Design, Synthesis, and Biological Activity of Methoctramine-Related Polyamines as Putative Gi Protein Activators

The universal template approach provided a prospect of modifying methoctramine (2) structure. Thus, polyamines 3−7 were designed in which the flexibility of the diaminohexane spacer of 2 was replaced by a bipiperidinyl moiety. In electrically stimulated guinea pig left atria, these novel polyamines,...

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Bibliographic Details
Published in:Journal of medicinal chemistry 2001-11, Vol.44 (24), p.4035-4038
Main Authors: Melchiorre, Carlo, Bolognesi, Maria L, Budriesi, Roberta, Ghelardini, Carla, Chiarini, Alberto, Minarini, Anna, Rosini, Michela, Tumiatti, Vincenzo, Wade, Erik J
Format: Article
Language:English
Subjects:
Biological and medical sciences
Medical sciences
Miscellaneous
Pharmacology. Drug treatments
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Summary:The universal template approach provided a prospect of modifying methoctramine (2) structure. Thus, polyamines 3−7 were designed in which the flexibility of the diaminohexane spacer of 2 was replaced by a bipiperidinyl moiety. In electrically stimulated guinea pig left atria, these novel polyamines, unlike prototype 2, displayed a potent intrinsic activity, which was in contrast with the muscarinic antagonism shown in binding studies by some of them (3 and 4) and was inhibited by benzalkonium chloride, an inhibitor of Gi proteins.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm0155594