Synthesis and biological evaluation of potential bisubstrate inhibitors of protein farnesyltransferase. Design and synthesis of functionalized imidazoles |
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Authors: | de Figueiredo Renata Marcia Coudray Laëtitia Dubois Joëlle |
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Institution: | Institut de Chimie des Substances Naturelles, CNRS, Avenue de la Terrasse, 91198, Gif-sur-Yvette cedex, France. |
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Abstract: | A novel series of compounds, derived from 2,5-functionalized imidazoles, have been synthesized as potential bisubstrate inhibitors of protein farnesyltransferase (FTase) using structure-based design. These compounds have a 1,4-diacid chain and a tripeptide connected by an imidazole ring. The synthetic strategy relies on the functionalization at the C-2 position of the heterocycle with the diacid side chain and peptide coupling at the C-5 position. Several new compounds were synthesized in good yields. Kinetic experiments on the most active compounds revealed different binding modes depending on the diacid chain length. |
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