Substituted 1,2,3-triazolo[1,5-a]quinazolines: synthesis and binding to benzodiazepine and adenosine receptors

• Published in: European journal of medicinal chemistry 2000-03, Vol.35 (3), p.333-341
• Main Authors: Bertelli, Lucia, Biagi, Giuliana, Giorgi, Irene, Livi, Oreste, Manera, Clementina, Scartoni, Valerio, Lucacchini, Antonio, Giannaccini, Gino, Barili, Pier Luigi
• Format: Article
• Language: English
• Subjects: 1,2,3-triazoles; 1,2,3-triazolo[1,5-a]quinazolines; A 1 and A 2A adenosine receptor binding; Animals; benzodiazepine receptor binding; Binding, Competitive - drug effects; Biological and medical sciences; Cattle; Chemical Phenomena; Chemistry, Physical; Gabaergic and benzodiazepinic system; In Vitro Techniques; Ligands; Magnetic Resonance Spectroscopy; Medical sciences; Neostriatum - drug effects; Neostriatum - metabolism; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems; Pharmacology. Drug treatments; Quinazolines - chemical synthesis; Quinazolines - pharmacology; Receptor, Adenosine A2A; Receptors, GABA-A - drug effects; Receptors, Purinergic P1 - drug effects; Structure-Activity Relationship; Triazoles - chemical synthesis; Triazoles - pharmacology
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/S0223-5234(00)90154-5

This paper reports the synthesis and evaluation of the biological affinity towards benzodiazepine and A 1 and A 2A adenosine receptors of some 3-ethoxycarbonyl or 3-phenyl-substituted 1,2,3-triazolo[1,5-a]quinazolines. Starting from the appropriate chloro-substituted phenylazides, the series of 7 or 8 chloro-substituted triazoloquinazolines were prepared. Nitration reactions of the triazoloquinazoline ring and chlorination reactions of the hydroxyl group in the 5 position of the same ring are also reported. By nucleophilic displacement of halogen, the corresponding 5-amino derivatives and some analogous derivatives bearing cyclohexylamino and p-toluidino substituents were obtained. The binding assays showed a generalized decrease in the affinity towards the benzodiazepine receptors and confirmed a moderate affinity towards the A 1 adenosine receptors in comparison with the previously studied triazoloquinazoline derivatives.