# US 6,221,856 B1 · Inositol derivatives for inhibiting superoxide anion production

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- Number: US 6,221,856 B1
- Document ID: US6221856B1
- Status: Granted
- Kind: B1
- Application number: 09/244,087
- Filed: 1999-02-03
- Granted: 2001-04-24
- Earliest claimed: 1999-02-03
- Assignees: Inologic, Inc.; The Regents of the University of California
- Inventors: Alexis E. Traynor-Kaplan; Carsten Schultz; Marco T. Rudolf
- Web page: https://patentgrep.com/patent/US6221856B1

## CPC

- A61K 31/6615: Compounds having two or more esterified phosphorus acid groups, e.g. inositol triphosphate, phytic acid
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 17/00: Drugs for dermatological disorders
- A61P 17/06: Antipsoriatics
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 39/02: Antidotes
- A61P 39/06: Free radical scavengers or antioxidants
- C07F 9/117: with cycloaliphatic alcohols
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07F: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM (metal-containing porphyrins C07D487/22)

## 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.

## Claims

### Claim 1

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.

### Claim 2 (depends on 1)

The method of claim 1, wherein the superoxide anion production is caused by inflammation.

### Claim 3 (depends on 2)

The method of claim 2, wherein the inflammation accompanies a condition selected from the group consisting of physical trauma, dermatitis, eczema, psoriasis, acute contact dermatitis, drug eruption, gastritis, inflammatory bowel disease, rheumatoid arthritis, non-rheumatoid arthritis, asthma, ischemia/reperfusion injury, ulcerative colitis, adult respiratory distress syndrome, smoke inhalation, heart attack, stroke, chronic lung disease, arthritis, alcoholic liver disease, xenobiotic toxicity and iron toxicity.

### Claim 4 (depends on 1)

The methods of claim 1, wherein the compound is administered in a composition comprising a pharmaceutically acceptable carrier or vehicle.

### Claim 5 (depends on 4)

The method of claim 4, wherein the composition further comprises a drug selected from the group consisting of a non-steroidal anti-inflammatory drug, a leukotriene antagonist and an anti-inflammatory agent.

### Claim 6 (depends on 5)

The method of claim 5, wherein the non-steroidal anti-inflammatory drug is selected from the group consisting of salicylic acid, acetylsalicylic acid, methyl salicylate, diflunisal, salsalate, olsalazine, sulfasalazine, acetaminophen, indomethacin, sulindac, etodolac, mefenamic acid, meclofenamate sodium, tolmetin, ketorolac, dichlofenac, ibuprofen, naproxen, naproxen sodium, fenoprofen, ketoprofen, flurbinprofen, oxaprozin, piroxicam, meloxicam, anpiroxicam, droxicam, pivoxicam, tenoxicam, nabumetome, phenylbutazone, oxyphenbutazone, antipyrine, aminopyrine, apazone and nimesulide.

### Claim 7 (depends on 5)

The method of claim 5, wherein the leukotriene antagonist is selected from the group consisting of zileuton, aurothioglucose, gold sodium thiomalate and auranofin.

### Claim 8 (depends on 5)

The method of claim 5, wherein the anti-inflammatory agent is selected from the group consisting of coichicine, allopurinol, probenecid, sulfinpyrazone and benzbromarone.

### Claim 9

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.

### Claim 10 (depends on 9)

The method of claim 9, wherein the superoxide anion production is caused by inflammation.

### Claim 11 (depends on 10)

The method of claim 10, wherein the inflammation accompanies a condition selected from the group consisting of physical trauma, dermatitis, eczema, psoriasis, acute contact dermatitis, drug eruption, gastritis, inflammatory bowel disease, rheumatoid arthritis, non-rheumatoid arthritis, asthma, ischemia/reperfusion injury, ulcerative colitis, adult respiratory distress syndrome, smoke inhalation, heart attack, stroke, chronic lung disease, arthritis, alcoholic liver disease, xenobiotic toxicity and iron toxicity.

