Back to results
US 2004/0110803 A1Published application
Methods and compositions for the use of D-malic acid to decrease serum triglyceride, cholesterol and lipoprotein levels
OwnerHossein Dovlatabadi, Ronald L. Jenkinsinventors
Life of this patent
Estimating the term…
Abstract
Compositions, methods and uses are provided for treating or preventing cardiovascular disease, including by decreasing serum cholesterol, triglyceride and lipoprotein cholesterol levels in a host that include administering an effective amount of D-malic acid or its pharmaceutically acceptable salt, prodrug or pharmaceutically acceptable derivative.
Claims47
A method for treating cardiovascular disease in a host comprising administering an effective amount of a compound of the following formula:
- 4
- or a pharmaceutically acceptable salt, prodrug or active derivative thereof, wherein:
- R1 and R2 are selected from the group consisting of OR4, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyi, substituted alkynyl, alkoxy, substituted alkyloxy, alkoxyalkyl, substituted alkoxyalkyl, NH2, NHR5, NR7R6, mono- or polyhydroxy-substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, acyloxy, substituted acyloxy, or haloalkyl;
- and,
- R3 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkyloxy, alkoxyalkyl, substituted alkoxyalkyl, mono- or polyhydroxy-substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, acyloxy, substituted acyloxy, alkylsulfonyl, arylsulfonyl, aralkylsulfonyl, amino acid residue, haloalkyl, or the carboxylic moiety of an ester;
- and,
- R4 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkyloxy, alkoxyalkyl, substituted alkoxyalkyl, substituted aryl, heteroaryl, substituted heteroaryl, acyloxy, or substituted acyloxy;
- and,
- R5, R6, and R7 are selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkyloxy, alkoxyalkyl, substituted alkoxyalkyl, substituted aryl, heteroaryl, substituted heteroaryl, acyloxy, or substituted acyloxy.
6 more elements
A method for decreasing the serum lipoprotein cholesterol level in a host comprising administering an effective amount of a compound of the following formula:
- 5
- or a pharmaceutically acceptable salt, prodrug or active derivative thereof, wherein:
- R1 and R2 are selected from the group consisting of OR4, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkyloxy, alkoxyalkyl, substituted alkoxyalkyl, NH2, NHR5, NR7R6, mono- or polyhydroxy-substituted alkyl aryl, substituted aryl, heteroaryl, substituted heteroaryl, acyloxy, substituted acyloxy, or haloalkyl;
- and,
- R3 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkyloxy, alkoxyalkyl, substituted alkoxyalkyl, mono- or polyhydroxy-substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, acyloxy, substituted acyloxy, alkylsulfonyl, arylsulfonyl, aralkylsulfonyl, amino acid residue, haloalkyl, or the carboxylic moiety of an ester;
- and,
- R4 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkyloxy, alkoxyalkyl, substituted alkoxyalkyl, substituted aryl, heteroaryl, substituted heteroaryl, acyloxy, or substituted acyloxy;
- and,
- R5, R6, and R7 are selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkyloxy, alkoxyalkyl, substituted alkoxyalkyl, substituted aryl, heteroaryl, substituted heteroaryl, acyloxy, or substituted acyloxy.
6 more elements
A method for decreasing the low density lipoprotein cholesterol level in a host comprising administering an effective amount of a compound of the following formula:
- 6
- or a pharmaceutically acceptable salt, prodrug or active derivative thereof, wherein:
- R1 and R2 are selected from the group consisting of OR4, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkyloxy, alkoxyalkyl, substituted alkoxyalkyl, NH2, NHR5, NR7R6, mono- or polyhydroxy-substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, acyloxy, substituted acyloxy, or haloalkyl;
- and,
- R3 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkyloxy, alkoxyalkyl, substituted alkoxyalkyl, mono- or polyhydroxy-substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, acyloxy, substituted acyloxy, alkylsulfonyl, arylsulfonyl, aralkylsulfonyl, amino acid residue, haloalkyl, or the carboxylic moiety of an ester;
- and,
- R4 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkyloxy, alkoxyalkyl, substituted alkoxyalkyl, substituted aryl, heteroaryl, substituted heteroaryl, acyloxy, or substituted acyloxy;
- and,
- R5, R6, and R7 are selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkyloxy, alkoxyalkyl, substituted alkoxyalkyl, substituted aryl, heteroaryl, substituted heteroaryl, acyloxy, or substituted acyloxy.
