Synthesis and biological evaluation of new muscarinic receptor antagonists bearing cyclic amidines as cationic heads.
Two classes of compounds, bearing a cyclic amidino moiety instead of the tertiary amino group of the classical antimuscarinic drugs like hexahydrodifenidol 3 were synthesized. Affinities (KD) for the three pharmacologically defined M1, M2 and M3 mAChR subtypes were measured in radioligand binding assays and in functional in vitro studies (KB) in guinea pig ileum and left atrium. The results showed that the replacement of the tertiary amino group in structural analogues of 3 with a cyclic amidino moiety afforded potent antimuscarinic compounds. The selectivity shown for smooth muscle preparations suggests their usefulness as antispasmodics.
Istituto de Angeli, Milano.
M
M
Nicola
G B
GB
Schiavi
R
R
Micheletti
A
A
Donetti
H
H
Ladinsky
M
M
Turconi
D000578:Amidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D002412:Cations / Q000737:chemistry; D006168:Guinea Pigs; D066298:In Vitro Techniques; D018727:Muscarinic Antagonists; D009130:Muscle, Smooth / Q000187:drug effects; D010276:Parasympatholytics / Q000138:chemical synthesis / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D011976:Receptors, Muscarinic / Q000378:metabolism
D000578:Amidines; D002412:Cations; D018727:Muscarinic Antagonists; D010276:Parasympatholytics; D011976:Receptors, Muscarinic