Potent and selective adenosine A(2A) receptor antagonists: [1,2,4]-triazolo[4,3-c]pyrimidin-3-ones

Joel M Harris; Bernard R Neustadt; Hongtao Zhang; Jean Lachowicz; Mary Cohen-Williams; Geoff Varty; Jinsong Hao; Andrew W Stamford

doi:10.1016/j.bmcl.2011.02.045

Potent and selective adenosine A(2A) receptor antagonists: [1,2,4]-triazolo[4,3-c]pyrimidin-3-ones

Bioorg Med Chem Lett. 2011 Apr 15;21(8):2497-501. doi: 10.1016/j.bmcl.2011.02.045. Epub 2011 Feb 24.

Authors

Joel M Harris¹, Bernard R Neustadt, Hongtao Zhang, Jean Lachowicz, Mary Cohen-Williams, Geoff Varty, Jinsong Hao, Andrew W Stamford

Affiliation

¹ Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. joel.harris@merck.com

PMID: 21398125
DOI: 10.1016/j.bmcl.2011.02.045

Abstract

Antagonism of the adenosine A(2A) receptor affords a possible treatment of Parkinson's disease. In the course of investigating pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine A(2A) antagonists, we prepared [1,2,4]-triazolo[4,3-c]pyrimidin-3-ones with potent and selective (vs A(1)) A(2A) antagonist activity. Structure-activity relationships are described for this series.

MeSH terms

Adenosine A2 Receptor Antagonists / chemical synthesis
Adenosine A2 Receptor Antagonists / chemistry*
Adenosine A2 Receptor Antagonists / therapeutic use
Humans
Parkinson Disease / drug therapy
Pyrimidinones / chemical synthesis
Pyrimidinones / chemistry
Pyrimidinones / therapeutic use
Receptor, Adenosine A2A / chemistry*
Receptor, Adenosine A2A / metabolism
Structure-Activity Relationship

Substances

Adenosine A2 Receptor Antagonists
Pyrimidinones
Receptor, Adenosine A2A