Bicyclic heteroarylamides having gpr68 modulating activity

Abstract

Disclosed are novel GPR68 modulators according to Formula (I), their pharmaceutically acceptable salts, and pharmaceutical compositions thereof. Also disclosed are methods of using such compounds and compositions to treat various diseases including cancer and proliferative diseases and disorders.

Description

[0001] BICYCLIC HETEROARYLAMIDES HAVING GPR68 MODULATING ACTIVITY

[0002] TECHNICAL FIELD

[0003] The present invention relates to novel GPR68 modulators, their pharmaceutically acceptable salts, and pharmaceutical compositions thereof. The present invention also relates to methods of using such compounds and compositions, including to treat various diseases and disorders; particularly cancer and / or proliferative diseases or disorders.

[0004] BACKGROUND

[0005] GPR68 (also known as ovarian cancer G protein -coupled receptor 1 or OGR1 ) is a protonsensing G-protein-coupled receptor (GPCR) that responds to extracellular acidity and regulates a variety of cellular functions. It has been found that GPR68 expression is highly upregulated in numerous types of cancer, such as colon cancer, medulloblastoma, head and neck cancer, pancreatic cancer and prostate cancer, and it has been suggested that GPR68 has key roles in tumour biology. As such, GPR68 is an attractive target for anti-cancer drug development. Until now, however, few compounds have been identified as selective GPR68 ligands / modulators.

[0006] An unmet medical need therefore exists for effective and safe GPR68 modulators.

[0007] The present invention has been devised to address at least one of the challenges described above.

[0008] SUMMARY OF THE INVENTION

[0009] Generally, provided herein are compounds and pharmaceutical compositions capable of modulating GPR68. Also provided are method of treatment and therapeutic I medical uses involving compounds or pharmaceutical compositions of this disclosure for for treating diseases, disorders or conditions associated with GPR68.

[0010] In an aspect of this disclosure, there is provided a compound of formula (1 ):

[0011] including any stereoisomer or mixture of stereoisomers including diastereomers and enantiomers, tautomer, isotopic form, pharmaceutically acceptable salt, solvate, prodrug, or pharmaceutically active metabolite thereof, or combinations thereof, wherein:

[0012] Q is O or S;

[0013] X1is selected from C and N;

[0014] X2is selected from CR5and N;

[0015] X3is selected from CR6and N;

[0016] X4is selected from CR7and N;

[0017] X5is selected from C and N; wherein X1, X2, X3, X4and X5are selected so that the ring labelled A is aromatic;

[0018] X6is selected from CR8R9, O and N;

[0019] X7is selected from CR10, CR11R12, O and N; q is 0 or 1 ; wherein when q is 0, X7is O or N; and when X7is O or N and q is 1 , X6is CR8R9;

[0020] L1is a bond, CrCe alkylene, CrCe haloalkylene, C3-C6 cycloalkylene, or a 5- or 6-membered heterocycloalkylene having one or more heteroatoms selected from N, O and S;

[0021] R1is selected from C1-C4 alkyl, C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11 - membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, C9-C10 bicyclic aryl, 5- or 6- membered heteroaryl having one or more ring members selected from N, O and S, 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, phenoxy, and 5- or 6- membered heteroaryloxy having one or more heteroatoms selected from N, O and S, wherein said alkyl, cycloalkyl, bicyclic cycloalkyl, heterocycloalkyl, bicyclic heterocycloalkyl, phenyl, bicyclic aryl, heteroaryl, bicyclic heteroaryl, phenoxy and heteroaryloxy are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, NR1aR1 b, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkyl-NR1aR1 b, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more ring members selected from N, O, S and SO2, benzyl, phenoxy, halophenoxy, 5- or 6- membered heteroaryloxy having one or more heteroatoms selected from N, O and S, and C1-C4 alkyl substituted by a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[0022] R1aand R1 bare each independently selected from H and C1-C4 alkyl;

[0023] R2is selected from H, C1-C4 alkyl and C3-C8 cycloakyl; or R1, R2and L1and the nitrogen atom to which R2and L1are attached form a 3- to 8- membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, 8- to 1 1 -membered bicyclic heterocycloalkyl having one or more heteroatoms selected from N, O and S, 5- or 6- membered heteroaryl having one or more ring members selected from N, O, S and SO2, or 8- to 10-membered bicyclic heteroaryl having one or more heteroatoms selected from N, O and S, wherein said heterocycloalkyl, bicyclic heterocycloalkyl, heteroaryl and bicyclic heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, NR1aR1 b, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy and C1-C4alkyl-NR1aR1 b;

[0024] R3is selected from H, OH, CN, NR3aR3b, C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, and 5- or 6- membered heteroaryl having one or more ring members selected from N, O, S and SO2, C1-C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, C3-C8 cycloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, C1-C4 alkyl-S-C1-C4 alkyl, and C1-C4 alkyl-SO2- C1-C4 alkyl, wherein said alkyl, cycloalkyl, heterocycloalkyl, phenyl and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, C1- C4alkyl, and NR3cR3d;

[0025] R3ais selected from H, C1-C4 alkyl, C1-C4 alkyl-OH, and C1-C4 alkyl-NR3eR3f;

[0026] R3b, R3c, R3d, R3eand R3fare each independently selected from H and C1-C4 alkyl;

[0027] R4is selected from C(O)OH, C(O)NR4aR4b, C(S)NR4aR4band 5- or 6-membered heteroaryl having one or more ring members selected from N, O, S and SO2;

[0028] R4aand R4bare each independently selected from H and C1-C4 alkyl; R5and R6are each independently selected from H, halogen, OH, CN, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 alkoxy-C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl and 5- or 6- membered heteroaryl having one or more ring members selected from N, O, S and SO2; or

[0029] R5and R6together with the carbon atoms to which they are attached form a 5- or 6- membered heterocycloalkyl having one or more heteroatoms selected from N, O and S; and R7, R8, R9, R10, R11, and R12are each independently selected from H, halogen, OH, CN, Cr C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl and 5- or 6- membered heteroaryl having one or more ring members selected from N, O, S and SO2.

[0030] In embodiments,

[0031] L1is a bond, CrCe alkylene, CrCe haloalkylene, C3-C6 cycloalkylene, or a 5- or 6-membered heterocycloalkylene having one or more heteroatoms selected from N, O and S;

[0032] R1is selected from C1-C4 alkyl, C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11 - membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, C9-C10 bicyclic aryl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, phenoxy, and 5- or 6- membered heteroaryloxy having one or more heteroatoms selected from N, O and S, wherein said alkyl, cycloalkyl, bicyclic cycloalkyl, heterocycloalkyl, bicyclic heterocycloalkyl, phenyl, bicyclic aryl, heteroaryl, bicyclic heteroaryl, phenoxy and heteroaryloxy are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, NR1aR1 b, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkyl-NR1aR1 b, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, benzyl, phenoxy, halophenoxy, 5- or 6- membered heteroaryloxy having one or more heteroatoms selected from N, O and S, and C1-C4 alkyl substituted by a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[0033] R1aand R1 bare each independently selected from H and C1-C4 alkyl;

[0034] R2is selected from H, C1-C4 alkyl and C3-C8 cycloakyl;

[0035] R3is selected from H, OH, CN, NR3aR3b, C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C1- C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, C3-C8 cycloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, C1-C4 alkyl-S-C1-C4 alkyl, and C1-C4 alkyl-SC>2- C1-C4 alkyl, wherein said alkyl, cycloalkyl, heterocycloalkyl, phenyl and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, C1-C4 alkyl, and NR3cR3d;

[0036] R3ais selected from H, C1-C4 alkyl, C1-C4 alkyl-OH, and C1-C4 alkyl-NR3eR3f;

[0037] R3b, R3c, R3d, R3eand R3fare each independently selected from H and C1-C4 alkyl;

[0038] R4is selected from C(O)OH, C(O)NR4aR4b, C(S)NR4aR4band 5- or 6-membered heteroaryl having one or more ring members selected from N, O, S and SO2;

[0039] R4aand R4bare each independently selected from H and C1-C4 alkyl;

[0040] R5and R6are each independently selected from H, halogen, OH, CN, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 alkoxy-C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S; or R5and R6together with the carbon atoms to which they are attached form a 5- or 6- membered heterocycloalkyl having one or more heteroatoms selected from N, O and S; and R7, R8, R9, R10, R11, and R12are each independently selected from H, halogen, OH, CN, Cr C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S.

[0041] In embodiments,

[0042] L1is a bond, CrCe alkylene, CrCe haloalkylene, C3-C6 cycloalkylene, or a 5- or 6-membered heterocycloalkylene having one or more heteroatoms selected from N, O and S;

[0043] R1is selected from C1-C4 alkyl, C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11 - membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, and phenoxy, wherein said alkyl, cycloalkyl, heterocycloalkyl, bicyclic cycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, bicyclic heteroaryl, and phenoxy are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, NR1aR1 b, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4alkoxy, C1-C4 haloalkoxy, C1-C4 alkyl-NR1aR1 b, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, benzyl, halophenoxy, and C1-C4 alkyl substituted by a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[0044] R1aand R1 bare each independently selected from H and C1-C4 alkyl;

[0045] R2is H;

[0046] R3is selected from H, CN, NR3aR3b, C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C1-C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, C3-C8 cycloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, C1-C4 alkyl-S-C1-C4 alkyl, and C1-C4 alkyl-SC>2-C1-C4 alkyl, wherein said alkyl, cycloalkyl, heterocycloalkyl, phenyl and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, and NR3cR3d;

[0047] R3ais selected from H, C1-C4 alkyl, and C1-C4 alkyl-NR3eR3f;

[0048] R3bis selected from H and C1-C4 alkyl;

[0049] R3cis selected from H and C1-C4 alkyl;

[0050] R3dis selected from C1-C4 alkyl;

[0051] R3eand R3fare each independently selected from C1-C4 alkyl;

[0052] R4is selected from C(O)OH, C(O)NR4aR4b, C(S)NR4aR4band 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0053] R4ais selected from H and C1-C4 alkyl;

[0054] R4bis H;

[0055] R5is selected from H, C1-C4 alkyl, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0056] R6is selected from H, C1-C4 alkyl, C1-C4 alkoxy, and C1-C4 alkoxy-C1-C4 alkyl; and R7, R8, R9, R10, R11, and R12are each H.

[0057] In embodiments,

[0058] L1is a bond, CrCe alkylene, CrCe haloalkylene, or C3-C6 cycloalkylene;

[0059] R1is selected from C1-C4 alkyl, C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11 - membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, and phenoxy, wherein said alkyl, cycloalkyl, heterocycloalkyl, bicyclic cycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, bicyclic heteroaryl, and phenoxy are each optionally substituted by one or more substituents independently selected from halogen, CN, OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkyl-NR1aR1 b, C3-C8 cycloalkyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, benzyl, and C1-C4 alkyl substituted by a 5- or 6- membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[0060] R1aand R1 bare each independently selected from H and C1-C4 alkyl;

[0061] R2is H;

[0062] R3is selected from H, CN, NR3aR3b, C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C1-C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, C3-C8 cycloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, C1-C4 alkyl-S-C1-C4 alkyl, and C1-C4 alkyl-SC>2-C1-C4 alkyl, wherein said alkyl, cycloalkyl, heterocycloalkyl, phenyl and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH and NR3cR3d;

[0063] R3ais selected from H and C1-C4 alkyl;

[0064] R3bis selected from C1-C4 alkyl;

[0065] R3cis selected from H and C1-C4 alkyl;

[0066] R3dis selected from C1-C4 alkyl;

[0067] R4is selected from C(O)OH, C(O)NR4aR4b, C(S)NR4aR4band 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0068] R4ais selected from H and C1-C4 alkyl;

[0069] R4bis H ;

[0070] R5is selected from H, C1-C4 alkyl, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0071] R6is selected from H, C1-C4 alkyl, C1-C4 alkoxy, and C1-C4 alkoxy-C1-C4 alkyl; and

[0072] R7, R8, R9, R10, R11, and R12are each H.

[0073] In embodiments,

[0074] L1is a bond, CrCe alkylene, or CrCe haloalkylene;

[0075] R1is selected from C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11- membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, and 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, wherein said cycloalkyl, bicyclic cycloalkyl, heterocycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, and bicyclic heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, CN, OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkyl- NR1aR1 b, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0076] R1aand R1 bare each independently selected from H and C1-C4 alkyl;

[0077] R2is H;

[0078] R3is selected from H, CN, NR3aR3b, C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C1-C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, C3-C8 cycloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, C1-C4 alkyl-S-C1-C4 alkyl, and C1-C4 alkyl-SC>2-C1-C4 alkyl, wherein said alkyl, cycloalkyl, heterocycloalkyl, phenyl and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH and NR3cR3d;

[0079] R3ais selected from H and C1-C4 alkyl;

[0080] R3bis selected from C1-C4 alkyl;

[0081] R3cis selected from H and C1-C4 alkyl;

[0082] R3dis selected from C1-C4 alkyl;

[0083] R4is selected from the following groups: wherein indicates the point of attachment to the rest of the compound;

[0084] R5is selected from H and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0085] R6is selected from H, C1-C4 alkyl, C1-C4 alkoxy, and C1-C4 alkoxy-C1-C4 alkyl; and

[0086] R7, R8, R9, R10, R11, and R12are each H.

[0087] In embodiments,

[0088] L1is a bond, CrCe alkylene, or C3-C6 cycloalkylene;

[0089] R1is selected from C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11- membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, and 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, wherein said cycloalkyl, heterocycloalkyl, bicyclic cycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, and bicyclic heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, and C1-C4 haloalkoxy;

[0090] R2is H;

[0091] R3is selected from H, CN, NR3aR3b, C1-C4 alkyl optionally substituted by OH, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C1-C4 alkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, C1-C4 haloalkoxy- C1-C4 alkyl,, C1-C4 alkyl-S-C1-C4 alkyl, and C1-C4 alkyl-SO2-C1-C4 alkyl;

[0092] R3ais H;

[0093] R3bis selected from C1-C4 alkyl;

[0094] R4is selected from the following groups: point of attachment to the rest of the compound;

[0095] R5is H;

[0096] R6is selected from H and C1-C4 alkyl; and R7, R8, R9, R10, R11, and R12are each H.

