CA2409221A1 - Prophylactic and therapeutic treatment of infectious and other diseases with mono- and disaccharide-based compounds - Google Patents

Prophylactic and therapeutic treatment of infectious and other diseases with mono- and disaccharide-based compounds Download PDF

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CA2409221A1
CA2409221A1 CA002409221A CA2409221A CA2409221A1 CA 2409221 A1 CA2409221 A1 CA 2409221A1 CA 002409221 A CA002409221 A CA 002409221A CA 2409221 A CA2409221 A CA 2409221A CA 2409221 A1 CA2409221 A1 CA 2409221A1
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CA2409221C (en
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David H. Persing
Richard Thomas Crane
Gary T. Elliott
J. Terry Ulrich
Michael J. Lacy
David A. Johnson
Jory R. Baldridge
Rong Wang
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Corixa Corp
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H13/00—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids
    • C07H13/02—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids
    • C07H13/04—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids having the esterifying carboxyl radicals attached to acyclic carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7024—Esters of saccharides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/02—Nasal agents, e.g. decongestants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H11/00—Compounds containing saccharide radicals esterified by inorganic acids; Metal salts thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H13/00—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids
    • C07H13/02—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids
    • C07H13/04—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids having the esterifying carboxyl radicals attached to acyclic carbon atoms
    • C07H13/06—Fatty acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
    • C07H15/02—Acyclic radicals, not substituted by cyclic structures
    • C07H15/14—Acyclic radicals, not substituted by cyclic structures attached to a sulfur, selenium or tellurium atom of a saccharide radical

Abstract

Methods and compositions for treating or ameliorating diseases and other conditions, such as infectious diseases, autoimmune diseases and allergies are provided. The methods employ mono- and disaccharide-based compounds for selectively stimulating immune responses in animals and plants.

Claims (29)

1. A method for ameliorating or substantially preventing an infectious disease, autoimmune disease or allergic condition in a subject comprising contacting the subject with an effective amount of one or more compounds having the formula:

and pharmaceutically acceptable salts thereof, wherein X is a member selected from the group consisting of -O- and NH-;
R1 and R2 are each members independently selected from the group consisting of (C2-C24)acyl;
R3 is a member selected from the group consisting of -H and -PO3R11R12, wherein R11 and R12 are each members independently selected from the group consisting of-H and (C1-C4)alkyl;
R4 is a member selected from the group consisting of -H, -CH3 and -PO3R13R14, wherein R13 and R14 are each members independently selected from the group consisting of-H and (C1-C4)alkyl; and Y is a radical selected from the group consisting of wherein the subscripts n, m, p and q are each independently an integer of from 0 to 6;
R5 is (C2-C24)acyl;
R6 and R7 are members independently selected from the group consisting of H and CH3;
R8 and R9 are members independently selected from the group consisting of H, OH, (C1-C4)alkoxy, -PO3H2, -OPO3H2, -SO3H, -OSO3H, -NR15R16, -SR15, -CN, -NO2, -CHO, -CO2R15, -CONR15R16, -PO3R15R16, -OPO3R15R16, -SO3R15 and -OSO3R15 wherein R15 and R16 are each members independently selected from the group consisting of H and (C1-C4)alkyl;
R10 is a member selected from the group consisting of H, CH3, -PO3H2, .omega.-phosphonooxy(C2-C24)alkyl, and .omega.-carboxy(C1-C24)alkyl; and Z is -O- or -S-;
with the proviso that when R3 is -PO3R11R12, R4 is other than -PO3R13R14, and with the further proviso that when R3 is -PO3H2, R4 is H, R10 is H, R1 is n-tetradecanoyl, R2 is n-octadecanoyl and R5 is n-hexadecanoyl, then X is other than -O-.
2. A method in accordance with claim 1, wherein the infectious disease is caused a bacteria selected from the group consisting of Pseudomonas, Escherichia, Klebsiella, Enterobacter, Proteus, Serratia, Candida and Staphylococcus.
3. A method in accordance with claim 1, wherein the infectious disease or condition is pneumonia.
4. A method in accordance with claim 3, wherein said pneumonia is nosocomial pneumonia.
5. A method in accordance with claim 3, wherein said pneumonia is in an HIV-positive patient.
6. A method in accordance with claim 1, wherein said infections disease or condition is a chronic infection.
7. A method in accordance with claim 6, wherein said chronic infection comprises chronic hepatitis, human papillomavirus, oral or vaginal candidiasis, periodontal disease or chronic rhinosinusitis due to fungal colonization.
8. A method in accordance with claim 1, wherein said allergic condition is selected from the group consisting of asthma, atopic dermatitis, seasonal allergic disorder and chronic rhinosinusitis.
9. A method in accordance with claim 1, wherein said autoimmune disease is selected from the group consisting of inflammatory bowel disease, rheumatoid arthritis, chronic arthritis, multiple sclerosis and psoriasis.
10. A method in accordance with claim 1, wherein said compound is administered to said animal by a route selected from the group consisting of parenteral, oral, intravenous, infusion, intranasal, inhalation, transdermal and transmucosal.
11. A method in accordance with claim 1, wherein at least two of said R1, R2 and R5 are selected from the group consisting of (C2-C6)acyl.
12. A method in accordance with claim 1, wherein two of said R1, R2 and R5 are selected from the group consisting of (C2-C6)acyl and the total number of carbon atoms in R1, R2 and R5 is from about 6 to about 22.
13. A method in accordance with claim l, wherein two of said R1, R2 and R5 are selected from the group consisting of (C2-C6)acyl and the total number of carbon atoms in R1, R2 and R5 is from about 12 to about 18.
14. A method in accordance with claim 1, wherein X and Z are both -O-.
15. A method in accordance with claim l, wherein R1, R2 and R5 are each independently selected from the group consisting of (C12-C24)acyl with the proviso that the total number of carbon atoms in R1, R2 and R5 is from about 44 to about 60.
16. A method in accordance with claim 14, wherein said total number of carbon atoms is from about 46 to about 52.
17. A method in accordance with claim 14, wherein X and Z are both -O-.
18. A method for the prophylactic treatment of a bacterial or viral infection in a subject comprising contacting the subject with an effective amount of one or more compounds having the formula:

