Synthesis and Antiobesity Properties of 6-(4-Chlorophenyl)-3-(4-((3,3-difluoro-1-hydroxycyclobutyl)methoxy)-3-methoxyphenyl)thieno[3,2-d]pyrimidin-4(3H)-one (BMS-814580): A Highly Efficacious Melanin Concentrating Hormone Receptor 1 (MCHR1) Inhibitor

  • J Med Chem. 2016 Oct 13;59(19):8848-8858. doi: 10.1021/acs.jmedchem.6b00676.
Saleem Ahmad  1 ,  William N Washburn  1 ,  Andres S Hernandez  1 ,  Sharon Bisaha  1 ,  Khehyong Ngu  1 ,  Wei Wang  1 ,  Mary Ann Pelleymounter  1 ,  Daniel Longhi  1 ,  Neil Flynn  1 ,  Anthony V Azzara  1 ,  Kenneth Rohrbach  1 ,  James Devenny  1 ,  Suzanne Rooney  1 ,  Michael Thomas  1 ,  Susan Glick  1 ,  Helen Godonis  1 ,  Susan Harvey  1 ,  Hongwei Zhang  1 ,  Brian Gemzik  1 ,  Evan B Janovitz  1 ,  Christine Huang  1 ,  Lisa Zhang  1 ,  Jeffrey A Robl  1 ,  Brian J Murphy  1
Affiliations
  • 1. Metabolic Diseases Chemistry, ‡Metabolic Diseases Biology, §PCO MAP, ∥PCO Discovery Toxicology, and ⊥PCO Bioanalytical Research, Bristol-Myers Squibb Research & Development , P.O. Box 4000, Princeton, New Jersey 08543, United States.
PMID: 27564419 DOI: 10.1021/acs.jmedchem.6b00676
Abstract

The potent MCHR1 in vitro and in vivo antagonist activity of a series of cyclic tertiary alcohols derived from compound 2b is described. Subsequent pharmacokinetic and pharmacodynamic studies identified BMS-814580 (compound 10) as a highly efficacious antiobesity agent with a relatively clean in vitro and in vivo safety profile.

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