Nicotinamide N-oxide (Synonyms: NSC 168416, NSC 30531)

Nicotinamide N-oxide, an in vivo nicotinamide metabolite, is a potent, and selective antagonist of the CXCR2 receptor. Human Endogenous Metabolite

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].

[1]. Real AM, et al. Nicotinamide N-oxidation by CYP2E1 in human liver microsomes. Drug Metab Dispos. 2013 Mar;41(3):550-3. [2]. Cutshall NS, et al. Nicotinamide N-oxides as CXCR2 antagonists. Bioorg Med Chem Lett. 2001 Jul 23;11(14):1951-4.