[0097] In embodiments,

[0098] L1is either a bond or CrCe alkylene;

[0099] R1is selected from C3-C8 cycloalkyl, C8-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11- membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, and 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, wherein said cycloalkyl, bicyclic cycloalkyl, heterocycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, and bicyclic heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, and C1-C4 haloalkoxy;

[0100] R2is H;

[0101] R3is selected from NR3aR3b, C1-C4 alkyl optionally substituted by one or more substituents independently selected from OH and NR3cR3d, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C3-C8 cycloalkoxy-C1-C4 alkyl, C1-C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, and alkyl-S-C1-C4 alkyl;

[0102] R3ais H;

[0103] R3bis selected from C1-C4 alkyl;

[0104] R4is selected from the following groups: point of attachment to the rest of the compound; R5, R7, R8, R9, R10, R11, and R12are each H ; and R6is selected from H and C1-C4 alkyl.

[0105] In embodiments, Q is O.

[0106] In embodiments, L is either a bond or methylene.

[0107] In embodiments, R1is selected from:

[0108] C3-C8 cycloalkyl optionally substituted by one or more substituents independently selected from halogen and C1-C4 haloalkoxy;

[0109] C8-C11 bicyclic cycloalkyl optionally substituted by one or more substituents independently selected from halogen , OH, C1-C4 alkyl and C1-C4 alkoxy;

[0110] 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2;

[0111] 8- to 1 1 -membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, optionally substituted by one or more substituents independently selected from halogen; phenyl optionally substituted by one or more substituents independently selected from halogen and C1-C4 alkyl;

[0112] 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, optionally substituted by one or more substituents independently selected from C1-C4 alkyl and C1-C4 haloalkyl; and

[0113] 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, optionally substituted substituted by one or more substituents independently selected from halogen and C1-C4 alkyl. In embodiments, R2is H.

[0114] In embodiments, R3is selected from:

[0115] - NR3aR3b; - C1-C4 alkyl optionally substituted by OH;

[0116] C3-C8 cycloalkyl;

[0117] 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[0118] 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0119] C1-C4 alkoxy-C1-C4 alkyl;

[0120] C3-C8 cycloalkyl-C1-C4 alkoxy;

[0121] C3-C8cycloalkoxy-C1-C4 alkyl;

[0122] C1-C4 haloalkoxy-C1-C4 alkyl; and - C1-C4 alkyl-S-C1-C4 alkyl; wherein

[0123] R3ais H; and

[0124] R3bis selected from C1-C4 alkyl. In embodiments, R3is selected from C1-C4 alkoxy-C1-C4 alkyl.

[0125] In embodiments, R4is selected from the following groups: , indicates the point of attachment to the rest of the compound.

[0126] In embodiments, R5is H.

[0127] In embodiments, R6is H or methyl. In embodiments, R7, R8, R9, R10, R11, and R12are each H.

[0128] In an aspect of this disclosure, there is provided a compound of formula (2a): including any stereoisomer or mixture of stereoisomers including diastereomers and enantiomers, tautomer, isotopic form, pharmaceutically acceptable salt, solvate, prodrug, or pharmaceutically active metabolite thereof, or combinations thereof, wherein Q is O or S;

[0129] X1is selected from C and N;

[0130] X2is selected from CR5and N;

[0131] X3is selected from CR6and N;

[0132] X4is selected from CR7and N;

[0133] X5is selected from C and N; wherein X1, X2, X3, X4and X5are selected so that the ring labelled A is aromatic;

[0134] X6is selected from CR8R9, O and N;

[0135] X7is selected from CR10, CR11R12, O and N; q is 0 or 1 ; wherein when q is 0, X7is O or N; and when X7is O or N and q is 1 , X6is CR8R9;

[0136] L1is a bond, CrCe alkylene, CrCe haloalkylene, C3-C6 cycloalkylene, or a 5- or 6-membered heterocycloalkylene having one or more heteroatoms selected from N, O and S;

[0137] R1is selected from C1-C4 alkyl, C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11 - membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, C9-C10 bicyclic aryl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, phenoxy, and 5- or 6- membered heteroaryloxy having one or more heteroatoms selected from N, O and S, wherein said alkyl, cycloalkyl, bicyclic cycloalkyl, heterocycloalkyl, bicyclic heterocycloalkyl, phenyl, bicyclic aryl, heteroaryl, bicyclic heteroaryl, phenoxy and heteroaryloxy are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, NR1aR1 b, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkyl-NR1aR1 b, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, benzyl, phenoxy, halophenoxy, 5- or 6- membered heteroaryloxy having one or more heteroatoms selected from N, O and S, and C1-C4 alkyl substituted by a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[0138] R1aand R1 bare each independently selected from H and C1-C4 alkyl;

[0139] R2is selected from H, C1-C4 alkyl and C3-C8 cycloakyl; or R1, R2and L1and the nitrogen atom to which R2and L1are attached form a 3- to 8- membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, 8- to 1 1 -membered bicyclic heterocycloalkyl having one or more heteroatoms selected from N, O and S, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, or 8- to 10-membered bicyclic heteroaryl having one or more heteroatoms selected from N, O and S, wherein said heterocycloalkyl, bicyclic heterocycloalkyl, heteroaryl and bicyclic heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, NR1aR1 b, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy and C1-C4 alkyl-NR1aR1 b;

[0140] R3is selected from H, OH, CN, NR3aR3b, C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, Cr C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, C3-C8 cycloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, C1-C4 alkyl-S-C1-C4 alkyl, and C1-C4 alkyl-SO2- C1-C4 alkyl, wherein said alkyl, cycloalkyl, heterocycloalkyl, phenyl and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, C1-C4 alkyl, and NR3cR3d;

[0141] R3ais selected from H, C1-C4 alkyl, C1-C4 alkyl-OH, and C1-C4 alkyl-NR3eR3f;

[0142] R3b, R3c, R3d, R3eand R3fare each independently selected from H and C1-C4 alkyl;

[0143] R4is selected from C(O)OH, C(O)NR4aR4b, C(S)NR4aR4band 5- or 6-membered heteroaryl having one or more heteroatoms selected from N, O and S; R4aand R4bare each independently selected from H and C1-C4 alkyl;

[0144] R5and R6are each independently selected from H, halogen, OH, CN, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 alkoxy-C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S; or R5and R6together with the carbon atoms to which they are attached form a 5- or 6- membered heterocycloalkyl having one or more heteroatoms selected from N, O and S; and R7, R8, R9, R10, R11, and R12are each independently selected from H, halogen, OH, CN, Cr C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S.

[0145] In embodiments,

[0146] L1is a bond, CrCe alkylene, CrCe haloalkylene, C3-C6 cycloalkylene, or a 5- or 6-membered heterocycloalkylene having one or more heteroatoms selected from N, O and S;

[0147] R1is selected from C1-C4 alkyl, C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11 - membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, C9-C10 bicyclic aryl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, phenoxy, and 5- or 6- membered heteroaryloxy having one or more heteroatoms selected from N, O and S, wherein said alkyl, cycloalkyl, bicyclic cycloalkyl, heterocycloalkyl, bicyclic heterocycloalkyl, phenyl, bicyclic aryl, heteroaryl, bicyclic heteroaryl, phenoxy and heteroaryloxy are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, NR1aR1 b, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkyl-NR1aR1 b, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, benzyl, phenoxy, halophenoxy, 5- or 6- membered heteroaryloxy having one or more heteroatoms selected from N, O and S, and C1-C4 alkyl substituted by a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[0148] R1aand R1 bare each independently selected from H and C1-C4 alkyl;

[0149] R2is selected from H, C1-C4 alkyl and C3-C8 cycloakyl;

[0150] R3is selected from H, OH, CN, NR3aR3b, C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C1- C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, C3-C8 cycloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, C1-C4 alkyl-S-C1-C4 alkyl, and C1-C4 alkyl-SC>2- C1-C4 alkyl, wherein said alkyl, cycloalkyl, heterocycloalkyl, phenyl and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, C1-C4 alkyl, and NR3cR3d;

[0151] R3ais selected from H, C1-C4 alkyl, C1-C4 alkyl-OH, and C1-C4 alkyl-NR3eR3f;

[0152] R3b, R3c, R3d, R3eand R3fare each independently selected from H and C1-C4 alkyl;

[0153] R4is selected from C(O)OH, C(O)NR4aR4b, C(S)NR4aR4band 5- or 6-membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0154] R4aand R4bare each independently selected from H and C1-C4 alkyl;

[0155] R5and R6are each independently selected from H, halogen, OH, CN, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 alkoxy-C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S; or R5and R6together with the carbon atoms to which they are attached form a 5- or 6- membered heterocycloalkyl having one or more heteroatoms selected from N, O and S; and R7, R8, R9, R10, R11, and R12are each independently selected from H, halogen, OH, CN, Cr C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S.

[0156] In embodiments,

[0157] L1is a bond, CrCe alkylene, CrCe haloalkylene, C3-C6 cycloalkylene, or a 5- or 6-membered heterocycloalkylene having one or more heteroatoms selected from N, O and S;

[0158] R1is selected from C1-C4 alkyl, C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11 - membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, 5- or 6- membered heteroaryl having one or more S and SO2. selected from N, O, S and SO2, 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, and phenoxy, wherein said alkyl, cycloalkyl, heterocycloalkyl, bicyclic cycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, bicyclic heteroaryl, and phenoxy are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, NR1aR1 b, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkyl-NR1aR1 b, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, benzyl, halophenoxy, and C1-C4 alkyl substituted by a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[0159] R1aand R1 bare each independently selected from H and C1-C4 alkyl;

[0160] R2is H;

[0161] R3is selected from H, CN, NR3aR3b, C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C1-C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, C3-C8 cycloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, C1-C4 alkyl-S-C1-C4 alkyl, and C1-C4 alkyl-SC>2-C1-C4 alkyl, wherein said alkyl, cycloalkyl, heterocycloalkyl, phenyl and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, and NR3cR3d;

[0162] R3ais selected from H, C1-C4 alkyl, and C1-C4 alkyl-NR3eR3f;

[0163] R3bis selected from H and C1-C4 alkyl;

[0164] R3cis selected from H and C1-C4 alkyl;

[0165] R3dis selected from C1-C4 alkyl;

[0166] R3eand R3fare each independently selected from C1-C4 alkyl;

[0167] R4is selected from C(O)OH, C(O)NR4aR4b, C(S)NR4aR4band 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0168] R4ais selected from H and C1-C4 alkyl;

[0169] R4bis H;

[0170] R5is selected from H, C1-C4 alkyl, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0171] R6is selected from H, C1-C4 alkyl, C1-C4 alkoxy, and C1-C4 alkoxy-C1-C4 alkyl; and R7, R8, R9, R10, R11, and R12are each H.

[0172] In embodiments,

[0173] L1is a bond, CrCe alkylene, CrCe haloalkylene, or C3-C6 cycloalkylene;

[0174] R1is selected from C1-C4 alkyl, C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11 - membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, 5- or 6- membered heteroaryl having one or more ring members selected from N, O, S and SO2, 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, and phenoxy, wherein said alkyl, cycloalkyl, heterocycloalkyl, bicyclic cycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, bicyclic heteroaryl, and phenoxy are each optionally substituted by one or more substituents independently selected from halogen, CN, OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkyl-NR1aR1 b, C3-C8 cycloalkyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, benzyl, and C1-C4 alkyl substituted by a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[0175] R1aand R1 bare each independently selected from H and C1-C4 alkyl;

[0176] R2is H;

[0177] R3is selected from H, CN, NR3aR3b, C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C1-C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, C3-C8 cycloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, C1-C4 alkyl-S-C1-C4 alkyl, and C1-C4 alkyl-SC>2-C1-C4 alkyl, wherein said alkyl, cycloalkyl, heterocycloalkyl, phenyl and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH and NR3cR3d;

[0178] R3ais selected from H and C1-C4 alkyl;

[0179] R3bis selected from C1-C4 alkyl;

[0180] R3cis selected from H and C1-C4 alkyl;

[0181] R3dis selected from C1-C4 alkyl;

[0182] R4is selected from C(O)OH, C(O)NR4aR4b, C(S)NR4aR4band 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0183] R4ais selected from H and C1-C4 alkyl;

[0184] R4bis H ;

[0185] R5is selected from H, C1-C4 alkyl, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0186] R6is selected from H, C1-C4 alkyl, C1-C4 alkoxy, and C1-C4 alkoxy-C1-C4 alkyl; and

[0187] R7, R8, R9, R10, R11, and R12are each H.

[0188] In embodiments,

[0189] L1is a bond, CrCe alkylene, or CrCe haloalkylene;

[0190] R1is selected from C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11- membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, and 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, wherein said cycloalkyl, bicyclic cycloalkyl, heterocycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, and bicyclic heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, CN, OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkyl- NR1aR1 b, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0191] R1aand R1 bare each independently selected from H and C1-C4 alkyl;

[0192] R2is H;

[0193] R3is selected from H, CN, NR3aR3b, C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C1-C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, C3-C8 cycloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, C1-C4 alkyl-S-C1-C4 alkyl, and C1-C4 alkyl-SC>2-C1-C4 alkyl, wherein said alkyl, cycloalkyl, heterocycloalkyl, phenyl and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH and NR3cR3d;

[0194] R3ais selected from H and C1-C4 alkyl;

[0195] R3bis selected from C1-C4 alkyl;

[0196] R3cis selected from H and C1-C4 alkyl;

[0197] R3dis selected from C1-C4 alkyl;

[0198] R4is selected from the following groups: wherein indicates the point of attachment to the rest of the compound;

[0199] R5is selected from H and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0200] R6is selected from H, C1-C4 alkyl, C1-C4 alkoxy, and C1-C4 alkoxy-C1-C4 alkyl; and

[0201] R7, R8, R9, R10, R11, and R12are each H.

[0202] In embodiments,

[0203] L1is a bond, CrCe alkylene, or C3-C6 cycloalkylene;

[0204] R1is selected from C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11- membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, and 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, wherein said cycloalkyl, heterocycloalkyl, bicyclic cycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, and bicyclic heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, and C1-C4 haloalkoxy;

[0205] R2is H;

[0206] R3is selected from H, CN, NR3aR3b, C1-C4 alkyl optionally substituted by OH, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C1-C4 alkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, C1-C4 haloalkoxy- C1-C4 alkyl,, C1-C4 alkyl-S-C1-C4 alkyl, and C1-C4 alkyl-SO2-C1-C4 alkyl;

[0207] R3ais H;

[0208] R3bis selected from C1-C4 alkyl;

[0209] R4is selected from the following groups: point of attachment to the rest of the compound;

[0210] R5is H;

[0211] R6is selected from H and C1-C4 alkyl; and R7, R8, R9, R10, R11, and R12are each H.

