Synthesis of alkyne derivatives of a novel triazolopyrazine as A(2A) adenosine receptor antagonists.
A novel [1,2,4]triazolo[1,5-a]pyrazine core was synthesized and coupled with terminal acetylenes. The structure-activity relationship of the alkynes from this novel template was studied for their in vitro and in vivo adenosine A(2A) receptor antagonism. Selected compounds from this series were shown to have potent in vitro and in vivo activities against adenosine A(2A) receptor. Compound 12, in particular, was found to be orally active at 3mg/kg in both a mouse catalepsy model and a 6-hydroxydopamine-lesioned rat model.
Yao
Gang
G
Departments of Medicinal Chemistry and Pharmacology, Biogen Idec, 14 Cambridge Center, Cambridge, MA 02142, USA. gang.yao@biogenidec.com
Haque
Serajul
S
Sha
Li
L
Kumaravel
Gnanasambandam
G
Wang
Joy
J
Engber
Thomas M
TM
Whalley
Eric T
ET
Conlon
Patrick R
PR
Chang
Hexi
H
Kiesman
William F
WF
Petter
Russell C
RC
D058917:Adenosine A2 Receptor Antagonists; D000284:Administration, Oral; D000480:Alkynes / Q000737:chemistry; D000818:Animals; D002375:Catalepsy / Q000188:drug therapy; D002540:Cerebral Cortex; D004195:Disease Models, Animal; D051379:Mice; D016627:Oxidopamine; D010300:Parkinson Disease / Q000188:drug therapy; D011719:Pyrazines / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis
D058917:Adenosine A2 Receptor Antagonists; D000480:Alkynes; D011719:Pyrazines; D014230:Triazoles; D016627:Oxidopamine