Zhao F, Darling JE, Gibbs RA, Hougland JL
Bioorg Med Chem Lett. 2015 May 15. pii: S0960-894X(15)00459-X. doi: 10.1016/j.bmcl.2015.05.009. [Epub ahead of print]
Inhibitors of ghrelin O-acyltransferase (GOAT) have untapped potential as therapeutics targeting obesity and diabetes. We report the first examples of GOAT inhibitors incorporating a triazole linkage as a biostable isosteric replacement for the ester bond in ghrelin and amide bonds in previously reported GOAT inhibitors. These triazole-containing inhibitors exhibit sub-micromolar inhibition of the human isoform of GOAT (hGOAT), and provide a foundation for rapid future chemical diversification and optimization of hGOAT inhibitors.
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