| CPC A61K 31/506 (2013.01) [A61K 31/517 (2013.01); A61K 31/53 (2013.01); A61K 31/5377 (2013.01); A61K 31/5386 (2013.01); A61K 31/69 (2013.01); A61K 45/06 (2013.01); A61P 35/00 (2018.01); C07D 401/14 (2013.01); C07D 405/14 (2013.01); C07D 409/14 (2013.01); C07D 413/14 (2013.01); C07D 471/04 (2013.01); C07D 498/08 (2013.01); C07F 5/027 (2013.01); C07B 2200/05 (2013.01); C07B 2200/07 (2013.01); C07B 2200/09 (2013.01); C07B 2200/13 (2013.01)] | 8 Claims |
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1. 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, unsubstituted or substituted hydrocarbon group which contains from 1 to 20 carbon atoms and 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 C1-6 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;
each Rx is independently selected from -halogen, —OH, unsubstituted or substituted —O-C1-6 alkyl, unsubstituted or substituted —NH-C1-6 alkyl, unsubstituted or substituted —N(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), unsubstituted or substituted-O-(C1-6 alkylene)-(carbocyclyl), unsubstituted or substituted-O-(C1-6 alkylene)-(substituted carbocyclyl), unsubstituted or substituted-O-(C1-6 alkylene)-(heterocyclyl), and unsubstituted or substituted-O-(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; and wherein the compound of Formula (I) is selected from the group consisting of:
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