3-Hydroxypyrimidine-2,4-diones as an Inhibitor Scaffold of HIV Integrase
Journal of Medicinal Chemistry2011Vol. 54(7), pp. 2282–2292
Citations Over TimeTop 11% of 2011 papers
Jing Tang, Kasthuraiah Maddali, Mathieu Métifiot, Yuk Y. Sham, Robert Vince, Yves Pommier, Zhengqiang Wang
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.
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