Recently,3-iodo-4-phenoxypyridinone derivatives (IOPYs) were identified as a novel class of highly potent non-nucleoside reverse transcriptase inhibitors (NNRTIs) with superior activity against both wild-type and mutant HIV-1strains at nanomole level.1 Additionally,diarylpyrimidine derivatives (DAPYs),another class of NNRTIs,also possess excellent potency2 against most HIV-1 mutant strains due to their flexible"Horseshoe"conformations.According to the X-ray crystal structures of the complexes of IOPY/DAPY with reverse transcriptase (RT),3,4 we found they occupied the same position in RT binding pocket and shared the similar binding mode.Based on the drug design principles of scaffold hoping and pharmacophoric pattern,we designed a series of 3-iodo-4-phenoxy-5-phenylamino-pyridinones (IOAPs) as hybrids of DAPYs and IOPYs.These are expected to have improved affinity and efficacy compared to their parent drugs.Docking studies were carried out to predict the molecular binding mode of the target compounds (grey:BA-PT,purple:TMC-125).