(3R) - N-(9-Amino-4-oxo-1-phenyl-3,4,6,7-tetrahydro [1,4]diazepino [6,7,1-hi]indol-3-yl)-2-methoxybenzamide

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (3R) - N-(9-Amino-4-oxo-1-phenyl-3,4,6,7-tetrahydro [1,4]diazepino [6,7,1-hi]indol-3-yl)-2-methoxybenzamide
• 英文别名: N-[(11R)-6-amino-12-oxo-9-phenyl-1,10-diazatricyclo[6.4.1.04,13]trideca-4(13),5,7,9-tetraen-11-yl]-2-methoxybenzamide
• 化学式: C₂₅H₂₂N₄O₃
• 分子量: 426.475
• InChiKey: IRYRZMDNUGMWSV-QHCPKHFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  32
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  97
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (3R)-3-amino-5-phenyl-3,4,6,7-tetrahydropyrrolo<3,2,1-jk><1,4>benzodiazepin-4(3H)-one 在 O-[(ethoxycarbonyl)cyanomethyleneamino]-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 硫酸 、 potassium nitrate 、 N,N-二异丙基乙胺 、 tin(ll) chloride 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 3.17h， 生成 (3R) - N-(9-Amino-4-oxo-1-phenyl-3,4,6,7-tetrahydro [1,4]diazepino [6,7,1-hi]indol-3-yl)-2-methoxybenzamide
  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

文献信息

• Diazépino-indoles inhibiteurs de phosphodiestérases 4
  申请人：INSTITUT DE RECHERCHE JOUVEINAL

  公开号：EP1132390A2

  公开（公告）日：2001-09-12

  Diazépino-indoles de formule (I) dans laquelle : A est aryle ou hétéroaryle mono- à trisubstitué, B est un groupe -OR1 ou -NR2R3, où R1, R2, R3 sont notamment hydrogènes, leurs formes racémiques, leurs énantiomères, et leurs sels pharmaceutiquement acceptables ; qui sont inhibiteurs de phosphodiestérases 4.

  式 (I) 的二氮杂吲哚 其中 ： A 是一至三取代的芳基或杂芳基、 B 是基团 -OR1 或 -NR2R3，其中 R1、R2 和 R3 尤其是氢、 它们的外消旋形式、它们的对映体以及它们的药学上可接受的盐； 是磷酸二酯酶 4 抑制剂。
• DIAZEPINO-INDOLES INHIBITEURS DE PHOSPHODIESTERASES 4
  申请人：INSTITUT DE RECHERCHE JOUVEINAL (I.R.J)

  公开号：EP0828742B1

  公开（公告）日：2001-12-19
• 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.