Synthesis and biological evaluation of 4-(hydroxyimino)arylmethyl diarylpyrimidine analogues as potential non-nucleoside reverse transcriptase inhibitors against HIV

A series of novel diarylpyrimidine analogues featuring a hydroxyiminomethyl group between the pyrimidine scaffold and the aryl wing I have been synthesized and tested in MT-4 cells culture as non-nucleoside reverse transcriptase inhibitors against human immunodeficiency virus (HIV). Most of these new congeners exhibited moderate to excellent activity against wild-type virus with an EC50 value ranging from 0.569 μM to 0.005 μM. 4-(4-((Hydroxyimino) (3-methoxyphenyl)methyl)pyrimidin-2-ylamino)benzonitrile (12n) was identified as the most active compound of this new series (EC50 = 0.025 μM, SI >1223) associated with moderate activity against HIV-1 double mutant strains (K103N + Y181C) (EC50 = 8.72 μM) in addition to its anti-HIV-2 activity with an EC50 value of 8.31 μM. Preliminary structure-activity relationship (SAR) among the newly synthesized DAPYs was also investigated.