Oxa-and thiadiazoles and their use as metalloproteinase inhibitors

1. A compound formula (IA) or (IB)

wherein

W represents HO(C═O)—, HONH(C═O)— or H(C═O)N(OH)—;

X represents —O— or —S—;

R 1 represents

hydrogen;

—OH or —SH;

fluoro or chloro;

—CF 3 ;

(C 1 -C 6 )alkyl;

(C 1 -C 6 )alkoxy;

(C 2 -C 6 )alkenyl; phenyl or substituted phenyl;

phenyl (C 1 -C 6 )alkyl or substituted phenyl(C 1 -C 6 )alkyl;

phenyl (C 2 -C 6 )alkenyl or substituted phenyl(C 2 -C 6 )alkenyl heterocyclyl or substituted heterocyclyl;

heterocyclyl(C 1 -C 6 )alkyl or substituted heterocyclyl(C 1 -C 6 )alkyl;

a group BSO n A- wherein n is 0, 1 or 2 and B is hydrogen or a (C 1 -C 6 )alkyl, phenyl, substituted phenyl, heterocyclyl, substituted heterocyclyl, (C 1 -C 6 )acyl, phenacyl or substituted phenacyl group, and A represents (C 1 -C 6 )alkylene;

—NH 2 , (C 1 -C 6 )alkylamino or di(C 1 -C 6 )alkylamino;

amino(C 1 -C 6 )alkyl, (C 1 -C 6 )alkylamino(C 1 -C 6 )alkyl, di(C 1 -C 6 )alkylamino(C 1 -C 6 )alkyl, hydroxy(C 1 -C 6 )alkyl, mercapto(C 1 -C 6 )alkyl or carboxy(C 1 -C 6 )alkyl wherein the amino-, hydroxy-, mercapto- or carboxyl-group are optionally protected or the carboxyl-group amidated; or

a cycloalkyl, cycloalkenyl or non-aromatic heterocyclic ring containing up to 3 heteroatoms, any of which may be (i) substituted by one or more substituents selected from C 1 -C 6 alkyl, C 2 -C 6 alkenyl, halo, cyano (—CN), —CO 2 H, —CO 2 R, —CONH 2 , —CONHR, —CON(R) 2 , —OH, —OR, oxo-, —SH, —SR, —NHCOR, and —NHCO 2 R wherein R is C 1 -C 6 alkyl or benzyl and/or (ii) fused to a cycloalkyl or heterocyclic ring;

R 2 represents a group R 10 —(X 1 ) p -(ALK) m - wherein

R 10 represents hydrogen, or a C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, cycloalkyl, aryl, or heterocyclyl group, any of which may be unsubstituted or substituted by (C 1 -C 12 )alkyl, (C 1 -C 12 )alkoxy, hydroxy, mercapto, (C 1 -C 12 )alkylthio, amino, halo (including fluoro, chloro, bromo and iodo), trifluoromethyl, cyano, nitro, oxo, —COOH, —CONH 2 , —COOR A , —NHCOR A , —CONHR A , —NHR A , —NR A R B , or —CONR A R B wherein R A and R B are independently a (C 1 -C 12 )alkyl group and

ALK represents a straight or branched divalent C 1 -C 6 alkylene, C 2 -C 6 alkenylene, or C 2 -C 6 alkynylene radical, and may be interrupted by one or more non-adjacent —NH—, —O— or —S-linkages,

X 1 represents —NH—, —O— or —S—, —NR c or —NCOR c wherein R c is a (C 1 -C 12 )alkyl group, and

m and p are independently 0 or 1;

