A series of novel 1,4-dihydrothieno[3′,2′:5,6]thiopyrano[4,3-c]-pyrazole-3-carboxamide derivatives were synthesized and evaluated for their inhibitory activity to human 5-lipo-oxygenase (5-LOX). Compound 7c was found to exhibit significant inhibition to human 5-LOX with IC50 value of 5.7 ± 0.9 μm. Compound 7c was further studied using molecular docking in order to delineate its structure–activity relationship and to gain insight into the design of effective 5-LOX inhibitors.