title: From ATP to AZD6140: the discovery of an orally active reversible P2Y12 receptor antagonist for the prevention of thrombosis.
abstract: Starting from adenosine triphosphate (ATP), the identification of a novel series of P2Y(12) receptor antagonists and exploitation of their SAR is described. Modifications of the acidic side chain and the purine core and investigation of hydrophobic substituents led to a series of neutral molecules. The leading compound, 17 (AZD6140), is currently in a large phase III clinical trial for the treatment of acute coronary syndromes and prevention of thromboembolic clinical sequelae.
authors.affiliation: AstraZeneca R&D Charnwood, Bakewell Road, Loughborough LE11 5RH, UK. brian.springthorpe@astrazeneca.com
authors.forename: Brian
authors.initials: B
authors.lastname: Springthorpe
authors.forename: Andrew
authors.initials: A
authors.lastname: Bailey
authors.forename: Patrick
authors.initials: P
authors.lastname: Barton
authors.forename: Timothy N
authors.initials: TN
authors.lastname: Birkinshaw
authors.forename: Roger V
authors.initials: RV
authors.lastname: Bonnert
authors.forename: Roger C
authors.initials: RC
authors.lastname: Brown
authors.forename: David
authors.initials: D
authors.lastname: Chapman
authors.forename: John
authors.initials: J
authors.lastname: Dixon
authors.forename: Simon D
authors.initials: SD
authors.lastname: Guile
authors.forename: Robert G
authors.initials: RG
authors.lastname: Humphries
authors.forename: Simon F
authors.initials: SF
authors.lastname: Hunt
authors.forename: Francis
authors.initials: F
authors.lastname: Ince
authors.forename: Anthony H
authors.initials: AH
authors.lastname: Ingall
authors.forename: Ian P
authors.initials: IP
authors.lastname: Kirk
authors.forename: Paul D
authors.initials: PD
authors.lastname: Leeson
authors.forename: Paul
authors.initials: P
authors.lastname: Leff
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Lewis
authors.forename: Barrie P
authors.initials: BP
authors.lastname: Martin
authors.forename: Dermot F
authors.initials: DF
authors.lastname: McGinnity
authors.forename: Michael P
authors.initials: MP
authors.lastname: Mortimore
authors.forename: Stuart W
authors.initials: SW
authors.lastname: Paine
authors.forename: Garry
authors.initials: G
authors.lastname: Pairaudeau
authors.forename: Anil
authors.initials: A
authors.lastname: Patel
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Rigby
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Riley
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Teobald
authors.forename: Wendy
authors.initials: W
authors.lastname: Tomlinson
authors.forename: Peter J H
authors.initials: PJ
authors.lastname: Webborn
authors.forename: Paul A
authors.initials: PA
authors.lastname: Willis
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000255:Adenosine Triphosphate / Q000627:therapeutic use*; D000284:Administration, Oral; D000818:Animals; D006801:Humans; D008565:Membrane Proteins / Q000037:antagonists & inhibitors*; D058919:Purinergic P2 Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D013927:Thrombosis / Q000517:prevention & control*; D000077486:Ticagrelor