Synthesis and beta-adrenergic activity of new completely aliphatic 3-(methyleneaminoxy)propanolamine derivatives.
In a previous paper, it had been found that completely aliphatic 3-(methylene aminoxy)propanolamine derivatives showed a good beta-blocking adrenergic activity directed prevalently towards beta 2-tracheal receptors. In an attempt to change the beta-adrenergic properties of these compounds from antagonist to agonist, while still retaining the beta 2-selectivity, a series of new completely aliphatic 3-(methyleneaminoxy)propanolamine derivatives were designed in which either a hydroxylic or a methoxylic group was present on the aliphatic portion linked to the oximic carbon. The synthesis of the new compounds and their beta-adrenergic activity, evaluated by means of functional tests on isolated preparations, are described and discussed; the results obtained are then rationalised on the basis of their conformational and reactivity characteristics, determined by means of theoretical methods.
Balsamo
A
A
Dipartimento di Scienze Farmaceutiche, Università di Pisa, Italy.
Gentili
D
D
Lapucci
A
A
Macchia
M
M
Martinelli
A
A
Orlandini
E
E
Ferni
G
G
Pinza
M
M
D018663:Adrenergic Agents; D000318:Adrenergic beta-Agonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008968:Molecular Conformation; D009130:Muscle, Smooth / Q000187:drug effects; D011412:Propanolamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D018663:Adrenergic Agents; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011412:Propanolamines