| Title of Invention | SPIROCYCLIC NITRILES AS PROTEASE INHIBITORS |
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| Abstract | Abstract SPIROCYCLIC NITRILES AS PROTEASE INHIBITORS The invention relates to substituted heterocyclic spiro compounds of formula (I) inhibiting cathepsins, to a method for the production thereof, and to the use of same as medicaments. |
| Full Text | Spirocyclic nitriles as protease inhibitors The invention relates to substituted carbo- and heterocyclic spiro compounds of the formula I which inhibit thiol proteases, to processes for their preparation and to the use thereof as medicaments. Proteolytic enzymes, known as proteases and peptidases, are very important enzymes which make up about 2% of the genes in the human organism, pathogenic microorganisms and also other life forms. Their particular significance is that they influence many physiological processes by playing an important role in the activation, synthesis or degradation of other proteins. This inevitably gives rise to a crucial regulatory function starting at conception, birth, growth, maturation, aging, diseases up to death. The balance of the different processes is of crucial significance for the life and survival of the organism. When there is an imbalance of protease-catalyzed processes as a result of endogenous or exogenous factors such as genetic predisposition or environmental factors, massive disruption can occur in the normal development process, acute to serious chronic health disorders up to and including life-threatening diseases. Equally, proteases are essential and responsible in replication and transmission processes of viral, bacterial and other parasitic organisms which are responsible, for instance, for infection disorders, and equally essential, of course, for all further physiological and pathophysiological processes in the plant and animal kingdom. Caused by this general great significance for our health, a multitude of protease inhibitors have already been developed, which are on the market or in all stages of development: not only as medicaments, but also as diagnostics, vaccines or food supplements. A distinction is drawn between 5 classes of proteolytic enzymes, divided according to the catalytically active radicals relevant for the enzymatic hydrolysis: aspartyl proteases, serine proteases, cysteine proteases, metalloproteases and threonine protreases. Inhibitors of all of these classes are the subject of connprehensive studies in a wide field for the control of various types of disorders. Several very effective protease inhibitors are on the market, for example ACE inhibitors, HIV-1 protease inhibitors, and also thrombin and elastase inhibitors, followed by a large number of inhibitors in clinical phases. A summary can be found, for instance, in Medicinal Chemistry, 2005, Vol. 1, No. 1 p. 71-104. Cysteine (thiol) proteases are divided into three main classes: Papain-like, ICE-like (caspases) and Picornaviral proteases. From the point of view of the mechanism, the hydrolysis of the amide bond proceeds in a similar way to that in the case of the class of the serine proteases, via an attack of the thiolate anion at the carbonyl carbon and formation of a tetrahedral transition state. The most prominent representatives of the papain superfamily, as the largest and most significant group of the thiol proteases, are the cathepsins which have a natural wide distribution in various tissues and to which an important function is attributed both in normal physiological and pathological processes. Particular emphasis should be given to intracellular protein degradation and remodeling processes. Accordingly, significance is ascribed to cysteine cathepsins in the following general disorder types: musculoskeletal disorders, particularly bone degradation disorders, inflammatory disorders, particularly arthritides, atherosclerotic disorders, emphysemas, dystrophies, cancers, disorders of the periodontal apparatus, infectious disorders (viral, parasitic and bacterial infections), neurodegenerative disorders, disorders of the immune system, ischemias, leukodystrophies, glomerulonephritis. According to the nature of the proteases, the pathogenic properties are exerted especially by three high-level mechanisms: the degradation of (connective) tissue, which initiates many types of symptoms and also further processes, the generation of pathogenic or bioactive proteins and peptides which themselves exert their action directly or in signal cascades, and antigen processing, for example the presentation of antigenic peptides at the cell surface, which then finally initiates an immune response. Known representatives of the cysteine cathepsins are particularly Cathepsin B, H, K, L, F, V, W, X, O, C and S (A.J. Barrett; N.D. Rawlings; J.F. Woessner; ed.; Handbook of Proteolytic Enzymes, 2nd. ed., 2004; Publisher: Elsevier, London). Cathepsin F was found for the first time in macrophages and is involved in antigen processing. Caused by the occurrence in stimulated lung macrophages, an important function in inflammatory respiratory pathway disorders has been postulated. Cathepsin L is involved in normal lysosomal proteolysis, but also in various disease events such as melanoma metastatis. Cathepsin S plays a key role in many processes which are of significance in the context of antigen presentation and are thus present to an enhanced degree in antigen-presenting cells. In this regard, inhibitors of cathepsin S are possibly active agents in the prevention, inhibition or treatment of immune or autoimmune disorders. Moreover, cathepsin S is also secreted by several antigen-presenting cells and thus plays a role in extracellular matrix interactions which likewise have crucial significance in many pathological processes. Emphasis is given here to various (auto)immune and inflammatory disorders; particularly Alzheimer's disease, Huntington's disease, juvenile diabetes, multiple sclerosis, pemphigus vulgaris. Graves' disease, Myasthenia gravis, systemic Lupus erythematosus, IBD, rheumatoid arthritis and Hashimoto's thyroiditis, MS, ALS, allerigic disorders such as asthma, allogenic immune responses such as rejection reactions in organ transplants or tissue grafts. Moreover, cathepsin S is connected with COPD (such as emphysema), bronchiolitis, excessive respiratory pathway elastolysis in asthma and bronchitis, pneumonitis, but also with cardiovascular disorders such as plaque ruptures and atheromers, and also endometriosis and chronic neuropathic pain. Cathepsin S is also connected with fibrillary disorders, and inhibitors can thus possibly be used for the treatment of systemic amyloidosis. Increased levels of cathepsin B and corresponding distributions are found in various tumors - a role in tumor invasion and metastatis is thus ascribed to cathepsin B. Enhanced cathepsin B activity is likewise found in rheumatoid arthritis, osteoarthritis, acute pancreatitis, inflammatory respiratory pathway disorders, Pneumocystis carinii and bone and joint disorders. A significant increase in synovial cathepsin B levels has been detected in osteoarthritis models. A review of cytokine-independent overexpression and relevance for osteoarthritis can be found in A. Baici et a!., Seminars in Arthritis and Rheumatism, 34, 6, Suppl. 2, 24-28 (2005). Cathepsin K expression is particularly marked (but not exclusively) in osteoclasts (for example D. Bromme et a!., J. Biol. Chem. 271, 2126-32 (1996)) and represents about 98% of the total cysteine protease activity there, mainly localized intracellularly within the lysosome. An autosomal recessive disruption of cathepsin K expression (absence through mutation), pycnodysostosis, is characterized by an osteopetrotic phenotype, with reduced bone resorption, ossification disorders and massive growth disorders. It has likewise been possible to show with cathepsin K antisense nucleotides and knockout mice that cathepsin K is responsible for osteoclast-mediated bone degradation. It is therefore assumed that inhibition of cathepsin K leads to reduced bone resorption and should thus constitute a possible therapy for all disorders which are characterized by elevated bone degradation, i.e. particularly for the treatment of osteoporosis. Caused by a significantly increased activity in the slightly acidic range between pH 4 and 8, enzymatic degradation of the collagen network in bone proceeds accompanied by acidolytic destruction of the mineral matrix. Here, particularly human collagen type I is affected as a main constituent of the protease in bone; this has been proven to be a very good substrate for cathepsin K. Therefore, other disorders which are accompanied by increased catabolic activity at the collagen level are also connected with cathepsins and particularly with cathepsin K. Foremost among these is osteoarthritis, characterized by an imbalance of cartilage matrix buildup and degradation, caused by catabolically active enzymes, for example metalloproteinases, among others. It is therefore obvious and has now also been proved that an inhibition of cathepsin K might likewise have favorable effects here on the disease process (synovial fibroblast-mediated collagen degradation by cathepsin K is described in W.-S. Hou etal.. Am. J. Pathol. 159, 2167-2177 (2001)). The significance of cathepsins K and S in musculoskeletal disorders such as osteoporosis and osteoarthritis is described in detail by D. Bromme et al., Advanced Drug Delivery Reviews 57, 973-993 (2005). Caused by the above-described detailed findings concerning cysteine cathepsins in various disease processes, they are considered to be very promising points of attack in drug development, such that an intensive search has connmenced for specific, group-specific or even unspecific inhibitors. Inhibitors of cysteine proteases have been known for sometime, for example cystatines as endogenous polypeptide inhibitors. Low molecular weight inhibitors were isolated from aspergilius for the first time in 1981. These are potent in-eversible inhibitors with low toxicity, but also inadequate specificity, since not only cathepsins B, K, L, S and H but also calpaines are widely inhibited. Since then, a multitude of inhibitors with different specificities or mechanisms has been found - therefore, both irreversibly covalently binding and reversibly covalently binding or reversibly noncovalently binding inhibitors have been found or synthesized. More recent developments have been described in detail (W. Kim, K. Kang, Expert Opin. Ther. Patents 13, 3, 419-32 (2002); U. B. Grabowska, Curr. Opin. Drug Disc Dev. 8, 5, 619-30 (2005); R. L. Thurmond et al., Curr. Opin. Invest. Drugs 6, 5, 473-482 (2005)). Reversibly covalently binding inhibitors are of particular interest. From this group, particularly the class of the nitriles has been identified as very promising. These are described in detail, for example in the applications WO99/24460, WO2000/55125, WO2004/052921 and also in WO2005/040142. In the effort to find effective compounds for treating disorders caused directly or indirectly by cysteine cathepsins, it has now been found that the inventive spiro compounds, spirocyclic nitriles, are strong inhibitors of the cysteine cathepsins, particularly of cathepsin K and/or S, while other cysteine proteases such as calpain are inhibited much more weakly, if at all. Moreover, the inventive compounds have improved bioavailability, which has also been shown already in vito in corresponding Caco permability tests. and/or all stereoisomeric forms of the compound of the formula I and/or mixtures of these forms in any ratio, and/or a physiologically tolerated salt of the compound of the formula I, and/or solvates or hydrates of the compound of the formula I, and/or prodrugs of the compound of the formula I, where unbridged, bridged or fused and is unsubstituted or independently, according to the ring size, mono-, di-, tri, tetra- or pentasubstituted by R4, or b) a saturated or partly saturated, three- to eleven-membered heterocycle which, according to the ring size, may contain one, two, three or four identical or different heteroatoms from the group of oxygen, nitrogen or sulfur, and in which the heterocycle is unbridged, bridged or fused and is unsubstituted or independently, according to the ring size, mono-, di-, tri-, tetra- or pentasubstituted by R4, where 3-biphenylyl, 4-biphenylyl, anthryl orfluoroenyl, where aryl is unsubstituted or mono-, di- or trisubstituted independently by R8, or -(Co-C4)-alkylene-Het, where Het is selected from the group of acridinyl, azepinyl, azetidinyl, aziridinyl, benzimidazolinyl, benzimidazolyl, benzofuranyl, benzothiofuranyl, benzothiophenyl, benzoxazolyl, benzthiazoiyi, benztriazolyl, benztetrazolyL benzisoxazoiyi, benzisothiazolyl, carbazolyl, 4aH-carbazolyl, carixdinyl, quinazolinyl, quinolinyi, 4H-quinotizinyl, quinoxalinyi, quinudidinyl, chromanyl, chromenyl, cinnolinyl, deca-hydroquinolinyl, dibenzofuranyl, dibenzothiophenyl, dihydrofuran[2,3-b]-tetrahydrofuranyl, dihydrofuranyi, dioxolyl, dioxanyl, 2H, 6H-1,5,2-dithiazinyl, furanyl, furazanyl, imidazoiidinyl, imidazolinyl, imidazolyl, 1 H-indazolyl, indolinyl, indolizinyl, indolyl, 3H-indolyl, isobenzofuranyl, isochromanyl, isoindazolyl, isoindollnyl, isoindolyl, isoquinolinyl (benzimidazolyl), isothiazolidinyl, 2-isothiazolinyl, isothiazolyl, isoxazolyl, isoxazolidinyl, 2-isoxazolinyl, morpholinyl, naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, oxazolidinyl, oxazolyl, oxazolidinyl, oxothiolanyl, pyrimidinyl, phenanthridinyl, phenanthroiinyl, phenazinyl, phenothiazinyl, phenoxathiinyl, phenoxazinyl, phthalazlnyl, piperazinyl, piperidinyl, pteridinyl, purynyl, pyranyl, pyrazinyl, pyroazolidinyl, pyrazolinyl, pyrazolyl, pyrldazinyl, pryidooxazolyl, pyridoimidazolyl, pyridothiazolyl, pyridothiophenyl, pyridinyl, pyridyl, pyrimidinyl, pyrroiictinyl, frroiinyl, 2H-pyrrolyl, pflrcrfyl, tetriycirofLa'anyl, tetrahydrotsoquinoiinyi, tetrahydroquindinyl, tetrahydropyridinyl, 6H-1,2,5-thiadazinyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, thianthrenyl, thiazolyl, thienyl, thienoimidazolyl, thienooxazolyl, thienopyridine, thienothiazolyl, thiomorpholinyl, thiophenyl, triazinyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl and xanthenyl, and this Het radical is unsubstituted or independently mono-, di- or trisubstituted by R8, or two adjacent R4, together with the ring atoms to which they are bonded, form a four- to eight-membered heterocycle or phenyl which, together with the sub-ring to which the heterocycle or the phenyl is fused, forms a bicyclic system, R8 is halogen, carbamimidoyi, -NO2, =0, -CF3, -SF5, -C(O)-O-R10, -CN, -C(0)-NH2, -OH, -NH2, -O-CF3, -S-CF3_ -C(O)-N(R10)-R20, -N(R10)-R20, -(C-|-C8)-alkyl, where alkyl is unsubstituted or mono-, di- or trisubstituted independently by fluorine, chlorine, bromine, iodine, -NH2, -OH, methoxy radical, -SO2-CH3 SO2-NH2 or -SO2-CF3 or is mono- to decasubstituted by fluorine, -0-{C1-C8)-alkyl, where alkyl is unsubstituted or mono-, dl-or trisubstituted independently by fluorine, chlorine, bromine, iodine, NH2, -OH, methoxy radicaL -SO2-CH3 or-S02-CF3 or is mono- to decasubstituted by fluorine, -S-(C1-C8)-alkyl, where alkyl is unsubstituted or mono-, di- or trisubstituted independently by fluorine, chlorine, bromine, iodine, NH2, -OH, methoxy radical, -SO2-CH3 or -SO2-CF3 or is mono- to decasubstituted by fluorine, -(Co-C4)-alkylene-(C3-C8)-cycloaIkyl or -0-(Co-C4)-alkylene-(C3-C8)-cycloalkyl, R9 is a halogen, -NO2, -CN, =0, =S, -OH, -CF3, -SF5, -C(O)-O-R10, -N(R21)-R22, -C(0)-N(R21)-R22, -(Go-C3)-alkylene-0-R10, -(Co-C3)-alkylene-S-R10, -S-R10, -Si-(CH3)3, -N(R10)-S(O)u-R10, where u is the integer 1 or 2, -SOp-RIO, where r is the integer 1 or 2, -S(O)v-N(R10)-R20, where v is the integer 1 or 2, -C(O)-R10, -(C-|-C8)-alkyl, -0-R19, -(C1-C8)-alkoxy, phenyl, phenyloxy-, -{C-t-CsHkjoroalkyi, -NH-C{0)-NH-R21, -O-C(O)-R10, -(C0-C4)-alkyl-C(O)-O-C(R19, R11)-0-C(0)-R12, -O-CF3, -(Co-C4)-alkyl-C(0)-0-C(R19, R11)-0-C(0)-0-R12, -O-C(O)-N-R10, -N(R21)-C(0)-R22, -NH-C(O)-O-R10, -S-GF3, Het, where Het is unsubstituted or mono-, di- or trisubstituted independently by R8, or is a radical from the following R10 and R20 are the same or different and are each independently a hydrogen atom, -(C1-C6halkyl -(Co-C4)-alkyl-0-(Co-C4)-alkyl,-(C1-C3)-fluoroaikyl,-(Co-C5)-aIkyl-(C3-C8)- cycloalkyl, -(Co-C2)-alkylene-aryl, where aryl is as defined above and is unsubstituted or mono-, dl- or trisubstituted independently by -(C-|-C6)-alkyl, -0-(C1-C6)-alkyl, halogen or-(C3-C8)-cycloalkyl, or -(Co-C2)-alkylene-Het, where Het is as defined above and is unsubstituted or mono-, di- or trisubstituted independently by -{C1-C6)-alkyl, -0-(C1-C6)-alkyl, halogen or-(C3-C8)-cycloalkyl, R19 and R11 are the same or different and are each independently a hydrogen atom or -(C1-C6)-alkyl, or R19 and R11, together with the carbon atom to which they are bonded, form a three- to six-membered cycloalkyi ring which is unsubstituted or mono-, di- or trisubstituted independently by R10, R12 is -(C1-C6)-aBcyi, -(C-i-C6)-alkyl-0H, -(C1-C6)-a!kyi-0-(C1-C6)-a!kyl, -(C3-C8)-cycloalkyl,-(C1-C6)-alkyl-0-(C1-C8)-alkyl-(C3-C8)-cycloalkyl, -(C1-C6)-alkyl-(C3-C8)-cycloalkyl where the cycloalkyi radical is unsubstituted or mono-, di- or trisubstituted independently by -OH, -0-(C-|-C4)-alkyl or R10, R21 and R22 are the same or different and are each independently a hydrogen atom, -(C1-C6)-alkyl where alkyl is unsubstituted or mono-, di- or trisubstituted independently by R8, -(Co-C6)-alkylene-(C3-C8)-cycloalkyl, -SOfRIO where t is the integer 1 or 2, - (C1-C3)-fluoroalkyl, -0-R12, -S-R12, -(Co-C6)-alkylene-aryl where aryl is as defined above and alkylene and aryl are each unsubstituted or mono-, di- or trisubstituted independently by R8 or -(Co-C6)-alkylene-Het where Het is as defined above and alkylene and Het are each unsubstituted or mono-, di- or trisubstituted independently by R8, R21 and R22, together with the nitrogen atom to which they are bonded, form a four- to eight-membered monocyclic heterocyclic ring which, as well as the nitrogen atom, may additionally contain, according to the ring size, one or two identical or different heteroatoms from the group of oxygen, nitrogen and sulfur, and in which the heterocycitc ring is unsubstituted or mono-, di- or trisubstituted independently by R8, R23 is a hydrogen atom, -OH or -0-(C-|-C4)-alkyl, X is a covalent bond, -N(R7)-, -0-, -S- or-(C(R13)(R14))n- where n is the integer 1,2 or 3, R7 is a hydrogen atom, -(Co-C4)-alkylene-(C3-C6)-cycloalkyl or -(C1-C6)-alkyl, R13 and R14 are the same or different and are each independently a hydrogen atom, -(Co-C4)-alkylene-(C3-C6)-cycloalkyl, -{C1-C3)-fluoroalkyl or -(C1-C4)-alkyl, R13 and R14, together with the carbon atom to which they are bonded, form a three- to six-membered cycloalkyl ring which is unsubstituted or mono-, di- or trisubstituted independently by R10, Y is a covalent bond, -C(0)-, -S(0)-, -S(02)-, -C(NR1)-, -C(S)-, -C(=N-CN)-, -C(=CHN02> or -CHiCFy, R1 is a hydrogen atom, -{C-|-C4)-atkyl or -(Co-C4)-alkylene-{C3-C6)-cyctoalkyl, R2 and R3 are the same or different and are each independently a hydrogen atom, -(C1-Cio)-alkyl.