Imidazo[1,2-b]pyridazines .21. Syntheses of some 3-acylaminomethyl-6-(chloro and iodo)-2-(substituted phenyl)-imidazo[1,2-b]pyridazines and -imidazo[1,2-a]pyridines and their interaction with central and mitochondrial benzodiazepine receptors

A series of 3-acylaminomethyl-6-(chloro, iodo and methyl)-2-(phenyl, 4'-t-butylphenyl, 4'-cyclohexylphenyl, biphenyl-4'-yl, 4'-chlorophenyl and 4'-iodophenyl)imidazo[1,2-b]pyridazines and imidazo[1,2-a]pyridines has been prepared and examined for interaction with central and mitochondrial (peripheral-type) benzodiazepine receptors. The imidazo[1:2-b] pyridazines were generally more selective for the mitochondrial receptors than the corresponding imidazo[1,2-a]pyridines. Of these compounds, 3-acetamidomethyl-2-(biphenyl-4'-yl)-6-chloromidazo[1,2-b]pyridazine (9) proved to be the most selective in studies of the displacement of [H-3]diazepam from peripheral-type and central benzodiazepine receptors (IC50 2.8 nM and 0% displacement at 1000 nM, respectively).