Claims
- 1. The compound of structural formula (VI) ##STR52## wherein R.sup.4 --(A).sub.a, R.sup.6 and R are each:
- ______________________________________Comp.No. R.sup.4(A)a R.sup.6 R______________________________________134 C(O)NH(CH.sub.2).sub.11 CH.sub.3 H C(O)CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.3135 C(O)NH(CH.sub.2).sub.9 CH.sub.3 H C(O)CH.sub.3136 (CH.sub.2).sub.13 CH.sub.3 H C(O)CH.sub.3137 C(O)NH(CH.sub.2).sub.6 OH H C(O)CH.sub.3138 C(O)NH(CH.sub.2).sub.11 CH.sub.3 H C(O)CH.sub.3139 C(O)NH(CH.sub.2).sub.11 OC.sub.6 H.sub.5 H C(O)CH.sub.3140 C(O)NH(CH.sub.2).sub.4 CHO H C(O)CH.sub.3145 C(O)NH(CH.sub.2).sub.6 NH.sub.2 H C(O)CH.sub.3146 C(O)(CH.sub.2).sub.12 CH.sub.3 H C(O)CH.sub.3141 ##STR53## H C(O)CH.sub.3142 ##STR54## H C(O)CH.sub.3143 ##STR55## H C(O)CH.sub.3144 ##STR56## H C(O)CH.sub.3.______________________________________
- 2. A compound selected from the group consisting of:
- (a) 3-hydroxyethyl-(1 S,3S,4S ,5R,6R,7RR)-1-[4-hydroxy-3,5-dimethyl-8-phenyl]oct-7-enyl-4,6,7-trihydroxy-6-O-(tetradeca-6,12-dienoyl-2,8-dioxabicyclo[3.2.1]octane-4,5-dicarboxylic acid,
- (b) 3-[(1',1'-diphenethyl)-hydroxymethyl]-(1S ,3S ,4S ,5R,6R,7RR)-1-[4-hydroxy-3,5-dimethyl-8-phenyl]oct-7-enyl-4,6,7-trihydroxy-6-O-(tetradeca-6,12-dienoyl-2,8-dioxabicyclo[3.2.1]octane-4,5-dicarboxylic acid,
- (c) 3-[(1',1'-dipropyl)-hydroxymethyl]-(1S,3S,4S,5R,6R,7RR)-1-[4-hydroxy-3,5-dimethyl-8-phenyl]oct-7-enyl-4,6,7-trihydroxy-6-O-(tetradeca-6,12-dienoyl-2,8-dioxabicyclo[3.2.1]octane-4,5-dicarboxylic acid,
- (d) 3-[(1',1'-diphenyl)-hydroxymethyl]-(1S,3S,4S,5R,6R ,7RR)-1-[4-hydroxy-3,5-dimethyl-8-phenyl]oct-7-enyl-4,6,7-trihydroxy-6-O-(tetradeca-6,12-dienoyl-2,8-dioxabicyclo[3.2.1]octane-4,5-dicarboxylic acid,
- (e) 3-[(1',1'-dibutyl)-hydroxymethyl]-(1S,3S,4S,5R,6R,7RR)-1-[4-hydroxy-3,5-dimethyl-8-phenyl]oct-7-enyl-4,6,7-trihydroxy-6-O-(tetradeca-6,12-dienoyl-2,8-dioxabicyclo[3.2.1]octane-4,5-dicarboxylic acid, and
- (f) 3-(2-hydroxymethyl ketone)-(1S,3S,4S,5R,6R,7RR)-1-[4-hydroxy-3,5-dimethyl-8-phenyl]oct-7-enyl-4,6,7-trihydroxy-6-O-(tetradeca-6,12-dienoyl-2,8-dioxabicyclo[3.2.1]octane-4,5-dicarboxylic acid.
- 3. A compound of structural formula (III) ##STR57## wherein R.sup.5, R.sup.6 and R are:
- ______________________________________Compound No. R.sup.5 R.sup.6 R______________________________________113 H H --CH(OAc)(CH.sub.2).sub.3 CH.sub.3119 H H --C(O)CH.sub.3120 H H --C(O)(CH.sub.2).sub.3 CH.sub.3122 H H --C(O)(2-CH.sub.3 --C.sub.6 H.sub.4)123 H H --C(O)--C.sub.6 H.sub.5124 H H --C(O)(CH.sub.2).sub.2 CH.sub.3125 H H --C(O)(CH.sub.2).sub.2 CH.sub.3126 H H --C(O)CH.sub.2 CH.sub.3127 H H --C(O)(CH.sub.2).sub.2 C.sub.6 H.sub.5.128 H H --CH.sub.3129 H H --CH.sub.2 F130 H H --CHF.sub.2231 H Hvinyl232 H Hbutenyl.______________________________________
- 4. A compound of structural formula (VII): ##STR58## wherein R, Z.sup.1 and Z.sup.2 are:
- __________________________________________________________________________Comp.No. R Z.sup.1 Z.sup.2__________________________________________________________________________147 CH.sub.3 OCH.sub.2 CH.sub.2 OCH.sub.3 OH148 CH.sub.3 OCH.sub.2 OC(O)C(CH.sub.3).sub.3 OH149 CH.sub.3 OCH.sub.2 OC(O)C(CH.sub.3).sub.3 OCH.sub.2 OC(O)C(CH.sub.3).sub.3150 CH.sub.3 OCH.sub.3 OH151 CH.sub.3 OH OCH.sub.3152 CH.sub.3 OCH.sub.2 C(O)N(CH.sub.3).sub.2 OH153 CH.sub.3 OH OCH.sub.2 C(O)N(CH.sub.3).sub.2154 CH.sub.3 OCH.sub.2 OC(O)CH.sub.3 OH155 CH.sub.3 OCH.sub.2 OC(O)CH.sub.3 OCH.sub.2 OC(O)CH.sub.3156 CH.sub.2 F OCH.sub.2 OC(O)C(CH.sub.3).sub.3 OH157 CH.sub.3 OCH(CH.sub.3)OC(O)OCH.sub.2 CH.sub.3 OH158 CH.sub.3 OCH(CH.sub.3)OC(O)C(CH.sub.3).sub.3 OH160 CH.sub.2 F OCH.sub.2 OC(O)C(CH.sub.3).sub.3 OCH.sub.2 OC(O)C(CH.sub.3).sub.3170 CH.sub.3 OCH(CH.sub.3 )OC(O)C(CH.sub.3).sub.3 OCH(CH.sub.3)OC(O)C(CH.sub.3).sub.3174 C(O)CH.sub.3 OCH.sub.3 OH175 C(O)CH.sub.3 OH OCH.sub.3176 C(O)CH.sub.3 OCH.sub.2 OC(O)C(CH.sub.3).sub.3 OH177 C(O)CH.sub.3 OH OCH.sub.2 OC(O)C(CH.sub.3).sub.3178 C(O)CH.sub.3 OCH.sub.2 OC(O)CH.sub.3 OH179 C(O)CH.sub.3 OH OCH.sub.2 OC(O)CH.sub.3180 C(O)CH.sub.3 OCH.sub.2 OC(O)CH.sub.3 OCH.sub.2 OC(O)CH.sub.3181 C(O)CH.sub.3 OCH.sub.3 OCH.sub.3182 C(O)CH.sub.3 OCH.sub.2 C(O)OC(CH.sub.3).sub.3 OH183 C(O)CH.sub.3 O(CH.sub.2).sub.2 CH(CH.sub.3).sub.2 OH159 CH.sub.3 ##STR59## OH171 CH.sub.3 ##STR60## OH172 CH.sub.3 OH ##STR61##173 CH.sub.3 ##STR62## ##STR63##__________________________________________________________________________
