β-Lactam congeners of orlistat as inhibitors of fatty acid synthase

β-Lactam derivatives of orlistat were prepared and their inhibitory activities toward the thioesterase domain of fatty acid synthase (FAS-TE) were evaluated using a recombinant form of the enzyme. While in general these derivatives showed lower potency compared to β-lactones, a reasonably potent, lead compound (−)-9 (IC50 = 8.6 μM) was discovered that suggests that this class of compounds should be evaluated further.

Figure optionsDownload as PowerPoint slide