstituted by identical or
different substituents from the group consisting
of hydrogen, (C1-C6)-alkyl, halogen, nitro, amino,
mono- (C1-C6) -alkylamino, di- (C1-C6) -alkylamino,
hydroxyl, (C1-Ce)-alkoxy, benzyloxy, carboxyl, (C1-
C6) -alkoxycarbonyl, (C1-C0) -alkoxycarbonylamino or
(C1-Ce)-alkyl which is mono- or polysubstituted by
fluorine, preferably trifluoromethyl, (C6-Cio)-aryl
and (C6-C:3) -aryl- (C1-Ce) -alkyl ;
a 3-, 4-, 5-, 6-, 7- or 8-cinnolinyl radical or
3-, 4-, 5-, 6-, 7-, or 8-cinnolinyl-(C1-C4)-alkyl
radical, where the (C^-C^)-alkyl radical may be
unsubstituted or mono- or polysubstituted by
identical or different substituents from the group
consisting of (Cx-C?)-alkyl, halogen and oxo (=0)
and the 3-, 4-, 5-, 6-, 7-, or 8-cinnolinyl
radical may be unsubstituted or mono- to
pentasubstituted by identical or different
substituents from the group consisting of

hydrogen, (C1-C6)-alkyl, halogen, nitro, amino,
. mono- (C1-C6) -alkylamino, di- (C1-C-) -alkylamino,
hydroxyl, (C1-C5) -alkoxy, benzyloxy, carboxyl, (d-
C6)-alkoxycarbonyl, (C:-Cf)-alkoxycarbonylamino or
(C1-C6)-alkyl which is mono- or polysubstituted by
fluorine, preferably trifluoromethyl, (C5-C:o) -aryl
and (C6-C10)-aryl-(C1-C6)-alkyl;
a 2-, 4-, 5-, 6-, 7- or 8-quinazolinyl radical or
2-, 4-, 5-, 6-, 7- or 8-quinazolinyl-(C1-C4)-alkyl
radical, where the (C:-C4)-alkyl radical may be
unsubstituted or mono- or polysubstituted by
identical or different substituents from the group
consisting of hydrogen, (C1-Cs) -alkyl, halogen and
oxo (=0) and the or [sic] 2-, 4-, 5-, 6-,, 7- or
8-quinazolinyl radical, may be unsubstituted or
mono- to pentasubstituted by identical or
different substituents from the group consisting
of hydrogen, (CN-Ce)-alkyl, halogen, nitro, amino,
mono- (C1-C5) -alkylamino, di- (d-C;) -alkylamino,
hydroxyl, (C1-C6)-alkoxy, benzyloxy, carboxyl, (C1-
Ce) -alkoxycarbonyl, (C:-C£) -alkoxycarbonylamino or
(C1-C6)-alkyl which is mono- or polysubstituted by
fluorine, preferably trifluoromethyl, (C6-Ci0)-aryl
and (C6-Cio)-aryl- (C1-C«) -alkyl;
a 2-, 3-, 5-, 6-, 7- or 8-quinoxalinyl radical or
2-, 3-, 5-, 6-, 7- or 8-quinoxalinyl-(C1-C4)-alkyl
radical, where the (C:-C unsubstituted or mono- or polysubstituted by
identical or different substituents from the group
consisting of (C1-Cs) -alkyl, halogen and oxo (=0)
and the or [sic] 2-, 3-, 5-, 6-, 7- or 8-
quinoxalinyl radical may be unsubstituted or mono-
to pentasubstituted by identical or different
substituents from the group consisting of
hydrogen, (C-.-C^)-alkyl, halogen, nitro, amino,
mono- (C:-C6) -alkylamino, di- (C:-C6) -alkylamino,
hydroxyl, (C:-C6) -alkoxy, benzyloxy, carboxyl, (C:-
C6) -alkoxycarbonyl, (C1-C6)-alkoxycarbonylamino or
(C1-C5)-alkyl which is mono- or polysubstituted by

fluorine, preferably trifluoromethyl, (C6-C10)-aryl
and (Co-Cn) -aryl- (C1-C6) -alkyl ;
a 1-, 4-, 5-, 6-, 7- or 8-phthalazinyl radical or
1-, 4-, 5-, 6-, 7- or 8-phthalazinyl- (C:-C4) -alkyl
radical, where the (C1-C4) -alkyl radical may be
unsubstituted or mono- or polysubstituted by
identical or different substituents from the group
consisting of (C1-Cg) -alkyl, halogen and oxo (=0)
and the or [sic] 1-, 4-, 5-, 6-, 7- or 8-
phthalazinyl radical may be unsubstituted or mono-
to pentasubstituted by identical or different
substituents from the group consisting of
hydrogen, (C-^-Ce) -alkyl, halogen, nitro, amino,
mono- (C1-Co) -alkylamino, di- (C1-Ce) -alkylamino,
hydroxyl, (C1-C5) -alkoxy, benzyloxy, carboxyl, (Cx-
C6) -alkoxycarbonyl, (CN-Co) -alkoxycarbonylamino or
(C1-Cs)-alkyl which is mono- or polysubstituted by
fluorine, preferably trifluoromethyl, (Cj-Ci;)-aryl
and (C6-C::.) -aryl- (C:-C6) -alkyl;
a 2-, 3-, 4-, 5-, 6-, 7- or 8-quinolyl radical or
2-, 3-, 4-, 5-, 6-, 7 or 8-quinolyl- (C1-C4) -alkyl
radical, where the (C1-C4)-alkyl radical may be
unsubstituted or mono- or polysubstituted by
identical or different substituents from the group
consisting of (C1-Cs) -alkyl, halogen and oxo (=0)
and the 2-, 3-, 4-, 5-, 6-, 7- or 8-quinolyl
radical may be unsubstituted or mono- to
hexasubstituted by identical or different
substituents from the group consisting of
hydrogen, (d-C6) -alkyl, preferably methyl,
particularly preferably 2-methyl, halogen, nitro,
amino, mono- (C1-Cs) -alkylamino, N, N-di- (C1-C6) -
alkylamino, hydroxyl, (C1-C6)-alkoxy, (C6-C14)-
aryl-(C1-C6)-alkyoxy [sic], preferably benzyloxy,
carboxyl, (C1-C6)-alkoxycarbonyl, (C:-C;)-
alkoxycarbonylamino or (C:-C-;) -alkyl which is mono-
or polysubstituted by halogen, preferably
trifluoromethyl, (C6-Ci4)-aryl and (C6-Ci4)-aryl-
(C1-C6)-alkyl, except for (C1-C6)-alkyl-, halogen-,

