Nicotinamide N-oxide, an in vivo nicotinamide metabolite, is a potent, and selective antagonist of the CXCR2 receptor. In Vitro: Nicotinamide is one of the forms of vitamin B₃. It is a precursor for nicotinamide adenine dinucleotide, which is best known as an electron carrier in oxidative phosphorylation and as a cofactor for many dehydrogenases. It is metabolized through two enzymatic systems. The first system starts with the methylation of nicotinamide by nicotinamide N-methyltransferase, which can subsequently be oxidized by aldehyde oxidase. The second enzymatic system oxidizes nicotinamide to nicotinamide N-oxide^[1]. A series of nicotinamide N-oxides is synthesized and shown to be novel, potent, and selective antagonists of the CXCR2 receptor. Compound 1 has demonstrated potent inhibition of neutrophil chemotaxis (IC₅₀=10 nM). Compound 2 is a selective antagonist of IL-8 binding (IC₅₀=110 nM) and potent inhibitor of neutrophil chemotaxis (IC₅₀=170 nM)^[2].