Dibenzodioxocinones—A new class of CETP inhibitors

Dibenzodioxocinones with high inhibitory potential for CETP and good plasma stability were prepared by semisynthesis from a natural product precursor. Derivatives of the natural product 11-hydroxy-3-[( S)-1-hydroxy-3-methylbutyl]-4-methoxy-9-methyl-5 H,7 H-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.