The class
Optimized dibenzodioxocinone derivatives yield low-nanomolar CETP inhibitors stable in rat plasma (Bioorg Med Chem Lett 2005)
Original title: Dibenzodioxocinones--a new class of CETP inhibitors
Starting from a natural product, researchers identified compound 2, a micromolar dibenzodioxocinone-derived CETP inhibitor from high-throughput screening, but found it suffered from very low stability in plasma. Partial synthesis-based optimization of the parent natural product scaffold produced low-nanomolar inhibitors with good stability in rat plasma, establishing dibenzodioxocinones as a new, druggable class of CETP inhibitors.
Original abstract
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.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.