Imidazo[1,2-b]Pyridazines. VIII. Syntheses and Central Nervous System Activities of Some 6-Benzylamino (and methoxybenzylamino)-3-methoxy-2-phenyl(Substituted phenyl or pyridinyl)imidazo[1,2-b]pyridazines

Abstract

Syntheses and IC₅₀ values for the displacement of ³H-diazepam from rat brain plasma membrane are reported for a series of 6-benzylamino(and methoxybenzylamino )-3-methoxy-2-phenyl(substituted phenyl and pyridinyl )imidazo[l,2-b]pyridazines (and their 6-anilino and 6-phenethylamino analogues). The results are compared with those reported previously (by us) for the 6-chloro, 6-phenoxy, 6-benzylthio, and 6-benzyloxy compounds.

In the imidazo[l,2-b]pyridazine ring system, 6-(o- and m- methoxybenzylamino ) groups were found to be beneficial to binding activity; eight compounds have been prepared with IC₅₀ values less than 2 nM (cf. ³H-diazepam with IC₅₀ of 4.2 nM ).2-(p-Aminopheny1)-3-methoxy- 6-(m- methoxybenzylamino )imidazo[1,2-b]pyridazine exhibited the highest activity with IC₅₀ 1.0 nM.