2-methyl-6-methylsulfonyl indole | 507272-15-3

• 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: 2-methyl-6-methylsulfonyl indole
• 英文别名: 6-methanesulfonyl-2-methyl-1H-indole；2-methyl-6-methylsulfonyl-1H-indole
• CAS: 507272-15-3
• 化学式: C₁₀H₁₁NO₂S
• 分子量: 209.269
• InChiKey: IGFNZUZQPDXVHU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  58.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-methyl-6-methylsulfonyl indole 在 Oxone 、 [双(三氟乙酰氧基)碘]苯 作用下， 以 甲醇 为溶剂， 生成 3-(4-Fluoro-benzenesulfinyl)-6-methanesulfonyl-2-methyl-1H-indole
  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：

  3-氨基茴香硫醚 在 4-二甲氨基吡啶 、 Oxone 、 sodium tetrahydroborate 、 三氟化硼 、 碘 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 、 乙腈 、 苯 为溶剂， 生成 2-methyl-6-methylsulfonyl indole
  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

• Indole derivatives as anti-inflammatory agents
  申请人：——

  公开号：US20030130337A1

  公开（公告）日：2003-07-10

  This invention relates to compounds, which are generally anti-inflammatory and analgesic compounds, and which are represented by Formula I: 1 wherein A is a —CH 2 —, —O—, —S—, or —S(O)—; and the other substituents are as defined in the specification; or individual isomers, mixtures of isomers, and pharmaceutically acceptable salts thereof. The invention further relates to pharmaceutical compositions containing such compounds and methods for their use as therapeutic agents

  本发明涉及一类化合物，通常为抗炎和镇痛化合物，其由以下式I表示：其中A为—CH2—、—O—、—S—或—S(O)—；其他取代基如规范中定义；或其个别异构体、异构体混合物和其药用可接受盐。该发明还涉及含有这类化合物的药物组合物以及它们作为治疗剂的使用方法。
• 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。
• [EN] INDOLE DERIVATIVES AS COX II INHIBITORS<br/>[FR] DERIVES D'INDOLE UTILES COMME INHIBITEURS DE COX II
  申请人：HOFFMANN LA ROCHE

  公开号：WO2003029212A1

  公开（公告）日：2003-04-10

  This present invention relates to indole derivatives of Formula (I); wherein A, Ar and R1 to R4 are as defines in the specification. The compounds are useful as a selective COX-II inhibitor and, therefore, may be used for the treatment of COX-II mediated diseases.

  本发明涉及公式（I）中的吲哚衍生物；其中A、Ar和R1至R4如规范中所定义。这些化合物可用作选择性COX-II抑制剂，因此可用于治疗COX-II介导的疾病。
• Preparation of 3-arylmethylindoles as selective COX-2 inhibitors
  作者：Jeffrey A Campbell、Viola Bordunov、Chris A Broka、John Dankwardt、Robert T Hendricks、James M Kress、Keith A.M Walker、Jin-Hai Wang

  DOI：10.1016/j.tetlet.2004.03.068

  日期：2004.5

  The 3-arylmethylation of indoles using TMSOTf/Et3SiH with a wide variety of substituted benzaldehydes has been accomplished. Under these mild Lewis acid mediated reductive conditions, it was demonstrated that indoles bearing both 6-MeSO2, and 2-methyl substituents could be 3-arylmethylated in good to excellent yields to afford the corresponding 3-arylmethyl indoles, effective as selective COX-2 inhibitors. I it addition, the viability of this method for the reductive alkylation of indoles by ketones was demonstrated and shown to be C-3 regioselective. For indoles bearing both a 6-MeSO2, and 2-cyano substituent where this indole reductive alkylation methodology was unsuccessful, all unprecedented Pd(0) mediated arylorganozinc Coupling With the requisite Substituted 3-methylcarbonatomethylindole proved Successful in affording the desired 2-cyano-6-MeSO2-3-arylmethylindoles effective as selective COX-2 inhibitors. (C) 2004 Elsevier Ltd. All rights reserved.
• INDOLE DERIVATIVES AS COX II INHIBITORS
  申请人：F. Hoffmann-La Roche AG

  公开号：EP1438289A1

  公开（公告）日：2004-07-21