Synthesis and biological evaluation of dihydroeptastatin, a novel inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase.

Article Details

Citation

Bone EA, Davidson AH, Lewis CN, Todd RS

Synthesis and biological evaluation of dihydroeptastatin, a novel inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase.

J Med Chem. 1992 Sep 4;35(18):3388-93.

PubMed ID
1527791 [ View in PubMed
]
Abstract

The total synthesis of the novel hydroxylated HMG-CoA reductase inhibitor dihydroeptastatin (7) is described. The key C-3 hydroxyl group is introduced via a Baeyer-Villiger reaction on the methyl ketone 17 which is obtained in three high-yielding steps from the known tricyclic lactone 12. In an isolated enzyme assay dihydroeptastatin had a similar IC50 to mevinolin but in cellular assays using Hep G2 and HES 9 cell lines, dihydroeptastatin was much less potent. No selectivity between the two cell lines was observed.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
Lovastatin3-hydroxy-3-methylglutaryl-coenzyme A reductaseIC 50 (nM)37N/AN/ADetails
Simvastatin3-hydroxy-3-methylglutaryl-coenzyme A reductaseIC 50 (nM)12N/AN/ADetails