Synthesis and bioactivity of 3,5-dimethylpyrazole derivatives as potential PDE4 inhibitors.
Bioorg Med Chem Lett
; 28(19): 3276-3280, 2018 10 15.
Article
em En
| MEDLINE
| ID: mdl-30131240
ABSTRACT
A series of 3,5-dimethylpyrazole derivatives containing 5-phenyl-2-furan moiety were designed and synthesized as phosphodiesterase type 4 (PDE4) inhibitors. Bioassay results showed that the title compounds exhibited considerable inhibitory activity against PDE4B and blockade of LPS-induced TNFα release. Among the designed compounds, compound If showed the best inhibitory activity against PDE4B with the IC50 value of 1.7⯵M, which also showed good in vivo activity in animal models of asthma/COPD and sepsis induced by LPS. The primary structure-activity relationship (SAR) study and docking results suggested that introduction of the substituent groups to the phenyl ring at the para-position, especially methoxy group, was helpful to enhance inhibitory activity against PDE4B.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pirazóis
/
Inibidores da Fosfodiesterase 4
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
China