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

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.

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. The preliminary pharmacological test showed that three compounds, 17, 21, and 30, have the good potency which are compared to the NOS inhibitor NG-nitroarginine(L-NNA), and could be used as lead compounds for exploring new iNOS inhibitors in the future.Figure optionsDownload as PowerPoint slide