Random chemistry as a new tool for the generation of small compound libraries: development of a new acetylcholinesterase inhibitor

Petra Kapková; Eberhard Heller; Matthias Unger; Gerd Folkers; Ulrike Holzgrabe

doi:10.1021/jm058041z

Random chemistry as a new tool for the generation of small compound libraries: development of a new acetylcholinesterase inhibitor

J Med Chem. 2005 Nov 17;48(23):7496-9. doi: 10.1021/jm058041z.

Authors

Petra Kapková¹, Eberhard Heller, Matthias Unger, Gerd Folkers, Ulrike Holzgrabe

Affiliation

¹ Institute of Pharmacy and Food Chemistry, University of Würzburg, Am Hubland, 97074 Würzburg, Germany.

PMID: 16279811
DOI: 10.1021/jm058041z

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetylcholine / chemistry*
Cholinesterase Inhibitors / chemical synthesis*
Cholinesterase Inhibitors / chemistry
Chromatography, High Pressure Liquid
Gamma Rays
Magnetic Resonance Spectroscopy
Methanol / chemistry
Pyridinium Compounds / chemistry
Pyridinium Compounds / radiation effects*
Spectrometry, Mass, Electrospray Ionization
Tacrine / analogs & derivatives*
Tacrine / chemical synthesis
Tacrine / chemistry
Tacrine / radiation effects*
Water / chemistry

Substances

(9-amino-5,6,7,8-tetrahydroacridin-4-yl)methanol
4,4'-bis-((2,6-dichloro-benzyloxyimino)methyl)-1,1'-propane-1,3-diyl-bis-pyridinium
Cholinesterase Inhibitors
Pyridinium Compounds
Water
Tacrine
Acetylcholine
Methanol