diethyl (2-(5-chloro-3-((3,5-dimethylphenyl)sulfonyl)-1H-indole-2-carboxamido)ethyl)phosphonate

• 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: diethyl (2-(5-chloro-3-((3,5-dimethylphenyl)sulfonyl)-1H-indole-2-carboxamido)ethyl)phosphonate
• 英文别名: 5-chloro-N-(2-diethoxyphosphorylethyl)-3-(3,5-dimethylphenyl)sulfonyl-1H-indole-2-carboxamide
• 化学式: C₂₃H₂₈ClN₂O₆PS
• 分子量: 526.978
• InChiKey: BEXQTWSIPQOUSL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  34
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  123
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  diethyl (2-(5-chloro-3-((3,5-dimethylphenyl)sulfonyl)-1H-indole-2-carboxamido)ethyl)phosphonate 在 三甲基溴硅烷 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 以18.6%的产率得到(2-(5-chloro-3-((3,5-dimethylphenyl)sulfonyl)-1H-indole-2-carboxamido)ethyl)phosphonic acid
  参考文献：
  名称：

  Discovery of novel indolylarylsulfones as potent HIV-1 NNRTIs via structure-guided scaffold morphing

  摘要：

  For more in-depth exploration of the chemical space around the entrance channel of HIV-1 reverse transcriptase (RT), a series of novel indolylarylsulfones (IASs) bearing different chiral N-substituted pyrrolidine, azetidine or substituted sulfonamide groups at indole-2-carboxamide were designed and synthesized as potent HIV NNRTIs by structure-guided scaffold morphing approach. All the IASs exhibited moderate to excellent potency against wild-type HIV-1 with EC50 values ranging from 0.0043 mu M to 4.42 mu M. Notably, compound 27 (EC50= 4.7 nM, SI = 5183) and 33 (EC50= 4.3 nM, SI = 7083) were identified as the most potent compounds, which were more active than nevirapine, lamivudine and efavirenz, and also reached the same order of etravirine. Furthermore, some compounds maintained excellent activity against various single HIV-1 mutants (L100I, K103 N, E138K, Y181C) as well as one double mutant (F227L/V106A) with EC50 values in low-micromolar concentration ranges. Notably, 34 displayed outstanding potency against F2271./V106A (EC50 = 0.094 M), and also showed exceptional activity against E138K (EC50 = 0.014 mu M), L100I (EC50 = 0.011 mu M) and K103 N (EC50 = 0.025 mu M). Additionally, most compounds showed markedly reduced cytotoxicity (CC50) compared to lead compounds, especially 36 (CC50> 234.91 mu M, SI > 18727) and 37 (CC50> 252.49 mu M, SI > 15152). Preliminary SARs and molecular modeling studies were also discussed in detail, which may provide valuable insights for further optimization. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.111619
• 作为产物：
  描述：

  ethyl 5-chloro-3-((3,5-dimethylphenyl)sulfonyl)-1H-indole-2-carboxylate 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 三乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 36.5h， 生成 diethyl (2-(5-chloro-3-((3,5-dimethylphenyl)sulfonyl)-1H-indole-2-carboxamido)ethyl)phosphonate
  参考文献：
  名称：

  Discovery of novel indolylarylsulfones as potent HIV-1 NNRTIs via structure-guided scaffold morphing

  摘要：

  For more in-depth exploration of the chemical space around the entrance channel of HIV-1 reverse transcriptase (RT), a series of novel indolylarylsulfones (IASs) bearing different chiral N-substituted pyrrolidine, azetidine or substituted sulfonamide groups at indole-2-carboxamide were designed and synthesized as potent HIV NNRTIs by structure-guided scaffold morphing approach. All the IASs exhibited moderate to excellent potency against wild-type HIV-1 with EC50 values ranging from 0.0043 mu M to 4.42 mu M. Notably, compound 27 (EC50= 4.7 nM, SI = 5183) and 33 (EC50= 4.3 nM, SI = 7083) were identified as the most potent compounds, which were more active than nevirapine, lamivudine and efavirenz, and also reached the same order of etravirine. Furthermore, some compounds maintained excellent activity against various single HIV-1 mutants (L100I, K103 N, E138K, Y181C) as well as one double mutant (F227L/V106A) with EC50 values in low-micromolar concentration ranges. Notably, 34 displayed outstanding potency against F2271./V106A (EC50 = 0.094 M), and also showed exceptional activity against E138K (EC50 = 0.014 mu M), L100I (EC50 = 0.011 mu M) and K103 N (EC50 = 0.025 mu M). Additionally, most compounds showed markedly reduced cytotoxicity (CC50) compared to lead compounds, especially 36 (CC50> 234.91 mu M, SI > 18727) and 37 (CC50> 252.49 mu M, SI > 15152). Preliminary SARs and molecular modeling studies were also discussed in detail, which may provide valuable insights for further optimization. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.111619

文献信息

• Discovery of novel indolylarylsulfones as potent HIV-1 NNRTIs via structure-guided scaffold morphing
  作者：Tong Zhao、Qing Meng、Dongwei Kang、Jianbo Ji、Erik De Clercq、Christophe Pannecouque、Xinyong Liu、Peng Zhan

  DOI：10.1016/j.ejmech.2019.111619

  日期：2019.11

  For more in-depth exploration of the chemical space around the entrance channel of HIV-1 reverse transcriptase (RT), a series of novel indolylarylsulfones (IASs) bearing different chiral N-substituted pyrrolidine, azetidine or substituted sulfonamide groups at indole-2-carboxamide were designed and synthesized as potent HIV NNRTIs by structure-guided scaffold morphing approach. All the IASs exhibited moderate to excellent potency against wild-type HIV-1 with EC50 values ranging from 0.0043 mu M to 4.42 mu M. Notably, compound 27 (EC50= 4.7 nM, SI = 5183) and 33 (EC50= 4.3 nM, SI = 7083) were identified as the most potent compounds, which were more active than nevirapine, lamivudine and efavirenz, and also reached the same order of etravirine. Furthermore, some compounds maintained excellent activity against various single HIV-1 mutants (L100I, K103 N, E138K, Y181C) as well as one double mutant (F227L/V106A) with EC50 values in low-micromolar concentration ranges. Notably, 34 displayed outstanding potency against F2271./V106A (EC50 = 0.094 M), and also showed exceptional activity against E138K (EC50 = 0.014 mu M), L100I (EC50 = 0.011 mu M) and K103 N (EC50 = 0.025 mu M). Additionally, most compounds showed markedly reduced cytotoxicity (CC50) compared to lead compounds, especially 36 (CC50> 234.91 mu M, SI > 18727) and 37 (CC50> 252.49 mu M, SI > 15152). Preliminary SARs and molecular modeling studies were also discussed in detail, which may provide valuable insights for further optimization. (C) 2019 Elsevier Masson SAS. All rights reserved.