Claims
- 1. A compound represented by the following general structural formula (II): ##STR33## wherein: q is 0 to 5;
- n is 2 to 7;
- R.sup.1 is C.sub.1-6 alkyl,
- R.sup.2 is hydrogen or hydroxy;
- R.sup.3 and R.sup.4 independently are hydrogen, C.sub.1-3 alkyl, C.sub.3-7 cycloalkyl, phenyl or phenyl substituted with X and Y and when q is 2 to 5, each of the R.sup.3 s and R.sup.4 s are independently hydrogen, C.sub.1-3 alkyl, C.sub.3-7 cycloalkyl or only one of the R.sup.3 s and R.sup.4 s is phenyl or substituted phenyl;
- A is ##STR34## in which R.sup.5 is hydrogen or hydroxy; B is ##STR35## in which R.sup.6 is hydrogen or hydroxy; a, b, c and d represent single bonds, one of a, b, c or d represents a double bond or both a and c or both b and d represent double bonds, provided that when a is a double bond, A is ##STR36## and when d is a double bond, ##STR37## X and Y independently are hydrogen, halogen, trifluoromethyl, C.sub.1-3 alkyl, nitro, cyano or a group selected from:
- (a) R.sup.7 O(CH.sub.2).sub.m in which m is 0 to 3 and R.sup.7 is hydrogen, C.sub.1-3 alkyl or hydroxy-C.sub.2-3 alkyl;
- (b) ##STR38## in which R.sup.8 is hydrogen, C.sub.1-3 alkyl, hydroxy-C.sub.2-3 alkyl, phenyl, naphthyl, amino-C.sub.1-3 alkyl, C.sub.1-3 alkylamino-C.sub.1-3 alkyl, di(C.sub.1-3 alkyl)amino-C.sub.1-3 alkyl, hydroxy-C.sub.2-3 aklylamino-C.sub.1-3 alkyl or di(hydroxy-C.sub.2-3 alkyl)amino-C.sub.1-3 alkyl;
- (c) ##STR39## in which R.sup.9 is hydrogen, C.sub.1-3 alkyl, hydroxy-C.sub.1-3 alkyl, C.sub.1-3 alkoxy-C.sub.1-3 alkyl, phenyl or naphthyl;
- (d) R.sup.10 R.sup.11 N(CH.sub.2).sub.m, ##STR40## ##STR41## in which R.sup.10 and R.sup.11 independently are hydrogen, C.sub.1-3 alkyl, hydroxy-C.sub.2-3 alkyl or together with the nitrogen atom to which they are attached form a heterocycle group selected from piperidinyl, pyrrolidinyl, piperazinyl, morpholinyl or thiomorpholinyl;
- (e) R.sup.12 S(O).sub.p (CH.sub.2).sub.m in which p is 0 to 2 and R.sup.12 is hydrogen, C.sub.1-3 alkyl, amino, C.sub.1-3 alkylamino or di(C.sub.1-3 alkyl)amino;
- Z is hydrogen, C.sub.1-5 alkyl or C.sub.1-5 alkyl substituted with a group selected from phenyl, dimethylamino or acetylamino; or
- a pharmaceutically acceptable salt of a compound of the formula (II) in which Z is hydrogen.
- 2. A compound of claim 1 wherein:
- q is 0, R.sup.2, R.sup.5 and R.sup.6 are hydrogen; and a, b, c, and d represent single bonds or both b and d represent double bonds.
- 3. A compound of claim 2 wherein n is 2 to 5.
- 4. A compound of claim 3 wherein n is 2.
- 5. A compound of claim 3 wherein n is 3.
- 6. A hypocholesterolemic, hypolipidemic pharmaceutical composition comprising a nontoxic therapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.
- 7. A composition according to claim 6 wherein R.sup.2, R.sup.3 and R.sup.4 are hydrogen; and a, b, c and d represent single bonds or b and d represent double bonds.
- 8. A composition according to claim 7 wherein n is 2 to 5.
- 9. 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-reabsorbable form in the gastrointestinal tract and a pharmaceutically acceptable carrier.
- 10. 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.
- 11. A method of claim 10 wherein R.sup.2, R.sup.3 and R.sup.4 are hydrogen and a, b, c and d represent single bonds or b and d represent double bonds.
- 12. A method of claim 11 wherein n is 2 to 5.
- 13. A compound of claim 4 which is 7-[1,2,6,7,8,8a(R)-hexahydro-2(S),6(R)-dimethyl-8(S)-(1-Ethoxycarbonylcyclopropanecarbonyloxy)-1(S)-naphthyl]-3(R),5(R)-dihydroxy-heptanoic acid.
- 14. A compound of claim 5 which is 7-[1,2,6,7,8,8a(R)-hexahydro-2(S),6(R)-dimethyl-8(S)-(1-Ethoxycarbonylcyclobutanecarbonyloxy)-1(S)-naphthyl]-3(R),5(R)-dihydroxy-heptanoic acid.
- 15. A composition according to claim 8 wherein the therapeutically active ingredient is selected from the group consisting of:
- 7-[1,2,6,7,8,8a(R)-hexahydro-2(S),6(R)-dimethyl-8(S)-(1-Ethoxycarbonylcyclopropanecarbonyloxy)-1(S)-naphthyl]-3(R),5(R)-dihydroxy-heptanoic acid;
- 7-[1,2,6,7,8,8a(R)-hexahydro-2(S),6(R)-dimethyl-8(S)-(1-Ethoxycarbonylcyclobutane carbonyloxy)-1(S)-naphthyl]-3(R),5(R)-dihydroxy-heptanoic acid.
- 16. A method of claim 12 wherein the therapeutically active ingredient is selected from the group consisting of:
- 7-[1,2,6,7,8,8a(R)-hexahydro-2(S),6(R)-dimethyl-8(S)-(1-Ethoxycarbonylcyclopropanecarbonyloxy)-1(S)-naphthyl]-3(R),5(R)-dihydroxy-heptanoic acid;
- 7-[1,2,6,7,8,8a(R)-hexahydro-2(S),6(R)-dimethyl-8(S)-(1-Ethoxycarbonylcyclobutanecarbonyloxy)-1(S)-naphthyl]-3(R),5(R)-dihydroxy-heptanoic acid.
Parent Case Info
This is a division of application Ser. No. 859,525 filed May 5, 1986, now U.S. Pat. No. 4,766,145.
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Divisions (1)
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Number |
Date |
Country |
Parent |
859525 |
May 1986 |
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