WO2004012737A1 - Use or arylsulfonamido-substituted hydroxamid acid matrix metalloproteinase inhibitors for the treatment or prevention of toxemia - Google Patents
Use or arylsulfonamido-substituted hydroxamid acid matrix metalloproteinase inhibitors for the treatment or prevention of toxemia Download PDFInfo
- Publication number
- WO2004012737A1 WO2004012737A1 PCT/EP2003/008316 EP0308316W WO2004012737A1 WO 2004012737 A1 WO2004012737 A1 WO 2004012737A1 EP 0308316 W EP0308316 W EP 0308316W WO 2004012737 A1 WO2004012737 A1 WO 2004012737A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- arylsulfonamido
- matrix metalloproteinase
- acid matrix
- toxin
- hydroxamic acid
- Prior art date
Links
- 239000002253 acid Substances 0.000 title claims abstract description 25
- 229940121386 matrix metalloproteinase inhibitor Drugs 0.000 title claims abstract description 24
- 239000003771 matrix metalloproteinase inhibitor Substances 0.000 title claims abstract description 24
- 206010004053 Bacterial toxaemia Diseases 0.000 title claims description 9
- 208000013222 Toxemia Diseases 0.000 title claims description 9
- 238000011282 treatment Methods 0.000 title claims description 7
- 230000002265 prevention Effects 0.000 title claims description 5
- NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical class C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 claims abstract description 23
- 231100000699 Bacterial toxin Toxicity 0.000 claims abstract description 19
- 239000000688 bacterial toxin Substances 0.000 claims abstract description 19
- 238000000034 method Methods 0.000 claims description 24
- 239000003053 toxin Substances 0.000 claims description 20
- 231100000765 toxin Toxicity 0.000 claims description 20
- 108700012359 toxins Proteins 0.000 claims description 20
- 102000005741 Metalloproteases Human genes 0.000 claims description 14
- 108010006035 Metalloproteases Proteins 0.000 claims description 14
- 241000124008 Mammalia Species 0.000 claims description 10
- 230000000694 effects Effects 0.000 claims description 10
- BSIZUMJRKYHEBR-QGZVFWFLSA-N n-hydroxy-2(r)-[[(4-methoxyphenyl)sulfonyl](3-picolyl)amino]-3-methylbutanamide hydrochloride Chemical group C1=CC(OC)=CC=C1S(=O)(=O)N([C@H](C(C)C)C(=O)NO)CC1=CC=CN=C1 BSIZUMJRKYHEBR-QGZVFWFLSA-N 0.000 claims description 9
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 8
- 241000894006 Bacteria Species 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 7
- -1 3- picolyl Chemical group 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- 241000193738 Bacillus anthracis Species 0.000 claims description 3
- 241000606124 Bacteroides fragilis Species 0.000 claims description 3
- 241000193163 Clostridioides difficile Species 0.000 claims description 3
- 241000193155 Clostridium botulinum Species 0.000 claims description 3
- 241000193449 Clostridium tetani Species 0.000 claims description 3
- 241000186227 Corynebacterium diphtheriae Species 0.000 claims description 3
- 241000607626 Vibrio cholerae Species 0.000 claims description 3
- 229940065181 bacillus anthracis Drugs 0.000 claims description 3
- 241000193830 Bacillus <bacterium> Species 0.000 claims description 2
- 241000606125 Bacteroides Species 0.000 claims description 2
- 241000193403 Clostridium Species 0.000 claims description 2
- 241000186216 Corynebacterium Species 0.000 claims description 2
- 241000607598 Vibrio Species 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 description 8
- 230000002401 inhibitory effect Effects 0.000 description 5
- 239000003242 anti bacterial agent Substances 0.000 description 4
- 239000002260 anti-inflammatory agent Substances 0.000 description 3
- 229940121363 anti-inflammatory agent Drugs 0.000 description 3
- 208000035143 Bacterial infection Diseases 0.000 description 2
- 208000025865 Ulcer Diseases 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 208000022362 bacterial infectious disease Diseases 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 230000036269 ulceration Effects 0.000 description 2
- RAZMTXWMIYPNTF-OAQYLSRUSA-N (2r)-n-butoxy-2-[(4-methoxyphenyl)sulfonyl-(pyridin-3-ylmethyl)amino]-3-methylbutanamide Chemical compound C=1C=C(OC)C=CC=1S(=O)(=O)N([C@H](C(C)C)C(=O)NOCCCC)CC1=CC=CN=C1 RAZMTXWMIYPNTF-OAQYLSRUSA-N 0.000 description 1
- 208000020084 Bone disease Diseases 0.000 description 1
- 108060005980 Collagenase Proteins 0.000 description 1
