N-(3-(7-methoxy-1-methyl-β-carbolin-9-yl)propyl)phthalimide | 1342261-17-9

• 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: N-(3-(7-methoxy-1-methyl-β-carbolin-9-yl)propyl)phthalimide
• 英文别名: 2-[3-(7-Methoxy-1-methylpyrido[3,4-b]indol-9-yl)propyl]isoindole-1,3-dione；2-[3-(7-methoxy-1-methylpyrido[3,4-b]indol-9-yl)propyl]isoindole-1,3-dione
• CAS: 1342261-17-9
• 化学式: C₂₄H₂₁N₃O₃
• 分子量: 399.449
• InChiKey: YUGBUPSIPXSAPY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  64.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(3-(7-methoxy-1-methyl-β-carbolin-9-yl)propyl)phthalimide 在 一水合肼 作用下， 以 乙醇 为溶剂， 生成 3-(7-methoxy-1-methyl-β-carbolin-9-yl)propylamine
  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：

  N-(3-溴丙基)苯二胺 、 肉叶云香碱 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 13.0h， 以60%的产率得到N-(3-(7-methoxy-1-methyl-β-carbolin-9-yl)propyl)phthalimide
  参考文献：
  名称：

  Synthesis and Biological Validation of a Harmine-Based, Central Nervous System (CNS)-Avoidant, Selective, Human β-Cell Regenerative Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase A (DYRK1A) Inhibitor

  摘要：

  Recently, our group identified that harmine is able to induce beta-cell proliferation both in vitro and in vivo, mediated via the DYRK1A-NFAT pathway. Since, harmine suffers from a lack of selectivity, both against other kinases and CNS off-targets, we therefore sought to expand structure-activity relationships for harmine's DYRK1A activity, to enhance selectivity for off-targets while retaining human beta-cell proliferation activity. We carried out optimization of the 9-N-position of harmine to synthesize 29 harmine-based analogs. Several novel inhibitors showed excellent DYRK1A inhibition and human beta-cell proliferation capability. An optimized DYRK1A inhibitor, 2-2c, was identified as a novel, efficacious in vivo lead candidate. 2-2c also demonstrates improved selectivity for kinases and CNS off-targets, as well as in vivo efficacy for beta-cell proliferation and regeneration at lower doses than harmine. Collectively, these findings demonstrate that 2-2c is a much improved in vivo lead candidate as compared to harmine for the treatment of diabetes.

  DOI：

  10.1021/acs.jmedchem.9b01379

文献信息

• WO2019183245A5
  申请人：——

  公开号：WO2019183245A5

  公开（公告）日：2022-03-25
• 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.
• 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
• KINASE INHIBITOR COMPOUNDS AND COMPOSITIONS AND METHODS OF USE
  申请人：Icahn School of Medicine at Mount Sinai

  公开号：US20210094950A1

  公开（公告）日：2021-04-01

  Described herein are compounds having the following structure: formula (I) or a stereoisomer, pharmaceutically acceptable salt, oxide, or solvate thereof. Also disclosed are compositions containing the compounds, methods of inhibiting activity of DYRK1 A in a cell, methods of increasing cell proliferation in a population of pancreatic beta cells, methods of treating a subject for a condition associated with insufficient insulin secretion, and methods of treating a subject for a neurological disorder.
• [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.