Discovery of N-benzyl-2-[(4S)-4-(1H-indol-3-ylmethyl)-5-oxo-1-phenyl-4,5-dihydro-6H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepin-6-yl]-N-isopropylacetamide, an orally active, gut-selective CCK1 receptor agonist for the potential treatment of obesity

  • Bioorg Med Chem Lett. 2010 Nov 15;20(22):6797-801. doi: 10.1016/j.bmcl.2010.08.115.
Richard L Elliott  1 ,  Kimberly O Cameron ,  Janice E Chin ,  Jeremy A Bartlett ,  Elena E Beretta ,  Yue Chen ,  Paul Da Silva Jardine ,  Jeffrey S Dubins ,  Melissa L Gillaspy ,  Diane M Hargrove ,  Amit S Kalgutkar ,  Janet A LaFlamme ,  Mary E Lame ,  Kelly A Martin ,  Tristan S Maurer ,  Nancy A Nardone ,  Robert M Oliver ,  Dennis O Scott ,  Dexue Sun ,  Andrew G Swick ,  Catherine E Trebino ,  Yingxin Zhang
Affiliations
  • 1. Department of Cardiovascular, Metabolic, and Endocrine Diseases, Pfizer Global Research and Development, Groton, CT 06340, United States.
PMID: 20851601 DOI: 10.1016/j.bmcl.2010.08.115
Abstract

We describe the design, synthesis, and structure-activity relationships of triazolobenzodiazepinone CCK1 receptor agonists. Analogs in this series demonstrate potent agonist activity as measured by in vitro and in vivo assays for CCK1 agonism. Our efforts resulted in the identification of compound 4a which significantly reduced food intake with minimal systemic exposure in rodents.