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.
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.
Bioorg Med Chem Lett. 2019 Feb 15;29(4):563-569. doi: 10.1016/j.bmcl.2018.12.062. Epub 2018 Dec 31.
This paper describes the synthesis of novel 7-amino-thiazolo[5,4-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 (A, A and A) and adenylyl cyclase activity (A and A) 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-thiazolo[5,4-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 A, A and A structures.
本文描述了新型 7-氨基噻唑并[5,4-d]嘧啶的合成，这些化合物在噻唑并嘧啶骨架的 2、5 和 7 位具有不同的取代基。合成的化合物 2-27 进行了放射性配体结合（A、A 和 A）和腺苷酸环化酶活性（A 和 A）测定，以评估它们在人类腺苷受体亚型上的亲和力和效力。本研究表明，7-氨基噻唑并[5,4-d]嘧啶衍生物对腺苷受体亚型的亲和力和选择性可以通过连接在双环骨架的 2、5 和 7 位的基团的性质来调节。为了合理化新合成化合物的假设结合模式，我们还在人 A、A 和 A 结构中进行了对接计算。
