ethyl 4-(hydroxymethyl)-4-methylpiperidine-1-carboxylate | 878167-04-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: ethyl 4-(hydroxymethyl)-4-methylpiperidine-1-carboxylate
• CAS: 878167-04-5
• 化学式: C₁₀H₁₉NO₃
• 分子量: 201.266
• InChiKey: GGGBFCHFVIFNBT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 4-(hydroxymethyl)-4-methylpiperidine-1-carboxylate 在 草酰氯 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 1.75h， 生成 ethyl 4-methyl-4-[[(3S)-3-(2-oxo-3H-indol-1-yl)pyrrolidin-1-yl]methyl]piperidine-1-carboxylate
  参考文献：
  名称：

  Discovery of NovelN-Substituted Oxindoles as Selective M₁and M₄Muscarinic Acetylcholine Receptors Partial Agonists

  摘要：

  Activation of the M-1 and M-4 muscarinic acetylcholine receptors is thought to play an important role in improving the symptoms of schizophrenia. However, discovery of selective agonists for these receptors has been a challenge, considering the high sequence homology and conservation of the orthosteric acetylcholine binding site among muscarinic acetylcholine receptor subtypes. We report in this study the discovery of novel N-substituted oxindoles as potent muscarinic acetylcholine receptor partial agonists selective for M-1 and M-4 over M-2, M-3, and M-5. Among these oxindoles, compound 1 showed high selectivity for the M-1 and M-4 receptors with remarkable penetration into the central nervous system. Compound 1 reversed methamphetamine- and apomorphine-induced psychosis-like behaviors with low potency to extrapyramidical and peripheral side effects.

  DOI：

  10.1021/ml300372f
• 作为产物：
  描述：

  N-Boc-4-哌啶甲酸乙酯 在 lithium aluminium tetrahydride 、 正丁基锂 、 二异丙胺 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 为溶剂， 反应 5.5h， 生成 ethyl 4-(hydroxymethyl)-4-methylpiperidine-1-carboxylate
  参考文献：
  名称：

  Discovery of NovelN-Substituted Oxindoles as Selective M₁and M₄Muscarinic Acetylcholine Receptors Partial Agonists

  摘要：

  Activation of the M-1 and M-4 muscarinic acetylcholine receptors is thought to play an important role in improving the symptoms of schizophrenia. However, discovery of selective agonists for these receptors has been a challenge, considering the high sequence homology and conservation of the orthosteric acetylcholine binding site among muscarinic acetylcholine receptor subtypes. We report in this study the discovery of novel N-substituted oxindoles as potent muscarinic acetylcholine receptor partial agonists selective for M-1 and M-4 over M-2, M-3, and M-5. Among these oxindoles, compound 1 showed high selectivity for the M-1 and M-4 receptors with remarkable penetration into the central nervous system. Compound 1 reversed methamphetamine- and apomorphine-induced psychosis-like behaviors with low potency to extrapyramidical and peripheral side effects.

  DOI：

  10.1021/ml300372f

文献信息

• Modulators of muscarinic receptors
  申请人：Makings R. Lewis

  公开号：US20080015179A1

  公开（公告）日：2008-01-17

  The present invention relates to modulators of muscarinic receptors. The present invention also provides compositions comprising such modulators, and methods therewith for treating muscarinic receptor mediated diseases.

  本发明涉及肌胆碱受体调节剂。本发明还提供包含这种调节剂的组合物，并提供了用于治疗肌胆碱受体介导疾病的方法。
• Modulators of Muscarinic Receptors
  申请人：Makings Lewis R.

  公开号：US20090227614A1

  公开（公告）日：2009-09-10

  The present invention relates to modulators of muscarnic receptors of formula (I). The present invention also provides impositions comprising such modulators, and methods therewith for treating muscarinic receptor mediated diseases.

  本发明涉及式(I)的肌肉乙酰胆碱受体调节剂。本发明还提供包含这种调节剂的制剂，并提供用于治疗肌肉乙酰胆碱受体介导疾病的方法。
• Spiro compounds as modulators of muscarinic receptors
  申请人：Vertex Pharmaceuticals Incorporated

  公开号：US07858635B2

  公开（公告）日：2010-12-28

  The present invention relates to spiro compounds of formula XX as modulators of muscarinic receptors, wherein R1, R2, R3, Z1, Z2, L, G, n, m, t and p are defined herein. The present invention also provides compositions comprising such modulators, and methods therewith for treating muscarinic receptor mediated diseases.

  本发明涉及公式XX的螺环化合物作为肌动蛋白受体调节剂，其中R1、R2、R3、Z1、Z2、L、G、n、m、t和p的定义如下。本发明还提供包含这样的调节剂的组合物，以及使用它们治疗肌动蛋白受体介导的疾病的方法。
• Spiroindoline modulators of muscarinic receptors
  申请人：Vertex Pharmaceuticals Incorporated

  公开号：US07879834B2

  公开（公告）日：2011-02-01

  The present invention relates to spiroindoline modulators of muscarinic receptors. The present invention also provides compositions comprising such spiroindoline modulators, and methods therewith for treating muscarinic receptor mediated diseases.

  本发明涉及毒蕈碱受体的螺内酰吲哚调节剂。本发明还提供包含此类螺内酰吲哚调节剂的组合物，并提供使用该组合物治疗毒蕈碱受体介导疾病的方法。
• Dihydrospiroindene modulators of muscarinic receptors
  申请人：Vertex Pharmaceuticals Incorporated

  公开号：US07786141B2

  公开（公告）日：2010-08-31

  The present invention relates to dihydrospiroindene modulators of muscarinic receptors. The present invention also provides compositions comprising such dihydrospiroindene modulators, and methods therewith for treating muscarinic receptor mediated diseases.

  本发明涉及用于调节毒蕈碱受体的二氢螺环吲哚类物质。本发明还提供包含这种二氢螺环吲哚类物质的组合物，并利用这些组合物的方法来治疗毒蕈碱受体介导的疾病。