Pharmacia Corporation

G.d. Searle & Company

Pfizer Corporation

Monsanto Company

Pharmacia & Upjohn Company

Elan Pharmaceuticals, Inc.

Pharmacia Corporation Global Patent Department

Elan Oharmaceuticals, Inc.

Yvette M Fobian

Deborah A Mischke

Michael B Tollefson

William F Vernier

Lijuan Jane Wang

Monica B Norton

Margaret Lanahan Grapperhaus

Mark A Massa

James A Sikorski

Melvin L Rueppel

Richard C Durley

Dale P Spangler

Brian S Hickory

Michele A Promo

Ashton T Hamme

Emily J Reinhard

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

Gary A DeCrescenzo

Steve A Kolodziej

Jeffery N Carroll

Darren J Kassab

Nathan W Stehle

John Jeffrey Talley

Daniel P Getman

David Louis Brown

David A Morgenstern

Michael K Stern

Michael D Rogers

Brent V Mischke

Susan C Howard

Todd J Johnson

Madeleine H Li

Jeffrey A Levine

Jeffrey N Carroll

Varghese John

Ish K Khanna

William L Neumann

Robert M Heintz

Dennis Patrick Riley

Arthur Glenn Romero

Patrick J Lennon

Alan Frank Gasiecki

Andrew Simon Bell

Robert Owen Hughes

Dafydd Rhys Owen

Daniela Salvemini

Barbara Jagodzinska

Michael John Palmer

E Jon Jacobsen

Karl W Aston

Todd M Maddux

Susan L Henke

David Graham Brown

Hui Li

Stephen A Kolodziej

John K Walker

John M Molyneaux

Christopher Phillips

Patrick B Mullins

Michelle A Schmidt

Carol Pearcy Howard

Joseph B Moon

Larry Fang

James A Sikorsky

Carrie L Kusturin

Steven E Heasley

Yiyuan Chen

Mark A Nagy

D Joseph Rogier, Jr

Thomas A Wynn

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

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

The present invention relates to compounds of formula (AA) (I) and (X): useful in treating Alzheimer's disease and other similar diseases. These compounds include inhibitors of the beta-secretase enzyme that are useful in the treatment of Alzheimer's disease and other diseases characterized by deposition of A beta peptide in a mammal. The compounds of the invention are useful in pharmaceutical compositions and methods of treatment to reduce A beta peptide formation.

1,3-Diamino-2-hydroxypropane pro-drug derivatives

Disclosed are compounds of formula X, which are useful in treating Alzheimer's disease and other similar diseases. Pharmaceutical compositions comprising compounds of formula X and methods of preparing the compounds of formula X are also disclosed.

Hydroxy alkyl amines

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

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

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

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Labadie, MO, United States of America

Yvette M Fobian