title: Synthesis of alkyne derivatives of a novel triazolopyrazine as A(2A) adenosine receptor antagonists.
abstract: 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.
authors.affiliation: Departments of Medicinal Chemistry and Pharmacology, Biogen Idec, 14 Cambridge Center, Cambridge, MA 02142, USA. gang.yao@biogenidec.com
authors.forename: Gang
authors.initials: G
authors.lastname: Yao
authors.forename: Serajul
authors.initials: S
authors.lastname: Haque
authors.forename: Li
authors.initials: L
authors.lastname: Sha
authors.forename: Gnanasambandam
authors.initials: G
authors.lastname: Kumaravel
authors.forename: Joy
authors.initials: J
authors.lastname: Wang
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Engber
authors.forename: Eric T
authors.initials: ET
authors.lastname: Whalley
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Conlon
authors.forename: Hexi
authors.initials: H
authors.lastname: Chang
authors.forename: William F
authors.initials: WF
authors.lastname: Kiesman
authors.forename: Russell C
authors.initials: RC
authors.lastname: Petter
mesh_terms: 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
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D000480:Alkynes; D011719:Pyrazines; D014230:Triazoles; D016627:Oxidopamine