Claims
- 1. A compound having a structure according to formula (I)
- 2. The compound according to claim 1 wherein G is —CH═CH— or —S—.
- 3. The compound according to claim 1 wherein A is covalent bond, O or S.
- 4. The compound according to claim 3 wherein A is O or S.
- 5. The compound according to claim 1 wherein R1 is hydrogen, alkyl, heteroalkyl or halogen.
- 6. The compound according to claim 1 wherein X and Y are both a covalent bond and Z is H, alkyl or aryl alkyl.
- 7. The compound according to claim 1 wherein X is C1-C3 alkyl substituted with a hydroxy group, Y is S, O or NR2, and Z is aryl, arylalkyl, heteroaryl, heteroarylalkyl or acylated amino-acid residue.
- 8. The compound according to claim 7 wherein Y is S.
- 9. The compound of claim 1, selected from the group consisting of:
4,4-Difluoro-4-(4′-methoxy-biphenyl-4-yl)-butyric acid, 4,4-Difluoro-4-(4′-methoxy-biphenyl-4-yl)-2-methyl-butyric acid, 2-Ethyl-4,4-difluoro-4-(4′-methoxy-biphenyl-4-yl)-butyric acid, 4,4-Difluoro-4-(4′-methoxy-biphenyl-4-yl)-2-propyl-butyric acid, 2-Benzyl-4-biphenyl-4-yl-4,4-difluoro-butyric acid, 2-Benzyl-4,4-difluoro-4-(4′-methoxy-biphenyl-4-yl)-butyric acid, 2-Benzyl-4,4-difluoro-4-(4′-ethoxy-biphenyl-4-yl)-butyric acid, 2-Benzyl-4,4-difluoro-4-[4′-(2-methoxy-ethoxy)-biphenyl-4-yl]-butyric acid, 2-Benzyl-4,4-difluoro-4-(4′-fluoro-biphenyl-4-yl)-butyric acid, 2-Benzyl-4,4-difluoro-4-(4′-chloro-biphenyl-4-yl)-butyric acid, 4,4-Difluoro-4-(4′-methoxy-biphenyl-4-yl)-2-pyridin-2-ylmethyl-butyric acid, 4,4-Difluoro-4-(4′-methoxy-biphenyl-4-yl)-2-pyridin-3-ylmethyl-butyric acid, 4,4-Difluoro-4-(4′-methoxy-biphenyl-4-yl)-2-pyridin-4-ylmethyl-butyric acid, 4,4-Difluoro-2-furan-2-ylmethyl-4-(4′-methoxy-biphenyl-4-yl)-butyric acid, 4,4-Difluoro-2-(1H-indol-2-ylmethyl)-4-(4′-methoxy-biphenyl-4-yl)-butyric acid, 4,4-Difluoro-4-(4′-methoxy-biphenyl-4-yl)-2-phenethyl-butyric acid, 4,4-Difluoro-4-(4′-methoxy-biphenyl-4-yl)-2-phenethyl-butyric acid, 2-[2,2-Difluoro-2-(4′-methoxy-biphenyl-4-yl)-ethyl]-5-phenyl-pentanoic acid, 2-[2,2-Difluoro-2-(4′-methoxy-biphenyl-4-yl)-ethyl]-4-hydroxy-5-phenylsulfanyl-pentanoic acid, 5-(Benzothiazol-2-ylsulfanyl)-2-[2,2-difluoro-2-(4′-methoxy-biphenyl-4-yl)-ethyl]-4-hydroxy-pentanoic acid, 2-[2,2-Difluoro-2-(4′-methoxy-biphenyl-4-yl)-ethyl]-5-(4,5-dihydro-thiazol-2-ylsulfanyl)-4-hydroxy-pentanoic acid, 2-[2,2-Difluoro-2-(4′-methoxy-biphenyl-4-yl)-ethyl]-4-hydroxy-5-(pyridin-2-ylsulfanyl)-pentanoic acid, 5-Benzylsulfanyl-2-[2,2-difluoro-2-(4′-methoxy-biphenyl-4-yl)-ethyl]-4-hydroxy-pentanoic acid, 2-[2,2-Difluoro-2-(4′-methoxy-biphenyl-4-yl)-ethyl]-4-hydroxy-5-(1-methyl-1H-imidazol-2-ylsulfanyl)-pentanoic acid, 2-[2,2-Difluoro-2-(4′-methoxy-biphenyl-4-yl)-ethyl]-4-hydroxy-5-(1-phenyl-1H-imidazol-2-ylsulfanyl)-pentanoic acid, 5-(4-Chloro-phenylsulfanyl)-2-[2,2-difluoro-2-(4′-methoxy-biphenyl-4-yl)-ethyl]-4-hydroxy-pentanoic acid, 5-(2-Acetylamino-2-carboxy-ethylsulfanyl)-2-[2,2-difluoro-2-(4′-methoxy-biphenyl-4-yl)-ethyl]-4-hydroxy-pentanoic acid, 2-[2-(4′-Ethoxy-biphenyl-4-yl)-2,2-difluoro-ethyl]-4-hydroxy-5-phenylsulfanyl-pentanoic acid, 2-{2,2-Difluoro-2-[4′-(2-methoxy-ethoxy)-biphenyl-4-yl]-ethyl}-4-hydroxy-5-phenylsulfanyl-pentanoic acid, and 2-[2,2-Difluoro-2-(4′-fluoro-biphenyl-4-yl)-ethyl]-4-hydroxy-5-phenylsulfanyl-pentanoic acid.
