Phosphorus-containing Inhibitors of HMG-CoA Reductase. 2. Synthesis and Biological Activities of a Series of Substituted Pyridines Containing a Hydroxyphosphinyl Moiety

J Med Chem. 1991 Sep;34(9):2804-15. doi: 10.1021/jm00113a019.

Abstract

A series of 2,3,4,(5),6-substituted pyridines containing a hydroxyphosphinyl functionally have been prepared and were evaluated for their ability to inhibit the enzyme HMG-CoA reductase. Systematic substitution of both R1-R4 and X-Y led to compounds of type 3-6 with in vitro potency greater than that of mevinolin (Na salt).

MeSH terms

  • Animals
  • Cholesterol / biosynthesis
  • Fibroblasts / metabolism
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors*
  • Hypolipidemic Agents
  • In Vitro Techniques
  • Liver / metabolism
  • Lovastatin / pharmacology
  • Organophosphorus Compounds / chemistry*
  • Oxidation-Reduction
  • Pyridines / chemical synthesis*
  • Pyridines / pharmacology
  • Rats
  • Skin / cytology
  • Skin / metabolism

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Hypolipidemic Agents
  • Organophosphorus Compounds
  • Pyridines
  • Cholesterol
  • Lovastatin