5-methyl-2-{2-[(phenylmethyl)oxy]ethyl}[1,2,4]triazolo[1,5-a]pyrimidin-7-ol | 1315607-36-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三唑并嘧啶类
• 英文名称: 5-methyl-2-{2-[(phenylmethyl)oxy]ethyl}[1,2,4]triazolo[1,5-a]pyrimidin-7-ol
• CAS: 1315607-36-3
• 化学式: C₁₅H₁₆N₄O₂
• 分子量: 284.318
• InChiKey: CNLQEMNQMPPYFJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  21.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  72.54
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  5-methyl-2-{2-[(phenylmethyl)oxy]ethyl}[1,2,4]triazolo[1,5-a]pyrimidin-7-ol 在 三氯氧磷 作用下， 反应 1.0h， 以75%的产率得到7-chloro-5-methyl-2-{2-[(phenylmethyl)oxy]ethyl}[1,2,4]triazolo[1,5-a]pyrimidine
  参考文献：
  名称：

  Structure-Guided Lead Optimization of Triazolopyrimidine-Ring Substituents Identifies Potent Plasmodium falciparum Dihydroorotate Dehydrogenase Inhibitors with Clinical Candidate Potential

  摘要：

  Drug therapy is the mainstay of antimalarial therapy, yet current drugs are threatened by the development of resistance. In an effort to identify new potential antimalarials, we have undertaken a lead optimization program around our previously identified triazolopyrimidine-based series of Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) inhibitors. The X-ray structure of PfDHODH was used to inform the medicinal chemistry program allowing the identification of a potent and selective inhibitor (DSM265) that acts through DHODH inhibition to kill both sensitive and drug resistant strains of the parasite. This compound has similar potency to chloroquine in the humanized SCID mouse P. falciparum model, can be synthesized by a simple route, and rodent pharmaco-kinetic studies demonstrated it has excellent oral bioavailability, a long half-life and low clearance. These studies have identified the first candidate in the triazolopyrimidine series to meet previously established progression criteria for efficacy and ADME properties, justifying further development of this compound toward clinical candidate status.

  DOI：

  10.1021/jm200592f
• 作为产物：
  描述：

  3-苄氧基丙酸甲酯 在 sodium ethanolate 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 5.5h， 生成 5-methyl-2-{2-[(phenylmethyl)oxy]ethyl}[1,2,4]triazolo[1,5-a]pyrimidin-7-ol
  参考文献：
  名称：

  Structure-Guided Lead Optimization of Triazolopyrimidine-Ring Substituents Identifies Potent Plasmodium falciparum Dihydroorotate Dehydrogenase Inhibitors with Clinical Candidate Potential

  摘要：

  Drug therapy is the mainstay of antimalarial therapy, yet current drugs are threatened by the development of resistance. In an effort to identify new potential antimalarials, we have undertaken a lead optimization program around our previously identified triazolopyrimidine-based series of Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) inhibitors. The X-ray structure of PfDHODH was used to inform the medicinal chemistry program allowing the identification of a potent and selective inhibitor (DSM265) that acts through DHODH inhibition to kill both sensitive and drug resistant strains of the parasite. This compound has similar potency to chloroquine in the humanized SCID mouse P. falciparum model, can be synthesized by a simple route, and rodent pharmaco-kinetic studies demonstrated it has excellent oral bioavailability, a long half-life and low clearance. These studies have identified the first candidate in the triazolopyrimidine series to meet previously established progression criteria for efficacy and ADME properties, justifying further development of this compound toward clinical candidate status.

  DOI：

  10.1021/jm200592f