[0212] In embodiments,

[0213] L1is either a bond or CrCe alkylene;

[0214] R1is selected from C3-C8 cycloalkyl, C8-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11- membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, and 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, wherein said cycloalkyl, bicyclic cycloalkyl, heterocycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, and bicyclic heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, and C1-C4 haloalkoxy;

[0215] R2is H;

[0216] R3is selected from NR3aR3b, C1-C4 alkyl optionally substituted by one or more substituents independently selected from OH and NR3cR3d, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C3-C8 cycloalkoxy-C1-C4 alkyl, C1-C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, and alkyl-S-C1-C4 alkyl;

[0217] R3ais H;

[0218] R3bis selected from C1-C4 alkyl;

[0219] R4is selected from the following groups: p and

[0220] R6is selected from H and C1-C4 alkyl.

[0221] In embodiments, Q is O.

[0222] In embodiments, L is either a bond or methylene.

[0223] In embodiments, R1is selected from:

[0224] C3-C8 cycloalkyl optionally substituted by one or more substituents independently selected from halogen and C1-C4 haloalkoxy;

[0225] C8-C11 bicyclic cycloalkyl optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl and C1-C4 alkoxy;

[0226] 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2;

[0227] 8- to 11 -membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, optionally substituted by one or more substituents independently selected from halogen; phenyl optionally substituted by one or more substituents independently selected from halogen and C1-C4 alkyl;

[0228] 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, optionally substituted by one or more substituents independently selected from C1-C4 alkyl and C1-C4 haloalkyl; and

[0229] 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, optionally substituted substituted by one or more substituents independently selected from halogen and C1-C4 alkyl. In embodiments, R2is H.

[0230] In embodiments, R3is selected from:

[0231] - NR3aR3b; - C1-C4 alkyl optionally substituted by OH;

[0232] C3-C8 cycloalkyl;

[0233] 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[0234] 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0235] C1-C4 alkoxy-C1-C4 alkyl;

[0236] C3-C8 cycloalkyl-C1-C4 alkoxy;

[0237] C3-C8cycloalkoxy-C1-C4 alkyl;

[0238] C1-C4 haloalkoxy-C1-C4 alkyl; and - C1-C4 alkyl-S-C1-C4 alkyl; wherein

[0239] R3ais H; and

[0240] R3bis selected from C1-C4 alkyl. In embodiments, R3is selected from C1-C4 alkoxy-C1-C4 alkyl.

[0241] In embodiments, R4is selected from the following groups: , indicates the point of attachment to the rest of the compound.

[0242] In embodiments, R5is H.

[0243] In embodiments, R6is H or methyl. In embodiments, R7, R8, R9, R10, R11, and R12are each H.

[0244] In an aspect of this disclosure, there is provided a compound of formula (2aa): including any stereoisomer or mixture of stereoisomers including diastereomers and enantiomers, tautomer, isotopic form, pharmaceutically acceptable salt, solvate, prodrug, or pharmaceutically active metabolite thereof, or combinations thereof, wherein Q is O or S;

[0245] X1is selected from C and N;

[0246] X2is selected from CR5and N;

[0247] X3is selected from CR6and N;

[0248] X4is selected from CR7and N;

[0249] X5is selected from C and N; wherein X1, X2, X3, X4and X5are selected so that the ring labelled A is aromatic;

[0250] X6is selected from CR8R9, O and N;

[0251] X7is selected from CR10, CR11R12, O and N; q is 0 or 1 ; wherein when q is 0, X7is O or N; and when X7is O or N and q is 1 , X6is CR8R9;

[0252] L1is a bond, CrCe alkylene, CrCe haloalkylene, C3-C6 cycloalkylene, or a 5- or 6-membered heterocycloalkylene having one or more heteroatoms selected from N, O and S;

[0253] R1is selected from C1-C4 alkyl, C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11 - membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, C9-C10 bicyclic aryl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, phenoxy, and 5- or 6- membered heteroaryloxy having one or more heteroatoms selected from N, O and S, wherein said alkyl, cycloalkyl, bicyclic cycloalkyl, heterocycloalkyl, bicyclic heterocycloalkyl, phenyl, bicyclic aryl, heteroaryl, bicyclic heteroaryl, phenoxy and heteroaryloxy are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, NR1aR1 b, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkyl-NR1aR1 b, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, benzyl, phenoxy, halophenoxy, 5- or 6- membered heteroaryloxy having one or more heteroatoms selected from N, O and S, and C1-C4 alkyl substituted by a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[0254] R1aand R1 bare each independently selected from H and C1-C4 alkyl;

[0255] R2is selected from H, C1-C4 alkyl and C3-C8 cycloakyl; or R1, R2and L1and the nitrogen atom to which R2and L1are attached form a 3- to 8- membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, 8- to 1 1 -membered bicyclic heterocycloalkyl having one or more heteroatoms selected from N, O and S, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, or 8- to 10-membered bicyclic heteroaryl having one or more heteroatoms selected from N, O and S, wherein said heterocycloalkyl, bicyclic heterocycloalkyl, heteroaryl and bicyclic heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, NR1aR1 b, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy and C1-C4 alkyl-NR1aR1 b;

[0256] R3is selected from H, OH, CN, NR3aR3b, C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, Cr C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, C3-C8 cycloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, C1-C4 alkyl-S-C1-C4 alkyl, and C1-C4 alkyl-SO2- C1-C4 alkyl, wherein said alkyl, cycloalkyl, heterocycloalkyl, phenyl and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, C1-C4 alkyl, and NR3cR3d;

[0257] R3ais selected from H, C1-C4 alkyl, C1-C4 alkyl-OH, and C1-C4 alkyl-NR3eR3f;

[0258] R3b, R3c, R3d, R3eand R3fare each independently selected from H and C1-C4 alkyl;

[0259] R4is selected from C(O)OH, C(O)NR4aR4b, C(S)NR4aR4band 5- or 6-membered heteroaryl having one or more heteroatoms selected from N, O and S; R4aand R4bare each independently selected from H and C1-C4 alkyl;

[0260] R5and R6are each independently selected from H, halogen, OH, CN, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 alkoxy-C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S; or R5and R6together with the carbon atoms to which they are attached form a 5- or 6- membered heterocycloalkyl having one or more heteroatoms selected from N, O and S; and R7, R8, R9, R10, R11, and R12are each independently selected from H, halogen, OH, CN, Cr C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S.

[0261] In embodiments,

[0262] L1is a bond, CrCe alkylene, CrCe haloalkylene, C3-C6 cycloalkylene, or a 5- or 6-membered heterocycloalkylene having one or more heteroatoms selected from N, O and S;

[0263] R1is selected from C1-C4 alkyl, C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11 - membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, C9-C10 bicyclic aryl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, phenoxy, and 5- or 6- membered heteroaryloxy having one or more heteroatoms selected from N, O and S, wherein said alkyl, cycloalkyl, bicyclic cycloalkyl, heterocycloalkyl, bicyclic heterocycloalkyl, phenyl, bicyclic aryl, heteroaryl, bicyclic heteroaryl, phenoxy and heteroaryloxy are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, NR1aR1 b, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkyl-NR1aR1 b, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, benzyl, phenoxy, halophenoxy, 5- or 6- membered heteroaryloxy having one or more heteroatoms selected from N, O and S, and C1-C4 alkyl substituted by a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[0264] R1aand R1 bare each independently selected from H and C1-C4 alkyl;

[0265] R2is selected from H, C1-C4 alkyl and C3-C8 cycloakyl;

[0266] R3is selected from H, OH, CN, NR3aR3b, C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C1- C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, C3-C8 cycloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, C1-C4 alkyl-S-C1-C4 alkyl, and C1-C4 alkyl-SC>2- C1-C4 alkyl, wherein said alkyl, cycloalkyl, heterocycloalkyl, phenyl and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, C1-C4 alkyl, and NR3cR3d;

[0267] R3ais selected from H, C1-C4 alkyl, C1-C4 alkyl-OH, and C1-C4 alkyl-NR3eR3f;

[0268] R3b, R3c, R3d, R3eand R3fare each independently selected from H and C1-C4 alkyl;

[0269] R4is selected from C(O)OH, C(O)NR4aR4b, C(S)NR4aR4band 5- or 6-membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0270] R4aand R4bare each independently selected from H and C1-C4 alkyl;

[0271] R5and R6are each independently selected from H, halogen, OH, CN, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 alkoxy-C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S; or R5and R6together with the carbon atoms to which they are attached form a 5- or 6- membered heterocycloalkyl having one or more heteroatoms selected from N, O and S; and R7, R8, R9, R10, R11, and R12are each independently selected from H, halogen, OH, CN, Cr C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S.

[0272] In embodiments,

[0273] L1is a bond, CrCe alkylene, CrCe haloalkylene, C3-C6 cycloalkylene, or a 5- or 6-membered heterocycloalkylene having one or more heteroatoms selected from N, O and S;

[0274] R1is selected from C1-C4 alkyl, C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11 - membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, and phenoxy, wherein said alkyl, cycloalkyl, heterocycloalkyl, bicyclic cycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, bicyclic heteroaryl, and phenoxy are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, NR1aR1 b, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4alkoxy, C1-C4 haloalkoxy, C1-C4 alkyl-NR1aR1 b, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, benzyl, halophenoxy, and C1-C4 alkyl substituted by a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[0275] R1aand R1 bare each independently selected from H and C1-C4 alkyl;

[0276] R2is H;

[0277] R3is selected from H, CN, NR3aR3b, C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C1-C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, C3-C8 cycloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, C1-C4 alkyl-S-C1-C4 alkyl, and C1-C4 alkyl-SC>2-C1-C4 alkyl, wherein said alkyl, cycloalkyl, heterocycloalkyl, phenyl and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, and NR3cR3d;

[0278] R3ais selected from H, C1-C4 alkyl, and C1-C4 alkyl-NR3eR3f;

[0279] R3bis selected from H and C1-C4 alkyl;

[0280] R3cis selected from H and C1-C4 alkyl;

[0281] R3dis selected from C1-C4 alkyl;

[0282] R3eand R3fare each independently selected from C1-C4 alkyl;

[0283] R4is selected from C(O)OH, C(O)NR4aR4b, C(S)NR4aR4band 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0284] R4ais selected from H and C1-C4 alkyl;

[0285] R4bis H;

[0286] R5is selected from H, C1-C4 alkyl, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0287] R6is selected from H, C1-C4 alkyl, C1-C4 alkoxy, and C1-C4 alkoxy-C1-C4 alkyl; and R7, R8, R9, R10, R11, and R12are each H.

[0288] In embodiments,

[0289] L1is a bond, CrCe alkylene, CrCe haloalkylene, or C3-C6 cycloalkylene;

[0290] R1is selected from C1-C4 alkyl, C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11 - membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, and phenoxy, wherein said alkyl, cycloalkyl, heterocycloalkyl, bicyclic cycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, bicyclic heteroaryl, and phenoxy are each optionally substituted by one or more substituents independently selected from halogen, CN, OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkyl-NR1aR1 b, C3-C8 cycloalkyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, benzyl, and C1-C4 alkyl substituted by a 5- or 6- membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[0291] R1aand R1 bare each independently selected from H and C1-C4 alkyl;

[0292] R2is H;

[0293] R3is selected from H, CN, NR3aR3b, C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C1-C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, C3-C8 cycloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, C1-C4 alkyl-S-C1-C4 alkyl, and C1-C4 alkyl-SC>2-C1-C4 alkyl, wherein said alkyl, cycloalkyl, heterocycloalkyl, phenyl and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH and NR3cR3d;

[0294] R3ais selected from H and C1-C4 alkyl;

[0295] R3bis selected from C1-C4 alkyl;

[0296] R3cis selected from H and C1-C4 alkyl;

[0297] R3dis selected from C1-C4 alkyl;

[0298] R4is selected from C(O)OH, C(O)NR4aR4b, C(S)NR4aR4band 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0299] R4ais selected from H and C1-C4 alkyl;

[0300] R4bis H ;

[0301] R5is selected from H, C1-C4 alkyl, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0302] R6is selected from H, C1-C4 alkyl, C1-C4 alkoxy, and C1-C4 alkoxy-C1-C4 alkyl; and

[0303] R7, R8, R9, R10, R11, and R12are each H.

[0304] In embodiments,

[0305] L1is a bond, CrCe alkylene, or CrCe haloalkylene;

[0306] R1is selected from C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11- membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, and 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, wherein said cycloalkyl, bicyclic cycloalkyl, heterocycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, and bicyclic heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, CN, OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkyl- NR1aR1 b, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0307] R1aand R1 bare each independently selected from H and C1-C4 alkyl;

[0308] R2is H;

[0309] R3is selected from H, CN, NR3aR3b, C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C1-C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, C3-C8 cycloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, C1-C4 alkyl-S-C1-C4 alkyl, and C1-C4 alkyl-SC>2-C1-C4 alkyl, wherein said alkyl, cycloalkyl, heterocycloalkyl, phenyl and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH and NR3cR3d;

[0310] R3ais selected from H and C1-C4 alkyl;

[0311] R3bis selected from C1-C4 alkyl;

[0312] R3cis selected from H and C1-C4 alkyl;

[0313] R3dis selected from C1-C4 alkyl;

[0314] R4is selected from the following groups: wherein indicates the point of attachment to the rest of the compound;

[0315] R5is selected from H and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0316] R6is selected from H, C1-C4 alkyl, C1-C4 alkoxy, and C1-C4 alkoxy-C1-C4 alkyl; and

[0317] R7, R8, R9, R10, R11, and R12are each H.

[0318] In embodiments,

[0319] L1is a bond, CrCe alkylene, or C3-C6 cycloalkylene;

[0320] R1is selected from C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11- membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, and 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, wherein said cycloalkyl, heterocycloalkyl, bicyclic cycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, and bicyclic heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, and C1-C4 haloalkoxy;

[0321] R2is H;

[0322] R3is selected from H, CN, NR3aR3b, C1-C4 alkyl optionally substituted by OH, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C1-C4 alkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, C1-C4 haloalkoxy- C1-C4 alkyl,, C1-C4 alkyl-S-C1-C4 alkyl, and C1-C4 alkyl-SO2-C1-C4 alkyl;

[0323] R3ais H;

[0324] R3bis selected from C1-C4 alkyl;

[0325] R4is selected from the following groups: point of attachment to the rest of the compound;

[0326] R5is H;

[0327] R6is selected from H and C1-C4 alkyl; and R7, R8, R9, R10, R11, and R12are each H.

