Venet Marc, End David, Angibaud Patrick
Johnson & Johnson Pharmaceutical Research, Campus de Maigremont, BP 615, 27106 Val de Reuil Cedex, France.
Curr Top Med Chem. 2003;3(10):1095-102. doi: 10.2174/1568026033452050.
R115777 (R)-6-amino[(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methyl]-4-(3-chlorophenyl)-1-methyl-2(1H)-quinolinone is a potent and selective inhibitor of farnesyl protein transferase with significant antitumor effects in vivo subsequent to oral administration in mice. Taking its roots into Janssen's ketoconazole and retinoic acid catabolism programs, our interest into Ras prenylation process led us stepwise to identify the key structural features of R115777. Methodology, structure activity relationships, and pharmacology will be presented. R115777 is currently in phase III clinical evaluation.
R115777（R）-6-氨基[（4-氯苯基）（1-甲基-1H-咪唑-5-基）甲基]-4-（3-氯苯基）-1-甲基-2（1H）-喹啉酮是一种强效且具有选择性的法尼基蛋白转移酶抑制剂，在小鼠口服给药后，在体内具有显著的抗肿瘤作用。基于杨森公司的酮康唑和视黄酸分解代谢项目，我们对Ras异戊二烯化过程的兴趣促使我们逐步确定了R115777的关键结构特征。本文将介绍其方法、构效关系和药理学。R115777目前正处于III期临床评估阶段。
