Combination therapy employing ileal bile acid transport inhibiting benzothiepines and HMG CO-A reductase inhibitors

A combination therapy method for the treatment or prophylaxis of a hyperlipidemic condition in a patient in need thereof, said method comprising administering to said patient a pharmaceutical composition comprising a first amount of an ileal bile acid transport (IBAT) inhibitor of formula (I), a second amount of an HMG Co-A reductase inhibitor, and a pharmaceutically acceptable carrier,

• wherein said formula (I) is represented by:
• wherein:
• q is an integer from 1 to 4;
• n is an integer from 0 to 2;
• R1 and R2 are independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, haloalkyl, alkylaryl, arylalkyl, alkoxy, alkoxyalkyl, dialkylamino, alkylthio, (polyalkyl)aryl, and cyc:loalkyl,
• wherein alkyl, alkenyl, alkynyl, haloalkyl, alkylaryl, arylalkyl, alkoxy, alkoxyalkyl, dialkylamino, alkyithici, (polyalkyl)aryl, and cycloalkyl optionally are substituted with one or more substituents selected from the group consisting of OR9, NR9R10, N+R9R10RwA−, SR9, S−R9R10A−, P+R9R10R11A−, S(O)R9, SO2R9, SO3R9, CO2R9, CN, halogen, oxo, and CONR9R10,
• wherein alkyl, alkenyl, alkynyl, alkylaryl, alkoxy, alkoxyalkyl, (polyalkyl)aryl, and cycloalkyl optionally have one or more carbons replaced by O, NR9, N+R9R10A−, S, SO, SO2, S+R9A−, P+R9R10A−, or phenylene,
• wherein R9, R10, and Rw are independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, acyl, heterocycle, heteroaryl, ammoniumalkyl, arylalkyl, and alkylammoniumalkyl;
• or
• R1 and R2 taken together with the carbon to which they are attached form G3-C10 cycloalkylidene;
• R3 and R4 are independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, acyloxy, aryl, heterocycle, heteroaryl, OR9, NR9R10, SR9, S(O)R9, SO2R9, and SO3R9, wherein R9 and R10 are as defined above;
• or
• R3 and R4 together form ═O, ═NOR11, ═S, ═NNR11R12, ═NR9, or ═CR11R12, wherein R11 and R12 are independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, aryl, arylalkyl, alkenylalkyl, alkynylalkyl, heterocycle, heteroaryl, carboxyalkyl, carboalkoxyalkyl, cycloalkyl, cyanoalkyl, OR9, NR9R10, SR9, S(O)R9, SO2R9, SO3R9, CO2R9, CN, halogen, oxo, and CONR9R10, wherein R9 and R10 are as defined above, provided that both R3 and R4 cannot be OH, NH2, or SH, or
• R11 and R12 together with the nitrogen or carbon atom to which they are attached form a cyclic ring;
• R5 and R6 are independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocycle, heteroaryl, quaternary heterocycle, quarternary heteroaryl, SR9, S(O)R9, SO2R9, and SO3R9,
• wherein alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocycle, heteroaryl, quatemary heterocycle, and quatemary heteroaryl can be substituted with one or more substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, polyalkyl, polyether, aryl, haloalkyl, cycloalkyl, heterocycle, heteroaryl, arylalkyl, quaternary heterocycle, quaternary heteroaryl, halogen, oxo, OR13, NR13R14, SR13, S(O)R13, SO2R13, SO3R13, NR13OR14, NR13NR14R15, NO2, CO2R13, CN, OM, SO2OM, SO2NR13R14, C(O)NR13R14, C(O)OM, COR13, P(O)R13R14, P+R13R14R15A−, P(OR13)OR14, S+R13R14A−, and N+R9R11R12A−,
• wherein:
• A− is a pharmaceutically acceptable anion and M is a pharmaceutically acceptable cation,
