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