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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...

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Autores principales: Mahajan, Pankaj S., Burke, Terrence R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2023
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.
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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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