Design and Synthesis of Conformationally Constrained RORγt Inverse Agonists.
RORγ
conformationally constrained scaffolds
interleukin 17
inverse agonists
u-shaped
Journal
ChemMedChem
ISSN: 1860-7187
Titre abrégé: ChemMedChem
Pays: Germany
ID NLM: 101259013
Informations de publication
Date de publication:
20 11 2019
20 11 2019
Historique:
received:
12
07
2019
revised:
04
10
2019
pubmed:
30
10
2019
medline:
23
9
2020
entrez:
30
10
2019
Statut:
ppublish
Résumé
Retinoic-acid-related orphan receptor γt (RORγt) inverse agonists could be used for the treatment of autoimmune diseases. Previously, we reported a novel quinazolinedione 1 a with a flexible linear linker as a novel RORγt inverse agonist. A U-shaped conformation in the complex structure of 1 a with RORγt protein was confirmed. Further improvement of the pharmacokinetic (PK) profiles was required because of the low drug exposure in mice upon oral administration (mouse AUC of 1 a: 27 ng ⋅ h ⋅ mL
Identifiants
pubmed: 31659845
doi: 10.1002/cmdc.201900416
doi:
Substances chimiques
Cyclopentanes
0
Furans
0
Nuclear Receptor Subfamily 1, Group F, Member 3
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1917-1932Informations de copyright
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
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