Mesoionic xanthine analogs: phosphodiesterase inhibitory and hypotensive activity
- 1 June 1981
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 24 (6), 658-661
- https://doi.org/10.1021/jm00138a002
Abstract
Several mesoionic thiazolo[3,2-a]pyrimidines and mesoionic 1,3,4-thiadiazolo[3,2-a]pyrimidines were evaluated as inhibitors of cAMP 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 (ethyl)) possess 20-40 times the 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 mesoionic derivatives displayed weak hypotensive effects in vivo [in rats].Keywords
This publication has 5 references indexed in Scilit:
- Imidazo[1,2‐α]pyrimidines and 1,2,4‐triazolo[1,5‐α]pyrimidines: Two new examples of mesoionic xanthine analogsJournal of Heterocyclic Chemistry, 1980
- Mesoionic Xanthine Analogs as Inhibitors of Cyclic AMP PhosphodiesteraseJournal of Pharmaceutical Sciences, 1978
- Selective inhibition of cyclic nucleotide phosphodiesterases by analogs of 1-methyl-3-isobutylxanthineBiochemistry, 1977
- Conformational transition accompanying the binding of calcium(2+) ion to the protein activator of 3',5'-cyclic adenosine monophosphate phosphodiesteraseBiochemistry, 1977
- Inhibition of separated forms of phosphodiesterases from pig coronary arteries by uracils and by 7-substituted derivatives of 1-methyl-3-isobutylxanthineJournal of Medicinal Chemistry, 1976