RESUMO
A series of phthalimide acid derivatives was synthesized and evaluated as leukotriene D(4) receptor antagonists. The tetrazolephthalimide LASSBio 552 (7) was shown to be able to inhibit the contractile activity induced by 100 nM of LTD(4) in guinea-pig tracheal strips with an IC(50) = 31.2 microM. In addition, LASSBio 552 (7) has been showed to present a better efficacy than zafirlukast (1) used as standard.
Assuntos
Antiasmáticos/síntese química , Antiasmáticos/farmacologia , Antagonistas de Leucotrienos , Proteínas de Membrana , Ftalimidas/síntese química , Ftalimidas/farmacologia , Animais , Antiasmáticos/química , Desenho de Fármacos , Cobaias , Técnicas In Vitro , Indóis , Modelos Moleculares , Conformação Molecular , Contração Muscular/efeitos dos fármacos , Fenilcarbamatos , Ftalimidas/química , Receptores de Leucotrienos/química , Sulfonamidas , Tetrazóis/química , Compostos de Tosil/farmacologia , Traqueia/efeitos dos fármacos , Traqueia/fisiologiaRESUMO
A series of pyrazolo[3,4-b]thieno[2,3-d]pyridine alkanoic acid derivatives has been synthesized and evaluated as thromboxane synthetase inhibitors and leukotriene D(4) receptor antagonists. The glutaric acid derivative LASSBio341 (6) was shown to be active in arachidonic acid-induced platelet aggregation (IC(50)=0.14 microM) and inhibition of the contraction of guinea pig tracheal strip induced with LTD(4) (IC(50) = 43.7 microM), displaying still in vivo anti-inflammatory profile.