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 human platelets evoked by collagen. One of the analogs, PBT-3, is particularly effective with an IC(50) = 8 x 10(-7) M. The other analogs are about 5-fold less active, but all analogs are about 500-fold more active than the native hepoxilins. The PBT analogs inhibit the collagen-enhanced formation of thromboxane A(2) and HHT but do not affect the formation of 12-HETE or the release of arachidonic acid except at doses higher than those needed to block platelet aggregation. These results demonstrate that these novel compounds may have potential for development into drugs in the treatment of thromboxane-mediated cardiovascular disease.