- 102000029816 Collagenase Human genes 0.000 description 1
- 108010026132 Gelatinases Proteins 0.000 description 1
- 102000013382 Gelatinases Human genes 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 208000037357 HIV infectious disease Diseases 0.000 description 1
- 102000000422 Matrix Metalloproteinase 3 Human genes 0.000 description 1
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 1
- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000010191 Osteitis Deformans Diseases 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 208000027868 Paget disease Diseases 0.000 description 1
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 1
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 210000002469 basement membrane Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229960002424 collagenase Drugs 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 208000027202 mammary Paget disease Diseases 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 208000028169 periodontal disease Diseases 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 108091007196 stromelysin Proteins 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
Classifications
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4406—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 3, e.g. zimeldine
-
- 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
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Definitions
- This invention relates to a method of preventing or treating toxemia by administering an effective amount of an arylsulfonamido-substituted hydroxamic acid matrix metalloproteinase inhibitor to a patient in need thereof.
- a number of bacterial toxins are activated by metalloproteinases or include metalloproteinase activity. It is an object of the present invention to prevent or reduce the effect of a bacterial toxin by inhibiting the metalloproteinase activity of the toxin or by inhibiting activation of the toxin by inhibiting a metalloprotease activating factor.
- Arylsulfonamido-substituted hydroxamic acid matrix metalloproteinase inhibitor compounds have been described in the art as useful for the treatment of gelatinase, stromelysin and collagenase dependent pathological conditions in mammals, including pathological conditions involving abnormal connective tissue and basement membrane matrix metabolism, such as arthritis (e.g. osteoarthritis and rheumatoid arthritis), tissue ulceration (e.g. corneal, epidermal and gastric ulceration), abnormal wound healing, periodontal disease, bone disease (e.g. Paget's disease and osteoporosis), tumor metastasis or invasion, as well as HIV-infection and associated disorders.
- arthritis e.g. osteoarthritis and rheumatoid arthritis
- tissue ulceration e.g. corneal, epidermal and gastric ulceration
- abnormal wound healing e.g. corneal, epidermal and gastric ulceration
- periodontal disease e.g. Paget's disease and osteo
- the present invention relates a method of for the prevention or treatment of toxemia in a . mammal exposed to a bacterial toxin activated by or possessing metalloproteinase activity, which comprises administering a therapeutically effective amount of a arylsulfonamido- substituted hydroxamic acid matrix metalloproteinase inhibitor to the mammal.
- the bacterial toxin activated by or possessing metalloproteinase activity may have an intrinsic metalloproteinase component.
- it is also intended to include toxins which do not have an intrinsic metalloproteinase component, but wherein the bacteria itself, the toxin or some other bacterial product acts through a pathway which interacts with a metalloproteinases or an associated pathways.
- Arylsulfonamido-substituted hydroxamic acid matrix metalloproteinase inhibitors suitable for use according to the present method are described in U.S. Patent Nos. 5,455,258 and 5,770,624, which are here incorporated by reference in their entirety.
- the compounds described in these patents the compounds N-hydroxy-(2R)-[[4-methoxybenzenesulfonyl](3- picolyl)amino]-3-methylbutanamide, as described in Example 1 of U.S. Patent No.
- hydrochloride salts of N-hydroxy-(2R)-[[4- ethoxybenzenesulfonyl](3-picolyl)amino]-2-trans-methoxycyclohexyl]acetamide and N- hydroxy-(2R)-[[4-ethoxybenzenesulfonyl](3-picolyl)amino]-2-trans- methoxycyclohexyl]acetamide are particularly useful pharmaceutically acceptable salt forms.
