| 主权项 |
1. A method for treating a Bruton's Tyrosine Kinase (Btk) mediated disorder in a subject comprising administering to the subject a compound of Formula (I) or a pharmaceutically acceptable salt thereof,in an amount effective to treat the Btk mediated disorder, thereby treating the subject,
wherein: X is CH, N, O or S; Y is C(R6), N, O or S; Z is CH, N or a 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 atom that R2 is attached to and the C atom that R3 is 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 the 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 the 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 the 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 cannot be O or S;when Z is CH or N then Y is C(R6) or N and X is CH or N; and0 to 2 atoms of B1, B2, B3 and B4 are N. |
