RESUMO
This review describes recent advances in the application of isocyanide-based multicomponent reactions (IMCRs) in drug discovery and summarizes the various chemotypes used to probe biological targets. In the past couple of years, IMCR-derived ligands have been used to develop agents against infectious diseases and to interfere with protein-protein interactions. Additionally, they were active against a variety of targets such as enzymes, GPCRs and ion channels. The rational for the chemical biologist to apply such diversity generating chemistries is also discussed.
Assuntos
Cianetos/química , Cianetos/farmacologia , Avaliação Pré-Clínica de Medicamentos/métodos , Animais , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Humanos , Ligação Proteica/efeitos dos fármacosRESUMO
We report the synthesis of kinase targeted libraries based on the thienopyrazole scaffold. Several thienopyrazole analogs have been identified as submicromolar inhibitors of KDR.
Assuntos
Química Farmacêutica/métodos , Desenho de Fármacos , Inibidores Enzimáticos/farmacologia , Fosfotransferases/química , Pirazóis/química , Pirazóis/síntese química , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/química , Avaliação Pré-Clínica de Medicamentos , Inibidores Enzimáticos/química , Humanos , Concentração Inibidora 50 , Modelos QuímicosRESUMO
We report the discovery of a novel class of glucocorticoid receptor (GR) antagonists based on the chromene molecular scaffold. The compounds exhibit good functional potency and an improved receptor selectivity profile for GR over other steroid receptors when compared to the classical steroidal GR-antagonist, RU-486.