Synthèse de nouveaux dérivés pyridopyrimidiniques, imidazopyridiniques et imidazopyridaziniques : évaluation de leurs propriétés biologiques (original) (raw)

2012

Abstract

Products belonging to the pyridopyrimidine family are characterized by their intense use in pharmacology. The increase of interest for this heterocyclic scaffold prompted different research teams around the world to study their chemically and biologically properties. In this work, we are interested in the functionalization of pyridopyrimidines and, more specifically, of the less described regioisomer, namely pyrido[3,2-d]pyrimidines. The target compounds were synthesized from 2,7-dichloropyrido[3,2-d]pyrimidine via nucleophilic aromatic substitution and palladium-catalyzed couplings and, in order to obtain potent kinases inhibitors. Our goal has been achieved with several elaborate molecules. These bioactive compounds inhibit kinases such as Cyclin Dependant Kinases (CDK), Glycogen Synthase 3 (GSK3) or Dual specificity tYRosine-phosphorylation-regulated Kinase 1A (DYRK1A) in the nanomolar range. These biological targets are mainly involved in degenerative process or down syndrome. These pharmacological results led us to extend our studies to other pyridopyrimidines, namely pyrido[2,3-d]pyrimidines as well as other types of polynitrogenated bicycles, namely imidazo[1,2- a]pyridine and imidazo[1,2-b]pyridazine.

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