(E)-1-(1-benzyl-3,6-dihydro-2H-pyridin-5-yl)-N-methoxymethanimine | 139886-42-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (E)-1-(1-benzyl-3,6-dihydro-2H-pyridin-5-yl)-N-methoxymethanimine
• CAS: 139886-42-3
• 化学式: C₁₄H₁₈N₂O
• 分子量: 230.31
• InChiKey: FGFORGFBAYWMRX-XNTDXEJSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  24.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (E)-1-(1-benzyl-3,6-dihydro-2H-pyridin-5-yl)-N-methoxymethanimine 以 甲醇 、 1,2-二氯乙烷 为溶剂， 反应 2.5h， 生成 RU 35963
  参考文献：
  名称：

  1-Alkyl-1,2,5,6-tetrahydropyridine-3-carboxaldehyde-O-alkyl-oximes: a new class of potent orally active muscarinic agonists related to arecoline

  摘要：

  On the basis of the knowledge acquired from basic studies of several known arecoline derivatives about the structural requirements for potent agonistic activity and oral efficacy, a series of 1-alkyl-1,2,5,6-tetrahydropyridine-3-carboxaldehyde-O-alkyl-oximes was synthesized and biologically evaluated in a battery of in vitro and in vivo assays. The most interesting molecules to emerge from the primary screening, 1,2,5,6-tetrahydropyridine-3-carboxaldehyde-O-methyloxime hydrochloride (11, RU 35963), 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxaldehyde-O-methyloxime hydrochloride (12, RU 35926), and 1,2,5,6-tetrahydropyridine-3-carboxaldehyde-O-propargyloxime hydrochloride (30, RU 47029) and 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxaldehyde-O-propargyloxime hydrochloride (33, RU 35986), were evaluated more extensively, and their cholinomimetic profile was compared with that of the parent molecule, arecoline. The pharmacological results after oral administration to mice and rats revealed that their efficacy is 2-3 orders of magnitude higher than that of arecoline, and, in addition, they show a longer duration of action. The 4 aldoximes showed anti-amnesic properties in many respects superior to those of arecoline. Their anti-amnesic doses were 2 orders of magnitude lower than those inducing obvious cholinergic symptoms, and 3-5 orders of magnitude lower than the lethal doses. These new compounds can be regarded as potential candidates for clinical studies in AD (Alzheimer's disease) patients.

  DOI：

  10.1016/0223-5234(91)90128-a
• 作为产物：
  描述：

  溴甲苯 、 RU 35963 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 (E)-1-(1-benzyl-3,6-dihydro-2H-pyridin-5-yl)-N-methoxymethanimine
  参考文献：
  名称：

  1-Alkyl-1,2,5,6-tetrahydropyridine-3-carboxaldehyde-O-alkyl-oximes: a new class of potent orally active muscarinic agonists related to arecoline

  摘要：

  On the basis of the knowledge acquired from basic studies of several known arecoline derivatives about the structural requirements for potent agonistic activity and oral efficacy, a series of 1-alkyl-1,2,5,6-tetrahydropyridine-3-carboxaldehyde-O-alkyl-oximes was synthesized and biologically evaluated in a battery of in vitro and in vivo assays. The most interesting molecules to emerge from the primary screening, 1,2,5,6-tetrahydropyridine-3-carboxaldehyde-O-methyloxime hydrochloride (11, RU 35963), 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxaldehyde-O-methyloxime hydrochloride (12, RU 35926), and 1,2,5,6-tetrahydropyridine-3-carboxaldehyde-O-propargyloxime hydrochloride (30, RU 47029) and 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxaldehyde-O-propargyloxime hydrochloride (33, RU 35986), were evaluated more extensively, and their cholinomimetic profile was compared with that of the parent molecule, arecoline. The pharmacological results after oral administration to mice and rats revealed that their efficacy is 2-3 orders of magnitude higher than that of arecoline, and, in addition, they show a longer duration of action. The 4 aldoximes showed anti-amnesic properties in many respects superior to those of arecoline. Their anti-amnesic doses were 2 orders of magnitude lower than those inducing obvious cholinergic symptoms, and 3-5 orders of magnitude lower than the lethal doses. These new compounds can be regarded as potential candidates for clinical studies in AD (Alzheimer's disease) patients.

  DOI：

  10.1016/0223-5234(91)90128-a

文献信息

• Dérivés de l'oxime du 1,2,5,6-tétrahydropyridin-3-carboxaldéhyde, leur procédé de préparation, leur application comme médicaments et les compositions les renfermant
  申请人：ROUSSEL-UCLAF

  公开号：EP0308283A1

  公开（公告）日：1989-03-22

  L'invention a pour objet les composés de formule (I) : dans laquelle R' représente un atome d'hydrogène, un radical alkyle linéaire, ramifié ou cyclique, saturé ou insaturé renfermant jusqu'à 8 atomes de carbone et R représente un radical alkyle linéaire, ramifié ou cyclique, saturé ou insaturé renfermant jusqu'à 18 atomes de carbone éventuellement substitué, un radical aryle renfermant jusqu'à 14 atomes de carbone éventuellement substitué, un radical aralkyle renfermant jusqu'à 18 atomes de carbone éventuellement substitué, ainsi que leurs sels d'addition avec les acides organiques ou minéraux, leur préparation, leur application comme médicaments et les compositions les renfermant.

  本发明的目的是式(I)化合物： 其中 R'代表氢原子，饱和或不饱和、直链、支链或环状烷基，最多含有 8 个碳原子，R 代表任选取代的饱和或不饱和、直链、支链或环状烷基，最多含有 18 个碳原子、含有多达 14 个碳原子的任选取代的芳基、含有多达 18 个碳原子的任选取代的芳烷基，以及它们与有机酸或矿物酸的加成盐、它们的制备、它们作为药物的用途和含有它们的组合物。
• US4921868A
  申请人：——

  公开号：US4921868A

  公开（公告）日：1990-05-01
• US5219872A
  申请人：——

  公开号：US5219872A

  公开（公告）日：1993-06-15
• US5231107A
  申请人：——

  公开号：US5231107A

  公开（公告）日：1993-07-27
• US5391754A
  申请人：——

  公开号：US5391754A

  公开（公告）日：1995-02-21