1-[2-(2-Benzoyl- and 2-benzylphenoxy)ethyl]uracils as potent anti-HIV-1 agents
| Autor: | Mikhail S. Novikov, Sergey N. Kochetkov, Kartik Temburnikar, Alexander V. Ivanov, Olga N. Ivanova, Katherine L. Seley-Radtke, Vladimir T. Valuev-Elliston, G. V. Gurskaya, Alexander Ozerov, Christophe Pannecouque, Jan Balzarini |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Nevirapine
Stereochemistry Clinical Biochemistry Mutant Non-nucleoside reverse transcriptase inhibitors Pharmaceutical Science Biochemistry Article Virus Cell Line Benzophenones Structure-Activity Relationship chemistry.chemical_compound Benzophenone Drug Resistance Viral Drug Discovery Reverse transcriptase medicine Humans Uracil Molecular Biology Alkyl ComputingMethodologies_COMPUTERGRAPHICS chemistry.chemical_classification Organic Chemistry virus diseases HIV Reverse Transcriptase Discovery and development of non-nucleoside reverse-transcriptase inhibitors Amino Acid Substitution chemistry HIV-1 Reverse Transcriptase Inhibitors Molecular Medicine medicine.drug |
| Zdroj: | Bioorganic & Medicinal Chemistry |
| ISSN: | 0968-0896 |
| Popis: | Graphical abstract Non-nucleoside reverse transcriptase inhibitors (NNRTI) are key components in highly active antiretroviral therapy for treating HIV-1. Herein we present the synthesis for a series of N1-alkylated uracil derivatives bearing ω-(2-benzyl- and 2-benzoylphenoxy)alkyl substituents as novel NNRTIs. These compounds displayed anti-HIV activity similar to that of nevirapine and several of them exhibited activity against the K103N/Y181C RT mutant HIV-1 strain. Further evaluation revealed that the inhibitors were active against most nevirapine-resistant mono- and di-substituted RTs with the exception of the V106A RT. Thus, the candidate compounds can be regarded as potential lead compounds against the wild-type virus and drug-resistant forms. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect