Tricyclic sulfones as potent, selective and efficacious RORγt inverse agonists - Exploring C6 and C8 SAR using late-stage functionalization.
Bioorg Med Chem Lett
; 30(23): 127521, 2020 12 01.
Article
em En
| MEDLINE
| ID: mdl-32882417
ABSTRACT
In order to rapidly develop C6 and C8 SAR of our reported tricyclic sulfone series of RORγt inverse agonists, a late-stage bromination was employed. Although not regioselective, the bromination protocol allowed us to explore new substitution patterns/vectors that otherwise would have to be incorporated at the very beginning of the synthesis. Based on the SAR obtained from this exercise, compound 15 bearing a C8 fluorine was developed as a very potent and selective RORγt inverse agonist. This analog's in vitro profile, pharmacokinetic (PK) data and efficacy in an IL-23 induced mouse acanthosis model will be discussed.
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Base de dados:
MEDLINE
Assunto principal:
Sulfonas
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Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares
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Compostos Heterocíclicos com 3 Anéis
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Melanose
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article