3-Cyclopentyl-1-methyl-2-(1,3-oxazol-4-yl)indole-6-carboxylic acid | 1393927-97-3

• 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: 3-Cyclopentyl-1-methyl-2-(1,3-oxazol-4-yl)indole-6-carboxylic acid
• 英文别名: 3-cyclopentyl-1-methyl-2-(1,3-oxazol-4-yl)indole-6-carboxylic acid
• CAS: 1393927-97-3
• 化学式: C₁₈H₁₈N₂O₃
• 分子量: 310.353
• InChiKey: KYYSAVFTFWAMQA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  68.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-{4-[(1-amino-cyclopentanecarbonyl)-amino]-phenyl}-acrylic acid ethyl ester 、 3-Cyclopentyl-1-methyl-2-(1,3-oxazol-4-yl)indole-6-carboxylic acid 在 水 作用下， 以 二甲基亚砜 为溶剂， 生成 3-[4-[[1-[[3-cyclopentyl-1-methyl-2-(1,3-oxazol-4-yl)indole-6-carbonyl]amino]cyclopentanecarbonyl]amino]phenyl]prop-2-enoic acid
  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