6-(3,5-dimethylbenzyl)-1-ethoxymethyl-5-iodouracil | 1353715-18-0

• 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: 6-(3,5-dimethylbenzyl)-1-ethoxymethyl-5-iodouracil
• 英文别名: 6-[(3,5-Dimethylphenyl)methyl]-1-(ethoxymethyl)-5-iodopyrimidine-2,4-dione
• CAS: 1353715-18-0
• 化学式: C₁₆H₁₉IN₂O₃
• 分子量: 414.243
• InChiKey: QULZTIRSUVIDDG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-(3,5-dimethylbenzyl)-1-ethoxymethyl-5-iodouracil 在 1H-1,2,4-三唑 、 三乙胺 、 三氯氧磷 、 ammonium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 1.5h， 以78%的产率得到4-amino-6-(3,5-dimethylbenzyl)-1-ethoxymethyl-5-iodouracil
  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 N,O-双三甲硅基乙酰胺 、 碘 、 sodium 、 lead dioxide 、 溶剂黄146 、 氯乙酸 、 锌 作用下， 以 四氢呋喃 、 乙醇 、 氯仿 、 水 为溶剂， 反应 45.67h， 生成 6-(3,5-dimethylbenzyl)-1-ethoxymethyl-5-iodouracil
  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

• 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
  作者：Xiaowei Wang、Jianfang Zhang、Yang Huang、Ruiping Wang、Liang Zhang、Kang Qiao、Li Li、Chang Liu、Yabo Ouyang、Weisi Xu、Zhili Zhang、Liangren Zhang、Yiming Shao、Shibo Jiang、Liying Ma、Junyi Liu

  DOI：10.1021/jm201506e

  日期：2012.3.8

  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.