A novel class of cholinergic agents structurally related to 2-morpholinol.
A series of esters and ethers of N-alkylmorpholin-2-ols, and their methiodides, which can be considered cyclic analogues of acetylcholine, were synthesized. The amines were obtained by acylation or etherification of morpholinols with the appropriate acyl chlorides and alcohols. All compounds were tested for their ability to interact with the muscarinic receptor M2 (guinea-pig atria) or M3 (rat ileum and urinary bladder) subtype. Some compounds, although endowed with relatively low potency, proved interesting for their organ selectivity. Some considerations on the structure-activity relationship are made and the results obtained with reference agonists and antagonists are also shown.
Feriani
A
A
Laboratori di Ricerca Glaxo, Verona, Italy.
Gaviraghi
G
G
Toson
G
G
Valsecchi
B
B
Caldirola
P
P
Ravasi
M
M
Merlini
L
L
Redaelli
C
C
Grana
E
E
Zonta
F
F
D000818:Animals; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009025:Morpholines / Q000138:chemical synthesis* / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D010277:Parasympathomimetics / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D009025:Morpholines; D010277:Parasympathomimetics