Antagonists of the human adenosine A2A receptor. Part 1: Discovery and synthesis of thieno[3,2-d]pyrimidine-4-methanone derivatives.
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.
Gillespie
Roger J
RJ
Vernalis (R&D) Ltd, 613 Reading Road, Winnersh, Wokingham RG41 5UA, UK.
Adams
David R
DR
Bebbington
David
D
Benwell
Karen
K
Cliffe
Ian A
IA
Dawson
Claire E
CE
Dourish
Colin T
CT
Fletcher
Allan
A
Gaur
Suneel
S
Giles
Paul R
PR
Jordan
Allan M
AM
Knight
Antony R
AR
Knutsen
Lars J S
LJ
Lawrence
Anthony
A
Lerpiniere
Joanne
J
Misra
Anil
A
Porter
Richard H P
RH
Pratt
Robert M
RM
Shepherd
Robin
R
Upton
Rebecca
R
Ward
Simon E
SE
Weiss
Scott M
SM
Williamson
Douglas S
DS
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
D058917:Adenosine A2 Receptor Antagonists; D000962:Antimalarials; D000978:Antiparkinson Agents; D011743:Pyrimidines; C529909:thieno(3,2-d)pyrimidine-4-methanone