• said alkyl, alkenyl, alkynyl, polyalkyl, polyether, aryl, haloalkyl, cycloalkyl, heterocycle, and heteroaryl can be fiarther substituted with one or more substiruents selected from the group consisting of OR7, NR7R8, SR7, S(O)R7, SO2R7, SO3R7, CO2R7, CN, oxo, CONR7R8, N+R7R8R9A−, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocycle, heteroaryl, arylalkyl, quaternary heterocycle, quaternary heteroaryl, P(O)R7R8, P+R7R8R9A−, and P(O)(OR7)OR8 and
• wherein said alkyl, alkenyl, alkynyl, polyalkyl, polyether, aryl, haloalkyl, cycloalkyl, heterocycle, and heteroaryl, can optionally have one or more carbons replaced by O, NR7, N+R7R8A−, S, SO, SO2, S+R7A−, PR7, P(O)R7, P+R7R8A−, or phenylene, and R13, R14, and R15 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, polyalkyl, aryl, arylalkyl, cycloalkyl, heterocycle, heteroaryl, quatemary heterocycle, quaternary hereroaryl, and quaternary heteroarylalkyl,
• wherein alkyl, alkenyl, alkynyl, arylalkyl, heterocycle, heteroaryl, and polyalkyl optionally have one or more carbons replaced by O, NR9, N+R9R10A−, S, SO, SO2, S+R9A−, PR9, P+R9R10A−, P(O)R9, phenylene, carbohydrate, amino acid, peptide, or polypeptide, and
• R13, R14 and R15 are optionally substituted with one or more groups selected from the group consisting of sulfoalkyl, heterocycle, heteroaryl, quatemary heterocycle, quaternary heteroaryl, OR9, NR9R10, N+R9R11R12A−, SR9, S(O)R9, SO2R9, SO3R9, oxo, CO2R9, CN, halogen, CONR9R10, SO2OM, SO2NR9R10, PO(OR16)OR17, P+R9R10R11A−, S+R9R10A−, and C(O)OM,
• wherein R16 and R17 are independently selected from the substituents constituting R9 and M;
• or
• R14 and R15, together with the nitrogen atom to which they are attached, form a cyclic ring;
• R7 and R8 are independently selected from the group consisting of hydrogen and alkyl;
• and
• one or more Rx are independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, polyalkyl, acyloxy, aryl, arylalkyl, halogen, haloalkyl, cycloalkyl, heterocycle, heteroaryl, polyether, quatemary heterocycle, quaternary heteroaryl, OR13, NR13R14, SR13, S(O)R13, S(O)2R13, SO3R13, S+R13R14A−, NR13OR14, NR13NR14R15, NO2, CO2R13, CN, OM, SO2OM, SO2NR13R14, NR14C(O)R13, C(O)NR13R14, NR14C(O)R13, C(O)OM, COR13, OR18, S(O)nNR18, NR13R18, NR18OR14, N+R9R10R12A−, P+R9R11R12A−, amino acid, peptide, polypeptide, and carbohydrate,
• wherein alkyl, alkenyl, alkynyl, cycloalkyl, aryl, polyalkyl, heterocycle, heteroaryl, acyloxy, arylalkyl, haloalkyl, polyether, quatemary heterocycle, and quaternary heteroaryl can be further substituted with OR9, NR9R10, N+R9R11R12A−, SR9, S(O)R9, SO2R9, SO3R9, oxo, CO2R9, CN, halogen, CONR9R10, SO2OM, SO2NR9R10, PO(OR16)OR17, P+R9R11R12A−, S+R9R10A−, or C(O)M, and
• wherein R18 is selected from the group consisting of acyl, arylalkoxycarbonyl, arylalkyl, heterocycle, heteroaryl, alkyl, quatemary heterocycle, and quaternary heteroaryl, wherein acyl, arylalkoxycarbonyl, arylalkyl, heterocycle, heteroaryl, alkyl, quaternary heterocycle, and quatemary heteroaryl optionally are substituted with one or more substituents selected from the group consisting of OR9, NR9R10, N+R9R11R12A−, SR9, S(O)R9, SO2R9, SO3R9, oxo, CO2R9, CN, halogen, CONR9R10, SO3R9, SO2OM, SO2NR9R10, PO(OR16)OR17 and C(O)OM,
• wherein in Rx, one or more carbons are optionally replaced by O, NR13, N+R13R14A−, S, SO, SO2, S+R13A−, PR13, P(O)R13, P+R13R14A−, phenylene, amino acid, peptide, polypeptide, carbohydrate, polyether, or polyalkyl,
