锍作为铵的替代物：一种具有脱敏活性的新型α7烟碱型乙酰胆碱受体部分激动剂。
Sulfonium as a Surrogate for Ammonium: A New α7 Nicotinic Acetylcholine Receptor Partial Agonist with Desensitizing Activity.
作者信息
Quadri Marta, Stokes Clare, Gulsevin Alican, Felts Ashley C J, Abboud Khalil A, Papke Roger L, Horenstein Nicole A
机构信息
Department of Chemistry, University of Florida , P.O. Box 117200, Gainesville, Florida 32611-7200, United States.
Department of Pharmacology and Therapeutics, University of Florida , P.O. Box 100267, Gainesville, Florida 32610, United States.
出版信息
J Med Chem. 2017 Sep 28;60(18):7928-7934. doi: 10.1021/acs.jmedchem.7b00875. Epub 2017 Sep 14.
Abstract
Weak partial agonists that promote a desensitized state of the α7 nicotinic acetylcholine receptor (nAChR) have been associated with anti-inflammatory effects. Exemplar compounds feature a tertiary or quaternary ammonium group. We report the synthesis, structure, and electrophysiological evaluation of 1-ethyl-4-phenylthiomorpholin-1-ium triflate, a weak partial agonist with a sulfonium isostere of the ammonium pharmacophore. These results offer new insights in understanding nAChR-ligand interactions and provide a new chemical space to target the α7 nAChR.
摘要
促进α7烟碱型乙酰胆碱受体（nAChR）脱敏状态的弱部分激动剂已被证实具有抗炎作用。典型化合物具有叔铵或季铵基团。我们报告了1-乙基-4-苯基硫代吗啉三氟甲磺酸盐的合成、结构和电生理评估，该化合物是一种具有铵药效团锍类似物的弱部分激动剂。这些结果为理解nAChR-配体相互作用提供了新的见解，并为靶向α7 nAChR提供了新的化学空间。
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