title: Part 2: Design, synthesis and evaluation of hydroxyproline-derived α2δ ligands.
abstract: 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.
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: D000588:Amines / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D002478:Cells, Cultured; D003509:Cyclohexanecarboxylic Acids / Q000737:chemistry / Q000493:pharmacokinetics; D004285:Dogs; D015195:Drug Design; D000077206:Gabapentin; D006801:Humans; D006909:Hydroxyproline / Q000138:chemical synthesis* / Q000737:chemistry; D008024:Ligands; D015394:Molecular Structure; D021122:Protein Subunits / Q000737:chemistry; D051381:Rats; D005680:gamma-Aminobutyric Acid / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D000588:Amines; D003509:Cyclohexanecarboxylic Acids; D008024:Ligands; D021122:Protein Subunits; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D006909:Hydroxyproline