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

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 phenyl ring are important for potency and full efficacy. Compound 26 combined good potency with a promising pharmacokinetic profile in mice, and lowered the glucose excursion in mice in an oral glucose-tolerance test.

Keywords: Agonist; GPCR; GPR119; Oral glucose tolerance test; Type 2 diabetes.