Heterocyclic amplifiers of phleomycin. III. 5-Substituted 1 H-Imidazo[4,5-b]pyrazines and 6-substituted Pyrazino[2,3-b]pyrazines

Abstract

A series of 1H-imidazo[4,5-b]pyrazines has been prepared from 5-bromopyrazine-2,3-diamine and 5-bromo-3-methylaminopyrazin-2-amine with diethoxymethyl acetate, acetic anhydride or potassium ethyl xanthate; and 6-substituted pyrazino[2,3-b]pyrazines from 5-bromopyrazine-2,3-diamine with α, β-dicarbonyl compounds. Reactions of these compounds have been examined.

Diazomethane methylation of 5-bromo-1H-imidazo[4,5-b]pyrazine-2(3H)-thione gave five dimethyl derivatives which have been identified as the 1,3- and the four N,S-dimethyl derivatives.

2-Bromo-6,7-dimethylpyrazino[2,3-b]pyrazine with 0.4 M and 2.0 M methanolic sodium methane-thiolate gave as principal products 2,3-dimethyl-6-methylthio- and 2,3-dimethyl-6,7-bismethylthio- pyrazino-[2,3-b]pyrazines, respectively.

The 1H-imidazo[4,5-b]pyrazines showed only slight activity as amplifiers of phleomycin.