5-(trifluoromethyl)-3-<3,5-dimethyl-4-<<3-<3-<(methylsulfonyl)methyl>-5-isoxazolyl>propyl>oxy>phenyl>-1,2,4-oxadiazole | 162854-21-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-(trifluoromethyl)-3-<3,5-dimethyl-4-<<3-<3-<(methylsulfonyl)methyl>-5-isoxazolyl>propyl>oxy>phenyl>-1,2,4-oxadiazole
• 英文别名: 5-{3-[2,6-Dimethyl-4-(5-trifluoromethyl-1,2,4-oxadiazol-3-yl) phenoxy]-propyl}-3-(methylsulfonylmethyl)isoxazole；3-[3,5-Dimethyl-4-[3-[3-[(methylsulfonyl)methyl]-5-isoxazolyl]propoxy]phenyl]-5-(trifluoromethyl)-1,2,4-oxadiazole；3-[3,5-dimethyl-4-[3-[3-(methylsulfonylmethyl)-1,2-oxazol-5-yl]propoxy]phenyl]-5-(trifluoromethyl)-1,2,4-oxadiazole
• CAS: 162854-21-9
• 化学式: C₁₉H₂₀F₃N₃O₅S
• 分子量: 459.446
• InChiKey: LSRYQBQIUWYKNC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  117
• 氢给体数：
  0
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  5-(trifluoromethyl)-3-<3,5-dimethyl-4-<<3-<3-<(methylsulfenyl)methyl>-5-isoxazolyl>propyl>oxy>phenyl>-1,2,4-oxadiazole 在 aluminum oxide 、 Oxone 作用下， 以 氯仿 为溶剂， 以100%的产率得到5-(trifluoromethyl)-3-<3,5-dimethyl-4-<<3-<3-<(methylsulfonyl)methyl>-5-isoxazolyl>propyl>oxy>phenyl>-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

• US5464848A
  申请人：——

  公开号：US5464848A

  公开（公告）日：1995-11-07
• US5643929A
  申请人：——

  公开号：US5643929A

  公开（公告）日：1997-07-01