N-(4-tert-butyl-1,3-thiazol-2-yl)-2-[(3R)-3-hydroxypiperidin-1-yl]-3-{(E)-2-[1-(4-methoxybenzyl)-1H-tetrazol-5-yl]vinyl}-4-oxo-4H-pyrido[1,2-a]pyrimidine-8-carboxamide | 475062-09-0

• 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: N-(4-tert-butyl-1,3-thiazol-2-yl)-2-[(3R)-3-hydroxypiperidin-1-yl]-3-{(E)-2-[1-(4-methoxybenzyl)-1H-tetrazol-5-yl]vinyl}-4-oxo-4H-pyrido[1,2-a]pyrimidine-8-carboxamide
• 英文别名: N-(4-tert-butyl-1,3-thiazol-2-yl)-2-[(3R)-3-hydroxypiperidin-1-yl]-3-[(E)-2-[1-[(4-methoxyphenyl)methyl]tetrazol-5-yl]ethenyl]-4-oxopyrido[1,2-a]pyrimidine-8-carboxamide
• CAS: 475062-09-0
• 化学式: C₃₂H₃₅N₉O₄S
• 分子量: 641.754
• InChiKey: RHFIBYXSXYUJKL-VDZCTEQFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  46
• 可旋转键数：
  9
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  179
• 氢给体数：
  2
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  N-(4-tert-butyl-1,3-thiazol-2-yl)-2-[(3R)-3-hydroxypiperidin-1-yl]-3-{(E)-2-[1-(4-methoxybenzyl)-1H-tetrazol-5-yl]vinyl}-4-oxo-4H-pyrido[1,2-a]pyrimidine-8-carboxamide 、 三氯乙酰异氰酸酯 以 乙酸乙酯 为溶剂， 反应 0.75h， 生成
  参考文献：
  名称：

  MexAB-OprM specific efflux pump inhibitors in Pseudomonas aeruginosa. Part 7: Highly soluble and in vivo active quaternary ammonium analogue D13-9001, a potential preclinical candidate

  摘要：

  A series of 4-oxo-4H-pyrido[1,2-a]pyrimidine derivatives, Substituted at the 2-position with piperidines bearing quaternary ammonium salt side chains, were synthesized and evaluated for their ability to potentiate the activity of the fluoroquinolone levofloxacin (LVFX) and the beta-lactam aztreonam (AZT) in Pseudomonas aeruginosa. Attachment of the charged entity using an N-ethylcarbamoyloxy linker led to the discovery of the highly soluble compound 22 (D13-9001), which maintained good potency in vitro and displayed excellent activity in vivo in a rat pneumonia model of P. aeruginosa. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.07.039
• 作为产物：
  描述：

  N-(4-tert-butyl-1,3-thiazol-2-yl)-2-hydroxy-3-{(E)-2-[1-(4-methoxybenzyl)-1H-tetrazol-5-yl]vinyl}-4-oxo-4H-pyrido[1,2-a]pyrimidine-8-carboxamide 、 (R)-(+)-3-羟基哌啶盐酸盐 在 N,N-二异丙基乙胺 、 氯磷酸二苯酯 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 1.83h， 以10.8 g的产率得到N-(4-tert-butyl-1,3-thiazol-2-yl)-2-[(3R)-3-hydroxypiperidin-1-yl]-3-{(E)-2-[1-(4-methoxybenzyl)-1H-tetrazol-5-yl]vinyl}-4-oxo-4H-pyrido[1,2-a]pyrimidine-8-carboxamide
  参考文献：
  名称：

  MexAB-OprM specific efflux pump inhibitors in Pseudomonas aeruginosa. Part 7: Highly soluble and in vivo active quaternary ammonium analogue D13-9001, a potential preclinical candidate

  摘要：

  A series of 4-oxo-4H-pyrido[1,2-a]pyrimidine derivatives, Substituted at the 2-position with piperidines bearing quaternary ammonium salt side chains, were synthesized and evaluated for their ability to potentiate the activity of the fluoroquinolone levofloxacin (LVFX) and the beta-lactam aztreonam (AZT) in Pseudomonas aeruginosa. Attachment of the charged entity using an N-ethylcarbamoyloxy linker led to the discovery of the highly soluble compound 22 (D13-9001), which maintained good potency in vitro and displayed excellent activity in vivo in a rat pneumonia model of P. aeruginosa. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.07.039