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Figure 5. Compound 4g reduced mean AF/AFL duration per dog
(874 ( 122 s vs 393 ( 166 s; p = 0.033; 3 mg/kg).
clinically relevant to the human condition. AF was induced
via burst pacing (10 s, 600 bpm). Following oral administra-
tion of 4g (n = 8, 3 mg/kg), the success rate of inducing AF for
5-10 min intervals decreased 63% (Figure 4), average AF
duration decreased 55% (Figure 5), and total AF burden
(total time in AF) decreased 52%.
In summary, 4g is a potent, selective blocker of the atrial
potassium channel Kv1.5. It demonstrated efficacy in clini-
cally relevant models of AF and mechanistic models of the
cardiac action potential. In addition, its pharmacokinetic and
pharmaceutical properties were acceptable for late stage pre-
clinical development, and KVI-020/WYE-160020 (4g) has
been advanced into development for the treatment of AF.
Acknowledgment. The authors thank the Department of
Analytical Chemistry group at Wyeth Research for support of
the studies described.
Supporting Information Available: Details of the synthesis
and characterization of 4a-q: protocols for in vitro and in vivo
experiments. This material is available free of charge via the
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