4-imidazopyridazin-1-yl-benzamides and 4-imidazotriazin-1-yl-benzamides as btk inhibitors

Compound according to formula I

• or a pharmaceutically acceptable salt thereof, wherein
• X is CH, N, O or S;
• Y is C(R6), N, O or S;
• Z is CH, N or bond;
• A is CH or N;
• B1 is N or C(R7);
• B2 is N or C(R8);
• B3 is N or C(R9);
• B4 is N or C(R10);
• R1 is R11C(O), R12S(O), R13SO2 or (1-6C)alkyl optionally substituted with R14;
• R2 is H, (1-3C)alkyl or (3-7C)cycloalkyl;
• R3 is H, (1-6C)alkyl or (3-7C)cycloalkyl);
• or
• R2 and R3 form, together with the N and C atom they are attached to, a (3-7C)heterocycloalkyl optionally substituted with one or more fluorine, hydroxyl, (1-3C)alkyl, (1-3C)alkoxy or oxo;
• R4 is H or (1-3C)alkyl;
• R5 is H, halogen, cyano, (1-4C)alkyl, (1-3C)alkoxy, (3-6C)cycloalkyl, any alkyl group of which is optionally substituted with one or more halogen;
• or R5 is (6-10C)aryl or (2-6C)heterocycloalkyl;
• R6 is H or (1-3C)alkyl;
• or
• R5 and R6 together may form a (3-7C)cycloalkenyl, or (2-6C)heterocycloalkenyl;
• each optionally substituted with (1-3C)alkyl, or one or more halogen;
• R7 is H, halogen or (1-3C)alkoxy;
• R8 is H or (1-3C)alkyl;
• or
• R7 and R8 form, together with the carbon atom they are attached to a (6-10C)aryl or (1-9C)heteroaryl;
• R9 is H, halogen or (1-3C)alkoxy
• R10 is H, halogen or (1-3C)alkoxy
• R11 is independently selected from a group consisting of (1-6C)alkyl, (2-6C)alkenyl and (2-6C)alkynyl each alkyl, alkenyl or alkynyl optionally substituted with one or more groups selected from hydroxyl, (1-4C)alkyl, (3-7C)cycloalkyl, [(1-4C)alkyl]amino, di[(1-4C)alkyl]amino, (1-3C)alkoxy, (3-7C)cycloalkoxy, (6-10C)aryl or (3-7C)heterocycloalkyl;
• or
• R11 is (1-3C)alkyl-C(O)—S-(1-3C)alkyl;
• or
• R11 is (1-5C)heteroaryl optionally substituted with one or more groups selected from halogen or cyano;
• R12 and R13 are independently selected from a group consisting of (2-6C)alkenyl or (2-6C)alkynyl both optionally substituted with one or more groups selected from hydroxyl, (1-4C)alkyl, (3-7C)cycloalkyl, [(1-4C)alkyl]amino, di[(1-4C)alkyl]amino, (1-3C)alkoxy, (3-7C)cycloalkoxy, (6-10C)aryl or (3-7C)heterocycloalkyl;
• or
• (1-5C)heteroaryl optionally substituted with one or more groups selected from halogen or cyano;
• R14 is independently selected from a group consisting of halogen, cyano or (2-6C)alkenyl or (2-6C)alkynyl both optionally substituted with one or more groups selected from hydroxyl, (1-4C)alkyl, (3-7C)cycloalkyl, [(1-4C)alkyl]amino, di[(1-4C)alkyl]amino, (1-3C)alkoxy, (3-7C)cycloalkoxy, (6-10C)aryl, (1-5C)heteroaryl or (3-7C)heterocycloalkyl;
• with the proviso that
• 0 to 2 atoms of X, Y, Z can simultaneously be a heteroatom;
• when one atom selected from X, Y is O or S, then Z is a bond and the other atom selected from X, Y can not be O or S;
• when Z is C or N then Y is C(R6) or N and X is C or N;
• 0 to 2 atoms of B1, B2, B3 and B4 are N.