Matrix metalloproteinase inhibitors

• US 6,600,057 B2
• Filed: 12/29/2000
• Issued: 07/29/2003
• Est. Priority Date: 12/29/2000
• Status: Expired due to Term

• Current Assignee: Avent Incorporated (Avanos Medical, Inc.)
• Original Assignee: Kimberly-Clark Worldwide Incorporated (Kimberly-Clark Corporation)
• Inventors: Quirk, Stephen
• Primary Examiner(s): Killos, Paul J.
• Application Number:
  US09/753,140
• Publication Number:
  US 20020086877A1
• Time in Patent Office: 942 Days
• Field of Search: 552/298, 514/533, 514/569, 514/680
• US Class Current: 552/298
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/4168 having a nitrogen attached in position 2, e.g. clonidine
• CPC Class Codes: A61K 31/4196 1,2,4-Triazoles
• CPC Class Codes: A61K 31/47 Quinolines; Isoquinolines
• CPC Class Codes: C07C 235/84 with the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 259/06 having carbon atoms of hydroxamic groups bound to hydrogen atoms or to acyclic carbon atoms
• CPC Class Codes: C07C 2603/24 Anthracenes; Hydrogenated anthracenes

Abstract

The present invention provides compounds that are effective in treating disorders caused by the enzymatic activity of matrix metalloproteinases. These disorders include, but are not limited to, rheumatoid arthritis, osteoarthritis, periodontal disease, aberrant angiogenesis, tumor invasion and metastasis, corneal ulceration, and in complications of diabetes. The present invention is also is useful for treating wounds.

Claims

1. A method of treating a disorder in a patient wherein the disorder is associated with matrix metalloproteinase comprising administering to the patient a therapeutically effective amount of dihydroxyanthaquinone-2-carboxylic acid or a derivative of dihydroxyanthaquinone-2-carboxylic acid.

2. The method of claim 1, wherein the dihydroxyanthaquinone-2-carboxylic acid or a derivative of dihydroxyanthaquinone-2-carboxylic acid is administered via oral, rectal, ophthalmic, intravitreal, intracameral. nasal, topical, buccal, sublingual, vaginal, parenteral, subcutaneous, intramuscular, intravenous, intradermal, intratracheal, or epidural routes.

3. The method of claim 1, wherein the disorder is a rheumatoid arthritis;

osteoarthritis;

osteopenias such as osteoporosis, periodontitis, gingivitis, corneal epidermal or gastric ulceration;

tumour metastasis, invasion and growth;

neuroinflammatory disorders, including those involving myelin degradation, for example multiple sclerosis; and

angiogenesis dependent diseases, which include angiofibromas, hemangioma, solid tumors, leukemia, metastasis, telangiectasia psoriasis scleroderma, pyogenic granuloma, Myocardial angiogenesis, plaque neovascularization, cororany collaterals, ischemic limb angiogenesis, corneal diseases, rubeosis, neovascular glaucoma, diabetic retinopathy, retrolental fibroplasia, arthritis, diabetic neovascularization, macular degeneration, wound healing, peptic ulcer, fractures, keloids, vasculogenesis, hematopoiesis, ovulation, menstruation, or placentation.

4. The method of claim 1, wherein the disorder is a wound.

5. The method of claim 1, wherein the derivative of dihydroxyanthaquinone-2-carboxylic acid has the following formula:

wherein R is;

6. The method of claim 1, wherein the derivative of dihydroxyanthaquinone-2-carboxylic acid is anthraquinyl-mercaptoethyamine.

7. The method of claim 1, wherein the derivative of dihydroxyanthaquinone-2-carboxylic acid is anthraquinyl-alanine hydroxamate.

8. The method of claim 1, wherein the dihydroxyanthaquinone-2-carboxylic acid or a derivative of dihydroxyanthaquinone-2-carboxylic acid is administered to the patient topically.