2-(1-methyl-1,2,5,6-tetrahydropyridin-3-yl)morpholine | 944937-08-0

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: 2-(1-methyl-1,2,5,6-tetrahydropyridin-3-yl)morpholine
• 英文别名: 2-(1-methyl-3,6-dihydro-2H-pyridin-5-yl)morpholine
• CAS: 944937-08-0
• 化学式: C₁₀H₁₈N₂O
• 分子量: 182.266
• InChiKey: ASJNQTBIACKZOO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  24.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(1-methyl-1,2,5,6-tetrahydropyridin-3-yl)morpholine 、 4-氯异硫氰酸苯酯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以92%的产率得到N-(4-chlorophenyl)-2-(1-methyl-3,6-dihydro-2H-pyridin-5-yl)morpholine-4-carbothioamide
  参考文献：
  名称：

  Muscarinic receptor 1 agonist activity of novel N-arylthioureas substituted 3-morpholino arecoline derivatives in Alzheimer’s presenile dementia models

  摘要：

  As part of our continuing effort aimed at the development of selective, efficacious and centrally active M1 muscarinic agonists for the treatment of Alzheimer's presenile dementia, a series of N-arylthioureas substituted 3-morpholino arecoline derivatives 9(a -j) were synthesized by using N-benzyl amino ethanol coupling with alpha-bromo acetyl pyridine followed by reduction and cyclization to develop a new class of M1 receptor agonists. Subsequently the synthesized compounds were subjected to in vitro radioligand M1 receptor affinity studies, IP3 formation studies and also to in vivo pharmacological evaluation of memory and learning in male Wistar rats. Derivatives with chloro (9f) and methoxy (9c) groups on the para position of the benzene ring attached to the nitrogen of thiourea showed several fold high affinity for the M1 receptor (in vitro) among all the synthesized molecules 9(a -j), and also significantly elevated IP3 levels and as well elicited beneficial effects in vivo in memory and learning models in rats (rodent memory evaluation, plus and Y maze studies). (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.06.053
• 作为产物：
  描述：

  3-(2-溴乙酰基)吡啶 在 palladium on activated charcoal 盐酸 、 sodium tetrahydroborate 、 硫酸 、 ammonium formate 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 55.0h， 生成 2-(1-methyl-1,2,5,6-tetrahydropyridin-3-yl)morpholine
  参考文献：
  名称：

  有效合成的2-（1-甲基-1,2,5,6-四氢吡啶-3-基）吗啉：一种有效的M 1选择性毒蕈碱激动剂

  摘要：

  2-（1-甲基-1,2,5,6-四氢吡啶-3-基）吗啉可用于合成有效的抗菌剂，包括槟榔碱衍生物，苯二甲恶嗪和多聚吗啉，并分9步合成，总收率为36％。3-乙酰基吡啶的溴化和具有环化作用的二醇的脱水对于该策略的成功至关重要。

  DOI：

  10.1016/j.tetlet.2007.04.135

文献信息

• Muscarinic receptor 1 agonist activity of novel N-aryl carboxamide substituted 3-morpholino arecoline derivatives in Alzheimer’s presenile dementia models
  作者：Manish Malviya、Y.C. Sunil Kumar、R.B. Mythri、C. Venkateshappa、M.N. Subhash、K.S. Rangappa

  DOI：10.1016/j.bmc.2009.06.032

  日期：2009.8

  Earlier we have reported the effect of arecoline thiazolidinone and morpholino arecoline derivatives as muscarinic receptor 1 agonists in Alzheimer’s presenile dementia models. To elucidate further our Structure–Activity Relationship (SAR) studies on the chemistry and muscarinic receptor 1 binding efficacy, a series of novel carboxamide derivatives of 2-(1-methyl-1,2,5,6-tetrahydropyridin-3-yl)morpholine

  先前我们已经报道了槟榔碱噻唑烷酮和吗啉代槟榔碱衍生物作为毒蕈碱受体1激动剂在阿尔茨海默氏痴呆症模型中的作用。为了进一步阐明我们关于化学和毒蕈碱受体1结合功效的结构-活性关系（SAR）研究，一系列新的2-（1-甲基-1,2,5,6-四氢吡啶-3-基）羧酰胺衍生物吗啉分子已被设计和合成为一类具有低毒性效应的新型M1受体激动剂，可增强阿尔茨海默氏早老性痴呆动物模型的记忆功能，并通过体外激活M1受体来调节大鼠脑皮质切片的APP分泌​​。结果表明化合物9b在对位具有甲基 与吗啉代槟榔碱的羧酰胺相连的芳基的位置可能以具有抗痴呆活性的有效分子的形式出现。
• Effect of novel N-aryl sulfonamide substituted 3-morpholino arecoline derivatives as muscarinic receptor 1 agonists in Alzheimer’s dementia models
  作者：Y.C. Sunil Kumar、Manish Malviya、J.N. Narendra Sharath Chandra、C.T. Sadashiva、C.S. Ananda Kumar、S.B. Benaka Prasad、D.S. Prasanna、M.N. Subhash、K.S. Rangappa

  DOI：10.1016/j.bmc.2008.03.019

  日期：2008.5

  A series of novel, potent, and selective muscarinic receptor 1 agonists (M1 receptor agonists) that employ a key N-substituted morpholine Arecoline moiety has been synthesized as part of research effort for the therapy of Alzheimer's diseases. The ester group of arecoline (which is reported as muscarinic agonist) has been replaced by N-substituted morpholine ring. The structure activity relationship reveals that the electron donating 4-substituted sulfonyl derivatives (9a, 9b, 9c, and 9e) on the nitrogen atom of the morpholine ring increases the affinity of M1 receptor binding 50- to 80-fold greater than the corresponding arecoline. Other derivatives also showed considerable M1 receptor binding affinity. (C) 2008 Elsevier Ltd. All rights reserved.