ZA200601501B

ZA200601501B - Bicyclic imino acid derivatives used as inhibitors of matrixmetalloproteinases

Info

Publication number: ZA200601501B
Application number: ZA200601501A
Authority: ZA
Inventors: Schudok Manfred; Matter Hans; Hofmeister Armin
Original assignee: Sanofi Aventis Deutschland
Priority date: 2003-09-27
Filing date: 2006-02-21
Publication date: 2007-04-25
Also published as: MA28075A1; KR20060086367A; IL174040A0; MEP33008A; EP1670766B1; JP2007506690A; EP1670766A1; NO20061837L; PE20050432A1; AU2004275937A1; BRPI0414594A; CA2539731A1; AR046165A1; UY28539A1; RS20060194A; WO2005030728A1; CN1856478A; JP4861179B2; TW200520755A; RU2006114352A

Description

Bicyclic imino acid derivatives used as inhibitors of matrix- ® metalloproteinases

The invention relates to n ovel derivatives of saturated bicyclic imino acids, such as, in particular, decahydroisoquinoline-1-carboxylic acid, to methods for preparing them, and to the use thereof as pharmaceuticals.

In diseases such as osteoarthritis and rheumatism, destruction of the joint takes place, with this destruction being caused, in particular, by the proteolytic breakdown of collagen due to collagenases. Collagenases belong to the metalioproteinase (MP) or matrix metalloproteinase (MMP) superfamily. The MMPs form a group of Zn-dependent enzymes which are involved in the biological breakdown of the extracellular matrix (D. Yip et al. in Investigational New Drags 17 (1999), 387-399 and Michaelides et al. in

Current Pharmaceutical Design 5 (1999) 787 — 819). These MMPs are, in particular, able to break down fibrillar and nonfibrillar collagen and also proteoglycans, both of which are important matrix constituents. MMPs are involved in processes of wound healing, tumor invasion and metastasis migration, and also in amgiogenesis, multiple sclerosis and heart failure (Michaelides, page 788; see above). In particular, they play an important role in the breakdown of the joint matrix in arthrosis and arthritis, whether this be osteoarthrosis, osteoarthritis or rheumatoid arthritis.

I'he activity of the MMPs iis furthermore essential for many of the processes which play a role in atherosclerotic plague formation, such as the infiltration of inflammatory cells amd smooth muscle cell migration, as well as proliferation and angiogenesis (S.J. George, Exp. Opin. Invest. Drugs (2000), 9 (5), 993-1007). Furthermore, the degradation of matrix by MMPs can cause anything from plaque instabilities through to ruptures, with these conditions being able to give rise to the clinical symptoms of atherosclerosis, unstable angina pectoris, myocardial infarction or stroke (E.J.M. Creemers et al., Circulation Res. 89, 201-210 (2001)). All in all, the

MMP family as a whole is able to break down all the components of the extracellular matrix of the blood vessels; in normal blood vessels, therefore, their activity is to a very great degree subject to regulatory mechanisms.

The increase in MMP activity during plaque formation and plaque instability is caused by an increase in cytokine-stimulated and growth factor- stimulated gene transcription, an increase in zymogen activation and an imbalance in the MIMP/TIMP (tissue inhibitors of metalloproteases) ratio. 1t therefore seems plausible that an MMP inhibition or the reattainment of the-

C MMP-TIMP balance, would be helpful in treating atherosclerotic diseases. It is likewise becoming ever more clear that an increase in MMP activity is at least partially responsible for other cardiovascular diseases in addition toe atherosclerosis, such as restenosis, dilated cardiomyopathy and thes previously mentioned myocardial infarction. it has been shown that administering synthetic inhibitors to experimental animal models of these diseases is able to achieve marked improvements, for example in regard to the formation of atherosclerotic lesions, neointima formation, left ventricular remodeling, pump performance malfunction or infarction healing. In various preclinical studies using MMP inhibitors, detailed tissue analyses indicated a reduction in collagen damage, an improvement in extracellular matrix remodeling and an improvement in the structure and function of cardiac muscle and blood vessels. Among these processes, matrix remodeling processes and MIMP-regulated fibroses, in particular, are regarded as being important components in the progression of heart diseases (infarction) (Drugs 61, 1239-1252 (2001)).

Under physiological conditions, MMPs cleave matrix proteins such ass collagen, laminin, proteoglycans, elastin or gelatine, and also process (i.e. activate or inactivate), by means of cleavage, a large number of othear proteins and enzy mes, which means that they play an important role in th-e entire body, with this role being particularly significant in the connective tissue and bones.

A large number of different MMP inhibitors are known (EP 0 606 046, WCQ 94/28889; WO 96/27583; cf. reviews such as Current Medicinal Chemistry 8, 425-74 (2001) as well). Following the first clinical studies in humans, it has now been found that MMPs give rise to side-effects. The side-effects &o be mentioned are musculoskeletal pain or anthralgias. The prior art makes it clear that it is expected that more selective inhibitors would be able &o reduce these side-effects (Yip, page 387, see above). Specificity towards

MMP-1 is particularly to be emphasized in this connection since these unwanted side-effects evidently appear to an increased extent when MMP- 1 is inhibited.

A disadvantage of the known MMP inhibitors is therefore that they frequently lack specificity. Most MMP inhibitors inhibit many MMPs simultareously because the catalytic domains of the MMPs possess similar structurees. As a consequence, the inhibitors also unde-sirably affect the [ enzyme=s which have a vital function (Massova |, et al., Thue FASEB Journal (1998) 112, 1075-1095).

In the endeavor to find effective compounds for treating connective tissue disease s, it has now been found that the derivatives whict are employed in accordamnce with the invention are powerful inhibitors of the matrix metalloproteinases MMP-2, MMP-3, MMP-8, MMP-9 armd MMP-13 while only hawing a weak inhibitory effect on MMP-1.

The invention therefore relates to a compound of the formula ni n2 R2 0 : ua) A—ring;—B——ringz-D——rings~E ring,

R4 0

R5 R1

R3 X Cn

Oo and/or to all the stereoisomeric forms of the compound of the formula and/or to mixtures of these forms in any ratio, and/or to a physiologically tolerated salt of the compound of the formula I, wherein

Ais -CCo-Cy)-alkylene,

B, D and E are identical or different and are, independen tly of each other, -(C=0-C4)-alkylene or the radical -B1-B2-B3- in which

B1 is -(CHa),-, in which nis the integer zero, 1 or 2,

B3 is -(CH2)m-, in which m is the integer zero, 1 or 2, withh the proviso that the sum of n and m amounts to zero, 1 or 2, and

B2 is 1) -C(O)- 2) -(C2-C4)-alkenylene, 3) -S(0)o-, where o is the integers zero, 1 or 2, 4) -N(R6)-, in which R6 is hydrogen atom, meth yl or ethyl, 5) -N(R6)-C(Y)-, in which Y is oxygen atom or sulfur atom and

