作者
Linus S. Lin,Thomas J. Lanza,James P. Jewell,Ping Liu,Shrenik K. Shah,Hongbo Qi,Xinchun Tong,Junying Wang,Suoyu Xu,Tung M. Fong,Chun-Pyn Shen,Julie Lao,Jing Xiao,Lauren P. Shearman,Donald Stribling,Kimberly Rosko,Alison M. Strack,Donald J. Marsh,Yue Feng,Sanjeev Kumar,Koppara Samuel,Wenji Yin,Lex H.T. Van der Ploeg,Mark T. Goulet,William K. Hagmann
摘要
The discovery of novel acyclic amide cannabinoid-1 receptor inverse agonists is described. They are potent, selective, orally bioavailable, and active in rodent models of food intake and body weight reduction. A major focus of the optimization process was to increase in vivo efficacy and to reduce the potential for formation of reactive metabolites. These efforts led to the identification of compound 48 for development as a clinical candidate for the treatment of obesity.