title: 2-Substituted piperazine-derived imidazole carboxamides as potent and selective CCK1R agonists for the treatment of obesity.
abstract: The discovery and structure-activity relationship of 1,2-diarylimidazole piperazine carboxamides bearing polar side chains as potent and selective cholecystokinin 1 receptor (CCK1R) agonists are described. Optimization of this series resulted in the discovery of isopropyl carboxamide 40, a CCK1R agonist with sub-nanomolar functional and binding activity as well as excellent potency in a mouse overnight food intake reduction assay.
authors.affiliation: Department of Medicinal Chemistry, Merck & Co., Inc., 126 East Lincoln Ave., PO Box 2000, Rahway, NJ 07065-0900, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Berger
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhu
authors.forename: Alexa R
authors.initials: AR
authors.lastname: Hansen
authors.forename: Bart
authors.initials: B
authors.lastname: Harper
authors.forename: Zhesheng
authors.initials: Z
authors.lastname: Chen
authors.forename: Tom G
authors.initials: TG
authors.lastname: Holt
authors.forename: James
authors.initials: J
authors.lastname: Hubert
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Lee
authors.forename: Jie
authors.initials: J
authors.lastname: Pan
authors.forename: Su
authors.initials: S
authors.lastname: Qian
authors.forename: Marc L
authors.initials: ML
authors.lastname: Reitman
authors.forename: Alison M
authors.initials: AM
authors.lastname: Strack
authors.forename: Drew T
authors.initials: DT
authors.lastname: Weingarth
authors.forename: Michael
authors.initials: M
authors.lastname: Wolff
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Macneil
authors.forename: Ann E
authors.initials: AE
authors.lastname: Weber
authors.forename: Scott D
authors.initials: SD
authors.lastname: Edmondson
mesh_terms: D000818:Animals; D019440:Anti-Obesity Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001569:Benzodiazepines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D019742:Chemokines, CC; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008744:Methylamines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D009765:Obesity / Q000188:drug therapy*; D000077489:Piperazine; D010879:Piperazines / Q000737:chemistry; D043886:Receptor, Cholecystokinin A / Q000819:agonists*; D011949:Receptors, Cholecystokinin / Q000819:agonists / Q000737:chemistry; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D019440:Anti-Obesity Agents; C511142:Ccl28 protein, mouse; D019742:Chemokines, CC; C488719:GI 181771X; D007211:Indoles; D008744:Methylamines; D010879:Piperazines; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin; C118846:SR 146131; D013844:Thiazoles; D001569:Benzodiazepines; D000077489:Piperazine