2-Substituted quinazolines: Partial agonistic and antagonistic ligands of the constitutive androstane receptor (CAR).
CAR
Gene activation
Metabolism
Nuclear receptors
Quinazolines
Xenobiotics
Journal
European journal of medicinal chemistry
ISSN: 1768-3254
Titre abrégé: Eur J Med Chem
Pays: France
ID NLM: 0420510
Informations de publication
Date de publication:
05 Nov 2023
05 Nov 2023
Historique:
received:
18
05
2023
revised:
05
07
2023
accepted:
07
07
2023
medline:
22
8
2023
pubmed:
21
7
2023
entrez:
20
7
2023
Statut:
ppublish
Résumé
Following the discovery of 2-(3-methoxyphenyl)-3,4-dihydroquinazoline-4-one and 2-(3-methoxyphenyl)quinazoline-4-thione as potent, but non-specific activators of the human Constitutive Androstane Receptor (CAR, NR1I3), a series of quinazolinones substituted at the C2 phenyl ring was prepared to examine their ability to selectively modulate human CAR activity. Employing cellular and in vitro TR-FRET assays with wild-type CAR or its variant 3 (CAR3) ligand binding domains (LBD), several novel partial human CAR agonists and antagonists were identified. 2-(3-Methylphenyl) quinazolinone derivatives 7d and 8d acted as partial agonists with the recombinant CAR LBD, the former in nanomolar units (EC
Identifiants
pubmed: 37473690
pii: S0223-5234(23)00597-4
doi: 10.1016/j.ejmech.2023.115631
pii:
doi:
Substances chimiques
Constitutive Androstane Receptor
0
Receptors, Cytoplasmic and Nuclear
0
Ligands
0
Quinazolines
0
Thiones
0
Receptors, Steroid
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
115631Informations de copyright
Copyright © 2023 Elsevier Masson SAS. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Petr Pavek reports financial support was provided by Czech Science Foundation. Milan Pour reports financial support was provided by Charles University. Petr Pavek reports financial support was provided by Charles University. Petr Pavek reports financial support was provided by Ministry of Education Youth and Sports of the Czech Republic.