nitro-, amino- and (C1-C6)-alkylamino-substituted
or unsubstituted 2-, 3-, 4- and 8-quinolyl and 2-,
3- and 4-quinolylmethyl in which the ring carbon
atoms of the pyridylmethyl moiety are
unsubstituted or substituted by (C1-C6)-alkyl,
(C1-C6)-alkoxy, nitro, amino and (C1-C6)-
alkoxycarbonylamino;
a 1-, 3-, 4-, 5-, 6-, 7- or 8-isoquinolyl radical
or 1-, 3-, 4-, 5-, 6-, 7- or 8-isoquinolyl-(C1-CJ -
alkyl radical, where the (C1-C4)-alkyl radical may
be unsubstituted or mono- or polysubstituted by
identical or different substituents from the group
consisting of (C1-C6) -alkyl, halogen and oxo (=0)
and the 1-, 3-, 4-, 5-, 6-, 7- or 8-isoquinolyl
radical may be unsubstituted or mono- to
hexasubstituted by identical or different
substituents from the group consisting of
hydrogen, (C1-C.5)-alkyl, halogen, nitro, amino,
mono- (C1-Ce) -alkylamino, di- (C:-Cs) -alkylarr.ino,
hydroxyl, (C1-C6) -alkoxy, benzyloxy, carboxyl, (C--
Ce) -alkoxycarbonyl, (C1-Ce) -alkoxycarbonylamino or
(C:-C6)-alkyl which is mono- or polysubstituted by
fluorine, preferably trifluoromethyl, (Ce-Cio)-aryl
and (C6-Cio) -aryl- (C1-Ce) -alkyl;
a 2-, 6-, 8- or 9- [9H] -purinyl radical or 2-, 6-,
8- or 9-[9H]-purinyl-(C1-C4)-alkyl radical, where
the (C1-C4)-alkyl radical may be unsubstituted or
mono- or polysubstituted by identical or different
substituents from the group consisting of (C1-C5)-
alkyl, halogen and oxo (=0) and the 2-, 6-, 8- or
9-[9H] -purinyl radical may be unsubstituted or
mono- to trisubstituted by identical or different
substituents from the group consisting of
hydrogen, (C—Ce)-alkyl, halogen, nitro, amino,
mono- (C-.-Cs) -alkylamino, di- (C:-C.O -alkylamino,
hydroxyl, (C-L-Co) -alkoxy, benzyloxy, carboxyl, (C-_-
CA)-alkoxycarbonyl, (C1-C6)-alkoxycarbonylamino or
(C;-Ce)-alkyl which is mono- or polysubstituted by

fluorine, preferably trifiuoromethyl, (C6-Cio) -aryl
and (C6-C::)-aryl- (C:-C6) -alkyl;
a 2-, 6-, 7- or 8- [1H] -purinyl radical or 2-, 6-,
7- or 8-[7tf]-purinyl-(d-d)-alkyl radical, where
the . (C1-C4)-alkyl radical may be unsubstituted or
mono- or polysubstituted by identical or different
substituents from the group consisting of (C1-C6)-
alkyl, halogen and oxo (=0) and the 2-, 6-, 7- or
8-[1H] -purinyl radical may be unsubstituted or
mono- to trisubstituted by identical or different
substituents from the group consisting of
hydrogen, (d~d)-alkyl, halogen, nitro, amino,
mono- (C1-C6) -alkylamino, di- (d-d) -alkylamino,
hydroxyl, (d-C6) -alkoxy, benzyloxy, carboxyl, (d~
C6)-alkoxycarbonyl, (C1-C6) -alkoxycarbonylamino or
(C1-C0) -alkyl which is mono- or polysubstituted by
fluorine, preferably trif Iuoromethyl, (d~Cio) -aryl
and (C6-Ci0)-aryl- (C1-C6) -alkyl;
a 1-, 2-, 3-, 4~, 5-, 6-, 7-, 8- or 9-acridinyl
radical or 1-, 2-, 3-, 4-, 5-, 6-, 7-, 8- or
9-acridinyl-(C1-C4)-alkyl radical, where the (d-
C6)-alkyl radical may be unsubstituted or mono- or
polysubstituted by identical or different
substituents from the group consisting of (C1-Cg)-
alkyl, halogen and oxo (=0) and the 1-, 2-, 3-,
4-, 5-, 6-, 7-, 8- or 9-acridinyl radical may be
unsubstituted or mono- to octasubstituted by
identical or different substituents from the group
consisting of hydrogen, (C1-C5)-alkyl, halogen,
nitro, amino, mono- (C1-Ce) -alkylamino, di-(C:-C6)-
alkylamino, hydroxyl, (C1-C6)-alkoxy, benzyloxy,
carboxyl, (C1-C6) -alkoxycarbonyl, (C1-C6)-
alkoxycarbonylamino or (C-.-Ce) -alkyl which is mono-
or polysubstituted by fluorine, preferably
trif Iuoromethyl, (C5-C:o) -aryl and (C6-C;;:) -aryl-
(C-_-C0) -alkyl;
a 1-, 2-, 3-, 4-, 6-, 7-, 8-, 9- or
10-phenanthridinyl radical or 1-, 2-, 3-, 4-, 6-,
7-, 8- or 9- or 10-phenanthridinyl- (C1-C6) -alkyl

radical, where the (C:-C6) -alkyl radical may be
, unsubstituted or mono- or polysubstiluted by
identical or different substituents from the group
consisting of hydrogen, (C:-Ci)-alkyl, halogen and
oxo (=0) and the 1-, 2-, 3-, 4-, 6-, 7-, 8-, 9- or
10-phenanthridinyl radical may be unsubstituted or
mono- to octasubstituted by identical or different
substituents from the group consisting of (C1-Cg)-
alkyl, halogen, nitro, amino, mono-(C1-Ce) -
alkylamino, di- (C1-Cg)-aikylamino, hydroxyl, (Cx-
C5)-alkoxy, (C6-C:o)-aryl-(C:-C6)-alkoxy, preferably
benzyloxy, carboxyl, (C:-C6)-alkoxycarbonyl, (C1-
C6) -alkoxy car bony 1 ami no or (C1-Ce) -alkyl which is
mono- or polysubstituted by fluorine, preferably
trifluoromethyl, (C6-Ci0)-aryl and (C6-Ci0) -aryl-
(C1-C6)-alkyl;
a 2-, 3-, 4-, 5,- [sic] or 6-pyridyl radical where
the 2-, 3-, 4-, 5,- [sic] or 6-pyridyl radical may
be unsubstituted or mono- to tetrasubscituted by
identical or different substituents from the group
consisting of hydrogen, (C1-Ce)-alkyl, halogen,
nitro, amino, mono-(C1-C5)-alkylamino, di-fCi-Ce)-
alkylamino, hydroxyl, (C1-Ce)-alkoxy, benzyloxy,
carboxyl, (d-C6) -alkoxycarbonyl, (C1-C6)-
alkoxycarbonylamino or (C1-Cg)-alkyl which is mono-
or polysubstituted by fluorine, preferably
trifluoromethyl, (C6-Cio)-aryl and (Cr--C;;)-aryl-
(C1-C6)-alkyl, with the proviso that zi# Z;, R2, R3
and R4 have the meaning given above or below,
without any limitations, and R represents (C2-C0)-
alkenyl, preferably allyl, (C2-C6)-alkynyl,
preferably ethynyl or propargyl, (C1-C*)-alkoxy-
(C1-C6)-alkyl, or straight-chain or branched cyano-
(C1-C6) -alkyl, preferably cyanomethyl, cr with the
proviso that Z2, R, R-, R3 and R.; have the meanings
described above or below, without any limitations,
and Zi denotes geminally attached hydrogen and
hydroxyl;

