1-methyl-1,2,5,6-tetrahydropyridin-3-carboxamide oxime | 114878-41-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 1-methyl-1,2,5,6-tetrahydropyridin-3-carboxamide oxime
• 英文别名: N'-hydroxy-1-methyl-3,6-dihydro-2H-pyridine-5-carboximidamide
• CAS: 114878-41-0
• 化学式: C₇H₁₃N₃O
• 分子量: 155.2
• InChiKey: UFZCNNHHVRDUED-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  61.8
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  丁酸酐 、 1-methyl-1,2,5,6-tetrahydropyridin-3-carboxamide oxime 反应 24.0h， 生成 1-Methyl-5-(5-propyl-[1,2,4]oxadiazol-3-yl)-1,2,3,6-tetrahydro-pyridine
  参考文献：
  名称：

  Muscarinic cholinergic agonists and antagonists of the 3-(3-alkyl-1,2,4-oxadiazol-5-yl)-1,2,5,6-tetrahydropyridine type. Synthesis and structure-activity relationships

  摘要：

  A series of 3-(3-alkyl-1,2,4-oxadiazol-5-yl)-1,2,5,6-tetrahydro-1-methylpyridines (2a-q) were synthesized and tested for central muscarinic cholinergic receptor binding affinity by using [H-3]oxotremorine-M and [H-3]QNB as ligands and in a functional assay using guinea pig ileum. The analogues with unbranched C1-8-alkyl substituents (2a-g) were agonist, whereas the compounds with branched or cyclic substituents (2h-m) were antagonists. The alkyl ether analogues (2o-q) were also agonists but had lower receptor binding affinity than the corresponding alkyl analogues. The 3-(5-alkyl-1,2,4-oxadiazol-3-yl)-1,2,5,6-tetrahydro-1-methylpyridine analogues had only very low affinity for the central muscarinic receptors and were weak antagonists in the ileum assay. A few 3-(3-butyl-1,2,4-oxadiazol-5-yl)-1,2,5,6-tetrahydro-1-methylpyridines substituted with methyl or hydrogen in the 1-, 5-, or 6-position were synthesized and tested. N-Desmethyl analogue 7 was a potent muscarinic agonist, whereas N-desmethyl-5-methyl analogue 11 and N-methyl-6-methyl analogue 13 both were antagonists with lower muscarinic receptor affinity. The 3-(3-butyl-1,2,4-oxadiazol-5-yl)quinuclidine (17) and tropane (15) analogues were both very potent antagonists with high affinity for central muscarinic receptors. The ratio [IC50(QNB)/IC50(Oxo-M)] x 0.162 proved to be a good indicator of the efficacy of the compounds in the guinea pig ileum assay.

  DOI：

  10.1021/jm00106a033
• 作为产物：
  描述：

  3-氰基-1-甲基-1,2,5,6-四氢吡啶 在 盐酸羟胺 、 sodium 作用下， 以 甲醇 为溶剂， 反应 20.0h， 生成 1-methyl-1,2,5,6-tetrahydropyridin-3-carboxamide oxime
  参考文献：
  名称：

  Muscarinic cholinergic agonists and antagonists of the 3-(3-alkyl-1,2,4-oxadiazol-5-yl)-1,2,5,6-tetrahydropyridine type. Synthesis and structure-activity relationships

  摘要：

  A series of 3-(3-alkyl-1,2,4-oxadiazol-5-yl)-1,2,5,6-tetrahydro-1-methylpyridines (2a-q) were synthesized and tested for central muscarinic cholinergic receptor binding affinity by using [H-3]oxotremorine-M and [H-3]QNB as ligands and in a functional assay using guinea pig ileum. The analogues with unbranched C1-8-alkyl substituents (2a-g) were agonist, whereas the compounds with branched or cyclic substituents (2h-m) were antagonists. The alkyl ether analogues (2o-q) were also agonists but had lower receptor binding affinity than the corresponding alkyl analogues. The 3-(5-alkyl-1,2,4-oxadiazol-3-yl)-1,2,5,6-tetrahydro-1-methylpyridine analogues had only very low affinity for the central muscarinic receptors and were weak antagonists in the ileum assay. A few 3-(3-butyl-1,2,4-oxadiazol-5-yl)-1,2,5,6-tetrahydro-1-methylpyridines substituted with methyl or hydrogen in the 1-, 5-, or 6-position were synthesized and tested. N-Desmethyl analogue 7 was a potent muscarinic agonist, whereas N-desmethyl-5-methyl analogue 11 and N-methyl-6-methyl analogue 13 both were antagonists with lower muscarinic receptor affinity. The 3-(3-butyl-1,2,4-oxadiazol-5-yl)quinuclidine (17) and tropane (15) analogues were both very potent antagonists with high affinity for central muscarinic receptors. The ratio [IC50(QNB)/IC50(Oxo-M)] x 0.162 proved to be a good indicator of the efficacy of the compounds in the guinea pig ileum assay.

