Claims
- 1. A compound having a structure according to Formula (I)
- 2. A compound according to claim 1 where the compound is of structure:
- 3. The compound of claim 2, wherein Ar is phenyl or substituted phenyl.
- 4. The compound of claim 3, wherein Ar is substituted phenyl and the substitution is with hydroxy, alkoxy, nitro or halo.
- 5. The compound of claim 4, wherein Ar is substituted with methoxy, bromo, nitro and butoxy.
- 6. The compound of claim 5, wherein Ar is substituted at the ortho or para position relative to the sulfonyl.
- 7. The compound of claim 3, wherein Y is independently one or more of hydroxy, SO2R5, alkoxy, amino, wherein amino is of formula NR6,R7, wherein R6 and R7 are independently chosen from hydrogen, alkyl, heteroalkyl, heteroaryl, aryl, SO2R8, COR9.
- 8. The compound of claim 7, wherein Y is independently one or more of hydroxy, amino, wherein amino is of formula NR6,R7, wherein R6 and R7 are independently chosen from hydrogen, alkyl, heteroalkyl, heteroaryl, aryl, SO2R8, COR9.
- 9. A compound according to claim 1 wherein the compound is chosen from;
(1N)-(4-Methoxyphenylsulfonyl)-(2R)-N-hydroxycarboxamido-(4S)-hydroxypyrrolidine; ((1N)-(4-Methoxyphenylsulfonyl)-(2R)-N-hydroxycarboxamido-(4S)-hydroxypyrrolidine; (1N)-(4-Methoxyphenylsulfonyl)-(2S)-N-hydroxycarboxamido-(4R)-hydroxypyrrolidine; (1N)-(4-Methoxyphenylsulfonyl)-(2S)-N-hydroxycarboxamido-(4S)-hydroxypyrrolidine; (1N)-(4-Methoxyphenylsulfonyl)-(2R)-N-hydroxycarboxamido-(4S)-methoxypyrrolidine; (1N)-(4-Methoxyphenylsulfonyl)-(2R)-N-hydroxycarboxamido-(4S)-(2-mercapto-benzothiazolyl)-pyrrolidine; (1N)-(4-Methoxyphenylsulfonyl)-(2R)-N-hydroxycarboxamido-(4R)-(2-mercaptobenzo-thiazolyl)-pyrrolidine; (1N)-(4-Methoxyphenylsulfonyl)-(2R)-N-hydroxycarboxamido-(4S)-[(1N)-methyl-2-mercaptoimidazyl]-pyrrolidine; (1N)-(4-Methoxyphenylsulfonyl)-(2R)-N-hydroxycarboxamido-(4R)-[(1N)-methyl-2-mercaptoimidazyl]-pyrrolidine; (1N)-(4-Methoxyphenylsulfonyl)-(2R)-N-hydroxycarboxamido-(4S)-phenoxypyrrolidine; (1N)-(4-Methoxyphenylsulfonyl)-(2R)-N-hydroxycarboxamido-(4S)-(4-benzyloxy)-phenoxypyrrolidine; (1N)-4-Methoxyphenylsulfonyl-(2R)-N-hydroxycarboxamido-(4S)-(3-N-phenylamino)-phenoxylpyrrolidine; (1N)-4-Methoxyphenylsulfonyl-(2R)-N-hydroxycarboxamido-(4S)-phenoxypyrrolidine; (1N)-4-Methoxyphenylsulfonamido-(2R)-N-hydroxycarboxamido-(4S)-mercaptophenylpyrrolidine; (1N)-(4-Methoxyphenylsulfonyl)-(2R)-N-hydroxycarboxamido-(4S)-(4-methoxyphenyl-thioloxy)-pyrrolidine; (1N)-(4-Methoxyphenylsulfonyl)-(2R)-N-hydroxycarboxamido-(4S)-(3-methoxy-mercaptophenyl)-pyrrolidine; (1N)-(4-Methoxyphenylsulfonyl)-(2R)-N-hydroxycarboxamido-(4S)-(nhexylamino)-pyrrolidine; (1N)-(4-Methoxyphenylsulfonyl)-(2R)-hydroxy carboxamido-(4S)-thiopyrrolidine; (±)-(1N)-(4-Methoxyphenylsulfonyl)-(2R)-N-hydroxycarboxamido-(3S)-phenylpyrrolidine; (1N)-(4-Methylphenylsulfonyl)-(2R)-N-hydroxycarboxamido-(4S)-hydroxypyrrolidine; (1N)-(3,4-Dimethoxyphenylsulfonyl)-(2R)-N-hydroxycarboxamido-(4R)-hydroxypyrrolidine; (1N)-(2-Nitro-4-methoxyphenylsulfonyl)-(2R)-N-hydroxycarboxamido-(4R)-hydroxypyrrolidine; (1N)-4-nButoxyphenylsulfonamido-(2R)-N-hydroxycarboxamido-(4R)-hydroxypyrrolidine; (1N)-(4-nButoxyphenylsulfonyl)-(2R)-N-hydroxycarboxamido-(4S)-hydroxypyrrolidine; (1N)-(4-nButoxyphenylsulfonyl)-(2R)-N-hydroxycarboxamido-(4S)-(2-mercapto-benzothiazolyl)-pyrrolidine; (1N)-(2-Nitro-4-methoxyphenylsulfonyl)-(2R)-N-hydroxycarboxamido-(4S)-(2-mercapto-benzothiazolyl)-pyrrolidine; (1N)-(4-Methoxyphenylsulfonyl)-(2R)-N-hydroxycarboxamido-(4S)-(4-methoxyphenyl-thioloxy)-pyrrolidine; (±)-(1N)-4-Methoxyphenylsulfonyl-(2R)-N-hydroxycarboxamido-5-pyrrolidinone; and (1N)-4-Methoxyphenylsulfonyl-(2R)-hydroxy-carboxamido-(4,4R)-hydroxy-ethylpyrrolidine.
