(R)-1-(4-benzoyl-2-methylpiperazin-1-yl)-2-(1H-pyrrolo[3,2-c]-pyridin-3-yl)ethane-1,2-dione | 357262-77-2

• 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: (R)-1-(4-benzoyl-2-methylpiperazin-1-yl)-2-(1H-pyrrolo[3,2-c]-pyridin-3-yl)ethane-1,2-dione
• 英文别名: (R)-N-(benzoyl)-3-methyl-N'-[(5-azaindol-3-yl)-oxoacetyl]-piperazine；1-[(2R)-4-benzoyl-2-methyl-piperazin-1-yl]-2-(1H-pyrrolo[3,2-c]pyridin-3-yl)ethane-1,2-dione；1-[(2R)-4-benzoyl-2-methylpiperazin-1-yl]-2-(1H-pyrrolo[3,2-c]pyridin-3-yl)ethane-1,2-dione
• CAS: 357262-77-2
• 化学式: C₂₁H₂₀N₄O₃
• 分子量: 376.415
• InChiKey: ZWGZFELFBFJIHY-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  86.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (R)-1-苯甲酰基-3-甲基哌嗪盐酸盐 、 oxo-(1H-pyrrolo[3,2-c]pyridin-3-yl)-acetic acid 在 N,N-二异丙基乙胺 、 3-(二乙氧基邻酰氧基)-1,2,3-苯并三嗪-4-酮 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以12.5 mg的产率得到(R)-1-(4-benzoyl-2-methylpiperazin-1-yl)-2-(1H-pyrrolo[3,2-c]-pyridin-3-yl)ethane-1,2-dione
  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

• Antiviral azaindole derivatives
  申请人：——

  公开号：US20020119982A1

  公开（公告）日：2002-08-29

  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。
• US6476034B2
  申请人：——

  公开号：US6476034B2

  公开（公告）日：2002-11-05
• US6632819B1
  申请人：——

  公开号：US6632819B1

  公开（公告）日：2003-10-14
• US6900323B2
  申请人：——

  公开号：US6900323B2

  公开（公告）日：2005-05-31
• 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-1<i>H</i>-pyrrolo[2,3-<i>c</i>]pyridin-3-yl)ethane-1,2-dione (BMS-488043), a Drug Candidate That Demonstrates Antiviral Activity in HIV-1-Infected Subjects
  作者：Tao Wang、Zhiwei Yin、Zhongxing Zhang、John A. Bender、Zhong Yang、Graham Johnson、Zheng Yang、Lisa M. Zadjura、Celia J. D’Arienzo、Dawn DiGiugno Parker、Christophe Gesenberg、Gregory A. Yamanaka、Yi-Fei Gong、Hsu-Tso Ho、Hua Fang、Nannan Zhou、Brian V. McAuliffe、Betsy J. Eggers、Li Fan、Beata Nowicka-Sans、Ira B. Dicker、Qi Gao、Richard J. Colonno、Pin-Fang Lin、Nicholas A. Meanwell、John F. Kadow

  DOI：10.1021/jm900843g

  日期：2009.12.10

  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.