Design and synthesis of 4-substituted benzamides as potent, selective, and orally bioavailable IKs blockers

被引：16

作者：

Lloyd, J ^{[1
]}

Schmidt, JB ^{[1
]}

Rovnyak, G ^{[1
]}

Ahmad, S ^{[1
]}

Atwal, KS ^{[1
]}

Bisaha, SN ^{[1
]}

Doweyko, LM ^{[1
]}

Stein, PD ^{[1
]}

Traeger, SC ^{[1
]}

Mathur, A ^{[1
]}

Conder, ML ^{[1
]}

DiMarco, J ^{[1
]}

Harper, TW ^{[1
]}

Jenkins-West, T ^{[1
]}

Levesque, PC ^{[1
]}

Normandin, DE ^{[1
]}

Russell, AD ^{[1
]}

Serafino, RP ^{[1
]}

Smith, MA ^{[1
]}

Lodge, NJ ^{[1
]}

机构：

[1] Bristol Myers Squibb Co, Pharmaceut Res Inst, Princeton, NJ 08543 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2001年 / 44卷 / 23期

关键词：

D O I：

10.1021/jm015505u

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 IF, blocker reported to date with > 5000-fold selectivity over other cardiac ion channels. Further modification produced 24A with 23% oral bioavailability.

引用

页码：3764 / 3767

页数：4

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