8-{[4-(dimethylamino)phenyl]amino}-N,1,4,4-tetramethyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 8-{[4-(dimethylamino)phenyl]amino}-N,1,4,4-tetramethyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
• 英文别名: Pyrazolo[4,3-h]quinazoline-3-carboxamide, 38；8-[4-(dimethylamino)anilino]-N,1,4,4-tetramethyl-5H-pyrazolo[4,3-h]quinazoline-3-carboxamide
• 化学式: C₂₂H₂₇N₇O
• 分子量: 405.503
• InChiKey: OGRGRBGYCZWQRA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  88
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  8-iodo-N,1,4,4-tetramethyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide 、 N,N-二甲基-对苯二胺 在 palladium diacetate 、 potassium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以44%的产率得到8-{[4-(dimethylamino)phenyl]amino}-N,1,4,4-tetramethyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
  参考文献：
  名称：

  Identification of N,1,4,4-Tetramethyl-8-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide (PHA-848125), a Potent, Orally Available Cyclin Dependent Kinase Inhibitor

  摘要：

  The discovery of a novel class of inhibitors of cyclin dependent kinases (CDKs) is described, Starting from compound 1, showing good potency as inhibitor of CDKs but being poorly selective against a panel of serine-threonine and tyrosine kinases, new analogues were synthesize cl, Enhancement in selectivity, antiproliferative activity against A2780 human ovarian carcinoma cells, and optimization of the physical properties and pharmacokinetic profile led to the identification of highly potent and orally available compounds. Compound 28 (PHA-848125), which in the preclinical xenograft A2780 human ovarian carcinoma model showed good efficacy and was well tolerated upon repeated daily treatments, was identified its a drug candidate for further development. Compound 28 is Currently undergoing phase I and phase II clinical trials.

  DOI：

  10.1021/jm9006559