Imidazo[1,2-b]pyridazines .24. Syntheses of some 3-(variously substituted) imidazo[1,2-b]pyridazines, 6-substituted 2-benzoylimidazo[1,2-b]pyridazines and pyrimido[1,2-b]pyridazin-5-ium-3-olates and their interaction with central and mitochondrial be

摘要

The syntheses of some ethyl 2-{2'-aryl-6'-(chloro, iodo and methoxy)imidazo[1,2-b]pyridazin-3'-yl}-2-(acetoxy, acylamino, hydroxy and methoxy)acetates, 6-methyl-2-(p-tolyl)- and 6-chloro-2-(4'-chlorophenyl)-3-trimethylammoniomethylimidazo[1,2-b]pyrid azine iodides (and reactions thereof), 2-benzoyl 6-substituted imidazo[1,2-b]pyridazines and 7-(methoxy, chloro and phenylthio)-2-phenylpyrimido[1,2-b]pyridazin-5-ium-3-olates are reported. The ability of these compounds to displace [H-3]diazepam [central benzodiazepine receptor (BZR)] and rat kidney membrane [mitochondrial (peripheral-type) benzodiazepine receptor (PBR)] has been examined. The most active compound was ethyl 2-{6'-chloro-2'-(p-tolyl)imidazo[1,2-b]pyridazin-3'-yl}-2-hydroxyacetate with IC50 24 nM for displacement from the BZR and 91% displacement at 1000 nM from the PBR; the most selective for the PBR was 6-methyl-3-methylsulfonylmethyl-2-(p-tol (PBR, IC50 92 nM; BZR, 15% inhibition of binding by [H-3]diazepam at 1000 nM).