Triamino derivatives of triazolotriazine and triazolopyrimidine as adenosine A2a receptor antagonists.
Piperazine derivatives of 2-furanyl[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 now demonstrate that potent and selective A(2a) receptor antagonists could still be obtained when the arylpiperazines are separated from the triazolotriazine core structure by an ethylenediamine spacer. Selected analogs bearing this triazolotriazine or the related triazolopyrimidine core structure have been found 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
Shields
Pamela
P
Peng
Bo
B
Kumaravel
Gnanasambandam
G
Jin
Xiaowei
X
Phadke
Deepali
D
Wang
Joy
J
Engber
Thomas
T
Ayyub
Eman
E
Petter
Russell C
RC
D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D000978:Antiparkinson Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D051379:Mice; D011743:Pyrimidines / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014227:Triazines / Q000138:chemical synthesis / Q000494:pharmacology; D014230:Triazoles / Q000138:chemical synthesis / Q000494:pharmacology
D058917:Adenosine A2 Receptor Antagonists; D000978:Antiparkinson Agents; D011743:Pyrimidines; D014227:Triazines; D014230:Triazoles