1221420-23-0Relevant articles and documents
Non-basic azolotriazinone MCHR1 antagonists for the treatment of obesity: An empirical brain-exposures-driven candidate selection for in vivo efficacy studies
Devasthale, Pratik,Wang, Wei,Mignone, James,Renduchintala, Kishore,Radhakrishnan, Sridhar,Dhanapal, Jayanthi,Selvaraj, Jagannath,Kuppusamy, Rajesh,Pelleymounter, Mary Ann,Longhi, Daniel,Huang, Ning,Flynn, Neil,Azzara, Anthony V.,Rohrbach, Kenneth,Devenny, James,Rooney, Suzanne,Thomas, Michael,Glick, Susan,Godonis, Helen,Harvey, Susan,Cullen, Mary Jane,Zhang, Hongwei,Caporuscio, Christian,Stetsko, Paul,Grubb, Mary,Huang, Christine,Zhang, Lisa,Freeden, Chris,Murphy, Brian J.,Robl, Jeffrey A.,Washburn, William N.
, p. 4412 - 4418 (2015/10/12)
Non-basic azolotriazinones were explored using an empirical free brain exposures-driven approach to identify potent MCHR1 antagonists for evaluation in in vivo efficacy studies. An optimized lead from this series, 1j (rMCHR1 Ki = 1.8 nM), demonstrated a 6.9% reduction in weight gain relative to vehicle in a rat model at 30 mg/kg after 4 days of once-daily oral treatment as a glycine prodrug. Despite a promising efficacy profile, an assessment of the biliary toxicity risk of this compound rendered this compound non-progressible.
