4-chloro-N-(3,4-dichlorophenyl)-3-nitrobenzamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-chloro-N-(3,4-dichlorophenyl)-3-nitrobenzamide
• 英文别名: N-(3,4-dichlorophenyl)-4-chloro-3-nitrobenzamide
• 化学式: C₁₃H₇Cl₃N₂O₃
• 分子量: 345.569
• InChiKey: CZKJNORWSDOONQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  74.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-chloro-N-(3,4-dichlorophenyl)-3-nitrobenzamide 在 5%-palladium/activated carbon 、 氢气 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 以73.2%的产率得到N-(3,4-dichlorophenyl)-4-chloro-3-aminobenzamide
  参考文献：
  名称：

  Design, synthesis and biological evaluation of bis-aryl ureas and amides based on 2-amino-3-purinylpyridine scaffold as DFG-out B-Raf kinase inhibitors

  摘要：

  By combining the scaffolds of UI-125 and Sorafenib, a series of bis-aryl ureas and amides based on 2-amino-3-purinylpyridine moiety were designed and synthesized as novel DFG-out B-Raf(V600E) inhibitors. Among them, 20c-e, 20g and 21h displayed potent antiproliferative activities against melanoma A375 (B-Raf(V600E)) cell lines with IC50 values of 3.190, 2276, 1.856, 1.632 mu M and 1.839 mu M, respectively, comparable with the positive control Vemurafenib (IC50 = 3.32 mu M). Selected compounds were tested for the ERK inhibition in human melanoma A375 (B-Raf(V600E)) and SK-MEL-2 (B-Raf(WT)) cell lines by Western blot. The results revealed that our compounds inhibited the proliferation of melanoma A375 cells (B-Raf(V600E)) through ERK pathway, without paradoxical activation of ERK in melanoma SK-MEL-2 cells (B-Rat(WT)). Eventually, 20g and 21h were selected to confirm their inhibitory effects on tumor growth in A375 xenograft models in mice. Compound 20g exhibited equivalent antitumor efficacy in vivo (T/C = 44.37%), compared to Sorafenib (T/C = 37.35%), by 23-day repetitive administration of a single dose of 50 mg/kg without significant body weight loss. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.10.039
• 作为产物：
  描述：

  3,4-二氯苯胺 、 4-氯-3-硝基苯甲酸 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以81.2%的产率得到4-chloro-N-(3,4-dichlorophenyl)-3-nitrobenzamide
  参考文献：
  名称：

  Design, synthesis and biological evaluation of bis-aryl ureas and amides based on 2-amino-3-purinylpyridine scaffold as DFG-out B-Raf kinase inhibitors

  摘要：

  By combining the scaffolds of UI-125 and Sorafenib, a series of bis-aryl ureas and amides based on 2-amino-3-purinylpyridine moiety were designed and synthesized as novel DFG-out B-Raf(V600E) inhibitors. Among them, 20c-e, 20g and 21h displayed potent antiproliferative activities against melanoma A375 (B-Raf(V600E)) cell lines with IC50 values of 3.190, 2276, 1.856, 1.632 mu M and 1.839 mu M, respectively, comparable with the positive control Vemurafenib (IC50 = 3.32 mu M). Selected compounds were tested for the ERK inhibition in human melanoma A375 (B-Raf(V600E)) and SK-MEL-2 (B-Raf(WT)) cell lines by Western blot. The results revealed that our compounds inhibited the proliferation of melanoma A375 cells (B-Raf(V600E)) through ERK pathway, without paradoxical activation of ERK in melanoma SK-MEL-2 cells (B-Rat(WT)). Eventually, 20g and 21h were selected to confirm their inhibitory effects on tumor growth in A375 xenograft models in mice. Compound 20g exhibited equivalent antitumor efficacy in vivo (T/C = 44.37%), compared to Sorafenib (T/C = 37.35%), by 23-day repetitive administration of a single dose of 50 mg/kg without significant body weight loss. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.10.039

文献信息

• A Route to (Het)arene-Annulated Pyrrolo[1,2-<i>d</i>][1,4]diazepines via the Expanded Intramolecular Paal–Knorr Reaction: Nitro Group and Furan Ring as Equivalents of Amino Group and 1,4-Diketone
  作者：Elena Y. Zelina、Tatyana A. Nevolina、Dmitry A. Skvortsov、Igor V. Trushkov、Maxim G. Uchuskin

  DOI：10.1021/acs.joc.9b01925

  日期：2019.11.1

  A straightforward protocol toward pharmacologically relevant (het)areno[x,y-b]pyrrolo[1,2-d][1,4]diazepines in good to high yields has been described. The designed approach consists of an acid-promoted furan ring opening in easily accessible N-(2-furylethyl)-2-nitroanilines or their heterocyclic analogues followed by the reductive cyclization of the corresponding nitro-1,4-diketones.

  已经描述了一种以药理学相关（het）areno [x，yb]吡咯并[1,2-d] [1,4]二氮杂pine的简单方法，其产率高至高。设计的方法包括在容易获得的N-（2-呋喃乙基）-2-硝基苯胺或它们的杂环类似物中酸促进呋喃开环，然后将相应的硝基-1,4-二酮还原环化。