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Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
Synthesis of novel MKC-442 analogues with potent activities against HIV-1
Nasser R El-Brollosy1, Erik B Pedersen, Claus Nielsen
1Nucleic Acid Center, Department of Chemistry, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark. EBP@Chen.sdu.dk
Abstract:
Bis(alken-1-yloxy)methanes 2 were synthesized by reacting 2-cyclohexenol, 3-cyclohexenylmethanol, cinnamyl alcohol and its alpha-methyl analogue with dibromomethane. Condensation of 2 with 5, 6-disubstituted uracil derivatives 1 resulted in the desired MKC-442 analogues 3-6. The most active compounds, N-1 cinnamyloxymethyl- and N-1 2-methyl-3-phenylallyloxymethyl substituted 5-ethyl-6-(3, 5-dimethylbenzyl)uracils (5b and 6b), showed activity against wild-type HIV-1 in the nanomolar range, and against Y181C andY181C+K103N, mutant strains known to be resistant to MKC-442, in the micromolar range.
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