5-tert-butyl-2-(2-hydroxyethyl)-1H-isoindole-1,3(2H)-dione | 104638-94-0

• 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: 5-tert-butyl-2-(2-hydroxyethyl)-1H-isoindole-1,3(2H)-dione
• 英文别名: 5-Tert-butyl-2-(2-hydroxyethyl)isoindole-1,3-dione
• CAS: 104638-94-0
• 化学式: C₁₄H₁₇NO₃
• 分子量: 247.294
• InChiKey: XCICMRYUBLCRIO-UHFFFAOYSA-N

物化性质

• 熔点：
  60-62 °C(Solv: acetone (67-64-1))
• 沸点：
  393.1±35.0 °C(Predicted)
• 密度：
  1.210±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  57.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  4-叔丁基邻苯二甲酸酐 、 C.I.酸性橙108 反应 2.0h， 以82%的产率得到5-tert-butyl-2-(2-hydroxyethyl)-1H-isoindole-1,3(2H)-dione
  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

• (Hetero)aroyl esters of 2-(N-phthalimido)ethanol and analogues: parallel synthesis, anti-HIV-1 activity and cytotoxicity
  作者：Sara Cesarini、Andrea Spallarossa、Angelo Ranise、Silvia Schenone、Paolo La Colla、Gabriella Collu、Giuseppina Sanna、Roberta Loddo

  DOI：10.1007/s00044-009-9192-x

  日期：2010.5

  The structural simplification of the non-nucleoside reverse transcriptase inhibitors (NNRTIs) O-(2-phthalimidoethyl)-N-(hetero)aroyl-N-arylthiocarbamates led us to design (hetero)aroyl esters of 2-(N-phthalimido)ethanol as a potential new class of anti-HIV-1 agents. The setup of a solution-phase parallel synthesis method allowed the rapid preparation of a high number of analogues. In cell-based assays, 20 of 34 esters showed anti-HIV-1 activity ranging from nanomolar to micromolar concentrations. The most potent esters had only a minor effect or were ineffective in enzyme assay against HIV-1 reverse transcriptase. Variations on the O-(2-phthalimidoethyl) moiety led to compounds devoid of antiretroviral activity, but cytotoxic, in particular those bearing the 4-chloro-3-nitrobenzoyl moiety. The most cytotoxic compound displayed a CC50 value of 1.6 mu M.