6 more elements
A method for decreasing the very low density lipoprotein cholesterol level in a host comprising administering an effective amount of a compound of the following formula:
- 7
- or a pharmaceutically acceptable salt, prodrug or active derivative thereof, wherein:
- R1 and R2 are selected from the group consisting of OR4, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkyloxy, alkoxyalkyl, substituted alkoxyalkyl, NH2, NHR5, NR7R6, mono- or polyhydroxy-substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, acyloxy, substituted acyloxy, or haloalkyl;
- and,
- R3 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkyloxy, alkoxyalkyl, substituted alkoxyalkyl, mono- or polyhydroxy-substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, acyloxy, substituted acyloxy, alkylsulfonyl, arylsulfonyl, aralkylsulfonyl, amino acid residue, haloalkyl, or the carboxylic moiety of an ester;
- and,
- R4 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkyloxy, alkoxyalkyl, substituted alkoxyalkyl, substituted aryl, heteroaryl, substituted heteroaryl, acyloxy, or substituted acyloxy;
- and,
- R5, R6, and R7 are selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkyloxy, alkoxyalkyl, substituted alkoxyalkyl, substituted aryl, heteroaryl, substituted heteroaryl, acyloxy, or substituted acyloxy.
6 more elements
A method for decreasing the serum triglyceride level in a host comprising administering an effective amount of a compound of the following formula:
- 8
- or a pharmaceutically acceptable salt, prodrug or active derivative thereof, wherein:
- R1 and R2 are selected from the group consisting of OR4, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkyloxy, alkoxyalkyl, substituted alkoxyalkyl, NH2, NHR5, NR7R6, mono- or polyhydroxy-substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, acyloxy, substituted acyloxy, or haloalkyl;
- and,
- R3 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkyloxy, alkoxyalkyl, substituted alkoxyalkyl, mono- or polyhydroxy-substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, acyloxy, substituted acyloxy, alkylsulfonyl, arylsulfonyl, aralkylsulfonyl, amino acid residue, haloalkyl, or the carboxylic moiety of an ester;
- and,
- R4 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkyloxy, alkoxyalkyl, substituted alkoxyalkyl, substituted aryl, heteroaryl, substituted heteroaryl, acyloxy, or substituted acyloxy;
- and,
- R5, R6, and R7 are selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkyloxy, alkoxyalkyl, substituted alkoxyalkyl, substituted aryl, heteroaryl, substituted heteroaryl, acyloxy, or substituted acyloxy.
6 more elements
A method for decreasing the total serum cholesterol level in a host comprising administering an effective amount of a compound of the following formula:
- 9
- or a pharmaceutically acceptable salt, prodrug or active derivative thereof, wherein:
- R1 and R2 are selected from the group consisting of OR4, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkyloxy, alkoxyalkyl, substituted alkoxyalkyl, NH2, NHR5, NR7R6, mono- or polyhydroxy-substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, aeyloxy, substituted acyloxy, or haloalkyl;
- and,
- R3 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkyloxy, alkoxyalkyl, substituted alkoxyalkyl, mono- or polyhydroxy-substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, acyloxy, substituted acyloxy, alkylsulfonyl, arylsulfonyl, aralkylsulfonyl, amino acid residue, haloalkyl, or the carboxylic moiety of an ester;
- and,
- R4 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkyloxy, alkoxyalkyl, substituted alkoxyalkyl, substituted aryl, heteroaryl, substituted heteroaryl, acyloxy, or substituted acyloxy;
- and,
- R5, R6, and R7 are selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkyloxy, alkoxyalkyl, substituted alkoxyalkyl, substituted aryl, heteroaryl, substituted heteroaryl, acyloxy, or substituted acyloxy.
6 more elements
A pharmaceutical composition for decreasing the serum lipoprotein cholesterol level in a host consisting essentially of a compound of the following formula:
- 10
- or a pharmaceutically acceptable salt, prodrug or active derivative thereof, wherein:
- R1 and R2 are selected from the group consisting of OR4, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkyloxy, alkoxyalkyl, substituted alkoxyalkyl, NH2, NHR5, NR7R6, mono- or polyhydroxy-substitUted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, acyloxy, substituted acyloxy, or haloalkyl;
- and,
- R3 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkyloxy, alkoxyalkyl, substituted alkoxyalkyl, mono- or polyhydroxy-substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, acyloxy, substituted acyloxy, alkylsulfonyl, arylsulfonyl, aralkylsulfonyl, amino acid residue, haloalkyl, or the carboxylic moiety of an ester;
- and,
- R4 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkyloxy, alkoxyalkyl, substituted alkoxyalkyl, substituted aryl, heteroaryl, substituted heteroaryl, acyloxy, or substituted acyloxy;
- and,
- R5, R6, and R7 are selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkyloxy, alkoxyalkyl, substituted alkoxyalkyl, substituted aryl, heteroaryl, substituted heteroaryl, acyloxy, or substituted acyloxy.
