Discovery of pyrazolo[3,4-d]pyrimidine derivatives as GPR119 agonists

Published in: Journal, Article, Volume : 24, Issue : 3, Pages : 949-953

DOI : 10.1016/j.bmcl.2013.12.063

Author : Gillespie, Paul; Goodnow, Robert A.; Saha, Goutam; Bose, Gopal; Moulik, Kakali; Zwingelstein, Catherine; Myers, Michael; Conde-Knape, Karin; Pietranico-Cole, Sherrie; So, Sung-Sau

Abstract : We designed and synthesized a novel series of phenylamino- and phenoxy-substituted pyrazolo[3,4-d]pyrimidine derivatives as GPR119 agonists. SAR studies indicated that electron-withdrawing substituents on the Ph ring are important for potency and full efficacy. Compound I combined good potency with a promising pharmacokinetic profile in mice, and lowered the glucose excursion in mice in an oral glucose-tolerance test.