• wherein in said polyalkyl, phenylene, amino acid, peptide, polypeptide, and carbohydrate, one or more carbons are optionally replaced by O, NR9, N+R9R10A−, S, SO, SO2, S+R9A−, PR9, P+R9R10A−, or P(O)R9;
• wherein quatemary heterocycle and quatemary heteroaryl are optionally substituted with one or more groups selected from the group consisting of alkyl, alkenyl, alkynyl, polyalkyl, polyether, aryl, haloalkyl, cycloalkyl, heterocycle, heteroaryl, arylalkyl, halogen, oxo, OR13, NR13R14, SR13, S(O)R13, SO2R13, SO3R13, NR13OR14, NR13NR14R15, NO2, CO2R13, CN, OM, SO2OM, SO2NR13R14, C(O)NR13R14, C(O)OM, COR13, P(O)R13R14, P+R13R14R15A−, P(OR13)OR14, S+R13R14A−, and N+R9R11R12A−,
• provided that both R5 and R6 cannot be hydrogen, OH, or SH, and R5 is OH, R1, R2, R3, R4, R7, and R8 cannot all be hydrogen;
• provided that when R5 or R6 is phenyl, only one of R1 or R2 is H;
• provided that when q=1 and Rx is styryl, anilido, or anilinocarbonyl, only one of R5 or R6 is alkyl;
• or
• a pharmaceutically acceptable salt, solvate, or prodrug thereof,
• wherein said first amount is provided in a dosage range from about 0.3 mg/kg bodyweight/day to about 100 mg/kg bodyweightlday and
• wherein said first and second amounts of said inhibitors together comprise an anti-hyperlipidemic condition effective amount.

An oral pharmaceutical composition comprising:

• a first amount of an ileal bile acid transport (IBAT) inhibitor of formula (I), a second amount of
• an HMG Co-A reductase inhibitor, and a pharmaceutically acceptable carrier,
• wherein said formula (I) is represented by:
• wherein:
• q is an integer trom 1 to 4;
• n is an integer from 0 to 2;
• R1 and R2 are independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, haloalkyl, alkylaryl, arylalkyl, alkoxy, alkoxyalkyl, dialkylamino, alkylthio, (polyalkyl)aryl, and cycloalkyl,
• wherein alkyl, alkenyl, alkynyl, haloalkyl, alkylaryl, arylalkyl, alkoxy, alkoxyalkyl, dialkylamino, alkyithia, (polyalkyl)aryl, and cycloalkyl optionally are substituted with one or more substiflients selected from the group consisting of OR9, NR9R10, N+R9R10RwA−, SR9, S+R9R10A−, P+R9R10R11A−, S(O)R9, SO2R9, SO3R9, CO2R9, CN, halogen, oxo, and CONR9R10,
• wherein alkyl, alkenyl, aikynyl, alkylaryl, alkoxy, alkoxyalkyl, (polyalkyl)aryl, and cycloalkyl optionally have one or more carbons replaced by O, NR9, N+R9R10A−, S, SO, SO2, S+R9A−, P+R9R10A−, or phenylene,
• wherein R9, R10, and Rw are independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, acyl, heterocycle, heteroaryl, ammoniumalkyl, arylalkyl, and alkylammoniumalkyl;
• or
• R1 and R2 taken together with the carbon to which they are attached form C3-C10 cycloalkylidene;
• R3 and R4 are independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, acyloxy, aryl, heterocycle, heteroaryl, OR9, NR9R10, SR9, S(O)R9, SO2R9, and SO3R9, wherein R9 and R10 are as defined above;
• or
• R3 and R4 together fomi ═O, ═NOR11, ═S, ═NNR11R12, ═NR9, or ═CR11R12, wherein R11 and R12 are independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, aryl, arylalkyl, alkenylalkyl, alkynylalkyl, heterocycle, heteroaryl, carboxyalkyl, carboalkoxyalkyl, cycloalkyl, cyanoalkyl, OR9, NR9R10, SR9, S(O)R9, SO2R9, SO3R9, CO2R9, CN, halogen, oxo, and CONR9R10, wherein R9 and R10 are as defined above, provided that both R3 and R4 cannot be OH, NH2, or SH, or
• R11 and R12 together with the nitrogen or carbon atom to which they are attached form a cyclic ring;
