Synthesis and Characterization of New V1A Antagonist Compounds: The Separation of Four Atropisomeric Stereoisomers

Autor:	Balázs Krámos, Zoltán Szakács, Imre Bata, Ferenc Baska, Csaba Szántay, Krisztina Temesvári, Krisztina Vukics, Éva Bozó, Zoltán Béni, Sándor Lévai, Katalin Domány-Kovács, Ildikó Magdó, Elemér Vass, Zsolt Szeleczky, István Greiner, János Kóti
Rok vydání:	2021
Předmět:	chemistry.chemical_compound Chemistry Stereochemistry Axial chirality In silico Drug Discovery Antagonist Diastereomer Molecular Medicine Enantiomer Ring (chemistry) Benzene Stereocenter
Zdroj:	Journal of Medicinal Chemistry. 64:10445-10468
ISSN:	1520-4804 0022-2623
Popis:	A new class of selective vasopressin receptor 1A (V1A) antagonists was identified, where "methyl-scan" was performed around the benzene ring of the 5-hydroxy-triazolobenzazepine core. This led to the synthesis of two 10-methyl derivatives, each possessing a chiral axis and a stereogenic center. The four atropisomeric stereoisomers (involving two enantiomer pairs and atropisomeric diastereomers) could be successfully isolated and spectroscopically characterized. According to the in vitro pharmacological profiles of the compounds, the human V1A receptor has a strong preference toward the isomers having an aR axial chirality, the most active isomer being the aR,5S isomer. Furthermore, the structure-activity relationships obtained for the isomers and for the newly synthesized analogues could be tentatively explained by an in silico study.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::a1131c30041ae03eeaa3142e7f9dce5a https://doi.org/10.1021/acs.jmedchem.1c00863 Zobrazit plný text záznamu