Hypercholesterolemia is known to be one of the prime risk factors of cardiovascular disease, such as arteriosclerosis, and there is still no effective antihypercholesterolemic agent commercially available that has been found wide patient acceptance. The bile acid sequestrants seem to be moderately effective but they must be comsumed in large quantities, i.e. several grams at a time and they are not very palatable.
There are agents known, however, that are very active antihypercholesterolemic agents that function by limiting cholesterol biosynthesis by inhibiting the enzyme, HMG-CoA reductase. These agents include the natural fermentation products compactin and mevinolin and a variety of semi-synthetic and totally synthetic analogs thereof. The naturally occurring compounds and their semisynthetic analogs have the following general structural formulae: ##STR2## wherein: R.sup.3 is hydrogen, C.sub.1-5 alkyl or C.sub.1-5 alkyl substituted with a member of the group consisting of phenyl, dimethylamino, or acetylamino;
R.sup.4 is: ##STR3## wherein Q is ##STR4## R.sup.5 is H or OH: R.sup.6 is hydrogen or methyl; and
a, b, c, and d represent optional double bonds, especially where b and d represent double bonds or a, b, c, and d are all single bonds. PA1 Active metabolites of mevinolin which possess a 2,3,5,6,7,8-hexahydronapthyl moiety and a 3-hydroxy group are disclosed and claimed in co-pending application Ser. No. 856,251, filed Apr. 28, 1986, now U.S. Pat. No. 4,738,982. These metabolites are represented by the following general structural formulae: ##STR5## PA1 R.sup.1 is hydrogen, C.sub.1-5 alkyl, C.sub.1-5 alkyl substituted with a member of the group consisting of phenyl, dimethylamino, or acetylamino
USPTO Backgrounds
USPTO Backgrounds