N-Propylnoraporphin-11- O-yl carboxylic esters as potent dopamine D 2 and serotonin 5-HT 1A receptor dual ligands

Abstract

A small series of N-propylnoraporphin-11- O-yl carboxylic esters with variant ester lengths were synthesized and their binding potencies at dopamine receptors (D 1, D 2) and serotonin receptors (5-HT 1A, 5-HT 2A) were evaluated. Monoesters 3a– f showed binding potency of 100 nM or less for the D 2 receptor, and potency of 10–30 nM for the 5-HT 1A receptor. Butyryl ester 3d was found to be the best compound possessing the highest potency for both receptors, with K i values of 55 and 12 nM for D 2 and 5-HT 1A 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 D 2 receptor. The dual binding profile of these monoesters for the D 2 and 5-HT 1A receptors may be useful for the treatment of neuropsychiatric disorders.