Inhibition of myeloperoxidase: Evaluation of 2H-indazoles and 1H-indazolones

Abstract Myeloperoxidase (MPO) produces hypohalous acids as a key component of the innate immune response; however, release of these acids extracellularly results in inflammatory cell and tissue damage. The two-step, one-pot Davis–Beirut reaction was used to synthesize a library of 2 H -indazoles and 1 H -indazolones as putative inhibitors of MPO. A structure–activity relationship study was undertaken wherein compounds were evaluated utilizing taurine-chloramine and MPO-mediated H 2 O 2 consumption assays. Docking studies as well as toxicophore and Lipinski analyses were performed. Fourteen compounds were found to be potent inhibitors with IC 50 values 2 O 2 /HOCl/HOBr system.