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US 6,686,467 B2Granted
Amide derivatives for the treatment of diseases mediated by cytokines
AssigneeZeneca Limited
InventorsDearg S Brown, George R Brown, Philip Cohen
Life of this patent
Estimating the term…
Abstract
The invention concerns the use of amide derivatives of formula (I) wherein: R1 and R2 are substituents such as hydroxy, C1-6alkoxy, mercapto, C1-6alkylthio, amino, C1-6alkylamino and di-(C1-6alkyl)amino; m and p are independently 0-3; R3 is C1-4alkyl; q is 0-4; and R4 is aryl or cycloalkyl; or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for use in the treatment of diseases or medical conditions mediated by cytokines
Claims19
A method of treating a disease or medical condition mediated by cytokines which comprises administering to a warm-blooded animal in need thereof an effective amount of a compound of the Formula I
- wherein:
- R1 and R2, which may be the same or different are selected from hydroxy, C1-6alkoxy, mercapto, C1-6alkylthio, amino, C1-6alkylamino, di-(C1-6alkyl)amino, carboxy, C1-6alkoxycarbonyl, carbamoyl, C1-6alkylcarbamoyl, di-C1-6alkylcarbamoyl, C1-6alkylsulphonyl, arylsulphonyl, C1-6alkylaminosulphonyl, di-(C1-6alkyl)aminosulphonyl, nitro, cyano, cyanoC1-6alkyl, hydroxyC1-6alkyl, aminoC1-6alkyl, C1-6alkanoylamino, C1-6alkoxycarbonylamino, C1-6alkanoyl, C1-6alkanoyloxy, C1-6alkyl, halo, trifluoromethyl, aryl, arylC1-6alkyl, arylC1-6alkoxy, heteroaryl, heteroarylC1-6alkyl, heterocyclyl and heterocyclylC1-6alkyl;
- m and p, are independently 0-3, and when m and/or p is 2 or 3 each R group may be the same or different;
- R3 is C1-4alkyl;
- q is 0;
- R4 is aryl or cycloalkyl wherein R4 optionally substituted with up to 3 substituents having any value defined for R1;
- provided that least one of R1, R2 or at least one substituent on R4 is heteroaryl, heteroarylC1-6alkyl, heterocyclyl or heterocyclylC1-6alkyl;
- or a pharmaceutically-acceptable salt or in vivo cleavable ester thereof.
5 more elements
A compound of the Formula I
- wherein:
- R1 is hydroxy, methoxy, ethoxy, propoxy, isopropoxy, butoxy, amino, methylamino, dimethylamino, carboxy, methoxycarbonyl, nitro, cyano, acetamido, acetyl, acetoxy, methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, fluoro, chloro, bromo, trifluoromethyl, pyrrolidin-1-yl, piperidino, morpholino, 4-thiamorpholino, piperazin-1-yl, 4-methylpiperazin-1-yl, 4-methylhomopiperazin-1-yl, pyrrolidin-1-ylmethyl, piperidinomethyl, 4-carbamoylpiperidin-1-ylmethyl, morpholinomethyl, 4-thiamorpholinomethyl, piperazin-1-ylmethyl, 4-methylpiperazin-1-ylmethyl, 4-ethylpiperazin-1-ylmethyl, 4-propylpiperazin-1-ylmethyl, 4-isopropylpiperazin-1-ylmethyl, 4-acetylpiperazin-1-ylmethyl and 4-methylhomopiperazin-1-ylmethyl;
- m is 1, 2 or 3;
- p is 0;
- R3 is methyl;
- q is 0;
- and
- R4 is phenyl which is optionally substituted with 1 or 2 substituents selected from hydroxy, methoxy, ethoxy, amino, methylamino, dimethylamino, methoxycarbonyl, nitro, cyano, acetamido, fluoro, chloro, bromo, trifluoromethyl, phenyl, benzyloxy, pyrrolidin-1-yl, piperidino, morpholino, 4-thiamorpholino, piperazin-1-yl, 4-methylpiperazin-1-yl, 4-methylhomopiperazin-1-yl, pyrrolidin-1-ylmethyl, piperidinomethyl, 4-carbamoylpiperidin-1-ylmethyl, morpholinomethyl, 4-thiamorpholinomethyl, piperazin-1-ylmethyl, 4-methylpiperazin-1-ylmethyl, 4-ethylpiperazin-1-ylmethyl, 4-propylpiperazin-1-ylmethyl, 4-isopropylpiperazin-1-ylmethyl, 4-acetylpiperazin-1-ylmethyl and 4-methylhomopiperazin-1-ylmethyl;
- provided that least one of R1 or at least one substituent on R4 is pyrrolidin-1-yl, piperidino, morpholino, 4-thiamorpholino, piperazin-1-yl, 4-methylpiperazin-1-yl, 4-methylhomopiperazin-1-yl, pyrrolidin-1-ylmethyl, piperidinomethyl, 4-carbamoylpiperidin-1-ylmethyl, morpholinomethyl, 4-thiamorpholinomethyl, piperazin-1-ylmethyl, 4-methylpiperazin-1-ylmethyl, 4-ethylpiperazin-1-ylmethyl, 4-propylpiperazin-1-ylmethyl, 4-isopropylpiperazin-1-ylmethyl, 4-acetylpiperazin-1-ylmethyl or 4-methylhomopiperazin-1-ylmethyl;
- or a pharmaceutically-acceptable salt or in vivo cleavable ester thereof.
