4-[5-(3-Nitro-phenyl)-2-oxo-3-(toluene-4-sulfonylamino)-2,3-dihydro-benzo[e][1,4]diazepin-1-yl]-butyric acid | 215511-89-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-[5-(3-Nitro-phenyl)-2-oxo-3-(toluene-4-sulfonylamino)-2,3-dihydro-benzo[e][1,4]diazepin-1-yl]-butyric acid
• 英文别名: 4-[3-[(4-methylphenyl)sulfonylamino]-5-(3-nitrophenyl)-2-oxo-3H-1,4-benzodiazepin-1-yl]butanoic acid
• CAS: 215511-89-0
• 化学式: C₂₆H₂₄N₄O₇S
• 分子量: 536.565
• InChiKey: NRPCVGDLIHCOCQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  38
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  170
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  4-[5-(3-Nitro-phenyl)-2-oxo-3-(toluene-4-sulfonylamino)-2,3-dihydro-benzo[e][1,4]diazepin-1-yl]-butyric acid 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 反应 12.0h， 以52%的产率得到4-[5-(3-Amino-phenyl)-2-oxo-3-(toluene-4-sulfonylamino)-2,3-dihydro-benzo[e][1,4]diazepin-1-yl]-butyric acid
  参考文献：
  名称：

  Design, syntheses, and activity of new 3-[(sulfonylaryl)-amino]-1,4-benzodiazepin-2-one derivatives as α-thrombin inhibitors

  摘要：

  Thrombin plays a central role in thrombosis. Because of the medical need for novel antithrombotic drugs, a search for structurally novel thrombin inhibitors was undertaken. In the absence of a crystal structure, a class was designed based on a modeling approach which involved placing the essential functional groups of the thrombin antagonist MD-805 [1] (Argatroban) into the benzodiazepine nucleus. The best superposition was obtained with a 1,4-benzodiazepin-2-one containing a 1,2,3,4-tetrahydro quinolylsulfonyl moiety in the 3-position, a guanidino-phenyl at the 5-position, and Ni-substituted with an acetic acid. Synthesis of these molecules provided compounds with an inhibitory activity with K-i in the range of 40-1000 mu M. A report on the crystal structure of thrombin*hirudin(55-65)*MD-805 complex [2] suggested subsequent molecular modeling investigations to rationalize the pharmacological results. (C) Elsevier, Paris.

  DOI：

  10.1016/s0223-5234(98)80048-2
• 作为产物：
  描述：

  benzyl N-[5-(3-nitrophenyl)-2-oxo-1,3-dihydro-1,4-benzodiazepin-3-yl]carbamate 在 吡啶 、 sodium hydroxide 、 氢溴酸 、 potassium carbonate 作用下， 以 甲醇 、 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 反应 30.42h， 生成 4-[5-(3-Nitro-phenyl)-2-oxo-3-(toluene-4-sulfonylamino)-2,3-dihydro-benzo[e][1,4]diazepin-1-yl]-butyric acid
  参考文献：
  名称：

  Design, syntheses, and activity of new 3-[(sulfonylaryl)-amino]-1,4-benzodiazepin-2-one derivatives as α-thrombin inhibitors

  摘要：

  Thrombin plays a central role in thrombosis. Because of the medical need for novel antithrombotic drugs, a search for structurally novel thrombin inhibitors was undertaken. In the absence of a crystal structure, a class was designed based on a modeling approach which involved placing the essential functional groups of the thrombin antagonist MD-805 [1] (Argatroban) into the benzodiazepine nucleus. The best superposition was obtained with a 1,4-benzodiazepin-2-one containing a 1,2,3,4-tetrahydro quinolylsulfonyl moiety in the 3-position, a guanidino-phenyl at the 5-position, and Ni-substituted with an acetic acid. Synthesis of these molecules provided compounds with an inhibitory activity with K-i in the range of 40-1000 mu M. A report on the crystal structure of thrombin*hirudin(55-65)*MD-805 complex [2] suggested subsequent molecular modeling investigations to rationalize the pharmacological results. (C) Elsevier, Paris.

  DOI：

  10.1016/s0223-5234(98)80048-2