ehyl 5-benzoyl-3-(4-(4-methylpiperazin-1-yl)benzamido)-5,6-dihydropyrrolo[3,4-c]pyrazole-1(4H)-carboxylate | 1430587-17-9

• 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: ehyl 5-benzoyl-3-(4-(4-methylpiperazin-1-yl)benzamido)-5,6-dihydropyrrolo[3,4-c]pyrazole-1(4H)-carboxylate
• 英文别名: Ethyl 5-benzoyl-3-[[4-(4-methylpiperazin-1-yl)benzoyl]amino]-4,6-dihydropyrrolo[3,4-c]pyrazole-1-carboxylate
• CAS: 1430587-17-9
• 化学式: C₂₇H₃₀N₆O₄
• 分子量: 502.573
• InChiKey: MMXHDMSTRUKHPZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  37
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  100
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ehyl 5-benzoyl-3-(4-(4-methylpiperazin-1-yl)benzamido)-5,6-dihydropyrrolo[3,4-c]pyrazole-1(4H)-carboxylate 在 三乙胺 作用下， 以 甲醇 为溶剂， 反应 4.0h， 以99%的产率得到N-(5-benzoyl-4,6-dihydro-1H-pyrrolo[3,4-c]pyrazol-3-yl)-4-(4-methylpiperazin-1-yl)benzamide
  参考文献：
  名称：

  The human Aurora kinase inhibitor danusertib is a lead compound for anti-trypanosomal drug discovery via target repurposing

  摘要：

  New drugs for neglected tropical diseases such as human African trypanosomiasis (HAT) are needed, yet drug discovery efforts are not often focused on this area due to cost. Target repurposing, achieved by the matching of essential parasite enzymes to those human enzymes that have been successfully inhibited by small molecule drugs, provides an attractive means by which new drug optimization programs can be pragmatically initiated. In this report we describe our results in repurposing an established class of human Aurora kinase inhibitors, typified by danusertib (1), which we have observed to be an inhibitor of trypanosomal Aurora kinase 1 (TbAUK1) and effective in parasite killing in vitro. Informed by homology modeling and docking, a series of analogs of I were prepared that explored the scope of the chemotype and provided a nearly 25-fold improvement in cellular selectivity for parasite cells over human cells. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.07.038
• 作为产物：
  描述：

  1-乙基氧基羰基-3-[4-(4-甲基-1-哌嗪)-苯甲酰基氨基]-5,6-二氢-吡咯并[3,4-c]吡唑 、 苯甲酰氯 在 吡啶 作用下， 反应 16.0h， 以21%的产率得到ehyl 5-benzoyl-3-(4-(4-methylpiperazin-1-yl)benzamido)-5,6-dihydropyrrolo[3,4-c]pyrazole-1(4H)-carboxylate
  参考文献：
  名称：

  The human Aurora kinase inhibitor danusertib is a lead compound for anti-trypanosomal drug discovery via target repurposing

  摘要：

  New drugs for neglected tropical diseases such as human African trypanosomiasis (HAT) are needed, yet drug discovery efforts are not often focused on this area due to cost. Target repurposing, achieved by the matching of essential parasite enzymes to those human enzymes that have been successfully inhibited by small molecule drugs, provides an attractive means by which new drug optimization programs can be pragmatically initiated. In this report we describe our results in repurposing an established class of human Aurora kinase inhibitors, typified by danusertib (1), which we have observed to be an inhibitor of trypanosomal Aurora kinase 1 (TbAUK1) and effective in parasite killing in vitro. Informed by homology modeling and docking, a series of analogs of I were prepared that explored the scope of the chemotype and provided a nearly 25-fold improvement in cellular selectivity for parasite cells over human cells. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.07.038