jm015505u_si_001.pdf (978.22 kB)
Design and Synthesis of 4-Substituted Benzamides as Potent, Selective, and Orally Bioavailable IKs Blockers
journal contribution
posted on 2001-10-17, 00:00 authored by John Lloyd, Joan B. Schmidt, George Rovnyak, Saleem Ahmad, Karnail S. Atwal, Sharon N. Bisaha, Lidia M. Doweyko, Philip D. Stein, Sarah C. Traeger, Arvind Mathur, Mary Lee Conder, John DiMarco, Timothy W. Harper, Tonya Jenkins-West, Paul C. Levesque, Diane E. Normandin, Anita D. Russell, Randolph P. Serafino, Mark A. Smith, Nicholas J. LodgeMultiple delayed rectifier potassium currents,
including IKs, are responsible for the repolarization and
termination of the cardiac action potential, and blockers of
these currents may be useful as antiarrhythmic agents.
Modification of compound 5 produced 19(S) that is the most
potent IKs blocker reported to date with >5000-fold selectivity
over other cardiac ion channels. Further modification produced
24A with 23% oral bioavailability.
