Design, synthesis, and biological activity of methoctramine-related polyamines as putative G(i) 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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| Veröffentlicht in: | Journal of medicinal chemistry 2001-11, Vol.44 (24), p.4035-4038 |
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| container_end_page | 4038 |
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| container_issue | 24 |
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| container_title | Journal of medicinal chemistry |
| container_volume | 44 |
| creator | Melchiorre, C Bolognesi, M L Budriesi, R Ghelardini, C Chiarini, A Minarini, A Rosini, M Tumiatti, V Wade, E J |
| description | 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 G(i) proteins. |
| doi_str_mv | 10.1021/jm0155594 |
| format | Article |
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| language | eng |
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| source | MEDLINE; American Chemical Society (ACS) Journals |
| subjects | Animals Atrial Function CHO Cells Cricetinae Diamines - chemistry Diamines - metabolism Drug Design Electric Stimulation GTP-Binding Protein alpha Subunits, Gi-Go - metabolism Guinea Pigs Heart Atria - drug effects Humans In Vitro Techniques Muscarinic Agonists - pharmacology Polyamines - chemical synthesis Polyamines - chemistry Polyamines - metabolism Polyamines - pharmacology Rats Receptors, Muscarinic - metabolism Structure-Activity Relationship |
| title | Design, synthesis, and biological activity of methoctramine-related polyamines as putative G(i) protein activators |
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