3-[2-(4-benzoylpiperazin-1-yl)-2-oxo-acetyl]-4-fluoro-N-methyl-1H-pyrrolo[2,3-c]pyridine-7-carboxamide | 959321-16-5

• 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: 3-[2-(4-benzoylpiperazin-1-yl)-2-oxo-acetyl]-4-fluoro-N-methyl-1H-pyrrolo[2,3-c]pyridine-7-carboxamide
• 英文别名: 3-[2-(4-benzoylpiperazin-1-yl)-2-oxoacetyl]-4-fluoro-N-methyl-1H-pyrrolo[2,3-c]pyridine-7-carboxamide
• CAS: 959321-16-5
• 化学式: C₂₂H₂₀FN₅O₄
• 分子量: 437.43
• InChiKey: WZSGGXYLZMXILD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  32
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  116
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-氟-1H-吡咯并[2,3-c]吡啶-7-甲腈 在 N-甲基吗啉 、 aluminum (III) chloride 、 N-甲基吗啉氧化物 、 氯化 1-乙基-3-甲基咪唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 74.0h， 生成 3-[2-(4-benzoylpiperazin-1-yl)-2-oxo-acetyl]-4-fluoro-N-methyl-1H-pyrrolo[2,3-c]pyridine-7-carboxamide
  参考文献：
  名称：

  Inhibitors of Human Immunodeficiency Virus Type 1 (HIV-1) Attachment. 12. Structure–Activity Relationships Associated with 4-Fluoro-6-azaindole Derivatives Leading to the Identification of 1-(4-Benzoylpiperazin-1-yl)-2-(4-fluoro-7-[1,2,3]triazol-1-yl-1H-pyrrolo[2,3-c]pyridin-3-yl)ethane-1,2-dione (BMS-585248)

  摘要：

  A series of highly potent HIV-1 attachment inhibitors with 4-fluoro-6-azaindole core heterocycles that target the viral envelope protein gp120 has been prepared. Substitution in the 7-position of the azaindole core with amides (12a,b), C-linked heterocycles (12c-I), and N-linked heterocycles (12m-u) provided compounds with subnanomolar potency in a pseudotype infectivity assay and good pharmacokinetic profiles in vivo. A predictive model was developed from the initial SAR in which the potency of the analogues correlated with the ability of the substituent in the 7-position of the azaindole to adopt a coplanar conformation by either forming internal hydrogen bonds or avoiding repulsive substitution patterns. 1-(4-Benzoylpiperazin-1-yl)-2-(4-fluoro-7-[1,2,3]triazol-1-yl-1H-pyrrolo[2,3-c]pyridin-3-yl)ethane-1,2-dione (BMS-585248, 12m) exhibited much improved in vitro potency and pharmacokinetic properties than the previous clinical candidate BMS-488043 (1). The predicted low clearance in humans, modest protein binding, and good potency in the presence of 40% human serum for 12m led to its selection for human clinical studies.

  DOI：

  10.1021/jm3016377

文献信息

• Inhibitors of Human Immunodeficiency Virus Type 1 (HIV-1) Attachment. 12. Structure–Activity Relationships Associated with 4-Fluoro-6-azaindole Derivatives Leading to the Identification of 1-(4-Benzoylpiperazin-1-yl)-2-(4-fluoro-7-[1,2,3]triazol-1-yl-1<i>H</i>-pyrrolo[2,3-<i>c</i>]pyridin-3-yl)ethane-1,2-dione (BMS-585248)
  作者：Alicia Regueiro-Ren、Qiufen M. Xue、Jacob J. Swidorski、Yi-Fei Gong、Marina Mathew、Dawn D. Parker、Zheng Yang、Betsy Eggers、Celia D’Arienzo、Yongnian Sun、Jacek Malinowski、Qi Gao、Dedong Wu、David R. Langley、Richard J. Colonno、Caly Chien、Dennis M. Grasela、Ming Zheng、Pin-Fang Lin、Nicholas A. Meanwell、John F. Kadow

  DOI：10.1021/jm3016377

  日期：2013.2.28

  A series of highly potent HIV-1 attachment inhibitors with 4-fluoro-6-azaindole core heterocycles that target the viral envelope protein gp120 has been prepared. Substitution in the 7-position of the azaindole core with amides (12a,b), C-linked heterocycles (12c-I), and N-linked heterocycles (12m-u) provided compounds with subnanomolar potency in a pseudotype infectivity assay and good pharmacokinetic profiles in vivo. A predictive model was developed from the initial SAR in which the potency of the analogues correlated with the ability of the substituent in the 7-position of the azaindole to adopt a coplanar conformation by either forming internal hydrogen bonds or avoiding repulsive substitution patterns. 1-(4-Benzoylpiperazin-1-yl)-2-(4-fluoro-7-[1,2,3]triazol-1-yl-1H-pyrrolo[2,3-c]pyridin-3-yl)ethane-1,2-dione (BMS-585248, 12m) exhibited much improved in vitro potency and pharmacokinetic properties than the previous clinical candidate BMS-488043 (1). The predicted low clearance in humans, modest protein binding, and good potency in the presence of 40% human serum for 12m led to its selection for human clinical studies.