a 2-, 3-, 4-, 5,- [sic] or 6-pyridyi-(C:-C6)-alkyl
radical, where the (C:-C£)-alkyl radical may be
unsubstituted or mono- or polysubstituted by
identical or different substituents from the group
consisting of (C1-C5)-alkyl, halogen and oxo (=0)
and the 2-, 3-, 4-, 5,- [sic] or 6-pyridyl radical
may be unsubstituted or mono- to tetrasubstituted
by identical or different substituents from the
group consisting of hydrogen, (C1-C0) -alkyl,
halogen, nitro, amino, mono-(C:-Cg)-alkylamino, di-
(C:-C6)-alkylamino, hydroxyl, (C:-C;) -alkoxy,
benzyloxy, carboxyl, (C1-Cg)-alkoxycarbonyl, (C:-
C6)-alkoxycarbonylamino or (C1-C6) -alkyl which is
mono- or polysubstituted by fluorine, preferably
trifluoromethyl, (C6-C;o)-aryl and (C6-C10) -aryl-
(C1-C6)-alkyl;
a 2-, 3-, 4,- [sic] or 5-thienyl radical or 2-,
3-, 4,- [sic] or 5-thienyl- (C1-C6) -alkyl radical,
where the (C;-C--)-alkyl radical may be
unsubstituted or mono- or polysubstituted by
identical or different substituents from the group
consisting of (C1-Cs) -alkyl, halogen and oxo (=0)
and the 2-, 3-, 4,- [sic] or 5-thienyl radical may
be unsubstituted or mono- to trisubstituted by
identical or different substituents from the group
consisting of hydrogen, (C1-Ce)-alkyl, halogen,
nitro, amino, mono- (C:-Cf) -alkylamino, di-(C1-Cs)-
alkylamino, hydroxyl, (C1-C6)-alkoxy, benzyloxy,
carboxyl, (C:-C6)-alkoxycarbonyl, (C1-Cs)-
alkoxycarbonylamino or (C;-C6) -alkyl which is mono-
or polysubstituted by fluorine, preferably
trifluoromethyl, (C5-C1:.) -aryl and (C6-Cio) -aryl-
(C:-C5)-alkyl;
a 2-, 4-, or 5-thiazolyl radical or 2-, 4-, or 5-
thiazolyl-(C1-Cf)-alkyl radical, where the (C1-C3)-
aikyl radical may be unsubstituted or mono- or
polysubstituted by identical or different
substituents from the group consisting of (C1-Ce)-
alkyl, halogen and oxo (=0) and the 2-, 4-, or 5-

thiazolyl' radical may be unsubstituted or mono- or
disubstituted by identical or different
substituents from the group consisting of
hydrogen, (d-C6) -alkyl, halogen, nitro, amino,
mono- (C;-C6) -alkylamino, di- (C:-C6) -alkylamino,
hydroxyl, (C1-Cs) -alkoxy, benzyloxy, carboxyl, (C1-
C6)-alkoxycarbonyl, (C1-Cs)-alkoxycarbonylamino or
(C1-Ce) -alkyl which is mono- or polysubstituted by
fluorine, preferably trifluoromethyl, (Ce-Cio)-aryl
and (C£-Cio)-aryl-(C1-Ce)-alkyl;
a 3-, 4-, or 5-isothiazolyl radical or 3-, 4- or
5-isothiazolyl-(C1-C6)-alkyl radical, where the
(C1-Ce)-alkyl radical may be unsubstituted or mono-
or polysubstituted by identical or different
substituents from the group consisting of (C1-Cg)-
alkyl, halogen and oxo (=0) and the 3-, 4- or 5-
isothiazolyl radical may be unsubstituted or mono-
or disubstituted by identical or different
substituents from the group consisting of
hydrogen, (C1-Ce)-alkyl, halogen, nitro, amino,
mono- (C1-Ce) -alkylamino, di- (C1-Ce) -alkylamino,
hydroxyl, (C1-C6)-alkoxy, benzyloxy, carboxyl, (C1-
Ce)-alkoxycarbonyl, (C1-C6)-alkoxycarbonylamino or
(C:-C6)-alkyl which is mono- or polysubstituted by
fluorine, preferably trifluoromethyl, (Cg-Cio)-aryl
and (Cf-Cio) -aryl- (Cx-C6) -alkyl;
a 2-, 4-, 5-, 6- or 7-benzothiazolyl radical or
2-, 4-, 5-, 6- or 7-benzothiazolyl- (C--Cs) -alkyl
radical, where the (C1-C6) -alkyl radical may be
unsubstituted or mono- or polysubstituted by
identical or different substituents from the group
consisting of (C1-Ce) -alkyl, halogen and oxo (=0)
and the 2-, 4-, 5-, 6- or 7-benzothiazolyl radical
may be unsubstituted or mono- to tetrasubstituted
by identical or different substituents from the
group consisting of hydrogen, (C^-Ce)-alkyl,
halogen, nitro, amino, mono-(C1-Ce)-alkylamino, di-
(C:-Co) -alkylamino, hydroxyl, (C1-C6) -alkoxy,
benzyloxy, carboxyl, (C1-Ce)-alkoxycarbonyl, (C;-

