Diaryltriazine derivatives, which are structurally related to diarylpyrimidines, are a representative class of HIV-1 reverse transcriptase inhibitors with remarkable antiviral activities against wild-type and several mutant strains of HIV-1. A series of novel diaryltriazines with a picolinonitrile moiety was reported as potent HIV-1 RT inhibitors in the patent WO2016059647(A2). Two representative compounds 5e (hydrochloride) and 6e (hydrochloride) exhibited outstanding activities against various HIV-1 strains in cell-based assays, which were superior to those of AZT. Moreover, modeling simulation study is performed and discussed in details, providing deep insights and valuable information to explain the excellent antiviral potency of 6e. Finally, several cases to improve anti-drug-resistance profiles by targeting highly conserved residues in HIV-1 RT are herein preliminarily summarized.
Keywords: Diaryltriazine; HIV-1 RT inhibitors; highly conserved residues; modeling simulation; picolinonitrile.