1. 5′-Nor carbocyclic nucleosides: unusual nonnucleoside inhibitors of HIV-1 reverse transcriptase
- Author
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Vladimir T. Valuev-Elliston, Mikhail S. Novikov, Alexander V. Ivanov, Denis A. Babkov, Katherine L. Seley-Radtke, Jan Balzarini, Elena S. Matyugina, Sergey N. Kochetkov, and Anastasia L. Khandazhinskaya
- Subjects
Pharmacology ,chemistry.chemical_classification ,biology ,Chemistry ,Stereochemistry ,Organic Chemistry ,Mutant ,Human immunodeficiency virus (HIV) ,Pharmaceutical Science ,Active site ,medicine.disease_cause ,Inhibitory postsynaptic potential ,Biochemistry ,Reverse transcriptase ,Enzyme ,Drug Discovery ,biology.protein ,medicine ,Molecular Medicine - Abstract
A new series of potential nonnucleoside inhibitors of HIV-1 reverse transcriptase (NNRTIs) based on the carbocyclic 5′-nor-uracil scaffold were designed and synthesized. Binding modes in the active site of the enzyme were studied computationally to provide insight on potential interactions. Several of the 2′,3′-dideoxy-2′,3′-didehydro-5′-nor-uridine analogues showed inhibitory activity against wild-type and mutant (L100I) HIV-RT with Ki 13–18 μM and 1–11 μM, respectively.
- Published
- 2013