A novel series of beta-amino amides incorporating fused heterocycles, i.e., triazolopiperazines, were synthesized and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-IV) for the treatment of type 2 diabetes. (2R)-4-Oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)- yl]-1-(2,4,5-trifluorophenyl)butan-2-amine (1) is a potent, orally active DPP-IV inhibitor (IC(50) = 18 nM) with excellent selectivity over other proline-selective peptidases, oral bioavailability in preclinical species, and in vivo efficacy in animal models. MK-0431, the phosphate salt of compound 1, was selected for development as a potential new treatment for type 2 diabetes.

中文翻译：

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（2R）-4-氧代-4- [3-（三氟甲基）-5,6-二氢[1,2,4]三唑并[4,3-a]吡嗪-7（8H）-yl] -1-（ 2,4,5-三氟苯基）丁-2-胺：一种有效的口服活性二肽基肽酶IV抑制剂，用于治疗2型糖尿病。

合成了一系列融合了杂环的新型β-氨基酰胺，即三唑并哌嗪，并将其评估为二肽基肽酶IV（DPP-IV）的抑制剂，用于治疗2型糖尿病。（2R）-4-Oxo-4- [3-（三氟甲基）-5,6-二氢[1,2,4]三唑并[4,3-a]吡嗪-7（8H）-yl] -1-（ 2,4,5-三氟苯基）丁-2-胺（1）是一种有效的口服DPP-IV抑制剂（IC（50）= 18 nM），对其他脯氨酸选择性肽酶具有优异的选择性，在临床前物种中具有口服生物利用度，以及在动物模型中的体内功效。选择化合物1的磷酸盐MK-0431作为潜在的2型糖尿病新疗法进行开发。