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 |
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Authors: | Ooms Frédéric Frédérick Raphaël Durant François Petzer Jacobus P Castagnoli Neal Van der Schyf Cornelis J Wouters Johan |
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Institution: | Facultés Universitaires Notre-Dame de la Paix, Laboratoire de Chimie Moléculaire Structurale, B-5000 Namur, Belgium. |
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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)indeno1,2-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. |
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