Heterocyclic derivatives, pharmaceutical compositions and their use in the treatment or amelioration of cancer

A compound of formula (I), or a pharmaceutically acceptable salt, solvate, cocrystal, tautomer, racemate, enantiomer, or diastereomer or mixture thereof

• wherein
• R1 is selected from halogen, an unsubstituted or substituted hydrocarbon group which contains from 1 to 20 carbon atoms, and an unsubstituted or substituted hydrocarbon group which contains from 1 to 20 carbon atoms and 1 to 15 heteroatoms selected from O, N and S;
• R21 is selected from hydrogen, unsubstituted or substituted C1-4 alkyl, unsubstituted or substituted C1-6 alkyl which contains one to three oxygen atoms between carbon atoms, and unsubstituted or substituted C3-6 cycloalkyl);
• R3 is selected from unsubstituted or substituted heterocyclyl, unsubstituted or substituted carbocyclyl, unsubstituted or substituted C1-6 alkylene-(heterocyclyl), unsubstituted or substituted C1-6 alkylene-(substituted heterocyclyl), unsubstituted or substituted C1-6 alkylene-(carbocyclyl) and unsubstituted or substituted C1-6 alkylene-(substituted carbocyclyl);
• each of X1, X2 and X3 is independently selected from N, CH and CRx, wherein at least one of said X1, X2 and X3 is N;
• R31 is selected from -hydrogen, —C1-6-alkyl, and —C1-6-alkyl substituted with one or more F;
• wherein R3 and any R31 are separate substituents or linked with each other;
• and
• E is either absent or is selected from —CH2—, —CHRx—, —CRx2—, —NH—, —NRx—, —O—, -L1-L2- and -L2-L1-, wherein L1 is selected from —CH2—, —CHRx—, —CRx2—, —NH—, —NRx— and —O— and L2 is selected from —CH2—, —CHRx— and —CRx2—;
• R6x is -halogen, —OH, ═O, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkyl substituted with one or more OH, monocyclic aryl unsubstituted or substituted with one or more Rxb, monocyclic heteroaryl unsubstituted or substituted with one or more Rxb, monocyclic cycloalkyl unsubstituted or substituted with one or more Rxb, monocyclic heterocycloalkyl unsubstituted or substituted with one or more Rxb, monocyclic cycloalkenyl unsubstituted or substituted with one or more Rxb, monocyclic heterocycloalkenyl unsubstituted or substituted with one or more Rxb, wherein said Rxb is independently selected from -halogen, —OH, ═O, C1-4 alkyl, C1-2 haloalkyl, C1-2 alkyl substituted with one or two OH;
• wherein Ring A is further unsubstituted or substituted with one or more groups Rx, wherein any two Rx groups at ring A are separate substituents or linked with each other, or any Rx group at ring A is a separate substituent or linked with R21;
• or wherein Ring A is further substituted with one group Rx so as to form together with R6x a bicyclic moiety having the following partial structure:
• wherein Ring B is an unsubstituted or substituted heterocycle or unsubstituted or substituted carbocycle;
• each Rx is independently selected from -halogen, —OH, —O-(unsubstituted or substituted C1-6 alkyl), —NH-(unsubstituted or substituted C1-6 alkyl), —N(unsubstituted or substituted C1-6 alkyl)2, ═O, -(unsubstituted or substituted C1-6 alkyl), unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted C1-6 alkylene carbocyclyl), unsubstituted or substituted —C1-6 alkylene-(substituted carbocyclyl), unsubstituted or substituted C1-6 alkylene-(heterocyclyl), unsubstituted or substituted —C1-6 alkylene-(substituted heterocyclyl), —O-(unsubstituted or substituted C1-6 alkylene)-(carbocyclyl), —O-(unsubstituted or substituted C1-6 alkylene)-(substituted carbocyclyl), —O-(unsubstituted or substituted C1-6 alkylene)-(substituted heterocyclyl), and —O-(unsubstituted or substituted C1-6 alkylene)-(substituted heterocyclyl), and
• wherein the substituent of the substituted hydrocarbon group, substituted C3-6 cycloalkyl, substituted heterocyclyl, substituted heterocycle, substituted carbocyclyl, substituted carbocycle and substituted C1-6 alkylene is independently selected from —C1-6 alkyl, —C1-6 alkyl substituted with one or more halogen, -halogen, —CN, —NO2, oxo, —C(O)R*, —COOR*, —C(O)NR*R*, —NR*R*, —N(R*)—C(O)R*, —N(R*)—C(O)—OR*, —N(R*)—C(O)—NR*R*, —N(R*)—S(O)2R*, —OR*, —O—C(O)R*, —O—C(O)—NR*R*, —SR*, —S(O)R*, —S(O)2R*, —S(O)2—NR*R*, —N(R*)—S(O)2—NR*R*, heterocyclyl, heterocyclyl substituted with halogen or C1-6 alkyl, carbocyclyl, and carbocyclyl substituted with halogen or C1-6 alkyl;
• wherein each R* is independently selected from H, C1-6 alkyl, C1-6 alkyl substituted with halogen, heterocyclyl, heterocyclyl substituted with halogen or C1-6 alkyl, carbocyclyl, and carbocyclyl substituted with halogen or C1-6 alkyl;
• wherein any two R* connected to the same nitrogen atom are either separate substituents or linked with each other, and
• wherein the substituent of the substituted C1-6 alkyl and of the substituted C1-6 alkylene is independently selected from -halogen, —CN, —NO2, oxo, —C(O)R**, —COOR**, —C(O)NR**R**, —NR**R**, —N(R**)—C(O)R**, —N(R**)—C(O)—OR**, —N(R**)—C(O)—NR**R**, —N(R**)—S(O)2R**, —OR**, —O—C(O)R**, —O—C(O)—NR**R**, —SR**, —S(O)R**, —S(O)2R**, —S(O)2—NR**R**, and —N(R**)—S(O)2—NR**R**;
• wherein R** is independently selected from H, C1-6 alkyl, C1-6 alkyl substituted with halogen, heterocyclyl, heterocyclyl substituted with halogen or C1-6 alkyl, carbocyclyl and carbocyclyl substituted with halogen or C1-6 alkyl;
• wherein any two R** connected to the same nitrogen atom are either separate substituents or linked with each other.