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Atropisomeric Racemization Kinetics of MRTX1719 Using Chiral Solvating Agent-Assisted (19)F NMR Spectroscopy
[Image: see text] With renewed interest in atropisomerism of drug molecules, efficient methods to experimentally determine torsion rotational energy barriers are needed. Here, we describe use of the chiral phosphoric acid solvating agent (+)-TiPSY to resolve the signals of atropisomers in (19)F NMR...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9476184/ https://www.ncbi.nlm.nih.gov/pubmed/36120049 http://dx.doi.org/10.1021/acsomega.2c03316 |
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author | Kulyk, Svitlana De Paul, Susan M. Marx, Matthew A. Peakman, Torren M. Smith, Christopher R. |
author_facet | Kulyk, Svitlana De Paul, Susan M. Marx, Matthew A. Peakman, Torren M. Smith, Christopher R. |
author_sort | Kulyk, Svitlana |
collection | PubMed |
description | [Image: see text] With renewed interest in atropisomerism of drug molecules, efficient methods to experimentally determine torsion rotational energy barriers are needed. Here, we describe use of the chiral phosphoric acid solvating agent (+)-TiPSY to resolve the signals of atropisomers in (19)F NMR and to use the data to study the kinetics of racemization and determine the rotational energy barrier of clinical compound MRTX1719. This method is complimentary to traditional chiral high-performance liquid chromatography (HPLC) and enhances the toolkit for chiral analysis techniques. |
format | Online Article Text |
id | pubmed-9476184 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-94761842022-09-16 Atropisomeric Racemization Kinetics of MRTX1719 Using Chiral Solvating Agent-Assisted (19)F NMR Spectroscopy Kulyk, Svitlana De Paul, Susan M. Marx, Matthew A. Peakman, Torren M. Smith, Christopher R. ACS Omega [Image: see text] With renewed interest in atropisomerism of drug molecules, efficient methods to experimentally determine torsion rotational energy barriers are needed. Here, we describe use of the chiral phosphoric acid solvating agent (+)-TiPSY to resolve the signals of atropisomers in (19)F NMR and to use the data to study the kinetics of racemization and determine the rotational energy barrier of clinical compound MRTX1719. This method is complimentary to traditional chiral high-performance liquid chromatography (HPLC) and enhances the toolkit for chiral analysis techniques. American Chemical Society 2022-08-31 /pmc/articles/PMC9476184/ /pubmed/36120049 http://dx.doi.org/10.1021/acsomega.2c03316 Text en © 2022 The Authors. Published 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 | Kulyk, Svitlana De Paul, Susan M. Marx, Matthew A. Peakman, Torren M. Smith, Christopher R. Atropisomeric Racemization Kinetics of MRTX1719 Using Chiral Solvating Agent-Assisted (19)F NMR Spectroscopy |
title | Atropisomeric Racemization
Kinetics of MRTX1719 Using
Chiral Solvating Agent-Assisted (19)F NMR Spectroscopy |
title_full | Atropisomeric Racemization
Kinetics of MRTX1719 Using
Chiral Solvating Agent-Assisted (19)F NMR Spectroscopy |
title_fullStr | Atropisomeric Racemization
Kinetics of MRTX1719 Using
Chiral Solvating Agent-Assisted (19)F NMR Spectroscopy |
title_full_unstemmed | Atropisomeric Racemization
Kinetics of MRTX1719 Using
Chiral Solvating Agent-Assisted (19)F NMR Spectroscopy |
title_short | Atropisomeric Racemization
Kinetics of MRTX1719 Using
Chiral Solvating Agent-Assisted (19)F NMR Spectroscopy |
title_sort | atropisomeric racemization
kinetics of mrtx1719 using
chiral solvating agent-assisted (19)f nmr spectroscopy |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9476184/ https://www.ncbi.nlm.nih.gov/pubmed/36120049 http://dx.doi.org/10.1021/acsomega.2c03316 |
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