6-溴-1-[(1S)-1-[[[(1,1-二甲基乙基)二甲基硅烷基]氧基]甲基]-2-甲基丙基]-7-氟-1,4-二氢-4-氧代-3-喹啉羧酸乙酯 | 934161-52-1

• 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
• 中文名称: 6-溴-1-[(1S)-1-[[[(1,1-二甲基乙基)二甲基硅烷基]氧基]甲基]-2-甲基丙基]-7-氟-1,4-二氢-4-氧代-3-喹啉羧酸乙酯
• 中文别名: 6-溴-1-[(1S)-1-[[[(1,1-二甲基乙基)二甲基甲硅烷基]氧基]甲基]-2-甲基丙基]-7-氟-1,4-二氢-4-氧代-3-喹啉羧酸乙酯
• 英文名称: 6-bromo-1-((S)-1-tert-butyldimethylsilyloxymethyl-2-methylpropyl)-7-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl ester
• 英文别名: 6-Bromo-1-[(1S)-1-[[[(1,1-dimethylethyl)dimethylsilyl]oxy]methyl]-2-methylpropyl]-7-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic Acid Ethyl Ester；ethyl 6-bromo-1-[(2S)-1-[tert-butyl(dimethyl)silyl]oxy-3-methylbutan-2-yl]-7-fluoro-4-oxoquinoline-3-carboxylate
• CAS: 934161-52-1
• 化学式: C₂₃H₃₃BrFNO₄Si
• 分子量: 514.507
• InChiKey: ABRLFILUFAWDIN-HXUWFJFHSA-N

物化性质

• 溶解度：
  可溶于二氯甲烷、乙酸乙酯、甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  31
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-chloro-2-fluorobenzylzinc bromide 、 6-溴-1-[(1S)-1-[[[(1,1-二甲基乙基)二甲基硅烷基]氧基]甲基]-2-甲基丙基]-7-氟-1,4-二氢-4-氧代-3-喹啉羧酸乙酯 在 tris-(dibenzylideneacetone)dipalladium(0) 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 反应 6.0h， 生成 (S)-6-(3-氯-2-氟苄基)-7-氟-1-(1-羟基-3-甲基丁烷-2-基)-4-氧代-1,4-二氢喹啉-3-羧酸
  参考文献：
  名称：

  [EN] STABLE CRYSTAL OF 4-OXOQUINOLINE COMPOUND
  [FR] CRISTAL STABLE DE COMPOSE 4-OXOQUINOLINE

  摘要：

  本发明提供了6-(3-氯-2-氟苯甲基)-1-[(S)-1-羟甲基-2-甲基丙基]-7-甲氧基-4-氧代-1,4-二氢喹啉-3-羧酸的晶体，该晶体显示出特定的粉末X射线衍射图样，其在粉末X射线衍射仪测量的衍射角2θ（°）处有特征性衍射峰。本发明的晶体在物理和化学稳定性方面表现出优越性。

  公开号：

  WO2005113508A1
• 作为产物：
  描述：

  5-溴-2,4-二氟苯甲酸 在 N,N-二甲基甲酰胺 咪唑 、 氯化亚砜 、 1,8-diazabicyclo-[5,4,0]-undecane 作用下， 以 DMF (N,N-dimethyl-formamide) 、 甲苯 为溶剂， 反应 54.5h， 生成 6-溴-1-[(1S)-1-[[[(1,1-二甲基乙基)二甲基硅烷基]氧基]甲基]-2-甲基丙基]-7-氟-1,4-二氢-4-氧代-3-喹啉羧酸乙酯
  参考文献：
  名称：

  [EN] STABLE CRYSTAL OF 4-OXOQUINOLINE COMPOUND
  [FR] CRISTAL STABLE DE COMPOSE 4-OXOQUINOLINE

  摘要：

  本发明提供了6-(3-氯-2-氟苯甲基)-1-[(S)-1-羟甲基-2-甲基丙基]-7-甲氧基-4-氧代-1,4-二氢喹啉-3-羧酸的晶体，该晶体显示出特定的粉末X射线衍射图样，其在粉末X射线衍射仪测量的衍射角2θ（°）处有特征性衍射峰。本发明的晶体在物理和化学稳定性方面表现出优越性。

  公开号：

  WO2005113508A1

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，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制药组合物；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；一种含有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，该剂用于与其他抗HIV剂进行多药疗法等。
• [EN] AN IMPROVED PROCESS FOR THE PREPARATION OF ELVITEGRAVIR<br/>[FR] PROCÉDÉ AMÉLIORÉ POUR LA PRÉPARATION D'ELVITEGRAVIR
  申请人：MATRIX LAB LTD

  公开号：WO2011004389A2

  公开（公告）日：2011-01-13

  The present invention relates to improved process for the preparation of elvitegravir (12), wherein the compound of formula (6) is protected with suitable protecting agents and further reacted with formula (9) in the presence of tetrakis(triphenylphosphine)-palladium (0) catalyst in tetrahydofuran to get corresponding condensed products, which are subjected to hydrolysis, de-protection to get compound of formula (11). The compound of formula (11) is optionally treated with amine to get amine addition salt of formula (11D), then setting free of amine salt in the presence of acid to get pure compound of formula (11). The pure compound of formula (11) is reacted with sodium alkoxide to get pure elvitegravir (12).

