Imidazo[1,2-a]quinoxalin-4-amines: A novel class of nonxanthine A1-adenosine receptor antagonists |
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Authors: | Stefano Ceccarelli Alessandra D'Alessandro Michela Prinzivalli Sergio Zanarella |
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Institution: | aBiomedica Foscama Research Centre, via Morolense 87, 03013 Ferentino (FR), Italy |
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Abstract: | The syntheses and A1 adenosine receptor affinities of a number of imidazo1,2-a]quinoxalin-4-amines are reported. Structure—activity relationships within the series and in comparison with other similar tricyclic nonxanthine adenosine antagonists are discussed, leading to a putative common binding mode of these nitrogen-containing heterocycles to A1 adenosine receptors. Secondary amino compounds displayed the best affinities toward A1 receptors, while the tertiary amines were almost devoid of activity, thus suggesting a crucial role for the hydrogen bond-forming 4-NH group. Remarkably higher potencies for 1-methyl and N-cyclopentyl derivatives were also found. 4-Cyclopentylamino-1-methylimidazo1,2-a]quinoxaline (TRFI 165) is the most potent compound in this series, having Ki(A1) = 7.9 nM. It is also provided with a good A1 selectivity both versus A2a and A3 subtypes and was selected for further pharmacological studies. |
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Keywords: | adenosine receptors imidazo[1 2-a]quinoxaline tricyclic heteroaromatic systems nonxanthine A1-adenosine antagonists IRFI 165 |
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