Matrix metalloproteinase inhibitors

摘要

Compounds of Formula (I): wherein: A represents bond, C_1-6alkyl or CH-CH-C_1-4alkyl; B represents bond, 0, S, SO, SO₂, CO, CR⁷R⁸, CO₂R¹⁴, CONR¹⁴R¹⁵, N(COR¹⁴)(COR¹⁵), N(SO₂R¹⁴)(COR¹⁵) or NR¹⁴R¹⁵; D represents bond, or C_1-6alkyl; E represents substituted aryl or substituted or unsubstituted heteroaryl; Q represents an optionally substituted 5- or 6-membered aryl or heteroaryl ring; X represents O, S, SO, SO₂, CO, CNR⁵, CNOR⁵, CNNR⁵R⁶, NR¹¹ or CR⁷R⁸; Y represents CR⁵OR¹¹, CR⁵SR¹¹, NOR⁵, CR⁵NR⁶R¹¹, SO, SO₂, CO, CNR⁵, CNOR⁵ or CS; R¹ and R^1' each independently represents H, C_1-6alkyl or C_1-4alkylaryl; R² represents CO₂R¹², CH₂OR¹² or CONR¹²R¹³, CONR¹²OR¹³, NR¹²COR¹³, SR¹², PO(OH)₂, PONHR¹² or SONHR¹²; R³ represents H, C_1-6alkyl or C_1-4alkylaryl; R⁴ represents optionally substituted aryl or heteroaryl; Z represents a bond, CH₂, O, S, SO, SO₂, NR⁵, OCR⁵R⁶, CR⁹R¹⁰O or Z, R⁴ and Q together form an optionally substituted fused tricyclic group; R⁵ and R⁶ each independently represent H, C_1-6 alkyl or C_1-4 alkylaryl; R⁷ and R⁸ each independently represent H, halo, C_1-6 alkyl or C_1-4 alkylaryl; R⁹ and R¹⁰ each independently represents H, C_1-6 alkyl optionally substituted by halo, cyano, OR¹¹ or NR⁶R¹¹, C_1-4 alkylaryl optionally substituted by halo, cyano, OR11 or NR⁶R¹¹, OR¹¹ or, together with the N to which they are attached, R⁹ and R¹⁰ form a heterocyclic group: R¹¹ represents H, C_1-6 alkyl, C_1-4 alkylaryl or COR⁵; R¹² and R¹³ each independently represent H, C_1-3 alkyl, C_1-3 alkylaryl or C_1-3 alkylheteroaryl or, together with the functionality to which they are attached, R¹² and R¹³ form a heterocyclic group: R¹⁴ and R¹⁵ each independently represent H, C_1-6 alkyl, C_1-4 alkylaryl or C_1-4 alkylheteroaryl or together with the functionality to which they are attached R¹⁴ and R¹⁵ form a heterocyclic or fused heterocyclic group; and physiologically functional derivatives thereof, corresponding processes for preparation, pharmaceutical formulations containing them and their use as inhibitors of matrix metallproteinase enzymes (MMPs).