Spirotetrahydronaphthalene analogues of sympathomimetic catecholamines. Synthesis and adrenergic activity of 5,6- and 6,7-dihydroxy-3,4-dihydrospiro[naphthalen-1 (2H)-3'-piperidines].
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.
Macchia
Bruno
B
Dipartimento di Scienze Farmaceutiche, Facoltà di Farmacia, Università di Pisa, Italy. bmacchia@farm.unipi.it
Manera
Clementina
C
Martinelli
Adriano
A
Nencetti
Susanna
S
Orlandini
Elisabetta
E
Breschi
Maria Cristina
MC
Martini
Claudia
C
Martinotti
Enrica
E
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*
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