Design, synthesis and biological evaluations of N-Hydroxy thienopyrimidine-2,4-diones as inhibitors of HIV reverse transcriptase-associated RNase H.

ABSTRACT: Human immunodeficiency virus (HIV) reverse transcriptase (RT) associated ribonuclease H (RNase H) is the only HIV enzymatic function not targeted by current antiviral drugs. Although various chemotypes have been reported to inhibit HIV RNase H, few have shown significant antiviral activities. We report herein the design, synthesis and biological evaluation of a novel N-hydroxy thienopyrimidine-2,3-dione chemotype (11) which potently and selectively inhibited RNase H with considerable potency against HIV-1 in cell culture. Current structure-activity-relationship (SAR) identified analogue 11d as a nanomolar inhibitor of RNase H (IC₅₀ = 0.04 μM) with decent antiviral potency (EC₅₀ = 7.4 μM) and no cytotoxicity (CC₅₀ > 100 μM). In extended biochemical assays co

SUBMITTER: Kankanala J 

PROVIDER: S-EPMC5682218 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature