Discovery of novel α7 nicotinic receptor antagonists

✍ Scribed by Youyi Peng; Qiang Zhang; Gretchen L. Snyder; Hongwen Zhu; Wei Yao; John Tomesch; Roger L. Papke; James P. O’Callaghan; William J. Welsh; Lawrence P. Wennogle

• Book ID: 104004575
• Publisher: Elsevier Science
• Year: 2010
• Tongue: English
• Weight: 904 KB
• Volume: 20
• Category: Article
• ISSN: 0960-894X
• DOI: 10.1016/j.bmcl.2010.06.103

✦ Synopsis

Two distinct families of small molecules were discovered as novel alpha7 nicotinic acetylcholine receptor (nAChR) antagonists by pharmacophore-based virtual screening. These novel antagonists exhibited selectivity for the neuronal alpha7 subtype over other nAChRs and good brain penetration. Neuroprotection was demonstrated by representative compounds 7i and 8 in a mouse seizure-like behavior model induced by the nerve agent diisopropylfluorophosphate (DFP). These novel nAChR antagonists have potential use as antidote for organophosphorus nerve agent intoxication.