methyl 1-(4-nitrobenzoyl)piperidine-4-carboxylate | 349613-86-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methyl 1-(4-nitrobenzoyl)piperidine-4-carboxylate
• CAS: 349613-86-1
• 化学式: C₁₄H₁₆N₂O₅
• mdl: MFCD02861699
• 分子量: 292.291
• InChiKey: ZZSXHZRZNTYACB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  92.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 1-(4-nitrobenzoyl)piperidine-4-carboxylate 在 氢气 、 钯 作用下， 以 乙醇 为溶剂， 20.0 ℃ 、303.99 kPa 条件下， 反应 0.5h， 以92%的产率得到methyl 1-(4-aminobenzoyl)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：

  4-哌啶甲酸甲酯 、 4-硝基苯甲酰氯 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 以88%的产率得到methyl 1-(4-nitrobenzoyl)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

文献信息

• Structure-Based Selectivity Optimization of Piperidine–Pteridine Derivatives as Potent Leishmania Pteridine Reductase Inhibitors
  作者：Paola Corona、Federica Gibellini、Andrea Cavalli、Puneet Saxena、Antonio Carta、Mario Loriga、Rosaria Luciani、Giuseppe Paglietti、Davide Guerrieri、Erika Nerini、Shreedhara Gupta、Véronique Hannaert、Paul A. M. Michels、Stefania Ferrari、Paola M. Costi

  DOI：10.1021/jm300563f

  日期：2012.10.11

  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.