title: Random chemistry as a new tool for the generation of small compound libraries: development of a new acetylcholinesterase inhibitor.
abstract: Random chemistry, the serendipitous generation of small compound libraries by gamma-irradiation of source compounds, presents a methodology providing reassembled and rearranged structures. The gamma-irradiation was applied to generate new acetylcholinesterase (AChE) inhibitors. The bioassay-guided fractionation as a deconvolution strategy was employed to analyze gained product mixture. The structure of the new highly potent AChE inhibitor, 9-amino-5,6,7,8-tetrahydroacridin-4yl)methanol (1), was elucidated by NMR spectroscopy and ESI (tandem) mass spectrometry.
authors.affiliation: Institute of Pharmacy and Food Chemistry, University of Würzburg, Am Hubland, 97074 Würzburg, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Kapková
authors.forename: Eberhard
authors.initials: E
authors.lastname: Heller
authors.forename: Matthias
authors.initials: M
authors.lastname: Unger
authors.forename: Gerd
authors.initials: G
authors.lastname: Folkers
authors.forename: Ulrike
authors.initials: U
authors.lastname: Holzgrabe
mesh_terms: D000109:Acetylcholine / Q000737:chemistry*; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D005720:Gamma Rays; D009682:Magnetic Resonance Spectroscopy; D000432:Methanol / Q000737:chemistry; D011726:Pyridinium Compounds / Q000737:chemistry / Q000528:radiation effects*; D021241:Spectrometry, Mass, Electrospray Ionization; D013619:Tacrine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000528:radiation effects*; D014867:Water / Q000737:chemistry
chemical_list: C507036:(9-amino-5,6,7,8-tetrahydroacridin-4-yl)methanol; C420025:4,4'-bis-((2,6-dichloro-benzyloxyimino)methyl)-1,1'-propane-1,3-diyl-bis-pyridinium; D002800:Cholinesterase Inhibitors; D011726:Pyridinium Compounds; D014867:Water; D013619:Tacrine; D000109:Acetylcholine; D000432:Methanol