[0328] In embodiments,

[0329] L1is either a bond or CrCe alkylene;

[0330] R1is selected from C3-C8 cycloalkyl, C8-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11- membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, and 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, wherein said cycloalkyl, bicyclic cycloalkyl, heterocycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, and bicyclic heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, and C1-C4 haloalkoxy;

[0331] R2is H;

[0332] R3is selected from NR3aR3b, C1-C4 alkyl optionally substituted by one or more substituents independently selected from OH and NR3cR3d, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C3-C8 cycloalkoxy-C1-C4 alkyl, C1-C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, and alkyl-S-C1-C4 alkyl;

[0333] R3ais H;

[0334] R3bis selected from C1-C4 alkyl;

[0335] R4is selected from the following groups: p and

[0336] R6is selected from H and C1-C4 alkyl.

[0337] In embodiments, Q is O.

[0338] In embodiments, L is either a bond or methylene.

[0339] In embodiments, R1is selected from:

[0340] C3-C8 cycloalkyl optionally substituted by one or more substituents independently selected from halogen and C1-C4 haloalkoxy;

[0341] C8-C11 bicyclic cycloalkyl optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl and C1-C4 alkoxy;

[0342] 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2;

[0343] 8- to 11 -membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, optionally substituted by one or more substituents independently selected from halogen; phenyl optionally substituted by one or more substituents independently selected from halogen and C1-C4 alkyl;

[0344] 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, optionally substituted by one or more substituents independently selected from C1-C4 alkyl and C1-C4 haloalkyl; and

[0345] 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, optionally substituted substituted by one or more substituents independently selected from halogen and C1-C4 alkyl. In embodiments, R2is H.

[0346] In embodiments, R3is selected from:

[0347] - NR3aR3b; - C1-C4 alkyl optionally substituted by OH;

[0348] C3-C8 cycloalkyl;

[0349] 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[0350] 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0351] C1-C4 alkoxy-C1-C4 alkyl;

[0352] C3-C8 cycloalkyl-C1-C4 alkoxy;

[0353] C3-C8cycloalkoxy-C1-C4 alkyl;

[0354] C1-C4 haloalkoxy-C1-C4 alkyl; and - C1-C4 alkyl-S-C1-C4 alkyl; wherein

[0355] R3ais H; and

[0356] R3bis selected from C1-C4 alkyl. In embodiments, R3is selected from C1-C4 alkoxy-C1-C4 alkyl.

[0357] In embodiments, R4is selected from the following groups: , indicates the point of attachment to the rest of the compound.

[0358] In embodiments, R5is H.

[0359] In embodiments, R6is H or methyl. In embodiments, R7, R8, R9, R10, R11, and R12are each H.

[0360] In an aspect of this disclosure, there is provided a compound of formula (2ab): including any stereoisomer or mixture of stereoisomers including diastereomers and enantiomers, tautomer, isotopic form, pharmaceutically acceptable salt, solvate, prodrug, or pharmaceutically active metabolite thereof, or combinations thereof, wherein Q is O or S;

[0361] X1is selected from C and N;

[0362] X2is selected from CR5and N;

[0363] X3is selected from CR6and N;

[0364] X4is selected from CR7and N;

[0365] X5is selected from C and N; wherein X1, X2, X3, X4and X5are selected so that the ring labelled A is aromatic;

[0366] X6is selected from CR8R9, O and N;

[0367] X7is selected from CR10, CR11R12, O and N; q is 0 or 1 ; wherein when q is 0, X7is O or N; and when X7is O or N and q is 1 , X6is CR8R9;

[0368] L1is a bond, CrCe alkylene, CrCe haloalkylene, C3-C6 cycloalkylene, or a 5- or 6-membered heterocycloalkylene having one or more heteroatoms selected from N, O and S;

[0369] R1is selected from C1-C4 alkyl, C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11 - membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, C9-C10 bicyclic aryl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, phenoxy, and 5- or 6- membered heteroaryloxy having one or more heteroatoms selected from N, O and S, wherein said alkyl, cycloalkyl, bicyclic cycloalkyl, heterocycloalkyl, bicyclic heterocycloalkyl, phenyl, bicyclic aryl, heteroaryl, bicyclic heteroaryl, phenoxy and heteroaryloxy are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, NR1aR1 b, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkyl-NR1aR1 b, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, benzyl, phenoxy, halophenoxy, 5- or 6- membered heteroaryloxy having one or more heteroatoms selected from N, O and S, and C1-C4 alkyl substituted by a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[0370] R1aand R1 bare each independently selected from H and C1-C4 alkyl;

[0371] R2is selected from H, C1-C4 alkyl and C3-C8 cycloakyl; or R1, R2and L1and the nitrogen atom to which R2and L1are attached form a 3- to 8- membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, 8- to 1 1 -membered bicyclic heterocycloalkyl having one or more heteroatoms selected from N, O and S, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, or 8- to 10-membered bicyclic heteroaryl having one or more heteroatoms selected from N, O and S, wherein said heterocycloalkyl, bicyclic heterocycloalkyl, heteroaryl and bicyclic heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, NR1aR1 b, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy and C1-C4 alkyl-NR1aR1 b;

[0372] R3is selected from H, OH, CN, NR3aR3b, C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, Cr C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, C3-C8 cycloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, C1-C4 alkyl-S-C1-C4 alkyl, and C1-C4 alkyl-SO2- C1-C4 alkyl, wherein said alkyl, cycloalkyl, heterocycloalkyl, phenyl and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, C1-C4 alkyl, and NR3cR3d;

[0373] R3ais selected from H, C1-C4 alkyl, C1-C4 alkyl-OH, and C1-C4 alkyl-NR3eR3f;

[0374] R3b, R3c, R3d, R3eand R3fare each independently selected from H and C1-C4 alkyl;

[0375] R4is selected from C(O)OH, C(O)NR4aR4b, C(S)NR4aR4band 5- or 6-membered heteroaryl having one or more heteroatoms selected from N, O and S; R4aand R4bare each independently selected from H and C1-C4 alkyl;

[0376] R5and R6are each independently selected from H, halogen, OH, CN, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 alkoxy-C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S; or R5and R6together with the carbon atoms to which they are attached form a 5- or 6- membered heterocycloalkyl having one or more heteroatoms selected from N, O and S; and R7, R8, R9, R10, R11, and R12are each independently selected from H, halogen, OH, CN, Cr C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S.

[0377] In embodiments,

[0378] L1is a bond, CrCe alkylene, CrCe haloalkylene, C3-C6 cycloalkylene, or a 5- or 6-membered heterocycloalkylene having one or more heteroatoms selected from N, O and S;

[0379] R1is selected from C1-C4 alkyl, C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11 - membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, C9-C10 bicyclic aryl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, phenoxy, and 5- or 6- membered heteroaryloxy having one or more heteroatoms selected from N, O and S, wherein said alkyl, cycloalkyl, bicyclic cycloalkyl, heterocycloalkyl, bicyclic heterocycloalkyl, phenyl, bicyclic aryl, heteroaryl, bicyclic heteroaryl, phenoxy and heteroaryloxy are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, NR1aR1 b, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkyl-NR1aR1 b, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, benzyl, phenoxy, halophenoxy, 5- or 6- membered heteroaryloxy having one or more heteroatoms selected from N, O and S, and C1-C4 alkyl substituted by a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[0380] R1aand R1 bare each independently selected from H and C1-C4 alkyl;

[0381] R2is selected from H, C1-C4 alkyl and C3-C8 cycloakyl;

[0382] R3is selected from H, OH, CN, NR3aR3b, C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C1- C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, C3-C8 cycloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, C1-C4 alkyl-S-C1-C4 alkyl, and C1-C4 alkyl-SC>2- C1-C4 alkyl, wherein said alkyl, cycloalkyl, heterocycloalkyl, phenyl and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, C1-C4 alkyl, and NR3cR3d;

[0383] R3ais selected from H, C1-C4 alkyl, C1-C4 alkyl-OH, and C1-C4 alkyl-NR3eR3f;

[0384] R3b, R3c, R3d, R3eand R3fare each independently selected from H and C1-C4 alkyl;

[0385] R4is selected from C(O)OH, C(O)NR4aR4b, C(S)NR4aR4band 5- or 6-membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0386] R4aand R4bare each independently selected from H and C1-C4 alkyl;

[0387] R5and R6are each independently selected from H, halogen, OH, CN, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 alkoxy-C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S; or R5and R6together with the carbon atoms to which they are attached form a 5- or 6- membered heterocycloalkyl having one or more heteroatoms selected from N, O and S; and R7, R8, R9, R10, R11, and R12are each independently selected from H, halogen, OH, CN, Cr C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S.

[0388] In embodiments,

[0389] L1is a bond, CrCe alkylene, CrCe haloalkylene, C3-C6 cycloalkylene, or a 5- or 6-membered heterocycloalkylene having one or more heteroatoms selected from N, O and S;

[0390] R1is selected from C1-C4 alkyl, C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11 - membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, and phenoxy, wherein said alkyl, cycloalkyl, heterocycloalkyl, bicyclic cycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, bicyclic heteroaryl, and phenoxy are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, NR1aR1 b, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4alkoxy, C1-C4 haloalkoxy, C1-C4 alkyl-NR1aR1 b, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, benzyl, halophenoxy, and C1-C4 alkyl substituted by a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[0391] R1aand R1 bare each independently selected from H and C1-C4 alkyl;

[0392] R2is H;

[0393] R3is selected from H, CN, NR3aR3b, C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C1-C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, C3-C8 cycloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, C1-C4 alkyl-S-C1-C4 alkyl, and C1-C4 alkyl-SC>2-C1-C4 alkyl, wherein said alkyl, cycloalkyl, heterocycloalkyl, phenyl and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, and NR3cR3d;

[0394] R3ais selected from H, C1-C4 alkyl, and C1-C4 alkyl-NR3eR3f;

[0395] R3bis selected from H and C1-C4 alkyl;

[0396] R3cis selected from H and C1-C4 alkyl;

[0397] R3dis selected from C1-C4 alkyl;

[0398] R3eand R3fare each independently selected from C1-C4 alkyl;

[0399] R4is selected from C(O)OH, C(O)NR4aR4b, C(S)NR4aR4band 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0400] R4ais selected from H and C1-C4 alkyl;

[0401] R4bis H;

[0402] R5is selected from H, C1-C4 alkyl, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0403] R6is selected from H, C1-C4 alkyl, C1-C4 alkoxy, and C1-C4 alkoxy-C1-C4 alkyl; and R7, R8, R9, R10, R11, and R12are each H.

[0404] In embodiments,

[0405] L1is a bond, CrCe alkylene, CrCe haloalkylene, or C3-C6 cycloalkylene;

[0406] R1is selected from C1-C4 alkyl, C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11 - membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, and phenoxy, wherein said alkyl, cycloalkyl, heterocycloalkyl, bicyclic cycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, bicyclic heteroaryl, and phenoxy are each optionally substituted by one or more substituents independently selected from halogen, CN, OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkyl-NR1aR1 b, C3-C8 cycloalkyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, benzyl, and C1-C4 alkyl substituted by a 5- or 6- membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[0407] R1aand R1 bare each independently selected from H and C1-C4 alkyl;

[0408] R2is H;

[0409] R3is selected from H, CN, NR3aR3b, C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C1-C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, C3-C8 cycloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, C1-C4 alkyl-S-C1-C4 alkyl, and C1-C4 alkyl-SC>2-C1-C4 alkyl, wherein said alkyl, cycloalkyl, heterocycloalkyl, phenyl and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH and NR3cR3d;

[0410] R3ais selected from H and C1-C4 alkyl;

[0411] R3bis selected from C1-C4 alkyl;

[0412] R3cis selected from H and C1-C4 alkyl;

[0413] R3dis selected from C1-C4 alkyl;

[0414] R4is selected from C(O)OH, C(O)NR4aR4b, C(S)NR4aR4band 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0415] R4ais selected from H and C1-C4 alkyl;

[0416] R4bis H ;

[0417] R5is selected from H, C1-C4 alkyl, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0418] R6is selected from H, C1-C4 alkyl, C1-C4 alkoxy, and C1-C4 alkoxy-C1-C4 alkyl; and

[0419] R7, R8, R9, R10, R11, and R12are each H.

[0420] In embodiments,

[0421] L1is a bond, CrCe alkylene, or CrCe haloalkylene;

[0422] R1is selected from C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11- membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, and 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, wherein said cycloalkyl, bicyclic cycloalkyl, heterocycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, and bicyclic heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, CN, OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkyl- NR1aR1 b, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0423] R1aand R1 bare each independently selected from H and C1-C4 alkyl;

[0424] R2is H;

[0425] R3is selected from H, CN, NR3aR3b, C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C1-C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, C3-C8 cycloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, C1-C4 alkyl-S-C1-C4 alkyl, and C1-C4 alkyl-SC>2-C1-C4 alkyl, wherein said alkyl, cycloalkyl, heterocycloalkyl, phenyl and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH and NR3cR3d;

[0426] R3ais selected from H and C1-C4 alkyl;

[0427] R3bis selected from C1-C4 alkyl;

[0428] R3cis selected from H and C1-C4 alkyl;

[0429] R3dis selected from C1-C4 alkyl;

[0430] R4is selected from the following groups: wherein indicates the point of attachment to the rest of the compound;

[0431] R5is selected from H and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0432] R6is selected from H, C1-C4 alkyl, C1-C4 alkoxy, and C1-C4 alkoxy-C1-C4 alkyl; and

[0433] R7, R8, R9, R10, R11, and R12are each H.