### Claim 12 (depends on 11)

The method of claim 11, wherein the compound is delivered in a composition comprising a pharmaceutically acceptable carrier or vehicle.

### Claim 13 (depends on 9)

The method of claim 9, wherein the composition further comprises a drug selected from the group consisting of a non-steroidal anti-inflammatory drug, a leukotriene antagonist and an anti-inflammatory agent.

### Claim 14 (depends on 13)

The method of claim 13, wherein the non-steroidal anti-inflammatory drug is selected from the group consisting of salicylic acid, acetylsalicylic acid, methyl salicylate, diflunisal, salsalate, olsalazine, sulfasalazine, acetaminophen, indomethacin, sulindac, etodolac, mefenamic acid, meclofenamate sodium, tolmetin, ketorolac, dichlofenac, ibuprofen, naproxen, naproxen sodium, fenoprofen, ketoprofen, flurbinprofen, oxaprozin, piroxicam, meloxicam, ampiroxicam, droxicam, pivoxicam, tenoxicam, nabumetome, phenylbutazone, oxyphenbutazone, antipyrine, aminopyrine, apazone and nimesulide.

### Claim 15 (depends on 13)

The method of claim 13, wherein the leukotriene antagonist is selected from the group consisting of zileuton, aurothioglucose, gold sodium thiomalate and auranofin.

### Claim 16 (depends on 13)

The method of claim 13, wherein the anti-inflammatory agent is selected from the group consisting of colchicine, allopurinol, probenecid, sulfinpyrazone and benzbromarone.

### Claim 17

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—.

### Claim 18 (depends on 17)

The method of claim 17, wherein the superoxide anion production is caused by inflammation.

### Claim 19 (depends on 18)

The method of claim 18, wherein the inflammation accompanies a condition selected from the group consisting of physical trauma, dermatitis, eczema, psoriasis, acute contact dermatitis, drug eruption, gastritis, inflammatory bowel disease, rheumatoid arthritis, non-rheumatoid arthritis, asthma, ischemia/reperfusion injury, ulcerative colitis, adult respiratory distress syndrome, smoke inhalation, heart attack, stroke, chronic lung disease, arthritis, alcoholic liver disease, xenobiotic toxicity and iron toxicity.

### Claim 20 (depends on 17)

The method of claim 17, wherein the compound is administered in a composition comprising a pharmaceutically acceptable carrier or vehicle.

### Claim 21 (depends on 20)

The method of claim 20, wherein the composition further comprises a drug selected from the group consisting of a non-steroidal anti-inflammatory drug, a leukotriene antagonist and an anti-inflammatory agent.

### Claim 22 (depends on 21)

The method of claim 21, wherein the non-steroidal anti-inflammatory drug is selected from the group consisting of salicylic acid, acetylsalicylic acid, methyl salicylate, diflunisal, salsalate, olsalazine, sulfasalazine, acetaminophen, indomethacin, sulindac, etodolac, mefenamic acid, meclofenamate sodium, tolmetin, ketorolac, dichlofenac, ibuprofen, naproxen, naproxen sodium, fenoprofen, ketoprofen, flurbinprofen, oxaprozin, piroxicam, meloxicam, ampiroxicam, droxicam, pivoxicam, tenoxicam, nabumetome, phenylbutazone, oxyphenbutazone, antipyrine, aminopyrine, apazone and nimesulide.

### Claim 23 (depends on 21)

The method of claim 21, wherein the leukotriene antagonist is selected from the group consisting of zileuton, aurothioglucose, gold sodium thiomalate and auranofin.

### Claim 24 (depends on 21)

The method of claim 21, wherein the anti-inflammatory agent is selected from the group consisting of colchicine, allopurinol, probenecid, sulfinpyrazone and benzbromarone.

### Claim 25

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—.

### Claim 26 (depends on 25)

The method of claim 25, wherein the superoxide anion production is caused by inflammation.