• R5 and R6 are independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocycle, heteroaryl, quatemary heterocycle, quartemary heteroaryl, SR9, S(O)R9, SO2R9, and SO3R9, wherein alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocycle, heteroaryl, quatemary heterocycle, and quatemary heteroaryl can be substituted with one or more substituent independently selected from the group consisting of alkyl, alkenyl, alkynyl, polyalkyl, polyether, aryl, haloalkyl, cycloalkyl, heterocycle, heteroaryl, arylalkyl, quaternary heterocycle, quatemary heteroaryl, halogen, oxo, OR13, NR13R14, SR13, S(O)R13, SO2R13, SO3R13, NR13OR14, NR13NR14R15, NO2, CO2R13, CN, OM, SO2OM, SO2NR13R14, C(O)NR13R14, C(O)OM, COR13, P(O)R13R14, P+R13R14R15A−, P(OR13)OR14, S+R13R14A−, and N+R9R11R12A−,
• wherein:
• A− is a pharmaceutically acceptable anion and M is a pharmaceutically acceptable cation, said alkyl, alkenyl, alkynyl, polyalkyl, polyether, aryl, haloalkyl, cycloalkyl, heterocycle, and heteroaryl can be further substituted with one or more substituents selected from the group consisting of OR7, NR7R, SR7, S(O)R7, SO2R7, SO3R7, CO2R7, CN, oxo, CONR7R8, N+R7R8R9A−, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocycle, heteroaryl, arylalkyl, quaternary heterocycle, quaternary heteroaryl, P(O)R7R8, P+R7R8R9A−, and P(O)(OR7)OR8 and
• wherein said alkyl, alkenyl, alkynyl, polyalkyl, polyether, aryl, haloalkyl, cycloalkyl, heterocycle, and heteroaryl, can optionally have one or more carbons replaced by O, NR7, N+R7R8A−, S, SO, SO2, S+R7A−, PR7, P(O)R7, P+R7R8A−, or phenylene, and R13, R14, and R15 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, polyalkyl, aryl, arylalkyl, cycloalkyl, heterocycle, heteroaryl, quaternary heterocycle, quaternary heteroaryl, and quatemary heteroarylalkyl,
• wherein alkyl, alkenyl, alkynyl, arylalkyl, heterocycle, heteroaryl, and polyalkyl optionally have one or more carbons replaced by O, NR9, N+R9R10A−, S, SO, SO2, S+R9A−, PR9, P+R9R10A−, P(O)R9, phenylene, carbohydrate, amino acid, peptide, or polypeptide, and
• R13, R14, and R15 are optionally substituted with one or more groups selected from the group consisting of sulfoalkyl, heterocycle, heteroaryl, quaternary heterocycle, quatemary heteroaryl, OR9, NR9R10, N+R9R11R12A−, SR9, S(O)R9, SO2R9, SO3R9, oxo, CO2R9, CN, halogen, CONR9R10, SO2OM, SO2NR9R10, PO(OR16)OR17, P+R9R10R11A−, S+R9R10A−, and C(O)OM,
• wherein R16 and R17 are independently selected from the substituents constituting R9 and M;
• or
• R14 and R15, together with the nitrogen atom to which they are attached, form a cyclic ring;
• R7 and R8 are independently selected from the group consisting of hydrogen and alkyl;
• and
• one or more Rx are independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, polyalkyl, acyloxy, aryl, arylalkyl, halogen, haloalkyl, cycloalkyl, heterocycle, heteroaryl, poiyether, quatemary heterocycle, quaternary heteroaryl, OR13, NR13R14, SR13, S(O)R13, S(O)2R13, SO3R13, S+R13R14A−, NR130R14, NR13NR14R15, NO2, CO2R13, CN, OM, SO2OM, SO2NR13R14, NR14C(O)R13, C(O)NR13R14, NR14C14O)R13, C(O)OM, COR13, OR15, S(O)nNR18, NR13R18, NR18OR14, N+R9R11R12A−, P+R9R11R12A−, amino acid, peptide, polypeptide, and carbohydrate,
• wherein alkyl, alkenyl, alkynyl, cycloalkyl, aryl, polyalkyl, heterocycle, heteroaryl, acyloxy, arylalkyl, haloalkyl, polyether, quaternary heterocycle, and quaternary heteroaryl can be further substituted with OR9, NR9R10, N+R9R11R12A−, SR9, S(O)R9, SO2R9, SO3R9, oxo, CO2R9, CN, halogen, CONR9R10, SO2OM, SO2NR9R10, PO(OR16)OR17, P+R9R11R12A−, S+R9R10A−, or C(O)M, and
