2-methyl-N-(2-naphthyl)-9H-purin-6-amine | 1163260-10-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 2-methyl-N-(2-naphthyl)-9H-purin-6-amine
• 英文别名: 2-methyl-N-naphthalen-2-yl-7H-purin-6-amine
• CAS: 1163260-10-3
• 化学式: C₁₆H₁₃N₅
• 分子量: 275.313
• InChiKey: FTOLTNPJCBKINU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  66.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  5-(methyl(ethoxy)methylene)-aminoimidazole-4-carboxamide 在 N,N-二甲基苯胺 、 三氯氧磷 作用下， 以 乙醇 为溶剂， 反应 1.5h， 生成 2-methyl-N-(2-naphthyl)-9H-purin-6-amine
  参考文献：
  名称：

  Bioisosteric Transformations and Permutations in the Triazolopyrimidine Scaffold To Identify the Minimum Pharmacophore Required for Inhibitory Activity against Plasmodium falciparum Dihydroorotate Dehydrogenase

  摘要：

  Plasmodium falciparum causes approximately 1 million deaths annually. However, increasing resistance imposes a continuous threat to existing drug therapies. We previously reported a number of potent and selective triazolopyrimidine-based inhibitors of P. falciparum dihydroorotate dehydrogenase that inhibit parasite in vitro growth with similar activity. Lead optimization of this series led to the recent identification of a preclinical candidate, showing good activity against P. falciparum in mice. As part of a backup program around this scaffold, we explored heteroatom rearrangement and substitution in the triazolopyrimidine ring and have identified several other ring configurations that are active as PfDHODH inhibitors. The imidazo[1,2-a]pyrimidines were shown to bind somewhat more potently than the triazolopyrimidines depending on the nature of the amino aniline substitution. DSM151, the best candidate in this series, binds with 4-fold better affinity (PfDHODH IC50 = 0.077 mu M) than the equivalent triazolopyrimidine and suppresses parasites in vivo in the Plasmodium berghei model.

  DOI：

  10.1021/jm300351w

文献信息

• [EN] DIHYDROOROTATE DEHYDROGENASE INHIBITORS WITH SELECTIVE ANTI-MALARIAL ACTIVITY<br/>[FR] INHIBITEURS DE DIHYDROOROTATE DÉSHYDROGÉNASE PRÉSENTANT UNE ACTIVITÉ ANTIPALUDÉENNE SÉLECTIVE
  申请人：UNIV TEXAS

  公开号：WO2009082691A1

  公开（公告）日：2009-07-02

  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 R1 through R33 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.

  根据公式（I），公式（II），公式（III），公式（V），公式（VI）或公式（VII）合成的化合物，以及符合公式（IV）或（公式VIII）的化合物的药物组合物，其中R1至R33被规定，选择性地抑制疟原虫脱氢鸟嘌呤酸脱氢酶。因此，一种预防和治疗疟疾的方法涉及与这些化合物以及其药用可接受的盐，溶剂化物，立体异构体，互变异构体和前药结合。
• 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。
• US9216983B2
  申请人：——

  公开号：US9216983B2

  公开（公告）日：2015-12-22
• Bioisosteric Transformations and Permutations in the Triazolopyrimidine Scaffold To Identify the Minimum Pharmacophore Required for Inhibitory Activity against <i>Plasmodium falciparum</i> Dihydroorotate Dehydrogenase
  作者：Alka Marwaha、John White、Farah El_Mazouni、Sharon A Creason、Sreekanth Kokkonda、Frederick S. Buckner、Susan A. Charman、Margaret A. Phillips、Pradipsinh K. Rathod

  DOI：10.1021/jm300351w

  日期：2012.9.13

  Plasmodium falciparum causes approximately 1 million deaths annually. However, increasing resistance imposes a continuous threat to existing drug therapies. We previously reported a number of potent and selective triazolopyrimidine-based inhibitors of P. falciparum dihydroorotate dehydrogenase that inhibit parasite in vitro growth with similar activity. Lead optimization of this series led to the recent identification of a preclinical candidate, showing good activity against P. falciparum in mice. As part of a backup program around this scaffold, we explored heteroatom rearrangement and substitution in the triazolopyrimidine ring and have identified several other ring configurations that are active as PfDHODH inhibitors. The imidazo[1,2-a]pyrimidines were shown to bind somewhat more potently than the triazolopyrimidines depending on the nature of the amino aniline substitution. DSM151, the best candidate in this series, binds with 4-fold better affinity (PfDHODH IC50 = 0.077 mu M) than the equivalent triazolopyrimidine and suppresses parasites in vivo in the Plasmodium berghei model.