[0434] In embodiments,

[0435] L1is a bond, CrCe alkylene, or C3-C6 cycloalkylene;

[0436] R1is selected from C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11- membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, and 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, wherein said cycloalkyl, heterocycloalkyl, bicyclic cycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, and bicyclic heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, and C1-C4 haloalkoxy;

[0437] R2is H;

[0438] R3is selected from H, CN, NR3aR3b, C1-C4 alkyl optionally substituted by OH, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C1-C4 alkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, C1-C4 haloalkoxy- C1-C4 alkyl,, C1-C4 alkyl-S-C1-C4 alkyl, and C1-C4 alkyl-SO2-C1-C4 alkyl;

[0439] R3ais H;

[0440] R3bis selected from C1-C4 alkyl;

[0441] R4is selected from the following groups: point of attachment to the rest of the compound;

[0442] R5is H;

[0443] R6is selected from H and C1-C4 alkyl; and R7, R8, R9, R10, R11, and R12are each H.

[0444] In embodiments,

[0445] L1is either a bond or CrCe alkylene;

[0446] R1is selected from C3-C8 cycloalkyl, C8-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11- membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, and 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, wherein said cycloalkyl, bicyclic cycloalkyl, heterocycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, and bicyclic heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, and C1-C4 haloalkoxy;

[0447] R2is H;

[0448] R3is selected from NR3aR3b, C1-C4 alkyl optionally substituted by one or more substituents independently selected from OH and NR3cR3d, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C3-C8 cycloalkoxy-C1-C4 alkyl, C1-C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, and alkyl-S-C1-C4 alkyl;

[0449] R3ais H;

[0450] R3bis selected from C1-C4 alkyl;

[0451] R4is selected from the following groups: p and

[0452] R6is selected from H and C1-C4 alkyl.

[0453] In embodiments, Q is O.

[0454] In embodiments, L is either a bond or methylene.

[0455] In embodiments, R1is selected from:

[0456] C3-C8 cycloalkyl optionally substituted by one or more substituents independently selected from halogen and C1-C4 haloalkoxy;

[0457] C8-C11 bicyclic cycloalkyl optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl and C1-C4 alkoxy;

[0458] 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2;

[0459] 8- to 11 -membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, optionally substituted by one or more substituents independently selected from halogen; phenyl optionally substituted by one or more substituents independently selected from halogen and C1-C4 alkyl;

[0460] 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, optionally substituted by one or more substituents independently selected from C1-C4 alkyl and C1-C4 haloalkyl; and

[0461] 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, optionally substituted substituted by one or more substituents independently selected from halogen and C1-C4 alkyl. In embodiments, R2is H.

[0462] In embodiments, R3is selected from:

[0463] - NR3aR3b; - C1-C4 alkyl optionally substituted by OH;

[0464] C3-C8 cycloalkyl;

[0465] 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[0466] 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0467] C1-C4 alkoxy-C1-C4 alkyl;

[0468] C3-C8 cycloalkyl-C1-C4 alkoxy;

[0469] C3-C8cycloalkoxy-C1-C4 alkyl;

[0470] C1-C4 haloalkoxy-C1-C4 alkyl; and - C1-C4 alkyl-S-C1-C4 alkyl; wherein

[0471] R3ais H; and

[0472] R3bis selected from C1-C4 alkyl. In embodiments, R3is selected from C1-C4 alkoxy-C1-C4 alkyl.

[0473] In embodiments, R4is selected from the following groups: , indicates the point of attachment to the rest of the compound.

[0474] In embodiments, R5is H.

[0475] In embodiments, R6is H or methyl. In embodiments, R7, R8, R9, R10, R11, and R12are each H.

[0476] In an aspect of this disclosure, there is provided a compound of formula (2ad): including any stereoisomer or mixture of stereoisomers including diastereomers and enantiomers, tautomer, isotopic form, pharmaceutically acceptable salt, solvate, prodrug, or pharmaceutically active metabolite thereof, or combinations thereof, wherein Q is O or S;

[0477] X1is selected from C and N;

[0478] X2is selected from CR5and N;

[0479] X3is selected from CR6and N;

[0480] X4is selected from CR7and N;

[0481] X5is selected from C and N; wherein X1, X2, X3, X4and X5are selected so that the ring labelled A is aromatic;

[0482] X6is selected from CR8R9, O and N;

[0483] X7is selected from CR10, CR11R12, O and N; q is 0 or 1 ; wherein when q is 0, X7is O or N; and when X7is O or N and q is 1 , X6is CR8R9;

[0484] L1is a bond, CrCe alkylene, CrCe haloalkylene, C3-C6 cycloalkylene, or a 5- or 6-membered heterocycloalkylene having one or more heteroatoms selected from N, O and S;

[0485] R1is selected from C1-C4 alkyl, C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 1 1 - membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, C9-C10 bicyclic aryl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, phenoxy, and 5- or 6- membered heteroaryloxy having one or more heteroatoms selected from N, O and S, wherein said alkyl, cycloalkyl, bicyclic cycloalkyl, heterocycloalkyl, bicyclic heterocycloalkyl, phenyl, bicyclic aryl, heteroaryl, bicyclic heteroaryl, phenoxy and heteroaryloxy are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, NR1aR1 b, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkyl-NR1aR1 b, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, benzyl, phenoxy, halophenoxy, 5- or 6- membered heteroaryloxy having one or more heteroatoms selected from N, O and S, and C1-C4 alkyl substituted by a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[0486] R1aand R1 bare each independently selected from H and C1-C4 alkyl;

[0487] R2is selected from H, C1-C4 alkyl and C3-C8 cycloakyl; or R1, R2and L1and the nitrogen atom to which R2and L1are attached form a 3- to 8- membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, 8- to 1 1 -membered bicyclic heterocycloalkyl having one or more heteroatoms selected from N, O and S, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, or 8- to 10-membered bicyclic heteroaryl having one or more heteroatoms selected from N, O and S, wherein said heterocycloalkyl, bicyclic heterocycloalkyl, heteroaryl and bicyclic heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, NR1aR1 b, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy and C1-C4 alkyl-NR1aR1 b;

[0488] R3is selected from H, OH, CN, NR3aR3b, C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, Cr C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, C3-C8 cycloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, C1-C4 alkyl-S-C1-C4 alkyl, and C1-C4 alkyl-SO2- C1-C4 alkyl, wherein said alkyl, cycloalkyl, heterocycloalkyl, phenyl and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, C1-C4 alkyl, and NR3cR3d;

[0489] R3ais selected from H, C1-C4 alkyl, C1-C4 alkyl-OH, and C1-C4 alkyl-NR3eR3f;

[0490] R3b, R3c, R3d, R3eand R3fare each independently selected from H and C1-C4 alkyl; R4is selected from C(O)OH, C(O)NR4aR4b, C(S)NR4aR4band 5- or 6-membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0491] R4aand R4bare each independently selected from H and C1-C4 alkyl;

[0492] R5and R6are each independently selected from H, halogen, OH, CN, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 alkoxy-C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S; or R5and R6together with the carbon atoms to which they are attached form a 5- or 6- membered heterocycloalkyl having one or more heteroatoms selected from N, O and S; and R7, R8, R9, R10, R11, and R12are each independently selected from H, halogen, OH, CN, Cr C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S.

[0493] In embodiments,

[0494] L1is a bond, CrCe alkylene, CrCe haloalkylene, C3-C6 cycloalkylene, or a 5- or 6-membered heterocycloalkylene having one or more heteroatoms selected from N, O and S;

[0495] R1is selected from C1-C4 alkyl, C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11 - membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, C9-C10 bicyclic aryl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, phenoxy, and 5- or 6- membered heteroaryloxy having one or more heteroatoms selected from N, O and S, wherein said alkyl, cycloalkyl, bicyclic cycloalkyl, heterocycloalkyl, bicyclic heterocycloalkyl, phenyl, bicyclic aryl, heteroaryl, bicyclic heteroaryl, phenoxy and heteroaryloxy are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, NR1aR1 b, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkyl-NR1aR1 b, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, benzyl, phenoxy, halophenoxy, 5- or 6- membered heteroaryloxy having one or more heteroatoms selected from N, O and S, and C1-C4 alkyl substituted by a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[0496] R1aand R1 bare each independently selected from H and C1-C4 alkyl;

[0497] R2is selected from H, C1-C4 alkyl and C3-C8 cycloakyl; R3is selected from H, OH, CN, NR3aR3b, C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, Ci- 04 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, C3-C8 cycloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, C1-C4 alkyl-S-C1-C4 alkyl, and C1-C4 alkyl-SO2- C1-C4 alkyl, wherein said alkyl, cycloalkyl, heterocycloalkyl, phenyl and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, C1-C4 alkyl, and NR3cR3d;

[0498] R3ais selected from H, C1-C4 alkyl, C1-C4 alkyl-OH, and C1-C4 alkyl-NR3eR3f;

[0499] R3b, R3c, R3d, R3eand R3fare each independently selected from H and C1-C4 alkyl;

[0500] R4is selected from C(O)OH, C(O)NR4aR4b, C(S)NR4aR4band 5- or 6-membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0501] R4aand R4bare each independently selected from H and C1-C4 alkyl;

[0502] R5and R6are each independently selected from H, halogen, OH, CN, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 alkoxy-C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S; or R5and R6together with the carbon atoms to which they are attached form a 5- or 6- membered heterocycloalkyl having one or more heteroatoms selected from N, O and S; and R7, R8, R9, R10, R11, and R12are each independently selected from H, halogen, OH, CN, Cr C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S.

[0503] In embodiments,

[0504] L1is a bond, CrCe alkylene, CrCe haloalkylene, C3-C6 cycloalkylene, or a 5- or 6-membered heterocycloalkylene having one or more heteroatoms selected from N, O and S;

[0505] R1is selected from C1-C4 alkyl, C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11 - membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, and phenoxy, wherein said alkyl, cycloalkyl, heterocycloalkyl, bicyclic cycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, bicyclic heteroaryl, and phenoxy are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, NR1aR1 b, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4alkoxy, C1-C4 haloalkoxy, C1-C4 alkyl-NR1aR1 b, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, benzyl, halophenoxy, and C1-C4 alkyl substituted by a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[0506] R1aand R1 bare each independently selected from H and C1-C4 alkyl;

[0507] R2is H;

[0508] R3is selected from H, CN, NR3aR3b, C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C1-C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, C3-C8 cycloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, C1-C4 alkyl-S-C1-C4 alkyl, and C1-C4 alkyl-SC>2-C1-C4 alkyl, wherein said alkyl, cycloalkyl, heterocycloalkyl, phenyl and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, and NR3cR3d;

[0509] R3ais selected from H, C1-C4 alkyl, and C1-C4 alkyl-NR3eR3f;

[0510] R3bis selected from H and C1-C4 alkyl;

[0511] R3cis selected from H and C1-C4 alkyl;

[0512] R3dis selected from C1-C4 alkyl;

[0513] R3eand R3fare each independently selected from C1-C4 alkyl;

[0514] R4is selected from C(O)OH, C(O)NR4aR4b, C(S)NR4aR4band 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0515] R4ais selected from H and C1-C4 alkyl;

[0516] R4bis H;

[0517] R5is selected from H, C1-C4 alkyl, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0518] R6is selected from H, C1-C4 alkyl, C1-C4 alkoxy, and C1-C4 alkoxy-C1-C4 alkyl; and

[0519] R7, R8, R9, R10, R11, and R12are each H.

[0520] In embodiments,

[0521] L1is a bond, CrCe alkylene, CrCe haloalkylene, or C3-C6 cycloalkylene;

[0522] R1is selected from C1-C4 alkyl, C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11 - membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, and phenoxy, wherein said alkyl, cycloalkyl, heterocycloalkyl, bicyclic cycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, bicyclic heteroaryl, and phenoxy are each optionally substituted by one or more substituents independently selected from halogen, CN, OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkyl-NR1aR1 b, C3-C8 cycloalkyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, benzyl, and C1-C4 alkyl substituted by a 5- or 6- membered heterocycloalkyl having one or more heteroatoms selected from N, O and S; R1aand R1 bare each independently selected from H and C1-C4 alkyl;

[0523] R2is H;

[0524] R3is selected from H, CN, NR3aR3b, C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C1-C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, C3-C8 cycloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, C1-C4 alkyl-S-C1-C4 alkyl, and C1-C4 alkyl-SC>2-C1-C4 alkyl, wherein said alkyl, cycloalkyl, heterocycloalkyl, phenyl and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH and NR3cR3d;

[0525] R3ais selected from H and C1-C4 alkyl;

[0526] R3bis selected from C1-C4 alkyl;

[0527] R3cis selected from H and C1-C4 alkyl;

[0528] R3dis selected from C1-C4 alkyl;

[0529] R4is selected from C(O)OH, C(O)NR4aR4b, C(S)NR4aR4band 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0530] R4ais selected from H and C1-C4 alkyl;

[0531] R4bis H ;

[0532] R5is selected from H, C1-C4 alkyl, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0533] R6is selected from H, C1-C4 alkyl, C1-C4 alkoxy, and C1-C4 alkoxy-C1-C4 alkyl; and

[0534] R7, R8, R9, R10, R11, and R12are each H.

[0535] In embodiments,

[0536] L1is a bond, CrCe alkylene, or CrCe haloalkylene;

[0537] R1is selected from C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11- membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, and 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, wherein said cycloalkyl, bicyclic cycloalkyl, heterocycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, and bicyclic heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, CN, OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkyl- NR1aR1 b, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0538] R1aand R1 bare each independently selected from H and C1-C4 alkyl;

[0539] R2is H;

[0540] R3is selected from H, CN, NR3aR3b, C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C1-C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, C3-C8 cycloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, C1-C4 alkyl-S-C1-C4 alkyl, and C1-C4 alkyl-SC>2-C1-C4 alkyl, wherein said alkyl, cycloalkyl, heterocycloalkyl, phenyl and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH and NR3cR3d;

[0541] R3ais selected from H and C1-C4 alkyl;

[0542] R3bis selected from C1-C4 alkyl;

[0543] R3cis selected from H and C1-C4 alkyl;

[0544] R3dis selected from C1-C4 alkyl;

[0545] R4is selected from the following groups: wherein indicates the point of attachment to the rest of the compound;

[0546] R5is selected from H and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0547] R6is selected from H, C1-C4 alkyl, C1-C4 alkoxy, and C1-C4 alkoxy-C1-C4 alkyl; and R7, R8, R9, R10, R11, and R12are each H.