• wherein R18 is selected from the group consisting of acyl, arylalkoxycarbonyl, arylalkyl, heterocycle, heteroaryl, alkyl, quaternary heterocycle, and quaternary heteroaryl, wherein acyl, arylalkoxycarbonyl, arylalkyl, heterocycle, heteroaryl, alkyl, quatemary heterocycle, and quaternary heteroaryl optionally are substituted with one or more substituents selected from the group consisting of OR9, NR9R10, N+R9R11R12A−, SR9, S(O)R9, SO2R9, SO3R9, oxo, CO2R9, CN, halogen, CONR9R10, SO3R9, SO2OM, SO2NR9R10, PO(OR16)OR17, and C(O)OM,
• wherein in Rx, one or more carbons are optionally replaced by O, NR13, N+R13R14A−, S, SO, SO2, S+R13A−, PR13, P(O)R13, P+R13R14A−, phenylene, amino acid, peptide, polypeptide, carbohydrate, polyether, or polyalkyl,
• wherein in said polyalkyl, phenylene, amino acid, peptide, polypeptide, and carbohydrate, one or more carbons are optionally replaced by O, NR9, N+R9R10A−, S, SO, SO2, S+R9A−, PR9, P+R9R10N, or P(O)R9;
• wherein quatemary heterocycle and quaternary heteroaryl are optionally substituted with one or more groups selected from the group consisting of alkyl, alkenyl, alkynyl, polyalkyl, polyether, aryl, haloalkyl, cycloalkyl, heterocycle, heteroaryl, arylalkyl, halogen, oxo, OR13, NR13R14, SR13, S(O)R13, SO2R13, SO3R13, NR13OR14, NR13NR14R15, NO2, CO2R13, CN, OM, SO2OM, SO2NR13R14, C(O)NR13R14, C(O)OM, COR13, P(O)R13R14, P+R13R14R15A−, P(OR13)OR14, S+R13R14A−, and N+R9R11R12A−,
• provided that both R5 and R6 cannot be hydrogen, OH, or SH, and R5 is OH, R1, R2, R3, R4, R7, and R8 cannot all be hydrogen;
• provided that when R5 or R6 is phenyl, only one of R1 or R2 is H;
• provided that when q=1 and Rx is styryl, anilido, or anilinocarbonyl, only one of R5 or R6 is alkyl;
• or
• a pharmaceutically acceptable salt, solvate, or prodrug thereof,
• wherein said first and second amounts of said inhibitors together comprise an anti-hyperlipidemic condition effective amount, and
• wherein said oral pharmaceutical composition is suitable for delivery of said anti-hyperlipidemic effective amount to the gastrointestinal tract of a patient by oral administration.

A combination therapy method for the treatment or prophylaxis of a hyperlipidemic condition in a patient in need thereof, said method comprising orally administering to said patient a pharmaceutical composition comprising a first amount of an ileal bile acid transport (IBAT) inhibitor of formula (I), a second amount of an HMG Co-A reductase inhibitor, and a pharmaceutically acceptable carrier,

• wherein said formula (I) is represented by:
• wherein:
• q is an integer from 1 to 4;
• n is an integer from 0 to 2;
• R1 and R2 are independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, haloalkyl, alkylaryl, arylalkyl, alkoxy, alkoxyalkyl, dialkylamino, alkylthio, (polyalkyl)aryl, and cycloalkyl,
• wherein alkyl, alkenyl, alkynyl, haloalkyl, alkylaryl, arylalkyl, alkoxy, alkoxyalkyl, dialkylamino, alkylthio, (polyalkyl)aryl, and cycloalkyl optionally are substituted with one or more substituents selected from the group consisting of OR9, NR9R10, N+R9R10RwA−, SR9, S+R9R10A−, P+R9R10R11A−, S(O)R9, SO2R9, SO3R9, CO2R9, CN, halogen, oxo, and CONR9R10,
