(2S,4S)-1-[2-(1,1-二甲基-3-氧代-3-吡咯烷-1-基丙酰基氨基)乙酰基]-4-氟-吡咯烷-2-甲腈：一种强效、选择性和口服生物可利用的二肽衍生的二肽基肽酶 IV 抑制剂。
(2S,4S)-1-[2-(1,1-dimethyl-3-oxo-3-pyrrolidin-1-yl-propylamino)acetyl]-4-fluoro-pyrrolidine-2-carbonitrile: a potent, selective, and orally bioavailable dipeptide-derived inhibitor of dipeptidyl peptidase IV.
机构信息
Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Zhunan Town, Miaoli Country, Taiwan, ROC.
出版信息
Bioorg Med Chem Lett. 2010 Jun 15;20(12):3596-600. doi: 10.1016/j.bmcl.2010.04.124. Epub 2010 May 17.
A series of 2-[3-[2-[(2S)-2-cyano-1-pyrrolidinyl]-2-oxoethylamino]-3-methyl-1-oxobutyl]-based DPP-IV inhibitors with various monocyclic amines were synthesized. The structure-activity relationships (SAR) led to the discovery of potent DPP-IV inhibitors, having IC(50) values of <100 nM with excellent selectivity over the closely related enzymes, DPP-II, DPP8, DPP9 and FAP (IC(50)>20 microM). Of these compounds, the analogues 12a, 12h and 12i exhibited a long-lasting ex vivo DPP-IV inhibition in rats.
合成了一系列基于 2-[3-[2-[(2S)-2-氰基-1-吡咯烷基]-2-氧代乙基氨基]-3-甲基-1-氧代丁基]-的 DPP-IV 抑制剂，这些抑制剂带有各种单环胺。结构-活性关系（SAR）导致发现了具有强效 DPP-IV 抑制活性的抑制剂，其对密切相关的酶 DPP-II、DPP8、DPP9 和 FAP 的 IC（50）值均小于 100 nM，具有优异的选择性（IC（50）>20 microM）。在这些化合物中，类似物 12a、12h 和 12i 在大鼠体内表现出持久的体外 DPP-IV 抑制作用。
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