6-Arylthio-3-hydroxypyrimidine-2,4-diones potently inhibited HIV reverse transcriptase-associated RNase H with antiviral activity.

ABSTRACT: Human immunodeficiency virus (HIV) reverse transcriptase (RT) associated ribonuclease H (RNase H) remains the only virally encoded enzymatic function not targeted by current drugs. Although a few chemotypes have been reported to inhibit HIV RNase H in biochemical assays, their general lack of significant antiviral activity in cell culture necessitates continued efforts in identifying highly potent RNase H inhibitors to confer antiviral activity. We report herein the design, synthesis, biochemical and antiviral evaluations of a new 6-arylthio subtype of the 3-hydroxypyrimidine-2,4-dione (HPD) chemotype. In biochemical assays these new analogues inhibited RT RNase H in single-digit nanomolar range without inhibiting RT polymerase (pol) at concentrations up to 10 μM, amounting to exceptional

SUBMITTER: Wang L 

PROVIDER: S-EPMC6112573 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature