N，N'-二取代3-氨基氮杂环庚烷-2-酮作为强效和特异性法尼基转移酶抑制剂的平行液相合成

Parallel liquid synthesis of N,N'-Disubstituted 3-amino azepin-2-ones as potent and specific farnesyl transferase inhibitors.

作者信息

Le Diguarher Thierry, Ortuno Jean Claude, Dorey Gilbert, Shanks David, Guilbaud Nicolas, Pierré Alain, Fauchère Jean Luc, Hickman John A, Tucker Gordon C, Casara Patrick J

机构信息

Department of Medicinal Chemistry, Institut de Recherches Servier, 125 chemin de Ronde, 78290 Croissy sur Seine, France.

出版信息

Bioorg Med Chem. 2003 Jul 17;11(14):3193-204. doi: 10.1016/s0968-0896(03)00218-9.

DOI:10.1016/s0968-0896(03)00218-9

PMID:12818682

Abstract

A rapid structure-activity study was performed by parallel liquid synthesis on N,N'-disubstitution of 3-amino azepin-2-one to afford potent and specific farnesyl transferase inhibitors with low nM enzymatic and cellular activities. The activities of the selected compounds were validated in vivo, and compounds 41a and 44a presented significant antitumour activity.

摘要

通过平行液相合成对3-氨基氮杂环庚烷-2-酮的N,N'-二取代进行了快速构效关系研究，以获得具有低纳摩尔酶活性和细胞活性的强效且特异性的法尼基转移酶抑制剂。所选化合物的活性在体内得到验证，化合物41a和44a表现出显著的抗肿瘤活性。