2-(2-fluorobenzyl)-1,2,3,4-tetrahydroisoquinoline | 827333-14-2

• 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: 2-(2-fluorobenzyl)-1,2,3,4-tetrahydroisoquinoline
• 英文别名: 2-[(2-fluorophenyl)methyl]-3,4-dihydro-1H-isoquinoline
• CAS: 827333-14-2
• 化学式: C₁₆H₁₆FN
• 分子量: 241.308
• InChiKey: CYDJHWYFIMZYCM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  3.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  四氢异喹啉 、 邻氟氯苄 在 potassium carbonate 作用下， 以 乙醇 为溶剂， 以50 %的产率得到2-(2-fluorobenzyl)-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  噻氯匹定衍生物和类似物作为外核苷酸酶 CD39 抑制剂的合成及构效关系

  摘要：

  噻氯匹定是噻吩并四氢吡啶家族的抗血栓形成前药。对于血小板抑制，它必须通过细胞色素 P450 酶进行氧化开环。生成的硫醇与嘌呤 P2Y 12的半胱氨酸残基反应血小板上的受体导致共价受体阻断。先前显示其完整、未代谢形式的噻氯匹定可抑制外核苷三磷酸二磷酸水解酶-1（NTPDase1，也称为分化簇 (CD) 39）。CD39 通过 ADP 催化 ATP 胞外水解为 AMP，AMP 进一步被 ecto-5'-核苷酸酶 (CD73) 水解为腺苷。CD39 抑制已被提议作为一种新策略来增加抗增殖 ATP 的细胞外浓度，同时降低免疫抑制和促癌腺苷水平。在本研究中，我们对作为 CD39 抑制剂的噻氯匹定衍生物和类似物进行了广泛的构效关系 (SAR) 分析，随后对所选化合物进行了深入表征。总共合成了 74 种化合物，其中 41 个是新的，以前没有在文献中描述过。苯并四氢吡啶，其中代谢不稳定的噻吩被苯环取代，被发现是一类新的变构

  DOI：

  10.1016/j.bioorg.2023.106460

文献信息

• Designing analogs of ticlopidine, a wall teichoic acid inhibitor, to avoid formation of its oxidative metabolites
  作者：Maya A. Farha、Kalinka Koteva、Robert T. Gale、Edward W. Sewell、Gerard D. Wright、Eric D. Brown

  DOI：10.1016/j.bmcl.2013.12.069

  日期：2014.2

  The thienopyridine antiplatelet agent, ticlopidine and its analog, clopidogrel, have been shown to potentiate the action of beta-lactam antibiotics, reversing the methicillin-resistance phenotype of methicillin- resistant Staphylococcus aureus (MRSA), in vitro. Interestingly, these thienopyridines inhibit the action of TarO, the first enzyme in the synthesis of wall teichoic acid, an important cell wall polymer in Gram-positive bacteria. In the human body, both ticlopidine and clopidogrel undergo a rapid P450-dependent oxidation into their respective antiplatelet-active metabolites, resulting in very low plasma concentrations of intact drug. Herein, a series of analogs of ticlopidine and clopidogrel that would avoid oxidative metabolism were designed, prepared and evaluated as inhibitors of TarO. Specifically, we replaced the P450-labile thiophene ring of ticlopidine and clopidogrel to a more stable phenyl group to generate 2-(2-chlorobenzyl)-1,2,3,4-tetrahydro-isoquinoline) (6) and (2-chloro-phenyl)-(3,4-dihydro-1H-isoquinolin- 2-yl)-acetic acid methyl ester (22), respectively. The latter molecules displayed inhibitory activity against TarO and formed the basis of a library of analogs. Most synthesized compounds exhibited comparable efficacy to ticlopidine and clopidogrel. So far, it was introduction of a trifluoromethyl group to compound 6, to generate 2-(2-trifluoromethyl-benzyl)-1,2,3,4-tetrahydro-isoquinoline (13) that exhibited enhanced activity against TarO. Compound 13 represents a novel stable inhibitor of TarO with synergistic impact on b-lactam antibiotics against MRSA and low potential for P-450 metabolism. (C) 2013 Elsevier Ltd. All rights reserved.
• NOVEL ANTIBACTERIAL COMBINATION THERAPY
  申请人：Brown Eric D.

  公开号：US20140088069A1

  公开（公告）日：2014-03-27

  An antibacterial composition is provided including a combination of a β-lactam antibiotic that has a binding affinity for bacterial penicillin-binding protein 2; and a non-antibiotic compound which may be a thienopyridine or a non-thienopyridine compound. A method of treatment using the composition is also provided.
• [EN] NOVEL ANTIBACTERIAL COMBINATION THERAPY<br/>[FR] NOUVEAU TRAITEMENT COMBINÉ ANTIBACTÉRIEN
  申请人：UNIV MCMASTER

  公开号：WO2012162814A1

  公开（公告）日：2012-12-06

  An antibacterial composition is provided including a combination of a β-lactam antibiotic that has a binding affinity for bacterial penicillin-binding protein 2; and a non-antibiotic compound which may be a thienopyridine or a non-thienopyridine compound. A method of treatment using the composition is also provided.