5-chloro-N-(4-chloro-5-isopropyl-3-methyl-1,3-thiazol-2(3H)-ylidene)-2-hydroxybenzenesulfonamide

• 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: 5-chloro-N-(4-chloro-5-isopropyl-3-methyl-1,3-thiazol-2(3H)-ylidene)-2-hydroxybenzenesulfonamide
• 英文别名: (NZ)-5-chloro-N-(4-chloro-5-isopropyl-3-methyl-thiazol-2-ylidene)-2-hydroxy-benzenesulfonamide；(NZ)-5-chloro-N-(4-chloro-3-methyl-5-propan-2-yl-1,3-thiazol-2-ylidene)-2-hydroxybenzenesulfonamide
• 化学式: C₁₃H₁₄Cl₂N₂O₃S₂
• 分子量: 381.304
• InChiKey: VTKAGCUSZSWYBW-SSZFMOIBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  104
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-chloro-N-(4-chloro-5-isopropyl-3-methyl-1,3-thiazol-2(3H)-ylidene)-2-hydroxybenzenesulfonamide 在 tris-(dibenzylideneacetone)dipalladium(0) 2,6-二甲基吡啶 、 4-二甲氨基吡啶 、 1,1'-双(二苯基膦)二茂铁 、 锌 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 5-chloro-N-(4-chloro-5-isopropyl-3-methyl-1,3-thiazol-2(3H)-ylidene)-2-cyanobenzenesulfonamide
  参考文献：
  名称：

  Studies of non-nucleoside HIV-1 reverse transcriptase inhibitors. Part 2: Synthesis and structure–activity relationships of 2-cyano and 2-hydroxy thiazolidenebenzenesulfonamide derivatives

  摘要：

  In a previous study, we described the structure-activity relationships (SARs) for a series of thiazolidenebenzenesulfonamide derivatives. These compounds were found to be highly potent inhibitors of the wild type (WT) and Y181C mutant reverse transcriptases (RTs) and modest inhibitors of K 103N RT. These molecules are thus considered to be a novel class of non-nucleoside HIV-1 RT inhibitors (NNRTIs). In this paper, we have examined the effects of substituents on both the thiazolidene and benzenesulfonamide moieties. Introduction of a 2-cyanophenyl ring into these moieties significantly enhanced anti-HIV-1 activity, whereas a 2-hydroxyphenyl group endowed potent activity against RTs, including K103N and Y181C mutants. Among the series of molecules examined, 101 and 18b (YM-228855), combinations of 2-cyanophenyl and 4-methyl-5-isopropylthiazole moieties, showed extremely potent anti-HIV-1 activity. The EC50 values of 101 and 18b were 0.0017 and 0.0018 muM, respectively. These values were lower than that of efavirenz (3). Compound 11g (YM-215389), a combination of 2-hydroxyphenyl and 4-chloro-5-isopropylthiazole moieties, proved to be the most active against both K103N and Y181C RTs with IC50 values of 0.043 and 0.013 muM, respectively. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.11.045
• 作为产物：
  描述：

  5-氯-2-甲氧基苯磺酰氯 在 吡啶 、 三溴化硼 、 sodium hydride 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 24.0h， 生成 5-chloro-N-(4-chloro-5-isopropyl-3-methyl-1,3-thiazol-2(3H)-ylidene)-2-hydroxybenzenesulfonamide
  参考文献：
  名称：

  Studies of non-nucleoside HIV-1 reverse transcriptase inhibitors. Part 2: Synthesis and structure–activity relationships of 2-cyano and 2-hydroxy thiazolidenebenzenesulfonamide derivatives

  摘要：

  In a previous study, we described the structure-activity relationships (SARs) for a series of thiazolidenebenzenesulfonamide derivatives. These compounds were found to be highly potent inhibitors of the wild type (WT) and Y181C mutant reverse transcriptases (RTs) and modest inhibitors of K 103N RT. These molecules are thus considered to be a novel class of non-nucleoside HIV-1 RT inhibitors (NNRTIs). In this paper, we have examined the effects of substituents on both the thiazolidene and benzenesulfonamide moieties. Introduction of a 2-cyanophenyl ring into these moieties significantly enhanced anti-HIV-1 activity, whereas a 2-hydroxyphenyl group endowed potent activity against RTs, including K103N and Y181C mutants. Among the series of molecules examined, 101 and 18b (YM-228855), combinations of 2-cyanophenyl and 4-methyl-5-isopropylthiazole moieties, showed extremely potent anti-HIV-1 activity. The EC50 values of 101 and 18b were 0.0017 and 0.0018 muM, respectively. These values were lower than that of efavirenz (3). Compound 11g (YM-215389), a combination of 2-hydroxyphenyl and 4-chloro-5-isopropylthiazole moieties, proved to be the most active against both K103N and Y181C RTs with IC50 values of 0.043 and 0.013 muM, respectively. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.11.045

文献信息

• Studies of non-nucleoside HIV-1 reverse transcriptase inhibitors. Part 2: Synthesis and structure–activity relationships of 2-cyano and 2-hydroxy thiazolidenebenzenesulfonamide derivatives
  作者：Naoyuki Masuda、Osamu Yamamoto、Masahiro Fujii、Tetsuro Ohgami、Jiro Fujiyasu、Toru Kontani、Ayako Moritomo、Masaya Orita、Hiroyuki Kurihara、Hironobu Koga、Shunji Kageyama、Mitsuaki Ohta、Hiroshi Inoue、Toshifumi Hatta、Masafumi Shintani、Hiroshi Suzuki、Kenji Sudo、Yasuaki Shimizu、Eiichi Kodama、Masao Matsuoka、Masatoshi Fujiwara、Tomoyuki Yokota、Shiro Shigeta、Masanori Baba

  DOI：10.1016/j.bmc.2004.11.045

  日期：2005.2

  In a previous study, we described the structure-activity relationships (SARs) for a series of thiazolidenebenzenesulfonamide derivatives. These compounds were found to be highly potent inhibitors of the wild type (WT) and Y181C mutant reverse transcriptases (RTs) and modest inhibitors of K 103N RT. These molecules are thus considered to be a novel class of non-nucleoside HIV-1 RT inhibitors (NNRTIs). In this paper, we have examined the effects of substituents on both the thiazolidene and benzenesulfonamide moieties. Introduction of a 2-cyanophenyl ring into these moieties significantly enhanced anti-HIV-1 activity, whereas a 2-hydroxyphenyl group endowed potent activity against RTs, including K103N and Y181C mutants. Among the series of molecules examined, 101 and 18b (YM-228855), combinations of 2-cyanophenyl and 4-methyl-5-isopropylthiazole moieties, showed extremely potent anti-HIV-1 activity. The EC50 values of 101 and 18b were 0.0017 and 0.0018 muM, respectively. These values were lower than that of efavirenz (3). Compound 11g (YM-215389), a combination of 2-hydroxyphenyl and 4-chloro-5-isopropylthiazole moieties, proved to be the most active against both K103N and Y181C RTs with IC50 values of 0.043 and 0.013 muM, respectively. (C) 2004 Elsevier Ltd. All rights reserved.