Discovery of N-benzyl-2-[(4S)-4-(1H-indol-3-ylmethyl)-5-oxo-1-phenyl-4,5-dihydro-6H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepin-6-yl]-N-isopropylacetamide, an orally active, gut-selective CCK1 receptor agonist for the potential treatment of obesity

Autor:	Melissa L. Gillaspy, Diane M. Hargrove, Mary E. Lame, Paul Da Silva Jardine, Dennis O. Scott, Catherine E. Trebino, Yingxin Zhang, Kimberly O. Cameron, Richard L. Elliott, Kelly A. Martin, Janice E. Chin, Elena E. Beretta, Swick Andrew Gordon, Jeffrey S. Dubins, Janet A. LaFlamme, Dexue Sun, Tristan S. Maurer, Nancy A. Nardone, Amit S. Kalgutkar, Jeremy A. Bartlett, Robert M. Oliver, Yue Chen
Rok vydání:	2010
Předmět:	Male Agonist Food intake medicine.drug_class Clinical Biochemistry Pharmaceutical Science Pharmacology Biochemistry Rats Sprague-Dawley Benzodiazepines Structure-Activity Relationship In vivo Drug Discovery medicine Animals Structure–activity relationship Receptor Molecular Biology Cholecystokinin Chemistry Organic Chemistry In vitro Rats Molecular Medicine Receptors Cholecystokinin Anti-Obesity Agents Cck1 receptor
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 20:6797-6801
ISSN:	0960-894X
Popis:	We describe the design, synthesis, and structure-activity relationships of triazolobenzodiazepinone CCK1 receptor agonists. Analogs in this series demonstrate potent agonist activity as measured by in vitro and in vivo assays for CCK1 agonism. Our efforts resulted in the identification of compound 4a which significantly reduced food intake with minimal systemic exposure in rodents.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::eeaaaf4e60123f7f9fd8e609d714c16d https://doi.org/10.1016/j.bmcl.2010.08.115 Zobrazit plný text záznamu Full Text from ScienceDirect