(E)-N-(2-Cyano-ethyl)-3-{2-(3-hydroxy-piperidin-1-yl)-8-[2-(4-isopropyl-thiazol-2-yl)-ethyl]-4-oxo-4H-pyrido[1,2-a]pyrimidin-3-yl}-acrylamide | 678186-76-0

• 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: (E)-N-(2-Cyano-ethyl)-3-{2-(3-hydroxy-piperidin-1-yl)-8-[2-(4-isopropyl-thiazol-2-yl)-ethyl]-4-oxo-4H-pyrido[1,2-a]pyrimidin-3-yl}-acrylamide
• CAS: 678186-76-0
• 化学式: C₂₇H₃₂N₆O₃S
• 分子量: 520.655
• InChiKey: BKCGLBLFDOXBCE-BQYQJAHWSA-N

物化性质

• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.06
• 重原子数：
  37.0
• 可旋转键数：
  9.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  123.62
• 氢给体数：
  2.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  (E)-N-(2-Cyano-ethyl)-3-{2-(3-hydroxy-piperidin-1-yl)-8-[2-(4-isopropyl-thiazol-2-yl)-ethyl]-4-oxo-4H-pyrido[1,2-a]pyrimidin-3-yl}-acrylamide 在 sodium azide 、 三氟甲磺酸酐 作用下， 以 二氯甲烷 为溶剂， 以46%的产率得到3-[5-((E)-2-{2-(3-Hydroxy-piperidin-1-yl)-8-[2-(4-isopropyl-thiazol-2-yl)-ethyl]-4-oxo-4H-pyrido[1,2-a]pyrimidin-3-yl}-vinyl)-tetrazol-1-yl]-propionitrile
  参考文献：
  名称：

  MexAB-OprM specific efflux pump inhibitors in Pseudomonas aeruginosa. Part 3: Optimization of potency in the pyridopyrimidine series through the application of a pharmacophore model

  摘要：

  The addition of substituents to the pyridopyrimidine scaffold of MexAB-OprM specific efflux pump inhibitors was explored. As predicted by a pharmacophore model, the incorporation substituents at the 2-position improved potency. Piperidines were found to be optimal, and further introduction of polar groups without compromising the activity was shown to be feasible. Careful positioning of the essential acidic moiety of the pharmacophore relative to the scaffold led to the discovery of vinyl tetrazoles with still greater potency. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.10.060
• 作为产物：
  描述：

  在 盐酸 、 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 1,4-二氧六环 、 二氯甲烷 为溶剂， 生成 (E)-N-(2-Cyano-ethyl)-3-{2-(3-hydroxy-piperidin-1-yl)-8-[2-(4-isopropyl-thiazol-2-yl)-ethyl]-4-oxo-4H-pyrido[1,2-a]pyrimidin-3-yl}-acrylamide
  参考文献：
  名称：

  MexAB-OprM specific efflux pump inhibitors in Pseudomonas aeruginosa. Part 3: Optimization of potency in the pyridopyrimidine series through the application of a pharmacophore model

  摘要：

  The addition of substituents to the pyridopyrimidine scaffold of MexAB-OprM specific efflux pump inhibitors was explored. As predicted by a pharmacophore model, the incorporation substituents at the 2-position improved potency. Piperidines were found to be optimal, and further introduction of polar groups without compromising the activity was shown to be feasible. Careful positioning of the essential acidic moiety of the pharmacophore relative to the scaffold led to the discovery of vinyl tetrazoles with still greater potency. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.10.060