Mesoionic Xanthine Analogues: Phosphodiesterase Inhibitory and Hypotensive Activity

Article abstract of DOI:10.1021/jm00138a002

Several mesoionic thiazolo<3,2-a>pyrimidines and mesoionic 1,3,4-thiadiazolo<3,2-a>pyrimidines were evaluated as inhibitors of cyclic-AMP phosphodiesterase.While small alkyl substituents at the 6 position have no significant effect on activity, phenyl and benzyl substituents enhance activity.Mesoionic structures such as 1 (R₂ = H; R₈ = Et) possess 20 to 40 times activity of theophylline when the R₆ substituent is phenyl or 4-chlorobenzyl.Methyl and ethyl substitution at the 2 position essentially abolishes activity.Although plagued by solubility problems, several of the mesoionic derivatives were found to display weak hypotensive effects in vivo.