1-benzyl-6-chloro-3-(3,5-dimethylbenzyl)uracil

• 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-benzyl-6-chloro-3-(3,5-dimethylbenzyl)uracil
• 英文别名: 1-Benzyl-6-chloro-3-[(3,5-dimethylphenyl)methyl]pyrimidine-2,4-dione
• 化学式: C₂₀H₁₉ClN₂O₂
• 分子量: 354.836
• InChiKey: ZFIFKXDGWUJBEA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  40.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-benzyl-6-chloro-3-(3,5-dimethylbenzyl)uracil 、 甲胺 在 sodium carbonate 作用下， 以 乙醇 为溶剂， 以92%的产率得到1-benzyl-3-(3,5-dimethylbenzyl)-6-methylaminouracil
  参考文献：
  名称：

  Synthesis and evaluation of novel 3-(3,5-dimethylbenzyl)uracil analogs as potential anti-HIV-1 agents

  摘要：

  A novel series of uracil derivatives with a 3,5-dimethylbenzyl group at the N-3-position were synthesized and evaluated as non-nucleoside HIV-1 reverse transcriptase inhibitors. Some of these compounds showed good-to-moderate activity with EC50 values in the submicromolar range. Among them, compound 10c showed significant potency against HIV-1 activity with an EC50 value of 0.03 mu M and a high selectivity index of 2863. Preliminary structure-activity relationships and molecular modeling analyses were used to explore the major interactions between HIV-1 reverse transcriptase and the potent inhibitor 10c, which may serve as an important lead for further optimization. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.06.061
• 作为产物：
  描述：

  3,5-二甲基苯甲醇 、 6-氯-1-(苯基甲基)-2,4(1H,3H)-嘧啶二酮 在 diamide 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 以100%的产率得到1-benzyl-6-chloro-3-(3,5-dimethylbenzyl)uracil
  参考文献：
  名称：

  1-取代的3-（3,5-二甲基苄基）尿嘧啶衍生物的合成及其抗HIV-1和抗HCMV活性。

  摘要：

  在碱存在下用烷基卤处理3-（3,5-二甲基苄基）尿嘧啶（3），得到1-取代的同类物。使用Mitsunobu反应将3与醇缩合也用作替代方法。根据先前建立的程序评估3-（3,5-二甲基苄基）尿嘧啶的1-取代类似物的抗HIV-1活性。看来1-氰甲基的氮对于抗HIV-1活性是重要的，表明与HIV-1逆转录酶的氨基酸残基相互作用。1-芳基甲基衍生物也显示出良好的抗HIV-1活性。并且2-和4-吡啶甲基衍生物的特别好。这些结果已通过Docking Studies使用“ Glide配体对接工作”程序进行了确认，

  DOI：

  10.1248/cpb.54.325

文献信息

• Synthesis and Anti-HIV-1 and Anti-HCMV Activity of 1-Substituted 3-(3,5-Dimethylbenzyl)uracil Derivatives
  作者：Tokumi Maruyama、Shigetada Kozai、Yosuke Demizu、Myriam Witvrouw、Christophe Pannecouque、Jan Balzarini、Robert Snoecks、Graciella Andrei、Erik De Clercq

  DOI：10.1248/cpb.54.325

  日期：——

  3-(3,5-Dimethylbenzyl)uracil (3) was treated with alkyl halides in the presence of alkali to give 1-substituted congeners. Condensation of 3 with alcohols using the Mitsunobu reaction was also employed as an alternative method. The anti-HIV-1 activity of 1-substituted analogues of 3-(3,5-dimethylbenzyl)uracil was evaluated according to previously established procedures. It appeared that the nitrogen

  在碱存在下用烷基卤处理3-（3,5-二甲基苄基）尿嘧啶（3），得到1-取代的同类物。使用Mitsunobu反应将3与醇缩合也用作替代方法。根据先前建立的程序评估3-（3,5-二甲基苄基）尿嘧啶的1-取代类似物的抗HIV-1活性。看来1-氰甲基的氮对于抗HIV-1活性是重要的，表明与HIV-1逆转录酶的氨基酸残基相互作用。1-芳基甲基衍生物也显示出良好的抗HIV-1活性。并且2-和4-吡啶甲基衍生物的特别好。这些结果已通过Docking Studies使用“ Glide配体对接工作”程序进行了确认，
• Synthesis and evaluation of novel 3-(3,5-dimethylbenzyl)uracil analogs as potential anti-HIV-1 agents
  作者：Norikazu Sakakibara、Takayuki Hamasaki、Masanori Baba、Yosuke Demizu、Masaaki Kurihara、Kohji Irie、Masatoshi Iwai、Eriko Asada、Yoshihisa Kato、Tokumi Maruyama

  DOI：10.1016/j.bmc.2013.06.061

  日期：2013.9

  A novel series of uracil derivatives with a 3,5-dimethylbenzyl group at the N-3-position were synthesized and evaluated as non-nucleoside HIV-1 reverse transcriptase inhibitors. Some of these compounds showed good-to-moderate activity with EC50 values in the submicromolar range. Among them, compound 10c showed significant potency against HIV-1 activity with an EC50 value of 0.03 mu M and a high selectivity index of 2863. Preliminary structure-activity relationships and molecular modeling analyses were used to explore the major interactions between HIV-1 reverse transcriptase and the potent inhibitor 10c, which may serve as an important lead for further optimization. (C) 2013 Elsevier Ltd. All rights reserved.