2. Academic Validation
  3. Discovery of new piperidine amide triazolobenzodiazepinones as intestinal-selective CCK1 receptor agonists

Discovery of new piperidine amide triazolobenzodiazepinones as intestinal-selective CCK1 receptor agonists

  • Bioorg Med Chem Lett. 2012 Apr 15;22(8):2943-7. doi: 10.1016/j.bmcl.2012.02.049.
Kimberly O Cameron 1,  Elena E Beretta,  Yue Chen,  Margaret Chu-Moyer,  Dilinie Fernando,  Hua Gao,  Jeffrey Kohrt,  Sophie Lavergne,  Paul Da Silva Jardine,  Angel Guzman-Perez,  Christopher Hoth,  David A Perry,  John R Hadcock,  Denise Gautreau,  Michael Makowski,  Sylvie Perez,  Jana Polivkova,  Lucy Rogers,  Dennis O Scott,  Andrew G Swick,  Lucinda Thiede,  Catherine E Trebino,  Richard V Trilles,  Julie Wilmowski,  Yingxin Zhang
Affiliations

Affiliation

  • 1 Department of Cardiovascular, Metabolic, and Endocrine Diseases, Pfizer Global Research and Development, Groton, CT 06340, USA. [email protected]
PMID: 22424974 DOI: 10.1016/j.bmcl.2012.02.049
Abstract

New cholecystokinin-1 receptor (CCK1R) agonist 'triggers' were identified using iterative library synthesis. Structural activity relationship studies led to the discovery of compound 10e, a potent CCK1R agonist that demonstrated robust weight loss in a diet-induced obese rat model with very low systemic exposure. Pharmacokinetic data suggest that efficacy is primarily driven through activation of CCK1R's located within the intestinal wall.

Figures