Design, synthesis, and evaluation of new type of l-amino acids containing pyridine moiety as nitric oxide synthase inhibitor

New amino acids 7–12 were designed and synthesized as candidate inhibitors of human nitric oxide synthase (NOS). The 2-aminopyridine-containing l-amino acids 8 had potent inhibitory activity toward all of the human NOS isozymes. However, the regioisomers 9 and 10, and 2-methylpyridine-containing compound 11 had much lower inhibitory activity. Human NOS isozymes were also inhibited by 7, which lacks an amino group on the pyridine moiety. A computational docking study was carried out to investigate the mechanism of the inhibitory effect.

We designed and synthesized a new class of nitric oxide synthase (NOS) inhibitors incorporating a picolyl group at the sulfur atom of cysteine and evaluated their structure–activity relationship.Figure optionsDownload as PowerPoint slide