18-methoxycoronaridine | 308123-59-3

• 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: 18-methoxycoronaridine
• 英文别名: (+)-18-Methoxycoronaridine；methyl (1R,15S,17S,18R)-17-(2-methoxyethyl)-3,13-diazapentacyclo[13.3.1.02,10.04,9.013,18]nonadeca-2(10),4,6,8-tetraene-1-carboxylate
• CAS: 308123-59-3
• 化学式: C₂₂H₂₈N₂O₃
• 分子量: 368.476
• InChiKey: DTJQBBHYRQYDEG-RLHIPHHXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  27
• 可旋转键数：
  5
• 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

ADMET

代谢

Unii-vg463bm9rl 组件 dtjqbbhyrqydeg-rlhiphhxsa-n 已知有人类代谢物，包括甲基 17-(2-羟基乙基)-3,13-二氮杂五环[13.3.1.02,10.04,9.013,18]nonadeca-2(10),4,6,8-四烯-1-羧酸酯。

Unii-vg463bm9rl component dtjqbbhyrqydeg-rlhiphhxsa-n has known human metabolites that include Methyl 17-(2-hydroxyethyl)-3,13-diazapentacyclo[13.3.1.02,10.04,9.013,18]nonadeca-2(10),4,6,8-tetraene-1-carboxylate.

来源:NORMAN Suspect List Exchange

反应信息

• 作为反应物：
  描述：

  18-methoxycoronaridine 在 氢氧化钾 、 双(三甲基硅烷基)氨基钾 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 18-Methoxycoronaridine
  参考文献：
  名称：

  Synthesis of enantiomerically pure (+)- and (−)-18-methoxycoronaridine hydrochloride and Their preliminary assessment as anti-addictive agents

  摘要：

  Chemical resolution of racemic 18-methoxycoronaridine (18-MC) was achieved by the formation of its diastereomeric sulfonamides with either (R)-(-)- or (S)-(+)-camphorsulfonyl chloride. Preliminary assessment of (+)-, (-)-, and (+/-)-18-MC . HCl showed similar effects on morphine self-administration in a rat model. and similar affinities at the kappa opioid receptors. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00033-0
• 作为产物：
  描述：

  7-Benzyl-9-(2-[1,3]dioxolan-2-yl-4-methoxy-butyl)-5,6,7,8,9,10,11,12-octahydro-7,12-diaza-cyclonona[a]indene-11-carboxylic acid methyl ester 在 palladium on activated charcoal 盐酸 、 氢气 作用下， 以 甲醇 、 水 、 溶剂黄146 、 乙酸乙酯 、 甲苯 为溶剂， 20.0~130.0 ℃ 、101.33 kPa 条件下， 反应 21.0h， 生成 18-methoxycoronaridine
  参考文献：
  名称：

  Total syntheses of racemic albifloranine and its anti-addictive congeners, including 18-methoxycoronaridine

  摘要：

  Condensation of methyl 3-benzyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole-5-carboxylate (12) with 4-(1,3-dioxolan-2-yl)-6-benzylaxyhexanal (11a) provided the tetracyclic intermediates methyl (3aSR,4RS,11bRS)-3-benzyl-2,3,3a,4,5,7-hexahydro-4-[2-zeta-(1,3-dioxalan-2-yl)-4-benzyloxy)-1-butyl]-1H-pyrrolo[2,3-d]carbazole-6-carboxylates (14a,15a), which were further elaborated to afford racemic albifloranine (3). The first total synthesis of albifloranine was completed in 13 steps, with an overall 7% yield. Ester and ether derivatives of albifloranine were synthesized for evaluation as anti-addictive agents. Among these, 18-methoxycoronaridine (20b) stands out as a nontoxic agent that significantly reduces demand for morphine, cocaine, nicotine and alcohol in rats. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(99)00513-x

文献信息

• Synthesis and Biological Evaluation of 18-Methoxycoronaridine Congeners. Potential Antiaddiction Agents
  作者：Martin E. Kuehne、Liwen He、Patrick A. Jokiel、C. J. Pace、M. W. Fleck、I. M. Maisonneuve、Stanley D. Glick、Jean M. Bidlack

  DOI：10.1021/jm020562o

  日期：2003.6.1

  Variation of the methoxycarbonyl and C-18 substituents of the antiaddictive compound 18-methoxycoronaridine, and contraction of its isoquinuclidine ring segment, provided 15 congeners for SAR evaluation at opioid and alpha3beta4 nicotinic acetylcholine receptors. The opioid activities were relatively low, and the alpha3beta4 nicotinic acetylcholine receptor activities were found to correlate with in vivo antiaddictive activities.