2-(1,1-difluoroethyl)-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-ol | 1281860-66-9

• 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-[1,2,4]triazolo[1,5-a]pyrimidin-7-ol
• CAS: 1281860-66-9
• 化学式: C₈H₈F₂N₄O
• 分子量: 214.175
• InChiKey: XXFSUEHQULDIBS-UHFFFAOYSA-N

物化性质

• 密度：
  1.57±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.25
• 重原子数：
  15.0
• 可旋转键数：
  1.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  63.31
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  2-(1,1-difluoroethyl)-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 N-(3-chlorophenyl)-2-(1,1-difluoroethyl)-5-methyl[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
• 作为产物：
  描述：

  二氟丙酸乙酯 、 2,3-Diamino-6-methyl-4(3H)-pyrimidinone 在 二氟丙酸乙酯 作用下， 生成 2-(1,1-difluoroethyl)-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-ol
  参考文献：
  名称：

  NEW SUBSTITUTED TRIAZOLOPYRIMIDINES AS ANTI-MALARIAL AGENTS

  摘要：

  本发明涉及在制造预防或治疗疟疾药物中使用三唑嘧啶衍生物的用途。具体而言，本发明涉及用于制备药物配方以抑制疟原虫增殖的三唑嘧啶衍生物。

  公开号：

  US20180065968A1

文献信息

• [EN] NEW SUBSTITUTED TRIAZOLOPYRIMIDINES AS ANTI-MALARIAL AGENTS<br/>[FR] NOUVELLES TRIAZOLOPYRIMIDINES SUBSTITUÉES UTILISÉES COMME AGENTS ANTI-PALUDISME
  申请人：UNIV TEXAS

  公开号：WO2016151521A1

  公开（公告）日：2016-09-29

  The present invention is related to a use of triazolopyrimidine derivatives in the manufacture of a medicament for preventing or treating malaria. Specifically, the present invention is related to triazolopyrimidine derivatives useful for the preparation of a pharmaceutical formulation for the inhibition of malaria parasite proliferation.

  本发明涉及三唑嘧啶衍生物在制造用于预防或治疗疟疾的药物中的应用。具体而言，本发明涉及三唑嘧啶衍生物，其可用于制备药物配方，以抑制疟原虫的增殖。
• Antimalarial agents that are inhibitors of dihydroorotate dehydrogenase
  申请人：Rathod Pradipsinh K.

  公开号：US09238653B2

  公开（公告）日：2016-01-19

  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.

  抑制寄生性二氢乳酸脱氢酶酶（DHOD）的酶抑制剂是治疗疟疾的候选药物。这种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。
• 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。
• [EN] ANTIMALARIAL AGENTS THAT ARE INHIBITORS OF DIHYDROOROTATE DEHYDROGENASE<br/>[FR] AGENTS ANTIPALUDIQUES INHIBITEURS DE LA DIHYDRO-OROTATE DÉSHYDROGÉNASE
  申请人：UNIV TEXAS

  公开号：WO2011041304A3

  公开（公告）日：2011-08-04
• METHODS AND COMPOSITIONS TO PREVENT ADDICTION
  申请人：Bhide Pradeep G.

  公开号：US20120302590A1

  公开（公告）日：2012-11-29

  Disclosed herein is a method of reducing or preventing the development of aversion to a CNS stimulant in a subject comprising, administering a therapeutic amount of the neurological stimulant and administering an antagonist of the kappa opioid receptor, to thereby reduce or prevent the development of aversion to the CNS stimulant in the subject. Also disclosed is a method of reducing or preventing the development of addiction to a CNS stimulant in a subject, comprising, administering the CNS stimulant and administering a mu opioid receptor antagonist to thereby reduce or prevent the development of addiction to the CNS stimulant in the subject. Also disclosed are pharmaceutical compositions comprising a central nervous system stimulant and an opioid receptor antagonist. Examples of central nervous system stimulants (such as methylphenidate) and opioid receptor antagonists (such as naltrexone) are provided.