Synthesis and biological evaluation of dihydroeptastatin, a novel inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase.
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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
Drug Target Property Measurement pH Temperature (°C) Lovastatin 3-hydroxy-3-methylglutaryl-coenzyme A reductase IC 50 (nM) 37 N/A N/A Details Simvastatin 3-hydroxy-3-methylglutaryl-coenzyme A reductase IC 50 (nM) 12 N/A N/A Details