5-{3-[2,6-Dimethyl-4-(5-trichloromethyl-1,2,4-oxadiazol-3-yl)-phenoxy]propyl}-3-methylisoxazole | 153168-16-2

• 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-trichloromethyl-1,2,4-oxadiazol-3-yl)-phenoxy]propyl}-3-methylisoxazole
• 英文别名: 3-<3,5-dimethyl-4-<<3-(3-methyl-5-isoxazolyl)propyl>oxy>phenyl>-5-(α,α,α-trichloromethyl)-1,2,4-oxadiazole；5-{3-[2,6-Dimethyl-4-(5-trichloromethyl-1,2,4-oxadiazol-3-yl)phenoxy]propyl}-3-methylisoxazole；3-[3,5-dimethyl-4-[3-(3-methyl-1,2-oxazol-5-yl)propoxy]phenyl]-5-(trichloromethyl)-1,2,4-oxadiazole
• CAS: 153168-16-2
• 化学式: C₁₈H₁₈Cl₃N₃O₃
• 分子量: 430.718
• InChiKey: YHXNWTZJAZKBCO-UHFFFAOYSA-N

物化性质

• 沸点：
  539.8±60.0 °C(Predicted)
• 密度：
  1.355±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 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：

  sodium ethanolate 、 5-{3-[2,6-Dimethyl-4-(5-trichloromethyl-1,2,4-oxadiazol-3-yl)-phenoxy]propyl}-3-methylisoxazole 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 以69%的产率得到5-{3-[2,6-Dimethyl-4-(5-ethoxy-1,2,4-oxadiazol-3-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：

  5-(3-氯丙基)-3-甲基异噁唑 在 盐酸羟胺 、 potassium carbonate 、 potassium iodide 、 三氯乙酸 作用下， 以 乙醇 为溶剂， 反应 79.0h， 生成 5-{3-[2,6-Dimethyl-4-(5-trichloromethyl-1,2,4-oxadiazol-3-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

文献信息

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

  公开号：US05349068A1

  公开（公告）日：1994-09-20

  Compounds of the formula ##STR1## wherein: R.sub.1 is alkyl, alkoxy, hydroxy, cycloalkyl, hydroxyalkyl, alkoxyalkyl or hydroxyalkoxy; Y is alkylene of 3 to 9 carbon atoms, R.sub.2 and R.sub.3 independently are hydrogen, alkyl, alkoxy, halo, trifluoromethyl and nitro; R.sub.4 is alkoxy, hydroxy, halomethyl, dihalomethyl, trihalomethyl, cycloalkyl, alkoxycarbonyl, hydroxyalkyl, alkoxyalkyl, alkanecarbonyloxyalkyl, cyano, 2,2,2-trifluoroethyl, (4-methylphenyl)sulfonyloxymethyl, N.dbd.Q or CON.dbd.Q, where N.dbd.Q is amino, alkylamino or dialkylamino; or pharmaceutically acceptable acid-addition salts thereof are useful as antiviral agents.

  化合物的公式为##STR1##其中：R.sub.1是烷基，烷氧基，羟基，环烷基，羟基烷基，烷氧基烷基或羟基烷氧基；Y是3到9个碳原子的烷基，R.sub.2和R.sub.3分别是氢，烷基，烷氧基，卤素，三氟甲基和硝基；R.sub.4是烷氧基，羟基，卤甲基，二卤甲基，三卤甲基，环烷基，烷氧羰基，羟基烷基，烷氧基烷基，烷基羧酸酯氧基烷基，氰基，2,2,2-三氟乙基，(4-甲基苯基)磺酰氧甲基，N.dbd.Q或CON.dbd.Q，其中N.dbd.Q是氨基，烷基氨基或二烷基氨基；或其药学上可接受的酸加成盐可用作抗病毒剂。
• 1,2,4-oxidiazolyl-phenoxyalkylisoxazoles and their use as antiviral
  申请人：Sanofi Winthrop, Inc.

