Colotta Vittoria, Catarzi Daniela, Varano Flavia, Calabri Francesca Romana, Filacchioni Guido, Costagli Chiara, Galli Alessandro
Dipartimento di Scienze Farmaceutiche, Universita' degli Studi di Firenze, Polo Scientifico, Via Ugo Schiff, 6, 50019 Sesto Fiorentino, (FI), Italy.
Bioorg Med Chem Lett. 2004 May 3;14(9):2345-9. doi: 10.1016/j.bmcl.2004.01.109.
The synthesis and Gly/NMDA, AMPA and KA receptor binding activities of some 3-hydroxy-quinazoline-2,4-dione derivatives are reported. The binding data, together with functional antagonism studies, showed that the 3-hydroxy-quinazoline-2,4-dione moiety can be considered a useful scaffold to obtain selective Gly/NMDA and AMPA receptor antagonists. In fact, introduction of chlorine atom(s) on precise position(s) of the benzofused moiety yielded Gly/NMDA selective antagonists, while the presence of the 6-(1,2,4-triazol-4-yl) group shifted the affinity and selectivity towards the AMPA receptor.
报道了一些3-羟基喹唑啉-2,4-二酮衍生物的合成及其与甘氨酸/N-甲基-D-天冬氨酸（Gly/NMDA）、α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）和海人藻酸（KA）受体的结合活性。结合数据以及功能拮抗研究表明，3-羟基喹唑啉-2,4-二酮部分可被视为获得选择性甘氨酸/NMDA和AMPA受体拮抗剂的有用骨架。事实上，在并苯部分的特定位置引入氯原子可产生甘氨酸/NMDA选择性拮抗剂，而6-(1,2,4-三唑-4-基)基团的存在则使对AMPA受体的亲和力和选择性发生改变。