R6 is defined as above,

6) -C(Y)-N(R6)-, in which Y is oxygen atom or sulfur atom and

RG is defined as above, @® 7) -N(R6)-SO2-, in which R6 is defined as abosve, 8) -S0.-N(R6)-, in which R6 is defined as abo-ve, 9) -N(R6)-SO,-N(R86)-, in which R6 is defined as above, 10) -N(R6)-C(Y)-N(R6)-, in which Y is oxygen atom or sulfur atom and R6 is defined as above, 11) -O-C(O)-N(R6)-, 12) -NH-C(O)-O-, 13) -O-, 14) -C(O)-O-, 15) -O-C(O)-, 16) -0O-C(0O)-O-, 17) -O-CH,-C(O)-, 18) -O-CH,-C(O)-O-, 19) -O-CH2-C(0)-N(R6)-, in which R6 is defined as above, 20) -C(O)-CHz-0O-, 21) -O-C(O)-CH2-O-, 22) -N(R6)-C(0)-CH2-0O-, in which R6 is defined as above, 23) -O-(CH):-O-, in which n is the integer 2 or 3, or 24) -O-(CH2)m-N(R6)-, in which m is the intege=r 2 or 3 and R6 is defined as above, 25) -N(R6)-(CH2)m-O-, in which m is the intege=r 2 or 3 and R6 is defined as above, 26) -N(R6)-N(R6)-, in which R6 is defined as above, 27) -N=N-, 28) -N(R6)-CH-N-, in which R6 is defined as atoove, 29) -N=CH-N(R6)-, in which R6 is defined as aloove, 30) -N(R6)-C(R7)=N-, in which R6 is defined ass above and R7 is ~NH-RS, 31) -N=C(R7)-N(R6)-, in which R6 is defined ass above and R7 is -NH-R8, or 32) -(C-Cg)-alkynylene, ring1, ring2 and ring3 are identical or different and are , independently of eachother, 1) covalent bond, 2) -(C¢-C14)-aryl, in which aryl is unsubstituted or substituted, independently of each other, once, twice or three times, by G, or

3) 4- to 15-membered Het ring, in which Het ring is unsubstituted or substituted , independently of each other, ( once, twice or three times, by" G, ring4 is 5 1) -(Cs-C14)-aryl, in which aryl is unsubstituted or substituted, independently of each other, ©nce, twice or three times, by G, 2) 4- to 15-membered Het ring, in which the Het ring is unsubstituted or substituted, independently of each other, once, twice or three times, by G, or 3) is one of the following radicals

H H and these radicals are unsubstituted or substituted once by

G,

Gis 1) hydrogen atom, 2) halogen, 3) =0, 4) -(C1-Ce)-alkyl, in which alkyl is unsubstituted or substituted, once, twice or three times, by halogen, -(C;-Cg)-cycloalkyl, - (C2-Ceg)-alkynyl, -(Cs-C14)-aryl or Het ring, 5) -(Cs-Cha)-aryl, 6) Het ring, 7) -C(0)-0-R10, in which R10 is a) -(C1-Ce)-alkyl, in which alkyl is unsubstituted or substituted, once or twice, by -(C3-Cg)-cycloalkyl, -(C2-Ce)-alkynyl, -CCs-C14)-aryl or Het ring, or b) -(Ce-C14)-aryl or H et ring, 8) -C(S)-0-R10, in which R10 is defined as above, 9) -C(0O)-NH-R11, in which R11 is a) -(C4-Ce)-alkyl, in “which alkyl is unsubstituted or substituted, once or twice, by -(C3-Cg)-cycloalkyl, -(Cg-C14)-aryl or Het ring, or b) -(Ce-C14)-aryl or Heet ring, 10) -C(S8)-NH-R11, in which R11 iss defined as above, 11) -O-R12,in which R12 is a) hydrogen atom, b) -(C1-Ce)-anlkyl, in which alkyl is unsubstituted or @ substitute d, once, twice or three times, by halogen, -(C;-Cg)-cycioalkyl, -(C2-Ce)-alkynyl, - (Cs-C1a)-aryl or Het ring, c) -(Ce-C1a)- aryl, d) Het ring, e) -C(0)-0O-R13, in which R13 is e)) -€C4-Cg)-alkkyl, in which alkyl is wnsubstituted or substituted, once or twice, by -(C3-Cs)-cycloalkyl, -(C2-Cs)- alkynyl, -(Cg-C14)-aryl, or Het ring, or e)2) -qCg-C14)-aryl or Het ring, f) -C(S)-0-R13, in which R13 is defined as above, a) -C(O)-NHI-R14, in which R14 is g)t) -{C+-Cg)-alkyl, in which alkyl is unsubstituted or substituted, once or twice, by -(C;-Cs)-cycloalkyl, -(C2-Ce)- alkynyl, -(Ce-C1a)-aryl or Het ring, or g)2) - (Ce-C14)-aryl or Het ring, or h) -C(S)-NH -R14, in which R14 is defined as above, 12) -C(O)-R10, in which R10 is defined as above, 13) -S(0)-R12, in whichm R12 is defined as above and p is the integers zero, 1 or 2, 14) -NO,, 15) -CN, or 16) -N(R15)-R12,in whic hR15 is 16)1) hydrogen atom, 16)2) -(C4-Cg)-alkyl, or 16)3) -SO.-(C4-Cep-alkyl, in which alkyl is unsubstituted or substituted, once or twice, by -(C3-Cg)-cycloalkyl, - (C2-Cs)-alkymyl, -(Ce-C14)-aryl or Het ring, and R12 is defined as above, or 17) -SO2-N(R12)-R1, in which R12 is defined as above and R1 is defined as below,

Xis -OH or -NH-OH, n1is the integer zero, 1, 2 or 3, n2is the integer zero, 1, 2, 3 or 4, with the proviso that the sum of n1 and n2 amounts to 1, 2, 3,4, 5, 6 or7,

R1, R2, R3, R4 and R5 are identical or different and are, independently of each other, @® 1) hydroge n atom, 2) -(C+1-Cs)—alkyl, in which alkyl is unsubstituted or substituted, once or twice, by -(C3-Cs)-cycloalkyl, -(C,-Cg)-alkynyl, -(C e-

C1a)-aryl or Het ring, 3. -C(0)-O -R8, in which R8 is 3)1) hydrogen atom, 3)2) -(C1-Ces)-alkyl, in which alkyl is unsubstituted or substituted, once or twice, by -(C3-Ce)-cycioalkyl, -(C2-Ce)-alkynyl, -(Ce-C14)-aryl or Het ring, or substituted once to five times, by fluorine, or 3)3) -(C¢-Cia)-aryl or Het ring, 4) -O-R8, i n which R8 has the abovementioned meaning, or 5) -(C3-C¢) -cycloalkyl.

