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.

中文翻译：

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GPR119激动剂2-（4-（甲基磺酰基）苯基）吡啶衍生物的设计，合成和生物学评估

这项研究描述了一系列新型小分子GPR119激动剂的设计，合成和生物学评估，这些激动剂具有增强的效力和适度的理化特性。其中，最有希望的化合物19和20分别在体外cAMP分析中获得EC ₅₀值为75和25 nM，并在正常小鼠的口服葡萄糖耐量试验（OGTT）中有效降低了血糖波动。此外，在由链脲佐菌素和高脂饮食诱导的患有2型糖尿病小鼠的OGTT中，与赋形剂对照组相比，化合物19还显示出血糖水平的显着降低，这表明其在体内和体外的诱人特性值得进一步开发。