Duan Yongli, Xu Shan, Xiong Hehua, Wang Linxiao, Zhao Bingbing, Wang Ping, Wang Caolin, Peng Yiqing, Cai Shifan, Luo Rong, Zheng Pengwu, Tang Qidong
Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, PR China.
Jiangxi Province Institute of Materia Medica, Nanchang 330000, PR China.
Bioorg Med Chem Lett. 2018 Feb 1;28(3):254-259. doi: 10.1016/j.bmcl.2017.12.063. Epub 2017 Dec 29.
A series of 2-substituted-4-phenoxypyridine derivatives were designed, synthesized, and evaluated for their antiproliferative activity against 4 cancer cell lines (A549, HT-29, H460, and U87MG) in vitro. Most compounds showed moderate to excellent potency. Nine tyrosine kinases (c-Met, Flt-3, ALK, VEGFR-2, VEGFR-3, PDGFR-α, PDGFR-β, c-Kit, and EGFR) were used to evaluate the inhibitory activities with the most promising analogue 39, which showed the Flt-3/c-Met IC values of 2.18/2.61 nM. Structure-activity relationship studies indicated that n-Pr served as R group showed a higher preference, and stronger mono-EWGs on the phenyl ring (such as R = 4-F) was benefited to the potency.
设计、合成了一系列2-取代-4-苯氧基吡啶衍生物，并在体外评估了它们对4种癌细胞系（A549、HT-29、H460和U87MG）的抗增殖活性。大多数化合物表现出中等至优异的活性。使用9种酪氨酸激酶（c-Met、Flt-3、ALK、VEGFR-2、VEGFR-3、PDGFR-α、PDGFR-β、c-Kit和EGFR）评估最有前景的类似物39的抑制活性，其Flt-3/c-Met IC值为2.18/2.61 nM。构效关系研究表明，作为R基团的正丙基表现出更高的偏好性，苯环上更强的单电子吸电子基团（如R = 4-F）有利于活性。
