N-(4-(7-methoxy-1-methyl-β-carbolin-9-yl)butyl)phthalimide | 1342261-18-0

• 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-(4-(7-methoxy-1-methyl-β-carbolin-9-yl)butyl)phthalimide
• 英文别名: 2-[4-(7-Methoxy-1-methylpyrido[3,4-b]indol-9-yl)butyl]isoindole-1,3-dione
• CAS: 1342261-18-0
• 化学式: C₂₅H₂₃N₃O₃
• 分子量: 413.476
• InChiKey: GXFVRQDLHJLGCX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  31
• 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：
  4

反应信息

• 作为反应物：
  描述：

  N-(4-(7-methoxy-1-methyl-β-carbolin-9-yl)butyl)phthalimide 在 氢溴酸 、 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成
  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-(4-溴丁基)邻苯二甲酰亚胺 、 肉叶云香碱 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以71.66 %的产率得到N-(4-(7-methoxy-1-methyl-β-carbolin-9-yl)butyl)phthalimide
  参考文献：
  名称：

  一种去氢骆驼蓬碱修饰药、制备方法及应用

  摘要：

  本发明涉及一种去氢骆驼蓬碱修饰药、制备方法及应用。通过对去氢骆驼蓬碱进行衍生化修饰，以去氢骆驼蓬碱作为疏水内核，二硫代二丙酸作为连接臂，聚乙二醇为亲水骨架材料，合成还原敏感两亲性聚合物材料去氢骆驼蓬碱接枝聚乙二醇，即去氢骆驼蓬碱修饰药；将其在水溶液中自组装，得到一种载药纳米胶束系统，用作药物递送的载体材料。本发明提供的去氢骆驼蓬碱修饰药应用于制备纳米胶束载药系统，由于其在水溶液中可自组装形成稳定的纳米级胶束体系，从而能够高效的递送药物到肿瘤部位，提高去氢骆驼蓬碱的抗肿瘤效果，降低毒副作用，同时改善水溶性，为去氢骆驼蓬碱在抗肿瘤方面的应用提供更多可能性。

  公开号：

  CN115887376A

文献信息

• 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
  作者：Kunal Kumar、Peng Wang、Jessica Wilson、Viktor Zlatanic、Cecilia Berrouet、Susmita Khamrui、Cody Secor、Ethan A. Swartz、Michael Lazarus、Roberto Sanchez、Andrew F. Stewart、Adolfo Garcia-Ocana、Robert J. DeVita

  DOI：10.1021/acs.jmedchem.9b01379

  日期：2020.3.26

  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.
• 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.