NOVEL 707 COMPOUNDS AND USE THEREOF

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FIELD : chemistry.SUBSTANCE : invention relates to novel isoquinolinone derivatives of formula (I), wherein Ris selected from H, (C-C)alkyl, (C-C)alkenyl, (CH)-X-Ar and (CRR)-X-Ar, where said (C-C)alkyl is optionally substituted with 1, 2 or 3 groups independently selected from -(C-C)alkoxy, -halogen, -OH, -heterocycloalkyl, (C-C)cycloalkyl and -NRR; Ris selected from H and (C-C)alkyl; R is selected from H, (C-C)alkyl and (CH)-Y; provided that when Ris (CH)-Y, Ris selected from H; Rand Rare independently selected from H, (C-C)alkyl and halogen; R is (C-C)cycloalkyl; Ris H; Ar is phenyl or heteroaryl, optionally substituted with 1, 2 or 3 groups independently selected from -(C-C)alkyl, -(CH)-O-(C-C)alkyl, -(CH)-S(O)(C-C)alkyl, -(CH)-N(R)-(C-C)alkyl, -(CH)-Z-(C-C)alkyl, -halogen, heterocycloalkyl, -C(O)NRR, -NRRand -C(O)OH, where (C-C)alkyl in each case is independently optionally substituted with 1, 2 or 3 groups, independently selected from -NRR; X is selected from a single bond; Y is NRR, where Rand Rtogether with a nitrogen atom with which they are bonded form a 5-7-member ring, optionally containing an additional heteroatom NR, where said ring is optionally substituted on the carbon atom with 1 or 2 substitutes independently selected from -(C-C)alkyl, where said -(C-C)alkyl is optionally substituted with -OH; and where Ris selected from H and (C-C)alkyl, where said (C-C)alkyl is optionally substituted with -OH; Z is selected from C(O)N(R); Rand Rare independently selected from H and (C-C)alkyl, where said (C-C)alkyl is optionally substituted with 1, 2 or 3 groups, independently selected from NRR; or Rand Rtogether with the nitrogen atom with which they are bonded form a 5-6-member ring, optionally containing an additional heteroatom, selected from NR; Rand Rare independently selected from H and (C-C)alkyl, where said (C-C)alkyl is optionally substituted with -(C-C)alkoxy, -OH; or Rand Rtogether with the nitrogen atom with which they are bonded form a 5-6-member ring optionally containing an additional heteroatom selected from NR; R, R, R, R, R, R, Rand Rare independently selected from H and (C-C)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 NRatoms; optionally having one double bond; the heteroaryl is a 6-member aromatic ring containing 1 N atom; R is selected from H, (C-C)alkyl and -C(O)O-(C-C)alkyl; Ris (C-C)alkyl; Ris 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