Journal
BIOORGANIC & MEDICINAL CHEMISTRY
Volume 13, Issue 7, Pages 2489-2499Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2005.01.043
Keywords
monoamine oxidase; tyramine oxidase; fluorinated phenylcyclopropylamine; irreversible inhibition; stereochemistry
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A series of para-ring-substituted (E)- and (Z)-1-aryl-2-fluorocyclopropylamines were examined as inhibitors of recombinant human liver monoamine oxidase A (MAO A) and B (MAO B). Unlike the parent 1-phenylcyclopropylamine, which is a selective inhibitor of MAO B, both (E)- and (Z)-diastereomers of derivatives having fluorine at the 2-position of the cyclopropane ring were potent and selective irreversible inhibitors of MAO A. Both electron releasing groups (Me, OMe) and electron attracting groups (Cl, F) substituted in the para-position caused a modest increase in activity. Geminal difluoro-substitution caused a loss of potency of 100-fold compared to either (E)- or (Z)-monofluorinated analogue. Surprisingly, (1S,2R)-2-fluoro-l-phenylcyclopropylamine and the (1R,2S)-enantiomer were essential equally potent as inhibitors of MAO A and MAO B. None of the tested 1-aryl-2-fluorocyclopropylamines exhibited significant inhibition of tyramine oxidase. (c) 2005 Elsevier Ltd. All rights reserved.
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