DSM216 | 1309374-57-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: DSM216
• 英文别名: 5-methyl-N-(4-(pyrrolidin-1-yl)phenyl)-[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
• CAS: 1309374-57-9
• 化学式: C₁₆H₁₄N₆
• 分子量: 290.327
• InChiKey: LUJPYQPWCCFILM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.97
• 重原子数：
  22.0
• 可旋转键数：
  3.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  60.04
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为产物：
  描述：

  7-羟基-5-甲基-1,3,4-三氮吲哚利嗪 在 三氯氧磷 作用下， 以 乙醇 为溶剂， 反应 0.75h， 生成 DSM216
  参考文献：
  名称：

  Lead Optimization of Aryl and Aralkyl Amine-Based Triazolopyrimidine Inhibitors of Plasmodium falciparum Dihydroorotate Dehydrogenase with Antimalarial Activity in Mice

  摘要：

  Malaria is one of the leading causes of severe infectious disease worldwide; yet, our ability to maintain effective therapy to combat the illness is continually challenged by the emergence of drug resistance. We previously reported identification of a new class of triazolopyrimidine-based Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) inhibitors with antimalarial activity, leading to the discovery of a new lead series and novel target for drug development. Active compounds from the series contained a triazolopyrimidine ring attached to an aromatic group through a bridging nitrogen atom. Herein, we describe systematic efforts to optimize the aromatic functionality with the goal of improving potency and in vivo properties of compounds from the series. These studies led to the identification of two new substituted aniline moieties (4-SF(5)-Ph and 3,5-Di-F-4-CF(3)-Ph), which, when coupled to the triazolopyrimidine ring, showed good plasma exposure and better efficacy in the Plasmodium berghei mouse model of the disease than previously reported compounds from the series.

  DOI：

  10.1021/jm200265b