ethyl 5-bromo-3-(3,5-dimethylphenylthio)-1H-indole-2-carboxylate | 540740-61-2

• 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: ethyl 5-bromo-3-(3,5-dimethylphenylthio)-1H-indole-2-carboxylate
• 英文别名: ethyl 5-bromo-3-(3,5-dimethylphenyl)sulfanyl-1H-indole-2-carboxylate
• CAS: 540740-61-2
• 化学式: C₁₉H₁₈BrNO₂S
• 分子量: 404.327
• InChiKey: RDKXPSAVNIYTDX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  67.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 5-bromo-3-(3,5-dimethylphenylthio)-1H-indole-2-carboxylate 在 间氯过氧苯甲酸 、 lithium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 27.0h， 生成 5-bromo-3-[(3,5-dimethylphenyl)sulfonyl]-1H-indole-2-carboxylic acid
  参考文献：
  名称：

  通过结构指导的支架变形和片段重排发现新型哌啶取代的吲哚基芳基砜作为有效的HIV NNRTIs

  摘要：

  为了进一步探索HIV-1逆转录酶（RT）入口通道周围的化学空间，通过结构引导支架将一系列在吲哚-2-甲酰胺上带有N-取代哌啶的新型吲哚基芳砜（IAS）鉴定为有效的HIV NNRTI。变形和片段重排。所有的国际会计表现出中度至对野生型优异效力HIV-1与EC 50值范围从0.62μM至0.006μM 8（EC 50  = 6 1nM）和18（EC 50 = 9 nM）被认为是最有效的化合物，其活性高于NVP和DLV，并达到EFV和E​​TV的相同数量级。此外，大多数化合物在低微摩尔至两位数纳摩尔浓度范围内保持高活性，抵御各种单一的HIV-1突变体（L100I，K103N，E138K，Y181C）和一个具有EC 50值的双重突变体（F227L / V106A）。特别地，8个显示出对L100I的出色效能（EC 50  = 17 nM，抗性是2.8倍），而18个对E138K突变体则相对更有效（EC

  DOI：

  10.1016/j.ejmech.2016.10.009
• 作为产物：
  描述：

  3,5-二甲基苯硫酚 在 三氟化硼乙醚 作用下， 以 二氯甲烷 为溶剂， 反应 7.5h， 生成 ethyl 5-bromo-3-(3,5-dimethylphenylthio)-1H-indole-2-carboxylate
  参考文献：
  名称：

  Novel Indolyl Aryl Sulfones Active against HIV-1 Carrying NNRTI Resistance Mutations:  Synthesis and SAR Studies

  摘要：

  The potent anti-HIV-1 activities of L-737,126 (2) and PAS sulfones prompted us to design and test against HIV-1 in acutely infected MT-4 cells a number of novel 1- and 3-benzenesulfonylindoles. Indoles belonging to the 1-benzenesulfonyl series were found poorly or totally inactive. On the contrary, some of the 3-benzenesulfonyl derivatives turned out to be as potent as 2, being endowed with potencies in the low nanomolar concentration range. In particular, (2-methylphenyl)sulfonyl (72) and (3-methylphenyl)sulfonyl (73) derivatives showed EC50 values of 1 nM. Introduction of two methyl groups at positions 3 and 5 of the phenyl ring of 2 furnished derivatives (80 and 83) which showed very potent and selective anti-HIV-1 activity not only against the wt strain, but also against mutants carrying NNRTI-resistant mutations at positions 103 and 181 of the reverse transcriptase gene.

  DOI：

  10.1021/jm0211063

文献信息

• 吲哚芳砜类衍生物及其制备方法与应用
  申请人：山东大学

  公开号：CN105968095B

  公开（公告）日：2018-10-30

  本发明公开了一种如通式I所示的吲哚芳砜类衍生物及其药学上可接受的盐、酯或前药，其制备方法以及含有一个或多个此类化合物的组合物在制备预防和治疗人免疫缺陷病毒(HIV)感染中的应用。
• Indolylarylsulfones Bearing Natural and Unnatural Amino Acids. Discovery of Potent Inhibitors of HIV-1 Non-Nucleoside Wild Type and Resistant Mutant Strains Reverse Transcriptase and Coxsackie B4 Virus
  作者：Francesco Piscitelli、Antonio Coluccia、Andrea Brancale、Giuseppe La Regina、Anna Sansone、Cesare Giordano、Jan Balzarini、Giovanni Maga、Samantha Zanoli、Alberta Samuele、Roberto Cirilli、Francesco La Torre、Antonio Lavecchia、Ettore Novellino、Romano Silvestri

