9-methoxy-1-phenyl-6,7-dihydro[1,4]diazepino[6,7,1-hi]indole-3,4-dione 3-oxime | 179024-58-9

• 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: 9-methoxy-1-phenyl-6,7-dihydro[1,4]diazepino[6,7,1-hi]indole-3,4-dione 3-oxime
• 英文别名: 11-Hydroxyimino-6-methoxy-9-phenyl-1,10-diazatricyclo[6.4.1.04,13]trideca-4(13),5,7,9-tetraen-12-one
• CAS: 179024-58-9
• 化学式: C₁₈H₁₅N₃O₃
• 分子量: 321.335
• InChiKey: AIPGVOQXOXIGLA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  74.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  9-methoxy-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 、 D-(+)-二对甲基苯甲酰酒石酸 、 氢气 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 80.0 ℃ 、800.01 kPa 条件下， 反应 2.08h， 生成 (3R)-4,7-Dimethylpyrazolo[5,1-c][1,2,4]-triazine-3-carboxylic acid (9-methoxy-4-oxo-1-phenyl-3,4,6,7-tetrahydro[1,4]diazepino[6,7,1-hi]indol-3-yl)-amide
  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：

  5-甲氧基吲哚啉 在 吡啶 、 三氯化铝 、 potassium tert-butylate 、 三氯化硼 、 亚硝酸异戊酯 作用下， 以 四氢呋喃 、 1,2-二氯乙烷 为溶剂， 生成 9-methoxy-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

文献信息

• 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-<i>h</i><i>i</i>]indoles:  Discovery of Potent, Selective Phosphodiesterase Type 4 Inhibitors
  作者：Catherine Burnouf、Eric Auclair、Nadine Avenel、Bernadette Bertin、Christèle Bigot、Alain Calvet、Kam Chan、Corinne Durand、Veronique Fasquelle、Frédéric Féru、Richard Gilbertsen、Henry Jacobelli、Adel Kebsi、Emmanuelle Lallier、Jacquie Maignel、Brigitte Martin、Stéphane Milano、Malika Ouagued、Yves Pascal、Marie-Pierre Pruniaux、Jocelyne Puaud、Marie-Noëlle Rocher、Christophe Terrasse、Roger Wrigglesworth、Annette M. Doherty

  DOI：10.1021/jm000315p

  日期：2000.12.1

  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.
• 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
  作者：Yves Pascal、Charles R Andrianjara、Eric Auclair、Nadine Avenel、Bernadette Bertin、Alain Calvet、Frédéric Féru、Sophie Lardon、Indres Moodley、Malika Ouagued、Adrian Payne、Marie-Pierre Pruniaux、Corinne Szilagyi

  DOI：10.1016/s0960-894x(99)00573-9

  日期：2000.1

  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.