3-amino-9-methyl-1-phenyl-6,7-dihydro-3H-[1,4]diazepino[6,7,1-hi]indol-4-one | 179024-54-5

• 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: 3-amino-9-methyl-1-phenyl-6,7-dihydro-3H-[1,4]diazepino[6,7,1-hi]indol-4-one
• 英文别名: (3R)-3-amino-9-methyl-1-phenyl-6,7-dihydro-3H-[1,4]diazepino[6,7,1-hi]indol-4-one；(11R)-11-amino-6-methyl-9-phenyl-1,10-diazatricyclo[6.4.1.04,13]trideca-4(13),5,7,9-tetraen-12-one
• CAS: 179024-54-5
• 化学式: C₁₈H₁₇N₃O
• 分子量: 291.352
• InChiKey: SCWSSRMZJRNWNQ-QGZVFWFLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  58.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2,4-二氯苯甲酸 、 3-amino-9-methyl-1-phenyl-6,7-dihydro-3H-[1,4]diazepino[6,7,1-hi]indol-4-one 在 O-[(ethoxycarbonyl)cyanomethyleneamino]-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 2,4-dichloro-N-[(11R)-6-methyl-12-oxo-9-phenyl-1,10-diazatricyclo[6.4.1.04,13]trideca-4(13),5,7,9-tetraen-11-yl]benzamide
  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
• 作为产物：
  描述：

  5-甲基二氢吲哚 在 Ru-carbon 吡啶 、 三氯化铝 、 potassium tert-butylate 、 氢气 、 三氯化硼 、 亚硝酸异戊酯 作用下， 以 四氢呋喃 、 甲醇 、 1,2-二氯乙烷 为溶剂， 生成 3-amino-9-methyl-1-phenyl-6,7-dihydro-3H-[1,4]diazepino[6,7,1-hi]indol-4-one
  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

• Method for preparing substituted [1,4]diazepino[6,7,1-hi]indol-4-ones
  申请人：Warner-Lambert LLC

  公开号：US06689881B1

  公开（公告）日：2004-02-10

  Method for the preparation of enantiomerically pure diazepino-indolone of formula which comprises the intramolecular cyclization of a product of formula where A, B, X1, X2, Z, Z1, Z2 and R are as defined in the description, in the presence of a weak Lewis acid catalyst.

  一种制备对映纯的式子为的二氮杂环吲哚酮的方法，包括在弱Lewis酸催化剂存在下进行式子的分子内环化，其中式子中的A、B、X1、X2、Z、Z1、Z2和R的定义如说明书所述。
• 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.
• J. Med. Chem. 2000, 43, 4850-4867
  作者：

  DOI：——

  日期：——
• DIAZEPINO-INDOLES INHIBITEURS DE PHOSPHODIESTERASES IV
  申请人：Pfizer

  公开号：EP0785789B1

  公开（公告）日：2002-09-11
• PHOSPHODIESTERASE 4-INHIBITING DIAZEPINOINDOLONES
  申请人：Pfizer Holding France

  公开号：EP0980374B1

  公开（公告）日：2003-02-12