3-methyl-4-phenylquinoline-2-carboxylic acid | 154419-39-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 3-methyl-4-phenylquinoline-2-carboxylic acid
• 英文别名: 4-phenyl-3-methylquinoline-2-carboxylic acid
• CAS: 154419-39-3
• 化学式: C₁₇H₁₃NO₂
• 分子量: 263.296
• InChiKey: YVHOTJIJEKQMHE-UHFFFAOYSA-N

物化性质

• 熔点：
  130-132 °C
• 沸点：
  434.1±45.0 °C(Predicted)
• 密度：
  1.248±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  50.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-methyl-4-phenylquinoline-2-carboxylic acid 在 盐酸 、 N-溴代丁二酰亚胺(NBS) 、 三氯氧磷 、 过氧化苯甲酰 作用下， 以 四氯化碳 、 乙醇 为溶剂， 反应 50.0h， 生成 9-phenylfuro[3,4-b]quinolin-3(1H)-one
  参考文献：
  名称：

  Anzini, Maurizio; Capelli, Andrea; Vomero, Salvatore, Heterocycles, 1994, vol. 38, # 1, p. 103 - 112

  摘要：

  DOI：
• 作为产物：
  描述：

  ethyl 4-phenyl-3-methylquinoline-2-carboxylate 在 水 、 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 1.5h， 以93%的产率得到3-methyl-4-phenylquinoline-2-carboxylic acid
  参考文献：
  名称：

  New iodinated quinoline-2-carboxamides for SPECT imaging of the translocator protein

  摘要：

  With the aim of developing new SPECT imaging agents for the translocator protein (TSPO), a small library of iodinated quinoline-2-carboxamides have been prepared and tested for binding affinity with TSPO. N,N-Diethyl-3-iodomethyl-4-phenylquinoline-2-carboxamide was found to have excellent affinity (K-i 12.0 nM), comparable to that of the widely used TSPO imaging agent PK11195. (c) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.12.061

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。
• Structure−Activity Relationships in Carboxamide Derivatives Based on the Targeted Delivery of Radionuclides and Boron Atoms by Means of Peripheral Benzodiazepine Receptor Ligands
  作者：Andrea Cappelli、Gal.la Pericot Mohr、Andrea Gallelli、Germano Giuliani、Maurizio Anzini、Salvatore Vomero、Massimo Fresta、Patrizia Porcu、Elisabetta Maciocco、Alessandra Concas、Giovanni Biggio、Alessandro Donati

  DOI：10.1021/jm034068b

  日期：2003.8.1

  as carriers of radionuclides and boron atoms. Some new ligands show enhanced affinity and steroidogenic activity with respect to reference compound 1 and are interesting candidates for radiolabeling and PET studies. Moreover, carborane derivative 3q, representing the first example of PBR ligand bearing a carborane cage, can be useful to explore an alternative mechanism in BNCT.

  为了将这些配体用作放射性核素和硼原子的载体，对2-喹啉羧酰胺外围苯并二氮杂receptor受体（PBR）配体的构效关系进行了研究。某些新的配体相对于参考化合物1表现出增强的亲和力和类固醇生成活性，并且是放射性标记和PET研究的有趣候选物。此外，代表带有碳硼烷笼的PBR配体的第一个例子的碳硼烷衍生物3q可用于探索BNCT中的另一种机理。
• Synthesis, labeling, and biological evaluation of halogenated 2-quinolinecarboxamides as potential radioligands for the visualization of peripheral benzodiazepine receptors
  作者：Andrea Cappelli、Mario Matarrese、Rosa Maria Moresco、Salvatore Valenti、Maurizio Anzini、Salvatore Vomero、Elia Anna Turolla、Sara Belloli、Pasquale Simonelli、Maria Azzurra Filannino、Michela Lecchi、Ferruccio Fazio

  DOI：10.1016/j.bmc.2006.02.004

  日期：2006.6

  The previous exploration of the structure-affinity relationships concerning 4-phenyl-2-quinolinecarboxamide peripheral benzodiazepine receptor (PBR) ligands 6 showed as an interesting result the importance of the presence of a chlorine atom in the methylene carbon at position 3 of the quinoline nucleus. The subnanomolar PBR affinity shown by N-benzyl-3-chloromethyl-N-methyl-4-phenyl-2-quinolinecarboxamide (6b) suggested its chlorine atom to be replaced with other halogens in order to optimize the interaction of the quinolinecarboxamide derivatives with PBR and to develop suitable candidates for positron emission tomography (PET) or single photon emission computed tomography (SPECT) studies. The binding studies led to the discovery of fluoromethyl derivative 6a, which showed an IC50 value of 0.11 nM and is, therefore, one of the most potent PBR ligands so far described. Fluoromethyl derivative 6a has been labeled with C-11 (t(1/2) = 20.4 min, beta(+) = 99.8%) starting from the corresponding des-methyl precursor (14) using [C-11]CH3I in the presence of tetrabutylammonium hydroxide in DMF with a 35-40% radiochemical yield (corrected for decay) and 1.5 Ci/mu mol of specific radioactivity. Ex vivo rat biodistribution and inhibition (following intravenous pre-administration of PK11195) studies showed that [C-11]6a rapidly and specifically accumulated in PBR-rich tissues such as heart, lung, kidney, spleen, and adrenal, and at a lower level in other peripheral organs and in the brain. The images obtained in mouse with small animal YAP-(S)PET essentially confirmed the result of the ex vivo biodistribution experiments. The biological data suggest that [C-11]6a is a promising radioligand for peripheral benzodiazepine receptor PET imaging in vivo. (c) 2006 Elsevier Ltd. All rights reserved.
• WO2019243616A5
  申请人：——

  公开号：WO2019243616A5

  公开（公告）日：2022-06-23
• TSPO BINDERS
  申请人：The University Court Of The University Of Glasgow

  公开号：EP3810575A1

  公开（公告）日：2021-04-28