MATRIX METALLOPROTEINASE INHIBITORS

摘要

Compounds of Formula (I), wherein R<1> represents optionally substituted -C4-12 alkyl, -C2-10alkylcycloalkyl, -C2-6 alkyl heterocycloalkyl, -C2-6alkylaryl, optionally substituted 5- or 6- membered aryl or heteroaryl, except pyridinyl. Z represents a bond, CH2, O, S, SO, SO2, NR<4>, OCR<4>R<5>, CR<4>R<5>O, or Z, R<1> and Q together form an optionally substituted fused tricyclic group; Q represents an optionally substituted 5- or 6- membered aryl or heteroaryl ring; X represents COR<3>; R<2> represents CONH2, CO2H, CO2R<7>, SO2R<7> or SO2NR<8>R<9>, except that R<2>; may not represent CO2R<7> when X is CONH2 ; R<3> represents OR<6>, or NR<8>R<9>; R<4> and R<5> each independently represents H, C1-6 alkyl or C1-4 alkylaryl; R<6> represents H or C1-6 alkyl; R<7> represents C1-6 alkyl; R<8 >and R<9> each independently represents H or C1-6 alkyl or R<8 >and R<9> together with the nitrogen atom to which they are attached form a 5- or 6- membered ring which may optionally include 1 or more further heteroatoms selected from O, S and N; and physiologically functional derivatives thereof with the exception of [3-(acetylamino)-4-cyclohexylphenyl]-butanedioic acid and 3-(acetylamino)-4-cyclohexylphenyl]-butanedioic acid diethyl ether; butanedioic acid [3-methoxy-4-(phenylmethoxy)phenyl]; butanedioic acid [4-(phenylmethoxy)phenyl]; with the proviso that when R<1> represents C4-12 alkyl, Z is other than a bond, O or CH2; and physiologically functional derivatives thereof , processes for their preparation, pharmaceutical formulations containing them and their use as inhibitors of matrix metallproteinase enzymes (MMPs) are described.