Synthesis and pharmacological evaluation of novel phenyl sulfonamide derivatives designed as modulators of pulmonary inflammatory response.
Molecules
; 17(12): 14651-72, 2012 Dec 10.
Article
em En
| MEDLINE
| ID: mdl-23222927
ABSTRACT
In this paper we report the design, synthesis and pharmacological evaluation of a new series of phenyl sulfonamide derivatives 2a-h and 3-8 planned by structural modification on the anti-inflammatory prototype LASSBio-468 (1). Among the synthesized analogues, the tetrafluorophthalimide LASSBio-1439 (2e) stands out showing an in vitro anti-TNF-α effect similar to the standard thalidomide. The relevance of tetrafluorination of the phthalimide nucleus was also confirmed by the anti-inflammatory profile of 2e, through oral administration, in a murine model of pulmonary inflammation. The corresponding tetrafluorocarboxyamide metabolite LASSBio-1454 (15), generated from partial hydrolysis of the derivative 2e, presented a significant in vitro effect and a pronounced anti-inflammatory activity in vivo.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ftalimidas
/
Pneumonia
/
Sulfonamidas
/
Fator de Necrose Tumoral alfa
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Molecules
Assunto da revista:
BIOLOGIA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Brasil