[0548] In embodiments,

[0549] L1is a bond, CrCe alkylene, or C3-C6 cycloalkylene;

[0550] R1is selected from C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11- membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, and 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, wherein said cycloalkyl, heterocycloalkyl, bicyclic cycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, and bicyclic heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, and C1-C4 haloalkoxy;

[0551] R2is H;

[0552] R3is selected from H, CN, NR3aR3b, C1-C4 alkyl optionally substituted by OH, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C1-C4 alkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, C1-C4 haloalkoxy- C1-C4 alkyl,, C1-C4 alkyl-S-C1-C4 alkyl, and C1-C4 alkyl-SO2-C1-C4 alkyl;

[0553] R3ais H;

[0554] R3bis selected from C1-C4 alkyl;

[0555] R4is selected from the following groups: indicates the point of attachment to the rest of the compound;

[0556] R5is H;

[0557] R6is selected from H and C1-C4 alkyl; and

[0558] R7, R8, R9, R10, R11, and R12are each H.

[0559] In embodiments,

[0560] L1is either a bond or CrCe alkylene;

[0561] R1is selected from C3-C8 cycloalkyl, C8-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11- membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, and 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, wherein said cycloalkyl, bicyclic cycloalkyl, heterocycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, and bicyclic heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, and C1-C4 haloalkoxy;

[0562] R2is H;

[0563] R3is selected from NR3aR3b, C1-C4 alkyl optionally substituted by one or more substituents independently selected from OH and NR3cR3d, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C3-C8 cycloalkoxy-C1-C4 alkyl, C1-C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, and alkyl-S-C1-C4 alkyl;

[0564] R3ais H;

[0565] R3bis selected from C1-C4 alkyl;

[0566] R4is selected from the following groups: p and

[0567] R6is selected from H and C1-C4 alkyl.

[0568] In embodiments, Q is O.

[0569] In embodiments, L is either a bond or methylene.

[0570] In embodiments, R1is selected from:

[0571] C3-C8 cycloalkyl optionally substituted by one or more substituents independently selected from halogen and C1-C4 haloalkoxy;

[0572] C8-C11 bicyclic cycloalkyl optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl and C1-C4 alkoxy;

[0573] 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2;

[0574] 8- to 11 -membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, optionally substituted by one or more substituents independently selected from halogen; phenyl optionally substituted by one or more substituents independently selected from halogen and C1-C4 alkyl;

[0575] 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, optionally substituted by one or more substituents independently selected from C1-C4 alkyl and C1-C4 haloalkyl; and

[0576] 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, optionally substituted substituted by one or more substituents independently selected from halogen and C1-C4 alkyl. In embodiments, R2is H.

[0577] In embodiments, R3is selected from: - NR3aR3b;

[0578] C1-C4 alkyl optionally substituted by OH;

[0579] C3-C8 cycloalkyl;

[0580] 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S; - 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0581] C1-C4 alkoxy-C1-C4 alkyl;

[0582] C3-C8 cycloalkyl-C1-C4 alkoxy;

[0583] C3-C8cycloalkoxy-C1-C4 alkyl; - C1-C4 haloalkoxy-C1-C4 alkyl; and

[0584] C1-C4 alkyl-S-C1-C4 alkyl; wherein

[0585] R3ais H; and

[0586] R3bis selected from C1-C4 alkyl.

[0587] In embodiments, R3is selected from C1-C4 alkoxy-C1-C4 alkyl.

[0588] In embodiments, R4is selected from the following groups: tindicates the point of attachment to the rest of the compound.

[0589] In embodiments, R5is H. In embodiments, R6is H or methyl. In embodiments, R7, R8, R9, R10, R11, and R12are each H.

[0590] In another aspect of this disclosure, there is provided a compound of formula (1) selected from Table 1. In another aspect there is provided a compound according to any one of compounds 1 to 242, or a stereoisomer or mixture of stereoisomers including diastereomers and enantiomers, tautomer, isotopic form, pharmaceutically acceptable salt, solvate, prodrug, or pharmaceutically active metabolite thereof, or combinations thereof; for example a compound selected from compounds 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37,

[0591] 38, 39, 40, 41 , 42, 43, 44, 45, 46, 47, 48, 49, 50, 51 , 52, 53, 54, 55, 56, 57, 58, 59, 60, 61 ,

[0592] 62, 63, 64, 65, 66, 67, 68, 69, 70, 71 , 72, 73, 74, 75, 76, 77, 78, 79, 80, 81 , 82, 83, 84, 85,

[0593] 86, 87, 88, 89, 90, 91 , 92, 93, 94, 95, 96, 97, 98, 99, 100, 101 , 102, 103, 104, 105, 106, 107,

[0594] 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125,

[0595] 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143,

[0596] 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161,

[0597] 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179,

[0598] 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197,

[0599] 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241 , and 242; for example a compound selected from 1, 2, 4, 5, 6, 7, 8, 9, 11, 14, 15, 18, 19, 20, 21 , 22,

[0600] 25, 26, 27, 28, 29, 30, 31 , 32, 33, 34, 35, 36, 37, 38, 39, 41 , 42, 43, 44, 45, 46, 47, 48, 49,

[0601] 50, 51 , 52, 53, 54, 55, 56, 57, 58, 59, 60, 61 , 62, 63, 64, 65, 66, 67, 68, 69, 70, 71 , 72, 73,

[0602] 74, 75, 76, 77, 78, 79, 80, 81 , 82, 83, 84, 85, 86, 87, 88, 91 , 92, 93, 94, 95, 96, 97, 98, 99,

[0603] 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117,

[0604] 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135,

[0605] 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171,

[0606] 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189,

[0607] 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231 , 232, 233, 234, 235, 236, 237, 238, 239, 240, 241 , and 242; for example a compound selected from 1,2,4, 5, 6, 9, 14, 18, 21 , 22, 25, 26, 27, 29, 30, 32, 33, 34, 35, 36, 37, 39, 41 , 42, 43, 44, 45, 46, 47, 48, 49, 50, 53, 54, 55, 56, 57, 58, 59, 60, 61 , 62, 63, 64, 65, 66, 67, 68, 69, 70, 71 , 72, 73, 74, 75, 76, 77, 78, 79, 80, 81 , 82, 83, 84, 85, 86, 87, 88, 91, 92, 93, 94, 95, 97, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111 , 112, 113, 114, 115, 116, 117, 118, 119, 120, 121 , 122, 123, 124, 125, 126, 127, 128, 129,

[0608] 130, 131 , 132, 133, 134, 135, 136, 137, 138, 139, 140, 141 , 142, 143, 144, 145, 146, 147, 148, 149, 150, 151 , 152, 153, 154, 155, 156, 157, 158, 159, 160, 161 , 162, 163, 164, 165,

[0609] 166, 167, 168, 169, 170, 171 , 172, 173, 174, 175, 176, 177, 178, 179, 180, 181 , 182, 183,

[0610] 184, 185, 186, 187, 188, 189, 190, 191 , 192, 193, 194, 195, 196, 197, 198, 199, 200, 201 ,

[0611] 202, 203, 204, 205, 206, 207, 208, 209, 210, 211 , 212, 213, 214, 215, 216, 217, 218, 219,

[0612] 220, 221 , 222, 223, 224, 225, 226, 227, 228, 229, 230, 231 , 232, 233, 234, 235, 236, 237, 238, 239, 240, 241 , and 242; for example a compound selected from 1 , 2, 4, 6, 21 , 26, 27, 33, 34, 37, 42, 43, 44, 46, 48, 53, 54, 55, 56, 57, 58, 59, 60, 61 , 64, 65, 66, 67, 68, 69, 70, 71 , 72, 73, 74, 75, 76, 78, 79,

[0613] 80, 81 , 82, 83, 85, 86, 87, 88, 91 , 92, 93, 94, 104, 105, 106, 107, 108, 109, 110, 111 , 112,

[0614] 113, 114, 115, 116, 117, 118, 119, 120, 121 , 122, 123, 126, 127, 128, 129, 130, 132, 133,

[0615] 134, 135, 136, 137, 138, 139, 140, 141 , 142, 143, 144, 145, 146, 147, 148, 149, 150, 151 ,

[0616] 152, 153, 154, 155, 156, 157, 158, 159, 160, 162, 163, 164, 165, 166, 167, 168, 169, 170,

[0617] 171 , 172, 173, 174, 175, 176, 177, 178, 179, 180, 181 , 182, 183, 184, 185, 189, 190, 191 ,

[0618] 192, 193, 194, 195, 196, 198, 199, 200, 201 , 202, 203, 204, 205, 206, 208, 209, 210, 211 ,

[0619] 212, 213, 214, 215, 216, 217, 218, 219, 220, 221 , 222, 223, 224, 225, 226, 227, 228, 229,

[0620] 230, 231 , 232, 233, 234, 235, 236, 237, 238, 239, 240, 241 , and 242; for example a compound selected from 27, 33, 34, 37, 46, 54, 56, 57, 58, 59, 60, 61 , 64, 66, 68, 70, 72, 73, 74, 75, 79, 80, 82, 83, 85, 87, 88, 91 , 92, 93, 105, 106, 107, 108, 109, 110, 111 , 112, 113, 114, 115, 116, 117, 118, 119, 120, 123, 128, 129, 130, 133, 134, 135, 136,

[0621] 137, 138, 139, 140, 141 , 142, 144, 145, 147, 148, 150, 151 , 152, 153, 157, 158, 159, 160,

[0622] 163, 164, 166, 167, 168, 169, 170, 173, 174, 175, 176, 177, 178, 179, 182, 183, 184, 189,

[0623] 191 , 192, 193, 194, 195, 196, 200, 201 , 202, 208, 209, 210, 211 , 214, 216, 217, 219, 222,

[0624] 223, 225, 226, 227, 228, 229, 230, 231 , 232, 233, 234, 235, 236, 237, 238, 239, 240, and

[0625] 242.

[0626] In another aspect of this disclosure, there is provided a compound of formula (1 ) as described above for use in medicine. In another aspect of this disclosure, there is provided a compound of formula (2aa) as described above for use in medicine. In another aspect of this disclosure, there is provided a compound of formula (2ab) as described above for use in medicine. In another aspect of this disclosure, there is provided a compound of formula (2ad) as described above for use in medicine.

[0627] In embodiments, the compound of formula (1 ), formula (2aa), (2ab), or (2ad) is for use in the treatment or prophylaxis of a cancer or proliferative disease or disorder. In embodiments, the cancer or proliferative disease or disorder is selected from: adrenal gland cancer, anal cancer, angiosarcoma, bladder cancer, blastic plasmacytoid dendritic cell neoplasm, bone cancer, brain cancer, breast cancer, bronchogenic carcinoma, central nervous system (CNS) cancer, cervical cancer, chondrosarcoma, colon cancer, colorectal cancer, cancer of connective tissue, esophageal cancer, embryonal carcinoma, fibrosarcoma, glioblastomas, medulloblastoma, head and neck cancer, hematological cancer, kidney cancer, leukemias (e.g., acute leukemia, acute lymphocytic leukemia, acute myelocytic leukemia, acute myeloblastic leukemia, acute promyelocytic leukemia, acute myelomonocytic leukemia, acute monocytic leukemia, acute erythroleukemia, chronic leukemia, chronic myelocytic leukemia, chronic lymphocytic leukemia), myelodysplastic syndrome, liposarcoma, liver cancer, lung cancer, lymphoid cancers (e.g., Hodgkin’s and non-Hodgkin’s lymphomas), mesothelioma, multiple myeloma, muscular cancer, myxosarcoma, neuroblastomas, ocular cancer, oral / digestive tract cancer, osteogenic sarcoma, ovarian cancer, papillary carcinoma, pancreatic cancer, polycythemia vera, prostate cancer, renal cancer, retinal cancer, skin cancer, small cell lung carcinoma, stomach cancer, testicular cancer, throat cancer, thyroid cancer, uterine cancer, vaginal cancer, vulvar cancer, gliomas, melanoma, non-small cell lung cancer and acute myeloid leukemia (AML).

[0628] In another aspect of this disclosure, there is provided a pharmaceutical composition comprising a compound of formula (1 ), formula (2aa), formula (2ab) or formula (2ad) as described above, or a stereoisomer or mixture of stereoisomers including diastereomers and enantiomers, tautomer, isotopic form, pharmaceutically acceptable salt, solvate, prodrug, or pharmaceutically active metabolite thereof, or combinations thereof, and at least one pharmaceutically acceptable diluent, excipient or carrier.

[0629] In another aspect of this disclosure, there is provided a pharmaceutical composition comprising a compound of formula (1 ), formula (2aa), formula (2ab), or formula (2ad) as described above, or a stereoisomer or mixture of stereoisomers including diastereomers and enantiomers, tautomer, isotopic form, pharmaceutically acceptable salt, solvate, prodrug, or pharmaceutically active metabolite thereof, or combinations thereof, and at least one pharmaceutically acceptable diluent, excipient or carrier for use for use in medicine.

[0630] In embodiments, the pharmaceutical composition comprising a compound of formula (1 ), formula (2aa), formula (2ab), or formula (2ad) is for use in the treatment or prophylaxis of a cancer or proliferative disease or disorder. In embodiments, the cancer or proliferative disease or disorder is selected from: adrenal gland cancer, anal cancer, angiosarcoma, bladder cancer, blastic plasmacytoid dendritic cell neoplasm, bone cancer, brain cancer, breast cancer, bronchogenic carcinoma, central nervous system (CNS) cancer, cervical cancer, chondrosarcoma, colon cancer, colorectal cancer, cancer of connective tissue, esophageal cancer, embryonal carcinoma, fibrosarcoma, glioblastomas, medulloblastoma, head and neck cancer, hematological cancer, kidney cancer, leukemias (e.g., acute leukemia, acute lymphocytic leukemia, acute myelocytic leukemia, acute myeloblastic leukemia, acute promyelocytic leukemia, acute myelomonocytic leukemia, acute monocytic leukemia, acute erythroleukemia, chronic leukemia, chronic myelocytic leukemia, chronic lymphocytic leukemia), myelodysplastic syndrome, liposarcoma, liver cancer, lung cancer, lymphoid cancers (e.g., Hodgkin’s and non-Hodgkin’s lymphomas), mesothelioma, multiple myeloma, muscular cancer, myxosarcoma, neuroblastomas, ocular cancer, oral / digestive tract cancer, osteogenic sarcoma, ovarian cancer, papillary carcinoma, pancreatic cancer, polycythemia vera, prostate cancer, renal cancer, retinal cancer, skin cancer, small cell lung carcinoma, stomach cancer, testicular cancer, throat cancer, thyroid cancer, uterine cancer, vaginal cancer, vulvar cancer, gliomas, melanoma, non-small cell lung cancer and acute myeloid leukemia (AML).