C6> -alkoxycarbonylamino or (d~d) -alkyl which is
mono- or. polysubstituted by fluorine, preferably
trifluoromethyl, (C6-Cio) -aryl and (d~do) -aryl-
(C^Ce)-alkyl;.
a 1-, 2-, 4- or 5-imidazolyl radical or 1-, 2-, 4-
or 5-imidazolyl-(C1-C6>-alkyl radical, where the
(C1-C6)-alkyl radical may be unsubstituted or mono-
or polysubstituted by identical or different■
substituents from the group consisting of (d~d)-
alkyl, halogen and oxo (=0) and the 1-, 2-, 4- or
5-imidazolyl radical may be unsubstituted or mono-
to trisubstituted by identical or different
substituents from the group consisting of
hydrogen, (d~d)-alkyl, halogen, nitro, amino,
mono- (C1-C6) -alkylamino, di- (d~d) -alkylamino,
hydroxyl, (d~d)-alkoxy, benzyloxy, carboxyl, (d~
d)-alkoxycarbonyl, (d_d)-alkoxycarbonylamino or
(d~d) -alkyl which is mono- or polysubstituted by
fluorine, preferably trifluoromethyl, (d-d:)-aryl
and (Cs-Cio) -aryl- (C;-C6) -alkyl;
a 1-, 3-, 4- or 5-pyrazolyl radical or 1-, 3-, 4-
or 5-pyrazolyl-(C1-C6)-alkyl radical, where the
(C1-C6)-alkyl radical may be unsubstituted or mono-
or polysubstituted by identical or different
substituents from the group consisting of (C1-C6)-
alkyl, halogen and oxo (=0) and the 1-, 3-, 4- or
5-pyrazolyl radical may be unsubstituted or mono-
to trisubstituted by identical or different
substituents from the group consisting of
hydrogen, (C1-Ce)-alkyl, halogen, nitro, amino,
mono- (C1-C6) -alkylamino, di- (d-C6) -alkylamino,
hydroxyl, (C1-C6) -alkoxy, benzyloxy, carboxyl, (d-
C6) -alkoxycarbonyl, (C1-C6) -alkoxycarbonylamino or
(d-d)-alkyl which is mono- or polysubstituted by
fluorine, preferably trifluoromethyl, (C^-C—.)-aryl
and (C6-Cio) -aryl- (C:-C6) -alkyl;
a 1-, 2,- [sic] 3,- [sic] 4,- [sic] or 5-pyrroiyl
radical or 1-, 2,- [sic] 3,- [sic] 4,- [sic] or
5-pyrrolyl-(C1-C6)-alkyl radical, where the (d-

C6)-alkyl radical may be unsubstituted or mono- or
polysubstituted by identical or different
substituents from the group consisting of (C1-C6)-
alkyl, halogen and oxo (=0) and the 1-, 2,- [sic]
3,- [sic] 4,- [sic] or 5-pyrrolyl radical may be
unsubstituted or mono- to tetrasubstituted by
identical or different substituents from the group
consisting of hydrogen, (C1-Ce)-alkyl, halogen,
nitro, amino, mono- (C1-C6> -alkylamino, di-(C1-C6>-
alkylamino, hydroxyl, (C:-C6)-alkoxy, benzyloxy,
carboxyl, (C1-Ce) -alkoxycarbonyl, (C:-C5)-
alkoxycarbonylamino or (C:-Cg)-alkyl which is mono-
or polysubstituted by fluorine, preferably
trif luoromethyl, (C6-Cio)-aryl and (C6-Cio) -aryl-
(d-C6)-alkyl;
a 1-, 3-, or 5-[1.2.4]-triazolyl radical or 1-, 3-
or 5-[1.2.4]-triazolyl-(C1-Cc)-alkyl radical, where
the (C1-C6) -alkyl radical may be unsubstituted or
mono- or polysubstituted by identical or different
substituents from the group consisting of
hydrogen, (C1-Ce) -alkyl, halogen and oxo (=0) and
the 1-, 3- or 5-[1.2.4]-triazolyl radical may be
unsubstituted or mono- or disubstituted by
identical or different substituents from the group
consisting of (C:-C6)-alkyl, halogen, nitro, amino,
mono- (C1-Ce) -alkylamino, di- (C1-C6) -alkylamino,
hydroxyl, (C1-C6)-alkoxy, benzyloxy, carboxyl, (C1-
Ce)-alkoxycarbonyl, (C:-C5)-alkoxycarbonylamino or
(C1-Cj)-alkyl which is mono- or polysubstituted by
fluorine, preferably trifluoromethyl, (Ce-C10)-aryl
and (C6-Cio) -aryl- (C1-C6) -alkyl;
a 1-, 4- or 5-[l.2.3]-triazolyl radical or 1-, 4-
or 5-[1.2.3]-triazolyl-(C1-C6)-alkyl radical, where
the (C1-Ce)-alkyl radical may be unsubstituted or
mono- or polysubstituted by identical or different
substituents from the group consisting of (C;-Ce)-
alkyl, halogen and oxo (=0) and the 1-, 4- or 5-
[1.2.3]-triazolyl radical may be unsubstituted or
mono- or disubstituted by identical or different

substituents . from the group consisting of
hydrogen, (C:-C£>-alkyl, halogen, nitro, amino,
mono- (C1-C6) -alkylamino, di- (C1-C6) -alkylamino,
hydroxyl, (C1-Ce) -alkoxy, benzyloxy, carboxyl, (C1-
Ce)-alkoxycarbonyl, (C1-Ce)-alkoxycarbonylamino or
(C1-Ce)-alkyl which is mono- or polysubstituted by
fluorine, preferably trifluoromethyl, (Co-Cio)-aryl
and (C6-C10)-aryl-(C1-C6)-alkyl;
a 1- or 5-[lH]-tetrazolyl radical or 1- or 5-[ltf]-
tetrazolyl-(C1-Ce)-alkyl radical, where the (C1-
Ce)-alkyl radical may be unsubstituted or mono- or
polysubstituted by identical or different
substituents from the group consisting of (C1-Cs)-
alkyl, halogen and oxo (=0) and the 1- or 5-[lH]-
tetrazolyl radical may be unsubstituted or
substituted by hydrogen, (C1-C6> -alkyl, halogen,
nitro, amino, mono- (C1-Ce) -alkylamino, di-(C1-Ce)-
alkylamino, hydroxyl, (C1-Cg)-alkoxy, benzyloxy,
carboxyl, (C:-C6)-alkoxycarbonyl, (Ci.-Co)-
alkoxycarbonylamino or (C1-C5)-alkyl which is mono-
or polysubstituted by fluorine, preferably
trif luoromethyl, (C6-Ci0) -aryl and (C6-Cio) -aryl-
(C1-Cs)-alkyl;
a 2- or 5-[2H] -tetrazolyl radical or 2- or 5-[2H]-
tetrazolyl-(C1-Ce)-alkyl radical, where the (C1-
Ce)-alkyl radical may be unsubstituted or mono- or
polysubstituted by identical or different
substituents from the group consisting of (C1-C6>-
alkyl, halogen and oxo (=0) and the 2- or 5-[2H]-
tetrazolyl radical may be unsubstituted or
substituted by hydrogen, (C1-Ce)-alkyl, halogen,
nitro, amino, mono- (C1-C6> -alkylamino, di-(C1-C6)-
alkylamino, hydroxyl, (C1-C6)-alkoxy, benzyloxy,
carboxyl, (C1-Ce) -alkoxycarbonyl, (C1-C6)-
alkoxycarbonylamino or (C;-Ce)-alkyl which is mono-
or polysubstituted by fluorine, preferably
trif luoromethyl, (Cs-Cio)-aryl and (Ce-C—)-aryl-
(Cx-Cs) -alkyl;

