A compound having the structure formula (I'): wherein either: X is or the structure formula (I') has the structure formula (IIa): or a pharmaceutically acceptable salt, or N -oxide thereof, or a solvate or hydrate thereof, wherein X 1 is -N=, -C =; X 2 is =C -, =N-, -N -; R Xa and R Xb are each hydrogen, or R Xa and R Xb combine with the atoms to which they are attached to form an Ar or Hca; -R X1 is halogen, cyano, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, -C 1 -C 6 alkoxy, -C 1 -C 6 haloalkoxy, oxo, -OR, -SR, -NR 2, -C R, -C OR, -C NR 2, - S 2 NR 2, -S 2 R, -OC R, -N C R, -OC OR, -OC NR 2, -N C OR, -N C NR 2, -N S 2 R, -OP 2, -CH 2 -OP, Cak(C 0 -C 6 alkyl), Ar(C 0 -C 6 alkyl) or Hca(C 0 -C 6 alkyl), wherein Cak, Ar and Hca are optionally substituted with one or two - R X2 groups, wherein each -R X2 is independently halogen, cyano, nitro, oxo, - OR, -SR, -NR 2, -C OR, -C NR 2, -C R, -S R, -S 2 R, - S OR, -S 2 OR, -S NR 2, -S 2 NR 2, -OC R, -OC OR, -OC NR 2, -N C R, -N C OR, -N C NR 2, - N S R, -N S 2 R, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl or Ar; Y 1 is CH or CF; Y 2 is N or CH; Y 3 is N or CH; Z is C 1 -C 6 alkyl, Ar(C 0 -C 6 alkyl) or Hca(C 0 -C 6 alkyl), each optionally substituted by 1, 2 or 3 -R Z1 groups; wherein each -R Z1 is independently halogen, cyano, C 1 -C 6 alkyl, Cak, C 1 -C 6 haloalkyl, -C 1 -C 6 alkoxy, oxo, -OR, -SR, -NR 2, -C R, - C OR, -C NR 2, -S 2 NR 2, -S 2 R, -OC R, -N C R, - OC OR, -OC NR 2, -N C OR, -N C NR 2, -N S 2 R, -OP 2 or -CH 2 -OP; each R is independently hydrogen or C 1 -C 6 alkyl; and R 1 is hydrogen or C 1 -C 6 alkyl; wherein Hca is a 3-15 membered ring or ring system comprising at least one ring and 1, 2, 3, or 4 O, S, or N atoms, provided no O or S is adjacent to another O or S; Het is a 5-15 membered aromatic ring or ring system comprising at least one ring and 1, 2, 3, or 4 O, S, or N atoms, provided no O or S is adjacent to another O or S; Cak is a 3-8 membered non-aromatic carbocyclic ring or ring system, which may be saturated or partially unsaturated; and Ar is a 6-16 membered aromatic ring or ring system having at least one carbocyclic aromatic ring optionally fused one or more aromatic or non-aromatic rings provided that when Y 3 is N or Z is C 1 -C 6 alkyl, X is X is or the structure formula (I') has the structure formula (IIa): or a pharmaceutically acceptable salt, or N -oxide thereof, or a solvate or hydrate thereof, X 1 is -N=, -C =; X 2 is =C -, =N-, -N -; R Xa and R Xb are each hydrogen, or R Xa and R Xb combine with the atoms to which they are attached to form an Ar or Hca; -R X1 is halogen, cyano, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, -C 1 -C 6 alkoxy, -C 1 -C 6 haloalkoxy, oxo, -OR, -SR, -NR 2, -C R, -C OR, -C NR 2, - S 2 NR 2, -S 2 R, -OC R, -N C R, -OC OR, -OC NR 2, -N C OR, -N C NR 2, -N S 2 R, -OP 2, -CH 2 -OP, Cak(C 0 -C 6 alkyl), Ar(C 0 -C 6 alkyl) or Hca(C 0 -C 6 alkyl), wherein Cak, Ar and Hca are optionally substituted with one or two - R X2 groups, wherein each -R X2 is independently halogen, cyano, nitro, oxo, - OR, -SR, -NR 2, -C OR, -C NR 2, -C R, -S R, -S 2 R, - S OR, -S 2 OR, -S NR 2, -S 2 NR 2, -OC R, -OC OR, -OC NR 2, -N C R, -N C OR, -N C NR 2, - N S R, -N S 2 R, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl or Ar; Y 1 is CH or CF; Y 2 is N or CH; Y 3 is N or CH; Z is C 1 -C 6 alkyl, Ar(C 0 -C 6 alkyl) or Hca(C 0 -C 6 alkyl), each optionally substituted by 1, 2 or 3 -R Z1 groups; wherein each -R Z1 is independently halogen, cyano, C 1 -C 6 alkyl, Cak, C 1 -C 6 haloalkyl, -C 1 -C 6 alkoxy, oxo, -OR, -SR, -NR 2, -C R, - C OR, -C NR 2, -S 2 NR 2, -S 2 R, -OC R, -N C R, - OC OR, -OC NR 2, -N C OR, -N C NR 2, -N S 2 R, -OP 2 or -CH 2 -OP; each R is independently hydrogen or C 1 -C 6 alkyl; and R 1 is hydrogen or C 1 -C 6 alkyl; wherein Hca is a 3-15 membered ring or ring system comprising at least one ring and 1, 2, 3, or 4 O, S, or N atoms, provided no O or S is adjacent to another O or S; Het is a 5-15 membered aromatic ring or ring system comprising at least one ring and 1, 2, 3, or 4 O, S, or N atoms, provided no O or S is adjacent to another O or S; Cak is a 3-8 membered non-aromatic carbocyclic ring or ring system, which may be saturated or partially unsaturated; and Ar is a 6-16 membered aromatic ring or ring system having at least one carbocyclic aromatic ring optionally fused one or more aromatic or non-aromatic rings Hca is a 3-15 membered ring or ring system comprising at least one ring and 1, 2, 3, or 4 O, S, or N atoms, provided no O or S is adjacent to another O or S; Het is a 5-15 membered aromatic ring or ring system comprising at least one ring and 1, 2, 3, or 4 O, S, or N atoms, provided no O or S is adjacent to another O or S; Cak is a 3-8 membered non-aromatic carbocyclic ring or ring system, which may be saturated or partially unsaturated; and Ar is a 6-16 membered aromatic ring or ring system having at least one carbocyclic aromatic ring optionally fused one or more aromatic or non-aromatic rings