Exploration of alternative structures of the substituted piperidine or piperazine ring which are characteristic in most of the reported GPR119 agonists provided novel spirocyclic cyclohexane derivatives. The representative 17 with a high three-dimensionality exhibited potent agonistic activity (EC₅₀ = 4 nM) with no CYP inhibitory activity (IC₅₀ >10 μM). Compound 17 also displayed hypoglycemic activity with insulin secretion dependent on glucose concentration in an intraperitoneal glucose tolerance test in rats.

中文翻译：

---

具有螺环结构的新型强效GPR119激动剂的设计与合成

对大多数报道的GPR119激动剂中特征在于的取代的哌啶或哌嗪环的替代结构的探索提供了新的螺环环己烷衍生物。具有高三维度的代表性17表现出有效的激动活性（EC ₅₀  = 4 nM），没有CYP抑制活性（IC ₅₀ > 10μM）。在大鼠腹膜内葡萄糖耐量试验中，化合物17还显示出降血糖活性，胰岛素分泌依赖于葡萄糖浓度。