SYNTHESIS AND STRUCTURE-ACTIVITY-RELATIONSHIPS OF NOVEL 2-AMINO ALKYLCHROMONES AND RELATED DERIVATIVES AS SIGMA-SITE-SELECTIVE LIGANDS

Starling from a random screening showing that 2-[(4-benzylpiperazinyl) methyl] chromone was a selective and potent sigma ligand, a series of analogues were synthesized. Introduction of a substituent on the chrom one moiety, replacement of methylenes by carbonyl groups and benzyl by aryl groups decrease the affinity for sigma sites. The result obtaine d after introduction of various substituents on the aromatic part of t he benzyl is strictly depending on the size and on the position of the se substituents. Stretching of the carbon chain between the phenyl and the piperazine does not strongly modify the affinity. 2-[4-(4'-methox y benzyl)-1-piperazinyl methyl] chromone has been tested in behavioral tests that permit to believe that such derivatives could be interesti ng for the treatment of psychosis. (C) Elsevier, Paris.