title: Potent biphenyl- and 3-phenyl pyridine-based inhibitors of acetyl-CoA carboxylase.
abstract: We report the synthesis and enzymatic evaluation of potent inhibitors of acetyl-CoA carboxylases (ACCs) containing biphenyl or 3-phenyl pyridine cores. These compounds inhibit both ACC1 and ACC2, or are moderately selective for either enzyme, depending on side chain substitution. Typical activities of the most potent compounds in this class are in the low double-digit to single-digit nanomolar range in in vitro assays using human ACC1 and ACC2 enzymes.
authors.affiliation: Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543-4000, USA. tasir.haque@bms.com
authors.forename: Tasir S
authors.initials: TS
authors.lastname: Haque
authors.forename: Ningning
authors.initials: N
authors.lastname: Liang
authors.forename: Rajasree
authors.initials: R
authors.lastname: Golla
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Seethala
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Ma
authors.forename: William R
authors.initials: WR
authors.lastname: Ewing
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Cooper
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Pelleymounter
authors.forename: Michael A
authors.initials: MA
authors.lastname: Poss
authors.forename: Dong
authors.initials: D
authors.lastname: Cheng
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000037:antagonists & inhibitors / Q000378:metabolism; D019440:Anti-Obesity Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D019440:Anti-Obesity Agents; D004791:Enzyme Inhibitors; D011725:Pyridines; C520105:ACACB protein, human; D000103:Acetyl-CoA Carboxylase