Inhibitors of cholesterol biosynthesis. 4. trans-6-[2-(substituted-quinolinyl)ethenyl/ethyl]tetrahydro-4-hydroxy-2 H-pyran-2-ones, a novel series of HMG-CoA reductase inhibitors

J Med Chem. 1991 Jan;34(1):367-73. doi: 10.1021/jm00105a057.


A series of substituted quinoline mevalonolactones were prepared and evaluated for their ability to inhibit the enzyme HMG-CoA reductase both in vitro and (cholesterol biosynthesis) in vivo. Since previous studies suggested that the 4-(4-fluorophenyl) and 2-(1-methylethyl) substituents afforded optimum potency, attention was focused on variations at position 6 of the quinoline ring. Biological evaluation of a small number of analogues bearing a variety of 6-substituents showed that modification at this position had little effect on potency. Several compounds (8b, 8e, and 11) were identified that showed comparable potency to compactin and mevinolin in both the in vitro and in vivo assays.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Anticholesteremic Agents / chemical synthesis*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors*
  • Indicators and Reagents
  • Liver / enzymology
  • Molecular Structure
  • Pyrones / chemical synthesis*
  • Pyrones / chemistry
  • Pyrones / pharmacology
  • Quinolines / chemical synthesis*
  • Quinolines / chemistry
  • Quinolines / pharmacology
  • Rats
  • Structure-Activity Relationship


  • Anticholesteremic Agents
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Indicators and Reagents
  • Pyrones
  • Quinolines