R 3 is C 1 -C 6 alkyl, phenyl, 2, 3-, or 4-pyridyl, 2- or 3-thienyl, 2-, 3-, or 4-hydroxyphenyl, 2-, 3-, or 4-methoxyphenyl, 2, 3-, or 4-pyridylmethyl, benzyl, 2, 3-, or 4-hydroxybenzyl, 2-, 3-, or 4-benzyloxybenzyl, 2-, 3-, or 4-C 1 -C 6 alkoxybenzyl, or benzyloxy(C 1 -C 6 alkyl)-; or

the characterizing group of a natural α-amino acid, in which any functional group may be protected, any amino group may be acylated and any carboxyl group present may be amidated; or

a group -[Alk] n R 6 where Alk is a C 1 -C 6 )alkyl or C 2 -C 6 )alkenyl group optionally interrupted by one or more —O—, or —S— atoms or —N(R 7 ) groups [where R 7 is a hydrogen atom or a (C 1 -C 6 )alkyl group], n is 0 or 1, and R 6 is an optionally substituted cycloalkyl or cycloalkenyl group; or

a benzyl group substituted in the phenyl ring by a group of formula —OCH 2 COR 8 where R 8 is hydroxyl, amino, (C 1 -C 6 )alkoxy, phenyl(C 1 -C 6 )alkoxy, (C 1 -C 6 )alkylamino, di((C 1 -C 6 )alkyl)amino, phenyl(C 1 -C 6 )alkylamino, the residue of an amino acid or acid halide, ester or amide derivative thereof, said residue being linked via an amide bond, said amino acid being selected from glycine, α or β alanine, valine, leucine, isoleucine, phenylalanine, tyrosine, tryptophan, seine, threonine, cysteine, methionine, asparagine, glutamine, lysine, histidine, arginine, glutamic acid, and aspartic acid; or

a heterocyclic(C 1 -C 6 )alkyl group, either being unsubstituted or mono- or di-substituted in the heterocyclic ring with halo, nitro, carboxy, (C 1 -C 6 )alkoxy, cyano, (C 1 -C 6 )alkanoyl, trifluoromethyl (C 1 -C 6 )alkyl, hydroxy, formyl, amino, (C 1 -C 6 )alkylamino, di-(C 1 -C 6 )alkylamino, mercapto, (C 1 -C 6 )alkylthio, hydroxy(C 1 -C 6 )alkyl, mercapto(C 1 C 6 )alkyl or C 1 -C 6 )alkylphenylmethyl; or

a group —CR a R b Rc in which;

each of R a , R b and R c is independently hydrogen, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 9 -C 6 )alkynyl, phenyl(C 1 -C 6 )alkyl, (C 3 -C 8 )cycloalkyl; or

R c is hydrogen and R a and R b are independently phenyl or heteroaryl such as pyridyl; or

R c is hydrogen, (C 1 -C 6 )alkyl, (C 9 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, phenyl(C 1 -C 6 )alkyl, or (C 3 -C 8 )cycloalkyl, and R a and R b together with the carbon atom to which they are attached form a 3 to 8 membered cycloalkyl or a 5- to 6-membered heterocyclic ring;

or R a , R b and R c together with the carbon atom to which they are attached form a tricyclic ring (for example adamantyl); or

R a and R b are each independently (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, phenyl(C 1 -C 6 )alkyl, or a group as defined for R c below other than hydrogen, or R a and R b together with the carbon atom to which they are attached form a cycloalkyl or heterocyclic ring, and R c is hydrogen, —OH, —SH, halogen, —CN, —CO 2 H, (C 1 -C 4 )perfluoroalkyl, —CH 2 OH, —CO 2 (C 1 -C 6 )alkyl, —O(C 1 -C 6 )alkyl, —O(C 2 -C 6 )alkenyl, —S(C 1 -C 6 )alkyl, —SO(C 1 -C 6 )alkyl, —SO 2 (C 1 -C 6 ) alkyl, —S(C 2 -C 6 )alkenyl, —SO(C 2 -C 6 )alkenyl, —SO 2 (C 2 -C 6 )alkenyl or a group -Q-W wherein Q represents a bond or —O—, —S—, —SO— or —SO 2 — and W represents a phenyl, phenylalkyl, (C 3 -C 8 )cycloalkyl, (C 3 -C 8 )cycloalkylalkyl, (C 4 -C 8 )cycloalkenyl, (C 4 -C 8 )cycloalkenylalkyl, heteroaryl or heteroarylalkyl group, which group W may optionally be substituted by one or more substituents independently selected from, hydroxyl, halogen, —CN, —CO 2 H, —CO 2 (C 1 -C 6 )alkyl, —CONH 2 , —CONH(C 1 -C 6 )alkyl, —CONH(C 1 -C 6 alkyl) 2 , —CHO, —CH 2 OH, (C 1 -C 4 )perfluoroalkyl, —O(C 1 -C 6 )alkyl, —S(C 1 -C 6 )alkyl, —SO(C 1 -C 6 )alkyl, —SO 2 (C 1 -C 6 )alkyl,

