Novel platelet antiaggregating substances

We describe herein a novel action of four stable analogs of the hepoxilins. These analogs inhibit to different degrees, the aggregation of washed huma n platelets evoked by collagen. One of the analogs, PBT-3, is particularly effective with an IC50 = 8 x 10(-7) M. The other analogs are about 5-fold l ess active, but all analogs are about 500-fold more active than the native hepoxilins. The PET analogs inhibit the collagen-enhanced formation of thro mboxane A(2) and HHT but do not affect the formation of 12-HETE or the rele ase of arachidonic acid except at doses higher than those needed to block p latelet aggregation. These results demonstrate that these novel compounds m ay have potential for development into drugs in the treatment of thromboxan e-mediated cardiovascular disease. (C) 2001 Academic Press.