ID-5841161 | 91769-08-3

• 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: ID-5841161
• 英文别名: 6-Methyl-4-p-anisidino-1,3,3a,7-tetraaza-inden；4-<4-Methoxy-anilino>-6-methyl-1,2,4-triazolo<2,3-a>pyrimidin；N-(4-methoxyphenyl)-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine；(4-methoxy-phenyl)-(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)-amine；7-p-anisidino-5-methyl-s-triazolo[1,5-a]pyrimidine；N-(4-methoxyphenyl)-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
• CAS: 91769-08-3
• 化学式: C₁₃H₁₃N₅O
• 分子量: 255.279
• InChiKey: DLVXCEBZMMWMQK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  64.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  7-氯-5-甲基-1,2,4-三唑并[1,5-Alpha]嘧啶 、 甲氧苯胺 以 乙醇 为溶剂， 生成 ID-5841161
  参考文献：
  名称：

  Identification of a Metabolically Stable Triazolopyrimidine-Based Dihydroorotate Dehydrogenase Inhibitor with Antimalarial Activity in Mice

  摘要：

  Plasmodium falciparum causes 1-2 million deaths annually. Yet current drug therapies are compromised by resistance. We previously described potent and selective triazolopyrimidine-based inhibitors of P. falciparum dihydroorotate dehydrogenase (PfDHODH) that inhibited parasite growth in vitro; however, they showed no activity in vivo. Here we show that lack of efficacy against P. berghei in mice resulted from a combination of poor plasma exposure and reduced potency against P. berghei DHODH. For compounds containing naphthyl (DSM1) or anthracenyl (DSM2), plasma exposure was reduced upon repeated dosing. Phenyl-substituted triazolopyrimidines were synthesized leading to identification of analogs with low predicted metabolism in human liver microsomes and which showed prolonged exposure in mice. Compound 21 (DSM74), containing p-trifluoromethylphenyl, suppressed growth of P. berghei in mice after oral administration. This study provides the first proof of concept that DHODH inhibitors can suppress Plasmodium growth in vivo, validating DHODH as a new target for antimalarial chemotherapy.

  DOI：

  10.1021/jm801343r

文献信息

• DIHYDROOROTATE DEHYDROGENASE INHIBITORS WITH SELECTIVE ANTI-MALARIAL ACTIVITY
  申请人：PHILLIPS Margaret

  公开号：US20090209557A1

  公开（公告）日：2009-08-20

  Compounds according to Formula I, Formula II, Formula III, Formula V, Formula VI, or to Formula VII, and pharmaceutical compositions of compounds that conform to Formula IV or Formula VIII: where R 1 through R 33 are prescribed, selectively inhibit P. falciparum dihydroorotate dehydrogenase. Accordingly, a method for preventing and treating malaria attaches to such compounds, as well as to pharmaceutically acceptable salts, solvates, stereoisomers, tautomers, and prodrugs thereof.

  按照公式I，公式II，公式III，公式V，公式VI或公式VII制备的化合物和符合公式IV或公式VIII的化合物的制药组合物：其中R1到R33被规定，可以选择性地抑制P. falciparum脱氢鞘氨酸脱氢酶。因此，一种预防和治疗疟疾的方法涉及到这些化合物，以及其药学上可接受的盐，溶剂化合物，立体异构体，互变异构体和前药。
• Cyclocondensation of N-aryl-3-oxobutanethioamides with 1H-1,2,4-triazol-5-amine
  作者：V. N. Britsun

  DOI：10.1134/s1070428008100229

  日期：2008.10

  Reactions of N-aryl-3-oxobutanethioamides with 1H-1,2,4-triazole-5-amine give mixtures of 7-arylamino-5-methyl[1,2,4]triazolo[1,5-a]pyrimidines, 5-methyl-4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidine-7-thione, 7-methyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidine-5-thione, and 5-arylamino-7-methyl[1,2,4]triazolo[ 1,5-a]pyrimidines whose ratio depends on the substituent in the aryl group of initial N-aryl-3-oxobutanethioamide and solvent nature (the presence of a proton-donor solvent).
• US9216983B2
  申请人：——

  公开号：US9216983B2

  公开（公告）日：2015-12-22
• Identification of a Metabolically Stable Triazolopyrimidine-Based Dihydroorotate Dehydrogenase Inhibitor with Antimalarial Activity in Mice
  作者：Ramesh Gujjar、Alka Marwaha、Farah El Mazouni、John White、Karen L. White、Sharon Creason、David M. Shackleford、Jeffrey Baldwin、William N. Charman、Frederick S. Buckner、Susan Charman、Pradipsinh K. Rathod、Margaret A. Phillips

  DOI：10.1021/jm801343r

  日期：2009.4.9

  Plasmodium falciparum causes 1-2 million deaths annually. Yet current drug therapies are compromised by resistance. We previously described potent and selective triazolopyrimidine-based inhibitors of P. falciparum dihydroorotate dehydrogenase (PfDHODH) that inhibited parasite growth in vitro; however, they showed no activity in vivo. Here we show that lack of efficacy against P. berghei in mice resulted from a combination of poor plasma exposure and reduced potency against P. berghei DHODH. For compounds containing naphthyl (DSM1) or anthracenyl (DSM2), plasma exposure was reduced upon repeated dosing. Phenyl-substituted triazolopyrimidines were synthesized leading to identification of analogs with low predicted metabolism in human liver microsomes and which showed prolonged exposure in mice. Compound 21 (DSM74), containing p-trifluoromethylphenyl, suppressed growth of P. berghei in mice after oral administration. This study provides the first proof of concept that DHODH inhibitors can suppress Plasmodium growth in vivo, validating DHODH as a new target for antimalarial chemotherapy.

表征谱图