Mesoionic xanthine analogues: antagonists of adenosine receptors.
A variety of mesoionic xanthines including mesoionic thiazolo[3,2-alpha]pyrimidines, benzothiazolopyrimidines, and 1,3,4-thiadiazolo[3,2-alpha]pyrimidines were antagonists of A1-adenosine receptors (inhibition of binding of [3H]-cyclohexyladenosine) and A2-adenosine receptors (inhibition of 2-chloroadenosine-elicited accumulations of cyclic AMP) in brain tissue. Most of the compounds were less potent than theophylline and none were remarkably selective for A1- or A2-adenosine receptors. However, members of the thiadiazolopyrimidine class of mesoionics exhibited very low or no activity as antagonists of A2-adenosine receptors while exhibiting activity only 2-4-fold lower than that of theophylline at A1-adenosine receptors. Unlike the case for theophylline, the presence of a phenyl substituent in the five-membered ring did not enhance the potency of a mesoionic thiadiazolopyrimidine. The nature of the substituents on the mesoionic ring did not appear to have marked effects on potency unlike the marked effect of the nature of 1,3-substituents on activity of nonmesoionic xanthines. The benzothiazolo[3,2-alpha]pyrimidines were the most potent antagonists, being nearly as potent as theophylline at A1-adenosine receptors and somewhat more potent than theophylline at A2-adenosine receptors.
D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D007202:Indicators and Reagents; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000378:metabolism; D011983:Receptors, Purinergic; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship; D014970:Xanthines / Q000138:chemical synthesis* / Q000494:pharmacology
D007202:Indicators and Reagents; D011956:Receptors, Cell Surface; D011983:Receptors, Purinergic; D014970:Xanthines; D000241:Adenosine