- 10. A pharmaceutical composition comprising:
(a) a safe and effective amount of a compound of claim 1; and (b) a pharmaceutically-acceptable carrier.
- 11. A pharmaceutical composition comprising:
(a) a safe and effective amount of a compound of claim 2; and (b) a pharmaceutically-acceptable carrier.
- 12. A pharmaceutical composition comprising:
(a) a safe and effective amount of a compound of claim 3; and (b) a pharmaceutically-acceptable carrier.
- 13. A pharmaceutical composition comprising:
(a) a safe and effective amount of a compound of claim 7; and (b) a pharmaceutically-acceptable carrier.
- 14. A method for preventing or treating a disease associated with unwanted metalloprotease activity in a mammalian subject, the method comprising administering said subject a safe and effective amount of a compound of claim 1.
- 15. A method for preventing or treating a disease associated with unwanted metalloprotease activity in a mammalian subject, the method comprising administering to said subject a safe and effective amount of a compound of claim 2.
- 16. A method for preventing or treating a disease associated with unwanted metalloprotease activity in a human or other animal subject, the method comprising administering to said subject a safe and effective amount of a compound of claim 3.
- 17. A method for preventing or treating a disease associated with unwanted metalloprotease activity in a mammalian subject, the method comprising administering to said subject a safe and effective amount of a compound of claim 7.
- 18. A method for preventing or treating a disorder modulated by metalloproteases, wherein the disorder is chosen from the group comprising, arthritis, cancer, cardiovascular disorders, skin disorders ocular disorders, inflammation and gum disease by administering to a mammal in need of such treatment, a safe and effective amount of a metalloprotease inhibitor according to claim 1.
- 19. A method for preventing or treating a disorder according to claim 18, wherein the disorder is arthritis, and is chosen from the group comprising, osteoarthritis and rheumatoid arthritis.
- 20. A method for preventing or treating a disorder according to claim 18, wherein the disorder is cancer, and the treatment prevents or arrests tumor growth and metastasis.
- 21. A method for the preventing or treating a disorder according to claim 18, wherein the disorder is a cardiovascular disorder chosen from the group compromising dilated cardiomyopathy, congestive heart failure, atherosclerosis, plaque rupture, reperfusion injury, ischemia, chronic obstructive pulmonary disease, angioplasty restenosis and aortic aneurysm.
- 22. A method for the preventing or treating a disorder according to claim 18, wherein the disorder is an ocular disorder, and is chosen from the group comprising, corneal ulceration, lack of corneal healing, macular degeneration, and pterygium.
- 23. A method for preventing or treating a disorder according to claim 18, wherein the disorder is gum disease, and is chosen from the group comprising, periodontal disease, and gingivitis.
- 24. A method for preventing or treating a disorder, according to claim 18, wherein the disorder is skin disorder chosen from the group comprising wrinkle repair and prevention, U. V. skin damage, epidermolysis bullosa, psoriasis, sclerodema, atopic dermatitis and scarring.
- 25. A method for preventing the loosening of prosthetic devices chosen from the group comprising joint replacements and dental prosthesis by administering to a mammal in need of such treatment, a safe and effective amount of a metalloprotease inhibitor according to claim 1.
- 26. A method for treating inflammatory conditions according to claim 18, chosen from the group comprising inflammatory bowel disease, Crohn's Disease, ulcerative colitis, pancreatitis, diverticulitis, acne inflammation, bronchitis, arthritis, asthma.
- 27. A method of treating multiple sclerosis, comprising administering to a mammal in need of such treatment, a safe and effective amount of a metalloprotease inhibitor according to claim 1.
- 28. A method for treating musculoskeletal disease or cachexia comprising administering to a mammal in need of such treatment, a safe and effective amount of a metalloprotease inhibitor according to claim 1.
CROSS REFERENCE
[0001] This application claims priority under Title 35, United States Code 119(e) from Provisional Application Serial No. 60/024,842, filed Aug. 28, 1996.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60024842 |
Aug 1996 |
US |
Divisions (2)
|
Number |
Date |
Country |
Parent |
09888675 |
Jun 2001 |
US |
Child |
10308780 |
Dec 2002 |
US |
Parent |
08918317 |
Aug 1997 |
US |
Child |
09888675 |
Jun 2001 |
US |