tert-butyl (2E)-3-(8-{[(4-tert-butyl-1,3-thiazol-2-yl)amino]carbonyl}-2-(4-{[4-(2-hydroxyethyl)piperazin-1-yl]methyl}phenyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-3-yl)acrylate | 918309-35-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 英文名称: tert-butyl (2E)-3-(8-{[(4-tert-butyl-1,3-thiazol-2-yl)amino]carbonyl}-2-(4-{[4-(2-hydroxyethyl)piperazin-1-yl]methyl}phenyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-3-yl)acrylate
• CAS: 918309-35-0
• 化学式: C₃₆H₄₄N₆O₅S
• 分子量: 672.849
• InChiKey: ACUCYNVMGHVKFK-VAWYXSNFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.83
• 重原子数：
  48.0
• 可旋转键数：
  9.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  129.37
• 氢给体数：
  2.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  tert-butyl (2E)-3-(8-{[(4-tert-butyl-1,3-thiazol-2-yl)amino]carbonyl}-2-(4-{[4-(2-hydroxyethyl)piperazin-1-yl]methyl}phenyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-3-yl)acrylate 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 1.5h， 以105 mg的产率得到(2E)-3-(8-{[(4-tert-butyl-1,3-thiazol-2-yl)amino]carbonyl}-2-(4-{[4-(2-hydroxyethyl)piperazin-1-yl]methyl}phenyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-3-yl)acrylic acid
  参考文献：
  名称：

  MexAB-OprM specific efflux pump inhibitors in Pseudomonas aeruginosa. Part 6: Exploration of aromatic substituents

  摘要：

  A series of 4-oxo-4H-pyrido[1,2-a]pyrimidine derivatives, derivatized at the 2-position with aromatic substituents, were synthesized by the Suzuki cross-coupling method and evaluated for their ability to potentiate the activity of the fluoroquinolone levofloxacin (LVFX) and the anti-pseudomonas beta-lactam aztreonam (AZT) in Pseudomonas aeruginosa. By incorporating hydrophilic substituents onto the aryl nucleus, we found a morpholine analogue that possessed improved solubility, retained activity in vitro, and displayed potentiation activity in vivo in a rat model of P. aeruginosa pneumonia. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.08.037
• 作为产物：
  描述：

  tert-butyl (2E)-3-(8-{[(4-tert-butyl-1,3-thiazol-2-yl)amino]carbonyl}-2-chloro-4-oxo-4H-pyrido[1,2-a]pyrimidin-3-yl)acrylate 在 四(三苯基膦)钯 1,3-二甲基巴比妥酸 、 四溴化碳 、 sodium carbonate 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 二氯甲烷 、 水 为溶剂， 反应 128.0h， 生成 tert-butyl (2E)-3-(8-{[(4-tert-butyl-1,3-thiazol-2-yl)amino]carbonyl}-2-(4-{[4-(2-hydroxyethyl)piperazin-1-yl]methyl}phenyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-3-yl)acrylate
  参考文献：
  名称：

  MexAB-OprM specific efflux pump inhibitors in Pseudomonas aeruginosa. Part 6: Exploration of aromatic substituents

  摘要：

  A series of 4-oxo-4H-pyrido[1,2-a]pyrimidine derivatives, derivatized at the 2-position with aromatic substituents, were synthesized by the Suzuki cross-coupling method and evaluated for their ability to potentiate the activity of the fluoroquinolone levofloxacin (LVFX) and the anti-pseudomonas beta-lactam aztreonam (AZT) in Pseudomonas aeruginosa. By incorporating hydrophilic substituents onto the aryl nucleus, we found a morpholine analogue that possessed improved solubility, retained activity in vitro, and displayed potentiation activity in vivo in a rat model of P. aeruginosa pneumonia. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.08.037