3-<3-(2,6-dimethyl-4-bromophenoxy)propyl>-3-methylisoxazole | 166100-49-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3-<3-(2,6-dimethyl-4-bromophenoxy)propyl>-3-methylisoxazole
• 英文别名: 5-[3-(4-bromo-2,6-dimethylphenoxy)propyl]-3-methylisoxazole；5-[3-(4-Bromo-2,6-dimethylphenoxy)propyl]-3-methyl-1,2-oxazole
• CAS: 166100-49-8
• 化学式: C₁₅H₁₈BrNO₂
• 分子量: 324.217
• InChiKey: KHXKNNQJMIEMQM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  35.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3,4,5-三氟苯硼酸 、 3-<3-(2,6-dimethyl-4-bromophenoxy)propyl>-3-methylisoxazole 在 四(三苯基膦)钯 碳酸氢钠 作用下， 以 异丙醇 为溶剂， 反应 1.0h， 以61%的产率得到5-[3-[2,6-Dimethyl-4-(3,4,5-trifluorophenyl)phenoxy]propyl]-3-methyl-1,2-oxazole
  参考文献：
  名称：

  Quantitative Structure−Activity Relationship Studies of [(Biphenyloxy)propyl]isoxazole Derivatives. Inhibitors of Human Rhinovirus 2 Replication

  摘要：

  The 50% cytotoxic concentration (CC50) in HeLa cells, the 50% inhibitory concentration (IC50) against human rhinovirus 2 (HRV-2), and the selectivity index (SI = CC50/IC50) of [(biphenyloxy)propyl]isoxazole derivatives were used to develop quantitative structure-activity relationships (QSAR) based on simplex representation of molecular structure. Statistic characteristics for partial least-squares models are quite satisfactory (R-2 = 0.838 - 0.918; Q(2) = 0.695 - 0.87) for prediction of CC50, IC50, and SI values and permit the virtual screening and molecular design of new compounds with strong anti-HRV-2 activity. The quality of prognosis for designed compounds was additionally estimated by analysis of domain applicability for each QSAR model. A hypothesis to the effect that terminal benzene substituents must have negative electrostatic potential and definite length (approximately 5.5-5.6 A) to possess strong antiviral activity has been suggested. The quality of developed analysis, i.e., high level of antiviral action of three new designed compounds, has been confirmed experimentally.

  DOI：

  10.1021/jm0704806
• 作为产物：
  描述：

  4-溴-2,6-二甲基苯酚 、 5-(3-bromopropyl)-3-methylisoxazole 在 N-甲基吡咯烷酮 、 potassium carbonate 、 potassium iodide 作用下， 反应 18.0h， 以69.5%的产率得到3-<3-(2,6-dimethyl-4-bromophenoxy)propyl>-3-methylisoxazole
  参考文献：
  名称：

  [(Biaryloxy)alkyl]isoxazoles: Picornavirus Inhibitors

  摘要：

  A series of biphenyl analogs, 6, of 5-[5-(2,6-dichloro-5-oxazolylphenoxy)pentyl]-3-methylisoxazole (2) have been synthesized and tested in vitro against 10 human rhinovirus serotypes in a TCID50 assay. The most potent compound in the series 6s, 3-[3-[2,6-dimethyl-4-(4-fluorophenyl)phenoxy]propyl]-3-methylisoxazole, was screened against an additional 84 serotypes. It was found to be active against 64 of the serotypes, while 87 serotypes were sensitive to 2 at <3 mu g/mL. On comparison of the active serotypes, 6s exhibited greater potency versus 2. Analogs 6a-c,s were examined for in vitro metabolic stability by monkey liver microsomal assay. These analogs exhibited a greater than 7-fold improvement (t(1/2) > 200 min) in metabolic stability compared with 2 (t(1/2) > 27 min).

  DOI：

  10.1021/jm00014a029

文献信息

• [(Biaryloxy)alkyl]isoxazoles: Picornavirus Inhibitors
  作者：Joseph W. Guiles、Guy D. Diana、Daniel C. Pevear

  DOI：10.1021/jm00014a029

  日期：1995.7

  A series of biphenyl analogs, 6, of 5-[5-(2,6-dichloro-5-oxazolylphenoxy)pentyl]-3-methylisoxazole (2) have been synthesized and tested in vitro against 10 human rhinovirus serotypes in a TCID50 assay. The most potent compound in the series 6s, 3-[3-[2,6-dimethyl-4-(4-fluorophenyl)phenoxy]propyl]-3-methylisoxazole, was screened against an additional 84 serotypes. It was found to be active against 64 of the serotypes, while 87 serotypes were sensitive to 2 at <3 mu g/mL. On comparison of the active serotypes, 6s exhibited greater potency versus 2. Analogs 6a-c,s were examined for in vitro metabolic stability by monkey liver microsomal assay. These analogs exhibited a greater than 7-fold improvement (t(1/2) > 200 min) in metabolic stability compared with 2 (t(1/2) > 27 min).
• Quantitative Structure−Activity Relationship Studies of [(Biphenyloxy)propyl]isoxazole Derivatives. Inhibitors of Human Rhinovirus 2 Replication
  作者：Victor E. Kuz'min、Anatoly G. Artemenko、Eugene N. Muratov、Ingrid L. Volineckaya、Vadim A. Makarov、Olga B. Riabova、Peter Wutzler、Michaela Schmidtke

  DOI：10.1021/jm0704806

  日期：2007.8.1

  The 50% cytotoxic concentration (CC50) in HeLa cells, the 50% inhibitory concentration (IC50) against human rhinovirus 2 (HRV-2), and the selectivity index (SI = CC50/IC50) of [(biphenyloxy)propyl]isoxazole derivatives were used to develop quantitative structure-activity relationships (QSAR) based on simplex representation of molecular structure. Statistic characteristics for partial least-squares models are quite satisfactory (R-2 = 0.838 - 0.918; Q(2) = 0.695 - 0.87) for prediction of CC50, IC50, and SI values and permit the virtual screening and molecular design of new compounds with strong anti-HRV-2 activity. The quality of prognosis for designed compounds was additionally estimated by analysis of domain applicability for each QSAR model. A hypothesis to the effect that terminal benzene substituents must have negative electrostatic potential and definite length (approximately 5.5-5.6 A) to possess strong antiviral activity has been suggested. The quality of developed analysis, i.e., high level of antiviral action of three new designed compounds, has been confirmed experimentally.