7-氯-5-甲基-2-(甲硫基)-[1,2,4]三唑并[1,5-A]嘧啶 | 101251-18-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三唑并嘧啶类
• 中文名称: 7-氯-5-甲基-2-(甲硫基)-[1,2,4]三唑并[1,5-A]嘧啶
• 英文名称: 5-chloro-7-methyl-2-methylthio-1,2,4-triazolo[1,5-a]pyrimidine
• 英文别名: 7-chloro-5-methyl-2-(methylthio)[1,2,4]triazolo[ 1,5-a]pyrimidine；7-chloro-5-methyl-2-methylsulfanyl-[1,2,4]triazolo[1,5-a]pyrimidine；7-Chloro-5-methyl-2-(methylthio)-[1,2,4]triazolo[1,5-a]pyrimidine；7-chloro-5-methyl-2-methylsulfanyl-[1,2,4]triazolo[1,5-a]pyrimidine
• CAS: 101251-18-7
• 化学式: C₇H₇ClN₄S
• 分子量: 214.678
• InChiKey: QEFWPDVSBZHJOK-UHFFFAOYSA-N

物化性质

• 密度：
  1.58±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  68.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  7-氯-5-甲基-2-(甲硫基)-[1,2,4]三唑并[1,5-A]嘧啶 在 sodium tungstate 、 双氧水 、 sodium hydride 、 溶剂黄146 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 生成 N-(3-chlorophenyl)-5-methyl-2-{[2-(methyloxy)ethyl]oxy}[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：

  5-methyl-2-methylsulfanyl-4H-[1,2,4]triazolo[1,5-a]pyrimidin-7-one 在 吡啶 、 三氯氧磷 作用下， 反应 6.0h， 以62%的产率得到7-氯-5-甲基-2-(甲硫基)-[1,2,4]三唑并[1,5-A]嘧啶
  参考文献：
  名称：

  在三唑上。XXXIX † ‡。1,2,4-三唑并[1,5 - a ]嘧啶-5-酮肟的合成与结构

  摘要：

  一些1,2,4-三唑并[1,5- a ]嘧啶-5-酮衍生物1及其脂环式稠环类似物2-3通过相应的“亚氨基氯化物” 4-6转化为肟7-9。使用相应的作为模型化合物制备的“苄基肟基”衍生物10-12的光谱数据，使用cmr证明了所获得产品的“ E ”异构体结构。

  DOI：

  10.1002/jhet.5570340522

文献信息

• On triazoles. XL [1]. Non catalytic dehalogenation of some 5-chloro-1,2,4-triazolo[1,5-<i>a</i>]pyrimidine derivatives
  作者：Gábor Berecz、József Reiter、János Császár

  DOI：10.1002/jhet.5570360515

  日期：1999.9

  A non catalytic dehalogenation method of type 4 5-chloro-1,2,4-triazolo[1,5-a]pyrimidine derivatives based on the hydrolysis of the corresponding type 5 p-toluenesulphonyl hydrazones with diluted aqueous sodium carbonate solution was elaborated. The method provides the required 5-unsubstituted derivatives 6 also in those cases when the simple hydrogenation is not possible. Using deuterium oxide as

  型的非催化脱卤方法4 5-氯1，2,4-三唑并[1,5一个基于相应的5型的水解]嘧啶衍生物p与稀释的碳酸钠水溶液甲苯磺酰腙进行详细阐述。在不可能简单氢化的情况下，该方法也提供了所需的5-未取代的衍生物6。使用氘化氢作为水解的溶剂，氘原子也可以插入衍生物6的5位。还分离了反应的不同副产物，并给出了其形成的可能解释。
• 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。
• 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.

  寄生性二氢乳酸脱氢酶酶（DHOD）的抑制剂是治疗疟疾的候选治疗药物。这种治疗剂的例子包括化合物：以及符合公式IX的三唑嘧啶类化合物：以及它们的溶剂化物、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
• US9238653B2
  申请人：——

  公开号：US9238653B2

  公开（公告）日：2016-01-19