The invention also rel ates to the compound of the formula | where

Ais -(Co-Cs)-alkyleme,

B, D and E are identical or different and are, independently of each other, -(Co-C4)-alkylene or the radical -B1-B2-B3- in which

B1is -(CH2)»—, in which n is the integer zero, 1 or 2,

B3is -(CH2)m—, in which m is the integer zero, 1 or 2, with the proviso that the sum of n and m amounts to zero, 1 or 2, and

B2 is 1) -C(O)- 2) -(C2-Cs)-alkenylene, 3) -S(0)o-, where o is the integers zero, 1 or 2, 4) -N(R6)-, in which R6 is hydrogen atom, methyl or ethyl, 5) -N(R6)-<C(Y)-, in which Y is oxygen atom or sulfur atom ard

R6 is defined as above, 6) -C(Y)-N (R6)-, in which Y is oxygen atom or sulfur atom amd

R6 is defined as above, 7) -N(R6)--SO--, in which R6 is defined as above, 8) -S0O,-N¢R6)-, in which R6 is defined as above, : 9) -N(R6)- SO,-N(R6)-, in which R6 is defined as above, 10) -N(R6)- C(Y)-N(R6)-, in which Y is oxygen atom or sulfur atom and R6 is defined as above, 11) -O-C(O)-N(R6)-, 12) -NH-C(Q)-0-,

13) -O-, 14) -C(0)-O-, ® 15) -0-C(O), 16) -0O-C(O)-O-, 17) -0O-CH=-C(O)-, 18) -0O-CHz=-C(0)-O-, 19) -O-CHz-C(O)-N(R6)-, in which R6 is defined as above, 20) -C(O)-CHz-O-, 21) -O-C(O)-CH2-O-, 22) -N(R6)-C(0)-CH,-O-, in which R6 is defined as above, 23) -O-(CH 2)-O-, in which n is the integer 2 or 3, or 24) -O-(CH 2)m-N(R6)-, in which m is the integer 2 or 3 and R6 is defined as above, 25) -N(R8)—(CH2)m-O-, in which m is the integer 2 or 3 and R6 is defined as above, 26) -N(R6)-N(R6)-, in which R6 is defined as above, 27) -N=N-, 28) -N(R6)-CH=N-, in which R6 is defined as above, 29) -N=CH -N(R6)-, in which R6 is defined as above, 30) -N(R6)-C(R7)=N-, in which R6 is defined as above and R7 is -NH-R 6, 31) -N=C(R7)-N(R6)-, in which R6 is defined as above and R7 is —NH-R 6, or 32) -(C,-Cg)-alkynylene, ring1, ring2 and ring3 are identical or different and are, independertly of each other, 1) covalent bond, 2) phenyl or naphthyl and are unsubstituted or substituted, indepe ndently of each other, once, twice or three times, by G, or 3) 4- to 15-membered Het ring, in which the Het ring is a radical from the series acridinyl, azepinyl, azetidinyl, azir idinyl, benzimidazalinyl, benzimidazolyl, benzofuaranyl, benzot hiofuranyl, benzothiophenyl, benzoxazolyl, benzot hiazolyl, benzotriazolyl, benzotetrazolyl, benzisoxazolyl, benzisothiazolyl, carbazolyl, 4aH-carbazolyl, carbolinyl, quinazolinyl, quinolinyl, 4H-quinol izinyl, quinoxalinyl, quinuclidinyl, chromanyl, chromenyl, cinn olinyl, deca-hydroquinolinyl, dibenzofuranyl, dibenzothioplhenyl,

Claims

Patent claims

® 1. A compound of the formula 2 ni 0 R2 I LL LS A—ring,—B—ring;~D——rings"E rng, No R4 R1 RO R3 Jy (1) 5 O and/or all the stereoisomeric forms of the compound of the formula 1 : and/or mixtures of these forms in any ratio, and/or a physiologically tolerated salt of the compound of the formula |, wherein Ais -(Co—-C,)-alkylene, B, D and E are identical or different and are, independently of each other, -(Co—Cs)-alkylene or the radical -B1-B2-B3- in which B1is -(CHby).-, in which n is the integer zero, 1 or 2, B3is -(CH2)m-, in which m is the integer zero, 1 or 2, with the proviso that the sum of n and m amounts to zero, 1 or 2, and B2 is 1) -C(O)- 2) -(C2—C4)-alkenylene, 3) -S(O),-, where o is the integers zero, 1 or 2, 4) -N(R6)-, in which R6 is hydrogen atom, methyl or ethyl, 5) -N(R6)-C(Y)-, in which Y is oxygen atom or sulfur atom and R6 is defined as above, 6) -C(Y’)-N(R6)-, in which Y is oxygen atom or sulfur atom and R6 is defined as above, 7) -N(R6)-SO--, in which R6 is defined as above, 8) -SO--N(R6)-, in which R6 is defined as above, 9) -N(R6)-S02-N(R6)-, in which R6 is defined as above, 10) -N(R6)-C(Y)-N(R6)-, in which Y is oxygen atom or sulfur atorm and RG is defined as above, 11) -O-C(O)-N(R6)-, 12) -NH-C(O)-O-, 13) -O-,

14) -C(0O)-O-,

15) -O-C(O)-,

[ 16) -O-C(0O)-O-, 17) -O-CH,-C(O)-, 18) -O-CH2-C(O)-O-,

19) -O-CH»-C(O)-N(R8)-, im which R6 is defined as above,

20) -C(O)-CH,-O-,

21) -0O-C(O)-CH,-O-,

22) -N(R6)-C(O)-CH,-O-, im which R6 is defined as above,

23) -O-(CH),-O-, in which nis the integer 2 or 3, or

24) -O-(CH2)n-N(R6)-, in wrhich m is the integer 2 or 3 and R6 is defined as above,

25) -N(R6)-(CH2)m-O-, in wrhich m is the integer 2 or 3 and R6 is : defined as above,

26) -N(R6)-N(R6)-, in which R6 is defined as above,

27) -N=N-,

28) -N(R6)-CH=N-, in which R6 is defined as above,

29) -N=CH-N(R6)-, in whic h R6 is defined as above,

30) -N(R6)-C(R7)=N-, in which R6 is defined as above and R7 is

—NH-RS,

31) -N=C(R7)-N(R6)-, in which R6 is defined as above and R7 is —NH-R6, or

32) -(CxCe)-alkynylene,

ring, ring2 and ring3 are identical or different and are,

independently of each other,

1) covalent bond,
2) -(Cs-C1s)-aryl, in whic h aryl is unsubstituted or substituted, independently of each other, once, twice or three times, by G, or
3) 4- to 15-membered Het ring, in which Het ring is unsubstituted or subsstituted, independently of each other, once, twice or three tirmes, by G, ring4 is 1) -(Ce-Cias)-aryl, in whicsh aryl is unsubstituted or substituted, independently of each other, once, twice or three times, by G,

2) 4- to 15-membered Het ring, in which the Het ring is unsubstituted or subsstituted, independently of each other, once, twice or three tirmes, by G, or

