叶酸拮抗剂。11. 6-[(芳氧基和芳硫基)甲基]-2,4-蝶啶二胺及-蝶啶二胺8-氧化物的合成与抗疟作用

Folate antagonists. 11. Synthesis and antimalarial effects of 6-[(aryloxy- and arylthio-)methyl]-2,4-pteridinediamines and -pteridinediamine 8-oxides.

作者信息

Werbel L M, Johnson J, Elslager E F, Worth D F

出版信息

J Med Chem. 1978 Apr;21(4):337-9. doi: 10.1021/jm00202a004.

DOI:10.1021/jm00202a004

Abstract

Condensation of 3-amino-6-(bromomethyl)-2-pyrazinecarbonitrile 4-oxide with 4-chlorophenol gave 3-amino-6-[(4-chlorophenoxy)methyl]-2-pyrazinecarbonitrile 4-oxide (1), which was deoxygenated to obtain the de-N-oxide 4. Cyclization of 4 and 1 produced 6-[(4-chlorophenoxy)methyl]-2,4-pteridinediamine and the 8-oxide, respectively. 6-[(Arylthio)methyl]-2,4-pteridinediamines and their 8-oxides were produced analogously. Controlled oxidation of the former gave the anticipated sulfoxide 12 and sulfone 13. None of these compounds showed significant activity when tested against lethal Plasmodium berghei infections in mice or a select list of bacteria in vitro.

摘要

3-氨基-6-(溴甲基)-2-吡嗪甲腈4-氧化物与4-氯苯酚缩合得到3-氨基-6-[(4-氯苯氧基)甲基]-2-吡嗪甲腈4-氧化物(1)，将其脱氧得到脱N-氧化物4。4和1环化分别生成6-[(4-氯苯氧基)甲基]-2,4-蝶啶二胺和8-氧化物。类似地制备了6-[(芳硫基)甲基]-2,4-蝶啶二胺及其8-氧化物。对前者进行可控氧化得到预期的亚砜12和砜13。在针对小鼠体内致命伯氏疟原虫感染或体外选定的一系列细菌进行测试时，这些化合物均未显示出显著活性。

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