1-(2-(2-benzyl-4-methylphenoxy)ethyl)pyrimidine-2,4(1H,3H)-dione | 898128-51-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-(2-(2-benzyl-4-methylphenoxy)ethyl)pyrimidine-2,4(1H,3H)-dione
• 英文别名: 1-[2-(2-benzyl-4-methylphenoxy)ethyl]uracil；1-[2-(2-Benzyl-4-methyl-phenoxy)ethyl]pyrimidine-2,4-dione；1-[2-(2-benzyl-4-methylphenoxy)ethyl]pyrimidine-2,4-dione
• CAS: 898128-51-3
• 化学式: C₂₀H₂₀N₂O₃
• 分子量: 336.39
• InChiKey: CSSBOMFJEJCGJQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-苄基-4-甲基苯酚 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 生成 1-(2-(2-benzyl-4-methylphenoxy)ethyl)pyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  Computationally-Guided Optimization of a Docking Hit to Yield Catechol Diethers as Potent Anti-HIV Agents

  摘要：

  A 5-mu M docking hit has been optimized to an extraordinarily potent (55 pM) non-nucleoside inhibitor of HIV reverse transcriptase. Use of free energy perturbation (PEP) calculations to predict relative free energies of binding aided the optimizations by identifying optimal substitution patterns for phenyl rings and a linker. The most potent resultant catechol diethers feature terminal uracil and cyanovinylphenyl groups. A halogen bond with Pro95 likely contributes to the extreme potency of compound 42. In addition, several examples are provided illustrating failures of attempted grafting of a substructure from a very active compound onto a seemingly related scaffold to improve its activity.

  DOI：

  10.1021/jm201134m

文献信息

• 1-[2-(2-Benzoyl- and 2-benzylphenoxy)ethyl]uracils as potent anti-HIV-1 agents
  作者：Mikhail S. Novikov、Olga N. Ivanova、Alexander V. Ivanov、Alexander A. Ozerov、Vladimir T. Valuev-Elliston、Kartik Temburnikar、Galina V. Gurskaya、Sergey N. Kochetkov、Christophe Pannecouque、Jan Balzarini、Katherine L. Seley-Radtke

  DOI：10.1016/j.bmc.2011.08.025

  日期：2011.10

  Non-nucleoside reverse transcriptase inhibitors (NNRTI) are key components in highly active antiretroviral therapy for treating HIV-1. Herein we present the synthesis for a series of N1-alkylated uracil derivatives bearing ω-(2-benzyl- and 2-benzoylphenoxy)alkyl substituents as novel NNRTIs. These compounds displayed anti-HIV activity similar to that of nevirapine and several of them exhibited activity

  非核苷逆转录酶抑制剂 (NNRTI) 是治疗 HIV-1 的高效抗逆转录病毒疗法的关键成分。在此，我们展示了一系列带有 ω-(2-苄基-和 2-苯甲酰基苯氧基) 烷基取代基的 N1-烷基化尿嘧啶衍生物作为新型 NNRTI 的合成。这些化合物显示出类似于奈韦拉平的抗 HIV 活性，其中一些化合物显示出针对 K103N/Y181C RT 突变体 HIV-1 菌株的活性。进一步评估表明，除 V106A RT 外，这些抑制剂对大多数耐奈韦拉平的单取代和双取代 RT 具有活性。因此，候选化合物可被视为针对野生型病毒和耐药形式的潜在先导化合物。
• CATECHOL DIETHERS AS POTENT ANTI-HIV AGENTS
  申请人：YALE UNIVERSITY

  公开号：US20140288017A1

  公开（公告）日：2014-09-25

  The present invention is directed to novel catechol diether compounds, pharmaceutical compositions therefrom and methods for inhibiting reverse transcriptase and treating HIV infections, especially included drug resistant strains of HIV 1 and 2 and/or secondary disease states and/or conditions which occur as a consequence of HIV infection.

  本发明涉及新型儿茶酚二醚化合物、其制药组合物以及抑制反转录酶和治疗HIV感染的方法，特别包括抗药性HIV 1和2以及/或作为HIV感染后果的二级疾病状态和/或条件。
• US9487476B2
  申请人：——

  公开号：US9487476B2

  公开（公告）日：2016-11-08
• [EN] CATECHOL DIETHERS AS POTENT ANTI-HIV AGENTS<br/>[FR] DIÉTHERS DE CATÉCHOL COMME AGENTS ANTI-HIV PUISSANTS
  申请人：UNIV YALE

  公开号：WO2013056003A2

  公开（公告）日：2013-04-18

  The present invention is directed to novel catechol diether compounds, pharmaceutical compositions therefrom and methods for inhibiting reverse transcriptase and treating HIV infections, especially included drug resistant strains of HIV 1 and 2 and/or secondary disease states and/or conditions which occur as a consequence of HIV infection.
• Computationally-Guided Optimization of a Docking Hit to Yield Catechol Diethers as Potent Anti-HIV Agents
  作者：Mariela Bollini、Robert A. Domaoal、Vinay V. Thakur、Ricardo Gallardo-Macias、Krasimir A. Spasov、Karen S. Anderson、William L. Jorgensen

  DOI：10.1021/jm201134m

  日期：2011.12.22

  A 5-mu M docking hit has been optimized to an extraordinarily potent (55 pM) non-nucleoside inhibitor of HIV reverse transcriptase. Use of free energy perturbation (PEP) calculations to predict relative free energies of binding aided the optimizations by identifying optimal substitution patterns for phenyl rings and a linker. The most potent resultant catechol diethers feature terminal uracil and cyanovinylphenyl groups. A halogen bond with Pro95 likely contributes to the extreme potency of compound 42. In addition, several examples are provided illustrating failures of attempted grafting of a substructure from a very active compound onto a seemingly related scaffold to improve its activity.