-(Co-C4)-alkylene-(C3-C8)-cycloalkyl, -(C1-C6HluoroalkyI, -(Co-C4)-alkylene-aryl, where aryl is unsubstituted or mono-, di- or trisubstituted independently by R8, -(Co-C4)-alkyiene-Het where Het is unsubstituted or mono-, di- or trisubstituted independently by R8, -(C']-C4)-alkylene-R15-R16 or -(Co-C4)-alkylene-C(R27)(R28)(R29), R27 is a hydrogen atom, halogen, -(C1-C9)-alkyl, -(C1-C3)-fluoroalkyl, -(Co-C4)-alkylene-(C3-C6)-cycloalkyl, -(Co-C4)-alkylene-aryl, where aryl is unsubstituted or mono-, di- or trisubstituted independently by R8, -(C0-C4)- alkylene-Het where Het is unsubstituted or mono-, di- or trisubstituted independently by R8, or -(Co-C4)-alkylene-R15-R16, R28 and R29 are the same or different and are each independently a hydrogen atom, -(C1-C4)-alkyl or halogen, R15 is -N{R17}-, -0-. -S-, -S(0)-, -S(02V. -C(0)-, -C{0)-0-, -O-C(O)-. -0-C(0)-0-,-N(R17)-C{0)-, -C(0)-N(R17)-, -S(02)-N(R17)-, -S(0)-N(R17)-, -N(R17)-S(02)-, -N(R17)-C(0)-0-, -0-C(0)-N(R17)-, -N(R17)-C(0)-N(R18)-, -N(R17)-C(N(R17))-N(R18)-, -N(R17)-C(N(R17))- or -N(R17)-S(02)-N(R18)-, where R17 and R18 are the same or different and are each independently a hydrogen atom or -(C1-C6)-alkyl, R16 is a hydrogen atom, -(C-|-C5)-alkyl, -(Co-C4)-alkylene-(C3-C6)-cycloalkyl, -(C1-C3)-fluoroalkyl, -(Co-C4)-alkylene-aryl, where aryl is unsubstituted or mono-, di- or trisubstituted independently by R8, -(Co-C4)-alkylene-Het where Het is unsubstituted or mono-, di- or trisubstituted independently by R8, R2 and R3, together with the carbon atom to which they are bonded, form a three- to six-membered cycloalkyi ring which is unsubstituted or mono-, di- or trisubstituted independently by R8, or R2 ajKi R3, togtier wfth the cstbtm atom to w*w± ne sere bcwided, ftarn a three- to six-membered heterocycloalky! radical which is unsubstituted or mono-, di- or trisubstituted independently by R10, and Z is the -N(R26)-(C(R24)(R25))m-CN radical where R26 is a hydrogen atom, -(C1-C4)-alkyl or -(Co-C4)-alkylene-(C3-C6)-cycloalkyl, R24 and R25 are the same or different and are each independently a hydrogen atom, -(Ci -C6)-alkyl, -(Co-C4)-alkyiene-(C3-C6)-cycloalkyl, -(C1-C3)-fluoroalkyl, -(C1-C4)-alkylene-R15-R16, -(Co-C4)-alkylene-aryl, where aryl is unsubstituted or mono-, di- or trisubstituted independently by R8, -(Co-C4)-alkylene-Het where Het is unsubstituted or mono-, di- or trisubstituted independently by R8, and m is the integer 1, 2 or 3, R24 and R25, together with the carbon atom to which they are bonded, form a three- to six-membered cycloalkyi ring which is unsubstituted or mono-, di- or trisubstituted independently by R10 or fluorine, or R24 and R25, together with the carbon atom to which they are bonded, fonn a three- to six-membered heterocydoalkyl radical which is unsubstituted or mono-, di- or trisutistituted independently by R1G or fluorine. where the dotted lines indicate the particular point of attachnrient to the second sub-ring, singJe bonds in the structures listed may be replaced partly by double bonds, or further ring systems may be fused on. and where the dotted lines indicate the particular point of attachment to the second sub-ring, single bonds in the structures listed may be replaced partly by double bonds, and the two sub-rings A and B are unsubstituted or independently mono- to tetrasubstituted by R4, and the X, Y, R1, R2, R3, R4 and Z radicals are each as defined above. bicyclo[4.2.0]octane, octahydroindene, decalin, decahydrobenzocycloheptene, dodecahydroheptalene, bicyclo[3.1.1]heptane, bicyclo[2.2.1]heptane, bicyclo[3.3.0]octane, bicyclo[2.2.2]octane, spiro[2.5]octane, spiro[3.4]octane, azepane, azepine, azetidine, aziridine, azirine, azocane, benzimidazoline, 2,3-dihydrobenzo[b]thiophene, 1,3-dihydrobenzo[c]thiophene, 2,3-dihydrobenzofuran, 2,3-dihydrobenzooxazole, 2,3-dihydrobenzothiazole, 1,3-dihydroisobenzofuran, 4,5-di-hydroisothiazole, 2,3-dihydroisoxazole, 2,5-dihydroisoxazole, 4,5-dihydroisoxazole, 5,6-dihydro-4H-[1,2]oxazine, benzo[1,3]dioxole, 1,4-diazepane, 1,2-diazepine, 1,3-diaze- pine, 1,4-diazepine, diaziridine, diazirine, 1,4-diazocane, dioxane, 1,3-dioxane, dioxazine, [1,3]dioxepane, 1,4-diozocane, dioxole, dioxolane, 1,3-dioxoIane, 1,3-di-oxolene, [1,3]dithiane, [1,3]dithiolane, hexahydropyridazine, hexahydropyrimidine, imidazoline, imidazolidine, indane, indoline, isoindoiine, isothiazolidine, isothiazoline, isoxazoline, isoxazoiidine, 2-isoxazoline, morpholine, [1,3,4]oxadiazinane, i1.3,5]oxadiazinane, [1,2,3]oxadiazoiidme, [1,3,4]oxadiazoiidine, 1,2-oxathiepane, 1,2-Qxathiolane, [1,3}oxathiolane, 1,4-oxazepane, 1,2-oxazine, 1,3-oxazine, 1,4-oxazine, oxazinane, 1,3-oxazinane, oxazocane, oxaziridine, oxazolidine, oxepane, oxetane, oxirane, oxocane, piperazine, piperidine, pyran, pyrazoline, pyrazolidine, pyrrolidine, pyrroiidinone, pyrroline, tetrahydroquinoline, tetrahydrofuran, tetrahydroisoquinoline, 1,2,3,4-tetrahydronaphthalene, tetrahydropyran, tetrahydropyridine, 1,2,3,4-tetrahydro-pyrimidine, 1,2,5,6-tetrahydropyrinnidine, tetrahydrothiophene, tetrazine, thiadiazine, [1,2,6]thiadiazinane, [1,3,4]thiadiazolidine, 1,2-thiazine, 1,3-thiazine, 1,4-thiazine, [1,2]thiazinane, [1,3]thiazinane, thiazolidine, thiazoline, thiepane, thietane, thiomorpholine, thiopyran, 1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazlne, [1,2,4]triazinane or [1,2,4]triazolidine, and in which the two sub-rings are each unsubstituted or independently, according to the ring size, nnono-, di-, tri-, tetra- or pentasubstituted by R4, where R4 is -NO2, -CN, =0, =S, -OH, -CF3, -SF5_ -(Co-C3)-alkylene-S-R10, -Si-(CH3)3, -O-CF3, -(Co-C3)-alkylene-C(0)-N(R21)-R22, -(Co-C3)-alkylene- C(O)-R10, -(Co-C33-akyiene-Ce-S{0)-R1D, -S-CFs -(Co-C3)-alkylene-S(0)2-R10, -(Co-C5)-alkylene-S(0)2-N(R21 )-R22, -(Co-C3)-alkylene-0-R10, -(Co-C3)-alkylene-N(R21 )-R22, -(Co-C3)-alkylene-N(R10)-S(0)2-R10,-(Co-C5)-alkylene-(C1-C3)-fluoroalkyl, -(Co-C5)-alkylene-(C3-C8)-cycloalkyl-R23,-(Co-C5)-alkylene-N(R10)-C(0)-R21, -(Co-C5)-alkylene-N(R10)-C(0)-N(R10)-R21, -{Co-C5>lkylene-NH-C(0)-0-R21, -(Co-C5)-alkylene-0-C(0)-N(R10)-R21, -(Co-C4)-alkyl, where alkyl is unsubstituted or mono-, di- or trisubstituted independently by R9, -(Co-C4)-alkylene-aryl, where aryl is selected from the group of phenyl, indanyl, indenyl, naphthyl, biphenylyl, 2-biphenylyl, 3-biphenylyl, 4-biphenylyl, anthryl or fluoroenyl, where aryl is unsubstituted or mono-, di- or trisubstituted independently by R8, or -(Co-C4)-alkylene-Het, where Het is selected from the group of achdinyl, azepinyl, azetidinyl, aziridinyl, benzimidazoiinyl, benzimidazolyl, benzofuranyl, benzothiofuranyl, benzothiophenyl. benzoxazolyl, benzthiazolyl, benztriazoiyl, benztetrazolyl benzisoxazoiyi, benzisothiazolyl, carbazolyl, 4aH-carbazolyl, carboHnyl, quinazoHnyl, quinolinyi, 4H-quinoliziny{, quinoxalinyl, quinudidinyl, chromanyl, chromenyl, cinnolinyl, deca-hydroquinolinyl, di benzofuranyl, dibenzothiophenyl, dihydrofuran[2,3-b]-tetrahydrofuranyl, dihydrofuranyl, dioxolyl, dioxanyl, 2H, 6H-1,5,2-dithiazinyl, furanyl, furazanyl, imidazolidinyl, imidazolinyl, imidazolyl, 1 H-indazolyl, indolinyl, indolizinyl, indolyl, 3H-indolyl, isobenzofuranyl, isochronnanyl, isoindazolyl, isoindolinyl, isoindolyl, isoquinolinyl (benzimidazolyl), isothiazolidinyl, 2-isothiazolinyl, isothiazolyl, isoxazolyl, isoxazolidinyl, 2-isoxazolinyl, morpholinyl, naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, oxazolidinyl, oxazolyl, oxazolidinyl, oxothiolanyl, pyrimidinyl, phenanthridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl, phenoxathiinyl, phenoxazinyl, phthalazinyl, piperazinyl, piperidinyl, pteridinyl, purynyl, pyranyl, pyrazinyl, pyroazolidinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pryidooxazolyl, pyridoimidazolyl, pyridothiazolyl, pyridothiophenyl, pyridinyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrroBnyi, 2H-{:rro (prolyl, trahydroftirarl, tetrahydrosoquinciDyl, tetrahydroquinolmyl, tetrahydropyridinyl, 6H-1,2,5-thiadazinyl, 1,2,3-thiacliazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, thianthrenyl, thiazolyl, thienyl, thienoimidazolyl, thienooxazolyl, thienopyridine, thienothiazolyl, thiomorpholinyl, thiophenyl, triazinyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl and xanthenyl, and this Het radical is unsubstituted or independently mono-, di- or trisubstituted by R8, R8 is halogen, carbamimidoyi, -NO2, =0, -CF3, -SF5, -C(O)-O-R10, -CN, -C(0)-NH2, - OH, -NH2, -O-CF3, -C(O)-N(R10)-R20, -N(R10)-R20, -(C3-C8)-cycloalkyl,-0-(C1-C8)-alkyl,-0-(Co-C4)-alkylene-(C3-C6)-cycloalkyl, (C-i-C8)-alkyl, -(Co-C4)-alkylene-(C3-C8)-cycloalkyl, where the alkyl radicals mentioned are each unsubstituted or mono-, di- or trisubstituted independently by halogen, NH2, -OH, -O-CH3, -SO2-CH3 or-S02-CF3, R9 is halogen, -NO2, -CN, =0, -OH, -CF3, -C(O)-O-R10, -N(R21)-R22, -C(0)-N(R21)-R22, -(C3-C8)-cycloalkyl, -(Co-C3)-alkylene-0-R10, -Si-(CH3)3, -N(R10)-S(O)ij-R10 where u Is the integer 1 or 2, -S-R10, -SO-RIO where r is the integer 1 or 2, -S(O)v-N(R10)-R20 where v is the integer 1 or 2, -C(O)-R10, -(C1-C8)-alkyl, -(C1-C8)-alkoxy, phenyl, phenyioxy-, -(0-03)- fluoroalkyl, -0-R19, -NH-C(O)-NH-R10, -(C0-C4)-alkyl-C(O)-O-G(R19, R11)-0-C(0)-R12, -NH-C(0)-NH-R21, -N(R21 )-C(0)-R22, -(Co-C4)-alkyl-C(0)-0-C(R19, R11 )-O-C(0)-0-R12, -NH-C(O)-O-R10, -O-CF3, Het, where Het is as defined above and is unsubstituted or mono-, di- or trisubstituted independently by R8, or a radical from the following list R10 and R20 are the same or different and are each independently a hydrogen atom, -(C1-G6)-alkyl, -(Co-C4)-alkyl-OH, -(C1-C3)-fluoroalkyl, -(Co-C4)-alkyl-0-(G-i-C4)-alkyl, -{Co-C5)-alkyl-(C3-C8)-cycloalkyl, -(Co-C2)-alkylene-aryl, where aryl is as defined above and is unsubstituted or mono-, di- or trisubstituted independently by-(C1-G6)-alkyl, -0-(C1-G6)-alkyl, halogen or -(G3-G8)-cycloalkyl, or -(Co-G2)-alkylene-Het where Het is as defined above and is unsubstituted or mono-, di- or trisubstituted independently by -(C1-G6)-alkyl, -0-(Gi-G6)-alkyl, halogen or-(G3-G8)-cycloalkyl, R19 and R11 are the same or different and are each independently a hydrogen atom or -(C1-C6)-alkyl, or R19 and R11, together with the carbon atom to which they are bonded, form a three- to six-membered cycloalkyi ring which is unsubstituted or mono-, di- or trisubstituted independently by R10. R12 is -(C-|-C6)-alkyl, -(C-j-C6)-alkyl-0H, -(C-i-C6)-alkyl-0-(C1-C6)-alkyl, -(Cs-Cgl-cycloafkyl, -(Ci -C6)-aIkyi-0-{Ci -C8)-alkyl-(C3-C8)-cycloa[kyl, -(C1-C6)-alkyl-(C3-C8)-cycloalkyl, where the cycloalkyi radical is unsubstituted or mono-, di- or trisubstituted independently by -OH, -0-(C1-C4)-alkyl or RIO, R21 and R22 are the same or different and are each independently a hydrogen atom, -(C1-C6)-alkyl, where alkyl is unsubstituted or mono-, di- or trisubstituted independently by R8, -0-R12, -(Co-C6)-alkylene-(C3-C8)-cycloalkyl, -SOt-R10, where t is the integer 1 or 2, -(C1-C3)-fluoroalkyl, -(Co-C6)-alkylene-aryl where aryl is as defined above and alkylene and aryl are unsubstituted or mono-, di- or trisubstituted independently by R8, or -(Co-C6)-alkylene-Het where Het is as defined above and alkylene and Het are unsubstituted or mono-, di- or trisubstituted independently by R8, R21 and R22, together with the nitrogen atom to which they are bonded, form a four- to eight-membered heterocyclic ring which, as well as the nitrogen atom, may ackfitkxiafiy ctmtam, acccwtfing to Ihe ring E. one cr t¥vo kjeniical ortSfeieiit heteroatoms from the group of oxygen, nitrogen or sulfur, and in which the heterocycle is unsubstituted or mono-, di- or trisubstituted independently by R8, R23 is a hydrogen atom, -OH or -0-(C1-C4)-alkyl, X is a covalent bond, -N(R7)- or -0-, where R7 is a hydrogen atom, -(Co-C4)-alkylene-(C3-C6)-cycloalkyl or-(C1-C4)-alkyl, Y is a covalent bond, -C{0)-, -C(S)-, -C(=N-CN)-, -C(=CHN02)- or -S(02)-, R1 is a hydrogen atom, R2 and R3 are the same or different and are each independently a hydrogen atom or -(C0-C3)-alkylene-C(R27)(R28)(R29), R27 is a hydrogen atom, halogen, -(C-|-C9)-alkyl, -(C1-C3)-fluoroalkyl, -(Co-C4)-alkylene-(C3-C6)-cycloalkyl, -(Co-C4)-alkylene-aryl where aryl is as defined above and is unsubstituted or mono-, di- or trisubstituted independently by R8, -(Co-C4)-alkylene-Het where Het is as defined above and is unsubstituted or mono-, di- or trisubstituted independently by R8, or -(Co-C4)-alkylene-R15-R16 R28 and R29 are the same or different and are each independently a hydrogen atom, -(C-|-C4)-alkyl or fluorine, R28 and R29, together with the carbon atom to which they are bonded, form a -(C3- C6)-cycloalkyl, R15 is -N(R17)-, -0-, -S-, -S(0)-, -S(02)-, -C(0)-, -C(0)-0-, -O-C(O)-, -N(R17)-C(0}-, -C(0)-N(R17)-, -S(02)-N(R17)-, -N(R17)-S(02)-, -N(R17)-C(0)-0-, -0-C(0)-N(R17)-, -N(R17)-C(0)-N(R18)- or -N(R17)-S(02)-N(R18)-, where R17 and R18 are the same or different and are each independently a hydrogen atom or -(C1-C6)-alkyl, R16 is a hydrogen atom, -(C1-C6)-alkyl, -(Co-C4)-alkylene-(C3-C6)-cycloalkyl, -(C-]- C3)-fluoroalkyl, -(Co-C4)-alkylene-aryl where aryl is as defined above and is unsubstituted or mono-, di- or trisubstituted independently by R8, -(C0-C4)- alkylene-Het where Het is as defined above and is unsubstituted or mono-, di- or trisubstituted independently by R8, R2 and R3, together with the carbon atom to which they are bonded, form a three- to six-membered cycloalkyi ring which is unsubstituted or mono-, di- or trisubstituted independently by R8, or R2 and R3, together with the carbon atom to which they are bonded, form a three- to six-membered heterocycloalkyl radical which is unsubstituted or mono-, di- or trisubstituted independently by R10, and Z is the -N(R26)-C(R24)(R25)-CN radical, where R26 is a hydrogen atom, -(C1-C4)-alkyl or-(Co-C4)-alkylene-(C3-C6)-cycloalkyl, R24 and R25 are the same or different and are each independently a hydrogen atom, -(C1-C6)-alkyl,-(Co-C4)-alkylene-(C3-C6)-cycloalkyl, -(C1-C3)-fluoroalkyl, -(Co-C4)-alkylene-aryl where aryl is as defined above and is unsubstituted or mono-, di- or trisubstituted independently by R8, -(C0-C4}- alkylene-Het wiiere Het is as defined above and is unsubstituted or mono-, di- or trisubstituted by R8, or-(C-|-C4)-alkylene-R15-R16, or R24 and R25. together with the cart>on atom to which they are bonded, form a three- to six-membered cycioalkyi ring Vktiich is unsubstituted or mono-, di- or trisubstituted independently by R10 or fluorine, R24 and R25, together with the carbon atom to which they are bonded, form a three- to six-membered heterocycloalkyi radical which is unsubstituted or mono-, di- or trisubstituted independently by R10 or fluorine. and in which the two sub-rings are each unsubstituted or independently, according to ttffi mg si7R, rTKMK)-, C1-, tri-, tia- or nissuts&Ld by R4, R4 is -NO2, -CN, =0, =S, -OH, -CF3, -SF5_ -(Co-C3)-alkylene-S-R10, O-CF3, -Si-(CH3)3, -O-CF3, -(Co-C5)-alkylene-0-C(0)-R21, -(Co-C5)-alkylene-C(0)-0-R10, -(Co-C3)-alkylene-0-R10, -(Co-C3)-alkylene-N(R21)-R22, -(C0-C3)-alkylene-N(R10)-S(O2)-R10, -(Co-C5)-alkylene-(C3-C8)-cycloalkyi-R23, -(Co-C5)-alkylene-(C1-C3)-fluoroalkyl,-(Co-C5)-alkylene-N(R10)-C(0)-R21, -(Co-C3)-alkylene-C(0)-N(R21)-R22, -(Co-C4)-alkyl where alkyl is unsubstituted or mono-, di- or trisubstituted independently by R9, -(Co-C4)-alkylene-aryl where aryl is selected from the group of phenyl, indanyl, indenyl, naphthyl, where aryl is unsubstituted or mono-, di- or trisubstituted independently by R8, or -(Co-C4)-alkylene-Het where Het is selected from the group of azetidinyl, benzimidazolinyl, benzimidazolyl, benzofuranyl, benzothiophenyl, benzoxazolyl, benzthiazolyl, benzisoxazolyl, benzisothiazolyl, quinolinyl, dioxolyl, dioxanyl, furanyl, imidazolidinyl, imidazolinyl. imidazolyl, indolinyl, indolyl, 3H-indolyl, isoindolinyl. isoindolyl, isoquinoiinyi. isothiazoiidinyl, 2-isothiazolinyi, isothiazolyl, isoxazoiy!. isoxazofidinyl, 2-isoxazoliny!. morpholinyl, octahydroisoquinolinyi, oxazoiyi, oxazoltdinyK pyrimtdinyl ptperazinyl, piperixjinyl, pyranyl, pyraztnyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolinyl, 2H-pyrrolyl, pyrrolyl, tetrahydrofuranyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, tetrahydropyridinyl, thiazolyl, thienyl, thienopyridinyl, thiomorpholinyl, thiophenyl, and this Het radical is unsubstituted or independently mono-, di- or trisubstituted byR8, R8 is halogen, carbamimidoyi, -NO2, =0, -CF3, -SF5, -C(O)-O-R10, -CN, -C(0)-NH2, -OH, -NH2, -O-CF3, -C(O)-N(R10)-R20, -N(R10)-R20, -(C3-C8)-cycloalkyl, -0-(C1-C8)-alkyl, -0-(Co-C4)-alkylene-(C3-C6)-cycloalkyl, - (C1-C8)-alkyl, -(Co-C4)-alkylene-(C3-C8)-cycloalkyl, where the alkyl radicals mentioned are each unsubstituted or mono-, di- or trisubstituted independently by halogen, NH2, -OH, -O-CH3, -SO2-CH3 or-S02-CF3, R9 is halogen, -NO2, -CN, =0, -OH, -CF3, -C(O)-O-R10, -C(0)-N(R21)-R22, -K(R21)-R22, -(C3-C8)-cycloaflcy}, -(Co-C3)-alkytene-0-R10, -SKCH3V3, -N(R10)-S(O)u-R10 where u is the integer 1 or 2, -S-R10, -SOrRIO wtrere r is the integer 1 or 2, -S(O)v-N(R10)-R20 where v is the integer 1 or 2, -C(O)-R10, -(C1-C8)-alkyl, -(C1-C8)-alkoxy, phenyl, phenyloxy-, -(C1-C3)-fluoroalkyl, -0-R19, -NH-C(O)-NH-R10, -(Co-C4)-alkyl-C(0)-0-C(R11, R19)-0-C(0)-R12, -NH-C(O)-NH-R21, -N(R21)-C(0)-R22, -(Co-C4)-alkyl-G(0)-0-C(R11, R19)-0-C(0)-0-R12, -NH-C(O)-O-R10, -O-CF3 or Het where Het is as defined above and is unsubstituted or mono-, di- or trisubstituted independently by R8, R10 and R20 are the same or different and are each independently a hydrogen atom, -(Gl-C6)-alkyl, -(Co-C4)-alkyi-OH, -(C1-C3)-fluoroalkyl, -(Co-C4)-alkyl-0-(C1-C4)-alkyl,-(Co-C5)-alkyl-(C3-C8)-cycloalkyl, -(Co-C2)-alkylene-aryl where aryl is as defined above and is unsubstituted or mono-, di- or trisubstituted independently by -(C1-C6)-alkyl, -0-(C-|-C6)-alkyl, halogen or -(C3-C8)-cycioalkyl, or -(Co-C2)-alkylene-Het where Het is as defined above and is unsubstituted or mono-, di- or trisubstituted independently by -(C1-CgValky!. -0-{C-j-C6)-aiky!. haJogen or-(C3-C8)-cycloalkyL R11 and R19 are the same or different and are each independently a hydrogen atom or -(C1-C6)-alkyl, R12 is -(C1-C6)-alkyl, -(C1-C6)-alkyl-0H, -(C1-C6)-alkyl-0-(C1-C6)-alkyl, -(C3-C8)-cycloalkyl, -(C1-C6)-alkyl-0-(C1-C8)-alkyl-(C3-C8)-cycloalkyl, -(C1-C6)-alkyl-(C3-C8)-cycloalkyl, where the cycloalkyi radical is unsubstituted or mono-, di- or trisubstituted independently by -OH, -0-(C1-C4)-alkyl or R10, R21 and R22 are the same or different and are each independently a hydrogen atom, -(C1-C6)-alkyl where alkyl is unsubstituted or mono-, di- or trisubstituted independently by R8, -(Co-C6)-alkylene-(C3-C8)-cycloalkyl, -SOt-R10 where t is the integer 1 or 2, -(C1-C3)-fluoroalkyl, -0-R12, -(Co-C6)-alkylene-aryl where aryl is as defined above and alkylene and aryl are each unsubstituted or mono-, di- or trisubstituted independently by R8 or -(Co-C6)-alkylene-Het where Het is as defined above and alkylene and Het are each unsubstituted or mono-, di- or trisubstituted independently by R8, R21 and R22, together with the nitrogen atom to which they are bonded, form a four- to eight-membered monocyclic heterocyclic ring which, as well as the nitrogen atom, additionally, according to the ring size, may contain one or two identical or different heteroatoms from the group of oxygen, nitrogen or sulfur and in which the heterocycle is unsubstituted or mono-, di- or trisubstituted independently by R8, R23 is a hydrogen atom, -OH or -0-(C1-C4)-alkyl, X is a covalent bond, -N(R7)- or -0-, where R7 is a hydrogen atom, -(Co-C4)-alkylene-(C3-C6)-cycloalkyl or -(C-|-C4)-alkyl, Y is -C(0)-, -C(S)- or -S(02)-, p is the integer 1 or 2, R27 is a hydrogen atom, -(C1-C6)-all R26 is a hydrogen atom, -(C1-C4)-alkyl or-(Co-C4)-alkylene-(C3-C6)-cycloalkyl, R24 and R25 are the same or different and are each independently a hydrogen atom, -(C1-C6)-alkyl, -(Co-C4)-alkylene-(C3-C6)-cyGloalkyl, -(C1-C3)-fluoroalkyl, -(CQ-C4)-alkylene-aryl where aryl is as defined above and is unsubstituted or mono-, di- or trisubstituted Independently by R8, or -(Co-C4)-alkylene-Het where Het is as defined above and is unsubstituted or mono-, di- or trisubstituted independently by R8, R24 and R25, together with the carbon atom to which they are bonded, form a three- to six-membered cycloalkyi ring which is unsubstituted or mono-, di- or trisubstituted independently by R10 or fluorine, R24 and R25, together with the carbon atom to which they are bonded, form a three- to six-membered heterocycloalkyi radical which is unsubstituted or mono-, di- or cyclobutane, cyclopentane, cyclohexane, cycloheptane, cyclooctane, bicyclo[4.2.0]octane, octahydroindene, decalin, decahydrobenzocycloheptene, dodecahydroheptalene, bicyclo[3.1.1]heptane, bicyclo[2.2.1]heptane, bicyclo[3.3.0]octane, bicyclo[2.2.2]octane, spiro[2.5]octane, spiro[3.4]octane, azepane, azepine, azetidine, aziridine, azirine, azocane, benzimidazoline, 2,3-dihydrobenzo[b]thiophene, 1,3-dihydrobenzo[c]thiophene, 2,3-dihydrobenzofuran, 2,3-dihydrobenzooxazole, 2,3-dihydrobenzothiazole, 1,3-dihydroisobenzofuran, 4,5-dihydroisothiazole, 2,3-dihydroisoxazole, 2,5-dihydroisoxazole, 4,5-dihydroisoxazole, 5,6-dihydro-4H-[1,2]oxazine, benzo[1,3]dioxole, 1,4-diazepane, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, diaziridine, diazirine, 1,4-diazocane, dioxane, 1,3-dioxane, dioxazine, [1,3]dioxepane, 1,4-diozocane, dioxole, dioxolane, 1,3-dioxolane, 1,3-dioxolene, [1,3]dithiane, [1,3]dithiolane, hexahydropyridazine, hexahydropyrimidine, imidazoiine, imidazolidine, indane, indoline, isoindoline, isothiazolidine, isothiazoline, isoxazoiine, isoxazolidine, 2-isoxazoiine, morphoiine, [1,3,4]oxadiazinane, [1,3,5]oxadJazinane, [1,2,3}oxadiazoiidine, [1,3,4]oxadiazoiidJne, 1,2-ox3thJepane, 1,2-oxathiolane, [1,3]oxathiolane, 1,4-oxazepane, 1,2-oxazine, 1,3-oxazine, 1,4-oxazine, oxazinane, 1,3-oxazinane, oxazocane, oxaziridine, oxazolidine, oxepane, oxetane, oxirane, oxocane, piperazine, piperidine, pyran, pyrazoline, pyrazolidine, pyrrolidine, pyrroiidinone, pyrroline, tetrahydroquinoline, tetraliydrofuran, tetrahydroisoquinoline, 1,2,3,4-tetrahydronaphthalene, tetrahydropyran, tetrahydropyridine, 1,2,3,4-tetrahydro-pyrimidine, 1,2,5,6-tetrahydropyrimidine, tetrahydrotfiiopliene, tetrazine, thiadiazine, [1,2,6]tiiladiazinane, [1,3,4]thiadiazolidine, 1,2-thiazine, 1,3-thiazine, 1,4-thiazine, [1,2]thiazinane, [1,3]thiazinane, thiazolidine, thiazoline, thiepane, thietane, thiomorpholine, thiopyran, 1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazine, [1,2,4]triazinane or [1,2,4]triazolidine, and in wliich the two sub-rings are eacin unsubstituted or independently, according to the ring size, mono-, di-, tri-, tetra- or pentasubstituted by R4, and the X, Y, R27, p, R26, R24, R25 and R4 radicals are each as defined under 4). azetidine, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 1,3-dihydroisobenzofuran, 2,3-dihydroisoxazole, 2,5-dihydroisoxazole, 4,5-dihydroisoxazole, 1,3-dioxane, dioxolane, 1,3-dioxolane, imidazolidine, indane, morphoiine, 1,3-oxazinane, oxazolidine, piperazine, piperidine, pyrrolidine, tetrahydrofuran, and 1,2,3,4-tetrahydronaphthalene, and in which the two sub-rings are each unsubstituted or independently, according to the ring size, mono-, di- or trisubstituted by R4, R4 is =0, =S, -(Co-C3)-alkylene-C(0)-0-R10, -(Co-C3)-alkylene-N(R21)-R22, -(Co-C3)-alkylene-NH-C(0)-R21,-(Co-C4)-alkylene-(C3-C6)-cycloalkyl-R23, -(Co-C3)-alkylene-0-R10, -(Co-C4)-alkylene-phenyl, where phenyl is unsubstituted or mono-, di- or trisubstituted independently by R8, or -(Co-C4)-alkyl where alkyl is unsubstituted or mono-, di- or trisubstituted independently by R9, R8 is fluorine, chlorine, bromine, -0-(C1-C3)-fluoroalkyl or -0-(C-|-C4)-alkyl, R9 is halogen. -NO2. -CN. =0, -OH. -CF3. -C(OVO-R10, -C(0}-N(R21)-R22. -N(R2r}-R22, -(C3-C8)-cycloalkyl. -(CrrC3)-alkylene-O-R10, -Si-{CH3}3. -N(R10)-S(O)u-R10 where u is the integer 1 or 2, -S-R10, -SOpRIO where r is the integer 1 or 2, -S(O)v-N(R10)-R20 where v is the integer 1 or 2, -C(O)-R10, -(C1-C8)-alkyl, -(C1-C8)-alkoxy, phenyl, phenyloxy-, -(C1-C3)-fluoroalkyl, -0-R19, -NH-C(O)-NH-R10, -(Co-C4)-alkyl-C(0)-0-C(R11 ,R19)-0-C(0)-R12, -NH-C(0)-NH-R21, -N(R21)-C{0)-R22, -(Co-C4)-alkyl-C(0)-0-C(R11, R19)-0-C(0)-0-R12, -NH-C(O)-O-R10or-O-CF3, R10 and R20 are the same or different and are each independently a hydrogen atom or -(C1-C6)-alkyl, R11 and R19 are the same or different and are each independently a hydrogen atom or -(C1-C6)-alkyl, R12 is-(C-|-C6)-alkyl, -(C1-C6)-alkyl-0H, -(C1-C6)-alkyl-0-(C1-C6)-aIkyl, -{C3-C8)-cydoalkyl, -(C1-C6)-alkyl-0-{C1-C8)-aa mono-, di- or trisubstituted independently by-OH, -0-(C1-C4)-alkyl or R10, R21 and R22 are the same or different and are each independently a hydrogen atom, -(Cl-C6)-alkyl, -(Co-C6)-alkylene-(C3-C8)-cycloalkyl, -0-R12, -SOt-R10 where t is the integer 1 or 2, or -(C1-C3)-fluoroalkyl, R23 is a hydrogen atom, -OH or -0-(C1-C4)-alkyl, X is a covalent bond or -N(R7)- where R7 is a hydrogen atom or -(C1-C4)-alkyl, Y is -C(0)- or -S(02)-, p is the integer 1 or 2, R26 is a hydrogen atom, R27 is a hydrogen atom, -(Ci -C6)-alkyl, -(Co-C4)-alkylene-(C3-C6)-cycloalkyl, -(Co-C2)-alkylene-phenyl where phenyl is unsubstituted or substituted by halogen, -(C1-C6)-alkyl, -0-(C1- C3)-fluoroalky! or-0-(C1-C6}-aikyK or-(Co-C2)-alkylene-pyridyl, R24 and R25 are the same or different and are each independently a hydrogen atom, -{C-!