methyl 2-oxo-2-(1H-pyrrolo[3,2-b]pyridin-3-yl)acetate

• 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: methyl 2-oxo-2-(1H-pyrrolo[3,2-b]pyridin-3-yl)acetate
• 英文别名: methyl α-oxo-4-azaindole-3-acetate；methyl (4-azaindol-3-yl)-oxoacetate
• 化学式: C₁₀H₈N₂O₃
• 分子量: 204.185
• InChiKey: JXRFNUSMOZOQDN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  72
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 2-oxo-2-(1H-pyrrolo[3,2-b]pyridin-3-yl)acetate 在 水 、 potassium carbonate 作用下， 以 甲醇 为溶剂， 反应 16.0h， 生成 2-氧代-1H-吡咯并[3,2-b]吡啶-3-乙酸
  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：

  甲基戊酰氯 、 4-氮杂吲哚 在 三氯化铝 作用下， 以 二氯甲烷 为溶剂， 以42%的产率得到methyl 2-oxo-2-(1H-pyrrolo[3,2-b]pyridin-3-yl)acetate
  参考文献：
  名称：

  An Effective Procedure for the Acylation of Azaindoles at C-3

  摘要：

  Conditions for attachment of acetyl chloride, benzoyl chloride, and chloromethyl oxalate to the 3-position of 4-, 5-, 6-, or 7-azaindoles were explored. Best results were achieved with an excess of AlCl3 in CH2Cl2 followed by the addition of an acyl chloride at room temperature.

  DOI：

  10.1021/jo020135i

文献信息

• 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。
• 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.
• An Effective Procedure for the Acylation of Azaindoles at C-3
  作者：Zhongxing Zhang、Zhong Yang、Henry Wong、Juliang Zhu、Nicholas A. Meanwell、John F. Kadow、Tao Wang

  DOI：10.1021/jo020135i

  日期：2002.8.1

  Conditions for attachment of acetyl chloride, benzoyl chloride, and chloromethyl oxalate to the 3-position of 4-, 5-, 6-, or 7-azaindoles were explored. Best results were achieved with an excess of AlCl3 in CH2Cl2 followed by the addition of an acyl chloride at room temperature.