—NO 2 , —NH 2 , —NH(C 1 -C 6 )alkyl, —N((C 1 -C 6 )alkyl) 2 , —NHCO(C 1 -C 6 )alkyl, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 1 -C 6 )alkynyl, (C 3 -C 6 )cycloalkyl, (C 4 -C 8 )cycloalkenyl, phenyl or benzyl;

R 4 represents optionally substituted

C 1 -C 6 alkyl,

C 2 -C 6 alkenyl,

C 2 -C 6 alkynyl,

C 1 -C 3 perfluoroalkyl,

cycloalkyl,

cycloalkyl(C 1 -C 6 alkyl),

cycloalkenyl,

cycloalkenyl(C 1 -C 6 alkyl)-,

phenyl,

phenyl(C 1 -C 6 alkyl)-,

naphthyl,

non-aryl heterocyclyl,

non-aryl heterocyclyl (C 1 -C 6 )alkyl-,

heteroaryl; or

heteroaryl(C 1 -C 6 alkyl)-;

or a pharmaceutically acceptable salt, hydrate or solvate thereof.

2. A compound as claimed in claim 1 wherein the compound has formula (IA).

3. A compound as claimed in claim 1 wherein the compound has formula (IB).

4. A compound as claimed in claim 1 wherein W is HONH(C═O)—.

5. A compound as claimed in claim 1 wherein X is —O—.

6. A compound as claimed in claim 1 wherein R 1 is hydrogen, hydroxy, fluoro, chloro, methyl, methoxy, trifluoromethyl, ethyl, n-propyl, allyl, phenylpropyl, cyclopropylmethyl, phenylprop-2-enyl, thienylsulphanylmethyl, thienylsulphinylmethyl, or thienylsulphonylmethyl; or

C 1 -C 4 alkyl, methyl, ethyl n-propyl or n-butyl, substituted by a phthalimido, 1,2-dimethyl-3,5-dioxo-1,2,4-triazolindin-4-yl, 3-methyl-2,5-dioxo-1-imidazolidinyl, 3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl, 2-methyl-3,5-dioxo-1,2,4-oxadiazol-4-yl, 3-methyl-2,4,5-trioxo-1-imidazolidinyl, 2,5-dioxo-3-phenyl -1-imidazolidinyl, 2-oxo-1-pyrrolidinyl, 2,5-dioxo-1-pyrrolidinyl or 2,6-dioxopiperidinyl, 5,5-dimethyl-2,4-dioxo-3-oxazolidinyl, hexahydro-1,3-dioxopyrazolo[1,2,a][1,2,4]-triazol-2-yl, or a naphththalimido (1,3-dihydro-1,3-dioxo-2H-benz[f]isoindol-2-yl), 1,3-dihydro-1-oxo-2H-benz[f]isoindol-2-yl, 1,3-dihydro-1,3-dioxo-2H-pyrrolo[3,4-b]quinolin-2-yl, or 2,3-dihydro -1,3-dioxo-1H-benz[d,e]isoquinolin-2-yl group; or

cyclohexyl, cyclooctyl, cycloheptyl, cyclopentyl, cyclobutyl, cyclopropyl, tetrahydropyranyl or morpholinyl.