a 2-, 4- or 6-[1.3 .5]-triazinyl radical or 2-, 4-
or 6-[1.3.5]-triazinyl-(C1-C6)-alkyl radical, where
the (C1-C6) -alkyl radical may be unsubstituted or
mono- or polysubstituted by identical or different
substituents from the group consisting of
hydrogen, (C1-C6)-alkyl, halogen and oxo (=0) and
the 2-, 4- or 6-[1.3 . 5]-triazinyl radical may be
unsubstituted or mono- or disubstituted by
identical or different substituents from the group
consisting of hydrogen, (C1-C5)-alkyl, halogen,
nitro, amino, mono- (C1-C6) -alkylamino, di-(C1-Cs)-
alkylamino, hydroxyl, (C-.-Cs)-alkoxy, benzyloxy,
carboxyl, (C1-C6)-alkoxycarbonyl, (C1-C6)-
alkoxycarbonylamino or (C1-C5)-alkyl which is mono-
or polysubstituted by fluorine, preferably
trifluoromethyl, (C6-C10) -aryl and (Ce-Cio) -aryl-
(C1-C6>-alkyl;
a 2-, 4- or 5-oxazolyl radical or 2-, 4- or 5-
oxazolyl-(C1-C6)-alkyl radical, where the (C:-Cs)-
alkyl radical may be unsubstituted or mono- or
polysubstituted by identical or different
substituents from the group consisting of (C1-Ce)-
alkyl, halogen and oxo (=0) and the 2-, 4-, or 5-
oxazolyl radical may be unsubstituted or mono- or
disubstituted by identical or different
substituents from the group consisting of
hydrogen, (C:~C6)-alkyl, halogen, nitro, amino,
mono- (C1-Ce) -alkylamino, di- (C:-Co) -alkylamino,
hydroxyl, (C:-C$) -alkoxy, benzyloxy, carboxyl, (C1-
Co)-alkoxycarbonyl, (C1-C6)-alkoxycarbonylamino or
(C1-Ce)-alkyl which is mono- or polysubstituted by
fluorine, preferably trifluoromethyl, (C6-C10)-aryl
and (C6-Cio)-aryl-(C1-C6)-alkyl;
a 3-, 4- or 5-isoxazolyl radical or 3-, 4- or 5-
isoxazolyl-(C:-C5)-alkyl radical, where the (C-:-
Ce)-alkyl radical may be unsubstituted or mono- or
polysubstituted by identical or different
substituents from the group consisting of (C1-C6)-
alkyl, halogen and oxo (=0) and the 3-, 4- or 5-

isoxazolyl radical may be unsubstituted or mono-
or disubstituted by identical or different
substituencs from the group consisting of
hydrogen, (C:-C6)-alkyl, halogen, nitro, amino,
mono- (C1-Cs) -alkylamino, di- (C1-C6) -alkylamino,
hydroxyl, (C:-C6)-alkoxy, benzyloxy, carboxyl, {Ci-
Ce) -alkoxycarbonyl, (Ci~C6)-alkoxycarbonylamino or
(C:-C6)-alkyl which is mono- or polysubstituted by
fluorine, preferably trifluoromethyl, (C6-C10)-aryl
and (C6-Cio) -aryl- (C1-C6) -alkyl;
a 1-, 2-, 3-, 4-, 5-, 6- or 7-indolyl radical or
1-, 2-, 3-, 4-, 5-, 6- or 7-indolyl-(C1-C6)-alkyl
radical, where the (C1-C6) -alkyl radical may be
unsubstituted or mono- or polysubstituted by
identical or different substituents from the group
consisting of (C1-C6) -alkyl, halogen and oxo (=0)
and the 1-, 2-, 3-, 4-, 5-, 6- or 7-indolyl
radical may be unsubstituted or mono- to
hexasubstituted by identical or different
substituents from the group consisting of
hydrogen, (C1-Ce)-alkyl, halogen, nitro, amino,
mono- (C1-C6) -alkylamino, di- (C1-C6) -alkylamino,
hydroxyl, (C1-Ce)-alkoxy, benzyloxy, carboxyl, (C1-
Cs)-alkoxycarbonyl, (C1-C0)-alkoxycarbonylamino or
(C:-C6)-alkyl which is mono- or polysubstituted by
fluorine, preferably trif luoromethyl, (C6-C10) -aryl
and (C6-C10)-aryl-(C1-C6)-alkyl, and also the
isomers, in particular tautomers, diastereomers
and enantiomers, and the pharmaceutically
acceptable salts, in particular acid addition
salts, thereof [lacuna].
According to a further embodiment, indole derivatives
of the general formula (1) are provided which are
characterized in that R, R2, R3, R4, Zl and Z2 have the
meanings described above and R: represents quinolyl
which is mono- or polysubstituted by straight-chain or
branched (C1-Cg-alkyl) or (C1-Cs) -alkoxy.

