3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors. 8. Side chain ether analogues of lovastatin.
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.
Lee
T J
TJ
Merck Sharp & Dohme Research Laboratories, West Point, Pennsylvania 19486.
Holtz
W J
WJ
Smith
R L
RL
Alberts
A W
AW
Gilfillan
J L
JL
D055598:Chemical Phenomena; D002621:Chemistry; D004952:Esters; D004987:Ethers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008148:Lovastatin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D004952:Esters; D004987:Ethers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C070474:6-(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; D008148:Lovastatin