Synthesis, structural reassignment, and biological activity of type B MAO inhibitors based on the 5H-indeno[1,2-c]pyridazin-5-one core

  • J Med Chem. 2006 Jun 15;49(12):3743-7. doi: 10.1021/jm051091j.
Raphaël Frédérick  1 ,  Willy Dumont ,  Frédéric Ooms ,  Lindsey Aschenbach ,  Cornelis J Van der Schyf ,  Neal Castagnoli ,  Johan Wouters ,  Alain Krief
Affiliations
  • 1. 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.
PMID: 16759116 DOI: 10.1021/jm051091j
Abstract

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.

Products