6-甲氧基-1-甲基-2,3,4,9-四氢-1H-吡啶并[3,4-b]吲哚 | 1210-56-6

• 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: 6-甲氧基-1-甲基-2,3,4,9-四氢-1H-吡啶并[3,4-b]吲哚
• 英文名称: 6-methoxy-1-methyl-1,2,3,4-tetrahydro-β-carboline
• 英文别名: 1-Methyl-6-methoxy-1,2,3,4-tetrahydro-β-carbolin；6-Methoxytetrahydroharman；Adrenoglomerulotropin；6-methoxy-1-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole
• CAS: 1210-56-6
• 化学式: C₁₃H₁₆N₂O
• 分子量: 216.283
• InChiKey: RDUORFDQRFHYBF-UHFFFAOYSA-N

物化性质

• 熔点：
  150-151°
• 沸点：
  356.7°C (rough estimate)
• 密度：
  1.0590 (rough estimate)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  37
• 氢给体数：
  2
• 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：

  6-甲氧基-1-甲基-2,3,4,9-四氢-1H-吡啶并[3,4-b]吲哚 在 palladium on activated charcoal 异丙苯 、 氢溴酸 、 sodium hydride 、 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 1,9-dimethyl-9H-pyrido[3,4-b]indol-6-ol
  参考文献：
  名称：

  6-Hydroxy- and 6-methoxy-β-carbolines as acetyl- and butyrylcholinesterase inhibitors

  摘要：

  In the course of studies directed toward the discovery of novel acetyl- and butyrylcholinesterase (AChE and BChE) inhibitors for the treatment of Alzheimer's disease, we focused on beta-carbolines (BCs). 6-Oxygenated P-carboline and P-carbolinium derivatives based on the serotonin template were synthesized and tested in vitro for their ability to inhibit AChE and BChE, respectively. Particularly the carbolinium salts, which can be formed by intracerebral methylation out of the tertiary-BC prodrugs, show inhibitory activity levels reaching those of galantamine, physostigmine, and rivastigmine. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.08.067
• 作为产物：
  描述：

  5-甲氧基色胺盐酸盐 在 盐酸 、 甲醇 、 水 作用下， 反应 12.0h， 生成 6-甲氧基-1-甲基-2,3,4,9-四氢-1H-吡啶并[3,4-b]吲哚
  参考文献：
  名称：

  6-Hydroxy- and 6-methoxy-β-carbolines as acetyl- and butyrylcholinesterase inhibitors

  摘要：

  In the course of studies directed toward the discovery of novel acetyl- and butyrylcholinesterase (AChE and BChE) inhibitors for the treatment of Alzheimer's disease, we focused on beta-carbolines (BCs). 6-Oxygenated P-carboline and P-carbolinium derivatives based on the serotonin template were synthesized and tested in vitro for their ability to inhibit AChE and BChE, respectively. Particularly the carbolinium salts, which can be formed by intracerebral methylation out of the tertiary-BC prodrugs, show inhibitory activity levels reaching those of galantamine, physostigmine, and rivastigmine. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.08.067

文献信息

• Design, synthesis and biological evaluation of novel carboline-cinnamic acid hybrids as multifunctional agents for treatment of Alzheimer’s disease
  作者：Qinghong Liao、Qi Li、Yifan Zhao、Pan Jiang、Yuhui Yan、Haopeng Sun、Wenyuan Liu、Feng Feng、Wei Qu

  DOI：10.1016/j.bioorg.2020.103844

  日期：2020.6

  Alzheimer's disease (AD) is a complex neurodegenerative disease with multiple pathological features. Multifunctional compounds able to simultaneously interact with several pathological components have been considered as a solution to treat the complex pathologies of neurodegenerative diseases. β-carboline and cinnamic acid have been extensively studied for their widespread biological effects in treatment

  阿尔茨海默氏病（AD）是一种具有多种病理特征的复杂神经退行性疾病。能够同时与几种病理学成分相互作用的多功能化合物已被视为治疗神经退行性疾病的复杂病理学的解决方案。β-咔啉和肉桂酸在AD治疗中具有广泛的生物学作用，因此已被广泛研究，由于其不良的溶解性和高毒性，其进一步的应用受到了限制。本文设计并合成了一系列咔啉-肉桂酸杂化物，以得到毒性低，理化特性好的新型多功能分子。特别地，e3和e12表现出对Aβ聚集的显着抑制作用（25μM时的抑制率分别为65％和72％），中等的BuChE抑制作用，极好的神经保护作用和低神经毒性。此外，在AD小鼠模型中，e3和e12可以将学习和记忆功能恢复到与对照相当的水平，并且在相对较高的600 mg / kg剂量下没有表现出任何急性毒性。因此，这些新化合物可以作为AD的多功能分子进行进一步研究。
• 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。
• Prodrugs of Heteraromatic Compounds
  申请人：Alkermes Pharma Ireland Limited

  公开号：US20160009713A1

  公开（公告）日：2016-01-14

  The present invention relates to prodrugs of parent drug compounds containing heteroaromatic NH groups.

