N-(ω-(4-(2-Methoxyphenyl)piperazin-1-yl)alkyl)carboxamides as Dopamine D2 and D3 Receptor Ligands

摘要: The dopamine D3 receptor is recognized as a potential therapeutic target for the treatment of various neurological and psychiatric disorders. Targetting high affinity versus D2 receptor-preferring ligands, partial agonist BP 897 was taken lead structure. Variations in spacer aryl moiety led to N-alkylated 1-(2-methyoxyphenyl)piperazines with markedly improved selectivity. Molecular modeling studies supported structural development. Pharmacophore models ligands were developed from their potentially bioactive conformation compared order get insight into molecular properties importance D2/D3 For 72 compounds presented here, an extended more linear aliphatic or spacers turned out be crucial Structural diversity (benzamides, heteroarylamides, arylimides) had major influence on (sub)nanomolar rec...