Claims
- 1. A compound represented by the following general structural formula (I'): ##STR35## wherein: n is 2 to 7;
- R.sup.1 is C.sub.1-6 alkyl; C.sub.1-6 alkyl substituted with a group selected from halogen or hydroxy; C.sub.1-6 alkylthio; phenylmethyl or 4-hydroxyphenylmethyl;
- A is ##STR36## b and d represent single bonds, or both b and d represent double bonds.
- 2. A compound of claim 1 wherein
- n is 2 to 5; and
- R.sup.1 is C.sub.1-6 alkyl; hydroxy-C.sub.1-6 alkyl; C.sub.1-6 alkylthio; phenylmethyl; or 4-hydroxyphenylmethyl.
- 3. A compound of claim 2 wherein n is 2.
- 4. A compound of claim 3 which is 6(R)-[2-[8(S)-(1-Methylcyclopropanecarbonyloxy)-2(S),6(R)-dimethyl-1,2,6,7,8,8a(R)-hexahydronaphthyl-1(S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
- 5. A compound of claim 2 wherein n is 3.
- 6. A compound of claim 5 which is 6(R)-[2-[8(S)-(1-Methylcyclobutanecarbonyloxy)-2(S),6(R)-dimethyl-1,2,6,7,8,8a(R)-hexahydronaphthyl-1(S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
- 7. A compound of claim 5 which is 6(R)-[2-[8(S)-(1-Methylthiocyclobutanecarbonyloxy)-2(S),6(R)-dimethyl-1,2,6,7,8,8a(R)-hexahydronaphthyl-1(S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
- 8. A compound of claim 5 which is 6(R)-[2-[8(S)-[1-(3-Hydroxypropyl)cyclobutanecarbonyloxy)-2(S),6(R)-dimethyl-1,2,6,7,8,8a(R)-hexahydronaphthyl-1(S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
- 9. A compound of claim 5 which is 6(R)-[2-[8(S)-[1-[(4-Hydroxyphenyl)methyl]cyclobutane-carbonyloxy)-2(S),6(R)-dimethyl-1,2,6,7,8,8a(R)-hexahydronaphthyl-1(S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
- 10. A compound of claim 5 which is 6(R)-[2-[8(S)-[(1-Hydroxymethyl)-cyclobutanecarbonyloxy)-2(S),6(R)-dimethyl-1,2,6,7,8,8a(R)-hexahydronaphthyl-1(S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
- 11. A compound of claim 5 which is 6(R)-[2-[8(S)-[1-(1-Phenylmethyl)-cyclobutanecarbonyloxy]-2(S),6(R)-dimethyl-1,2,6,7,8,8a(R)-hexahydronaphthyl-1(S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
- 12. A compound of claim 2 wherein n is 4.
- 13. A compound of claim 12 which is 6(R)-[2-[8(S)-(1-Methylcyclopentanecarbonyloxy)-2(S),6(R)-dimethyl-1,2,6,7,8,8a(R)-hexahydronaphthyl-1(S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
- 14. A compound of claim 12 which is 6(R)-[2-[8(S)-(1-Methylthiocyclopentanecarbonyloxy)-2(S),6(R)-dimethyl-1,2,6,7,8,8a(R)-hexahydronaphthyl-1(S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
- 15. A compound of claim 2 wherein n is 5.
- 16. A compound of claim 15 which is 6(R)-[2-[8(S)-(1-Methylcyclohexanecarbonyloxy)-2(S),6(R)-dimethyl-1,2,6,7,8,8a(R)-hexahydronaphthyl-1(S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
- 17. A hypocholesterolemic, hypolipidemic pharmaceutical composition comprising a nontoxic therapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.
- 18. A composition according to claim 17 wherein:
- n is 2 to 5; and
- R.sup.1 is C.sub.1-6 alkyl; hydroxy-C.sub.1-6 alkyl; C.sub.1-6 alkylthio; or phenylmethyl; or 4-hydroxyphenylmethyl.
