Design and synthesis of novel platelet fibrinogen receptor antagonists with 2H-1,4-benzoxazine-3(4H)-one scaffold. A systematic study

New platelet glycoprotein IIb/IIIa (GP IIb/IIIa, integrin αIIbβ3) antagonists were prepared on a 2H-1,4-benzoxazine-3(4H)-one scaffold. Their anti-aggregatory activities in human platelet rich plasma and their affinity towards αIIbβ3 and αVβ3 integrins were assessed. Various substitution positions and side chain variations were studied. In contrast to the generally accepted model, compounds containing ethyl esters as aspartate mimetics were in general more active than the corresponding free acids. We suggest an explanation for the observed behaviour of these new compounds.