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 repr...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.展开更多
基金National Natural Science Foundation(Grant No.21572011,81537410)Ministry of Science and Technology(Grant No.2014ZX09507003-006-004)
文摘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.
