Biphenyl sulfonamides useful as matrix metalloproteinase inhibitors
This invention relates to a group of biphenyl sulfonamide compounds and derivatives which inhibit matrix metalloproteinase enzymes and thus are useful for treating diseases resulting from connective tissue breakdown, such as heart disease, multiple sclerosis, arthritis, atherosclerosis, and osteopor...
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| Format | Patent |
| Language | English |
| Published |
03.02.2004
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| Abstract | This invention relates to a group of biphenyl sulfonamide compounds and derivatives which inhibit matrix metalloproteinase enzymes and thus are useful for treating diseases resulting from connective tissue breakdown, such as heart disease, multiple sclerosis, arthritis, atherosclerosis, and osteoporosis.
Inhibitors of MMP enzymes are cyclic sulfonamides of Formula I or a pharmaceutically acceptable salt thereof, and cyclic sulfonamides of Formula III or a pharmaceutically acceptable salt thereof,wherein Rand Rinclude hydrogen, alkyl, and substituted alkyl; Rand Rinclude hydrogen, halo, and alkyl; X is OH or NHOH: Z is (CH): and Y is S, SO or SO. The compounds of Formulas I and III are useful for the treatment of diseases mediated by an MMP enzyme, including cancer, osteoarthritis, rheumatoid arthritis, heart failure, and inflammation. |
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| AbstractList | This invention relates to a group of biphenyl sulfonamide compounds and derivatives which inhibit matrix metalloproteinase enzymes and thus are useful for treating diseases resulting from connective tissue breakdown, such as heart disease, multiple sclerosis, arthritis, atherosclerosis, and osteoporosis.
Inhibitors of MMP enzymes are cyclic sulfonamides of Formula I or a pharmaceutically acceptable salt thereof, and cyclic sulfonamides of Formula III or a pharmaceutically acceptable salt thereof,wherein Rand Rinclude hydrogen, alkyl, and substituted alkyl; Rand Rinclude hydrogen, halo, and alkyl; X is OH or NHOH: Z is (CH): and Y is S, SO or SO. The compounds of Formulas I and III are useful for the treatment of diseases mediated by an MMP enzyme, including cancer, osteoarthritis, rheumatoid arthritis, heart failure, and inflammation. |
| Author | Sliskovic, Drago Robert Barvian, Nicole Chantel Patt, William Chester O'Brien, Patrick Michael |
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| References | (1 081 137) 20010300 (WO 97/44315) 19971100 (WO 01/63244) 20010800 D R Close {Ann. Rheum. Dis 60, pp. iii62-iii67 (2002)}. Chen, James, et al, "Structure-Based Design of a Novel, Potent, and Selective Inhibitor for MMP-13 Utilizing NMR Spectroscopy and Computer-Aided Molecular Design", J. Am. Chem. Soc., 2000, 122; pp 9648-9654. Derwent Abstract, 97-332465/30. Peterson, Jr. et al. (5948780) 19990900 (WO 96/33172) 19961000 Clark, Ian, et al, "Matrix metalloproteinase inhibitors in the treatment of arthritis", Current Opinions in Anti-inflammatory & Immunomodulatory Investigational Drugs, 2000; 2(1), pp 16-25. Derwent Abstract, 96-485703/48. Skiles et al. {Annual Reports in Medicinal Chemisty-36, Chapter 15, pp. 167-176, 2000}. (WO 98/08822) 19980300 (WO 00/09492) 20000200 Robert A. Greenwald {Annals of New York Academy of Sciences 878:413-419 (1999)}. Bender et al. (6008243) 19991200 Derwent Abstract, 98-447147/38. Jackson et al. {Inflamma. Res 50, 183-186 (2001)}. (WO 98/34918) 19980800 Almstead, Neil G., et al, "Design, Synthesis, and Biological Evaluation of Potent Thiazine- and Thiazepine-Based Matrix Metalloproteinase Inhibitors", J. Med. Chem., 1999, 42, pp 4547-4562 XP-000919158. Derwent Abstract, 2000-301906/32. Coussens et al. {Science vol. 295, Mar. 29, pp. 2387-2392, (2002)}. Montana, John, et al, "The design of selective non-substrate-based matrix metalloproteinase inhibitors", Current Opinion in Drug Discovery & Development, 2000; 3(4), pp 353-361. European Search Report for EP 02 00 2814. Skiles et al. {Current Medicinal Chemistry, 8, 425-474 (2001)}. Derwent Abstract, 2000-205958/18. (WO 97/20824) 19970600 |
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