- the toxemia is most commonly caused by infection with a toxin-producing bacteria.
- the infection may be systemic or local.
- Administration of the arylsulfonamido-substituted hydroxamic acid matrix metalloproteinase inhibitor should occur as soon as possible after exposure to the toxin producing bacteria or the toxin as the case may be.
- the mammal is in particular a human.
- the bacterial toxin activated by or possessing metalloproteinase activity is especially a toxin from a bacteria of a genus selected from Bacillus, Bacteroides, Clostridium, Corynebacterium and Vibrio.
- the bacterial toxin activated by or possessing metalloproteinase activity is especially a toxin produced by a bacteria selected from Bacillus anthracis, Bacteroides fragilis, Clostridium botulinum, Clostridium difficile, Clostridium tetani, Corynebacterium diphtheriae and Vibrio cholera.
- the compounds, including their salts, can also be used in the form of their hydrates, or include other solvents used for their crystallization.
- the arylsulfonamido-substituted hydroxamic acid matrix metalloproteinase inhibitor is generally administered enterally, such as orally or rectally, transdermally and parenterally, such as intravenously, as a pharmaceutically formulation comprising an effective amount of the arylsulfonamido-substituted hydroxamic acid matrix metalloproteinase inhibitor and one or more pharmaceutically acceptable carriers.
- Pharmaceutically acceptable carriers are known to those of skill in the art.
- the pharmaceutical formulations contain an effective metalloproteinase inhibiting amount of a arylsulfonamido-substituted hydroxamic acid matrix metalloproteinase inhibitor either alone, or in combination with another therapeutic agent, particularly an antibiotic or an anti- inflammatory agent, particularly an anti-inflammatory agent with cyclooxygenase inhibiting activity or a steroid.
- a compound of the invention may be administered either simultaneously, before or after the other active ingredient, either separately by the same or different route of administration or together in the same pharmaceutical formulation.
- the present invention further comprises a method of for the prevention or treatment of toxemia in a mammal exposed to a bacterial toxin activated by or possessing metalloproteinase activity, which comprises administering a therapeutically effective amount of a arylsulfonamido-substituted hydroxamic acid matrix metalloproteinase inhibitor in combination with an antibiotic or an antiinflammatory agent, or both, to the mammal.
- the dosage of the arylsulfonamido-substituted hydroxamic acid matrix metalloproteinase inhibitor administered is dependent on the species of mammal, the body weight, age and individual condition, and on the form of administration, and can be determined by one of skill in the art.
- a typical dosage to a mammal of about 50 to 70kg is in the range from 50 to 1800 mg/day, particularly 600 mg/day of the arylsulfonamido-substituted hydroxamic acid matrix metalloproteinase inhibitor.
Abstract
Thoxemia caused by a bacterial toxin is prevented or treated by administration of a arylsulfonamido-substituted hydroxamic acid matrix metalloproteinase inhibitor.
Description
USE OF ARYLSULFONAMIDO-SUBSTITUTED HYDROXAMID ACID MATRIX METALLOPROTEINASE INHI ITORS FOR THE TREATMENT OR PREVENTION OF TOXEMIA
Method of Preventing or Treating Toxemia using arylsulfonamido-substituted hydroxamic acid matrix metalloproteinase inhibitors
This invention relates to a method of preventing or treating toxemia by administering an effective amount of an arylsulfonamido-substituted hydroxamic acid matrix metalloproteinase inhibitor to a patient in need thereof.
Background
Many of the deleterious effects of bacterial infection are caused by toxins which the bacteria produce. Although many bacterial infections can be successfully treated with antibiotics, toxemia resulting from the bacterial production of toxin can lead to seriously adverse effects, including death, when antibiotics are not administered promptly or are ineffective. Thus, in addition to antibacterial treatments, there is also a great need for agents that neutralize or reduce the toxicity of the such bacterial toxins.
A number of bacterial toxins are activated by metalloproteinases or include metalloproteinase activity. It is an object of the present invention to prevent or reduce the effect of a bacterial toxin by inhibiting the metalloproteinase activity of the toxin or by inhibiting activation of the toxin by inhibiting a metalloprotease activating factor.
