Synthesis and biological evaluation of imidazo[1,2-[Formula: see text]]pyridazines as inhibitors of TNF-[Formula: see text] production.

Tumor necrosis factor-alpha (TNF-[Formula: see text] is an important pro-inflammatory cytokine responsible for a diverse range of inflammatory diseases including rheumatoid arthritis. In the present manuscript, our medicinal chemistry efforts on the design, synthesis and TNF-[Formula: see text] evaluation of a series of 3, 6-disubstituted imidazo[1,2-b]pyridazine is described. The best compounds were 3-pyridyl and (4-(methylsulfonyl)phenyl) analogs 8q and 8w, showing inhibition of TNF-[Formula: see text] production with IC[Formula: see text]values of 0.9 and 0.4 [Formula: see text]M, respectively. The identified leads have potential for further development for treatment of inflammatory diseases.