title: Conformationally restrained analogues of sympathomimetic catecholamines. Synthesis and adrenergic activity of 5,6- and 6,7-dihydroxy-3,4-dihydrospiro[naphthalen-1(2H)-2',5'-morpholines].
abstract: The 5,6- (10a) and 6,7-dihydroxy-3,4-dihydrospiro[naphthalen-1(2H)-)-2',5'-morpholine](11a) and their N-isopropyl derivatives (10b and 11b) (DDSNMs), which can be viewed as the result of the combination of the structure of the 2-(3,4-dihydroxyphenyl)morpholine 5a or 5b (DPMs) with the structure of the corresponding 1-(aminomethyl)-5,6-dihydroxy- (8a or 8b) or 1-(aminomethyl)-6,7-dihydroxy-1,2,3,4-tetrahydro-1-naphthalen-ol (9a or 9b) (1-AMDTNs) were synthesised. The new compounds DDSNMs 10a,b and 11a,b were assayed for their alpha- and beta-adrenergic properties by means of binding experiments and functional tests and the results were compared with those obtained for catecholamines 1a, b and the previously described morpholine (5) and tetrahydronaphthalene (8, 9) derivatives. The affinity and activity indices thus obtained indicate in general a low ability of the new compounds 10 and 11 to interact with the alpha- and beta-adrenoceptors, which, in all cases, was lower than that of the corresponding morpholine (5) and tetrahydronaphthalene (8, 9) analogues.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Facolta di Farmacia, Universitá di Pisa, Via Bonanno 6, 56100 Pisa, Italy. balsamo@far.unipi.it
authors.forename: Aldo
authors.initials: A
authors.lastname: Balsamo
authors.forename: Annalina
authors.initials: A
authors.lastname: Lapucci
authors.forename: Clementina
authors.initials: C
authors.lastname: Manera
authors.forename: Adriano
authors.initials: A
authors.lastname: Martinelli
authors.forename: Susanna
authors.initials: S
authors.lastname: Nencetti
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Orlandini
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Calderone
authors.forename: Gino
authors.initials: G
authors.lastname: Giannaccini
authors.forename: Paola
authors.initials: P
authors.lastname: Nieri
mesh_terms: D000322:Adrenergic Agonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D058646:Adrenergic alpha-1 Receptor Agonists; D058647:Adrenergic alpha-2 Receptor Agonists; D058665:Adrenergic beta-1 Receptor Agonists; D058666:Adrenergic beta-2 Receptor Agonists; D000818:Animals; D001921:Brain / Q000187:drug effects; D002395:Catecholamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002417:Cattle; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects; D008297:Male; D008968:Molecular Conformation; D009025:Morpholines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013566:Sympathomimetics / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014649:Vas Deferens / Q000187:drug effects
chemical_list: D000322:Adrenergic Agonists; D058646:Adrenergic alpha-1 Receptor Agonists; D058647:Adrenergic alpha-2 Receptor Agonists; D058665:Adrenergic beta-1 Receptor Agonists; D058666:Adrenergic beta-2 Receptor Agonists; D002395:Catecholamines; D009025:Morpholines; D013141:Spiro Compounds; D013566:Sympathomimetics