2-Aminopyrimidines as dual adenosine A1/A2A antagonists.

摘要: In this study thirteen 2-aminopyrimidine derivatives were synthesised and screened as potential antagonists of adenosine A1 A2A receptors in order to further investigate the structure activity relationships class compounds. 4-(5-Methylfuran-2-yl)-6-[3-(piperidine-1-carbonyl)phenyl]pyrimidin-2-amine (8m) was identified a compound with high affinities for both receptors, an A2AKi value 6.34 nM A1Ki 9.54 nM. The effect selected compounds on viability cultured cells assessed preliminary results indicate low cytotoxicity. In vivo efficacy at illustrated 8k 8m since these attenuated haloperidol-induced catalepsy rats. A molecular docking revealed that interactions between binding site most likely involve Phe168 Asn253, which are similar structurally related receptor antagonists.