1-甲基-2,3,4,9-四氢-1H-吡啶并[3,4-b]吲哚-6-醇 | 3000-36-0

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 哈马拉生物碱
• 中文名称: 1-甲基-2,3,4,9-四氢-1H-吡啶并[3,4-b]吲哚-6-醇
• 英文名称: Shepherdine
• 英文别名: 1,2,3,4-tetrahydro-6-hydroxy-1-methyl-β-carboline；1-methyl-6-hydroxy-1,2,3,4-tetrahydro-β-carboline；6-hydroxy-1-methyl-1,2,3,4-tetrahydro-β-carboline；6-hydroxy-1-methyl-1,2,3,4-terahydro-β-carboline；1-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-6-ol；6-hydroxy-1-methyl-tetrahydro-β-carboline；6-Hydroxytetrahydroharman
• CAS: 3000-36-0
• 化学式: C₁₂H₁₄N₂O
• 分子量: 202.256
• InChiKey: GHKJDZJAHHVUTD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  48
• 氢给体数：
  3
• 氢受体数：
  2

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  1-甲基-2,3,4,9-四氢-1H-吡啶并[3,4-b]吲哚-6-醇 在 caesium carbonate 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.5h， 生成 6-(benzyloxy)-1-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole
  参考文献：
  名称：

  发现四氢ß-咔啉衍生物作为新型磷酸二酯酶4抑制剂

  摘要：

  摘要磷酸二酯酶4是负责释放促炎性介质的许多细胞中第二信使cAMP降解的主要酶。抑制这种酶可以帮助控制各种炎症，例如哮喘，慢性阻塞性肺疾病，关节炎和牛皮癣。在这项研究中，通过结合他达拉非和吡拉米司的药效学特征，设计了两个新颖的四氢-β-咔啉系列。合成了22种化合物，并评估了其对磷酸二酯酶4的抑制作用，其中四种显示出比参考化合物IBMX更高的活性。对接研究表明，所制备的化合物与关键的Gln443相互作用，并且与疏水口袋Q2具有可变的相互作用。这是四氢-β-咔啉作为抑制磷酸二酯酶4的支架的首次报道。当前，进行了取代基的进一步优化以微调疏水相互作用并增强该新型抑制剂系列的效力。 图形概要

  DOI：

  10.1007/s00044-017-2011-x
• 作为产物：
  描述：

  5-羟基色胺盐酸盐 以 水 为溶剂， 反应 12.5h， 生成 1-甲基-2,3,4,9-四氢-1H-吡啶并[3,4-b]吲哚-6-醇
  参考文献：
  名称：

  中央哺乳动物生物碱1-甲基-6-羟基-1,2,3,4-四氢-β-咔啉的氧化化学和生物化学。

  摘要：

  已在热解石墨电极（PGE）的中性水溶液中研究了哺乳动物中央生物碱1-甲基-6-羟基-1,2,3,4-四氢-β-咔啉（1）的电化学氧化。1的伏安图显示两个紧密间隔的氧化峰Ia和IIa。在电位小于峰值Ia的峰值电位（Ep）的情况下，1被氧化成自由基中间体，该中间体二聚化得到5,5'-bi（1-methyl-6-hydroxy-1,2,3， 4-四氢-β-咔啉）（5和6）。在比峰1a的电位更强的Ep上，假定的自由基中间体被进一步电氧化为以C（5）为中心的碳正离子，在离子-底物反应中与1反应生成5和6或与水反应生成最终的1-甲基1,2,3,4-四氢-β-咔啉-5,6-二酮（12）。二聚体5和6在PGE处产生两个可逆的氧化峰，第二个对应于在1伏安图中观察到的峰IIa。由于5和6是易于氧化的化合物，因此它们仅在受控电势电氧化的初始阶段被观察到1.酪氨酸酶/ O2，人铜蓝蛋白/ O2和过氧化物酶/ H2

  DOI：

  10.1021/jm00079a010

文献信息

• Synthesis and study of the influence of certain products of serotonin metabolism, β-carbolines and related compounds, on the voluntary consumption of alcohol in animals
  作者：Yu. V. Burov、V. A. Zagorevskii、V. N. Zhukov、N. N. Novikova、I. D. Silenko

  DOI：10.1007/bf00764690

  日期：1983.8

  metabolite of ethanol [4]. The incorporation of these compounds into the mechanism of formation of alcohol dependence may be determined by their ability to intervene in certain neurochemical processes [4], in particular, the serotoninergic processes. Moreover, the high affinity for the benzodiazepine receptor [5] suggests possible intervention of the compounds under consideration in the emotional processes

