methyl 1-benzyl-3-[(Z)-(3-oxo-1-azabicyclo[2.2.2]octan-2-ylidene)methyl]indole-6-carboxylate | 1428773-95-8

• 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-benzyl-3-[(Z)-(3-oxo-1-azabicyclo[2.2.2]octan-2-ylidene)methyl]indole-6-carboxylate
• CAS: 1428773-95-8
• 化学式: C₂₅H₂₄N₂O₃
• 分子量: 400.477
• InChiKey: XAQSJSJAHZGBQD-UCQKPKSFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  51.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  C₁₈H₁₈N₂O₃ 、 alkaline earth salt of/the/ methylsulfuric acid 在 苄基三乙基氯化铵 、 sodium hydroxide 作用下， 以 二氯甲烷 、 水 为溶剂， 生成 methyl 1-benzyl-3-[(Z)-(3-oxo-1-azabicyclo[2.2.2]octan-2-ylidene)methyl]indole-6-carboxylate
  参考文献：
  名称：

  Characterization of the intrinsic activity for a novel class of cannabinoid receptor ligands: Indole quinuclidine analogs

  摘要：

  Our laboratory recently reported that a group of novel indole quinuclidine analogs bind with nanomolar affinity to cannabinoid type-1 and type-2 receptors. This study characterized the intrinsic activity of these compounds by determining whether they exhibit agonist, antagonist, or inverse agonist activity at cannabinoid type-1 and/or type-2 receptors. Cannabinoid receptors activate Gi/G -proteins that then proceed to inhibit activity of the downstream intracellular effector adenylyl cyclase. Therefore, intrinsic activity was quantified by measuring the ability of compounds to modulate levels of intracellular cAMP in intact cells. Concerning cannabinoid type-1 receptors endogenously expressed in Neuro2A cells, a single analog exhibited agonist activity, while eight acted as neutral antagonists and two possessed inverse agonist activity. For cannabinoid type-2 receptors stably expressed in CHO cells, all but two analogs acted as agonists; these two exceptions exhibited inverse agonist activity. Confirming specificity at cannabinoid type-1 receptors, modulation of adenylyl cyclase activity by all proposed agonists and inverse agonists was blocked by co-incubation with the neutral cannabinoid type-1 antagonist 0-2050. All proposed cannabinoid type-1 receptor antagonists attenuated aclenyly1 cyclase modulation by cannabinoid agonist CP-55,940. Specificity at cannabinoid type-2 receptors was confirmed by failure of all compounds to modulate adenylyl cyclase activity in CHO cells devoid of cannabinoid type-2 receptors. Further characterization of select analogs demonstrated concentration-dependent modulation of adenylyl cyclase activity with potencies similar to their respective affinities for cannabinoicl receptors. Therefore, indole quinuclidines are a novel structural class of compounds exhibiting high affinity and a range of intrinsic activity at cannabinoid type-1 and type-2 receptors. (C) 2014 Elsevier B.V. All rights reserved

  DOI：

  10.1016/j.ejphar.2014.05.007

文献信息

• Characterization of the intrinsic activity for a novel class of cannabinoid receptor ligands: Indole quinuclidine analogs
  作者：Lirit N. Franks、Benjamin M. Ford、Nikhil R. Madadi、Narsimha R. Penthala、Peter A. Crooks、Paul L. Prather

  DOI：10.1016/j.ejphar.2014.05.007

  日期：2014.8

  Our laboratory recently reported that a group of novel indole quinuclidine analogs bind with nanomolar affinity to cannabinoid type-1 and type-2 receptors. This study characterized the intrinsic activity of these compounds by determining whether they exhibit agonist, antagonist, or inverse agonist activity at cannabinoid type-1 and/or type-2 receptors. Cannabinoid receptors activate Gi/G -proteins that then proceed to inhibit activity of the downstream intracellular effector adenylyl cyclase. Therefore, intrinsic activity was quantified by measuring the ability of compounds to modulate levels of intracellular cAMP in intact cells. Concerning cannabinoid type-1 receptors endogenously expressed in Neuro2A cells, a single analog exhibited agonist activity, while eight acted as neutral antagonists and two possessed inverse agonist activity. For cannabinoid type-2 receptors stably expressed in CHO cells, all but two analogs acted as agonists; these two exceptions exhibited inverse agonist activity. Confirming specificity at cannabinoid type-1 receptors, modulation of adenylyl cyclase activity by all proposed agonists and inverse agonists was blocked by co-incubation with the neutral cannabinoid type-1 antagonist 0-2050. All proposed cannabinoid type-1 receptor antagonists attenuated aclenyly1 cyclase modulation by cannabinoid agonist CP-55,940. Specificity at cannabinoid type-2 receptors was confirmed by failure of all compounds to modulate adenylyl cyclase activity in CHO cells devoid of cannabinoid type-2 receptors. Further characterization of select analogs demonstrated concentration-dependent modulation of adenylyl cyclase activity with potencies similar to their respective affinities for cannabinoicl receptors. Therefore, indole quinuclidines are a novel structural class of compounds exhibiting high affinity and a range of intrinsic activity at cannabinoid type-1 and type-2 receptors. (C) 2014 Elsevier B.V. All rights reserved