2. Academic Validation
  3. Discovery of N-[(1S,2S)-3-(4-Chlorophenyl)-2- (3-cyanophenyl)-1-methylpropyl]-2-methyl-2- {[5-(trifluoromethyl)pyridin-2-yl]oxy}propanamide (MK-0364), a novel, acyclic cannabinoid-1 receptor inverse agonist for the treatment of obesity

Discovery of N-[(1S,2S)-3-(4-Chlorophenyl)-2- (3-cyanophenyl)-1-methylpropyl]-2-methyl-2- {[5-(trifluoromethyl)pyridin-2-yl]oxy}propanamide (MK-0364), a novel, acyclic cannabinoid-1 receptor inverse agonist for the treatment of obesity

  • J Med Chem. 2006 Dec 28;49(26):7584-7. doi: 10.1021/jm060996+.
Linus S Lin 1,  Thomas J Lanza Jr,  James P Jewell,  Ping Liu,  Shrenik K Shah,  Hongbo Qi,  Xinchun Tong,  Junying Wang,  Suoyu S Xu,  Tung M Fong,  Chun-Pyn Shen,  Julie Lao,  Jing Chen Xiao,  Lauren P Shearman,  D Sloan Stribling,  Kimberly Rosko,  Alison Strack,  Donald J Marsh,  Yue Feng,  Sanjeev Kumar,  Koppara Samuel,  Wenji Yin,  Lex H T Van der Ploeg,  Mark T Goulet,  William K Hagmann
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. [email protected]
PMID: 17181138 DOI: 10.1021/jm060996+
Abstract

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.

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