A novel series of thromboxane A(2) synthetase inhibitors with free radicalscavenging and anti-peroxidative activities

A novel series of indoline derivatives with imidazole and carboxyl moieties were synthesized and evaluated for their thromboxane A(2) (TXA(2)) synthet ase inhibiting, radical scavenging and anti-peroxidative activities. Among the compounds synthesized, 3-{5-substituted-3-[2-(imidazol-1-yl)ethyl]indol in-1-yl}propionic acids showed free radical scavenging activity and inhibit ory effects on lipid-peroxidation of rat brain homogenate and on arachidona te-induced TXA(2)-dependent aggregation of rabbit platelets. The anti-plate let and anti-peroxidative activities were related to the lipophilicity of t he 5-substituent, The 5-hexyloxy derivative (13) showed about 35-fold highe r inhibitory activity on TXA(2) synthesis than that of ozagrel and about 10 0-fold higher activity on lipid peroxidation than that of alpha -tocopherol , Compound 13 showed in vivo anti-thrombotic effect in mice and ex vivo ant i-peroxidative activity in rats.