新型反式-2-芳基环丙胺类似物作为强效和选择性二肽基肽酶IV抑制剂。
Novel trans-2-aryl-cyclopropylamine analogues as potent and selective dipeptidyl peptidase IV inhibitors.
作者信息
Tsai Ting-Yueh, Hsu Tsu, Chen Chiung-Tong, Cheng Jai-Hong, Yeh Teng-Kuang, Chen Xin, Huang Chung-Yu, Chang Chung-Nien, Yeh Kai-Chia, Hsieh Su-Huei, Chien Chia-Hui, Chang Yi-Wei, Huang Chih-Hsiang, Huang Yu-Wen, Huang Chen-Lung, Wu Ssu-Hui, Wang Min-Hsien, Lu Cheng-Tai, 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. 2009 Mar 15;17(6):2388-99. doi: 10.1016/j.bmc.2009.02.020. Epub 2009 Feb 20.
A series of trans-2-aryl-cyclopropylamine derived compounds were synthesized and evaluated their biological activities against DPP-IV. The structure-activity relationships (SAR) led to the discovery of novel series of DPP-IV inhibitors, having IC(50) values of <100 nM with excellent selectivity over the closely related enzymes, DPP8, DPP-II and FAP. The studies identified a potent and selective DPP-IV inhibitor 24b, which exhibited the ability to both significantly inhibit plasma DPP-IV activity in rats and improve glucose tolerance in lean mice and diet induced obese mice.
合成了一系列反式-2-芳基环丙胺衍生化合物，并评估了它们对二肽基肽酶-IV（DPP-IV）的生物活性。构效关系（SAR）研究发现了一系列新型DPP-IV抑制剂，其半数抑制浓度（IC50）值<100 nM，对密切相关的酶二肽基肽酶8（DPP8）、二肽基肽酶II（DPP-II）和成纤维细胞活化蛋白（FAP）具有优异的选择性。研究确定了一种强效且选择性的DPP-IV抑制剂24b，它既能显著抑制大鼠血浆中的DPP-IV活性，又能改善瘦小鼠和饮食诱导肥胖小鼠的糖耐量。
Zotero 插件