6-(2,3-dichlorobenzyl)-7-fluoro-1-(2-hydroxyethyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid

• 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-(2,3-dichlorobenzyl)-7-fluoro-1-(2-hydroxyethyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
• 英文别名: 6-[(2,3-Dichlorophenyl)methyl]-7-fluoro-1-(2-hydroxyethyl)-4-oxo-quinoline-3-carboxylic acid；6-[(2,3-dichlorophenyl)methyl]-7-fluoro-1-(2-hydroxyethyl)-4-oxoquinoline-3-carboxylic acid
• 化学式: C₁₉H₁₄Cl₂FNO₄
• 分子量: 410.229
• InChiKey: DRDHSNVHWKKIHX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  27
• 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：
  77.8
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  1-(2-tert-butyldimethylsilyloxyethyl)-6-(2,3-dichlorobenzyl)-7-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl ester 在 乙醇 、 水 、 sodium hydroxide 、 溶剂黄146 作用下， 反应 1.0h， 生成 6-(2,3-dichlorobenzyl)-7-fluoro-1-(2-hydroxyethyl)-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

• 4-Oxoquinoline compound and use thereof as HIV integrase inhibitor
  申请人：Satoh Motohide

  公开号：US20060217413A1

  公开（公告）日：2006-09-28

  An anti-HIV agent containing, as an active ingredient, a 4-oxoquinoline compound represented by the following formula [I] wherein each symbol is as defined in the specification, or a pharmaceutically acceptable salt thereof. The compound of the present invention has HIV integrase inhibitory action and is useful as an anti-HIV agent for the prophylaxis or therapy of AIDS. Moreover, by a combined use with other anti-HIV agents such as protease inhibitors, reverse transcriptase inhibitors and the like, the compound can become a more effective anti-HIV agent. Since the compound has high inhibitory activity specific for integrases, it can provide a safe pharmaceutical agent with a fewer side effects for human.

  一种抗HIV剂，其包含以下式[I]所表示的活性成分4-氧喹啉化合物，其中每个符号如规范中所定义，或其药学上可接受的盐。本发明的化合物具有HIV整合酶抑制作用，并可用作预防或治疗艾滋病的抗HIV剂。此外，与其他抗HIV剂（如蛋白酶抑制剂、反转录酶抑制剂等）联合使用，该化合物可以成为更有效的抗HIV剂。由于该化合物具有针对整合酶的高抑制活性，因此可以为人类提供更安全的药物，副作用更少。
• 4-OXOQUINOLINE COMPOUND AND USE THEREOF AS PHARMACEUTICAL AGENT
  申请人：Japan Tobacco Inc.

  公开号：US20150174117A1

  公开（公告）日：2015-06-25

  An anti-HIV agent containing, as an active ingredient, a 4-oxoquinoline compound represented by the following formula [I] wherein each symbol is as defined in the specification, or a pharmaceutically acceptable salt thereof. The compound of the present invention has HIV integrase inhibitory action and is useful as an anti-HIV agent for the prophylaxis or therapy of AIDS. Moreover, by a combined use with other anti-HIV agents such as protease inhibitors, reverse transcriptase inhibitors and the like, the compound can become a more effective anti-HIV agent. Since the compound has high inhibitory activity specific for integrases, it can provide a safe pharmaceutical agent with a fewer side effects for human.

  一种抗HIV剂，其活性成分为以下式[I]所代表的4-氧喹啉化合物，其中每个符号在规范中定义，或其药学上可接受的盐。本发明的化合物具有HIV整合酶抑制作用，并且可用作预防或治疗艾滋病的抗HIV剂。此外，通过与其他抗HIV剂（如蛋白酶抑制剂，逆转录酶抑制剂等）的联合使用，该化合物可以成为更有效的抗HIV剂。由于该化合物具有高度特异性的整合酶抑制活性，因此可以提供一种对人体副作用较少的安全药物。
• 4-OXOQUINOLINE COMPOUND AND USE THEREOF AS HIV INTEGRASE INHIBITOR
  申请人：SATOH Motohide

