来自阿格列汀的高效去肽基肽酶 IV 抑制剂，具有药效团杂交和先导优化

分类： 物理学 >> 普通物理:统计和量子力学,量子信息等 提交时间： 2017-11-17

Hui Xie Lili Zeng Shaogao Zeng Xin Lu Xin Zhao Guicheng ZhangZhengchao Tu Hongjiang Xu Ling Yang Xiquan Zhang Wenhui Hua

摘要： The structural superposition of DPP-IV complex with Alogliptin and Linagliptin displayed a similar binding mode. The butynyl of Linagliptin and cyanobenzyl of Alogliptin occupy the S1 pocket which therefore could be mutually switched. Thus a pharmacophore hybridization of Alogliptin was initiated and led to a novel DPP-IV inhibitor 61. Though it did not exhibit desired activity (IC50= 0.2 礛), the butynyl compound acts as a lead compound triggered a following structural optimization. A novel series of potent DPP-IV inhibitors represented by compound 77 (IC50= 0.36 nM) were obtained with a robust pharmacokinetic profile and better in vitro and in vivo efficacy than Alogliptin.

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