GPR119 is a promising target for discovery of anti-type 2 diabetes mellitus agents. We described the optimisation of a novel series of pyrimido[5,4-b][1,4]oxazine derivatives as GPR119 agonists. Most designed compounds exhibited good agonistic activities. Among them, compound 10 and 15 demonstrated the potent EC50 values (13 and 12 nM, respectively) and strong inherent activities. Moreover, significant hypoglycaemic effect of compound 15 was observed by reducing the blood glucose AUC0-2h at the dose of 30 mg/kg, which is stronger than Vildagliptin (23.4% reduction vs. 17.9% reduction).

中文翻译：

---

优化新型4、8-二取代的二氢嘧啶基[5,4-b] [1,4]恶嗪衍生物作为有效的GPR 119激动剂。

GPR119是发现抗2型糖尿病药物的有希望的靶标。我们描述了作为GPR119激动剂的一系列新的嘧啶并[5,4-b] [1,4]恶嗪衍生物的优化。大多数设计的化合物表现出良好的激动活性。其中，化合物10和15表现出有效的EC50值（分别为13和12 nM）和强大的固有活性。此外，通过以30 mg / kg的剂量降低血糖AUC0-2h，观察到化合物15的显着降血糖作用，这比维格列汀强（降幅23.4％对降幅17.9％）。