Methylene amine substituted arylindenopyrimidines as potent adenosine A(2A)/A(1) antagonists

Brian C Shook; Stefanie Rassnick; Daniel Hall; Kenneth C Rupert; Geoffrey R Heintzelman; Kristen Hansen; Devraj Chakravarty; James L Bullington; Robert H Scannevin; Brian Magliaro; Lori Westover; Karen Carroll; Lisa Lampron; Ronald Russell; Shawn Branum; Kenneth Wells; Sandra Damon; Scott Youells; Xun Li; Mel Osbourne; Keith Demarest; Yuting Tang; Kenneth Rhodes; Paul F Jackson

doi:10.1016/j.bmcl.2010.03.042

Methylene amine substituted arylindenopyrimidines as potent adenosine A(2A)/A(1) antagonists

Bioorg Med Chem Lett. 2010 May 1;20(9):2864-7. doi: 10.1016/j.bmcl.2010.03.042. Epub 2010 Mar 11.

Affiliation

¹ Johnson & Johnson Pharmaceutical Research and Development, L.L.C., Welsh and McKean Roads, PO Box 776, Spring House, PA 19477, United States. [email protected]

PMID: 20347304
DOI: 10.1016/j.bmcl.2010.03.042

Abstract

A novel series of arylindenopyrimidines were identified as A(2A) and A(1) receptor antagonists. The series was optimized for in vitro activity by substituting the 8- and 9-positions with methylene amine substituents. The compounds show excellent activity in mouse models of Parkinson's disease when dosed orally.

MeSH terms

Adenosine A1 Receptor Antagonists*
Adenosine A2 Receptor Antagonists*
Amines / chemical synthesis
Amines / chemistry*
Amines / therapeutic use
Animals
Catalepsy / drug therapy
Disease Models, Animal
Mice
Neurotransmitter Agents / chemical synthesis
Neurotransmitter Agents / chemistry*
Neurotransmitter Agents / therapeutic use
Pyrimidines / chemical synthesis
Pyrimidines / chemistry*
Pyrimidines / therapeutic use
Receptor, Adenosine A1 / metabolism
Receptor, Adenosine A2A / metabolism
Structure-Activity Relationship

Substances

Adenosine A1 Receptor Antagonists
Adenosine A2 Receptor Antagonists
Amines
Neurotransmitter Agents
Pyrimidines
Receptor, Adenosine A1
Receptor, Adenosine A2A