title: Discovery of new piperidine amide triazolobenzodiazepinones as intestinal-selective CCK1 receptor agonists.
abstract: New cholecystokinin-1 receptor (CCK1R) agonist 'triggers' were identified using iterative library synthesis. Structural activity relationship studies led to the discovery of compound 10e, a potent CCK1R agonist that demonstrated robust weight loss in a diet-induced obese rat model with very low systemic exposure. Pharmacokinetic data suggest that efficacy is primarily driven through activation of CCK1R's located within the intestinal wall.
authors.affiliation: Department of Cardiovascular, Metabolic, and Endocrine Diseases, Pfizer Global Research and Development, Groton, CT 06340, USA. kimberly.o.cameron@pfizer.com
authors.forename: Kimberly O
authors.initials: KO
authors.lastname: Cameron
authors.forename: Elena E
authors.initials: EE
authors.lastname: Beretta
authors.forename: Yue
authors.initials: Y
authors.lastname: Chen
authors.forename: Margaret
authors.initials: M
authors.lastname: Chu-Moyer
authors.forename: Dilinie
authors.initials: D
authors.lastname: Fernando
authors.forename: Hua
authors.initials: H
authors.lastname: Gao
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Kohrt
authors.forename: Sophie
authors.initials: S
authors.lastname: Lavergne
authors.forename: Paul Da Silva
authors.initials: Pda S
authors.lastname: Jardine
authors.forename: Angel
authors.initials: A
authors.lastname: Guzman-Perez
authors.forename: Christopher
authors.initials: C
authors.lastname: Hoth
authors.forename: David A
authors.initials: DA
authors.lastname: Perry
authors.forename: John R
authors.initials: JR
authors.lastname: Hadcock
authors.forename: Denise
authors.initials: D
authors.lastname: Gautreau
authors.forename: Michael
authors.initials: M
authors.lastname: Makowski
authors.forename: Sylvie
authors.initials: S
authors.lastname: Perez
authors.forename: Jana
authors.initials: J
authors.lastname: Polivkova
authors.forename: Lucy
authors.initials: L
authors.lastname: Rogers
authors.forename: Dennis O
authors.initials: DO
authors.lastname: Scott
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Swick
authors.forename: Lucinda
authors.initials: L
authors.lastname: Thiede
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Trebino
authors.forename: Richard V
authors.initials: RV
authors.lastname: Trilles
authors.forename: Julie
authors.initials: J
authors.lastname: Wilmowski
authors.forename: Yingxin
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D055808:Drug Discovery; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D051379:Mice; D008820:Mice, Obese; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D043886:Receptor, Cholecystokinin A / Q000819:agonists*; D013329:Structure-Activity Relationship; D015431:Weight Loss / Q000187:drug effects
chemical_list: D000577:Amides; D010880:Piperidines; D043886:Receptor, Cholecystokinin A; C032727:piperidine