2,6-Diaryl-4-phenacylaminopyrimidines as potent and selective adenosine A(2A) antagonists with reduced hERG liability

作者：Moorjani Manisha^*; Zhang Xiaohu; Chen Yongsheng; Lin Emily; Rueter Jaimie K; Gross Raymond S; Lanier Marion C; Tellew John E; Williams John P; Lechner Sandra M; Malany Siobhan; Santos Mark; Ekhlassi Paddi; Castro Palomino Julio C; Crespo Maria I; Prat Maria; Gual Silvia; Diaz Jose Luis; Saunders John; Slee Deborah H

来源：Bioorganic & Medicinal Chemistry Letters, 2008, 18(4): 1269-1273.

DOI：10.1016/j.bmcl.2008.01.036

• A(2A) antagonists
• adenosine receptor
• Parkinson's disease
• phenacylaminopyrimidines
• hERG

In this report, the design and synthesis of a series of pyrimidine based adenosine A(2A) antagonists are described. The strategy and outcome of expanding SAR exploration to attenuate hERG and improve selectivity over A(1) are discussed. Compound 33 exhibited excellent potency, selectivity over A1, and reduced hERG liability.

• 出版日期2008-2-15