ethyl 6-benzyl-4-oxo-1,4-dihydroquinoline-3-carboxylate | 254883-06-2

• 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: ethyl 6-benzyl-4-oxo-1,4-dihydroquinoline-3-carboxylate
• 英文别名: 6-benzyl-4-oxo-1,4-dihydroquinolin-3-carboxylate ethyl ester；6-benzyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl ester；ethyl 6-benzyl-4-oxo-1,4-dihydroquinolin-3-carboxylate；ethyl 6-benzyl-1,4-dihydro-4-oxoquinoline-3-carboxylate；ethyl 6-benzyl-4-oxo-1H-quinoline-3-carboxylate
• CAS: 254883-06-2
• 化学式: C₁₉H₁₇NO₃
• 分子量: 307.349
• InChiKey: WQYYZNGOTUCWQX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 6-benzyl-4-oxo-1,4-dihydroquinoline-3-carboxylate 在 氨 、 三氯氧磷 作用下， 以 (2S)-N-methyl-1-phenylpropan-2-amine hydrate 为溶剂， 生成 ethyl 6-benzyl-4-chloroquinoline-3-carboxylate
  参考文献：
  名称：

  Efflux pump inhibitors

  摘要：

  描述了具有外流泵抑制剂活性的化合物。还描述了使用这种外流泵抑制剂化合物的方法以及包括这种化合物的药物组合物。

  公开号：

  US06399629B1
• 作为产物：
  描述：

  氨基二苯甲烷 以 二苯醚 、 甲苯 为溶剂， 生成 ethyl 6-benzyl-4-oxo-1,4-dihydroquinoline-3-carboxylate
  参考文献：
  名称：

  源自喹诺酮类抗生素的新型 HIV-1 整合酶抑制剂。

  摘要：

  病毒酶整合酶对于 1 型人类免疫缺陷病毒 (HIV-1) 的复制至关重要，并且是抗逆转录病毒药物的剩余目标。在这里，我们描述了喹诺酮类抗生素的修饰，以生产新型整合酶抑制剂 JTK-303 (GS 9137)，该抑制剂阻止病毒酶的链转移。它具有喹诺酮类抗生素的核心结构，在链转移试验中的 IC50 为 7.2 nM，在急性 HIV-1 感染试验中的 EC50 为 0.9 nM。

  DOI：

  10.1021/jm0600139

文献信息

• [EN] AGENTS FOR USE IN THE TREATMENT OF CARDIOVASCULAR AND INFLAMMATORY DISEASES STRUCTURALLY BASED ON 4(1 H)-QUINOLONE<br/>[FR] AGENTS DESTINÉS À ÊTRE UTILISÉS DANS LE TRAITEMENT DE MALADIES CARDIOVASCULAIRES ET INFLAMMATOIRES AYANT UNE STRUCTURE BASÉE SUR LA 4(1H)-QUINOLONE
  申请人：UCL BUSINESS PLC

  公开号：WO2015189560A1

  公开（公告）日：2015-12-17

  The present invention provides a compound of formula I, a tautomer thereof, or a pharmaceutically acceptable salt or N-oxide thereof for use in the treatment or prevention of a cardiovascular disease or of an inflammatory disease or condition:

  本发明提供了一种式I的化合物，其互变异构体，或其药用可接受的盐或N-氧化物，用于治疗或预防心血管疾病或炎症性疾病或症状。
• Use of 2-[18F]fluoroethylazide for the Staudinger ligation – Preparation and characterisation of GABAA receptor binding 4-quinolones
  作者：Alessandra Gaeta、John Woodcraft、Stuart Plant、Julian Goggi、Paul Jones、Mark Battle、William Trigg、Sajinder K. Luthra、Matthias Glaser

  DOI：10.1016/j.bmcl.2010.05.106

  日期：2010.8

  The labelling reagent 2-[18F]fluoroethylazide was used in a traceless Staudinger ligation. This reaction was employed to obtain the GABAA receptor binding 6-benzyl-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid (2-[18F]fluoroethyl) amide. The radiotracer was prepared with a non-decay corrected radiochemical yield of 7%, a radiochemical purity >95% and a specific radioactivity of 0.9 GBq/μmol. The compound

