MEDI 25 |
| Helicobacter pylori, a Gram-negative bacterium, has been shown to cause gastritis and gastric ulcers, and has been linked to some gastric cancers. High-throughput screening efforts had previously identified benzodiazepines as selective inhibitors of H. pylori glutamate racemase (MurI), an enzyme essential for cell-wall biosynthesis. An analog program was carried out to increase enzyme inhibitory potency, improve antibacterial activity, and optimize physical properties for oral administration. The HTS hit (I) was transformed into an advanced lead compound (II) with improved physical properties. The precedented synthetic methods for making benzodizepines involves many steps and the use of toxic reagents. An alternative, more robust synthesis was designed to allow for the rapid synthesis of a larger range of analogs including the incorporation of heteroatoms into the benzodiazepine core.
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General Oral Session
1:30 PM-4:50 PM, Sunday, August 19, 2007 BCEC -- 210A, Oral
Division of Medicinal Chemistry |
