Novel diarylpyrimidines and diaryltriazines as potent HIV-1 NNRTIs with dramatically improved solubility: a patent evaluation of US20140378443A1.

Diarylpyrimidine and diaryltriazine derivatives, two representative structurally related classes of HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) with robust potencies against wild-type and several mutant strains of HIV-1, have attracted more and more attention in the last decade. However, they have been suffering from poor aqueous solubility. A series of novel diarylpyrimidines and diaryltriazines with solubilizing substituents attached to the central rings were reported as potent NNRTIs in the patent US20140378443A1. Some compounds exhibited potencies against wild-type HIV-1 which were comparable or even superior to those of dapivirine, etravirine and rilpivirine. In addition, dramatically enhanced solubilities were observed for these new compounds. Moreover, some structure optimization strategies for improving aqueous solubility are detailed in this review, providing new insights into development of next-generation NNRTIs endowed with favorable solubility. We anticipate that application of these strategies will ultimately lead to discovery of new anti-HIV drug candidates.