Arylsulfonamido-substituted hydroxamic acid matrix metalloproteinase inhibitor compounds have been described in the art as useful for the treatment of gelatinase, stromelysin and collagenase dependent pathological conditions in mammals, including pathological conditions involving abnormal connective tissue and basement membrane matrix metabolism, such as arthritis (e.g. osteoarthritis and rheumatoid arthritis), tissue ulceration (e.g. corneal, epidermal and gastric ulceration), abnormal wound healing, periodontal disease, bone disease (e.g. Paget's disease and osteoporosis), tumor metastasis or invasion, as well as HIV-infection and associated disorders.
Detailed Description
The present invention relates a method of for the prevention or treatment of toxemia in a . mammal exposed to a bacterial toxin activated by or possessing metalloproteinase activity, which comprises administering a therapeutically effective amount of a arylsulfonamido- substituted hydroxamic acid matrix metalloproteinase inhibitor to the mammal.
The bacterial toxin activated by or possessing metalloproteinase activity may have an intrinsic metalloproteinase component. However, in this application, it is also intended to include toxins which do not have an intrinsic metalloproteinase component, but wherein the bacteria itself, the toxin or some other bacterial product acts through a pathway which interacts with a metalloproteinases or an associated pathways.
Arylsulfonamido-substituted hydroxamic acid matrix metalloproteinase inhibitors suitable for use according to the present method are described in U.S. Patent Nos. 5,455,258 and 5,770,624, which are here incorporated by reference in their entirety. Among the compounds described in these patents, the compounds N-hydroxy-(2R)-[[4-methoxybenzenesulfonyl](3- picolyl)amino]-3-methylbutanamide, as described in Example 1 of U.S. Patent No. 5,455,258, and N-hydroxy-(2R)-[[4-ethoxybenzenesulfonyl](3-picolyl)amino]-2-trans- methoxycyclohexyl]acetamide, as described in Example 2(p) of U.S. Patent No. 5,770,624, and pharmaceutically acceptable salts thereof, are particularly useful, especially N-butyloxy- (2R)-[[4-methoxybenzenesulfonyl](3-picolyl)amino]-3-methylbutanamide and pharmaceucically acceptable salts therof. The hydrochloride salts of N-hydroxy-(2R)-[[4- ethoxybenzenesulfonyl](3-picolyl)amino]-2-trans-methoxycyclohexyl]acetamide and N- hydroxy-(2R)-[[4-ethoxybenzenesulfonyl](3-picolyl)amino]-2-trans- methoxycyclohexyl]acetamide are particularly useful pharmaceutically acceptable salt forms.
The toxemia is most commonly caused by infection with a toxin-producing bacteria. The infection may be systemic or local. Administration of the arylsulfonamido-substituted hydroxamic acid matrix metalloproteinase inhibitor should occur as soon as possible after exposure to the toxin producing bacteria or the toxin as the case may be.
The mammal is in particular a human.
The bacterial toxin activated by or possessing metalloproteinase activity is especially a toxin from a bacteria of a genus selected from Bacillus, Bacteroides, Clostridium, Corynebacterium and Vibrio. The bacterial toxin activated by or possessing metalloproteinase activity is especially a toxin produced by a bacteria selected from Bacillus anthracis, Bacteroides fragilis, Clostridium botulinum, Clostridium difficile, Clostridium tetani, Corynebacterium diphtheriae and Vibrio cholera.
In view of the close relationship between the free compounds and the compounds in the form of their salts, whenever a compound is referred to in this context, a corresponding salt is also intended, provided such is possible or appropriate under the circumstances.
The compounds, including their salts, can also be used in the form of their hydrates, or include other solvents used for their crystallization.
The arylsulfonamido-substituted hydroxamic acid matrix metalloproteinase inhibitor is generally administered enterally, such as orally or rectally, transdermally and parenterally, such as intravenously, as a pharmaceutically formulation comprising an effective amount of the arylsulfonamido-substituted hydroxamic acid matrix metalloproteinase inhibitor and one or more pharmaceutically acceptable carriers. Pharmaceutically acceptable carriers are known to those of skill in the art.
