3-<3,5-dimethyl-4-(4-pentyn-1-yloxy)phenyl>-5-methyl-1,2,4-oxadiazole | 134472-30-3

• 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-dimethyl-4-(4-pentyn-1-yloxy)phenyl>-5-methyl-1,2,4-oxadiazole
• 英文别名: 3-(3,5-dimethyl-4-(pent-4-yn-1-yloxy)phenyl)-5-methyl-1,2,4-oxadiazole；3-[3,5-dimethyl-4-(3-ethinylpropoxy)phenyl]-5-methyl-1,2,4-oxadiazole；3-[3,5-dimethyl-4-(3-ethynylpropoxy)phenyl]-5-methyl-1,2,4-oxadiazole；3-(3,5-dimethyl-4-pent-4-ynoxyphenyl)-5-methyl-1,2,4-oxadiazole
• CAS: 134472-30-3
• 化学式: C₁₆H₁₈N₂O₂
• 分子量: 270.331
• InChiKey: IXWXFOPNCDUDRN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 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：

  3-<3,5-dimethyl-4-(4-pentyn-1-yloxy)phenyl>-5-methyl-1,2,4-oxadiazole 在 sodium hydroxide 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 26.33h， 生成 5-(3-(2,6-dimethyl-4-(5-methyl-1,2,4-oxadiazol-3-yl)phenoxy)propyl)isoxazole-3-carboxylic acid
  参考文献：
  名称：

  WIN 61893类似物的乙酯和羧酸衍生物的多态和溶剂化物结构及其在溶液中的稳定性†

  摘要：

  3-乙基酯-（1）和3-羧酸-异恶唑（2合成了抗病毒药物类似物WIN 61893的衍生物，并通过X射线晶体学和NMR光谱进行了表征。结晶实验基于它们与溶剂分子形成分子间氢键相互作用的能力，为乙酯衍生物提供了两个多晶型结构，为羧酸衍生物提供了两个溶剂化结构。衍生物的构型在很大程度上取决于平面异恶唑和苯基-恶二唑环体系相对于彼此的取向，并且发现它们具有垂直，线性或倾斜的构型。此外，还观察到羧酸衍生物在DMSO溶液中通过脱羧反应发生异恶唑环裂解，并在几天内转化为β-酮腈开环产物。

  DOI：

  10.1039/c4ce01152j
• 作为产物：
  描述：

  3,5-dimethyl-4-(pent-4-yn-1-yloxy)benzonitrile 在 吡啶 、 盐酸羟胺 、 potassium carbonate 作用下， 以 乙醇 为溶剂， 反应 19.0h， 生成 3-<3,5-dimethyl-4-(4-pentyn-1-yloxy)phenyl>-5-methyl-1,2,4-oxadiazole
  参考文献：
  名称：

  WIN 61893类似物的乙酯和羧酸衍生物的多态和溶剂化物结构及其在溶液中的稳定性†

  摘要：

  3-乙基酯-（1）和3-羧酸-异恶唑（2合成了抗病毒药物类似物WIN 61893的衍生物，并通过X射线晶体学和NMR光谱进行了表征。结晶实验基于它们与溶剂分子形成分子间氢键相互作用的能力，为乙酯衍生物提供了两个多晶型结构，为羧酸衍生物提供了两个溶剂化结构。衍生物的构型在很大程度上取决于平面异恶唑和苯基-恶二唑环体系相对于彼此的取向，并且发现它们具有垂直，线性或倾斜的构型。此外，还观察到羧酸衍生物在DMSO溶液中通过脱羧反应发生异恶唑环裂解，并在几天内转化为β-酮腈开环产物。

  DOI：

  10.1039/c4ce01152j

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。
• 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。
• 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。
• 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.
• Picornavirus Inhibitors: Trifluoromethyl Substitution Provides a Global Protective Effect against Hepatic Metabolism
  作者：Guy D. Diana、Patrick Rudewicz、Daniel C. Pevear、Theodore J. Nitz、Suzanne C. Aldous、David J. Aldous、David T. Robinson、Tandy Draper、Frank J. Dutko、Christopher Aldi、Guy Gendron、R. Christopher Oglesby、Deborah L. Volkots、Michael Reuman、Thomas R. Bailey、Richard Czerniak、Tracey Block、Robert Roland、James Oppermann

  DOI：10.1021/jm00008a014

  日期：1995.4.1

  Several modifications of the oxazoline ring of WIN 54954, a broad spectrum antipicornavirus compound, have been prepared in order to address the acid lability and metabolic instability of this compound. We have previously shown that the oxadiazole analogue 3 displayed comparable activity against a variety of rhinoviruses and appeared to be stable to acid. A monkey liver microsomal assay was developed to examine the metabolic stability in vitro of both compounds, and it was determined that WIN 54954 displayed 18 metabolic products while 3 was converted to 8 products. Two major products of 3 were determined by LC-MS/MS to be monohydroxylated at each of the terminal methyl groups. Replacement of the methyl on the isoxazole ring with a trifluoromethyl group, while preventing hydroxylation at this position, did not reduce the sensitivity of the molecule to microsomal metabolism at other sites. However, the (trifluoromethyl)oxadiazole 9 not only prevented hydroxylation at this position but also provided protection at the isoxazole end of the molecule, resulting in only two minor products to the extent of 4%. The major product was identified as the monohydroxylated compound 23. The global metabolic protective effect of trifluoromethyl group on the oxadiazole ring was further demonstrated by examining a variety of analogues including heterocyclic replacements of the isoxazole ring. In each case, the trifluoromethyl analogue displayed a protective effect when compared to the corresponding methyl analogue.