3) is one of the following radicals

® oo =X =o H H and thesse radicals are unsubstituted or substituted once by G, : Gis 1) hsydrogen atom, 2) healogen, 3) =0, 4) -{C4-Ce)-alkyl, in which alkyl is unsubstituted or substituted, once, twice or three times, by halogen, -(C3-Cs)-cycloalkyl, -(C2-Cg)-alkynyl, -(Ce-C1a)-aryl or Het ring, 5) -€(Cg-Cis)-aryl, 6) Het ring, 7) -C(0)-0-R10, in which R10 is a) -(Ci-Ce)-alkyl, in which alkyl is unsubstituted or substituted, once or twice, by -(C3-Cg)-cycloalkyl, -(C,-Cs)-alkynyl, -(Cs-C14)-aryl or Het ring, or bb) -(Ces-Cis)-aryl or Het ring, 8) -€C(S)-0-R10, in which R10 is defined as above, 9) -C(0)-NH-R11, in which R11 is a) -(C4-Ce)-alkyl, in which alkyl is unsubstituted or substituted, once or twice, by -(C3-Cg)-cycloalkyl, -(Cs-C14)-aryl or Het ring, or b) -(Cs-Cis)-aryl or Het ring, 10) -C(S)-NH-R11, in which R11 is defined as above, 11) -O-R12, in which R12 is a) hydrogen atom, b) -(C4-Ce)-alkyl, in which alkyl is unsubstituted or substituted, once, twice or three times, by halogen, -(Cs-Cg)-cycloalkyl, -(C.-Ce)-alkynyl, -(Cs-C14)-aryl or Het ring, c) -(Ce-C14)-aryi, d) Hetring, e) -C(0)-0-R13, in which R13 is e)1) -(Ci-Celalkyl, in which alkyl is unsubstituted or substituted, once or ( twice, by -(Cs-Cg)-cycloalkyl, -(C2-Cs)- alkyny{, -(Cs-C14)-aryl, or Het ring, or e)2) -(Cs-C 14)-aryl or Het ring, fy) -C(S)-O-R13, i n which R13 is defined as above, g) -C(O)-NH-R14 , in which R14 is ay) -(C4-Cg)-alkyl, in which alkyl is unsub stituted or substituted, once or twice, by -(C3-Ce)-cycloalkyl, -(C2-Cs)- alkyny~l, -(C¢-C14)-aryl or Het ring, or g)2) -(Ce-C=14)-aryl or Het ring, or h) -C(S)-NH-R14 , in which R14 is defined as above, 12) -C(0)-R10, in which R10 is defined as above, 13) -S(0),-R12, in which R12 is defined as above and p is the integers zero, 1 or 2, 14) -NOg, 15) -CN, 16) -N(R15)-R12, in whic hR15 is 16)1) hydrogen atom, 16)2) -(C4-Ce)-alkyl, or 16)3) -S0O--(C4-Cg)-alkyl, in which alkyl is unsubstituted or substituted, once or twice, by -(C3-Cg)- cycloalkyl, -(C2-Cs)-alkynyl, -(Cs-C1s)-aryl or Het ring, and R12 is defined as above, or 17) -SO2-N(R12)-R1, in which R12 is defined as above and R1 is defined as below, Xis -OH or -NH-OH, n1is the integer zero, 1, 2 or 3, n2is the integer zero, 1, 2, 3 or 4, with the proviso that the sum of n1 and n2 amounts to 1, 2, 3,4, 5,6 or 7, R1, R2, R3, R4 and R5 are identical or different and are, independently of each oth er, 1) hydrogen atom, 2) -(C4-Cg)-alkyl, in which a lkyl is unsubstituted or substituted, once or twice, by -(Cs-Cs)-cycloalkyl, -(C2-Cg)-alkynyl, -(Ce- Cis)-aryl or Het ring, 3) -C(0)-0-R8, in which R8 &s 3)1) hydrogen atom,

3)2) -(C1-Cg)-alkyl, in which alkyl is unsu bstituted or substituted, once or twice, by -(C3;-C=g)-cycloalkyl, ) -(C2-Ce)-alkynyl, -(Ce-C14)-aryl or Het ring, or substituted once to five times, by fluorine, or 3)3) -(Ce-C1as)-aryl or Het ring, 4) -O-R8, in which R8 has the abovementioned meaning, or 5) -(Cs-Ce)-cycloalkyl.

2. A cormpound of the formula | as claimed in claim 1, Ais -(Co-Cs)-alkylene, B, D and E are identical or different and are, independently of each other, —(Co-C4)-alkylene or the radical -B1-B2-B3- in which B1is -(CH2)n-, in which n is the integer zero, 1 or 2, : B3is -(CHz)m-, in which m is the integer zero, 1 or 2, with th e proviso that the sum of n and m amounts to zero.. 1 or 2, and B2 is 1) -C(O)- 2) -(C,-C4)-alkenylene, 3) -S(0)o-, where o is the integers zero, 1 or 2, 4) -N(R6)-, in which R6 is hydrogen atom, methyl or ethyl, 5) -N(R6)-C(Y)-, in which Y is oxygen atom or sul fur atom and R6 is defined as above, 6) -C(Y)-N(R6)-, in which Y is oxygen atom or sul fur atom and R6 is defined as above, 7) -N(R6)-SO,-, in which R6 is defined as above, : 8) -S0,-N(R6)-, in which R6 is defined as above, 9) -N(R6)-SO,-N(R6)-, in which R6 is defined as ab ove, 10) -N(R6)-C(Y)-N(R6)-, in which Y is oxygen atom Or sulfur atom and R6 is defined as above, 11) -0-C(O)-N(R6)-, 12) -NH-C(O)-O-, 13) -O-, 14) -C(0)-0O-, 15) -0-C(O)-, 16) -0-C(0)-0-, 17) -O-CH,-C(O)-, 18) -0-CH,-C(0)-0O-, 19) -O-CH,-C(0O)-N(R6)-, in which R6 is defined as aabove, 20) -C(0)-CH2-O-,

21) -O-C(O)-CH,-0-, 22) -N(R6)-C(0O)-CH2-O-, in which R6 is defined as above,

[ 23) -O-(CH),-0-, in which n is the integer 2 or 3, or 24) -O-(CH2)m-N(R8)-, in which m is the integer 2 or 3 and R6 is defined as above, 25) -N(R6)-(CH2)m-O-, in which m is the integer 2 or 3 and R6 is defined as above, 26) -N(R6)-N(R6)-, in which R6 is defined as above, 27) -N=N-, 28) -N(R6)-CH=N-, in which R6 is defined as above, 29) -N=CH-N(R6)-, in which R6 is defined as above, 30) -N(R6)-C(R7)=N-, in which R6 is defined as above and R7 is -NH-RS, : 31) -N=C(R7)-N(R6)-, in which R6 is defined as above and R7 is -NH-R6, or

32) -(C,-Cg)-alkynylene, ring1 ., ring2 and ring3 are identical or different and are, independently of ea«ch other, 1) covalent bond,

2) phenyl or naphthyl and are unsubstituted or substituted, independently of each other, once, twice or &hree times, by G, or

