Discovery of MK-7725, A Potent, Selective Bombesin Receptor Subtype-3 Agonist for the Treatment of Obesity

  • ACS Med Chem Lett. 2012 Jan 21;3(3):252-6. doi: 10.1021/ml200304j.
Harry R Chobanian  1 ,  Yan Guo  1 ,  Ping Liu  1 ,  Marc Chioda  1 ,  Thomas J Lanza Jr  1 ,  Linda Chang  1 ,  Theresa M Kelly  1 ,  Yanqing Kan  1 ,  Oksana Palyha  1 ,  Xiao-Ming Guan  1 ,  Donald J Marsh  1 ,  Joseph M Metzger  1 ,  Judith N Gorski  1 ,  Kate Raustad  1 ,  Sheng-Ping Wang  1 ,  Alison M Strack  1 ,  Randy Miller  1 ,  Jianmei Pang  1 ,  Maria Madeira  1 ,  Kathy Lyons  1 ,  Jasminka Dragovic  1 ,  Marc L Reitman  1 ,  Ravi P Nargund  1 ,  Linus S Lin  1
Affiliations
  • 1. Departments of Medicinal Chemistry, Metabolic Disorders, Pharmacology, and Drug Metabolism, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
PMID: 24900461 DOI: 10.1021/ml200304j
Abstract

Extensive structure-activity relationship studies of a series derived from atropisomer 1, a previously described chiral benzodiazepine sulfonamide series, led to a potent, brain penetrant and selective compound with excellent preclinical pharmacokinetic across species. We also describe the utilization of a high throughput mouse pharmacodynamic assay which allowed for expedient assessment of pharmacokinetic and brain distribution.

Keywords
BRS-3; Bombesin receptor subtype-3; MK-7725; agonist; atropisomer; benzodiazepine sulfonamide; obesity.
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