Recent developments of thromboxane modulators

Thromboxane A(2) (TXA(2)) is a labile product formed from arachidonic acid by the way of cyclooxygenase and thromboxane synthase. An overproduction of TXA(2) has been detected in a series of diseases where this eicosanoid is assumed to contribute to the underlying pathomechanisms by its potent stimu lation of platelet aggregation and smooth muscle contraction. indeed, liter ature supports participation of TXA(2) in several physiopathological mechan isms such as tumour growth and metastasis, pre-eclampsia, asthma, pulmonary hypertension and in the progression of ischaemic injury after coronary art ery occlusion. This evidence provides a strong rationale for pursuing TXA(2 ) blocking strategies in drug development. Therefore, TXA(2) receptor antag onists, thromboxane synthase inhibitors and drugs which combine both activi ties have been developed. Of the 28 thromboxane modulator patents reviewed from January 1997 to December 2000, 16 relate to thromboxane receptor antag onists (TXRAs), seven to thromboxane synthase inhibitors and five to agents combining both activities. Of these patents, 19 claim new chemical structu res, five claim a new use, one claims combination therapy and three claim p rocesses. This article focuses on latest discoveries and developments of no vel TXA(2) modulators described in these patents.