(4-chlorophenyl)(2-(4-(pyrimidin-2-yl)piperazin-1-yl)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)methanone | 1609485-40-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: (4-chlorophenyl)(2-(4-(pyrimidin-2-yl)piperazin-1-yl)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)methanone
• 英文别名: (4-chlorophenyl)-[2-(4-pyrimidin-2-ylpiperazin-1-yl)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl]methanone
• CAS: 1609485-40-6
• 化学式: C₂₂H₂₂ClN₇O
• 分子量: 435.916
• InChiKey: PQPTVVNFJSVKJN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  31
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  78.4
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  6-苯甲基-5,6,7,8-四氢-1H-哌啶并[4,3-D]2,4-二嘧啶酮 在 ammonium hydroxide 、 palladium 10% on activated carbon 、 氢气 、 sodium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 锌 、 三氯氧磷 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醇 、 二氯甲烷 为溶剂， 反应 64.0h， 生成 (4-chlorophenyl)(2-(4-(pyrimidin-2-yl)piperazin-1-yl)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)methanone
  参考文献：
  名称：

  Identification and optimization of novel Hsp90 inhibitors with tetrahydropyrido[4,3-d]pyrimidines core through shape-based screening

  摘要：

  Rapid Overlay of Chemical Structures (ROCS), which can rapidly identify potentially active compounds by shape comparison, is recognized as a powerful virtual screening tool. By ROCS, a class of novel Hsp90 inhibitors was identified. The calculated binding mode of the most potent hit 36 guided us to design and synthesize a series of analogs (57a-57h). Over 100-fold improvement was achieved in the target-based assay. The most potent compound 57h inhibited Hsp90 with IC50 0.10 +/- 0.01 mu M. It also showed much improved cell potency and ligand efficiency. Our study showed that ROCS is efficient in the identification of novel cores of Hsp90 inhibitors. 57h can be ideal leads for further optimization. (C) 2014 Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2014.03.061

文献信息

• Identification and optimization of novel Hsp90 inhibitors with tetrahydropyrido[4,3-d]pyrimidines core through shape-based screening
  作者：Hao-Peng Sun、Jian-Min Jia、Fen Jiang、Xiao-Li Xu、Fang Liu、Xiao-Ke Guo、Bahidja Cherfaoui、Hao-Ze Huang、Yang Pan、Qi-Dong You

  DOI：10.1016/j.ejmech.2014.03.061

  日期：2014.5

  Rapid Overlay of Chemical Structures (ROCS), which can rapidly identify potentially active compounds by shape comparison, is recognized as a powerful virtual screening tool. By ROCS, a class of novel Hsp90 inhibitors was identified. The calculated binding mode of the most potent hit 36 guided us to design and synthesize a series of analogs (57a-57h). Over 100-fold improvement was achieved in the target-based assay. The most potent compound 57h inhibited Hsp90 with IC50 0.10 +/- 0.01 mu M. It also showed much improved cell potency and ligand efficiency. Our study showed that ROCS is efficient in the identification of novel cores of Hsp90 inhibitors. 57h can be ideal leads for further optimization. (C) 2014 Published by Elsevier Masson SAS.