Design of dual-acting thromboxane antagonist-synthase inhibitors by a mutual prodrug approach

A mutual prodrug approach to dual acting thromboxane receptor antagonist - thromboxane synthase inhibitor compounds is reported in which TXA2 antagonist and inhibitory 1,3-dioxanes with hexenoic acid side chains, were linked by diester and diamide groups. When linking of the components was achieved via di O-alkyl carboxylic esters of catechol, both TXA2 receptor antagonist activity and TXA2 synthase inhibition were observed for a single enantiomer (16) in ex vivo tests following oral dosing to dogs at 5 mg/kg.