| 主权项 |
1. A compound of formula (I): or a tautomeric or stereochemically isomeric form, N-oxide, pharmaceutically acceptable salt or solvate thereof; wherein X is CH and Y is CR9, or one of X or Y is CR9 and the other is nitrogen, or X and Y are nitrogen; W is either absent or selected from CR6R7, CH2—CH2, CH2—O, O—CH2, C═O, SO2, O, NR8, CH2—NR8 and NR8—CH2; when W is CR6R7, CH2—CH2, CH2—O, O—CH2, C═O, SO2, CH2—NR8 or NR8—CH2, then R1a, R1b, R2a, R2b, R3a, R3b, R4a and R4b are independently selected from hydrogen, halogen, C1-4 alkyl, carboxyl, hydroxyl, hydroxyC1-4 alkyl, C1-4 alkyoxy, C3-6 cycloalkyl, haloC1-4 alkyl, methoxymethyl and nitrile, or R2a and R2b, or R4a and R4b can together represent ═O, or R1a and R1b, R2a and R2b, R3a and R3b or R4a and R4b can join together to form cyclopropyl or oxetanyl, or R1a and R3a, or R1a and R2a, or R2a and R3a, or R2a and R4a, or R3a and R4a, or R1b and R3b, or R1b and R2b, or R2b and R3b, or R2b and R4b, or R3b and R4b can join together to form a C1-4 bridged alkyl group, when W is NR8, then R1a, R1b, R2a, R2b, R3a, R3b, R4a and R4b are independently selected from hydrogen, halogen, C1-4 alkyl, carboxyl, hydroxyl, hydroxyC1-4 alkyl, C1-4 alkyoxy, C3-6 cycloalkyl, haloC1-4 alkyl, methoxymethyl and nitrile, or R2a and R2b, or R4a and R4b can together represent ═O, or R1a and R1b, R2a and R2b, R3a and R3b or R4a and R4b can join together to form cyclopropyl or oxetanyl, or R1a and R3a, or R1a and R2a, or R2a and R3a, or R2a and R4a, or R3a and R4a, or R1b and R3b, or R1b and R2b, or R2b and R3b, or R2b and R4b, or R3b and R4b can join together to form a C1-4 bridged alkyl group, or R2a/2b or R4a/4b can join together with the nitrogen atom at W to form a fused heterocyclic group with 5 or 6 ring members which can be optionally substituted by one or more substituents R10, provided that when X and Y are other than both nitrogen, R4a and R4b do not together represent ═O when R5 is 1,1-difluoroethyl and R8 is methyl; when W is O, then R1a, R1b, R2a, R2b, R3a, R3b, R4a, and R4b are independently selected from hydrogen, halogen, C1-4 alkyl, carboxyl, hydroxyl, hydroxyC1-4 alkyl, C1-4 alkyoxy, C3-6 cycloalkyl, haloC1-4 alkyl, methoxymethyl and nitrile, or R2a and R2b, or R4a and R4b can together represent ═O, or R1a and R1b, R2a and R2b, R3a and R3b or R4a and R4b can join together to form cyclopropyl or oxetanyl, or R1a and R3a, or R1a and R2a, or R2a and R3a, or R2a and R4a, or R3a and R4a, or R1b and R3b, or R1b and R2b, or R2b and R3b, or R2b and R4b, or R3b and R4b can join together to form a C1-4 bridged alkyl group, provided that when X and Y are other than both nitrogen:
R1a, R1b, R2a, R2b, R3a, R3b, R4a and R4b are not all hydrogen, orwhen one of R1a or R1b or R3a or R3b is methyl or ethyl the remaining R1a, R1b, R2a, R2b, R3a, R3b, R4a and R4b groups are not all hydrogen, orwhen R2a and R4a are methyl then R1a, R1b, R2b, R3a, R3b and R4b are not all hydrogen, orR1a or R3b is not methoxymethyl when R5 is 1,1-difluoropropyl; when W is absent, then R1a, R1b, R2a, R2b, R3a, R3b, R4a and R4b are independently selected from hydrogen, halogen, C1-4 alkyl, carboxyl, hydroxyl, hydroxyC1-4 alkyl, C1-4 alkyoxy, C3-6 cycloalkyl, haloC1-4 alkyl, methoxymethyl and nitrile, or R2a and R2b, or R4a and R4b can together represent ═O, or R1a and R1b, R2a and R2b, R3a and R3b or R4a and R4b can join together to form cyclopropyl or oxetanyl, or R1a and R3a, or R1a and R2a, or R2a and R3a, or R2a and R4a, or R3a and R4a, or R1b and R3b, or R1b and R2b, or R2b and R3b, or R2b and R4b, or R3b and R4b can join together to form a C1-4 bridged alkyl group, or R2a/2b and R4a/4b can join together to form a fused phenyl or pyridinyl group which can be optionally substituted by one or more substituents R10, provided that when X and Y are other than both nitrogen:
R1a, R1b, R2a, R2b, R3a, R3b, R4a and R4b are not all hydrogen, orwhen one of R2a or R2b or R4a or R4b is fluorine the remaining R1a, R1b, R2a, R2b, R3a, R3b, R4a and R4b groups are not all hydrogen, orwhen R2a and R2b, or R4a and R4b join to form ═O then the remaining R1a, R1b, R2a, R2b, R3a, R3b, R4a and R4b groups are not all hydrogen, orR2a and R2b, or R4a and R4b are not both fluorine when R5 is 2,4-difluorobenzyl; R5 is selected from: benzyl optionally substituted on the phenyl group by one or two substituents selected from fluorine and nitrile, and optionally substituted on the methylene by hydroxyl; and C2-4 alkyl substituted by one or two substituents selected from fluorine and hydroxyl; R6 and R7 are independently selected from hydrogen, hydroxyl and fluorine; R8 is selected from hydrogen, C1-4 alkyl, —SO2-C1-4 alkyl, —SO2—NH(C1-4 alkyl), —SO2—N(C1-4 alkyl)2, —C(═O)—NH—SO2-C1-4 alkyl, —C(═O)—NH—SO2-phenyl, —C(═O)—N(C1-4 alkyl)2, pyrimidinyl, —C(═O)-phenyl, —C(═O)—C3-6 cycloalkyl and —C(═O)—C1-4 alkyl, wherein the alkyl or cyclic groups can be optionally substituted by one or more R10; R9 is selected from hydrogen and nitrile; and R10 is independently selected from hydrogen, halogen, C1-4 alkyl, carboxyl, hydroxyl, hydroxyC1-4 alkyl, C1-4 alkyoxy, C3-6 cycloalkyl, haloC1-4 alkyl, methoxymethyl and nitrile. |
