HIV-1 NNRTIs: structural diversity, pharmacophore similarity, and implications for drug design.

摘要: Nonnucleoside reverse transcriptase inhibitors (NNRTIs) nowadays represent very potent and most promising anti-AIDS agents that specifically target the HIV-1 (RT). However, effectiveness of NNRTI drugs can be hampered by rapid emergence drug-resistant viruses severe side effects upon long-term use. Therefore, there is an urgent need to develop novel, highly NNRTIs with broad spectrum antiviral activity improved pharmacokinetic properties, more efficient strategies facilitate shorten drug discovery process would extremely beneficial. Fortunately, structural diversity provided a wide space for novel lead discovery, pharmacophore similarity gave valuable hints optimization. More importantly, continued efforts in development computational tools increased crystallographic information on RT/NNRTI complexes, structure-based approaches using combination traditional medicinal chemistry, biology, chemistry are being used increasingly design NNRTIs. First, this review covers two decades research various families based their chemical scaffolds, then describes We have attempted assemble comprehensive overview general optimization reported literature during last decade. The successful applications strategies, crystallography, designing highlighted. Future directions also outlined.