N-(4-tert-butyl-1,3-thiazol-2-yl)-2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidine-8-carboxamide | 712267-68-0

• 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-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidine-8-carboxamide
• 英文别名: N-(4-tert-butyl-1,3-thiazol-2-yl)-2-hydroxy-4-oxopyrido[1,2-a]pyrimidine-8-carboxamide
• CAS: 712267-68-0
• 化学式: C₁₆H₁₆N₄O₃S
• 分子量: 344.394
• InChiKey: KULJHWDGIWGKGM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  123
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-(4-tert-butyl-1,3-thiazol-2-yl)-2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidine-8-carboxamide 在 sodium methylate 、 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 四氢呋喃 、 甲醇 、 乙酸乙酯 为溶剂， 生成
  参考文献：
  名称：

  MexAB-OprM specific efflux pump inhibitors in Pseudomonas aeruginosa. Part 4: Addressing the problem of poor stability due to photoisomerization of an acrylic acid moiety

  摘要：

  Exchange of the ethylene tether in a series of pyridopyrimidine-based MexAB-OprM specific efflux pump inhibitors to an amide bond stabilized the olefin of the acrylic acid moiety, preventing facile photoisomerization to the Z-isomer. Furthermore, the activity was drastically improved in the amide tether variants, providing extremely potent acrylic acid and vinyl tetrazole analogues. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.03.007
• 作为产物：
  描述：

  2-乙酰基氨基异烟酸 在 盐酸 、 4-二甲氨基吡啶 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 乙醇 、 二氯甲烷 、 xylene 为溶剂， 生成 N-(4-tert-butyl-1,3-thiazol-2-yl)-2-hydroxy-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 4: Addressing the problem of poor stability due to photoisomerization of an acrylic acid moiety

  摘要：

  Exchange of the ethylene tether in a series of pyridopyrimidine-based MexAB-OprM specific efflux pump inhibitors to an amide bond stabilized the olefin of the acrylic acid moiety, preventing facile photoisomerization to the Z-isomer. Furthermore, the activity was drastically improved in the amide tether variants, providing extremely potent acrylic acid and vinyl tetrazole analogues. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.03.007

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.