N-(Alkyl)-2-amino-1,4-pyrazine Derivatives: Synthesis and Antioxidative Properties of 3- and 3,5-p-Hydroxyphenyl-Substituted Compounds

Abstract

2-Amino-5-(p-hydroxyphenyl)-1,4-pyrazine and 2-amino-3,5-bis(p-hydroxyphenyl)-1,4-pyrazine are endowed with excellent antioxidative properties. For a possible development in medicinal chemistry, the lipophilicity of these lead compounds has to be increased. Therefore various methods of N-alkylation were systematically explored. The best results were obtained by quenching aminopyrazinyl anion with alkyl iodides, and by coupling aldehydes (reductive amination) in the presence of phenylsilane and tin catalyst.
Aminopyrazines equipped with linear alkyl side-chains of at least six carbons showed improved radical-scavenging properties in lipidic media.

Key words

pyrazines - alkylations - heterocycles - amines - reductions - antioxidants

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