8-Hydroxy-3-methoxy-5H-pyrido [2, 1-c] pyrazin-5-one (compound 1) isolated from Solanum cathayanum was identified as an inducible nitric oxide synthase (iNOS) inhibitor with IC50 value 30 μM. Induced-fit docking (IFD) was performed to investigate the interaction mechanism between compound 1 and iNOS. The Glide Gscore and IFD score of compound 1 are –6.99 and –766.90, respectively. Hydroxyl group of compound 1 has hydrogen bond interaction with cofactor iron protoporphyrin. The derivatives of compound 1 as novel iNOS inhibitors were designed using combinatorial virtual screening technology. The IFD scores of top 5 compounds range from –769.00 to –775.32. The selected top compounds have more binding sites than compound 1, and interact with both iron protoporphyrin and key residues such as Gln257, Tyr341, Met368, and Glu371.