[0631] Within the scope of this disclosure it is expressly intended that the various aspects, embodiments, examples and alternatives set out in the preceding paragraphs, in the claims and / or in the following description and drawings, and in particular the individual features thereof, may be taken independently or in any combination. That is, all embodiments and / or features of any embodiment can be combined in any way and / or combination, unless such features are incompatible. More particularly, it is specifically intended that any embodiment of any aspect may form an embodiment of any other aspect, and all such combinations are encompassed within the scope of the invention. The applicant reserves the right to change any originally filed claim or file any new claim accordingly, including the right to amend any originally filed claim to depend from and / or incorporate any feature of any other claim although not originally claimed in that manner.

[0632] DETAILED DESCRIPTION

[0633] Described herein are compounds and compositions (e.g. organic molecules, research tools, pharmaceutical formulations and therapeutics); uses for the compounds and compositions of the disclosure (in vitro and in vivo) ; as well as corresponding methods, whether diagnostic, therapeutic or for research applications. The chemical synthesis and biological testing of the compounds of the disclosure are also described. Beneficially, the compounds, compositions, uses and methods have utility in research towards and / or the treatment of diseases or disorders in animals, such as humans. Diseases or disorders which may benefit from GPR68 modulation include, cancer and / or oncologic disease.

[0634] However, the compounds of the disclosure may also or alternatively be useful as lead molecules for the selection, screening and development of further derivatives that may have one or more improved beneficial drug property, as desired.

[0635] The disclosure also encompasses salts, solvates, tautomers, enantiomers and functional derivatives of the compounds described herein. These compounds may be useful in the treatment of various diseases or disorders; particularly those which may benefit from modulation of GPR68.

[0636] GPR68 modulators are useful in compositions and methods suitable for treating many disorders, and particularly cancer and / or proliferative diseases or disorders. In some embodiments, the disease is selected from the group consisting of adrenal gland cancer, anal cancer, angiosarcoma, bladder cancer, blastic plasmacytoid dendritic cell neoplasm, bone cancer, brain cancer, breast cancer, bronchogenic carcinoma, central nervous system (CNS) cancer, cervical cancer, chondrosarcoma, colon cancer, colorectal cancer, cancer of connective tissue, esophageal cancer, embryonal carcinoma, fibrosarcoma, glioblastomas, medulloblastoma, head and neck cancer, hematological cancer, kidney cancer, leukemias (e.g., acute leukemia, acute lymphocytic leukemia, acute myelocytic leukemia, acute myeloblastic leukemia, acute promyelocytic leukemia, acute myelomonocytic leukemia, acute monocytic leukemia, acute erythroleukemia, chronic leukemia, chronic myelocytic leukemia, chronic lymphocytic leukemia), myelodysplastic syndrome, liposarcoma, liver cancer, lung cancer, lymphoid cancers (e.g., Hodgkin’s and non-Hodgkin’s lymphomas), mesothelioma, multiple myeloma, muscular cancer, myxosarcoma, neuroblastomas, ocular cancer, oral / digestive tract cancer, osteogenic sarcoma, ovarian cancer, papillary carcinoma, pancreatic cancer, polycythemia vera, prostate cancer, renal cancer, retinal cancer, skin cancer, small cell lung carcinoma, stomach cancer, testicular cancer, throat cancer, thyroid cancer, uterine cancer, vaginal cancer, vulvar cancer, gliomas, melanoma, non-small cell lung cancer and acute myeloid leukemia (AML). In some embodiments, the disease is selected from the group consisting of colon cancer, medulloblastoma, head and neck cancer, myelodysplastic syndrome, pancreatic cancer, prostate cancer and melanoma. GPR68 modulators are also useful in compositions and methods suitable for treating fibrotic disease and inflammatory disease.

[0637] Definitions

[0638] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art (e.g. in organic, physical or theoretical chemistry; biochemistry and molecular biology).

[0639] Unless otherwise indicated, the practice of the present invention employs conventional techniques in chemistry and chemical methods, biochemistry, molecular biology, pharmaceutical formulation, and delivery and treatment regimens for patients, which are within the capabilities of a person of ordinary skill in the art. Such techniques are also described in the literature cited herein, each of which is herein incorporated by reference in its entirety.

[0640] Prior to setting forth the detailed description of the invention, a number of definitions are provided that will assist in the understanding of the invention.

[0641] In accordance with the invention, the terms ‘molecule’ or ‘molecules’ are used interchangeably with the terms ‘compound’ or ‘compounds’, and sometimes the term ‘chemical structure’. The term ‘drug’ is typically used in the context of a pharmaceutical, pharmaceutical composition, medicament or the like, which has a known or predicted physiological or in vitro activity of medical significance; but such characteristics and qualities are not excluded in a molecule or compound of the invention. The term ‘drug’ is therefore used interchangeably with the alternatives terms and phrases ‘therapeutic (agent)’, ‘pharmaceutical (agent)’, and ‘active (agent)’. Therapeutics of the invention also encompass compositions and pharmaceutical formulations comprising the compounds of the invention.

[0642] It will be appreciated that certain compounds provided herein may contain one or more centres of asymmetry and may therefore be prepared and isolated in a mixture of isomers such as a racemic mixture, or in an enantiomerically pure form.

[0643] A compound or molecule as disclosed herein is meant to include all stereoisomers, geometric isomers, tautomers, and isotopically enriched variants of the structures depicted. Compounds herein identified by name or structure as one particular tautomeric form are intended to include other tautomeric forms unless otherwise specified. The term ‘tautomer’, as used herein refers to compounds whose structures differ markedly in arrangement of atoms, but which exist in easy and rapid equilibrium, and it is to be understood that compounds provided herein may be depicted as different tautomers, and when compounds have tautomeric forms, all tautomeric forms are intended to be within the scope of the disclosure, and the naming of the compounds does not exclude any tautomer.

[0644] The term ‘substantially free of other stereoisomers’ as used herein means less than 10% of other stereoisomers, preferably less than 5% of other stereoisomers, more preferably less than 2% of other stereoisomers and most preferably less than 1 % of other stereoisomers are present.

[0645] Prodrugs and solvates of the compounds of the invention are also encompassed within the scope of the invention. The term ‘prodrug’ means a compound (e.g. a drug precursor) that is transformed in vivo to yield a compound of the invention or a pharmaceutically acceptable salt, solvate or ester of the compound. The transformation may occur by various mechanisms (e.g. by metabolic or chemical processes), such as by hydrolysis of a hydrolysable bond, e.g. in blood (see Higuchi & Stella (1987), “Pro-drugs as Novel Delivery Systems”, vol. 14 of the A.C.S. Symposium Series; (1987), “Bioreversible Carriers in Drug Design”, Roche, ed., American Pharmaceutical Association and Pergamon Press). The compositions and medicaments of the invention therefore may comprise prodrugs of the compounds of the invention. In some aspects and embodiments, the compounds of the disclosure are themselves prodrugs which may be metabolised in vivo to give the therapeutically effective compound. For example, a sulfoxide prodrug may be metabolized in vivo to the therapeutically active sulfone (see Basarab G.S. et al., (2008), Bioorg Med Chem Lett, 18(16), 4716-4722; Gibhard L. et al., (2008), Antimicrobial Agents and Chemotherapy, 62(12), 00261 -18).

[0646] The term ‘pharmaceutically acceptable salt’ as used herein refers to a salt that is not biologically or otherwise undesirable (e.g., not toxic or otherwise harmful). Thus, a ‘pharmaceutically acceptable’ compound is compatible chemically and / or toxicologically with the other ingredients comprising a formulation and / or the subject being treated therewith. A salt of a compound of the disclosure is formed between an acid and a basic group of the compound, or a base and an acidic group of the compound. For example, when the compounds of the disclosure contain at least one basic group (i.e., groups that can be protonated), the disclosure includes the compounds in the form of their acid addition salts with organic or inorganic acids such as, for example, but not limited to salts with hydrogen chloride, hydrogen bromide, phosphoric acid, sulfuric acid, nitric acid, benzenesulfonic acid, acetic acid, citric acid, glutamic acid, lactic acid, and methanesulfonic acid. When compounds of the disclosure contain one or more acidic groups (e.g., a carboxylic acid), the disclosure includes the pharmaceutically acceptable salts of the compounds formed with but not limited to alkali metal salts, alkaline earth metal salts or ammonium salts. Examples of such salts include, but are not limited to, sodium salts, potassium salts, calcium salts, magnesium salts or salts with ammonia or organic amines such as, for example, ethylamine, ethanolamine, triethanolamine or amino acids. Additional examples of such salts can be, found in Stahl, P. H. et al. Pharmaceutical Salts: Properties, Selection, and Use, 2ndRevised Edition, Wiley, 2011 .

[0647] In the context of the present disclosure, the terms ‘individual’, ‘subject’, or ‘patient’ are used interchangeably to indicate an animal that may be suffering from a medical (pathological) condition and may be responsive to a molecule, pharmaceutical drug, medical treatment or therapeutic treatment regimen of the disclosure. The animal is suitably a mammal, such as a human, cow, sheep, pig, dog, cat, bat, mouse or rat. In particular, the subject may be a human.

[0648] As used herein, the terms ‘treat’ ‘treating’ or ‘treatment’ include their generally accepted meanings in relation to therapeutic or palliative measures. Beneficial or desired clinical results in relation to the management and care of a patient or potential patient include, but are not limited to, alleviation or relief, in whole or in part, of symptoms associated with a disease, disorder or condition, diminishment of the extent of the disease, disorder or condition, a stabilized (i.e., not worsening) state of disease, delay or slowing of disease progression, amelioration or palliation of the disease state (e.g., one or more symptoms of the disease, disorder or condition), and remission (whether partial or total), whether detectable or undetectable. ‘Treatment’ can also mean prolonging survival as compared to expected survival if not receiving treatment.

[0649] The term ‘preventing’ as used herein means the prevention of the onset, recurrence or spread, in whole or in part, of the disease or condition as described herein, or a symptom thereof.

[0650] The term ‘therapeutically effective amount’ as used herein refers to that amount of compound of the disclosure that will elicit the biological or medical response of a tissue, system, animal, or human that is being sought by a researcher, veterinarian, medical doctor or other. As will be recognized by a person of ordinary skill in the art, a therapeutically effective amount of the compounds of the disclosure will vary and will depend on the disease treated, the severity of the disease, the route of administration, and the gender, age, and general health condition of the subject to whom the compound is being administered. The therapeutically effective amount may be administered as a single dose once a day, or as split doses administered multiple (e.g., two, three or four) times a day. The therapeutically effective amount may also be administered through continuous dosing, such as through infusion or with an implant.

[0651] Compounds provided herein may also contain unnatural proportions of atomic isotopes at one or more of the atoms that constitute such compounds. That is, an atom, in particular when mentioned in relation to a compound according to any of the formulas disclosed herein comprises all isotopes and isotopic mixtures of that atom, either naturally occurring or synthetically produced, either with natural abundance or in an isotopically enriched form. For example, when hydrogen is mentioned, it is understood to refer to1H,2H,3H or mixtures thereof; when carbon is mentioned, it is understood to refer to11C,12C,13C,14C or mixtures thereof; when nitrogen is mentioned, it is understood to refer to13N,14N,15N or mixtures thereof; when oxygen is mentioned, it is understood to refer to140,150,16O,170,18O or mixtures thereof; and when fluoro is mentioned, it is understood to refer to18F,19F or mixtures thereof; unless expressly noted otherwise. For example, in deuteroalkyl and deuteroalkoxy groups, where one or more hydrogen atoms are specifically replaced with deuterium (2H). As some of the aforementioned isotopes are radioactive, the compounds provided herein therefore also comprise compounds with one or more isotopes of one or more atoms, and mixtures thereof, including radioactive compounds, wherein one or more non-radioactive atoms has been replaced by one of its radioactive enriched isotopes. Radiolabelled compounds are useful as therapeutic agents, e.g., cancer therapeutic agents, research reagents, e.g., assay reagents, and diagnostic agents, e.g., in vivo imaging agents. All isotopic variations of the compounds provided herein, whether radioactive or not, are intended to be encompassed within the scope of the present disclosure.

[0652] In this regard, the term ‘deuterium’ as used herein refers to an isotope of hydrogen that has one proton and one neutron in its nucleus and that has twice the mass of ordinary hydrogen. Deuterium herein is represented by the symbol ‘D’. The term ‘deuterated’ by itself or used to modify a compound or group as used herein refers to the presence of at least one deuterium atom attached to carbon. For example, the term ‘deuterated compound’ refers to a compound which contains one or more carbon-bound deuterium(s). In a deuterated compound of the present disclosure, when a particular position is designated as having deuterium, it is understood that the abundance of deuterium at that position is substantially greater than the natural abundance of deuterium, which is about 0.015%. The term ‘undeuterated’ or ‘non-deuterated’ as used herein refers to the ratio of deuterium atoms of which is not more than the natural isotopic deuterium content, which is about 0.015%; in other words, all hydrogens are present at their natural isotopic percentages. Unless otherwise stated, when a position is designated specifically as ‘H’ or ‘hydrogen’, the position is understood to have hydrogen at its natural abundance isotopic composition. However, it is explicitly intended that where H (or hydrogen) is mentioned as a substituent group in any of the aspects and embodiments of this disclosure, deuterium may also be a potential substituent at that position and can be considered implicitly recited as an optional substituent at each such position.

[0653] The term ‘isotopic enrichment factor’ as used herein refers to the ratio between the isotope abundance and the natural abundance of a specified isotope.

[0654] The term ‘isotopologue’ as used herein refers to a species in which the chemical structure differs from a specific compound of the disclosure only in the isotopic composition thereof.

