Novel diaryltriazines with a picolinonitrile moiety as potent HIV-1 RT inhibitors: a patent evaluation of WO2016059647(A2)

ABSTRACT

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
• picolinonitrile
• modeling simulation
• highly conserved residues

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

The authors were supported by the Key Project of National Natural Science Foundation of China for International Cooperation (No. 81420108027), the National Natural Science Foundation of China (No. 81273354), Young Scholars Program of Shandong University (YSPSDU, No. 2016WLJH32, to P.Z.) and Major Project of Science and Technology of Shandong Province (No. 2015ZDJS04001).