5-[1-(naphthalen-1-yl)-1H-1,2,3-triazol-4-yl]thiophene-2-sulfonamide | 1449785-76-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 5-[1-(naphthalen-1-yl)-1H-1,2,3-triazol-4-yl]thiophene-2-sulfonamide
• 英文别名: 5-(1-Naphthalen-1-Yl-1,2,3-Triazol-4-Yl)thiophene-2-Sulfonamide；5-(1-naphthalen-1-yltriazol-4-yl)thiophene-2-sulfonamide
• CAS: 1449785-76-5
• 化学式: C₁₆H₁₂N₄O₂S₂
• 分子量: 356.429
• InChiKey: KNFVNHRBTIJTNM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  128
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N-[(dimethylamino)methylidene]-5-[2-(trimethylsilyl)ethynyl]thiophene-2-sulfonamide 在 copper(ll) sulfate pentahydrate 、 四丁基氟化铵 作用下， 以 四氢呋喃 、 水 、 叔丁醇 为溶剂， 反应 3.83h， 生成 5-[1-(naphthalen-1-yl)-1H-1,2,3-triazol-4-yl]thiophene-2-sulfonamide
  参考文献：
  名称：

  5-Substituted-(1,2,3-triazol-4-yl)thiophene-2-sulfonamides strongly inhibit human carbonic anhydrases I, II, IX and XII: Solution and X-ray crystallographic studies

  摘要：

  We report here a series of 2-thiophene-sulfonamides incorporating 1-substituted aryl-1,2,3-triazolyl moieties, prepared by click chemistry from 5-ethynylthiophene-2-sulfonamide and substituted aryl azides. The new sulfonamides were investigated as inhibitors of the zinc metalloenzyme CA (EC 4.2.1.1), and more specifically against the human (h) cytosolic isoforms hCA I and II and the transmembrane, tumor-associated ones hCA IX and XII: The new compounds were medium-weak hCA I inhibitors (K(I)s in the range of 224-7544 nM), but were compactly, highly effective, low nanomolar hCA II inhibitors (K(I)s of 2.2-7.7 nM). The tumor-associated hCA IX was inhibited with K(I)s ranging between 5.4 and 811 nM, whereas hCA XII with inhibition constants in the range of 3.4-239 nM. The X-ray crystal structure of the adducts of two such compounds bound to hCA II (one incorporating 1-naphthyl, the other one 3-cyanophenyl moieties) evidenced the reasons of the high affinity for hCA II. Highly favorable, predominantly hydrophobic interactions between the sulfonamide scaffold and the hCA II active site were responsible for the binding, in addition to the coordination of the sulfamoyl moiety to the zinc ion. The tails of the two inhibitors adopted very diverse orientations when bound to the active site, with the naphthyltriazolyl moiety orientated towards the hydrophobic half of the active site, and the 3-cyanophenyl one pointing towards the hydrophilic half. These data may be used for the structure-based drug design of even more effective hCA II inhibitors, with potential use as antiglaucoma agents or as diuretics. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.06.041

文献信息

• 5-Substituted-(1,2,3-triazol-4-yl)thiophene-2-sulfonamides strongly inhibit human carbonic anhydrases I, II, IX and XII: Solution and X-ray crystallographic studies
  作者：Janis Leitans、Agnese Sprudza、Muhammet Tanc、Igor Vozny、Raivis Zalubovskis、Kaspars Tars、Claudiu T. Supuran

  DOI：10.1016/j.bmc.2013.06.041

  日期：2013.9

  We report here a series of 2-thiophene-sulfonamides incorporating 1-substituted aryl-1,2,3-triazolyl moieties, prepared by click chemistry from 5-ethynylthiophene-2-sulfonamide and substituted aryl azides. The new sulfonamides were investigated as inhibitors of the zinc metalloenzyme CA (EC 4.2.1.1), and more specifically against the human (h) cytosolic isoforms hCA I and II and the transmembrane, tumor-associated ones hCA IX and XII: The new compounds were medium-weak hCA I inhibitors (K(I)s in the range of 224-7544 nM), but were compactly, highly effective, low nanomolar hCA II inhibitors (K(I)s of 2.2-7.7 nM). The tumor-associated hCA IX was inhibited with K(I)s ranging between 5.4 and 811 nM, whereas hCA XII with inhibition constants in the range of 3.4-239 nM. The X-ray crystal structure of the adducts of two such compounds bound to hCA II (one incorporating 1-naphthyl, the other one 3-cyanophenyl moieties) evidenced the reasons of the high affinity for hCA II. Highly favorable, predominantly hydrophobic interactions between the sulfonamide scaffold and the hCA II active site were responsible for the binding, in addition to the coordination of the sulfamoyl moiety to the zinc ion. The tails of the two inhibitors adopted very diverse orientations when bound to the active site, with the naphthyltriazolyl moiety orientated towards the hydrophobic half of the active site, and the 3-cyanophenyl one pointing towards the hydrophilic half. These data may be used for the structure-based drug design of even more effective hCA II inhibitors, with potential use as antiglaucoma agents or as diuretics. (C) 2013 Elsevier Ltd. All rights reserved.