(4,7-dimethoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)oxoacetic acid ethyl ester | 452296-81-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• 英文名称: (4,7-dimethoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)oxoacetic acid ethyl ester
• 英文别名: Ethyl (4,7-dimethoxy-6-azaindol-3-yl)-oxoacetate；Ethyl(4,7-dimethoxy-6-azaindol-3-yl)-oxoacetate；ethyl 2-(4,7-dimethoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-oxoacetate
• CAS: 452296-81-0
• 化学式: C₁₃H₁₄N₂O₅
• 分子量: 278.265
• InChiKey: KCVRXDOZIALZNU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  90.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (4,7-dimethoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)oxoacetic acid ethyl ester 在 水 、 potassium carbonate 作用下， 以 甲醇 为溶剂， 反应 6.0h， 以60%的产率得到potassium (4,7-dimethoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)-oxoacetate
  参考文献：
  名称：

  Inhibitors of Human Immunodeficiency Virus Type 1 (HIV-1) Attachment. 5. An Evolution from Indole to Azaindoles Leading to the Discovery of 1-(4-Benzoylpiperazin-1-yl)-2-(4,7-dimethoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)ethane-1,2-dione (BMS-488043), a Drug Candidate That Demonstrates Antiviral Activity in HIV-1-Infected Subjects

  摘要：

  Azaindole derivatives derived from the screening lead 1-(4-benzoylpiperazin-1-yl)-2-(1H-indol-3-yl)ethane-1,2-dione (1) were prepared and characterized to assess their potential as inhibitors of HIV-1 attachment. Systematic replacement of each of the unfused carbon atoms in the phenyl ring of the indole moiety by a nitrogen atom provided four different azaindole derivatives that displayed it clear SAR for antiviral activity and all of which displayed marked improvements in pharmaceutical properties. Optimization of these azaindole leads resulted in the identification of two compounds that were advanced to clinical studies: (R)-1-(4-benzoyl-2-methylpiperazin-1-yl)-2-(4-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)ethane-1,2-dione (BMS-377806, 3) and 1-(4-benzoylpiperazin-1-yl)-2-(4,7-dimethoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)ethane-1,2-dione (BMS-488043, 4). In a preliminary clinical study, 4 administered as monotherapy for 8 days, reduced viremia in HIV-1-infected Subjects, providing proof of concept for this mechanistic class.

  DOI：

  10.1021/jm900843g
• 作为产物：
  描述：

  4,7-二甲氧基-1H-吡咯[2,3-C]吡啶 、 草酰氯单乙酯 在 aluminum (III) chloride 作用下， 以 二氯甲烷 为溶剂， 反应 2.5h， 以87%的产率得到(4,7-dimethoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)oxoacetic acid ethyl ester
  参考文献：
  名称：

  Inhibitors of Human Immunodeficiency Virus Type 1 (HIV-1) Attachment. 5. An Evolution from Indole to Azaindoles Leading to the Discovery of 1-(4-Benzoylpiperazin-1-yl)-2-(4,7-dimethoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)ethane-1,2-dione (BMS-488043), a Drug Candidate That Demonstrates Antiviral Activity in HIV-1-Infected Subjects

  摘要：

  Azaindole derivatives derived from the screening lead 1-(4-benzoylpiperazin-1-yl)-2-(1H-indol-3-yl)ethane-1,2-dione (1) were prepared and characterized to assess their potential as inhibitors of HIV-1 attachment. Systematic replacement of each of the unfused carbon atoms in the phenyl ring of the indole moiety by a nitrogen atom provided four different azaindole derivatives that displayed it clear SAR for antiviral activity and all of which displayed marked improvements in pharmaceutical properties. Optimization of these azaindole leads resulted in the identification of two compounds that were advanced to clinical studies: (R)-1-(4-benzoyl-2-methylpiperazin-1-yl)-2-(4-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)ethane-1,2-dione (BMS-377806, 3) and 1-(4-benzoylpiperazin-1-yl)-2-(4,7-dimethoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)ethane-1,2-dione (BMS-488043, 4). In a preliminary clinical study, 4 administered as monotherapy for 8 days, reduced viremia in HIV-1-infected Subjects, providing proof of concept for this mechanistic class.

  DOI：

  10.1021/jm900843g

文献信息

• Prodrugs of piperazine and substituted piperidine antiviral agents
  申请人：Ueda Yasutsugu

  公开号：US20050209246A1

  公开（公告）日：2005-09-22

  This invention provides for prodrug Compounds I, pharmaceutical compositions thereof, and their use in treating HIV infection. wherein: X is C or N with the proviso that when X is N, R 1 does not exist; W is C or N with the proviso that when W is N, R 2 does not exist; V is C; E is hydrogen or a pharmaceutically acceptable salt thereof; and Y is selected from the group consisting of Also, this invention provides for intermediate Compounds II useful in making prodrug Compounds I. wherein: L and M are independently selected from the group consisting of C 1 -C 6 alkyl, phenyl, benzyl, trialkylsilyl, -2,2,2-trichloroethoxy and 2-trimethylsilylethoxy.

