4-[(1H-imidazol-4-yl) methyl] benzamidines and benzylamidines: Novel antagonists of the histamine H3 receptor

Article abstract of DOI:10.1016/S0960-894X(98)00399-0

A series of amidine substituted phenyl-, benzyl-, and phenethylimidazoles based on the known H₃ against SKandF 91606 (4) has been synthesized and tested as ligands for the histamine H₃ receptor. Insertion of a phenyl ring between the imidazole ring and the amidine moiety produces antagonists. The benzyl series was found to be the most potent and was further investigated. Compounds 9c and 18 (entries 5 and 12, Table 1) are potent ligands for the H₃ receptor with K(i) values of 16 nM and 7.2 nM respectively. In vivo, both compounds were shown to be equipotent to thioperamide (2), the standard H₃ antagonist.