3) 4- to 15-membered Het ring, in which the Hest ring is a radical from the series acridinyl, azepinyl, aze tidinyl, aziridinyl,

benzimidazalinyl, benzimidazolyl, benzofuranyl, benzothiofuranyl, benzothiophenyl, benzoxazolyl, benzothiazolyl, benzotriazolyl, benzotetrazolyl, benzisoxazolyl, benzisothiazolyl, carbazolyl, 4aH-carbazolyl, carbolinyl, quinazolinyl, quinolinyl, 4H-quinolizinyl,

quinoxalinyl, quinuclidinyl, chromanyl, chro menyl, cinnolinyl, deca-hydroquinolinyl, dibenzofuranyl, d ibenzothiophenyl, dihydrofuran[2,3-b]tetrahydrofuranyl, dihydrofuranyl, dioxolyl, dioxanyl, 2H,6H-1,5,2-dithiazinyl, furanyl, furazanyl, imidazolidinyl, imidazolinyl, imidazolyl, 1H-irmdazolyl, indolinyl,

indolizinyl, indolyl, 3H-indolyl, isobenzofuraryl, isochromanyl, isoindazolyl, isoindolinyl, isoindolyl, isoquinolinyl (benzimidazolyl), isothiazolidinyl, 2-isothiazolinyl, isothiazolyl, isoxazolyl, isoxazolidinyl, 2-isoxazolinyl, = morpholinyl, naphthyridinyl, octahydroisoquinolinyl, ox adiazolyl, 1,2,3-

oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4- oxadiazoly!l, oxazolidinyl, oxazolyl, oxothiolanyl, pyrimidinyl, ® phenanthridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl, phenoxathiinyl, phenoxazinyl, phthalazinyl, piperaziny|, piperidinyl , pteridinyl, purinyl, pyranyl, pyrazinyl, pyroazolid inyl, pyrazolinyl, pyrazolyl, pyridaziny=l, pyridooxazzolyl, pyridoimidazolyl, pyridothiazoly=l, pyridothiophenyl, pyridinyl, pyridyl, pyrimidinyl, pyrrolidiny~l, pyrrolinyl, 2H-pyrrolyl, pyrrolyl, tetrahydrofurany~l, tetrahydro isoquinolinyl, tetrahydroquinolinyl, tetrahydro- pyridinyl, 6H-1,2,5-thiadazinyl, 1,2,3-thiadiazolyl, 1,2,4-thia- diazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, thianthreny~i, thiazolyl, thienyl, thienothiazolyl, thienooxazoly~l, : thienoimid azolyl, thiomorpholinyl, thiophenyl, triazinyl, 1,2,3- triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl arsd xanthenyl, and these radicals are unsubstituted ofr substituted, independently of each other, once, twice or three times, by G, ring4 is 1) -(Cs-Cra)-aryl, in which aryl is a radical from the series pheny~l, naphthyl, 1-naphthyl, 2-naphthyl, anthryl and fluorenyl, an d these radicals are unsubstituted or substituted, independently of each other, once, twice or three times, by G, 2) 4- to 15-mxembered Het ring, in which the Het ring is a radical from the series acridinyl, azepinyl, azetidinyl, aziridinyi, benzimida zalinyl, benzimidazolyl, benzofurany~l, benzothiofuranyi, benzothiophenyl, benzoxazoly-I, benzothia=olyl, benzotriazolyl, benzotetrazoly~l, benzisoxa=zolyl, benzisothiazolyl, carbazolyl, 4aH-carbazoly-l, carbolinyl, quinazolinyl, quinolinyl, 4H-quinoliziny1, quinoxalinyl, quinuclidinyl, chromanyl, chromenyl, cinnoliny=1, deca-hydroquinolinyl, dibenzofuranyl, dibenzothiopheny-l, dihydrofuran[2,3-b]tetrahydrofuranyl, dihydrofuranyl, dioxoly-l, dioxanyl, 2H,6H-1,5,2-dithiazinyl, furanyl, furazany-l, imidazolidi nyl, imidazolinyl, imidazolyl, 1H-indazolyl, indoliny-l, indoliziny!, indolyl, 3H-indolyl, isobenzofuranyl, isochromany-I, isoindazolwl, isoindolinyl, isoindolyl, isoquinolinyyl (benzimidaazolyl), isothiazolidinyl, 2-isothiazolinyl, isothiazoly-1, isoxazolyl, isoxazolidinyl, 2-isoxazolinyl, 2'-methylbiphenyl-2-

ol, morpholinyl, naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5- [ oxadiazolyl, 1,3,4-oxadiazolyl, oxazolidinyl, oxazolyl, oxothiolanyl, pyrimidinyl, phenanthridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl, phenoxathiiny!, phenoxazinyl, phthalazinyl, pipe razinyl, piperidinyl, pteridinyl, purinyl, pyranyl, pyrazinyl, pyroazolidinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridooxazolyl, pyridoimidazolyl, pyridothiazolyl, pyridothiophenyl, pyridinyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolinyl, 2H-pryrrolyl, pyrrolyl, tetrahydrofuranyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, tetrahydro- pyridinyl, 6H-1,2 5-thiadazinyl, 1,2,3-thiadiazolyl, 1,2,4-thia- diazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, thianthrenyl, : thiazolyl, thienwl, thienothiazolyl, thienooxazolyl, thienoimidazolyl, thwiomorpholinyl, thiophenyl, triazinyl, 1,2,3- triazolyl, 1,2,4-tria=zolyl, 1,2,5-triazolyl, 1,3,4-triazolyl and xanthenyl, and are unsubstituted or substituted, independently of each other, once, twice or three times, by G, or 3) is one of the following radicals H H and thesc radicals are unsubstituted or substituted once by G, Gis 1) hydrogen atom, 2) halogen, 3) =0, : 4) -(C1-Ce)-alky l, in which alkyl is unsubstituted or substituted, once, twice or three times, by halogen, -(C3-Cs)-cycloalkyl, -(C2-Cg)-alkynyl, -(Ce-Cis)-aryl or Het ring, whesre aryl and Het ring are defined as above, 5) -(Ce-C14)-aryll, where aryl is defined as above, 6) Het ring, where Het ring is defined as above, 7) -C(0)-0-R10», in which R10 is a) -(Cq-Ce»-alkyl, in which alkyl is unsubstituted or substitu ted, once or twice, by -(C3-Cg)-cycloalkyl,

-(C2-Ce)-alkynyl, -(Ce-C14)-aryl or Heat ring, where aryl and Het ring are defined as abowe, or ( b) -(Ce-Cua)-aryl or Het ring, where aryl and Het ring are defined as above, 8) -C(8)-0-R10, where R10 is defined as abowe, 9) -C(O)-NH-R11, in which R11 is a) -(C4+-Cg)-alkyl, in which alkyl is unsubstituted or substituted, once or twice, by -(C3-Cs)-cycloalkyl, -(C2-Ce)-alkynyl, -(C¢-C14)-ary! or Heat ring, where aryl and Het ring are defined as abowe, or b) -(Ce-C14)-aryl or Het ring, where aryl and Het ring are defined as above,

