6-{4-[3-(4-chlorophenyl)thioureido]phenylsulfanyl}-N-methylnicotinamide

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 6-{4-[3-(4-chlorophenyl)thioureido]phenylsulfanyl}-N-methylnicotinamide
• 英文别名: 6-[4-[(4-chlorophenyl)carbamothioylamino]phenyl]sulfanyl-N-methylpyridine-3-carboxamide
• 化学式: C₂₀H₁₇ClN₄OS₂
• 分子量: 428.966
• InChiKey: CZQONVGHRLZEDG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  123
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  6-氯烟酸甲酯 在 potassium tert-butylate 、 potassium carbonate 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 37.0h， 生成 6-{4-[3-(4-chlorophenyl)thioureido]phenylsulfanyl}-N-methylnicotinamide
  参考文献：
  名称：

  Design and discovery of thioether and nicotinamide containing sorafenib analogues as multikinase inhibitors targeting B-Raf, B-RafV600E and VEGFR-2

  摘要：

  New sorafenib derivatives containing thioether and nicotinamide moiety were designed and synthesized as B-Raf, B-Raf(V600E) and VEGFR-2 multikinase inhibitors. Their in vitro enzymatic inhibitory activities against B-Raf, B-Raf(V600E) and VEGFR-2 and their antiproliferative activities against HCT-116 and B16BL6 cell lines were evaluated and described. Most of the compounds showed potent activities against both cell lines and specific kinases. Compounds a1, b1 and c4, which exhibited the most potent inhibitory activities against B-Raf with IC50 of 21 nM, 27 nM and 17 nM, B-Raf(V600E) with IC50 of 29 nM, 28 nM and 16 nM, VEGFR-2 with IC50 of 84 nM, 46 nM and 63 nM, respectively, and good antiproliferative activities, also demonstrated competitive antiangiogenic activities to sorafenib in in vitro HUVEC tube formation assay. (C) 2018 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2018.03.039

文献信息

• Design and discovery of thioether and nicotinamide containing sorafenib analogues as multikinase inhibitors targeting B-Raf, B-RafV600E and VEGFR-2
  作者：Shaofeng Sun、Zuopeng He、Mindong Huang、Ningning Wang、Zongzhong He、Xiangkai Kong、Jianwen Yao

  DOI：10.1016/j.bmc.2018.03.039

  日期：2018.5

  New sorafenib derivatives containing thioether and nicotinamide moiety were designed and synthesized as B-Raf, B-Raf(V600E) and VEGFR-2 multikinase inhibitors. Their in vitro enzymatic inhibitory activities against B-Raf, B-Raf(V600E) and VEGFR-2 and their antiproliferative activities against HCT-116 and B16BL6 cell lines were evaluated and described. Most of the compounds showed potent activities against both cell lines and specific kinases. Compounds a1, b1 and c4, which exhibited the most potent inhibitory activities against B-Raf with IC50 of 21 nM, 27 nM and 17 nM, B-Raf(V600E) with IC50 of 29 nM, 28 nM and 16 nM, VEGFR-2 with IC50 of 84 nM, 46 nM and 63 nM, respectively, and good antiproliferative activities, also demonstrated competitive antiangiogenic activities to sorafenib in in vitro HUVEC tube formation assay. (C) 2018 Elsevier Ltd. All rights reserved.