-C4)-alkyl or -(Co-C4)-alkylene-{C3-C5)-cycloalkyi, R24 and R25, together with the carbon atom to which they are bonded, fomn a cycloalkyi ring which is selected from the group of cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl, and is unsubstituted or mono-, di- or trisubstituted independently by R10 or fluorine, R24 and R25, together with the carbon atom to which they are bonded, form a three- to six-membered heterocycloalkyi radical selected from the group of aziridine, azetidine, diazetidine, diaziridine, hexohydropyridazine, hexohydropyrimidine, imidazolidine, morpholine, oxadiazinane, oxadiazolidine, oxathianane, oxathiolane, oxazetidine, oxazolidine, oxetane, oxirane, piperazine, piperidine, pyrazolidine, pyrrolidine, tetrahydrofuran, tetrahydropyran, tetrahydrothiophene, tetrahydrothiopyran, tetrazinane, thiadiazolidine, thiazetidine, thiaziridine, thiazoiidine, thietane, thiirane, thiomorpholine, triazetidine, triazinane or triazolidine, which is unsubstituted or mono-, di- or trisubstituted independently by R10 or fluorine. 7) The invention further provides the compound of the fomnula la where the sub-ring —is selected from the group of azetidine, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 1,3-dihydroisobenzofuran, 1,3-dioxane, 1,3-dioxolane, imidazolidine, indane, morpholine, 1,3-oxazinane, piperazine, piperidine, pyrrolidine, tetrahydrofuran, and 1,2,3,4-tetrahydronaphthalene, the sub-ring '- is selected from the group of azetidine, cyclopropyl, cyclopentyl, cyclohexyl, morpholine, oxazolidine, piperidine and pyrrolidine, and in which the two sub-rings are unsubstituted or independently, according to the ring size, mono-, di- or tri-substituted by R4 where R4 is -0-(C-|-C4)-alkyl, =0, -(Co-C4)-alkylene-(C3-C6)-cycloalkyl, -(C1-C4)-alkyl or -(Co-C4)-alkylene-phenyl where phenyl is unsubstituted or substituted by F, CI, Bror-0-(C1-C4)-alkyl, X is a covalent bond or -NH-, Y is -Ct'O h or -S(02. p is the integer 1, R27 is a hydrogen atom, -(C1-C6)-alkyl, 4-F-benzyi or benzyl, R26 is a hydrogen atonn, R24 and R25 are the same or different and are each independently a hydrogen atom, methyl or ethyl, R24 and R25, together with the carbon atom to which they are bonded, form a cyclopropyl or cyclobutyl radical, or R24 and R25, together with the carbon atom to which they are bonded, form a piperidine ring which is unsubstituted or substituted by -(C1-C4)-alkyl. 8) The invention further provides compounds of the formula I or la from the group of N-[(S)-1-(1-cyanocyclopropylcarbamoyl)-3,3-difluorobutyl]-3-azaspiro[5.5]undecane-3- carboxamide, N-[(S)-1-(1-cyanocyclopropylcarbamoyl)-3,3-difluorobutyl]-8-azaspiro[4.5]decane-8- carboxamide, N-[(S)-1 -(1 -cyanocyclopropylcarbamoyi )-3,3-dif luorobutyl]- 1,4-dioxa-8-azaspiro[4.5]decane-8-carboxamide, N-[(S)-1-(1-cyanocyclopropylcarbamoyl)-3,3-difluorobutyl]-2-azaspiro[5.5]undecane-2- carboxamide, N-[(S)-1-(1-cyanocyclopropylcarbamoyl)-3,3-difluorohexyl]-8-azaspiro[4.5]decane-8- carboxamide, N-[(S)-1-(1-cyanocyclopropylcarbamoyl)-3,3-difluorohexyI]-3-azaspiro[5.5]undecane-3- carboxamide, N-[(S)-1 -(1 -cyanocyclopropylcarbamoyl)-3,3-difluorobutyl]-2-(4-methoxyphenyI)-1 -oxo- 2,8-diazaspiro[4.5]decane-8-carboxamide, N-[(S)-1-(1-cyanocyclopropylcarbamoyl)-3,3-difluorobutyl]-4-oxo-1-phenyl-1,3,8-tri- azaspiro[4.5]decane-8-carboxamide, N-[(S)-1-(1-cyanocyclopropylcarbamoyl)-3,3-difluorobutyl]-1,5-dioxa-9-aza- spiro[5.5]undecane-9-carboxamide, N-{(S)-1-(1-cyanocyciopropylcarbamoyl )-3,3-dtfiuorobutyl]-1-0X0-2,8- diazaspirD[4.5jdecane-8-carboxamide, N-[(S)-1 -(1 -cyanocyctopropy{carbarrKDyl}-3,3-dl!jorobutyl]-2-methyl-1 -oxo-2 diazaspiro[4.5]deGane-8-carboxamide, N-[(S)-1-(1-cyanocyclopropylcarbamoyl)-3,3-difluorobutyl]-3,3-dimethyl-1-oxa-5,9- diazaspiro[5.5]undeGane-9-carboxamide, N-[(S)-1-(1-cyanocyGlopropylcarbamoyl)-3,3-difluoro-4-phenylbutyl]-8- azaspiro[4.5]decane-8-carboxamide, N-[(S)-1 -(1 -cyanocyclopropylcarbamoyl)-3,3-difluorobutyl]-2,4-dioxo-1,3,8- triazaspiro[4.5]deGane-8-carboxamide, N-[(S)-1-(1-GyanoGyGlopropylcarbamoyl)-3,3-difluorobutyl]-2-azaspiro[4.4]nonane-2- oarboxamide, N-[(S)-1-(1-GyanoGyGlopropylGarbamoyl)-3,3-difluorobutyI]-2-benzyl-1-oxo-2,8- diazaspiro[4.5]deGane-8-Garboxamide, N-[(S)-1-(1-GyanoGyGlopropylGarbamoyt)-3,3-difluorobutyl]-2-(4-fluoro phenyl)-1-oxo-2,8-diazaspiro[4.5]decane-8-Garboxamide, N-[(S -1 -{1 -cyarvocy ciopropylcarbaTioyI )-3-methylbufylj-1,4-diQxaspirot4.5]decane-S- carboxamide, N- [(S)-1 -(1 -cyanoGyGlopropylcarbamoyl)-3,3-difluorobutyl]-3-phenyl-1,5-dioxa-9- azaspiro[5.5]undeGane-9-carboxannide, N-[1-(1-cyanoGyGlopropylcarbamoyl)GyGlohexyl]-8-azaspiro[4.5]decane-8-Garboxamide, N-[(S)-(1-cyanocyclopropylcarbamoyl)cyclohexylmethyl]-8-azaspiro[4.5]decane-8- oarboxamide, N-[(S)-1-(1-cyanoGyGlopropylcarbamoyl)-3,3-difluorobutyl]-9-butyl-3,9- diazaspiro[5.5]undeGane-3-carboxamide, N-[(S)-1-(1-GyanoGyGlopropylGarbamoyI)-3,3-difluorobutyl]-9-cyclopropyl-3,9- diazaspiro[5.5]undeGane-3-Garboxamide, N-[(S)-1-(1-GyanoGyGlopropylGarbamoyl)-3-methylbutyl]spiro[2.3]hexane-1- Garboxamide, N-[(S)-1-(1-cyanocyclopropylcarbamoyl)-3,3-clifluoro-4-phenylbutyl]-8- azaspiro[4.5]clecane-8-carboxamide, N-[(S)-1-(1-cyanocyclopropylcarbamoyl)-3,3-difluorobutyl]spiro[2.3]hexane-1- carboxamide, N-[(S)-1-(1-cyanocydopropyicarbamoy!)-3,3-difiuorobutyi]-2,2-dimethyl-1-oxa-8- azaspiro[4.5]decane-8-carboxamide. N-[(S)-1 -(1 -cyanocyclopropylcarbamoyl)-3,3- dif!uorobutyi]-2-azaspiro[4.5}decar)e-2-carbQxarn4de, N-[(S)-1-(1-cyanocyclopropylcarbamoyl)3,3-difluorobutyl]-7-cyclopropyl-2,7- diazaspiro[3.5]nonane-2-carboxaraide, N-[(S)-1-(1-cyanocyclopropylcarbannoyl)-3,3-drfluorobutyl]-2-cyclopropyl-2,7- diazaspiro[3.5]nonane-7-carboxamide, N-[(S)-1-(1-cyanocyclopropylcarbamoyl)-3,3-difluorobutyl]-2-propyl-2,7- diazaspiro[3.5]nonane-7-carboxannide, N-(1-cyanocyclopropyl)-(S)-2-(8-azaspiro[4.5]decane-8-sulfonylamino)-4,4- difluoropentoxide, N-[(S)-1 -(1 -cyanocyclopropyIcarbamoyI)-3,3-difluorobutyl]-4-cyclopropyl-1 -oxa-4,9- diazaspiro[5.5]undecane-9-carboxamide, N-[(S)-1-(1-cyanocyclopropylcarbamoyl)-3,3-difluorobutyl]-9-cyclopropyl-1-oxa-4,9- diazaspiro[5.5]undecane-4-carboxamide, N-[(S)-1-(1-cyanocyclopropylcarbamoyl)-3,3-difluorobutyl]-2-cyclopropy(methyl-3-oxo- 2,8-diazaspiro[4.5]decane-8-carboxamide, N-[(S)-1-(1-cyanocyclopropyicarbamoyi)-3.3-difluorohexyr]-2-(4-methoxyphenyl)-1-oxo- 2,8-diazaspiro[4.5]decane-8-cartx)xamide, N-{(S)-1 -(1 -cyanocydopropy1carbamoyi)-3, 3HJifhjorolTexyl]-2-(4-methox diazaspiro[4.5]decane-8-carboxamide, N-[(S)-1-(1-cyanocyclopropylcarbamoyl)-3,3-difluorohexyl]-2-cyclopropyl-2,7- diazaspiro[3.5]nonane-7-carboxamide, N-[(S)-1-(1-cyanocyclopropylcarbamoyl)-3,3-difluorohexyl]-2-cyclopropyl-2,8- diazaspiro[4.5]decane-8-carboxamide, N-[(S)-1 -(1 -cyanocyclopropylcarbamoyl)-3,3-dif luorohexyl]-9-cyclopropyl-3,9- diazaspiro[5.5]undecane-3-carboxamide, N-[(S)-1-(1-cyanocyclopropylcarbamoyl)-3,3-difluorohexyl]-7-cyclopropyl-2,7- diazaspiro[3.5]nonane-2-carboxamide, N-[(S)-1-(1-cyanocyclopropylcarbamoyl)-3,3-difluorohexyl]-7-propyl-2,7- diazaspiro[3.5]nonane-2-carboxamide, N-[(S)-1-(1-cyanocyclopropylcarbamoyl)-3,3-difluoro-4-phenylbutyl]-9-cyclopropyl-3,9- diazaspiro[5.5]undecane-3-carboxamide, IS)-1-{lKyanocyckjcctrnoyl)-3,3KiffliJori>4-ptr»j diazaspiro[3.5]nonane-7-carboxamide, N-[(S)-1-(1-cyanocyclopropylcarbamoyl)-3,3-difluoro-4-phenylbutyl]-2-propyl-2,7- diazaspiro[3.5]nonane-7-carboxamide, N-[(S)-1-(1-cyanocyclopropylcarbamoyl)-3,3-difluoro-4-phenylbutyl]-7-cyclopropyl-2,7- diazaspiro[3.5]nonane-2-carboxamide, N-[(S)-1-(1-cyanocyclopropylcarbamoyl)-3,3-difluorobutyl]-6-azaspiro[2.5]octane-6- carboxamide, N-[(S)-1-(cyanomethylcarbamoyl)-3,3-difluorobutyl]-6-azaspiro[2.5]octane-6- carboxamide, N-[(S)-1-(1-cyanocyclopropylcarbamoyl)-3,3-difluorohexyl]-6-azaspiro[2.5]octane-6- carboxamide, N-[(S)-1-(4-cyano-1-methylpiperidin-4-ylcarbamoyl)-3,3-difluorobutyl]-6- azaspiro[2.5]octane-6-carboxamide, N-[(S)-1-(4-cyano-1-methylpiperidin-4-ylcarbamoyl)-3,3-difluorohexyl]-6- azaspiro[2.5]octane-6-carboxamide, N-[(S}-1-{1-cyanocyclopropylcarbamoyl)-3,3-dtfiuoropenty!]- or N-[(S)-1-(1- c>'anocyc±)propyicart)amoyl)-3.3HJifluoiT)-4-phenylbutyi]-6-azasp carboxamJde. The terms "(C1-C3)-alkyl", "(C1-C4)-alkyl" or "(C1-Cio)-alkyl" are understood to mean hydrocarbyl radicals whose carbon chain is straight or branched and contains from 1 to 3, from 1 to 4 or from 1 to 10 carbon atoms, for example methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, isopentyl, neopentyl, hexyl, 2,3-dimethylbutyl, neohexyl, heptyl, octanyl, nonanyl ordecanyl. The terms "-(Co-C3)-alkylene", "-(Co-C4)-alkylene" or "-(Co-C5)-alkylene" are understood to mean hydrocarbyl radicals whose carbon chain is straight or branched and contains from 1 to 3, from 1 to 4 or from 1 to 5 carbon atoms, for example methylene, ethylene, propylene, isopropylene, isobutylene, butylene, tert-butylene, isopentylene or neopentylene. "-Co-Alkylene" is a covalent bond. The term "(C-|-C8)-alkoxy" is understood to mean radicals such as -0-(C1-C8)-alkyl where -(C1-C8)-alkyl is bonded by a carbon atom to an oxygen atom. Ttre radical "-C(O)-" is uncterstood to mean a keto or aldehyde radical. The "carbamimidoyi" radical is understood to mean a -C(NH2)=NH radical. The term "-(C3-C8)-cycloalkyl" is understood to mean radicals which derive from 3- to 8-membered monocycles such as the monocycles cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane or cyclooctane. The term "aryl" is understood to mean aromatic carbon radicals having from 6 to 14 carbon atoms in the ring. Aryl radicals are, for example, phenyl, indanyl, indenyl, naphthyl, 1,2,3,4-tetrahydronaphthyl, biphenylyl, 2-biphenylyl, 3-biphenylyl, 4-biphenyiyl, anthryl orfluorenyl. The term "a saturated or partly unsaturated -(C3-C1-|)-cycloalkyl in which cycloalkyi is unbridged, bridged or fused" is understood to mean radicals, for example compounds which derive from 3- to 11-membered mono-, bicycles, bridged cycles or spirocycles: for example from the monocycles such as cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane or cyclooctane, for example from the bicycles such as bicycloheptane, bicyclo[4.2.0]octane, octahydroindene, decalin, decahydro-benzocycloheptene or dodecahydroheptalene, for example from the bridged cycles such as bicycio[3.1.1]heptane, bicyclo[2.2.1]heptan€, bicyclo[3.3.0]octane or bicydo[2.2.2]octane, or for example, from the spirocycles such as spiro[2.5]octane and 3piro[3.4]octane. The term "a saturated or partly unsaturated three- to eleven-membered heterocycle which, according to the ring size, may contain one, two, three or four identical or different heteroatoms from the group of oxygen, nitrogen and sulfur, and in which the heterocycle is unbridged, bridged or fused" is understood to mean ring systems which have from three to eleven ring atoms and contain, as well as the carbon atoms, according to the ring size, one, two, three or four identical or different heteroatoms from the group of oxygen, nitrogen and sulfur. Examples of these ring systems are ring systems such as azepane, azepine, azetidine, aziridine, azirine, azocane, benzimidazoline, 2,3-dihydrobenzo[b]thiophene, 1,3-dihydrobenzo[c]thiophene, 2,3-dihydrobenzofuran, 2,3-dihydrobenzooxazole, 2,3-dihydrobenzothiazole, 1,3-dihydroisobenzofuran, 2,3-dihydroisoxazole, 2,5-dihydroisoxazole, 4,5-dihydro-isoxazole, benzo[1,3]dioxole, 1,4-diazepane, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, diaziridine, diazirine, 1,4-diazocane, dioxane, 1,3-dioxane, dioxazin, 1,4-dJozocane, dioxole, dkixolana 1,3-dioxolane, 1,3-dioxolene, unidazDiine, Imidazolidine, indane, indoline, isoindoline, isothiazolidine, isothrazoline, isoxazoline, isoxazolidine, 2-isoxazoline, morpholine, 1,2-oxathiepane, 1,2-oxathiolane, 1,4-oxazepane, 1,2-oxazine, 1,3-oxazine, 1,4-oxazine, oxazinane, 1,3-oxazinane, oxazocane, oxaziridine, oxazolidine, oxetane, oxirane, oxocane, piperazine, piperidine, pyran, pyrazoline, pyrazolidine, pyrrolidine, pyrrolidinone, pyrroline, tetrahydroquinoline, tetrahydrofuran, tetrahydroisoquinoline, 1,2,3,4-tetrahydronaphthalene, tetrahydropyran, tetrahydropyridine, tetrazine, thiadiazine, 1,2-thiazine, 1,3-thiazine, 1,4-thiazine, thiazolidine, thiazoline, thietane, thiomorpholine, thiopyran, 1,2,3-triazine, 1,2,4-triazine or 1,3,5-triazine. Spiro compounds are compounds of two or three rings in which, in each case, one ring atom belongs to two rings in common. Preference is given to spiro compounds which consist of two rings in which, in each case, one ring atom belongs to two ring atoms in common. This ring atom is eitlier a carbon atom or a nitrogen atom, preferably a carbon atom. Ttie spiro linkage of the two sub-rings may be via all conceivable positions. Prefened spiro compounds in all possible stereoisomeric forms are: The term "halogen" is understood to mean fluorine, chlorine, bromine or iodine, preferably fluorine, chlorine or bromine, especially fluorine. The term "Het ring" or "Het" is understood to mean ring systems which have 3 from 15 carbon atoms, are present in one, two or three ring systems bonded to one another and which, according to the ring size, contain one, two, three or four identical or different heteroatoms from the group of oxygen, nitrogen or sulfur. Examples of these ring systems are the acridinyl, azepanyl, azepinyl, azetidinyl, aziridinyl, benzimidazolinyl, benzimidazolyl, benzofuranyl, benzothiofuranyl, benzothiophenyl, benzoxazolyl, bTztl'zdyl, benztriazdyl, baizlfitrazc, benzxazil, benzathezolyl, caiszD 4aH-carbazolyl, carbolinyl, qumazdinyl, quinoltnyl, 4H-quinolizinyl, quinoxalinyi, quinuclidinyl, chromanyl, chromenyl, cinnolinyl, decahydroquinolinyl, dibenzofuranyl, dibenzothiophenyl, dihydrofuran[2,3-b]-tetrahydrofuranyl, dihydrofuranyl, dioxolyl, dioxanyl, 2H, 6H-1,5,2-dithiazinyl, furanyl, furazanyl, homomorpholinyl, imidazolidinyl, imidazolinyl, imidazolyl, 1 H-indazolyl, indolinyl, indolizinyl, indolyl, 3H-indolyl, isobenzofuranyi, isochromanyl, isoindazolyl, isoindolinyl, isoindolyl, isoquinolinyl (benzimidazolyl), isothiazolidinyl, 2-isothiazolinyl, isothiazolyl, isoxazolyl, isoxazolidinyl, 2-isoxazolinyl, morpholinyl, naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, oxazolidinyl, oxazolyl, oxazolidinyl, oxothiolanyl, pyrimidinyl, phenanthridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl, phenoxathiinyl, phenoxazinyl, phthalazinyl, piperazinyl, piperidinyl, pteridinyl, purinyl, pyranyl, pyrazinyl, pyroazolidinyl, pyrazolinyl, pyrazolyl. pyridazinyl, pyridooxazolyl, pyridoimidazolyl, pyridothiazolyl, pyridothiophenyl, pyridinyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolinyl, 2H-pyrrolyl, pyrrolyl, tetrahydrofuranyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, tetrahydropyridinyl, 6H-1,2,5-thiadazinyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, thianthrenyl, thiazoly!, thienyi, thienoimidazojyi, thienooxazoiy!, thienopyridine, thienothiazolyl, thjomorpholinyi, throphenyi, triazinyi, 1,Z3-triazDlyi, 1,2,4-triazolyl, 1,2,5-triazotyl, 1,3.4-triazolyl and xanthenyl radixials. The term "-(C1-C3)-fluoroalkyl" is understood to mean a partially or completely fluorinated alkyl radical which derives, for example, from the following radicals: -CF3, -CHF2, -CH2F, -CHF-CF3, -CHF-CHF2, -CHF-CH2F, -CH2-CF3, -CH2-CHF2, -CH2-CH2F, -CF2-CF3, -CF2-CHF2, -CF2-CH2F, -CH2-CHF-CF3, -CH2-CHF-CHF2, -CH2-CHF-CH2F, -CH2-CH2-CF3, -CH2-CH2-CHF2, -CH2-CH2-CH2F, -CH2-CF2-CF3, -CH2-CF2-CHF2, -CH2-CF2-CH2F, -CHF-CHF-CF3, -CHF-CHF-CHF2, -CHF-CHF-CH2F, -CHF-CH2-CF3, -CHF-CH2-CHF2, -CHF-CH2-CH2F, -CHF-CF2-CF3, -CHF-CF2-CHF2, -CHF-CF2-CH2F, -CF2-CHF-CF3, -CF2-CHF-CHF2, -CF2-CHF-CH2F, -CF2-CH2-CF3, -CF2-CH2-CHF2. -CF2-CH2-CH2F, -CF2-CF2-CF3, -CF2-CF2-CHF2 or -CF2-CF2-CH2F. The temns "R2 and R3", "R19 and R11", "R13 and R14" or "R24 and R25, together with thecartxHi atom tovirfifchthey atx)rKJed, fwrnathree-tosixHTiember cydoaHcy ring" are understood to mean cycloalkyi radicals such as cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl. The terms "R2 and R3" or "R24 and R25, together with the carbon atom to which they are bonded, form a three- to six-membered heterocycle alkyl radical" are understood to mean radicals such as aziridine, azetidine, diazetidine, diaziridine, hexohydropyridazine, hexohydropyrimidine, imidazolidine, morpholine, oxadiazinane, oxadiazolidine, oxathianane, oxathiolane, oxazetidine, oxazolidine, oxetane, oxirane, piperazine, piperidine, pyrazolidine, pyrrolidine, tetrahydrofuran, tetrahydropyran, tetrahydrothiophene, tetrahydrothiopyran, tetrazinane, thiadiazolidine, thiazetidine, thiaziridine, thiazolidine, thietane, thiirane, thiomorpholine, triazetidine, triazinane or triazolidine. The term "R21 and R22 together with the nitrogen atom to which they are bonded form a four- to eight-membered monocyclic heterocyclic ring which, as well as the nitrogen atom, may additionally, according to the ring size, also contain one or two identical or different heteroatoms from the group of oxygen, nitrogen and sulfur" is understood to mean radicals such as azepane, azepine, azetidine, dioxazole, dioxazine, 1,4-diazepane. 