title: Potent oxadiazole CGRP receptor antagonists for the potential treatment of migraine.
abstract: A pharmacophore model was built, based on known CGRP receptor antagonists, and this was used to aid the identification of novel leads. Analogues were designed, modelled and synthesised which incorporated alternative 'LHS' fragments linked via either an amide or urea to a privileged 'RHS' fragment commonly found in CGRP receptor antagonists. As a result a novel series of oxadiazole CGRP receptor antagonists has been identified and the subsequent optimisation to enhance both potency and bioavailability is presented.
authors.affiliation: Department of Medicinal Chemistry, Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK. paula.l.nichols@gsk.com
authors.forename: Paula L
authors.initials: PL
authors.lastname: Nichols
authors.forename: Jonathan
authors.initials: J
authors.lastname: Brand
authors.forename: Michael
authors.initials: M
authors.lastname: Briggs
authors.forename: Mathilde
authors.initials: M
authors.lastname: D'Angeli
authors.forename: Jennifer
authors.initials: J
authors.lastname: Farge
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Garland
authors.forename: Paul
authors.initials: P
authors.lastname: Goldsmith
authors.forename: Rio
authors.initials: R
authors.lastname: Hutchings
authors.forename: Ian
authors.initials: I
authors.lastname: Kilford
authors.forename: Ho Y
authors.initials: HY
authors.lastname: Li
authors.forename: David
authors.initials: D
authors.lastname: MacPherson
authors.forename: Fiona
authors.initials: F
authors.lastname: Nimmo
authors.forename: Francis Dominic
authors.initials: FD
authors.lastname: Sanderson
authors.forename: Sanjeet
authors.initials: S
authors.lastname: Sehmi
authors.forename: Nicola
authors.initials: N
authors.lastname: Shuker
authors.forename: John
authors.initials: J
authors.lastname: Skidmore
authors.forename: Michael
authors.initials: M
authors.lastname: Stott
authors.forename: Jennifer
authors.initials: J
authors.lastname: Sweeting
authors.forename: Hasmi
authors.initials: H
authors.lastname: Tajuddin
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Takle
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Trani
authors.forename: Ian D
authors.initials: ID
authors.lastname: Wall
authors.forename: Robert
authors.initials: R
authors.lastname: Ward
authors.forename: David M
authors.initials: DM
authors.lastname: Wilson
authors.forename: David
authors.initials: D
authors.lastname: Witty
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D015195:Drug Design; D008881:Migraine Disorders / Q000188:drug therapy*; D008958:Models, Molecular; D015394:Molecular Structure; D010069:Oxadiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use*; D051381:Rats
chemical_list: D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D010069:Oxadiazoles