Design, synthesis, and biological evaluation of 2-(phenoxyaryl)-3-urea derivatives as novel P2Y1 receptor antagonists

A novel series of 2-(phenoxyaryl)-3-urea derivatives were designed, synthesized, and biologically evaluated for their anti-thrombotic activity. Most of compounds exhibited good inhibition against P2Y(1) receptor. Among them, three compounds 11, 12, and 13 demonstrated good P2Y(1) receptor antagonistic potency in vitro (IC50 = 0.62 mu M, 0.82 mu M, and 0.21 mu M, respectively). In antiplatelet aggregation study, four compounds 2, 3, 9, and 13 showed good antiplatelet activity. The possible binding modes of compounds with P2Y(1) receptor were also explored by molecular docking simulation. The docking studies demonstrated that compound 13 interacted well with Phe119 through hydrophobic interaction and modestly improved the P2Y(1) receptor antagonistic activity, making it justifiable for further investigation. (C) 2018 Published by Elsevier Masson SAS.