Novel 2-aryalkylthio-4-amino-6-benzylpyrimidines (3a-i), which can be considered as S-DABO and TMC-125 analogue hybrid molecules, have been designed and synthesized as inhibitors of HIV-1 RT. The results clearly indicated that the changes at the N(3)/C(4) position of pyrimidine ring could affect the hydrogen bonds strength and number between N(3)/C(4) and the Lys101 residue which are indispensable for anti-HIV-1 RT activity. The biological activity results are also in accordance with the docking study.