6-(2,3-dichlorobenzyl)-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)-1-(2-hydroxyethyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
• 英文别名: 6-(2,3-dichlorobenzyl)-1,4-dihydro-1-(2-hydroxyethyl)-4-oxo-3-quinolinecarboxylic acid；6-[(2,3-Dichlorophenyl)methyl]-1-(2-hydroxyethyl)-4-oxo-quinoline-3-carboxylic acid；6-[(2,3-dichlorophenyl)methyl]-1-(2-hydroxyethyl)-4-oxoquinoline-3-carboxylic acid
• 化学式: C₁₉H₁₅Cl₂NO₄
• 分子量: 392.238
• InChiKey: JZCZZGZHZXJOHY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  26
• 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：
  5

反应信息

• 作为产物：
  描述：

  1-(2-acetoxyethyl)-6-(2,3-dichlorobenzyl)-4-oxo-1,4-dihydroquinoline-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， 以72%的产率得到6-(2,3-dichlorobenzyl)-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

• [EN] NOVEL 4-OXOQUINOLINE COMPOUND AND USE THEREOF AS HIV INTEGRASE INHIBITOR<br/>[FR] NOUVEAU COMPOSÉ 4-OXOQUINOLINE ET UTILISATION DE CELUI-CI COMME INHIBITEUR D'INTÉGRASE DE VIH
  申请人：JAPAN TOBACCO INC

  公开号：WO2005113509A1

  公开（公告）日：2005-12-01

  Provision of a compound having an anti-HIV activity, particularly an integrase inhibitory activity.A 4-oxoquinoline compound represented by the following formula [I] or a pharmaceutically acceptable salt thereof: wherein each symbol is as defined in the specification.The present invention also relates to a pharmaceutical composition containing the 4-oxoquinoline compound or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier; an integrase inhibitor, an antiviral agent, anti-HIV agent and the like, which contains the 4-oxoquinoline compound or a pharmaceutically acceptable salt thereof as an active ingredient; an anti-HIV composition containing the 4-oxoquinoline compound or a pharmaceutically acceptable salt thereof, and one or more other kinds of anti-HIV activity substances as active ingredients; an anti-HIV agent containing the 4-oxoquinoline compound or a pharmaceutically acceptable salt thereof as an active ingredient, which is used for a multiple drug therapy with other anti-HIV agent(s), and the like.

  提供一种具有抗HIV活性的化合物，特别是整合酶抑制活性。一种由以下式[I]表示的4-氧喹啉化合物或其药学上可接受的盐：其中每个符号如规范中所定义。本发明还涉及含有4-氧喹啉化合物或其药学上可接受的盐以及药学上可接受的载体的药物组合物；一种整合酶抑制剂，抗病毒剂，抗HIV剂等，其中包含4-氧喹啉化合物或其药学上可接受的盐作为活性成分；一种抗HIV组合物，含有4-氧喹啉化合物或其药学上可接受的盐，以及一种或多种其他抗HIV活性物质作为活性成分；一种抗HIV剂，含有4-氧喹啉化合物或其药学上可接受的盐作为活性成分，用于与其他抗HIV剂进行多药疗法等。
• 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。
• Novel 4-oxoquinoline compound and use thereof as HIV integrase inhibitor
  申请人：Satoh Motohide

  公开号：US20060019906A1

  公开（公告）日：2006-01-26

  Provision of a compound having an anti-HIV activity, particularly an integrase inhibitory activity. A 4-oxoquinoline compound represented by the following formula [I] or a pharmaceutically acceptable salt thereof: wherein each symbol is as defined in the specification. The present invention also relates to a pharmaceutical composition containing the 4-oxoquinoline compound or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier; an integrase inhibitor, an antiviral agent, anti-HIV agent, and the like, which contains the 4-oxoquinoline compound or a pharmaceutically acceptable salt thereof as an active ingredient; an anti-HIV composition containing the 4-oxoquinoline compound or a pharmaceutically acceptable salt thereof, and one or more other kinds of anti-HIV activity substances as active ingredients; an anti-HIV agent containing the 4-oxoquinoline compound or a pharmaceutically acceptable salt thereof as an active ingredient, which is used for a multiple drug therapy with other anti-HIV agent(s), and the like.

  提供一种具有抗HIV活性，特别是整合酶抑制活性的化合物。该化合物为以下式[I]所表示的4-氧喹啉化合物或其药学上可接受的盐：其中每个符号如说明书中所定义。本发明还涉及含有4-氧喹啉化合物或其药学上可接受的盐以及药学上可接受的载体的制药组合物；含有4-氧喹啉化合物或其药学上可接受的盐作为活性成分的整合酶抑制剂、抗病毒剂、抗HIV剂等；含有4-氧喹啉化合物或其药学上可接受的盐以及一种或多种其他种类的抗HIV活性物质作为活性成分的抗HIV组合物；含有4-氧喹啉化合物或其药学上可接受的盐作为活性成分的抗HIV剂，可用于与其他抗HIV剂进行多种药物疗法等。
• 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。