Objective To synthesize novel cyanopyrrolidine-bearing compounds as dipeptidyl peptidase 4 (DPP4) inhibitors and characterize their biological activities in vitro. Methods Eleven analogues of carbonitrilpyrrolidine were designed and synthesized by substitution reaction of (S)-2-(2-cyanopyrrolidin-l-yl)acetyl bromide with substituted phenyl piperazine pyridazinones. Results The structures of the compounds were characterized by 'H-NMR and MS spectra. Biological evaluation indicated that most of the compounds exhibited moderate inhibitory activities against DPP4. Conclusion The preliminary bioassay indicates that all the synthesized compounds have moderate DPP-4 inhibition activity, especially the compounds 1j and Ik with inhibition rates reaching 26.14% and 34.15% at the concentration of l×105 nmol/L, respectively.%目的 设计合成底物类似的氰基吡咯烷类二肽基肽酶(DPP-4)抑制剂,对其进行体外活性测试.方法 以氰基吡咯烷为基本骨架,引入不同的取代基,设计了11个DPP-4抑制剂.以L-脯氨酰胺为原料制备溴乙酰氰基吡咯烷,再与不同取代的苯基哌嗪哒嗪酮经亲核取代反应得目标化合物.结果 所得目标化合物经1H-NMR、MS确认结构,并以西他列汀为对照药,对其进行体外活性筛选.所有目标化合物均有一定的抑制活性.结论 活性测试显示11个目标位均有一定的DPP-4抑制活性,其中化合物1j和1k的抑制活性更强,在105 nmol/L水平的抑制率分别是1j (26.14％)、1k (34.15％).
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