Design, synthesis, and preliminary evaluation of 4-(6-(3-nitroguanidino)hexanamido)pyrrolidine derivatives as potential iNOS inhibitors Original Research Article

A series of 4-(6-(3-nitroguanidino)hexanamido)pyrrolidine derivatives were synthesized and evaluated for their abilities to inhibit inducible nitric oxide synthase (iNOS) isoform. All target compounds were prepared in 11 steps from commercially trans-4-hydroxy-l-proline. The preliminary pharmacological test showed that three compounds, 17, 21, and 30, have the good potency (IC50 = 2.36, 2.68, 2.5 μM, respectively) which are compared to the NOS inhibitor NG-nitroarginine(L-NNA) (IC50 = 14.74 μM), and could be used as lead compounds for exploring new iNOS inhibitors in the future.