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.
Anti-HIV Agents ; chemical synthesis ; chemistry ; pharmacology ; Drug Resistance, Viral ; HIV Infections ; drug therapy ; HIV-1 ; drug effects ; Humans ; Molecular Structure ; Nitriles ; chemical synthesis ; chemistry ; pharmacology ; Pyridazines ; chemical synthesis ; chemistry ; pharmacology ; Pyrimidines ; chemical synthesis ; chemistry ; pharmacology ; Reverse Transcriptase Inhibitors ; chemical synthesis ; chemistry ; pharmacology ; Rilpivirine