3-<3,5-dichloro-4-(4-pentyn-1-yloxy)phenyl>-5-methyl-1,2,4-oxadiazole | 146464-51-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-<3,5-dichloro-4-(4-pentyn-1-yloxy)phenyl>-5-methyl-1,2,4-oxadiazole
• 英文别名: 3-[3,5-dichloro-4-(3-ethinylpropoxy)phenyl]-5-methyl-1,2,4-oxadiazole；3-(3,5-Dichloro-4-pent-4-ynoxyphenyl)-5-methyl-1,2,4-oxadiazole
• CAS: 146464-51-9
• 化学式: C₁₄H₁₂Cl₂N₂O₂
• 分子量: 311.167
• InChiKey: PMPGUCDGDMARMQ-UHFFFAOYSA-N

物化性质

• 沸点：
  458.5±55.0 °C(Predicted)
• 密度：
  1.307±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  48.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methoxyacetaldehyde oxime 、 3-<3,5-dichloro-4-(4-pentyn-1-yloxy)phenyl>-5-methyl-1,2,4-oxadiazole 在 吡啶 、 N-氯代丁二酰亚胺 、 三乙胺 作用下， 生成 5-{3-[2,6-Dichloro-4-(5-methyl-1,2,4-oxadiazol-3-yl)phenoxy]propyl}-3-methoxymethylisoxazole
  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：

  羟敌草腈 在 吡啶 、 盐酸羟胺 、 potassium carbonate 、 potassium iodide 作用下， 以 乙醇 为溶剂， 反应 43.0h， 生成 3-<3,5-dichloro-4-(4-pentyn-1-yloxy)phenyl>-5-methyl-1,2,4-oxadiazole
  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

• 1,2,4-oxadiazolyl-phenoxyalkylisoxazoles and their use as antiviral
  申请人：Sterling Drug Inc.

  公开号：US05175177A1

  公开（公告）日：1992-12-29

  Compounds of the formula ##STR1## wherein: Y is alkylene of 3 to 9 carbon atoms; R.sub.1 is lower-alkyl, lower-alkoxy-(C.sub.1-3 -alkyl), lower-alkoxycarbonyl, cyclopropyl or trifluoromethyl; R.sub.2 and R.sub.3 independently are hydrogen, lower-alkyl, halogen, lower-alkoxy, nitro, trifluoromethyl or hydroxy; and R.sub.4 is hydrogen or lower-alkyl; where lower-alkyl and lower-alkoxy, each occurrence, have from 1-5 carbon atoms; with the proviso that when R.sub.1 is lower-alkyl, at least one of R.sub.2 and R.sub.3 is hydroxy; or pharmaceutically acceptable acid-addition salts thereof are useful as antiviral agents, particularly against picornaviruses, including numerous strains of rhinovirus.

  化合物的式子为##STR1##其中：Y是3至9个碳原子的烷基；R.sub.1是低烷基，低烷氧基-(C.sub.1-3-烷基)，低烷氧羰基，环丙基或三氟甲基；R.sub.2和R.sub.3各自独立地是氢，低烷基，卤素，低烷氧基，硝基，三氟甲基或羟基；R.sub.4是氢或低烷基；其中每个低烷基和低烷氧基都有1-5个碳原子；但是当R.sub.1是低烷基时，R.sub.2和R.sub.3中至少有一个是羟基；或其药学上可接受的酸加合盐可用作抗病毒剂，特别是对抗许多种鼻病毒的抗病毒剂。
• 1,2,4-Oxadiazolyl-phenoxy-alkylisoxazoles and their use as antiviral agents
  申请人：STERLING WINTHROP INC.

  公开号：EP0523803A1

  公开（公告）日：1993-01-20

  Compounds of the formula wherein:    Y is alkylene of 3 to 9 carbon atoms;    R₁ is lower-alkyl, lower-alkoxy-(C₁₋₃-alkyl), lower-alkoxycarbonyl, cyclopropyl or trifluoromethyl;    R₂ and R₃ independently are hydrogen, lower-alkyl, halogen, lower-alkoxy, nitro, trifluoromethyl or hydroxy; and    R₄ is hydrogen or lower-alkyl; where lower-alkyl and lower-alkoxy, each occurrence, have from 1-5 carbon atoms;    with the proviso that when R₁ is lower-alkyl, at least one of R₂ and R₃ is hydroxy; or pharmaceutically acceptable acid-addition salts thereof, are useful as antiviral agents, particularly against picornaviruses, including numerous strains of rhinovirus.

  式中的化合物 其中 Y 是 3 至 9 个碳原子的亚烷基； R₁ 是低级烷基、低级烷氧基（C₁₋₃-烷基）、低级烷氧基羰基、环丙基或三氟甲基； R₂ 和 R₃ 独立地为氢、低级烷基、卤素、低级烷氧基、硝基、三氟甲基或羟基；以及 R₄ 是氢或低级烷基；其中低级烷基和低级烷氧基各自具有 1-5 个碳原子； 但当 R₁ 是低级烷基时，R₂ 和 R₃ 中至少有一个是羟基；或其药学上可接受的酸加成盐、 可用作抗病毒剂，尤其是抗皮卡病毒，包括多种鼻病毒株。
• US5175177A
  申请人：——

  公开号：US5175177A

  公开（公告）日：1992-12-29