(E)-3-[4-[[1-[[2-(5-chloropyridin-2-yl)-3-cyclopentyl-1-methylindole-6-carbonyl]amino]cyclobutanecarbonyl]amino]phenyl]prop-2-enoic acid | 494856-45-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (E)-3-[4-[[1-[[2-(5-chloropyridin-2-yl)-3-cyclopentyl-1-methylindole-6-carbonyl]amino]cyclobutanecarbonyl]amino]phenyl]prop-2-enoic acid
• CAS: 494856-45-0
• 化学式: C₃₄H₃₃ClN₄O₄
• 分子量: 597.113
• InChiKey: DSQHZRQDKSGPJS-CXUHLZMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  43
• 可旋转键数：
  8
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  113
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  6-吲哚甲酸 在 正丁基锂 、 20% Pd(OH)2/C 、 水 、 氢气 、 溴 、 sodium acetate 、 palladium diacetate 、 potassium carbonate 、 三对苯甲基膦 、 potassium hydroxide 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 醋酸异丙酯 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， -71.0~75.0 ℃ 、101.33 kPa 条件下， 反应 48.67h， 生成 (E)-3-[4-[[1-[[2-(5-chloropyridin-2-yl)-3-cyclopentyl-1-methylindole-6-carbonyl]amino]cyclobutanecarbonyl]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