1-{4-[3-(4-chloro-3-hydroxyphenyl)-4-(pyridin-4-yl)-1H-pyrazol-1-yl]phenyl}-3-(4-chloro-3-(trifluoromethyl)phenyl)urea | 1350473-93-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-{4-[3-(4-chloro-3-hydroxyphenyl)-4-(pyridin-4-yl)-1H-pyrazol-1-yl]phenyl}-3-(4-chloro-3-(trifluoromethyl)phenyl)urea
• 英文别名: 1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(4-(3-(4-chloro-3-hydroxyphenyl)-4-(pyridin-4-yl)-1H-pyrazol-1-yl)phenyl)urea；1-[4-[3-(4-chloro-3-hydroxyphenyl)-4-pyridin-4-ylpyrazol-1-yl]phenyl]-3-[4-chloro-3-(trifluoromethyl)phenyl]urea
• CAS: 1350473-93-6
• 化学式: C₂₈H₁₈Cl₂F₃N₅O₂
• 分子量: 584.384
• InChiKey: LYBMXFWAIVMRTJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  40
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  92.1
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-氯-3-甲氧基苯甲酸甲酯 在 copper(l) iodide 、 palladium on activated charcoal 、 氢气 、 三溴化硼 、 potassium carbonate 、 L-脯氨酸 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 40.0h， 生成 1-{4-[3-(4-chloro-3-hydroxyphenyl)-4-(pyridin-4-yl)-1H-pyrazol-1-yl]phenyl}-3-(4-chloro-3-(trifluoromethyl)phenyl)urea
  参考文献：
  名称：

  New diarylureas and diarylamides containing 1,3,4-triarylpyrazole scaffold: Synthesis, antiproliferative evaluation against melanoma cell lines, ERK kinase inhibition, and molecular docking studies

  摘要：

  Synthesis of a new series of diarylureas and diarylamides possessing 1,3,4-triarylpyrazole scaffold is described. Their in vitro antiproliferative activities against 9 human melanoma cell lines were tested. Compounds 12, 13, 15, and 21-23 showed the highest potency against A375P melanoma cell line. In addition, compounds 10-15 and 19-24 showed high potency over the NCl 8 tested melanoma cell-lines panel. The IC50 values for compound 23 were 0.36 mu M and 0.84 mu M over LOX IMVI and M14 cell lines, respectively. Compounds 21 and 23 showed high, dose-dependent inhibition of ERK kinase. Virtual screening was carried out through docking of compound 21 into the domain of V600E-B-RAF and the binding mode was studied. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.08.013

文献信息

• New diarylureas and diarylamides containing 1,3,4-triarylpyrazole scaffold: Synthesis, antiproliferative evaluation against melanoma cell lines, ERK kinase inhibition, and molecular docking studies
  作者：Won-Kyoung Choi、Mohammed I. El-Gamal、Hong Seok Choi、Daejin Baek、Chang-Hyun Oh

  DOI：10.1016/j.ejmech.2011.08.013

  日期：2011.12

  Synthesis of a new series of diarylureas and diarylamides possessing 1,3,4-triarylpyrazole scaffold is described. Their in vitro antiproliferative activities against 9 human melanoma cell lines were tested. Compounds 12, 13, 15, and 21-23 showed the highest potency against A375P melanoma cell line. In addition, compounds 10-15 and 19-24 showed high potency over the NCl 8 tested melanoma cell-lines panel. The IC50 values for compound 23 were 0.36 mu M and 0.84 mu M over LOX IMVI and M14 cell lines, respectively. Compounds 21 and 23 showed high, dose-dependent inhibition of ERK kinase. Virtual screening was carried out through docking of compound 21 into the domain of V600E-B-RAF and the binding mode was studied. (C) 2011 Elsevier Masson SAS. All rights reserved.