1281860-46-5Relevant academic research and scientific papers
6-Biphenylmethyl-3-hydroxypyrimidine-2,4-diones potently and selectively inhibited HIV reverse transcriptase-associated RNase H
Wang, Lei,Tang, Jing,Huber, Andrew D.,Casey, Mary C.,Kirby, Karen A.,Wilson, Daniel J.,Kankanala, Jayakanth,Parniak, Michael A.,Sarafianos, Stefan G.,Wang, Zhengqiang
, p. 680 - 691 (2018/07/29)
Human immunodeficiency virus (HIV) reverse transcriptase (RT)-associated ribonuclease H (RNase H) remains an unvalidated drug target. Reported HIV RNase H inhibitors generally lack significant antiviral activity. We report herein the design, synthesis, biochemical and antiviral evaluations of a new 6-biphenylmethyl subtype of the 3-hydroxypyrimidine-2,4-dione (HPD) chemotype. In biochemical assays, analogues of this new subtype potently inhibited RT RNase H in low nanomolar range without inhibiting RT polymerase (pol) or integrase strand transfer (INST) at the highest concentrations tested. In cell-based assays, a few analogues inhibited HIV in low micromolar range without cytotoxicity at concentrations up to 100 μM.
3-Hydroxypyrimidine-2,4-diones as an Inhibitor Scaffold of HIV Integrase
Tang, Jing,Maddali, Kasthuraiah,Metifiot, Mathieu,Sham, Yuk Y.,Vince, Robert,Pommier, Yves,Wang, Zhengqiang
, p. 2282 - 2292 (2011/06/17)
Integrase (IN) represents a clinically validated target for the development of antivirals against human immunodeficiency virus (HIV). Inhibitors with a novel structure core are essential for combating resistance associated with known IN inhibitors (INIs). We have previously disclosed a novel dual inhibitor scaffold of HIV IN and reverse transcriptase (RT). Here we report the complete structure-activity relationship (SAR), molecular modeling, and resistance profile of this inhibitor type on IN inhibition. These studies support an antiviral mechanism of dual inhibition against both IN and RT and validate 3-hydroxypyrimidine-2,4-diones as an IN inhibitor scaffold.
