4-[2-(4-chlorophenyl)acetamido]-3-chlorobenzenesulfonamide | 1446750-84-0

• 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-[2-(4-chlorophenyl)acetamido]-3-chlorobenzenesulfonamide
• 英文别名: 2-(4-chlorophenyl)-N-(2-chloro-4-sulfamoylphenyl)acetamide
• CAS: 1446750-84-0
• 化学式: C₁₄H₁₂Cl₂N₂O₃S
• 分子量: 359.233
• InChiKey: MRESXFBRGBARJF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  97.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-氨基-3-氯苯磺酰胺 、 对氯苯乙酰氯 在 三乙胺 作用下， 以 乙腈 为溶剂， 以60%的产率得到4-[2-(4-chlorophenyl)acetamido]-3-chlorobenzenesulfonamide
  参考文献：
  名称：

  A Class of Sulfonamides with Strong Inhibitory Action against the α-Carbonic Anhydrase from Trypanosoma cruzi

  摘要：

  Trypanosoma cruzi, the causative agent of Chagas disease, encodes for an alpha-carbonic anhydrase (CA, EC 4.2.1.1) possessing high catalytic activity (TcCA) which was recently characterized (Pan et al. J. Med. Chem. 2013, 56, 1761-1771). A new class of sulfonamides possessing low nanomolar/subnanomolar TcCA inhibitory activity is described here. Aromatic/heterocydic sulfonamides incorporating halogeno/methoxyphenacetamido tails inhibited TcCA with K(I)s in the range of 0.5-12.5 nM, being less effective against the human off-target isoforms hCA I and II. A homology model of TcCA helped us to rationalize the excellent inhibition profile of these compounds against the protozoan enzyme, a putative new antitrypanosoma drug target. These compounds were ineffective antitrypanosomal agents in vivo due to penetrability problems of these highly polar molecules that possess sulfonamide moieties.

  DOI：

  10.1021/jm400418p

文献信息

• Inhibition of tumor-associated human carbonic anhydrase isozymes IX and XII by a new class of substituted-phenylacetamido aromatic sulfonamides
  作者：Atilla Akdemir、Özlen Güzel-Akdemir、Andrea Scozzafava、Clemente Capasso、Claudiu T. Supuran

  DOI：10.1016/j.bmc.2013.06.029

  日期：2013.9

  Here, we investigate 28 structurally new sulfonamides and their subsequent testing for enzyme inhibition of cytosolic and tumor-associated carbonic anhydrases (CAs, EC 4.2.1.1). The compounds showed very potent inhibition of four physiologically relevant human (h) CA isoforms, namely hCA I, II, IX and XII. Interestingly, the K-I values were in the nanomolar range for the tumor-associated hCA IX and hCA XII. Docking studies have revealed details regarding the very favorable interactions between the scaffolds of this new class of inhibitors and the active sites of the investigated CA isoforms. As there are reported cases of tumors overexpressing both CA II and IX, such potent inhibitors for the two isoforms as those detected in this work, may have applications for targeting more than one CA present in tumors. (C) 2013 Elsevier Ltd. All rights reserved.
• A Class of Sulfonamides with Strong Inhibitory Action against the α-Carbonic Anhydrase from <i>Trypanosoma cruzi</i>
  作者：Özlen Güzel-Akdemir、Atilla Akdemir、Peiwen Pan、Alane B. Vermelho、Seppo Parkkila、Andrea Scozzafava、Clemente Capasso、Claudiu T. Supuran

  DOI：10.1021/jm400418p

  日期：2013.7.25

  Trypanosoma cruzi, the causative agent of Chagas disease, encodes for an alpha-carbonic anhydrase (CA, EC 4.2.1.1) possessing high catalytic activity (TcCA) which was recently characterized (Pan et al. J. Med. Chem. 2013, 56, 1761-1771). A new class of sulfonamides possessing low nanomolar/subnanomolar TcCA inhibitory activity is described here. Aromatic/heterocydic sulfonamides incorporating halogeno/methoxyphenacetamido tails inhibited TcCA with K(I)s in the range of 0.5-12.5 nM, being less effective against the human off-target isoforms hCA I and II. A homology model of TcCA helped us to rationalize the excellent inhibition profile of these compounds against the protozoan enzyme, a putative new antitrypanosoma drug target. These compounds were ineffective antitrypanosomal agents in vivo due to penetrability problems of these highly polar molecules that possess sulfonamide moieties.