| 主权项 |
1. A compound of formula (I):wherein:
R1 and R2 are independently selected from H, (C1-C6)alkyl, (C1-C6)alkoxy, halo, CF3, and CN; R1a is H; R3 is H; R4 is selected from H, methyl, ethyl, methoxy, ethoxy, Cl, Br, CN, phenyl, and CONH2, wherein said methyl is optionally substituted with NR12R13; R5 is selected from heterocycloalkyl and NR16R17; R6 is selected from H, alkyl, (C1-C4)alkoxy, and (C3-C6)cycloalkyl; R7 is selected from H, (C1-C4)alkyl, (C1-C4)alkoxy, and (C3-C6)cycloalkyl; R16 is selected from H, aryl, (C3-C7)cycloalkyl andwherein said (C3-C7)cycloalkyl may be optionally substituted with an aryl group;
R17 is selected from H, (C1-C6)alkyl, aryl, heteroaryl, heterocycloalkyl and (C3-C7)cycloalkyl, wherein said (C1-C6)alkyl may be optionally substituted with 1, 2 or 3 groups independently selected from (C1-C6)alkoxy, (C3-C10)cycloalkyl, heterocycloalkyl, heteroaryl and NR20R21; as to R22 and R23:
R22 and R23 are independent substituents such that:
R22 is selected from H, (C1-C6)alkyl, (C1-C6)alkoxy, OH, NR29R30, heterocycloalkyl and aryl, wherein said (C1-C6)alkyl may be optionally substituted with 1, 2 or 3 R28 groups; and wherein said aryl may be optionally substituted with 1, 2 or 3 groups independently selected from (C1-C6)alkyl, (C1-C6)alkoxy, halo, CF3 and OH; andR23 is selected from H and (C1-C6)alkyl; or R22 and R23, together with the carbon atom to which they are attached, form a (C3-C7)cycloalkyl or heterocycloalkyl ring; X is a bond or a (CR24R25)n group; as to R24 and R25:
R24 and R25 are independently selected from H, (C1-C6)alkyl, (C1-C6)alkoxy, OH, heterocycloalkyl and NR39R40; orR24 and R25, together with the carbon atom to which they are attached, form a heterocycloalkyl ring; Z is an aryl or heteroaryl ring, wherein said aryl or heteroaryl ring is substituted with R26 and R27; as to R26 and R27:
R26 and R27 are independent substituents such that:
R26 is selected from H, (C1-C6)alkyl, (C1-C6)alkoxy, OH, aryl, O-aryl, halo, heterocycloalkyl, O-heterocycloalkyl, heteroaryl, O-heteroaryl, cycloalkyl, O-cycloalkyl, S(O)pR34, NR34R35 and CONR34R35, wherein said (C1-C6)alkyl or said (C1-C6)alkoxy may be optionally substituted with 1, 2 or 3 groups independently selected from halo, OH, heterocycloalkyl or NR34R35; andR27 is selected from H, halo and (C1-C6)alkyl, wherein said (C1-C6)alkyl may be optionally substituted with 1, 2 or 3 halo groups; orR26 and R27, together, form a methylenedioxy group when attached to adjacent carbon atoms of the aryl or heteroaryl ring; each occurrence of R28 is independently selected from NR29R30, halo, CH2CF3, CF3, heterocycloalkyl, (C1-C6)alkoxy, OR36, COOR42, CONR31R32 and SO2NR37R38; R29 and R30 are independently selected from H, (C1-C6)alkyl, (C3-C7)cycloalkyl, SO2R41 and C(O)R41, wherein said (C1-C6)alkyl may be optionally substituted with, OH, NR56R57 or heterocycloalkyl; as to R31 and R32:
R31 and R32 are independently selected from H, (C1-C6)alkyl and (C3-C7)cycloalkyl; orR31 and R32, together with the nitrogen atom to which they are attached, form a 4 to 7 membered ring, optionally containing a further heteroatom selected from NR33, S and O; as to R34 and R35:
