Design, synthesis, crystallographic studies, and preliminary biological appraisal of new substituted triazolo[4,3-b]pyridazin-8-amine derivatives as tankyrase inhibitors
Searching for selective tankyrases (TNKSs) inhibitors, a new small series of 6,8-disubstituted triazolo[4,3-b]piridazines has been synthesized and characterized biologically. Structure-based optimization of the starting hit compound NNL (3) prompted us to the discovery of 4-(2-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-8-ylamino)ethyl)phenol (12), a low nanomolar selective TNKSs inhibitor working a