Synthesis and anti-platelet activity of novel arylsulfonate–acylhydrazone derivatives, designed as antithrombotic candidates

In this work, we describe a new class of promising anti-platelet drug candidates with significant antithrombotic activity in vivo. This new series of compounds was structurally planned by modification of known thrombin inhibitors based on the use of acylhydrazone subunit, as a nonpeptide scaffold, and variations at P1 moiety. Three different families of arylsulfonate–acylhydrazone derivatives were designed. The bioassays indicated the first class of derivatives represented by 4f (LASSBio-693) and 4j (LASSBio-743), which were active in inhibiting the platelet aggregation induced by thrombin. The second class represented by compounds 4e (LASSBio-774) and 4h (LASSBio-480) that selectively inhibit the platelet aggregation involving TXA2 formation. Finally, the third class of derivatives was identified acting as a novel symbiotic agent able to inhibit the platelet aggregation induced by collagen or AA and by thrombin, represented by compounds 4b (LASSBio-694) and 4g (LASSBio-770).

Three different families of novel arylsulfonate–acylhydrazone derivatives, planned by modification on classical thrombin inhibitor using the N-acylhydrazone (NAH) subunit as a nonpeptide scaffold, were designed, synthesized and evaluated for their ability to inhibit platelet aggregation.Figure optionsDownload as PowerPoint slide