  这项发明提供了前药化合物I，其药物组成物以及它们在治疗HIV感染中的用途。 其中： X为C或N，但当X为N时，R1不存在； W为C或N，但当W为N时，R2不存在；V为C；E为氢或其药用可接受盐；以及 Y从以下组中选择： 此外，这项发明提供了制备前药化合物I的有用中间体化合物II。 其中： L和M独立地选自C1-C6烷基，苯基，苯甲基，三烷基硅基，-2,2,2-三氯乙氧基和2-三甲基硅基乙氧基的组。
• Antiviral azaindole derivatives
  申请人：——

  公开号：US20030181463A1

  公开（公告）日：2003-09-25

  The present invention is directed to a series of chemical entities that express HIV-1 inhibitory activities.

  本发明涉及一系列具有HIV-1抑制活性的化学实体。
• PRODRUGS OF PIPERAZINE AND SUBSTITUTED PIPERIDINE ANTIVIRAL AGENTS
  申请人：Ueda Yasutsugu

  公开号：US20100210599A1

  公开（公告）日：2010-08-19

  This invention provides for prodrug Compounds I, pharmaceutical compositions thereof, and their use in treating HIV infection. wherein: X is C or N with the proviso that when X is N, R 1 does not exist; W is C or N with the proviso that when W is N, R 2 does not exist; V is C; E is hydrogen or a pharmaceutically acceptable salt thereof; and Y is selected from the group consisting of Also, this invention provides for intermediate Compounds II useful in making prodrug Compounds I. wherein: L and M are independently selected from the group consisting of C 1 -C 6 alkyl, phenyl, benzyl, trialkylsilyl, -2,2,2-trichloroethoxy and 2-trimethylsilylethoxy.

  本发明提供了前药化合物I、其制药组合物以及它们在治疗HIV感染方面的使用。其中：X是C或N，但当X为N时，R1不存在；W是C或N，但当W为N时，R2不存在；V是C；E是氢或其药学上可接受的盐；Y选择自下列组合中的一种：此外，本发明还提供了制备前药化合物I有用的中间体化合物II，其中：L和M独立地选择自C1-C6烷基、苯基、苄基、三烷基硅基、-2,2,2-三氯乙氧基和2-三甲基硅基乙氧基的组合中。
• SALTS OF PRODRUGS OF PIPERAZINE AND SUBSTITUTED PIPERIDINE ANTIVIRAL AGENTS
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：US20130253196A1

  公开（公告）日：2013-09-26

  This invention provides for prodrug Compounds I, pharmaceutical compositions thereof, and their use in treating HIV infection. wherein: X is C or N with the proviso that when X is N, R 1 does not exist; W is C or N with the proviso that when W is N, R 2 does not exist; V is C; E is hydrogen or a pharmaceutically acceptable salt thereof; and Y is selected from the group consisting of Also, this invention provides for intermediate Compounds II useful in making prodrug Compounds I. wherein: L and M are independently selected from the group consisting of C 1 -C 6 alkyl, phenyl, benzyl, trialkylsilyl, -2,2,2-trichloroethoxy and 2-trimethylsilylethoxy.

  这项发明提供了前药化合物I，其制药组合物以及它们在治疗HIV感染方面的应用。其中：X为C或N，但当X为N时，R1不存在；W为C或N，但当W为N时，R2不存在；V为C；E为氢或其药学上可接受的盐；Y为从以下组中选择的：此外，这项发明还提供了制备前药化合物I有用的中间体化合物II。其中：L和M独立地选择自C1-C6烷基、苯基、苄基、三烷基硅基、-2,2,2-三氯乙氧基和2-三甲基硅基乙氧基的组中。
• Salts of prodrugs of piperazine and substituted piperidine antiviral agents
  申请人：Ueda Yasutsugu

  公开号：US08461333B2

  公开（公告）日：2013-06-11

  This invention provides for prodrug Compounds I, pharmaceutical compositions thereof, and their use in treating HIV infection. wherein: X is C or N with the proviso that when X is N, R1 does not exist; W is C or N with the proviso that when W is N, R2 does not exist; V is C; E is hydrogen or a pharmaceutically acceptable salt thereof; and Y is selected from the group consisting of Also, this invention provides for intermediate Compounds II useful in making prodrug Compounds I. wherein: L and M are independently selected from the group consisting of C1-C6 alkyl, phenyl, benzyl, trialkylsilyl, -2,2,2-trichloroethoxy and 2-trimethylsilylethoxy.

  本发明提供了前药化合物I，其药物组成物以及它们在治疗HIV感染中的使用。其中：X为C或N，但当X为N时，R1不存在；W为C或N，但当W为N时，R2不存在；V为C；E为氢或其药学上可接受的盐；Y被选自以下一组：此外，本发明还提供了有用于制备前药化合物I的中间体化合物II。其中：L和M从以下一组中独立选择：C1-C6烷基、苯基、苄基、三烷基硅基、-2,2,2-三氯乙氧基和2-三甲基硅基乙氧基。