摘要
A series of lH-pyrrolo[3,2-b]pyridine (3a-3f) and fUroP,2-b]pyridine derivatives (4a-4g) were evaluated on human a7 nicotinic acetylcholine receptors (nAChRs) using two-electrode voltage clamp (TEVC) recording. A representative 2-(2-methoxyphenyl)- furo[3,2-b]pyridine 4f as negative allosteric modulator (NAM) selectively inhibited alpha7 nAChR over a3p4, a4p2 nAChRs and 5-HT3a receptor, with a potency of IC50 of 5.51 |1M and a maximum inhibition rate of 87.8%. The preliminary analysis of structure-activity relationship (SAR) suggested that compound 4f could serve as a basis for further discovery of potent and selective a7 nAChR NAMs.
作者基于课题组先前得到的脱硫催化产物吡咯并[3,2-b]吡啶和呋喃并[3,2-b]吡啶类新型结构,通过双电极电压钳电生理技术记录表达人源α7乙酰胆碱受体通道的非洲爪蟾卵母细胞对合成的化合物进行了活性评价。在100μM的乙酰胆碱作用下,代表性呋喃并[3,2-b]吡啶化合物4f对α7烟碱型乙酰胆碱受体最大抑制率达87.8%和IC_(50)为5.51μM。化合物4f对α7烟碱型乙酰胆碱受体具有亚型选择性,是一类具有潜在研究价值的负向变构调节剂。
基金
National Natural Science Foundation(Grant No.21572011,81537410)
Ministry of Science and Technology(Grant No.2014ZX09507003-006-004)
