tetrahydroharmol | 17952-75-9

• 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: tetrahydroharmol
• 英文别名: 1-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-7-ol
• CAS: 17952-75-9
• 化学式: C₁₂H₁₄N₂O
• 分子量: 202.256
• InChiKey: AZTMWIPCEFFOJD-UHFFFAOYSA-N

物化性质

• 沸点：
  430.0±40.0 °C(Predicted)
• 密度：
  1.239±0.06 g/cm3(Predicted)
• 物理描述：
  Solid
• 熔点：
  254-255°C

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

反应信息

• 作为反应物：
  描述：

  tetrahydroharmol 在 manganese(IV) oxide 、 5%-palladium/activated carbon 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 哈尔酚
  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
• 作为产物：
  描述：

  哈尔酚 在 乙醇 、 sodium 作用下， 生成 tetrahydroharmol
  参考文献：
  名称：

  Platonowa et al., Zhurnal Obshchei Khimii, 1956, vol. 26, p. 3220,3221; engl. Ausg. S. 3593, 3594

  摘要：

  DOI：

文献信息

• [EN] CARBOLINE AND BETACARBOLINE DERIVATIVES FOR USE AS HDAC ENZYME INHIBITORS<br/>[FR] DERIVES DE CARBOLINE ET DE BETACARBOLINE INHIBITEURS DE L'ENZYME HDAC
  申请人：CHROMA THERAPEUTICS LTD

  公开号：WO2004113336A1

  公开（公告）日：2004-12-29

  Compounds of formula (IA) and (IB) are inhibitors of histone deacetylase activity and useful for the treatment of, inter alia, cancers: wherein fused rings A1 and A2 are optionally substituted; linker radical R1 represents a radical of formula

  式（IA）和（IB）的化合物是组蛋白去乙酰化酶活性的抑制剂，用于治疗癌症等疾病：其中融合的环A1和A2可以选择性地被取代；连接基团R1代表一个公式的基团。
• Platonowa et al., Zhurnal Obshchei Khimii, 1956, vol. 26, p. 3220,3221; engl. Ausg. S. 3593, 3594
  作者：Platonowa 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.