Discovery of phenoxyindazoles and phenylthioindazoles as RORγ inverse agonists.
Bioorg Med Chem Lett
; 26(23): 5802-5808, 2016 12 01.
Article
in En
| MEDLINE
| ID: mdl-27815118
ABSTRACT
Targeting the IL17 pathway and more specifically the nuclear receptor RORγ is thought to be beneficial in multiple skin disorders. The Letter describes the discovery of phenoxyindazoles and thiophenoxy indazoles as potent RORγ inverse agonists. Optimization of the potency and efforts to mitigate the phototoxic liability of the series are presented. Finally, crystallization of the lead compound revealed that the series bound to an allosteric site of the nuclear receptor. Such compounds could be useful as tool compounds for understanding the impact of topical treatment on skin disease models.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Nuclear Receptor Subfamily 1, Group F, Member 3
/
Indazoles
Limits:
Humans
Language:
En
Journal:
Bioorg Med Chem Lett
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2016
Type:
Article
Affiliation country:
France