FIELD: medicine.
SUBSTANCE: invention refers to new compounds of formula I, to its pharmaceutically acceptable salts exhibiting properties of inhibitors of cytokine production, such as TNF (tumour necrosis factor) and various members of interleukins (IL) family, and properties of kinase inhibitors, particularly p38α kinase. The invention also concerns methods for producing; pharmaceutical compositions and application thereof for making the medicines for treating diseases affected by the compound of the invention with specified activity. In formula I , m represents 0, 1 or 2; R1 represents halogeno, hydroxy, (1-6C) alkyl, (1-6C)alkoxy, (2-6C)alkenyl, (2-6C) alkinyl, (1-6C)alkylthio, (1-6C)alkylsulphinyl, (1-6C)alkylsulphonyl, amino-(2-6C) alkoxy, (1-6C)alkylamino-(2-6C)alkoxy, di-[(1-6C)alkyl]amino-(2-6C)alkoxy, N-(1-6C)alkylcarbamoyl - (1-6C)alkoxy, di[(1-6C) alkyl]amino-(1-6C)alkyl, hydroxy-(2-6C)alkylamino, heteroaryl-(1-6C)alkoxy, heterocyclyl, heterocyclyloxy and heterocyclyl-(1-6C)alkoxy and wherein any heteroaryl or heterocyclyl group in substitute representing R1, can probably have 1 or 2 substitutes chosen from hydroxy, halogeno, (1-6C) alkyl, (2-6C)alkinyl, (3-6C)cycloalkyl, (3-6C)cycloalkyl-(1-6C)alkyl, (1-6C)alkoxycarbonyl, (2-6C) alkanoyl, halogen-(1-6C)alkyl, hydroxy-(1-6C)alkyl, (1-6C)alkoxy-(1-6C)alkyl, cyano-(1-6C)alkyl, carboxy- (1-6C)alkyl and methylsulphonyl and wherein any said substitute representing R1 which contains group CH2 attached to 2 carbon atoms, or group CH3 attached to carbon or nitrogen atom, can probably have with each specified group CH2 or CH3, one or two substitutes chosen from halogeno, hydroxy, amino, triflouromethyl, oxo, carboxy, acetamido, (1-6C)alkyl, (3-6C)cycloalkyl, (1-6C)alkoxy, (1-6C)alkyamino, di-[(1-6C)alkyl]amino, hydroxy-(1-6C)alkyl, (1-6C)alkoxy-(1-6C)alkyl, halogen-(1-6C)alkyl, (1-6C)alkoxycarbonyl, carbamoyl, N, N-di-[(1-6)alkyl]carbamoyl, (1-6C)alkylsulphonyl, heteroaryl, heteroaryl-(1-6)alkyl and heterocyclyloxy and wherein any heterocyclyl group in substitute representing R1, can probably have 1 oxo-subsitute; R2 represents trifluoromethyl or (1-6C)alkyl; R3 represents hydrogen or (1-6C)alkyl; and R4 represents (3-6C)cycloalkyl, and R4 can be optionally substituted with one or more substitutes chosen from (1-6C)alkyl; and wherein heteroaryl represents aromatic 5- or 6-merous monocyclic ring containing one or two heteroatoms chosen from oxygen, nitrogen and sulphur; heterocyclyl represents saturated 3-10-merous monocyclic or bicyclic ring, each containing one or two heteroatoms chosen from oxygen, nitrogen and sulphur.
EFFECT: improved efficiency.
24 cl, 16 tbl, 66 ex
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Authors
Dates
2009-12-10—Published
2004-10-22—Filed