8-氯-7-甲氧基-1-甲基-9h-吡啶并[3,4-b]吲哚 | 606928-39-6

• 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: 8-氯-7-甲氧基-1-甲基-9h-吡啶并[3,4-b]吲哚
• 英文名称: 8-chloro-harmine
• 英文别名: 8-chloroharmine；8-Chloro-7-methoxy-1-methyl-9H-beta-carboline；8-chloro-7-methoxy-1-methyl-9H-pyrido[3,4-b]indole
• CAS: 606928-39-6
• 化学式: C₁₃H₁₁ClN₂O
• 分子量: 246.696
• InChiKey: WJJJTGYCCILDEL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  17
• 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-氯-7-甲氧基-1-甲基-9h-吡啶并[3,4-b]吲哚 在 sodium hydride 、 一水合肼 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-(8-chloro-7-methoxy-1-methyl-9H-pyrido[3,4-b]indol-9-yl)butan-1-amine
  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：

  3-(2-Aminoethyl)-7-chlor-6-methoxy-indol 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-氯-7-甲氧基-1-甲基-9h-吡啶并[3,4-b]吲哚
  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

• Synthesis and isolation of chloro-β-carbolines obtained by chlorination of β-carboline alkaloids in solution and in solid state
  作者：Maria A. Ponce、Olga I. Tarzi、Rosa Erra-Balsells

  DOI：10.1002/jhet.5570400304

  日期：2003.5

  Rf, 1H nmr, 13C nmr and ms) together with the preparation, isolation and charaterization, for the first time, of the chloroderivatives obtained from harmine (3a-3c), harmol (4a-4b) and 7-acetylharmol (5a-5c). As chlorinating reagent N-chlorosuccinimide and N-chlorobenzotriazole in solution as well as the β-carboline -N-chlorosuccinimide solid mixture have been used and their uses have been compared.

  在不同的实验条件下，β-咔啉（1-5）会被N-氯琥珀酰亚胺和N-氯苯并三唑进行亲电芳香取代。虽然6-氯和8-氯去甲harmane（1A和1B）和6-氯和8-氯harmane（图2a和2b中通过氯化与次氯酸钠去甲harmane获得）（1）和harmane （ 2）近期被分离出来并进行了全面表征，因此从未描述过正丁烷和异丁烷的其他氯代衍生物。二氯衍生物1c和1c的制备，后续分离，纯化和全面表征报告了2c（mp，R f，1 H nmr，13 C nmr和ms）以及从harmine （3a-3c），harmol （4a-4b ）获得的氯衍生物的制备，分离和表征）和7-乙酰基甘露醇（5a-5c）。作为溶液中的N-氯琥珀酰亚胺和N-氯苯并三唑以及β-咔啉-N-氯琥珀酰亚胺固体混合物作为氯化试剂，已经对其用途进行了比较。异丁烷的其他一氯衍生物的Gc（t R）和gc-ms（m / z）数据（1d）还包括痕