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US 6,221,856 B1Granted
Inositol derivatives for inhibiting superoxide anion production
AssigneesInologic, Inc., The Regents of the University of California
InventorsAlexis E. Traynor-Kaplan, Carsten Schultz, Marco T. Rudolf
Life of this patent
Estimating the term…
Abstract
Inositol derivatives, compositions comprising inositol derivatives, and methods for using compositions comprising inositol derivatives as agents for inhibiting superoxide anion production are described. The inositol derivatives are obtainable via conventional organic synthesis. The inositol derivatives inhibit superoxide anion produced by neutrophils and macrophages which cause tissue damage.
Claims50
A method for inhibiting superoxide anion production, comprising administering to a mammal in need of such inhibition a therapeutically effective amount of a compound havin the formula (I):
- or a racemate thereof, or a pharmaceutically acceptable salt thereof,
- wherein each RW is independently selected from the group consisting of hydrogen, —OH, —C1-C20 straight or branched chain alkyl,—C2-C20 straight or branched chain alkenyl or alkynyl, —OC(O)C1-C20 straight or branched chain alkyl, —OC(O)C2-C20 straight or branched chain alkenyl or alkynyl, —OC1-C20 straight or branched chain alkyl, and —OC2-C20 straight or branched chain alkenyl or alkynyl;
- each R2 is independently selected from the group consisting of hydrogen and —C(R3)(R3)OC(O)C1-C4 straight or branched chain alkyl;
- and
- each R3 is independently selected from the group consisting of hydrogen, —C1-C12 alkyl, phenyl, and benzyl, or both R3 taken together form a 5- or 6-membered ring, said R3, except hydrogen, being unsubstituted or substituted with one or more halogen, —OH, C1-C6 alkyl, NO2, —OC1-C6 alkyl, and —OC(O)C1-C6 alkl groups.
2 more elements
A method for inhibiting superoxide anion production, comprising contacting a cell or tissue with an effective amount of a compound having the general formula (I):
- or a racemate thereof, or a pharmaceutically acceptable salt thereof,
- wherein each R1 is independently selected from the group consisting of hydrogen, —OH, —C1-C20 straight or branched chain alkyl,—C2-C20 straight or branched chain alkenyl or alkynyl, —OC(O)C1-C20 straight or branched chain alkyl, —OC(O)C2-C20 straight or branched chain alkenyl or alkynyl, —OC1-C20 straight or branched chain alkyl, and —OC2-C20 straight or branched chain alkenyl or alkynyl;
- each R2 is independently selected from the group consisting of hydrogen and —C(R3)(R3)OC(O)C1-C4 straight or branched chain alkyl;
- and
- each R3 is independently selected from the group consisting of hydrogen, —C1-C12 alkyl, phenyl, and benzyl, or both R3 taken together form a 5- or 6-membered ring, said R3, except hydrogen, being unsubstituted or substituted with one or more halogen, —OH, C1-C6 alkyl, NO2, —OC1-C6 alkyl, and —OC(O)C1-C6 alkyl groups.
2 more elements
A method for inhibiting superoxide anion production, comprising administering to a mammal in need of such inhibition a therapeutically effective amount of a compound having the general formula (II):
- or an L-enantiomer or racemate thereof, or a pharmaceutically acceptable salt thereof,
- wherein each R1 is independently selected from the group consisting of hydrogen, —OH, —C1-C20 straight or branched chain alkyl, —C2-C20 straight or branched chain alkenyl or alkynyl, —OC(O)C1-C20 straight or branched chain alkyl —OC(O)C2-C20 straight or branched chain alkenyl or alkynyl, —OC1-C20 straight or branched chain alkyl, and —OC2-C20 straight or branched chain alkenyl or alkynyl;
- each R2 is independently selected from the group consisting of hydrogen and —C(R3)(R3)OC(O)C1-C4 straight or branched chain alkyl;
- each R3 is independently selected from the group consisting of hydrogen, —C1-C12 alkyl, phenyl, benzyl, or both R3 taken together form a 5- or 6-membered ring, said R3, except hydrogen, being unsubstituted or substituted with one or more halogen, —OH, C1-C6 alkyl, NO2, —OC1-C6 alkyl, and —OC(O)C1-C6 alkyl groups;
- each R5is independently selected from the group consisting of hydrogen and —CH2CH(XR6)CH2XR6;
- each R6 is independently selected from the group consisting of hydrogen, —C1-C23 straight or branched chain alkyl —C2-C23 alkenyl and —C4-C23 alkadienyl;
- and
- each X is independently selected from the group consisting of —OC(O)—, —SC(O)—, —OC(S)—, —S— and —O—.
