6-benzyl-1-(((4-fluorobenzyl)oxy)methyl)-5-isopropyl-3-methylpyrimidine-2,4(1H,3H)-dione | 1281859-62-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 6-benzyl-1-(((4-fluorobenzyl)oxy)methyl)-5-isopropyl-3-methylpyrimidine-2,4(1H,3H)-dione
• 英文别名: 6-Benzyl-1-[(4-fluorophenyl)methoxymethyl]-5-isopropyl-3-methyl-pyrimidine-2,4-dione；6-benzyl-1-[(4-fluorophenyl)methoxymethyl]-3-methyl-5-propan-2-ylpyrimidine-2,4-dione
• CAS: 1281859-62-8
• 化学式: C₂₃H₂₅FN₂O₃
• 分子量: 396.462
• InChiKey: GSKSPIMUCMVHNA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  49.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-(chloromethoxymethyl)-4-fluorobenzene 在 N,O-双三甲硅基乙酰胺 、 四丁基碘化铵 、 caesium carbonate 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 6-benzyl-1-(((4-fluorobenzyl)oxy)methyl)-5-isopropyl-3-methylpyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  3-Hydroxypyrimidine-2,4-diones as an Inhibitor Scaffold of HIV Integrase

  摘要：

  Integrase (IN) represents a clinically validated target for the development of antivirals against human immunodeficiency virus (HIV). Inhibitors with a novel structure core are essential for combating resistance associated with known IN inhibitors (IN Is). We have previously disclosed a novel dual inhibitor scaffold of HIV IN and reverse transcriptase (RT). Here we report the complete structure activity relationship (SAR), molecular modeling, and resistance profile of this inhibitor type on IN inhibition. These studies support an antiviral mechanism of dual inhibition against both IN and RT and validate 3-hydroxypyrimidine-2,4-diones as an IN inhibitor scaffold.

  DOI：

  10.1021/jm1014378

文献信息

• 6-Biphenylmethyl-3-hydroxypyrimidine-2,4-diones potently and selectively inhibited HIV reverse transcriptase-associated RNase H
  作者：Lei Wang、Jing Tang、Andrew D. Huber、Mary C. Casey、Karen A. Kirby、Daniel J. Wilson、Jayakanth Kankanala、Michael A. Parniak、Stefan G. Sarafianos、Zhengqiang Wang

  DOI：10.1016/j.ejmech.2018.07.035

  日期：2018.8

  Human immunodeficiency virus (HIV) reverse transcriptase (RT)-associated ribonuclease H (RNase H) remains an unvalidated drug target. Reported HIV RNase H inhibitors generally lack significant antiviral activity. We report herein the design, synthesis, biochemical and antiviral evaluations of a new 6-biphenylmethyl subtype of the 3-hydroxypyrimidine-2,4-dione (HPD) chemotype. In biochemical assays

  人类免疫缺陷病毒（HIV）逆转录酶（RT）相关的核糖核酸酶H（RNase H）仍然是未经验证的药物靶标。据报道，HIV RNase H抑制剂通常缺乏显着的抗病毒活性。我们在此报告了3-羟基嘧啶-2,4-二酮（HPD）化学型的新的6-联苯甲基亚型的设计，合成，生化和抗病毒评估。在生化分析中，这种新亚型的类似物可在低纳摩尔范围内有效抑制RT RNase H，而在测试的最高浓度下却不会抑制RT聚合酶（pol）或整合酶链转移（INST）。在基于细胞的测定中，一些类似物在低微摩尔范围内抑制HIV，浓度高达100μM，却没有细胞毒性。