### Claim 27 (depends on 26)

The method of claim 26, wherein the inflammation accompanies a condition selected from the group consisting of physical trauma, dermatitis, eczema, psoriasis, acute contact dermatitis, drug eruption, gastritis, inflammatory bowel disease, rheumatoid arthritis, non-rheumatoid arthritis, asthma, ischemia/reperfusion injury, ulcerative colitis, adult respiratory distress syndrome, smoke inhalation, heart attack, stroke, chronic lung disease, arthritis, alcoholic liver disease, xenobiotic toxicity and iron toxicity.

### Claim 28 (depends on 25)

The method of claim 25, wherein the compound is delivered in a composition comprising a pharmaceutically acceptable carrier or vehicle.

### Claim 29 (depends on 28)

The method of claim 28, wherein the composition further comprises a drug selected from the group consisting of a non-steroidal anti-inflammatory drug, a leukotriene antagonist and an anti-inflammatory agent.

### Claim 30 (depends on 28)

The method of claim 28, wherein the non-steroidal anti-inflammatory drug is selected from the group consisting of salicylic acid, acetylsalicylic acid, methyl salicylate, diflunisal, salsalate, olsalazine, sulfasalazine, acetaminophen, indomethacin, sulindac, etodolac, mefenamic acid, meclofenamate sodium, tolmetin, ketorolac, dichlofenac, ibuprofen, naproxen, naproxen sodium, fenoprofen, ketoprofen, flurbinprofen, oxaprozin, piroxicam, meloxicam, ampiroxicam, droxicam, pivoxicam, tenoxicam, nabumetome, phenylbutazone, oxyphenbutazone, antipyrine, aminopyrine, apazone and nimesulide.

### Claim 31 (depends on 28)

The method of claim 28, wherein the leukotriene antagonist is selected from the group consisting of zileuton, aurothioglucose, gold sodium thiomalate and auranofin.

### Claim 32 (depends on 28)

The method of claim 28, wherein the anti-inflammatory agent is selected from the group consisting of colchicine, allopurinol, probenecid, sulfinpyrazone and benzbromarone.

### Claim 33 (depends on 1)

The method of claim 1, wherein the compound of formula (I) is selected from the group consisting of:
D-myo-inositol 1,4,5,6-tetrakisphosphate;
D-2,3-di-O-methyl-myo-inositol 1,4,5,6-tetrakisphosphate octakis(acetoxymethyl) ester;
D-2-O-butyryl-3-O-methyl-myo-inositol 1,4,5,6-tetrakisphosphate octakis(acetoxymethyl) ester;
D-2-O-butyl-3-O-butyryl-myo-inositol 1,4,5,6-tetrakisphosphate octakis(acetoxymethyl) ester;
D-2,3-di-O-butyl-myo-inositol 1,4,5,6-tetrakisphosphate octakis(acetoxymethyl) ester;
D-3-O-butyl-2-O-butyryl-myo-inositol 1,4,5,6-tetrakisphosphate octakis(acetoxymethyl) ester;
D-2,3-di-O-butyryl-myo-inositol 1,4,5,6-tetrakisphosphate octakis(acetoxymethyl) ester;
a racemate thereof; and
a pharmaceutically acceptable salt thereof.

### Claim 34 (depends on 9)

The method of claim 9, wherein the compound of formula (I) is selected from the group consisting of:
D-myo-inositol 1,4,5,6-tetrakisphosphate;
D-2,3-di-O-methyl-myo-inositol 1,4,5,6-tetrakisphosphate octakis(acetoxymethyl) ester;
D-2-O-butyryl-3-O-methyl-myo-inositol 1,4,5,6-tetrakisphosphate octakis(acetoxymethyl) ester;
D-2-O-butyl-3-O-butyryl-myo-inositol 1,4,5,6-tetrakisphosphate octakis(acetoxymethyl) ester;
D-2,3-di-O-butyl-myo-inositol 1,4,5,6-tetrakisphosphate octakis(acetoxymethyl) ester;
D-3-O-butyl-2-O-butyryl-myo-inositol 1,4,5,6-tetrakisphosphate octakis(acetoxymethyl) ester;
D-2,3-di-O-butyryl-myo-inositol 1,4,5,6-tetrakisphosphate octakis(acetoxymethyl) ester;
a racemate thereof; and
a pharmaceitucally acceptable salt thereof.

