Part 3: Design and synthesis of proline-derived α2δ ligands

Abstract A potent series of substituted (2 S ,4 S )-benzylproline α 2 δ ligands have been designed from the readily available starting material (2 S ,4 R )-hydroxy- l -proline. The ligands have improved pharmacokinetic profile over the (4 S )-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.