The pharmaceutical formulations contain an effective metalloproteinase inhibiting amount of a arylsulfonamido-substituted hydroxamic acid matrix metalloproteinase inhibitor either alone, or in combination with another therapeutic agent, particularly an antibiotic or an anti- inflammatory agent, particularly an anti-inflammatory agent with cyclooxygenase inhibiting activity or a steroid.
In conjunction with another active ingredient, a compound of the invention may be administered either simultaneously, before or after the other active ingredient, either separately by the same or different route of administration or together in the same pharmaceutical formulation. Thus, the present invention further comprises a method of for the prevention or treatment of toxemia in a mammal exposed to a bacterial toxin activated by or possessing metalloproteinase activity, which comprises administering a therapeutically effective amount of a arylsulfonamido-substituted hydroxamic acid matrix metalloproteinase
inhibitor in combination with an antibiotic or an antiinflammatory agent, or both, to the mammal.
The dosage of the arylsulfonamido-substituted hydroxamic acid matrix metalloproteinase inhibitor administered is dependent on the species of mammal, the body weight, age and individual condition, and on the form of administration, and can be determined by one of skill in the art. A typical dosage to a mammal of about 50 to 70kg is in the range from 50 to 1800 mg/day, particularly 600 mg/day of the arylsulfonamido-substituted hydroxamic acid matrix metalloproteinase inhibitor.
Claims
1. A method for the prevention or treatment of toxemia in a mammal exposed to a bacterial toxin activated by or possessing metalloproteinase activity, which comprises administering a therapeutically effective amount of a arylsulfonamido-substituted hydroxamic acid matrix metalloproteinase inhibitor to the mammal.
2. A method of claim 1 wherein the arylsulfonamido-substituted hydroxamic acid matrix metalloproteinase inhibitor is selected from N-hydroxy-(2R)-[[4-methoxybenzenesulfonyl](3- picolyl)amino]-3-methylbutanamide and N-hydroxy-(2R)-[[4-ethoxybenzenesulfonyl](3- picolyl)amino]-2-trans-methoxycyclohexyl]acetamide, or a pharmaceutically acceptable salt thereof.
3. A method of claim 1 wherein the arylsulfonamido-substituted hydroxamic acid matrix metalloproteinase inhibitor is selected from N-hydroxy-(2R)-[[4-methoxybenzenesulfonyl](3- picolyl)amino]-3-methylbutanamide.
4. A method of claim 1 wherein the bacterial toxin is a toxin produced by bacteria of a genus selected from Bacillus, Bacteroides, Clostridium, Corynebacterium and Vibrio.
5. A method of claim 1 wherein the bacterial toxin is a toxin produced by a bacteria selected from Bacillus anthracis, Bacteroides fragilis, Clostridium botulinum, Clostridium difficile, Clostridium tetani, Corynebacterium diphtheriae and Vibrio cholera.
6. A method of claim 1 wherein the bacterial toxin is a toxin produced by Bacillus anthracis.
7. A method of claim 1 wherein the bacterial toxin is a toxin produced by Bacteroides fragilis.
8. A method of claim 1 wherein the bacterial toxin is a toxin produced by Clostridium botulinum.
9. A method of claim 1 wherein the bacterial toxin is a toxin produced by Clostridium difficile.
10. A method of claim 1 wherein the bacterial toxin is a toxin produced by Clostridium tetani.
11. A method of claim 1 wherein the bacterial toxin is a toxin produced by Corynebacterium diphtheriae.
12. A method of claim 1 wherein the bacterial toxin is a toxin produced by Vibrio cholera.
13. A method of claim 6 wherein the arylsulfonamido-substituted hydroxamic acid matrix metalloproteinase inhibitor is selected from N-hydroxy-(2R)-[[4-methoxybenzenesulfonyl](3- picolyl)amino]-3-methylbutanamide.
14. A method of claim 7 wherein the arylsulfonamido-substituted hydroxamic acid matrix metalloproteinase inhibitor is selected from N-hydroxy-(2R)-[[4-methoxybenzenesulfonyl](3- picolyl)amino]-3-methylbutanamide.
15. A method of claim 8 wherein the arylsulfonamido-substituted hydroxamic acid matrix metalloproteinase inhibitor is selected from N-hydroxy-(2R)-[[4-methoxybenzenesulfonyl](3- picolyl)amino]-3-methylbutanarnide.
