Patent EA-002594-B1 (EA)
Title: Arylsulfonylamino hydroxamic acid derivatives
Inventor: ROBINSON RALPH PELTON JR
IPC: A61P19/02
Filed: 1998-01-12
Abstract: 1. A compound of the formula   or the pharmaceutically acceptable salts thereof, wherein R<1> and R<2> are each independently selected from (C1-C6)alkyl, or R<1> and R<2> may be taken together to form a (C3-C6)cycloalkyl or a group of the formula   wherein n and m are independently 1 or 2 and X is O; and Q is (C6-C10)aryl,(C6-C10)aryloxy(C6-C10)aryl, (C6-C10)aryl(C6-C10)aryl, (C2-C9)heteroaryl (C2-C9)heteroaryl, (C1-C6)alkoxy(C6-C10)aryl, (C6-C10)aryl(C1-C6)alkoxy(C6-C10)aryl, wherein each aryl group is optionally substituted by fluoro, chloro, or (C1-C6)alkoxy, and wherein (C6-C10)aryl is phenyl or naphthyl, and (C2-C9)heteroaryl is mono- or bicyclic heterocyclic aromatic ring, comprising 1 to 4 heteroatoms, selected from N, S or O. 2. A compound according to Claim 1, wherein R<1> and R<2> are taken together to form a (C3-C6)cycloalkyl or a group of the formula   wherein n and m are independently 1 or 2 and X is O. 3. A compound according to Claim 2, wherein R<1> and R<2> are taken together to form a (C3-C6)cycloalkyl. 4. A compound according to Claim 1, wherein Q is (C6-C10)aryl, (C6-C10)aryl(C6-C10)aryl, (C6-C10)aryloxy(C6-C10)aryl, (C2-C9)heteroaryl(C2-C9)heteroaryl. 5. A compound according to Claim 4, wherein Q is (C6-C10)aryloxy(C6-C10)aryl. 6. A compound according to Claim 1, wherein R<1> and R<2> are each independently (C1-C6)alkyl. 7. A compound according to Claim 1, wherein R<1> and R<2> are taken together to form a (C3-C6)cycloalkyl or a group of the formula   wherein n and m are independently 1 or 2 and X is O; and Q is (C6-C10)aryl, (C6-C10)aryl(C6-C10)aryl, (C6-C10)aryloxy(C6-C10)aryl, (C2-C9)heteroaryl(C2-C9)heteroaryl. 8. A compound according to Claim 1, wherein R<1> and R<2> are taken together to form (C3-C6)cycloalkyl; and Q is (C6-C10)aryl, (C6-C10)aryl(C6-C10)aryl, (C6-C10)aryloxy(C6-C10)aryl, (C2-C9)heteroaryl (C2-C9)heteroaryl. 9. A compound according to Claim 1, wherein R<1> and R<2> are each independently (C1-C6)alkyl; and Q is (C6-C10)aryl, (C6-C10)aryloxy(C6-C10)aryl, (C2-C9)heteroaryl (C2-C9)heteroaryl. 10. A compound according to Claim 1, wherein R<1> and R<2> are each independently (C1-C6)alkyl; and Q is (C6-C10)aryloxy(C6-C10)aryl. 11. A compound according to Claim 1, wherein said compound is selected from the group consisting of: 1-[4-(4-fluorophenoxy)benzenesulfonylamino]cyclopropane-1-carboxylic acid hydroxyamide; 1-[4-(4-chlorophenoxy)benzenesulfonylamino]cyclopropane-1-carboxylic acid hydroxyamide; 1-[4-(4-fluorophenoxy)benzenesulfonylamino]cyclobutane-1-carboxylic acid hydroxyamide; 1-[4-(4-fluorophenoxy)benzenesulfonylamino]cyclopentane-1-carboxylic acid hydroxyamide; 1-[4-(4-fluorophenoxy)benzenesulfonylamino]cyclohexane-1-carboxylic acid hydroxyamide; 2-[4-(4-fluorophenoxy)benzenesulfonylamino]-N-hydroxy-2-methyl-propionamide; N-hydroxy-2-methyl-2-(5-pyridin-2-ylthiophene-2-sulfonylamino)propionamide; 1-(5-pyridin-2-yl-thiophene-2-sulfonylamino)cyclopentane-1-carboxylic acid hydroxyamide; and 1-(4'-fluorobiphenyl-4-sulfonylamino)cyclopentane-1-carboxylic acid hydroxyamide. 12. A pharmaceutical composition for (a) the treatment of a condition selected from the group consisting of arthritis, cancer, tissue ulceration, mucular degeneration, restenosis, periodontal disease, epidermolysis bullosa, scleritis, 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. 13. A pharmaceutical composition for (a) the treatment of a condition selected from the group consisting of arthritis, cancer, tissue ulceration, mucular degeneration, restenosis, periodontal disease, epidermolysis bullosa, scleritis 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. 14. A method for the inhibition of (a) matrix metalloproteinases or (b) 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. 15. 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 characterized by matrix metalloproteinase activity, AIDS, sepsis, septic shock 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. 16. A method for treating a condition selected from the group consisting of arthritis, cancer, tissue ulceration, macular degeneration, restenosis, periodontal disease, epidermolysis bullosa, scleritis and other diseases characterized by matrix metalloproteinase activity, AIDS, sepsis, septic shock 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.