Metalloproteinase inhibitors

A compound of general formula (I)

• wherein:
• X is a —CO2H or —CONHOH group;
• R1 is 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 C1-C6 alkyl, C2C6 alkenyl, halo, cyano (—CN), —CO2H, —CO2R, —CONH2, —CONHR, —CON(R)2, —OH, —OR, oxo-, —SH, —SR, —NHCOR and —NHCO2R wherein R is C1-C6 alkyl or benzyl and/or (ii) fused to a cycloalkyl or heterocyclic ring;
• R2 is a C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkenyl, phenyl(C1-C6 alkyl)-, heteroaryl(C1-C6 alkyl)-, cycloalkyl(C1-C6 alkyl)-, cycloalkenyl(C1-C6 alkyl)-, phenoxy(C1-C6 alkyl)-, heteroaryloxy(C1-C6 alkyl)-, phenyl(C1-C6 alkyl)O(C1-C6 alkyl)-, heteroaryl(C1-C6 alkyl)O(C1-C6 alkyl)-, phenyl(C1-C6 alkyl)S(C1-C6 alkyl)-, or heteroaryl(C1-C6 alkyl)S(C1-C6 alkyl)- group, any one of which may be optionally substituted by C1-C6 alkyl, C1-C6 alkoxy, halo, cyano (—CN), phenyl, substituted phenyl or heteroaryl.
• R3 is C1-C6 alkyl, benzyl, 2,- 3-, or 4-hydroxybenzyl, 2,- 3-, or 4-benzyloxybenzyl, 2,- 3-, or 4-C1-C6 alkoxybenzyl, or benzyloxy(C1-C6alkyl)-;
• or the characterizing group of a natural a 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)nR6 where Alk is a (C1-C6)alkylene or (C2-C6)alkenylene group optionally interrupted by one or more —O—, or —S— atoms or —N(R7)- groups, where R7 is a hydrogen atom or a (C1-C6)alkyl group, n is 0 or 1, and R6 is an optionally substituted cycloalkyl or cycloalkenyl group;
• or
• a benzyl group subsituted in the phenyl ring by a group of formula —OCH2COR8 wherein R8 is hydroxyl, amino, (C1-C6)alkoxy, phenyl(C1-C6)alkoxy, (C1-C6)alkylamino, di((C1-C6)alkyl)amino, phenyl(C1-C6)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, serine, threonine, cysteine, methionine, asparagine, glutamine, lysine, histidine, arginine, glutamic acid, and aspartic acid;
• or
• a heterocyclic((C1-C6)alkyl group, either being unsubstituted or mono- or di-substituted in the heterocyclic ring with halo, nitro, carboxy, (C1-C6)alkoxy, cyano, (C1-C6)alkanoyl, trifluoromethyl (C1-C6)alkyl, hydroxy, formyl, amino, (C1-C6)alkylamino, di-(C1-C6)alkylamino, mercapto, (C1-C6)alkylthio, hydroxy(C1-C6)alkyl, mercapto(C1-C6)alkyl or (C1-C6)alkylphenylmethyl;
• or
• a group —CRaRbRc in which:
• each of Ra, Rb and Rc is independently hydrogen, (C1-C6)alkyl, (C2C6)alkenyl, (C2-C6)alkynyl, phenyl(C1-C6)alkyl, (C3-C8)cycloalkyl;
• or
• Rc is hydrogen, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, phenyl(C1-C6)alkyl, or (C3-C8)cycloalkyl, and Ra and Rb 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
• Ra, Rb and Rc together with the carbon atom to which they are attached form a tricyclic ring;
• or
• Ra and Rb are each independently (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, phenyl (C1-C6)alkyl, or a group as defined for Rc below other than hydrogen, or Ra and Rb together with the carbon atom to which they are attached form a cycloalkyl or heterocyclic ring, and Rc is hydrogen, —OH, —SH, halogen, —CN, —CO2H, (C1-C4)perfluoroalkyl, —CH2OH, —CO2(C1-C6)alkyl, —O(C1-C6)alkyl, —O(C2-C6)alkenyl, —S(C1-C6)alkyl, —SO(C1-C6)alkyl, —SO2(C1-C6) alkyl, —S(C2-C6)alkenyl, —SO(C2-C6)alkenyl, —SO2(C2-C6)alkenyl or a group —Q—W wherein Q represents a bond or —O—, —S—, —SO—or —SO2— and W represents a phenyl, phenylalkyl, (C3-C8)cycloalkyl, (C3-C8)cycloalkylalkyl, (C4-C8)cycloalkenyl, (C4-C8)cycloalkenylalkyl, heteroaryl or heteroarylalkyl group, which group W may optionally be substituted by one or more substituents independently selected from, hydroxyl, halogen, —CN, —CO2H, —CO2(C1-C6)alkyl, —CONH2, —CONH(C1-C6)alkyl, —CONH(C1-C6)alkyl)2, —CHO, —CH2OH, (C1-C4)perfluoroalkyl, —O(C1-C6)alkyl, —S(C1-C6)alkyl, —SO(C1-C6)alkyl, —SO2(C1-C6)alkyl, —NO2, —NH2, —NH(C1-C6)alkyl, —N((C1-C6)alkyl)2, —NHCO(C1-C6)alkyl, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C8)cycloalkyl, (C4-C8)cycloalkenyl, phenyl or benzyl;
• R4 is hydrogen or a C1-C6 alkyl group, phenyl (C1-C6 alkyl) or heterocyclyl (C1-C6 alkyl);
• R5 is hydrogen or a C1-C6 alkyl group;
• or, when R5 is hydrogen, R3 and R4 taken together with the carbon atoms to which they are attached form a 2-hydroxycyclohexyl or C6 sugar (hexose) ring;
• or R4 and R5 taken together with the carbon atom to which they are attached form a 5 or 6-members carbocyclic or heterocyclic ring;
• or a pharmaceutically acceptable salt, hydrate or solvate thereof.