and pharmaceutically acceptable salts thereof, wherein X is a member selected from the group consisting of -O- and NH-;
R1 and R2 are each members independently selected from the group consisting of (C2-C24)acyl;
R3 is a member selected from the group consisting of -H and -PO3R11R12, wherein R11 and R12 are each members independently selected from the group consisting of-H and (C1-C4)alkyl;
R4 is a member selected from the group consisting of -H, -CH3 and -PO3R13R14, wherein R13 and R14 are each members independently selected from the group consisting of-H and (C1-C4)alkyl; and Y is a radical selected from the group consisting of wherein the subscripts n, m, p and q are each independently an integer of from 0 to 6;
R5 is (C2-C24)acyl;
R6 and R7 are members independently selected from the group consisting of H and CH3;
R8 and R9 are members independently selected from the group consisting of H, OH, (C1-C4)alkoxy, -PO3H2, -OPO3H2, -SO3H, -OSO3H, -NR15R16, -SR15, -CN, -NO2, -CHO, -CO2R15, -CONR15R16, -PO3R15R16, -OPO3R15R16, -SO3R15 and -OSO3R15 wherein R15 and R16 are each members independently selected from the group consisting of H and (C1-C4)alkyl;
R10 is a member selected from the group consisting of H, CH3, -PO3H2, .omega.-phosphonooxy(C2-C24)alkyl, and .omega.-carboxy(C1-C24)alkyl; and Z is -O- or -S-;
with the proviso that when R3 is -PO3R11R12, R4 is other than -PO3R13R14, and with the further proviso that when R3 is PO3H2, R4 is H, R10 is H, R1 is n-tetradecanoyl, R2 is n-octadecanoyl and R5 is n-hexadecanoyl, then X is other than -O-.
19. A method in accordance with claim 18, wherein said infection is a nosocomial infection.
20. A method in accordance with claim 19, wherein said nosocomial infection is a pneumonia.
21. A method in accordance with claim 18, wherein said infection is in an HIV-positive patient.
22. A method in accordance with claim 21, wherein the infection in said HIV-positive patient is pneumonia.
23. A method in accordance with claim 22, wherein said infection is caused by P. carinii.
24. A pharmaceutical composition formulated and administered in the absence of exogenous antigen comprising one or more compounds having the formula:

