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

Abstract

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.

Keywords:

• diarylpyrimidines
• drug design
• fluorine atom
• HIV inhibitors
• non-nucleoside reverse transcriptase inhibitors

Declaration of interest

The authors were supported by the National Natural Science Foundation of China (NSFC) Projects for International Cooperation and Exchange program under grant number 81420108027, and by the NSFC under grant numbers 81102320, 81273354 and 81573347. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

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