(3R)-1-(8-{[(4-tert-butyl-1,3-thiazol-2-yl)amino]carbonyl}-3-{(E)-2-[1-(4-methoxybenzyl)-1H-tetrazol-5-yl]vinyl}-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)piperidin-3-yl [3-(dimethylamino)propyl]carbamate

• 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: (3R)-1-(8-{[(4-tert-butyl-1,3-thiazol-2-yl)amino]carbonyl}-3-{(E)-2-[1-(4-methoxybenzyl)-1H-tetrazol-5-yl]vinyl}-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)piperidin-3-yl [3-(dimethylamino)propyl]carbamate
• 英文别名: [(3R)-1-[8-[(4-tert-butyl-1,3-thiazol-2-yl)carbamoyl]-3-[(E)-2-[1-[(4-methoxyphenyl)methyl]tetrazol-5-yl]ethenyl]-4-oxopyrido[1,2-a]pyrimidin-2-yl]piperidin-3-yl] N-[3-(dimethylamino)propyl]carbamate
• 化学式: C₃₈H₄₇N₁₁O₅S
• 分子量: 769.928
• InChiKey: HYARFXQCUHNQNL-FCAYZRQCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  55
• 可旋转键数：
  15
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  201
• 氢给体数：
  2
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  (3R)-1-(8-{[(4-tert-butyl-1,3-thiazol-2-yl)amino]carbonyl}-3-{(E)-2-[1-(4-methoxybenzyl)-1H-tetrazol-5-yl]vinyl}-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)piperidin-3-yl [3-(dimethylamino)propyl]carbamate 、 溴乙酸叔丁酯 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 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-[(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 、 Carbonyldiimidazole 、 N,N-二甲基-1,3-二氨基丙烷 以 二氯甲烷 为溶剂， 以100 mg的产率得到(3R)-1-(8-{[(4-tert-butyl-1,3-thiazol-2-yl)amino]carbonyl}-3-{(E)-2-[1-(4-methoxybenzyl)-1H-tetrazol-5-yl]vinyl}-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl)piperidin-3-yl [3-(dimethylamino)propyl]carbamate
  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

文献信息

• 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
  作者：Ken-ichi Yoshida、Kiyoshi Nakayama、Masami Ohtsuka、Noriko Kuru、Yoshihiro Yokomizo、Atsunobu Sakamoto、Makoto Takemura、Kazuki Hoshino、Hiroko Kanda、Hironobu Nitanai、Kenji Namba、Kumi Yoshida、Yuichiro Imamura、Jason Z. Zhang、Ving J. Lee、William J. Watkins

  DOI：10.1016/j.bmc.2007.07.039

  日期：2007.11

  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.