N,1,4,4-tetramethyl-8-[(4-morpholin-4-ylphenyl)amino]-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide | 802539-82-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: N,1,4,4-tetramethyl-8-[(4-morpholin-4-ylphenyl)amino]-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
• 英文别名: Pyrazolo[4,3-h]quinazoline-3-carboxamide, 30；N,1,4,4-tetramethyl-8-(4-morpholin-4-ylanilino)-5H-pyrazolo[4,3-h]quinazoline-3-carboxamide
• CAS: 802539-82-8
• 化学式: C₂₄H₂₉N₇O₂
• 分子量: 447.54
• InChiKey: GPJNTQGFTWMDLA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  33
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  97.2
• 氢给体数：
  2
• 氢受体数：
  7

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 、 4-(4-吗啉基)苯胺 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61%的产率得到N,1,4,4-tetramethyl-8-[(4-morpholin-4-ylphenyl)amino]-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

文献信息

• Identification of <i>N</i>,1,4,4-Tetramethyl-8-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-4,5-dihydro-1<i>H</i>-pyrazolo[4,3-<i>h</i>]quinazoline-3-carboxamide (PHA-848125), a Potent, Orally Available Cyclin Dependent Kinase Inhibitor
  作者：Maria Gabriella Brasca、Nadia Amboldi、Dario Ballinari、Alexander Cameron、Elena Casale、Giovanni Cervi、Maristella Colombo、Francesco Colotta、Valter Croci、Roberto D’Alessio、Francesco Fiorentini、Antonella Isacchi、Ciro Mercurio、Walter Moretti、Achille Panzeri、Wilma Pastori、Paolo Pevarello、Francesca Quartieri、Fulvia Roletto、Gabriella Traquandi、Paola Vianello、Anna Vulpetti、Marina Ciomei

  DOI：10.1021/jm9006559

  日期：2009.8.27

  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.