Wang Liutang, Zhang Bin, Ji Jianxin, Li Bogang, Yan Jufang, Zhang Weiyu, Wu Yong, Wang Xuechao
West China School of Pharmacy, Sichuan University, Chengdu, PR China.
Eur J Med Chem. 2009 Aug;44(8):3318-22. doi: 10.1016/j.ejmech.2009.03.021. Epub 2009 Mar 26.
To find potent and selective inhibitors of dipeptidyl peptidase IV (DPP-IV), we synthesized a series of 2-cyanopyrrolidine derivatives with constrained imidazolidin ring and tested their activities against DPP-IV. Most of them exhibited submicromolar inhibitory activities against DPP-IV. The most potent compound among these is (S)-1-(2-(2-(3-(3,4-dimethoxyphenyl)-2-oxoimidazolidin-1-yl)ethyl-amino)acetyl)pyrrolidine-2-carbonitrile (6n), which is a 2 nM DPP-IV inhibitor.
为了找到二肽基肽酶IV（DPP-IV）的强效和选择性抑制剂，我们合成了一系列带有受限咪唑烷环的2-氰基吡咯烷衍生物，并测试了它们对DPP-IV的活性。其中大多数对DPP-IV表现出亚微摩尔级的抑制活性。这些化合物中最有效的是（S）-1-（2-（2-（3-（3,4-二甲氧基苯基）-2-氧代咪唑烷-1-基）乙基氨基）乙酰基）吡咯烷-2-腈（6n），它是一种2 nM的DPP-IV抑制剂。
