[en] The synthesis and enzyme inhibitor properties of reversible type B monoamine oxidase inhibitors are described. These compounds belong to the 5H-indeno[1,2-c]pyridazine family and possess a hydrophobic benzyloxy or 4,4,4-trifluorobutoxy side chain which, in contrast to a previous assignment, has been unambiguously located at C(8) of the heterocyclic moiety. Investigation of the regioisomeric structures establishes that substitution of the 5H-indeno[1,2-c]pyridazin-5-one core at C(7) vs C(8) dramatically influences the MAO-inhibiting properties of these compounds.
Disciplines :
Chemistry
Author, co-author :
Frédérick, Raphaël; Laboratoire de Chimie Biologique Structurale, Drug Design and Discovery Center, Facultés Universitaires N.D de la Paix, 61 rue de Bruxelles, B-5000 Namur, Belgium
Dumont, Willy; Laboratoire de Chimie Organique de Synthèse (COS), Facultés Universitaires N.D de la Paix, B-5000 Namur, Belgium
Ooms, Frédéric ; Université de Liège - ULiège > HEC Liège Research > HEC Liège Research: Strategy & Performance for the Society ; Laboratoire de Chimie Biologique Structurale, Drug Design and Discovery Center, Facultés Universitaires N.D de la Paix, B-5000 Namur, Belgium ; Euroscreen S.A., 1070 Bruxelles, Belgium
Aschenbach, Lindsey; Department of Chemistry, Virginia Tech., Blacksburg, VA 02461-0212, United States
Van der Schyf, Cornelis J; Department of Pharmaceutical Sciences, Texas Tech. University Health Sciences Center, School of Pharmacy, Amarillo, TX 79106, United States
Castagnoli, Neal; Department of Chemistry, Virginia Tech., Blacksburg, VA 02461-0212, United States
Wouters, Johan; Laboratoire de Chimie Biologique Structurale, Drug Design and Discovery Center, Facultés Universitaires N.D de la Paix, B-5000 Namur, Belgium
Krief, Alain; Laboratoire de Chimie Organique de Synthèse (COS), Facultés Universitaires N.D de la Paix, B-5000 Namur, Belgium
Language :
English
Title :
Synthesis, structural reassignment, and biological activity of type B MAO inhibitors based on the 5H-indeno[1,2-c]pyridazin-5-one core.
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