New 1,2,3-triazolo[1,5-a]quinoxalines: synthesis and binding to benzodiazepine and adenosine receptors. II

• Published in: European journal of medicinal chemistry Vol. 37; no. 7; pp. 565 - 571
• Main Authors: Biagi, Giuliana, Giorgi, Irene, Livi, Oreste, Scartoni, Valerio, Betti, Laura, Giannaccini, Gino, Trincavelli, Maria Letizia
• Format: Journal Article
• Language: English
• Published: PARIS CEDEX 15 Elsevier Masson SAS 01.07.2002; Elsevier
• Subjects: 1,2,3-triazolo[1,5-a]quinoxalines; Adenosine receptor binding; Animals; Benzodiazepine receptor binding; Biological and medical sciences; Brain Chemistry; Cattle; Chemistry, Medicinal; GABA-A Receptor Antagonists; Gabaergic and benzodiazepinic system; Life Sciences & Biomedicine; Ligands; Medical sciences; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Purinergic P1 Receptor Antagonists; Quinoxalines - chemical synthesis; Quinoxalines - metabolism; Radioligand Assay; Receptor, Adenosine A2A; Receptors, GABA-A - metabolism; Receptors, Purinergic P1 - metabolism; Science & Technology; Structure-Activity Relationship; Adenosine receptor binding; 1,2,3-triazolo[1,5-a]quinoxalines; Benzodiazepine receptor binding; benzodiazepine receptor binding; adenosine receptor binding; Bovine; Angular nitrogen heterocycle; Ligand; Central nervous system; Lactam; A1 Adenosine receptor; Benzodiazepine receptor; Tricyclic compound; Ketone; In vitro; A2A adenosine receptor; Ester; Vertebrata; Biological fixation; Mammalia; Structure activity relation; Animal; Affinity; Aromatic compound; Artiodactyla; Chemical synthesis; Ungulata; Brain (vertebrata)
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/S0223-5234(02)01376-4

On pursuing research about 1,2,3-triazolo[1,5-a]quinoxalines, in this paper we report synthesis and binding assays toward the benzodiazepine and A 1 and A 2A adenosine receptors, of a new series of derivatives, bearing some structural changes (introduction of fluorine and trifluoromethyl in the seventh position, amino substituents in the fourth position, benzyl group in the fifth position and aroyl substituents in the third position). The biological tests have shown that only the 7-fluorosubstituted compounds 3a and 4a and the N-benzyl derivative 7 have a good affinity toward the benzodiazepine receptors, while only the 7-trifluoromethyl substituted compound 3b presents a moderate affinity with low selectivity toward the A 1 adenosine receptors. The other structural modifications strongly decreased biological activity.