Tricyclic pyrazol amine derivatives

A compound of Formula (I*):

• wherein:
• X1 denotes a nitrogen atom or CR3;
• X2, X5 are independently from one another nitrogen or carbon atoms;
• U denotes an aromatic 6-membered ring having optionally 1, 2 or 3 nitrogen atoms, including X5, or an unsaturated or aromatic 5-membered ring having 1 to 3 heteroatoms selected from N, S or O, including the meaning of X5;
• Z denotes an unsaturated or aromatic 5-membered heterocyclic ring having 2 nitrogen atoms, including the meaning of X2;
• T denotes S, SO or SO2;
• R1 denotes H, A, Hal, CN, NO2, N(R6)2, OR6, Ar, Het, Y, —NR6COR6, CON(R6)2, —NR6COAr, NR6COHet, COHet, —NR6SO2R6, or CO2R6, including CO2Y;
• R2 denotes H, Ar, Het, A, or Cyc;
• R3 denotes H or Y;
• R4 denotes H, Y, (CH2)nAr, (CH2)nCyc, (CH2)nHet, (CH2)nOY, (CH2)nNHY, or (CH2)nNH2, or if X1 is CR3, R4 denotes H, Y, (CH2)nAr, (CH2)nCyc, (CH2)nHet, (CH2)nOY, (CH2)nNHY, (CH2)nNH2 or Hal;
• R5 denotes H, Y or Ar, when R5 is Y and r is 2, two R5 groups may be linked together to provide with the morpholine group to which they are linked, a bridged system;
• R6 is H, A, Cyc or Ar;
• u is 0, 1, 2, 3, or 4;
• r is 0, 1 or 2;
• g is 1 or 2;
• Ar denotes a monocyclic or fused bicyclic, unsaturated or aromatic carbocyclic ring having 6 to 14 carbon atoms, which is unsubstituted or monosubstituted, disubstituted or trisubstituted by Hal, OCF3, NO2, CN, perfluoroalkyl, A, OR6, N(R6)2, COR6, —CO2R6, CON(R6)2, COHet, —NHCOR6, —NHSO2A, —NHSO2Ar, —NHSO2—N(R6)2, N(H)1-qAqCOR6, N(H)1-qAqSO2—N(H)2-m(A)m, —N(H)1-qAqCON(H)2-mA)m, —SO2A, —SO2Ar, —SO2N(H)2-m(A)m, —SO2Het, —(CH2)n—N(R6)2, —(CH2)n—OR6, —(CH2)n—N(R6)SO2A, —(CH2)n—N(R6)SO2R6, Het2, —(CH2)n-Het2, or —(CHY)n-Het2;
• Het denotes a monocyclic or bicyclic saturated, unsaturated or aromatic heterocyclic ring having 1, 2, 3 or 4 N, O and/or S atoms and eventually comprising a SO2 or a CO group, which is unsubstituted or monosubstituted, disubstituted or trisubstituted by Hal, OCF3, NO2, CN, perfluoroalkyl, A, OR6, N(R6)2, COR6, —CO2R6, CON(R6)2, —NHCOR6, —NHSO2A, —NHSO2R6, —NHSO2—N(H)2-m(A)m, N(H)1-qAqCOR6, N(H)1-qAqSO2—N(H)2-m(A)m, —N(H)1-qAqCON(H)2-m(A)m, —SO2A, —SO2Ar, —SO2N(H)2-m(A)m, COHet, —SO2Het, —(CH2)n—N(H)2-m(A)m, —(CH2)n—OR6, —(CH2)n—N(R6)SO2A, —(CH2)n—N(R6)SO2R6, Het2, —(CH2)nHet2;
• or —(CHY)n-Het2;
• Het2 denotes
• Cyc denotes a saturated or unsaturated carbocyclic ring having 3 to 8 carbon atoms, which is unsubstituted, mono-substituted, di-substituted or tri-substituted by Hal, OCF3, NO2, CN, perfluoroalkyl, A, OR6, N(R6)2, COR6, CON(R6)2, —NHCOR6, —NHSO2A, —NHSO2R6, —NHSO2—N(H)2-m(A)m, N(H)1-qAqCOR6, N(H)1-qAqSO2—N(H)2-m(A)m, —N(H)1-qAqCON(H)2-m(A)m, —COOR6, —SO2A, —SO2Ar, —SO2N(H)2-m(A)m, —SO2Het, —(CH2)p—N(H)2-m(A)m, —(CH2)n—OR6, —(CH2)n—N(R6) SO2A, —(CH2)n—N(R)SO2R6, Het2, —(CH2)n-Het2;
• or —(CHY)n-Het2;
• A is a branched or linear alkyl having 1 to 12 C-atoms, wherein one or more H-atoms may be replaced by Hal, Ar, Het, Cyc, OR6, —CN, —CO2Y, CO2H or N(R6)2 and wherein one or more non-adjacent CH2-groups may be replaced by O, NR6, CO, CONR6, NR6CO, OCO, — and/or by —CH═CH— or C≡C— groups, or denotes cycloalkyl or cycloalkylalkylene having 3-7 ring C atoms;
• Y denotes a branched or linear alkyl having 1 to 8 carbon atoms;
• Hal denotes F, Cl, Br or I;
• q is 0 or 1;
• m is 0, 1 or 2;
• n is 1, 2, 3, or 4;
• and pharmaceutically acceptable, solvates, tautomers, salts, hydrates and stereoisomers thereof, including mixtures thereof in all ratios,
• with the proviso that compound of formula (B1) is excluded:

A compound of Formula (I*):

