An interdisciplinary approach to the design of new structures active at the beta-adrenergic receptor. Aliphatic oxime ether derivatives.
On the basis of results previously obtained from structural and theoretical studies on beta-adrenergic drugs, a series of aliphatic oxime ether derivatives (AOEDs) was synthesized. As expected, pharmacological in vitro tests showed that compounds examined exhibit a marked and competitive antagonism at beta-adrenoceptors; the beta 2/beta 1 selectivity ratio indicated that they are more active on the tracheal than on the cardiac beta-receptor. The chemical reactivity of the AOEDs was studied through the calculation of the electrostatic molecular potential (EMP) on a model compound in its preferred conformation. The results showed that the EMP trend agrees with that previously calculated for other beta-blocking drugs.
Macchia
B
B
Balsamo
A
A
Lapucci
A
A
Martinelli
A
A
Macchia
F
F
Breschi
M C
MC
Fantoni
B
B
Martinotti
E
E
D000319:Adrenergic beta-Antagonists / Q000138:chemical synthesis*; D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008958:Models, Molecular; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014132:Trachea / Q000187:drug effects; D014649:Vas Deferens / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D007545:Isoproterenol