1-[5-(3,5-dimethylphenoxy)pentyl]uracil | 1445849-41-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 1-[5-(3,5-dimethylphenoxy)pentyl]uracil
• 英文别名: 1-[5-(3,5-Dimethylphenoxy)pentyl]pyrimidine-2,4-dione；1-[5-(3,5-dimethylphenoxy)pentyl]pyrimidine-2,4-dione
• CAS: 1445849-41-1
• 化学式: C₁₇H₂₂N₂O₃
• 分子量: 302.373
• InChiKey: JLCMFDSKRICSHF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.41
• 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：

  1-[5-(3,5-dimethylphenoxy)pentyl]uracil 、 methyl 4-((5-bromopentyl)oxy)benzoate 在 potassium carbonate 、 sodium hydroxide 作用下， 以 N,N-二甲基甲酰胺 、 乙醇 、 水 为溶剂， 反应 73.0h， 以81%的产率得到4-[5-[3-[5-(3,5-dimethylphenoxy)pentyl]-2,6-dioxo-3,6-dihydropyrimidin-1(2H)-yl]pentyloxy] benzoic acid
  参考文献：
  名称：

  Antiviral Activity of N1,N3-Disubstituted Uracil Derivatives against SARS-CoV-2 Variants of Concern

  摘要：

  尽管 COVID-19 疫苗已被广泛使用，但为治疗感染 SARS-CoV-2 的病人而寻找有效的抗病毒药物仍然具有现实意义。基因变异导致新的变异株（VOC）不断出现。以抗体为基础的治疗效果明显下降，这引起了人们对开发针对 VOC 具有高活性谱的新型抗病毒药物的关注。我们合成了新的尿嘧啶衍生物类似物，其中尿嘧啶在 N1 和 N3 位被取代。我们在 Vero E6 细胞中研究了其对 VOC（包括目前广泛流行的 SARS-CoV-2 Omicron）的抗病毒活性。所有合成的化合物都显示出了广泛的抗病毒效果。此外，我们还发现这些化合物能抑制重组 SARS-CoV-2 RdRp 的活性。我们的研究表明，这些基于尿嘧啶的非核苷类似物将来可用于治疗感染循环 SARS-CoV-2 变体的患者。

  DOI：

  10.3390/ijms231710171
• 作为产物：
  描述：

  1-Bromo-5-(3,5-dimethylphenoxy)pentane 、 2,4-二(三甲硅氧基)嘧啶 以 neat (no solvent) 为溶剂， 反应 1.0h， 生成 1-[5-(3,5-dimethylphenoxy)pentyl]uracil
  参考文献：
  名称：

  Synthesis and anti-HCMV activity of 1-[ω-(phenoxy)alkyl]uracil derivatives and analogues thereof

  摘要：

  HCMV infection represents a life-threatening condition for immunocompromised patients and newborn infants and novel anti-HCMV agents are clearly needed. In this regard, a series of 1-[omega-(phenoxy)alkyl]uracil derivatives were synthesized and examined for antiviral properties. Compounds 17, 20, 24 and 28 were found to exhibit highly specific and promising inhibitory activity against HCMV replication in HEL cell cultures with EC50 values within 5.5-12 mu M range. Further studies should be undertaken to elucidate the mechanism of action of these compounds and the structure-activity relationship for the linker region. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.05.009

文献信息

• Synthesis and anti-HCMV activity of 1-[ω-(phenoxy)alkyl]uracil derivatives and analogues thereof
  作者：Mikhail S. Novikov、Denis A. Babkov、Maria P. Paramonova、Anastasia L. Khandazhinskaya、Alexander A. Ozerov、Alexander O. Chizhov、Graciela Andrei、Robert Snoeck、Jan Balzarini、Katherine L. Seley-Radtke

  DOI：10.1016/j.bmc.2013.05.009

  日期：2013.7

  HCMV infection represents a life-threatening condition for immunocompromised patients and newborn infants and novel anti-HCMV agents are clearly needed. In this regard, a series of 1-[omega-(phenoxy)alkyl]uracil derivatives were synthesized and examined for antiviral properties. Compounds 17, 20, 24 and 28 were found to exhibit highly specific and promising inhibitory activity against HCMV replication in HEL cell cultures with EC50 values within 5.5-12 mu M range. Further studies should be undertaken to elucidate the mechanism of action of these compounds and the structure-activity relationship for the linker region. (C) 2013 Elsevier Ltd. All rights reserved.
• Antiviral Activity of N1,N3-Disubstituted Uracil Derivatives against SARS-CoV-2 Variants of Concern
  作者：Andrei E. Siniavin、Mikhail S. Novikov、Vladimir A. Gushchin、Alexander A. Terechov、Igor A. Ivanov、Maria P. Paramonova、Elena S. Gureeva、Leonid I. Russu、Nadezhda A. Kuznetsova、Elena V. Shidlovskaya、Sergei I. Luyksaar、Daria V. Vasina、Sergei A. Zolotov、Nailya A. Zigangirova、Denis Y. Logunov、Alexander L. Gintsburg

  DOI：10.3390/ijms231710171

  日期：——

  Despite the widespread use of the COVID-19 vaccines, the search for effective antiviral drugs for the treatment of patients infected with SARS-CoV-2 is still relevant. Genetic variability leads to the continued circulation of new variants of concern (VOC). There is a significant decrease in the effectiveness of antibody-based therapy, which raises concerns about the development of new antiviral drugs with a high spectrum of activity against VOCs. We synthesized new analogs of uracil derivatives where uracil was substituted at the N1 and N3 positions. Antiviral activity was studied in Vero E6 cells against VOC, including currently widely circulating SARS-CoV-2 Omicron. All synthesized compounds of the panel showed a wide antiviral effect. In addition, we determined that these compounds inhibit the activity of recombinant SARS-CoV-2 RdRp. Our study suggests that these non-nucleoside uracil-based analogs may be of future use as a treatment for patients infected with circulating SARS-CoV-2 variants.

  尽管 COVID-19 疫苗已被广泛使用，但为治疗感染 SARS-CoV-2 的病人而寻找有效的抗病毒药物仍然具有现实意义。基因变异导致新的变异株（VOC）不断出现。以抗体为基础的治疗效果明显下降，这引起了人们对开发针对 VOC 具有高活性谱的新型抗病毒药物的关注。我们合成了新的尿嘧啶衍生物类似物，其中尿嘧啶在 N1 和 N3 位被取代。我们在 Vero E6 细胞中研究了其对 VOC（包括目前广泛流行的 SARS-CoV-2 Omicron）的抗病毒活性。所有合成的化合物都显示出了广泛的抗病毒效果。此外，我们还发现这些化合物能抑制重组 SARS-CoV-2 RdRp 的活性。我们的研究表明，这些基于尿嘧啶的非核苷类似物将来可用于治疗感染循环 SARS-CoV-2 变体的患者。