1. Structure-activity relationship of dopaminergic halogenated 1-benzyl-tetrahydroisoquinoline derivatives
- Author
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Almudena Bermejo, Ricardo D. Enriz, Sebastian A. Andujar, Vanessa Romero, Noureddine El Aouad, Diego Cortes, M. Dolores Ivorra, Nuria Cabedo, Fernando D. Suvire, Angel Serrano, Paloma Marín, and Inmaculada Berenguer
- Subjects
inorganic chemicals ,Halogenation ,Stereochemistry ,Chemical synthesis ,Receptors, Dopamine ,Structure-Activity Relationship ,chemistry.chemical_compound ,Structure–activity relationships ,Dopamine ,Tetrahydroisoquinolines ,Biogenic amine ,Drug Discovery ,medicine ,Animals ,Structure–activity relationship ,Rats, Wistar ,Neurotransmitter ,Dopamine receptors ,STRUCTURE-ACTIVITY RELATIONSHIPS ,Pharmacology ,chemistry.chemical_classification ,1-Halogenated benzyl-7-chloro-6-hydroxy-tetrahydroisoquinolines ,Dopamine uptak ,Receptors, Dopamine D2 ,Receptors, Dopamine D1 ,Otras Ciencias Químicas ,Organic Chemistry ,Dopaminergic ,Ciencias Químicas ,General Medicine ,Binding ,1-Halogenated benzyl-7-chloro-6-hydroxytetrahydroisoquinolines ,Rats ,chemistry ,Dopamine receptor ,DOPAMINE UPTAKE ,Catecholamine ,Female ,CIENCIAS NATURALES Y EXACTAS ,Protein Binding ,medicine.drug - Abstract
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 D(1)-like and/or D(2)-like dopamine receptors in striatal membranes, although they were unable to inhibit [(3)H]-dopamine uptake in striatal synaptosomes. The halogen placed on the benzylic ring in 1-benzyl-THIQs, compounds of the series 1, 2'-bromobenzyl derivatives with K(i) values into the nanomolar range, and the series 2, 2',4'-dichlorobenzyl-THIQ homologues, proves to be an important factor to modulate affinity at dopamine receptor. (C) 2009 Elsevier Masson SAS. All rights reserved., This research was supported by the Spanish "Ministerio de Educacion y Ciencia" grant SAF 2007-63142. I. Berenguer acknowledges the fellowship of Generalitat Valenciana. S. Andujar acknowledges the fellowship of CONICET-Argentina.
- Published
- 2009
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