On the basis of structural information for the cyclic hexapeptide endothelin (ET) receptor antagonist, TAK-044, a series of thieno [2, 3-d] pyrimidine-2, 4-dione derivatives bearing a carboxyl group and aromatic rings that were important for receptor binding were designed, synthesized, and evaluated for ET receptor binding affinities and inhibitory activities against ET-induce vasconstriction. Optimization of each substituent in the thieno [2, 3-d] ...
