Literature

Abstract

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.

DOI： 10.1021/jm1014378

3-Hydroxypyrimidine-2,4-diones as an Inhibitor Scaffold of HIV Integrase

Journal of Medicinal Chemistry 2011.0

N-3 Hydroxylation of Pyrimidine-2,4-diones Yields Dual Inhibitors of HIV Reverse Transcriptase and Integrase

ACS Medicinal Chemistry Letters 2011.0

3-Hydroxypyrimidine-2,4-dione-5-N-benzylcarboxamides Potently Inhibit HIV-1 Integrase and RNase H

Journal of Medicinal Chemistry 2016.0

1-Hydroxypyrido[2,3-d]pyrimidin-2(1H)-ones as novel selective HIV integrase inhibitors obtained via privileged substructure-based compound libraries

Bioorganic & Medicinal Chemistry 2017.0

4-Substituted 2-Hydroxyisoquinoline-1,3(2H,4H)-diones as a Novel Class of HIV-1 Integrase Inhibitors

ACS Medicinal Chemistry Letters 2013.0

Design and synthesis of N-methylpyrimidone derivatives as HIV-1 integrase inhibitors