  本发明涉及改进的工艺，用于制备埃来替格韦（12），其中式（6）化合物受到适当的保护剂保护，并在四氢呋喃中在四苯基膦钯（0）催化剂的存在下与式（9）进一步反应，以得到相应的缩合产物，这些产物经过水解、脱保护后得到式（11）的化合物。式（11）的化合物可以选择用胺进行处理，以得到式（11D）的胺加成盐，然后在酸的存在下释放胺盐以得到纯的式（11）化合物。纯的式（11）化合物与钠烷基化合物反应，得到纯的埃来替格韦（12）。
• [EN] COMBINATIONS COMPRISING A 4-ISOQUINOLONE DERIVATIVE AND ANTI-HIV AGENTS<br/>[FR] ASSOCIATIONS COMPRENANT UN DÉRIVÉ DE 4-ISOQUINOLONE ET DES AGENTS ANTI-VIH
  申请人：JAPAN TOBACCO INC

  公开号：WO2005112930A1

  公开（公告）日：2005-12-01

  The present invention relates to a combination therapy for treating an HIV infection or inhibiting integrase comprising (S)-6-(3-chloro-2-fluorobenzyl)-1-(1-hydroxymethyl-2-methylpropyl)-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ('Compound A') or a pharmaceutically acceptable solvate or salt thereof in combination with at least one other anti-HIV agent. In some embodiments of the present invention, the other anti-HIV agents are chosen from reverse transcriptase inhibitors and protease inhibitors. In certain embodiments of the present invention, the other anti-HIV agents are chosen from AZT, 3TC, PMPA, efavirenz, indinavir, nelfinavir, a combination of AZT/3TC, and a combination of PMPA/3TC. Since Compound A has a high inhibitory activity specific for integrases, when used in combinations with other anti-HIV agents it can provide a combination therapy with fewer side effects for humans.

  本发明涉及一种联合治疗艾滋病毒感染或抑制整合酶的组合疗法，包括（S）-6-（3-氯-2-氟苯基）-1-（1-羟甲基-2-甲基丙基）-7-甲氧基-4-氧代-1,4-二氢喹啉-3-羧酸（“化合物A”）或其药学上可接受的溶剂化合物或盐与至少一种其他抗艾滋病毒药物的联合使用。在本发明的某些实施例中，其他抗艾滋病毒药物选择自反转录酶抑制剂和蛋白酶抑制剂。在本发明的某些实施例中，其他抗艾滋病毒药物选择自AZT、3TC、PMPA、依法韦仑、吲哚那韦、奈非那韦、AZT/3TC的组合和PMPA/3TC的组合。由于化合物A对整合酶具有高度的抑制活性，当与其他抗艾滋病毒药物联合使用时，可为人类提供更少的副作用的联合治疗。
• [EN] 4-OXOQUINOLINE COMPOUNDS AND UTILIZATION THEREOF AS HIV INTEGRASE INHIBITORS<br/>[FR] COMPOSES 4-OXOQUINOLINIQUES ET LEUR UTILISATION COMME INHIBITEUR DE LA VIH-INTEGRASE
  申请人：JAPAN TOBACCO INC

  公开号：WO2004046115A1

  公开（公告）日：2004-06-03

  4-Oxoquinoline compounds represented by the following general formula [I]: [I] wherein each symbol has the meaning as defined in the description; or pharmaceutically acceptable salts thereof and anti-HIV agents containing these compounds. Because of having an activity of inhibiting HIV integrase, the above compounds are useful as anti-HIV agents in remedies or preventives for AIDS. By using together with other anti-HIV agents such as a protease inhibitor and a reverse transcriptase inhibitor, the above compounds can be used as more efficacious anti-HIV agents. Because of having a high inhibitory activity specific to the integrase, furthermore, these compounds are usable as drugs which are safe to the human body with little side effect.

  以下为4-氧基喹啉化合物的一般式[I]：[I]，其中每个符号的含义如描述中所定义；或其药学上可接受的盐和含有这些化合物的抗HIV制剂。由于具有抑制HIV整合酶的活性，上述化合物在治疗或预防艾滋病的药物中作为抗HIV制剂是有用的。通过与其他抗HIV药物（如蛋白酶抑制剂和反转录酶抑制剂）一起使用，上述化合物可用作更有效的抗HIV药物。此外，由于具有高特异性整合酶抑制活性，这些化合物可用作对人体安全且副作用较小的药物。
• 4-oxoquinoline compound and use thereof as pharmaceutical agent
  申请人：Japan Tobacco Inc.

  公开号：US07176220B2

  公开（公告）日：2007-02-13

  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，其有效成分为以下式[I]所示的4-氧喹啉化合物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，该化合物可成为更有效的抗HIV药剂。由于该化合物对整合酶具有高度的抑制活性，因此可以提供一种对人类副作用较少的安全药物。