Potent Kv1.3 inhibitors from correolide-modification of the C18 position.
Bioorg Med Chem Lett
; 15(2): 447-51, 2005 Jan 17.
Article
en En
| MEDLINE
| ID: mdl-15603971
Kv1.3, the voltage-gated potassium channel in human T cells, represents a new target for treating immunosuppression and autoimmune diseases. Correolide (1), a pentacyclic natural product, is a potent and selective Kv1.3 channel blocker. Simplification of correolide via removal of its E-ring generates enone 4, whose modification produced a new series of tetracyclic Kv1.3 blockers. The structure-activity relationship for this class of compounds in two functional assays, Rb_Kv and human T cell proliferation, is presented herein. The most potent analog 43 is 15-fold more potent than correolide as inhibitor of human T cell proliferation.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Triterpenos
/
Activación del Canal Iónico
/
Canales de Potasio con Entrada de Voltaje
/
Bloqueadores de los Canales de Potasio
/
Proliferación Celular
Límite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2005
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Reino Unido