1.2-diazepine, K3-diazepine, 1.4-diazepine, imidazole, imidazoline, imidazolidina, isothiazole, isothiazolidine, isothiazoline, isoxazole, isoxazoline, isoxazolidine, 2-isoxazoline, morpholine, [1,4]oxazepane, oxazole, piperazine, piperidine, pyrazine, pyrazole, pyrazoline, pyrazolidine, pyridazine, pyridine, pyrimidine pyrrole, pyrrolidine, pyrrolidinone, pyrroline, tetrahydropyridine, tetrazine, tetrazole, thiazole, thiadiazole, thiazolidine, thiazoline, thiomorpholine, 1,2,3-trlazine, 1,2,4-triazine, 1,3,5-triazine, 1,2,3-triazole or 1,2,4-triazole. The term "two adjacent R4, together with the ring atoms to which they are bonded, form a four- to eight-membered heterocycle or phenyl which, together with the sub-ring to which the heterocycle or the phenyl is fused, forms a bicyclic system" is understood to mean compounds which consist of two connected ring systems in which one ring constitutes the sub-ring — or '■— and the other ring forms a partly saturated or aromatic ring system which, according to the ring size, contains one, two or three identical or different heteroatoms from the group of oxygen, nitrogen and sulfur. Exanf of tiije rir syaris are radicals sudi s£ benzcwmtazole, benzolsothiazole, benzoisoxazole, benzo[1,3]dloxcrfe, benzofuranyl, benzothiazole, benzoisoxazole, benzothiofuran, benzothiophene, benzo[1,3]oxathiole, benzoxazole, benzothiazole, benzotriazolyl, quinazoline, quinazolone, quinoline, 4H-quinolizine, quinoxaline, chromane, chromene, cinnoline, 2,3-dihydrobenzo[1,4]dioxine, 2,3-dihydrobenzofuranyl, 1,3-dihydroisobenzofuran, 3,4-dihydro-2H-benzo[1,4]oxazine, 2,3-dihydrobenzooxazole, 2,3-dihydrobenzothiazole, 1,3-dihydrobenzo[c]thiophene, 2,3-dihydrobenzo[b]thiophene, Indazole, indole, indoline, isobenzofuran, isoquinoline, isochromane, isoindazole, isoindole, isoindoline, 7-oxa-bicyclo[4.2.0]octa-1,3,5-triene, phthalazine, 2,3,4,5-tetrahydro-1 H-benzo[b]azepine, 6,7,8,9-tetrahydro-5-oxa-9-aza-benzocycloheptene, 3,4,5,6-tetrahydro-2H-benzo[b][1,4]oxazozine, tetrahydroquinoline, 1,2,3,4-tetrahydroquinoxaline or tetrahydroisoquinoline. The inventive compounds can be prepared by well-known processes or by processes described here, The invention further relates to a process for preparing the compounds of the formulae I and la and/or a stereoisomeric form of the compound of the formulae I and la and/or a physiologically compatible salt of the compound of the formulae I and la and/or a solvate or hydrate of the compound of the formulae I and la and/or an N-oxide of the compounds of the formula I, which comprises where X, R1, R2 and R3 are each as defined in the compound of the formula I, PG is an ester protecting group and "activated" means that the amine is present in an activated form, for example as a chlorocarbonyl compound, to give a compound of the formula IVa or IVb and reacting the resulting compounds of the formiila IVa or IVb, after converting b) reacting a compound of the formula Va or Vb where A, B, X and Y are each as to give a compound of the formula IVa or IVb, and reacting the resulting compound of the formula IVa or IVb, after converting the ester protecting group to the carboxylic acid, with Z to give the compound of the formula I, or c) reacting a compound of the formula Vila or Vllb where A, B and X are each as defined in the compound of the formula I to give a compound of the formula Villa or Vlllb and reacting the resulting compound of the formula Villa or Vlllb, after converting the ester to the corresponding carboxylic acid, with Z to give the compound of the formulae I and la, or under b), to give the inventive compound of tlie formulae I and la, or e) separating a compound of the formulae I and la prepared by processes a), b), c) or d), or a suitable precursor of the formulae I and la which, owing to its chemical structure, occurs in enantiomeric or diastereomeric forms, into the pure enantiomers or diastereomers by salt formation with enantiomerically pure salts or bases, chromatography on chiral stationary phases or derivatization by means of chkal aiantiomericaJJy pure compounds such as arwKi adds, separating the diastereomers thus obtained, and eliminating tiie chiral auxiliary groups, or f) either isolating the compound of the formulae I and la prepared by processes a), b), c) or d) in free form or releasing it from physiologically incompatible salts or, in the case of the presence or acidic or basic groups, converting it to physiologically acceptable salts, or g) converting the compound of the formulae I and la prepared by processes a), b), c) or d), or a suitable precursor of the formulae I and la which, owing to its chemical structure, is capable of forming an N-oxide to an N-oxide or, in the case of the presence of an N-oxide, converting it to the free amine or the salt of an amine. The synthesis of the inventive products can also proceed on the basis of three starting nnaterials, any variation of the components which lead to the inventive structures being possible. For the sake of simplicity, the possible syntheses are described through these three components; however, this is not intended to constitute any restriction on the It is a preferred route to prepare, from these three starting materials by selection of suitable derivatives of these components, for example protected or modified precursors or precursors with defined stereochemistry, the inventive compounds through suitable coupling reactions, possibly after activation with reactive reagents such as known peptide coupling reagents or reagents which lead to activated urea precurscxs. Methods of peptkje coupling are described, for instance, in Bodanszl chlorosulfonic acid or sulfur trioxide for the preparation of activated sulfonylurea precursors. It is equally possible for the sequence of coupling to be varied, or else the individual component or the two-component unit (which has been obtained by coupling two adjacent individual components) on which the activation is undertaken, or for different protecting groups to be used, foHowed by the addition of the component which is stili absent or of the components which are still absent it is also possible to change the protecting groups, for example protecting group detachments on completion of coupling or at the end of the synthesis, to prepare the compound of the formulae I and la. The component B - amino acid derivative - used is a suitable ester, for example a methyl ester, but many other ester protecting groups are also possible. This derivative is activated on the nitrogen to give a urea precursor, for example by reaction with triphosgene, diphosgene or phosgene itself to give an isocyanate, so that a urea s forTTrod tjy stjseqiTt iBaction wfth the sptro-annme A. However, many other types of activation are also possible; for example, reaction with carbonyldiimidazole affords the activated imidazolide, reaction with 4-nitrophenyl chloroformate affords the corresponding carbamate, and reaction with various similar activating carbonate reagents such as bis-succinimidyl carbonate or bis(4-nitrophenyl) carbonate affords corresponding derivatives. The analogous sulfur-containing derivatives (thiourea analogs) can be obtained correspondingly by the use of thiophosgene. However, it has to be taken into account that the strength of activation by the reagents listed is different, i.e. the subsequent reaction with the secondary spiro-amine can proceed at different speed or else afford very different yields or by-products. Moreover, it might be necessary to achieve a preactivation by silylating the amine with, for example, trimethylsilyl chloride or bistrimethylsiliylacetamide or bistrifluoromethyltrimethylsilylacetamide in order that the actually activated urea precursor can form more easily. In addition, it might be advantageous in some cases to proceed from a free amino acid and to silylate it both on the nitrogen and on the Next, the ester is cleaved under conditions which cause a minimum level of side reactions on the molecule, in the case of the methyl ester preferably under basic conditions, for example with NaOH or LiOH as a base, and it is advisable to avoid base excesses or long reaction times. In the case of a silyl protecting group, it may, though, also be sufficient to achieve ester cleavage by aqueous treatment, possibly with addition of a little mineral acid. Before the amide bond can be fonned with the 3rd component, the aminonitriie, the carboxylic acid is generally released from the salt with a mineral add after the basic cleavage. Subsequently, the peptide coupling can be effected by a multitude of methods known to those skilled in the art, as already mentioned above, if appropriate with addition of further auxiliary reagents for increasing the coupling efficiency or suppressing racemization. Route 1 b: amino acid derivative, but ratlier on component A, the spiro-amine. Since it is, however, a secondary amine, reactivities and yields are often changed compared to route 1a. For example, it is, though, possible to activate the spiro-amine as the chlorocarbonyl derivative by reaction with phosgene, triphosgene or diphosgene, and then to react the latter with the atx)vementioned amino acid ester. The abovementioned amino acid can also be used in ttie activated sitylated form. The further reaction, i.e. release of the carboxyiic add and coupling with the amine component C, is then effected as described under 1a. The starting material is a suitable N-terminally protected amino acid derivative B. This is first coupled with the aminonltrile C; in this reaction, the known methods of peptide bond formation can again be used Subsequently, tiie N-temifii pwrtectkig group is eliminated and the elimination product is converted to tiie activated urea precursor as described under la. Under some circumstances, it is of particular significance here to use the protecting groups whose detachment conditions are compatible with the functionalities on the overall molecule B-C. This activated derivative, for example the isocyanate, is subsequently reacted with the spiro-amine to give the inventive compound I. Route 2b Attemativeiy. it is also Dossibie here, anatogousiy to the route desaibed under 1 b first to activate the spiro-amine A in order then to perform the reaction with component B-C to give the urea. The synthesis of sulfonylureas is widely described. A frequently used method proceeds from an activation of the amines to give sulfonyl chlorides by reaction with preferably chlorosulfonic acid, and subsequent chlorination of the resulting sulfonic acid with, for e)mple, phosphorus pentachtoride or fKahoais oxychloride. foUcwed by the reaction with the second amino component and a suitable base. Equally, it is also possible to use SO3 in the first stage of the synthesis. Moreover, it is also possible to achieve the desired conversion with sulfonyl chloride. Preference is given to undertaking the reaction on the secondary spiro-amine unit, followed by the reaction, for example, of the amino acid-amine, protected as the ester. Subsequently, the ester is cleaved and reacted with the aminonitrile unit. Alternatively, it is also possible to react the activated spiro unit with the amino acid-amidonitrile, prepared from the N-terminally protected amino acid by coupling with the aminonitrile unit followed by the protecting group detachment. Bisamides are prepared starting from amino acid units according to the following scheme: Wnen tns spiro unit is not present as a secondary amine but rather as a carboxyiic acid, there is attachment to the amino acid via an amkle bond. This can be effected in the synthesis either first, in which case an amino acid ester is used, followed as described above in the analogous case 1 b by ester cleavage and amide coupling with the aminonitrile unit, or, when an amino acid-amidonitrile unit is used, as the second coupling stage in the synthesis, in each case accompanied by appropriate protecting group manipulations, as described above in case 2b. Optically active carbon atoms in the inventive compounds of the formulae I and la may each independently be present in R or S configuration. The compounds of the formulae I and la may be present in the form of the pure enantiomers or pure diastereomers or in the form of mixtures in any proportions of the enantiomers and/or diastereomers, for example in the form of their racemates or enantiomeric diastereomer pairs. The present invention thus relates to pure enantiomers and mixtures of the enantiomers, and equally to pure diastereomers and mixtures of the diastereomers. The invention likewise encompasses mixtures of two ctf- of more than ttK) sterecas(xners of the fomnulae I and la and likewise all possible mixing ratbs of these stereoisomers in the mixtures. In the case that the compounds of the formulae I and la are present in the form of E or Z isomers, or cis or transisomers, or as a "spiran", the invention relates in each case both to the pure E and pure Z isomers, and to the pure cis or pure transisomers, and likewise, entirely analogously, to the corresponding spiroisomers, and also E/Z or cis/trans mixtures in any ratio. The invention likewise encompasses all tautomeric forms of the inventive compounds of the formulae 1 and la. The compound of the formulae I and la is, when it occurs as a mixture of diastereomers or enantiomers or is obtained as mixtures thereof in the synthesis selected, separated into the pure stereoisomers, either by chromatography on a chiral or achiral support material, or, when the racemic compound of the formulae I and la is capable of salt formation, by fractional crystallization of the diastereomeric salts fornned with an optically active base or acid as an auxiliary. Suitable chiral stationary phases for thin-layer or column chromatography separation of enantiomers are, for example, modified silica gel supports (so-called Pirkle phases) and high molecular weight carbohydrates such as triacetylceJiubse. For analytical purposes, gas chromatography methods on chiral stationary phases can also be employed after appropriate derivatization known to those skilled In the art. For enantiomer separation of the racemic carboxylic acids, an optically active, generally commercially available base such as (-)-nicotine, (+)- and (-)-phenylethylamine, quinine bases, L-lysine or L- and D-arginine are used to form the differently soluble diastereomeric salts, the less soluble component is isolated as a solid, the more soluble diastereomer is separated from the mother liquor, and the pure enantiomers are obtained from the diastereomeric salts thus obtained. In a manner similar in principle, the racemic compounds of the formulae I and la which contain a basic group, for example an amino group, can be converted to the pure enantiomers with optically active acids, for example (+)-camphor-10-sulfonic acid, D- and L-tartaric acid, D- and L-lactic acid, and also (+)- and (-)-mandelic acid. It is also possible to convert chiral compounds which contain alcohol or amine functions to the corresponding esters or amides with correspondingly activated or optionally N-protected enatiomerically pure amino acids, or, conversely, to convert chiral carboxylic acids to the amides with carboxy-protected enantiomerlcally pure amino acids, or to the corresponding chiral esters with enantiomericaUy pure hydroxycarlxjxylic adds such as lactic acid. The chirality of the amino acid or alcohol radical introduced in enantiomericaUy pure form can then be utilized to separate the isomers by undertaking a separation of the diastereomers now present by crystallization or chromatography on suitable stationary phases, and then detaching the entrained chiral molecular moiety again by means of suitable methods. Furthermore, the possibility arises for some of the inventive compounds to use diastereomerically or enantiomericaUy pure starting materials to prepare the skeleton structures. This also allows different or simplified processes for purifying the end products to be used. These starting materials have been prepared beforehand in enantiomericaUy or diastereomerically pure form by literature processes. To this end, for example, it is also possible to use enzymatic processes. It is possible either to use those enzymatic processes which proceed enantio- or diastereoselectively in one synthesis step, i.e. afford one compound selectively, or else in the sense of a kinetic enzymatic synthesis or cleavage in such a way that, for example, an enantiomer or diastereomer already present is converted highly preferentially in the enzymatic reaction, for example in the sense of a selective acylation or esterification or acyl cleavage or ester cteavage. Reactions used successfufiy are, for example, acylation reactbns with lipases or acylase cleavages of N-acety! cximpounds, or protease-mediated esterifications in organic solvents or ester cleavages, but many other possibilities are also conceivable. When amino acid derivatives are used, they are frequently commercially available already in enantiomerically pure form. In the case of non-proteinogenic amino acids, they may, however, often also be prepared from enantiomerically or diastereomerically pure natural precursors, for example from proteinogenic amino acids or else other natural chiral starting materials of the chiral pool, or else these precursors are obtained in optically pure form by one of the separation methods mentioned or by use of different types of enzymatic processes and used correspondingly in the synthesis. Acidic or basic products of the compound of the formulae I and la may be present in the form of their salts or in free form. Preference is given to pharmacologically acceptable salts, for example alkali metaJ or alkaline earth metal salts or hydrochlorides, hydrobromides, sulfates, hemisulfates, ail possible phosphates and salts of the amino acids, natural bases or carboxylic acids. The present invention also includes all solvates of the compounds of the general formulae I and la, such as stoichiometric or nonstoichiometric hydrates or alcohol adducts. The preparation of physiologically compatible salts from compounds of the formulae I and la capable of salt formation, including their stereoisomeric forms, is effected in a manner known per se. The acidic compounds of the formulae I and la form stable alkali metal, alkaline earth metal or optionally substituted ammonium salts with basic reagents such as hydroxides, carbonates, hydrogencarbonates, alkoxides and ammonia, or organic basis, for example methylamine, dimethylamine, ethylamine, trimethyl or triethylamine, ethanolamine, diethanolamine or triethanolamine, trometamol or else basic amino acids, for instance lysine, ornithine or arginine. When the compounds of the formulae I and la have basic groups, it is also possible to prepare stable acid addition salts with strong acid. For this purpose, useful acids are both inorganic and organic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, hemisulfjric acid, phosphoric actd, nitric acid, methanesulfonic acid, benzenesulfonic add, p-totuenesuifonic add, 4-bromot)enzenesu{fonic add, cydohexylamidosutfonic add, trifluoromethyfsutfonlc add, 2-hydroxyethanesJulfonic add, formic add, acetic add, oxalic acid, tartaric acid, succinic acid, glycerolphosphoric acid, lactic acid, malic acid, adipic acid, citric acid, fumaric acid, maleic acid, malonic acid, benzoic acid, sorbic acid, gluconic add, glucuronic acid, palmitic acid, stearic acid or trifluoroacetic acid. Hydrates of the compounds of the formulae I and la can be prepared, for example, by (re)crystallization from an organic-aqueous solvent mixture, for example by using such organic solvents as dioxane, tetrahydrofuran, ethanol or methanol. Conversely, it is also possible to prepare free acid or free base forms of the compounds of the formulae I and la from the corresponding salts. For example, a compound of the formulae I and la can be released from its acid salt form by treatment v\/ith suitable bases (such as ammonia solution, sodium hydroxide solution). In some special cases, treatment with oxiranes can also bring about a release; for example, hydrochlorides can be released by treatment with methyloxirane, particulariy in the case of amino acid derivatives. Com]X)unds of the formuJae I and la which are present in the form of their base salt form can be converted to the free acid form by treatment with suitable acids (citric acid, hydrochloric acid or sulfuric acid). Nitrogen compounds of the formulae I and la may also be present in the form of their N-oxides. These can be prepared by various processes which are known to those skilled in the art. For example, a nonoxidized form of a compound of the formulae I and la can be oxidized to the corresponding N-oxides by treatment with a suitable oxidizing agent (trifluoroperacetic add, permaleic acid, perbenzoic acid, peracetic acid, meta-chloroperbenzoic acid) in suitable inert organic solvents. Alternatively, the N-oxides of the compounds of the formulae 1 and la can also be prepared by using starting materials or intermediates in the form of their N-oxides or preparing them as such. Compounds of the formulae I and la in their nonoxidized form can also be prepared from the N-oxides of the compounds of the formulae I and la by treatment with reducing reagents (such as sulfur, sulfur dioxide, triphenylphosphine, various borohydrides, phosphorus trichloride or-bromide and the like) in suitable inert organic solvents. Compounds of tiie fonnulae i and ia which simuttaneousty bear a basic and an acidic group, for example an amino or guanidino group and a cart)Oxy! group, may likewise be present in the form of their zwitterions (betaines), which are likewise included within the scope of the present invention. The invention likewise encompasses all salts of the compounds of the formulae I and la which, owing to their low physiological tolerability, cannot be used directly in active pharmaceutical ingredients, but, for example, are used as intermediates on the route to the preparation of the inventive compounds, or else as starting materials for the synthesis of the physiologically tolerable salts. The invention further encompasses derivatives and modifications of the compounds of the formulae I and la, for example prodrugs, protected forms and other physiologically tolerable derivatives, and equally active or secondarily activable metabolites of the compounds of the formulae I and la. In particular, the invention encompasses prodrugs and protected forms of the compounds of the formulae I and la which can be converted to the compounds of the formulae I and la under physiological conditions. Suitable prodrugs of the compounds of the formiiiae I and la are in particular those chemically modffied cterivatives who properties are modified in a desired manner, for example in relation to improved solubility, bioavailability, absorption, or prolonged exposure or duration of action. The possible prodrugs are known to those skilled in the art and widely described in the literature. The invention also relates to medicaments characterized by an active content of at least one compound of the formulae I and la and/or of a physiologically compatible salt of the compound of the formulae I and la and/or a stereoisomeric or non-stereoisomeric form of the compound of the formulae I and la, together with a pharmaceutically suitable and physiologically compatible carrier, additive and/or other active ingredients and auxiliaries. Owing to the pharmacological properties, the inventive compounds are suitable for the prophylaxis, secondary prevention and therapy of all of those disorders treatable by an inhibition of the cysteine proteases, particularly of the cathepsins. They are suitable both for acute treatment and for long-term therapy. Cathepsin inhibitors can be used in the case of abnormally elevated bone degradation, allergies, Alzheimer's disease, amyioidosis, ARDS. arterial thromt>osis, asthma, atheromas, atherosclerosis, autoimmune disorders, t>acterial infections, twnnchioiitis, cerebral hemorrhage, cerebrovascular ischemea, Huntington's chorea, chronic inflammations, CIPD (chronic inflammatory demyelinizing polyradiculoneuropathy), Creutzfeldt-Jakob disease, Crohn's disease, diabetes (particularly the juvenile form), emphysema, encephalomyelitis, endometriosis, inflammatory respiratory disorders, inflammatory pancreatitis, epilepsy, disorders characterized by enhanced angiogenesis, excessive respiratory pathway elastolysis, tissue grafts, gingivitis, glomerulonephritis, glucocorticoid-induced osteoporosis. Graves' disease, Guillain-Barre syndrome, Hashimoto's thyroiditis, hepatitis, HIV infection, Huntington's disease, hypercalcemia, IBD, immune