| abstract |
FIELD: pharmacology. n SUBSTANCE: invention relates to a compound of formula (III) n n n n or a pharmaceutically acceptable salt thereof, wherein W is S; Y is N; X is N; R 1 is selected from (a) C 1 -C 6 alkyl optionally substituted with amino, methylamino, dimethylamino, C 1 -C 6 alkoxy or isoindolyl; (B) -NR 8 R 7 , -CH 2 NR 7 R 8 , where R 7 and R 8 are joined to form optionally substituted C 3 -C 7 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 C 1 -C 6 alkyl, C 1 -C 6 alkoxy, methoxyethyl, 1-methoxypropane, isopropyloxymethyl, isopropyloxyethyl, -C(O(CH 2 )-methyl, -C(O)(CH 2 )-O-isopropyl, C 1 -C 6 haloalkyl, -S(O) 2 -methyl, -S(O) 2 -isopropyl, oxo, -C(O)(C 1 -C 2 )alkyl-N(methyl) 2 , -C(O)(C 2 )alkyl-(pyrrolidine), t-butyl-C(O)- or phenyl; or (c) -O-(tetrahydro-2H-pyran); each of R 2 , R 3 and R 5 are hydrogen; R 4 is selected from C 3 -C 6 cycloalkyl, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl and optionally substituted heteroaryl selected from pyridine, pyrazole, pyridazine, pyrimidine. The said heteroaryl is optionally substituted with 1 to 2 substituents selected from C 1 -C 6 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. n EFFECT: heterocyclic amines having inhibitory activity against an interleukin 1 receptor associated kinase 1 and interleukin 1 receptor associated kinase 4. n 24 cl, 4 tbl, 431 ex |