According to a further embodiment, indole derivatives
of the general - formula (1) are provided which are
characterized in that R, R2, R3, R4, Zl and Z2 have the
meanings described above and Ri represents 2-methyl-6-
quinolyl.
According to a further embodiment, indole derivatives
of the general formula (1) are provided which are
characterized in that R, R2, R3, R4 Zl and Z2 have the
meanings described above and Ri denotes (2-methyl)-6-
quinolyl, R2 denotes 4-chlorobenzyl, R3 and R4 each
denote hydrogen and Zi and Z2 each denote oxygen.
According to a further aspect of the invention, a
process for preparing indole derivatives of the general
formula (1) according to any of claims 1 to 5 is
[lacuna] which is characterized in that an indole
precursor of the general formula (2)

in which R2, R3 and R4 have the meanings mentioned
above is reacted with a compound of the general formula
(3)

in which Zl and Z2 have the meaning mentioned above and
Yl and Y2 independently of one another represent a
suitable leaving group, such as halogen, (C1-C6)-
alkoxy, -O-tosyl, -O-mesyl or -Nl-imidazole, and then
with an amine of the general formula (4) or (5)

in which R and Rl have the meanings mentioned above,
giving the desired indole derivative of the general
formula (1) (with amine 4) or the compound of the
general formula (6) (with amine 5)

in which Rl, R2, R3, R4, Zl and Z2 have the meanings
mentioned above, using, if appropriate, diluents and
auxiliaries, where the compound of the general formula
(6) may subsequently be reacted with a compound of the
general formula (7)

in which R has the meaning mentioned above and Y3
represents a suitable electrophilic leaving group, such
as halogen, (C1-C6)-alkoxy, -O-tosyl, -O-mesyl or -Nl-

imidazole, giving' the desired compound (1) , where R
does not denote hydrogen, using, if appropriate,
diluents and auxiliaries.
Synthesis routes;
The compounds of the general formula 1 can be obtained
according to Scheme 1 below:

Furthermore, the compounds of the general formula 1 can
also be obtained by the synthesis route of Scheme 2:
Scheme 2

The compounds of the general formula 1 in which R=
methyl, benzyl, propargyl or cyanomethyl and Ri, R2, R3
and R4 have the meanings given for the general formula
1 can also be prepared according to the synthesis route
of Scheme 3:

The starting materials (2), (3) and (4) are either
commercially available or can be prepared by procedures
known per se. The starting materials (2), (3) and (4)

are useful intermediates for preparing the indole
derivatives of the formula (I) according to the
invention.
For the preparation of starting materials and target
compounds, reference may be made, for example, to the
following standard works of organic synthesis, the
content of which is hereby explicitly included into the
disclosure of the present application:
1) Houben-Weyl, Volume E 7a (part 1) pp. 290-492/
pp. 571-740
Houben-Weyl, Volume E 7a (part 2) pp. 119-156,
pp. 205-686, pp. 157-204
2) Monograph "Heterocyclic Compounds" (Elderfield) ,
Volume 1, pp. 119-207, pp. 397-616
Volume 3, pp. 1-274
Volume 6, pp. 101-135, pp. 234-323
3) Monograph "Comprehensive Organic Chemistry" (S.D.
Barton, W.D. Ollis)
Volume 4, pp. 155-204, pp. 205-232, pp. 493-564
The solvents and auxiliaries to be used, if
appropriate, and the reaction parameters to be used,
such as reaction temperature and reaction time, are
known to the person skilled in the art owing to his
expert knowledge.
The indole derivatives of the general formula (1)
according to the invention are suitable as medicaments,
in particular as antitumor agents, for treating
mammals, in particular man, but also domestic animals
such as horses, cattle, dogs, cats, hares, sheep,
poultry and the like.
According to a further aspect of che invention, a
method for controlling tumors in mammals, in particular
man, is provided which is characterized in that at
least one indole derivative of the general formula (1)

is administered to a mammal in an amount effective for
the treatment , of the tumor. The therapeutically
effective dose of the indole derivative according to
the invention in question which is to be administered
for the treatment depends inter alia on the nature and
the stage of the oncosis, the age and the sex of the
patient, the type of administration and the duration of
the treatment. Administration can take place orally,
rectally, buccally (for example sublingually),
parenterally (for example subcutaneously, intra-
muscularly, intradermally or intravenously) , topically
or transdermally.
According to a further aspect of the invention,
medicaments for the treatment of tumors, are provided
which are characterized in that they comprise, as
active ingredient, at least one indole derivative
according to any of claims 1 to 5 or a pharmaceutically
acceptable salt thereof, if appropriate together with
customary pharmaceutically acceptable auxiliaries,
additives and carriers. These can be solid, semisolid,
liquid or aerosol preparations. Suitable solid
preparations are, for example, capsules, powders,
granules, tablets. Suitable semisolid preparations are,
for example, ointments, creams, gels, pastes,
suspensions, oil-in-water and water-in-oil emulsions.
Suitable liquid preparations are, for example, sterile
aqueous preparations for parenteral administration
which are isotonic with the blood of the patient.
The invention is to be illustrated in more detail by
the example below, without being restricted to the
example.
Working examples
Example 1 (Reaction according to Scheme 1, 1. step):
Preparation of 1-(4-chlorobenzyl)indole

A solution of 5.86 g (0.05 mol) of indole in 25 ml of
DMSO is added to a mixture of 1.32 g of sodium
hydroxide (0.055 mol, suspension in mineral oil) in
50 ml of dimethyl sulfoxide. The mixture is heated at
60°C for 1.3 hours and then allowed to cool, and 17.7 g
(0.11 mol) of 4-chlorobenzyl chloride are added
dropwise. The solution is heated at 60°C, allowed to
stand overnight and then poured with stirring into
200 ml of water. The mixture is extracted repeatedly
with a total of 75 ml of CH2CI2, the organic phase is
dried with anhydrous sodium sulfate and filtered and
the filtrate is concentrated under reduced pressure.
Yield: 11.5 g (95% of theory)
Example 2 (Reaction according to the 2. step of Scheme
1) :
Preparation of N-(2~methyl~6-quinolyl)-[1-(4-
chlorobenzyl)indole-3-yljglyoxylamide (D-69429)
At 0°C and under nitrogen, a solution of 10.2 g
(42.2 mmol) of 1-(4-chlorobenzyl) indole in 50 ml of
ether is added dropwise to a solution of 5.50 ml of
oxalyl chloride in 50 ml of ether. The mixture is
heated at reflux for 2 hours and the solvent is then
evaporated. 100 ml of tetrahydrofuran were then added
to the residue and the solution was cooled to -4°C and
treated dropwise with a solution of 15.66 g (99.0 mmol)
of 6-amino-2-methylquinoline in 350 ml of THF. The
mixture is heated at reflux for 4 hours and allowed to
stand at room temperature overnight. The 6-amino-2~
methylquinoline hydrochloride is filtered off with
suction, the precipitate is washed with THF, the
filtrate is concentrated under reduced pressure and the
residue is recrystallized from methyl ethyl ketone/
methylene chloride.
Yield: 14.8 g (77.3% of theory)

