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

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2023 May 13

PMID 37175271

Authors

Samuele Ciceri

Diego Colombo

Enrico M A Fassi

Patrizia Ferraboschi

Giovanni Grazioso

Paride Grisenti

Marco Iannone

Carlo Castellano

Fiorella Meneghetti

Affiliations

Soon will be listed here.

Abstract

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.

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