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 α- and β-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 α- and β-adrenoceptors, which, in all cases, was lower than that of the corresponding morpholine ( 5) and tetrahydronaphthalene ( 8, 9) analogues.