title: Spirotetrahydronaphthalene analogues of sympathomimetic catecholamines. Synthesis and adrenergic activity of 5,6- and 6,7-dihydroxy-3,4-dihydrospiro[naphthalen-1 (2H)-3'-piperidines].
abstract: The 5,6- (5a) and 6,7-dihydroxy-3,4-dihydrospiro[naphthalen-1 (2H)-3'-piperidine] (6a) and their N-isopropyl derivatives (5b and 6b), DDSNPs, were synthesized. These compounds can be viewed as the result of the combination of the structure of the 3-(3,4-dihydroxyphenyl)-piperidine 2a or 2b, with the structure of the corresponding 1-(aminomethyl)-5,6-dihydroxy-(3a or 3b) or 1-(aminomethyl)-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (4a or 4b), 1-AMDTNs. The new compounds (5a, b and 6a, 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 3-(3,4-dihydroxyphenyl)piperidine (3-DPP; 2) and 1-AMDTNs (3, 4). Comparison of the affinity and activity data of novel derivatives with those of reference compounds 2, 3 and 4 shows a general low ability of DDSNPs 5 and 6 to interact with both alpha and beta- adrenoceptors.
authors: Dipartimento di Scienze Farmaceutiche, Facoltà di Farmacia, Università di Pisa, Italy. bmacchia@farm.unipi.it
authors: Bruno
authors: B
authors: Macchia
authors: Clementina
authors: C
authors: Manera
authors: Adriano
authors: A
authors: Martinelli
authors: Susanna
authors: S
authors: Nencetti
authors: Elisabetta
authors: E
authors: Orlandini
authors: Maria Cristina
authors: MC
authors: Breschi
authors: Claudia
authors: C
authors: Martini
authors: Enrica
authors: E
authors: Martinotti
mesh_terms: D000818:Animals; D002395:Catecholamines / Q000494:pharmacology*; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D006168:Guinea Pigs; D008297:Male; D009928:Organ Specificity; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013141:Spiro Compounds / Q000494:pharmacology*; D013566:Sympathomimetics / Q000494:pharmacology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
chemical_list: C470176:5,6-dihydroxy-3,4-dihydrospiro(naphthalene-1(2H)-3'-piperidine); C470175:6,7-dihydroxy-3,4-dihydrospiro(naphthalene-1(2H)-3'-piperidine); D002395:Catecholamines; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D013141:Spiro Compounds; D013566:Sympathomimetics; D013764:Tetrahydronaphthalenes