3-and 6-Substituted 2-amino-4,5,6,7-tetrahydrothieno[2,3-c]pyridines as A1 adenosine receptor allosteric modulators and antagonists
3-and 6-Substituted 2-amino-4,5,6,7-tetrahydrothieno[2,3-c]pyridines as A1 adenosine receptor allosteric modulators and antagonists
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DOI：
10.1016/j.bmc.2009.08.024
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发表时间：
2009-10-15
影响因子：
3.5
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.
制备了一系列2-amino-4，5，6，7-tetrahydrothieno[2，3-c]pyridines，并对其作为A(1)腺苷受体潜在的变构调节剂进行了评价。探索了一系列2-amino-4，5，6，7-tetrahydrothieno[2，3-c]pyridines的3位和6位的构效关系。尽管发现3-和6-取代的2-amino-4，5，6，7-tetrahydrothieno[2，3-c]pyridines在相对较高的浓度下能够识别激动剂占据的A(1)AR上的变构位点，但我们在该支架上进行的结构修饰比变构性质更有利于表达正构拮抗剂的性质。本研究已确定2-amino-4，5，6，7-tetrahydrothieno[2，3-c]pyridines为A(1)AR的一类新的正构拮抗剂，并强调了控制变构调节的结构元件与A(1)AR激动剂功能的正构拮抗之间的密切关系。(C)2009爱思唯尔有限公司。保留所有权利。
A series of 2-amino-4,5,6,7-tetrahydrothieno[2,3-c]pyridines were prepared and evaluated as potential allosteric modulators at the A(1) adenosine receptor. The structure-activity relationships of the 3- and 6-positions of a series of 2-amino-4,5,6,7-tetrahydrothieno[2,3-c]pyridines were explored. Despite finding that 3- and 6-substituted 2-amino-4,5,6,7-tetrahydrothieno[2,3-c]pyridines possess the ability to recognize an allosteric site on the agonist-occupied A(1)AR at relatively high concentrations, the structural modifications we have performed on this scaffold favor the expression of orthosteric antagonist properties over allosteric properties. This research has identified 2-amino-4,5,6,7-tetrahydrothieno[2,3-c]pyridines as novel class of orthosteric antagonist of the A(1)AR and highlighted the close relationship between structural elements governing allosteric modulation and orthosteric antagonism of agonist function at the A(1)AR. (c) 2009 Elsevier Ltd. All rights reserved.