1. Molecular design, synthesis and biological evaluation of BP-O-DAPY and O-DAPY derivatives as non-nucleoside HIV-1 reverse transcriptase inhibitors.
- Author
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Yang S, Pannecouque C, Daelemans D, Ma XD, Liu Y, Chen FE, and De Clercq E
- Subjects
- Anti-HIV Agents chemical synthesis, Anti-HIV Agents chemistry, Benzophenones chemical synthesis, Benzophenones chemistry, Cell Line, Tumor, Dose-Response Relationship, Drug, HIV Reverse Transcriptase metabolism, HIV-1 drug effects, HIV-2 drug effects, Humans, Microbial Sensitivity Tests, Models, Molecular, Molecular Structure, Pyrimidines chemical synthesis, Pyrimidines chemistry, Reverse Transcriptase Inhibitors chemical synthesis, Reverse Transcriptase Inhibitors chemistry, Structure-Activity Relationship, Anti-HIV Agents pharmacology, Benzophenones pharmacology, Drug Design, HIV Reverse Transcriptase antagonists & inhibitors, Pyrimidines pharmacology, Reverse Transcriptase Inhibitors pharmacology
- Abstract
This paper reports the synthesis and antiviral evaluation of a series of non-nucleoside reverse transcriptase inhibitors (NNRTIs) that combine the peculiar structural features of diarylpyrimidine derivatives (DAPYs) and benzophenone derivatives (BPs). The DAPY derivatives bearing benzoyl or alkoxyl substitutes on the A-ring showed the inhibitory activity against wild-type HIV-1 at the cellular level within the range of EC50 values from micromolar to nanomolar. Among these compounds, 1u exhibited the most potent anti-HIV-1 activity (EC50 = 0.06 ± 0.01 μM, SI > 6260), which were about 1.8-fold more active than nevirapine (NVP) and delavirdine (DLV). In addition, the binding modes with HIV-1 RT and the preliminary SAR studies of these derivatives were also considered for further investigation., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)
- Published
- 2013
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