3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors. 8. Side chain ether analogues of lovastatin

T J Lee; W J Holtz; R L Smith; A W Alberts; J L Gilfillan

doi:10.1021/jm00112a024

3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors. 8. Side chain ether analogues of lovastatin

J Med Chem. 1991 Aug;34(8):2474-7. doi: 10.1021/jm00112a024.

Authors

T J Lee¹, W J Holtz, R L Smith, A W Alberts, J L Gilfillan

Affiliation

¹ Merck Sharp & Dohme Research Laboratories, West Point, Pennsylvania 19486.

PMID: 1875344
DOI: 10.1021/jm00112a024

Abstract

A general route for preparing side chain ether analogues of lovastatin is presented. These analogues proved to be weaker inhibitors of HMG-CoA reductase than the corresponding side chain ester analogues. Interestingly, inhibitory potency was enhanced markedly when the 4-fluoro group was incorporated in the aromatic moiety of the side chain benzyl group of 2d.

Publication types

Comparative Study

MeSH terms

Chemical Phenomena
Chemistry
Esters
Ethers
Hydroxymethylglutaryl-CoA Reductase Inhibitors*
Lovastatin / analogs & derivatives*
Lovastatin / chemical synthesis
Lovastatin / pharmacology
Molecular Structure
Structure-Activity Relationship

Substances

Esters
Ethers
Hydroxymethylglutaryl-CoA Reductase Inhibitors
6-(2-(8-((4-fluorobenzyl)oxy)-1,2,6,7,8,8a-hexahydro-2,6-dimethyl-1-naphthyl)ethyl)-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one
Lovastatin