Inhibition of separated forms of phosphodiesterases from pig coronary arteries by uracils and by 7-substituted derivatives of 1-methyl-3-isobutylxanthine.

摘要: A series of 7-substituted 1-methyl-3-isobutylxanthines was designed in an attempt to increade the specificity 1-methyl-3-isobutylxanthine (MIX) structure for one two cyclic nucleotide phosphodiesterase peaks isolated by DEAE-cellulose chromatography soluble fraction intima + media layer pig coronary arteries. 1,3-dialkyluracils low potency as inhibitors either peak I or II. The xanthines were prepared alkylation MIX with corresponding alkyl aralkyl halide DMF containing K2CO3. These compounds were, general, much less potent II activity than MIX, but some them retained and, therefore, relatively specific inhibition I. 7-Bzl-MIX most selective compound tested; it a inhibitor effective activity. Substitution electron-withdrawing (nitro) electron-donating (methoxy) groups on 7-benzyl moiety reduced effectiveness Chlorobenzyl substitution increased slightly over benzyl not selectivity between peaks.