Structure–activity relationship of dopaminergic halogenated 1-benzyl-tetrahydroisoquinoline derivatives

NOUREDDINE EL AOUAD, INMACULADA BERENGUER, VANESSA ROMERO, PALOMA MARıN, A´ NGEL SERRANO, SEBASTIAN ANDUJAR, FERNANDO SUVIRE, ALMUDENA BERMEJO, M. DOLORES IVORRA, RICARDO D. ENRIZ, NURIA CABEDO, DIEGO CORTES

EUROPEAN JOURNAL OF MEDICAL CHEMISTRY

Año: 2009 p. 4616 - 4621

0223-5234

Two series of halogenated 1-benzyl-7-chloro-6-hydroxy-tetrahydroisoquinolines were prepared to explore the influence of each series on the affinity for dopamine receptors. All the compounds displayed a high affinity for D1-like and/or D2-like dopamine receptors in striatal membranes, although they were unable to inhibit [3H]-dopamine uptake in striatal synaptosomes. The halogen placed on the benzylic ring in 1-benzyl-THIQs, compounds of the series 1, 20-bromobenzyl derivatives with Ki values into the nanomolar range, and the series 2, 20,40-dichlorobenzyl-THIQ homologues, proves to be an important factor to modulate affinity at dopamine receptor.