Design and Synthesis of 4-Substituted Benzamides as Potent, Selective, and Orally Bioavailable I Ks Blockers
Multiple delayed rectifier potassium currents, including I Ks, 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 I Ks blocker...
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| Veröffentlicht in: | Journal of medicinal chemistry 2001-11, Vol.44 (23), p.3764-3767 |
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| container_end_page | 3767 |
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| container_issue | 23 |
| container_start_page | 3764 |
| container_title | Journal of medicinal chemistry |
| container_volume | 44 |
| creator | Lloyd, John Schmidt, Joan B Rovnyak, George Ahmad, Saleem Atwal, Karnail S Bisaha, Sharon N Doweyko, Lidia M Stein, Philip D Traeger, Sarah C Mathur, Arvind Conder, Mary Lee DiMarco, John Harper, Timothy W Jenkins-West, Tonya Levesque, Paul C Normandin, Diane E Russell, Anita D Serafino, Randolph P Smith, Mark A Lodge, Nicholas J |
| description | Multiple delayed rectifier potassium currents, including I Ks, 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 I Ks blocker reported to date with >5000-fold selectivity over other cardiac ion channels. Further modification produced 24A with 23% oral bioavailability. |
| doi_str_mv | 10.1021/jm015505u |
| format | Article |
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| language | eng |
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| source | ACS Publications |
| title | Design and Synthesis of 4-Substituted Benzamides as Potent, Selective, and Orally Bioavailable I Ks Blockers |
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