  标记试剂2- [ 18 F]氟乙基叠氮化物用于无痕Staudinger连接。该反应用于获得结合了6-苄基-4-氧代-1，4-二氢喹啉-3-羧酸（2- [ 18 F]氟乙基）酰胺的GABA A受体。制备的放射性示踪剂的无衰减校正放射化学产率为7％，放射化学纯度> 95％，比放射性为0.9 GBq /μmol。该化合物在正常大鼠中脑渗透率低。还已经制备了一系列对GABA A受体具有纳摩尔至亚纳摩尔亲和力的氟代烷基4-喹诺酮类似物。
• Quinolone Carboxylic Acids as a Novel Monoketo Acid Class of Human Immunodeficiency Virus Type 1 Integrase Inhibitors
  作者：Motohide Sato、Hiroshi Kawakami、Takahisa Motomura、Hisateru Aramaki、Takashi Matsuda、Masaki Yamashita、Yoshiharu Ito、Yuji Matsuzaki、Kazunobu Yamataka、Satoru Ikeda、Hisashi Shinkai

  DOI：10.1021/jm900460z

  日期：2009.8.13

  Human immunodeficiency virus type 1 (HIV-1) integrase is a crucial target for antiretroviral drugs, and several keto-enol acid class (often referred to as diketo acid class) inhibitors have clinically exhibited marked antiretroviral activity. Here, we show the synthesis and the detailed structure-activity relationship of the quinolone carboxylic acids as a novel monoketo acid class of integrase inhibitors. 6-(3-Chloro-2-fluorobenzyl)- 1-((2,S)-1-hydroxy-3,3-dimethylbutan-2-yl)-7-methoxy-4-oxo- 1,4-dihydroquinoline-3-carboxylic acid 51, which showed an IC50 of 5.8 nM in the strand transfer assay and an ED50 of 0.6 nM in the antiviral assay, and 6-(3-chloro-2-fluorobenzyl)-1-((2S)-1-hydroxy-3-methylbutan-2-yl)-7-methoxy-4-oxo-4-dihydroquinoline-3-carboxylic acid 49, which had an IC50 of 7.2 nM and an ED50 of 0.9 nM, were the most potent compounds in this class. The monoketo acid 49 was much more potent at inhibiting integrase-catalyzed strand transfer processes than 3'-processing reactions, as is the case with the keto-enol acids. Elvitegravir 49 was chosen as a candidate for further studies and is currently in phase 3 clinical trials.
• 4-Quinolone Derivatives:  High-Affinity Ligands at the Benzodiazepine Site of Brain GABA_A Receptors. Synthesis, Pharmacology, and Pharmacophore Modeling
  作者：Erik Lager、Pierre Andersson、Jakob Nilsson、Ingrid Pettersson、Elsebet Østergaard Nielsen、Mogens Nielsen、Olov Sterner、Tommy Liljefors

  DOI：10.1021/jm058057p

  日期：2006.4.1

  The 3-ethoxycarbonyl-4-quinolone compound I has previously been identified via a database search as an interesting lead compound for ligand binding at the benzodiazepine site of GABA(A) receptors (Kahnberg et al. J. Mol. Graphics Modelling 2004, 23, 253-261). Pharmacophore-guided optimization of this lead compound yielded a number of high-affinity ligands for the benzodiazepine site including compounds 20 and 23-25 displaying sub-nanomolar affinities. A few of the compounds have been tested on the alpha(1)beta(2)gamma(2s) and alpha(3)beta(2)gamma(2s) GABA(A) receptor subtypes, and two of the compounds (5 and 19) display selectivity for alpha(1) versus alpha(3)-containing receptors by a factor of 22 and 27, respectively. This selectivity for alpha(1)beta(2)gamma(2s) is in the same range as that for the well-known alpha(1) subunit selective compound zolpidem.
• Ruthenium arene complexes as HIV-1 integrase strand transfer inhibitors
  作者：Mauro Carcelli、Alessia Bacchi、Paolo Pelagatti、Gabriele Rispoli、Dominga Rogolino、Tino W. Sanchez、Mario Sechi、Nouri Neamati

  DOI：10.1016/j.jinorgbio.2012.09.021

  日期：2013.1

  The quinolone HL1 and the hydroxypyrimidine-carboxamide HL2 were designed and synthesized as models of the HIV integrase strand transfer inhibitors Elvitegravir and Raltegravir (brand name Isentress), with the aim to study their complexing behavior and their biological activity. The Ru(arene) complexes [RuCl(eta(6)-p-cym)L-1], [RuCl(eta(6)-p-cym)L-2] and [RuCl(hexamethylbenzene)(L)2] were also synthesized and spectroscopically characterized and their X-ray diffraction structures were discussed. The ligands and the complexes showed inhibition potency in the sub/low-micromolar concentration range in anti-HIV-1 integrase enzymatic assays, with selectivity toward strand transfer catalytic process, without any significant cytotoxicity on cancer cells. (C) 2012 Elsevier Inc. All rights reserved.