2-(1,1-difluoroethyl)-5-methyl-[N-[4-(pentafluorosulfanyl)phenyl]1,2,4]triazolo[1,5-a]pyrimidin-7-amine | 1282041-89-7

• 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: 2-(1,1-difluoroethyl)-5-methyl-[N-[4-(pentafluorosulfanyl)phenyl]1,2,4]triazolo[1,5-a]pyrimidin-7-amine
• 英文别名: 2-(trifluoromethyl)-N-(4-(sulfurpentafluoro)phenyl)-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-amine；DSM196；DSM265；5-methyl-2-(trifluoromethyl)-N-(4-(pentafluorosulfur)phenyl)-[1,2,4]triazolo[1,5-a]pyrimidin-7-amine；5-methyl-N-[4-(pentafluoro-$l^{6}-sulfanyl)phenyl]-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyrimidin-7-amine；5-methyl-N-[4-(pentafluoro-λ6-sulfanyl)phenyl]-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
• CAS: 1282041-89-7
• 化学式: C₁₃H₉F₈N₅S
• 分子量: 419.301
• InChiKey: PHPXBFMLYCJALY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  27
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  56.1
• 氢给体数：
  1
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  2-(trifluoromethyl)-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-ol 在 三氯氧磷 作用下， 以 乙醇 为溶剂， 反应 1.0h， 生成 2-(1,1-difluoroethyl)-5-methyl-[N-[4-(pentafluorosulfanyl)phenyl]1,2,4]triazolo[1,5-a]pyrimidin-7-amine
  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

文献信息

• ANTIMALARIAL AGENTS THAT ARE INHIBITORS OF DIHYDROOROTATE DEHYDROGENASE
  申请人：Rathod Pradipsinh K.

  公开号：US20120302586A1

  公开（公告）日：2012-11-29

  Inhibitors of parasitic dihydroorotate dehydrogenase enzyme (DHOD) are candidate therapeutics for treating malaria. Illustrative of such therapeutic agents include the compound: and a triazolopyrimidine class of compounds that conform to Formula IX: and their solvates, stereoisomers, tautomers and pharmaceutically acceptable salts.

  抑制寄生虫脱氢酶酶（DHOD）的药物是治疗疟疾的候选治疗药物。这类治疗药物的例子包括化合物：以及符合公式IX的三唑嘧啶类化合物及其溶剂化物、立体异构体、互变异构体和药学上可接受的盐。
• US9238653B2
  申请人：——

  公开号：US9238653B2

  公开（公告）日：2016-01-19
• Structure-Guided Lead Optimization of Triazolopyrimidine-Ring Substituents Identifies Potent <i>Plasmodium falciparum</i> Dihydroorotate Dehydrogenase Inhibitors with Clinical Candidate Potential
  作者：Jose M. Coteron、María Marco、Jorge Esquivias、Xiaoyi Deng、Karen L. White、John White、Maria Koltun、Farah El Mazouni、Sreekanth Kokkonda、Kasiram Katneni、Ravi Bhamidipati、David M. Shackleford、Iñigo Angulo-Barturen、Santiago B. Ferrer、María Belén Jiménez-Díaz、Francisco-Javier Gamo、Elizabeth J. Goldsmith、William N. Charman、Ian Bathurst、David Floyd、David Matthews、Jeremy N. Burrows、Pradipsinh K. Rathod、Susan A. Charman、Margaret A. Phillips

  DOI：10.1021/jm200592f

  日期：2011.8.11

  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.