and pharmaceutically acceptable salts thereof, wherein X is a member selected from the group consisting of -O- and NH-;
R1 and R2 are each members independently selected from the group consisting of (C2-C24)acyl;
R3 is a member selected from the group consisting of -H and -PO3R11R12, wherein R11 and R12 axe each members independently selected from the group consisting of-H and (C1-C4)alkyl;
R4 is a member selected from the group consisting of -H, -CH3 and -PO3R13R14, wherein R13 and R14 are each members independently selected from the group consisting of-H and (C1-C4)alkyl; and Y is a radical selected from the group consisting of wherein the subscripts n, m, p and q are each independently an integer of from 0 to 6;
R5 is (C2-C24)acyl;
R6 and R7 are members independently selected from the group consisting of H and CH3;
R8 and R9 are members independently selected from the group consisting of H, OH, (C1-C4)alkoxy, -PO3H2, -OPO3H2, -SO3H, -OSO3H, -NR15R16, -SR15, -CN, -NO2, -CHO, -CO2R15, -CONR15R16, -PO3R15R16, -OPO3R15R16, -SO3R15 and -OSO3R15 wherein R15 and R16 are each members independently selected from the group consisting of H and (C1-C4)alkyl;

R10 is a member selected from the group consisting of H, CH3, -PO3H2, .omega.-phosphonooxy(C2-C24)alkyl, and .omega.-carboxy(C1-C24)alkyl; and Z is -O- or -S-;
with the proviso that when R3 is -PO3R11R12, R4 is other than -PO3R13R14, and with the further proviso that when R3 is -PO3H2, R4 is H, R10 is H, R1 is n-tetradecanoyl, R2 is n-octadecanoyl and R5 is h-hexadecanoyl, then X is other than -O-.
25. A pharmaceutical composition in accordance with claim 24, further comprising one or more surfactants.
26. A pharmaceutical composition in accordance with claim 25, wherein said one or more surfactants is selected from the group consisting of dimyristoyl phosphatidyl glycerol (DPMG), dipalmitoyl phosphatidyl glycerol (DPPG), distearoyl phosphatidyl glycerol (DSPG), dimyristoyl phosphatidylcholine (DPMC), dipalmitoyl phosphatidylcholine (DPPC), distearoyl phosphatidylcholine (DSPC);
dimyristoyl phosphatidic acid (DPMA), dipalmitoyl phosphatidic acid (DPPA), distearoyl phosphatidic acid (DSPA); dimyristoyl phosphatidyl ethanolamine (DPME), dipalmitoyl phosphatidyl ethanolamine (DPPE) and distearoyl phosphatidyl ethanolamine (DSPE).
27. A method for ameliorating or substantially preventing an infectious disease, autoimmune disease or allergic condition in a subject comprising contacting the subject with an effective amount of an compound selected from the group consisting of MonoPhosphoryl Lipid A (MPL) and a L-Seryl Aminoalkyl Glucosaminide Phosphate compound (AGP).
28. The method of claim 27 wherein said L-Seryl Aminoalkyl Glucosaminide Phosphate compound is selected from the group consisting of RC-526, RC-554, RC-555, RC-537, RC-527, RC-538, RC-560 and RC-512.
29. The method of claim 27 wherein said L-Seryl Aminoalkyl Glucosaminide Phosphate compound is selected from the group consisting of RC-538, RC-560 and RC-512.
CA2409221A 2000-05-19 2001-05-18 Prophylactic and therapeutic treatment of infectious and other diseases with mono- and disaccharide-based compounds Expired - Lifetime CA2409221C (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US20582000P 2000-05-19 2000-05-19
US60/205,820 2000-05-19
US28156701P 2001-04-04 2001-04-04
US60/281,567 2001-04-04
PCT/US2001/016327 WO2001090129A2 (en) 2000-05-19 2001-05-18 Prophylactic and therapeutic treatment of infectious, autoimmune and allergic diseases with mono and disaccharide-base compounds

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CA2409221A1 true CA2409221A1 (en) 2001-11-29
CA2409221C CA2409221C (en) 2010-10-26

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AU (3) AU2001269695B2 (en)
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CA (1) CA2409221C (en)
CY (1) CY1108211T1 (en)
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