伏康京碱 | 510-22-5

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 依波格型生物碱
• 中文名称: 伏康京碱
• 英文名称: voacangine
• 英文别名: methyl (1S,15R,17S,18S)-17-ethyl-7-methoxy-3,13-diazapentacyclo[13.3.1.02,10.04,9.013,18]nonadeca-2(10),4(9),5,7-tetraene-1-carboxylate
• CAS: 510-22-5
• 化学式: C₂₂H₂₈N₂O₃
• 分子量: 368.476
• InChiKey: MMAYTCMMKJYIAM-PHKAQXKASA-N

物化性质

• 熔点：
  223-224℃ (dec.)
• 密度：
  1.25±0.1 g/cm3 (20 ºC 760 Torr)
• 溶解度：
  DMF：16mg/mL； DMSO：16mg/mL； DMSO:PBS(pH 7.2) (1:3): 0.33 mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  54.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  伏康京碱 在 盐酸 、 potassium hydroxide 作用下， 以 乙醚 、 乙醇 为溶剂， 反应 0.08h， 生成 伊菠加因盐酸盐
  参考文献：
  名称：

  A Single Administration of the Atypical Psychedelic Ibogaine or Its Metabolite Noribogaine Induces an Antidepressant-Like Effect in Rats

  摘要：

  Anecdotal reports and open-label case studies in humans indicated that the psychedelic alkaloid ibogaine exerts profound antiaddictive effects. Ample preclinical evidence demonstrated the efficacy of ibogaine, and its main metabolite, noribogaine, in substance-use-disorder rodent models. In contrast to addiction research, depression-relevant effects of ibogaine or noribogaine in rodents have not been previously examined. We have recently reported that the acute ibogaine administration induced a long-term increase of brain-derived neurotrophic factor mRNA levels in the rat prefrontal cortex, which led us to hypothesize that ibogaine may elicit antidepressant-like effects in rats. Accordingly, we characterized behavioral effects (dose- and time-dependence) induced by the acute ibogaine and noribogaine administration in rats using the forced swim test (FST, 20 and 40 mg/kg i.p., single injection for each dose). We also examined the correlation between plasma and brain concentrations of ibogaine and noribogaine and the elicited behavioral response. We found that ibogaine and noribogaine induced a dose- and time-dependent antidepressant-like effect without significant changes of animal locomotor activity. Noribogaine's FST effect was short-lived (30 min) and correlated with high brain concentrations (estimated >8 mu M of free drug), while the ibogaine's antidepressant-like effect was significant at 3 h. At this time point, both ibogaine and noribogaine were present in rat brain at concentrations that cannot produce the same behavioral outcome on their own (ibogaine similar to 0.5 mu M, noribogaine similar to 2.5 mu M). Our data suggests a polypharmacological mechanism underpinning the antidepressant-like effects of ibogaine and noribogaine.

  DOI：

  10.1021/acschemneuro.0c00152
• 作为产物：
  描述：

  stemmadenine acetate 在 还原型辅酶II(NADPH)四钠盐 作用下， 以 aq. buffer 为溶剂， 反应 29.0h， 生成 伏康京碱
  参考文献：
  名称：

  Biosynthesis of an Anti-Addiction Agent from the Iboga Plant

  摘要：

  (-)-伊博加碱和(-)-瓦松加宁是来自植物的精神活性物质，作为治疗阿片类药物成瘾的治疗方法显示出潜力。然而，这些化合物由难以获取的植物产生，使得这些化学品难以大规模使用。在这里，我们报告了(-)-瓦松加宁及其去酯化产物的全生物合成，后者通过加热转化为(-)-伊博加碱，从而实现这些化合物的生物催化生产。值得注意的是，(-)-伊博加碱和(-)-瓦松加宁的对映异构体与该天然产物中其他主要生物碱相反。因此，这一发现为研究对映选择性酶促形式Diels-Alder反应提供了见解。

  DOI：

  10.1021/jacs.9b05999

文献信息

• Novel Bicyclic Pyridinones
  申请人：Pettersson Martin Youngjin

  公开号：US20120252758A1

  公开（公告）日：2012-10-04

  Compounds and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula I as defined herein. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.

  所述化合物及其药用可接受的盐被披露，其中所述化合物具有如本文所定义的Formula I的结构。相应的药物组合物、治疗方法、合成方法和中间体也被披露。
• Heteroaryl-Substituted Hexahydropyrano[3,4-d][1,3]Thiazin-2-Amine Compounds
  申请人：Pfizer Inc.

  公开号：US20140228356A1

  公开（公告）日：2014-08-14

  The present invention is directed to compounds, tautomers and pharmaceutically acceptable salts of the compounds which are disclosed, wherein the compounds have the structure of Formula I, and the variables R 1 and R 2 are as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.

  本发明涉及所披露的化合物、互变异构体和该化合物的药用可接受盐，其中该化合物具有如下式的结构， 变量R1和R2如规范中所定义。还披露了相应的药用组合物、治疗方法、合成方法和中间体。
• Heterocyclic Substituted Hexahydropyrano[3,4-d][1,3]Thiazin-2-Amine Compounds
  申请人：PFIZER INC.

  公开号：US20130296308A1

  公开（公告）日：2013-11-07

  Compounds, tautomers and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula I, as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.

  揭示了化合物、互变异构体和该化合物的药学上可接受的盐，其中该化合物具有如规范中定义的Formula I的结构。还披露了相应的药物组合物、治疗方法、合成方法和中间体。
• AMINO-HETEROCYCLIC COMPOUNDS
  申请人：Claffey Michelle M.

  公开号：US20100190771A1

  公开（公告）日：2010-07-29

  The invention provides PDE9-inhibiting compounds of Formula (I), and pharmaceutically acceptable salts thereof, wherein R 1 , R 2 , R 3 , A, and n are as defined herein. Pharmaceutical compositions containing the compounds of Formula I, and uses thereof in treating neurodegenerative and cognitive disorders, such as Alzheimer's disease and schizophrenia, are also provided.

  这项发明提供了式（I）中的PDE9抑制化合物，以及其药学上可接受的盐，其中R1、R2、R3、A和n的定义如本文所述。还提供了含有式I中化合物的药物组合物，并且提供了在治疗神经退行性和认知障碍疾病，如阿尔茨海默病和精神分裂症中的用途。
• Novel Cyclopropabenzofuranyl Pyridopyrazinediones
  申请人：Pfizer Inc.

  公开号：US20160222007A1

  公开（公告）日：2016-08-04

  Compounds and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula I wherein X, R 1 , R 2a , R 2b , R 4a , R 4b , R 5a , R 5b , R 6 , R 7 , R 10 , R 11 , and y are as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.

  揭示了化合物及其在药学上可接受的盐，其中该化合物具有Formula I的结构 其中X，R 1 ，R 2a ，R 2b ，R 4a ，R 4b ，R 5a ，R 5b ，R 6 ，R 7 ，R 10 ，R 11 和y如规范中所定义。还公开了相应的药物组合物、治疗方法、合成方法和中间体。