| Autor: |
Szeleczky, Zsolt, Szakács, Zoltán, Bozó, Éva, Baska, Ferenc, Vukics, Krisztina, Lévai, Sándor, Temesvári, Krisztina, Vass, Elemér, Béni, Zoltán, Krámos, Balázs, Magdó, Ildikó, Szántay, Csaba, Kóti, János, Domány-Kovács, Katalin, Greiner, István, Bata, Imre |
| Zdroj: |
Journal of Medicinal Chemistry; July 2021, Vol. 64 Issue: 14 p10445-10468, 24p |
| Abstrakt: |
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 vitropharmacological profiles of the compounds, the human V1Areceptor has a strong preference toward the isomers having an aRaxial chirality, the most active isomer being the aR,5Sisomer. Furthermore, the structure–activity relationships obtained for the isomers and for the newly synthesized analogues could be tentatively explained by an in silicostudy. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
|