impairment, interstitial cystitis, bone fracture, bone loss, cancers, lupus erythematosus, malaria, metachromic leukodystrophy, metastasizing osteogenesis, metastatis, multiple sclerosis, multiple myeloma, muscular dystrophy, myasthenia gravis, neurodegenerative disorders, neuropathic pain, (particularly chronic neuropathic pain; but also diabetic neuropathy, post-therapeutic neuralgia, trigeminal neuralgia, painful diabetic poiyneuropathy, post-stroke pain, post-amputation pain, myelopatiiic or radiculopathic pain, atypical facial pain and causalgia-iike syndromes), organ rejection in transplants, osteoarthritis, osteogenesis imperfecta, osteoporosis, Paget's disease, pancreatitis, Parkinson's disease, pemphigus vulgaris, periodontitis, plaque rupture, Pneumocystis carinii, pneumonitis, psoriasis, restenosis, rheumatoid arthritis, scleroderma, systemic lupus erythematosus, trauma (brain, spinal cord), tumor cell invasion, viral infections, tooth loss, and preferably, but not exclusively, in the following types of cancer: breast cancer, intestinal cancer, ovarian cancer, cervical cancer, skin cancer, brain tumor, Kaposi's sarcoma, leukemia (B- and T-C6ll), lung cancer, lymph node cancer, pancreatic cancer, prostrate cancer and sarcomas. Since many compounds of this invention are particularly inhibitors of the cysteine cathepsins B, K and S, it is possible with preference to treat disorders in which said cathepsins contribute to the pathology or/and symptoms. This relates particularly to: pain, especially neuropathic pain, osteoarthritis, osteoporosis and various cancer types. This likewise relates to various (auto)immune disorders, particularly of the rheumatoid type, which have likewise already been listed above, and disorders characterized by excessive elastolysis, particularly of the COPD type, and related disorders listed above, and aiso cardiovascuiar disorders characterized by vascular changes, such as atherosclerosis. The inventive medicaments can be administered extravasculariy, for example intramuscularly, subcutaneously, intraocularly, intraarticularly, intrasynovially, perorally, orally (buccally, perlingually, sublingually), rectally, vaginally, (trans)dermally, pulmonally (inhalatively) or nasally or intravascularly, for example intravenously, intraarterially, or intracardially, in each case as an injection or infusion. Preference is given to the oral administration form. The invention also relates to a process for producing a medicament, which comprises bringing a compound of the formulae I and la into a suitable administration form with a pharmaceutically suitable and physiologically compatible carrier and optionally further suitable active ingredients, additives or auxiliaries. Suitable soJid or pharmaceutical formulation forms are, for exanple, granules, powders, coated tablets, tablets, (micro)capsules, suppositories, syrups, juices, suspensions, emulsions, drops or injectable solutions, and also preparations with protracted active ingredient release in whose production customary auxiliaries such as carriers, disintegrants, binders, coatings, swelling agents, glidants or lubricants, flavorings, sweeteners and solubilizers are used. Frequently used auxiliaries include magnesium carbonate, titanium dioxide, lactose, mannitol and other sugars, talc, milk protein, gelatine, starch, cellulose and derivatives thereof, animal and vegetable oils such as fish oil, sunflower oil, groundnut oil or sesame oil, polyethylene glycol and solvents such as sterile water and mono- or polyhydric alcohols such as glycerol. Moreover, it is also possible, particularly in the production of suspensions, to use compounds with quite particular, specifically established surface properties. These include, for example, dry and wet grinding, micronization, spray drying, production of nanocrystals and similar processes, in which changing the surface properties allows, for example, improvement in solubilities or especially dissolution kinetics, which achieves, for example, improved uptake of the particular compound into the organism. The phamnaceutica! preparations are preferabfy produced and administered in dosage units, each unit containrng a particular dose of the inventive compound of the formulae i and la as an active constituent. !n tfie case of solid dosage units such as tablets, capsules, coated tablets or suppositories, this dose may be up to about 5000 mg, but preferably from about 50 to 1000 mg, and, in the case of injection solutions in ampule form, up to about 500 mg, but preferably from about 20 to 200 mg. For the treatment of an adult patient of about 70 kg in weight, according to the activity of the compound of the formulae I and la, daily doses of from about 2 mg to 5000 mg of active ingredient, preferably from about 10 mg to 1000 mg, are indicated. Under some circumstances, however, higher or lower daily doses may also be appropriate. The daily dose can be administered either by a single dose in the form of a single dosage unit or else a plurality of smaller dosage units; or else by multiple administration of divided doses at particular intervals. Inhibitors of the aforementioned type can be administered even as a monotherapy or in combination or together with other medicaments. End products are generally determined by mass spectrometry methods (FAB-, ESI-MS) and H NMR (generally, unless stated otherwise, 500 MHz in DMS0-D6); in each case, the main peak or the two main peaks are specified. Temperatures are stated in degrees Celsius. Abbreviations used are either explained or correspond to the customary conventions. Starting materials or synthesis intermediates are either obtainable commercially or are prepared as cited or described. 1-Oxa-8-azaspiro[4.5]decane, 2-oxa-8-azaspiro[4.5]decane, 2-oxa-7-azaspiro[4.5]decane, 1-oxa-7-azaspiro[4.5]decane, 2-oxa-7-azaspiro[3.5]nonane and also analogous or alkyl-substituted or -disubstituted derivatives are prepared as described in WO01/87838. 1,4-Dioxa-8-azaspiro[4.5]decane, 1-oxa-4,8-diazaspiro[4.5]decane, 1,5-dioxa-9- azaspiro[5.5]undecane, 1-oxa-5,9-diazaspiro[5.5]undecane or similar and substituted derivatives are prepared as in EP 0621267, Tlie known metlnod can lil piperidone) wtth diols and a catalytic amount of p-toiuenesulfonic acid on a water separator. 3Azasp!ro[5.5]undecane is also obtainable, for example, from 3- azaspiro[5.5]undecane-2,4-dione; the same applies for similar carbocyclic spiro compounds. The reduction can be effected with LiAIH4. 2-Methyl-2,8-diazaspiro[4.5]decan-1-one, differently 2-substituted derivatives, analogous ureas and amines are described in J. Med. Chem. 47 (8), 2037-61 (2004), or can be obtained from the products described here by further reactions, for example reduction. Likewise described in this publication are substituted spiro-hydantoins and lactams with inverse amide formation (i.e. 2,8-diazaspiro[4.5]decan-3-one and derivatives), and also imides. Many different spirocyclic indanes, indenes, tetralones and tetralins are commercially available. The preparation of 6-azaspiro[2.5]octane and many further spiro compounds is described in Bull. Soc Chim. France 10, 2572-81 (1964). Abbreviations used: bis(2-methoxyethyi)aminosulfur trifluoride BAST tert-butyl tBu 2,2'-bis(diphenylphosphino)-1,1 '-binaphthyl Binap bis(oxo-3-oxazolidinyl)phosphoryl chloride BOP-CI dibenzylideneacetone dba dichloromethane DCM dicyclohexylcarbodiimide DCC diethylphosphoryl cyanide DEPC diisopropylethylamine DIPEA 4-dimethylaminopyridine DMAP N,N-dimethylformamide DMF dimethyl sulfoxide DMSO 1,1 '-bis(diphenylphosphino)ferrocene DPPF 1-(3-dimethylaminopropyl)-3-ethylcarbocliimide hydrochloride EDCI equivalents eq. saturated sat. O-iT-azabenzotriazoi-l -yi,t-N. N. N, N'- tetramethyluronium hexafiuorophosphate HATU 7-aza-1 -hydroxybenzotriazole HOAt lithium diisopropylamide LDA methanol MeOH methylmagnesium chloride solution MeMgCI sol. methyl tert-butyl ether MTBE N-bromosuccinimide NBS N-chlorosuccinimide NCS N-iodosuccinimide NIS N-ethylmorpholine NEM room temperature from 20X to 25°C RT broad singlet Sb tetrahydrofuran THF trifluoroacetic acid TFA 0-((ethoxyGarbonyl)canomethyleneamino}- N,N,N',N'-tetramethyluronium tetrafluoroborate TOTU Examples The examples which follow were prepared analogously to the general or specific methods specified above. Example 1: Methyl (S)-2-benzyloxycarbonylamino-3-chlorocarbonylpropionate Z-asp-OMe (175 g, 622 mmol) was dissolved in THF (1750 ml) and admixed with 2 ml of DMF. 86.9 g (684 mmol) of oxalyl chloride were dissolved in 200 ml of THF (slightly exothermic), cooled back to room temperature (RT) and added dropwise to the solution of the amino acid over 1 hour (h). After a further hour at RT, the solution was initially sparged with nitrogen for 10 min, concentrated on a rotary evaporator at a maximum of 30°C and coevaporated repeatedly with toluene. The resulting dirty white solid was dried to constant weight under in-house vacuum (about 1.5 mbar) and reacted further without further purification. Yield: 186.6 g (quantitative). Example 2; Methyl (S)-2-fc)enzyioxycarbonyiamino-4-oxopentanoate Goppeni j bromide [60.9 g, 425 mmol, 1.2 equivaients (eq. )j was introduced into a 3 liter 4-neck fiask (with dropping funnei, intemaJ thermometer, argors inlet, rubber septa, in a cooling bath) and admixed with 250 ml of THF. A separate flask was initially charged at 10°C with lithium bromide (75 g, 864 mmol, 2.4 eq.) and admixed with 470 ml of THF under argon. On completion of dissolution and recooling to RT, this solution was transferred to the suspension of the copper bromide. The resulting colorless to slightly greenish solution was cooled to -60°C, and methylmagnesium chloride (141 ml of a 3.0 M solution in THF, 423 mmol) was added within 15 min. A thick yellowish precipitate formed and the temperature rose to RT. After cooling again to -60°C, the solution from example 1 (prepared from 106 g of methyl (S)-2-benzyloxycarbonylamino-3-chlorocarbonylpropionate, 353 mmol, and 360 ml of THF) was added over about 30 min and the temperature was kept below -25°C. After the addition had ended, the mixture was stirred for another 1 h, and solid ammonium chloride (30 g) was added at-15°C. After a further 2 h, the mixture was filtered, the filtrate was diluted with 400 ml of heptane and 200 ml of saturated ammonium chloride solution were aided. Once the mixture had be&\ sttred at RT few 1 h, the ornic phase was removed and washed repeatedly, and the aqueous phases were reextracted with ethyl acetate. The combined organic phases were dried over sodium sulfate, concentrated on a rotary evaporator under reduced pressure and chromatographed on 1 kg of silica gel with 1:3 to 1:1 ethyl acetate/heptane. After the products had been combined and dried under reduced pressure, 83 g (84% yield) of a white solid were obtained. H NMR (300 MHz, CDCI3): 7.4 (m, 5H); 5.78 (m, 1H); 5.18 (s. 2H); 4.6 (s, 1H); 3.75 ("s", 3H); 3.3-2.9 (2dd, 2H); 2.2 (s, 3H) Example 3: Methyl (S)-2-benzyloxycarbonylamino-4-oxoheptanoate The preparation was effected analogously to example 2, with the difference that N-propylmagnesium chloride (2 M in diethyl ether) was now used and a chromatographic purification was dispensed with. Instead, the resulting dark crude product was taken up in 1:1 DCM/heptane and filtered tiirougii Celite. After treatment with activated carbon and filtration, the desired product was obtained in 93% yield. H NMR (300 MHz, CDCI3): 7.4 (m, 5H); 5.78 (m, 1H); 5.17 (s, 2H); 4.6 (s, 1H); 3.73 ("s", 3H); 3.3-2.9 (2dd, 2H); 2.4 (m, 2H); 1.6 (m, 2H, overlapping); 0.9 (m, 3H) Exampie 4: Methyi (SV2-benzytoxycartxDnyiamino-4.4-difiuoropentaoate BAST (Deoxofiuor, 60 g, 271 mmoL Z95 eq,) was initiafly ctiaiged in a 1 liter flask made of inert plastic and admixed with the ketone from example 2, dissolved/suspended in 40 ml of dichloromethane. After a reaction time of 1 day and again after 12 h, in each case 25 ml (113 mmol) of BAST were added and the mixture was stirred further at RT. After a further 12 h, dichloromethane was added and the resulting solution was rapidly added dropwise to an ice-cold saturated sodium hydrogencarbonate solution while keeping the temperature below 30'C. The organic phase was removed, the aqueous phase was extracted repeatedly with dichloromethane and the combined organic phases were washed with water, 1 N HCl and saturated in NaCl solution, dried over sodium solvate and concentrated under reduced pressure. The brown oil was then chromatographed on silica gel (3:1 heptane/MTBEto2:1). Product fractions were combined and concentrated by evaporation under reduced pressure. Yield: 22.3 g, 56%. ""H NMR (300 MHz, CDCI3): 7.4 (m, 5H); 5.45 (m. 1H); 5.18 (s, 2H); 4.6 (s, 1H); 3.78 (V, 3H); 2.4 (m, 2H); 1.7 (m, 3H) Example 5: Methyl (S)-2-benzyloxycarbonylamino-4,4-difluoroheptanoate The preparation was effected analogously to example 4. H NMR (300 MHz, CDCI3): 7.4 (m, 5H); 5.46 (m, 1H); 5.17 (s, 2H); 4.6 (m, 1H); 3.77 ("s", 3H); 2.4 (m, 2H); 1.8 (m, 2H, overlapping); 1.5 (m, 2H); 0.95 (m, 3H) All further reactions in the series of the 4,4-difluoroheptanoic acid derivatives to give the inventive end products were conducted entirely analogously to the corresponding pentanoic acid derivatives. Example 6: Methyl (S)-2-amino-4,4-difluoropentanoate hydrobromide 10 g of the compound from example 4 were admixed at RT with 35 ml of 33% HBr in glacial acetic acid and stirred for 40 min. Subsequently, 400 ml of cold diethyl ether were added and the reaction mixture was stored at 4°C for 3 h. The precipitated product was filtered off with suction through a glass frit, washed thoroughly with cold ether and freed of solvent residues under reduced pressure. It can be used directly in ine next resCTon. Vleld: 6.6/ g (82%) 'H NMR- 8.5 (Sb, 3H): 4.3 (t 1H): 3.76 (s, 3H); 2.53 (m, 2H); 1.7 (t 3H). Example 7: Methyl (S)-4,4-difluoro-2-isocyanatopentanoate The compound from example 6 (6.76 g, 28.8 mmol) was initially charged and dissolved in 240 ml of dichloromethane and 9.46 ml (117 mmol, 4.05 eq) of pyridine, cooled down to 0°C in an ice bath for 15 min and admixed with 19.86 ml of a 20% phosgene solution in toluene (37.54 mmol, 1.3 eq) within 20 - 30 seconds. The mixture was stirred at 0°C for a further 2 h, then the reaction mixture was extracted with cold half-molar HCI and ice. The water phases were reextracted with dichloromethane, and the combined organic phases were washed with ice and saturated NaCI solution, then dried over MgS04 and filtered off from the desiccant. Concentration by evaporation under reduced pressure left 5.21 g of brown oil (corresponded to a yield of 94%), which was reacted further directly. Example 8: (S)-2-{(3-Azaspiro{5.5]und«;ane-3H:a1x>nyl)amkTOJH},4Kltfkj Example 9; N-[(S)-1-(1-cyanocyclopropylcarbamoyl)-3,3-clifluorobutyl]-3- azaspiro[5.5]undecane-3-carboxamicle The crude product from example 8, (S)-2-[(3-azaspiro[5.5]undecane-3-carbonyl)amlno]- 4,4-difluoropentanoic acid, was dissolved in 6 ml of 2:1 THF/DMF and admixed witli 161.8 mg (1.365 mmol, 1.05 eq.) of 1-amino-1-cyciopropyinitrile hydrochloride and 176.8 mg {1.5 mmol, 1 eq.j of 1-hydroxy-7-azabenzotriazoje, cooled to 0°C and admixed with 250 mg (1.3 mmol, 1 eq.) of EDC! and with 0.496 ml (3.9 mmol, 3 eq.) of N-ethylmorpholine. Subsequently, the mixture was stirred at 0°C to RT for 2 h, THF was distilled off under reduced pressure, ethyl acetate was added and the mixture was extracted by shaking with highly dilute HCI, sat. NaHCOa solution and sat. NaCI solution. After concentration of the organic phase, a preparative HPLC separation (Merck Hibar Purospher RP18, 250x25, Standard-Gradient of acetonitrile-water-TFA) was performed directly. Product fractions were combined and freeze-dried. Yield: 222 mg, 43% of theory. H NMR: 8.82 (s, 1H); 6.6 (s, 1H); 4.31 (m, 1H); 3.28 (about, 4H); 2.29 (m, 2H); 1.7-1.1 (mm, about 20H); MS (ESI*): 397.17 Example 10: 8-azaspiro[4.5]decane-8-carbonyl chloride 1.57 ml of phosgene (20% solution in toluene, 2.96 mmol) were initially charged in 5 ml of dichloroethane and cooled to -20°C, then a mixture of 8-azaspiro-[4,5]decane (750 mg, Z96 mnrKJ) and triethylarrune (1 ml 9 mmd, 3.1 eq.) was added slowly. After 30 min, the mixture was allowed to come to RT; after 1 h, according to LC-MS, a little starting material was still present but also three new peaks. Subsequently, the mixture was added to 2 N aqueous HCI, the aqueous phase was extracted with dichloromethane, and the organic phase was washed with saturated NaHCOs solution and dried over sodium sulfate; subsequently, the mixture was concentrated by rotary evaporation under reduced pressure. Crude yield: 592 mg The material was reacted further directly without further purification. General method: see example 19. Example 11: Benzyl (S)-4-carboxymethyl-5-oxooxazolidine-3-carboxylate The compound is commercially available or can be prepared by literature methods by refluxing Z-Asp-OH with paraformaldehyde on a water separator in benzene. Example 12: Benzyl (S)-4-chlorocarbonylmethyl-5-oxooxazolidlne-3-carboxylate The compound from example 11 was converted analogously to the manner described in example 1 to benzyl (S)-4-chiorocarbonylmethyl-5-oxooxazolidine-3-carboxylate. The product thus obtained was used without further purification in the subsequent reaction. Example 13: Benzyl (S)-5-oxo-4-(2-oxopropy!)oxazDlJdine-3-cartx)xy!ate CuBr (24,54 g, 168 mmol, 1.2 eq.) and LiBr (29.18 g, 336 mmol, 2.4 eq.) were initially charged in a baked-out flask under argon, then dissolved in 600 ml of absolute THF and stirred at RT for 20 min. This gave a clear yellow-orange solution. The mixture was then cooled to -78°C, and MeMgCI solution (55.46 ml, 168 mmol, 1.2 eq.) was added dropwise thereto. This led to a yellow suspension which was difficult to stir, so that a further 75 ml of THF were added dropwise; the mixture was subsequently stirred at -60°C for 15 min. The carbonyl chloride from example 12 dissolved in about 150 ml of THF (41.67 g, 140 mmol) was initially stirred at -60'C and then slowly added dropwise. The reaction mixture thus formed was stirred at this temperature for 1 h. The workup was effected by adding about 100 ml of saturated NH4CI solution; the mixture was stirred vigorously at -60°C for 10 min, then 200 ml of heptane and 60 ml of water were added and the mixture was stirred at RT for a further 15 min. The phases were separated, and the aqueous phase was admixed with 50 ml of 1 M HCI (green solution) and extracted t: with abcxjt 100 ml erf ethyl acetate. The contaned cxganfc ph> were washed with 2 M HCI solution, saturated NaHCOs and saturated NaCI solution, dried over sodium sulfate and concentrated under reduced pressure. Subsequently, purification was effected by means of silica gel flash chromatography (5:1-2:1 heptane/ethyl acetate); production fractions were combined and freed of solvent residues under reduced pressure. Yield: 21.6 g, 56% of theory H NMR (250 MHz, 390 K, DMS0-d6): 7.35 (s, 5H); 5.43; 5.22 (2 d, 2H); 5.13 (d, 2H); 4.4 (dd, 1H); 3.26, 3.04 (each 2 dd, 2H); 2.07 (s, 3H). Example 14: Benzyl (S)-4-(2,2-difluoropropyl)-5-oxooxazolidine-3-carboxylate 15.52 g of the compound from example 13 (56 mmol) were suspended in 5 ml of dichloromethane and admixed with stirring with 25 g (20.8 ml, 2.02 eq.) of BAST. For 14 days, the mixture was stirred under argon. Intermediate LC-MS spectra showed that the conversion was not yet complete after 3 and 9 days. For workup, the reaction solution was added dropwise to a cooled sodium hydrogencarbonate solution (vigorous gas evolution) and stirred further for about 30 min (no gas evolution), and the aqueous solution was then extracted by shaking tvyce with DCM. The aqueous phase was adjusted to pH 3 with dilute HC! solution and extracted by shaking with DCM twice more. Tne organic phases were combined and washed with saturated NaCl solution, dried over sodium sulfate and concentrated by evaporation under reduced pressure. The residue was chromatographed through silica gel with DCM/methanol (to 0-6% methanol), and product fractions were combined and freed of solvent residues under reduced pressure. Yield; 8 g, corresponds to 48% of theory. Example 15: (S)-2-Benzyloxycarbonylamino-4,4-difluoropentanoic acid The compound from example 14 (4.9 g, 16.37 mmol) was dissolved in 30 ml of acetone and cooled to 0°C, and then 1 N sodium hydroxide solution (32.74 ml, 32.74 mmol, 2 eq.) was added. For about 2.5 h, the reaction mixture was stirred at room temperature; reaction monitoring by LC-MS indicated complete conversion. This was followed by addition of 20 ml of 1 N HCI, distilling-off of acetone under reduced pressure and adjustment of the solution to pH 3 to 4. The mixture was extracted twice by shaking with ethyl acetate. The organic phase was washed with saturated NaCI solution, dried over sodium sulfate and concentrated by evaporation to dryness under reduced pressure. The crude product was chromatogrhed using sBka geJ with a DCM/methanol gradient (0-6% methanol). Yield: 4.7 g (quantitative). Example 16: (S)-2-tert-Butoxycarbonylamino-4,4-difluoropentanpic acid The compound from example 15 (2.99 g, 10.44 mmol) was dissolved in 40 ml of methanol and 580 mg of 10% Pd/C were added. Hydrogenation was effected at 2 bar for 3 h. Only a vanishingly small Z elimination was detected. Another 300 mg of catalyst were added and hydrogenation was effected for a further 2 h - low conversion. The same amount of catalyst was added again and hydrogenation was effected overnight; only then was the conversion complete. The mixture was