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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分类:
物理学
>>
普通物理:统计和量子力学,量子信息等
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引用:
ChinaXiv:201711.02421
(或此版本
ChinaXiv:201711.02421V1)
DOI:10.12074/201711.02421V1
CSTR:32003.36.ChinaXiv.201711.02421.V1
- 推荐引用方式:
Hui Xie,Lili Zeng,Shaogao Zeng,Xin Lu,Xin Zhao,Guicheng ZhangZhengchao Tu,Hongjiang Xu,Ling Yang,Xiquan Zhang,Wenhui Hua.(2017).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.中国科学院科技论文预发布平台.[ChinaXiv:201711.02421]
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