Abstract: Molecular modeling analysis of 2-alkylsulfanyl-6-benzyl-3,4-dihydro-pyrimidin-4(3H) -one(S-DABOs) type non-nucleoside reverse transcriptase inhibitors(NNRTIs) gave support to the design of new oxophenethyl-S-DACOs derivatives as highly potent and specific NNRTIs.To follow up on the novel S-DACO derivatives,a series of novel 2-(phenylaminocarbonylmethylthio)-6-cyclohexylmethyl-pyrimidin-4(3H)-ones have been designed and synthesized in this paper.All of the new compounds were evaluated tested for their cytotoxicitities and anti-HIV-1 activities in MT-4 cells infected by the HIV-1ⅢB,and compared with NVP as reference drug.The results indicated that most of these new compounds showed moderate to potent activities against wild-type HIV-1with an EC50 ranging from 2.58mol/L to 0.18mol/L.Among them,4b was identified as the most promising compound with an EC50 value of 1.64mol/L, and a CC50 value of 296.8mol/L.The SI value was greater than 203.6,which is much better than that for the reference drugs of NVP.The structure-activity relationships(SAR) of the newly synthesized compounds are presented.