3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors. 6. Trans-6-[2-(substituted-1-naphthyl)ethyl(or ethenyl)]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-ones

J Med Chem. 1990 Feb;33(2):758-65. doi: 10.1021/jm00164a047.

Abstract

A variety of trans-6-[2-(substituted-1-naphthyl)ethyl(or ethenyl)]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-ones were prepared and, upon conversion to their 3,5-dihydroxy carboxylates, were found to have good inhibitory activity against the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase, the rate-determining enzyme in cholesterogenesis. The most active compounds are 2,4,6- and 2,4,7-trichloro derivatives and would be expected to display about the same potency as the standard compactin upon resolution.

MeSH terms

  • Chemical Phenomena
  • Chemistry
  • Chemistry, Physical
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors*
  • In Vitro Techniques
  • Naphthalenes / chemical synthesis*
  • Naphthalenes / metabolism
  • Naphthalenes / pharmacology
  • Pyrans / chemical synthesis*
  • Pyrans / metabolism
  • Pyrans / pharmacology
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Naphthalenes
  • Pyrans