RESUMO
A potent series of substituted (2S,4S)-benzylproline α(2)δ ligands have been designed from the readily available starting material (2S,4R)-hydroxy-L-proline. The ligands have improved pharmacokinetic profile over the (4S)-phenoxyproline derivatives described previously and have potential for development as oral agents for the treatment of neuropathic pain. Compound 16 has been progressed to clinical development.
Assuntos
Desenho de Fármacos , Prolina/química , Prolina/síntese química , Animais , Humanos , Concentração Inibidora 50 , Ligantes , Estrutura Molecular , Dor , Prolina/farmacologia , Ratos , SuínosRESUMO
Conformational constraint has been used to design a potent series of α(2)δ ligands derived from the readily available starting material (2S,4R)-hydroxy-l-proline. The ligands have improved physicochemistry and potency compared to their linear counterparts (described in our earlier publication) and the lead compound has been progressed to clinical development.