New aporphines containing C10 nitrogen substituents (viz. nitro, aniline or amide moieties), were synthesized and evaluated for affinity at human serotonin 5-HT(1A) and 5-HT(2A) receptors and at human dopamine D(1), D(2) and D(5) receptors. Two series of analogs were investigated: series A which contain a sole C10 nitrogen substituent on the tetracyclic aporphine core and series B which are 1,2,10-trisubstituted aporphines. Remarkably, compounds from both series lacked affinity for the D(5) receptor, thus attaining D(1) versus D(5) selectivity. Compound 20c was the most potent D(1) ligand identified. Docking studies at D(1) and D(5) receptors indicate that the binding mode of 20c at the D(1) receptor allows for stronger hydrophobic contacts, (primarily with Phe residues) as compared to the D(5) receptor, accounting for its D(1) versus D(5) selectivity. Considering the lack of affinity for the D(5) receptor (and low affinity at other receptors tested), compound 20c represents an interesting starting point for further structural diversification of aporphines as sub-type selective D(1) receptor tools. CI - Copyright (c) 2020 Elsevier Ltd. All rights reserved.