3-(2-Chloro-phenylsulfanyl)-6-methanesulfonyl-1H-indole-2-carboxylic acid methyl ester | 714243-39-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 3-(2-Chloro-phenylsulfanyl)-6-methanesulfonyl-1H-indole-2-carboxylic acid methyl ester
• CAS: 714243-39-7
• 化学式: C₁₇H₁₄ClNO₄S₂
• 分子量: 395.887
• InChiKey: LVUBAVACPUYPLR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.16
• 重原子数：
  25.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  76.23
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  3-(2-Chloro-phenylsulfanyl)-6-methanesulfonyl-1H-indole-2-carboxylic acid methyl ester 在 lithium hydroxide 、 草酰氯 、 氨 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 为溶剂， 生成 3-(2-chlorophenyl)sulfanyl-6-methylsulfonyl-1H-indole-2-carboxamide
  参考文献：
  名称：

  Rational design of 6-methylsulfonylindoles as selective cyclooxygenase-2 inhibitors

  摘要：

  The introduction of 3-arylmethyl, 3-aryloxy and 3-arylthio moieties into a 6-methylsulfonylindole framework using rational drug design led to potent, selective COX-2 inhibitors having efficacy in a rat carrageenan air pouch model. Incorporation of a conformationally more rigid 3-aroyloxy substituent onto the 6-methylsulfonylindole scaffold led to selective, but considerably less potent COX-2 inhibitors. Variation of the hydrophilicity and size of the indole 2-substituent of 3-arylthio-6-methylsulfonylindole inhibitors led to modulation of the COX-2 human whole blood (HWB) potency and selectivity. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.06.075
• 作为产物：
  描述：

  4-(甲基巯基)苯甲醛 在 Oxone 、 sodium methylate 、 [双(三氟乙酰氧基)碘]苯 作用下， 以 四氢呋喃 、 甲醇 、 甲苯 为溶剂， 反应 51.0h， 生成 3-(2-Chloro-phenylsulfanyl)-6-methanesulfonyl-1H-indole-2-carboxylic acid methyl ester
  参考文献：
  名称：

  Rational design of 6-methylsulfonylindoles as selective cyclooxygenase-2 inhibitors

  摘要：

  The introduction of 3-arylmethyl, 3-aryloxy and 3-arylthio moieties into a 6-methylsulfonylindole framework using rational drug design led to potent, selective COX-2 inhibitors having efficacy in a rat carrageenan air pouch model. Incorporation of a conformationally more rigid 3-aroyloxy substituent onto the 6-methylsulfonylindole scaffold led to selective, but considerably less potent COX-2 inhibitors. Variation of the hydrophilicity and size of the indole 2-substituent of 3-arylthio-6-methylsulfonylindole inhibitors led to modulation of the COX-2 human whole blood (HWB) potency and selectivity. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.06.075

文献信息

• A new synthesis of 3-arylthioindoles as selective COX-2 inhibitors using PIFA
  作者：Jeffrey A Campbell、Chris A Broka、Leyi Gong、Keith A.M Walker、Jin-Hai Wang

  DOI：10.1016/j.tetlet.2004.03.153

  日期：2004.5

  The direct 3-arylthiolation of 2-substituted indoles using phenyliodine(III)bis trifluoroacetate (PIFA) in (CF3)2CHOH with a wide variety of benzenethiols has been accomplished. In particular, indoles bearing a 6-MeSO2 and either a 2-methyl or 2-carboxymethyl substituent could be 3-arylthiolated in good to excellent yields to afford the corresponding 3-arylthioindoles as selective COX-2 inhibitors

  使用（CF 3）2 CHOH中的苯基碘（III）双三氟乙酸酯（PIFA）与多种苯硫醇进行了2-取代的吲哚的直接3-芳基硫醇化反应。尤其是，带有6-MeSO 2和2-甲基或2-羧甲基取代基的吲哚可以良好的产率以优异的产率被3-芳基硫醇化，以提供相应的3-芳基硫吲哚作为选择性COX-2抑制剂。在改变2-CO 2 Et吲哚的5-取代基的电子性质的研究中，发现随着取代基变得更吸电子，反应的产率提高。该结果与提出的涉及中间体3-IPh吲哚配合物的苯硫醇置换的机理相一致。