- 19. A composition according to claim 18 wherein the therapeutically active ingredient is selected from the group consisting of:
- (1) 6(R)-[2-[8(S)-(1-Methylcyclopropanecarbonyloxy)-2(S),6(R)-dimethyl-1,2,6,7,8,8a(R)-hexahydronaphthyl-1(S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one;
- (2) 6(R)-[2-[8(S)-(1-Methylcyclobutanecarbonyloxy)-2(S),6(R)-dimethyl-1,2,6,7,8,8a(R)-hexahydronaphthyl-1(S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one;
- (3) 6(R)-[2-[8(S)-(1-Methylthiocyclobutanecarbonyloxy)-2(S),6(R)-dimethyl-1,2,6,7,8,8a(R)-hexahydronaphthyl-1(S)]ethyl]-4(R)hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one;
- (4) 6(R)-[2-[8(S)-[1-(3-Hydroxypropyl)cyclobutane-carbonyloxy]-2(S),6(R)-dimethyl-1,2,6,7,8,8a(R)-hexahydronaphthyl-1(S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one;
- (5) 6(R)-[2-[8(S)-[1-[(4-Hydroxyphenyl)methyl]cyclobutanecarbonyloxy]-2(S),6(R)-dimethyl-1,2,6,7,8,8a(R)-hexahydronaphthyl-1(S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one;
- (6) 6(R)-[2-[8(S)-[(1-Hydroxymethyl)cyclobutanecarbonyloxy]-2(S),6(R)-dimethyl-1,2,6,7,8,8a(R)-hexahydronaphthyl-1(S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one;
- (7) 6(R)-[2-[8(S)-[1-(1-Phenylmethyl)cyclobutanecarbonyloxy]-2(S),6(R)-dimethyl-1,2,6,7,8,8a(R)-hexahydronaphthyl-1(S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one;
- (8) 6(R)-[2-[8(S)-(1-Methylcyclopentanecarbonyloxy)-2(S),6(R)-dimethyl-1,2,6,7,8,8a(R)-hexahydronaphthyl-1(S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one;
- (9) 6(R)-[2-[8(S)-(1-Methylthiocyclopentanecarbonyloxy)-2(S),6(R)-dimethyl-1,2,6,7,8,8a(R)-hexahydronaphthyl-1(S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one;
- (10) 6(R)-[2-[8(S)-(1-Methylcyclohexanecarbonyl)-2(S),6(R)-dimethyl-1,2,6,7,8,8a(R)-hexahydronaphthyl-1(S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
- 20. A hypocholesterolemic, hypolipidemic 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-reabsorable form in the gastrointestinal tract and a pharmaceutically acceptable carrier.
- 21. A method of inhibiting cholesterol biosynthesis comprising the administration to a subject in need of such treatment a nontoxic therapeutically effective amount of a compound of claim 1.
- 22. A method of claim 21 wherein:
- n is 2 to 5; and
- R.sup.1 is C.sub.1-6 alkyl; hydroxy-C.sub.1-6 alkyl; C.sub.1-6 alkylthio; phenylmethyl; or 4-hydroxyphenylmethyl.
- 23. A method of claim 22 wherein the therapeutically active ingredient is selected from the group consisting of:
- (1) 6(R)-[2-[8(S)-(1-Methylcyclopropanecarbonyloxy)-2(S),6(R)-dimethyl-1,2,6,7,8,8a(R)-hexahydronaphthyl-1(S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one;
- (2) 6(R)-[2-[8(S)-(1-Methylcyclobutanecarbonyloxy)-2(S),6(R)-dimethyl-1,2,6,7,8,8a(R)-hexahydronaphthyl-1(S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one;
- (3) 6(R)-[2-[8(S)-(1-Methylthiocyclobutanecarbonyloxy)-2(S),6(R)-dimethyl-1,2,6,7,8,8a(R)-hexahydronaphthyl-1(S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one;
- (4) 6(R)-[2-[8(S)-[1-(3-Hydroxypropyl)cyclobutane-carbonyloxy]-2(S),6(R)-dimethyl-1,2,6,7,8,8a(R)-hexahydronaphthyl-1(S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one;
- (5) 6(R)-[2-[8(S)-[1-[(4-Hydroxyphenyl)methyl]cyclobutanecarbonyloxy]-2(S),6(R)-dimethyl-1,2,6,7,8,8a(R)-hexahydronaphthyl-1(S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one;
- (6) 6(R)-[2-[8(S)-[(1-Hydroxymethyl)cyclobutanecarbonyloxy]-2(S),6(R)-dimethyl-1,2,6,7,8,8a(R)-hexahydronaphthyl-1(S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one;
- (7) 6(R)-[2-[8(S)-[1-(1-Phenylmethyl)cyclobutanecarbonyloxy]-2(S),6(R)-dimethyl-1,2,6,7,8,8a(R)-hexahydronaphthyl-1(S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one;
- (8) 6(R)-[2-[8(S)-(1-Methylcyclopentanecarbonyloxy)-2(S),6(R)-dimethyl-1,2,6,7,8,8a(R)-hexahydronaphthyl-1(S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one;
- (9) 6(R)-[2-[8(S)-(1-Methylthiocyclopentanecarbonyloxy)-2(S),6(R)-dimethyl-1,2,6,7,8,8a(R)-hexahydronaphthyl-1(S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one;
- (10) 6(R)-[2-[8(S)-(1-Methylcyclohexanecarbonyl)-2(S),6(R)-dimethyl-1,2,6,7,8,8a(R)-hexahydronaphthyl-1(S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one.
Parent Case Info
This is a continuation of application Ser. No. 589,524 now abandoned, filed May 5, 1986.
US Referenced Citations (7)
Foreign Referenced Citations (3)
Number |
Date |
Country |
2155927 |
May 1973 |
FRX |
2168881 |
Sep 1973 |
FRX |
59-122483A |
Jul 1984 |
JPX |
Continuations (1)
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Number |
Date |
Country |
Parent |
859524 |
May 1986 |
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