Synthesis of [1,2,4]triazolo[1,5-a]pyrazines as adenosine A2A receptor antagonists.
Potent and selective antagonists of the adenosine A2A receptor often contain a nitrogen-rich fused-ring heterocyclic core. Replacement of the core with an isomeric ring system has previously been shown to improve target affinity, selectivity, and in vivo activity. This paper describes the preparation, by a novel route, of A2A receptor antagonists containing the [1,2,4]triazolo[1,5-a]pyrazine nucleus, which is isomeric with the [1,2,4]triazolo[1,5-c]pyrimidine core of a series of known A2A antagonists with in vivo activity in animal models of Parkinson's disease.
Dowling
James E
JE
Biogen Idec, Inc., 14 Cambridge Center, Cambridge, MA 02142, USA. james.dowling@biogenidec.com
Vessels
Jeffrey T
JT
Haque
Serajul
S
Chang
He Xi
HX
van Vloten
Kurt
K
Kumaravel
Gnanasambandam
G
Engber
Thomas
T
Jin
Xiaowei
X
Phadke
Deepali
D
Wang
Joy
J
Ayyub
Eman
E
Petter
Russell C
RC
D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D001921:Brain / Q000648:ultrastructure; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D004195:Disease Models, Animal; D010300:Parkinson Disease / Q000188:drug therapy; D011719:Pyrazines / Q000138:chemical synthesis* / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D013329:Structure-Activity Relationship
D058917:Adenosine A2 Receptor Antagonists; D011719:Pyrazines