Allosteric Modulators of the Adenosine A1 Receptor: Synthesis and Pharmacological Evaluation of 4-Substituted 2-Amino-3-benzoylthiophenes
Allosteric Modulators of the Adenosine A1 Receptor: Synthesis and Pharmacological Evaluation of 4-Substituted 2-Amino-3-benzoylthiophenes
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DOI：
10.1021/jm9002582
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发表时间：
2009-07-23
影响因子：
7.3
通讯作者：
Scammells, Peter J.
中科院分区：
文献类型：
--
作者：
Aurelio, Luigi;Valant, Celine;Scammells, Peter J.
使用完整 CHO 细胞中 A A(1)AR 介导的 ERK 1/2 磷酸化功能分析筛选了一系列 4-取代 2-氨基-3-苯甲酰噻吩，以鉴定潜在的激动作用以及变构调节正构激动剂 R-PIA 活性的能力。随后利用 ERK 1/2 测定以及 [S-35]GTP gamma S 与活化 G 蛋白结合的第二次测定对两种化合物（9a 和 9o）进行更详细的浓度反应实验。
A series of 4-substituted 2-amino-3-benzoylthiophenes was screened using a functional assay of A A(1)AR-mediated phosphorylation of ERK 1/2 in intact CHO cells to identify both potential agonistic effects as well the ability to allosterically modulate the activity of the orthosteric agonist, R-PIA. More detailed concentration-response experiments were subsequently performed on two compounds (9a and 9o) utilizing both the ERK 1/2 assay as well as a second assay of [S-35]GTP gamma S binding to activated G proteins.