Novel human adenosine receptor antagonists based on the 7-amino-thiazolo[5,4-d]pyrimidine scaffold. Structural investigations at the 2-, 5- and 7-positions to enhance affinity and tune selectivity |
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Authors: | Flavia Varano Daniela Catarzi Matteo Falsini Diego Dal Ben Michela Buccioni Gabriella Marucci Rosaria Volpini Vittoria Colotta |
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Institution: | 1. Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino, Sezione di Farmaceutica e Nutraceutica, Università degli Studi di Firenze, via Ugo Schiff, 6, 50019 Sesto Fiorentino, Italy;2. Scuola di Scienze del Farmaco e dei Prodotti della Salute, Università degli Studi di Camerino, Via S. Agostino 1, 62032 Camerino, MC, Italy |
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Abstract: | This paper describes the synthesis of novel 7-amino-thiazolo5,4-d]pyrimidines bearing different substituents at positions 2, 5 and 7 of the thiazolopyrimidine scaffold. The synthesized compounds 2–27 were evaluated in radioligand binding (A1, A2A and A3) and adenylyl cyclase activity (A2B and A2A) assays, in order to evaluate their affinity and potency at human adenosine receptor subtypes. The current study allowed us to support that affinity and selectivity of 7-amino-thiazolo5,4-d]pyrimidine derivatives towards the adenosine receptor subtypes can be modulated by the nature of the groups attached at positions 2, 5 and 7 of the bicyclic scaffold. To rationalize the hypothetical binding mode of the newly synthesized compounds, we also performed docking calculations in human A2A, A1 and A3 structures. |
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Keywords: | G protein coupled receptors Adenosine receptors Adenosine receptor antagonists Thiazolopyrimidine derivatives Bicyclic heteroaromatic system |
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