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US 6,214,857 B1Granted
Substituted alkanohydroxamic acids and method of reducing TNFα levels
AssigneeCelgene Corporation
InventorsGeorge W. Muller, Hon-Wah Man
Life of this patent
Estimating the term…
Abstract
Imido and amido substituted alkanohydroxamic acids reduce the levels of TNFα and inhibit phosphodiesterase in a mammal. A typical embodiment is 3-(3-cyclopentyloxy-4-methoxyphenyl)-N-hydroxy-3-phthalimidopropionamide.
Claims18
A method of reducing levels of TNFα in a mammal which comprises administering thereto an effective amount of a hydroxamic acid derivative selected from the group consisting of
- (a) a compound of formula:
- wherein
- a carbon atom designated by * constitutes a center of chirality;
- each of R1 and R2,
- (i) when R1 and R2 taken independently of R2 and R1, respectively, is hydrogen or lower alkyl, or
- (ii) when taken together with the carbon atoms to which each is bound as depicted in the formula, is o-phenylene, o-naphthylene or cyclohexene-1,2-diyl, unsubstituted or substituted with 1 to 4 substituents each selected independently from the group consisting of nitro, cyano, trifluoromethyl, carbethoxy, carbopropoxy, acetyl, carbamoyl, acetoxy, carboxy, hydroxy, amino, alkylamino, diakylamino, acylamino, alkyl of 1 to 10 carbon atoms, alkoxy of 1 to 10 carbon atoms, and halo;
- R4 is hydrogen, alkyl of 1 to 6 carbon atoms, phenyl, or benzyl;
- R4′ is hydrogen or alkyl of 1 to 6 carbon atoms;
- R5 is —CH2,—CH2—CO—, —CO—, —SO2, —S—, or —NHCO—;
- R3 is phenyl substituted with 1 to 4 substituents selected from the group consisting of is nitro, cyano, trifluoromethyl, carbethoxy, carbomethoxy, acetyl, carbamoyl, acetoxy carboxy, hydroxy, amino, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, cycloalkoxy of 3 to 6 carbon atoms, C4-C6-cycloalkylidenemethyl, C3-C10-alkylidenemethyl, indanyloxy, or halo;
- and
- n has a value of 0, 1, or 2;
- and
- (b) acid addition salts of said compound which contain a nitrogen atom capable of being protonated.
11 more elements
A method of inhibiting matrix metalloproteinases in a mammal which comprises administering thereto an effective amount of a hydroxamic acid derivative selected from the group consisting of
- (a) a compound of formula:
- wherein
- a carbon atom designated by * constitutes a center of chirality;
- each of R1 and R2,
- (i) when R1 and R2 taken independently of R2 and R1, respectively, is hydrogen or lower alkyl, or
- (ii) when taken together with the carbon atoms to which each is bound as depicted in the formula, is o-phenylene, o-naphthylene or cyclohexene-1,2-diyl, unsubstituted or substituted with 1 to 4 substituents each selected independently from the group consisting of nitro, cyano, trifluoromethyl, carbethoxy carbopropoxy, acetyl, carbamoyl, acetoxy, carboxy, hydroxy, amino, alkylamino, diakylamino, acylamino, alkyl of 1 to 10 carbon atoms. alkoxy of 1 to 10 carbon atoms, and halo;
- R4 is hydrogen, alkyl of 1 to 6 carbon atoms, phenyl, or benzyl;
- R4′ is hydrogen or alkyl of 1 to 6 carbon atoms;
- R5 is —CH2,—CH2—CO—, —CO—, —SO2, —S—, or —NHCO—;
- R3 is phenyl substituted with 1 to 4 substituents selected from the group consisting of is nitro, cyano, trifluoromethyl, carbethoxy, carbomethoxy, acetyl, carbamoyl, acetoxy carboxy, hydroxy, amino, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, cycloalkoxy of 3 to 6 carbon atoms, C4-C6-cycloalkylidenemethyl, C3-C10-alkylidenemethyl, indanyloxy, or halo;
- and
- n has a value of 0, 1, or 2;
- and
- (b) acid addition salts of said compound which contain a nitrogen atom capable of being protonated.
11 more elements
A hydroxamic acid derivative selected from the group consisting of
- (a) a compound of formula:
- wherein
- a carbon atom designated by * constitutes a center of chirality;
- each of R1 and R2,
- (i) when R1 and R2 taken independently of R2 and R1, respectively, is hydrogen or lower alkyl, or
- (ii) when taken together with the carbon atoms to which each is bound as depicted in the formula, is o-phenylene, o-naphthylene, or cyclohexene-1,2-diyl, unsubstituted or substituted with 1 to 4 substituents each selected independently from the group consisting of nitro, cyano, trifluoromethyl, carbethoxy, carbopropoxy, acetyl, carbamoyl, acetoxy, carboxy, hydroxy, amino, alkylamino, diakylamino, acylamino, alkyl of 1 to 10 carbon atoms, alkoxy of 1 to 10 carbon atoms, and halo;
- R4 is hydrogen, alkyl of 1 to 6 carbon atoms, phenyl, or benzyl;
- R4′ is hydrogen or alkyl of 1 to 6 carbon atoms;
- R5 is —CH2,—CH2—CO—, —CO—, —SO2, —S—, or —NHCO—;
- R3 is phenyl substituted with 1 to 4 substituents selected from the group consisting of is nitro, cyano, trifluoromethyl, carbethoxy, carbomethoxy, acetyl, carbamoyl, acetoxy, carboxy, hydroxy, amino, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, cycloalkoxy of 3 to 6 carbon atoms, C4-C6-cycloalkylidenemethyl, C3-C10-alkylidenemethyl, indanyloxy, or halo;
- and
- n has a value of 0, 1, or 2;
- and
- (b) acid addition salts of said compound which contain a nitrogen atom capable of being protonated.
11 more elements
Dependencies are inferred from the claim text.