Structural optimization of 6-aryl pyridazin-3-ones as novel potent PDE4 inhibitors

Abstract

The synthesis and structure-activity relationship (SAR) analysis of series of 4,5- dihydropyridazin-3-one derivatives as PDE4 inhibitors are described. Topological explorations at the position N-2 of the pyridazine ring allowed identification of additional interactions with PDE4 binding site, leading to significantly more potent compounds (10v, IC50 ∼20 nM) with increased water solubility.