The N-isopropyl- (3a-g) and N-tert-butyl-substituted (4a-g) (Z)-N-(3-(amino)-2-hydroxypropylidene)-(arylmethyloxy)amines were synthesized in order to compare their beta 1- and beta 2-adrenergic properties with those of their previously studied corresponding analogues with the E configuration (1a-g and 2a-g). Compounds 3 and 4 were tested for their affinity for beta 1-a and beta 2-adrenoceptors by radioligand binding experiments, and the compounds with the highest affinity were also assayed for their activity towards the same types of beta-adrenoceptors by functional tests on isolated preparations. The Z-methyloxyiminomethyl (Z-MOIM) compounds 3 and 4 proved to possess, on the whole, affinity (Ki) and activity (PIC50) indices similar to those of the E isomers 1 and 2, thus indicating that for the MOIM-type beta-adrenergic antagonists 1-4, the type of configuration around the MOIM double bond does not have any appreciable effect either on the affinity or on the activity towards beta-adrenoceptors. These results are rationalized on the basis of the steric and electronic analogies existing between the MOIM groups of 1-4 in the two types of configurations (E and Z).
|Autori:||A. BALSAMO; M.C. BRESCHI; G. CHIELLINI; A. LAPUCCI; N. LAZZERI; M. MACCHIA; A. MARTINELLI; E. MICALI; S.NENCETTI; ROSSELLO A|
|Titolo:||Synthesis and ß-Adrenergic Properties Of (Z)-N-[3-(Alkylamino)-2-hydroxypropilidene](aryl-methyloxy)amines: Effects Of The Configuration Around The Methyloxyiminomethyl(MOIM) Double Bond On The Biopharmacological Properties Of MOIM-type ß-Blocking Agents|
|Anno del prodotto:||1998|
|Digital Object Identifier (DOI):||10.1016/S0968-0896(98)00172-2|
|Appare nelle tipologie:||1.1 Articolo in rivista|