Phosphorus-containing inhibitors of HMG-CoA reductase. 2. Synthesis and biological activities of a series of substituted pyridines containing a hydroxyphosphinyl moiety

J A Robl; L A Duncan; J Pluscec; D S Karanewsky; E M Gordon; C P Ciosek Jr; L C Rich; V C Dehmel; D A Slusarchyk; T W Harrity

doi:10.1021/jm00113a019

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.

Authors

J A Robl¹, L A Duncan, J Pluscec, D S Karanewsky, E M Gordon, C P Ciosek Jr, L C Rich, V C Dehmel, D A Slusarchyk, T W Harrity, et al.

Affiliation

¹ Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000.

PMID: 1895299
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