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Synthetic Approaches to a Key Pyridone-carboxylic Acid Precursor Common to the HIV-1 Integrase Strand Transfer Inhibitors Dolutegravir, Bictegravir, and Cabotegravir
[Image: see text] Dolutegravir (DTG), Bictegravir (BIC), and Cabotegravir (CAB) are the second-generation integrase strand transfer inhibitors (INSTIs) that have been FDA-approved for the treatment of HIV-1 infection. Preparation of these INSTIs utilizes the common intermediate 1-(2,2-dimethoxyethyl...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10204085/ https://www.ncbi.nlm.nih.gov/pubmed/37229216 http://dx.doi.org/10.1021/acs.oprd.3c00063 |
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author | Mahajan, Pankaj S. Burke, Terrence R. |
author_facet | Mahajan, Pankaj S. Burke, Terrence R. |
author_sort | Mahajan, Pankaj S. |
collection | PubMed |
description | [Image: see text] Dolutegravir (DTG), Bictegravir (BIC), and Cabotegravir (CAB) are the second-generation integrase strand transfer inhibitors (INSTIs) that have been FDA-approved for the treatment of HIV-1 infection. Preparation of these INSTIs utilizes the common intermediate 1-(2,2-dimethoxyethyl)-5-methoxy-6-(methoxycarbonyl)-4-oxo-1,4-dihydropyridine-3-carboxylic acid (6). Presented herein is a literature and patent review of synthetic routes used to access the pharmaceutically important intermediate 6. The review highlights the ways in which small fine-tuned synthetic modifications have been used to achieve good yields and regioselectivity of ester hydrolysis. |
format | Online Article Text |
id | pubmed-10204085 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-102040852023-05-24 Synthetic Approaches to a Key Pyridone-carboxylic Acid Precursor Common to the HIV-1 Integrase Strand Transfer Inhibitors Dolutegravir, Bictegravir, and Cabotegravir Mahajan, Pankaj S. Burke, Terrence R. Org Process Res Dev [Image: see text] Dolutegravir (DTG), Bictegravir (BIC), and Cabotegravir (CAB) are the second-generation integrase strand transfer inhibitors (INSTIs) that have been FDA-approved for the treatment of HIV-1 infection. Preparation of these INSTIs utilizes the common intermediate 1-(2,2-dimethoxyethyl)-5-methoxy-6-(methoxycarbonyl)-4-oxo-1,4-dihydropyridine-3-carboxylic acid (6). Presented herein is a literature and patent review of synthetic routes used to access the pharmaceutically important intermediate 6. The review highlights the ways in which small fine-tuned synthetic modifications have been used to achieve good yields and regioselectivity of ester hydrolysis. American Chemical Society 2023-04-20 /pmc/articles/PMC10204085/ /pubmed/37229216 http://dx.doi.org/10.1021/acs.oprd.3c00063 Text en Not subject to U.S. Copyright. Published 2023 by American Chemical Society https://creativecommons.org/licenses/by-nc-nd/4.0/Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Mahajan, Pankaj S. Burke, Terrence R. Synthetic Approaches to a Key Pyridone-carboxylic Acid Precursor Common to the HIV-1 Integrase Strand Transfer Inhibitors Dolutegravir, Bictegravir, and Cabotegravir |
title | Synthetic Approaches
to a Key Pyridone-carboxylic
Acid Precursor Common to the HIV-1 Integrase Strand Transfer
Inhibitors Dolutegravir, Bictegravir, and Cabotegravir |
title_full | Synthetic Approaches
to a Key Pyridone-carboxylic
Acid Precursor Common to the HIV-1 Integrase Strand Transfer
Inhibitors Dolutegravir, Bictegravir, and Cabotegravir |
title_fullStr | Synthetic Approaches
to a Key Pyridone-carboxylic
Acid Precursor Common to the HIV-1 Integrase Strand Transfer
Inhibitors Dolutegravir, Bictegravir, and Cabotegravir |
title_full_unstemmed | Synthetic Approaches
to a Key Pyridone-carboxylic
Acid Precursor Common to the HIV-1 Integrase Strand Transfer
Inhibitors Dolutegravir, Bictegravir, and Cabotegravir |
title_short | Synthetic Approaches
to a Key Pyridone-carboxylic
Acid Precursor Common to the HIV-1 Integrase Strand Transfer
Inhibitors Dolutegravir, Bictegravir, and Cabotegravir |
title_sort | synthetic approaches
to a key pyridone-carboxylic
acid precursor common to the hiv-1 integrase strand transfer
inhibitors dolutegravir, bictegravir, and cabotegravir |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10204085/ https://www.ncbi.nlm.nih.gov/pubmed/37229216 http://dx.doi.org/10.1021/acs.oprd.3c00063 |
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