7-氟-1,3-二氢-5-(3-硝基苯基)-2H-1,4-苯并二氮杂-2-酮 | 1043425-40-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 中文名称: 7-氟-1,3-二氢-5-(3-硝基苯基)-2H-1,4-苯并二氮杂-2-酮
• 英文名称: 7-fluoro-1,3-dihydro-5-(3-nitrophenyl)-2H-1,4-benzodiazepin-2-one
• 英文别名: 7-Fluoro-5-(3-nitrophenyl)-1,3-dihydro-1,4-benzodiazepin-2-one；7-fluoro-5-(3-nitrophenyl)-1,3-dihydro-1,4-benzodiazepin-2-one
• CAS: 1043425-40-6
• 化学式: C₁₅H₁₀FN₃O₃
• 分子量: 299.261
• InChiKey: WJZRGTXPIXJUCO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  87.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  7-氟-1,3-二氢-5-(3-硝基苯基)-2H-1,4-苯并二氮杂-2-酮 、 氯磷酸二乙酯 在 potassium tert-butylate 作用下， 以 四氢呋喃 为溶剂， 反应 0.67h， 生成
  参考文献：
  名称：

  Ethyl 8-Fluoro-6-(3-nitrophenyl)-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate as Novel, Highly Potent, and Safe Antianxiety Agent

  摘要：

  Ethyl 8-fluoro-6-(4-nitrophenyl)- and ethyl 8-fluoro-6-(3-nitrophenyl)-4H-imidazo[1,5-a][1,4]benzodiazepine 3-carboxylate 6 and 7 were synthesized as central benzodiazepine receptor (CBR) ligands and tested for their ability to displace [3 H]flumazenil from bovine and human cortical brain membranes. Both compounds showed high affinity for bovine and human CBR. In particular, compound 7 emerged as the most interesting compound, having a partial agonist profile in vitro while possessing useful activity in various animal models of anxiety. In accordance with its partial agonist profile, compound 7 was devoid of typical benzodiazepine, side effects. The homology model of the GABA(A) receptor developed by Cromer et al. was used to assess the binding modes of ligands 6 and 7. From our docking results, the partial agonist activity elicited by compound 7 is likely to be due to the 3'-nitro substituent, which is in the appropriate position to interact with Thr193 of the gamma(2)-subunit by means of a hydrogen bond.

  DOI：

  10.1021/jm8002944
• 作为产物：
  描述：

  以 乙醇 为溶剂， 反应 3.0h， 生成 7-氟-1,3-二氢-5-(3-硝基苯基)-2H-1,4-苯并二氮杂-2-酮
  参考文献：
  名称：

  Ethyl 8-Fluoro-6-(3-nitrophenyl)-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate as Novel, Highly Potent, and Safe Antianxiety Agent

  摘要：

  Ethyl 8-fluoro-6-(4-nitrophenyl)- and ethyl 8-fluoro-6-(3-nitrophenyl)-4H-imidazo[1,5-a][1,4]benzodiazepine 3-carboxylate 6 and 7 were synthesized as central benzodiazepine receptor (CBR) ligands and tested for their ability to displace [3 H]flumazenil from bovine and human cortical brain membranes. Both compounds showed high affinity for bovine and human CBR. In particular, compound 7 emerged as the most interesting compound, having a partial agonist profile in vitro while possessing useful activity in various animal models of anxiety. In accordance with its partial agonist profile, compound 7 was devoid of typical benzodiazepine, side effects. The homology model of the GABA(A) receptor developed by Cromer et al. was used to assess the binding modes of ligands 6 and 7. From our docking results, the partial agonist activity elicited by compound 7 is likely to be due to the 3'-nitro substituent, which is in the appropriate position to interact with Thr193 of the gamma(2)-subunit by means of a hydrogen bond.

  DOI：

  10.1021/jm8002944

文献信息

• Ethyl 8-Fluoro-6-(3-nitrophenyl)-4<i>H</i>-imidazo[1,5-<i>a</i>][1,4]benzodiazepine-3-carboxylate as Novel, Highly Potent, and Safe Antianxiety Agent
  作者：Maurizio Anzini、Carlo Braile、Salvatore Valenti、Andrea Cappelli、Salvatore Vomero、Luciana Marinelli、Vittorio Limongelli、Ettore Novellino、Laura Betti、Gino Giannaccini、Antonio Lucacchini、Carla Ghelardini、Monica Norcini、Francesco Makovec、Gianluca Giorgi、R. Ian Fryer

  DOI：10.1021/jm8002944

  日期：2008.8.1

  Ethyl 8-fluoro-6-(4-nitrophenyl)- and ethyl 8-fluoro-6-(3-nitrophenyl)-4H-imidazo[1,5-a][1,4]benzodiazepine 3-carboxylate 6 and 7 were synthesized as central benzodiazepine receptor (CBR) ligands and tested for their ability to displace [3 H]flumazenil from bovine and human cortical brain membranes. Both compounds showed high affinity for bovine and human CBR. In particular, compound 7 emerged as the most interesting compound, having a partial agonist profile in vitro while possessing useful activity in various animal models of anxiety. In accordance with its partial agonist profile, compound 7 was devoid of typical benzodiazepine, side effects. The homology model of the GABA(A) receptor developed by Cromer et al. was used to assess the binding modes of ligands 6 and 7. From our docking results, the partial agonist activity elicited by compound 7 is likely to be due to the 3'-nitro substituent, which is in the appropriate position to interact with Thr193 of the gamma(2)-subunit by means of a hydrogen bond.