Rational design and synthesis of potent and long-lasting glutamic acid-based dipeptidyl peptidase IV inhibitors
- 作者：Ting-Yueh Tsai ; Tsu Hsu ; Chiung-Tong Chen ; Jai-Hong Cheng ; Mei-Chun Chiou ; Chih-Hsiang Huang ; Ya-Ju Tseng ; Teng-Kuang Yeh ; Chung-Yu Huang ; Kai-Chia Yeh ; Yu-Wen Huang ; Ssu-Hui Wu ; Min-Hsien Wang ; Xin C
- 关键词：Glutamic acid ; DPP-IV ; Inhibitor
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2009
- 期刊代码：10_0960894x
- 类别：ch
- 出版时间：1 April 2009
- 卷：19
- 期：7
- 页码：1908-1912
- 文件大小：1650 K
摘要
A series of (2S)-cyanopyrrolidines with glutamic acid derivatives at the P2 site have been prepared and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-IV). The structure–activity relationships (SAR) led to the discovery of potent 3-substituted glutamic acid analogues, providing enhanced chemical stability and excellent selectivity over the closely related enzymes, DPP8, DPP-II and FAP. Compound 13f exhibited the ability to both significantly decrease the glucose excursion and inhibit plasma DPP-IV activity.