(E)-ethyl 3-(4-fluorophenyl)-8-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)-5,6,7,8-tetrahydro-3H-[1,2,4]-oxadiazolo[4,3-a]pyridine-3-carboxylate | 1080670-23-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (E)-ethyl 3-(4-fluorophenyl)-8-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)-5,6,7,8-tetrahydro-3H-[1,2,4]-oxadiazolo[4,3-a]pyridine-3-carboxylate
• 英文别名: ethyl (3S,8E)-3-(4-fluorophenyl)-8-[[3-methoxy-4-(4-methylimidazol-1-yl)phenyl]methylidene]-6,7-dihydro-5H-[1,2,4]oxadiazolo[4,3-a]pyridine-3-carboxylate
• CAS: 1080670-23-0
• 化学式: C₂₇H₂₇FN₄O₄
• 分子量: 490.534
• InChiKey: WUWGDNOJBFNWJS-LZNHGYHVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  36
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  78.2
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (E)-ethyl 3-(4-fluorophenyl)-8-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)-5,6,7,8-tetrahydro-3H-[1,2,4]-oxadiazolo[4,3-a]pyridine-3-carboxylate 在 sodium tetrahydroborate 、 sodium hydride 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 2.25h， 生成 (S,E)-3-(4-fluorophenyl)-8-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)-3-(methoxymethyl)-5,6,7,8-tetrahydro-3H-[1,2,4]oxadiazolo[4,3-a]pyridine
  参考文献：
  名称：

  Cyclic Hydroxyamidines as Amide Isosteres: Discovery of Oxadiazolines and Oxadiazines as Potent and Highly Efficacious γ-Secretase Modulators in Vivo

  摘要：

  Cyclic hydroxyamidines were designed and validated as isosteric replacements of the amide functionality. Compounds with these structural motifs were found to be metabolically stable and to possess highly desirable pharmacokinetic profiles. These designs were applied in the identification of gamma-secretase modulators leading to highly efficacious agents for reduction of central nervous system A beta(42) in various animal models.

  DOI：

  10.1021/jm201407j
• 作为产物：
  描述：

  ethyl 8-(diethoxyphosphoryl)-3-(4-fluorophenyl)-5,6,7,8-tetrahydro-3H-[1,2,4]oxadiazolo[4,3-a]pyridine-3-carboxylate 在 potassium tert-butylate 、 二乙胺 作用下， 以 四氢呋喃 、 正己烷 、 异丙醇 为溶剂， 反应 1.25h， 生成 (E)-ethyl 3-(4-fluorophenyl)-8-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)-5,6,7,8-tetrahydro-3H-[1,2,4]-oxadiazolo[4,3-a]pyridine-3-carboxylate 、 (E)-ethyl 3-(4-fluorophenyl)-8-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)-5,6,7,8-tetrahydro-3H-[1,2,4]-oxadiazolo[4,3-a]pyridine-3-carboxylate
  参考文献：
  名称：

  Cyclic Hydroxyamidines as Amide Isosteres: Discovery of Oxadiazolines and Oxadiazines as Potent and Highly Efficacious γ-Secretase Modulators in Vivo

  摘要：

  Cyclic hydroxyamidines were designed and validated as isosteric replacements of the amide functionality. Compounds with these structural motifs were found to be metabolically stable and to possess highly desirable pharmacokinetic profiles. These designs were applied in the identification of gamma-secretase modulators leading to highly efficacious agents for reduction of central nervous system A beta(42) in various animal models.

  DOI：

  10.1021/jm201407j