Synthesis and structure-activity relationship of novel diarylpyrimidines with hydromethyl linker (CH(OH)-DAPYs) as HIV-1 NNRTIs

A series of 26 diarylpyrimidines, characterized by the hydroxymethyl linker between the left wing benzene ring and the central pyrimidine, were synthesized and evaluated for in vitro anti-HIV activity. Most of the compounds exhibited moderate to excellent activities against wild-type HIV-1. Among them, compound 10i, bearing a chlorine atom at the C-2 position of left benzene ring, was the best congener and showed potent activity against wild-type HIV-1 with an EC50 value of 0.009 μM, along with moderate activities against the double RT mutant (K103N + Y181C) HIV-1(IIIB) and HIV-2(ROD) with an EC50 value of 6.2 and 6.0 μM, respectively. The preliminary structure-activity relationship (SAR) of this new series of compounds was also investigated.