G.d. Searle & Company

Pharmacia Corporation

Abbvie Inc.

Other

Monsanto Company

G.d. Searle LLC

Clara I Villamil

Daniel Paul Becker

Daniel L Flynn

Alan E Moormann

Roger A Nosal

John Nicholas Freskos

Joseph J McDonald

Thomas E Barta

Daniel P Getman

Gary A DeCrescenzo

Louis J Bedell

Susan Landis Hockerman

Terri L Boehm

Deborah A Mischke

Joseph Gerace Rico

Hui Li

Yvette M Fobian

Brent V Mischke

Jeffery N Carroll

Nathan W Stehle

Steve A Kolodziej

Robert M Heintz

William F Vernier

Darren J Kassab

Madeleine H Li

John Jeffrey Talley

Michael B Tollefson

Lijuan Jane Wang

Monica B Norton

Norman A Abood

Robert L Shone

Lori A Schretzman

Bruce Clapham

Alan E Moorman

Brian M Bax

Patrick B Mullins

Anil Vasudevan

Kevin R Woller

Shashidhar N Rao

Michael S Dappen

Susan C Howard

Stephen A Kolodziej

Carol Pearcy Howard

Jeffrey N Carroll

Gunnar J Hanson

Ish K Khanna

Philip R Kym

Marlon D Cowart

David Louis Brown

Robert J Altenbach

Margaret Lanahan Grapperhaus

Michael J Dart

Mark A Massa

Masateru Miyano

Arthur Gomtsyan

John R Koenig

Michael E Kort

Alan Frank Gasiecki

Huaqing Liu

Robert G Schmidt

David J Calderwood

Tammie K Jinkerson

Marc J Scanio

Eric A Voight

Mark A Matulenko

Michael Z Hoemann

Kathy A Sarris

Ryan G Keddy

Kerren Kalai Swinger

Noel S Wilson

Kelly Mullen

Phil B Cox

Gagandeep K Somal

Gary A De Crescenzo

Theresa R Fletcher

Michelle A Schmidt

Ana Aguirre

Philip Cox

Bin Li

Yiyuan Chen

Mark A Nagy

Thomas A Wynn

Rao N Shashidhar

Gary A DeCrezcenzo

Compounds of formula (I) and pharmaceutically acceptable salts, esters, amides, or radiolabelled forms thereof, wherein R, Z, Z, and n are as defined in the specification, are useful in treating conditions or disorders prevented by or ameliorated by Tropomysin receptor kinases (Trk). Methods for making the compounds are disclosed. Also disclosed are pharmaceutical compositions of compounds of formula (I), and methods for using such compounds and compositions.

Furo-3-carboxamide derivatives and methods of use

Disclosed herein are modulators of TRPV3 of formula (I) wherein X, X, R, R, R, and n are as defined in the specification. Compositions comprising such compounds and methods for treating conditions and disorders using such compounds and compositions are also presented.

TRPV3 modulators

The present invention is directed to novel compounds of Formula (I) pharmaceutically acceptable salts, biologically active metabolites, pro-drugs, racemates, enantiomers, diastereomers, solvates and hydrates thereof wherein the variables are defined as herein. The compounds of Formula (I) are useful as kinase inhibitors and as such would be useful in treating certain conditions and diseases, especially inflammatory conditions and diseases and proliferative disorders and conditions, for example, cancers.

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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 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

This invention is directed to aromatic sulfone hydroxamic acids (including hydroxamates) and salts thereof that, inter alia, inhibit matrix metalloproteinase (also known as 'matrix metalloprotease' or 'MMP') activity and/or aggrecanase activity. This invention also is directed to a prevention or treatment method that comprises administering such a compound or salt in an MMP-inhibiting and/or aggrecanase-inhibiting effective amount to an animal, particularly a mammal having (or disposed to having) a pathological condition associated with MMP and/or aggrecanase activity.

Aromatic sulfone 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 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. Also disclosed are metalloprotease inhibitor compounds having those selective activities, processes for manufacture of such compounds and pharmaceutical compositions using an inhibitor. A contemplated compound corresponds in structure to formula B, below,

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. Also disclosed are metalloprotease inhibitor compounds having those selective activities, processes for manufacture of such compounds and pharmaceutical compositions using an inhibitor.

Sulfonyl aryl hydroxamates and their use as matrix metalloprotease inhibitors

This invention is directed to aromatic sulfone hydroxamates (also known as &ldquo;aromatic sulfone hydroxamic acids&rdquo;) and salts thereof that, inter alia, inhibit matrix metalloproteinase (also known as &ldquo;matrix metalloprotease&rdquo; or &ldquo;MMP&rdquo;) activity and/or aggrecanase activity. This invention also is directed to a prevention or treatment method that comprises administering such a compound or salt in an MMP-inhibiting and/or aggrecanase-inhibiting effective amount to an animal, particularly a mammal having (or disposed to having) a pathological condition associated with MMP and/or aggrecanase activity.

Aromatic sulfone hydroxamates and their use as protease inhibitors

2-Amino-benzoxazinones for the treatment of viral infections

This invention is directed to aromatic sulfone hydroxamates (also known as aromatic sulfone hydroxamic acids) and salts thereof that, inter alia, tend to inhibit matrix metalloproteinase (also known as matrix metalloprotease or MMP) activity and/or aggrecanase activity. This invention also is directed to a treatment method that comprises administering such a compound or salt in an MMP-inhibiting and/or aggrecanase-inhibiting effective amount to an animal, particularly a mammal having (or disposed to having) a pathological condition associated with MMP activity and/or aggrecanase activity.

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

Aromatic sulfonyl alpha-cycloamino hydroxamic acid compounds

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Glenview, IL, United States of America

Clara I Villamil