期刊
BIOORGANIC & MEDICINAL CHEMISTRY
卷 22, 期 3, 页码 1077-1088出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2013.12.035
关键词
Heterocycles; Inflammation; Ligand-gated ion channel; Negative allosteric modulator; Neuropathic pain; P2X4 receptor; Structure-activity relationship; Synthesis; Tricyclics
资金
- BMBF (German Federal Ministry for Education and Research) within the BioPharma initiative 'Neuroallianz'
Antagonists for the P2 receptor subtype P2X4, an ATP-activated cation channel receptor, have potential as novel drugs for the treatment of neuropathic pain and other inflammatory diseases. In the present study, a series of 47 carbamazepine derivatives including 32 novel compounds were designed, synthesized, and evaluated as P2X4 receptor antagonists. Their potency to inhibit ATP-induced calcium influx in 1321N1 astrocytoma cells stably transfected with the human P2X4 receptor was determined. Additionally, species selectivity (human, rat, mouse) and receptor subtype selectivity (P2X4 vs P2X1, 2, 3, 7) were investigated for selected derivatives. The most potent compound of the present series, which exhibited an allosteric mechanism of P2X4 inhibition, was N,N-diisopropyl-5H-dibenz[b,f] azepine-5-carboxamide (34, IC50 of 3.44 mu M). The present study extends the so far very limited knowledge on structure-activity relationships of P2X4 receptor antagonists. (C) 2013 Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据