Imidazo[1,2-b]pyridazines. XV. Synthesis and Anxiolytic Activity of Some 3-(Benzamidomethyl and fluorobenzamidomethyl)-6-(fluoro, chloro and methylthio)-2-(4-tolyl and 3,4-methylenedioxyphenyl)imidazo[1,2-b]pyridazines

Abstract

Syntheses are reported for some 3-( benzamido-and fluorobenzamido -methyl)-6-( fluoro , chloro and methylthio )-2(4-methyl-, 4-t-butyl-, 4-cyclohexyl- and 3,4-methylenedioxy-phenyl) imidazo-[1,2-b] pyridazines from the relevant 3-unsubstituted imidazo [1,2-b] pyridazines and the N-( hydroxymethyl ) benzamides. In tests of the ability of these compounds to displace [3H]diazepam from rat brain membrane, 3-(3- or 4-fluorobenzamidomethyl)-2-(3,4-methylenedioxyphenyl)-6-methylthioimidazo[1,2-b]- pyridazine bound most strongly, with IC50 2nM; but in behavioural tests in rats the most active compounds were 6-chloro(and methylthio )-3-(2-fluorobenzamidomethyl)-2-(3,4-methylenedioxyphenyl) imidazo [1,2-b] pyridazines which showed a significant anxiolytic activity at 2.5 mg/kg.