Melting point: 182-185°C
Preparation of the hydrochloride:
The equivalent amount of hydrochloric acid, dissolved
in isopropanol, is added to 0.453 g (1 mmol) of N-(2-
methyl-6-quinolyl) - [1-^ (4-chlorobenzyl) indol-3-
yl]glyoxylamide in 20 ml of hot ethanol, the mixture is
heated at 70-80°C and the solution is, at 40°C and
under reduced pressure, evaporated to dryness. Repeated
additional evaporation with toluene gave the colorless
and crystalline hydrochloride.
Yield: 0.49 g (100% of theory)
m.p.; 196°C
Preparation of the methanesulfonate:
A mixture of 0.453 g (1 mmol) of N- (2-methyl-6-
quinolyl)-[1-(4-chlorobenzyl)indol-3-yl]glyoxylamide
and 0.67 ml of methanesulfonic acid in 15 ml of
dichloromethane is heated at 50°C for 30 minutes, the
resulting solution is concentrated at 35°C under
reduced pressure, the residue is additionally
evaporated with methyl tert-butyl ether repeatedly, and
the resulting residue is dried at 35°C under reduced
pressure.
Yield: 0.46 g (84% of theory)
m.p'. : > 230°C
Example 3 (Reaction according to Scheme 3):
Preparation of N-propargyl-N-(2-methyl-6-quinolyl)-
[1-(4-chlorobenzyl)indol-3-yl]glyoxylamide
At room temperature and under nicrogen, a suspension of
2.32 g (5.13 mmol) of N-(2-methyl-6-quinolyl))-[1-(4-
chlorobenzyl)indol-3-yl]glyoxylamide in 20 ml of DMF is
added to a suspension of 0.154 g of sodium hydride
(5.13 mmol, suspension in mineral oil) in 10 ml of DMF.

This resulted in strong foaming, with the mixture
turning yellow. A solution of 0.382 g (5.13 mmol) of
propargyl chloride in 10 ml of DMF is added dropwise,
and the mixture is, under nitrogen gas, stirred at room
temperature for 24 hours and allowed to stand at room
temperature for 4 days. The dark-brown solution is then
poured into 120 ml of ice water and extracted in
portions with 250 ml of methylene chloride, and the
combined organic phases are dried using anhydrous
sodium sulfate. The extract is concentrated under
reduced pressure and the residue is purified using a
silica gel column (silica gel 60, from Merck AG,
Darmstadt, Germany) and the mobile phase methylene
chloride/ethanol (97:3, v/v).
Yield: 1.98 g (78.6% of theory)
Mass spectrum: m/e= 491.9 (M*)
Biological tests
1. Antiproliferative action in various tumor cell
lines
In a proliferation test, the antiproliferative activity
of the substance D-69429 was examined using established
tumor cell lines. In the test used, the cellular
dehydrogenation activity is determined, which makes it
possible to determine the vitality of the cell and,
indirectly, the cell count. The cell lines used are the
human cervical carcinoma cell line KB/HeLa (ATCC
CCL17), the murine lymphocyte leukaemia L1210 (ATCC
CCL-219), the human breast adenocarcinoma line MCF7
(ATCC HTB22) and the ovary adenocarcinoma line SKOV-3
(ATCC HTB77). These are established cell lines which
are very well characterized and were obtained from ATCC
and cultured.
The results shown in Tab. 1 demonstrate the highly
potent antiproliferative action of D-69429 in the cell

lines SKOV-3, L-1210 and HeLa/KB. Owing to the
particularly slow growth of the MCF7 line, the effect
of D-69429 in the test period of 48 h is only small
(18% inhibition at 3.16 ng/ml; thus stated as >3.16).
2. Method
XTT Test for cellular dehydrogenase activity
The adherently growing tumor cell lines HeLa/KB, SKOV-3
and MCF7 and the L1210 leukaemia line, which grows in
suspension, were cultivated under standard conditions
in an incubator with gas inlet at 37°C, 5% C02 and 95%
atmospheric humidity. On Test Day 1, the adherent cells
are detached using trypsin/EDTA and pelleted by
centrifugation. The cell pellet is then resuspended in
the RPMI culture medium at the appropriate cell count
and transferred to a 96-well microtiter plate. The
plates are then cultivated overnight in the incubator
with gas inlet. The test substances are made up as
stock solutions in DMSO and, on Test Day 2, diluted
with culture medium to the corresponding
concentrations. The substances in the culture medium
are then added to the cells and incubated in the
incubator with gas inlet for 45 h. Cells which have not
been treated with test substance serve as control.
For the XTT assay, 1 mg/ml of XTT (sodium 3'-[l-
(phenylaminocarbonyl) -3 , 4-tetrazolium] -bis (4-methoxy-6-
nitro)benzenesulfonic acid) is dissolved in RPMI-1640
medium without Phenol Red. Additionally, a 0.3 83 mg/ml
solution of PMS (N-methyldibenzopyrazine methyl
sulfate) in phosphate-buffered saline (PBS) is
prepared. On Test Day 4, 75 ul/well of the XTT-PMS
mixture are pipetted onto the cell plates, which by now
have been incubated with the test substances for 4 5 h.
To this end, the XTT solution is mixed with the PMS
solution in a ratio of 50; i (v/v) shortly before use.
The cell plates are then incubated in the incubator

with gas inlet for a further 3 h, and the optical
density (OD490nm) is determined in a photometer.
Using the OD490nm obtained, the inhibition in percent
relative to the control is calculated. The
antiproliferative activity is estimated using
regression analysis.

Example I
Tablet containing 50 mg of active compound
Composition:
(1) Active compound 50.0 mg
(2) Lactose 98.0 mg
(3) Maize starch 50.0 mg
(4) Polyvinylpyrrolidone 15.0 mg
(5) Magnesium stearate 2.0 mg
Total: 215.0 mg
Preparation:
(1), (2) and (3) are mixed and granulated with an
aqueous solution of (4). The dried granules are admixed
with (5). This mixture is tabletted.
Example II
Capsule containing 50 mg of active compound
Composition:
(1) Active compound 50.0 mg
(2) Maize starch, dried 58.0 mg
(3) Lactose powder 50.0 mg
(4) Magnesium stearate 2.0 mg
Total: 160.0 mg
Preparation:
(1) is ground with (3) . This ground material is added
with vigorous mixing to the mixture of (2) and (4).
This powder mixture is, on a capsule filling machine,
filled into hard gelatine capsules size 3.

We Claim:
1. The general formula (I) the substituents should at least be

R denotes a
- hydrogen
- straight-chain or branched (C1-C6) -alkylcarbonyl
- straight-chain or branched (C1 -C6)-alkyloxycarbonyl
Rl denotes
- pyrido[2,3-b]pyrazinyl
- indazolyl
- isothiazolyl
- indolyl
- isoxazolyl
optionally substituted by a (C1-C6) alkyl group or (C1-C6)-alkoxy
group
R2 denotes benzyl, substituted with halogen
R3, R4 denote hydrogen
Z1,Z2 denote O,S.

