Synthesis of novel β-lactone inhibitors of fatty acid synthase

…, M Zancanella, LM Knowles, P Cieplak…

Index: Richardson, Robyn D.; Knowles, Lynn M.; Cieplak, Piotr; Smith, Jeffrey W.; Ma, Gil; Oyola, Yatsandra; Zancanella, Manuel; Romo, Daniel Journal of Medicinal Chemistry, 2008 , vol. 51, # 17 p. 5285 - 5296

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Citation Number: 45

Abstract

Fatty acid synthase (FAS) is necessary for growth and survival of tumor cells and is a promising drug target for oncology. Here, we report on the syntheses and activity of novel inhibitors of the thioesterase domain of FAS. Using the structure of orlistat as a starting point, which contains a β-lactone as the central pharmacophore, 28 novel congeners were synthesized and examined. Structural features such as the length of the α-and β-alkyl ...

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