(3R)-3-t-Butyloxycarbonylamino-N-(9-amino-4-oxo-1-phenyl-3,4,6,7-tetrahydro [1,4 ]diazepino [6,7,1-hi]indol-3-yl) isonicotinamide | 321527-83-7

• 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)-3-t-Butyloxycarbonylamino-N-(9-amino-4-oxo-1-phenyl-3,4,6,7-tetrahydro [1,4 ]diazepino [6,7,1-hi]indol-3-yl) isonicotinamide
• 英文别名: tert-butyl N-[4-[[(11R)-6-amino-12-oxo-9-phenyl-1,10-diazatricyclo[6.4.1.04,13]trideca-4(13),5,7,9-tetraen-11-yl]carbamoyl]pyridin-3-yl]carbamate
• CAS: 321527-83-7
• 化学式: C₂₈H₂₈N₆O₄
• 分子量: 512.568
• InChiKey: SJARNHOILQJSKN-DEOSSOPVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  38
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  139
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (3R)-3-t-Butyloxycarbonylamino-N-(9-amino-4-oxo-1-phenyl-3,4,6,7-tetrahydro [1,4 ]diazepino [6,7,1-hi]indol-3-yl) isonicotinamide 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以23%的产率得到(3R)-3-Amino-N-(9-amino-4-oxo-1-phenyl-3, 4, 6, 7-tetrahydro [1,4]diazepino [6,7,1-hi]indol-3-yl)isonicotinamide
  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：

  (3R)-3-amino-5-phenyl-3,4,6,7-tetrahydropyrrolo<3,2,1-jk><1,4>benzodiazepin-4(3H)-one 在 硫酸 、 potassium nitrate 、 三乙胺 、 bromo-tris(1-pyrrolidinyl)phosphonium hexafluorophosphate 、 tin(ll) chloride 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 15.17h， 生成 (3R)-3-t-Butyloxycarbonylamino-N-(9-amino-4-oxo-1-phenyl-3,4,6,7-tetrahydro [1,4 ]diazepino [6,7,1-hi]indol-3-yl) isonicotinamide
  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

• Pharmaceutical composition for preventing or treating a disease associated with an excess of IL-12-production
  申请人：——

  公开号：US20020119967A1

  公开（公告）日：2002-08-29

  This invention relates to the use of a PDE4 inhibitor or a pharmacologically acceptable salt thereof for manufacturing a medicament for preventing or treating a disease associated with an excess in IL-12 production.

  本发明涉及使用PDE4抑制剂或其药理学上可接受的盐来制造用于预防或治疗与IL-12过度产生相关的疾病的药物。
• Diazepinoindoles for the treatment of chronic obstructive pulmonary disease
  申请人：——

  公开号：US20020010175A1

  公开（公告）日：2002-01-24

  The present invention relates to the use of diazepinoindoles of the formula (I): 1 in which A is aryl or nitrogen-containing heteroaryl, and B is a hydroxyl or amino radical, for the treatment of chronic obstructive pulmonary disease.

  本发明涉及使用式(I)中的二氮杂并吲哚，其中A是芳基或含氮杂环芳基，B是羟基或氨基基团，用于治疗慢性阻塞性肺疾病。
• Use of diazepinoindoles for the treatment of chronic obstructive pulmonary disease
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP1161950A1

  公开（公告）日：2001-12-12

  The present invention relates to the use of diazepinoindoles of the formula (I):    in which A is aryl or nitrogen-containing heteroaryl, and B is a hydroxyl or amino radical,    for the treatment of chronic obstructive pulmonary disease.

  本发明涉及式(I)的重氮吲哚的用途： 其中 A 是芳基或含氮杂芳基，B 是羟基或氨基、 用于治疗慢性阻塞性肺病。
• Use od diazepinoindoles for the treatment of chronic obstructive pulmonary disease
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP1161949A1

  公开（公告）日：2001-12-12

  The present invention relates to the use of diazepinoindoles of the formula (I):    in which A is aryl or nitrogen-containing heteroaryl, and B is a hydroxyl or amino radical,    for the treatment of chronic obstructive pulmonary disease.

  本发明涉及式(I)的重氮吲哚的用途： 其中 A 是芳基或含氮杂芳基，B 是羟基或氨基、 用于治疗慢性阻塞性肺病。
• Pharmaceutical compositions based on a scopineester and nicotinamide derivatives
  申请人：Meade J. Montague Christopher

  公开号：US20050154006A1

  公开（公告）日：2005-07-14

  The present invention relates to novel pharmaceutical compositions based on a scopineester of formula 1 wherein X − has the meanings specified in the description and claims and one ore more, preferably one nicotinamide derivative, processes for preparing them and their use in the treatment of respiratory diseases.

  本发明涉及基于式 1 的莨菪酯的新型药物组合物 其中 X - 具有在说明书和权利要求书中规定的含义，以及一种或多种，最好是一种烟酰胺衍生物，制备它们的工艺及其在治疗呼吸系统疾病中的用途。