Discovery of Potent Inhibitors against P‑Glycoprotein-Mediated Multidrug Resistance Aided by Late-Stage Functionalization of a 2‑(4-(Pyridin-2-yl)phenoxy)pyridine Analogue

SIS3 is a specific inhibitor of Smad3 that inhibits the TGFβ1-induced phosphorylation of Smad3. In this article, a variety of SIS3 derivatives were designed and synthesized to discover potential inhibitors against P-glycoprotein-mediated multidrug resistance aided by late-stage functionalization of...

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Bibliographic Details
Published in:Journal of medicinal chemistry 2020-05, Vol.63 (10), p.5458-5476
Main Authors: Ma, Yao, Yin, Dawei, Ye, Jingjia, Wei, Xiduan, Pei, Yameng, Li, Xueyuan, Si, Guangxu, Chen, Xuan-Yu, Chen, Zhe-Sheng, Dong, Yi, Zou, Feng, Shi, Wei, Qiu, Qianqian, Qian, Hai, Liu, Gang
Format: Article
Language:English
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Summary:SIS3 is a specific inhibitor of Smad3 that inhibits the TGFβ1-induced phosphorylation of Smad3. In this article, a variety of SIS3 derivatives were designed and synthesized to discover potential inhibitors against P-glycoprotein-mediated multidrug resistance aided by late-stage functionalization of a 2-(4-(pyridin-2-yl)­phenoxy)­pyridine analogue. A novel class of potent P-gp reversal agents were investigated, and a lead compound 37 was identified as a potent P-gp reversal agent with strong bioactivity and outstanding affinity for P-gp.
ISSN:0022-2623
1520-4804
DOI:10.1021/acs.jmedchem.0c00337