3-isopropyl-6-nitro-3H-quinazolin-4-one | 900513-08-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 3-isopropyl-6-nitro-3H-quinazolin-4-one
• 英文别名: 6-Nitro-3-propan-2-ylquinazolin-4-one；6-nitro-3-propan-2-ylquinazolin-4-one
• CAS: 900513-08-8
• 化学式: C₁₁H₁₁N₃O₃
• 分子量: 233.227
• InChiKey: TZKIIBVEPUNRSC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  78.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-isopropyl-6-nitro-3H-quinazolin-4-one 在 palladium on activated charcoal 吡啶 、 copper(l) iodide 、 溴 、 甲酸铵 、 溶剂黄146 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 3.75h， 生成 8-(3-isopropyl)-9-oxo-8,9-dihydrothiazolo[5,4-f]quinazoline-2-carbonitrile
  参考文献：
  名称：

  Thiazolo[5,4-f]quinazolin-9-ones, inhibitors of glycogen synthase kinase-3

  摘要：

  In an effort to identify new protein kinase inhibitors with increased potency and selectivity, we have developed the microwave-assisted synthesis of thiazolo[5,4-f]quinazolin-9-ones. The effects of eighteen derivatives on CDK1/cyclin B, CDK5/p25, and GSK-3 were investigated. Several turned out to inhibit GSK-3 in the micromolar range. Molecular modeling studies suggest that the most selective GSK-3 inhibitors 7a-d bind into the ATP-binding site through a key hydrogen bond interaction with Val135 and target the specific hydrophobic backpocket of the enzyme. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.04.006
• 作为产物：
  描述：

  2-碘代丙烷 、 6-硝基喹唑啉-4(3H)-酮 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.08h， 以90%的产率得到3-isopropyl-6-nitro-3H-quinazolin-4-one
  参考文献：
  名称：

  Novel 9-oxo-thiazolo[5,4-f]quinazoline-2-carbonitrile derivatives as dual cyclin-dependent kinase 1 (CDK1)/glycogen synthase kinase-3 (GSK-3) inhibitors: Synthesis, biological evaluation and molecular modeling studies

  摘要：

  Continuous efforts in microwave-assisted synthesis and the structure-activity relationships' (SARs) studies of novel modified 9-oxo-thiazolo[5,4-f]quinazoline-2-carbonitriles, allowed identification of new amidine and imidate derivatives as potent and dual CDK1/GSK-3 inhibitors. Combination of lead optimization and molecular modeling studies allowed identification of a dual CDK1/GSK-3 inhibitor (compound 13d) with submicromolar values. (c) 2007 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2007.09.020

文献信息

• Thiazolo[5,4-f]quinazolin-9-ones, inhibitors of glycogen synthase kinase-3
  作者：Alexandra Testard、Cédric Logé、Benoît Léger、Jean-Michel Robert、Olivier Lozach、Mélina Blairvacq、Laurent Meijer、Valérie Thiéry、Thierry Besson

  DOI：10.1016/j.bmcl.2006.04.006

  日期：2006.7

  In an effort to identify new protein kinase inhibitors with increased potency and selectivity, we have developed the microwave-assisted synthesis of thiazolo[5,4-f]quinazolin-9-ones. The effects of eighteen derivatives on CDK1/cyclin B, CDK5/p25, and GSK-3 were investigated. Several turned out to inhibit GSK-3 in the micromolar range. Molecular modeling studies suggest that the most selective GSK-3 inhibitors 7a-d bind into the ATP-binding site through a key hydrogen bond interaction with Val135 and target the specific hydrophobic backpocket of the enzyme. (c) 2006 Elsevier Ltd. All rights reserved.
• Novel 9-oxo-thiazolo[5,4-f]quinazoline-2-carbonitrile derivatives as dual cyclin-dependent kinase 1 (CDK1)/glycogen synthase kinase-3 (GSK-3) inhibitors: Synthesis, biological evaluation and molecular modeling studies
  作者：Cédric Logé、Alexandra Testard、Valérie Thiéry、Olivier Lozach、Mélina Blairvacq、Jean-Michel Robert、Laurent Meijer、Thierry Besson

  DOI：10.1016/j.ejmech.2007.09.020

  日期：2008.7

  Continuous efforts in microwave-assisted synthesis and the structure-activity relationships' (SARs) studies of novel modified 9-oxo-thiazolo[5,4-f]quinazoline-2-carbonitriles, allowed identification of new amidine and imidate derivatives as potent and dual CDK1/GSK-3 inhibitors. Combination of lead optimization and molecular modeling studies allowed identification of a dual CDK1/GSK-3 inhibitor (compound 13d) with submicromolar values. (c) 2007 Elsevier Masson SAS. All rights reserved.