Design, synthesis, and pharmacological evaluation of quinazoline derivatives as novel and potent pan-JAK inhibitors.
Bioorg Chem
; 140: 106765, 2023 11.
Article
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| MEDLINE
| ID: mdl-37582330
ABSTRACT
Janus kinases (JAKs) play a critical role in modulating the function and expression of inflammatory cytokines related to rheumatoid arthritis (RA). Herein, we report the design, synthesis, and structure-activity relationships (SARs) of a series of novel quinazoline derivatives as JAK inhibitors. Among these inhibitors, compound 11n showed high potency against JAKs (JAK1/JAK2/JAK3/TYK2, IC50 = 0.40, 0.83, 2.10, 1.95 nM), desirable metabolic characters, and excellent pharmacokinetic properties. In collagen-induced arthritis (CIA) models, compound 11n exhibited significant reduction in joint swelling with good safety, which could be served as a potential therapeutic candidate for the treatment of inflammatory diseases.
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Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Artritis Reumatoide
/
Inhibidores de las Cinasas Janus
Idioma:
En
Revista:
Bioorg Chem
Año:
2023
Tipo del documento:
Article