Design, synthesis, and biological activity of methoctramine-related polyamines as putative G(i) protein activators

The universal template approach provided a prospect of modifying methoctram ine (2) structure. Thus, polyamines 3-7 were designed in which the flexibil ity of the diamino-hexane spacer of 2 was replaced by a bipiperidinyl moiet y. In electrically stimulated guinea pig left atria, these novel polyamines , unlike prototype 2, displayed a potent intrinsic activity, which was in c ontrast 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.