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Elagolix Sodium Salt and Its Synthetic Intermediates: A Spectroscopic, Crystallographic, and Conformational Study

Elagolix sodium salt is the first marketed orally active non-peptide gonadotropin-releasing hormone receptor antagonist (GnRHR-ant) for the management of hormone dependent diseases, such as endometriosis and uterine fibroids. Despite its presence on the market since 2018, a thorough NMR analysis of...

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Autores principales: Ciceri, Samuele, Colombo, Diego, Fassi, Enrico M. A., Ferraboschi, Patrizia, Grazioso, Giovanni, Grisenti, Paride, Iannone, Marco, Castellano, Carlo, Meneghetti, Fiorella
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10180344/
https://www.ncbi.nlm.nih.gov/pubmed/37175271
http://dx.doi.org/10.3390/molecules28093861
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author Ciceri, Samuele
Colombo, Diego
Fassi, Enrico M. A.
Ferraboschi, Patrizia
Grazioso, Giovanni
Grisenti, Paride
Iannone, Marco
Castellano, Carlo
Meneghetti, Fiorella
author_facet Ciceri, Samuele
Colombo, Diego
Fassi, Enrico M. A.
Ferraboschi, Patrizia
Grazioso, Giovanni
Grisenti, Paride
Iannone, Marco
Castellano, Carlo
Meneghetti, Fiorella
author_sort Ciceri, Samuele
collection PubMed
description Elagolix sodium salt is the first marketed orally active non-peptide gonadotropin-releasing hormone receptor antagonist (GnRHR-ant) for the management of hormone dependent diseases, such as endometriosis and uterine fibroids. Despite its presence on the market since 2018, a thorough NMR analysis of this drug, together with its synthetic intermediates, is still lacking. Hence, with the aim of filling this literature gap, we here performed a detailed NMR investigation, which allowed the complete assignment of the (1)H, (13)C, and (15)N NMR signals. These data allowed, with the support of the conformational analysis, the determination of the stereochemical profile of the two atropisomers, detectable in solution. Moreover, these latter were also detected by means of cellulose-based chiral HPLC, starting from a sample prepared through an implemented synthetic procedure with respect to the reported ones. Overall, these results contribute to further understanding of the topic of atropisomerism in drug discovery and could be applied in the design of safe and stable analogs, endowed with improved target selectivity.
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spelling pubmed-101803442023-05-13 Elagolix Sodium Salt and Its Synthetic Intermediates: A Spectroscopic, Crystallographic, and Conformational Study Ciceri, Samuele Colombo, Diego Fassi, Enrico M. A. Ferraboschi, Patrizia Grazioso, Giovanni Grisenti, Paride Iannone, Marco Castellano, Carlo Meneghetti, Fiorella Molecules Article Elagolix sodium salt is the first marketed orally active non-peptide gonadotropin-releasing hormone receptor antagonist (GnRHR-ant) for the management of hormone dependent diseases, such as endometriosis and uterine fibroids. Despite its presence on the market since 2018, a thorough NMR analysis of this drug, together with its synthetic intermediates, is still lacking. Hence, with the aim of filling this literature gap, we here performed a detailed NMR investigation, which allowed the complete assignment of the (1)H, (13)C, and (15)N NMR signals. These data allowed, with the support of the conformational analysis, the determination of the stereochemical profile of the two atropisomers, detectable in solution. Moreover, these latter were also detected by means of cellulose-based chiral HPLC, starting from a sample prepared through an implemented synthetic procedure with respect to the reported ones. Overall, these results contribute to further understanding of the topic of atropisomerism in drug discovery and could be applied in the design of safe and stable analogs, endowed with improved target selectivity. MDPI 2023-05-03 /pmc/articles/PMC10180344/ /pubmed/37175271 http://dx.doi.org/10.3390/molecules28093861 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ciceri, Samuele
Colombo, Diego
Fassi, Enrico M. A.
Ferraboschi, Patrizia
Grazioso, Giovanni
Grisenti, Paride
Iannone, Marco
Castellano, Carlo
Meneghetti, Fiorella
Elagolix Sodium Salt and Its Synthetic Intermediates: A Spectroscopic, Crystallographic, and Conformational Study
title Elagolix Sodium Salt and Its Synthetic Intermediates: A Spectroscopic, Crystallographic, and Conformational Study
title_full Elagolix Sodium Salt and Its Synthetic Intermediates: A Spectroscopic, Crystallographic, and Conformational Study
title_fullStr Elagolix Sodium Salt and Its Synthetic Intermediates: A Spectroscopic, Crystallographic, and Conformational Study
title_full_unstemmed Elagolix Sodium Salt and Its Synthetic Intermediates: A Spectroscopic, Crystallographic, and Conformational Study
title_short Elagolix Sodium Salt and Its Synthetic Intermediates: A Spectroscopic, Crystallographic, and Conformational Study
title_sort elagolix sodium salt and its synthetic intermediates: a spectroscopic, crystallographic, and conformational study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10180344/
https://www.ncbi.nlm.nih.gov/pubmed/37175271
http://dx.doi.org/10.3390/molecules28093861
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