Synthesis, structural reassignment, and biological activity of type B MAO inhibitors based on the 5H-indeno[1,2-c]pyridazin-5-one core.
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.
Frédérick
Raphaël
R
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
W
Ooms
Frédéric
F
Aschenbach
Lindsey
L
Van der Schyf
Cornelis J
CJ
Castagnoli
Neal
N
Wouters
Johan
J
Krief
Alain
A
D018360:Crystallography, X-Ray; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D066298:In Vitro Techniques; D007192:Indenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology; D015394:Molecular Structure; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011724:Pyridazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D007192:Indenes; D008996:Monoamine Oxidase Inhibitors; D011724:Pyridazines