methyl 1-(3-ethyl-4-nitrobenzoyl)piperidine-4-carboxylate | 1395515-85-1

• 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-(3-ethyl-4-nitrobenzoyl)piperidine-4-carboxylate
• 英文别名: Methyl 1-(3-ethyl-4-nitrobenzoyl)piperidine-4-carboxylate
• CAS: 1395515-85-1
• 化学式: C₁₆H₂₀N₂O₅
• 分子量: 320.345
• InChiKey: ZAOKERRPMFIRTI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 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-(3-ethyl-4-nitrobenzoyl)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 170.0h， 生成 Methyl 1-[4-[(2,4-diaminopteridin-6-yl)methylamino]-3-ethylbenzoyl]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：

  3-ethyl-4-nitrobenzoic acid 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 8.0h， 生成 methyl 1-(3-ethyl-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.