Novel fluorine-containing DAPY derivatives as potent HIV-1 NNRTIs: a patent evaluation of WO2014072419

Diarylpyrimidine (DAPY) derivatives, one family of HIV non-nucleoside reverse transcriptase (RT) inhibitors (NNRTIs) with superior activities against wild-type (WT) HIV-1 and NNRTI-resistant strains, have attracted much attention in the past decade. A series of DAPY derivatives featuring a fluorine atom on the central ring were reported as novel NNRTIs in the patent WO2014072419. Some compounds exhibited robust potency against both WT and mutant strains, which were approximately equal to or higher than those of the reference drug TMC120. Moreover, it has become evident that fluorinated molecules have a remarkable record in many other potent NNRTIs. Thus, this survey provides a sampling of renowned fluorinated NNRTIs and their mode of action, with an analysis clarifying the functional roles and impact of fluorine substitution on antiviral potency. We envision that fluorinated NNRTIs will play a continuing role in affording anti-HIV drug candidates for therapeutic applications.