7. A compound as claimed in claim 1 wherein R 1 is hydrogen, hydroxy, C 2 -C 4 alkenyl or C 1 -C 4 alkoxy.

8. A compound as claimed in claim 1 wherein R 1 is hydrogen, hydroxy, fluoro, methoxy, cyclopentyl, n-propyl, or allyl.

9. A compound as claimed in claim 1 wherein R 2 is C 1 -C 12 alkyl, C 3 -C 6 alkenyl or C 3 -C 6 alkynyl;

cycloalkyl(C 1 -C 6 alkyl)-;

phenyl(C 1 -C 6 alkyls, phenyl(C 3 -C 6 alkenyl)- or phenyl(C 3 -C 6 alkynyl)- optionally substituted in the phenyl ring;

heteroaryl(C 1 -C 6 alkyl)-, heteroaryl(C 3 -C 6 alkenyl)- or heteroaryl(C 3 -C 6 alkynyl)- optionally substituted in the heteroaryl ring;

4-phenylphenyl(C 1 -C 6 alkyl), 4-phenylphenyl(C 3 -C 6 alkenyl)-, 4-phenylphenyl(C 3 -C 6 alkynyly, 4-heteroarylphenyl(C 1 -C 6 alkyl)-, 4-heteroarylphenyl(C 3 -C 6 alkenyl), 4-heteroarylphenyl(C 3 -C 6 alkynyl)-, optionally substituted in the terminal phenyl or heteroaryl ring;

or phenoxy(C 1 -C 6 alkyl)- or heteroaryloxy(C 1 -C 6 alkyl)- optionally substituted in the phenyl or heteroaryl ring.

10. A compound as claimed in claim 1 wherein R 2 is methyl, ethyl, n- or iso-propyl, n-, iso- or tert-butyl, n-phenyl, n-hexyl, n-heptyl, n-nonyl, n-decyl, prop-2-yn-1-yl, cyclohexylethyl, cyclopentylmethyl, 3-phenylprop-2-yn -1-yl, 3-(2-chlorophenyl)prop-2-yn -1-yl, benzyl phenylpropyl, 4-chlorophenylpropyl, 4-methylphenylpropyl, 4-methoxyphenylpropyl, phenoxybutyl, 3-(4-pyridylphenyl)propyl-, 3-(4-(4-pyridyl)phenyl)prop-2-yn-1-yl, 3-(4-phenylphenyl)propyl-, 3-(4-phenyl)phenyl)prop-2-yn-1-yl or 3-[(4-chlorophenyl)phenyl]propyl-.

11. A compound as claimed in claim 1 wherein R 2 is C 1 -C 4 alkyl, 3-8 membered cycloalkyl-C 1 -C 4 alkyl- optionally containing 1-3 heteroatoms in the ring selected from N, O and S, or aryl-C 1 -C 4 alkyl.

12. A compound as claimed in claim 1 wherein R 2 is benzyl, n-butyl, iso-butyl, n-hexyl, cyclopentylmethyl, 4-ethoxyphenylpropyl or phenylpropyl.

13. A compound as claimed in claim 1 wherein R 3 is benzyl, phenyl, cyclohexylmethyl, pyridin-3-ylmethyl, tert-butoxymethyl, iso-propyl, iso-butyl, sec-butyl, tert-butyl, 1-benzylthio-1-methylethyl, 1-methythio-1-methylethyl, or 1-mercapto-1-methylethyl.

14. A compound as claimed in claim 1 wherein R 3 is (C 1 -C 4 )alkyl or aryl- is (C 1 -C 4 )alkyl.

15. A compound as claimed in claim 1 wherein R 3 is benzyl, tert-butoxymethyl, iso-propyl, tert-butyl, or iso-butyl.

16. A compound as claimed in claim 1 wherein R 4 is optionally substituted (C 1 -C 6 )alkyl; (C 3 -C 8 )cycloalkyl; phenyl; monocyclic heterocyclic; or monocyclic heteroaryl.

17. A compound as claimed in claim 1 wherein R 4 is C 1 -C 4 alkyl; heteroaryl; 3-8 membered cycloalkyl optionally containing 1-3 heteroatoms in the ring selected from N, O and S; or heteroaryl-C 1 -C 4 alkyl.

18. A compound as claimed in claim 1 wherein R 4 is optionally substituted methyl, ethyl, n- or iso-propyl, prop-2-yl, tert-butyl, cyclopropyl, cyclopentyl; phenyl; morpholino; thienyl or furanyl.

