ethyl 8-(diethoxyphosphoryl)-3-(4-fluorophenyl)-5,6,7,8-tetrahydro-3H-[1,2,4]oxadiazolo[4,3-a]pyridine-3-carboxylate | 1080671-49-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: ethyl 8-(diethoxyphosphoryl)-3-(4-fluorophenyl)-5,6,7,8-tetrahydro-3H-[1,2,4]oxadiazolo[4,3-a]pyridine-3-carboxylate
• 英文别名: Ethyl 8-diethoxyphosphoryl-3-(4-fluorophenyl)-5,6,7,8-tetrahydro-[1,2,4]oxadiazolo[4,3-a]pyridine-3-carboxylate
• CAS: 1080671-49-3
• 化学式: C₁₉H₂₆FN₂O₆P
• 分子量: 428.397
• InChiKey: XPRTWFULGRNOAG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  29
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  86.7
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  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 sodium tetrahydroborate 、 potassium tert-butylate 、 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 3.5h， 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：

  N-<1-chloro-2-(diethoxyphosphoryl)ethylidene>hydroxylamine 在 potassium tert-butylate 、 三乙胺 、 sodium iodide 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 生成 ethyl 8-(diethoxyphosphoryl)-3-(4-fluorophenyl)-5,6,7,8-tetrahydro-3H-[1,2,4]oxadiazolo[4,3-a]pyridine-3-carboxylate
  参考文献：
  名称：

  WO2008/137139

  摘要：

  公开号：

文献信息

• GAMMA SECRETASE MODULATORS
  申请人：Zhu Zhaoning

  公开号：US20110257156A1

  公开（公告）日：2011-10-20

  In its many embodiments, the present invention provides novel heterocyclic compounds as modulators of gamma secretase, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the central nervous system using such compounds or pharmaceutical compositions.
• 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.
• WO2008/137139
  申请人：——

  公开号：——

  公开（公告）日：——