Piperidinyl- and piperazinyl-sulfonylmethyl hydroxamic acids and their use as protease inhibitors

• Main Authors: FOBIAN YVETTE M, RICO JOSEPH G, KASSAB DARREN J, BECKER DANIEL P, KOLODZIEJ STEPHEN A, SCHMIDT MICHELLE A, TALLEY JOHN J, MULLINS PATRICK B, WYNN THOMAS A, GASIECKI ALAN F, FRESKOS JOHN N, NAGY MARK A, MCDONALD JOSEPH J, KHANNA ISH K, GRAPPERHAUS MARGARET L, BARTA THOMAS E, STEHLE NATHAN W, MASSA MARK A, BROWN DAVID L, CARROLL JEFFERY N, BOEHM TERRI L, WANG LIJUAN J, VILLAMIL CLARA I, MISCHKE DEBORAH A, MISCHKE BRENT V, HOCKERMAN SUSAN L, NORTON MONICA B, BEDELL LOUIS J, HEINTZ ROBERT M, CHEN YIYUAN, VERNIER WILLIAM F
• Format: Patent
• Language: English
• Published: 10.10.2006
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

This invention is directed generally to proteinase (also known as "protease") inhibitors, and, more particularly, to piperidinyl- and piperazinyl-sulfonylmethyl hydroxamic acids that, inter alia, inhibit matrix metalloproteinase (also known as "matrix metalloprotease" or "MMP") activity and/or aggrecanase activity. Such hydroxamic acids generally correspond in structure to the following formula: (wherein A1, A2, Y, E1, E2, E3, and Rx are as defined in this specification), and further include salts of such compounds. This invention also is directed to compositions of such hydroxamic acids, intermediates for the syntheses of such hydroxamic acids, methods for making such hydroxamic acids, and methods for treating conditions (particularly pathological conditions) associated with MMP activity and/or aggrecanase activity.