  本发明涉及含有杂芳基NH基团的母药化合物的前药。
• [EN] MULTI- API LOADING PRODRUGS<br/>[FR] PROMÉDICAMENTS CHARGÉS DE MULTIPLES PRINCIPES ACTIFS
  申请人：ALKERMES INC

  公开号：WO2012088441A1

  公开（公告）日：2012-06-28

  The present invention accomplishes this by having multiple molecules of parent drugs attached to carrier moieties and by extending the period during which the parent drug is released and absorbed after administration to the patient and providing a longer duration of action per dose than the parent drug itself. Prodrug conjugates are suitable for sustained delivery of heteroaryl, lactam- amide-, imide-, sulfonamide-, carbamate-, urea-, benzamide-, acylaniline-, cyclic amide- and tertiary amine-containing parent drugs that are substituted at the amide nitrogen or oxygen atom with labile aldehyde-linked prodrug moieties. The carrier groups of the prodrugs can be hydrophobic to reduce the polarity and solubility of the parent drug under physiological conditions.

  本发明通过将多个母药分子附着在载体基团上，并延长母药在患者服用后释放和吸收的时间，从而实现此目的，并提供每剂次比母药本身更长的作用时间。前药偶联物适用于异杂环、内酰胺、酰胺、磺酰胺、氨基甲酸酯、脲、苯甲酰胺、酰基苯胺、环状酰胺和三级胺含有母药，该母药在酰胺氮或氧原子处以不稳定的醛类前药基团取代。前药的载体基团可以是疏水性的，在生理条件下降低母药的极性和溶解度。
• Compounds useful as antiproliferative agents
  申请人：Whitby Research, Inc.

  公开号：US05314908A1

  公开（公告）日：1994-05-24

  Melatonin compounds are disclosed of the formula ##STR1## where R is hydrogen or C.sub.1 to C.sub.6 linear or branched alkylene substituted with phenyl; R.sub.1 is hydrogen, substituted benzyl, naphthylmethyl or taken together with R.sub.2 and the two carbon atoms of the five-membered hetero ring form the group ##STR2## where R.sub.1 ' is C.sub.1 to C.sub.6 linear or branched alkanoyl and R.sub.1 " is hydrogen, C.sub.1 to C.sub.6 linear or branched alkyl or phenyl optionally substituted with one or more halogen, amino, nitro, hydroxy, alkyl, alkoxy or haloalkyl; R.sub.2 is hydrogen, 1-pyrrolyl, 1-pyrrolyl substituted with one or more alkyl or alkoxy, the group --(CH.sub.2).sub.m --NHR.sub.2 '1, where m is 1 to 3 and R.sub.2 ' is phenyl sulfonyl, the phenyl group optionally substituted with alkyl, or --C(O)--R.sub.2 ", where R.sub.2 " is C.sub.1 to C.sub.6 linear or branched alkylene substituted with a substituent selected from the group consisting of hydrogen, phenyl, alkoxy, alkoxy substituted with phenyl, carboxylic acid or the alkyl esters thereof, carbamoyloxy alkyl, substituted carbamoyloxy alkyl and amino or 5-(2-alkanoyl) tetrazole; R.sub.3, R.sub.4, R.sub.5 and R.sub.6 are the same or different and are hydrogen, C.sub.1 to C.sub.6 linear or branched alkyl, C.sub.1 to C.sub.6 linear or branched alkoxy, phenoxy or phenoxy substituted with one or more C.sub.1 to C.sub.6 linear or branched alkyl. The compounds display melatonin antagonist and are antiproliferative agents.

  该文披露了化合物的褪黑激素配方，其中R为氢或被苯基取代的C1到C6直链或支链烷基；R1为氢，取代苯甲基，萘甲基或与R2和五元杂环的两个碳原子一起形成如下基团：其中R1'为C1到C6直链或支链烷酰基，R1"为氢，C1到C6直链或支链烷基或苯基，其可选择性地被一个或多个卤素，氨基，硝基，羟基，烷基，烷氧基或卤代烷基取代；R2为氢，1-吡咯基，1-吡咯基，它被一个或多个烷基或烷氧基取代，该基团-(CH2)m-NHR2'1，其中m为1到3，R2'为苯基磺酰基，苯基可选择性地被烷基取代，或-C（O）-R2"，其中R2"为C1到C6直链或支链烷基，其被从氢，苯基，烷氧基，被苯基取代的烷氧基，羧酸或其烷基酯，氨基甲酰氧基烷基，取代的氨基甲酰氧基烷基和氨基或5-（2-烷酰基）四唑的取代基中选择的一种取代；R3，R4，R5和R6相同或不同，为氢，C1到C6直链或支链烷基，C1到C6直链或支链烷氧基，苯氧基或被一个或多个C1到C6直链或支链烷基取代的苯氧基。这些化合物表现出褪黑激素拮抗剂和抗增殖剂的特性。