Application of the Huisgen cycloaddition and 'click' reaction toward various 1,2,3-triazoles as HIV non-nucleoside reverse transcriptase inhibitors
| Autor: | Adriaan E. Basson, Willem A. L. van Otterlo, Clinton G. L. Veale, Stephen C. Pelly, Nicole Pribut |
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| Rok vydání: | 2016 |
| Předmět: |
Stereochemistry
Anti-HIV Agents Clinical Biochemistry Triazole Human immunodeficiency virus (HIV) Pharmaceutical Science Microbial Sensitivity Tests 010402 general chemistry medicine.disease_cause 01 natural sciences Biochemistry Nucleoside Reverse Transcriptase Inhibitor chemistry.chemical_compound Structure-Activity Relationship Drug Discovery medicine Lersivirine Molecular Biology Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Organic Chemistry virus diseases HIV Triazoles Reverse transcriptase Cycloaddition HIV Reverse Transcriptase 0104 chemical sciences chemistry Cyclization Click chemistry Molecular Medicine Reverse Transcriptase Inhibitors Click Chemistry |
| Zdroj: | Bioorganicmedicinal chemistry letters. 26(15) |
| ISSN: | 1464-3405 |
| Popis: | The development of novel anti-HIV agents remains an important medicinal chemistry challenge given that no cure for the disease is imminent, and the continued use of current NNRTIs inevitably leads to problems associated with resistance. Inspired by the pyrazole-containing NNRTI lersivirine (LSV), we embarked upon a study to establish whether 1,2,3-triazole heterocycles could be used as a new scaffold for the creation of novel NNRTIs. An especially attractive feature of triazoles used for this purpose is the versatility in accessing variously functionalised systems using either the thermally regulated Huisgen cycloaddition, or the related 'click' reaction. Employing three alternative forms of these reactions, we were able to synthesise a range of triazole compounds and evaluate their efficacy in a phenotypic HIV assay. To our astonishment, even compounds closely mimicking LSV were only moderately effective against HIV. |
| Databáze: | OpenAIRE |
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