Biaryl sulfonamides and methods for using same
AssigneeWyeth
InventorsJason Shaoyun Xiang, Steve Yikkai Tam, Yonghan Hu, Phaik-Eng Sum, David Brian How, Darrin William Hopper, Matthew Douglas Vera, Joshua James Sabatini, Thomas Saltmarsh Rush, III, Elisabeth Ann Morris, Katy Evangelia Georgiadis
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Abstract
The present invention relates to biaryl sulfonamides and their use as, for example, metalloproteinase inhibitors.
Claims18
A method for modulating the activity of a metalloproteinase comprising contacting said metalloproteinase with an effective amount of a compound of formula I:
- wherein:
- R1 is H or C1-C6 alkyl;
- R2 is H, C1-C6 alkyl, (CH2)nR2′, phenyl, or benzyl;
- n is 0-6;
- R2′ is aryl, heteroaryl, cycloalkyl, or heterocycloalkyl;
- R3 is, independently with respect to each occurrence, H, halogen, OC(halogen)3, C(halogen)3, alkoxy, or C1-C6 alkyl;
- X is selected from CH2O, OCH2, C(R3)═C(R3), C(R3)2—C(R3)2, CH2NHC(═O), O(C═O)NH, O, C(═O)CH2, SO2CH2C(═O)NH, SO2NH, OC(═O), CH2S(O), and CH2S(O)2;
- and
- Z is at least one aryl or heteroaryl moiety.
A method for treating a patient suspected of suffering from a disease associated with excessive metalloproteinase activity, comprising the step of administering to the patient a therapeutically effective amount of the compound of a compound of formula I:
- wherein:
- R1 is H or C1-C6 alkyl;
- R2 is H, C1-C6 alkyl, (CH2)nR2′, phenyl, or benzyl;
- n is 0-6;
- R2′ is aryl, heteroaryl, cycloalkyl, or heterocycloalkyl;
- R3 is, independently with respect to each occurrence, H, halogen, OC(halogen)3, C(halogen)3, alkoxy, or C1-C6 alkyl;
- X is selected from CH2O, OCH2, C(R3)═C(R3), C(R3)2—C(R3)2, CH2NHC(═O), O(C═O)NH, O, C(═O)CH2, SO2CH2C(═O)NH, SO2NH, OC(═O), CH2S(O), and CH2S(O)2;
- and
- Z is at least one aryl or heteroaryl moiety wherein said disease is osteoarthritis, rheumatoid arthritis, asthma, chronic obstructive pulmonary disease D, atherosclerosis, age-related macular degeneration, myocardial infarction, corneal ulceration and other ocular surface diseases, hepatitis, aortic aneurysms, tendonitis, central nervous system diseases, abnormal wound healing, angiogenesis, restenosis, cirrhosis, multiple sclerosis, glomerulonephritis, graft versus host disease, diabetes, inflammatory bowel disease, shock, invertebral disc degeneration, stroke, osteopenia, or periodontal diseases.
Dependencies are inferred from the claim text.