N'-(4-bromophenyl)-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine-7-sulfonohydrazide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 英文名称: N'-(4-bromophenyl)-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine-7-sulfonohydrazide
• 英文别名: N'-(4-bromophenyl)-2-oxo-1,3,4,5-tetrahydro-1-benzazepine-7-sulfonohydrazide
• 化学式: C₁₆H₁₆BrN₃O₃S
• 分子量: 410.291
• InChiKey: DQJJIJMDSUPRAV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  95.7
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1,3,4,5-四氢-2H-1-苯并氮杂卓-2-酮 在 氯磺酸 作用下， 以 四氯化碳 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 N'-(4-bromophenyl)-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine-7-sulfonohydrazide
  参考文献：
  名称：

  Phenyl Benzenesulfonylhydrazides Exhibit Selective Indoleamine 2,3-Dioxygenase Inhibition with Potent in Vivo Pharmacodynamic Activity and Antitumor Efficacy

  摘要：

  Tryptophan metabolism has been recognized as an important mechanism in immune tolerance. Indoleamine 2,3-dioxygenase plays a key role in local tryptophan metabolism via the kynurenine pathway and has emerged as a therapeutic target for cancer immunotherapy. Our prior study identified phenyl benzenesulfonyl hydrazide 2 as a potent in vitro (though not in vivo) inhibitor of indoleamine 2,3-dioxygenase. Further lead optimization to improve in vitro potencies and pharmacokinetic profiles resulted in N'-(4-bromophenyl)-2-oxo-2,3-dihydro-1H-indole-5-sulfonyl hydrazide 40, which demonstrated 59% oral bioavailability and 73% of tumor growth delay without apparent body weight loss in the murine CT26 syngeneic model, after oral administration of 400 mg/kg. Accordingly, 40, is proposed as a potential drug lead worthy of advanced preclinical evaluation.

  DOI：

  10.1021/acs.jmedchem.5b01640