Pharmacia Corporation

G.d. Searle & Company

Monsanto Company

G.d. Searle LLC

Pharmacia & Upjohn Company

Brent V Mischke

John Nicholas Freskos

Gary A DeCrescenzo

Joseph J McDonald

Daniel P Getman

Daniel Paul Becker

Thomas E Barta

Robert M Heintz

Louis J Bedell

Clara I Villamil

Shashidhar N Rao

Terri L Boehm

David Louis Brown

Yvette M Fobian

Susan Landis Hockerman

Susan C Howard

Patrick B Mullins

John Jeffrey Talley

Ish K Khanna

Deborah A Mischke

Michael B Tollefson

Lijuan Jane Wang

Margaret Lanahan Grapperhaus

Mark A Massa

Monica B Norton

William F Vernier

Joseph Gerace Rico

Alan Frank Gasiecki

Andrew Simon Bell

Robert Owen Hughes

Dafydd Rhys Owen

Jeffery N Carroll

Michael John Palmer

E Jon Jacobsen

Darren J Kassab

Todd M Maddux

David Graham Brown

Nathan W Stehle

S Zaheer Abbas

Stephen A Kolodziej

John M Molyneaux

Madeleine H Li

John K Walker

Christopher Phillips

Michelle A Schmidt

Joseph B Moon

Yiyuan Chen

Steven E Heasley

Mark A Nagy

Thomas A Wynn

Rao N Shashidhar

D Joseph Rogier, Jr

Zaheer S Abbas

Compounds and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula I: wherein R, R, Rand Rare as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, synthetic methods, and intermediates are also disclosed.

Pyridine [3,4-b] pyrazinones

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 &#x201c;MMP&#x201d;) activity and/or aggrecanase activity. Such hydroxamic acids generally correspond in structure to the following formula: (wherein A, A, Y, E, E, E, and Rare 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.

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

A sulfonyl aromatic or heteroaromatic ring hydroxamic acid compound that inter alia inhibits matrix metalloprotease activity is disclosed as are a treatment process that comprises administering a contemplated sulfonyl aromatic or heteroaromatic ring hydroxamic acid compound in a MMP enzyme-inhibiting effective amount to a host having a condition associated with pathological matrix metalloprotease activity. A contemplated compound corresponds in structure to the formula  wherein W and the R groups are defined elsewhere.

Sulfonyl aryl or heteroaryl hydroxamic acid compounds

A sulfonyl aromatic or heteroaromatic ring hydroxamic acid compound that inter alia inhibits matrix metalloprotease activity is disclosed as are a treatment process that comprises administering a contemplated sulfonyl aromatic or heteroaromatic ring hydroxamic acid compound in a MMP enzyme-inhibiting effective amount to a host having a condition associated with pathological matrix metalloprotease activity.

This invention is directed to proteinase (protease) inhibitors, and more particularly to thiol sulfonamide inhibitors for matrix metalloproteinase 13(MMP-13), compositions of proteinase inhibitors, intermediates for the syntheses of proteinase inhibitors, processes for the preparation of proteinase inhibitors and processes for treating pathological conditions associated with pathological matrix metalloproteinase activity related to MMP-13.

Thiol sulfonamide metalloprotease inhibitors

An aromatic sulfonyl aipha-hydroxy hydroxamic acid compound that inter alia inhibits matrix metalloprotease activity is disclosed, as is a treatment process that comprises administering a contemplated aromatic sulfonyl alpha-hydroxy hydroxamic acid compound in an MMP enzyme-inhibiting effective amount to a host having a condition associated with pathological matrix metalloprotease activity.

Aromatic sulfonyl alpha-hydroxy hydroxamic acid compounds

Sulfonyl aryl hydroxamates and their use as matrix metalloprotease inhibitors

A sulfonyl divalent aromatic or heteroaromatic ring hydroxamic acid compound that inter alia inhibits matrix metalloprotease activity is disclosed as are a treatment process that comprises administering a contemplated sulfonyl divalent aromatic or heteroaromatic ring hydroxamic acid compound in a MMP enzyme-inhibiting effective amount to a host having a condition associated with pathological matrix metalloprotease activity.

Sulfonyl divalent aryl or heteroaryl hydroxamic acid compounds

A family of molecules is disclosed that inhibit matrix metalloprotease (MMP) activity, and particularly inhibit the activity of one or more of MMP-2, MMP-9, or MMP-13, while generally exhibiting little activity against MMP-1. A contemplated compound also exhibits little inhibition of the production of TNF. A contemplated compound is an &agr;-amino-&bgr;-sulfonyl carbocyclo, heterocyclo, aryl, or heteroaryl hydroxamic acid. Also disclosed are processes for preparing a contemplated compound and for treating a mammal having a condition associated with pathological matrix metalloprotease activity.

&agr;-amino-&bgr;-sulfonyl hydroxamic acid compounds

An N-hydroxy sulfonyl butanamide compound that inter alia inhibits matrix metalloprotease activity is disclosed as are a treatment process that comprises administering a contemplated N-hydroxy sulfonyl butanamide compound in a MMP enzyme-inhibiting effective amount to a host having a condition associated with pathological matrix metalloprotease activity.

N-hydroxy 4-sulfonyl butanamide compounds

An aromatic sulfonyl alpha-hydroxy hydroxamic acid compound that, inter alia, inhibits matrix metalloprotease activity is disclosed, as is a treatment process that comprises administering a contemplated aromatic sulfonyl alpha-hydroxy hydroxamic acid compound in an MMP enzyme-inhibiting effective amount to a host having a condition associated with pathological matrix metalloprotease activity.

This invention is directed to proteinase (protease) inhibitors, and more particularly to thiol sulfone inhibitors for matrix metalloproteinase 13(MMP-13), compositions of proteinase inhibitors, intermediates for the syntheses of proteinase inhibitors, processes for the preparation of proteinase inhibitors and processes for treating pathological conditions associated with pathological matrix metalloproteinase activity related to MMP-13.

Thiol sulfone metalloprotease inhibitors

Growing community of inventors

Defiance, MO, United States of America

Brent V Mischke