8-Chloro-6,7-dihydro-[1]benzoxepino[4,5-c]quinoline | 151080-38-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噁庚英
• 英文名称: 8-Chloro-6,7-dihydro-[1]benzoxepino[4,5-c]quinoline
• CAS: 151080-38-5
• 化学式: C₁₇H₁₂ClNO
• 分子量: 281.741
• InChiKey: ZGSUWNUGAKCBNL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  20
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  22.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  8-Chloro-6,7-dihydro-[1]benzoxepino[4,5-c]quinoline 在 sodium hydride 、 N,N-二甲基甲酰胺 作用下， 反应 0.33h， 生成 3-ethenyl-4-(2-hydroxyphenyl)-2-(4-methyl-1-piperazinyl)quinoline
  参考文献：
  名称：

  Synthesis of 6,7-Dihydro-8-(4-methyl-1-piperazinyl)-[1]benzoxepino[4,5-c]quinoline as Potential 5-HT3 Receptor Ligand

  摘要：

  Two synthetic routes to the achievement of the title compound are described. The [1]benzoxepino[4,5-c]quinoline nucleus was prepared by nucleophilic aromatic fluoride displacement-cyclization and functionalized with N-methylpiperazine moiety. Alternatively the oxepino ring closure is shifted as the final step. An oxepine ring cleavage occurred in compounds (9) and (3); a mechanistical interpretation is proposed.

  DOI：

  10.3987/com-92-6276
• 作为产物：
  描述：

  2-氨基-2-氟苯甲酮 在 lithium aluminium tetrahydride 、 potassium tert-butylate 、 sodium hydride 、 N,N-二甲基甲酰胺 、 三氯氧磷 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 反应 5.58h， 生成 8-Chloro-6,7-dihydro-[1]benzoxepino[4,5-c]quinoline
  参考文献：
  名称：

  Synthesis of 6,7-Dihydro-8-(4-methyl-1-piperazinyl)-[1]benzoxepino[4,5-c]quinoline as Potential 5-HT3 Receptor Ligand

  摘要：

  Two synthetic routes to the achievement of the title compound are described. The [1]benzoxepino[4,5-c]quinoline nucleus was prepared by nucleophilic aromatic fluoride displacement-cyclization and functionalized with N-methylpiperazine moiety. Alternatively the oxepino ring closure is shifted as the final step. An oxepine ring cleavage occurred in compounds (9) and (3); a mechanistical interpretation is proposed.

  DOI：

  10.3987/com-92-6276

文献信息

• Mapping the Peripheral Benzodiazepine Receptor Binding Site by Conformationally Restrained Derivatives of 1-(2-Chlorophenyl)-<i>N</i>-methyl-<i>N</i>-(1-methylpropyl)-3-isoquinolinecarboxamide (PK11195)
  作者：Andrea Cappelli、Maurizio Anzini、Salvatore Vomero、Pier G. De Benedetti、Maria Cristina Menziani、Gianluca Giorgi、Cristina Manzoni

  DOI：10.1021/jm960516m

  日期：1997.8.1

  in binding studies using [3H]-1, and most of these showed PBR affinities in the nanomolar range. The essential role of the carbonyl moiety as a primary pharmacophoric element in the recognition by and the binding to PBR has been confirmed, and the restricted range of the carbonyl orientations, which characterizes the most potent ligands, points to a specific hydrogen-bonding interaction, mainly directed

  研究与1-（2-氯苯基）-N-甲基-N-（1-甲基丙基）-3-异喹啉羧酰胺（PK11195，1）相关的外围苯并二氮杂receptor受体（PBR）配体结合位点的合成计算方法）在其受体​​内已被开发出来。为了系统地探测PBR结合位点，已经设计了一系列的1构象受约束的衍生物。这些化合物的合成涉及钯催化的偶联和酰胺化作为关键步骤。使用[3H] -1在结合研究中测试了29个1的刚性和半刚性衍生物，其中大多数显示PBR亲和力在纳摩尔范围内。已经确认了羰基部分作为主要药效学元素在通过PBR识别并与PBR结合中的重要作用，并且羰基取向的范围受到限制，表征最有效的配体的特征是当电子键合时，特定的氢键相互作用（主要由几何因素决定）。此外，从报道的QSAR模型中发现，短程分散相互作用在调节结合亲和力以及因此在稳定配体-受体复合物中的根本重要性。
• Novel, Potent, and Selective 5-HT3 Receptor Antagonists Based on the Arylpiperazine Skeleton: Synthesis, Structure, Biological Activity, and Comparative Molecular Field Analysis Studies
  作者：Maurizio Anzini、Andrea Cappelli、Salvatore Vomero、Gianluca Giorgi、Thierry Langer、Michel Hamon、Nacera Merahi、Boris M. Emerit、Alfredo Cagnotto、Malgorzata Skorupska、Tiziana Mennini、Julia C. Pinto

