(S,E)-9-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)-benzylidene)-4-(3,4,5-trifluorophenyl)-3,4,6,7,8,9-hexahydropyrido[2,1-c][1,2,4]oxadiazine | 1352130-02-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (S,E)-9-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)-benzylidene)-4-(3,4,5-trifluorophenyl)-3,4,6,7,8,9-hexahydropyrido[2,1-c][1,2,4]oxadiazine
• 英文别名: (S,E)-9-(3-Methoxy-4-(4-methyl-1H-imidazol-1-YL)benzylidene)-4-(3,4,5-trifluorophenyl)-3,4,6,7,8,9-hexahydropyrido[2,1-C][1,2,4]oxadiazine；(4S,9E)-9-[[3-methoxy-4-(4-methylimidazol-1-yl)phenyl]methylidene]-4-(3,4,5-trifluorophenyl)-4,6,7,8-tetrahydro-3H-pyrido[2,1-c][1,2,4]oxadiazine
• CAS: 1352130-02-9
• 化学式: C₂₅H₂₃F₃N₄O₂
• 分子量: 468.478
• InChiKey: WGSSDSCDGURRHH-CRAILRFSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  34
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  51.9
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (S,E)-1-(2-(aminooxy)-1-(3,4,5-trifluorophenyl)ethyl)-3-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)piperidin-2-one 在 四磷十氧化物 作用下， 以 乙醇 为溶剂， 以84.6%的产率得到(S,E)-9-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)-benzylidene)-4-(3,4,5-trifluorophenyl)-3,4,6,7,8,9-hexahydropyrido[2,1-c][1,2,4]oxadiazine
  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

文献信息

• GAMMA SECRETASE MODULATORS
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP2365976B1

  公开（公告）日：2015-04-15
• US8673900B2
  申请人：——

  公开号：US8673900B2

  公开（公告）日：2014-03-18
• Cyclic Hydroxyamidines as Amide Isosteres: Discovery of Oxadiazolines and Oxadiazines as Potent and Highly Efficacious γ-Secretase Modulators in Vivo
  作者：Zhong-Yue Sun、Theodros Asberom、Thomas Bara、Chad Bennett、Duane Burnett、Inhou Chu、John Clader、Mary Cohen-Williams、David Cole、Michael Czarniecki、James Durkin、Gioconda Gallo、William Greenlee、Hubert Josien、Xianhai Huang、Lynn Hyde、Nicholas Jones、Irina Kazakevich、Hongmei Li、Xiaoxiang Liu、Julie Lee、Malcolm MacCoss、Mihir B. Mandal、Troy McCracken、Amin Nomeir、Robert Mazzola、Anandan Palani、Eric M. Parker、Dmitri A. Pissarnitski、Jun Qin、Lixin Song、Giuseppe Terracina、Monica Vicarel、Johannes Voigt、Ruo Xu、Lili Zhang、Qi Zhang、Zhiqiang Zhao、Xiaohong Zhu、Zhaoning Zhu

  DOI：10.1021/jm201407j

  日期：2012.1.12

  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.