2-[4-chloro-5-methyl-2-(3-trifluoromethylbenzylthio)benzenesulfonyl]-3-(4-sulfamoylbenzyl)guanidine

• 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: 2-[4-chloro-5-methyl-2-(3-trifluoromethylbenzylthio)benzenesulfonyl]-3-(4-sulfamoylbenzyl)guanidine
• 英文别名: 1-[4-Chloro-5-methyl-2-[[3-(trifluoromethyl)phenyl]methylsulfanyl]phenyl]sulfonyl-2-[(4-sulfamoylphenyl)methyl]guanidine；1-[4-chloro-5-methyl-2-[[3-(trifluoromethyl)phenyl]methylsulfanyl]phenyl]sulfonyl-2-[(4-sulfamoylphenyl)methyl]guanidine
• 化学式: C₂₃H₂₂ClF₃N₄O₄S₃
• 分子量: 607.098
• InChiKey: JWZXMNMNQPNTAV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  38
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  187
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  N-{4-chloro-5-methyl-2-[(3-trifluoromethylbenzyl)thio]benzenesulfonyl}cyanamide potassium salt 、 mafenide hydrochloride 在 对甲苯磺酸 作用下， 以 甲苯 为溶剂， 反应 16.0h， 以76%的产率得到2-[4-chloro-5-methyl-2-(3-trifluoromethylbenzylthio)benzenesulfonyl]-3-(4-sulfamoylbenzyl)guanidine
  参考文献：
  名称：

  Carbonic anhydrase inhibitors. Synthesis, and molecular structure of novel series N-substituted N′-(2-arylmethylthio-4-chloro-5-methylbenzenesulfonyl)guanidines and their inhibition of human cytosolic isozymes I and II and the transmembrane tumor-associated isozymes IX and XII

  摘要：

  A series of novel N-substituted N'-(2-arylmethylthio-4-chloro-5-methylbenzenesulfonyl)guanidines 9 -41 have been synthesized and investigated as inhibitors of four isoforms of zinc enzyme carbonic anhydrase (CA.EC 4.2.1.1), that is the cytosolic CA I and II, and cancer-associated isozymes CA IX and XII. Against the human CA I investigated compounds showed K-I in the range of 87-6506 nM, toward hCA II ranging from 7.8 to 4500 nM, against hCA IX in the range of 4.7-416 nM and against hCA XII at range of 0.96-540 nM. Compounds 10, 12-14, 16, 18-20, 24-26, 31 and 32 exhibited a powerful inhibitory potency toward hCA IX (K-I = 4.7-21 nM) in comparison to the reference sulfonamides AAZ, MZA, EZA, DCP and IND (K-I = 24-50 nM). Compound 14 was the most potent inhibitor of hCA I = 87 nM), hCA IX (K-I = 4.7 nM) and hCA XII (K-I = 0.96 nM), while 26 was the most effective inhibitor of hCA II (K-I = 7.8 nM). The most promising compound 32 exerted the highest selectivity ratios toward hCA IX versus hCA I (hCA I/hCA IX = 261) and hCA II (hCA II/hCA IX = 26). The in vitro antitumor activity of compounds 10, 13, 14, 21, 22, 25, 32, 38 and 41 was evaluated at the US National Cancer Institute (NCI) against a panel of 60 human tumor cell lines. The most active antitumor agents 21 and 25, inhibiting 32-35 human tumor cell lines with GI(50) in the range of 2.1-5.0 mu M also showed relatively high inhibitory activity toward hCA IX and XII with K-I from 18 to 40 nM. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.10.081