3-amino-9-methoxy-1-phenyl-6,7-dihydro-3H-[1,4]diazepino[6,7,1-hi]indol-4-one | 179024-56-7

• 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-methoxy-1-phenyl-6,7-dihydro-3H-[1,4]diazepino[6,7,1-hi]indol-4-one
• 英文别名: (3R,S)-3-amino-9-methoxy-1-phenyl-6,7-dihydro-3H-[1,4]diazepino[6,7,1-hi]indol-4-one；11-Amino-6-methoxy-9-phenyl-1,10-diazatricyclo[6.4.1.04,13]trideca-4(13),5,7,9-tetraen-12-one
• CAS: 179024-56-7
• 化学式: C₁₈H₁₇N₃O₂
• 分子量: 307.352
• InChiKey: OXNJEXXVDKLIPL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  67.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-amino-9-methoxy-1-phenyl-6,7-dihydro-3H-[1,4]diazepino[6,7,1-hi]indol-4-one 在 D-(+)-二对甲基苯甲酰酒石酸 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 0.08h， 生成 (3R)-Isoquinoline-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：

  9-methoxy-1-phenyl-6,7-dihydro[1,4]diazepino[6,7,1-hi]indole-3,4-dione 3-oxime 在 5percent Ru/C 氢气 作用下， 以 甲醇 为溶剂， 80.0 ℃ 、800.01 kPa 条件下， 反应 2.0h， 以67%的产率得到3-amino-9-methoxy-1-phenyl-6,7-dihydro-3H-[1,4]diazepino[6,7,1-hi]indol-4-one
  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

• Phosphodiesterase 4-inhibiting diazepinoindolones
  申请人：Warner-Lambert Company

  公开号：US06239130B1

  公开（公告）日：2001-05-29

  The present invention presents compounds that inhibit phosphodiesterase 4 having Formula (I). The present invention also provides methods of using the compounds of Formula (I) to prevent or treat asthma, atopic dermatitis, rheumatoid arthritis, inflammatory bowel disorders, pulmonary hypertension, liver injury, bone loss, septic shock, or multiple sclerosis, and to pharmaceutical compositions that contain the compounds of Formula (I).

  本发明提供了抑制磷酸二酯酶4的化合物，其具有化学式(I)。本发明还提供了利用化合物化学式(I)预防或治疗哮喘、特应性皮炎、类风湿性关节炎、炎症性肠道疾病、肺动脉高压、肝损伤、骨质流失、脓毒性休克或多发性硬化症的方法，以及含有化合物化学式(I)的药物组合物。
• 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。
• PHOSPHODIESTERASE 4-INHIBITING DIAZEPINOINDOLONES
  申请人：Pfizer Holding France

  公开号：EP0980374B1

  公开（公告）日：2003-02-12
• US6239130B1
  申请人：——

  公开号：US6239130B1

  公开（公告）日：2001-05-29
• 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.