5-cyclopropyl-3-<3,5-dimethyl-4-(4-pentyn-1-yloxy)phenyl>-1,2,4-oxadiazole | 153168-55-9

• 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-cyclopropyl-3-<3,5-dimethyl-4-(4-pentyn-1-yloxy)phenyl>-1,2,4-oxadiazole
• 英文别名: 5-Cyclopropyl-3-[3,5-dimethyl-4-(3-ethinylpropoxy)phenyl]-1,2,4-oxadiazole；5-Cyclopropyl-3-(3,5-dimethyl-4-pent-4-ynoxyphenyl)-1,2,4-oxadiazole
• CAS: 153168-55-9
• 化学式: C₁₈H₂₀N₂O₂
• 分子量: 296.369
• InChiKey: FVWKKAHZQDUAGF-UHFFFAOYSA-N

物化性质

• 沸点：
  462.6±55.0 °C(predicted)
• 密度：
  1.147±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 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：

  propionaldehyde oxime 、 5-cyclopropyl-3-<3,5-dimethyl-4-(4-pentyn-1-yloxy)phenyl>-1,2,4-oxadiazole 在 吡啶 、 N-氯代丁二酰亚胺 、 TEA 作用下， 生成 5-cyclopropyl-3-<3,5-dimethyl-4-<<3-(3-ethyl-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
• 作为产物：
  描述：

  环丙基甲酰氯 、 N'-hydroxy-3,5-dimethyl-4-(pent-4-yn-1-yloxy)benzimidamide 在 吡啶 作用下， 以66.2%的产率得到5-cyclopropyl-3-<3,5-dimethyl-4-(4-pentyn-1-yloxy)phenyl>-1,2,4-oxadiazole
  参考文献：
  名称：

  1,2,4-oxadiazolyl-phenoxyalkylisoxazoles and their use as antiviral

  摘要：

  公式为##STR1##的化合物，其中：R.sub.1为烷基，烷氧基，羟基，环烷基，羟基烷基，烷氧基烷基，羟基烷氧基，烷基硫代烷基，烷基亚砜基烷基，烷基磺酰基烷基，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为碳原子数为3至9的烷基，R.sub.2和R.sub.3独立地为氢，烷基，烷氧基，卤素，氰基，三氟甲基和硝基；R.sub.4为烷氧基，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，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.dbd.Q或CON.dbd.Q，其中N.dbd.Q为氨基，烷基氨基或二烷基氨基；R.sub.5为氢或卤素或烷基。

  公开号：

  US05464848A1

文献信息

• 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
• 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