19. A compound as claimed in claim 2 wherein R 1 is —OH; W is —C(═O)NHOH, X is —O— and R 3 is tert-butyl.

20. A compound as claimed in claim 2 wherein R 1 is —OH; W is —C(═O)NHOH, X is —O—, R 3 is tert-butyl, and R 2 is C 1 -C 12 alkyl, or phenyl(C 1 -C 12 alkyl)- or heteroaryl(C 1 -C 6 )alkyl)- which are optionally substituted in the phenyl or heteroaryl ring.

21. A compound as claimed in claim 2 wherein R 1 is —OH; W is —C(═O)NHOH, X is —O—, R 3 is tert-butyl, and R 2 is phenylpropyl- or ethoxyphenylpropyl.

22. A compound as claimed in claim 2 wherein R 1 is —OH; W is —C(═O)NHOH, X is —O—, R 3 is tert-butyl, and R 4 is branched C 1 -C 12 alkyl, cycloalkyl, phenyl, heteroaryl, phenyl(C 1 -C 6 alkyl)- or heteroaryl(C 1 -C 6 )alkyl)-.

23. A compound as claimed in claim 2 wherein R 1 is —OH; W is —C(═O)NHOH, X is —O—, R 3 is tert-butyl, R 2 is ethoxyphenylpropyl, and R 4 is phenyl or heteroaryl.

24. A compound as claimed in claim 3 wherein W is —C(═O)NHOH and X is —O—.

25. A compound as claimed in claim 3 wherein W is —C(═O)NHOH, X is —O—, and R 3 is tert-butyl.

26. A compound as claimed in claim 3 wherein W is —C(═O)NHOH, X is —O—, and R 1 is —OH, C 1 -C 6 alkoxy, or C 2 -C 6 alkenyl.

27. A compound as claimed in claim 3 wherein W is —C(═O)NHOH, X is —O—, R 1 is —OH, C 1 -C 6 alkoxy, or C 2 -C 6 alkenyl, R 3 is tert-butyl or benzyl and R 4 is isopropyl.

28. A compound selected from the group consisting of:

3R-[2,2-Dimethyl-1S-(5-phenyl-[1,2,4]oxadiazol-3-yl)-propylcarbamoyl]-2S-hydroxy-5-methyl-hexanohydroxamic acid;

3R-[2,2-dimethyl-1S-(5-phenyl-[1,2,4]oxadiazol-3-yl)-propylcarbamoyl]-2R-hydroxy-5-methyl-hexanohydroxamic acid;

3R-[2,2-Dimethyl-1S-(3-phenyl-[1,2,4]oxadiazol-5-yl)-propylcarbamoyl]-2S-hydroxy-5-methyl-hexanohydroxamic acid;

2R-[3-(4-Ethoxy-phenyl)-propyl]-N1-[1S-(5-thiophen-2-yl)-[1,2,4]oxadiazol-3-yl)-2,2-dimethyl-propyl]-3S,N4-dihydroxy-succinamide;

2S-Hydroxy-3R-[1S-(5-isopropyl-[1,2,4]oxadiazol-3-yl)-2,2-dimethyl-propylcarbamoyl]-5-methyl hexanohydroxamic acid;

2S-Hydroxy-3R-[1S-(5-furan-2-yl-[1,2,4]oxadiazol-3-yl)-2,2-dimethyl-propylcarbamoyl]-5-methyl hexanohydroxamic acid;

2S-Hydroxy-3R-[1S-(5-cyclopentylmethyl-[1,2,4]oxadiazol-3-yl)-2,2-dimethyl-propylcarbamoyl]-5-methyl hexanohydroxamic acid;

2S-Hydroxy-3R-[1S-(5-thiophen-2-ylmethyl-[1,2,4]oxadiazol-3-yl)-2,2-dimethyl-propylcarbamoyl]-5-methyl hexanohydroxamic acid;

