compound, method for the treatment of a human or animal subject suffering from, or susceptible to an autoimmune disorder or an inflammatory condition, use of a compound, pharmaceutical composition, and process for the preparation of compounds

摘要

"COMPOUND, METHOD FOR THE TREATMENT OF A HUMAN OR ANIMAL INDIVIDUAL SUFFERING FROM, OR SUITABLE TO AN AUTOMUNE DISORDER OR INFLAMMATORY CONDITION, USE OF A COMPOUND, PHARMACEUTICAL COMPOSITION, AND PREPARATION FOR THE PROCESS. Compounds of formula (I) are described: wherein: A represents a bond, C 1-6 alkyl or CH = CHC 1-4 alkyl; B represents bond, O, S, SO, SO ~ 2 ~, CO, CR¬ 7¬R¬ 8¬, CO¬ 2¬R¬ 14¬, CONR¬ 14¬R¬ 15¬, N (COR¬ 14¬ ) (COR¬ 15¬), N (SO¬ 2¬R¬ 14¬) (COR¬ 15¬) or NR¬ 14¬R¬ 15¬; D represents bond, or C 1-6 alkyl; E represents substituted or unsubstituted aryl or substituted heteroaryl; Q represents an optionally substituted 5- or 6-membered heteroaryl or aryl ring; X represents O, S, SO, SO ~ 2 ~, CO, CNRS, CNOR¬ 5¬, CNNR¬ 5¬R¬ 6¬, NR¬ 11¬ or CR¬ 7¬R¬ 8¬; Y represents CR¬ 5¬OR¬ 11¬, CR¬ 5¬SR¬ 11¬, NOR¬ 5¬, CR¬ 5¬NR¬ 6¬R¬ 11¬, SO, SO ~ 2 ~, CO, CNR¬ 5 ¬, CNOR¬ 5¬ or CS; R¬ 1¬ and R¬1¬ 39, each independently representing H, C 1-6 alkyl or C 1-4 alkylaryl; R¬ 2¬; represents CO ~ 2 ~ R¬ 12¬, CH ~ 2 ~ OR¬ 12¬ or CONR¬ 12¬R¬ 13¬, CONR¬ 12¬OR¬ 13¬, NR¬ 12¬COR¬ 13¬, SR¬ 12¬ , PO (OH) ~ 2 ~, PONHR¬ 12¬ or DREAM 12¬; R 3 represents H, C 1-6 alkyl or C 1-4 alkylaryl; R¬ 4¬ represents optionally substituted heteroaryl or aryl; Z represents a bond. CH ~ 2 ~, O, S, SO, SO ~ 2 ~, NR¬ 5¬, OCR¬ 5¬R¬ 6¬, CR¬ 9¬R¬ 10¬O or Z, R¬ 4¬ and Q together form an optionally substituted fused tricyclic group; R 5 and R 6 each independently represent H, C 1-6 alkyl or C 1-4 alkylaryl; R 7 and R 8 each independently representing H, halo, C 1-6 alkyl or C 1-4 alkylaryl; R 9 and R 10 each independently represent H, C 1-6 alkyl optionally substituted by halo, cyano, OR 11 or NR 6 R 11, C 1- 4-alkylaryl optionally substituted by halo, cyano, OR¬ 11¬ or NR¬ 6¬R¬ 11¬, OR¬ 11¬ or, together with the N to which they are attached, R¬ 9¬ and R¬ 10¬ form a heterocyclic group: R 11 is H, C 1-6 alkyl, C 1-4 alkylaryl or COR 5; R 12 and R 13 each independently represent H, C 1-3 alkyl, C 1-3 alkylaryl or C 1-3 alkyl heteroaryl or together with the functionality to which they are attached, R 12 and R 13 form a heterocyclic group: R 14 and R 15 each independently represent H, C 1-6 alkyl, C 1-4. C 1-4 alkylaryl or C 1-4 alkylheteroaryl or, together with the functionality to which they are attached, R 14 and R 15 form a fused heterocyclic or heterocyclic group: and physiologically functional derivatives thereof, processes for their preparation, pharmaceutical formulations containing them, and their use as matrix metalloproteinase enzyme (MMPs) inhibitors.