Analysis of structure-activity relationship of indol-3-yl-N-phenylcarbamic amides as potent STING inhibitors.
Bioorg Med Chem
; 95: 117502, 2023 11 15.
Article
em En
| MEDLINE
| ID: mdl-37866089
ABSTRACT
A structure-activity relationship (SAR) study of stimulator of interferon gene (STING) inhibition was performed using a series of indol-3-yl-N-phenylcarbamic amides and indol-2-yl-N-phenylcarbamic amides. Among these analogs, compounds 10, 13, 15, 19, and 21 inhibited the phosphorylation of STING and interferon regulatory factor 3 (IRF3) to a greater extent than the reference compound, H-151. All five analogs showed stronger STING inhibition than H-151 on the 2',3'-cyclic GMP-AMP-induced expression of interferon regulatory factors (IRFs) in a STINGR232 knock-in THP-1 reporter cell line. The half-maximal inhibitory concentration of the most potent compound, 21, was 11.5 nM. The molecular docking analysis of compound 21 and STING combined with the SAR study suggested that the meta- and para-positions of the benzene ring of the phenylcarbamic amide moiety could be structurally modified by introducing halides or alkyl substituents.
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1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Amidas
/
Nucleotidiltransferases
Idioma:
En
Revista:
Bioorg Med Chem
Ano de publicação:
2023
Tipo de documento:
Article