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 BENZODIAZEPINE RECEPTORS

The syntheses of some ethyl 2-{2'-aryl-6'-(chloro, iodo and methoxy)im idazo[1,2-b]pyridazin-3'-yl}-2-(acetoxy, acylamino, hydroxy and methox y)acetates, 6-methyl-2-(p-tolyl)- and )-3-trimethylammoniomethylimidaz o[1,2-b]pyridazine iodides (and reactions thereof), 2-benzoyl 6-substi tuted imidazo[1,2-b]pyridazines and 7-(methoxy, chloro and o)-2-phenyl pyrimido[1,2-b]pyridazin-5-ium-3-olates are reported. The ability of t hese compounds to displace [H-3]diazepam [central benzodiazepine recep tor (BZR)] and rat kidney membrane [mitochondrial (peripheral-type) be nzodiazepine receptor (PBR)] has been examined. The most active compou nd was ethyl yl)imidazo[1,2-b]pyridazin-3'-yl}-2-hydroxyacetate with I C50 24 nM for displacement from the BZR and 91% displacement at 1000 n M from the PBR; the most selective for the PBR was 6-methyl-3-methylsu lfonylmethyl-2-(p-tol (PBR, IC50 92 nM; BZR, 15% inhibition of binding by [H-3]diazepam at 1000 nM).