  DOI：

  10.1021/jm00106a033

文献信息

• Lipophillically-substituted piperidine oxadiazolyl compounds and their
  申请人：A/S Ferrosan

  公开号：US04837241A1

  公开（公告）日：1989-06-06

  New piperidine compounds having the formula ##STR1## wherein at least one of R.sup.3, R.sup.4, and R.sup.5 are ##STR2## and the other independently are H, C.sub.1-6 -alkyl, wherein R' is H, C.sub.1-8 -alkyl, phenyl, thienyl, cyclopropyl, or C.sub.1-3 -alkoxymethyl; and R.sup.1 and R.sup.6 independently are H or C.sub.1-6 -alkyl, and wherein ##STR3## and salts thereof with pharmaceutically-acceptable acids. The new compounds are useful in improving the cognitive functions of the forebrain and hippocampus of mammals, and are therefore useful in the treatment of Alzheimer's disease.

  新的哌啶化合物具有以下结构式：其中R.sup.3、R.sup.4和R.sup.5中至少有一个是##STR2##，另外的独立地是H、C.sub.1-6-烷基，其中R'是H、C.sub.1-8-烷基、苯基、噻吩基、环丙基或C.sub.1-3-烷氧甲基；R.sup.1和R.sup.6独立地是H或C.sub.1-6-烷基，其中##STR3##及其与药用可接受酸的盐。这些新化合物对改善哺乳动物前脑和海马的认知功能有用，因此对治疗阿尔茨海默病有用。
• HETEROARYL-SUBSTITUTED PIPERIDINES
  申请人：Heimbach Dirk

  公开号：US20090306139A1

  公开（公告）日：2009-12-10

  The invention relates to novel heteroaryl-substituted piperidines, to processes for their preparation, to their use for the treatment and/or prophylaxis of diseases and to their use for preparing medicaments for the treatment and/or prophylaxis of diseases, in particular of cardiovascular diseases and tumour diseases.

  这项发明涉及新颖的杂环取代哌啶，涉及它们的制备过程，涉及它们用于治疗和/或预防疾病以及用于制备治疗和/或预防疾病的药物，特别是心血管疾病和肿瘤疾病。
• Lipophilically-substituted piperidine oxadiazolyl compounds and their
  申请人：A/S Ferrosan

  公开号：US04933353A1

  公开（公告）日：1990-06-12

  New piperidine compounds having the formula ##STR1## wherein at least one of R.sup.3, R.sup.4, and R.sup.5 are ##STR2## and the other independently are H, C.sub.1-6 -alkyl, wherein R' is H, C.sub.1-8 -alkyl, phenyl, thienyl, cyclopropyl, or C.sub.1-3 -alkoxymethyl; and R.sup.1 and R.sup.6 independently are H or C.sub.1-6 -alkyl, and wherein ##STR3## and salts thereof with pharmaceutically-acceptable acids. The new compounds are useful in improving the cognitive functions of the forebrain and hippocampus of mammals, and are therefore useful in the treatment of Alzheimer's disease.

  新的哌啶化合物具有以下式子：##STR1## 其中R.sup.3、R.sup.4和R.sup.5中至少有一个为##STR2## 另外两个独立地为H、C.sub.1-6-烷基，其中R'为H、C.sub.1-8-烷基、苯基、噻吩基、环丙基或C.sub.1-3-烷氧甲基；而R.sup.1和R.sup.6独立地为H或C.sub.1-6-烷基，其中##STR3##，以及与药学上可接受的酸形成的盐。这些新化合物有助于改善哺乳动物的前脑和海马的认知功能，因此对于治疗阿尔茨海默病有用。
• Heteroaryl-substituted piperidines
  申请人：Bayer Pharma Aktiengesellschaft

  公开号：US08119663B2

  公开（公告）日：2012-02-21

  The invention relates to novel heteroaryl-substituted piperidines, to processes for their preparation, to their use for the treatment and/or prophylaxis of diseases and to their use for preparing medicaments for the treatment and/or prophylaxis of diseases, in particular of cardiovascular diseases and tumor diseases.

  本发明涉及新型杂环芳基取代哌啶，其制备过程，以及它们用于治疗和/或预防疾病的用途，以及用于制备治疗和/或预防疾病的药物，特别是心血管疾病和肿瘤疾病。
• Piperidine compounds and their preparation and use
  申请人：NOVO NORDISK A/S

  公开号：EP0259621A2

  公开（公告）日：1988-03-16

  New piperidine compounds having the formula wherein at least one of R³, R⁴, and R⁵ are and the other independently are H or C1-6-alkyl, wherein Rʹ is H, C1-8-alkyl, phenyl, thienyl, cyclopropyl, or C1-3-alkoxymethyl; and R¹ and R⁶ independently are H or C1-6-alkyl and a salt thereof with a pharmaceutically-acceptable acid. The new compounds are useful in improving the cognitive functions of the forebrain and hippocampus of mammals, and are useful in the treatment of Alzheimer's disease.

  具有以下式子的新哌啶化合物 式中 R³、R⁴ 和 R⁵ 中至少有一个是 和 R⁵ 中至少有一个是 H 或 C1-6-烷基、 其中 Rʹ 是 H、C1-8-烷基、苯基、噻吩基、环丙基或 C1-3- 烷氧基甲基；以及 R¹和 R⁶各自为 H 或 C1-6- 烷基 及其与药学上可接受的酸的盐。 新化合物有助于改善哺乳动物前脑和海马的认知功能，并可用于治疗阿尔茨海默氏症。