Substituted thieno[2,3-d]pyrimidines as adenosine A2A receptor antagonists

Brian C Shook; Devraj Chakravarty; J Kent Barbay; Aihua Wang; Kristi Leonard; Vernon Alford; Mark T Powell; Stefanie Rassnick; Robert H Scannevin; Karen Carroll; Nathaniel Wallace; Jeffrey Crooke; Mark Ault; Lisa Lampron; Lori Westover; Kenneth Rhodes; Paul F Jackson

doi:10.1016/j.bmcl.2013.02.078

Substituted thieno[2,3-d]pyrimidines as adenosine A2A receptor antagonists

Bioorg Med Chem Lett. 2013 May 1;23(9):2688-91. doi: 10.1016/j.bmcl.2013.02.078. Epub 2013 Feb 27.

Authors

Brian C Shook¹, Devraj Chakravarty, J Kent Barbay, Aihua Wang, Kristi Leonard, Vernon Alford, Mark T Powell, Stefanie Rassnick, Robert H Scannevin, Karen Carroll, Nathaniel Wallace, Jeffrey Crooke, Mark Ault, Lisa Lampron, Lori Westover, Kenneth Rhodes, Paul F Jackson

Affiliation

¹ Janssen Research & Development, LLC, Welsh and McKean Roads, PO Box 776, Spring House, PA 19477, USA. bshook@its.jnj.com

PMID: 23522563
DOI: 10.1016/j.bmcl.2013.02.078

Abstract

A novel series of benzyl substituted thieno[2,3-d]pyrimidines were identified as potent A2A receptor antagonists. Several five- and six-membered heterocyclic replacements for the optimized methylfuran were explored. Select compounds effectively reverse catalepsy in mice when dosed orally.

MeSH terms

Adenosine A2 Receptor Antagonists / chemistry*
Adenosine A2 Receptor Antagonists / pharmacokinetics
Adenosine A2 Receptor Antagonists / therapeutic use
Animals
Brain / metabolism
Catalepsy / drug therapy
Half-Life
Humans
Kinetics
Mice
Protein Binding
Pyrimidines / chemistry*
Pyrimidines / pharmacokinetics
Pyrimidines / therapeutic use
Rats
Receptor, Adenosine A2A / chemistry
Receptor, Adenosine A2A / metabolism*

Substances

Adenosine A2 Receptor Antagonists
Pyrimidines
Receptor, Adenosine A2A