4,5-二氢-8-[[2-甲氧基-5-(4-甲基-1-哌嗪)苯基]氨基]-1-甲基-1H-吡唑并[4,3-h]喹唑啉-3-羧酰胺 | 1034614-73-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 4,5-二氢-8-[[2-甲氧基-5-(4-甲基-1-哌嗪)苯基]氨基]-1-甲基-1H-吡唑并[4,3-h]喹唑啉-3-羧酰胺
• 英文名称: 8-{[2-methoxy-5-(4-methylpiperazin-1-yl)phenyl]amino}-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
• 英文别名: 1H-Pyrazolo[4,3-h]quinazoline-3-carboxamide, 4,5-dihydro-8-[[2-methoxy-5-(4-methyl-1-piperazinyl)phenyl]amino]-1-methyl-；8-[2-methoxy-5-(4-methylpiperazin-1-yl)anilino]-1-methyl-4,5-dihydropyrazolo[4,3-h]quinazoline-3-carboxamide
• CAS: 1034614-73-7
• 化学式: C₂₃H₂₈N₈O₂
• 分子量: 448.528
• InChiKey: SWTRIZHCIUWGAU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  33
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  114
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  8-氨基-1-甲基-4,5-二氢-1H-吡唑[4,3-H]喹唑啉-3-甲酸乙酯 在 tris-(dibenzylideneacetone)dipalladium(0) 、 ammonia borane 、 sodium hexamethyldisilazane 、 caesium carbonate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 0.25h， 生成 4,5-二氢-8-[[2-甲氧基-5-(4-甲基-1-哌嗪)苯基]氨基]-1-甲基-1H-吡唑并[4,3-h]喹唑啉-3-羧酰胺
  参考文献：
  名称：

  CN116332942

  摘要：

  公开号：

文献信息

• Identification of 4,5-Dihydro-1<i>H</i>-pyrazolo[4,3-<i>h</i>]quinazoline Derivatives as a New Class of Orally and Selective Polo-Like Kinase 1 Inhibitors
  作者：Italo Beria、Dario Ballinari、Jay Aaron Bertrand、Daniela Borghi、Roberto Tiberio Bossi、Maria Gabriella Brasca、Paolo Cappella、Michele Caruso、Walter Ceccarelli、Antonella Ciavolella、Cinzia Cristiani、Valter Croci、Anna De Ponti、Gabriele Fachin、Ronald Dale Ferguson、Jacqueline Lansen、Jurgen Karl Moll、Enrico Pesenti、Helena Posteri、Rita Perego、Maurizio Rocchetti、Paola Storici、Daniele Volpi、Barbara Valsasina

  DOI：10.1021/jm901713n

  日期：2010.5.13

  Polo-like kinase 1 (Plk1) is a fundamental regulator of mitotic progression whose overexpression is often associated with oncogenesis and therefore is recognized as an attractive therapeutic target in the treatment of proliferative diseases. Here we discuss the structure-activity relationship of the 4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline class of compounds that emerged from a high throughput screening (HTS) campaign as potent inhibitors of Plk1 kinase. Furthermore, we describe the discovery of 49, 8-[2-methoxy-5-(4-methylpiperazin-1-yl)phenyl]amino}-1-methyl-4,5-dihydro-1H-pyrazolo-[4,3-h]quinazoline-3-carboxamide, as a highly potent and specific ATP mimetic inhibitor of Plk1 (IC(50) = 0.007 mu M) as well as its crystal structure in complex with the methylated Plk1(36-345) construct. Compound 49 was active in cell proliferation against different tumor cell lines with 1050 values in the submicromolar range and active in vivo in the HCT116 xenograft model where it showed 82% tumor growth inhibition after repeated oral administration.
• CN116332942
  申请人：——

  公开号：——

  公开（公告）日：——