title: Part 3: Design and synthesis of proline-derived α2δ ligands.
abstract: 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.
authors.affiliation: Sandwich Laboratories, Pfizer Global Research and Development, Sandwich, Kent, UK. david.rawson@pfizer.com
authors.forename: David J
authors.initials: DJ
authors.lastname: Rawson
authors.forename: Delphine
authors.initials: D
authors.lastname: Brugier
authors.forename: Anthony
authors.initials: A
authors.lastname: Harrison
authors.forename: Jo
authors.initials: J
authors.lastname: Hough
authors.forename: Julie
authors.initials: J
authors.lastname: Newman
authors.forename: Joe
authors.initials: J
authors.lastname: Otterburn
authors.forename: Graham N
authors.initials: GN
authors.lastname: Maw
authors.forename: Jenny
authors.initials: J
authors.lastname: Price
authors.forename: Lisa R
authors.initials: LR
authors.lastname: Thompson
authors.forename: Paul
authors.initials: P
authors.lastname: Turnpenny
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Warren
mesh_terms: D000818:Animals; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D008024:Ligands; D015394:Molecular Structure; D010146:Pain; D011392:Proline / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D013552:Swine
chemical_list: D008024:Ligands; D011392:Proline