  表明某些天然血清素代谢物 [i] 及其环状类似物，代表 8-咔啉类化合物，可能在酒精依赖的形成和表现过程中发挥重要作用，因为它们干预调节酒精消耗量 [2, 3]，是 5-羟色胺及其代谢物与乙醛（乙醇的代谢物）发生~nu~uo 环化的产物 [4]。这些化合物与酒精依赖形成机制的结合可能取决于它们干预某些神经化学过程的能力 [4]，特别是 5-羟色胺能过程。此外，对苯二氮卓受体的高亲和力 [5] 表明考虑中的化合物可能干预与酒精吸引力相关的情绪过程。
• Formation of 3,4,5,6-Tetrahydro-7-hydroxy-6-methyl-1H-azepino[5,4,3-cd]indole in the Reaction of Serotonin with Acetaldehyde in Water in the Presence of Either L-Amino Acid, Nicotine or Fluoride
  作者：Masanori Somei、Minoru Seto

  DOI：10.3987/com-02-9686

  日期：——

  Possible formation of a new compound, 3,4,5,6-tetrahydro-7-hydroxy-6-methyl-1H-azepino[5,4,3-cd]indole (4a), in serotonergic neuron after drinking ethanol is chemically suggested by reacting serotonin with acetaldehyde in water in the presence of either L-amino acid, nicotine or fluoride.
• Influence of Glutathione on the Oxidation of 1-Methyl-6-hydroxy- 1,2,3,4-tetrahydro-β-carboline:  Chemistry of Potential Relevance to the Addictive and Neurodegenerative Consequences of Ethanol Abuse
  作者：Qing-Ping Han、Glenn Dryhurst

  DOI：10.1021/jm9504870

  日期：1996.1.1

  Recent evidence suggests that intraneuronal metabolism of ethanol by catalase/H2O2 and an ethanol-inducible form of cytochrome P450 together generate acetaldehyde and oxygen radicals including the hydroxyl radical (HO.). Within the cytoplasm of serotonergic neurons, these metabolic processes would thus provide acetaldehyde, which would react with unbound 5-hydroxytryptamine (5-HT) to give 1-methyl-6-hydroxy-1,2,3,4-tetrahydro-beta-carboline (1), known to be formed at elevated levels in the brain following ethanol drinking, and HO. necessary to oxidize this alkaloid. In this study, it is demonstrated that the HO.-mediated oxidation of 1 at physiological pH yields 1-methyl-1,2,3,4-tetrahydro-beta-carboline-5,6-dione (8) that reacts avidly with free glutathione (GSH), a significant constituent of axons and nerve terminals, to give diastereomers of 8-S-glutathionyl-1-methyl-1,2,3,4-tetrahydro-beta-carboline-5,6-dione (9A and 9B). In the presence of free GSH, ascorbic acid, other intraneuronal antioxidants/reductants, and molecular oxygen diastereomers, 9A/9B redox cycle in reactions that generate H2O2 and, via trace transition metal ion catalyzed decomposition of the latter compound, HO.. Further reactions of 9A/9B with GSH and/or HO. generate several additional glutathioxyl conjugates that also redox cycle in the presence of intraneuronal reductants and molecular oxygen forming H2O2 and HO.. Thus, intraneuronal formation of 1 and HO. as a consequence of ethanol drinking and resultant endogenous synthesis of 8, 9A, and 9B would, based on these in vitro chemical studies, be expected to generate elevated fluxes of H2O2 and HO. leading to oxidative damage to serotonergic axons and nerve terminals and the irreversible loss of GSH, both of which occur in the brain as a consequence of ethanol drinking. Furthermore, deficiencies of 5-HT and loss of certain serotonergic pathways in the brain have been linked to the preference for and addiction to ethanol.
• YAMANO, TOSHIO;MIURA, RETSU;KANASHIRO, MASARKU;UEMURA, TOMIHIKO, BIOORG. CHEM., 16,(1988) N 2, 189-205
  作者：YAMANO, TOSHIO、MIURA, RETSU、KANASHIRO, MASARKU、UEMURA, TOMIHIKO

  DOI：——

  日期：——
• VACCIN THÉRAPEUTIQUE CONTRE LE CANCER À BASE DE PROTÉINES DE STRESS RENDUES IMMUNOGÈNES
  申请人：Goldfish

  公开号：EP3057981A1

  公开（公告）日：2016-08-24