发明名称 4-IMIDAZOPYRIDAZIN-1-YL-BENZAMIDES AND 4-IMIDAZOTRIAZIN-1-YL-BENZAMIDES AS BTK INHIBITORS
摘要 The present invention relates to 6-5 membered fused pyridine ring compounds according to formula (I) or a pharmaceutically acceptable salt thereof or to pharmaceutical compositions comprising these compounds and to their use in therapy. In particular, the present invention relates to the use of 6-5 membered fused pyridine ring compounds according to formula I in the treatment of Brutons Tyrosine Kinase (Btk) mediated disorders.;
申请公布号 US2014155385(A1) 申请公布日期 2014.06.05
申请号 US201214233418 申请日期 2012.07.11
申请人 Barf Tjeerd A.;Jans Christian Gerardus Johannes Maria;Man Petrus Antonius De Adrianus;Oubrie Arthur A.;Raaijmakers Hans C.A.;Rewinkel Johannes Bernardus Maria;Sterrenburg Jan-Gerard;Wijkmans Jacobus C.H.M. 发明人 Barf Tjeerd A.;Jans Christian Gerardus Johannes Maria;Man Petrus Antonius De Adrianus;Oubrie Arthur A.;Raaijmakers Hans C.A.;Rewinkel Johannes Bernardus Maria;Sterrenburg Jan-Gerard;Wijkmans Jacobus C.H.M.
分类号 C07D487/04;A61K31/55;A61K31/506;A61K31/4985;A61K31/501 主分类号 C07D487/04
代理机构 代理人
主权项 1. 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.
地址 Ravenstein NL