title: Mesoionic xanthine analogues: phosphodiesterase inhibitory and hypotensive activity.
abstract: Several mesoionic thiazolo[3,2-alphapyrimidines and mesoionic 1,3,4-thiadiazol[3,2-alpha-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 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 of the mesoionic derivatives were found to display weak hypotensive effects in vivo.
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D000959:Antihypertensive Agents; D001794:Blood Pressure / Q000187:drug effects; D002417:Cattle; D066298:In Vitro Techniques; D008297:Male; D011744:Pyrimidinones / Q000138:chemical synthesis*; D051381:Rats; D013329:Structure-Activity Relationship; D013829:Thiadiazines / Q000138:chemical synthesis; D013843:Thiazines / Q000138:chemical synthesis
chemical_list: D000959:Antihypertensive Agents; D011744:Pyrimidinones; D013829:Thiadiazines; D013843:Thiazines; D015105:3',5'-Cyclic-AMP Phosphodiesterases