3-(7-oxy-1-methyl-9-H-b-carbolin)propyl tert-butyl carbamate | 1342260-94-9

• 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: 3-(7-oxy-1-methyl-9-H-b-carbolin)propyl tert-butyl carbamate
• 英文别名: tert-butyl N-[3-[(1-methyl-9H-pyrido[3,4-b]indol-7-yl)oxy]propyl]carbamate
• CAS: 1342260-94-9
• 化学式: C₂₀H₂₅N₃O₃
• 分子量: 355.437
• InChiKey: VFDRDGDGXSCOEC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  76.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(7-oxy-1-methyl-9-H-b-carbolin)propyl tert-butyl carbamate 在 盐酸 作用下， 以 甲醇 为溶剂， 生成 3-((1-methyl-9H-pyrido[3,4-b]indol-7-yl)oxy)propan-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-nitroethenyl)-1H-indol-6-ol 在 盐酸 、 manganese(IV) oxide 、 lithium aluminium tetrahydride 、 5%-palladium/activated carbon 、 caesium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 3-(7-oxy-1-methyl-9-H-b-carbolin)propyl tert-butyl carbamate
  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

• Structure–Activity Relationships and Biological Evaluation of 7-Substituted Harmine Analogs for Human β-Cell Proliferation
  作者：Kunal Kumar、Peng Wang、Ethan A. Swartz、Susmita Khamrui、Cody Secor、Michael B. Lazarus、Roberto Sanchez、Andrew F. Stewart、Robert J. DeVita

  DOI：10.3390/molecules25081983

  日期：——

  pathway. We explore structure–activity relationships of the 7-position of harmine for both DYRK1A kinase inhibition and β-cell proliferation based on our related previous structure–activity relationship studies of harmine in the context of diabetes and β-cell specific targeting strategies. 33 harmine analogs of the 7-position substituent were synthesized and evaluated for biological activity. Two novel

  最近，我们已经证明，harmine 通过 DYRK1A-NFAT 途径介导体外和体内 β 细胞增殖。我们基于我们之前在糖尿病和 β 细胞特异性靶向策略中对harmine 的相关构效关系研究，探索了harmine 的7 位对DYRK1A 激酶抑制和β 细胞增殖的构效关系。合成了 33 种 7 位取代基的苦胺类似物并评估了其生物活性。确定了两种新型抑制剂，它们显示出 DYRK1A 抑制和人类 β 细胞增殖能力。DYRK1A 抑制剂化合物 1-2b 在高三倍的浓度下诱导的 β 细胞增殖是harmine 的一半。
• Beta-Carbolines as Inhibitors of Haspin and DYRK Kinases
  申请人：Higgins Jonathan

  公开号：US20130231360A1

  公开（公告）日：2013-09-05

  The present disclosure is directed to compounds of Formula (I) which are inhibitors of Haspin kinase and DYRK kinases. The compounds of the present disclosure, and compositions thereof, are useful in the treatment of disease related to Haspin kinase and DYRK kinase expression and/or activity.