Claims for Patent: 7,923,446

Summary for Patent: 7,923,446

Title:	Biaryl sulfonamides and methods for using same
Abstract:	The present invention relates to biaryl sulfonamides and their use as, for example, metalloproteinase inhibitors.
Inventor(s):	Xiang; Jason Shaoyun (Winchester, MA), Tam; Steve Yikkai (Wellesley, MA), Hu; Yonghan (Burlington, MA), Sum; Phaik-Eng (Pomona, NY), How; David Brian (Nyack, NY), Hopper; Darrin William (New York, NY), Vera; Matthew Douglas (West Haverstraw, NY), Sabatini; Joshua James (White Plains, NY), Rush, III; Thomas Saltmarsh (Lexington, MA), Morris; Elisabeth Ann (Sherborn, MA), Georgiadis; Katy Evangelia (Belmont, MA)
Assignee:	Wyeth LLC (Madison, NJ)
Application Number:	11/756,253
Patent Claims:	1. A method for modulating the activity of a metalloproteinase comprising contacting said metalloproteinase with an effective amount of a compound of formula I: ##STR00139## wherein: R.sup.1 is H or C.sub.1-C.sub.6 alkyl; R.sup.2 is H, C.sub.1-C.sub.6 alkyl, (CH.sub.2).sub.nR.sup.2', phenyl, or benzyl; n is 0-6; R.sup.2' is aryl, heteroaryl, cycloalkyl, or heterocycloalkyl; R.sup.3 is, independently with respect to each occurrence, H, halogen, OC(halogen).sub.3, C(halogen).sub.3, alkoxy, or C.sub.1-C.sub.6 alkyl; X is selected from CH.sub.2O, OCH.sub.2, C(R.sup.3).dbd.C(R.sup.3), C(R.sup.3).sub.2--C(R.sup.3).sub.2, CH.sub.2NHC(.dbd.O), O(C.dbd.O)NH, O, C(.dbd.O)CH.sub.2, SO.sub.2CH.sub.2C(.dbd.O)NH, SO.sub.2NH, OC(.dbd.O), CH.sub.2S(O), and CH.sub.2S(O).sub.2; and Z is at least one aryl or heteroaryl moiety. 2. The method of claim 1 further comprising determining the activity of said metalloproteinase. 3. The method of claim 2 wherein said determination is made before said contacting step. 4. The method of claim 2 wherein said determination is made after said contacting step. 5. The method of claim 1, wherein the metalloproteinase is Aggrecanase-1. 6. The method of claim 5, wherein the configuration at the alpha carbon of the compound is R. 7. The method of claim 1, wherein the metalloproteinase is Collagenase-3. 8. 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: ##STR00140## wherein: R.sup.1 is H or C.sub.1-C.sub.6 alkyl; R.sup.2 is H, C.sub.1-C.sub.6 alkyl, (CH.sub.2).sub.nR.sup.2', phenyl, or benzyl; n is 0-6; R.sup.2' is aryl, heteroaryl, cycloalkyl, or heterocycloalkyl; R.sup.3 is, independently with respect to each occurrence, H, halogen, OC(halogen).sub.3, C(halogen).sub.3, alkoxy, or C.sub.1-C.sub.6 alkyl; X is selected from CH.sub.2O, OCH.sub.2, C(R.sup.3).dbd.C(R.sup.3), C(R.sup.3).sub.2--C(R.sup.3).sub.2, CH.sub.2NHC(.dbd.O), O(C.dbd.O)NH, O, C(.dbd.O)CH.sub.2, SO.sub.2CH.sub.2C(.dbd.O)NH, SO.sub.2NH, OC(.dbd.O), CH.sub.2S(O), and CH.sub.2S(O).sub.