Ooms Frédéric, Frédérick Raphaël, Durant François, Petzer Jacobus P, Castagnoli Neal, Van der Schyf Cornelis J, Wouters Johan
Facultés Universitaires Notre-Dame de la Paix, Laboratoire de Chimie Moléculaire Structurale, B-5000 Namur, Belgium.
Bioorg Med Chem Lett. 2003 Jan 6;13(1):69-73. doi: 10.1016/s0960-894x(02)00838-7.
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.
为了开发一种用于可逆性单胺氧化酶B（MAO-B）抑制的药效团模型，对几种强效可逆性MAO-B抑制剂的立体电子性质进行了研究。该研究表明，强效且选择性的MAO-B抑制需要重要的特定氢键和疏水相互作用。这些要求被应用于新型可逆性和选择性MAO-B抑制剂3-甲基-8-(4,4,4-三氟丁氧基)茚并[1,2-c]哒嗪-5-酮的设计与合成中，该抑制剂作为MAO-B抑制剂的选择性比MAO-A高约7000倍，其对MAO-B的抑制常数（K(i(MAO-B))）处于低纳摩尔范围。
