Imidazodiazepinediones: a new class of adenosine receptor antagonists.
A series of imidazo[4,5-e][1-4]diazepine-5,8-diones were synthesized from hypoxanthines. Certain of these cyclic homologues of caffeine, theophylline, theobromine, 3-isobutyl-1-methylxanthine, and enprofylline were inhibitors of binding of adenosine analogues to rat brain A1 and A2 adenosine receptors and were antagonists of A2 adenosine receptors stimulatory to adenylate cyclase in rat PC12 cell membranes. Activity at adenosine receptors was lower than the corresponding xanthines, perhaps because imidazodiazepinediones contain a boat-shaped seven-membered ring rather than the planar heteroaryl ring system of the xanthines. The imidazodiazepinediones had low affinity for brain benzodiazepine sites.
Laboratory of Bioorganic Chemistry, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
J W
JW
Daly
I
I
Hide
P K
PK
Bridson
D000241:Adenosine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019830:Adenosine-5'-(N-ethylcarboxamide); D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001381:Azepines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001667:Binding, Competitive; D002462:Cell Membrane / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D003975:Diazepam / Q000378:metabolism; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D066298:In Vitro Techniques; D008968:Molecular Conformation; D010660:Phenylisopropyladenosine / Q000378:metabolism; D051381:Rats; D011983:Receptors, Purinergic / Q000378:metabolism*; D013329:Structure-Activity Relationship
D001381:Azepines; D007093:Imidazoles; D011983:Receptors, Purinergic; D010660:Phenylisopropyladenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); D000262:Adenylyl Cyclases; D000241:Adenosine; D003975:Diazepam