filtered off from the catalyst and concentrated by evaporation. The residue was partly dissolved in dioxane/water (40 ml), and sodium carbonate (700 mg, 0.6 eq), 10.4 ml of 1 N NaOH solution (10.4 mmol, 1 eq.) and 2,6 g of di-tert-butyl dicarbonate (11.94 mmol, 1.14 eq.) were added. After about 2 h, the conversion was complete. The solution was extracted with ether and the ether phase was discarded. Subsequently, the aqueous phase was acidified to pH 3 with 1 N HCI and extracted twice with ethyl acetate. The organic phase was washed with a saturated a NaCl solution, dried over sodium sulfate, filtered off from the desiccanl and oDncenirated by evaporation under reduced pressure. Yield: 950 mg, 36% of theory. H NMR: 12.8 (s, 1H); 7.25 (d, 1H); 4.11 (t, 1H); 2.3 (m, br., 2H); 1.6 (t, 3H); 1.37 (s, 9H). Example 17: tert-Butyl [(S)-1-(1-cyanocyclopropylcarbamoyl)-3,3-difluorobutyl] carbamate 1.35 g (5.33 mmol) of the product from example 16, 810 mg (6.83 mmol, 1.3 eq.) of 1-amino-1-cyclopropylnitrile hydrochloride and 943 mg (6.93 mmol, 1.3 eq.) of HOAt were dissolved or suspended in 18 ml of dichloromethane, cooled to 0°C and then admixed with 1.33 g (6.93 mmol, 1.3 eq.) of EDCI and 1.76 ml (1.596 g, 13.86 mmol, 2.6 eq.) of NEM. The mixture was stirred at 0°C to RT for 16 h. The reaction mixture was then diluted with 40 ml of DCM and extracted by shaking with 1 N HCI solution, saturated sodium hydrogencarbonate solution and saturated NaCI solution. The organic phase was dried over sodium sulfate and concentrated by evaporation under reduced pressure. The product was sufficiently ctean for further reactions. Yield: 1.5 g, 89% of theory. Example 18: N-(1 -cyanocyclopropyl)-(S)-2-amino-4,4-difluoropentanamide To detach the Boc protecting group, the compound from example 17 (580 mg, 1.83 mmol) was admixed with 10 ml of 1:1 TFA/DCM and stirred at RT for 30 min. Subsequently, the mixture was concentrated by evaporation under reduced pressure and subjected to azeotropic distillation with dichloromethane and toluene, and solvent residues were removed under high vacuum. The product was present as the trifluoroaceate. Yield: 340 mg. Example 19: General preparation method: reaction of an N-carbonyl chloride with C-terminally protected amino acid units 1 mmol of the free amino acid which has been C-terminally protected or is present as the amide (for example the product from example 18 after it has been released by basic treatment) was dissolved in 10 ml of THF and coded tc OC. The acid chloride from example 10 (1 mmol dtssolved in 5 mi of coid Tnr) was then added slowly in two portions over 60 min. Sutisequentfy, the mixture was stirred further ovemiglit. The reaction mixture was added to 50 ml of dichloromethane, washed with water and saturated NaHCOs solution, dried over sodium sulfate and concentrated by a rotary evaporation. The resulting oily product was subsequently in each case purified directly by HPLC (RP-18, acetonitrile-water), and product fractions were freeze-dried. The yields in this process of urea formation were from about 10 to 50% of theory). Example 20: Benzyl (S)-5-oxo-4-(2-oxo-3-phenylpropyl)oxazolidine-3-carboxyiate Analogously to example 13, benzyl (S)-5-oxo-4-(2-oxo-3-phenylpropyl)oxazolidine-3-carboxylate was prepared starting from benzyl (S)-4-chlorocarbonylmethyl-5-oxo-oxazolidine-3-carboxylate (5.00 g, 16.8 mmol) and 15 ml of a 20% benzylmagnesium chloride solution (20.2 mmol, 1.2 eq) in THF. The product was obtained as a yellow oil. Yield: 5.0 g, 84% of theory. Exampte 21: Benl (S)-4-3i3henyxq:yl)-5-o)ax33es&«-3-ca1x3xyJate Analogously to example 14, benzyl (S)-4-(2,2-difluoro-3-phenylprt)pyl)-5-oxo-oxazolidine-3-carboxylate was prepared starting from benzyl (S)-5-oxo-4-(2-oxo-3-phenylpropyl)oxazolidine-3-carboxylate (5.00 g, 14.2 mmol) and BAST (12.5 g, 56.60 mmol, 4 eq.). After chromatography on silica gel (dichloromethane/methanol), pure benzyl (S)-4-(2,2-difluoro-3-phenylpropyl)-5-oxooxazolidine-3-carboxylate was obtained in the form of a yellow oil. Yield: 1.2 g, 23% of theory Example 22: (S)-2-Benzyloxycarbonylamino-4,4-difluoro-5-phenylpentanoic acid Analogously to example 15, (S)-2-benzyloxycarbonylamino-4,4-difluoro-5-phenylpentanoic acid was prepared starting from benzyl (S)-4-(2,2-difluoro-3-phenylpropyl)-5-oxooxazolidine-3-carboxylate (1.2 g, 3.20 mmol). The product was obtained in the form of a yellow oil which was used directly for the subsequent reactions. Yield: 1.02 g, 88% of theory. Example 23: Methyl (S)-2-beri2yloxycartx)nyiamino4,4-d{fluoro-5-phenylpentanoate TnTTsethyisiiy) ditarlde (0.61 g, 5.61 mmoi, 2 eq) was added dropwise to a solution of (SV2-ben2yloxycartxmylaTiino-4,4-difluoro-5-phenylpentanoiG acid (1.02 g, 2.81 mmoJ) in 40 ml of methanol. After the addition had ended, the mixture was stirred at RT for 3 h. The solvent was removed under reduced pressure and the residue was used crude in the reaction which followed. Yield: 1.0 g, 94% of theory. Example 24: Methyl (S)-2-amino-4,4-difluoro-5-phenylpentanoate In a three-neck flask, methyl (S)-2-benzyloxycarbonylamino-4,4-dlfluoro-5-phenyl-pentanoate (1.0 g, 2.65 mmol) was dissolved in 25 ml of methanol. After repeated evacuation and sparging with argon, 350 mg of Pd/C (10%) were added. After degassing and sparging with argon again, the argon atmosphere was replaced by hydrogen (balloon with H2 gas). The mixture was stirred at RT for 3 h. Owing to incomplete conversion, a further 350 mg of catalyst were added and the mixture was hydrogenated at RT for a further 5 h. On completion of conversion, the reaction mixture was filtered The mixture was washed with 20 nnl of metharMDl and tlie fatrate was concentrated by evaporation under reduced pressure. A waxy residue was obtained which, as well as the desired product, also contained smaller amounts of the monodefluorinated and didefluorinated product. This residue was used without further purification for the further reaction. Yield: 530 mg, 82% of theory. Example 25: Methyl (S)-4,4-difluoro-2-isocyanato-5-phenylpentanoate Under argon, methyl (S)-2-amino-4,4-difluoro-5-phenylpentanoate (400 mg, 1.64 mmol) was dissolved in 20 ml of dichloromethane. At RT, pyridine (520 mg, 4 eq.) was added dropwise and the resulting solution was stirred for 15 minutes. The mixture was then cooled to 0°C and admixed with 20% phosgene solution in toluene (2.16 ml, 4.1 mmol, 2.5 eq.). The mixture was stirred at RT for 90 minutes and then the solvent was removed under reduced pressure. The mixture was codistilled with 10 ml of toluene twice more. The crude product thus obtained was used for the reactions which followed without further purification. Yield: 425 mg, 96% of theory Example 26: Methyl (Sr2-[(8-azaspirof4.5]decan.e-S-carbonyl)amino]-4,4-difluoro-5-phenyipentanoate Methyl (S)-4,4-difiuoro-2-isocyanato-5-phenylpentanoate (425 mg, 1.58 mmol) were dissolved in 25 ml of dichloromethane. 8-Azaspiro[4.5]decane (220 mg, 1.58 mmol, 1 eq.) and DIPEA (269 |jl, 204 mg, 1.58 mmol, 1 eq.) were added to this solution which was stined at RT overnight. The solvent was removed under reduced pressure and the residue was purified by preparative HPLC (gradient: acetonitrile/water and addition of 0.05% TFA). The product-containing fractions were combined and freed from the solvent under reduced pressure. Yield: 245 mg, 38% of theory. , Example 27: (S)-2-[(8-Azaspiro[4.5]decane-8-carbonyl)amino]-4,4-difluoro-5-phenyl-pentanoic acid Methyl (S)-2-[(8-azaspiro[4.5]decane-8-carbonyl)amino]-4,4-difluoro-5-phenylpentanoate (240 mg, 0.59 mmol) was dissolved in a mixture of 15 ml of THF and 5 mJ of methanoL A solution of 42 mg of LiOH (1.76 nrunoL 3 eq.) in 5 nrJ of water was added and the mixture was stinted at RT for 3 h. After the reactton had ended, the reaction mixture was acidified to pH=3 by adding a 2 M HCI solution. The organic solvent was removed under reduced pressure and the remaining aqueous phase was extracted with ethyl acetate. Subsequently, the organic phase was washed another three times with water and once with saturated NaCl solution, dried over MgS04 and freed from the solvent under reduced pressure. The product was obtained in the form of a yellow solid which was used in the reaction which followed without further purification. Yield: 192 mg, 82% of theory. Example 28: N-[(S)-1-(1-Cyanocyclopropylcarbamoyl)-3,3-difluoro-4-phenylbutyl]-8-azaspiro[4.5]decane-8-carboxamide DIPEA (331 Ml. 252 mg, 1.95 mmol, 4 eq.), HATU (185 mg, 0.49 mmol, 1 eq.) and . 1-aminocyclopropanecarbonitrile hydrochloride (58 mg, 0.49 mmol, 1 eq.) were added successively to a solution of the (S)-2-[(8-azaspiro[4.5]decane-8-Garbonyl)amino]-4,4-difluoro-5-phenylpentanoic acid obtained as a crude product (192 mg, 0.49 mmol) in 10 m! of DMF. The reaction mixture was stirred at RT ovemigM and, the next day, concentrated under reduced pressure. Tne residue thus oistamed was purified by preparative f-iPLC (gradient: acetorwtrileMoter and addition of 0.05% TFA). The title compound was obtained in the form of a colorless crystalline material. Yield: 34 mg, 15% of theory. H NMR: 8.83 (s, 1H); 7.48-7.15 (m, 5H); 6.62 (s, 1H); 4.39 (m, 1H); 3.30-3.15 (m, 6H); 2.39 (m, 1H); 2.22 (m, 1H); 1.65-1.05 (mm, about 16H); MS (ESf): 459.2 Example 29: tert-Butyl 9-cyclopropyl-3,9-diazaspiro[5.5]undecane-3-carboxylate tert-Butyl 3,9-diazaspiro[5.5]undecane-3-carboxylate (250 mg, 0.98 mmol) were dissolved in 10 ml of absolute methanol. 3 g of molecular sieves (3 A, which had been dried beforehand under high vacuum) were added to this solution. Under argon, glacial acetic acid (0.55 ml, 10 eq.), [(1-ethoxycyclopropyl)oxy]trimethyisilane (0.69 ml, 3.5 eq.) and 4.4 ml of a 1 M NaCNBHa solution in THF (4.4 mmol, 4.5 eq.) were then added successively. After stirring at RT for 20 minutes, the mixture was heated to 60°C and stirred at this temperature for about 15 h. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. The residue \h/as tcen up in dichloromethane, washed successively with 1 M NaOH solution and NaCl solution, and dried over MgS04. After the solvent had been removed under reduced pressure, the product was obtained as a colorless oil. Yield: 318 mg (quant.) Example 30: 3-Cyclopropyl-3,9-diazaspiro[5.5]undecane The tert-butyl 9-cyclopropyl-3,9-diazaspiro[5.5]undecane-3-carboxylate obtained as a crude product (318 mg, 0.98 mmol) was dissolved in 6 ml of dichloromethane and admixed with 1 ml of a 4 M HCI solution in dioxane (4 mmol, 4 eq.) with ice bath cooling. The mixture was stirred at RT for about 16 h. The solvent was evaporated under reduced pressure. The residue was taken up in 20 ml of water and lyophilized. Thus, 3-cyciopropyl-3,9-diazaspiro[5.5]undecane hydrochloride was obtained as a crude product in the form of a colorless amorphous material which was clean enough for further reactions. Yield: 252 mg, quantitative. The piperidine derivative thus obtained was converted to the end products, which are listed in table 1a and 1b, as in the above-described examples. Exam.pie 31: tert-Buty! 9-buty!-3,9-diaz3spiro{5.5}undecane-3-caji30xylate tert-Butyl 3,9-diazaspiro[5.5]undecane-3-carboxylate (150 mg, 0.59 mmol) was dissolved in 10 ml of absolute dichloromethane and admixed with butyraldehyde (52 pi, 1 eq.). With ice bath cooling, 17 JJI of glacial acetic acid (0.5 eq.) and sodium triacetoxyborohydride (137 mg, 1.1 eq.) were added. The mixture was stirred at RT for 16 h. Owing to incomplete reaction, butyraldehyde (52 [JI, 1 eq.), glacial acetic acid (17 |jl, 0.5 eq.) and sodium triacetoxyborohydride (137 mg, 1.1 eq.) were again added. After stirring at RT for a further 4 h, a little water was added and the reaction mixture was washed with saturated NH4CI solution. The organic phase was dried over MgS04 and freed from the solvent under reduced pressure. The product was obtained as a coloriess oil. Yield: 211 mg (quant.) Example 32: 3-Butyl-3,9-diazaspiro[5.5]undecane The tert-butyl 9-bLttyl-3,9-diazaspirQ{5.5]undecane-3-carboxylaie obtained as a cructe product (183 mg, 0.59 mmol) was dissolved in 4 ml of dichloromethane and admixed with 0.6 ml of a 4 M HCI solution in dioxane (2.4 mmol, 4 eq.) with ice bath cooling. The mixture was stirred at RT for about 16 h. The solvent was removed under reduced pressure. The residue was taken up in 20 ml of water and lyophilized. Thus, 3-butyl- 3,9-diazaspiro[5.5]undecane hydrochloride was obtained as a crude product in the form of a coloriess amorphous material which was clean enough for further reactions. Yield: 176 mg, quantitative. The piperidine derivative thus obtained was converted to the end products, which are listed in table la and lb, as in the above-described examples. Example 33: 1,4-Dioxaspiro[4.5]decane-8-carboxylic acid 3.0 g (14 mmol) of the ethyl ester precursor, ethyl 1,4-dioxaspiro[4.5]decane-8-carboxylate, were dissolved in 5 ml of methanol and admixed at RT slowly with 28 ml (2 eq.) of 1 M LiOH solution. The mixture was stirred overnight; HPLC-MS indicated complete reaction. Methanol was distilled off under reduced pressure and the residue was acidified cautbusiy with 1 mi of HCi such that no acid excess was present. The mixture was extracted with ethyi acetate, and the ethyl acetate phase was dried over sodium sulfate and then concentrated by evaporation under reduced pressure. Yield: 2.25 g, 86% of theory. Example 34: tert-Butyl [(S)-1-(1-cyanocyclopropylcarbamoyl)-3-methylbutyl]carbamate 5 g of Boc-(S)-Leu-OH (21.6 mmol), 3.3 g of 1-aminocyclopropanecarbonitrile hydrochloride (28.1 mmol, 1.3 eq.) and 3.8 g of HOBt (28.1 mmol, 1.3 eq.) were suspended in 60 ml of dichloromethane and admixed at 0°C successively with 5.4 g of EDCI (28.1 mmol, 1.3 eq.) and 7.15 ml of NEM (6.5 g, 56.2 mmol, 2.6 eq.). The mixture was stirred at 0°C to RT overnight, extracted by shaking under acidic (1 M HCI solution), basic (saturated NaHCOs solution) and neutral (saturated NaCI solution) conditions, and dried over sodium sulfate, and the solvent was distilled off under reduced pressure. The mixture was then chromatographed on silica gel in ethyl acetate/heptane. Yield: 3.62 g, 57% of theory. H NMR: 8.82 (s, 1H); 6.92 (d, 1H); 3.86 (m, 1H); 1.55 (m, 1H); 1.47 (m, 2H); 1.36 (s, 9H): 1.09 (m, 2H): 0.86 (dd, 6H); MS (ESJ): 296 . Example 35: N-[(S)-1-(1-cyanocyclopropylcarbamoyl)-3-methylbutyl]-1,4-dioxaspiro[4.5]decane-8-carboxamide The product from example 34, tert-butyl [(S)-1-(1-cyanocyclopropylcarbamoyl)-3-methylbutyl]carbamate, (1.1 g, 3.72 mmol) was admixed with 20 ml of 1:1 TFA/dichloromethane and stirred at RT for 30 min. Subsequently, the mixture was concentrated by evaporation under reduced pressure and taken up again in dichloromethane and toluene, and solvent and TFA residues were removed under reduced pressure. The resulting N-terminally protected product was reacted further directly. 283 mg (1.5 mmol) thereof were admixed at 0°C with 136 mg of HOAt (1 mmol, 0.67 eq.), 195 mg of 1,4-dioxaspiro[4.5]decane-8-carboxylic acid from example 33 (1 mmol, 0.67 eq.), 268 mg of EDCI (1.4 mmol, 0.93 eq.) and 0.32 ml of NEM (2.5 mmol) in 2.5 ml of THF and 0.25 ml of DMF, and the mixture was stirred at 0°C to RT overnight. Subsequently, the solvent was distilled off under reduced pressure, and the residue was taken up in ethyl acetate and extracted by shaking with saturated sodium hydrogencarbonate solution and saturated NaCI solution. Drying over sodium sulfate and evaporating-off the solvent were followed by purification using RP-HPLC (gradient acelDriitriieAAater and addition of G.05% TFA;, Tne product fractions were combined and freeze-dried. Yield: 25 mg (without mixed fratSions), corresponds to 7% of theory. H NMR: 8.81 (s, 1H); 7.84 (d, 1H); 4.20 (m, 1H); 3.83 (s, 4H); 2.22 (m, 1H); 1.75-0.8 (3m, about 13 H; 1.05 (m, 2H); 0.82 (dd, 6H); MS (ESI*): 364.2 . The examples listed in table la were prepared in a manner analogous to that described above. Table la shows the examples with accompanying characterization: Further spirocyclic amines which have been used hereinafter for the preparation of further inventive examples were prepared as follows: the spirocyclic amines 7-cyclo-propyl-2,7-diazaspiro[3.5]-nonane, 7-propyl-2,7-diazaspiro[3.5]nonane, 2-cyclopropyl-2,8-diazaspiro[4.5]decane, 2-cyclopropyl-2,7-diazaspiro[3.5]nonane, 2-propyl-2,7-dJazaspiro[3.5]nonane, 9-cyclopropyl-1-oxa-4,9-diazaspiro[5.5]undecane and 4-cyclo-propyl-1-oxa-4,9-diazaspirG[5.5]undecane were prepared according to the above-described examples 29-32 starting from the tert-butyloxycarbonyl-protected precursors which are commercially available. 2-Cyclopropylmethyl-2,8-cliazaspiro[4.5]decan-3-one was obtained by alkylating tert-butyl 3-0X0-2,8-diazaspiro[4.5]decane-8-carboxylate (commercially available) with cyclopropylmethyl bromide and subsequent elimination of the tert-butyloxycarbonyl protecting group with TFA. 6-Azaspiro[2.5]octane can be prepared according to the KerattJE (Bufl. Soc Chffn. France 10, 2572-81 (1964)) or se s des3t>ed t>3fw by cyclopropanating tert-butyl 4-methylenepiperidine-1-carboxylate and then detaching the tert-butyloxycarbonyl protecting group. In a baked-out dry flask under protective gas (argon), a mixture of 9.90 g of zinc dust (151 mmol)and 1.50 g of CuCI (15.15 mmol) in 20 ml of abs. diethyl ether was stirred at 50°C (bath temperature) for approx. 100 min. The mixture was cooled to 15°C (bath temperature). 6.1 ml of diiodomethane (75.0 mmol), 7.8 ml of abs. dimethoxyethane and finally 4.27 g of tert-butyl 4-methylenepiperidine-1-carboxylate (21.7 mmol) were successively and rapidly added dropwise. The reaction mixture was heated gradually to 50°C (bath temperature) and stirred at this temperature for approx. 20 h. After this time, owing to still incomplete conversion, another 20 ml of diethyl ether and 6.1 ml of diiodomethane were added with cooling. The reaction mixture was heated to 50°C (bath temperature) for a further 8 h. Cooling was followed by dilution with THF and filtration through Cellte. The filtrate was admixed with 4.3 g of p-toiuenesulfonic acid and a few drops of waier, and then concentrated under reducec pressure. The crude proxjuct thus obtained was dissolved in 100 ml of THF and admixed with 7.09 g of Boc anhydride (1.5 eq.) and 5.5 ml of DIPEA (1.5 eq.). The mixture was stirred at RT for 48 h and then concentrated under reduced pressure. The residue thus obtained was stirred with approx. 150 ml of diethyl ether. The mixture was filtered with suction and the filter residue was washed thoroughly with diethyl ether. The filtrate thus obtained was concentrated. What remained was an oil which was taken up in 200 ml of dichloromethane and was washed twice with sat. NaHCOs solution and once with dil. HCI solution (pH = 5). The organic phase was dried over MgS04 and then concentrated under reduced pressure. In this way, 2.8 g of tert-butyl 6-azaspiro[2.5]octane-6-carboxylate were obtained as a light-colored oil. This oil was dissolved in 5 ml of dichloromethane and admixed with a mixture of 10 ml of TFA and 0.5 ml of water. After stirring at RT for 48 h, the reaction solution was concentrated under reduced pressure and codistilled with toluene three times more. In this way, 6-azaspiro[2.5]octane was obtained as a TFA salt in the form of a brown oil which was clean enough for further readjons. Yield: 1.50 g (31 % of theory) MS (ESf): 112. The 6-azaspiro[2.5]octane thus obtained was converted to the inventive compounds which have been described in examples 61-63 and 68-70. Example 59: Methyl (S)-2-amino-4,4-difluoropentanoate hydrochloride At approx. 5°C (ice bath cooling), 8.2 ml of thionyl chloride (112.6 mmol; 1.5 eq.) were added dropwise to 100 ml of methanol (p.a.) under argon. The mixture was allowed to come to RT within 30 min and stirred for a further 30 min. 19.0 g of (S)-2-tert-butoxycarbonylamino-4,4-difluoropentanoic acid (75.0 mmol) were added in portions to this reaction mixture. Tine reaction mixture was stirred at RT for 2 h. Thereafter, the reaction mixture was warmed to 35°C (internal temperature) and stirred at this temperature for another 3 h. Subsequently, the mixture was concentrated under reduced pressure, which afforded methyl (S)-2-amino-4,4-difluoropentanoate hydrochtoride as a slightty brownish crystaiiine solid which was dean enough for further reactions. Ylekj; 13.5 g (89% of theory;. Under argon, 2.0 g of methyl (S)-2-amino-4,4-difluoropentanoate hydrochloride (9.8 mmol) were dissolved in 80 ml of dichloromethane, admixed with 3.2 ml of pyridine (4 eq.) and cooled to approx. 5°C (ice bath). After 10 min, 6.7 ml (1.3 eq.) of a 20% phosgene solution in toluene were slowly added dropwise. The resulting suspension was stirred with ice bath cooling for 3 h and then concentrated under reduced pressure. The residue thus obtained was taken up in toluene and filtered. After the solvent had been removed under reduced pressure, methyl (S)-4,4-difluoro-2-isocyanatopentanoate was obtained as a brown oil which was used in the subsequent reaction without further purification. Yield: 1.1 g (58% of theory). A solution of 0.75 g of 6-azaspiro[2.5]octane trifluoroacetate (3.30 mmol, 1 eq.) and 0,75 ml of DIPEA (1.3 eq.) in 6 ml of dichloroethane was added under argon to a solution of 0.65 g of methyl (S)-4,4-difluoro-2-isocyanatopentanoate (3.36 mmol) in 4 ml of dichloroethane. The reaction mixture was stirred at RT overnight. The mixture was diluted with 10 ml of dichloromethane and washed with saturated NaHCOs solution. The organic phase was dried over MgS04 and then concentrated under reduced pressure. The residue thus obtained was purified by preparative HPLC (gradient: acetonitrile/water and addition of 0.05% TFA. The product-containing fractions were combined and freeze-dried. 