Macrocyclic pyridazinone derivatives

A method of treating a disease related to IRAK overexpression, the method comprising:

• administering an effective amount of a compound to a subject in need thereof,
• wherein the compound is a compound of formula (I)
• wherein
• R1, R3 denote each, independently of one another H, (CH2)pCON(R5)2, OA, Hal, COOH, COOA, (CH2)pNHCOA, (CH2)pHet1, (CH2)pNR2R5, or OH;
• R2 denotes H or linear or branched alkyl with 1, 2 or 3 C atoms, wherein one or two H atoms of the alkyl group are optionally replaced by OR6, NR5R6, NHCOR5, CONR5R6;
• R4 denotes H or A;
• R5 denotes H or linear or branched alkyl with 1, 2 or 3 C atoms;
• R6 denotes H or linear or branched alkyl with 1, 2 or 3 C atoms;
• Z is absent or denotes Ar-diyl or Het-diyl;
• L denotes (CH2)n wherein one or two CH2 groups are optionally replaced by O and/or a CH═CH-group, and/or wherein one or two H atoms are optionally replaced by OR2, NR2R5 or Het1;
• Ar-diyl denotes 1,2-, 1,3- or 1,4-phenylen optionally substituted with from 1 to 5 groups independently selected from the group consisting of Hal, CN, —CF3, —OCF3, OH, O-A, SO2-A, COOH, COOA, —CO-A, O-phenyl, SO2-phenyl, SO2—CF3, Het2 and A;
• Het-diyl denotes an unsaturated, saturated or aromatic 5- or 6-membered heterocycle comprising 1 to 2 N, O and/or S atoms, which are optionally unsubstituted or mono-, di- or trisubstituted by Hal, CN, —CF3, —OCF3, O-A, SO2-A, COOH, COOA, —CO-A, O-phenyl, SO2-phenyl, SO2—CF3, Het2 and/or A;
• A denotes an unbranched or branched alkyl comprising 1 to 10 C atoms, in which 1 to 5H atoms are optionally replaced by F and/or in which one or two non-adjacent CH2 groups are optionally replaced by O;
• Het1 denotes morpholinyl, piperidinyl or pyrrolidinyl;
• Het2 denotes morpholinyl, piperidinyl or pyrrolidinyl;
• Hal denotes F, Cl, Br, I;
• n denotes 1, 2, 3, 4, 5 or 6;
• p denotes 0, 1 or 2;
• or wherein the compound is a pharmaceutically acceptable salt of a compound of formula (I);
• wherein said disease related to IRAK overexpression is selected from the group consisting of systemic lupus erythematosus, lupus nephritis and rheumatoid arthritis.