A new series of nonpeptide AT(1) receptor antagonists were recently developed, based on the structure of irbesartan (Le Bourdonnec et al. J. Med. Chem. 2000, 43, 2685-2697). The lead compound 1 displayed high selectivity for the AT(1) receptor subtype but lower binding affinity than irbesartan. As expected from molecular modeling studies, extension of the pyrazolidine-3,5-dione scaffold to the six-membered heterocycle tetrahydropyridazine-3,6-dione led to an enhancement of the binding affinity toward the AT(1) receptor.