2-[4-[7-methoxy-1-(trifluoromethyl)-9H-pyrido[3,4-b]indol-9-yl]butyl]-1H-isoindole-1,3(2H)-dione | 1362737-58-3

• 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: 2-[4-[7-methoxy-1-(trifluoromethyl)-9H-pyrido[3,4-b]indol-9-yl]butyl]-1H-isoindole-1,3(2H)-dione
• 英文别名: 2-[4-[7-Methoxy-1-(trifluoromethyl)pyrido[3,4-b]indol-9-yl]butyl]isoindole-1,3-dione；2-[4-[7-methoxy-1-(trifluoromethyl)pyrido[3,4-b]indol-9-yl]butyl]isoindole-1,3-dione
• CAS: 1362737-58-3
• 化学式: C₂₅H₂₀F₃N₃O₃
• 分子量: 467.447
• InChiKey: HPUIWTHORGXEBA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  64.4
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-[4-[7-methoxy-1-(trifluoromethyl)-9H-pyrido[3,4-b]indol-9-yl]butyl]-1H-isoindole-1,3(2H)-dione 在 一水合肼 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 7-methoxy-1-(trifluoromethyl)-9H-pyrido[3,4-b]indole-9-butanamine
  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-氨基乙基)-6-甲氧基吲哚 在 盐酸 、 manganese(IV) oxide 、 5%-palladium/activated carbon 、 sodium hydride 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-[4-[7-methoxy-1-(trifluoromethyl)-9H-pyrido[3,4-b]indol-9-yl]butyl]-1H-isoindole-1,3(2H)-dione
  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

• ALKYL-AMINE HARMINE DERIVATIVES FOR PROMOTING BONE GROWTH
  申请人：Osteoqc Inc.

  公开号：EP2968284A2

  公开（公告）日：2016-01-20
• [EN] ALKYL-AMINE HARMINE DERIVATIVES FOR PROMOTING BONE GROWTH<br/>[FR] DÉRIVÉS D'ALKYL-AMINE HARMINE POUR FAVORISER LA CROISSANCE OSSEUSE
  申请人：OSSIFI INC

  公开号：WO2014153203A2

  公开（公告）日：2014-09-25

  In one aspect, the invention provides compounds of Formula I, and salts, hydrates and isomers thereof. In another aspect, the invention provides a method of promoting bone formation in a subject in need thereof by administering to the subject a therapeutically effective amount of a compound of Formula I, Formula II, or Formula III. The present invention also provides orthopedic and periodontal devices, as well as methods for the treatment of renal disease and cancer, using a compound of Formula I, Formula II, or Formula III.
• 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.