title: The discovery of biaryl carboxamides as novel small molecule agonists of the motilin receptor.
abstract: Optimisation of urea (5), identified from high throughput screening and subsequent array chemistry, has resulted in the identification of pyridine carboxamide (33) which is a potent motilin receptor agonist possessing favourable physicochemical and ADME profiles. Compound (33) has demonstrated prokinetic-like activity both in vitro and in vivo in the rabbit and therefore represents a promising novel small molecule motilin receptor agonist for further evaluation as a gastroprokinetic agent.
authors.affiliation: Immuno-Inflammation Centre of Excellence for Drug Discovery, GlaxoSmithKline, Medicines Research Centre, Gunnels Wood Road, Stevenage, Herts SG1 2NY, UK. sue.m.westaway@gsk.com
authors.forename: Susan M
authors.initials: SM
authors.lastname: Westaway
authors.forename: Samantha L
authors.initials: SL
authors.lastname: Brown
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Conway
authors.forename: Tom D
authors.initials: TD
authors.lastname: Heightman
authors.forename: Christopher N
authors.initials: CN
authors.lastname: Johnson
authors.forename: Kate
authors.initials: K
authors.lastname: Lapsley
authors.forename: Gregor J
authors.initials: GJ
authors.lastname: Macdonald
authors.forename: David T
authors.initials: DT
authors.lastname: MacPherson
authors.forename: Darren J
authors.initials: DJ
authors.lastname: Mitchell
authors.forename: James W
authors.initials: JW
authors.lastname: Myatt
authors.forename: Jon T
authors.initials: JT
authors.lastname: Seal
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Stanway
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Stemp
authors.forename: Mervyn
authors.initials: M
authors.lastname: Thompson
authors.forename: Paolo
authors.initials: P
authors.lastname: Celestini
authors.forename: Andrea
authors.initials: A
authors.lastname: Colombo
authors.forename: Alessandra
authors.initials: A
authors.lastname: Consonni
authors.forename: Stefania
authors.initials: S
authors.lastname: Gagliardi
authors.forename: Mauro
authors.initials: M
authors.lastname: Riccaboni
authors.forename: Silvano
authors.initials: S
authors.lastname: Ronzoni
authors.forename: Michael A
authors.initials: MA
authors.lastname: Briggs
authors.forename: Kim L
authors.initials: KL
authors.lastname: Matthews
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Stevens
authors.forename: Victoria J
authors.initials: VJ
authors.lastname: Bolton
authors.forename: Izzy
authors.initials: I
authors.lastname: Boyfield
authors.forename: Emma M
authors.initials: EM
authors.lastname: Jarvie
authors.forename: Sharon C
authors.initials: SC
authors.lastname: Stratton
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Sanger
mesh_terms: D000818:Animals; D002244:Carbon / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D005755:Gastrins / Q000737:chemistry; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008956:Models, Chemical; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011964:Receptors, Gastrointestinal Hormone / Q000819:agonists* / Q000737:chemistry; D018013:Receptors, Neuropeptide / Q000819:agonists* / Q000737:chemistry
chemical_list: C540149:GSK326416; D005755:Gastrins; D011725:Pyridines; D011964:Receptors, Gastrointestinal Hormone; D018013:Receptors, Neuropeptide; C050802:motilin receptor; D002244:Carbon