2,4-二氨基-5-羟基-6-甲基嘧啶盐酸盐 | 66204-88-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 2,4-二氨基-5-羟基-6-甲基嘧啶盐酸盐
• 英文名称: 2,4-diamino-5-hydroxy-6-methylpyrimidine hydrochloride
• 英文别名: 2,4-diamino-6-methyl-pyrimidin-5-ol; hydrochloride；2,4-Diamino-6-methyl-pyrimidin-5-ol; Hydrochlorid；2,4-Diamino-6-methyl-5-pyrimidinol hydrochloride；2,4-diamino-6-methylpyrimidin-5-ol;hydrochloride
• CAS: 66204-88-4
• 化学式: C₅H₈N₄O*ClH
• 分子量: 176.606
• InChiKey: WICDURBEMOASKW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.08
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  98
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2,4-二氨基-5-羟基-6-甲基嘧啶盐酸盐 、 3,4-二氯氯苄 在 甲氧基乙醇钠 、 potassium iodide 作用下， 以 乙二醇甲醚 为溶剂， 反应 48.0h， 以38%的产率得到5-(3,4-dichloro-benzyloxy)-6-methyl-pyrimidine-2,4-diamine
  参考文献：
  名称：

  Folate-Synthesizing Enzyme System as Target for Development of Inhibitors and Inhibitor Combinations against Candida albicansSynthesis and Biological Activity of New 2,4-Diaminopyrimidines and 4‘-Substituted 4-Aminodiphenyl Sulfones

  摘要：

  The paper describes the design, synthesis, and testing of inhibitors of folate-synthesizing enzymes and of whole cell cultures of Candida albicans. The target enzymes used were dihydropteroic acid synthase (SYN) and dihydrofolate reductase (DHFR). Several series of new 2,4-diaminopyrimidines were synthesized and tested as inhibitors of DHFR and compared with their activity against DHFR derived from mycobacteria and Escherichia coli. To test for selectivity, also rat DHFR was used. A series of substituted 4-aminodiphenyl sulfones was tested for inhibitory activity against SYN and the I-50 values compared to those obtained previously against Plasmodium berghei- and E. coli-derived SYN. Surprisingly, QSAR equations show very similar structural dependencies. To find an explanation for the large difference in the I-50 values observed for enzyme inhibition (SYN, DHFR) and for inhibition of cell cultures of Candida, mutant strains with overexpressed efflux pumps and strains in which such pumps are deleted were included in the study and the MICs compared. Efflux pumps were responsible for the low activity of some of the tested derivatives, others showed no increase in activity after pumps were knocked out. In this case it may be speculated that these derivatives are not able to enter the cells.

  DOI：

  10.1021/jm030931w
• 作为产物：
  描述：

  2,4-diamino-6-methylpyrimidine hydrogen sulfate 在 盐酸 作用下， 生成 2,4-二氨基-5-羟基-6-甲基嘧啶盐酸盐
  参考文献：
  名称：

  Folate-Synthesizing Enzyme System as Target for Development of Inhibitors and Inhibitor Combinations against Candida albicansSynthesis and Biological Activity of New 2,4-Diaminopyrimidines and 4‘-Substituted 4-Aminodiphenyl Sulfones

  摘要：

  The paper describes the design, synthesis, and testing of inhibitors of folate-synthesizing enzymes and of whole cell cultures of Candida albicans. The target enzymes used were dihydropteroic acid synthase (SYN) and dihydrofolate reductase (DHFR). Several series of new 2,4-diaminopyrimidines were synthesized and tested as inhibitors of DHFR and compared with their activity against DHFR derived from mycobacteria and Escherichia coli. To test for selectivity, also rat DHFR was used. A series of substituted 4-aminodiphenyl sulfones was tested for inhibitory activity against SYN and the I-50 values compared to those obtained previously against Plasmodium berghei- and E. coli-derived SYN. Surprisingly, QSAR equations show very similar structural dependencies. To find an explanation for the large difference in the I-50 values observed for enzyme inhibition (SYN, DHFR) and for inhibition of cell cultures of Candida, mutant strains with overexpressed efflux pumps and strains in which such pumps are deleted were included in the study and the MICs compared. Efflux pumps were responsible for the low activity of some of the tested derivatives, others showed no increase in activity after pumps were knocked out. In this case it may be speculated that these derivatives are not able to enter the cells.

  DOI：

  10.1021/jm030931w

文献信息

• 2,4-Diamino-5-alkyloxy-pyrimidines
  申请人：Beecham Group Limited

  公开号：US04179562A1

  公开（公告）日：1979-12-18

  Compounds of the formula ##STR1## and pharmaceutically acceptable salts thereof and antimalarial and antibacterial compositions containing an effective amount of active agent and a pharmaceutically acceptable carrier particularly in oral dosage form wherein R is hydrogen, methyl or ethyl; X is alkylene of 1-10 carbon atoms; Y is oxygen, sulphur or a bond, and Ar is an optionally substituted aryl moiety; are useful for their antimalarial and antibacterial activity.

  式为##STR1##的化合物及其药学上可接受的盐，以及含有效剂量的活性成分和药学上可接受的载体的抗疟和抗菌组合物，特别是口服剂型，其中R是氢、甲基或乙基；X是1-10个碳原子的烷基；Y是氧、硫或键；Ar是可选取代的芳基基团；它们对于其抗疟和抗菌活性是有用的。
• Folate-Synthesizing Enzyme System as Target for Development of Inhibitors and Inhibitor Combinations against <i>Candida </i><i>a</i><i>lbicans</i>Synthesis and Biological Activity of New 2,4-Diaminopyrimidines and 4‘-Substituted 4-Aminodiphenyl Sulfones
  作者：Thomas Otzen、Ellen G. Wempe、Brigitte Kunz、Rainer Bartels、Gudrun Lehwark-Yvetot、Wolfram Hänsel、Klaus-Jürgen Schaper、Joachim K. Seydel

  DOI：10.1021/jm030931w

  日期：2004.1.1

  The paper describes the design, synthesis, and testing of inhibitors of folate-synthesizing enzymes and of whole cell cultures of Candida albicans. The target enzymes used were dihydropteroic acid synthase (SYN) and dihydrofolate reductase (DHFR). Several series of new 2,4-diaminopyrimidines were synthesized and tested as inhibitors of DHFR and compared with their activity against DHFR derived from mycobacteria and Escherichia coli. To test for selectivity, also rat DHFR was used. A series of substituted 4-aminodiphenyl sulfones was tested for inhibitory activity against SYN and the I-50 values compared to those obtained previously against Plasmodium berghei- and E. coli-derived SYN. Surprisingly, QSAR equations show very similar structural dependencies. To find an explanation for the large difference in the I-50 values observed for enzyme inhibition (SYN, DHFR) and for inhibition of cell cultures of Candida, mutant strains with overexpressed efflux pumps and strains in which such pumps are deleted were included in the study and the MICs compared. Efflux pumps were responsible for the low activity of some of the tested derivatives, others showed no increase in activity after pumps were knocked out. In this case it may be speculated that these derivatives are not able to enter the cells.