methyl 1-(5-nitropicolinoyl)piperidine-4-carboxylate | 1395515-75-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: methyl 1-(5-nitropicolinoyl)piperidine-4-carboxylate
• 英文别名: Methyl 1-(5-nitropyridine-2-carbonyl)piperidine-4-carboxylate；methyl 1-(5-nitropyridine-2-carbonyl)piperidine-4-carboxylate
• CAS: 1395515-75-9
• 化学式: C₁₃H₁₅N₃O₅
• 分子量: 293.279
• InChiKey: ZEHIGCFELMPWEM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  105
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 1-(5-nitropicolinoyl)piperidine-4-carboxylate 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 、 N,N-二甲基乙酰胺 为溶剂， 20.0 ℃ 、303.99 kPa 条件下， 反应 168.5h， 生成 Methyl 1-[5-[(2,4-diaminopteridin-6-yl)methylamino]pyridine-2-carbonyl]piperidine-4-carboxylate
  参考文献：
  名称：

  Structure-Based Selectivity Optimization of Piperidine–Pteridine Derivatives as Potent Leishmania Pteridine Reductase Inhibitors

  摘要：

  The upregulation of pteridine reductase (PTR1) is a major contributor to antifolate drug resistance in Leishmania spp., as it provides a salvage pathway that bypasses dihydrofolate reductase (DHFR) inhibition. The structure-based optimization of the PTR1 inhibitor methyl-1-[4-(2,4-diaminopteridin-6-ylmethylamino)benzoyl]-piperidine-4-carboxylate (1) led to the synthesis of a focused compound library which showed significantly improved selectivity for the parasite's folate-dependent enzyme. When used in combination with pyrimethamine, a DHFR inhibitor, a synergistic effect was observed for compound 5b. This work represents a step forward in the identification of effective antileishmania agents.

  DOI：

  10.1021/jm300563f
• 作为产物：
  描述：

  5-硝基-2-吡啶羧酸 在 氯化亚砜 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 生成 methyl 1-(5-nitropicolinoyl)piperidine-4-carboxylate
  参考文献：
  名称：

  Structure-Based Selectivity Optimization of Piperidine–Pteridine Derivatives as Potent Leishmania Pteridine Reductase Inhibitors

  摘要：

  The upregulation of pteridine reductase (PTR1) is a major contributor to antifolate drug resistance in Leishmania spp., as it provides a salvage pathway that bypasses dihydrofolate reductase (DHFR) inhibition. The structure-based optimization of the PTR1 inhibitor methyl-1-[4-(2,4-diaminopteridin-6-ylmethylamino)benzoyl]-piperidine-4-carboxylate (1) led to the synthesis of a focused compound library which showed significantly improved selectivity for the parasite's folate-dependent enzyme. When used in combination with pyrimethamine, a DHFR inhibitor, a synergistic effect was observed for compound 5b. This work represents a step forward in the identification of effective antileishmania agents.

  DOI：

  10.1021/jm300563f