D and L-N-[(1-benzyl-1H-imidazol-5-yl)-alkyl]-amino acids as angiotensin II AT-1 antagonists

A series of D and L-N-[(1-benzyl-1H-imidazol-5-yl)-alkyl] - aromatic amino acids (2 to 9) and several achiral analogs (1,10,11) were found to be potent AII antagonists (nM range). Among chiral pairs the D isomer had the highest affinity for the binding site. A D-phenylalanine analog, 3, was the most potent (IC50 3.8 nM) and had activity in vivo similar to SK&F 108566 when given i.v. but was only marginally active when given i.d.