• wherein:
• X1 denotes a nitrogen atom or CR3;
• X2, X5 are independently from one another nitrogen or carbon atoms;
• U denotes an aromatic 6-membered ring having optionally 1, 2 or 3 nitrogen atoms, including X5, or an unsaturated or aromatic 5-membered ring having 1 to 3 heteroatoms selected from N, S or O, including the meaning of X5;
• Z denotes an unsaturated or aromatic 5-membered heterocyclic ring having 2 nitrogen atoms, including the meaning of X2;
• T denotes S, SO or SO2;
• R1 denotes H, A, Hal, CN, NO2, N(R6)2, OR6, Ar, Het, Y, —NR6COR6, CON(R6)2, —NR6COAr, NR6COHet, COHet, —NR6SO2R6, or CO2R6, including CO2Y;
• R2 denotes H, Ar, Het, A, or Cyc;
• R3 denotes H, or Y;
• R4 denotes H, Y, (CH2)nAr, (CH2)nCyc, (CH2)nHet, (CH2)nOY, (CH2)nNHY, (CH2)nNH2, or if X1 is CR3, R4 denotes H, Y, (CH2)nAr, (CH2)nCyc, (CH2)nHet, (CH2)nOY, (CH2)nNHY, (CH2)nNH2 or Hal;
• R5 denotes H, Y or Ar, when R5 is Y and r is 2, two R5 groups may be linked together to provide with the morpholine group to which they are linked, a bridged system;
• R6 is H, A, Cyc or Ar;
• u is 0, 1, 2, 3, or 4;
• r is 0, 1 or 2;
• g is 1 or 2;
• Ar denotes a monocyclic or fused bicyclic, unsaturated or aromatic carbocyclic ring having 6 to 14 carbon atoms, which is unsubstituted or monosubstituted, disubstituted or trisubstituted by Hal, OCF3, NO2, CN, perfluoroalkyl, A, OR6, N(R6)2, COR6, —CO2R6, CON(R6)2, COHet, —NHCOR6, —NHSO2A, —NHSO2Ar, —NHSO2—N(R6)2, N (H)1-qAqCOR6, N(H)1-qAqSO2—N(H)2-m(A)m, —N(H)1-qAqCON(H)2-m(A)m, —SO2A, —SO2Ar, —SO2N(H)2-m(A)m, —SO2Het, —(CH2)n—N(R6)2, —(CH2)n—OR6, —(CH2)n—N(R6)SO2A, —(CH2)n—N(R6)SO2R6, Het2, —(CH2)n-Het2, —(CHY)n-Het2;
• Het denotes a monocyclic or bicyclic saturated, unsaturated or aromatic heterocyclic ring having 1, 2, 3 or 4 N, O and/or S atoms and eventually comprising a SO2 or a CO group, which is unsubstituted or monosubstituted, disubstituted or trisubstituted by Hal, OCF3, NO2, CN, perfluoroalkyl, A, OR6, N(R6)2, COR6, —CO2R6, CON(R6)2, —NHCOR6, —NHSO2A, —NHSO2R6, —NHSO2—N(H)2-m(A)m, N(H)1-qAqCOR6, N(H)1-qAqSO2—N(H)2-m(A)m, —N(H)1-qAqCON(H)2-m(A)m, —SO2A, —SO2Ar, —SO2N(H)2-m(A)m, COHet, —SO2Het, —(CH2)n—N(H)2-m(A)m, —(CH2)n—OR6, —(CH2)n—N(R6)SO2A, —(CH2)n—N(R6)SO2R6, Het2, —(CH2)n-Het2;
• —(CHY)n-Het2;
• Het2 denotes
• Cyc denotes a saturated or unsaturated carbocyclic ring having 3 to 8 carbon atoms, which is unsubstituted, mono-substituted, di-substituted or tri-substituted by Hal, OCF3, NO2, CN, perfluoroalkyl, A, OR6, N(R6)2, COR6, CON(R6)2, —NHCOR6, —NHSO2A, —NHSO2R6, —NHSO2—N(H)2-m(A)m, N(H)1-qAqCOR6, N(H)1-qAqSO2—N(H)2-m(A)m, —N(H)1-qAqCON(H)2-m(A)m, —COOR6, —SO2A, —SO2Ar, —SO2N(H)2-m(A)m, —SO2Het, —(CH2)p—N(H)2-m(A)m, —(CH2)n—OR6, —(CH2)n—N(R6)SO2A, —(CH2)n—N(R6)SO2R6, Het2, —(CH2)n-Het2;
• —(CHY)n-Het2;
• A is a branched or linear alkyl having 1 to 12 C-atoms, wherein one or more H-atoms may be replaced by Hal, Ar, Het, Cyc, OR6, —CN, —CO2Y, CO2H or N(R6)2 and wherein one or more non-adjacent CH2-groups may be replaced by O, NR6, CO, CONR6, NR6CO, OCO, — and/or by —CH═CH—C≡C— or groups, or denotes cycloalkyl or cycloalkylalkylene having 3-7 ring C atoms;
• Y denotes a branched or linear alkyl having 1 to 8 carbon atoms;
• Hal denotes F, Cl, Br or I;
• q is 0 or 1;
• m is 0, 1 or 2;
• n is 1, 2, 3, or 4;
• and pharmaceutically acceptable solvates, tautomers, salts, hydrates and stereoisomers thereof, including mixtures thereof in all ratios, for use as a medicament.

A kit consisting of separate packs of:

• a) an effective amount of a compound of the formula (I*);
• and/or pharmaceutically acceptable solvates, salts, hydrates and stereoisomers thereof, including mixtures thereof in all ratios;
• and
• b) an effective amount of an additional active ingredient.