Further structure-activity relationships study of hybrid 7-{[2-(4-phenylpiperazin-1-yl)ethyl]propylamino}-5,6,7,8-tetrahydronaphthalen-2-ol analogues: identification of a high-affinity D3-preferring agonist with potent in vivo activity with long duration of action.

摘要: This paper describes an extended structure–activity relationships study of aminotetralin−piperazine-based hybrid molecules developed earlier for dopamine D2/D3 receptors. Various analogues as positional isomers have been where location the phenolic hydroxyl group has varied on aromatic ring. Between two catechol derivatives, compound 6e with a methylene linker length exhibited higher affinity and selectivity D3 over D2 receptors 6f four linkers (D2/D3 = 50.6 vs 7.51 6f, respectively). In general, (−)-isomer was more potent than (+)-isomeric counterpart. Binding results indicated highest in (−)-10 (Ki 0.35 nM; 71). 5-hydroxy series, by (−)-25 0.82 31.5). Most compounds binding functional affinities at sub-nanomolar level receptor. assays were carried out w...