Document Report Card

Basic Information

ID: ALA1136363

Journal: Bioorg Med Chem Lett

Title: 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.

Authors: Ooms F, Frédérick R, Durant F, Petzer JP, Castagnoli N, Van der Schyf CJ, Wouters J.

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 K(i(MAO-B)) in the low nanomolar range.

CiteXplore: 12467619

DOI: 10.1016/s0960-894x(02)00838-7