- 5. A compound of structural formula (VIII): ##STR64## wherein R, R.sup.1, R.sup.4 (A).sub.a and Z.sup.1 are:
- ______________________________________R R.sup.1 R.sup.4 (A).sub.a Z.sup.1______________________________________CH.sub.3 bb dd ##STR65##C(O)CH.sub.3 aa cc OHC(O)CH.sub.3 aa cc OCH.sub.2 OC-t-BuC(O)CH.sub.3 aa cc ##STR66##C(O)CH.sub.3 bb dd OHC(O)CH.sub.3 bb dd OCH.sub.2 OC-t-Bu.C(O)CH.sub.3 bb dd ##STR67##CH.sub.3 aa cc OHCH.sub.3 aa cc OCH.sub.2 OC-t-BuCH.sub.3 aa cc ##STR68##CH.sub.3 bb dd OHCH.sub.3 bb dd OCH.sub.2 OC-t-Bu.CH.sub.3 bb dd ##STR69##______________________________________
- 6. A compound of structural formula (IX): ##STR70## wherein R, R.sup.1, and R.sup.4 --(A).sub.a -- are:
- __________________________________________________________________________CompNo R.sup.1 R R.sup.4 (A).sub.a__________________________________________________________________________184 --(CH.sub.2).sub.2 CH(CH.sub.3)CH.sub.2 CH(CH.sub.3)CH.sub.2 C.sub.6 H.sub.5 --C(O)(CH.sub.2).sub.3 CH.sub.3 p.sup.2185 --(CH.sub.2).sub.2 CH(CH.sub.3)CH(OAc)CH(CH.sub.3)CH.sub.2 C.sub.6 H.sub.5 --C(O)(CH.sub.2).sub.3 CH.sub.3 p.sup.2.__________________________________________________________________________
- 7. A pharmaceutical composition comprising a nontoxic therapeutically effective amount of a compound of claim 2 and a pharmaceutically acceptable carrier.
- 8. A pharmaceutical composition comprising a nontoxic therapeutically effective amount of a compound of claim 2 in combination with a pharmaceutically acceptable non-toxic cationic polymer capable of binding bile acids in a non-resorbable form in the gastrointestinal tract and a pharmaceutically acceptable carrier.
- 9. A pharmaceutical composition comprising a nontoxic therapeutically effective amount of a compound of claim 2 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 epoxidase inhibitor,
- (d) probucol,
- (e) niacin,
- (f) gemfibrozil,
- (g) clofibrate, and
- (h) LDL-receptor gene inducer.
- 10. 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 2.
- 11. A method of treating hypercholesterolemia comprising the administration to a subject in need of such treatment 20 to 100 mg of a compound of claim 2.
- 12. A method of inhibiting squalene synthase comprising the administration to a subject in need of such treatment a nontoxic therapeutically effective amount of a compound of claim 2.
- 13. A method for inhibiting fungal growth in a living organism in need of such treatment comprising the oral, systemic, topical or parenteral administration to the living organism of an antifungally effective amount of a compound of claim 2.
- 14. The method of claim 13 wherein the living organism is a plant, and the compound is administered by topical application to the plant or to the soil in which the plant grows.
- 15. The method of claim 13 wherein the living organism is a vertebrate.
CROSS REFERENCE TO RELATED APPLICATIONS
This application is a continuation in part of U.S. patent application Ser. No. 07/916,774, filed Jul. 17, 1992, presently abandoned.
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Continuation in Parts (1)
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Number |
Date |
Country |
Parent |
916774 |
Jul 1992 |
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