Pharmacia Corporation

Theresa R Fletcher

Gunnar J Hanson

Michael L Vazquez

Michael John Clare

Richard M Weier

Richard A Partis

Timothy J Hagen

Michael B Tollefson

Suzanne S Metz

Francis J Koszyk

Michael A Stealey

Patrick J Lennon

Bruce C Hamper

He Huang

Xiangdong Xu

Arija A Bergmanis

Subo Liao

Lifeng Geng

Shuyuan Liao

Joyce Zuowu Crich

Thomas Dale Owen

Stephen C Houdek

Dominique Bonafoux

Scott B Mohler

Serge G Wolfson

Donna M Iula

Angela M Scates

Maria Nguyen

David S Oburn

Daniel P Getman

John Nicholas Freskos

Daniel Paul Becker

Deborah A Mischke

Joseph J McDonald

Thomas E Barta

Clara I Villamil

Joseph Gerace Rico

Susan Landis Hockerman

Terri L Boehm

Louis J Bedell

Jeffery N Carroll

Nathan W Stehle

Stephen A Kolodziej

Madeleine H Li

Patrick B Mullins

Carol Pearcy Howard

Gary A DeCrezcenzo

The present invention relates to substituted pyrazolyl derivatives, compositions comprising such, intermediates, methods of making substituted pyrazolyl derivatives, and methods for treating cancer, inflammation, and inflammation-associated disorders, such as arthritis.

Substituted pyrazolyl compounds for the treatment of inflammation

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 Rand Rare both hydrido or Rand Rtogether 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. Rin 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.

Aromatic sulfone hydroxamic acid metalloprotease inhibitor

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Kirkwood, MO, United States of America

Theresa R Fletcher