  DOI：10.1021/jm00014a021

  日期：1995.7

  5-HT3 receptor antagonists with potencies in the same range as the best known 5-HT3 receptor antagonists ondansetron, tropisetron, and zacopride. The crystal and molecular structures of compounds 5f,j,n were determined by single-crystal X-ray diffraction and used as starting structures for molecular modeling studies. Comparative molecular field analysis (CoMFA) was applied to binding constants of compounds

  描述了一系列稠合喹啉衍生物的合成和药理学评估，这些衍生物在哌嗪或[喹啉核]的2-位上带有[氮]的碱性氮上。5-HT受体结合研究表明，对于大多数研究的化合物，其对5-HT3受体亚型的纳摩尔亲和力。最具活性的化合物苯并吡喃并[3,4-c]喹啉衍生物5f的Ki值与报道的Quipazine非常相似，并且选择性有所提高。对三种选定化合物进行的功能和体内测试表明，5f，j，n是有效的5-HT3受体拮抗剂，其效力与最著名的5-HT3受体拮抗剂恩丹西酮，托吡司琼和扎克必利相同。化合物5f，j的晶体和分子结构 n通过单晶X射线衍射确定，并用作分子建模研究的起始结构。比较分子场分析（CoMFA）用于化合物5a-p和6a-h的结合常数。从部分最小二乘计算得出的交叉验证的r2表明，对所研究化合物系列中的亲和力值具有良好的预测能力。以实际pKi值与预测pKi值的关系图的形式提供了预测能力的证据。CoMFA衍生模型的
• Characterization of quinoline derivatives. Part 3. Mass spectrometry and X-ray crystallography of biologically interesting arylquinolines 1Part 2 of this paper has been submitted to Acta Cryst. 1
  作者：Gianluca Giorgi、Andrea Cappelli、Maurizio Anzini、Salvatore Vomero

  DOI：10.1016/s0022-2860(98)00371-8

  日期：1998.10

  The structural characterization of a novel series of biologically interesting arylquinolines based on four-ring fused heterocyclic systems is carried out. Chlorinated precursors 1-5 as well as final products 6-8, active as potent and selective 5-HT3 receptor antagonists, are characterized in the gas phase by low- and high-resolution mass spectrometry and tandem mass spectrometry. For the 4-methyl-1-piperazinylbenzophenanthridine derivative 6 the crystal and molecular structures were also determined. These data, compared to those obtained for its analogous benzopyrane (7) and benzoxepine (8) derivatives, allow for an evaluation of the influence exerted by the ring fused at the face c of the quinoline on the conformational properties of the molecule. (C) 1998 Elsevier Science B.V. All rights reserved.
• Molecular structure and dynamics of some potent 5-HT 3 receptor antagonists. Insight into the interaction with the receptor
  作者：Andrea Cappelli、Alessandro Donati、Maurizio Anzini、Salvatore Vomero、Pier G. De Benedetti、Maria Cristina Menziani、Thierry Langer

  DOI：10.1016/0968-0896(96)00122-8

  日期：1996.8

  The molecular structure and the dynamic behaviour of some potent 5-HT3 antagonists structurally related to quipazine have been investigated by NMR spectroscopy and by computational methods in order to gain insight into the structure-activity relationships at a molecular level. The role of the different dynamic behaviour of these compounds in the binding to 5-HT3 receptors is discussed. A model of ligand-receptor interaction has been developed on the basis of molecular orbital calculations and on the reference ligands quipazine, ondansetron and LY278584. The interaction model proposed herein rationalizes the observed agonist-antagonist shift between quipazine and investigated compounds with the assumption of different but overlapping binding domains for antagonists and agonists at the 5-HT3 receptor. Copyright (C) 1996 Elsevier Science Ltd