5,7-Dihydroxy-2-aminotetralin derivatives: synthesis and assessment of dopaminergic and adrenergic actions.
Replacement of the catechol 3,4-dihydroxylation pattern of certain adrenergic beta-phenethylamines by a resorcinol 3,5-dihydroxylation pattern has led to a greater selectivity of adrenergic agonist effects in certain molecules. This strategy has been applied to a series of dopaminergic agents derived from 2-aminotetralin, leading to a 5,7-dihydroxylation pattern. Traditional literature approaches to formation of a tetralin ring with this oxygenation pattern failed. A method was used which involved cyclization of 3,5-dimethoxybenzylsuccinic acid derivatives with pyridinium poly(HF) and subsequent modification of the tetralin ring. The resorcinol-derived 2-aminotetralins were less potent and less active dopaminergic agents than their catechol-derived isomers (5,6-dihydroxy and/or 6,7-dihydroxy). Certain of the subject compounds demonstrated alpha- and beta 1-adrenoceptor activating properties.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D055598:Chemical Phenomena; D002621:Chemistry; D004285:Dogs; D004298:Dopamine / Q000502:physiology*; D005260:Female; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009281:Naphthalenes / Q000138:chemical synthesis*; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects; D011954:Receptors, Dopamine / Q000187:drug effects; D013566:Sympathomimetics / Q000138:chemical synthesis*; D013764:Tetrahydronaphthalenes / Q000138:chemical synthesis* / Q000494:pharmacology
D009281:Naphthalenes; D011941:Receptors, Adrenergic; D011954:Receptors, Dopamine; D013566:Sympathomimetics; D013764:Tetrahydronaphthalenes; C029218:5,7-dihydroxy-2-aminotetralin; D004298:Dopamine