Patent EA-002546-B1 (EA)
Title: Arylsulfonyl hydroxamic acid derivatives
Inventor: MCCLURE KIM FRANCIS
IPC: A61P35/00
Filed: 1998-01-16
Abstract: 1. A compound of the formula   or the pharmaceutically acceptable salt thereof, wherein the broken line represents an optional double bond; X is carbon; Y is carbon or sulfur, R<1>, R<2>, R<3>, R<4>, R<5>, R<6> and R<9> are hydrogen; R<7> is hydrogen atom, (C1-C6)alkyl or -NHCOO(C1-6) alkyl; R<8> is hydrogen atom or (C1-C6)alkyl; Q is (C6-C10)aryl(C6-C10)aryl or (C6-C10)aryl(C1-C6)alkoxy(C6-C10)aryl optionally substituted by fluoro, chlolo, (C1-C8)alkyl, (C6-C10)alkoxy or perfluoro (C1-3)alkyl; with the proviso that when Y is sulfur, then R<5>and R<6> are absent; with the proviso that when the broken line represents a double bond, R<4>and R<6> are absent; 2. A compound of Claim 1, wherein Y is sulfur. 3. A compound according to Claim 1, wherein Q is (C6-C10)aryl(C6-C10)aryl, (C6-C10)aryl(C1-C6)alkoxy(C6-C10)aryl, wherein each terminal aryl group is optionally substituted by fluoro. 4. A compound according to Claim 1, wherein R<7> is hydrogen. 5. A compound according to Claim 1, wherein Y is carbon; Q is (C6-C10)aryl(C1-C6)alkoxy(C6-C10)aryl. 6. A compound according to Claim 1, wherein at least one of R<7> - R<8> is radical other than hydrogen. 7. A compound according to Claim 3, wherein at least one of R<7> - R<8> is radical other than hydrogen. 8. A compound according to Claim 1, wherein at least one of R<7> - R<8> is (C1-C6)alkyl. 9. A compound according to Claim 3, wherein at least one of R<7> - R<8> is (C1-C6)alkyl. 10. A compound according to Claim 1, wherein at least one of R<7> - R<8> is methyl. 11. A compound according to Claim 3, wherein at least one of R<7> - R<8> is methyl. 12. A compound according to Claim 1, wherein each of R<7> - R<8> is methyl. 13. A compound according to Claim 3, wherein each of R<7> - R<8> is methyl. 14. A compound according to Claim 1, wherein said compound is selected from the group consisting of: (2R,3S)-(1-[4-(4-fluorobenzyloxy)-benzenesulfonyl]-2-hydrocarbamoylpiperidin-3-yl)-carbamic acid isopropyl ester; 3-(_S_)-4-(4'-fluorobiphenyl-4-sulfonyl)-2,2-dimethylthiomorpholine-3-carboxylic acid hydroxyamide; 3-(_S_)-4-[4-(4'-fluorobenzyloxy)benzenesulfonyl)]-2,2-dimethylthiomorpholine-3-carboxylic acid hydroxyamide; 15. A pharmaceutical composition for (a) the treatment of a condition selected from the group consisting at arthritis, cancer, tissue ulceration, macular degeneration, restenosis, periodontal disease, epidermolysis bullosa, sclaritis, in combination with standard NSAID'S and analgesics and in combination with cytotoxic anticancer agents, and other diseases characterized by matrix metalloproteinase activity, AIDS, sepsis, septic shock and other diseases involving the production of tumor necrosis factor (TNF) or (b) the inhibition of matrix metalloproteinases or the production of tumor necrosis factor (TNF) in a mammal, including a human, comprising an amount of a compound of Claim 1 effective in such treatment and a pharmaceutically acceptable carrier. 16. A method for the inhibition of matrix metalloproteinases or the production of tumor necrosis factor (TNF) in a mammal, including a human, comprising administering to said mammal an effective amount of a compound of Claim 1. 17. A method for treating a condition selected from the group consisting of arthritis, cancer, tissue ulceration, macular degeneration, restenosis, periodontal disease, epidermolysis bullosa, scleritis, compounds of formula I may be used in combination with standard NSAID'S and analgesics and in combination with cytotoxic anticancer agents, and other diseases involving the production of tumor necrosis factor (TNF) in a mammal, including a human, comprising administering to said mammal an amount of a compound of Claim 1, effective in treating such a condition.