Details

Autor(en) / Beteiligte

• Cameron, Kimberly O.
• Beretta, Elena E.
• Chen, Yue
• Chu-Moyer, Margaret
• Fernando, Dilinie
• Gao, Hua
• Kohrt, Jeffrey
• Lavergne, Sophie
• Jardine, Paul Da Silva
• Guzman-Perez, Angel
• Hoth, Christopher
• Perry, David A.
• Hadcock, John R.
• Gautreau, Denise
• Makowski, Michael
• Perez, Sylvie
• Polivkova, Jana
• Rogers, Lucy
• Scott, Dennis O.
• Swick, Andrew G.
• Thiede, Lucinda
• Trebino, Catherine E.
• Trilles, Richard V.
• Wilmowski, Julie
• Zhang, Yingxin

Titel

Discovery of new piperidine amide triazolobenzodiazepinones as intestinal-selective CCK1 receptor agonists

Ist Teil von

• Bioorganic & medicinal chemistry letters, 2012-04, Vol.22 (8), p.2943-2947

Ort / Verlag

Amsterdam: Elsevier Ltd

Erscheinungsjahr

2012

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Compound 10e was identified as a potent CCK1 receptor agonist (IC50=20.3nM, EC50=25.4nM). Compound 10e demonstrated significant weight loss effects in an obese rat model despite low oral bioavailability (F=0.13%). 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.