Discovery and development of diarylpyrimidines (DAPYs) as next- generation HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs)

The new HIV-1 NNRTI drug Etravirine (TMC125) and a promising drug candidate Rilpivirine (TMC278) in phase III clinical trial are compounds belonging to the diarylpyrimidine (DAPY) family.  They are extremely high potent against both wild-type and many drug-resistant HIV-1 strains, providing new hope for HIV-infected patients who fail to use current drugs due to the emergence of drug-resistant HIV mutants.  The discovery and development of DAPY derivatives as next-generation NNRTI drugs depend on multidisciplinary coordination and their success has encouraged new researches to explore more next-generation NNRTIs with new scaffolds.  This review described the story of discovery and development of DAPY derivatives as next-generation NNRTIs and related progress.