| Abstract: | This study describes the design, synthesis, and biological evaluation of a series of novel small molecule GPR119 agonists with improved potency and moderate physiochemical characteristics. Among them, the most promising compounds 19 and 20 were obtained with EC50 values of 75 and 25 nM, respectively, in vitro cAMP assays and effectively decreased blood glucose excursion in oral glucose tolerance test (OGTT) of normal mice. Furthermore, in OGTT with type 2 diabetic mice induced by streptozotocin and high‐fat diet, compound 19 also showed significant reduction in blood glucose level compared to vehicle control group, which demonstrated an attractive in vitro and in vivo profile for further development. |
