Novel bis-,tris-, and tetrakis-tertiary amino analogs as antagonists at neuronal nicotinic receptors that mediate nicotine-evoked dopamine release

作者：Zhang Zhenfa; Zheng Guangrong; Pivavarchyk Marharyta; Deaciuc A Gabriela; Dwoskin Linda P; Crooks Peter A^*

来源：Bioorganic & Medicinal Chemistry Letters, 2011, 21(1): 88-91.

DOI：10.1016/j.bmcl.2010.11.070

• nAChR antagonists
• Smoking cessation
• Tobacco dependency

A series of tertiary amine analogs derived from lead azaaromatic quaternary ammonium salts has been designed and synthesized. The preliminary structure-activity relationships of these new analogs suggest that such tertiary amine analogs, which potently inhibit nicotine-evoked dopamine release from rat striatum, represent drug-like inhibitors of alpha 6-containing nicotinic acetylcholine receptors. The bis-tertiary amine analog 7 exhibited an IC(50) of 0.95 nM, while the tris-tertiary amine analog 19 had an IC50 of 0.35 nM at nAChRs mediating nicotine-evoked dopamine release.

• 出版日期2011-1