2-(2-Furanyl)-7-phenyl[1,2,4]triazolo[1,5-c]pyrimidin-5-amine analogs: highly potent, orally active, adenosine A2A antagonists. Part 1.
The structure-activity relationship of this novel class of compounds based on 2-(2-furanyl)-7-phenyl[1,2,4]-triazolo[1,5-c]pyrimidin-5-amine, 1, and its analogs was evaluated for their in vitro and in vivo adenosine A(2A) receptor antagonism. Several compounds displayed oral activity at 3 mg/kg in a rat catalepsy model. Specifically, compound 8g displayed an excellent in vitro profile, as well as a highly promising in vivo profile.
Department of Medicinal Chemistry-CV & CNS, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
Julius J
JJ
Matasi
John P
JP
Caldwell
Hongtao
H
Zhang
Ahmad
A
Fawzi
Mary E
ME
Cohen-Williams
Geoffrey B
GB
Varty
Deen B
DB
Tulshian
D058917:Adenosine A2 Receptor Antagonists; D000284:Administration, Oral; D000818:Animals; D002375:Catalepsy / Q000188:drug therapy; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D008297:Male; D015394:Molecular Structure; D011743:Pyrimidines / Q000737:chemistry / Q000145:classification / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use
C505707:2-(2-furanyl)-7-phenyl(1,2,4)triazolo(1,5-c)pyrimidin-5-amine; D058917:Adenosine A2 Receptor Antagonists; D011743:Pyrimidines; D014230:Triazoles