IMIDAZO[1,2-B]PYRIDAZINES .20. SYNTHESES OF SOME 3-ACYLAMINOMETHYL-6-(CHLORO, FLUORO, METHOXY, METHYLTHIO, PHENOXY AND PHENYLTHIO)-2-(PHENYL, 4-T-BUTYLPHENYL, 4-CYCLOHEXYLPHENYL, BETA-NAPHTHYL AND STYRYL)IMIDAZO[1,2-B]PYRIDAZINES AND THEIR INTERACTION WITH CENTRAL AND PERIPHERAL-TYPE BENZODIAZEPINE RECEPTORS

Some 3-(aliphatic and aromatic) acylaminomethyl derivatives of 6-(chlo ro, fluoro, methoxy, methylthio, phenoxy and phenylthio)-2-(phenyl, 4- t-butylphenyl, 4-cyclohexylphenyl, beta-naphthyl and styryl)imidazo[1, 2-b]pyridazines have been prepared and tested for binding to central b enzodiazepine receptors present in rat brain membrane, and to peripher al-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 select ively to peripheral-type benzodiazepine receptors. For example, 4''-fl uorobenzamidomethyl)imidazo[1,2-b]pyridazine in tests for the displace ment of [H-3]diazepam from both peripheral-type and central benzodiaze pine receptors gave IC50 <1.0 nM and 9% displacement at 1000 nM, respe ctively. Steric effects appeared to be more restrictive in the interac tion of these ligands with central benzodiazepine receptors rather tha n with peripheral-type benzodiazepine receptors; X-ray structure analy ses of two typical compounds are reported.