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

• Published in: Bioorganic & medicinal chemistry letters Vol. 20; no. 9; pp. 2864 - 2867
• Main Authors: Shook, Brian C, Rassnick, Stefanie, Hall, Daniel, Rupert, Kenneth C, Heintzelman, Geoffrey R, Hansen, Kristen, Chakravarty, Devraj, Bullington, James L, Scannevin, Robert H, Magliaro, Brian, Westover, Lori, Carroll, Karen, Lampron, Lisa, Russell, Ronald, Branum, Shawn, Wells, Kenneth, Damon, Sandra, Youells, Scott, Li, Xun, Osbourne, Mel, Demarest, Keith, Tang, Yuting, Rhodes, Kenneth, Jackson, Paul F
• Format: Journal Article
• Language: English
• Published: England 01.05.2010
• Subjects: 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
• ISSN: 1464-3405
• DOI: 10.1016/j.bmcl.2010.03.042

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.