5 more elements
A method for inhibiting superoxide anion production, comprising contacting a cell or tissue with an effective amount of a compound having the general formula (II):
- or an L-enantioner or racemate thereof, or a pharmaceutically acceptable salt thereof,
- wherein each R1 is independently selected from the group consisting of hydrogen, —OH, —C1-C2. straight or branched chain alkyl, —C2-C20 straight or branched chain alkenyl or alkynyl, —OC(O)C1-C20 straight or branched chain alkyl, —OC(O)C2-C20 straigt or branched chain alkenyl or alkynyl, —OC1-C20 straight or branched chain alkyl, and —OC2-C20 straight or branched chain alkenyl or alkynyl;
- each R2 is independently selected from the group consisting of hydrogen and —C(R3)(R3)OC(O)C1-C4 straight or branched chain alkyl;
- each R3 is independently selected from the group consisting of hydrogen, —C1-C12 alkyl, phenyl, benzyl, or both le taken together form a 5- or 6-membered ring, said R3, except hydrogen, being unsubstituted or substituted with one or more halogen, —OH, C1-C6 alkyl, NO2, —OC1-C6 alkyL, and —OC(O)C1-C6 alkyl groups;
- each R6 is independently selected from the group consisting of hydrogen and —CH2CH(XR6)CH2XR6;
- each R6 is independently selected from the group consisting of hydrogen, —C1-C23 straight or branched chain alkyl, —C2-C23 alkenyl and —C4-C23 alkadienyl;
- and
- each X is independently selected from the group consisting of —OC(O)—, —SC(O)—, —OC(S)—, —S— and —O—.
5 more elements
A compound having the formula (I):
- or a racemate thereof, or a pharmaceutically acceptable salt thereof,
- wherein each R1 is independently selected from the group consisting of hydrogen, —OH, —C1-C20 straight or branched chain alkyl,—C2-C20 straight or branched chain alkenyl or alkynyl, —OC(O)C1-C20 straight or branched chain alkyl, —OC(O)C2-C20 straight or branched chain alkenyl or alkynyl, —OC1-C20 straight or branched chain alkyl, and —OC2-C20 straight or branched chain alkenyl or alkynyl;
- each R2 is independently selected from the group consisting of hydrogen and —C(R3)(R3)OC(O)C1-C4 straight or branched chain alkyl;
- and
- each R3 is independently selected from the group consisting of hydrogen, —C1-C12 alkyl, phenyl, and benzyl, or both R3 taken together form a 5- or 6-membered ring, said R3, except hydrogen, being unsubstituted or substituted with one or more halogen, —OH, C1-C6 alkyl, NO2, —OC1-C6 alkyl, and —OC(O)C1-C6 alkyl groups,
- with the proviso that the compound of formula (I) is not:
- D- or D,L-myoinositol 1,4,5,6-tetrakisphosphate;
- D- or D,L-2,3-di-O-methyl-myo-inositol 1,4,5,6-tetrakisphosphate octakis(acetoxymethyl) ester;
- D- or D,L-2-O-butyryl-3-O-methyl-myo-inositol 1,4,5,6-tetrakisphosphate octakis(acetoxymethyl) ester;
- D- or D,L-2-O-butyl-3-O-butyryl-myo-inositol 1,4,5,6-tetrakisphosphate octakis(acetoxymethyl) ester;
- D- or D,L-2,3-dideoxy-myo-inositol 1,4,5,6-tetrakisphosphate octakis(acetoxymethyl)ester;
- D- or D,L-2,3-di-O-butyl-myo-inositol 1,4,5,6-tetrakisphosphate octakis(acetoxymethyl) ester;
- D- or D,L-3-O-butyl-2-O-butyryl-myo-inositol 1,4,5,6-tetrakisphosphate octakis(acetoxymethyl) ester;
- D- or D,L-2,3-di-O-butyryl-myo-inositol 1,4,5,6-tetrakisphosphate octakis(acetoxymethyl) ester;
- D- or D,L-3-O-butyryl-2-deoxy-myo-inositol 1,4,5,6-tetrakisphosphate octakis(acetoxymethyl) ester;
- D,L-2-O-butyryl-1-deoxy-myo-inositol 3,4,5,6-tetrakisphosphate octakis(acetoxymethyl) ester;
- D,L-1-O-butyryl-2-O-methyl-myo-inositol 3,4,5,6-tetrakisphosphate octakis(acetoxymethyl) ester;
- or
- D,L-1,2-cyclohexylidene-myo-inositol 1,4,5,6-tetrakisphosphate octakis(acetoxymethyl)ester.
