New aromatic substituted pyrazoles as selective inhibitors of human adipocyte fatty acid-binding protein.
Bioorg Med Chem Lett
; 21(10): 2949-52, 2011 May 15.
Article
em En
| MEDLINE
| ID: mdl-21481589
ABSTRACT
a-FABP is indespensible in inflammation and may serve as a new potential drug target for inflammation related diseases. We have successfully designed and synthesized a series of aromatic substituted pyrazoles as new human a-FABP inhibitors. The compounds strongly bound to the hydrophobic binding pocket of a-FABP, while showed significantly lower binding affinities to the closely related homologue protein h-FABP. The most potent and selective compound 5 g bound to a-FABP with an apparent K(i) value below 1.0 nM, while did not inhibit h-FABP at 50 µM and thus represents one of the most potent and selective a-FABP inhibitors to date. The strong binding capacity of these inhibitors was further validated by their effective blockade of inflammatory responses as determined by the production of pro-inflammatory cytokines upon LPS stimulation. Compound 5 g may serve as a lead compound for developing new effective therapeutic agent for prevention and treatment of atherosclerosis, type 2 diabetes and other inflammatory and metabolic related diseases.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pirazóis
/
Adipócitos
/
Proteínas de Ligação a Ácido Graxo
/
Anti-Inflamatórios
Limite:
Humans
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article