A series of 18 cycloalkyl arylpyrimidines (CAPYs) were designed from lead compounds diarylpyrimidines (DAPYs), synthesized and evaluated for in vitro anti-HIV activity. Among them, the compound 1p displayed potent anti-HIV-1 activity against WT HIV-1 with an EC50 value of 0.055 μM and a selectivity index (SI)> 7290. The preliminary structure–activity relationship (SAR) of this new series of compounds was also investigated, which enriched ...