CARTER, PERCY H.,珀希Ｈ. 卡特,DUNCIA, JOHN V.,约翰Ｖ. 当希亚,約翰Ｖ. 當希亞,MUDRYK, BOGUSLAW M,玻嘉斯洛Ｍ. 玛卓克,玻嘉斯洛Ｍ. 瑪卓克,RANDAZZO, MICHAEL E.,麦可Ｅ. 蓝道佐,麥可Ｅ. 藍道佐,XIAO, ZILI,肖自力,YANG, MICHAEL G.,麦可Ｇ. 杨,麥可Ｇ. 楊,ZHA,珀希H. 卡特,约翰V. 当希亚,約翰V. 當希亞,玻嘉斯洛M. 玛卓克,玻嘉斯洛M. 瑪卓克,麦可E. 蓝道佐,麥可E. 藍道佐,麦可G. 杨,麥可G. 楊
申请号：
TW096127304
公开号：
TWI421249B
申请日:
2007.07.26
申请国别(地区):
TW
年份:
2014
代理人:
摘要：
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.本發明係提供MCP－1受體活性之新穎拮抗劑或部份催動劑/拮抗劑：N－((1R,2S,5R)－5－(第三－丁基胺基)－2－((S)－2－酮基－3－(6－(三氟甲基)喹唑啉－4－基胺基)四氫吡咯－1－基)環己基)乙醯胺，或其藥學上可接受之鹽、溶劑合物或前體藥物，具有所要藥理學特性之令人意外組合。亦提供本發明之結晶型。含有彼等之醫藥組合物，及使用彼等作為藥劑以治療炎性疾病、過敏性、自身免疫、代謝、癌症及/或心血管疾病之方法，亦為本發明之目的。本揭示內容亦提供製備式(I)化合物之方法，該化合物包括N－((1R,2S,5R)－5－(第三－丁基胺基)－2－((S)－2－酮基－3－(6－(三氟甲基)喹唑啉－4－基胺基)四氫吡咯－1－基)環己基)乙醯胺：其中R1,R8,R9,R10及均如本文中所述。本文亦提供一些化合物，其係為此方法之有用中間物。
