| 主权项 |
1. The compound according to formula (RI) wherein Het is selected from the group consisting of: formula (a′), (b′), (c′), and (d′): wherein each X independently is C or N; wherein at least one X is N; each of R1a, R1b, R1c, R1d is halogen; and R1b or R1d is absent when the X to which it is bound is N; each R2 is —(CR8R9)m—R10; m is an integer from 0 to 6; each R8 and R9 are independently selected from the group consisting of: H, C1-C10alkyl and C3-C7cycloalkyl; or R8 and R9 are taken together form a 4 to 6 membered saturated ring that optionally contains one or more heteroatoms selected from the group consisting of: N, S and O; each R10 is independently selected from the group consisting of: H, halogen, OH, CN, CF2H, CF3, C1-C6 alkyl, C3-C7cycloalkyl, C(═O)C1-C6alkyl, C(═O)C3-C7cycloalkyl, C(═O)NR8R9, C(═O)OR8, SO2R8, C(═O)N(R8)SO2R9, C(═O)N(R8)SO2N(R8R9), NR8R9, NR8C(═O)OR9, OC(═O)R8, O-benzyl, NR8SO2R9, SO2NR8R9, SO2R8, OC(═O)NR8R9, OC(═O)NR8R12, N(R8)C(═O)N(R8R9), R11, N(R8)C(═O)OR12, OR11, C(═O)R11, and a 4 to 6 membered saturated ring containing one oxygen atom; R11 phenyl, pyridinyl or pyrazolyl; wherein each phenyl, pyridinyl or pyrazolyl can be optionally substituted with one or more substituents each independently selected from the group consisting of: CF3, CH3, OCH3, OCF3, and halogen; R12 is C1-C6 alkyl or C3-C7cycloalkyl; wherein each C1-C6 alkyl or C3-C7cycloalkyl is substituted with one or more substituents each independently selected from the group consisting of: CF3, CH3, OCH3, OCF3, and halogen; each Z independently is C or N, provided that at least two Z are C; Q and V each independently represent C═O, SO2 or CR20R21; p and s independently represent an integer from 0 to 3, wherein the sum of p and s minimally should be 2, and when p=0 or s=0 then the carbon atom marked with * is directly bound to W; R20 and R21 are each independently selected from the group consisting of: hydrogen, hydroxyl, C1-C3alkyl, C3-C7cycloalkyl, CF3, OCH3, OCF3, and halogen; R22 is selected from the group consisting of: hydrogen, hydroxyl, C1-C6alkyl, C3-C7cycloalkyl, CF3, OCH3, OCF3, and halogen; W is selected from the group consisting of: SO, SO2, S, C, O, and N, wherein such C or N is optionally substituted with one or more R23; R23 is selected from the group consisting of: hydrogen, hydroxyl, C1-C6alkyl, C3-C7cycloalkyl, C1-C6alkyl-R24, SO2R24 SO2N(R24)2, aryl, heteroaryl, C(═O)OR24, OR24, C(═O)R24, C(═O)N(R24)2, OC(═O)N(R24)2, P(═O)—(O—C1-C6-alkyl)2, N(R24)2, NR25C(═O)OR24, NR25C(═O)N(R24)2, NR25SO2R24, and a 4 to 6 membered saturated ring containing one oxygen atom, wherein any of such C1-C6alkyl, C3-C7cycloalkyl, aryl or heteroaryl is optionally substituted with one or more substituents each independently selected from the group consisting of: halogen, OH, CN, and OCH3; R24 is selected from the group of: hydrogen, OH, halogen, C1-C6alkyl, C3-C7cycloalkyl, C(═O) C1-C6alkyl, C(═O) C3-C7cycloalkyl, aryl, heteroaryl, benzyl, and a 4 to 6 membered saturated ring containing one oxygen atom; wherein any of such C1-C6alkyl, C3-C7cycloalkyl, C(═O) C1-C6alkyl, C(═O) C3-C7cycloalkyl, aryl, heteroaryl, and benzyl is optionally substituted with one or more substituents each independently selected from the group consisting of: halogen, CF3, OH, CN, OCH3, OC(═O)CH3), and C1-C3alkyl substituted with at least one CN; R25 is selected from the group consisting of hydrogen and C1-C3 alkyl; aryl represents phenyl or naphthalenyl; heteroaryl represents a monocyclic 5 to 6 membered aromatic heterocycle containing one or more heteroatoms each independently selected from the group consisting of: O, S and N; or a bicyclic 8 to 12 membered aromatic heterocycle containing one or more heteroatoms each independently selected from the group consisting of: O, S and N; or a pharmaceutically acceptable addition salt or a solvate thereof. |
