RESUMO
Selective inhibitors of protein tyrosine phosphatases (PTPases) are of great interest as therapeutic agents and research tools. Several phenylalanine derivatives (1, 2) designed as phosphotyrosine mimetics or irreversible active site inhibitors were successfully synthesized, then incorporated into a combinatorial library based on a peptidomimetic beta-strand template.
Assuntos
Fosfotirosina/análogos & derivados , Fosfotirosina/síntese química , Materiais Biomiméticos/síntese química , Técnicas de Química Combinatória/métodos , Desenho de Fármacos , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Biblioteca de Peptídeos , Fenilalanina/análogos & derivados , Fenilalanina/farmacologia , Estrutura Secundária de Proteína , Proteínas Tirosina Fosfatases/antagonistas & inibidores , Relação Estrutura-AtividadeRESUMO
A novel alpha-addition of propiolates to urazoles followed by Michael addition of a variety of nucleophiles has been developed for rapid production and optimization of peptidomimetic drug leads. This technology has produced a number of highly potent and selective inhibitors of the serine protease, thrombin.
Assuntos
Trombina/antagonistas & inibidores , Triazóis/síntese química , Alcinos/química , Técnicas de Química Combinatória , Mimetismo Molecular , Propionatos/química , Inibidores de Serina Proteinase/síntese química , Inibidores de Serina Proteinase/farmacologia , Relação Estrutura-Atividade , Triazóis/químicaRESUMO
The discovery of a sulphonamide by-product with VLA-4 antagonistic activity led to a series of potent, small molecule VLA-4 antagonists. Synthesis, SAR and in vivo evaluation of the selected compound will be presented.