New 2-thioether-substituted apomorphines as potent and selective dopamine D2 receptor agonists

Abstract A set of novel apomorphine derivatives were synthesized with diversely functionalized side chains in the proximity of position 2 of the aporphine skeleton. Amino and/or carboxylic functions were introduced to this region of the backbone to test their pharmacological effects. During the synthesis of 2-( S -3-mercaptopropionic acid)-derivative a heteroring-fused congener was also isolated. The structural elucidation confirmed that the formation of this product was in accordance with our previous observations on the reaction of thebaine ( 2 ) with thiosalycilic acid. All the novel apomorphine congeners 4a – g were neuropharmacologically characterized to discover their dopaminergic profiles. Two derivatives were identified as D 2 full agonists equipotent with apomorphine ( 1 ) having significantly increased D 2 /D 1 selectivity ratios.