TY - JOUR
T1 - 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
AU - Ooms, Frédéric
AU - Frédérick, Raphaël
AU - Durant, François
AU - Petzer, Jacobus P.
AU - Castagnoli, Neal
AU - Van der Schyf, Cornelis J.
AU - Wouters, Johan
PY - 2003/1/6
Y1 - 2003/1/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0037421086&partnerID=8YFLogxK
U2 - 10.1016/S0960-894X(02)00838-7
DO - 10.1016/S0960-894X(02)00838-7
M3 - Article
C2 - 12467619
AN - SCOPUS:0037421086
SN - 0960-894X
VL - 13
SP - 69
EP - 73
JO - Bioorganic & Medicinal Chemistry Letters
JF - Bioorganic & Medicinal Chemistry Letters
IS - 1
ER -