Ethyl 5-[(1-aminocyclobutanecarbonyl)amino]-1-methylindole-2-carboxylate | 1393928-31-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: Ethyl 5-[(1-aminocyclobutanecarbonyl)amino]-1-methylindole-2-carboxylate
• 英文别名: ethyl 5-[(1-aminocyclobutanecarbonyl)amino]-1-methylindole-2-carboxylate
• CAS: 1393928-31-8
• 化学式: C₁₇H₂₁N₃O₃
• 分子量: 315.372
• InChiKey: WJSOLBNAJSJDMS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  86.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-Cyclopentyl-1-methyl-2-(6-methyl-3-pyridyl)indole-6-carboxylic acid 、 Ethyl 5-[(1-aminocyclobutanecarbonyl)amino]-1-methylindole-2-carboxylate 以 二甲基亚砜 为溶剂， 生成
  参考文献：
  名称：

  Discovery of the First Thumb Pocket 1 NS5B Polymerase Inhibitor (BILB 1941) with Demonstrated Antiviral Activity in Patients Chronically Infected with Genotype 1 Hepatitis C Virus (HCV)

  摘要：

  Combinations of direct acting antivirals (DAAs) that have the potential to suppress emergence of resistant virus and that can be used in interferon-sparing regimens represent a preferred option for the treatment of chronic HCV infection. We have discovered allosteric (thumb pocket 1) non-nucleoside inhibitors of HCV NS5B polymerase that inhibit replication in replicon systems. Herein, we report the late-stage optimization of indole-based inhibitors, which began with the identification of a metabolic liability common to many previously reported inhibitors in this series. By use of parallel synthesis techniques, a sparse matrix of inhibitors was generated that provided a collection of inhibitors satisfying potency criteria and displaying improved in vitro ADME profiles. "Cassette" screening for oral absorption in rat provided a short list of potential development candidates. Further evaluation led to the discovery of the first thumb pocket 1 NS5B inhibitor (BILB 1941) that demonstrated antiviral activity in patients chronically infected with genotype 1 HCV.

  DOI：

  10.1021/jm3006788
• 作为产物：
  描述：

  1-氨基环丁甲酸 在 吡啶 、 2-唑烷酮 、 五氯化磷 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 22.0h， 生成 Ethyl 5-[(1-aminocyclobutanecarbonyl)amino]-1-methylindole-2-carboxylate
  参考文献：
  名称：

  Discovery of the First Thumb Pocket 1 NS5B Polymerase Inhibitor (BILB 1941) with Demonstrated Antiviral Activity in Patients Chronically Infected with Genotype 1 Hepatitis C Virus (HCV)

  摘要：

  Combinations of direct acting antivirals (DAAs) that have the potential to suppress emergence of resistant virus and that can be used in interferon-sparing regimens represent a preferred option for the treatment of chronic HCV infection. We have discovered allosteric (thumb pocket 1) non-nucleoside inhibitors of HCV NS5B polymerase that inhibit replication in replicon systems. Herein, we report the late-stage optimization of indole-based inhibitors, which began with the identification of a metabolic liability common to many previously reported inhibitors in this series. By use of parallel synthesis techniques, a sparse matrix of inhibitors was generated that provided a collection of inhibitors satisfying potency criteria and displaying improved in vitro ADME profiles. "Cassette" screening for oral absorption in rat provided a short list of potential development candidates. Further evaluation led to the discovery of the first thumb pocket 1 NS5B inhibitor (BILB 1941) that demonstrated antiviral activity in patients chronically infected with genotype 1 HCV.

  DOI：

  10.1021/jm3006788