摘要: A novel dipeptidyl peptidase IV inhibitor hit (5, IC50 = 0.86 mu M) was structurally derived from our recently disclosed preclinical candidate 4 by replacing the cyanobenzyl with a butynyl based on pharmacophore hybridization. A hit-to-lead optimization effort was then initiated to improve its potency. Most N-substituted analogs exhibited good in vitro activity, and compound 180 (IC50 = 1.55 nM) was identified to be a potent dipeptidyl peptidase IV inhibitor with a significantly improved pharmacokinetic properties (bioavailablity: 41% vs 82.9%; T-1/2: 2 h vs 4.9 h). (C) 2013 Elsevier Ltd. All rights reserved.
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分类:
生物学
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生态学
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引用:
ChinaXiv:201711.02424
(或此版本
ChinaXiv:201711.02424V1)
doi:10.12074/201711.02424
CSTR:32003.36.ChinaXiv.201711.02424.V1
- 推荐引用方式:
Zeng, SG (Zeng, Shaogao),Xie, H (Xie, Hui),Zeng, LL (Zeng, Li-li),Lu, X (Lu, Xin),Zhao, X (Zhao, Xin),Zhang, GC (Zhang, Gui-cheng),Tu, ZC (Tu, Zheng-chao),Xu, HJ (Xu, Hong-jiang),Yang, L (Yang, Ling),Zhang, XQ (Zhang, Xi-quan),Hu, WH (Hu, Wenhui).(2017).Discovery of potent dipeptidyl peptidase IV inhibitors through pharmacophore hybridization and hit-to-lead optimization.中国科学院科技论文预发布平台.[ChinaXiv:201711.02424]
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