Time-dependence and preliminary SAR studies in inhibition of nitric oxide synthase isoforms by homologues of thiocitrulline

Treatment of Nα-Cbz-Nε-(2-hydroxyethylaminothiocarbonyl)-l-lysine N-(2-hydroxyethyl)amide with boiling hydrochloric acid gave Nε-(4,5-dihydrothiazol-2-yl)-l-lysine. This was a weak and non-isoform selective inhibitor of NOS, whereas Nε-aminothiocarbonyl-l-lysine and its methyl ester were potent, with IC50=13 and 18 μM, respectively, against human iNOS and IC50=3 and 8 μM, respectively, against rat nNOS. Time dependence was observed for inhibition of nNOS by the ester.