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

Julius J Matasi; John P Caldwell; Hongtao Zhang; Ahmad Fawzi; Mary E Cohen-Williams; Geoffrey B Varty; Deen B Tulshian

doi:10.1016/j.bmcl.2005.05.086

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

Bioorg Med Chem Lett. 2005 Aug 15;15(16):3670-4. doi: 10.1016/j.bmcl.2005.05.086.

Authors

Julius J Matasi¹, John P Caldwell, Hongtao Zhang, Ahmad Fawzi, Mary E Cohen-Williams, Geoffrey B Varty, Deen B Tulshian

Affiliation

¹ Department of Medicinal Chemistry-CV & CNS, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.

PMID: 15978806
DOI: 10.1016/j.bmcl.2005.05.086

Abstract

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.

MeSH terms

Adenosine A2 Receptor Antagonists*
Administration, Oral
Animals
Catalepsy / drug therapy
Disease Models, Animal
Drug Evaluation, Preclinical
Male
Molecular Structure
Pyrimidines / chemistry
Pyrimidines / classification
Pyrimidines / pharmacology*
Pyrimidines / therapeutic use
Rats
Structure-Activity Relationship
Triazoles / chemistry
Triazoles / pharmacology*
Triazoles / therapeutic use

Substances

2-(2-furanyl)-7-phenyl(1,2,4)triazolo(1,5-c)pyrimidin-5-amine
Adenosine A2 Receptor Antagonists
Pyrimidines
Triazoles