  DOI：10.1021/jm801470b

  日期：2009.4.9

  New potent indolylarylsulfone (IAS) HIV-I NNRTIs were obtained by coupling natural and unnatural amino acids to the 2-carboxamide and introducing different electron-withdrawing substituents at position 4 and 5 of the indole nucleus. The new IASs inhibited the HIV-1 replication in human T-lymphocyte (CEM) cells at low/subnanomolar concentration and were weakly cytostatic. Against the mutant L100I, K103N, and Y181C RT HIV-1 strains in CEM cells, sulfones 3, 4, 19, 27, and 31 were comparable to EFV. The new IASs were inhibitors to Coxsackie B4 virus at low micromolar (2-9 mu M) concentrations. Superimposition of PLANTS docked conformations of IASs 19 and 9 revealed different hydrophobic interactions of the 3,5-dimethylphenyl group, for which a staking interaction with Tyr181 aromatic side chain was observed. The binding mode of 19 was not affected by the L100I mutation and was consistent with the interactions reported for the WT strain.
• Novel Indolyl Aryl Sulfones Active against HIV-1 Carrying NNRTI Resistance Mutations:  Synthesis and SAR Studies
  作者：Romano Silvestri、Gabriella De Martino、Giuseppe La Regina、Marino Artico、Silvio Massa、Laura Vargiu、Massimo Mura、Anna Giulia Loi、Tiziana Marceddu、Paolo La Colla

  DOI：10.1021/jm0211063

  日期：2003.6.1

  The potent anti-HIV-1 activities of L-737,126 (2) and PAS sulfones prompted us to design and test against HIV-1 in acutely infected MT-4 cells a number of novel 1- and 3-benzenesulfonylindoles. Indoles belonging to the 1-benzenesulfonyl series were found poorly or totally inactive. On the contrary, some of the 3-benzenesulfonyl derivatives turned out to be as potent as 2, being endowed with potencies in the low nanomolar concentration range. In particular, (2-methylphenyl)sulfonyl (72) and (3-methylphenyl)sulfonyl (73) derivatives showed EC50 values of 1 nM. Introduction of two methyl groups at positions 3 and 5 of the phenyl ring of 2 furnished derivatives (80 and 83) which showed very potent and selective anti-HIV-1 activity not only against the wt strain, but also against mutants carrying NNRTI-resistant mutations at positions 103 and 181 of the reverse transcriptase gene.
• Discovery of novel piperidine-substituted indolylarylsulfones as potent HIV NNRTIs via structure-guided scaffold morphing and fragment rearrangement
  作者：Xiao Li、Ping Gao、Boshi Huang、Zhongxia Zhou、Zhao Yu、Zheng Yuan、Huiqing Liu、Christophe Pannecouque、Dirk Daelemans、Erik De Clercq、Peng Zhan、Xinyong Liu

  DOI：10.1016/j.ejmech.2016.10.009

  日期：2017.1

  chemical space around the entrance channel of HIV-1 reverse transcriptase (RT), a series of novel indolylarylsulfones (IASs) bearing N-substituted piperidine at indole-2-carboxamide were identified as potent HIV NNRTIs by structure-guided scaffold morphing and fragment rearrangement. All the IASs exhibited moderate to excellent potency against wild-type HIV-1 with EC50 values ranging from 0.62 μM to 0.006 μM

  为了进一步探索HIV-1逆转录酶（RT）入口通道周围的化学空间，通过结构引导支架将一系列在吲哚-2-甲酰胺上带有N-取代哌啶的新型吲哚基芳砜（IAS）鉴定为有效的HIV NNRTI。变形和片段重排。所有的国际会计表现出中度至对野生型优异效力HIV-1与EC 50值范围从0.62μM至0.006μM 8（EC 50  = 6 1nM）和18（EC 50 = 9 nM）被认为是最有效的化合物，其活性高于NVP和DLV，并达到EFV和E​​TV的相同数量级。此外，大多数化合物在低微摩尔至两位数纳摩尔浓度范围内保持高活性，抵御各种单一的HIV-1突变体（L100I，K103N，E138K，Y181C）和一个具有EC 50值的双重突变体（F227L / V106A）。特别地，8个显示出对L100I的出色效能（EC 50  = 17 nM，抗性是2.8倍），而18个对E138K突变体则相对更有效（EC