Discovery of Novel alpha7 Nicotinic Receptor Antagonists

Details

• Personal Author:
  O'Callaghan JP ; Papke RL ; Peng Y ; Snyder GL ; Tomesch J ; Welsh WJ ; Wennogle LP ; Yao W ; Zhang Q ; Zhu H
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Air Movements Atmosphere Coal Coal Mining Explosions Mining Occupational Health Oxygen Safety
• Keywords:
  Acetylcholine Receptors Alpha-particles Alpha7 Antagonists Author Keywords: Nicotinic Biological-warfare-agents Brain-function Intoxicants Molecular-biology Molecular-structure Nerves Neurological-reactions Neuropharmacology Neuroprotection Organo-phosphorus-compounds Pharmacophore

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• ISSN:
  0960-894X
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Florida ; New Jersey ; New York ; OSHA Region 2 ; OSHA Region 3 ; OSHA Region 4 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  20
• Issue:
  16
• NIOSHTIC Number:
  nn:20037273
• Citation:
  Bioorg Med Chem Lett 2010 Aug; 20(16):4825-4830
• Contact Point Address:
  L.P. Wennogle, Intra-Cellular Therapies, Inc., New York, NY, 10032
• Email:
  wennogle@intracellulartherapies.com
• Federal Fiscal Year:
  2010
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  Bioorganic & Medicinal Chemistry Letters
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:ab390150c672116c423d2b80b5692f99b8c8b31641ad8a39a27886423cd53e3c804d4899c0c6cbe79a59e8b6fab25361dd34cbec8f25cc47527deb6790f45b2f
• Download URL:
  https://stacks.cdc.gov/view/cdc/188390/cdc_188390_DS1.pdf
• File Type:
  [PDF - 881.61 KB ]