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

US7119203B2 · kind B2 · utility

Assignee

• Pharmacia Corporation · SE

Inventors

• Thomas E. Barta · Evanston, US
• Daniel P. Becker · Glenview, US
• Louis Bedell · Rantoul, US
• Terri Boehm · Ballwin, US
• David L. Brown · Chesterfield, US
• Jeffery Carroll · Columbia, US
• Yiyuan Chen · Skokie, US
• Yvette M. Fobian · Labadie, US
• John N. Freskos · Clayton, US
• Alan F. Gasiecki · Vernon Hills, US
• Margaret L. Grapperhaus · Glen Carbon, US
• Robert M. Heintz · Ballwin, US
• Susan L. Hockerman · Kirkwood, US
• Darren Kassab · Wildwood, US
• Ish Khanna · Vernon Hills, US
• Stephen Kolodziej · Ballwin, US
• Mark A. Massa · Ballwin, US
• Joseph McDonald · Ballwin, US
• Brent V. Mischke · Defiance, US
• Deborah A. Mischke · Defiance, US
• Patrick Mullins · East Lyme, US
• Mark A. Nagy · San Diego, US
• Monica B. Norton · Chesterfield, US
• Joseph G. Rico · Ballwin, US
• Michelle Schmidt · Millstadt, US
• Nathan Stehle · Ballwin, US
• John J. Talley · Chesterfield, US
• William Vernier · Chesterfield, US
• Clara I. Villamil · Glenview, US
• Lijuan Wang · Wildwood, US

Key dates

• Filing date: Apr 25, 2003
• Grant date: Oct 10, 2006
• Expiry date: Jul 13, 2023

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D471/04
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

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.