2-Arylthiomorpholine derivatives as potent and selective monoamine oxidase B inhibitors

Bioorganic & Medicinal Chemistry
Susan LührPatricio Iturriaga-Vásquez

Abstract

2-Arylthiomorpholine and 2-arylthiomorpholin-5-one derivatives, designed as rigid and/or non-basic phenylethylamine analogues, were evaluated as rat and human monoamine oxidase inhibitors. Molecular docking provided insight into the binding mode of these inhibitors and rationalized their different potencies. Making the phenylethylamine scaffold rigid by fixing the amine chain in an extended six-membered ring conformation increased MAO-B (but not MAO-A) inhibitory activity relative to the more flexible alpha-methylated derivative. The presence of a basic nitrogen atom is not a prerequisite in either MAO-A or MAO-B. The best K(i) values were in the 10(-8)M range, with selectivities towards human MAO-B exceeding 2000-fold.

References

Oct 26, 2000·Protein Expression and Purification·P Newton-VinsonD E Edmondson

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Citations

Aug 23, 2011·Amino Acids·Bonaiuto EmanuelaMaria Luisa Di Paolo
May 1, 2012·Journal of Chemical Information and Modeling·Gerald Zapata-TorresCristian Celis-Barros
Mar 6, 2016·Progress in Neuro-psychopharmacology & Biological Psychiatry·Zdeněk Fišar
Mar 3, 2020·Mini Reviews in Medicinal Chemistry·Su-Min WuJuan Sun
Mar 23, 2019·Malaria Journal·Andreas MaschConrad Kunick
May 1, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Guillermo Moya-AlvaradoOlimpo García-Beltrán
Apr 29, 2015·Journal of Medicinal Chemistry·Simone Carradori, Romano Silvestri

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