Synthesis and adrenergic properties of new duplicated analogs of methoxamine.
New duplicated analogs of the alpha 1-selective agonist methoxamine and of its cyclic derivative 5,8-dimethoxy-1,2,3,4-tetrahydro-2-naphthylamine have been synthesized and tested for their adrenergic properties. All the compounds prepared, presenting a polymethylene spacer of varying length between two units of the active structure, turned out to be completely devoid of any alpha-stimulating activity. Surprisingly, some of them showed a marked beta-adrenergic agonistic effect, being the most interesting compound active at nanomolar concentration.
Departament de Farmacologia I Quimica Terapeutica, Facultat de Farmacia, Universitat de Barcelona, Spain.
F
F
Perez
G
G
Rosell
D
D
Mauleon
G
G
Carganico
D000316:Adrenergic alpha-Agonists / Q000138:chemical synthesis / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000138:chemical synthesis / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000138:chemical synthesis / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008729:Methoxamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D051381:Rats; D013564:Sympathetic Nervous System / Q000187:drug effects*; D014132:Trachea / Q000187:drug effects; D014649:Vas Deferens / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D008729:Methoxamine