5-bromo-6-(3,5-dimethylbenzyl)pyrimidine-2,4(1H,3H)-dione | 1204750-11-7

• 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: 5-bromo-6-(3,5-dimethylbenzyl)pyrimidine-2,4(1H,3H)-dione
• 英文别名: 5-bromo-6-[(3,5-dimethylphenyl)methyl]-1H-pyrimidine-2,4-dione
• CAS: 1204750-11-7
• 化学式: C₁₃H₁₃BrN₂O₂
• 分子量: 309.162
• InChiKey: FUZASQLWMJHKFF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  58.2
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-bromo-6-(3,5-dimethylbenzyl)pyrimidine-2,4(1H,3H)-dione 在 1H-1,2,4-三唑 、 N,O-双三甲硅基乙酰胺 、 三乙胺 、 三氯氧磷 作用下， 以 1,4-二氧六环 、 氯仿 为溶剂， 反应 6.0h， 生成 4-amino-1-benzyloxymethyl-6-(3,5-dimethylbenzyl)-5-bromouracil
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of 1-[(2-Benzyloxyl/alkoxyl)methyl]-5-halo-6-aryluracils as Potent HIV-1 Non-nucleoside Reverse Transcriptase Inhibitors with an Improved Drug Resistance Profile

  摘要：

  Because the emergence of drug-resistant mutants has limited the efficacy of non-nucleoside reverse transcriptase inhibitors (NNRTIs), it is essential to develop new antivirals with better drug resistance and pharmacokinetic profiles. Here we designed and synthesized a series of 1-[(2-benzyloxyl/alkoxyl)methyl]-5-halo-6-aryluracils, the HEPT analogues, and evaluated their biological activity using nevirapine and 18 (TNK-651) as reference compounds. Most of these compounds, especially 6b, 7b, 9b, 11b, and 7c, exhibited highly potent anti-HIV-1 activity against both wild-type and NNRTI-resistant HIV-1 strains. Compound 7b, which had the highest selectivity index (SI = 38 215), is more potent than nevirapine and 18. These results suggest that the introduction of a halogen at the C-5 position may contribute to the effectiveness of these compounds against RTI-resistant variants. In addition, meta substituents on the C-6 aromatic moiety could significantly enhance activity against NNRTI-resistant HIV-1 strains. These compounds can be further developed as next-generation NNRTIs with an improved antiviral efficacy and drug-resistance profile.

  DOI：

  10.1021/jm201506e
• 作为产物：
  描述：

  3,5-二甲基苯基乙腈 在 溴 、 sodium 、 lead dioxide 、 溶剂黄146 、 氯乙酸 、 锌 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 41.17h， 生成 5-bromo-6-(3,5-dimethylbenzyl)pyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of 1-[(2-Benzyloxyl/alkoxyl)methyl]-5-halo-6-aryluracils as Potent HIV-1 Non-nucleoside Reverse Transcriptase Inhibitors with an Improved Drug Resistance Profile

  摘要：

  Because the emergence of drug-resistant mutants has limited the efficacy of non-nucleoside reverse transcriptase inhibitors (NNRTIs), it is essential to develop new antivirals with better drug resistance and pharmacokinetic profiles. Here we designed and synthesized a series of 1-[(2-benzyloxyl/alkoxyl)methyl]-5-halo-6-aryluracils, the HEPT analogues, and evaluated their biological activity using nevirapine and 18 (TNK-651) as reference compounds. Most of these compounds, especially 6b, 7b, 9b, 11b, and 7c, exhibited highly potent anti-HIV-1 activity against both wild-type and NNRTI-resistant HIV-1 strains. Compound 7b, which had the highest selectivity index (SI = 38 215), is more potent than nevirapine and 18. These results suggest that the introduction of a halogen at the C-5 position may contribute to the effectiveness of these compounds against RTI-resistant variants. In addition, meta substituents on the C-6 aromatic moiety could significantly enhance activity against NNRTI-resistant HIV-1 strains. These compounds can be further developed as next-generation NNRTIs with an improved antiviral efficacy and drug-resistance profile.

  DOI：

  10.1021/jm201506e

文献信息

• Novel synthetic route for 5-substituted 6-arylmethylluracils from 2,4,6-trichloropyrimidines
  作者：Yasser M. Loksha

  DOI：10.1002/jhet.239

  日期：2009.11

  synthesized by bromination of 6‐arylmethylluracils (5a, 5b, 5c, 5d) with N‐bromosuccinimide (NBS). Refluxing 2‐(2,6‐dichloro‐5‐ethylpyrimidin‐4‐yl)‐2‐(3,5‐dimethylphenyl)acetonitrile (3f) with sodium methoxide followed by oxidation afforded (3,5‐dimethylphenyl)(5‐ethyl‐2,6‐dimethoxypyrimidin‐4‐yl)methanone (7). Addition of methylmagnesium bromide to compound 7 gave the tertiary alcohol derivative 8 which

  用苄基氰化物衍生物（2a，2b）的钠盐处理2,4,6-三氯嘧啶（1a，1b），得到5-取代的4-芳基（氰基甲基）-2,6-二氯嘧啶（3a，3b，3c，3d，3e，3f）。用碘甲烷将化合物3a，3b烷基化，得到4-（1-芳基-1-氰基乙基）-2,6-二氯嘧啶（4a，4b）。化合物3a，3b，3c，3d，3e，将3f和4a，4b用浓盐酸水解，得到5-取代的6-芳基烷基尿嘧啶5a，5b，5c，5d，5e，5f，5g，5h。通过用N溴化6-芳基甲基尿嘧啶（5a，5b，5c，5d）合成了5-溴-6-芳甲基尿嘧啶（6a，6b，6c，6d）溴代琥珀酰亚胺（NBS）。用甲醇钠将2-（2,6-二氯-5-乙基嘧啶-4-基）-2-（3,5-二甲基苯基）乙腈（3f）回流，然后氧化得到（3,5-二甲基苯基）（5-乙基-2,6-二甲氧基嘧啶-4-基）甲酮（7）。在化合物7中添加甲基溴化镁后得到叔醇衍生物8，该叔醇衍生