Modification, Biological Evaluation and SAR Studies of Novel 1H-Pyrazol Derivatives Containing N,N-Disubstituted Urea Moiety as Potential Anti-melanoma Agents

文献类型： 外文期刊

第一作者： Ruan, Ban-Feng

作者： Ruan, Ban-Feng;Lin, Meng-Xue;Shao, Qin;Wang, Tian-Hong;Zhang, Qing;Dong, Yu-Lu;Bu, Chao-Nan;Xu, Hua-Jian;Li, Qing-Shan;Zhou, Ben-Guo

作者机构：

关键词： melanoma; BRAF; 1H-pyrazole-4-amines; 1H-pyrazole-4-ureas; SAR

期刊名称：CHEMISTRY & BIODIVERSITY （ 影响因子：2.408； 五年影响因子：2.351 ）

ISSN： 1612-1872

年卷期： 2018 年 15 卷 6 期

页码：

收录情况： SCI

摘要： Malignant melanomas are amongst the most aggressive cancers. BRAF Inhibitors have exhibited therapeutic effects against BRAF-mutant melanoma. In continuation of our earlier studies on anti-melanoma agents based on 1H-pyrazole skeleton, two sets of novel compounds that include 1H-pyrazole-4-amines FA1 - FA13 and corresponding urea derivatives FN1 - FN13 have been synthesized and evaluated for their BRAF(V600E) inhibitory and antiproliferation activities. Compound FN10 displayed the most potent biological activity against BRAF(V600E) (IC50 = 0.066 m) and the A375 human melanoma cell line (GI(50) = 0.81 m), which was comparable to the positive control vemurafenib, and more potent than our previously reported 1H-pyrazole-3-amines and their urea derivatives. The results of SAR studies and molecular docking can guide further optimization and may help to improve potency of these pyrazole-based anti-melanoma agents.

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