ethyl (3-exo)-3-{[(3S)-3-(2-oxo-2, 3-dihydro-1H-indole-1-yl)pyrrolidine-1-yl]methyl}-8-azabicyclo[3.2.1]octane-8-carboxylate | 1422035-83-3

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 托烷生物碱
• 英文名称: ethyl (3-exo)-3-{[(3S)-3-(2-oxo-2, 3-dihydro-1H-indole-1-yl)pyrrolidine-1-yl]methyl}-8-azabicyclo[3.2.1]octane-8-carboxylate
• 英文别名: danipon
• CAS: 1422035-83-3
• 化学式: C₂₃H₃₁N₃O₃
• 分子量: 397.517
• InChiKey: PNUNTGVSYVVWCT-FFGOWVMKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.05
• 重原子数：
  29.0
• 可旋转键数：
  4.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  53.09
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  ethyl (3-exo)-3-{[(3S)-3-(2-oxo-2, 3-dihydro-1H-indole-1-yl)pyrrolidine-1-yl]methyl}-8-azabicyclo[3.2.1]octane-8-carboxylate 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 以66%的产率得到ethyl (1R,3s,5S)-3-(((S)-3-(2-oxoindolin-1-yl)pyrrolidin-1-yl)methyl)-8-azabicyclo[3.2.1]octane-8-carboxylate hydrochloride
  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：

  邻溴苯乙酸 在 palladium diacetate 、 三乙酰氧基硼氢化钠 、 potassium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 三氟乙酸 、 2-二环己基磷-2,4,6-三异丙基联苯 、 苯硼酸 作用下， 以 二氯甲烷 、 叔丁醇 为溶剂， 反应 32.0h， 生成 ethyl (3-exo)-3-{[(3S)-3-(2-oxo-2, 3-dihydro-1H-indole-1-yl)pyrrolidine-1-yl]methyl}-8-azabicyclo[3.2.1]octane-8-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

• Discovery of Novel<i>N</i>-Substituted Oxindoles as Selective M₁and M₄Muscarinic Acetylcholine Receptors Partial Agonists
  作者：Takaaki Sumiyoshi、Takeshi Enomoto、Kentaro Takai、Yoko Takahashi、Yasuko Konishi、Yoshiharu Uruno、Kengo Tojo、Atsushi Suwa、Harumi Matsuda、Tomokazu Nakako、Mutsuko Sakai、Atsushi Kitamura、Yasuaki Uematsu、Akihiko Kiyoshi

  DOI：10.1021/ml300372f

  日期：2013.2.14

  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.