3,5-dimethyl-4-<<3-(3-methyl-5-isoxazolyl)propyl>oxy>benzoic acid | 134472-32-5

• 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: 3,5-dimethyl-4-<<3-(3-methyl-5-isoxazolyl)propyl>oxy>benzoic acid
• 英文别名: 3,5-Dimethyl-4-[3-(3-methylisoxazol5yl)propyloxy]benzoic acid；3,5-Dimethyl-4-[3-(3-methyl-1,2-oxazol-5-yl)propoxy]benzoic acid
• CAS: 134472-32-5
• 化学式: C₁₆H₁₉NO₄
• 分子量: 289.331
• InChiKey: RVVXFVBDPPZNTK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  72.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3,5-dimethyl-4-<<3-(3-methyl-5-isoxazolyl)propyl>oxy>benzoic acid 在 四丁基氟化铵 、 六甲基二硅氮烷 、 N,N'-羰基二咪唑 作用下， 以 氯苯 为溶剂， 反应 120.0h， 生成 5-{3-[2,6-dimethyl-4-(5-methyl-1,3,4-oxadiazol-2-yl)phenoxy]propyl}-3-methylisoxazole
  参考文献：
  名称：

  Oxadiazoles as Ester Bioisosteric Replacements in Compounds Related to Disoxaril. Antirhinovirus Activity

  摘要：

  A series of 1,2,4-oxadiazoles has been prepared as ester bioisosteres and tested against 15 human rhinovirus serotypes, and the MIC(80), the concentration which inhibits 80% or 12 of the serotypes tested, was determined. Homologation of the alkyl group attached to the oxadiazole ring resulted in a reduction in activity with increased chain length. Introduction of hydrophilic groups in this position rendered the compounds inactive. Increasing the length of the side chain attached to the isoxazole ring resulted in an increase in activity. Replacement of the methyl with alkoxyalkyl substituents retained activity; however, introduction of a hydroxyl group on to the side chain reduced activity. Compound 8a, where both the isoxazole and oxadiazole rings were substituted with methyl groups, was one of the most active compounds in the series. A comparison was made between 8a and the two isomeric oxadiazoles 41 and 46, and an attempt was made to explain the difference in activity by examining electrostatic potential maps and by an energy profiling study. No conclusive results were obtained from these studies.

  DOI：

  10.1021/jm00041a022
• 作为产物：
  描述：

  4-羟基-3,5-二甲基苯甲酸甲酯 在 sodium hydroxide 、 水 、 potassium carbonate 、 potassium iodide 作用下， 以 乙醇 为溶剂， 反应 25.0h， 生成 3,5-dimethyl-4-<<3-(3-methyl-5-isoxazolyl)propyl>oxy>benzoic acid
  参考文献：
  名称：

  Oxadiazoles as Ester Bioisosteric Replacements in Compounds Related to Disoxaril. Antirhinovirus Activity

  摘要：

  A series of 1,2,4-oxadiazoles has been prepared as ester bioisosteres and tested against 15 human rhinovirus serotypes, and the MIC(80), the concentration which inhibits 80% or 12 of the serotypes tested, was determined. Homologation of the alkyl group attached to the oxadiazole ring resulted in a reduction in activity with increased chain length. Introduction of hydrophilic groups in this position rendered the compounds inactive. Increasing the length of the side chain attached to the isoxazole ring resulted in an increase in activity. Replacement of the methyl with alkoxyalkyl substituents retained activity; however, introduction of a hydroxyl group on to the side chain reduced activity. Compound 8a, where both the isoxazole and oxadiazole rings were substituted with methyl groups, was one of the most active compounds in the series. A comparison was made between 8a and the two isomeric oxadiazoles 41 and 46, and an attempt was made to explain the difference in activity by examining electrostatic potential maps and by an energy profiling study. No conclusive results were obtained from these studies.

  DOI：

  10.1021/jm00041a022

文献信息

• Oxadiazolyl-phenoxyalkylisoxazoles and their use as antiviral agents
  申请人：STERLING WINTHROP INC.

  公开号：EP0413289A2

  公开（公告）日：1991-02-20

  Compounds of the formulas wherein: Y is an alkylene bridge of 3-9 carbon atoms; R′ is lower-alkyl or hydroxy-lower-alkyl of 1-5 carbon atoms; R₁ and R₂ are hydrogen, halogen, lower-alkyl, lower-alkoxy, nitro, lower-alkoxycarbonyl or trifluoromethyl; and R₈ is hydrogen or lower-alkyl of 1-5 carbon atoms, with the proviso that when R₈ is hydrogen R′ is hydroxy-­lower-alkyl, are useful as antiviral agents, particularly against picornaviruses, including numerous strains of rhinovirus.

  分子式如下的化合物 其中 Y 是 3-9 个碳原子的烯桥； R′ 是 1-5 个碳原子的低级烷基或羟基低级烷基； R₁ 和 R₂ 是氢、卤素、低级烷基、低级烷氧基、硝基、低级烷氧羰基或三氟甲基；以及 R₈ 是氢或 1-5 个碳原子的低级烷基，但当 R₈ 是氢时，R′ 是羟基-低级烷基、 可用作抗病毒剂，尤其是抗皮卡病毒，包括多种鼻病毒。
• US5110821A
  申请人：——

  公开号：US5110821A

  公开（公告）日：1992-05-05
• US5464848A
  申请人：——

  公开号：US5464848A

  公开（公告）日：1995-11-07
• Oxadiazoles as Ester Bioisosteric Replacements in Compounds Related to Disoxaril. Antirhinovirus Activity
  作者：Guy D. Diana、Deborah L. Volkots、Theodore J. Nitz、Thomas R. Bailey、Melody A. Long、Niranjan Vescio、Suzanne Aldous、Daniel C. Pevear、Frank J. Dutko

  DOI：10.1021/jm00041a022

  日期：1994.7

  A series of 1,2,4-oxadiazoles has been prepared as ester bioisosteres and tested against 15 human rhinovirus serotypes, and the MIC(80), the concentration which inhibits 80% or 12 of the serotypes tested, was determined. Homologation of the alkyl group attached to the oxadiazole ring resulted in a reduction in activity with increased chain length. Introduction of hydrophilic groups in this position rendered the compounds inactive. Increasing the length of the side chain attached to the isoxazole ring resulted in an increase in activity. Replacement of the methyl with alkoxyalkyl substituents retained activity; however, introduction of a hydroxyl group on to the side chain reduced activity. Compound 8a, where both the isoxazole and oxadiazole rings were substituted with methyl groups, was one of the most active compounds in the series. A comparison was made between 8a and the two isomeric oxadiazoles 41 and 46, and an attempt was made to explain the difference in activity by examining electrostatic potential maps and by an energy profiling study. No conclusive results were obtained from these studies.