1-phenyl-6,7-dihydro[1,4]diazepino[6,7,1-hi]indole-3,4-dione 3-oxime | 126167-36-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 英文名称: 1-phenyl-6,7-dihydro[1,4]diazepino[6,7,1-hi]indole-3,4-dione 3-oxime
• 英文别名: 6,7-Dihydro-1-phenylpyrrolo[3,2,1-jk][1,4]benzodiazepine-3,4-dione 3-oxime；11-hydroxyimino-9-phenyl-1,10-diazatricyclo[6.4.1.04,13]trideca-4(13),5,7,9-tetraen-12-one
• CAS: 126167-36-0
• 化学式: C₁₇H₁₃N₃O₂
• 分子量: 291.309
• InChiKey: BVODAASSBVPSNE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.91
• 重原子数：
  22.0
• 可旋转键数：
  1.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  67.48
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  1-phenyl-6,7-dihydro[1,4]diazepino[6,7,1-hi]indole-3,4-dione 3-oxime 在 5percent Ru/C O-[(ethoxycarbonyl)cyanomethyleneamino]-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 硫酸 、 N-乙酰-L-苯丙氨酸 、 氢气 、 potassium nitrate 、 N,N-二异丙基乙胺 、 tin(ll) chloride 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 乙酸乙酯 为溶剂， 80.0 ℃ 、800.01 kPa 条件下， 反应 5.25h， 生成 [4-((R)-9-amino-4-oxo-1-phenyl-3,4,6,7-tetrahydro[1,4]diazepino[6,7,1-hi]indol-3-ylcarbamoyl)phenyl]carbamic acid tert-butyl ester
  参考文献：
  名称：

  Synthesis, Structure−Activity Relationships, and Pharmacological Profile of 9-Amino-4-oxo-1-phenyl-3,4,6,7-tetrahydro[1,4]diazepino[6,7,1-hi]indoles:  Discovery of Potent, Selective Phosphodiesterase Type 4 Inhibitors

  摘要：

  The synthesis, structure-activity relationships, and biological properties of a novel series of; potent and selective phosphodiesterase type 4 (PDE4) inhibitors are described. These new aminodiazepinoindoles displayed in vitro PDE4 activity with submicromolar IC50 values and PDE4 selectivity vs PDE1, -3, and -5. Specifically, one compound (CI-1044, 10e) provided efficient in vitro inhibition of TNF alpha release from hPBMC and; hWB with IC50:values of 0.34 and 0.84 muM, respectively. This compound was found to exhibit potent in vivo activity in antigen-induced eosinophil recruitment in Brown-Norway rats (ED50 = 3.2 mg/kg po) and in production of TNF alpha in Wistar fats (ED50 = 2.8; mg/kg po). No emetic side effects at therapeutic doses were observed in ferrets.

  DOI：

  10.1021/jm000315p
• 作为产物：
  描述：

  2,3-二氢-1H-吲哚-7-基(苯基)甲酮 在 吡啶 、 potassium tert-butylate 、 亚硝酸异戊酯 作用下， 以 四氢呋喃 为溶剂， 生成 1-phenyl-6,7-dihydro[1,4]diazepino[6,7,1-hi]indole-3,4-dione 3-oxime
  参考文献：
  名称：

  Synthesis and structure–activity relationships of 4-oxo-1-phenyl-3,4,6,7-tetrahydro-[1,4]diazepino[6,7,1- hi ]indoles: novel PDE4 inhibitors

  摘要：

  A novel series of benzodiazepine derivatives have been discovered as inhibitors of PDE4 enzymes. We have found that our compounds are selective versus other PDE enzymes, and that the activity can be modulated by specific structural modifications. One compound exhibited a strong eosinophilic infiltration inhibiting action on sensitized Brown-Norway rats (compound 9, 5.1 mg/kg p.o.), moreover this compound is not emetic at 3 mg/kg i.v. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(99)00573-9