Balanced angiotensin II receptor antagonists. II.1,2 4-aminomethyl- and acylaminomethylimidazoles

The introduction of aminomethyl and acylaminometyl substituents at the imidazole 4-position of 1- biphenylmethylimidazole-5-carboxylates imparts affinity for the AT(2) receptor. The highest affinity was found with the 4-(2-pyridyl)-piperazin-l-ylmethyl group and the use of hexanoylsulfonamide as a tetrazole replacement, which led to XM953 (18d), with an AT(2) IC50 of 20 nM and an AT(2)/AT(1) IC50 ratio of 3.