Tricyclic dihydroquinazolinones as novel 5-HT2C selective and orally efficacious anti-obesity agents
Saleem Ahmad1, Khehyong Ngu, Keith J Miller
1Research & Development, Bristol-Myers Squibb Co, PO Box 4000, Princeton, NJ 08543, United States. saleem.ahmad@bms.com
Abstract:
Agonists of the 5-HT(2C) receptor have been shown to suppress appetite and reduce body weight in animal models as well as in humans. However, agonism of the related 5-HT(2B) receptor has been associated with valvular heart disease. Synthesis and biological evaluation of a series of novel and highly selective dihydroquinazolinone-derived 5-HT(2C) agonists with no detectable agonism of the 5-HT(2B) receptor is described. Among these, compounds (+)-2a and (+)-3c were identified as potent and highly selective agonists which exhibited weight loss in a rat model upon oral dosing.
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