Rational approaches towards reversible inhibition of type B monoamine oxidase. Design and evaluation of a novel 5H-Indeno[1,2-c]pyridazin-5-one derivative

Frédéric Ooms, Raphaël Frédérick, François Durant, Jacobus P. Petzer, Neal Castagnoli, Cornelis J. Van der Schyf, Johan Wouters

Research output: Contribution to journalArticle

Abstract

The stereoelectronic properties of several potent reversible monoamine oxidase B (MAO-B) inhibitors were studied with a view to develop a pharmacophore model for reversible MAO-B inhibition. This study suggested that important specific H-bond and hydrophobic interactions are required for potent and selective MAO-B inhibition. These requirements were applied in the design and synthesis of a novel reversible and selective MAO-B inhibitor, 3-methyl-8-(4,4,4-trifluoro-butoxy)indeno[1,2-c]pyridazin-5-one, that is ca. 7000 times more selective as an inhibitor for MAO-B than for MAO-A, with Ki(MAO-B) in the low nanomolar range.

Original languageEnglish
Pages (from-to)69-73
Number of pages5
JournalBioorganic & Medicinal Chemistry Letters
Volume13
Issue number1
DOIs
Publication statusPublished - 6 Jan 2003

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