N-((1R,2S,5R)-5-(tert-butylamino)-2-((S)-2-oxo-3-(6-(trifluoromethyl)quinazolin-4-ylamino) pyrrolidin-1-yl)cyclohexyl)acetamide and other modulators of chemokine receptor activity, crystalline forms and process

US7629351B2 · kind B2 · utility

Assignee

• Bristol-Myers Squibb Company · US

Inventors

• Percy H. Carter · Princeton, US
• John V. Duncia · Newtown, US
• Boguslaw M. Mudryk · Plainsboro, US
• Michael E. Randazzo · Tampa, US
• Zili Xiao · Plainsboro, US
• Michael G. Yang · Narberth, US
• Rulin Zhao · Pennington, US

Key dates

• Filing date: Jul 25, 2007
• Grant date: Dec 8, 2009
• Expiry date: Nov 27, 2027

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D317/72
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

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 R1, R8,R9, R10, andare as described herein. Compounds that are useful intermediates of the process are also provided herein.