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

Ooms, Frédéric;Frédérick, Raphaël;Durant, François;Petzer, Jacobus P;Wouters, Johan;et.al.
(2003) Bioorganic & Medicinal Chemistry Letters : the tetrahedron journal for research at the interface of chemistry and biology — Vol. 13, n° 1, p. 69-73 (2003)

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  • Ooms, FrédéricUnamur
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  • Frédérick, Raphaëlorcid-logoUCLouvain
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  • Durant, FrançoisUnamur
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  • Petzer, Jacobus P
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  • Wouters, JohanUnamur
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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)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.
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Ooms, F., Frédérick, R., Durant, F., Petzer, J. P., Castagnoli, N., Van der Schyf, C. J., & Wouters, J. (2003). 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. Bioorganic & Medicinal Chemistry Letters : the tetrahedron journal for research at the interface of chemistry and biology, 13(1), 69-73. https://doi.org/10.1016/S0960-894X(02)00838-7 (Original work published 2003)