Imidazo[1,2-b]pyridazines. XX syntheses of some 3-acylaminomethyl-6-(chloro, fluoro, methoxy, methylthio, phenoxy and phenylthio)-2-(phenyl, 4-t-butylphenyl, 4-cyclohexylphenyl, β-naphthyl and styryl)imidazo[1,2-b]pyridazines and their interaction with central and peripheral-type benzodiazepine receptors

Article abstract of DOI:10.1071/ch9960451

Some 3-(aliphatic and aromatic)acylaminomethyl derivatives of 6-(chloro, fluoro, methoxy, methylthio, phenoxy and phenylthio)-2-(phenyl, 4-t-butylphenyl, 4-cyclohexylphenyl, β-naphthyl and styryl)imidazo[1,2-b]pyridazines have been prepared and tested for binding to central benzodiazepine receptors present in rat brain membrane, and to peripheral-type (mitochondrial) benzodiazepine receptors present in rat kidney membrane. Some of these compounds which contained 2-(4-t-butylphenyl, 4-cyclohexylphenyl and styryl) substituents bound strongly and selectively to peripheral-type benzodiazepine receptors. For example, 2-(4′-t-butylphenyl)-6-chloro-2-(4″-fluorobenzamidomethyl)imidazo[1, 2-b]pyridazine in tests for the displacement of [³H]diazepam from both peripheral-type and central benzodiazepine receptors gave IC₅₀ <1.0 nM and 9% displacement at 1000 nM, respectively. Steric effects appeared to be more restrictive in the interaction of these ligands with central benzodiazepine receptors rather than with peripheral-type benzodiazepine receptors; X-ray structure analyses of two typical compounds are reported.