16 more elements
A compound having the formula (II):
- or an L-enantiomer or racemate thereof, or a pharmaceutically acceptable salt thereof,
- wherein each R1 is independently selected from the group consisting of hydrogen, —OH, —C1-C20 straight or branched chain alkyl, —C2-C20 straight or branched chain alkenyl or alkynyl, —OC(O)C1-C20 straight or branched chain alkyl, —OC(O)C2-C20 straight or branched chain alkenyl or alkynyl, —OC1-C20 straight or branched chain alky, and —OC2-C20 straight or branched chain alkenyl or alkynyl;
- each R2 is independently selected from the group consisting of hydrogen and —C(R3)(R3)OC(O)C1-C4 straight or branched chain alkyl;
- each R3 is independently selected from the group consisting of hydrogen, —C1-C12 alkyl phenyl, and benzyl, or both R3 taken together form a 5- or 6-membered ring, said R3, except hydrogen, being unsubstituted or substituted with one or more halogen, —OH, C1-C6 alkyl, NO2, —OC1-C6 alkyl, and —OC(O)C1-C6 alkyl groups;
- each R5 is independently selected from the group consisting of hydrogen and CH2CH(XR6)CH2XR6;
- each R6 is independently selected from the group consisting of hydrogen, —C1-C23 straight or branched chain alkyl, —C2-C23 alkenyl and —C4-C23 alkadienyl;
- and
- each X is independently selected from the group consisting of —OC(O)—, —C(O)—, —OC(S)—, —S— and —O—,
- with the proviso that the compound of formula (II) is not:
- sn-di-O-palmitoyl-D,L-6-O-butyryl-phosphatidylinositol 3,4,5-trisphosphate eptakis(acetoxymethyl)ester;
- sn-di-O-octanoyl-D,L-6-O-butyryl-phosphatidylinositol 3,4,5-trisphosphate eptakis(acetoxymethyl)ester;
- sn-di-O-palhnitoyl-D,L-2-O-butyryl-phosphatidylinositol 3,4,5-trisphosphate eptakis(acetoxymethyl)ester;
- sn-di-O-octanoyl-D,L-2-O-butyryl-phosphatidylinositol 3,4,5-trisphosphate eptakis(acetoxymethyl)ester;
- sn-di-O-palmitoyl-D,L-2,6-di-O-butyryl-phosphatidylinositol 3,4,5-trisphosphate heptakis(acetoxymethyl)ester;
- sn-di-O-octanoyl-D,L-2,6-di-O-butyryl-phosphatidylinositol 3,4,5-trisphosphate heptakis(acetoxymethyl)ester;
- D- or D,L-phosphatidylinositol 3,4,5-trisphosphate;
- sn-di-O-lauryl-D- or sn-di-O-lauryl-D,L-phosphatidylinositol 3,4,5-trisphosphate heptakis(acetoxymethyl)ester;
- sn-di-O-octanoyl-D- or sn-di-O-octanoyl-D,L-phosphatidylinositol 3,4,5-trisphosphate heptakis(acetoxymethyl)ester;
- or
- sn-di-O-palmitoyl-D- or sn-di-O-palmitoyl-D,L-phosphatidylinositol 3,4,5-trisphosphate heptakis(acetoxymethyl)ester.
17 more elements
Dependencies are inferred from the claim text.