5-氨基-2,3-二氢苯并呋喃-7-羧酸甲酯 | 1616110-67-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 香豆素
• 中文名称: 5-氨基-2,3-二氢苯并呋喃-7-羧酸甲酯
• 英文名称: methyl 5-amino-2,3-dihydrobenzofuran-7-carboxylate
• 英文别名: Methyl 5-amino-2,3-dihydrobenzofuran-7-carboxylate；methyl 5-amino-2,3-dihydro-1-benzofuran-7-carboxylate
• CAS: 1616110-67-8
• 化学式: C₁₀H₁₁NO₃
• 分子量: 193.202
• InChiKey: VHUHNEWQERKNBR-UHFFFAOYSA-N

物化性质

• 沸点：
  393.9±42.0 °C(Predicted)
• 密度：
  1.290±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  61.6
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 危险性防范说明：
  P264,P270,P301+P312,P330
• 危险性描述：
  H302

反应信息

• 作为反应物：
  描述：

  5-氨基-2,3-二氢苯并呋喃-7-羧酸甲酯 在 盐酸 、 tetrafluoroboric acid 、 sodium nitrite 作用下， 以 四氢呋喃 、 水 、 5,5-dimethyl-1,3-cyclohexadiene 为溶剂， 反应 2.0h， 以14%的产率得到methyl 5-Fluoro-2,3-dihydrobenzofuran-7-carboxylate
  参考文献：
  名称：

  Discovery and Structure–Activity Relationship of Novel 2,3-Dihydrobenzofuran-7-carboxamide and 2,3-Dihydrobenzofuran-3(2H)-one-7-carboxamide Derivatives as Poly(ADP-ribose)polymerase-1 Inhibitors

  摘要：

  Novel substituted 2,3-dihydrobenzofuran-7-carboxamide (DHBF-7-carboxamide) and 2,3-dihydrobenzofuran-3(2H)-one-7-carboxamide (DHBF-3-one-7-carboxamide) derivatives were synthesized and evaluated as inhibitors of poly(ADP-ribose)polymerase-1 (PARP-1). A structure-based design strategy resulted in lead compound 3 (DHBF-7-carboxamide; IC50 = 9.45 mu M). To facilitate synthetically feasible derivatives, an alternative core was designed, DHBF-3-one-7-carboxamide (36, IC50 = 16.2 mu M). The electrophilic 2-position of this scaffold was accessible for extended modifications. Substituted benzylidene derivatives at the 2-position were found to be the most potent, with 3',4'-dihydroxybenzylidene 58 (IC50 = 0.531 mu M) showing a 30-fold improvement in potency. Various heterocycles attached at the 4'-hydroxyl/4'-amino of the benzylidene moiety resulted in significant improvement in inhibition of PARP-1 activity (e.g., compounds 66-68, 70, 72, and 73; IC50 values from 0.718 to 0.079 mu M). Compound 66 showed selective cytotoxicity in BRCA2-deficient DT40 cells. Crystal structures of three inhibitors (compounds (-)-13c, 59, and 65) bound to a multidomain PARP-1 structure were obtained, providing insights into further development of these inhibitors.

  DOI：

  10.1021/jm5002502
• 作为产物：
  描述：

  2,3-二氢苯并呋喃 在 正丁基锂 、 四甲基乙二胺 、 硫酸 、 palladium 10% on activated carbon 、 氢气 、 硝酸 、 三氟乙酸 作用下， 以 乙醇 、 正己烷 为溶剂， 20.0 ℃ 、413.7 kPa 条件下， 反应 28.5h， 生成 5-氨基-2,3-二氢苯并呋喃-7-羧酸甲酯
  参考文献：
  名称：

  Discovery and Structure–Activity Relationship of Novel 2,3-Dihydrobenzofuran-7-carboxamide and 2,3-Dihydrobenzofuran-3(2H)-one-7-carboxamide Derivatives as Poly(ADP-ribose)polymerase-1 Inhibitors

  摘要：

  Novel substituted 2,3-dihydrobenzofuran-7-carboxamide (DHBF-7-carboxamide) and 2,3-dihydrobenzofuran-3(2H)-one-7-carboxamide (DHBF-3-one-7-carboxamide) derivatives were synthesized and evaluated as inhibitors of poly(ADP-ribose)polymerase-1 (PARP-1). A structure-based design strategy resulted in lead compound 3 (DHBF-7-carboxamide; IC50 = 9.45 mu M). To facilitate synthetically feasible derivatives, an alternative core was designed, DHBF-3-one-7-carboxamide (36, IC50 = 16.2 mu M). The electrophilic 2-position of this scaffold was accessible for extended modifications. Substituted benzylidene derivatives at the 2-position were found to be the most potent, with 3',4'-dihydroxybenzylidene 58 (IC50 = 0.531 mu M) showing a 30-fold improvement in potency. Various heterocycles attached at the 4'-hydroxyl/4'-amino of the benzylidene moiety resulted in significant improvement in inhibition of PARP-1 activity (e.g., compounds 66-68, 70, 72, and 73; IC50 values from 0.718 to 0.079 mu M). Compound 66 showed selective cytotoxicity in BRCA2-deficient DT40 cells. Crystal structures of three inhibitors (compounds (-)-13c, 59, and 65) bound to a multidomain PARP-1 structure were obtained, providing insights into further development of these inhibitors.

  DOI：

  10.1021/jm5002502