[1,2,4]Triazolo[4,3-a]quinoxalin-4-amines: a new class of A1 receptor selective adenosine antagonists

• Published in: Journal of medicinal chemistry Vol. 31; no. 5; pp. 1011 - 1014
• Main Authors: Trivedi, Bharat K, Bruns, Robert F
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 01.05.1988
• Subjects: Animals; Brain - drug effects; Brain - metabolism; Chemical Phenomena; Chemistry; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings; In Vitro Techniques; Organic chemistry; Preparations and properties; Quinoxalines - chemical synthesis; Quinoxalines - pharmacology; Rats; Receptors, Purinergic - drug effects; Receptors, Purinergic - metabolism; Structure-Activity Relationship; Triazoles - chemical synthesis; Triazoles - pharmacology; Amidine; Angular nitrogen heterocycle; Orthoester; Aromatic compound; Adenosine receptor; Tricyclic compound; Hydrazine; Biological activity
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00400a021

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.