MEDI 27 |
| T-type calcium channels are low-voltage activated ion channels that play an important role in regulating a variety of biological processes, both peripherally and in the CNS. Several drugs such as mibefradil, ethosuximide, and pimozide have been reported to inhibit T-type calcium channels; however, their poor selectivity makes it difficult to conclusively determine the consequences of T-type calcium channel inhibition. Here, we report for the first time a class of truly selective and potent T-type channel antagonists derived from 1, 4-substituted piperidines. These inhibitors were identified though HTS screening followed by lead optimization to minimize hERG and L-type calcium channel activities. SAR and in vivo data of key compounds will be discussed in detail. |
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General Oral Session
1:30 PM-4:50 PM, Sunday, August 19, 2007 BCEC -- 210A, Oral
Division of Medicinal Chemistry |