6-bromo-1-fluoroisoquinoline | 891785-25-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 6-bromo-1-fluoroisoquinoline
• 英文别名: Isoquinoline, 6-bromo-1-fluoro-
• CAS: 891785-25-4
• 化学式: C₉H₅BrFN
• 分子量: 226.048
• InChiKey: BNZRFLMNPXIRMT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  12.9
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-bromo-1-fluoroisoquinoline 在 tris(dibenzylideneacetone)dipalladium (0) 、 三(邻甲基苯基)磷 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 6-{5-[(2S)-2-amino-3-(1H-indol-3-yl)propoxy]pyridin-3-yl}-1-fluoroisoquinoline
  参考文献：
  名称：

  Isoquinoline–pyridine-based protein kinase B/Akt antagonists: SAR and in vivo antitumor activity

  摘要：

  The structure-activity relationships of a series of isoquinoline-pyridine-based protein kinase B/Akt antagonists have been investigated in an effort to improve the major short-comings of the lead compound 3, including poor pharmacokinetic profiles in several species (e.g., mouse iv t(1/2) = 0.3 h, po F= 0%). Chlorination at C-1 position of the isoquinoline improved its pharmacokinetic property in mice (iv t(1/2) = 5.0 h, po F = 51%) but resulted in > 500-fold drop in potency. In a mouse MiaPaCa-2 xenograft model, an amino analog 10y significantly slowed the tumor growth, however was accompanied by toxicity. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.03.041
• 作为产物：
  描述：

  6-溴-2H-异喹啉-1-酮 在 perfluoro-2-methyl-2-pentene 、 三乙胺 作用下， 以 乙腈 为溶剂， 以15%的产率得到6-bromo-1-fluoroisoquinoline
  参考文献：
  名称：

  Isoquinoline–pyridine-based protein kinase B/Akt antagonists: SAR and in vivo antitumor activity

  摘要：

  The structure-activity relationships of a series of isoquinoline-pyridine-based protein kinase B/Akt antagonists have been investigated in an effort to improve the major short-comings of the lead compound 3, including poor pharmacokinetic profiles in several species (e.g., mouse iv t(1/2) = 0.3 h, po F= 0%). Chlorination at C-1 position of the isoquinoline improved its pharmacokinetic property in mice (iv t(1/2) = 5.0 h, po F = 51%) but resulted in > 500-fold drop in potency. In a mouse MiaPaCa-2 xenograft model, an amino analog 10y significantly slowed the tumor growth, however was accompanied by toxicity. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.03.041

文献信息

• Discovery of <i>N</i>-(4-[¹⁸F]Fluoro-5-methylpyridin-2-yl)isoquinolin-6-amine (JNJ-64326067), a New Promising Tau Positron Emission Tomography Imaging Tracer
  作者：Frederik J. R. Rombouts、Lieven Declercq、José-Ignacio Andrés、Astrid Bottelbergs、Lu Chen、Laura Iturrino、Joseph E. Leenaerts、Jonas Mariën、Fengbin Song、Cindy Wintmolders、Stijn Wuyts、Chunfang A. Xia、Paula te Riele、Guy Bormans、Rik Vandenberghe、Hartmuth Kolb、Diederik Moechars

  DOI：10.1021/acs.jmedchem.8b01759

  日期：2019.3.28

  and spread of aggregated tau protein track well with neurodegeneration and cognitive decline, making the imaging of aggregated tau a compelling biomarker. A structure-activity relationship exploration around an isoquinoline hit, followed by an exploration of tolerated fluorination positions, allowed us to identify 9 (JNJ-64326067), a potent and selective binder to aggregated tau with a favorable pharmacokinetic

  在阿尔茨海默氏病中，聚集的tau蛋白的密度和扩散与神经退行性变和认知能力下降密切相关，从而使聚集的tau成像成为令人信服的生物标记。围绕异喹啉命中进行结构-活性关系探索，然后探索耐受的氟化位置，使我们能够鉴定出9（JNJ-64326067），这是一种有效且选择性的聚集tau蛋白，具有良好的药代动力学特征且无明显脱靶捆绑。这在使用[18F] 9的大鼠和猴子正电子发射断层扫描研究中得到了证实。
• Access to <i>N</i>-Aryl (Iso)quinolones via Aryne-Induced Three-Component Coupling Reaction
  作者：Qiang Yan、Zhe Zhuang、Rong Fan、Jingwen Wang、Tuanli Yao、Jiajing Tan

  DOI：10.1021/acs.orglett.3c04385

  日期：2024.3.8

  N-Aryl (iso)quinolones are of increasing interest in material and medicinal chemistry, although general routes for their provision remain underexplored, especially when compared with its N-alkyl counterparts. Herein, we report a modular and transition-metal-free, aryne-induced three-component coupling protocol that allows the facile synthesis of structurally diverse N-aryl (iso)quinolones from readily

  N-芳基（异）喹诺酮类药物在材料和药物化学领域越来越受到关注，尽管其提供的一般途径尚未得到充分探索，特别是与N-烷基对应物相比。在此，我们报告了一种模块化且不含过渡金属的芳炔诱导的三组分偶联方案，该方案允许在水存在下从易于获得的卤代-(异)喹啉中轻松合成结构多样的N-芳基(异)喹诺酮。初步结果强调了我们的方法通过放大合成、下游衍生化以及涉及其他类型芳炔前体的灵活合成的适用性。
• Isoquinoline–pyridine-based protein kinase B/Akt antagonists: SAR and in vivo antitumor activity
  作者：Gui-Dong Zhu、Jianchun Gong、Akiyo Claiborne、Keith W. Woods、Viraj B. Gandhi、Sheela Thomas、Yan Luo、Xuesong Liu、Yan Shi、Ran Guan、Shayna R. Magnone、Vered Klinghofer、Eric F. Johnson、Jennifer Bouska、Alexander Shoemaker、Anatol Oleksijew、Vincent S. Stoll、Ron De Jong、Tilman Oltersdorf、Qun Li、Saul H. Rosenberg、Vincent L. Giranda

  DOI：10.1016/j.bmcl.2006.03.041

  日期：2006.6

  The structure-activity relationships of a series of isoquinoline-pyridine-based protein kinase B/Akt antagonists have been investigated in an effort to improve the major short-comings of the lead compound 3, including poor pharmacokinetic profiles in several species (e.g., mouse iv t(1/2) = 0.3 h, po F= 0%). Chlorination at C-1 position of the isoquinoline improved its pharmacokinetic property in mice (iv t(1/2) = 5.0 h, po F = 51%) but resulted in > 500-fold drop in potency. In a mouse MiaPaCa-2 xenograft model, an amino analog 10y significantly slowed the tumor growth, however was accompanied by toxicity. (c) 2006 Elsevier Ltd. All rights reserved.