title: 2-Amino- and 2-guanidino-1,2,3,4-tetrahydro-1,4-epoxynaphthalenes as conformationally defined analogues of alpha-adrenergic agents.
abstract: The exo- and endo-2-amino-5,8-dimethoxy-1,2,3,4-tetrahydro-1,4-epoxynaphthalenes++ + (3b and 4b, respectively) were prepared and evaluated as conformationally defined analogues of the alpha 1-agonist methoxamine. Only compound 3b exhibited significant alpha 1-agonist activity in the field stimulated rat vas deferens assay. Since 3b closely approximates the antiperiplanar form of (1R,2S)-(-)-erythro-methoxamine, the results suggest that methoxamine interacts with the alpha 1-adrenoceptor in the trans extended form. The exo-guanidino derivative 5 was found to be a partial alpha 1-agonist. Among the exo- and endo-2-amino-1,2,3,4-tetrahydro-1,4-epoxynaphthalenes (3a and 4a, respectively) prepared as rigid analogues of norephedrine, compound 3a possessed agonist activity at both alpha 1- and alpha 2-adrenoceptors, whereas 4a was inactive at either receptor.
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004852:Epoxy Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D004988:Ethers, Cyclic / Q000138:chemical synthesis*; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D008968:Molecular Conformation; D009281:Naphthalenes / Q000138:chemical synthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D013329:Structure-Activity Relationship; D013764:Tetrahydronaphthalenes / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000316:Adrenergic alpha-Agonists; D004852:Epoxy Compounds; D004988:Ethers, Cyclic; D009281:Naphthalenes; D011942:Receptors, Adrenergic, alpha; D013764:Tetrahydronaphthalenes; C052398:2-amino-5,8-dimethoxy-1,2,3,4-tetrahydro-1,4-epoxynaphthalene; C052399:2-guanidino-5,8-dimethoxy-1,2,3,4-tetrahydro-1,4-epoxynaphthalene; D008729:Methoxamine