Indazolyl triazol derivatives

A method for the treatment and/or prevention of disorders related to IRAK comprising administering to a patient an effective amount of a compound of Formula (I):

• Wherein
• Q denotes Ar or Het,
• E denotes —(CH2)mCO—, —(CH2)mSO2, —(CH2)q—, —(CH2)mNHCO—, or a single bond,
• R1 denotes H, OH, NH—C1-C6-alkyl, OC1-C6-alkyl, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, Cyc, Hal, Het1, O-Het1, CO-Het1, NH-Het1, CO—Ar1, O—Ar1, Ar1, NH—Ar1, —(CH2)qHet1, —CONH—(CH2)qHet1, —CONH-Het1, —(CH2)qO-Het1, —(CH2)qO—Ar1, —(CH2)qAr1, —CONH—(CH2)qAr1, —CONH—Ar1, —CONHC3-C6-cycloalkyl, —(CH2)qHal, —(CH2)qCyc, CF3, —(CH2)qNH—(CH2)q-Het1, —(CH2)qNH—(CH2)q—Ar1, wherein NH—C1-C6-alkyl, OC1-C6-alkyl, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C3-C6-cycloalkyl may be further substituted by 1 to 3 groups independently selected from OC1-C3-alkyl, OH, CONH2, NH2,
• R2 denotes H, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, Hal, CF3, preferably H,
• R3 denotes Het1, Ar1, NRaRb, COOH, —(CH2)qHet1, —(CH2)qAr1, —(CH2)qNRaRb, —(CH2)qCOOH, or C1-C6-alkyl wherein 1 to 3 hydrogen atoms may be independently replaced by OH or CF3.
• R4 denotes H, C1-C6-alkyl, C2-C6-alkenyl, Hal;
• Ra denotes H, linear, branched or cyclic C1-C6-alkyl,
• Rb denotes H, Hetb, Arb, —CO-Hetb, —CO—Arb, a C3-C8-cycloalkyl or a linear or branched alkyl having 1 to 6 carbon atoms, wherein 1 to 3 hydrogen atoms may be replaced by Hetb, Arb, NH2, N(C1-C6-alkyl)2, NH(C1-C6-alkyl), N(C1-C6-alkyl)(C3-C8-cycloalkyl), NH(C3-C8-cycloalkyl), O(C1-C6-alkyl), CN, OH, CF3, Hal,
• n is 0, 1, 2, 3 or 4,
• m is 0, 1, 2, 3 or 4,
• q is 1, 2, or 3,
• s is 0, 1, 2 or 3
• Hal denotes Cl, Br, I, F, preferably Cl or F.
• Ar denotes a divalent monocyclic or fused bicyclic arylen group having 6 to 14 carbon atoms, which may be further substituted with 1 to 4 substitutents selected from Hal, C1-C6-alkyl, —(CH2)mOC1-C6-alkyl, CN, OH, NO2, CF3, —(CH2)mCOOH, —(CH2)mCOOC1-C6-alkyl;
• Het denotes a divalent monocyclic or fused bicyclic unsaturated, saturated or aromatic heterocyclic group having 1 to 5 heteroatom independently selected from N, O, S and/or a group —C═O, which may be further substituted with 1 to 4 substituent selected from Hal, C1-C6-alkyl, —(CH2)mOC1-C6-alkyl, CN, OH, NO2, CF3, —(CH2)mCOOH, —(CH2)mCOOC1 —C6-alkyl;
• Ar1 denotes a monocyclic or bicyclic, aromatic carbocyclic ring having 6 to 14 carbon atoms, which is unsubstituted or monosubstituted, disubstituted or trisubstituted by Hal, —CF3, —OCF3, —NO2, —CN, perfluoroalkyl, Hal, —CF3, —OCF3, —NO2, —CN, perfluoroalkyl, linear or branched C1-C6-alkyl, cycloalkyl, —OH, —OC1-C6-alkyl, —COC1-C6-alkyl, —NH2, —COH, —COOH, —CONH2, a group Rb such as —CH2O(C1-C6-alkyl), —SO2NRaRb or SO2(C1-C6alkyl).
• Het1 denotes a monocyclic or bicyclic (fused, bridged or spiro) saturated, unsaturated or aro-matic heterocyclic ring having 1 to 4 heteroatom independently selected from N, O, S and/or a CO group, which is unsubstituted or monosubstituted, disubstituted or trisubstituted by Hal, —CF3, —OCF3, —NO2, —CN, perfluoroalkyl, linear or branched C1-C6-alkyl, C3-C8-cycloalkyl, —OH, —OC1-C6-alkyl, —NH2, —N(C1-C6-alkyl)2, —COH, —COOH, —CONH2, —COC1-C6-alkyl, —NHCO(C3-C6cycloalkyl), a group Rb, —SO2NRaRb or SO2(C1-C6alkyl).
• Hetb denotes a monocyclic or bicyclic (fused or spiro) saturated, unsaturated or aromatic heterocyclic ring having 1 to 4 heteroatom independently selected from N, O, S and/or a CO group, which is unsubstituted or monosubstituted, disubstituted or trisubstituted by Hal, —CF3, —OCF3, —NO2, —CN, perfluoroalkyl, —OH, —OC1-C6-alkyl, —NH2, —COH, —COOH, —CONH2, or by a linear or branched C1-C6-alkyl wherein 1 to 3 hydrogen atoms may be replaced by NH2, N(C1-C6-alkyl)2, NH(C1-C6-alkyl), N(C1-C6-alkyl)(C3-C8-cycloalkyl), NH(C3-C8-cycloalkyl), O(C1-C6-alkyl), CN, OH, CF3, Hal, C3-C8-cycloalkyl, or by a 4 to 8-membered heterocyclic ring containing an heteroatom selected from O, S and N,
• Arb denotes a monocyclic or bicyclic, aromatic carbocyclic ring having 6 to 14 carbon atoms, which is unsubstituted or monosubstituted, disubstituted or trisubstituted by Hal, —CF3, —OCF3, —NO2, —CN, perfluoroalkyl, Hal, —CF3, —OCF3, —NO2, —CN, perfluoroalkyl, —OH, —OC1-C6-alkyl, —NH2, —COH, —COOH, —CONH2, or by a linear or branched C1-C6-alkyl wherein 1 to 3 hydrogen atoms may be replaced by NH2, N(C1-C6-alkyl)2, NH(C1-C6-alkyl), N(C1-C6-alkyl)(C3-C8-cycloalkyl), NH(C3-C8-cycloalkyl), O(C1-C6-alkyl), CN, OH, CF3, Hal, C3-C8-cycloalkyl, or by a 4 to 8-membered heterocyclic ring containing an heteroatom selected from O, S and N,
• Cyc denotes a saturated or unsaturated carbocyclic ring having 3 to 8 carbon atoms, preferrably 5 or 6 carbon atoms, wherein 1 to 5 H atoms are replaced by Hal, —CF3, —OCF3, —NO2, —CN, perfluoroalkyl, Hal, —CF3, —OCF3, —NO2, —CN, perfluoroalkyl, linear or branched C1-C6-alkyl, cycloalkyl, —OH, —OC1-C6-alkyl, —COC1-C6-alkyl, —NH2, —COH, —COOH, —CONH2, a group Rb such as —CH2O(C1-C6-alkyl), —SO2NRaRb or SO2(C1-C6alkyl).
• or a pharmaceutically acceptable derivative, solvate. tautomer, salt, hydrate or stereoisomer thereof, including mixtures thereof in all ratios.