8-Methoxyharman | 212332-24-6

• 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
• 英文名称: 8-Methoxyharman
• 英文别名: 8-methoxy-1-methyl-9H-β-carboline；8-Methoxy-1-methyl-9H-β-carbolin；8-methoxy-1-methyl-9H-pyrido[3,4-b]indole
• CAS: 212332-24-6
• 化学式: C₁₃H₁₂N₂O
• 分子量: 212.251
• InChiKey: OJKIFIATSFTXLQ-UHFFFAOYSA-N

物化性质

• 熔点：
  238-239 °C
• 沸点：
  421.4±40.0 °C(Predicted)
• 密度：
  1.252±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  37.9
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  8-Methoxyharman 生成 8-methoxy-1,2-dimethyl-9H-β-carbolinium; methyl sulfate
  参考文献：
  名称：

  Doig et al., Journal of the Chemical Society, 1952, p. 3912,3915

  摘要：

  DOI：
• 作为产物：
  描述：

  2-(7-甲氧基-1H-吲哚-3-基)乙基氯化铵 在 盐酸 、 manganese(IV) oxide 、 5%-palladium/activated carbon 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 8-Methoxyharman
  参考文献：
  名称：

  Structure–activity relationship study of beta-carboline derivatives as haspin kinase inhibitors

  摘要：

  Haspin is a serine/threonine kinase that phosphorylates Thr-3 of histone H3 in mitosis that has emerged as a possible cancer therapeutic target. High throughput screening of approximately 140,000 compounds identified the beta-carbolines harmine and harmol as moderately potent haspin kinase inhibitors. Based on information obtained from a structure-activity relationship study previously conducted for an acridine series of haspin inhibitors in conjunction with in silico docking using a recently disclosed crystal structure of the kinase, harmine analogs were designed that resulted in significantly increased haspin kinase inhibitory potency. The harmine derivatives also demonstrated less activity towards DYRK2 compared to the acridine series. In vitro mouse liver microsome stability and kinase profiling of a representative member of the harmine series (42, LDN-211898) are also presented. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.01.028

文献信息

• Spaeth; Lederer, Chemische Berichte, 1930, vol. 63, p. 2102,2106
  作者：Spaeth、Lederer

  DOI：——

  日期：——
• 395. The synthesis of 5- and 7-methoxytryptophan, and of some derivatives
  作者：R. H. Marchant、D. G. Harvey

  DOI：10.1039/jr9510001808

  日期：——
• An unusually simple procedure for the synthesis of canthin-alkaloid derivatives using dialkyl oxalates as new regioselective N-alkylating agents
  作者：Ilona Matus、János Fischer

  DOI：10.1016/s0040-4039(01)80824-8

  日期：——
• Doig et al., Journal of the Chemical Society, 1952, p. 3912,3915
  作者：Doig et al.

  DOI：——

  日期：——
• Structure–activity relationship study of beta-carboline derivatives as haspin kinase inhibitors
  作者：Gregory D. Cuny、Natalia P. Ulyanova、Debasis Patnaik、Ji-Feng Liu、Xiangjie Lin、Ken Auerbach、Soumya S. Ray、Jun Xian、Marcie A. Glicksman、Ross L. Stein、Jonathan M.G. Higgins

  DOI：10.1016/j.bmcl.2012.01.028

  日期：2012.3

  Haspin is a serine/threonine kinase that phosphorylates Thr-3 of histone H3 in mitosis that has emerged as a possible cancer therapeutic target. High throughput screening of approximately 140,000 compounds identified the beta-carbolines harmine and harmol as moderately potent haspin kinase inhibitors. Based on information obtained from a structure-activity relationship study previously conducted for an acridine series of haspin inhibitors in conjunction with in silico docking using a recently disclosed crystal structure of the kinase, harmine analogs were designed that resulted in significantly increased haspin kinase inhibitory potency. The harmine derivatives also demonstrated less activity towards DYRK2 compared to the acridine series. In vitro mouse liver microsome stability and kinase profiling of a representative member of the harmine series (42, LDN-211898) are also presented. (C) 2012 Elsevier Ltd. All rights reserved.