Dopamine/Serotonin Receptor Ligands VI. Dibenz[g,j]-1-oxa-4-azacycloundecene and Dibenz[d,g]-2-azacycloundecene: Synthesis of Two New Heterocyclic Ring Systems as Potential Ligands for Dopamine Receptor Subtypes

2-(2-Hydroxyethyl)-N-[2-phenoxyethyl]benzamides and 2-(2hydroxyethyl)-N-[2-phenylpropyl]benzamides have been prepared from 2-phenoxyethyl-or 2-phenylpropylamines and isochroman-1-one.Applying Bischler-Napieralski reaction, a tetracyclic isoquinolino[2,1-d][1,4]benzoxazepine and a isoquinolino[1,2-a][2]benzazepine could be obtained.The titled compounds representing novel 11 membered heterocycles could be prepared by subsequent ring cleavage under Birch conditions after quaternisation with methyl iodide.They are considered to be ligands for dopamine receptors.NMR spectral data indicate different conformations for the two azacycloundecene derivatives.Heterocyclic compounds containing constrained indolyland phenylalkylamin-structures, like the benz[d]indolo[2,3-g]azecine (LE 300), 2 have shown to be potent and selective Dopamine D 1 /D 5receptor subtype antagonists. 1,3In further studies, the 3-hydroxydibenz[d,g]azecine (LE 404)was found to be an even more potent ligand at the human cloned D 1 /D 5 -receptor subtypes. 4 Hence we focused our interests on the dibenzo derivatives and synthesized the dibenz[g,j]-1oxa-4-azacycloundecene (1a) and the dibenz[d,g]-2-azacycloundecene (1b) in order to investigate the tolerance of the receptor for the expansion of the 10-membered condensed azecines to 11-membered ring systems and for the different electronical situation in the heterocyclus created by incorporation of an oxygen atom.Meise and coworkers have reported the synthesis O CH