强效且长效的基于谷氨酸的二肽基肽酶IV抑制剂的合理设计与合成
Rational design and synthesis of potent and long-lasting glutamic acid-based dipeptidyl peptidase IV inhibitors.
作者信息
Tsai Ting-Yueh, Hsu Tsu, Chen Chiung-Tong, Cheng Jai-Hong, Chiou Mei-Chun, Huang Chih-Hsiang, Tseng Ya-Ju, Yeh Teng-Kuang, Huang Chung-Yu, Yeh Kai-Chia, Huang Yu-Wen, Wu Ssu-Hui, Wang Min-Hsien, Chen Xin, Chao Yu-Sheng, Jiaang Weir-Torn
机构信息
Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, No. 35, Keyan Rd., Zhunan Town, Miaoli Country 350, Taiwan, ROC.
出版信息
Bioorg Med Chem Lett. 2009 Apr 1;19(7):1908-12. doi: 10.1016/j.bmcl.2009.02.061. Epub 2009 Feb 21.
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.
已制备了一系列在P2位点带有谷氨酸衍生物的(2S)-氰基吡咯烷，并将其作为二肽基肽酶IV（DPP-IV）抑制剂进行了评估。构效关系（SAR）促使发现了强效的3-取代谷氨酸类似物，其具有更高的化学稳定性，并且对密切相关的酶DPP8、DPP-II和FAP具有出色的选择性。化合物13f表现出既能显著降低血糖波动又能抑制血浆DPP-IV活性的能力。
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