R34 and R35 are independently selected from H, (C1-C6)alkyl, (C3-C7)cycloalkyl, C-linked heterocycloalkyl and C(O)O(C1-C6)alkyl, wherein said (C1-C6)alkyl may be optionally substituted by OH, halo, (C1-C6)alkoxy, NR58R59, C(O)OH and heterocycloalkyl; orR34 and R35, together with the nitrogen to which they are attached, form a 4 to 7 membered ring; R36 is selected from H, (C1-C6)alkyl and heterocycloalkyl, wherein said (C1-C6)alkyl may be optionally substituted with heterocycloalkyl; R12, R13, R20, R21, R33, R37, R38, R39, R40, R41 and R42 are independently selected from H and (C1-C6)alkyl; n is 1 or 2; each occurrence of p is independently selected from 0, 1 or 2; cycloalkyl is a non-aromatic carbocyclic ring, optionally fused to an aryl group, wherein said cycloalkyl ring optionally contains, where possible, up to 2 double bonds; and wherein, unless otherwise stated, said cycloalkyl may be optionally substituted with 1 or 2 substituents independently selected from (C1-C6)alkyl, (C1-C6)alkoxy, OH, CN, CF3, halo and NR43R44; heterocycloalkyl is a C-linked or N-linked 3 to 9 membered non-aromatic, mono- or bi-cyclic ring, optionally fused to an aryl or heteroaryl group, wherein said heterocycloalkyl ring:
contains:
1 or 2 NR45 atoms,one N— atom,one N— atom and one NR45,one N— atom, one NR45 and an S(O)p or an O atom,one N— atom and an S(O)p or an O atom,one S atom, orone O atom;optionally contains, where possible, 1 or 2 double bonds; andis optionally substituted on carbon with 1 or 2 substituents independently selected from (C1-C6)alkyl, (C1-C6)alkoxy, OH, CN, CF3, halo, ═O, NR46R47, —C(O)NR46R47, bivalent substituent —OCH2CH2O— (wherein the terminal oxygen atoms are attached to the same ring carbon atom), bivalent substituent —CH2NHCH2— (wherein the terminal carbon atoms are attached to the same ring carbon atom), a tetrahydro-1,1-dioxido-3-thienyl group, and aryl, wherein said (C1-C6)alkyl may be optionally substituted by aryl, (C1-C6)alkoxy or OH; and wherein each aryl group may be optionally substituted with (C1-C6)alkoxy (which in turn may be optionally substituted by NR34R35), (C1-C6)alkyl, OH, CF3 and halo; aryl is an aromatic ring containing 6 or 10 carbon atoms; wherein, unless otherwise stated, said aryl may be optionally substituted with 1, 2 or 3 substituents independently selected from (C1-C6)alkyl, (C1-C6)alkoxy, OH, halo, CN, CF3 and NR48R49; heteroaryl is a 5, 6, 9 or 10 membered aromatic ring, containing from 1 or 2 N atoms and, optionally, an NR50 atom, or one NR50 atom and an S or an O atom, or one S atom, or one O atom; wherein, unless otherwise stated, said heteroaryl may be optionally substituted with 1, 2 or 3 substituents independently selected from (C1-C6)alkyl, (C1-C6)alkoxy, OH, halo, CN, CF3 and NR51R52; R45 is selected from H, (C1-C6)alkyl, C(O)(C1-C6)alkyl, C(O)O(C1-C6)alkyl and aryl, wherein said (C1-C6)alkyl is optionally substituted with a group selected from (C1-C3)alkoxy, OH, halo, heterocycloalkyl and NR29R30; and wherein said C(O)O(C1-C6)alkyl is optionally substituted with an aryl group; R50 is selected from H, (C1-C6)alkyl and C(O)O(C1-C6)alkyl, wherein said (C1-C6)alkyl may be optionally substituted with a group selected from (C1-C3)alkoxy, OH, halo, (C3-C6)cycloalkyl and NR53R54; R43, R44, R46, R47, R48, R49, R51, R52, R53, R54, R56, R57 and R59 are each independently selected from H and (C1-C6)alkyl; R58 is selected from H and (C1-C6)alkyl wherein said (C1-C6)alkyl may be optionally substituted with a group selected from (C1-C3)alkoxy and OH; or a pharmaceutically acceptable salt thereof. |
