4-<<3-(3-ethyl-5-isoxazolyl)propyl>oxy>-3,5-dimethylbenzonitrile | 130226-12-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 4-<<3-(3-ethyl-5-isoxazolyl)propyl>oxy>-3,5-dimethylbenzonitrile
• 英文别名: 3,5-Dimethyl-4-[3-(3-ethylisoxazol-5-yl) propyloxy]benzo-nitrile；3,5-Dimethyl-4-[3-(3-ethylisoxazol-5-yl)propyloxy]benzonitrile；5-[3-(2,6-dimethyl-4-cyanophenoxy)propyl]-3-ethylisoxazole；4-[3-(3-ethyl-1,2-oxazol-5-yl)propoxy]-3,5-dimethylbenzonitrile
• CAS: 130226-12-9
• 化学式: C₁₇H₂₀N₂O₂
• 分子量: 284.358
• InChiKey: OYUGAXUJXYSPMI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  59
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-<<3-(3-ethyl-5-isoxazolyl)propyl>oxy>-3,5-dimethylbenzonitrile 在 吡啶 、 盐酸羟胺 、 potassium carbonate 作用下， 以 乙醇 为溶剂， 反应 19.0h， 生成 1,2,4-Oxadiazole, 5-ethyl-3-[4-[3-(3-ethyl-5-isoxazolyl)propoxy]-3,5-dimethylphenyl]-
  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：

  5-氯戊炔 在 吡啶 、 N-氯代丁二酰亚胺 、 potassium carbonate 、 三乙胺 、 potassium iodide 作用下， 以 various solvent(s) 为溶剂， 反应 26.0h， 生成 4-<<3-(3-ethyl-5-isoxazolyl)propyl>oxy>-3,5-dimethylbenzonitrile
  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：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。
• 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。
• 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.
• 1,2,4-Oxadiazolyl-phenoxyalkylisoxazoles and their use as antiviral agents
  申请人：SANOFI

  公开号：EP0566199B1

  公开（公告）日：2000-03-01
• US4942241A
  申请人：——

  公开号：US4942241A

  公开（公告）日：1990-07-17