6-(3-chlorobenzyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid | 1177255-93-4

• 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: 6-(3-chlorobenzyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
• 英文别名: 6-[(3-chlorophenyl)methyl]-4-oxo-1H-quinoline-3-carboxylic acid
• CAS: 1177255-93-4
• 化学式: C₁₇H₁₂ClNO₃
• 分子量: 313.74
• InChiKey: TVDJKFVGGSSMOS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  66.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  6-(3-chlorobenzyl)-4-oxo-1,4-dihyroquinoline-3-carboxylic acid ethyl ester 在 乙醇 、 水 、 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 3.5h， 生成 6-(3-chlorobenzyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
  参考文献：
  名称：

  Quinolone Carboxylic Acids as a Novel Monoketo Acid Class of Human Immunodeficiency Virus Type 1 Integrase Inhibitors

  摘要：

  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.

  DOI：

  10.1021/jm900460z

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。
• SUBSTITUTED QUINOLONES AND METHODS OF USE
  申请人：ChemoCentryx, Inc.

  公开号：EP1954274B8

  公开（公告）日：2011-01-12
• EP1954274A4
  申请人：——

  公开号：EP1954274A4

  公开（公告）日：2009-01-07
• AGENTS FOR USE IN THE TREATMENT OF CARDIOVASCULAR AND INFLAMMATORY DISEASES STRUCTURALLY BASED ON 4(1 H)-QUINOLONE
  申请人：UCL Business PLC

  公开号：EP3145914A1

  公开（公告）日：2017-03-29
• [EN] SUBSTITUTED QUINOLONES AND METHODS OF USE<br/>[FR] QUINOLONES SUBSTITUEES ET PROCEDES D'UTILISATION
  申请人：CHEMOCENTRYX INC

  公开号：WO2007059108A2

  公开（公告）日：2007-05-24

  [EN] Substituted quinolone compounds and compositions are provided along with methods for the use of those compounds in the treatment of diseases and disorders such as cancer.
  [FR] La présente invention concerne des composés quinolone substituée et des compositions ainsi que des procédés d'utilisation de ces composés dans le traitement de maladies et de troubles tels qu'un cancer.