365.0 mg of methyl (S)-2-[(6-azaspiro[2.5]octane-6-carbonyl)amino]-4,4- difluoropentanoate (1.2 mmol) were dissolved in a mixture of 10.8 ml of THF and 3.6 ml of methanol. 3.6 ml of an aqueous 1 M LiOH solution (3 eq.) were added to this solution. The mixture was stirred at 45°C (bath temperature) for one hour and then 3.6 ml of 1 M HCI solution were added. The mixture was concentrated under reduced pressure and codistilled with DMF twice more. The (S)-2-[(6-azaspiro[2.5]octane-6- carbonyl)amino]-4,4-difluoropentanoic acid thus obtained was clean enough for the next reaction. Yield: 400 mg (quant.) 142.3 mg of 1-aminocyclopropanecarbonitrile hydrochloride (1.2 mmol, 1,0 eq.), 163.3 mg of HOAt (1.0 eq.), 0.61 mi of DIPEA (3 eq.) and 456 mg of HATU (1.0 eq.) were added successively to a solution of 348.0 mg of (S)-2-[(6-azaspiro[2.5]octane-6-carbonyl)amino]-4,4-difluoropentanoic acid (1.2 mmol) in 5 ml of DMF. The reaction mixture was stirred at RT for 24 h and then concentrated under reduced pressure. The residue was taken up in 10 ml of dichloromethane, washed with a little sat. NaHCOs solution and then a little dilute HCI solution (pH=5), and dried over MgS04. The residue thus obtained was purified by preparative HPLC (gradient: acetonitrile/water and addition of 0.05% TFA). The product-containing fractions were combined and freeze-dried. In this way, N-[(S)-1-(1-cyanocyclopropylcarbamoyl)-3,3-difluorobutyl]-6-azaspiro[2.5]octane-6-carboxamide was obtained as a colorless amorphous solid. Yield: 200 mg , 47% of theory. MS (ES!*): 355.1. 'H NMR: S.35 (s. 1H;; 5.6S (d. 1H): 4.30 (m. 1H); 3.30-3.40 (m. AH): 2.30 (m, 2H); 1.60 (t 3H); 1.50 (m. 2H); 1.25 (m, 4H): 1.10 (m, ZH): 0.30 (s, 4H). In a baked-out, argon-purged flask, 3.7 g of lithium bromide (2.4 eq.) and 4.38 g (1.2 eq) of CuBr-Me2S were dissolved in 55 ml of abs. THF and stirred at RT for 20 min. The resulting yellow solution was cooled to -70°C and admixed with 16.2 ml (1.2 eq.) of benzylmagnesium chloride solution (20% in THF). After a further 20 min at -70°C, a solution of 5.32 g of methyl (S)-2-benzyloxycarbonylamino-3-chlorocarbonylpropionoate (example 1) (17.75 mmol) in 15 ml of THF was added. After 2 h, the mixture was heated slowly to -35°C and 50 ml of a sat. NH4CI solution were added. The reaction mixture was diluted with 400 ml of dehloromethane and viied with 100 ml of a 2 M HCI solution. The aqueous phase was washed twice more with 50 ml of dichloromethane. The combined organic phases were washed successively with 2 M HCI solution, sat. NaHCOs solution and sat. NaCI solution, dried over MgS04 and concentrated under reduced pressure. Methyl (S)-2-benzyloxycarbonylamino-4-oxo-5-phenylpentanoate was obtained as a yellow oil which was used in the next stage without further purification. Yield: 6.39 g (quant.) Example 65: Methyl (S)-2-benzyloxycarbonylamino-4,4-difluoro-5-phenylpentanoate In a Teflon vessel, 6.3 g of methy! (S}-2-benzybxycart)onyiamino-4H3xo-5-phenylpentanoate (17.7 mmo!) were dissolved in 10 mf of dichiorDmethane. Under araon, 5 g of BAST (1.28 eq.) were added. Tne reaction mixture was stirred at 40°C (bath temperature) for 20 h. Another 5 g of BAST (1.28 eq.) were added and the mixture was stirred at 40°C for a further 20 h. The reaction mixture was added dropwise to 500 ml of an Ice-cooled NaHCOs solution and diluted with 200 ml of dichloromethane. The phases were separated and the aqueous phase was washed twice with 100 ml of dichloromethane. The combined organic phases were washed with a 1 M HCI solution and with sat. NaCI solution, dried over MgS04 and concentrated under reduced pressure. The residue (dark brown oil) was purified by flash chromatography on silica gel with a heptane/ethyl acetate mixture. Methyl (S)-2-benzyloxycarbonylamino-4,4-difluoro-5-phenylpentanoate was obtained as a yellow waxy substance. Yield: 3.03 g (45% of theory). 3.0 g of methyl (S)-2-benzyloxycarbonylamino-4,4-difluoro-5-phenylpentanoate (8.0 mmol) were admixed with 8.0 ml (5 eq.) of a 30% HBr solution in glacial acetic acid with ice bath cooling and stirred for 3 h. 100 ml of diethyl ether were added and the resulting precipitate was filtered off with suction. The crude product thus obtained was purified by preparative HPLC (gradient: acetonitrile/water and addition of 0.05% TFA). The amorphous solid obtained after freeze-drying was taken up in dichloromethane and washed with sat. NaHCOs solution. The organic phase was dried over MgS04 and concentrated under reduced pressure. Thus, methyl (S)-2-amino-4,4-difluoro-5-phenyl-pentanoate was obtained as a yellow oil. 817 mg of methyl (S)-2-amino-4,4-difluoro-5-phenyipentanoate (3.36 mmol) were dissolved in 20 ml of dichlorometliane, admixed with 1.08 ml of pyridine (4 eq.) and cooled to approx. 5°C (ice bath). After 10 min, 2.3 ml (1.3 eq.) of a 20% phosgene solution in toluene were added dropwise. The resulting suspension was stirred with ice bath cooling for 4 h and then concentrated under reduced pressure. The residue thus obtained was taken up in toluene and filtered. After the solvent had been removed under reduced pressure, methyl (S)-4,4-difluoro-2-isocyanato-5-phenylpentanoate was obtained as an orange oil which was used without further purification in the subsequent reaction. Yield: 943 mg (quant.) Methyl (S)-2-[(6-azaspiro[2.5]octane-6-carbonyl)amino]-4,4-difluoro-5- phenylpentanoate was prepared analogously to example 61, starting from 904 mg of methyl (S)-4,4-difluoro-2-isocyanato-5-phenylpentanoate (3.36 mmol) and 907 mg of 6- azaspiro[2.5]octane trifluoroacetate (1.2 eq.). Chromatographic separation by preparative HPLC (gradient: acetonitrile/water and addition of 0.05% TFA) gave methyl (S)-2-[(6-azaspiro[2.5]octane-6-carbonyl)amino]-4,4-difluoro-5-phenylpentanoate as a yellow oil. Yield: 234 mg (18% of theory) Example 69: (S)-2-[(6-Azaspiro[2.5]octane-6-carbonyl)amino]-4,4-difluoro-5-phenylpentanoic acid (SV2-[(6-Azaspiro[2.5}odane-6-<:art>onyi)amirKD]-4.4-diflLK5ro-5-phenyfDen acid was prepared analogously to example 62, starting from 234 mg of methyi (S)-2-[(6-azaspiro[2.5]octane-6-carbonyl)amino]-4-,4-d}fliJoro-5-phenylpentanoats (0.62 mmol). Chromatographic separation by preparative HPLC (gradient: acetonitrile/water and addition of 0.05% TFA) gave (S)-2-[(6-azaspiro[2.5]octane-6-carbonyl)amino]-4,4-difluoro-5-phenylpentanoic acid as a colorless amorphous solid. Yield: 41 mg (18% of theory). 13.3 mg of 1-aminocyclopropanecarbonitrile hydrochloride (1.0 eq.), 15.2 mg of HOAt (1.0 eq.), 57 pi of DIPEA (3 eq.) and 42.5 mg of HATU (1.0 eq.) were added successively to a solution of 41.0 mg of (S)-2-t(6-azaspiro[2.5]octane-6-carbonyl)amino]-4,4-difluoro-5-phenylpentanoic acid (0.11 mmol) in 5 ml of DMF. The reaction mixture was stirred at RT for 4 h and then concentrated under reduced pressure. The residue thus obtained was purified by preparative HPLC (gradient: acetonltrile/water and addition of 0.05% TFA). The product-containing fractions were combined and freeze-dried. In this way, N-[(S)-1-(1-cyanocyclopropylcarbamoyl)-3,3-difluoro-4-phenylbutyl]-6-azaspiro[2.5]octane-6-carboxamide was obtained as a colorless amorphous solid. Yield: 30 mg, 62% of theory. H NMR: 8.85 (s, 1H); 7.22-7.40 (m, 5H); 6.68 (d, 1H); 4.40 (m, 1H); 3.20-3.40 (m, 6H); i 2.15-2.40 (m, 2H); 1,48 (d, 2H); 1.25 (t, 4H);1.10 (d, 2H); 0.30 (s, 4H); MS(ESr): 431.3. After addition of 1.5 ml of triethyiamJne (1.5 eq.), the mixture was cooled to 0°C. At this temperature, a solution of 0.48 ml of chorosulfonic acid (7.2 mmol, 1 eq.) in 5 ml of dichloromethane and then 1.9 ml of pyridine (3.2 eq.) were added. The mixture was stirred at RT for 48 h. The reaction mixture was washed with a 1 M HCI solution and the aqueous phase was removed. Thereafter, the organic phase was shaken with an NaaCOs solution. The aqueous phase thus obtained was then washed three times more with a little diethyl ether. The aqueous phase was concentrated under reduced pressure and codistilled three times more with 20 ml of toluene each time. The residue was taken up in water and lyophilized. The colorless residue thus obtained was treated three times with 10 ml each time of ethanol. The combined alcoholic phases were concentrated under reduced pressure and codistilled twice more with toluene. The residue thus obtained (1.58 g of 8-azaspiro[4.5]decane-8-sulfonic acid sodium salt) was suspended in 30 ml of toluene and admixed under argon with 1.65 g of phosphorus pentachloride (1.1 eq.) The reaction mixture thus obtained was stirred at 100°C for 18 h. AHer cooling, the reaction nrusdure was fiHer&i off from undissolve OMistitLnts and the filtrate was concentrated under reduced pressure. In this way, 8-azaspiro[4.5]decane-8-sulfonyl chloride was obtained as a colorless oil which was used in the next reaction without further purification. Yield: 520 mg (30% of theory). In a reaction vessel, 100 mg of methyl (S)-2-amino-4,4-difluoropentanoate hydrochloride (0.49 mmol) were admixed with 320 mg of N,0-bis(trimethylsilyl)- acetamide (3.2 eq.) in 3 ml of acetonitrile. The reaction mixture was treated at 100°C in a microwave for 30 min. 128 mg of 8-azaspiro[4.5]decane-8-sulfonyl chloride (1.1 eq.), dissolved in 2.5 ml of acetonitrile, were then added and the resulting reaction mixture was treatec at 10O'C in a microwave for a further 2.5 h. Tne reaction mixture was concentrated under reduced pressure and the resulting reskJue was purmed by preparative HPLC (gradient: acetonitrile/water and addition of 0.05% TFA). Methyl (S)- 2-(8-azaspiro[4.5]decane-8-sulfonylamino)-4,4-difluoropentanoate was obtained as a colorless amorphous material. Yield: 75 mg, (41 % of theory) MS (ESI*): 369. (S)-2-(8-Azaspiro[4.5]decane-8-sulfonylamino)-4,4-difluoropentanoic acid was prepared analogously to example 62 starting from 50 mg of methyl (S)-2-(8-azaspiro[4.5]decane-8-sulfonylamino)-4,4-difluoropentanoate (0.14 mmol). Yield: 30 mg (62% of theory) 12.0 mg of 1-aminocycbpfopanecarbonitrite hydrochloride (1.2 eq.), 13.8 mg of HOAt (1.2 eq.), 33 |j,l of N-ethylmorpholine (3 eq.) and 19.5 mg of EDCI (1.2 eq.) were added successively to a solution of 30.0 mg of (S)-2-(8-azaspiro[4.5]decane-8-sulfonylamino)-4,4-difluoropentanoic acid (0.08 mmol) in 2 ml of THF and 1 ml of dichloromethane. The reaction mixture was stirred at RT for 4 h and then concentrated under reduced pressure. The residue thus obtained was purified by preparative HPLC (gradient: acetonitrile/water and addition of 0.05% TFA). The product-containing fractions were combined and freeze-dried. In this way, N-(1-cyanocyclopropyl)-(S)-2-(8-azaspiro[4.5]decane-8-sulfonylamino)-4,4-difluoropentamide was obtained as a colorless amorphous material. Yield: 20 mg, 56% of theory. H NMR: 9.1 (s, 1H); 7.85 (d, 1H); 3.85 (m, 1H); 3.00 (m, 4H); 2.15 (m, 2H); 1.65 (t, 3H); 1.55 (m, 4H), 1.50 (m, 2H); 1.40 (t, 4H); 1.37 (m, 4H); 1.10 (m, 2H); MS (ESr): 419.1 . Analogously to the examples described In detail above (examples 1-35 and 58-74), the following further compounds were prepared. These further compounds are shown in table 1 b) with accompanying characterization: Pharmacological examples: Determination of the enzymatic activity of the catalytic domain of human Cathepsin B. This protein is obtained as an inactive enzyme from Sigma, Wiesbaden, Germany (catalog No. C8571). The enzyme is activated as follows: 25 |jg of enzyme are diluted with acetate buffer to a concentration of 12.5 pg/ml. 1 part by volume of enzyme is admixed with 20 parts by volume of cysteine solution and diluted with the acetate/Hepes buffer to a concentration of 0.11 |jg/ml and incubated at 37°C for 5 minutes. To measure the enzyme activity, 10 |jl of enzyme solution are incubated with 10 pi of a 3% (v/v) aqueous dimethyl sulfoxide solutbn (reaction 1) for 10 minutes. To measure the enzyme inhftyitor actlvtty, 10 [A of enzyme sokition are fncutfed wfth 10 pi of a 3% (v/v) aqueous dimethyl sulfoxide solution which contains the enzyme inhibitor (reaction 2). Both in reaction 1 and in reaction 2, after addition of 10 |jl of a 3% (v/v) aqueous dimethyl sulfoxide solution which contains 0.3 mmol/l of the substrate, the enzyme reaction is monitored by fluorescence spectroscopy (360 nm (excitation) / 465 nm (emission)). The enzyme activity is shown as fluorescence increase/minute. The inhibitor action is calculated as the percentage inhibition by the following formula: % inhibition = 100 - [(fluorescence increase/minute in reaction 2) / (fluorescence increase/minute in reaction 1) x 100], The IC50, which is the inhibitor concentration required for a 50% inhibition in the enzyme activity, is determined graphically by plotting the percentage inhibitions at different inhibitor concentrations. The acetate buffer contains 0.1 mol/l of sodium acetate, 0.1 mol/l of sodium chloride and 0.001% Piuronic (Sigma, Detsenhofen, Germany) pH 4.5. The cysteine solution conl3ins 0.3 moil of cysteine in water. The acetate'l-iepes Duffer cofitains 0.15 mc4/! of sodium acetate, 0.15 vnoU\ of Hepes, 0.3 nxM of sodium chkxide and 0.001% Piuronic (Sigma, Deisenhofen, Germany) pH 6.5. The enzyme solution contains 0.11 pg/ml of the enzyme domain. The substrate solution contains 0.3 mmol/l of the fluorogenic substrate 2-Arg-Arg-AMC (Bachem, Heidelberg, Germany). Determination of the enzymatic activity of the catalytic domain of human Cathepsin K. This protein is obtained as an inactive enzyme from Sanofi-Aventis, Frankfurt, Germany. The enzyme is activated as follows: 1 part by volume of enzyme is admixed with 4 parts by volume of cysteine solution and diluted with the acetate/Hepes buffer to a concentration of 0.22 pg/ml. To measure the enzyme activity, 10 pi of enzyme solution are incubated with 10 pi of a 3% (v/v) aqueous dimethyl sulfoxide solution (reaction 1) for 10 minutes. To measure the enzyme inhibitor activity, 10 pi of enzyme solution are incubated with 10 pi of a 3% (Wv) aqious dimethyl sutfoxide solution which contakis the eaizynie inhibttcH" (reaction 2). Both in reaction 1 and in reaction 2, after addition of 10 pi of a 3% (v/v) aqueous dimethyl sulfoxide solution which contains 0.3 mmol/l of the substrate, the enzyme reaction is monitored by fluorescence spectroscopy (360 nm (excitation) / 465 nm (emission)). The enzyme activity is shown as fluorescence increase/minute. The inhibitor action is calculated as the percentage inhibition by the following formula: % inhibition = 100 - [(fluorescence increase/minute in reaction 2) / (fluorescence increase/minute in reaction 1) x 100]. The IC50, which is the inhibitor concentration required for a 50% inhibition in the enzyme activity, is determined graphically by plotting the percentage inhibitions at different inhibitor concentrations. The cysteine solution contains 0.3 mol/l of cysteine in water. The acetate/Hepes buffer contains 0.15 mol/l of sodium acetate, 0.15 mol/l of Hepes, 0.3 mol/l of sodium chloride and 0.001% Pluronic (Sigma, Deisenhofen, Germany) pH 6.5. The enzyme solution contains 0.22 pg/ml of the enzyme domain. The substrate solution contains 0.3 mmolyl of the fiuorogenic substrate Boc-Ala-Giy- Pro-Arg-AMC (Bachen- Heidefoerg, Germany;.. Determination of the enzymatic activity of the catalytic domain of human Cathepsin S. This protein is obtained as an inactive enzyme from R&D Systems, Wiesbaden, Germany (catalog No. 1183-CY). The enzyme is activated as follows: 5 parts by volume of enzyme are incubated with 20 parts by volume of acetate buffer and 50 parts by volume of cysteine solution at 37°C for 5 minutes. After the activation of the enzyme, it is diluted with the Tris/HCI buffer to a concentration of 0.65pg/ml. To measure the enzyme activity, 10 pi of enzyme solution are incubated with 10 pi of a 3% (v/v) aqueous dimethyl sulfoxide solution (reaction 1) for 10 minutes. To measure the enzyme inhibitor activity, 10 pi of enzyme solution are incubated with 10 pi of a 3% (v/v) aqueous dimethyl sulfoxide solution which contains the enzyme inhibitor (reaction 2). Both in reaction 1 and in reaction 2, after addition of 10 pi of a 1.5% (v/v) aqueous dimethyl sulfoxide solution which contains 0.15 mmol/l of the substrate, the enzyme reaction is monitored by fluorescence spectroscopy (360 nm (excitation) / 465 nm (nission)). The enzyme activity is shown as fluorescence increase/minute. The inhibitor action is calculated as the percentage inhibition by the following formula: % inhibition = 100 - [(fluorescence increase/minute in reaction 2) / (fluorescence increase/minute in reaction 1) x 100]. The IC50, which is the inhibitor concentration required for a 50% inhibition in the enzyme activity, is determined graphically by plotting the percentage inhibitions at different inhibitor concentrations. The acetate buffer contains 0.05 mol/l of sodium acetate, 0,1 mol/l of sodium chloride and 0.001% Pluronic (Sigma, Deisenhofen, Germany) pH 5.5. The cysteine solution contains 0.3 mol/l of cysteine in water. The Tris/HCI buffer contains 0.1 mol/l of Tris/HCI, 0.04 mol/l of EDTA and 0.001% Pluronic pH=7.5. The enzyme solution contains 0.65 pg/ml of the enzyme domain. The substrate solution contains 0.15 mmol/l of the fluorogenic substrate Z-Val-Val-Arg-AMC (Bachem, Heidelberg, Germany). CaCo2/TC7 prmeabiiay determinions for forecastk the absorfon erf the yiventive compounds: (Caco-2/TC7 permeability test) Caco-2/TC-7 cells from Sanofi are used. In addition, HTS Multiwell plates (24-well, non-coated, Becton Dickinson, surface area of the Becton Dickinson Filter 0.3 cm2) are used. The cell density on the filters was 2x10 /cm2, and 1.3 x 10"* /cm2 on the T-75 flasks (Costar with vent-cap) for the cell line growth. The incubation conditions are 37'C, 95% air humidity, 10% CO2. The medium is changed three times per week (DMEM, Glutamax I, nonessential AA, penicillin/streptomycin, FBS 20%). Permeability assay conditions: asymmetric conditions for the screening with apical buffer HBSS (with 10 mM HEPES and 0.5% BSA at pH 6.5) and basal buffer HBSS (with 10 [JM HEPES and 5% BSA at pH 7.4). The permeability experiments were performed at 37°C with agitation for 2 h. The samples were analyzed by LC-MS. The results were reported as the mean Papp value (single point, cm/sec) (permeability coefficient): B2: basolatera! amount of the compound to be anaiyzed after 2 n [Ao]: apical concentration of the test sotution S: "insert area": 0.3 cm2 t: time: 2 h Claims 1. A compound of the formula I, and/or all stereoisomerlc forms of the compound of the formula la and/or mixtures of these forms in any ratio, and/or a physiologically tolerated salt of the compound of the formula la, and/or solvates or hydrates of the compound of the formula la, where unbridged, bridged or fused and is unsubstituted or independently, according to the ring size, mono-, di-, tri, tetra- or pentasubstituted by R4, or b) a saturated or partly saturated, three- to eleven-membered heterocycle which, according to the ring size, may contain one, two, three or four identical or different heteroatoms from the group of oxygen, nitrogen or sulfur, and in which the heterocycle is unbridged, bridged or fused and is unsubstituted or independently, according to the ring size, mono-, di-, tri-, tetra- or pentasubstituted by R4, where R4 is -NO2, -CN, =0, =S, -OH, -CF3, -SFs -(Co-C3)-alkylene-S-R10. -O-CF3, -Si-(CH3)3, -(Co-C5)-alkylene-0-C(0)-R21, -(Co-C5)-alkylene-C(0)-0-R10, -(Co-C3)-alkylene-0-R10, -(Co-C3)-alkylene-N(R21 )-R22, -(Co-C3)-alkylene- N(R10)-S(O2)-R10,-(Co-C5)-alkylene-(C3-C8)-cycloalkyl-R23,-S-CF3, -(Co-C5)-alkylene-(C1-C3)-fluoroalkyl, -(Co-C5)-alkylene-N(R10)-C(O)-R21, -(Co-C3)-alkylene-C(0)-N(R21 )-R22, -(Co-C4)-alkyl where alkyl is unsubstituted AMENDED SHEET or mono-, di- or trisubstituted independently by R9, -(Co-C4)-alkylene-aryl where aryl is selected from the group of phenyl, indanyl, indenyl, naphthyl, where aryl is unsubstituted or mono-, di- or trisubstituted independently by R8, or -(Co-C4)-alkylene-Het where Het is selected from the group of azetidinyl. benzimidazoJinyi. benzimidazQlyl iDenzofurHny*, benzothbphenyl. berzDxazDiy-benzthiazolyl, benzisoxazoiyi. benzisothiazoiyi. quinoiinyi. dioxofyi. dioxanyt, furanyl, imidazolidinyl, imidazoltnyl, imidazoiyi, indoiinyi, indoiyi, SH-indcHyl, isoindolinyl, isoindolyl, isoquinolinyl, isothiazolidinyl, 2-isothiazolinyl, isothiazolyl, isoxazolyl, isoxazolidinyl, 2-isoxazolinyl, morpholinyl, octahydroisoquinolinyl, oxazolyl, oxazolidinyl, pyrimidinyl, piperazinyl, piperidinyl, pyranyl, pyrazinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrroiidinyl, pyrroiinyl, 2H-pyrrolyl, pyrrolyl, tetrahydrofuranyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, tetrahydropyridinyi, thiazolyl, thienyl, thienopyridinyl, thiomorpholinyl, thiophenyl, and this Het radical is unsubstituted or independently mono-, di- or trisubstituted byR8, R8 is halogen, carbamimidoyi, -NO2, =0, -CF3, -SF5, -C(O)-O-R10, -CN, -C(0)-NH2, -OH, -NH2, -O-CF3, -C(O)-N(R10)-R20, -N(R10)-R20, -(C3-C8)-cycloalkyl, -0-(C1-C8)-alkyl, -0-(Co-C4)-alkylene-(C3-C6)-cycloalkyl, -(C-j-Cgraikyl, -(Co-C4)-alkylene-{C3-C8)-cycloalkyl, where the alky! radicals maT&jnai! are each unsubstituted cw morK}-, di- or trisubtuted independently by halogen. NH2, -OH, -O-CH3, -SO2-CH3 or-S02-CF3, R9 is halogen, -NO2, -ON, =0. -OH, -CF3, -C(O)-O-R10, -C(0)-N(R21)-R22, -N(R21)-R22, -(C3-C8)-cycloalkyl, -(Co-C3)-alkylene-0-R10, -Si-(CH3)3, -N(R10)-S(O)u-R10 where u is the integer 1 or 2, -S-R10, -SOp-RIO where r is the integer 1 or 2, -S(O)v-N(R10)-R20 where v is the integer 1 or 2, -C(O)-R10, -(Cl-C8)-alkyl, -(C-|-C8)-alkoxy, phenyl, phenyloxy-, -(C1-C3)-fluoroalkyl, -0-R19, -NH-C(O)-NH-R10, -(G0-C4)-alkyl-C(O)-O-G(R11, R19)-0-C(0)-R12, -NH-C(0)-NH-R21, -N(R21)-C(0)-R22, -(Co-C4)-alkyl-C(0)-0-C(R11, R19)-0-C(0)-0-R12, -NH-C(O)-O-R10, -O-CF3 or Het where Het is as defined above and is unsubstituted or mono-, di- or trisubstituted independently by RB, R10 and R20 are the same or different and are each independently a hydrogen atom, -(C-|-C6)-alkyl, -(Co-C4)-alkyl-OH, -(C1-C3)-fluoroalkyl, -(Co-C4)-alkyl-0-(C1-C4)-alkyl,-(Co-C5)-alkyl-(C3-C8)-cycioalkyl, -(Co-C2)-alkylene-aryl where aryi is as defined above and is unsubstituted or mono-, di- or trisubstitutBd indK>ender!tfv bv --C-.