noribogaine hydrochloride | 110514-35-7

• 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
• 英文名称: noribogaine hydrochloride
• 英文别名: Noribogainehydrochloride；(1R,15R,17S,18S)-17-ethyl-3,13-diazapentacyclo[13.3.1.02,10.04,9.013,18]nonadeca-2(10),4(9),5,7-tetraen-7-ol;hydrochloride
• CAS: 110514-35-7
• 化学式: C₁₉H₂₄N₂O*ClH
• 分子量: 332.873
• InChiKey: BFLJLOKFWZLUTR-IMLBMZRZSA-N

物化性质

• 熔点：
  >173°C (dec.)
• 溶解度：
  DMSO（轻微）、甲醇（轻微、加热、超声处理）

计算性质

• 辛醇/水分配系数(LogP)：
  4.06
• 重原子数：
  23
• 可旋转键数：
  1
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  39.3
• 氢给体数：
  3
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  noribogaine hydrochloride 在 咪唑 、 sodium hexamethyldisilazane 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 为溶剂， 反应 20.58h， 生成
  参考文献：
  名称：

  Compositions comprising noribogaine and an excipient to facilitate transport across the blood brain barrier

  摘要：

  这项发明通常涉及包含诺利波甲碱和辅助剂以促进穿越血脑屏障的组合物。

  公开号：

  US08637648B1
• 作为产物：
  描述：

  伏康京碱 在 盐酸 、 碘 、 氢化铝 、 potassium hydroxide 作用下， 以 乙醚 、 乙醇 、 乙腈 为溶剂， 反应 3.08h， 生成 noribogaine hydrochloride
  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

文献信息

• N-substituted noribogaine prodrugs
  申请人：Mash Deborah C.

  公开号：US08741891B1

  公开（公告）日：2014-06-03

  This invention relates generally to prodrugs of noribogaine. This invention also relates to pharmaceutical compositions comprising the prodrugs of noribogaine as well as method of treating pain, addiction and/or stress using such compounds and/or pharmaceutical compositions.

  这项发明通常涉及诺利波甲醇的前药。该发明还涉及包含诺利波甲醇前药的药物组合物，以及使用这些化合物和/或药物组合物治疗疼痛、成瘾和/或压力的方法。
• Structurally modified ibogaine analogs exhibit differing affinities for NMDA receptors
  作者：Richard T. Layer、Phil Skolnick、Craig M. Bertha、Upul K. Bandarage、Martin E. Kuehne、Piotr Popik

  DOI：10.1016/0014-2999(96)00304-4

  日期：1996.8

  d]cyclohepten-5,10- imine ([3H]MK-801) binding to NMDA receptors were examined. This series of analogs included the putative ibogaine metabolite O-desmethylibogaine, its metabolism resistant analog O-t-butyl-O-desmethylibogaine, the iboga alkaloids (+/-)-ibogamine, (+/-)-coronaridine, tabernanthine, harmaline, and the indolotropanes endo-3-(1-methylindol-2-yl)-8-methyl-8-azabicyclo[3.2.1]loctane (RS 075194-190)

  基于临床前的发现和人类的轶事证据，已证明这种精神活性的吲哚生物碱伊博加因具有抗成瘾性。先前的研究表明，NMDA受体的阻滞至少可以介导伊博加因的某些假定的抗成瘾作用。一系列ibogaine类似物抑制（+）-[3-3H] 5-甲基-10,11-二氢-5H-二苯并-[a，d]环庚-5,10-亚胺（[3H] MK -801）检查与NMDA受体的结合。该系列类似物包括推定的伊博加因代谢产物O-去甲基伊博加因，其抗代谢的类似物Ot-丁基-O-去甲基伊博加因，伊博加生物碱（+/-）-伊巴胺，（+/-）-可乐萘啶，Tabernanthine，harmaline和Indolotropanes endo-3-（1-methylindol-2-yl）-8-methyl-8-azabicyclo [3.2.1] loctane（RS 075194-190），exo-3-（1-甲基吲哚-2-基）-8-甲基-8-氮杂双环[3
• NORIBOGAINE SALT ANSOLVATES
  申请人：Gless, JR. Richard D.

  公开号：US20130072472A1

  公开（公告）日：2013-03-21

  Stable noribogaine salt ansolvates are useful for preparing pharmaceutical compositions and for alleviating nociceptive pain in a patient. Such ansolvates can be prepared by slurrying solvated forms, preferably MeOH solvated noribogaine hydrochloride in EtOH/water.

  稳定的无溶剂盐态诺比冈可用于制备药物组合物并缓解患者的疼痛。这样的无溶剂盐态可以通过在EtOH /水中搅拌溶剂化形式，最好是MeOH溶剂化的诺比冈盐酸盐制备而成。
• [EN] NORIBOGAINE COMPOSITIONS<br/>[FR] COMPOSITIONS DE NORIBOGAÏNE
  申请人：DEMERX INC

  公开号：WO2012012764A1

  公开（公告）日：2012-01-26

  Disclosed are noribogaine compositions comprising a very high level of the 2(R), 4(S), 5(S), 6(S) and 18(R) enantiomer and not more than 0.5 wt% of ibogaine relative to the total amount of noribogaine.

  公开的是含有非常高水平的2（R），4（S），5（S），6（S）和18（R）对映体的诺利波甲酸组合物，相对于诺利波甲酸的总量不超过0.5重量％的伊波甲酸。
• [EN] METHODS AND COMPOSITIONS FOR PREPARING NORIBOGAINE FROM VOACANGINE<br/>[FR] PROCÉDÉS ET COMPOSITIONS POUR PRÉPARER UNE NORIBOGAÏNE À PARTIR DE VOACANGINE
  申请人：DEMERX INC

  公开号：WO2012103028A3

  公开（公告）日：2012-12-06