| abstract |
An indolylmaleimide derivative, characterized in that it comprises a compound of the formula (1) wherein: Ra is H; alkyl of 1 to 4 carbon atoms; or C1-4 alkyl substituted by OH, NH2, NH-C1-4 alkyl, carbon atoms or N (C1-4 dialkyl) 2; Rb is H; or C1-4 alkyl; R is a radical of the formula (a), (b), (c), (d), (e) or (f) where: each of R1, R4, R7 R8, R11 and R14 is OH; SH; a heterocyclic residue; NR16R17, wherein each of R16 and R17 is independently H or alkyl of 1 to 4 carbon atoms, or R16 and R17 form, together with the nitrogen atom to which they are linked, a heterocyclic residue; or a radical of the formula alpha: -X-Rc-Y wherein X is a direct bond, O, S or NR18, where R18 is H or C1-4 alkyl, Rc is C1-4 alkylene, or alkylene of C1-4 where a CH2 is replaced by CRxRy, where one of Rx and Ry is H and the other is CH3, each of Rx and Ry is CH3, or Rx and Ry together form -CH2-; CH2-, and Y is linked to the terminal carbon atom, and is selected from OH, a heterocyclic residue, and - NR19R20, wherein each of R19 and R20 is independently H, C3-6 cycloalkyl, cycloalkyl of 3 to 6 carbon atoms-C1-4 alkyl, C1-4 arylalkyl, or C1-4 alkyl optionally substituted on the terminal carbon atom by OH, or R19 and R20 form, together with the nitrogen atom with the which are linked, a heterocyclic residue; each of R2, R3, R5, R6, R9, R10, R12, R13, R15 and R'15 is independently H, halogen, C1-4 alkyl, CF3, OH, SH, NH2, alkoxy of 1 to 4 atoms carbon, C1-4 thioalkyl, C1-4 NH-alkyl, N (C1-4 dialkyl) 2, or CN; E is -N = and G is -CH =, or E is -CH = and G is -N =; and ring A is optionally substituted, or a salt thereof. They have interesting pharmaceutical properties, for example in the treatment and / or in the prevention of acute or chronic inflammatory diseases or disorders mediated by T cells, autoimmune diseases, graft rejection, or cancer, a process for their preparation, a pharmaceutical composition and a combination comprising said derivatives |