title: 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.
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.
authors: 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.
authors: Saleem
authors: S
authors: Ahmad
authors: 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.
authors: William N
authors: WN
authors: Washburn
authors: 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.
authors: Andres S
authors: AS
authors: Hernandez
authors: 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.
authors: Sharon
authors: S
authors: Bisaha
authors: 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.
authors: Khehyong
authors: K
authors: Ngu
authors: 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.
authors: Wei
authors: W
authors: Wang
authors: 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.
authors: Mary Ann
authors: MA
authors: Pelleymounter
authors: 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.
authors: Daniel
authors: D
authors: Longhi
authors: 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.
authors: Neil
authors: N
authors: Flynn
authors: 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.
authors: Anthony V
authors: AV
authors: Azzara
authors: 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.
authors: Kenneth
authors: K
authors: Rohrbach
authors: 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.
authors: James
authors: J
authors: Devenny
authors: 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.
authors: Suzanne
authors: S
authors: Rooney
authors: 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.
authors: Michael
authors: M
authors: Thomas
authors: 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.
authors: Susan
authors: S
authors: Glick
authors: 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.
authors: Helen
authors: H
authors: Godonis
authors: 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.
authors: Susan
authors: S
authors: Harvey
authors: 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.
authors: Hongwei
authors: H
authors: Zhang
authors: 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.
authors: Brian
authors: B
authors: Gemzik
authors: 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.
authors: Evan B
authors: EB
authors: Janovitz
authors: 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.
authors: Christine
authors: C
authors: Huang
authors: 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.
authors: Lisa
authors: L
authors: Zhang
authors: 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.
authors: Jeffrey A
authors: JA
authors: Robl
authors: 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.
authors: Brian J
authors: BJ
authors: Murphy
mesh_terms: D000818:Animals; D019440:Anti-Obesity Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D004285:Dogs; D054879:Halogenation; D006801:Humans; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D009765:Obesity / Q000188:drug therapy*; D011743:Pyrimidines / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D019440:Anti-Obesity Agents; C103263:MCHR1 protein, human; D011743:Pyrimidines; D017481:Receptors, Somatostatin; C000601850:thieno(2,3-d)pyrimidine