  公开号：US05643929A1

  公开（公告）日：1997-07-01

  Compounds of the formula ##STR1## wherein: R.sub.1 is alkyl, alkoxy, hydroxy, cycloalkyl, hydroxyalkyl, alkoxyalkyl, hydroxyalkoxy, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, alkoxycarbonyl, carboxy, or cyanomethyl; Y is alkylene of 3 to 9 carbon atoms, R.sub.2 and R.sub.3 independently are hydrogen, alkyl, alkoxy, halo, cyano, trifluoromethyl and nitro; R.sub.4 is alkoxy, hydroxy, halomethyl, dihalomethyl, trihalomethyl, dihaloethyl, cycloalkyl, heterocyclyl, alkoxycarbonyl, hydroxyalkyl, alkoxyalkyl, alkanecarbonyloxyalkyl, cyano, halo, thioalkyl, alkylthioalkyl, alkylthio, thio, 2,2,2-trifluoro-ethyl, (4-methylphenyl)sulfonyloxymethyl, N=Q or CON=Q, where N=Q is amino, alkylamino or dialkylamino; R.sub.5 is hydrogen or halo or alkyl.

  化合物的公式为##STR1##其中：R.sub.1是烷基，烷氧基，羟基，环烷基，羟基烷基，烷氧基烷基，羟基烷氧基，烷基硫醚基，烷基亚磺酰基，烷基磺酰基，氨基烷基，烷基氨基烷基，二烷基氨基烷基，烷氧羰基，羧基或氰甲基；Y是3到9个碳原子的烷基，R.sub.2和R.sub.3独立地是氢，烷基，烷氧基，卤素，氰基，三氟甲基和硝基；R.sub.4是烷氧基，羟基，卤甲基，二卤甲基，三卤甲基，二卤乙基，环烷基，杂环基，烷氧羰基，羟基烷基，烷氧基烷基，烷基羧酸酯氧基烷基，氰基，卤素，硫代烷基，烷基硫代烷基，烷基硫，硫，2,2,2-三氟乙基，(4-甲基苯基)磺酰氧甲基，N=Q或CON=Q，其中N=Q是氨基，烷基氨基或二烷基氨基；R.sub.5是氢，卤素或烷基。
• 1,2,4-Oxadiazolyl-phenoxyalkylisoxazoles and their use a s antiviral agents
  申请人：STERLING WINTHROP INC.

  公开号：EP0566199A1

  公开（公告）日：1993-10-20

  Compounds of the formula wherein : R1 is alkyl, alkoxy, hydroxy, cycloalkyl, hydroxyalkyl, alkoxyalkyl or hydroxyalkoxy ; Y is alkylene of 3 to 9 carbon atoms, R2 and R3 independently are hydrogen, alkyl, alkoxy, halo, trifluoromethyl or nitro ; R4 is alkoxy, hydroxy, halomethyl, dihalomethyl, trihalomethyl, cycloalkyl, alkoxycarbonyl, hydroxyalkyl, alkoxyalkyl, alkanecarbonyloxyalkyl, cyano, 2,2,2-trifluoroethyl, (4-methylphenyl)sulfonyloxymethyl, N=Q or CON=Q, where N=Q is amino, alkylamino or dialkylamino; or pharmaceutically acceptable acid-addition salts thereof are useful as antiviral agents. Preferred compounds are those wherein Y is alkylene of 3 to 5 carbon atoms and especially when R2 and R3 are in the 2- and 6- positions of the phenyl ring.

  式中的化合物 其中： R1 是烷基、烷氧基、羟基、环烷基、羟基烷基、烷氧基烷基或羟基烷氧基； Y 是 3 至 9 个碳原子的亚烷基、 R2 和 R3 分别是氢、烷基、烷氧基、卤代、三氟甲基或硝基； R4 是烷氧基、羟基、卤代甲基、二卤代甲基、三卤代甲基、环烷基、烷氧基羰基、羟基烷基、烷氧基烷基、烷羰氧基烷基、氰基、2,2,2-三氟乙基、（4-甲基苯基）磺酰氧基甲基、N=Q 或 CON=Q，其中 N=Q 是氨基、烷基氨基或二烷基氨基；或其药学上可接受的酸加成盐可用作抗病毒剂。 优选的化合物是其中 Y 为 3 至 5 个碳原子的亚烷基，特别是当 R2 和 R3 位于苯基环的 2- 和 6- 位时。
• 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
• US5349068A
  申请人：——

  公开号：US5349068A

  公开（公告）日：1994-09-20