Bristol-myers Squibb Compnay

Bristol-myers Squibb Pharma Company

Wei Han

Jennifer X Qiao

Zilun Hu

Donald J P Pinto

Michael J Orwat

Yun-Long Li

Mimi Lifen Quan

Patrick Y S Lam

Donald J Pinto

Stephanie L Koch

Joanne M Smallheer

Timur Gungor

Shuaige Wang

Andrew Paul Combs

Eddy W Yue

Peter W Glunz

Xiaojun Zhang

Robert A Copeland

C Anne Higley

Susan V DiMeo

Brent Dale Douty

Sarah R Friedrich

Charles F Albright

Randine L Dowling

Nilsa R Graciani

Pearl S Huang

Stephanie Koch

Patrick Lam

The present invention provides compounds of Formula (I): or stereoisomers, tautomers, pharmaceutically acceptable salts, solvates, or prodrugs thereof, wherein the variables A, L, R, and Rare as defined herein. The compounds of Formula (I) are useful as selective inhibitors of serine protease enzymes of the coagulation cascade and/or contact activation system; for example thrombin, factor Xa, factor XIa, factor IXa, factor VIIa and/or plasma kallikrein. In particular, it relates to compounds that are selective factor XIa inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and/or inflammatory disorders using the same.

Thiophene derivatives as factor XIa inhibitors

The present application describes sulfonylaminovalerolactams and derivatives thereof of Formula I: or pharmaceutically acceptable salt forms thereof, wherein ring G is a mono- or bicyclic carbocycle or heterocycle. Compounds of the present invention are useful as inhibitors of trypsin-like serine proteases, specifically factor Xa.

Sulfonylaminovalerolactams and derivatives thereof as factor Xa inhibitors

Novel heterocyclic dihydropyrimidine compounds useful as inhibitors of potassium channel function (especially inhibitors of the K1 subfamily of voltage gated Kchannels, especially inhibitors K1.5 which has been linked to the ultra-rapidly activating delayed rectifier, which have the structure stereoisomers including enantiomers thereof and diastereomers thereof, or a pharmaceutically acceptable salt thereof,wherein  wherein R, R, R, R, R, R, R, Rand Rare defined herein. Methods of using such compounds in the prevention and treatment of arrhythmia and I-associated conditions, and pharmaceutical compositions containing such compounds are also provided.

Substituted pyrazolo[1,5-a]pyrimidines as potassium channel activators

The present application describes lactam-containing compounds and derivatives thereof of Formula I:P-P-M-MIor pharmaceutically acceptable salt forms thereof, wherein ring P, if present is a 5-7 membered carbocycle or heterocycle and ring M is a 5-7 membered carbocycle or heterocycle. Compounds of the present invention are useful as inhibitors of trypsin-like serine proteases, specifically factor Xa.

Lactam-containing compounds and derivatives thereof as factor Xa inhibitors

The present application describes 1,1-disubstituted cycloalkyl compounds and derivatives thereof, or pharmaceutically acceptable salt forms thereof, which are useful as inhibitors of factor Xa.

1, 1-disubstituted cycloalkyl derivatives as factor Xa inhibitors

The present application describes sulfonylaminovalerolactams and derivatives thereof of Formula Ia-If: or pharmaceutically acceptable salt forms thereof, wherein ring G is a mono- or bicyclic carbocycle or heterocycle. Compounds of the present invention are useful as inhibitors of trypsin-like serine proteases, specifically factor Xa.

The present application describes monocyclic and bicyclic lactams and derivatives thereof of Formulae Ia&#x2013;e: wherein one of one of Tand Tis carbonyl, thiocarbonyl, or sulfonyl or pharmaceutically acceptable salt forms thereof. Compounds of the present invention are useful as inhibitors of trypsin-like serine proteases, specifically factor Xa.

Monocyclic and bicyclic lactams as factor Xa inhibitors

The present application describes sulfonylaminovalerolactams and derivatives thereof of Formula Ia&#x2013;If: or pharmaceutically acceptable salt forms thereof, wherein ring G is a mono- or bicyclic carbocycle or heterocycle. Compounds of the present invention are useful as inhibitors of trypsin-like serine proteases, specifically factor Xa.

The present application describes glycinamidic compounds and derivatives thereof, or pharmaceutically acceptable salt forms thereof, which are useful as inhibitors of factor Xa.

Glycinamides as factor Xa inhibitors

The present application describes lactam-containing compounds and derivatives thereof of Formula I: P-P-M-M I or pharmaceutically acceptable salt forms thereof, wherein ring P, if present is a 5&#x2013;7 membered carbocycle or heterocycle and ring M is a 5&#x2013;7 membered carbocycle or heterocycle. Compounds of the present invention are useful as inhibitors of trypsin-like serine proteases, specifically factor Xa.

The present application describes lactam-containing compounds and derivatives thereof of Formula I:or pharmaceutically acceptable salt forms thereof, wherein ring P, if present is a 5-7 membered carbocycle or heterocycle and ring M is a 5-7 membered carbocycle or heterocycle. Compounds of the present invention are useful as inhibitors of trypsin-like serine proteases, specifically factor Xa.

This invention is directed to antineoplastic agents conjugated to enzyme-cleavable peptides comprising the amino acid recognition sequence of a membrane-bound and/or cell-secreted peptidase, and to the use of such conjugated compounds as chemotherapeutic agents in the targeted treatment of cancers.

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Yardley, PA, United States of America

Wei Han