Design, synthesis, and biological evaluation of semicarbazide-sensitive amine oxidase (SSAO) inhibitors with anti-inflammatory activity.
J Med Chem
; 49(7): 2166-73, 2006 Apr 06.
Article
en En
| MEDLINE
| ID: mdl-16570912
ABSTRACT
In an attempt to examine the effect of inhibition of semicarbazide-sensitive amine oxidase (SSAO; EC 1.4.3.6, also known as VAP-1) as a novel anti-inflammatory target, the structure/mechanism based design and synthesis of a series of novel hydrazino-containing small molecules are described. The in vitro biological results show that compounds 4a,c are highly potent SSAO inhibitors with notable selectivity toward SSAO over monoamine oxidases A and B (MAO-A and MAO-B). SAR studies based on compound 4c were performed, and the results are discussed. The most potent and selective compound, 4a (IC(50) = 2 nM), is an orally active, competitive, and apparently irreversible inhibitor of SSAO that is effective at reducing disease incidence and severity in an in vivo animal disease model of multiple sclerosis.
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Bases de datos:
MEDLINE
Asunto principal:
Antiinflamatorios no Esteroideos
/
Amina Oxidasa (conteniendo Cobre)
/
Hidrazinas
Tipo de estudio:
Diagnostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Med Chem
Asunto de la revista:
QUIMICA
Año:
2006
Tipo del documento:
Article
País de afiliación:
Estados Unidos