Pharmacia Corporation

G.d. Searle & Company

Pfizer Corporation

Pharmacia Corporation Global Patent Department

William F Vernier

Deborah A Mischke

Yvette M Fobian

Michael B Tollefson

Lijuan Jane Wang

Margaret Lanahan Grapperhaus

Mark A Massa

Monica B Norton

Emily J Reinhard

Melvin L Rueppel

Richard C Durley

Dale P Spangler

Brian S Hickory

Michele A Promo

Ashton T Hamme

James A Sikorski

Barry L Parnas

John Nicholas Freskos

Daniel Paul Becker

Joseph J McDonald

Thomas E Barta

Clara I Villamil

Joseph Gerace Rico

Susan Landis Hockerman

Terri L Boehm

Louis J Bedell

Nathan W Stehle

Daniel P Getman

Gary A DeCrescenzo

Jeffery N Carroll

Steve A Kolodziej

Darren J Kassab

Susan C Howard

Stephen A Kolodziej

Madeleine H Li

John Jeffrey Talley

Ish K Khanna

Robert M Heintz

David Louis Brown

Alan Frank Gasiecki

Brent V Mischke

Shridhar G Hegde

Hui Li

Michelle A Schmidt

Carol Pearcy Howard

Patrick B Mullins

Jeffrey N Carroll

Thomas A Wynn

David R Anderson

James A Sikorsky

Yiyuan Chen

Mark A Nagy

The invention relates to substituted aryl and heteroaryl (R)-Chiral Halogenated 1-Substitutedamino-(n+1)-Alkanol compounds useful as inhibitors of cholesteryl ester transfer protein (CETP; plasma lipid transfer protein-I) and compounds, compositions and methods for treating atherosclerosis and other coronary artery diseases. Novel high yield, stereoselective processes for the preparation of the chiral substituted alkanol compounds from chiral and achiral intermediates are described.

(R)-chiral halogenated substituted fused heterocyclic amino compounds useful for inhibiting cholesterol ester transfer protein activity

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 method of making aminocyanopyridine compounds which are capable of inhibiting mitogen activated protein kinase-activated protein kinase-2 is described.

Method of making tricyclic aminocyanopyridine compounds

The invention relates to substituted aryl and heteroaryl (R)-Chiral Halogenated 1-Substitutedamino-(n&plus;1)-Alkanol compounds useful as inhibitors of cholesteryl ester transfer protein (CETP; plasma lipid transfer protein-I) and compounds, compositions and methods for treating atherosclerosis and other coronary artery diseases. Novel high yield, stereoselective processes for the preparation of the chiral substituted alkanol compounds from chiral and achiral intermediates are described. Preferred (R)-Chiral 1-Substitutedamino-(n&plus;1)-Alkanol compounds are substituted (R)-Chiral N,N-bis-phenyl aminoalcohols. A preferred specific (R)-Chiral N,N-bis phenyl aminoclcohol is the compound.

(R)-Chiral halogenated substituted n,n-bis-phenyl aminoalcohol compounds useful for inhibiting cholesteryl ester transfer protein activity

The invention relates to substituted polycyclic aryl and heteroaryl tertiary-heteroalkylamine compounds useful as inhibitors of cholesteryl ester transfer protein (CETP; plasma lipid transfer protein-I) and compounds, compositions and methods for treating atherosclerosis and other coronary artery diseases. Preferred tertiary-heteroalkylamine compounds are substituted N,N-disubstituted reverse aminoalcohols. A preferred specific N,N-disubstituted reverse aminoalcohols is the compound:

Use of substituted N, N-disubstituted reverse aminoalcohol compounds useful for inhibiting cholesteryl ester transfer protein 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,

Aromatic sulfone hydroxamic acid metalloprotease inhibitor

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.

