Druggability modification strategies of the diarylpyrimidine-type non-nucleoside reverse transcriptase inhibitors.

作者: Chunlin Zhuang , Li Ding , Fener Chen

DOI: 10.1002/MED.21760

关键词:

摘要: Drug discovery of human immunodeficiency virus (HIV) is a hot field in medicinal chemistry community for many years. The diarylpyrimidines (DAPYs) are the second-generation non-nucleoside reverse transcriptase inhibitors (NNRTIs) targeting transcriptase, playing great irreplaceable role HIV transcriptional therapy. However, fast-growing drug-resistant mutations as nonnegligible challenge still unpredictably appeared clinical practice, leading to deactivate or reduce existing drugs. In last 20 years, more and novel DAPY derivatives have developed with purpose counter mutants. Nevertheless, most them dissatisfactory pharmacokinetics (PK) poor antiviral activity toward resistant mutant strains. this article, we will analyze NNRTI promising druggability, summarize series druggability modification strategies improve activity, toxicity PK properties recent prospects DAPYs directions future efforts be discussed.

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