tert-butyl 4-(isoquinolin-4-yl)piperazine-1-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: tert-butyl 4-(isoquinolin-4-yl)piperazine-1-carboxylate
• 英文别名: 4-(4-Isoquinolinyl)-1-piperazinecarboxylic acid 1,1-dimethylethyl ester；tert-butyl 4-isoquinolin-4-ylpiperazine-1-carboxylate
• 化学式: C₁₈H₂₃N₃O₂
• 分子量: 313.4
• InChiKey: BINHFZKINOADDT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  45.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(isoquinolin-4-yl)piperazine-1-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 以67%的产率得到4-(1-piperazinyl)isoquinoline
  参考文献：
  名称：

  2-substituted 1,2-benzisothiazole derivatives and their use as serotonin antagonists (5-HT1A, 5HT1B and 5-HT1D)

  摘要：

  在这里，取代基具有描述中指示的含义，它们的制备和用途作为5-羟色胺拮抗剂。

  公开号：

  US06346622B1
• 作为产物：
  描述：

  4-溴异喹啉 、 N-Boc-哌嗪 在 tris-(dibenzylideneacetone)dipalladium(0) 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 sodium t-butanolate 作用下， 以 甲苯 为溶剂， 反应 2.0h， 以81%的产率得到tert-butyl 4-(isoquinolin-4-yl)piperazine-1-carboxylate
  参考文献：
  名称：

  2-substituted 1,2-benzisothiazole derivatives and their use as serotonin antagonists (5-HT1A, 5HT1B and 5-HT1D)

  摘要：

  在这里，取代基具有描述中指示的含义，它们的制备和用途作为5-羟色胺拮抗剂。

  公开号：

  US06346622B1

文献信息

• 2-substituted 1,2-benzisothiazole derivatives and their use as serotonin antagonists (5-HT1A, 5HT1B and 5-HT1D)
  申请人：Abbott Laboratories

  公开号：US06346622B1

  公开（公告）日：2002-02-12

  where the substituents have the meanings indicated in the description, their preparation and use as serotonin antagonists.

  在这里，取代基具有描述中指示的含义，它们的制备和用途作为5-羟色胺拮抗剂。
• Discovery of 4-Piperazine Isoquinoline Derivatives as Potent and Brain-Permeable Tau Prion Inhibitors with CDK8 Activity
  作者：Jean-Marc M. Grandjean、Alexander Y. Jiu、John W. West、Atsushi Aoyagi、Daniel G. Droege、Manuel Elepano、Makoto Hirasawa、Masakazu Hirouchi、Ryo Murakami、Joanne Lee、Koji Sasaki、Shimpei Hirano、Takao Ohyama、Benjamin C. Tang、Roy J. Vaz、Masahiro Inoue、Steven H. Olson、Stanley B. Prusiner、Jay Conrad、Nick A. Paras

  DOI：10.1021/acsmedchemlett.9b00480

  日期：2020.2.13

  Tau prions feature in the brains of patients suffering from Alzheimer's disease and other tauopathies. For the development of therapeutics that target the replication of tau prions, a high-content, fluorescence-based cell assay was developed. Using this high-content phenotypic screen for nascent tau prion formation, a 4-piperazine isoquinoline compound (1) was identified as a hit with an EC50 value of 390 nM and 0.04 K-p,K-uu. Analogs were synthesized using a hypothesis-based approach to improve potency and in vivo brain penetration resulting in compound 25 (EC50 = 15 nM; K-p,K-uu = 0.63). We investigated the mechanism of action of this series and found that a small set of active compounds were also CDK8 inhibitors.