RESUMO
We describe a novel series of imidazopyridine substituted phenylalanines which are potent VLA-4 antagonists. A wide variety of substituents are tolerated as replacements for the pendant 3-pyridyl ring. A clear structure-activity relationship was identified around the substitution of the 3-amino-cyclobut-2-enone portion of the molecule.
Assuntos
Química Farmacêutica/métodos , Integrina alfa4beta1/antagonistas & inibidores , Fenilalanina/química , Piridinas/química , Animais , Desenho de Fármacos , Humanos , Concentração Inibidora 50 , Integrina alfa4beta1/sangue , Camundongos , Modelos Químicos , Conformação Molecular , Ligação Proteica , Ratos , Relação Estrutura-AtividadeRESUMO
A series of bicyclic heteroaryl ring systems was considered as a replacement for the 3-cyclopentyloxy-4-methoxyphenyl moiety in rolipram resulting in the discovery of 8-methoxyquinoline-5-carboxamides as potent inhibitors of phosphodiesterase type 4 (PDE4).
Assuntos
3',5'-AMP Cíclico Fosfodiesterases/antagonistas & inibidores , Amidas/uso terapêutico , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Inibidores de Fosfodiesterase/uso terapêutico , Amidas/farmacologia , Antiasmáticos/farmacologia , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4 , Humanos , Inibidores de Fosfodiesterase/farmacologiaRESUMO
The synthesis and pharmacological profile of a novel series of 7-methoxy-furo[2,3-c]pyridine-4-carboxamides is described. Some of these compounds were found to be potent inhibitors of phosphodiesterase type 4 (PDE4).