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. 9. The method of claim 1, wherein Z is pyridine, pyrimidine, pyrazine, pyridazine, phenyl, naphthalene, furan, thiophene, pyrrole, pyrazole, imidazole, oxazole, isoxazole, thiazole, benzothiazole, quinoline, or isoquinoline, or ##STR00141## wherein: U is selected from S, O, C(R.sup.3).dbd.C(R.sup.3), C(R.sup.3).dbd.N, and N(R.sup.4); W is selected from C(R.sup.3), and N; M is selected from C(R.sup.3), and N; L is selected from S, O, C(R.sup.3).dbd.C(R.sup.3), C(R.sup.3).dbd.N, and N(R.sup.4); R.sup.4 and R.sup.5 are, independently with respect to each occurrence, a bond to the other, H, C.sub.1-C.sub.6 alkyl, or phenyl; and R.sup.7 is selected from a bond to R.sup.3, H, halogen, C(halogen).sub.3, NR.sup.4R.sup.5, N[(CH.sub.2).sub.2].sub.2O, N[(CH.sub.2).sub.2].sub.2NR.sup.4, NHSO.sub.2R.sup.4, NR.sup.4C(.dbd.O)R.sup.5, NHC(.dbd.O)OR.sup.4, NO.sub.2, SO.sub.2NR.sup.4R.sup.5, SO.sub.2R.sup.4, OR.sup.4, C(.dbd.O)R.sup.4, COOR.sup.4, CONR.sup.4R.sup.5, CN, phenyl, heteroaryl, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, or C.sub.2-C.sub.6 alkynyl. 10. The method of claim 9, wherein R.sup.7 is substituted with NR.sup.4R.sup.5, N[(CH.sub.2).sub.2].sub.2O, N[(CH.sub.2).sub.2].sub.2NR.sup.4, NHSO.sub.2R.sup.4, NR.sup.4C(.dbd.O)R.sup.5, NHC(.dbd.O)OR.sup.4, NO.sub.2, SO.sub.2NR.sup.4R.sup.5, SO.sub.2R.sup.4, OR.sup.8, C(.dbd.O)R.sup.4, COOR.sup.4, CONR.sup.4R.sup.5, CN, phenyl, or heteroaryl, wherein R.sup.8 is selected from H, phenyl, heteroaryl, and C.sub.1-C.sub.6 alkyl and wherein R.sup.8 is H, phenyl, heteroaryl, or C.sub.1-C.sub.6 alkyl. 11. The method of claim 10, wherein R.sup.8 is CH.sub.3, phenyl, and benzyl. 12. The method of claim 10, wherein R.sup.8 is substituted with NR.sup.4R.sup.5, N[(CH.sub.2).sub.2].sub.2O, N[(CH.sub.2).sub.2].sub.2NR.sup.4, NR.sup.4SO.sub.2R.sup.5, NR.sup.4C(.dbd.O)R.sup.5, NHC(.dbd.O)OR.sup.4, NO.sub.2, SO.sub.2NR.sup.4R.sup.5, SO.sub.2R.sup.4, C(.dbd.O)R.sup.4, COOR.sup.4, CONR.sup.4R.sup.5, CN, phenyl, or heteroaryl. 13. The method of claim 1, wherein R.sup.1 is H or branched alkyl. 14. The method of claim 13, wherein R.sup.1 is isopropyl. 15. The method of claim 1, wherein R.sup.3 is halogen, CF.sub.3, OCH.sub.3, or CH.sub.3. 16. The method of claim 1, wherein X is CH.sub.2O, OCH.sub.2, C(R.sup.3).dbd.C(R.sup.3), or CH.sub.2NHC(.dbd.O). 17. The method of claim 9, wherein R.sup.7 is CH.sub.3, ethyl, isopropyl, CF.sub.3, CN, or OCH.sub.3. 18. The compound of claim 1, wherein Z is bicyclic.

Details for Patent 7,923,446

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Smith & Nephew, Inc.	SANTYL	collagenase	Ointment	101995	06/04/1965		2023-12-04