• wherein alkyl, alkenyl, alkynyl, alkylaryl, alkoxy, alkoxyalkyl, (polyalkyl)aryl, and cycloalkyl optionally have one or more carbons replaced by O, NR9, N+R9R10A−, S, SO, SO2, S+R9A−, P+R9R10A−, or phenylene,
• wherein R9, R10, and Rw are independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, acyl, heterocycle, heteroaryl, ammoniumalkyl, arylalkyl, and alkylammoniumalkyl;
• or
• R1 and R2 taken together with the carbon to which they are attached form C3-C10 cycloalkylidene;
• R3 and R4 are independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, acyloxy, aryl, heterocycle, heteroaryl, OR9, NR9R10, SR9, S(O)R9, SO2R9, and SO3R9, wherein R9 and R10 are as defined above;
• or
• R3 and R4 together form ═O, ═NOR11, S, ═NNR11R12, ═NR9, or ═CR11R12, wherein R11 and R12 are independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, aryl, arylalkyl, alkenylalkyl, alkynylalkyl, heterocycle, heteroaryl, carboxyalkyl, carboalkoxyalkyl, cycloalkyl, cyanoalkyl, OR9, NR9R10 SR9, S(O)R9, SO2R9, SO3R9, CO2R9, CN, halogen, oxo, and CONR9R10, wherein R9 and R10 are as defined above, provided that both R3 and R4 cannot be OH, NH2, or SH, or
• R11 and R12 together with the nitrogen or carbon atom to which they are attached form a cyclic ring;
• R5 and R6 are independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocycle, heteroaryl, quatemary heterocycle, quartemary heteroaryl, SR9, S(O)R9, SO2R9, and SO3R9,
• wherein alkyl, alkenyl, aikynyl, aryl, cycloalkyl, heterocycle, heteroaryl, quatemary heterocycle, and quaternary heteroaryl can be substituted with one or more substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, polyalkyl, polyether, aryl, haloalkyl, cycloalkyl, heterocycle, heteroaryl, arylalkyl, quaternary heterocycle, quatemary heteroaryl, halogen, oxo, OR13, NR13R14, SR13, S(O)R13, SO2R13, SO3R13, NR13OR14, NR13NR14R15, NO2, CO2R13, CN, OM, SO2OM, SO2NR13R14, C(O)NR13R14, C(O)OM, COR13, P(O)R13R14, P+R13R14R15A−, P(OR13)OR14 , S+R13R14A−, and N+R9R11R12A−,
• wherein:
• A− is a phannaceutically acceptable anion and M is a pharmaceutically acceptable cation, said alkyl, alkenyl, alkynyl, polyalkyl, polyether, aryl, haloalkyl, cycloalkyl, heterocycle, and heteroaryl can be fi,irther substituted with one or more substituents selected from the group consisting of OR7, NR7R8, SR7, S(O)R7, SO2R7, SO3R7, CO2R7, CN, oxo, CONR7R8, N+R7R8R9A−, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocycle, heteroaryl, arylalkyl, quatemary heterocycle, quaternary heteroaryl, P(O)R7R8, P+R7R8R9A−, and P(O)(OR7)OR8 and
• wherein said alkyl, alkenyl, alkynyl, polyalkyl, polyether, aryl, haloalkyl, cycloalkyl, heterocycle, and heteroaryl, can optionally have one or more carbons replaced by O, NR7, N+R7R8A−, S, SO, SO2, S+R7A−, PR7, P(O)R7, P+R7R8A−, or phenylene, and R13, R14, and R15 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, polyalkyl, aryl, arylalkyl, cycloalkyl, heterocycle, heteroaryl, quatemary heterocycle, quaternary heteroaryl, and quatemary heteroarylalkyl,
• wherein alkyl, alkenyl, alkynyl, arylalkyl, heterocycle, heteroaryl, and polyalkyl optionally have one or more carbons replaced by O, NR9, N+R9R10A−, S, SO, SO2, S+R9A−, PR9, P+R9R10A−, P(O)R9, phenylene, carbohydrate, amino acid, peptide, or polypeptide, and
• R13, R14, and R15 are optionally substituted with one or more groups selected from the group consisting of sulfoalkyl, heterocycle, heteroaryl, quatemary heterocycle, quaternary heteroaryl, OR9, NR9R10, N+R9R11R12A−, SR9, S(O)R9, SO2R9, SO3R9, oxo, CO2R9, CN, halogen, CONR9R10, SO2OM, SO2NR9R10, PO(OR16)OR17, P+R9R10R11A−, S+R9R10A−, and C(O)OM,
