发现非肽小分子α9α10 型烟碱型乙酰胆碱受体拮抗剂作为新型镇痛药治疗神经性和紧张性炎症性疼痛。
Discovery of non-peptide, small molecule antagonists of α9α10 nicotinic acetylcholine receptors as novel analgesics for the treatment of neuropathic and tonic inflammatory pain.
机构信息
College of Pharmacy, Department of Pharmaceutical Sciences, University of Kentucky, Lexington, KY 40536 0082, USA.
出版信息
Bioorg Med Chem Lett. 2011 Apr 15;21(8):2476-9. doi: 10.1016/j.bmcl.2011.02.043. Epub 2011 Feb 23.
Abstract
A series of azaaromatic quaternary ammonium analogs has been discovered as potent and selective α9α10 nicotinic acetylcholine receptor (nAChR) antagonists. The preliminary structure-activity relationships of these analogs suggest that increased rigidity in the linker units results in higher potency in inhibition of α9α10 nAChRs and greater selectivity over α7 nAChRs. These analogs represent a new class of analgesic for the treatment of neuropathic and tonic inflammatory pain.
摘要
一系列氮杂芳基季铵类似物已被发现为强效和选择性的α9α10 烟碱型乙酰胆碱受体（nAChR）拮抗剂。这些类似物的初步结构-活性关系表明，连接单元的刚性增加会导致对α9α10 nAChR 的抑制作用更强，对α7 nAChR 的选择性更高。这些类似物代表了一类新型的镇痛药，可用于治疗神经性和紧张性炎症性疼痛。
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