10) -C(S)-NH-R11, in which R11 is defined as above, : 11) -O-R12, in which R12 is a) hydrogen atom,

b) -(C+-Ce)-alkyl, in which alkyl is unsubstituted or substituted, once, twice or three times, by halogen, -(C;-Cs)-cycloalkyl, -(C2-Ce)-alkynyl, - (Cs-C1a)-aryl or Het ring, where aryl and Het ring are defined as above,

c) -(Ce-C14)-aryl, where aryl is defined as above,

d) Het ring, where Het ring is defined as above,

e) -C(0)-0-R13, in which R13 is e)l ) -(C4-Ce)-alkyl, in which alkyl is unsubstituted or substituted, once or twice, by -(C3-Ce)-cycloalkyl, -(C2-Ce)- alkynyl, -(Ce-C14)-aryl, or Hest ring, where aryl and Het ring are defined as above, or

€)2) -(Ce-Cis)-aryl or Het ring, where aryl and

Het ring are defined as abowe,

f) -C(S)-0-R13, in which R13 is defined as above,

a) -C(O)-NH-R14, in which R14 is a) -(C+-Ce)-alkyl, in which alkyl is unsubstituted or substituted, once or twice, by -(C3-Cs)-cycloalkyl, -(C2-Cg)- alkynyl, -(Ce-C1s)-aryl or Heat ring, where aryl and Het ring are defined as above, or g)2) -(Ce-Cis)-aryl or Het ring, where aryl and Het ring are defined as abowe, or h) -C(S)-NH-R14, in which R14 is defined as above, 12) -C(0)-R10, in which R10 is defined as above, C 13) -S(0),-R12, in which R12 is defined as above and p is the integers zero, 1 or 2, 14) -NO,, 15) -CN, or 16) -N(R15)-R12, in which R15 is 16)1) hydrogen atom, 16)2) -(C4-Cg)-alkyl or 16)3) -SO,-(C4-Ce)-alkyl, in which alkyl is unsubstituted or substituted, once or twice, by -(C3-Ce)-cycloalkyl, - (C2-Cs)-alkynyl, -(Cs-C1a)-aryl or Het ring, and R12 is defined as above, : 17) -S0,-N(R12)-R1, in which R12 is defined as above and R1 is defined as below, Xis -OH or -NH-OH, n1tis the integer 1 or 2, n2 is the integer 2 or 3, R1, R2, R3, R4 and R5 are identical or differe nt and are, independently of each other, 1) hydrogen atom, 2) -(C+-Ce)-alkyl, in which alkyl is unsubstituted o r substituted, once or twice, by -(C3-Ce)-cycloalkyl, -(C2-Cs)-alkynyl, -(Ce- Cia4)-aryl or Het ring, 3) -C(0)-0O-R8, in which R8 is 3)1) hydrogen atom, 3)2) -(C+-Ce)-alkyl, in which alkyl is unsubstituted or substituted, once or twice, by -(C3-Cg)-cycloalkyl, -(Co-Ce)-alkynyl, -(Ce-Cia)-aryl or Het ring, or is substituted once to five times by fluorine, or 3)3) -(Ce-C1s)-aryl or Het ring, 4) -0-R8, in which R8 has the abovementioned meaning, or 5) -(C3-Cg)-cycloalkyl.

3. A compound of the formula | as claimed in claim 1 or 2, wherein Ais -(Cy-Cs)-alkylene, B, DD and E are identical or different and are, independently of each othesr, -(Co-Cq4)-alkylene or the radical -B1-B2-B3- in which B1is -(CHz).-, in which n is the integer zero, 1 or 2,

B3is -(CHz)m-, in which m is the integer zero, 1 or 2, with the proviso that the sum of n and m amounts to zero, 1 or 2, ® and B2is 1) -(Co-C2)-alkylene, 2) ethenylene, 3) ethynylene, 4) -C(O)- 5) -N(R6)-C(O)-, in which R6 is hydrogen atom, methyl or ethyl, 6) -C(O)-N(R6)-, in which R6 is defined as above, 7) -O-, or 8) -S-, ring1, ring2 and rimg3 are identical or different and are, independently of each other, 1) covalent bond, 2) phenyl or naphthyl and are unsubstituted or substituted, independently off each other, once or twice, by G, or 3) Het ring, in whi ch the Het ring is a radical from the series dihydrofuranyl, furanyl, pyridinyl, pyrimidinyl, pyrrolyl, thiadiazolyl, thiaazolyl or thiophenyl, and the radicals are unsubstituted ow substituted, independently of each other, once or twice, by G, ring4 is 1) phenyl or naphthyl and is unsubstituted or substituted, independently of each other, once or twice, by G,

2) Het ring, in which the liet ring is a radical from the series benzofuranyl, dihydrofuranyl, dibenzofuranyl, dibenzothiopherwyl, furanyl, 2'-methylbiphenyl-2-ol, morpholinyl, piperazinyl, piperidinyl, pyridinyl, pyrimidinyl,

pyridothiophenyl , pyrrolyl, pyrrolidinyl, thiazolyl or thiophenyl and is unsubstituted or substituted, independently of each other, once or twice, by G, or

3) the following rad ical

OTTO and this radical iss unsubstituted or substituted once by G,

Gis 1) hydrogen atom, 2) Br, Clor F, ® 3) -(C4-Cy)-alkyl, im which alkyl is unsubstituted or substituted once or twice by F, phenyl, -Cs-cycioalkyl or Het ring, where Het ring is defined as above, 4) phenyl, 5) Het ring, where Het ring is defined as above, 6) -C(0)-0-R10, in which R10 is a) -(C4-Cs)-alkwyl, in which alkyl is unsubstituted or substituted, once or twice, by cyclopropyl, phenyl or Het ring, where Het ring is defined as above, b) phenyl, or Cc) Het ring, wheere Het ring is defined as above, 7) -C(O)-NH-R11, in which R11 is a) -(C1-Ce)-alkwyl, in which alkyl is unsubstituted or substituted, once or twice, by cyclopropyl, phenyl or Het ring, where Het ring is defined as above, b) phenyl, or c) Het ring, wheere Het ring is defined as above, 8) -0-R12,in which R12 is a) hydrogen atom,

b) -(C1-Ce)-alkwyl, in which alkyl is unsubstituted or substituted, once, twice or three times, by halogen, cysclopropyl, phenyl or Het ring, where

Het ring is dlefined as above,

Cc) phenyl,

d) Het ring, whaere Het ring is defined as above,

e) -C(0)-0O-R1 3, in which R13 is e)l) -(C+-Ce)-alkkyl, in which alkyl is unssubstituted or substituted, once or twice, by cyclopropyl, phenyl or Het ring, where Het ring is defined as above, or e)2) phenyl or Het ring, where Het ring is defined as above,