16. A method of claim 9 wherein the arylsulfonamido-substituted hydroxamic acid matrix metalloproteinase inhibitor is selected from N-hydroxy-(2R)-[[4-methoxybenzenesulfonyl](3- picolyl)amino]-3-methylbutanamide.
17. A method of claim 10 wherein the arylsulfonamido-substituted hydroxamic acid matrix metalloproteinase inhibitor is selected from N-hydroxy-(2R)-[[4-methoxybenzenesulfonyl](3- picolyl)amino]-3-methylbutanamide.
18. A method of claim 11 wherein the arylsulfonamido-substituted hydroxamic acid matrix metalloproteinase inhibitor is selected from N-hydroxy-(2R)-[[4-methoxybenzenesulfonyl](3- picolyl)amino]-3-methylbutanamide.
19. A method of claim 12 wherein the arylsulfonamido-substituted hydroxamic acid matrix metalloproteinase inhibitor is selected from N-hydroxy-(2R)-[[4-methoxybenzenesulfonyl](3- picolyl)amino]-3-methylbutanamide.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU2003253346A AU2003253346A1 (en) | 2002-07-29 | 2003-07-28 | Use or arylsulfonamido-substituted hydroxamid acid matrix metalloproteinase inhibitors for the treatment or prevention of toxemia |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US39929102P | 2002-07-29 | 2002-07-29 | |
| US60/399,291 | 2002-07-29 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2004012737A1 true WO2004012737A1 (en) | 2004-02-12 |
Family
ID=31495740
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/EP2003/008316 WO2004012737A1 (en) | 2002-07-29 | 2003-07-28 | Use or arylsulfonamido-substituted hydroxamid acid matrix metalloproteinase inhibitors for the treatment or prevention of toxemia |
Country Status (2)
| Country | Link |
|---|---|
| AU (1) | AU2003253346A1 (en) |
| WO (1) | WO2004012737A1 (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5455258A (en) * | 1993-01-06 | 1995-10-03 | Ciba-Geigy Corporation | Arylsulfonamido-substituted hydroxamic acids |
| US5770624A (en) * | 1995-12-15 | 1998-06-23 | Novartis Corp. | Certain alpha-substituted arylsulfonamido acetohydroxamic acids |
| WO2002038796A2 (en) * | 2000-11-08 | 2002-05-16 | Beth Israel Deaconess Medical Center, Inc. | Methods for determining protease cleavage site motifs |
-
2003
- 2003-07-28 AU AU2003253346A patent/AU2003253346A1/en not_active Abandoned
- 2003-07-28 WO PCT/EP2003/008316 patent/WO2004012737A1/en not_active Application Discontinuation
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5455258A (en) * | 1993-01-06 | 1995-10-03 | Ciba-Geigy Corporation | Arylsulfonamido-substituted hydroxamic acids |
| US5770624A (en) * | 1995-12-15 | 1998-06-23 | Novartis Corp. | Certain alpha-substituted arylsulfonamido acetohydroxamic acids |
| WO2002038796A2 (en) * | 2000-11-08 | 2002-05-16 | Beth Israel Deaconess Medical Center, Inc. | Methods for determining protease cleavage site motifs |
Non-Patent Citations (2)
| Title |
|---|
| JENG A Y ET AL: "Sulfonamide-based hydroxamic acids as potent inhibitors of mouse macrophage metalloelastase", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, OXFORD, GB, vol. 8, no. 8, 21 April 1998 (1998-04-21), pages 897 - 902, XP004136987, ISSN: 0960-894X * |
| SCOZZAFAVA A ET AL: "Protease inhibitors - Part 5. Alkyl/arylsulfonyl- and arylsulfonylureido-/arylureido- glycine hydroxamate inhibitors of Clostridium histolyticum collagenase", EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, EDITIONS SCIENTIFIQUE ELSEVIER, PARIS, FR, vol. 35, no. 3, March 2000 (2000-03-01), pages 299 - 307, XP004341234, ISSN: 0223-5234 * |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2003253346A1 (en) | 2004-02-23 |
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