-O'kvl -0--C-:-C;:;ailcv-: halogen or -(Cs-Csl-cydoalkyi, or -(Co-C2)-alkyfene-Het where Net is as defined above and is unsubstituted or mono-, di- or trisubstituted independently by -(C1-C6)-alkyl, -0-(C1-C6)-alkyl, halogen or -(C3-C8)-cycloalkyl, R11 and R19 are the same or different and are each independently a hydrogen atom or -(C1-C6)-alkyl, R12 is -(C1-C6)-alkyl, -(C-|-C6)-alkyl-0H, -(C1-C6)-alkyl-0-(C1-C6)-alkyl, -(C3-C8)-cycloalkyl, -(C-)-C6)-alkyl-0-(C1-C8)-alkyl-(C3-C8)-cycloalkyl, -(C1-C6)-alkyl-(C3-C8)-cycloalkyl, where the cycloalkyi radical is unsubstituted or mono-, di- or trisubstituted independently by -OH, -0-(C1-C4)-alkyl or R10, R21 and R22 are the same or different and are each independently a hydrogen atom, -(C1-C5)-alkyl where alkyl is unsubstituted or mono-, di- or trisubstituted independently by R8, -(Co-C6)-alkylene-(C3-C8)-cycloalkyl, -SOt-R10 where t is the integer 1 or 2, -(C1-C3)-fluoroalkyl, -0-R12, -(Co-C6)-alkylene-aryl where cff B {fefined above ssvi afytene and sffyi are as:h uiubstiiuted cr mony-, di- or trisubstituted independently by R8 or -(Co-C6)-a1kylene-Het where Het is as defined above and alkylene and Het are each unsubstituted or mono-, di- or trisubstituted independently by R8, R21 and R22, together with the nitrogen atom to which they are bonded, form a four- to eight-membered monocyclic heterocyclic ring which, as well as the nitrogen atom, additionally, according to the ring size, may contain one or two identical or different heteroatoms from the group of oxygen, nitrogen or sulfur and in which the heterocycle is unsubstituted or mono-, di- or trisubstituted independently by R8, R23 is a hydrogen atom, -OH or -0-(C1-C4)-alkyl, X is a covalent bond, -N(R7)- or -0-, where R7 is a hydrogen atom, -(Co-C4)-alkylene-(C3-C6)-cycloalkyl or -(C1-C4)-alkyl, Y is -C(0)-, -C(S)- or -S(02)-, p is the integer 1 or 2, R27 is a hydrogen atorrL -iC'-C'r-alkyl. haiogeri. -(Co-C4)-aikylene-(C3-C6)-cydoaik>i. -(Co-C4)-aikyierje-Het where Het Is as defined above and is unsubstituted or substituted by halogen, -(C1-CgValkyl, -0-(C1-C3)-fluoroalkyl or-0-(C-|-C6)-alkyl, or -(Co-C2)-alkylene-phenyl where phenyl is unsubstituted or substituted by halogen, -(C1-C6)-alkyl, -0-(C1-C3)-fluoroalkyl or-0-(C1-C6)-alkyl, R26 is a hydrogen atom, -(C1-C4)-alkyl or-(Co-C4)-alkylene-(C3-C5)-cycloalkyl, R24 and R25 are the same or different and are each independently a hydrogen atom, -(C1-C6)-alkyl, -(C1-C3)-fluoroalkyl, -(Co-C4)-aIkylene-(C3-C6)-cycloaIkyl, -(Co-C4)-alkylene-aryl where aryl is as defined above and is unsubstituted or mono-, di- or trisubstituted independently by R8, or -(Co-C4)-alkylene-Het where Het is as defined above and is unsubstituted or mono-, di- or trisubstituted independently by R8, R24 and R25, together with the carbon atom to which they are bonded, form a iiwe- to sixH7>embered cydoaUcyl ring which is unsubstituted or mono-, di- or trisubstituted independently by R10 or fluorine, R24 and R25, together with the carbon atom to which they are bonded, form a three- to six-membered heterocycloalkyl radical which is unsubstituted or mono-, di- or trisubstituted independently by R10 or fluorine. where the clotted lines indicate the particular point of attachment to the second sub-ring, single bonds in the structures listed may be replaced partly by double bonds, or further ring systems may be fused on, and bonds, and the two sub-rings A and B are unsubstitut or independently monc-to tetrasubstituted by R4, and the X, Y, R27, p, R26, R24, R25 and R4 radicals are each as defined in claim 1. cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane, cyclooctane, bicyclo[4.2.0]octane, octahydroindene, decalin, decahydrobenzocycloheptene, dodecahydroheptalene, bicyclo[3.1.1]heptane, bicyclo[2.2.1]heptane, bicyclo[3.3.0]octane, bicyclo[2.2.2]octane, spiro[2.5]octane, spiro[3.4]octane, azepane, azepine, azetidine, aziridine, azirine, azocane, benzimidazoline, 2,3-dlhydrobenzo[b]thiophene, 1,3-dihydrobenzo[c]thiophene, 2,3-dihydrobenzofuran, 2,3-dihydrobenzooxazole, 2,3-dihydrobenzothiazole, 1,3-dihydroisobenzofuran, 4,5-dihydroisothiazole, 2,3-drnydrojsoxazole, 2,5-dTtTydroTsoxazote, 4,5-dThydrois3xazoie, 5,6-dinydro-4H-[1,2]oxazine, benzo[1,3]dioxole, 1,4-diazepane, 1,2-dlazepine, 1,3-diazepine, 1,4-diazepine, diaziridine, diazirine, 1,4-diazocane, dioxane, 1,3-dioxane, dioxazine, [1,3]dioxepane, 1,4-diozocane, dioxole, dioxolane, 1,3-dioxolane, 1,3-dioxolene, [1,3]dithiane, [1,3]dithiolane, hexahydropyridazine, hexahydropyrimidine, imidazoline, imidazolidine, indane, indoline, isoindoline, isothiazolidine, isothiazoline, isoxazoline, isoxazolidine, 2-isoxazoline, morpholine, [1,3,4]oxadiazinane, [1,3,5]oxadiazinane, [1,2,3]oxadiazolidine, [1,3,4]oxadiazolidine, 1,2-oxathiepane, 1,2-oxathiolane, [1,3]oxathiolane, 1,4-oxazepane, 1,2-oxazine, 1,3-oxazine, 1,4-oxazine, oxazinane, 1,3-oxazlnane, oxazocane, oxaziridine, oxazolidine, oxepane, oxetane, oxirane, oxocane, piperazlne, piperidine, pyran, pyrazoline, pyrazolidine, pyrrolidine, pyrrolidlnone, AMENDED SHEET pyrroline, tetrahydroquinoline, tetrahydrofuran, tetrahydroisoquinoline, 1,2,3,4-tetrahydronaphthalene, tetrahydropyran, tetrahydropyridine, 1,2,3,4-tetrahydro-pyrimidine, 1,2,5,6-tetrahydropyrimidine, tetrahydrothiophene, tetrazine, thiadiazine, [1,2,6]thiadiazinane, [1,3,4]thiadiazolidine, 1,2-thiazine, 1.3-thiazine, 1,4-thiazine. [1,2]ttiiazinane, [1,3]1t!iazinarie, thiazolidine, thiazoiine, ttiiepanc. thietane, thramorpiiofme, mtopyran. 1 ,3-iTiazine, 1 .4-triszine. 1,3,5-ir(azine. [1,2,4]triazinaRe or [1,2,4]triazofidlne, and in which the two sub-rings are each unsubstituted or independently, according to the ring size, mono-, di-, tri-, tetra-or pentasubstituted by R4, and the radicals X, Y, R27, p, R26, R24, R25 and R4 are each as defined in claim 1. of azetidine, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 1,3- dihydroisobenzofuran, 2,3-dihydroisoxazole, 2,5-dihydroisoxazole, 4,5- dihydroisoxazole, 1,3-dioxane, dioxolane, 1,3-dioxolane, imidazolidine, indane, morpholine, 1,3-oxazinane, oxazolidine, piperazine, piperidine, pyrrolidine, tetrahydrofuran, and 1,2,3,4-tetrahydronaphthalene, and in which the two sub-rings are each unsubstituted or independently, aGcacdmg to the ring size, memo-, di- or trisubstituted by R4, R4 is =0. =S, -(Co-C3)-ali -(Co-C3)-alkylene-0-R10, -(Co-C4)-alkylene-phenyl, where phenyl is unsubstituted or mono-, di- ortrisubstituted independently by R8, or -(Co-C4)-alkyl where alkyl is unsubstituted or mono-, di- ortrisubstituted independently by R9, R8 is fluorine, chlorine, bromine, -0-(C1-C3)-fluoroalkyl or-0-(C-|-C4)-alkyl, R9 is halogen, -NO2, -CN, =0, -OH, -CF3, -C(O)-O-R10. -C(0)-N{R21)-R22, -N(R21)-R22, -(C3-C8)-cycloalkyl, -(Co-C3)-alkylene-0-R10, -Si-(CH3)3, -N(R10)-S(O)u-R10 where u is the integer 1 or 2, -S-R10, -SOpRIO where r is the integer 1 or 2, -S(O)v-N(R10)-R20 where v is the integer AMENDED SHEET 1 or 2, -C(O)-R10, -(C1-C8)-alkyl, -(C1-C8)-alkoxy, phenyl, phenyloxy-, -(C1-C3)-fluoroalkyl, -0-R19, -NH-C(O)-NH-R10, -(Co-C4)-alkyl-C(0)-0-C(R11,R19)-0-C(0)-R12,-NH-C(0)-NH-R21, -N(R21)-C(0)-R22, -(Co-C4)-alkyl-C(0)-0-C(R11, R19}-O-C(O)-0-R12, -NH-C(O)-O-R10 or-0-CF3, R10 and R20 are the same or different and are each independently a hydrogen atom or-(C1-C5)-alkyl, R11 and R19 are the same or different and are each independently a hydrogen atom or -(C1-C6)-alkyl, R12 is -(C1-C6)-alkyl, -(C1-C6)-alkyl-0H, -(C1-C6)-alkyl-0-(C1-C6)-alkyl, -(C3-C8)-cycloalkyl,-(C1-C6)-alkyl-0-(C1-C8)-alkyl-(C3-C8)-cycloalkyl, -(C1-C6)-alkyl-(C3-C8)-cycloalkyl, where the cycloalkyi radical is unsubstituted or mono-, di- ortrisubstituted independently by-OH, -0-(C1-C4)-alkyl or R10, R21 and R22 are the same or different and are each independently a hydrogen atom, -(C1-C6)-alkyl, -0-R12, -(Co-C6)-alkyIene-(C3-C8)-cycloalkyl, -SOfRIO where t is the integer 1 or 2, or -(C1-C3)-fluoroalkyi, R23 is a hydrogen atom, -OH or-0-(C-|-C4)-alkyl, X is a covalent bond or -N(R7)- where R7 is a hydrcgen atom or -(C-| -C4)-alkyl, Yis-C(0)-or-S(02)-, p is the integer 1 or 2, R26 is a hydrogen atom, R27 is a hydrogen atom, -(Co-C4)-alkylene-(C3-C6)-cycloalkyl, -(C1-C6)-alkyl, -(Co-C2)-alkyiene-phenyI where phenyl is unsubstituted or substituted by halogen, -(C1-C6)-alkyl, -0-(C1-C3)-fluoroalkyl or-0-(C1-C6)- alkyl, or-(Co-C2)-alkylene-pyridyl, R24 and R25 are the same or different and are each independently a hydrogen atom, -(C1-C4)-alkyl or-(Go-C4)-alkylene-(C3-C6)-cycloalkyl, R24 and R25, together with the carbon atom to which they are bonded, form a cycloalkyi ring which is selected from the group of cyclopropyl, cyclobutyl. cyclopentyl and cyclohexyl, and is unsubstituted or mono-, di- ortrisubstituted independently by R10 or fluorine, R24 and R25, together with the carbon atom to which they are bonded, form a three- to six-membered heterocycloalkyi radical selected from the group of aziridine, azetidine, diazetidine, diaziridine, hexohydropyridazine, hexohydropyrimidine, imidazolidine, morpholine, oxadiazinane, oxadiazolidlne, oxathianane, oxathiolane, oxazetidine, oxazolidine, oxetane, oxirane, piperazine, piperidlne, pyrazolidine, pyrrolidine, tetrahydrofuran, tetrahydropyran, tetrahydrothiophene, tetrahydrothiopyran, tetrazinane, thiadiazolidine, thiazetidine, thiaziridine, thiazolidine, thietane, thiirane, thiomorpholine, triazetidine, triazinane ortriazolidine, which is unsubstituted or mono-, di- or trisubstituted independently by R10 or fluorine. A compound of the formula la as claimed in one or more of claims 1 to 4 where cyclopentyl, cyclohexyl, 1,3-dihydroisobenzofuran, 1,3-dioxane, 1,3-dioxolane, imidazolidine, indane, morpholine, 1,3-oxazinane, piperazine, piperidine, pyrrolidine, tetrahydrofuran, and 1,2,3,4-tetrahydronaphthalene, cyclopentyi, cyctotrexyl, morpholine, oxazolicfine, piperidine and pyrrulkJir»e, and in which the two sub-rings are unsubstituted or independently, according to the ring size, mono-, di- ortri-substituted by R4 where R4 is -0-(C1-C4)-alkyl, =0, -(Co-C4)-alkylene-(C3-C6)-cycloalkyl, -(C'i-C4)-alkyl or-(Co-C4)-alkylene-phenyl where phenyl is unsubstituted or substituted by F, CI, Bror-0-(C1-C4)-alkyl, X is a covalent bond or -NH-, Y is -C(0)- or -S(02)-, p is the integer 1, R27 is a hydrogen atom, -(C1-C6)-alkyl, 4-F-benzyl or benzyl, R26 is a hydrogen atom, cyclopentyl and cyclohexyl, and is unsubstituted or mono-, di- ortrisubstituted independently by R10 or fluorine, R24 and R25, togetlner with the carbon atom to which they are bonded, form a three- to six-membered heterocycloalkyi radical selected from the group of aziridine, azetidine, diazetidine, diaziridine, hexohydropyridazine, hexohydropyrimidine, imidazolidine, morpholine, oxadiazinane, oxadiazolidine, oxathianane, oxathiolane, oxazetidine, oxazolidine, oxetane, oxirane, piperazine, piperldine, pyrazolidine, pyrrolidine, tetrahydrofuran, tetrahyd ropy ran, tetrahydrothiophene, tetrahydrothiopyran, tetrazinane, thiadiazolidine, thiazetidine, thiaziridine, thiazolidine, thietane, thiirane, thiomorpholine, triazetidine, triazinane or triazolidine, which is unsubstituted or mono-, di- or trisubstituted independently by R10 or fluorine. cyclopentyl, cyclohexyl, 1,3-dlhydrolsobenzofuran, 1,3-dioxane, 1,3-dioxolane, imidazolidine, indane, morpholine, 1,3-oxazinane, piperazine, piperidine, pyrrolidine, tetrahydrofuran, and 1,2,3,4-tetrahydronaphthalene, -(C1-C4)-alkyl or-(Co-C4)-alkylene-phenyl where phenyl is unsubstituted or substituted by F, CI, Bror-0-(C1-C4)-alkyl, X is a covalent bond or -NH-, Y is -C(0)- or -S(02)-, p is the integer 1, R27 is a hydrogen atom, -(C1-C6)-alkyl, 4-F-benzyl or benzyl, R26 is a hydrogen atom. R24 and R25 are the same or different and are each independently a hydrogen atom, methyl or ethyl, R24 and R25, together with the carbon atom to which they are bonded, form a cyclopropyl or cyclobutyl radical, or R24 and R25, together with the carbon atom to which they are bonded, form a piperidine ring which is unsubstituted or substituted by -(C1-C4)-alkyl. A compound of the formula la as claimed in one or more of claims 1 to 5, which is the compound N-[(S)-1-(1-cyanocyclopropylcarbamoyl)-3,3-difluorobutyl]-3-azaspiro[5.5]undecane-3-carboxamide, N-[(S)-1 -(1 -cyanocyclopropylcarbamoyl)-3,3-difluorobutyl]-8-a2aspiro[4.5]decane-8-carboxamide, N-[(S)-1-(1-cyanocyclopropylcarbamoyl)-3,3-difluorobutyl]- 1,4-dioxa-8-azaspiro[4.5]decane-8-carboxamide, N-[(S)-1 -(1-cyanocyclo-propylcarbamoyl)-3,3-difluorobutyl]-2-azaspiro[5.5]undecane-2-carboxamide, N-[(S)-1-(1-cyanocyclopropylcarbamoyl)-3,3-difluorohexyl]-8-aza-spiro[4.5]decane-8-carboxamide, N-[(S)-1-(1-cyanocyclopropylcarbamoyl)-3,3-difluorohexyI]-3-azaspiro[5.5]undecane-3-carboxamide, N-[(S)-1 -(1 -cyanocyclopropylcarbamoyl)-3,3-difluorobutyl]-2-(4-methoxyphenyl)-1-oxo-2,8-di-azasplro[4.5]decane-8-carboxamide, N-[(S)-1 -(1 -cyanocyclopropylcarbamoyl)-3,3-difluorobutyl]-4-oxo-1 -phenyl-1,3,8-triazaspiro[4.5]decane-8-carboxamide, N-[{S)-1-{1-<:yaito n-> phenyl)-1 -oxo-2,8-cliazaspiro[4.5]decane-8-carboxamide, N-[(S)-1 -(1 -cyanocyclopropylcarbamoyl)-3-methylbutyl]-1,4-dioxaspiro[4.5]decane-8-carboxamide, N-[(S)-1 -(1 -cyanocyclopropylcarbamoyl)-3,3-difluorobutyl]-3-phenyl-1,5-dioxa-9-azaspiro[5.5]undecane-9-carboxamide, N-[1 -(1 -cyano-cyclopropyIcarbamoyl)cyclohexyl]-8-azaspiro[4.5]decane-8-carboxamide, N-[(S)-1-(1-cyanocyclopropylcarbamoyl)-cyclohexylmethyi-8-azaspiro[4.5]decane-8-carboxamide, N-[{S)-1 -(1 -cyanocycbpropylcarbaiTioy!)-3,3-dif!uorobutyl}-9-butyl-3,9-diazaspiro[5.5]undecane-3-carboxamide, N-[(S)-1-(1-cyanocyclopropylcarbamoyl)-3,3-difluorobutyl]-9-cyclopropyl-3,9-diazaspiro[5.5]undecane-3-carboxamide, N-[(S)-1-(1-cyanocyclo-propylcarbamoyl)-3-methylbutyl]spiro[2.3]hexane-1-carboxamide, N-[(S)-1-(1-cyanocyclopropylcarbamoyl)-3,3-difluoro-4-phenylbutyl]-8-azaspiro[4.5]decane-8-carboxamide, N-[(S)-1 -(1 -cyanocyclopropyl-carbamoyl)-3,3-difluorobutyl]spiro[2.3]hexane-1-carboxamide, N-[(S)-1-(1-cyanocyclopropylcarbamoyl)-3,3-difluorobutyl]-2,2-dimethyl-1-oxa-8-azaspiro[4.5]decane-8-carboxamide, N-[(S)-1-cyanocyclopropylcarbamoyl)-3,3- N-[(S)-1-(1-cyanocyclopropylcarbamoyl)-3,3-difluorobutyl]-7-cyciopropyl-2,7-diazaspiro[3.5]nonane-2-carboxamide, N-[(S)-1 -(1 -cyanocyclopropylcarbamoyl)-3,3-difluoro-butyl]-2-cyclopropyl-2,7-diazaspiro[3.5]nonane-7-carboxamide, N-[(S)-1-(1-cyanocyclopropylcarbamoyl)-3,3-difluorobutyl]-2-propyl-2,7- diazaspiro[3.5]nonane-7-carboxamide, N-(1-cyanocyclopropyl)-(S)-2-(8-azaspiro[4.5]clecane-8-sulfonylamino)-4,4-difiuoropentanamide, N-[(S)-1-(1-cyanocyclopropylcarbamoyl)-3,3-difluorobutyl]-4-cyclopropyl-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxamide, N-[(S)-1-(1-cyanocyclopropylcarbamoyl)-3,3-difluorobutyl]-9-cyclopropyl-1-oxa-4,9-diazaspiro[5.5]undecane-4-carboxamide, N-[(S)-1-(1- cyan(x;yclopropylcarbanx)yl)-3,3 carboxamide, N-[(S)-1-(1-cyanocyclopropylcarbamoyl)-3,3-difluoropentyl]- or N- [(S)-1-(1-cyanocyclopropylcarbamoyl)-3,3-difluoro-4-phenylbutyl]-6- azaspiro[2.5]octane-6-carboxamide. 7. A process for preparing the compound of the formula la and/or a stereoisomeric form of the compound of the formula la and/or a physiologically compatible salt of the compound of the formula la and/or a sdvate or hydrate of the compound of the formula la and/or an N-oxide of the compounds of the formulae la as claimed in one or more of claims 1 to 6, which comprises and reacting the resulting compounds of the formula IVa or IVb, after converting the ester to the carboxylic acid, with Z to give the compound of the formula la, or b) reacting a compound of the formula Va or Vb where A, B, X and Y are each as defined in the compound of the formula la to give a compound of the formula IVa or IVb, and reacting the resulting compound of the formula IVa or IVb, after converting the ester protecting group to the carboxylic acid, with Z to give the compound of the formula la, or c) reacting a compound of the formula Vila or Vllb where A, B and X are to give a compound of the formula Villa or Vlllb and reacting the resulting compound of the formula Villa or Vlllb, after converting the ester to the corresponding cart)oxyfic acid, with Z to give the compound ofthe"formula ia, or and then converting the compound X thus obtained in a protecting group elimination to give a compound of the formula XI and then reacting this compound XI with a compound Va or Vb, as detailed under b), to give the compound of the formula la, or e) separating a compound of the formula la prepared by processes a), b), c) or d), or a suitable precursor of the formula la which, owing to its chemical structure, occurs in enantiomeric or diastereomeric forms, into the pure enantiomers or diastereomers by salt formation with enantiomerically pure salts or bases, chromatography on chiral stationary phases or derivatization by means of chiral enantiomerically pure compounds such as amino acids, separating the diastereomers thus obtained, and eliminating the chiral auxiliary groups, or f) either isolating the compound of the formula la prepared by processes a), b), c) or d) in free form or releasing it from physiologically incompatible salts or, in the case of the presence or acidic or basic groups, converting it to physiologically acceptable salts, or g) converting the compound of the formula la prepared by processes a), b), c) or d), or a suitable precursor of the formula la which, owing to its chemical structure, is capable of forming an N-oxide to an N-oxide or, in the case of the presence of an N-oxide, converting it to the free amine or the salt of an amine. A medicament characterized by a compound of the formula ia according to one or more of claims 1 to 6 together with a pharmaceutically suitable and physiologically compatible carrier, additive and/or other active ingredients and/or excipients. The use of the compound of the formula la as claimed in one or more of claims 1 to 6 for producing a medicament for the prophylaxis, secondary prevention and therapy of abnormally elevated bone degradation, allergies, Alzheimer's disease, amyloidosis, ARDS, arterial thrombosis, asthma, atheromas, atherosclerosis, autoimmune disorders, bacterial infections, bronchiolitis, cerebral hemorrhage, cerebrovascular ischemia, Huntington's chorea, chronic inflammations, CIPD (chronic inflammatory demyelinizing polyradiculoneuropathy), Creutzfeldt-Jakob disease, Crohn's disease, diabetes, particularly the juvenile form, emphysema, encephalomyelitis, endometriosis, inflammatory respiratory disorders, inflammatory pancreatitis, epilepsy, disorders characterized by enhanced angiogenesis, excessive respiratory pathway elastolysis, tissue grafts, gingivitis, glomerulonephritis, glucocorticoid-induced osteoporosis, Graves' disease, Guillain-Barre syndrome, Hashimoto's thyroiditis, hepatitis, HIV infection, Huntington's disease, hypercalcemia, IBD, immune impairment, interstitial cystitis, bone fracture, bone loss, cancers, lupus erythematosus, malaria, metachromic leukodystrophy, metastasizing osteogenesis, metastatis, multiple sclerosis, multiple myeloma, muscular dystrophy, myasthenia gravis, neurodegenerative disorders, neuropathic pain, chronic or diabetic neuropathy, post-therapeutic neuralgia, trigeminal neuralgia, painful diabetic polyneuropathy, post-stroke pain, post-amputation pain, myelopathic or radiculopathic pain, atypical facial pain and causalgia-like syndromes, organ rejection in transplants, osteoarthritis, osteogenesis imperfecta, osteoporosis, Paget's disease, pancreatitis, Parkinson's disease, pemphigus vulgaris, periodontitis, plaque rupture, Pneumocystis carinii, pneumonitis, psoriasis, restenosis, rheumatoid arthritis, scleroderma, systemic lupus erythematosus, brain trauma, spinal cord trauma, tumor cell invasion, viral infections, tooth loss, breast cancer, intestinal cancer,- ovarian cancer, cervical cancer, skin cancer, brain tumor, Kaposi's saxaxna, B- arKi T-ceU leukemia, fung camf, iymf rxxie cancer, pancreatic cancer, prostrate cancer and sarcomas. |
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| Patent Number | 278157 | |||||||||||||||
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| Indian Patent Application Number | 6565/CHENP/2008 | |||||||||||||||
| PG Journal Number | 52/2016 | |||||||||||||||
| Publication Date | 16-Dec-2016 | |||||||||||||||
| Grant Date | 15-Dec-2016 | |||||||||||||||
| Date of Filing | 01-Dec-2008 | |||||||||||||||
| Name of Patentee | SANOFI-AVENTIS | |||||||||||||||
| Applicant Address | 174, AVENUE DE FRANCE, 75013 PARIS, | |||||||||||||||
Inventors:
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| PCT International Classification Number | C07D211/66 | |||||||||||||||
| PCT International Application Number | PCT/EP07/04550 | |||||||||||||||
| PCT International Filing date | 2007-05-23 | |||||||||||||||
PCT Conventions:
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