Aromatic sulfone hydroxamic acid metalloprotease inhibitor

US6890937B2 · 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
• Jeffery Carroll · Columbia, US
• Gary A. DeCrezcenzo · Holden, US
• Theresa Fletcher · Kirkwood, US
• John N. Freskos · Clayton, US
• Daniel P. Getman · Chesterfield, US
• Gunnar J. Hanson · Cambridge, US
• Susan L. Hockerman · Kirkwood, US
• Carol Howard · Fenton, US
• Stephen Kolodziej · Ballwin, US
• Madeleine Li · Vernon Hills, US
• Joseph McDonald · Ballwin, US
• Deborah A. Mischke · Defiance, US
• Patrick Mullins · East Lyme, US
• Joseph G. Rico · Ballwin, US
• Nathan Stehle · Ballwin, US
• Clara I. Villamil · Glenview, US

Key dates

• Filing date: Jan 7, 2003
• Grant date: May 10, 2005
• Expiry date: Jan 7, 2023

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D417/12
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

A treatment process is disclosed that comprises administering an effective amount of an aromatic sulfone hydroxamic acid that exhibits excellent inhibitory activity of one or more matrix metalloprotease (MMP) enzymes, such as MMP-2, MMP-9, and MMP-13, while exhibiting substantially less inhibition at least of MMP-1 to a host having a condition associated with pathological matrix metalloprotease activity. The administered enzyme inhibitor corresponds in structure to formula (I), below, or a pharmaceutically acceptable salt thereof, wherein R1 and R2 are both hydrido or R1 and R2 together with the atoms to which they are bonded form a 5- to 8-membered ring containing one, two, or three heteroatoms in the ring that are oxygen, sulfur, or nitrogen. R3 in formula (I) is an optionally substituted aryl or optionally substituted heteroaryl radical. Also disclosed are metalloprotease inhibitor compounds having those selective activities, processes for manufacture of such compounds and pharmaceutical compositions using an inhibitor.