Novel Agents Combining Platelet Activating Factor (PAF) Receptor Antagonist with Thromboxane Synthase Inhibitor (TxSI)

Compounds 1 or 2 which possess dual-acting PAF antagonist/TxSI in a previous paper were modified and evaluated for the dual-acting activity. It was found that several compounds were potent dual-acting PAF antagonist/TxSI in and ex vivo. 6-(2-Chlorophenyl)-3-[4-[(E/Z)-6-ethoxycarbonyl-1-(3-pyridyl)-1-hexenyl]phenylmethyl]-8,11-dimethyl-2,3,4,5-tetrahydro-8H-pyrido[4′,3′: 4,5]thieno[3,2-f][1, 2 and 4]triazolo[4,3-a] [1 and 4]diazepine (12) is excellent orally dual-acting PAF antagonist/TxSI.