1986-81-8

Nicotinamide is one of the forms of vitamin B ₃ . 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. 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 (IC ₅₀ =10 nM). Compound 2 is a selective antagonist of IL-8 binding (IC ₅₀ =110 nM) and potent inhibitor of neutrophil chemotaxis (IC ₅₀ =170 nM).