Claims for Patent: 5,859,061

Summary for Patent: 5,859,061

Title:	Bis-sulfonamides hydroxamic acids as MMP inhibitors
Abstract:	The present invention provides a compound of formula I ##STR1## or pharmaceutically acceptable salts thereof wherein R.sup.1 and R.sup.2 are the same or different and are C.sub.1-10 alkyl, phenyl, hetero-aryl, or phenyl substituted with C.sub.1-4 alkyl, OR.sup.3, NHR.sup.3, CONHR.sup.3, NHCOR.sup.3, or halo; wherein R.sup.3 is H, or C.sub.1-4 alkyl; and n is 1, 2, 3, 4, 5, or 6. The compounds are inhibitors of matrix metalloproteinases involved in tissue degradation.
Inventor(s):	Jacobsen; Eric Jon (Plainwell, MI), Skaletzky; Louis L. (Kalamazoo, MI)
Assignee:	Pharmacia & Upjohn Company (Kalamazoo, MI)
Application Number:
Patent Claims:	1. A compound of formula I ##STR13## or pharmaceutically acceptable salts thereof wherein R.sup.1 and R.sup.2 are the same or different and are a) C.sub.1-10 alkyl, b) phenyl, c) hetero-aryl, or d) phenyl substituted with C.sub.1-4 alkyl, OR.sup.3, NHR.sup.3, CONHR.sup.3, NHCOR.sup.3, SO.sub.2 NHR.sup.3, or halo; R.sup.3 is a) H, or b) C.sub.1-4 alkyl; and n is 1, 2, 3, 4, 5, or 6. 2. A compound of claim 1 wherein R.sup.1 and R.sup.2 are selected from the group consisting of phenyl, 4-methylphenyl, 4-methoxyphenyl, 4-fluorophenyl. 3. A compound of claim 1 which is a. N-Hydroxy-2,4-bis-[[4-methylphenylsulfonyl]amino] butanamide, b. (R)-N-Hydroxy-2,4-bis-[[4-methylphenylsulfonyl]amino] butanamide, c. (S)-N-Hydroxy-2,4-bis-[[4-methylphenylsulfonyl]amino] butanamide, d. N-Hydroxy-2,3-bis-[[4-methylphenylsulfonyl]amino] propionamide, e. N-Hydroxy-2,4-bis-[[4-fluorophenylsulfonyl]amino] butanamide, f. (S)-N-Hydroxy-2,4-bis-[[phenylsulfonyl]amino] butanamide, g. N-Hydroxy-2,5-bis-[[4-methylphenylsulfonyl]amino] valeramide, h. N-Hydroxy-2,4-bis-[[4-methoxyphenylsulfonyl]amino] butanamide, or i. N-Hydroxy-4-[(4-methylphenylsulfonylamino)-2-(4-methoxyphenylsulfonylamino )] butanamide, j. N-Hydroxy-4-[(4-methoxyphenylsulfonylamino)-2-(4-methylphenylsulfonylamino )] butanamide, k. N-Hydroxy-4-[(4-fluorophenylsulfonylamino)-2-(4-methylphenylsulfonylamino) ] butanamide, l. N-Hydroxy-4-[4-methylphenylsulfonylamino)-2-(4-methoxyphenylsulfonylamino) ] butanamide, or m. N-Hydroxy-4-[(4-fluorophenylsulfonylamino)-2-(4-methoxyphenylsulfonylamino )] butanamide. 4. A compound of claim 1 which is a. N-Hydroxy-2,4-bis-[[4-methylphenylsulfonyl]amino] butanamide, b. (R)-N-Hydroxy-2,4-bis-[[4-methylphenylsulfonyl]amino] butanamide, or c. N-Hydroxy-2,4-bis-[[4-methoxyphenylsulfonyl]amino] butanamide. 5. A compound of claim 1 wherein n is 2. 6. A method of inhibiting excess matrix metalloproteinase which comprises administering to a patient in need thereof an effective amount of a compound of claim 1. 7. A method of claim 6 wherein matrix metalloproteinases comprises stromelysin, collagenase, and gelatinase. 8. A method of treating a human suffering from or susceptible to diseases involving connective tissue degradation which comprises administering to a patient in need thereof an effective amount of a compound of claim 1. 9. A method of claim 6 wherein the diseases related to connective tissue degradation are osteoarthrits, rheumatoid arthritis, septic arthritis, osteopenias such as osteoporosis, tumor metastasis (invasion and growth), periodontitis, gingivitis, corneal ulceration, dermal ulceration, gastric ulceration and other diseases related to connective tissue degradation. 10. The method of claim 6 wherein the effective amount of the compound of claim 1 is administered orally, parenterally, or topically in a pharmaceutical composition. 11. The method of claim 8 wherein the effective amount of the compound of claim 1 is administered orally, parenterally, or topically in a pharmaceutical composition. 12. The method of claim 6 or 8 wherein said compound is administered in an amount of from about 0.1 to about 100 mg/kg of body weight/day. 13. A pharmaceutical composition which comprises an amount of the compound of claim 1 effective to inhibit excess matrix metalloproteinase and a pharmaceutically acceptable carrier.

Details for Patent 5,859,061

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Smith & Nephew, Inc.	SANTYL	collagenase	Ointment	101995	06/04/1965		2039-03-29