3-<3,5-dimethyl-4-<<3-<3-(trifluoromethyl)-5-isoxazolyl>propyl>oxy>phenyl>-5-methyl-1,2,4-oxadiazole

• 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-<<3-<3-(trifluoromethyl)-5-isoxazolyl>propyl>oxy>phenyl>-5-methyl-1,2,4-oxadiazole
• 英文别名: 5-{3-[2,6-Dimethyl-4-(5-methyl-1,2,4-oxadiazol-3-yl)phenoxy]propyl}-3-trifluoromethylisoxazole；3-[3,5-dimethyl-4-[3-[3-(trifluoromethyl)-1,2-oxazol-5-yl]propoxy]phenyl]-5-methyl-1,2,4-oxadiazole
• 化学式: C₁₈H₁₈F₃N₃O₃
• 分子量: 381.354
• InChiKey: ZBKSFPHDEQYTBI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 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：
  9

反应信息

• 作为产物：
  描述：

  7-[2,6-Dimethyl-4-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenoxy]-1,1,1-trifluoro-hept-3-yn-2-one oxime 以 苯 为溶剂， 反应 18.0h， 生成 3-<3,5-dimethyl-4-<<3-<3-(trifluoromethyl)-5-isoxazolyl>propyl>oxy>phenyl>-5-methyl-1,2,4-oxadiazole
  参考文献：
  名称：

  Picornavirus Inhibitors: Trifluoromethyl Substitution Provides a Global Protective Effect against Hepatic Metabolism

  摘要：

  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.

  DOI：

  10.1021/jm00008a014

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.

  分子式为##STR1##的化合物，其中：Y为3到9个碳原子的烷基；R.sub.1为低烷基，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独立地为氢，低烷基，卤素，低烷氧基，硝基，三氟甲基或羟基；R.sub.4为氢或低烷基；其中，每次出现的低烷基和低烷氧基均具有1-5个碳原子；但当R.sub.1为低烷基时，至少有R.sub.2和R.sub.3中的一个为羟基；或其药学上可接受的酸加成盐可用作抗病毒剂，特别是对抗多种鼻病毒菌株的畏克病毒。
• 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。
• US5175177A
  申请人：——

  公开号：US5175177A

  公开（公告）日：1992-12-29