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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Bibliographic Details
Published in:Molecules (Basel, Switzerland) Switzerland), 2023-05, Vol.28 (9), p.3861
Main Authors: Ciceri, Samuele, Colombo, Diego, Fassi, Enrico M A, Ferraboschi, Patrizia, Grazioso, Giovanni, Grisenti, Paride, Iannone, Marco, Castellano, Carlo, Meneghetti, Fiorella
Format: Article
Language:English
Subjects:
Acids
atropisomerism
Cellulose
Conformational analysis
crystal structure
Crystallography
Drug approval
Drug development
Drug discovery
Endometriosis
Fatty Alcohols
Female
Fibroids
GnRHR antagonist
Gonadotropin-Releasing Hormone
Gonadotropins
Humans
Hydrocarbons, Fluorinated
Intermediates
Liquid chromatography
NMR
Nuclear magnetic resonance
Organic compounds
Palladium
Peptides
Pituitary (anterior)
Pituitary hormones
Pyrimidines
Salt
Sodium
Sodium Chloride
Sodium Chloride, Dietary
Sodium salts
Synthesis
uterine fibroids
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Summary: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 H, C, and 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.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules28093861