tert-butyl 2-[5-(3-isocyanophenyl)-3-[(4-methylphenyl)sulfonylamino]-2-oxo-3H-1,4-benzodiazepin-1-yl]acetate | 215511-97-0

• 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: tert-butyl 2-[5-(3-isocyanophenyl)-3-[(4-methylphenyl)sulfonylamino]-2-oxo-3H-1,4-benzodiazepin-1-yl]acetate
• CAS: 215511-97-0
• 化学式: C₂₉H₂₈N₄O₅S
• 分子量: 544.631
• InChiKey: WARZRBOIDWRFSS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  39
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  118
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  tert-butyl 2-[5-(3-isocyanophenyl)-3-[(4-methylphenyl)sulfonylamino]-2-oxo-3H-1,4-benzodiazepin-1-yl]acetate 在 溴-1,4-二氧六环复合物 作用下， 以 二氯甲烷 为溶剂， 反应 0.25h， 以99%的产率得到tert-butyl 2-[5-[3-(dibromomethylideneamino)phenyl]-3-[(4-methylphenyl)sulfonylamino]-2-oxo-3H-1,4-benzodiazepin-1-yl]acetate
  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：

  tert-butyl 2-[5-(3-aminophenyl)-3-[(4-methylphenyl)sulfonylamino]-2-oxo-3H-1,4-benzodiazepin-1-yl]acetate 在 乙酸酐 、 三乙胺 、 三苯基膦 作用下， 以 四氯化碳 、 氯仿 为溶剂， 反应 3.25h， 生成 tert-butyl 2-[5-(3-isocyanophenyl)-3-[(4-methylphenyl)sulfonylamino]-2-oxo-3H-1,4-benzodiazepin-1-yl]acetate
  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