f) -C(S)-0-R13, in which R13 is defined as above,

or a) -C(O)-NH-R:14, in which R14 is g)t) -(C4-Cg)-alkkyl, in which alkyl is unssubstituted or substituted, once or twice, by phenyl or Het ring, where Het ring is defined as above, or ¢ a)2) phenyl or Het ring, where Het ring is defined as above, 9) -C(0)-R10, in which R10 is defined as above, 10) -S(O),-R12, in which R12 is defined as above a nd p is the integers 1 or 2, 11) -NO., 12) -CN, or 13) -N(R15)-R12, in which R15 is 13)1) hydrogen atom, or 13)2) -(C4-Ce)-alkyl and R12 is defined as above , Xis -OH or -NH-OH, n1is the integer 1 or 2, n2is the integer 2 or 3, R1, R2 and R3 are in each case hydrogen atom, R4 and R5 are identical or different and are, independently of each other, 1) hydrogen atom, 2) methyl, 3) ethyl, or 4) -OH.
4. A cornpound of the formula | as claimed in one or more of claims 1 to 3, wherein Ais -(Co-Cs)-alkylene, B, D and E are identical or different and are, independently of each other, -(Co-C4)-alkylene or the radical -B1-B2-B3- in which B1is -(CH2).-, in which n is the integer zero, 1 or 2, B3is -(CH2)m-, in which m is the integer zero, 1 or 2, with the proviso that the sum of n and m amounts to zero, 1 or 2, and B2is 1) -(Co-Cp)-alkylene, 2) ethenylene, or 3) ethynylene, ring1, ring2 and ring3 are identical or different and are, indepesndently of each other, 1) covalent bond,

a) -(C1-Csq)-alkyl, in which alkyl is unsubstituted or substituted, once or twice, by cyclopropyl, phenyl ® or Het ring, where Het ring is defined as above, b) phenyl or naphthyl, or c) Het ring, where Het ring is defined as above, 8) -0O-R12,in which R12 is a) hydrogen atom, b) -(C1=Ce)-alkyl, in which alkyl is unsubstituted or substituted, once, twice or three times, by halo gen, cyclopropyl, phenyl or Het ring, where Het ring is defined as above, c) phenyl, d) Het ring, where Het ring is defined as above, e) -C(O)-0-R13, in which R13 is e)1) -(C1-Ce)-alkyl, in which alkyl is unsubstituted or substituted, once or twice, by cyclopropyl, phenyl, naphthyl, or Het ring, where Het ring is defined as above, or e)2) phenyl or Het ring, where Het ring is defined as above, f) -C(S)-0-R13, in which R13 is defined as above, or g) -C(O)-NH-R14, in which R14 is g)1) -(C1-Ce)-alkyl, in which alkyl is unsubstituted or substituted, once or twice, by phenyl or Het ring, where Het ring is defined as above, or g)2) phenyl or Het ring, where Het ring is defined as above, 9) -C(0O)-R10, in which R10 is defined as above, 10) -S(0),-R12Z, in which R12 is defined as above and p is the integers 1 or 2, 11) -NO., 12) -CN, or 13) -N(R15)-R12, in which R15 is 13)1) hydrogen atom, or 13)2) -(C41~Ce)-alkyl and R12 is defined as above, Xis -OH or -NH-OH,

n1is the integer 2, n2 is the integer 3, ® R1, R2, R3, R4 and R5 are in each case hydrogen atom.
5. A compound of the formula | as claimed in one or more of claims 1 to 4, wherein Ais a covalent bond or —CH>-CHo-, B, D and E are identical or different and are, independently of each other, -(Co-C4)-alkylene or the radicaal -B1-B2-B3- in which B1is -(CH2),-, in which n is the integer zero, 1 or 2, B3is -(CH2)m- in which m is the imteger zero, 1 or 2, with the proviso that the sum of n an d m amounts to zero, 1 or 2, and B2is : 1) -C(O)- 2) -(C2-C4)-alkynylene, 3) -S(0)o-, where o is the integgers zero or 1, 4) -N(R6)-C(Y)-, in which Y is oxygen atom and R6 is hydrogen atom, 5) -C(Y)-N(R6)-, in which Y is oxygen atom and R6 is hydrogen atom, or 6) -O-, ring1, ring2 and ring3 are identical or different and are, independently of each other, 1) covalent bond, 2) phenyl and are unsubstituted or substituted, independently of each other, once or twice, bey G, or 3) Het ring, in which the Het ring is a radical from the series furanyl, pyridinyl, pyrimidinyl or thiophenyl, and are unsubstituted or substituteed, independently of each other, once or twice, by G, ring is 1) phenyl and is unsubstituted or substituted, independently of each other, once or twice, bey G, 2) Het ring, in which the Het ring is a radical from the series benzofuranyl, dibenzofuran yl, furanyl, 2’-methylbiphenyl-2-ol, morpholinyl, piperazinyl, ppiperidinyl, pyridinyl, pyrimidinyl, pyridothiophenyl, pyrrolyl, pyrrolidinyl, thiazolyl or thiophenyl and is unsubstituted or substituted, independently of each other, once or twice, by G, or

3) the following radical ° Eye 0 N Oo and this radical is unsubstituted or substituted once by G, Gis 1) hydrogen atom,

2) Br, ClorF,

3) -(C1-Cy4)-alkyl, in which alkyl is unsubstituted or substituted once, twice or three times, by Br, CI, F, -Cs- cycloalkyl, phenyl or Het ring, where Het ring is defined as above,

4) phenyl,

5) Hetring, where Het ring is defined as above,
6) -C(0)-0-R10, in which R10 is a) -(C4+-Ce)-alkyl, in vwhich alkyl is unsubstituted or substituted, once or twice, by cyclopropyl, phenyl or Het ring, where Het ring is defined as above,

b) phenyl, or c) Hetring, where He tring is defined as above,
7) -C(0)-NH-R11, in which R11 is a) -(C+-Ce)-alkyl, in vwhich alkyl is unsubstituted or substituted, once or twice, by cyclopropyl, phenyl or Het ring, where Het ring is defined as above,

b) phenyl, or c) Hetring, where ie tring is defined as above,
8) -0-R12, in which R12 is a) hydrogen atom,

b) -(C+-Cs)-alkyl, in vvhich alkyl is unsubstituted or substituted, once, twice or three times, by halogen, cyclopropyl, phenyl or Het ring, where

Het ring is defined as above,

c) phenyl,

d) Hetring, where He tring is defined as above,

e) -C(0)-0-R13, in which R13 is e)1) -(C+-Ce)-al kyl, in which alkyl is unsubstituted or substituted, once or twice, by cyclopropyl, phenyl or Het ring, where Het ring is defined as above, or e)2) phenyl or Het rings, where Het ring is defined as above, ® f) -C(S)}-0-R13, in which R13 is defined as above, or g) -C(O)-NH-R14, in which R14 is gy) -(C1-Ce)-alkyl, in which alkyl is unsubstituted or substituted, once or twice, by phenyl or Het ring, where Het ring is defined as above, or g)2) phenyl or Het ring, where Het ring is defined as above, 9) -C(O)-R10, in which R10 is defined as above, 10) -S(0),-R12, in which R12 is defined as above and p is : the integers zero, 1 or 2, 11) -NO,, 12) -CN, or 13) -N(R15)-R12, in which R15 is 13)1) hydrogen atom, or 13)2) -(C4-Cg)-alkyl and R12 is defined as above, Xis -NH-OH, n1is the integer 2, n2is the integer 3, and R1, R2, R3, R4 and R5 are in each case hydrosgen atom.