2. Indole derivative as claimed in claim 1 wherein R, R2, R3, R4, Z1 and
Z2 have the meanings described above and Rl represents quinolyl
which is mono- or polysubstituted by straight-chain or branched (C1-
C6-alkyl) or (C1-C6)-alkoxy.
3. Indole derivative as claimed in any of claims 1 to 2, wherein R, R2,
R3, R4, Zl and Z2 have the meanings described above and R1
represents 2-methyl-6-quinolyl.
4. Indole derivative as claimed in any of claims 1 to 3, wherein R, R2,
R3, R4, Zl and Z2 have the meanings described above and Rl
denotes (2-methyl)-6-quinolyl, R2 denotes 4-chlorobenzyl, R3 and R4
each denote hydrogen and Z1 and Z2 each denote oxygen.

5. Indole derivative of the general formula (1) according to any of claims 1 to 4 for use as
medicaments.
6. Indole derivatives of the general formula (1) to any of claims 1 to 4 is used for
preparing a medicament for treating tumors in mammals.
7. Process for preparing indoles derivatives of the general formula (1) as claimed in any of
claims 1 to 4 wherein an indole precursor of the general formula (2)

in which R2, R3, and R4 have the meanings mentioned above is reacted with a
compound of the general formula (3)

in which Z1 and Z2 have the meaning mentioned above and Y1 and Y2
independently of one another represent a suitable leaving group, such as halogen,
(C1-C6) -alkoxy, -O-tosyl, -O-mesyl or -N1-imidazole, and then with an amine
of the general formula (4) or (5).

in which R and R1 have the meanings mentioned above, giving the desired
compound of the general formula (1) (with amine 4) or the compound of the
general formula (6) (with amine 5)

in which R1, R2, R3, R4, Z1 and Z2 have the meanings mentioned above, using,
if appropriate, diluents and auxiliaries, where the compound of the general
formula (6) may subsequently be reacted with a compound of the general formula
(7)

in which R has the meaning mentioned above and Y3 represents a suitable
electrophilic leaving group, such as halogen, (C1 -C6)-alkoxy, -O-tosyl, -O-mesyl
or -N1-imidazole, giving the desired compound (1), where R does not denote
hydrogen, using, if appropriate, diluents and auxiliaries.

The general formula (1) the substituents should at least be

R denotes a
- Hydrogen
- straight-chain or branched (C1-C6)-alkylcarbonyl
- straight-chain or branched (C1-C6)-alkyloxycarbonyl
R1 denotes
- 5-,6-, 7-quinolyl
- pyrido[2,3-b]pyrazinyl
- indazolyl
- isothiazolyl
- indolyl
- isoxazolyl
optionally substituted by a (C1-C6) alkyl group or (C1-C6)-alkoxy group
R2 denotes benzyl, substituted with halogen
R3, R4 denote hydrogen
Z1, Z2 denote O, S

Documents:

01386-kolnp-2008-abstract.pdf

01386-kolnp-2008-claims.pdf

01386-kolnp-2008-correspondence others.pdf

01386-kolnp-2008-description complete.pdf

01386-kolnp-2008-form 1.pdf

01386-kolnp-2008-form 2.pdf

01386-kolnp-2008-form 3.pdf

01386-kolnp-2008-form 5.pdf

1386-KOLNP-2008-ABSTRACT 1.1.pdf

1386-KOLNP-2008-AMANDED CLAIMS.pdf

1386-KOLNP-2008-CORRESPONDENCE.pdf

1386-KOLNP-2008-CORRESPONDENCE1.1.pdf

1386-KOLNP-2008-DESCRIPTION (COMPLETE) 1.1.pdf

1386-KOLNP-2008-EXAMINATION REPORT REPLY RECIEVED.pdf

1386-KOLNP-2008-EXAMINATION REPORT.pdf

1386-KOLNP-2008-FORM 1-1.1.pdf

1386-KOLNP-2008-FORM 18.1.pdf

1386-kolnp-2008-form 18.pdf

1386-KOLNP-2008-FORM 2-1.1.pdf

1386-KOLNP-2008-FORM 26.1.pdf

1386-KOLNP-2008-FORM 26.pdf

1386-KOLNP-2008-FORM 3-1.1.pdf

1386-KOLNP-2008-FORM 3.pdf

1386-KOLNP-2008-FORM 5-1.1.pdf

1386-KOLNP-2008-FORM 5.pdf

1386-KOLNP-2008-FORM-27-1.1.pdf

1386-KOLNP-2008-FORM-27.pdf

1386-KOLNP-2008-GRANTED-ABSTRACT.pdf

1386-KOLNP-2008-GRANTED-CLAIMS.pdf

1386-KOLNP-2008-GRANTED-DESCRIPTION (COMPLETE).pdf

1386-KOLNP-2008-GRANTED-FORM 1.pdf

1386-KOLNP-2008-GRANTED-FORM 2.pdf

1386-KOLNP-2008-GRANTED-SPECIFICATION.pdf

1386-KOLNP-2008-OTHERS.pdf

1386-KOLNP-2008-PCT SEARCH REPORT.pdf

1386-KOLNP-2008-PETITION UNDER RULE 137.pdf

1386-KOLNP-2008-REPLY TO EXAMINATION REPORT.pdf

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Patent Number

250149

Indian Patent Application Number

1386/KOLNP/2008

PG Journal Number

50/2011

Publication Date

16-Dec-2011

Grant Date

12-Dec-2011

Date of Filing

07-Apr-2008

Name of Patentee

ZENTARIS GMBH

Applicant Address

WEISMULLERSTRASSE 50, D-60314 FRANKFURT

Inventors:

#	Inventor's Name	Inventor's Address
1	EMIG, PETER	LUDWIG-ERHARDT-STR. 22, 63486 BRUCHKOBEL
2	AUE, BEATE	VALENTIN-HOCK-STR. 32, 63762 GROSSOSTHEIS/RINGHEIM
3	REICHERT, DIETMAR	ELSAVASTR. 79, 63863 ESCHAU
4	BAASNER, SILKE	DITTERSDDORFER STR. 42, 61137 SCHONECK
5	NICKEL, BERND	ALLEESTR. 35, 64367 MUHLTAL
6	GUNTHER, ECKHARD	WINGERTSTR. 176, 63477 MAINTAL
7	BACHER, GERALD	KRIEGERSTR. 62, 82110 GERMERING

PCT International Classification Number

C07D 401/12

PCT International Application Number

PCT/EP2001/008644

PCT International Filing date

2001-07-26

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1	100 37 310.0	2000-07-28	Germany