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

Jing Tang, Kasthuraiah Maddali, Mathieu Metifiot, Yuk Y. Sham, Robert Vince, Yves Pommier, Zhengqiang Wang

Research output: Contribution to journalArticle

41 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2282-2292
Number of pages11
JournalJournal of medicinal chemistry
Volume54
Issue number7
DOIs
StatePublished - Apr 14 2011

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