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
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
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DOI：
10.1021/acs.jmedchem.0c00337
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发表时间：
2020-05-28
影响因子：
7.3
通讯作者：
Liu, Gang
中科院分区：
文献类型：
--
作者：
Ma, Yao;Yin, Dawei;Liu, Gang
SIS3 是 Smad3 的特异性抑制剂，可抑制 TGF beta 1 诱导的 Smad3 磷酸化。在本文中，设计并合成了多种 SIS3 衍生物，以借助 2-(4-(吡啶-2-基)苯氧基)吡啶类似物的后期功能化来发现针对 P-糖蛋白介导的多药耐药性的潜在抑制剂。研究了一类新型强效 P-gp 逆转剂，并确定先导化合物 37 是一种强效 P-gp 逆转剂，具有很强的生物活性和对 P-gp 的出色亲和力。
SIS3 is a specific inhibitor of Smad3 that inhibits the TGF beta 1-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.