• wherein R16 and R17 are independently selected from the substituents constituting R9 and M;
• or
• R14 and R15, together with the nitrogen atom to which they are attached, form a cyclic ring;
• R7 and R8 are independently selected from the group consisting of hydrogen and alkyl;
• and
• one or more Rx are independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, polyalkyl, acyloxy, aryl, arylalkyl, halogen, haloalkyl, cycloalkyl, heterocycle, heteroaryl, polyether, quaternary heterocycle, quatemary heteroaryl, OR13, NR13R14, SR13, S(O)R13, S(O)2R13, SO3R13, S+R13R14A−, NR13OR14, NR13NR14R15, NO2, CO2R13, CN, OM, SO2OM, SO2NR13R14, NR14C(O)R13, C(O)NR13R14, NR14C(O)R13, C(O)OM, COR13, OR18, S(O)nNR18, NR13R18, NR18OR14, N+R9R11R12A−, P+R9R11R12A−, amino acid, peptide, polypeptide, and carbohydrate,
• wherein alkyl, alkenyl, aikynyl, cycloalkyl, aryl, polyalkyl, heterocycle, heteroaryl, acyloxy, arylalkyl, haloalkyl, polyether, quatemary heterocycle, and quatemary heteroaryl can be further substituted with OR9, NR9R10, N+R9R11R12A−, SR9, S(O)R9, SO2R9, SO3R9, oxo, CO2R9, CN, halogen, CONR9R10, SO2OM, SO2NR9R10, PO(OR16)OR17, P+R9R11R12A−, S+R9R10A−, or G(O)M, and
• wherein R18 is selected from the group consisting of acyl, arylalkoxycarbonyl, arylalkyl, heterocycle, heteroaryl, alkyl, quaternary heterocycle, and quatemary heteroaryl, wherein acyl, arylalkoxycarbonyl, arylalkyl, heterocycle, heteroaryl, alkyl, quaternary heterocycle, and quaternary heteroaryl optionally are substituted with one or more substituents selected from the group consisting of OR9, NR9R10, N+R9R11R12A−, SR9, S(O)R9, SO2R9, SO3R9, oxo, CO2R9, CN, halogen, CONR9R10, SO3R9, SO2OM, SO2NR9R10, PO(OR16)OR17, and C(O)OM,
• wherein in Rx, one or more carbons are optionally replaced by O, NR13, N+R13R14A−, S, SO, SO2, S+R13A−, PR13, P(O)R13, P+R13R14A−, phenylene, amino acid, peptide, polypeptide, carbohydrate, polyether, or polyalkyl,
• wherein in said polyalkyl, phenylene, amino acid, peptide, polypeptide, and carbohydrate, one or more carbons are optionally replaced by O, NR9, N+R9R10A−, S, SO, SO2, S+R9A−, PR9, P+R9R10A−, or P(O)R9;
• wherein quatemary heterocycle and quaternary heteroaryl are optionally substituted with one or more groups selected from the group consisting of alkyl, alkenyl, alkynyl, polyalkyl, polyether, aryl, haloalkyl, cycloalkyl, heterocycle, heteroaryl, arylalkyl, halogen, oxo, OR13, NR13R14, SR13, S(O)R13, SO2R13, SO3R13, NR13OR14, NR13NR14R15, NO2, CO2R13, CN, OM, SO2OM, SO2NR13R14, C(O)NR13R14, C(O)OM, COR13, P(O)R13R14, P+R13R14R15A−, P(OR13)OR14, S+R13R14A−, and N+R9R11R12A−,
• provided that both R5 and R6 cannot be hydrogen, OH, or SH, and R5 is OH, R1, R2, R3, R4, R7, and R8 cannot all be hydrogen;
• provided that when R5 or R6 is phenyl, only one of R1 or R2 is H;
• provided that when q═1 and Rx is styryl anilido or anilinocarbonyl only one of R5 or R6 is alkyl;
• or
• a pharmaceutically acceptable salt, solvate, or prodrug thereof,
• wherein said first and second amounts of said inhibitors together comprise an anti-hyperlipidemic condition effective amount, and
• wherein said pharmaceutical composition is suitable for delivery of said anti-hyperlipidemic effective amount to the gastrointestinal tract of said patient by oral administration.