5-{3-[2,6-dimethyl-4-(5-methyl-1,2,4-oxadiazol-3-yl)phenoxy]propyl}-3-ethylisoxazole

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-{3-[2,6-dimethyl-4-(5-methyl-1,2,4-oxadiazol-3-yl)phenoxy]propyl}-3-ethylisoxazole
• 英文别名: 3-[4-[3-(3-ethyl-1,2-oxazol-5-yl)propoxy]-3,5-dimethylphenyl]-5-methyl-1,2,4-oxadiazole
• 化学式: C₁₉H₂₃N₃O₃
• 分子量: 341.41
• InChiKey: RPKUHTLCBUAJKP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  74.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  丁醛肟 、 propionaldehyde oxime 、 N-氯代丁二酰亚胺 、 1,2,4-恶二唑 、 5-{3-[2,6-dimethyl-4-(5-methyl-1,2,4-oxadiazol-3-yl)phenoxy]propyl}-3-ethylisoxazole 在 吡啶 silica gel 作用下， 以 ethyl acetate n-hexane 、 三乙胺 、 N-甲基吡咯烷酮 为溶剂， 生成 3-{3,5-Dimethyl-4-[3-(3-propyl-isoxazol-5-yl)-propoxy]-phenyl}-5-methyl-[1,2,4]oxadiazole
  参考文献：
  名称：

  1,2,4-oxadiazolyl-phenoxyalkylisoxazoles and their use as antiviral

  摘要：

  化学式为##STR1##的化合物，其中：Y是3-9个碳原子的烷基桥；R'是1-5个碳原子的低烷基或羟基低烷基；R.sub.1和R.sub.2是氢、卤素、低烷基、低烷氧基、硝基、低烷氧羰基或三氟甲基；R.sub.8是氢或1-5个碳原子的低烷基，但当R.sub.8为氢时，R'为羟基低烷基。这些化合物可用作抗病毒剂，特别是对抗多种鼻病毒菌株的小核糖病毒。

  公开号：

  US05175178A1
• 作为产物：
  描述：

  N'-hydroxy-3,5-dimethyl-4-(pent-4-yn-1-yloxy)benzimidamide 在 吡啶 、 N-氯代丁二酰亚胺 、 三乙胺 作用下， 反应 3.0h， 生成 5-{3-[2,6-dimethyl-4-(5-methyl-1,2,4-oxadiazol-3-yl)phenoxy]propyl}-3-ethylisoxazole
  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。
• US5175178A
  申请人：——

  公开号：US5175178A

  公开（公告）日：1992-12-29
• 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.
• 1,2,4-oxadiazolyl-phenoxyalkylisoxazoles and their use as antiviral
  申请人：Sterling Drug Inc.

  公开号：US05175178A1

  公开（公告）日：1992-12-29

  Compounds of the formulas ##STR1## wherein: Y is an alkylene bridge of 3-9 carbon atoms; R' is lower-alkyl or hydroxy-lower-alkyl of 1-5 carbon atoms; R.sub.1 and R.sub.2 are hydrogen, halogen, lower-alkyl, lower-alkoxy, nitro, lower-alkoxycarbonyl or trifluoromethyl; and R.sub.8 is hydrogen or lower-alkyl of 1-5 carbon atoms, with the proviso that when R.sub.8 is hydrogen R' is hydroxy-lower-alkyl, are useful as antiviral agents, particularly against picornaviruses, including numerous strains of rhinovirus.

  化学式为##STR1##的化合物，其中：Y是3-9个碳原子的烷基桥；R'为1-5个碳原子的低碳基或羟基低碳基；R.sub.1和R.sub.2为氢、卤素、低碳基、低碳氧基、硝基、低碳氧羰基或三氟甲基；R.sub.8为氢或1-5个碳原子的低碳基，但当R.sub.8为氢时，R'为羟基低碳基。这些化合物可用作抗病毒剂，特别是对抗多种鼻病毒菌株，包括脊髓灰质炎病毒。