6-amino-7-(1-benzyl-1H-benzo[d]imidazol-2-yl)-5-(2-furylmeth yl)-5H-pyrrolo[2,3-dicarbonitrile | 302804-09-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡嗪类
• 英文名称: 6-amino-7-(1-benzyl-1H-benzo[d]imidazol-2-yl)-5-(2-furylmeth yl)-5H-pyrrolo[2,3-dicarbonitrile
• 英文别名: 6-amino-7-(1-benzylbenzimidazol-2-yl)-5-(furan-2-ylmethyl)pyrrolo[2,3-b]pyrazine-2,3-dicarbonitrile
• CAS: 302804-09-7
• 化学式: C₂₇H₁₈N₈O
• 分子量: 470.493
• InChiKey: LHYNSJOPCOMFKU-UHFFFAOYSA-N

物化性质

• 沸点：
  811.4±75.0 °C(Predicted)
• 密度：
  1.43±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  36
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  135
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  6-amino-7-(1-benzyl-1H-benzo[d]imidazol-2-yl)-5-(2-furylmeth yl)-5H-pyrrolo[2,3-dicarbonitrile 在 一水合肼 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以67%的产率得到3-(1-benzyl-1-benzo[d]imidazol-2-yl)-1-(2-furylmethyl)-1H-pyrrolo[2',3':5,6]pyrazino[2,3-d]pyridazine-2,5,8-triamine
  参考文献：
  名称：

  摘要：

  DOI：

  10.1023/a:1015695522610
• 作为产物：
  描述：

  5,6-二氯-2,3-二氰基吡嗪 以 N,N-二甲基甲酰胺 为溶剂， 生成 6-amino-7-(1-benzyl-1H-benzo[d]imidazol-2-yl)-5-(2-furylmeth yl)-5H-pyrrolo[2,3-dicarbonitrile
  参考文献：
  名称：

  Novel 5,7-disubstituted 6-amino-5H-pyrrolo[3,2-b]pyrazine-2,3-dicarbonitriles, the promising protein kinase inhibitors with antiproliferative activity

  摘要：

  New derivatives of pyrrolo[2,3-b]pyrazine were synthesized and tested on a panel of cultured human tumor cell lines. It was found that 6-amino-5-(3-chlorophenylamino)-7-(1-methyl-1H-benzo[dlimidazol-2-yl]-5H-pyrrolo[3,2-b]pyrazine-2,3-dicarbonitrile (4j) exhibited a significant antiproliferative activity: GI50 for cell lines RXF 393 (renal cancer) and BT-549 (breast cancer) were 14 and 82 nM, respectively. To identify possible molecular targets, docking of the most active compounds into the active sites of cyclin-dependent kinases was performed. Molecular modeling of the inhibitor-enzyme complexes showed the differences in the binding poses of new pyrrolo[2,3-b]pyrazine derivatives in the kinase ATP-binding site compared with known pyrrolo[2,3-b]pyrazine inhibitors called aloisines. The patterns of drug kinase interactions correlated well with antiproliferative activities of novel derivatives. Key interactions and binding mode of docked compounds are discussed. (c) 2006 Elsevier SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2006.03.019

文献信息

• ——
  作者：Yu. M. Volovenko、G. G. Dubinina

  DOI：10.1023/a:1015695522610

  日期：——
• Novel 5,7-disubstituted 6-amino-5H-pyrrolo[3,2-b]pyrazine-2,3-dicarbonitriles, the promising protein kinase inhibitors with antiproliferative activity
  作者：G.G. Dubinina、M.O. Platonov、S.M. Golovach、P.O. Borysko、A.O. Tolmachov、Y.M. Volovenko

  DOI：10.1016/j.ejmech.2006.03.019

  日期：2006.6

  New derivatives of pyrrolo[2,3-b]pyrazine were synthesized and tested on a panel of cultured human tumor cell lines. It was found that 6-amino-5-(3-chlorophenylamino)-7-(1-methyl-1H-benzo[dlimidazol-2-yl]-5H-pyrrolo[3,2-b]pyrazine-2,3-dicarbonitrile (4j) exhibited a significant antiproliferative activity: GI50 for cell lines RXF 393 (renal cancer) and BT-549 (breast cancer) were 14 and 82 nM, respectively. To identify possible molecular targets, docking of the most active compounds into the active sites of cyclin-dependent kinases was performed. Molecular modeling of the inhibitor-enzyme complexes showed the differences in the binding poses of new pyrrolo[2,3-b]pyrazine derivatives in the kinase ATP-binding site compared with known pyrrolo[2,3-b]pyrazine inhibitors called aloisines. The patterns of drug kinase interactions correlated well with antiproliferative activities of novel derivatives. Key interactions and binding mode of docked compounds are discussed. (c) 2006 Elsevier SAS. All rights reserved.