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3-Hydroxypyrimidine-2,4-diones as an inhibitor scaffold of HIV integrase.

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.

SUBMITTER: Tang J

PROVIDER: S-EPMC3072462 | biostudies-other | 2011 Apr

REPOSITORIES: biostudies-other

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3-Hydroxypyrimidine-2,4-diones as an inhibitor scaffold of HIV integrase.

Tang Jing J Maddali Kasthuraiah K Metifiot Mathieu M Sham Yuk Y YY Vince Robert R Pommier Yves Y Wang Zhengqiang Z

Journal of medicinal chemistry 20110307 7

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 in ...[more]

PMID: 21381765

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