FIELD: chemistry.
SUBSTANCE: invention relates to novel isoquinolinone derivatives of formula (I) 
, wherein R1 is selected from H, (C1-C6)alkyl, (C2-C6)alkenyl, (CH2)a-X-Ar and (CR101R102)a-X-Ar, where said (C1-C6)alkyl is optionally substituted with 1, 2 or 3 groups independently selected from -(C1-C6)alkoxy, -halogen, -OH, -heterocycloalkyl, (C3-C7)cycloalkyl and -NR8R9; R2 is selected from H and (C1-C6)alkyl; R is selected from H, (C1-C6)alkyl and (CH2)d-Y; provided that when R3 is (CH2)d-Y, R2 is selected from H; R4 and R5 are independently selected from H, (C1-C6)alkyl and halogen; R is (C3-C7)cycloalkyl; R7 is H; Ar is phenyl or heteroaryl, optionally substituted with 1, 2 or 3 groups independently selected from -(C1-C6)alkyl, -(CH2)e-O-(C1-C6)alkyl, -(CH2)e-S(O)f(C1-C6)alkyl, -(CH2)e-N(R10)-(C1-C6)alkyl, -(CH2)e-Z-(C1-C6)alkyl, -halogen, heterocycloalkyl, -C(O)NR8R9, -NR8R9 and -C(O)OH, where (C1-C6)alkyl in each case is independently optionally substituted with 1, 2 or 3 groups, independently selected from -NRI2R13; X is selected from a single bond; Y is NR16R17, where R16 and R17 together with a nitrogen atom with which they are bonded form a 5-7-member ring, optionally containing an additional heteroatom NR27, where said ring is optionally substituted on the carbon atom with 1 or 2 substitutes independently selected from -(C1-C6)alkyl, where said -(C1-C6)alkyl is optionally substituted with -OH; and where R27 is selected from H and (C1-C6)alkyl, where said (C1-C6)alkyl is optionally substituted with -OH; Z is selected from C(O)N(R18); R8 and R9 are independently selected from H and (C1-C6)alkyl, where said (C1-C6)alkyl is optionally substituted with 1, 2 or 3 groups, independently selected from NR19R20; or R8 and R9 together with the nitrogen atom with which they are bonded form a 5-6-member ring, optionally containing an additional heteroatom, selected from NR21; R12 and R13 are independently selected from H and (C1-C6)alkyl, where said (C1-C6)alkyl is optionally substituted with -(C1-C6)alkoxy, -OH; or R12 and R13 together with the nitrogen atom with which they are bonded form a 5-6-member ring optionally containing an additional heteroatom selected from NR24; R10, R18, R19, R20, R21, R22, R23 and R24 are independently selected from H and (C1-C6)alkyl; a is selected from 1, 2, 3, 4, 5 and 6; d equals 0 or 1; e equals 0; f is independently selected from 1 and 2; where the heterocycloalkyl is a 5-6-member non-aromatic cyclic ring bonded at a C atom, having 1-2 NR28 atoms; optionally having one double bond; the heteroaryl is a 6-member aromatic ring containing 1 N atom; R is selected from H, (C1-C6)alkyl and -C(O)O-(C1-C6)alkyl; R101 is (C1-C6)alkyl; R102 is H; or pharmaceutically acceptable salts thereof or N-oxides. The invention also relates to methods of producing said compounds and use thereof as a p38 kinase inhibitor.
EFFECT: improved method.
13 cl, 4 dwg, 1 tbl, 128 ex
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