A novel class of potent nonglycosidic and nonpeptidic pan-selectin inhibitors.
J Med Chem
; 49(20): 5988-99, 2006 Oct 05.
Article
em En
| MEDLINE
| ID: mdl-17004713
ABSTRACT
An early step of the inflammatory response, the rolling of leukocytes on activated endothelial cells, is mediated by selectin/carbohydrate interactions. The tetrasaccharide sialy Lewisx is a ligand for E-, P-, and L-selectin and therefore serves as a lead structure for the development of analogues. A combination of synthesis and structure-based design allowed rapid optimization. The current lead 2a was evaluated in our E-selectin cell flow chamber assay where it proved to inhibit rolling and adhesion with an IC50 of 28+/-7 microM. The assays used are predictive for the in vivo efficacy of test compounds as shown for 2a in a proteose peptone induced peritonitis model of acute inflammation in mice.
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Base de dados:
MEDLINE
Assunto principal:
Anti-Inflamatórios não Esteroides
/
Selectinas
/
Para-Aminobenzoatos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article