4-(5-acetyl-2-(1-cyano-2-oxo-2-phenylethylidene)-1,3,4-thiadiazol-3(2H)-yl)benzenesulfonamide | 1529774-42-2

• 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-(5-acetyl-2-(1-cyano-2-oxo-2-phenylethylidene)-1,3,4-thiadiazol-3(2H)-yl)benzenesulfonamide
• CAS: 1529774-42-2
• 化学式: C₁₉H₁₄N₄O₄S₂
• 分子量: 426.477
• InChiKey: JGFXATCMLNIQDT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.41
• 重原子数：
  29.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  133.69
• 氢给体数：
  1.0
• 氢受体数：
  8.0

反应信息

• 作为产物：
  描述：

  (E)-2-benzoyl-3-mercapto-3-(phenylamino)acrylonitrile 、 2-oxo-N'-(4-sulfamoylphenyl)propanehydrazonoyl chloride 在 三乙胺 作用下， 生成 4-(5-acetyl-2-(1-cyano-2-oxo-2-phenylethylidene)-1,3,4-thiadiazol-3(2H)-yl)benzenesulfonamide
  参考文献：
  名称：

  一系列新的磺酰胺结合芳酰hydr，[1,2,4]三唑并[3,4-b] [1,3,4]噻二嗪基或2-抑制人碳酸酐酶同工酶I，II，IX和XII （氰基苯基亚甲基）-1,3,4-噻二唑-3（2H）-基部分。

  摘要：

  一系列苯磺酰胺与芳酰hydr，哌啶基，砜，[1,2,4]三唑并[3,4-b] [1,3,4]噻二嗪基-或2-（氰基苯基-亚甲基）-1,3,4-研究了噻二唑-3（2H）-基部分作为四种α-碳酸酐酶（CAs，EC 4.2.1.1），人（h）亚型hCA I，II（胞质，脱靶酶）和hCA IX和XII（跨膜，与肿瘤相关的同工型）。用这些磺酰胺类药物观察到的针对hCA II的纳摩尔活性较低（KI值为0.56-17.1 nM），而这些化合物对慢胞质异构体hCA I的抑制作用较小（KI值为86.4 nM-32.8 µM）。尽管某些衍生物结合了较大的双环部分以及2-噻吩基片段，但大多数这些磺酰胺均能显着抑制CA IX，KI的范围为4.5-47.0 nM，表现出对这种同工型的较弱活性（KIs在50.1-553 nM之间）。所有研究的化合物还以0.85-376 nM的KIs抑制CA XII。最好的抑制剂是那些含有大的[1

  DOI：

  10.3109/14756366.2013.877897

文献信息

• Inhibition of carbonic anhydrases from the extremophilic bacteria Sulfurihydrogenibium yellostonense (SspCA) and S. azorense (SazCA) with a new series of sulfonamides incorporating aroylhydrazone-, [1,2,4]triazolo[3,4-b][1,3,4]thiadiazinyl- or 2-(cyanophenylmethylene)-1,3,4-thiadiazol-3(2H)-yl moieties
  作者：Ahmed M. Alafeefy、Hatem A. Abdel-Aziz、Daniela Vullo、Abdul-Malek S. Al-Tamimi、Nabila A. Al-Jaber、Clemente Capasso、Claudiu T. Supuran

  DOI：10.1016/j.bmc.2013.11.042

  日期：2014.1

  A series of new sulfonamides was prepared starting from 2-oxo-N'-(4-sulfamoylphenyl)-propanehydrazonoyl chloride, a sulfanilamide derivative, which was reacted with aroylhydrazides, amines, or thiols. A library of derivatives incorporating aroylhydrazone, [1,2,4] triazolo[3,4-b][1,3,4]thiadiazinyl- or 2-(cyanophenyl-methylene)-1,3,4-thiadiazol-3(2H)-yl moieties was thus synthesized. The new compounds were investigated as inhibitors of four alpha-carbonic anhydrases (CAs, EC 4.2.1.1), the human (h) isoforms hCA I and II, and the bacterial ones recently isolated from the extremophilic bacteria Sulfurihydrogenibium yellostonense (SspCA) and Sulfurihydrogenibium azorense (SazCA). Low nanomolar activity was observed against hCA II (K(I)s of 0.56-17.1 nM) whereas hCA I was less inhibited by these compounds (K(I)s of 86.4 nM-32.8 mu M). The bacterial CAs were also effectively inhibited by these derivatives (K(I)s in the range of 0.77-234 nM against SazCA, and of 6.2-89.1 against SspCA, respectively), with several low nanomolar/subnanomolar inhibitors detected against both of them. As SspCA and SazCA are among the most thermostable and catalytically active CAs, it is of interest to find modulators of their activity for potential biotechnologic applications. (C) 2013 Elsevier Ltd. All rights reserved.
• Inhibition of human carbonic anhydrase isozymes I, II, IX and XII with a new series of sulfonamides incorporating aroylhydrazone-, [1,2,4]triazolo[3,4-b][1,3,4]thiadiazinyl- or 2-(cyanophenylmethylene)-1,3,4-thiadiazol-3(2H)-yl moieties
  作者：Ahmed M. Alafeefy、Hatem A. Abdel-Aziz、Daniela Vullo、Abdul-Malek S. Al-Tamimi、Amani S. Awaad、Menshawy A. Mohamed、Clemente Capasso、Claudiu T. Supuran

  DOI：10.3109/14756366.2013.877897

  日期：2015.1.2

  56-17.1 nM) with these sulfonamides, whereas the slow cytosolic isoform hCA I was less inhibited by these compounds (KIs of 86.4 nM-32.8 µM). Most of these sulfonamides significantly inhibited CA IX, with KIs in the range of 4.5-47.0 nM, although some of the derivatives incorporating bulkier bicyclic moieties, as well as 2-thienyl fragments, showed a weaker activity against this isoform (KIs in the range

  一系列苯磺酰胺与芳酰hydr，哌啶基，砜，[1,2,4]三唑并[3,4-b] [1,3,4]噻二嗪基-或2-（氰基苯基-亚甲基）-1,3,4-研究了噻二唑-3（2H）-基部分作为四种α-碳酸酐酶（CAs，EC 4.2.1.1），人（h）亚型hCA I，II（胞质，脱靶酶）和hCA IX和XII（跨膜，与肿瘤相关的同工型）。用这些磺酰胺类药物观察到的针对hCA II的纳摩尔活性较低（KI值为0.56-17.1 nM），而这些化合物对慢胞质异构体hCA I的抑制作用较小（KI值为86.4 nM-32.8 µM）。尽管某些衍生物结合了较大的双环部分以及2-噻吩基片段，但大多数这些磺酰胺均能显着抑制CA IX，KI的范围为4.5-47.0 nM，表现出对这种同工型的较弱活性（KIs在50.1-553 nM之间）。所有研究的化合物还以0.85-376 nM的KIs抑制CA XII。最好的抑制剂是那些含有大的[1