5-溴-2,3-二氢-1-苯并呋喃-7-甲酰胺 | 882291-61-4

• 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-溴-2,3-二氢-1-苯并呋喃-7-甲酰胺
• 英文名称: 5-bromo-2,3-dihydrobenzofuran-7-carboxamide
• 英文别名: Maybridge KM07182SC；5-bromo-2,3-dihydro-1-benzofuran-7-carboxamide
• CAS: 882291-61-4
• 化学式: C₉H₈BrNO₂
• 分子量: 242.072
• InChiKey: JHHRFZWCOAWUOB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  52.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  2,3-二氢苯并呋喃 在 N-甲基吗啉 、 ammonium hydroxide 、 正丁基锂 、 四甲基乙二胺 、 溴 、 sodium acetate 、 溶剂黄146 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 12.0h， 生成 5-溴-2,3-二氢-1-苯并呋喃-7-甲酰胺
  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

文献信息

• [EN] ARYL AND HETEROARYL COMPOUNDS AND METHODS TO MODULATE COAGULATION<br/>[FR] COMPOSES ARYLE ET HETEROARYLE ET PROCEDES DE MODULATION DE LA COAGULATION
  申请人：TRANSTECH PHARMA INC

  公开号：WO2004014844A2

  公开（公告）日：2004-02-19

  This invention provides certain compounds, methods of their preparation, pharmaceutical compositions comprising the compounds, and their use in treating human or animal disorders. The compounds of the invention are useful as antagonists, or more preferably, partial antagonist of factor IX and thus, may be used to inhibit the intrinsic pathway of blood coagulation. The compounds are useful in a variety of applications including the management, treatment and/or control of diseases caused in part by the intrinsic clotting pathway utilizing factor IX. Such diseases or disease states include stroke, myocardial infarction, aneurysm surgery, and deep vein thrombosis associated with surgical procedures, long periods of confinement, and acquired or inherited pro-coagulant states.
• Discovery and Structure–Activity Relationship of Novel 2,3-Dihydrobenzofuran-7-carboxamide and 2,3-Dihydrobenzofuran-3(2<i>H</i>)-one-7-carboxamide Derivatives as Poly(ADP-ribose)polymerase-1 Inhibitors
  作者：Maulik R. Patel、Aaditya Bhatt、Jamin D. Steffen、Adel Chergui、Junko Murai、Yves Pommier、John M. Pascal、Louis D. Trombetta、Frank R. Fronczek、Tanaji T. Talele

  DOI：10.1021/jm5002502

  日期：2014.7.10

  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.