1-phenyl-6,7-dihydro-3H-[1,4]diazepino[6,7,1-hi]indol-4-one | 27158-79-8

• 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-3H-[1,4]diazepino[6,7,1-hi]indol-4-one
• 英文别名: 1-phenyl-6,7-dihydro-3H-[1,4]diazepino[6,7,1-hi]indol-4-one；1,2-Dihydro-7-phenylpyrrolo<3,2,1-jk><1,4>benzodiazepin-4(5H)-on；1,2-Dihydro-7-phenylpyrrolo<3,2,1-jk><1,4>benzodiazepin-on；Pyrrolo(3,2,1-jk)(1,4)benzodiazepin-4(3H)-one, 6,7-dihydro-1-phenyl-；9-phenyl-1,10-diazatricyclo[6.4.1.04,13]trideca-4(13),5,7,9-tetraen-12-one
• CAS: 27158-79-8
• 化学式: C₁₇H₁₄N₂O
• 分子量: 262.311
• InChiKey: DMBFAKKWMRMRJD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  32.7
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-phenyl-6,7-dihydro-3H-[1,4]diazepino[6,7,1-hi]indol-4-one 在 5percent Ru/C O-[(ethoxycarbonyl)cyanomethyleneamino]-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 硫酸 、 N-乙酰-L-苯丙氨酸 、 potassium tert-butylate 、 氢气 、 potassium nitrate 、 N,N-二异丙基乙胺 、 tin(ll) chloride 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 乙酸乙酯 、 甲苯 为溶剂， -5.0~80.0 ℃ 、800.01 kPa 条件下， 反应 35.75h， 生成 (3R)-4-amino-N-(9-amino-4-oxo-1-phenyl-3,4,6,7-tetrahydro[1,4]diazepino [6,7,1-hi]indol-3-yl)-3,5-dichlorobenzamide
  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：

  吲哚啉 在 吡啶 、 三氯化铝 、 三氯化硼 作用下， 以 1,2-二氯乙烷 为溶剂， 生成 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

• Succinoylamino carbocycles and heterocycles as inhibitors of a-beta protein production
  申请人：——

  公开号：US20020055501A1

  公开（公告）日：2002-05-09

  This invention relates to novel carbocycles and heterocycles having drug and bio-affecting properties, their pharmaceutical compositions and methods of use. These novel compounds inhibit the processing of amyloid precursor protein and, more specifically, inhibit the production of A&bgr;-peptide, thereby acting to prevent the formation of neurological deposits of amyloid protein. More particularly, the present invention relates to the treatment of neurological disorders related to &bgr;-amyloid production such as Alzheimer's disease and Down's Syndrome.

  本发明涉及具有药物和生物影响性质的新型碳环和杂环，它们的制药组合物和使用方法。这些新化合物抑制淀粉样前体蛋白的加工，更具体地抑制Aβ-肽的产生，从而防止淀粉样蛋白的神经沉积物形成。更具体地，本发明涉及与β-淀粉样肽产生相关的神经系统疾病的治疗，如阿尔茨海默病和唐氏综合症。
• J. Med. Chem. 2000, 43, 4850-4867
  作者：

  DOI：——

  日期：——
• CALVET, ALAIN PIERRE;JUNIEN, JEAN-LOUIS;PASCAL, YVES ROBERT ALAIN;PASCAUD+
  作者：CALVET, ALAIN PIERRE、JUNIEN, JEAN-LOUIS、PASCAL, YVES ROBERT ALAIN、PASCAUD+

  DOI：——

  日期：——
• US6525044B2
  申请人：——

  公开号：US6525044B2

  公开（公告）日：2003-02-25
• [EN] HETEROCYCLIC COMPOUNDS USEFUL FOR THE TREATMENT OF INFLAMMATORY AND ALLERGIC DISORDERS, PHARMACEUTICAL COMPOSITIONS CONTAINING THEM, AND METHODS OF PREPARING THEM<br/>[FR] COMPOSES HETEROCYCLIQUES UTILISES POUR LE TRAITEMENT DE TROUBLES INFLAMMATOIRES ET ALLERGIQUES, COMPOSITIONS PHARMACEUTIQUES CONTENANT CES COMPOSES ET PROCEDES PERMETTANT DE LES PREPARER
  申请人：GLENMARK PHARMACEUTICALS SA

  公开号：WO2006051390A1

  公开（公告）日：2006-05-18

  [EN] The present invention relates to new phosphodiesterase type 4 (PDE4) inhibitors of the formula (1) and analogs, tautomers, enantiomers, diasteromers, regioisomers, stereoisomers, polymorphs, N-oxides, pharmaceutically acceptable solvates and pharmaceutically acceptable salts thereof, pharmaceutical compositions containing them, and methods of treating allergic and inflammatory diseases, such as asthma or chronic obstructive pulmonary disease (COPD), with them.
  [FR] Cette invention concerne des nouveaux inhibiteurs de phosphodiestérases de type 4 (PDE4) représentés par la formule (1) et des analogues, des tautomères, des énantiomères, des diastéromères, des régioisomères, des stéréoisomères, des polymorphes, des N-oxydes, des solvates acceptables sur le plan pharmaceutique, et des sels de ceux-ci acceptables sur le plan pharmaceutique. Cette invention concerne également des compositions pharmaceutiques les contenant, ainsi que des méthodes permettant de traiter des troubles inflammatoires et allergiques, tels que l'asthme ou une maladie pulmonaire obstructive (COPD) au moyen de ces composés.