121040-58-2Relevant academic research and scientific papers
Imidazopyridazines. VI. Syntheses and Central Nervous System Activities of Some 6-(Alkoxy- and methylthio-phenoxy and methoxybenzylthio)-3-methoxy-2-phenyl(substituted phenyl and pyridinyl)imidazopyridazines
Barlin, Gordon B.,Davies, Les P.,Ireland, Stephen J.,Ngu, Maria M.L.
, p. 1735 - 1748 (2007/10/02)
Series of 6-(alkoxy- and methylthio-phenoxy)-2-phenyl(substituted phenyl and pyridinyl)imidazopyridazines and 3-methoxy-6-(methoxybenzylthio)-2-phenyl(substituted phenyl and pyridinyl)imidazopyridazines have been prepared and subsesquently tested for their ability to inhibit GABA-stimulated 3H-diazepam binding to rat brain plasma membranes.The 6-(alkoxy- and methylthio-phenoxy) and 6-(methoxybenzylthio) compounds were much more effective in the displacement studies than the parent 6-phenoxy or 6-benzylthio compounds respectively.3-Methoxy-6-(2'-methoxyphenoxy)-2-phenylimidazopyridazine (GBLD-167, IC50 70 nM) was 16 times more effective than its 3-methoxy-6-phenoxy analogue (GBLD-214, IC50 1120 nM) and the 3-methoxy-6-(2'-methoxybenzylthio)-2-phenyl compound (GBLD-163, IC50 9 nM) was two and a half times more active than its 6-benzylthio-3-methoxy analogue (GBLD-137, IC50 22nM).The most active member of the 6-phenoxy series was the 2-(4'-fluorophenyl)-3-methoxy-6-(2''-methoxyphenoxy) compound (GBLD-255, IC50 30nM) and, within the 6-benzylthio series, the 2-(4'-fluorophenyl, 3'-aminophenyl, and pyridin-3'-yl)-3-methoxy-6-(3''-methoxybenzylthio) compounds (GBLD-233, 301 and 296) all gave IC50 5nM.A Hansch-type analysis of the results for these two closely related series of compounds indicates that electron-donating substituents in 2-(para substituted phenyl) derivatives favour binding, but bulky substituents hinder this effect.
