Merck + Co., Inc.

Biogen Ma Inc.

Sunesis Pharmaceuticals, Inc.

Other

Merck Sharp + Dohme Corp.

Brigham Young University

Ross A Miller

Guy R Humphrey

Andrew S Thompson

Brian T Hopkins

Patrick R Conlon

Tracy J Jenkins

Timothy Raymond Chan

Michael J Humora

Xianglin Shi

Xiongwei Cai

Paul B Savage

Nobuyoshi Yasuda

Raman Kumar Bakshi

Peter Emmanuel Maligres

Steven A Weissman

James A McCauley

Edward G Corley

Aaron S Cote

Jared Lynn Randall

Wenjie Li

David R Lieberman

Andrew L Forman

J Michael Macphee

Thomas Elliott Jacks

Scott S Ceglia

Michael J Macphee

Paul F McKenzie

David M Lashen

Sean R Holihan

Pascal H Toma

Andrew Thompson

Steven Weissman

The present invention provides compounds and compositions thereof which are useful as inhibitors of Bruton's tyrosine kinase and which exhibit desirable characteristics for the same.

Pyrimidinyl tyrosine kinase inhibitors

Disclosed herein are methods of making ceragnenin compounds for treating, preventing, or diagnosing diseases, disorders, or conditions associated with bacterial or viral infections, cancer, inflammation, and osteogenesis. Ceragenin compounds display broad-spectrum antibacterial activity utilizing a mode of action similar to antimicrobial peptides, but without the high synthesis costs and susceptibility to proteolytic degradation. Ceragenin compounds reproduce the amphiphilic morphology found in many antimicrobial peptides and display potent and diverse biological activities, including anti-bacterial, anti-cancer, anti-inflammatory, bone growth promotion, and wound healing promotion.

Methods for the synthesis of ceragenins

The present invention provides a compound, solid forms, and compositions thereof, which are useful as inhibitors of Bruton's tyrosine kinase and which exhibit desirable characteristics for the same. The present invention also provides methods of making provided compound and solid forms.

Inhibitors of Bruton's tyrosine kinase

Processes for preparing certain N-arylalkyl-1-(alkyl or aralkyl)-2-acylaminoalkyl-5-hydroxy-6-oxo-1,6-dihydropyrimidine-4-carboxamides are disclosed. In one embodiment, the process comprises acylating the free amine in the corresponding N-arylalkyl-1-(alkyl or aralkyl)-2-aminoalkyl-5-ester protected hydroxy-6-oxo-1,6-dihydropyrimidine-4-carboxamide and then deprotecting the 5-hydroxy by base hydrolysis. The hydroxypyrimidinone carboxamide products of the process are HTV integrase inhibitors which are useful for treating HTV infection, treating AIDS, or delaying the onset or progression of AIDS. Certain esterified N-arylalkyl hydroxypyrimidinone carboxamides that can be employed as process intermediates are also disclosed. 

Process for preparing N-substituted hydroxypyrimidinone carboxamides

An efficient process is disclosed for producing a compound that is an inhibitor of CETP. The last step of the process is the coupling of an oxazolidinone derivative with a biphenyl moiety to provide a compound of formula (I). In a specific embodiment of this synthesis, a crystalline product is produced which is characterized as a non-solvated crystalline polymorph.

Process for synthesizing a CETP inhibitor

Process for the synthesis of carbapenem intermediates, and compounds produced

The instant invention involves a process for oxidizing compounds containing an allylic group, i.e. those containing an allylic hydrogen or allylic alcohol group, to the corresponding enones, using a ruthenium-based catalyst in the presence of a hydroperoxide. Particularly, &Dgr;-5-steroidal alkenes can be oxidized to the corresponding &Dgr;-5-7-keto alkenes.

Process for oxidation of steroidal compounds having allylic groups

Crystalline salts of an amorphous, unstable carbapenem antibiotic having the formula:

Crystalline salts of a carbapenem antibiotic

The novel process of this invention involves the stereoselective synthesis of certain 16-substituted 4-aza-5&agr;-androst-1-en-3-ones, and the useful intermediates obtained therein.

Intermediates and process for the synthesis of azasteroids

A process for synthesizing a compound of formula I: is disclosed wherein R represents halo or C.sub.1-6 alkyl, unsubstituted or substituted with OP, wherein P represents a protecting group.

Process for synthesizing carbapenem intermediates

The novel process of this invention involves the reduction of certain .DELTA.-5 steroidal alkenes to selectively produce either the 5.alpha. or 5.beta. reduction products. Particularly, this invention involves reduction of .DELTA.-5 steroidal alkenes using a rhodium based catalyst in the presence of hydrogen to selectively yield 5.alpha. steroids or alternatively reduction of .DELTA.-5 steroidal alkenes in an ionizing medium with a trialkylsilane to selectively yield 5.beta. steroids.

Process for the stereoselective reduction of steroid enelactams

Growing community of inventors

South Plainfield, NJ, United States of America

Ross A Miller