6 more elements
A pharmaceutical composition for decreasing the serum total cholesterol level in a host consisting essentially of a compound of the following formula:
- 11
- or a pharmaceutically acceptable salt, prodrug or active derivative thereof, wherein:
- R1 and R2 are selected from the group consisting of OR4, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkyloxy, alkoxyalkyl, substituted alkoxyalkyl, NH2, NHR5, NR7R6, mono- or polyhydroxy-substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, acyloxy, substituted acyloxy, or haloalkyl;
- and,
- R3 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkyloxy, alkoxyalkyl, substituted alkoxyalkyl, mono- or polyhydroxy-substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, acyloxy, substituted acyloxy, alkylsulfonyl, arylsulfonyl, aralkylsulfonyl, amino acid residue, haloalkyl, or the carboxylic moiety of an ester;
- and,
- R4 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkyloxy, alkoxyalkyl, substituted alkoxyalkyl, substituted aryl, heteroaryl, substituted heteroaryl, acyloxy, or substituted acyloxy;
- and,
- R5, R6, and R7 are selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkyloxy, alkoxyalkyl, substituted alkoxyalkyl, substituted aryl, heteroaryl, substituted heteroaryl, acyloxy, or substituted acyloxy.
6 more elements
A pharmaceutical composition for decreasing the serum triglyceride level in a host consisting essentially of a compound of the following formula:
- 12
- or a pharmaceutically acceptable salt, prodrug or active derivative thereof, wherein:
- R1 and R2 are selected from the group consisting of OR4, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkyloxy, alkoxyalkyl, substituted alkoxyalkyl, NH2, NHR5, NR7R6, mono- or polyhydroxy-substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, acyloxy, substituted acyloxy, or haloalkyl;
- and,
- R3 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkyloxy, alkoxyalkyl, substituted alkoxyalkyl, mono- or polyhydroxy-substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, acyloxy, substituted acyloxy, alkylsulfonyl, arylsulfonyl, aralkylsulfonyl, amino acid residue, haloalkyl, or the carboxylic moiety of an ester;
- and,
- R4 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkyloxy, alkoxyalkyl, substituted alkoxyalkyl, substituted aryl, heteroaryl, substituted heteroaryl, acyloxy, or substituted acyloxy;
- and,
- R5, R6, and R7 are selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkyloxy, alkoxyalkyl, substituted alkoxyalkyl, substituted aryl, heteroaryl, substituted heteroaryl, acyloxy, or substituted acyloxy.
6 more elements
A method for treating hyperlipidemia comprising administering to a host an effective amount of a compound of the following formula:
- 13
- or a pharmaceutically acceptable salt, prodrug or active derivative thereof, wherein:
- R1 and R2 are selected from the group consisting of OR4, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkyloxy, alkoxyalkyl, substituted alkoxyalkyl, NH2, NHR5, NR7R6, mono- or polyhydroxy-substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, acyloxy, substituted acyloxy, or haloalkyl;
- and,
- R3 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkyloxy, alkoxyalkyl, substituted alkoxyalkyl, mono- or polyhydroxy-substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, acyloxy, substituted acyloxy, alkylsulfonyl, arylsulfonyl, aralkylsulfonyl, amino acid residue, haloalkyl, or the carboxylic moiety of an ester;
- and,
- R4 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkyloxy, alkoxyalkyl, substituted alkoxyalkyl, substituted aryl, heteroaryl, substituted heteroaryl, acyloxy, or substituted acyloxy;
- and,
- R5, R6, and R7 are selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkyloxy, alkoxyalkyl, substituted alkoxyalkyl, substituted aryl, heteroaryl, substituted heteroaryl, acyloxy, or substituted acyloxy.
6 more elements
Dependencies are inferred from the claim text.