6. A compound of the formula | as claimed in orme or more of claims 1 to 5, which is a compound from the series 2-(4’-nitrobiphenyl-4-sulfonyl)decahydroisoquiroline-1-(N- hydroxy)carboxamide, 2-(4'-chlorobiphenyl-4-sulfonyl)decahydroisoquiinoline-1-carboxylic acid, 2-(4'-chlorobiphenyl-4-sulfonyl)decahydroisogquiinoline-1-(N- hydroxy )carboxamide, 2-(6-phenoxypyridine-3-sulfonyl)decahydroisoquinoline-1-carboxylic acid; trifluoroacetate, 2-(6-phenoxypyridine-3-sulifonyl)decahydroisocqquinoline-1-(N- hydroxy)carboxamide; trifluoroacetate, 2-[2-(4'-chlorobiphenyl-4-yl)ethanesulfonyllJdeccahydroisoquinoline-1- carboxylic acid, /

2-[2-¢4'-chlorobiphenyl-4-yl)ethanesulfonylldecahydroisoquineline-1- (N-hy/droxy)carboxamide,

C 2-[4-(pyridin-4-yloxy)benzenesulfonylldecahydroisoquinoline- 1- carboxylic acid; trifluoroacetate,

2-[4-(pyridin-4-yloxy)benzenesulfonyljdecahydroisoquinoline—1-(N- hydroxy)carboxamide; trifluoroacetate, 2-[4-q4-methoxyphenoxy)benzenesulfonylldecahydroisoquinoline-1- carboxylic acid, 2-[4-(4-methoxyphenoxy)benzenesulfonyl]decahydroisoquincline-1-

(N-hwdroxy)carboxamide,

2-{4- [4-(2,2,2-trifluoroethoxy)phenoxy]benzenesulfonyl}decatydro- isoquiinoline-1-carboxylic acid, 2-{4-[4-(2,2,2-trifluoroethoxy)phenoxy]benzenesulfonyl}decatydro- isoquiinoline-1-(N-hydroxy)carboxamide,

2-[4'=(2,2,2-trifluoroethoxy)biphenyl-4-sulfonylldecahydroiso- quinoline-1-carboxylic acid, 2-(4'-isopropoxycarbonylaminobiphenyl-4-sulfonyl)decahydroiso- quinoline-1- carboxylic acid,

[4'-(1 -hydroxycarbamoyloctahydroisoquinoline-2-sulfonyl)biphhenyl-4-

yl]ca rboxamide isopropyl! ester, 2-[4'-(2,2,2-trifluoroethoxy)biphenyl-4-sulfonyl]decahydroiso- quinoline-1-(N-hydroxy)carboxamide,

2-(4' -trifluoromethoxybiphenyl-4-sulfonyl)decahydroisoquinol ine-1- (N-hydroxy)carboxamide,

2-[4—(4-fluorophenoxy)benzenesulfonylldecahydroisoquinolirme-1-(N- hydroxy)carboxamide, 2-[4—(4-trifluoromethoxyphenoxy)benzenesulfonylldecahydro iso- quin oline-1-(N-hydroxy)carboxamide, 2-[4—(4-trifluoromethoxyphenoxy)benzenesulfonylldecahydrosiso-

quin oline-1- carboxylic acid, 2-(biiphenyl-4-sulfonyl)decahydroisoquinoline-1 -(N-hydroxy)car- boxamide, 2-(biiphenyl-4-sulfonyl)decahydroisoquinoline-1-carboxylic acid, 2-[4~(4-cyanophenoxy)benzenesulfonylldecahydroisoquinolirie-1-(N-

hydroxy)carboxamide,

2-(d ibenzofuran-2-sulfonyl)decahydroisoquinoline-1-carboxy-lic acid, 2-(d ibenzofuran-2-sulfonyl)decahydroisoquinoline-1-(N-hydreoxy)car- boxamide, or A

2-[4-(4-fluorophenoxy)beanzenesulfonyl]-6-methoxydecahydroiso- quinoline-1-(N-hydroxy)carboxamide, and also all the isomeric forms ( of the abovementioned compounds.

7. A process for preparing the compound of the formula | as claimed in one or more of claims 1 &o 6, which comprises a) reacting a compowund of the formula IV, 0) n2\R2 Re 0) SE (Iv) R5 R3 in which Re is a hydroge=n atom or an ester-protecting group, with a compound of the ®ormula V, 2 Rz—S— A —Ting,——B—ring;~D—rings~E ring, (V) @) in which A, B, D, E and rring1, ring2, ring3 and ring4 are defined as in formula |, and in which Rz is chlorine atom, imidazoyl or OH, in the presence of a base or following silylation with a suitable silylating agent, or usin g a suitable dehydrating agent when Rz = OH, to give a compound of the formula VI, n2 'e) R2 \ Re oO R4 N 0 ' . R5R3 $— A ——ring,—B—ring;—D——ring;"E—ring, (V1) oO in which A, B, D, E, Re and ring1, ring2, ring3 and ring4 are defined as above, or b) when Re = ester reacting a compound of the formula Vi prepared as described in a) with a solution of alkali such as NaOH or ( LiOH, and then treating the prod uct with acid, to give the carboxylic acid according to the invention of the formula |, in which X = OH (corresponding to VII), with modifications in one of the side chains of the rings ring1-ringd also having previously been made, where appropriate; or converting said ester, by treating it with a mineral acid, such as hydrochloric acid, into the free carboxylic acid VII n2 0 - ry ~OH R4 : N, 0 . . R5R3 8— A—ring,— BB—ring;-D—ring;-E—ring, (vi) O and then converting this into the hydroxamic acid according to the invention, in which X = NH-OH, of the formula |, or c) using salt formation wit h enantiomerically pure acids or bases, chromatography on chiral stationary phases, or derivatization with chiral, enantiomerically pure compounds such as amino acids, separation of the resulting diastereomers and elimination of the chiral auxiliary groups, to separate a compound of formula prepared as described in procedure a), or a suitable precursor of the formula |, which arises in enantiomeric forms due to its chemical structure, into the pure enantiomeers, or d) either isolating the comp ound of the formula | prepared as described in procedures b) or c) in free form, or, when acid or basic groups are present, converting it into physiologically tolerated salts.

8. A pharmaceutical, which comprises an effective content of at least one compound of the formula | a s claimed in one or more of claims 1 to 6 together with a pharmaceutically suitable and physiologically tolerated carrier substance, additive and/or other active compounds and auxiliary substances.
9. The use of the compound of formula | as claimed in one or more of ® claims 1 to 6 for producing a pharmaceutical for the prophylaxis and therapy of degenerative joint diseases such &s osteoarthroses, spondyloses and chondrolysis following joint traurma or a relatively long period of joint immobilization following meniscus injuries or patella injuries or ligament ruptures, diseases of the connective tissue such as collagenoses, periodontal diseases, wound healing disturbances and chronic diseases of the locomoteory apparatus such as inflammatory, immunologically determined or metabolism- determined acute and chronic arthritides, arthropathies, myalgias and disturbances of bone metabolism, for the treatment of ulceration, atherosclerosis and stenoses, for the treatment of : inflammations, cancer diseases, tumor metastases formation, cachexia, anorexia, heart failure and septic shock, or for the prophylaxis of myocardial and cerebral infarctions -