- 10. A compound having a structure according to formula (II)
- 11. A pharmaceutical composition comprising:
(a) a safe and effective amount of a compound of claim 1; and (b) a pharmaceutically-acceptable carrier.
- 12. A method for treating a metalloprotease related disorder in a mammalian subject, the method comprising administering to a mammal in need of such treatment a safe and effective amount of a compound according to claim 1.
- 13. The method of claim 12, wherein the disorder is selected from the group consisting of arthritis, cancer, cardiovascular disorders, skin disorders, ocular disorders, inflammatory conditions and gum disease.
- 14. The method of claim 13, wherein the disorder is an arthritis, and is selected from the group consisting of osteoarthritis and rheumatoid arthritis.
- 15. The method of claim 13, wherein the disorder is cancer, and the treatment prevents or arrests tumor growth and metastasis.
- 16. The method of claim 13, wherein the disorder is a cardiovascular disorder selected from the group consisting of dilated cardiomyopathy, congestive heart failure, atherosclerosis, plaque rupture, reperfusion injury, ischemia, chronic obstructive pulmonary disease, angioplasty restenosis and aortic aneurysm.
- 17. The method of claim 13, wherein the disorder is an ocular disorder, and is selected from the group consisting of corneal ulceration, lack of corneal healing, macular degeneration, retinopathy and pterygium.
- 18. The method of claim 13, wherein the disorder is a gum disease, and is selected from the group consisting of periodontal disease and gingivitis.
- 19. The method of claim 13, wherein the disorder is a skin disorder selected from the group consisting of wrinkle repair and prevention, U.V. skin damage, epidermolysis bullosa, psoriasis, sclerodema, atopic dermatitis and scarring.
- 20. The method of claim 13, wherein the disorder is an inflammatory condition selected from the group consisting of inflammatory bowel disease, Crohn's Disease, ulcerative colitis, pancreatitis, diverticulitis, acne inflammation, bronchitis, arthritis and asthma.
- 21. The method of claim 12, wherein the disorder is multiple sclerosis.
- 22. The method of claim 12, wherein the disorder is the loosening of prosthetic devices.
- 23. The method of claim 22, wherein the loosening of prosthetic devices is selected from joint replacements and dental prosthesis.
- 24. The method of claim 12, wherein the disorder is musculoskeletal disease or cachexia.
- 25. The method of claim 12, wherein the disorder is selected from chronic heart failure, myocardial infarction and progressive ventricular dilation.
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This is a continuation-in-part under 35 U.S.C. §120 of PCT International Application Serial No. PCT/US01/08781, filed Mar. 20, 2001; which claims priority to Provisional Application Serial No. 60/191,296, filed Mar. 21, 2000.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60191296 |
Mar 2000 |
US |
Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
PCT/US01/08781 |
Mar 2001 |
US |
Child |
10246179 |
Sep 2002 |
US |