Pharmacia Corporation

G.d. Searle & Company

Angus Chemical Company

G.d. Searle LLC

Other

Decode Genetics Ehf

Decode Genectics Ehf.

Louis J Bedell

John Nicholas Freskos

Daniel Paul Becker

Thomas E Barta

Joseph J McDonald

Gary A DeCrescenzo

Clara I Villamil

Daniel P Getman

Susan Landis Hockerman

Deborah A Mischke

Joseph Gerace Rico

Terri L Boehm

Brent V Mischke

Yvette M Fobian

Jeffery N Carroll

Nathan W Stehle

Steve A Kolodziej

William F Vernier

Shashidhar N Rao

Darren J Kassab

Madeleine H Li

John Jeffrey Talley

Robert M Heintz

Michael B Tollefson

Lijuan Jane Wang

Monica B Norton

Mark E Gurney

Vincent Premaratna Sandanayaka

Jasbir Singh

Rama K Mishra

Lei Zhao

Susan C Howard

Hui Li

Vincent Nocito

Stephen A Kolodziej

Peng Yu

Carol Pearcy Howard

Patrick B Mullins

Jeffrey N Carroll

Bjorn Mamat

Gunnar J Hanson

Ish K Khanna

David Louis Brown

Margaret Lanahan Grapperhaus

Mark A Massa

Alan Frank Gasiecki

Matthew I Levinson

Michelle A Schmidt

Theresa R Fletcher

Mark A Nagy

Thomas A Wynn

Rao N Shashidhar

Gary A DeCrezcenzo

Mathew I Levinson

Yiyuan Chen

The present invention relates to a chemical genus of biaryl substituted heterocycle inhibitors of LTA4H (leukotriene A4 hydrolase) useful for the treatment and prevention and prophylaxis of inflammatory diseases and disorders. The compounds have general formula &#x3a8;:  An example is 

Biaryl substituted heterocycle inhibitors of LTA4H for treating inflammation

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

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.

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

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Mt. Prospect, IL, United States of America

Louis J Bedell