The tetrahydrobenzocycloheptene analogs 7-10 of norepinephrine (NE, 1) and isoproterenol (ISO, 2) were synthesized and tested for their alpha- and beta-adrenergic properties by means of functional tests on isolated preparations. The conformational profile of 7 was studied by means of theoretical calculations. The results of the pharmacological tests showed that, in general, the cyclization of NE (1) and ISO (2) to their semirigid analogs 7-10 leads to a marked reduction or even to the disappearance of the adrenergic activity of the corresponding open-chain compounds 1 and 2. Possible rationalizations of the differences in alpha(2)-adrenergic activity shown by the benzocycloheptene derivative 7 and the corresponding previously studied tetrahydronaphthalene derivative 3 are suggested on the basis of a comparison of their stereostructures in the preferred conformations.
|Autori:||MACCHIA B; BRESCHI MC; GENTILI D; LAPUCCI A; MACCHIA M; MANERA C; MARTINELLI A; MARTINOTTI E; NENCETTI S; NIERI P|
|Titolo:||CONFORMATIONALLY RESTRAINED ANALOGS OF SYMPATHOMIMETIC CATECHOLAMINES - SYNTHESIS AND ADRENERGIC ACTIVITY OF TETRAHYDROBENZOCYCLOHEPTENE DERIVATIVES|
|Anno del prodotto:||1994|
|Digital Object Identifier (DOI):||10.1016/0223-5234(94)90133-3|
|Appare nelle tipologie:||1.1 Articolo in rivista|