(S)-2-((1-(benzylsulfonyl)piperidine-2-carbonyl)oxy)ethyl nicotinate

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (S)-2-((1-(benzylsulfonyl)piperidine-2-carbonyl)oxy)ethyl nicotinate
• 英文别名: 2-[(2~{s})-1-(Phenylmethyl)sulfonylpiperidin-2-Yl]carbonyloxyethyl Pyridine-3-Carboxylate；2-[(2S)-1-benzylsulfonylpiperidine-2-carbonyl]oxyethyl pyridine-3-carboxylate
• 化学式: C₂₁H₂₄N₂O₆S
• 分子量: 432.497
• InChiKey: KUWLHSSIHRTCQU-IBGZPJMESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  30
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  111
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-羟基乙基吡啶-3-羧酸酯 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 48.0h， 生成 (S)-2-((1-(benzylsulfonyl)piperidine-2-carbonyl)oxy)ethyl nicotinate
  参考文献：
  名称：

  Development, synthesis and structure–activity-relationships of inhibitors of the macrophage infectivity potentiator (Mip) proteins of Legionella pneumophila and Burkholderia pseudomallei

  摘要：

  The bacteria Burkholderia pseudomallei and Legionella pneumophila cause severe diseases like melioidosis and Legionnaire's disease with high mortality rates despite antibiotic treatment. Due to increasing antibiotic resistances against these and other Gram-negative bacteria, alternative therapeutical strategies are in urgent demand. As a virulence factor, the macrophage infectivity potentiator (Mip) protein constitutes an attractive target. The Mip proteins of B. pseudomallei and L. pneumophila exhibit peptidyl-prolyl cis/trans isomerase (PPIase) activity and belong to the PPIase superfamily. In previous studies, the pipecolic acid moiety proved to be a valuable scaffold for inhibiting this PPIase activity. Thus, a library of pipecolic acid derivatives was established guided by structural information and computational analyses of the binding site and possible binding modes. Stability and toxicity considerations were taken into account in iterative extensions of the library. Synthesis and evaluation of the compounds in PPlase assays resulted in highly active inhibitors. The activities can be interpreted in terms of a common binding mode obtained by docking calculations. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.08.025

文献信息

• Development, synthesis and structure–activity-relationships of inhibitors of the macrophage infectivity potentiator (Mip) proteins of Legionella pneumophila and Burkholderia pseudomallei
  作者：Florian Seufert、Maximilian Kuhn、Michael Hein、Matthias Weiwad、Mirella Vivoli、Isobel H. Norville、Mitali Sarkar-Tyson、Laura E. Marshall、Kristian Schweimer、Heike Bruhn、Paul Rösch、Nicholas J. Harmer、Christoph A. Sotriffer、Ulrike Holzgrabe

  DOI：10.1016/j.bmc.2016.08.025

  日期：2016.11

  The bacteria Burkholderia pseudomallei and Legionella pneumophila cause severe diseases like melioidosis and Legionnaire's disease with high mortality rates despite antibiotic treatment. Due to increasing antibiotic resistances against these and other Gram-negative bacteria, alternative therapeutical strategies are in urgent demand. As a virulence factor, the macrophage infectivity potentiator (Mip) protein constitutes an attractive target. The Mip proteins of B. pseudomallei and L. pneumophila exhibit peptidyl-prolyl cis/trans isomerase (PPIase) activity and belong to the PPIase superfamily. In previous studies, the pipecolic acid moiety proved to be a valuable scaffold for inhibiting this PPIase activity. Thus, a library of pipecolic acid derivatives was established guided by structural information and computational analyses of the binding site and possible binding modes. Stability and toxicity considerations were taken into account in iterative extensions of the library. Synthesis and evaluation of the compounds in PPlase assays resulted in highly active inhibitors. The activities can be interpreted in terms of a common binding mode obtained by docking calculations. (C) 2016 Elsevier Ltd. All rights reserved.