摘要: Followed pharmacological evaluation exposed an extensive hepatic first pass effect within our recently disclosed DPP-IV inhibitors bearing thienopyrimidine scaffold. Through scaffold replacement with pyrrolopyrimidine, compound 1a had substantially improved the metabolic stability (from 6.6% to 65.07%), yet with severely poor absorptive property. Further modification by incorporation with varied substituents and structure conversion yielded both permeable and metabolic stable compounds. The whole pharmacokinetic- property based optimization had succeeded in balancing overall properties and resulted in the compound 1j, that with excellent efficacy to be a potential anti-diabetic candidate.
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分类:
生物学
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生态学
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引用:
ChinaXiv:201711.02425
(或此版本
ChinaXiv:201711.02425V1)
DOI:10.12074/201711.02425V1
CSTR:32003.36.ChinaXiv.201711.02425.V1
- 推荐引用方式:
Hui Xie,Saogao Zeng,Lili Zeng,Xiaobing Lan,Guicheng Zhang,Li Liu,Xin Lu,Na Chen,Zhiyuan Li,Zengzhao Tu,Hongjiang Xu,Ling Yang,Xiquan Zhang,Wenhui Hu.Discovery of novel pyrrolopyrimidine analogues as potent dipeptidyl peptidase IV inhibitors based on a pharmacokinetic property-driven optimization.中国科学院科技论文预发布平台.[ChinaXiv:201711.02425V1]
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