Structure activity relationships of resorcinol substituted ring systems.
Dopamine receptor agonist activity was evaluated using resorcinol derivatives of the following ring systems: dopamine, aminotetralin, indan, benzocycloheptane, octahydrobenzo(f)quinoline and octahydrobenzo[g]quinoline. The compounds were evaluated for biological activity using in vitro binding assays, anesthetized cat blood pressure and heart rate, cat cardioaccelerator nerve preparation and rotations of rats with unilateral denervation of the caudate nucleus. Resorcinol substitutions were chosen because one hydroxyl group corresponded to the alpha-conformer of dopamine and the second hydroxyl group corresponded to the beta-conformer of dopamine. Dopamine receptor activity was found primarily with derivatives of aminotetralin and octahydrobenzo[f]quinoline while the other ring systems yielded compounds which were quite inactive. The active resorcinol derivatives were found in the same ring systems where catechol substitution was active in ring positions corresponding to either the alpha- or beta-conformer of dopamine. Likewise in those ring systems where catechol substitution corresponding to the beta-conformer of dopamine were quite inactive, resorcinol substitution in these series was not favorable for activity. The ring systems requirements for alpha- and beta-adrenoceptor agonist activity did not follow the same structural pattern as found for dopamine receptor agonist activity.
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D004298:Dopamine / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D009474:Neurons / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D012118:Resorcinols / Q000494:pharmacology*; D013134:Spiperone / Q000494:pharmacology; D013239:Stereotyped Behavior / Q000187:drug effects; D013329:Structure-Activity Relationship
D011954:Receptors, Dopamine; D017981:Receptors, Neurotransmitter; D012118:Resorcinols; D013134:Spiperone; D001058:Apomorphine; D004298:Dopamine; C031389:resorcinol