[1,2,4]Triazolo[4,3-a]quinoxalin-4-amines: a new class of A1 receptor selective adenosine antagonists.
Several [1,2,4]triazolo[4,3-a]quinoxalines that were reported as antidepressants in the patent literature were found to possess moderate affinity for the adenosine A1 and A2 receptors. On the basis of structural parallels with adenine and adenosine, the N-cyclopentyl derivative was synthesized and found to have improved affinity and selectivity for the A1 receptor. In the N-cyclopentyl series, affinity was optimal with trifluoromethyl substitution at the 1-position, resulting in a compound (9) with 7.3 nM A1 affinity and 138-fold selectivity for the A1 receptor.
Trivedi
B K
BK
Department of Chemistry, Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, Michigan 48105.
Bruns
R F
RF
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D066298:In Vitro Techniques; D011810:Quinoxalines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D011983:Receptors, Purinergic / Q000187:drug effects* / Q000378:metabolism; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology
D011810:Quinoxalines; D011983:Receptors, Purinergic; D014230:Triazoles