Dibenzodioxocinones—A new class of CETP inhibitors

Derivatives of the natural product 11-hydroxy-3-[(S)-1-hydroxy-3-methylbutyl]-4-methoxy-9-methyl-5H,7H-dibenzo[b,g][1,5]dioxocin-5-one 1 were studied as novel CETP inhibitors. Compound 2 was identified from HTS as a micromolar inhibitor. The compound suffered from very low stability in plasma. Optimisation by partial synthesis started from 1 and led to low-nanomolar inhibitors with good stability in rat plasma.

Graphical abstractDibenzodioxocinones with high inhibitory potential for CETP and good plasma stability were prepared by semisynthesis from a natural product precursor.Figure optionsDownload full-size imageDownload as PowerPoint slide