Discovery of novel alpha7 nicotinic receptor antagonists.
Peng-Y; Zhang-Q; Snyder-GL; Zhu-H; Yao-W; Tomesch-J; Papke-RL; O'Callaghan-JP; Welsh-WJ; Wennogle-LP
Bioorg Med Chem Lett 2010 Aug; 20(16):4825-4830
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.
Molecular-biology; Molecular-structure; Nerves; Neuropharmacology; Organo-phosphorus-compounds; Biological-warfare-agents; Intoxicants; Alpha-particles; Brain-function; Neurological-reactions;
Author Keywords: Nicotinic; acetylcholine receptors; alpha7 antagonists; Pharmacophore; Neuroprotection
L.P. Wennogle, Intra-Cellular Therapies, Inc., New York, NY, 10032
Bioorganic & Medicinal Chemistry Letters