| Abstract
| - Prompted by pharmacophore and docking based models, we have synthesized and tested anumber of N-alkyl and N-acyl-(7-substituted-2-phenylimidazo[1,2-a][1,3,5]triazin-4-yl)amines(ITAs, 7) designed as a new class of A1 adenosine receptor (A1AR) antagonists. Binding affinitiesat the A1AR, A2AAR, and A3AR were determined using bovine cerebral membranes. Most ofthe compounds displayed Ki values at the A1AR in the submicromolar or even in the lownanomolar range, thus confirming the rationale leading to their synthesis. All or most of theligands turned out to be selective for the A1AR over the A2AAR and A3AR subtypes, respectively.Structure-affinity relationships at the A1AR were rationalized by docking simulations in termsof putative ligand/receptor interactions. Among the ITAs investigated, 1-[(7-methyl-2-phenylimidazo[1,2-a][1,3,5]triazin-4-yl)amino]acetone (7j) exhibited the best combination of affinityat the A1AR (Ki = 12 nM) and selectivity over the A2AAR and A3AR subtypes (Kis > 10000nM).
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