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The development of an effective synthetic route of rilpivirine
BACKGROUND: Rilpivirine (RPV) was approved by the U.S. FDA (Food and Drug Administration) in 2011 to treat individuals infected with human immunodeficiency virus 1 (HIV-1). Significantly, rilpivirine is three fold more potent than etravirine. Once-daily, it is used with a low oral dose (25 mg/tablet...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017658/ https://www.ncbi.nlm.nih.gov/pubmed/33810807 http://dx.doi.org/10.1186/s13065-021-00749-y |
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author | Zhang, Tao Yang, Jiapei Zhou, Zhongxia Fu, Zhipeng Cherukupalli, Srinivasulu Kang, Dongwei Zhan, Peng Liu, Xinyong |
author_facet | Zhang, Tao Yang, Jiapei Zhou, Zhongxia Fu, Zhipeng Cherukupalli, Srinivasulu Kang, Dongwei Zhan, Peng Liu, Xinyong |
author_sort | Zhang, Tao |
collection | PubMed |
description | BACKGROUND: Rilpivirine (RPV) was approved by the U.S. FDA (Food and Drug Administration) in 2011 to treat individuals infected with human immunodeficiency virus 1 (HIV-1). Significantly, rilpivirine is three fold more potent than etravirine. Once-daily, it is used with a low oral dose (25 mg/tablet), decreasing the drug administration and bringing a better choice to the patients. However, there are many shortcomings in the existing synthesis route of RPV, such as the high cost, prolonged reaction time and low yield (18.5%). RESULTS: This article describes our efforts to develop an efficient and practical microwave-promoted method to synthesize rilpivirine using less toxic organic reagents and low boiling solvents. The last step's reaction time decreased from 69 h to 90 min through this optimized synthetic procedure, and the overall yield improved from 18.5 to 21%. In addition, the yield of intermediate 3 increased from 52 to 62% compared to the original patent. CONCLUSION: Overall, through a series of process optimization, we have developed a practical synthesis method of rilpivirine, which is easy to scale with higher yield and shorter reaction time. |
format | Online Article Text |
id | pubmed-8017658 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-80176582021-04-02 The development of an effective synthetic route of rilpivirine Zhang, Tao Yang, Jiapei Zhou, Zhongxia Fu, Zhipeng Cherukupalli, Srinivasulu Kang, Dongwei Zhan, Peng Liu, Xinyong BMC Chem Research Article BACKGROUND: Rilpivirine (RPV) was approved by the U.S. FDA (Food and Drug Administration) in 2011 to treat individuals infected with human immunodeficiency virus 1 (HIV-1). Significantly, rilpivirine is three fold more potent than etravirine. Once-daily, it is used with a low oral dose (25 mg/tablet), decreasing the drug administration and bringing a better choice to the patients. However, there are many shortcomings in the existing synthesis route of RPV, such as the high cost, prolonged reaction time and low yield (18.5%). RESULTS: This article describes our efforts to develop an efficient and practical microwave-promoted method to synthesize rilpivirine using less toxic organic reagents and low boiling solvents. The last step's reaction time decreased from 69 h to 90 min through this optimized synthetic procedure, and the overall yield improved from 18.5 to 21%. In addition, the yield of intermediate 3 increased from 52 to 62% compared to the original patent. CONCLUSION: Overall, through a series of process optimization, we have developed a practical synthesis method of rilpivirine, which is easy to scale with higher yield and shorter reaction time. Springer International Publishing 2021-04-01 /pmc/articles/PMC8017658/ /pubmed/33810807 http://dx.doi.org/10.1186/s13065-021-00749-y Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Article Zhang, Tao Yang, Jiapei Zhou, Zhongxia Fu, Zhipeng Cherukupalli, Srinivasulu Kang, Dongwei Zhan, Peng Liu, Xinyong The development of an effective synthetic route of rilpivirine |
title | The development of an effective synthetic route of rilpivirine |
title_full | The development of an effective synthetic route of rilpivirine |
title_fullStr | The development of an effective synthetic route of rilpivirine |
title_full_unstemmed | The development of an effective synthetic route of rilpivirine |
title_short | The development of an effective synthetic route of rilpivirine |
title_sort | development of an effective synthetic route of rilpivirine |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017658/ https://www.ncbi.nlm.nih.gov/pubmed/33810807 http://dx.doi.org/10.1186/s13065-021-00749-y |
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