
%0 Journal Article
%A Barlin, GB 
%A Davies, LP 
%A Harrison, PW 
%A Ireland, SJ 
%A Willis, AC 
%T Imidazo[1,2-b]Pyridazines. XXI. Syntheses of Some 3-Acylaminomethyl-6-(chloro, fluoro, methoxy, methylthio, phenoxy and phenylthio)-2-(phenyl, 4-t-butylphenyl, 4-cyclohexylphenyl, &#946;-naphthyl and styryl)imidazo[1,2-b]pyridazines and Their Interaction With Central and Peripheral-Type Benzodiazepine Receptors
%J Australian Journal of Chemistry
%D 1996/04/01
%V 49
%N 4
%P 451-461
%K 
%R https://doi.org/10.1071/CH9960451
%U https://www.publish.csiro.au/paper/CH9960451 
%X Some 3-(aliphatic and aromatic) acylaminomethyl derivatives of 6-( chloro, fluoro, methoxy, methylthio, phenoxy and phenylthio )-2-(phenyl, 4-t-butylphenyl, 4-cyclohexylphenyl, &#946;- 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&#8242;-t-butylphenyl)-6-chloro-2-(4&#8243;-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. 