  公开号：US20130172344A1

  公开（公告）日：2013-07-04

  An anti-HIV agent containing, as an active ingredient, a 4-oxoquinoline compound represented by the following formula [I] wherein each symbol is as defined in the specification, or a pharmaceutically acceptable salt thereof. The compound of the present invention has HIV integrase inhibitory action and is useful as an anti-HIV agent for the prophylaxis or therapy of AIDS. Moreover, by a combined use with other anti-HIV agents such as protease inhibitors, reverse transcriptase inhibitors and the like, the compound can become a more effective anti-HIV agent. Since the compound has high inhibitory activity specific for integrases, it can provide a safe pharmaceutical agent with a fewer side effects for human.

  一种抗HIV药剂，其含有以下式[I]所表示的4-氧喹啉化合物作为活性成分，其中每个符号如规范中所定义，或其药学上可接受的盐。本发明的化合物具有HIV整合酶抑制作用，可用于预防或治疗艾滋病的抗HIV药剂。此外，与其他抗HIV药剂（如蛋白酶抑制剂、反转录酶抑制剂等）联合使用，该化合物可以成为更有效的抗HIV药剂。由于该化合物具有针对整合酶的高抑制活性，因此可以提供一种对人体副作用更少的安全药物。
• 4-oxoquinoline compound and use thereof as hiv integrase inhibitor
  申请人：Japan Tobacco Inc.

  公开号：EP2161258A2

  公开（公告）日：2010-03-10

  An anti-HIV agent containing, as an active ingredient, a 4-oxoquinoline compound represented by the following formula [I] wherein each symbol is as defined in the specification, or a pharmaceutically acceptable salt thereof. The compound of the present invention has HIV integrase inhibitory action and is useful as an anti-HIV agent for the prophylaxis or therapy of AIDS. Moreover, by a combined use with other anti-HIV agents such as protease inhibitors, reverse transcriptase inhibitors and the like, the compound can become a more effective anti-HIV agent. Since the compound has high inhibitory activity specific for integrases, it can provide a safe pharmaceutical agent with a fewer side effects for human.

  一种抗HIV剂，其包含一个由以下式[I]表示的4-氧喹啉化合物作为活性成分，其中每个符号如规范中所定义，或其药学上可接受的盐。本发明的化合物具有HIV整合酶抑制作用，并且可用作预防或治疗艾滋病的抗HIV剂。此外，与其他抗HIV剂（如蛋白酶抑制剂，逆转录酶抑制剂等）的联合使用，该化合物可以成为更有效的抗HIV剂。由于该化合物具有特异性高的整合酶抑制活性，因此可以提供一种具有更少副作用的安全药物。
• 4-Oxoquinoline compounds and utilization thereof as hiv integrase inhibitors
  申请人：Satoh Motohide

  公开号：US20050239819A1

  公开（公告）日：2005-10-27

  An anti-HIV agent containing, as an active ingredient, a 4-oxoquinoline compound represented by the following formula [I] wherein each symbol is as defined in the specification, or a pharmaceutically acceptable salt thereof. The compound of the present invention has HIV integrase inhibitory action and is useful as an anti-HIV agent for the prophylaxis or therapy of AIDS. Moreover, by a combined use with other anti-HIV agents such as protease inhibitors, reverse transcriptase inhibitors and the like, the compound can become a more effective anti-HIV agent. Since the compound has high inhibitory activity specific for integrases, it can provide a safe pharmaceutical agent with a fewer side effects for human.

  一种含有4-氧喹啉化合物的抗HIV剂，该4-氧喹啉化合物由下式[I]所表示的活性成分组成，其中每个符号如规范中所定义，或其药学上可接受的盐。本发明的化合物具有HIV整合酶抑制作用，并可用作预防或治疗艾滋病的抗HIV剂。此外，与其他抗HIV剂（如蛋白酶抑制剂，逆转录酶抑制剂等）联合使用，该化合物可以成为更有效的抗HIV剂。由于该化合物具有高度特异性的整合酶抑制活性，因此可以为人类提供具有较少副作用的安全药物。