### Claim 35 (depends on 17)

The method of claim 17, wherein the compound of formula (II) is selected from the group consisting of:
sn-di-O-palmnitoyl-D,L-6-O-butyryl-phosphatidylinositol 3,4,5-trisphosphate heptakis(acetoxymethyl)ester, or a D- or L-enantiomer thereof;
sn-di-O-octanoyl-D,L-6-O-butyryl-phosphatidylinositol 3,4,5-trisphosphate heptakis(acetoxymethyl)ester, or a D- or L-enantiomer thereof;
sn-di-O-palnitoyl-D,L-2-O-butyryl-phosphatidylinositol 3,4,5-trisphosphate heptakis(acetoxymethyl)ester, or a D- or L-enantiomer thereof;
sn-di-O-octanoyl-D,L-2-O-butyryl-phosphatidylinositol 3,4,5-trisphosphate heptakis(acetoxymethyl)ester, or a D- or L-enantiomer thereof;
sn-di-O-palmitoyl-D,L-2,6-di-O-butyryl-phosphatidylinositol 3,4,5-trisphosphate heptakis(acetoxymethyl)ester, or a D- or L-enantiomer thereof;
sn-di-O-octanoyl-D,L-2,6-di-O-butyryl-phosphatidylinositol 3,4,5-trisphosphate heptakis(acetoxymethyl)ester, or a D- or L-enantiomer thereof;
D-phosphatidylinositol 3,4,5-trisphosphate, or its corresponding L-enantiomer or racemate thereof;
sn-di-O-lauryl-D-phosphatidylinositol 3,4,5-trisphosphate heptakis(acetoxymethyl)ester, or its corresponding L-enantiomer or racemate thereof; and
sn-di-O-octanoyl-D-phosphatidylinositol 3,4,5-trisphosphate heptakis(acetoxymethyl)ester, or its corresponding L-enantiomer or racemate thereof;
sn-di-O-palmitoyl-D-phosphatidylinositol 3,4,5-trisphosphate heptakis(acetoxymethyl)ester, or its corresponding L-enantiomer or racemate thereof; and
pharmaceutically acceptable salts thereof.

### Claim 36 (depends on 25)

The method of claim 25, wherein the compound of formula (II) is selected from the group consisting of
sn-di-O-palmitoyl-D,L-6-O-butyryl-phosphatidylinositol 3,4,5-trisphosphate heptakis(acetoxymethyl)ester, or a D- or L-enantiomer thereof;
sn-di-O-octanoyl-D,L-6-O-butyryl-phosphatidylinositol 3,4,5-trisphosphate heptakis(acetoxymethyl)ester, or a D- or L-enantiomer thereof;
sn-di-O-palmitoyl-D,L-2-O-butyryl-phosphatidylinositol 3,4,5-trisphosphate heptakis(acetoxymethyl)ester, or a D- or L-enantiomer thereof;
sn-di-O-octanoyl-D,L-2-O-butyryl-phosphatidylinositol 3,4,5-trisphosphate heptakis(acetoxymethyl)ester, or a D- or L-enantiomer thereof;
sn-di-O-palrnitoyl-D,L-2,6-di-O-butyryl-phosphatidylinositol 3,4,5-trisphosphate heptakis(acetoxymethyl)ester, or a D- or L-enantiomer thereof;
sn-di-O-octanoyl-D,L-2,6-di-O-butyryl-phosphatidylinositol 3,4,5-trisphosphate heptakis(acetoxymethyl)ester, or a D- or L-enantiomer thereof;
D-phosphatidylinositol 3,4,5-trisphosphate, or its corresponding L-enantiomer or racemate thereof;
sn-di-O-lauryl-D-phosphatidylinositol 3,4,5-trisphosphate heptakis(acetoxymethyl)ester, or its corresponding L-enantiomer or racemate thereof;
sn-di-O-octanoyl-D-phosphatidylinositol 3,4,5-trisphosphate heptakis(acetoxymethyl)ester, or its corresponding L-enantiomer or racemate thereof, sn-di-O-palrnitoyl-D-phosphatidylinositol 3,4,5-trisphosphate heptakis(acetoxymethyl)ester, or its corresponding L-enantiomer or racemate thereof; and
pharmaceutically acceptable salts thereof.

