title: Antagonists of the human adenosine A2A receptor. Part 1: Discovery and synthesis of thieno[3,2-d]pyrimidine-4-methanone derivatives.
abstract: The (-)-(11R,2'S)-enantiomer of the antimalarial drug mefloquine has been found to be a reasonably potent and moderately selective adenosine A(2A) receptor antagonist. Further investigation of this compound has led to the discovery of a series of keto-aryl thieno[3,2-d]pyrimidine derivatives, which are potent and selective antagonists of the adenosine A(2A) receptor. These derivatives show selectivity against the A(1) receptor. Furthermore, some of these compounds have been shown to have in vivo activity in a commonly used model, suggesting the potential for the treatment of Parkinson's disease.
authors.affiliation: Vernalis (R&D) Ltd, 613 Reading Road, Winnersh, Wokingham RG41 5UA, UK.
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Gillespie
authors.forename: David R
authors.initials: DR
authors.lastname: Adams
authors.forename: David
authors.initials: D
authors.lastname: Bebbington
authors.forename: Karen
authors.initials: K
authors.lastname: Benwell
authors.forename: Ian A
authors.initials: IA
authors.lastname: Cliffe
authors.forename: Claire E
authors.initials: CE
authors.lastname: Dawson
authors.forename: Colin T
authors.initials: CT
authors.lastname: Dourish
authors.forename: Allan
authors.initials: A
authors.lastname: Fletcher
authors.forename: Suneel
authors.initials: S
authors.lastname: Gaur
authors.forename: Paul R
authors.initials: PR
authors.lastname: Giles
authors.forename: Allan M
authors.initials: AM
authors.lastname: Jordan
authors.forename: Antony R
authors.initials: AR
authors.lastname: Knight
authors.forename: Lars J S
authors.initials: LJ
authors.lastname: Knutsen
authors.forename: Anthony
authors.initials: A
authors.lastname: Lawrence
authors.forename: Joanne
authors.initials: J
authors.lastname: Lerpiniere
authors.forename: Anil
authors.initials: A
authors.lastname: Misra
authors.forename: Richard H P
authors.initials: RH
authors.lastname: Porter
authors.forename: Robert M
authors.initials: RM
authors.lastname: Pratt
authors.forename: Robin
authors.initials: R
authors.lastname: Shepherd
authors.forename: Rebecca
authors.initials: R
authors.lastname: Upton
authors.forename: Simon E
authors.initials: SE
authors.lastname: Ward
authors.forename: Scott M
authors.initials: SM
authors.lastname: Weiss
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Williamson
mesh_terms: D058917:Adenosine A2 Receptor Antagonists; D000962:Antimalarials / Q000138:chemical synthesis / Q000627:therapeutic use*; D000978:Antiparkinson Agents / Q000138:chemical synthesis / Q000627:therapeutic use*; D006801:Humans; D008956:Models, Chemical; D020734:Parkinsonian Disorders / Q000188:drug therapy*; D011743:Pyrimidines / Q000138:chemical synthesis / Q000627:therapeutic use*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D000962:Antimalarials; D000978:Antiparkinson Agents; D011743:Pyrimidines; C529909:thieno(3,2-d)pyrimidine-4-methanone