8-ethyl-9-oxo-8,9-dihydrothiazolo[5,4-f]quinazoline-2-carbonitrile | 873850-18-1

• 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: 8-ethyl-9-oxo-8,9-dihydrothiazolo[5,4-f]quinazoline-2-carbonitrile
• 英文别名: 8-ethyl-9-oxo-[1,3]thiazolo[5,4-f]quinazoline-2-carbonitrile
• CAS: 873850-18-1
• 化学式: C₁₂H₈N₄OS
• 分子量: 256.288
• InChiKey: WEBAHWNYXXIYMX-UHFFFAOYSA-N

物化性质

• 熔点：
  >260 °C
• 沸点：
  476.0±55.0 °C(Predicted)
• 密度：
  1.52±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  18.0
• 可旋转键数：
  1.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  71.57
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  8-ethyl-9-oxo-8,9-dihydrothiazolo[5,4-f]quinazoline-2-carbonitrile 、 正丁醇 在 sodium hydroxide 作用下， 反应 0.25h， 以67%的产率得到8-Ethyl-9-oxo-8,9-dihydro-thiazolo[5,4-f]quinazoline-2-carboximidic acid butyl ester
  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
• 作为产物：
  描述：

  5-bromo-6-[(4-chloro-5H-1,2,3-dithiazol-5-ylidene)amino]-3-ethyl-3H-quinazolin-4-one 在 吡啶 、 copper(l) iodide 作用下， 反应 0.02h， 以93%的产率得到8-ethyl-9-oxo-8,9-dihydrothiazolo[5,4-f]quinazoline-2-carbonitrile
  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.