7 more elements
A compound of the Formula I
- wherein:
- R1 is hydroxy, C1-6alkoxy, carboxy, C1-6alkoxycarbonyl, nitro, cyano, C1-6alkanoylamino, C1-6alkanoyl, C1-6alkyl, halo or trifluoromethyl;
- m is 0-3 and when m is 2 or 3 each R1 group is the same or different;
- p is 0;
- R3 is methyl;
- q is 0;
- and
- R4 is phenyl which is substituted with 1 or 2 substituents selected from amino, C1-6alkylamino, di-(C1-6alkyl)amino, aminoC1-6alkyl, heteroaryl, heteroarylC1-6alkyl, heterocyclyl and heterocyclylC1-6alkyl, and when there is 1 substituent it is located at the 3-position and when there are 2 substituents, which may be the same or different, they are located at the 3- and 4-positions;
- provided that at least one substituent on R4 is heteroaryl, heteroarylC1-6alkyl, heterocyclyl or heterocyclylC1-6alkyl;
- or a pharmaceutically-acceptable salt or in vivo cleavable ester thereof.
7 more elements
A compound of the Formula I
- wherein:
- R1 is amino, C1-6alkylamino, di-(C1-6alkyl)amino, aminoC1-6alkyl, heteroaryl, heteroarylC1-6alkyl, heterocyclyl or heterocyclylC1-6alkyl, provided that at least one R1 is heteroaryl, heteroarylC1-6alkyl, heterocyclyl or heterocyclylC1-6alkyl;
- m is 1 with the R1 group located at the 3-position or m is 2 with the R1 groups, which may be the same or different, located at the 3- and 4-positions;
- p is 0;
- R3 methyl;
- q is 0;
- and
- R4 is phenyl which is optionally substituted with 1 or 2 substituents, which may be the same or different, selected from hydroxy, C1-6alkoxy, carboxy, C1-6alkoxycarbonyl, cyano, C1-6alkyl, halo and trifluoromethyl;
- or a pharmaceutically-acceptable salt or in vivo cleavable ester thereof.
6 more elements
A compound of the Formula I
- wherein:
- R1 is amino, C1-6alkylamino, di-(C1-6alkyl)amino, aminoC1-6alkyl, heteroaryl, heteroarylC1-6alkyl, heterocyclyl or heterocyclylC1-6alkyl;
- m is 1 with the R1 group located at the 3-position or m is 2 with the R1 groups, which may be the same or different, located at the 3- and 4-positions;
- p is 0;
- R3 methyl;
- q is 0;
- and
- R4 is phenyl which is substituted with 1 or 2 substituents selected from amino, C1-6alkylamino, di-(C1-6alkyl)amino, aminoC1-6alkyl, heteroaryl, heteroarylC1-6alkyl, heterocyclyl and heterocyclylC1-6alkyl, and when there is 1 substituent it is located at the 3-position and when there are 2 substituents, which may be the same or different, they are located at the 3- and 4-positions;
- provided that at least one of R1 or at least one substituent on R4 is heteroaryl, heteroarylC1-6alkyl, heterocyclyl or heterocyclylC1-6alkyl;
- or a pharmaceutically-acceptable salt thereof.
7 more elements
Dependencies are inferred from the claim text.