O-[2-(5-tert-butyl-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl] 4-methylphenylthiocarbamate | 1152595-37-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: O-[2-(5-tert-butyl-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl] 4-methylphenylthiocarbamate
• 英文别名: O-[2-(5-tert-butyl-1,3-dioxo-isoindolin-2-yl)ethyl] N-(p-tolyl)carbamothioate；O-[2-(5-tert-butyl-1,3-dioxoisoindol-2-yl)ethyl] N-(4-methylphenyl)carbamothioate
• CAS: 1152595-37-3
• 化学式: C₂₂H₂₄N₂O₃S
• 分子量: 396.51
• InChiKey: LNKRMYDGSXJIGR-UHFFFAOYSA-N

物化性质

• 熔点：
  118-120 °C(Solvent: Diethyl ether)
• 沸点：
  525.1±60.0 °C(predicted)
• 密度：
  1.259±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  90.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  5-tert-butyl-2-(2-hydroxyethyl)-1H-isoindole-1,3(2H)-dione 、 对甲苯异硫氰酸酯 在 sodium hydride 、 水 、 氯化铵 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 24.0h， 以22%的产率得到O-[2-(5-tert-butyl-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl] 4-methylphenylthiocarbamate
  参考文献：
  名称：

  Novel modifications in the series of O-(2-phthalimidoethyl)-N-substituted thiocarbamates and their ring-opened congeners as non-nucleoside HIV-1 reverse transcriptase inhibitors

  摘要：

  The structure-activity relationships (SARs) of N-aryl-O-(2-phthalimidoethyl)thiocarbamates (C-TCs) and their imide ring-opened congeners (O-TCs) as non-nucleoside HIV-1 reverse transcriptase inhibitors were further investigated. The SAR strategy involved modifications of the N-phenyl ring followed by the hybridization of the most promising N-aryl and O-(2-phthalimidoethyl)substructures. The role of stereochemistry and tert-butyl substitution of the phthalimidoethyl moiety on activity was also investigated. Seventy-six analogues were prepared by parallel solution-phase synthesis. Twenty-two C-TCs displayed nanomolar activity against wild-type HIV-1 and a number of analogues were effective against the Y181C mutant. Compound 56 combined the highest activity so far identified against Y181C (EC50=1.3 mu M) with good potency against the K103R mutant (EC50=4.8 mu M). Docking simulations helped to rationalize the SARs. (c) 2008 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2008.09.024

文献信息

• Novel modifications in the series of O-(2-phthalimidoethyl)-N-substituted thiocarbamates and their ring-opened congeners as non-nucleoside HIV-1 reverse transcriptase inhibitors
  作者：Andrea Spallarossa、Sara Cesarini、Angelo Ranise、Olga Bruno、Silvia Schenone、Paolo La Colla、Gabriella Collu、Giuseppina Sanna、Barbara Secci、Roberta Loddo

  DOI：10.1016/j.ejmech.2008.09.024

  日期：2009.4

  The structure-activity relationships (SARs) of N-aryl-O-(2-phthalimidoethyl)thiocarbamates (C-TCs) and their imide ring-opened congeners (O-TCs) as non-nucleoside HIV-1 reverse transcriptase inhibitors were further investigated. The SAR strategy involved modifications of the N-phenyl ring followed by the hybridization of the most promising N-aryl and O-(2-phthalimidoethyl)substructures. The role of stereochemistry and tert-butyl substitution of the phthalimidoethyl moiety on activity was also investigated. Seventy-six analogues were prepared by parallel solution-phase synthesis. Twenty-two C-TCs displayed nanomolar activity against wild-type HIV-1 and a number of analogues were effective against the Y181C mutant. Compound 56 combined the highest activity so far identified against Y181C (EC50=1.3 mu M) with good potency against the K103R mutant (EC50=4.8 mu M). Docking simulations helped to rationalize the SARs. (c) 2008 Elsevier Masson SAS. All rights reserved.