FIELD: pharmacology.
SUBSTANCE: invention relates to a compound of formula (III)
or a pharmaceutically acceptable salt thereof, wherein W is S; Y is N; X is N; R1 is selected from (a) C1-C6 alkyl optionally substituted with amino, methylamino, dimethylamino, C1-C6 alkoxy or isoindolyl; (B) -NR8R7, -CH2NR7R8, where R7 and R8 are joined to form optionally substituted C3-C7 non-aromatic ring which is pyrrolidine, morpholine, piperazine, piperidine, 1,4-diazepane, azepane, azetidine, 2-azabicyclo[2.2.1]heptane or 2,5-diazabicyclo[2.2.1]heptane and optionally substituted by one or more C1-C6alkyl, C1-C6alkoxy, methoxyethyl, 1-methoxypropane, isopropyloxymethyl, isopropyloxyethyl, -C(O(CH2)-methyl, -C(O)(CH2)-O-isopropyl, C1-C6haloalkyl, -S(O)2-methyl, -S(O)2-isopropyl, oxo, -C(O)(C1-C2)alkyl-N(methyl)2, -C(O)(C2)alkyl-(pyrrolidine), t-butyl-C(O)- or phenyl; or (c) -O-(tetrahydro-2H-pyran); each of R2, R3 and R5 are hydrogen; R4 is selected from C3-C6cycloalkyl, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl and optionally substituted heteroaryl selected from pyridine, pyrazole, pyridazine, pyrimidine. The said heteroaryl is optionally substituted with 1 to 2 substituents selected from C1-C6 alkyl and CN. The invention also relates to specific compounds as defined in the claims. The compounds of the invention are intended for the manufacture of a pharmaceutical composition having an inhibitory activity against an interleukin 1 receptor associated kinase 1 (IRAK-1) and an interleukin 1 receptor associated kinase 4 (IRAK-4). The compounds of the invention are also useful in a method for treatment of a disorder sensitive to inhibition of IRAK-1-mediated signalling.
EFFECT: heterocyclic amines having inhibitory activity against an interleukin 1 receptor associated kinase 1 and interleukin 1 receptor associated kinase 4.
24 cl, 4 tbl, 431 ex
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