Indolylmaleimide derivatives
OwnerRainer Albert, Nigel Cooke +7inventors
InventorsRainer Albert, Nigel Cooke, Sylvain Cottens, Claus Ehrhardt, Jean-Pierre Evenou, Richard Sedrani, Peter Von Matt, Jurgen Wagner, Gerhard Zenke
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Abstract
Indolylmaleimide derivatives comprising either a substituted phenyl, naphthyl, tetrahydronaphthyl, quinazolinyl, quinolyl, isoquinolyl or pyrimidinyl residue have interesting pharmaceutical properties, e.g. in the treatment and/or prevention of T-cell mediated acute or chronic inflammatory diseases or disorders, autoimmune diseases, graft rejection or cancer.
Claims11
A compound of formula I
- wherein
- Ra is H;
- C,1-4alkyl;
- or C1-4alkyl substituted by OH, NH2, NHC1-4alkyl or N(di-C1-4alkyl)2;
- Rb is H;
- or C1-4alkyl;
- R is a radical of formula (a), (b), (c), (d), (e) or (f)
- wherein
- each of R1, R4, R7, R8, R11, and R14 is OH;
- SH;
- a heterocyclic residue;
- NR16R17 wherein each of R16 and R17, independently, is H or C1-4alkyl or R16 and R17 form together with the nitrogen atom to which they are bound a heterocyclic residue;
- or a radical of formula α
- —X—Rc—Y (α)
- wherein X is a direct bond to O, S or NR18 wherein R18 is H or C1-4alkyl, Rc is C1-4alkylene or C1-4alkylene wherein one CH2 is replaced by CRxRy wherein one of Rx and Ry is H and the other is CH3, each of Rx and Ry is CH3 or Rx and Ry form together —CH2—CH2—, and Y is bound to the terminal carbon atom and is selected from OH, a heterocyclic residue and —NR19R20 wherein each of R19 and R20 independently is H, C3-6cycloalkyl, C3-6cycloalkyl-C1-4alkyl, aryl-C1-4alkyl or C1-4alkyl optionally substituted on the terminal carbon atom by OH, or R19 and R20 form together with the nitrogen atom to which they are bound a heterocyclic residue;
- each of R2, R3, R5, R6, R9, R10, R12, R13, R15 and R′15, independently, is H, halogen, C1-4alkyl, CF3, OH, SH, NH2, C1-4alkoxy, C1-4alkylthio, NHC1-4alkyl, N(di-C1-4alkyl)2 or CN;
- either 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.
A compound according to any of the preceding claims wherein R is a radical of formula (d), (e) or (f).
A combination comprising a) an inhibitor of PKC and of T-cell activation and proliferation and b) at least one second agent selected from an immunosuppressant, immunomodulatory, anti-inflammatory, antiproliferative or anti-diabetic drug.
Dependencies are inferred from the claim text.