Cholesterol lowering agents

Claim 2

A compound of structure (I): ##STR6## wherein Z is selected from the group consisting of: a) H; b) C 1-5 alkyl; c) C 1-5 alkyl substituted with a member of the group consisting of i) phenyl, ii) phenyl substituted with methyl, methoxy, halogen (Cl, Br, I, F) or hydroxy; or a pharmaceutically acceptable salt of a compound of formula (I).

Claim 3

A compound of claim 1 wherein Z is hydrogen.

Claim 4

A compound of claim 2 wherein Z is methyl.

Claim 5

A compound of claim 1 prepared from the fermentation of Aspergillus versicolor MF2664 (ATCC 74035) and isolated therefrom.

Claim 6

A compound of molecular formula C 31 H 40 O 8 and molecular weight 540 characterized by (a) the 13 C NMR chemical shifts (125 MHz) as measured in CDCl 2 at 20° C.; 12.3, 13.3, 14.8, 17.8, 21.0, 23.3, 27.3, 35.6, 40.2, 44.1, 47.3, 53.3, 70.2, 78.2, 79.7, 91.9, 119.7, 128.2, 128.3, 128.9, 129.1, 130.4, 130.6, 136.1, 137.0, 140.5, 142.8, 145.7, 171.5, 175.6, 209.1 ppm; (b) the 13 C NMR chemical shifts (125 MHz) as measured in CD 3 CN/CD 2 Cl 2 at 20° C.; 11.9, 13.2, 14.8, 18.1, 21.1, 23.3, 27.6, 35.8, 40.4, 44.9, 47.8, 54.2, 70.2, 78.0, 80.2, 92.0, 120.9, 128.5, 128.6, 129.2, 129.3, 131.1, 131.5, 136.2, 137.2, 141.3, 141.6, 145.2, 168.0, 175.4, 209.9 ppm; (c) an 1 H NMR spectrum (500 MHz) in CD 2 Cl 2 , as shown in FIG. 1; (d) UV spectrum in methanol wherein λ max is at 240 and 340 nm; (e) IR spectrum wherein representative peaks are 1726, 1709, 1610, 1570, 1455 and 1410 cm -1 .

Claim 7

A compound of molecular formula C 31 H 40 O 8 and molecular weight 540 characterized by (a) the 13 C NMR chemical shifts (125 MHz) as measured in CDCl 2 at 20° C.; 12.3, 13.3, 14.8, 17.8, 21.0, 23.3, 27.3, 35.6, 40.2, 44.1, 47.3, 53.3, 70.2, 78.2, 79.7, 91.9, 119.7, 128.2, 128.3, 128.9, 129.1, 130.4, 130.6, 136.1, 137.0, 140.5, 142.8, 145.7, 171.5, 175.6, 209.1 ppm; (b) the 13 C NMR chemical shifts (125 MHz) as measured in CD 3 CN/CD 2 Cl 2 at 20° C.; 11.9, 13.2, 14.8, 18.1, 21.1, 23.3, 27.6, 35.8, 40.4, 44.9, 47.8, 54.2, 70.2, 78.0, 80.2, 92.0, 120.9, 128.5, 128.6, 129.2, 129.3, 131.1, 131.5, 136.2, 137.2, 141.3, 141.6, 145.2, 168.0, 175.4, 209.9 ppm; (c) an 1 H NMR spectrum (500 MHz) in CD 2 Cl 2 , as shown in FIG. 1; (d) UV spectrum in methanol wherein λ max is at 240 and 340 nm; (e) IR spectrum wherein representative peaks are 1726, 1709, 1610, 1570, 1455 and 1410 cm -1 .

Claim 8

A pharmaceutical composition comprising a nontoxic therapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.

Claim 9

A composition of claim 6 wherein the therapeutically effective compound is selected from the group consisting of: ##STR7##

Claim 10

A pharmaceutical composition comprising a nontoxic therapeutically effective amount of a compound of claim 1 in combination with a pharmaceutically acceptable nontoxic cationic polymer capable of binding bile acids in a non-reabsorbable form in the gastrointestinal tract and pharmaceutically acceptable carrier.

Claim 11

A pharmaceutical composition comprising a nontoxic therapeutically effective amount of a compound of claim 1 in combination with a nontoxic therapeutically effective amount of a cholesterol lowering agent selected from the group consisting of: (a) HMG-CoA reductase inhibitor; (b) HMG-CoA synthase inhibitor; (c) Squalene synthetase inhibitor; (d) Squalene expoxidase inhibitor; (e) Probucol; (f) Niacin; (g) Gemfibrozil; and (h) Clofibrate.

Claim 12

A composition comprising a nontoxic therapeutically effective amount of a compound of claim 1 and an HMG-CoA reductase inhibitor.

Claim 13

A composition of claim 10 wherein the HMG-CoA reductase inhibitor is selected from lovastatin, simvastatin, pravastatin and fluvastatin.

Claim 14

A method of treating hypercholesterolemia comprising the administration to a subject in need of such treatment a nontoxic therapeutically effective amount of a compound of claim 1.

Claim 15

A method of claim 12 wherein the therapeutically effective compound is selected from the group consisting of: ##STR8##