2S-Hydroxy-3R-[1S-(5-ethyl-[1,2,4]oxadiazol-3-yl)-2,2-dimethyl-propylcarbamoyl]-5-methyl hexanohydroxamic acid;

2S-Hydroxy-3R-[1S-(5-cyclopentyl-[1,2,4]oxadiazol-3-yl)-2,2-dimethyl-propylcarbamoyl]-5-methyl hexanohydroxamic acid;

2S-Hydroxy-3R-[1S-(5-benzyl-[1,2,4]oxadiazol-3-yl)-2,2-dimethyl-propylcarbamoyl]-5-methyl hexanohydroxamic acid;

2S-Hydroxy-3R-[1S-(5-isobutyl-[1,2,4]oxadiazol-3-yl)-2,2-dimethyl-propylcarbamoyl]-5-methyl hexanohydroxamic acid;

2S-Hydroxy-3R-[1S-(5-tert-butyl-[1,2,4]oxadiazol-3-yl)-2,2-dimethyl-propylcarbamoyl]-5-methyl hexanohydroxamic acid;

3R-[1S-(5-thiophen-2-yl-[1,2,4]oxadiazol-3-yl)-2,2-dimethyl-propylcarbamoyl]-5-methyl hexanohydroxamic acid;

2S-Hydroxy-3R-[1S-(5-(2,2-dimethyl-propyl)-[1,2,4]oxadiazol-3-yl)-2,2-dimethyl-propylcarbamoyl]-5-methyl hexanohydroxamic acid;

2S-Hydroxy-3R-[1S-(5-p-tolyl-[1,2,4]oxadiazol-3-yl)-2,2-dimethyl-propylcarbamoyl]-5-methyl hexanohydroxamic acid;

2S-Hydroxy-3R-[1S-(5-cyclopropyl-[1,2,4]oxadiazol-3-yl)-2,2-dimethyl-propylcarbamoyl]-5-methyl hexanohydroxamic acid;

2S-Hydroxy-3R-[1S-(5-methyl-[1,2,4]oxadiazol-3-yl)-2,2-dimethyl-propylcarbamoyl]-5-methyl hexanohydroxamic acid;

2S-Hydroxy-3R-[1S-(3-isopropyl-[1,2,4]oxadiazol-3-yl)-2,2-dimethyl-propylcarbamoyl]-5-methyl hexanohydroxamic acid;

2S,N1-Dihydroxy-3R-isobutyl-N4-[2-methyl-1S-(3-phenyl-[1,2,4]oxadiazol-5-yl)-propyl]-succinamide;

2S-Allyl-5-methyl-3R-[2-phenyl-1S-(3-phenyl-[1,2,4]oxadiazol-5-yl)-ethylcarbamoyl]-hexanohydroxamic acid;

2S-Allyl-5-methyl-3R-[2-phenyl-1S-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-ethylcarbamoyl]-hexanohydroxamic acid;

2S-Allyl-3R-[2,2-dimethyl-1S-(3-methyl-[1,2,4]oxadiazol-5-yl)-propylcarbamoyl]-5-methyl-hexanohydroxamic acid;

3R-[2,2-Dimethyl-1S-(3-phenyl-[1,2,4]oxadiazol-5-yl)-propylcarbamoyl]-5-methyl-hexanohydroxamic acid;

2S-Methoxy-5-methyl-3R-[1S-(3-methyl-[1,2,4]oxadiazol-5-yl)-2-phenyl-ethylcarbamoyl]-hexanohydroxamic acid;

3R-[2,2-Dimethyl-1S-(3-phenyl-[1,2,4]oxadiazol-5-yl)-propylcarbamoyl]-heptadecanoic acid;

3R-[2,2-Dimethyl-1S-(3-phenyl-[1,2,4]oxadiazol-5-yl)-propylcarbamoyl]-nonadecanoic acid;

6-(4-Chloro-phenyl)-3R-[2,2-dimethyl-1S-(5-phenyl-[1,2,4]oxadiazol-3-yl)-propylcarbamoyl]-hexanoic acid;

