N-Propylnoraporphin-11-O-yl carboxylic esters as potent dopamine D2 and serotonin 5-HT1A receptor dual ligands

A small series of N-propylnoraporphin-11-O-yl carboxylic esters with variant ester lengths were synthesized and their binding potencies at dopamine receptors (D1, D2) and serotonin receptors (5-HT1A, 5-HT2A) were evaluated. Monoesters 3a–f showed binding potency of 100 nM or less for the D2 receptor, and potency of 10–30 nM for the 5-HT1A receptor. Butyryl ester 3d was found to be the best compound possessing the highest potency for both receptors, with Ki values of 55 and 12 nM for D2 and 5-HT1A receptors, respectively. There is no correlation between the binding potency and the length of the monoesters, but the diesters 9 and 10 were inactive for the D2 receptor. The dual binding profile of these monoesters for the D2 and 5-HT1A receptors may be useful for the treatment of neuropsychiatric disorders.

A small series of N-propylnoraporphin-11-O-yl carboxylic esters with variant ester lengths were synthesized. Although the diesters 9 and 10 were inactive for the D2 receptor, all of the aporphine monoesters displayed high dual binding profile for the D2 and 5-HT1A receptors, with butyryl ester 3d as the best possessing the highest potency for both receptors, with Ki values of 55 and 12 nM, respectively.Figure optionsDownload as PowerPoint slide