Bristol-myers Squibb Compnay

Michael E Randazzo

Bruce A Ellsworth

Janak Singh

Rulin Zhao

Jack Z Gougoutas

Chiajen Lai

Boguslaw Mudryk

Prashant P Deshpande

Gerard Crispino

Theodor W Denzel

Robert Zahler

John V Duncia

Michael G Yang

David R Kronenthal

Gregory S Bisacchi

William A Slusarchyk

Percy H Carter

James Clifford Sutton

Zili Xiao

John J Venit

Victor W Rosso

Jingyang Zhu

Zhongping Shi

Gary D Madding

Jason G Chen

Mark D Schwinden

Atul S Kotnis

D David Hennings

Zhongmin Xu

Robert P Discordia

Steven M Seiler

Uwe Treuner

Francis J Okuniewicz

Susanne Kiau

Boguslaw M Mudryk

The present invention provides a novel antagonist or partial agonists/antagonist of MCP-1 receptor activity: N-((1R,2S,5R)-5-(tert-butylamino)-2-((S)-2-oxo-3-(6-(trifluoromethyl)quinazolin-4-ylamino) pyrrolidin-1-yl)cyclohexyl)acetamide, or a pharmaceutically acceptable salt, solvate or prodrug, thereof, having an unexpected combination of desirable pharmacological characteristics. Crystalline forms of the present invention are also provided. Pharmaceutical compositions containing the same and methods of using the same as agents for the treatment of inflammatory diseases, allergic, autoimmune, metabolic, cancer and/or cardiovascular diseases is also an objective of this invention. The present disclosure also provides a process for preparing compounds of Formula (I), including N-((1R,2S,5R)-5-(tert-butylamino)-2-((S)-2-oxo-3-(6-(trifluoromethyl)quinazolin-4-ylamino)pyrrolidin-1-yl)cyclohexyl)acetamide: wherein R, R, R, R, and are as described herein. Compounds that are useful intermediates of the process are also provided herein.

Substituted pyrrolidine-2-one compounds

Method for the production of C-aryl glucoside SGLT2 inhibitors useful for the treatment of diabetes and related diseases. and intermediates thereof. The C-aryl glucosides may be complexed with amino acid complex forming reagents.

Methods of producing C-aryl glucoside SGLT2 inhibitors

The present invention provides a novel antagonist or partial agonists/antagonist of MCP-1 receptor activity: N-((1R,2S,5R)-5-tert-butylamino)-2-((S)-2-oxo-3-(6-(trifluoromethyl)quinazolin-4-ylamino)pyrrolidin-1-yl)cyclohexyl)acetamide, or a pharmaceutically acceptable salt, solvate or prodrug, thereof, having an unexpected combination of desirable pharmacological characteristics. Crystalline forms of the present invention are also provided. Pharmaceutical compositions containing the same and methods of using the same as agents for the treatment of inflammatory diseases, allergic, autoimmune, metabolic, cancer and/or cardiovascular diseases is also an objective of this invention. The present disclosure also provides a process for preparing compounds of Formula (I), including N-((1R,2S,5R)-5-(tert-butylamino)-2-((S)-2-oxo-3-(6-trifluoromethyl)quinazolin-4-ylamino)pyrrolidin-1-yl)cyclohexyl)acetamide: wherein R, R,R, R, and are as described herein. Compounds that are useful intermediates of the process are also provided herein.

[object Object]

Provided is a dynamic resolution method of enriching a desired isomer of an alpha-substituted carboxylic acid relative to an undesired isomer, the method comprising: (a) in a solvent, contacting the alpha-substituted carboxylic acid, wherein the alpha substitution is with a leaving group and wherein the alpha carbon is chiral, with a homochiral amine to form a salt that is partially insoluble under selected reaction conditions, wherein the homochiral amine is selected so that the solubility of the amine salt of the undesired alpha-substituted carboxylic acid is greater than that of the amine salt of the desired alpha-substituted carboxylic acid under the selected reaction conditions; (b) reacting under the selected reaction conditions the salt with a nucleophile, wherein the reacting is effective in producing a net increase in the less soluble amine salt of the alpha-substituted carboxylic acid, and wherein the selected conditions are selected to (i) promote nucleophilic substitution of the nucleophile and the leaving group or (ii) to produce the increase in the less soluble amine salt in the absence of a strong base; and (c) maintaining the reaction for a period of time effective to increase the amount of the desired alpha-substituted carboxylic acid isomer.

Dynamic resolution of isomers and resolved isomers

Beta lactam compounds and their use as inhibitors of tryptase

Growing community of inventors

East Windsor, NJ, United States of America

Michael E Randazzo