3-{4-[(1-amino-cyclopentanecarbonyl)-amino]-phenyl}-acrylic acid ethyl ester | 808126-08-1

• 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: 3-{4-[(1-amino-cyclopentanecarbonyl)-amino]-phenyl}-acrylic acid ethyl ester
• 英文别名: Ethyl 3-[4-[(1-aminocyclopentanecarbonyl)amino]phenyl]prop-2-enoate
• CAS: 808126-08-1
• 化学式: C₁₇H₂₂N₂O₃
• 分子量: 302.373
• InChiKey: YIKQXTMHTMGGQJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  81.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-[4-(4-carbamoyl-4'-chloro-biphen-2-ylmethoxy)-2-fluoro-phenyl]-1-cyclohexyl-1H-benzimidazole-5-carboxylic acid 、 3-{4-[(1-amino-cyclopentanecarbonyl)-amino]-phenyl}-acrylic acid ethyl ester 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 盐酸 、 sodium hydroxide 、 水 作用下， 以 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 0.5h， 以64%的产率得到3-(4-{[1-({2-[4-(4-carbamoyl-4'-chloro-biphen-2-ylmethoxy)-2-fluorophenyl]-1-cyclohexyl-1H-benzoimidazole-5-carbonyl}-amino)-cyclopentanecarbonyl]-amino}-phenyl)-acrylic acid
  参考文献：
  名称：

  [EN] NITROGEN-CONTAINING HETEROARYL DERIVATIVES FOR THE TREATMENT OF HCV-INFECTION
  [FR] DERIVES HETEROARYLES CONTENANT DE L'AZOTE

  摘要：

  公开号：

  WO2004108687A3
• 作为产物：
  描述：

  环亮氨酸 在 2-唑烷酮 、 potassium phosphate 、 五氯化磷 作用下， 以 乙腈 为溶剂， 生成 3-{4-[(1-amino-cyclopentanecarbonyl)-amino]-phenyl}-acrylic acid ethyl ester
  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