Recent developments of thromboxane modulators

Thromboxane A₂ (TXA₂) is a labile product formed from arachidonic acid by the way of cyclooxygenase and thromboxane synthase. An overproduction of TXA₂ has been detected in a series of diseases where this eicosanoid is assumed to contribute to the underlying pathomechanisms by its potent stimulation of platelet aggregation and smooth muscle contraction. Indeed, literature supports participation of TXA₂ in several physiopathological mechanisms such as tumour growth and metastasis, pre-eclampsia, asthma, pulmonary hypertension and in the progression of ischaemic injury after coronary artery occlusion. This evidence provides a strong rationale for pursuing TXA₂ blocking strategies in drug development. Therefore, TXA₂ receptor antagonists, thromboxane synthase inhibitors and drugs which combine both activities have been developed. Of the 28 thromboxane modulator patents reviewed from January 1997 to December 2000, 16 relate to thromboxane receptor antagonists (TXRAs), seven to thromboxane synthase inhibitors and five to agents combining both activities. Of these patents, 19 claim new chemical structures, five claim a new use, one claims combination therapy and three claim processes. This article focuses on latest discoveries and developments of novel TXA₂ modulators described in these patents.