6-(4-Chloro-phenyl)-3R-[2,2-dimethyl-1R-(5-phenyl-[1,2,4]oxadiazol-3-yl)-propylcarbamoyl]-hexanoic acid;

3R-[2,2-Dimethyl-1S-(5-thiophen-2-yl-[1,2,4]oxadiazol-3-yl)-propylcarbamoyl]-2S-hydroxy-5-methyl-hexanoic acid;

3R-[1S-(5-Furan-2-yl-[1,2,4]oxadiazol-3-yl)-2,2-dimethyl-propylcarbamoyl]-2S-hydroxy-5-methyl-hexanoic acid;

2R-Cyclopentylmethyl-3S,N4-dihydroxy-N1-[1S-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-2,2-dimethyl-propyl]-succinamide;

2R-[3-(3,5-Bis-trifluoromethyl-phenyl)-propyl]-N1-[2,2-dimethyl-1S-(5-thiophen-2-yl-[1,2,4]oxadiazol-3-yl)-propyl]-3S,N4-dihydroxy-succinamide;

2R-[3-(3,5-Bis-trifluoromethyl-phenyl)-propyl]-N1-[1S-(5-furan-2-yl-[1,2,4]oxadiazol-3-yl)-2,2-dimethyl-propyl]-3S,N4-dihydroxy-succinamide;

2R-[3-(4-Ethoxy-phenyl)-propyl]-N1-[1S-(5-furan-2-yl-[1,2,4]oxadiazol-3-yl)-2,2-dimethyl-propyl]-3S,N4-dihydroxy-succinamide;

3-Cyclopentyl-N-[2,2-dimethyl-1S-(3-phenyl-[1,2,4]oxadiazol-5-yl)-propyl]-2R-[(formyl-hydroxy-amino)-methyl]-propionamide;

3-Cyclopentyl-N-[2,2-dimethyl-1S-(5-phenyl-[1,2,4]oxadiazol-3-yl)-propyl]-2R-[(formyl-hydroxy-amino)-methyl]-propionamide;

and pharmaceutically acceptable salts, hydrates or solvates thereof.

29. A pharmaceutical or veterinary composition comprising a compound as claimed in claim 1 .

30. A process for the preparation of a compound as claimed in claim 1 in which W is a hydroxamic acid group HONH(C═O), which process causing an acid of general formula (IIA) or (IIB)

or an activated derivative thereof to react with hydroxylamine, O-protected hydroxylamine, or an N,O-diprotected hydroxylamine, or a salt thereof, X, R 1 , R 2 , R 3 , and R 4 being as defined in claim 1 except that any substituents in R 1 , R 2 , R 3 , and R 4 which are potentially reactive with hydroxylamine, O-protected hydroxylamine, the N,O-diprotected hydroxylamine or their salts are optionally themselves protected from such reaction, then removing any protecting groups from the resultant hydroxamic acid moiety and from any protected substituents in R 1 , R 2 , R 3 , and R 4 .

31. A process for the preparation of a compound as claimed in claim 1 wherein W is an N-formylhydroxylamino group H(C═O)NH(OH)— which process comprises N-formulation of the corresponding compound in which W is —NH(OP) wherein P is an O-protecting group, then removing the O-protecting group P.

32. A process for the preparation of a compound as claimed in claim 1 wherein W is a carboxylic acid group —COON, which process comprises: coupling an acid of formula (III) or an activated derivative thereof

with an amine of formula (IVA) or (IVB)

wherein X, R 1 R 2 , R 3 , and R 4 are as defined in claim 1 except that any substituents in R 1 , R 2 , R 3 , and R 4 which are potentially reactive in the coupling reaction may themselves be protected from such reaction, and R 11 represents a hydroxy protecting group, and subsequently removing the protecting group R 11 and any protecting groups from R 1 R 2 , R 3 , and R 4 .

33. 2S-Hydroxy-3R-[1S-(5-thiophen-2-yl-[1,2,4]oxadiazol-3-yl)-2,2-dimethyl-propylcarbamoyl]-5-methyl hexanohydroxamic acid and pharmaceutically acceptable salts, hydrates or solvates thereof.