(Z)-tert-butyl 4-((2-(N'-hydroxycarbamimidoyl)benzo[b]thiophen-3-yl)oxy)piperidine-1-carboxylate | 1581303-59-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (Z)-tert-butyl 4-((2-(N'-hydroxycarbamimidoyl)benzo[b]thiophen-3-yl)oxy)piperidine-1-carboxylate
• CAS: 1581303-59-4
• 化学式: C₁₉H₂₅N₃O₄S
• 分子量: 391.491
• InChiKey: CCZJVFUOYBYFED-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.77
• 重原子数：
  27.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  97.38
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (Z)-tert-butyl 4-((2-(N'-hydroxycarbamimidoyl)benzo[b]thiophen-3-yl)oxy)piperidine-1-carboxylate 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 甲苯 、 乙腈 为溶剂， 反应 36.25h， 生成 tert-butyl 4-((2-(5-(3-methoxybenzyl)-1,2,4-oxadiazol-3-yl)benzo[b]thiophen-3-yl)oxy)piperidine-1-carboxylate
  参考文献：
  名称：

  Design and Synthesis of High Affinity Inhibitors of Plasmodium falciparum and Plasmodium vivax N-Myristoyltransferases Directed by Ligand Efficiency Dependent Lipophilicity (LELP)

  摘要：

  N-Myristoyltransferase (NMT) is an essential eukaryotic enzyme and an attractive drug target in parasitic infections such as malaria. We have previously reported that 2-(3-(piperidin-4-yloxy)benzo[b]thiophen-2-yl)-5-((1,3,5-trimethyl-1H-pyrazol-4-yl)methyl)-1,3,4-oxadiazole (34c) is a high affinity inhibitor of both Plasmodium falciparum and P. vivax NMT and displays activity in vivo against a rodent malaria model. Here we describe the discovery of 34c through optimization of a previously described series. Development, guided by targeting a ligand efficiency dependent lipophilicity (LELP) score of less than 10, yielded a 100-fold increase in enzyme affinity and a 100-fold drop in lipophilicity with the addition of only two heavy atoms. 34c was found to be equipotent on chloroquine-sensitive and -resistant cell lines and on both blood and liver stage forms of the parasite. These data further validate NMT as an exciting drug target in malaria and support 34c as an attractive tool for further optimization.

  DOI：

  10.1021/jm500066b
• 作为产物：
  描述：

  tert-butyl 4-((2-cyanobenzo[b]thiophen-3-yl)oxy)piperidine-1-carboxylate 在 羟胺 作用下， 以 乙醇 、 水 为溶剂， 反应 4.0h， 以99%的产率得到(Z)-tert-butyl 4-((2-(N'-hydroxycarbamimidoyl)benzo[b]thiophen-3-yl)oxy)piperidine-1-carboxylate
  参考文献：
  名称：

  Design and Synthesis of High Affinity Inhibitors of Plasmodium falciparum and Plasmodium vivax N-Myristoyltransferases Directed by Ligand Efficiency Dependent Lipophilicity (LELP)

  摘要：

  N-Myristoyltransferase (NMT) is an essential eukaryotic enzyme and an attractive drug target in parasitic infections such as malaria. We have previously reported that 2-(3-(piperidin-4-yloxy)benzo[b]thiophen-2-yl)-5-((1,3,5-trimethyl-1H-pyrazol-4-yl)methyl)-1,3,4-oxadiazole (34c) is a high affinity inhibitor of both Plasmodium falciparum and P. vivax NMT and displays activity in vivo against a rodent malaria model. Here we describe the discovery of 34c through optimization of a previously described series. Development, guided by targeting a ligand efficiency dependent lipophilicity (LELP) score of less than 10, yielded a 100-fold increase in enzyme affinity and a 100-fold drop in lipophilicity with the addition of only two heavy atoms. 34c was found to be equipotent on chloroquine-sensitive and -resistant cell lines and on both blood and liver stage forms of the parasite. These data further validate NMT as an exciting drug target in malaria and support 34c as an attractive tool for further optimization.

  DOI：

  10.1021/jm500066b