1-(4-((2,4-diaminopteridin-6-yl)methylamino)benzoyl)piperidine-4-carboxamide | 1166855-26-0

• 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: 1-(4-((2,4-diaminopteridin-6-yl)methylamino)benzoyl)piperidine-4-carboxamide
• 英文别名: 1-[4-[(2,4-Diaminopteridin-6-yl)methylamino]benzoyl]piperidine-4-carboxamide
• CAS: 1166855-26-0
• 化学式: C₂₀H₂₃N₉O₂
• 分子量: 421.462
• InChiKey: LMKXBYYGJWCTTQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  179
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  1-(4-((2,4-diaminopteridin-6-yl)methylamino)benzoyl)piperidine-4-carboxamide 在 水 、 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 3.08h， 以92%的产率得到N-[4-(2,4-diaminopteridin-6-ylmethylamino)benzoyl]-N-piperidin-4-carboxylic acid
  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：

  哌啶-4-甲酰胺 在 palladium 10% on activated carbon 、 氢气 、 碳酸氢钠 作用下， 以 乙醇 、 N,N-二甲基乙酰胺 、 水 为溶剂， 20.0~100.0 ℃ 、303.99 kPa 条件下， 反应 175.83h， 生成 1-(4-((2,4-diaminopteridin-6-yl)methylamino)benzoyl)piperidine-4-carboxamide
  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

• SPECIFIC INHIBITORS OF PTERIDINE REDUCTASE WITH ANTIPARASITIC ACTION
  申请人：Tydock Pharma S.r.l.

  公开号：EP2234998A2

  公开（公告）日：2010-10-06
• [EN] SPECIFIC INHIBITORS OF PTERIDINE REDUCTASE WITH ANTIPARASITIC ACTION<br/>[FR] INHIBITEURS SPÉCIFIQUES DE LA PTÉRIDINE RÉDUCTASE À ACTION ANTIPARASITAIRE
  申请人：TYDOCKPHARMA S R L

  公开号：WO2009080367A2

  公开（公告）日：2009-07-02

  The processes for the preparation of alkyl derivatives of N-[4-(2,4-diaminopteridin-6- ylmethylamino)benzoyl]-N-piperidin-2-carboxylic acid and N-[4-(2,4-diaminopteridin-6- ylmethylamino)benzoyl] -N-piperidin-4-carboxylic acid and of N-[4-(2,4-diaminopteridin-6- ylmethylamino)benzoyl]-N-pyrrolidin-2-carboxylic acid and N-[4-(2,4-diaminopteridin-6- ylmethylamino)benzoyl]-N-pyrrolidin-4-carboxylic acid. Their specific properties of inhibition versus Pteridine reductase of parasitic species. The processes for the preparation of alkyl derivatives of 1-[4-(quinoxalin-2- ylamino)benzoyl]piperidin-mono and di-carboxylic acid and alkyl derivatives of 1-[4- (quinoxalin-2-ylamino)benzoyl]pyrrolidin-mono and di-carboxylic acid. The specific properties of inhibition versus Pteridine reductase of parasitic species. The processes for the preparation of alkyl derivatives of 4-(6,7-dimethoxy-quinoxalin-2- ylmethoxy)benzoic acid and alkyl derivatives of 2-(phenylsulfanil)-quinoxalin-5,7-diamine and their specific properties of inhibition versus Pteridine reductase of bacterial species. The pharmaceutical composition and their use in the treatment and prevention of parasitic infections caused by Leishmania and Tripanosoma and their antiparasitic action in combination with Pyrimetamine.
• 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.