| Abstract
| - Some pyrazolotriazolopyrimidines bearing different heteroarylcarbamoylamino moieties at the N5-positionare described. We previously reported the synthesis of a water soluble compound with high potency andselectivity versus the human A3 adenosine receptor as antagonist, and herein we present an enlarged seriesof compounds related to the previously mentioned one. These compounds showed A3 adenosine receptoraffinity in the nanomolar range and different levels of selectivity evaluated in radioligand binding assays athuman A1, A2A, A2B, and A3 adenosine receptors. In particular, the effect of the heteroaryl substituents atthe N5 position has been analyzed. This study allows us to recognize that the presence of a pyridiniummoiety in this position not only increases water solubility but also improves or retains potency and selectivityat the human A3 adenosine receptors. In contrast, replacement of pyridine with different heterocycles producesloss of affinity and selectivity at the human A3 adenosine receptors. A molecular modeling study has beencarried out with the aim to explain these various binding profiles.
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