methyl 3-[(3,5-dimethylphenyl)sulfonyl]-5-chloro-1H-indole-2-carboxylate | 473257-83-9

• 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: methyl 3-[(3,5-dimethylphenyl)sulfonyl]-5-chloro-1H-indole-2-carboxylate
• 英文别名: methyl 5-chloro-3-[(3,5-dimethylphenyl)sulfonyl]-1H-indole-2-carboxylate；Methyl 5-chloro-3-(3,5-dimethylphenylsulfonyl)-indole-2-carboxylate；methyl 5-chloro-3-(3,5-dimethylphenyl)sulfonyl-1H-indole-2-carboxylate
• CAS: 473257-83-9
• 化学式: C₁₈H₁₆ClNO₄S
• 分子量: 377.848
• InChiKey: FCOVPCKXCOADDJ-UHFFFAOYSA-N

物化性质

• 熔点：
  234-236 °C
• 沸点：
  620.8±55.0 °C(Predicted)
• 密度：
  1.385±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  84.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 3-[(3,5-dimethylphenyl)sulfonyl]-5-chloro-1H-indole-2-carboxylate 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 1.5h， 以82%的产率得到5-chloro-3-(3,5-dimethylphenyl)sulfonyl-1H-indole-2-carbohydrazide
  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
• 作为产物：
  描述：

  3,5-二甲基苯硫酚 在 三氟化硼乙醚 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 、 氯仿 为溶剂， 反应 9.0h， 生成 methyl 3-[(3,5-dimethylphenyl)sulfonyl]-5-chloro-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

• Phenylindoles for the treatment of HIV
  申请人：——

  公开号：US20020193415A1

  公开（公告）日：2002-12-19

  The invention as disclosed herein is a method and composition for the treatment of HIV in humans and other host animals, that includes the administration of an effective HIV treatment amount of a phenylindole as described herein or a pharmaceutically acceptable salt or prodrug thereof, optionally in a pharmaceutically acceptable carrier. The compounds of this invention either possess antiviral (i.e., anti-HIV) activity, or are metabolized to a compound that exhibits such activity.

  本发明公开了一种用于治疗人类和其他宿主动物体内的HIV的方法和组合物，包括根据本文所述的给予有效的HIV治疗量的苯基吲哚或其药学上可接受的盐或前药，可选地在药学上可接受的载体中。本发明的化合物具有抗病毒（即抗HIV）活性，或者经代谢后形成具有该活性的化合物。
• Design, Molecular Modeling, Synthesis, and Anti-HIV-1 Activity of New Indolyl Aryl Sulfones. Novel Derivatives of the Indole-2-carboxamide
  作者：Rino Ragno、Antonio Coluccia、Giuseppe La Regina、Gabriella De Martino、Francesco Piscitelli、Antonio Lavecchia、Ettore Novellino、Alberto Bergamini、Chiara Ciaprini、Anna Sinistro、Giovanni Maga、Emanuele Crespan、Marino Artico、Romano Silvestri

  DOI：10.1021/jm0512490

  日期：2006.6.1

  and 9 were found active in the sub-nanomolar range of concentration in both MT-4 and C8166 cell-based anti-HIV assays. These compounds, and in particular compound 9, also showed excellent inhibitory activity against both HIV-112 and HIV-AB1 primary isolates in lymphocytes and against HIV WT in macrophages.

  分子建模研究和更新的高度预测性3-D QSAR模型导致发现异常有效的吲哚基芳基砜（IAS），其特征在于在吲哚-2-甲酰胺上存在吡咯烷-2-酮核或在其上存在一些取代基吲哚-2-碳酰肼。在基于MT-4和C8166细胞的抗HIV分析中，发现化合物7和9在亚纳摩尔浓度范围内具有活性。这些化合物，特别是化合物9，对淋巴细胞中的HIV-112和HIV-AB1主要分离物以及巨噬细胞中的HIV WT也显示出优异的抑制活性。
• Docking and 3-D QSAR Studies on Indolyl Aryl Sulfones. Binding Mode Exploration at the HIV-1 Reverse Transcriptase Non-Nucleoside Binding Site and Design of Highly Active <i>N</i>-(2-Hydroxyethyl)carboxamide and <i>N</i>-(2-Hydroxyethyl)carbohydrazide Derivatives
  作者：Rino Ragno、Marino Artico、Gabriella De Martino、Giuseppe La Regina、Antonio Coluccia、Alessandra Di Pasquali、Romano Silvestri

  DOI：10.1021/jm040854k

  日期：2005.1.1

  Three-dimensional quantitative structure-activity relationship (3-D QSAR) studies and docking simulations were developed on indolyl aryl sulfones (L, Ss), a class of novel HIV-1 non-nucleoside reverse transcriptase (RT) inhibitors (Silvestri, et al. J. Med. Chem. 2003, 46, 2482-2493) highly active against wild type and some clinically relevant resistant strains (Y181C. the double mutant K103N-Y181C, and the K103R-V179D-P225H strain, highly resistant to efavirenz). Predictive 3-D QSAR models using the combination of GRID and GOLPE programs were obtained using a receptor-based alignment by means of docking IASs into the non-nucleoside binding site (NNBS) of RT. The derived 3-D QSAR models showed conventional correlation (r(2)) and cross-validated (q(2)) coefficients values ranging from 0.79 to 0.93 and from 0.59 to 0.84. respectively. All described models were validated by an external test set compiled from previously reported pyrryl aryl sulfones (Artico, et al. J. Med. Chem. 1996, 39, 522-530). The most predictive 3-D QSAR model was then used to predict the activity of novel untested LASs. The synthesis of six designed derivatives (prediction set) allowed disclosure of new IASs endowed with high anti-HIV-1 activities.
• PHENYLINDOLES FOR THE TREATMENT OF HIV
  申请人：Idenix (Cayman) Limited

  公开号：EP1390029A1

  公开（公告）日：2004-02-25
• EP1390029A4
  申请人：——

  公开号：EP1390029A4

  公开（公告）日：2005-11-30