Biaryl and heteroaryl derivatives of SCH 58261 as potent and selective adenosine A2A receptor antagonists

被引：19
|
作者：
Shah, Unmesh [1 ]
Boyle, Craig D. [1 ]
Chackalamannil, Samuel [1 ]
Neustadt, Bernard R. [1 ]
Lindo, Neil [1 ]
Greenlee, William J. [1 ]
Foster, Carolyn [1 ]
Arik, Leyla [1 ]
Zhai, Ying [1 ]
Ng, Kwokei [1 ]
Wang, Shiyong [1 ]
Monopoli, Angela [1 ]
Lachowicz, Jean E. [1 ]
机构：
[1] Schering Plough Corp, Res Inst, Kenilworth, NJ 07033 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 14期
关键词：
adenosine; A(2A); A(2A) receptor; A(2A) antagonist; A(2A) receptor antagonist; SCH; 58261; Parkinson's Disease;
D O I：
10.1016/j.bmcl.2008.05.074
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
SCH 58261 is a reported adenosine A(2A) receptor antagonist, which is active in rat in vivo models of Parkinson's Disease upon ip administration. However, it has poor selectivity versus the A(1) receptor and does not demonstrate oral activity. We report the design and synthesis of biaryl and heteroaryl analogs of SCH 58261 which improve the A(2A) receptor binding selectivity as well as the pharmacokinetic properties of SCH 58261. In particular, the quinoline 25 has excellent A(2A) receptor in vitro binding affinity and selectivity, sustained rat plasma levels upon oral dosing, and is active orally in a rat behavioral assay. (C) 2008 Elsevier Ltd. All rights reserved.
引用
收藏
页码：4199 / 4203
页数：5
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