Synthesis and structure-activity relationships of heteroaryl substituted-3,4-diamino-3-cyclobut-3-ene-1,2-dione CXCR2/CXCR1 receptor antagonists.
Bioorg Med Chem Lett
; 18(4): 1318-22, 2008 Feb 15.
Article
em En
| MEDLINE
| ID: mdl-18242983
ABSTRACT
Comprehensive SAR studies were undertaken in the 3,4-diaminocyclobut-3-ene-1,2-dione class of CXCR2/CXCR1 receptor antagonists to explore the role of the heterocycle on chemokine receptor binding affinities, functional activity, as well as oral exposure in rat. The nature of the heterocycle as well as the requisite substitution pattern around the heterocycle was shown to have a dramatic effect on the overall biological profile of this class of compounds. The furyl class, particularly the 4-halo adducts, was found to possess superior binding affinities for both the CXCR2 and CXCR1 receptors, functional activity, as well as oral exposure in rat versus other heterocyclic derivatives.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ciclobutanos
/
Receptores de Interleucina-8A
/
Receptores de Interleucina-8B
/
Diaminas
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article