methyl 1-acetyl-3-[(Z)-(3-oxo-1-azabicyclo[2.2.2]octan-2-ylidene)methyl]indole-6-carboxylate | 1428773-92-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: methyl 1-acetyl-3-[(Z)-(3-oxo-1-azabicyclo[2.2.2]octan-2-ylidene)methyl]indole-6-carboxylate
• CAS: 1428773-92-5
• 化学式: C₂₀H₂₀N₂O₄
• 分子量: 352.39
• InChiKey: PSESRZIGNQQNBH-ZDLGFXPLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  68.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 1-acetyl-3-[(Z)-(3-oxo-1-azabicyclo[2.2.2]octan-2-ylidene)methyl]indole-6-carboxylate 在 sodium hydroxide 作用下， 以 水 为溶剂， 生成 C₁₈H₁₈N₂O₃
  参考文献：
  名称：

  Evaluation of (Z)-2-((1-benzyl-1H-indol-3-yl)methylene)-quinuclidin-3-one analogues as novel, high affinity ligands for CB1 and CB2 cannabinoid receptors

  摘要：

  A small library of N-benzyl indolequinuclidinone (IQD) analogs has been identified as a novel class of cannabinoid ligands. The affinity and selectivity of these IQDs for the two established cannabinoid receptor subtypes, CB1 and CB2, was evaluated. Compounds 8 (R = R-2 = H, R-1 = F) and 13 (R = COOCH3, R-1 = R-2 = H) exhibited high affinity for CB2 receptors with K-i values of 1.33 and 2.50 nM, respectively, and had lower affinities for the CBI receptor (K-i values of 9.23 and 85.7 nM, respectively). Compound 13 had the highest selectivity of all the compounds examined, and represents a potent cannabinoid ligand with 34-times greater selectivity for CB2R over CB1R. These findings are significant for future drug development, given recent reports demonstrating beneficial use of cannabinoid ligands in a wide variety of human disease states including drug abuse, depression, schizophrenia, inflammation, chronic pain, obesity, osteoporosis and cancer. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.02.025
• 作为产物：
  描述：

  3-甲酰吲哚-6-羧酸甲酯 在 三乙胺 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 methyl 1-acetyl-3-[(Z)-(3-oxo-1-azabicyclo[2.2.2]octan-2-ylidene)methyl]indole-6-carboxylate
  参考文献：
  名称：

  Evaluation of (Z)-2-((1-benzyl-1H-indol-3-yl)methylene)-quinuclidin-3-one analogues as novel, high affinity ligands for CB1 and CB2 cannabinoid receptors

  摘要：

  A small library of N-benzyl indolequinuclidinone (IQD) analogs has been identified as a novel class of cannabinoid ligands. The affinity and selectivity of these IQDs for the two established cannabinoid receptor subtypes, CB1 and CB2, was evaluated. Compounds 8 (R = R-2 = H, R-1 = F) and 13 (R = COOCH3, R-1 = R-2 = H) exhibited high affinity for CB2 receptors with K-i values of 1.33 and 2.50 nM, respectively, and had lower affinities for the CBI receptor (K-i values of 9.23 and 85.7 nM, respectively). Compound 13 had the highest selectivity of all the compounds examined, and represents a potent cannabinoid ligand with 34-times greater selectivity for CB2R over CB1R. These findings are significant for future drug development, given recent reports demonstrating beneficial use of cannabinoid ligands in a wide variety of human disease states including drug abuse, depression, schizophrenia, inflammation, chronic pain, obesity, osteoporosis and cancer. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.02.025