### Claim 37

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.

### Claim 38

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.

### Claim 39 (depends on 37)

A pharmaceutical composition, comprising a therapeutically effective amount of a compound of claim 37 or a pharmaceutically acceptable salt thereof, and a physiologically acceptable carrier or vehicle.

### Claim 40 (depends on 39)

The composition of claim 39, further comprising a therapeutic agent selected from the group consisting of a non-steroidal anti-inflammatory drug, a leukotriene antagonist and an anti-inflammatory agent.

### Claim 41 (depends on 40)

The composition of claim 40, wherein the non-steroidal anti-inflammatory drug is selected from the group consisting of salicylic acid, acetylsalicylic acid, methyl salicylate, diflunisal, salsalate, olsalazine, sulfasalazine, acetaminophen, indomethacin, sulindac, etodolac, mefenamic acid, meclofenamate sodium, tolmetin, ketorolac, dichlofenac, ibuprofen, naproxen, naproxen sodium, fenoprofen, ketoprofen, flurbinprofen, oxaprozin, piroxicam, meloxicam, ampiroxicamn, droxicam, pivoxicam, tenoxicam, nabumetome, phenylbutazone, oxyphenbutazone, antipyrine, aminopyrine, apazone and nimesulide.

### Claim 42 (depends on 40)

The composition of claim 40, wherein the leukotriene antagonist is selected from the group consisting of zileuton, aurothioglucose, gold sodium thiomalate and auranofin.

### Claim 43 (depends on 40)

The composition of claim 40, wherein the anti-inflammatory agent is selected from the group consisting of colchicine, allopurinol, probenecid, sulfinpyrazone and benzbromarone.

### Claim 44 (depends on 39)

The composition of claim 39, wherein the composition is in the form of a tablet, pellet, capsule, capsule containing liquid, suppository, solution, emulsion, aerosol, spray or suspension.

### Claim 45 (depends on 38)

A pharmaceutical composition, comprising a therapeutically effective amount of a compound of claim 38 or a pharmaceutically acceptable salt thereof, and a physiologically acceptable carrier or vehicle.

### Claim 46 (depends on 45)

The composition of claim 45, further comprising a therapeutic agent selected from the group consisting of a non-steroidal anti-inflammatory drug, a leukotriene antagonist and an anti-inflammatory agent.

### Claim 47 (depends on 46)

The composition of claim 46, wherein the non-steroidal anti-inflammatory drug is selected from the group consisting of salicylic acid, acetylsalicylic acid, methyl salicylate, diflunisal, salsalate, olsalazine, sulfasalazine, acetaminophen, indomethacin, sulindac, etodolac, mefenamic acid, meclofenamate sodium, tolmetin, ketorolac, dichlofenac, ibuprofen, naproxen, naproxen sodium, fenoprofen, ketoprofen, flurbinprofen, oxaprozin, piroxicam, meloxicam, ampiroxicam, droxicam, pivoxicam, tenoxicam, nabumetome, phenylbutazone, oxyphenbutazone, antipyrine, aminopyrine, apazone and nimesulide.

### Claim 48 (depends on 46)

The composition of claim 46, wherein the leukotriene antagonist is selected from the group consisting of zileuton, aurothioglucose, gold sodium thiomalate and auranofin.

### Claim 49 (depends on 46)

The composition of claim 46, wherein the anti-inflammatory agent is selected from the group consisting of colchicine, allopurinol, probenecid, sulfinpyrazone and benzbromarone.

### Claim 50 (depends on 45)

The composition of claim 45, wherein the composition is in the form of a tablet, pellet, capsule, capsule containing liquid, suppository, solution, emulsion, aerosol, spray or suspension.