Current Awareness
New potent and selective human adenosine A3 receptor antagonists

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State of the art in the A3 receptor antagonist field

In the past few years, different classes of compounds have been reported to be A3 receptor antagonists. Eight classes of compounds with non-xanthine structures have been synthesized: dihydropyridine and pyridine analogs15., 16., flavonoid17, isoquinoline18 and triazoloquinazoline derivatives19, and triazolonaphthiridine and thiazolopyrimidine analogs20 (Fig. 1). Recently, a new chemical entity, a 2-arylpyrazolo[3,4-c]quinoline derivative, was reported to display good affinity and selectivity

The Ferrara University approach

With respect to the triazoloquinazoline class of compounds, Jacobson and co-workers19 started from the experimental observation that CGS15943 possesses affinity for the human A3 receptor (Ki=14 nm). In fact, acylation of CGS15943 with a phenylacetyl group at the amino function at position 5 produced MRS1220, a potent but not highly selective A3 receptor antagonist.

In the past few years, we have synthesized (using the general formula in Fig. 2a) more than 100 pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c

[3H]MRE3008F20: a new selective and potent human A3 receptor antagonist radioligand

The lack of a radiolabeled selective A3 receptor antagonist has been the major drawback for an adequate characterization of this receptor subtype. Until now, the agonist [125I]ABMECA has been widely used as a high-affinity radioligand for A3 receptors4, even if it exhibits a moderate A3–A1 selectivity. Antagonists are generally considered to be more acceptable tools than agonists to characterize receptors because results obtained using agonists are complicated by different receptor states and

Concluding remarks

The A3 receptor subtype appears to be the target of drugs that have potential use in several important pathologies. The importance of A3 receptors in the pathophysiology of many disorders is demonstrated by the enormous increase in scientific interest in this field of research. Indeed, in the past few months, several studies on the synthesis of new ligands and the role of the A3 receptor in different diseases have been reported. In particular, the synthesis of 5-N-(substituted

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