The invention relates to substituted aryl and heteroaryl (R)-Chiral Halogenated 1-Substitutedamino-(n&plus;1 )-Alkanol compounds useful as inhibitors of cholesteryl ester transfer protein (CETP; plasma lipid transfer protein-I) and compounds, compositions and methods for treating atherosclerosis and other coronary artery diseases. Novel high yield, stereoselective processes for the preparation of the chiral substituted alkanol compounds from chiral and achiral intermediates are described. Preferred (R)-Chiral 1-Substitutedamino-(n&plus;1)-Alkanol compounds are substituted (R)-Chiral N-benzyl-N-phenyl aminoalcohols. A preferred specific (R)-Chiral N-benzyl-N-phenyl aminoalcohol is the compound:

(R)-chiral halogenated substituted n-benzyl-n-phenyl aminoalcohol compounds useful for inhibiting cholesteryl ester transfer protein activity

The invention relates to substituted polycyclic aryl and heteroaryl tertiary-heteroalkylamine compounds useful as inhibitors of cholesteryl ester transfer protein (CETP; plasma lipid transfer protein-I) and compounds, compositions and methods for treating atherosclerosis and other coronary artery diseases. Preferred tertiary-heteroalkylamine compounds are substituted N-benzyl-N-phenyl aminoalcohols. A preferred specific N-benzyl-N-phenyl aminoalcohol is the compound:

Substituted n-benzyl-n-phenyl aminoalcohol compounds useful for inhibiting cholesteryl ester transfer protein activity

The invention relates to substituted polycyclic aryl and heteroaryl tertiary-heteroalkylamine compounds useful as inhibitors of cholesteryl ester transfer protein (CETP; plasma lipid transfer protein-I) and compounds, compositions and methods for treating atherosclerosis and other coronary artery diseases. Preferred tertiary-heteroalkylamine compounds are substituted N-fused-phenyl-N-benzyl aminoalcohols. A preferred specific N-fused-phenyl-N-benzyl aminoalcohol is the compound:

Substituted N-fused-phenyl-N-benzyl aminoalcohol compounds useful for inhibiting cholesteryl ester transfer protein activity

The invention relates to substituted polycyclic aryl and heteroaryl tertiary-heteroalkylamine compounds useful as inhibitors of cholesteryl ester transfer protein (CETP; plasma lipid transfer protein-I) and compounds, compositions and methods for treating atherosclerosis and other coronary artery diseases. Preferred tertiary-heteroalkylamine compounds are substituted N,N-disubstituted non-fused heterocyclo amines. A preferred specific N,N-disubstituted non-fused heterocyclo amine is the compound:

Substituted N,N-disubstituted non-fused heterocyclo amino compounds useful for inhibiting cholesteryl ester transfer protein activity

The invention relates to substituted polycyclic aryl and heteroaryl tertiary-heteroalkylamine compounds useful as inhibitors of cholesteryl ester transfer protein (CETP; plasma lipid transfer protein-I) and compounds, compositions and methods for treating atherosclerosis and other coronary artery diseases. Preferred tertiary-heteroalkylamine compounds are substituted N,N-disubstituted fused-heterocyclo amines. A preferred specific N,N-disubstituted fused-heterocyclo amine is the compound:

Substituted N,N-disubstituted fused-heterocyclo amino compounds useful for inhibiting cholesteryl ester transfer protein activity

The invention relates to substituted polycyclic aryl and heteroaryl tertiary-heteroalkylamine compounds useful as inhibitors of cholesteryl ester transfer protein (CETP; plasma lipid transfer protein-I) and compounds, compositions and methods for treating atherosclerosis and other coronary artery diseases. Preferred tertiary-heteroalkylamine compounds are substituted N-phenoxy-N-phenyl aminoalcohols. A preferred specific N-phenoxy-N-phenyl aminoalcohol is the compound:

Substituted N-phenoxy-N-phenyl aminoalcohol compounds useful for inhibiting cholesteryl ester transfer protein activity

Growing community of inventors

St. Louis, MO, United States of America

William F Vernier