A series of novel S-DABO derivatives with the substituted 1,2,3-triazole moiety on the C-2 side chain were synthesized by using the simple and efficient CuAAC reaction, and biologically evaluated as inhibitors of HIV-1. Among them, the most active HIV-1 inhibitors was compound 4-((4-((4-(2,6-dichlorobenzyl)-5-methyl-6-oxo-1,6-dihydropyrimidin-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)methyl)benzenesulfonamide (B5b7), which exhibited similar HIV-1 inhibitory potency (EC50 = 3.22 μM) compared with 3TC (EC50 = 2.24 μM). None of these compounds demonstrated inhibition against HIV-2 replication. The preliminary structure-activity relationship (SAR) of these new derivatives was discussed briefly.This article is protected by copyright. All rights reserved.