Studies on adenosine A2a receptor antagonists: comparison of three core heterocycles.
Piperazine and (R)-2-(aminomethyl)pyrrolidine derivatives of [1,2,4]triazolo[1,5-a][1,3,5]triazine have recently been shown to be potent and selective adenosine A(2a) receptor antagonists. We have replaced the triazolotriazine core structure with two different heterocyclic cores. One of these, the one deriving from [1,2,4]triazolo[1,5-c]pyrimidine, appears to be particularly effective and selected analogs from this series have been shown to be orally active in a mouse catalepsy model of Parkinson's disease.
Vu
Chi B
CB
Biogen Idec, Inc., Department of Medicinal Chemistry, 14 Cambridge Center, Cambridge, MA 02142, USA. chi.vu@biogenidec.com
Pan
Deborah
D
Peng
Bo
B
Sha
Li
L
Kumaravel
Gnanasambandam
G
Jin
Xiaowei
X
Phadke
Deepali
D
Engber
Thomas
T
Huang
Carol
C
Reilly
Jennifer
J
Tam
Stacy
S
Petter
Russell C
RC
D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D002375:Catalepsy / Q000188:drug therapy; D051379:Mice; D011743:Pyrimidines / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000494:pharmacology
D058917:Adenosine A2 Receptor Antagonists; D000978:Antiparkinson Agents; D011743:Pyrimidines; D014230:Triazoles