[0655] The term ‘alkyl’ refers to a monovalent, optionally substituted, saturated aliphatic hydrocarbon radical. Any number of carbon atoms may be present, but typically the number of carbon atoms in the alkyl group may be from 1 to about 20, from 1 to about 12, from 1 to about 6 or from 1 to about 4. Usefully, the number of carbon atoms is indicated, for example, a Ci C4 alkyl refers to any alkyl group containing 1 to 4 carbon atoms in the chain. An alkyl group may be a straight chain (i.e. linear), branched chain, or cyclic. ‘Lower alkyl’ refers to an alkyl of 1 to 6 carbon atoms in the chain, and may have from 1 to 4 carbon atoms, or 1 to 2 carbon atoms. Thus, representative examples of lower alkyl radicals include methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, isopropyl, isobutyl, isopentyl, amyl (C5H11), sec-butyl, tert-butyl, sec-amyl, tert-pentyl, 2-ethylbutyl, 2,3-dimethylbutyl, and the like. ‘Higher alkyl’ refers to alkyls of 7 carbons and above, including n-heptyl, n-octyl, n-nonyl, n-decyl, n- dodecyl, n-tetradecyl, n-hexadecyl, n-octadecyl, n-eicosyl, and the like, along with branched variations thereof. A linear carbon chain of say 4 to 6 carbons would refer to the chain length not including any carbons residing on a branch, whereas in a branched chain it would refer to the total number. Optional substituents for alkyl and other groups are described below.

[0656] The term ‘alkoxy’ refers to a monovalent radical of the formula RO-, where R is any alkyl, alkenyl or alkynyl as defined herein. Alkoxy groups may be optionally substituted by any of the optional substituents described herein. ‘Lower alkoxy’ has the formula RO-, where the R group is a lower alkyl, alkenyl or alkynyl. Representative alkoxy radicals include methoxy, ethoxy, n-propoxy, n-butoxy, n-pentyloxy, n-hexyloxy, isopropoxy, isobutoxy, isopentyloxy, amyloxy, sec-butoxy, tert-butoxy, tert-pentyloxy, and the like. Preferred alkoxy groups are methoxy and ethoxy

[0657] The term ‘cycloalkyl’ as used herein refers to a cyclized alkyl ring having the indicated number of carbon atoms in a specified range. Thus, for example, ‘C3-C6 cycloalkyl’ encompasses each of cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

[0658] The term ‘aryl’ as used herein refers to a substituted or unsubstituted aromatic carbocyclic radical containing from 5 to about 15 carbon atoms (‘C6-Ci5 aryl’); suitably 5 to 12 carbon atoms (‘C5-C12 aryl’) and more suitably 5 or 6 carbon atoms. An aryl group may have only one individual carbon ring, or may comprise one or more fused rings in which at least one ring is aromatic in nature. A ‘phenyl’ is a radical formed by removal of a hydrogen atom from a benzene ring, and may be substituted or unsubstituted. A ‘phenoxy’ group, therefore, is a radical of the formula RO-, wherein R is a phenyl radical. ‘Benzyl’ is a radical of the formula R-CH2-, wherein R is phenyl, and ‘benzyloxy’ is a radical of the formula RO-, wherein R is benzyl. The point of attachment to the base molecule on such fused aryl ring systems may be a C atom of the aromatic portion or a C or a N atom of the non-aromatic portion of the ring system. Non-limiting examples of aryl radicals include, phenyl, naphthyl, anthracenyl, benzyl, biphenyl, furanyl, pyridinyl, indanyl, anthraquinolyl, tetrahydronaphthyl, a benzoic acid radical, a furan-2-carboxylic acid radical, and the like.

[0659] A ‘heteroaryl’ group is herein defined as a substituted or unsubstituted ‘aryl’ group in which one or more carbon atoms in the ring structure has been replaced with a heteroatom, such as nitrogen, oxygen or sulphur. Generally, the heteroaryl group contains one, two or three heteroatoms; particularly one or two heteroatoms. Particularly suitable heteroatoms are N and O; and a preferred heteroatom is N. Exemplary heteroaryl groups include: furan, benzofuran, isobenzofuran, pyrrole, indole, isoindole, thiophene, benzothiophene, benzo[c]thiophene, imidazole, benzimidazole, purine, pyrazole, indazole, oxazole, benzoxazole, isoxazole, benzisoxazole, thiazole, benzothiazole, pyridine, quinoline, isoquinoline, pyrazine, quinoxaline, acridine, pyrimidine, quinazoline, pyridazine and cinnoline.

[0660] Heteroaryl groups include but are not limited to thienyl (thiophenyl), benzo[b]thienyl, naphtho[2,3- b]thienyl, thianthrenyl, furyl (furanyl), isobenzofuranyl, chromenyl, xanthenyl, phenoxanthiinyl, pyrrolyl, including without limitation 2H-pyrrolyl, imidazolyl, pyrazolyl, pyridyl (pyridinyl), including without limitation 2-pyridyl, 3-pyridyl, and 4-pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolizinyl, isoindolyl, 3H-indolyl, indolyl, indazolyl, purinyl, 4H- quinolizinyl, isoquinolyl, quinolyl, phthalzinyl, naphthyridinyl, quinozalinyl, cinnolinyl, pteridinyl, carbazolyl, b-carbolinyl, phenanthridinyl, acrindinyl, pyrimidinyl, phenanthrolinyl, phenazinyl, thiazolyl, isothiazolyl, phenothiazinyl, oxazolyl, isoxazolyl, furazanyl, phenoxazinyl, 1 ,4- dihydroquinoxaline-2, 3-dione, 7-aminoisocoumarin, pyrido[1 ,2- a]pyrimidin-4-one, pyrazolo[1 ,5- a]pyrimidinyl, including without limitation pyrazolo[1 ,5- a]pyrim idin-3-yl, 1 ,2-benzoisoxazol-3- yl, benzimidazolyl, 2-oxindolyl and 2- oxobenzimidazoly, oxadiazolyl, and thiadiazolyl. Where the heteroaryl group contains a nitrogen atom in a ring, such nitrogen atom may be in the form of an N-oxide, e.g., a pyridyl N-oxide, pyrazinyl N-oxide and pyrimidinyl N-oxide.

[0661] The terms ‘heterocycle’ or ‘heterocyclic’ group as used herein refer to a monovalent radical of from about 4- to about 15- ring atoms I members, and preferably 4-, 5- or 6- ring members. Generally, the heterocyclic group contains one, two or three heteroatoms, selected independently from nitrogen, oxygen and sulphur. Particularly suitable heteroatoms are N and O; and a preferred heteroatom is N. A heterocyclic group may have only one individual ring, or may comprise one or more fused rings in which at least one ring contains a heteroatom. It may be fully saturated or partially saturated, and may be substituted or unsubstituted as in the case or aryl and heteroaryl groups. Representative examples of unsaturated 5-membered heterocycles with only one heteroatom include 2- or 3-pyrrolyl, 2- or 3-furanyl, and 2- or 3-thiophenyL Corresponding partially saturated or fully saturated radicals include 3-pyrrolin-2-yl, 2- or 3-pyrrolindinyl, 2- or 3-tetrahydrofuranyl, and 2- or 3- tetrahydrothiophenyl. Representative unsaturated 5-membered heterocyclic radicals having two heteroatoms include imidazolyl, oxazolyl, thiazolyl, pyrazolyl, and the like. The corresponding fully saturated and partially saturated radicals are also included. Representative examples of unsaturated 6-membered heterocycles with only one heteroatom include 2-, 3-, or 4-pyrid iny 1 , 2H-pyranyl, and 4H-pryanyL Corresponding partially saturated or fully saturated radicals include 2-, 3-, or 4-piperidinyl, 2-, 3-, or 4- tetrahydropyranyl and the like. Representative unsaturated 6-membered heterocyclic radicals having two heteroatoms include 3- or 4-pyridazinyl, 2-, 4-, or 5-pyrimidinyl, 2- pyrazinyl, morpholino, and the like. The corresponding fully saturated and partially saturated radicals are also included, e.g. 2-piperazine. The heterocyclic radical is bonded through an available carbon atom or heteroatom in the heterocyclic ring directly to the entity or through a linker such as an alkylene such as methylene or ethylene.

[0662] The term ‘cycloaryl’ refers to a polycyclic group wherein an aryl group is fused to a 5 - or 6- membered aliphatic ring. For example, C6-C12 cycloaryl means a C6-C12 aryl fused to a 5- or 6-membered aliphatic ring. The term ‘heteroaryloxy’ or ‘heteroaryloxyl’ as used herein refers to an -O- heteroaryl group.

[0663] The disclosure encompasses fused ring systems, for example, ‘bicyclic’ or ‘tricyclic’ ring systems. In the context of the present disclosure, it is specifically intended that a fused ring system may include more than one fused aromatic ring, more than one fused non-aromatic I aliphatic ring, or one or more aromatic ring fused to one or more non-aromatic I aliphatic ring, such as a fusion of an aryl group with a cycloalkyl (or cycloalkenyl) group. Furthermore, it is intended that a fused ring system termed a bicyclic (or tricyclic) aryl is attached to the associated molecule via an aryl group, whereas a bicyclic (or tricyclic) cycloalkyl I cycloalkenyl is attached to the associated molecule via the cycloalkyl I cycloalkenyl group.

[0664] Similarly, in the context of fused ring systems, it is specifically intended that a bicyclic (or tricyclic) heteroaryl or heterocycloalkyl I heterocycloalkenyl need not contain heteroatoms in each of the fused ring systems. Rather, a bicyclic of tricyclic heteroaryl group may have one or more heteroatoms in any ring of the fused ring system, and not necessarily in the aryl ring that is the point of attachment to the associated molecule. Likewise, a bicyclic of tricyclic heterocycloalkyl or heterocycloalkenyl group may have one or more heteroatoms in any ring of the fused ring system, and not necessarily in the heterocycloalkyl or heterocycloalkenyl ring that is the point of attachment to the associated molecule.

[0665] The term ‘substituted’ means that one or more hydrogen atoms (attached to a carbon or heteroatom) is replaced with a selection from the indicated group of substituents, provided that the designated atom’s normal valency under the existing circumstances is not exceeded. The group may be optionally substituted with particular substituents at positions that do not significantly interfere with the preparation of compounds falling within the scope of this invention and on the understanding that the substitution(s) does not significantly adversely affect the biological activity or structural stability of the compound. Combinations of substituents are permissible only if such combinations result in stable compounds. By ‘stable compound’ or ‘stable structure’, it is meant a compound that is sufficiently robust to survive isolation to a useful degree of purity from a reaction mixture and / or formulation into an efficacious therapeutic agent. The term ‘optionally substituted’ or ‘optional substituents’ as used herein means that the groups in question are either unsubstituted or substituted with one or more of the substituents specified. When the groups in question are substituted with more than one substituent, the substituents may be the same or different. By ‘optionally substituted’ it is meant that the group concerned is either unsubstituted, or at least one hydrogen atom is replaced with one of the specified substituent groups, radicals or moieties. When used herein, the term ‘independently’ (e.g. in the phrase ‘independently selected from’), in reference to the substitution of a parent moiety with one or more substituents, means that the parent moiety may be substituted with any of the listed substituents, either individually or in combination, and any number of chemically possible substituents may be used. In any of the embodiments, where a group is substituted, it may contain up to 5, up to 4, up to 3, or 1 and 2 substituents. As a non-limiting example, useful substituents include: phenyl or pyridine, independently substituted with one or more lower alkyl, lower alkoxy or halo substituents, such as: chlorophenyl, dichlorophenyl, trichlorophenyl, tolyl, xylyl, 2- chloro-3-methylphenyl, 2,3-dichloro- 4-methylphenyl, etc.

[0666] As used herein, the term ‘geminal’ refers to substituent atoms or groups attached to the same atom in a molecule. As used herein, the term ‘vicinal’ refers to substituent atoms or groups attached to adjacent atoms in a molecule. The stereochemical relationship between the substituent atoms or groups can be cis, trans, undefined, or unresolved.

[0667] Any radical I group I moiety described herein that may be substituted (or optionally substituted) may be substituted with one or more (e.g. one, two, three, four or five) substituents, which are independently selected from the designated group of substituents. Thus, substituents may be selected from the group: halogen (or ‘halo’, e.g. F, Cl and Br), hydroxyl (-OH), amino (-NH2), thiol (-SH), cyano (-CN), (lower) alkyl, (lower) alkoxy, (lower) alkenyl, (lower) alkynyl, aryl, heteroaryl, (lower) alkylthio, oxo, haloalkyl, hydroxyalkyl, nitro (-NO2), phosphate, azido (-N3), alkoxycarbonyl, carboxy, alkylcarboxy, alkylamino, dialkylamino, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, thioalkyl, alkylsulfonyl, arylsulfinyl, alkylaminosulfonyl, arylaminosulfonyl, alkylsulfonylamino, arylsulfonylamino, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, arylcarbamoyl, alkylcarbonylamino, arylcarbonylamino, cycloalkyl, heterocycloalkyl, unless otherwise indicated. Alternatively, where the substituents are on an aryl or other cyclic ring system, two adjacent atoms may be substituted with a methylenedioxy or ethylenedioxy group. More suitably, the substituents are selected from: halogen, hydroxy, amino, thiol, cyano, (Ci-Ce)alkyl, (Ci-Ce)alkoxy, (Cr Ce)alkenyl, (CrCejalkynyl, aryl, aryl(Ci-Ce)alkyl, aryl(Ci-Ce)alkoxy, heteroaryl, (Cr Ce)alkylthio, oxo, halo(CrC6)alkyl, hydroxy(Ci-Ce)alkyl, nitro, phosphate, azido, (Cr Ce)alkoxycarbonyl, carboxy, (CrCejalkylcarboxy, (CrCejalkylamino, di(Ci-C6)alkylamino, amino(Ci-C6)alkyl, (Ci-C6)alkylamino(Ci-C6)alkyl, di(Ci-C6)alkylamino(Ci-C6)alkyl, thio(Cr Ce)alkyl, (CrCejalkylsulfonyl, arylsulfinyl, (CrCejalkylaminosulfonyl, arylaminosulfonyl, (Cr Cejalkylsulfonylamino, arylsulfonylamino, carbamoyl, (Ci-Cejalkylcarbamoyl, di(Cr Cejalkylcarbamoyl, arylcarbamoyl, (CrCejalkylcarbonylamino, arylcarbonylamino, (C1- Cejcycloalkyl, and heterocycloalkyl. Still more suitably, the substituents are selected from one or more of: fluoro, chloro, bromo, hydroxy, (Ci-Ce)alkyl, (Ci-Ce)haloalkyl, (CrCeJalkoxy, (C5-Ce)aryl, a 5- or 6-membered heteroaryl, (C4-C6)cycloalkyl, a 4- to 6-membered heterocycloalkyl, cyano, (Ci-Ce)alkylthio, amino, -NH(alkyl), -NH((Ci-C6)cycloalkyl), -N((Cr Ce)alkyl)2, -OC(O)-(CrC6)alkyl, -OC(O)-(C5-Ce)aryl, -OC(0)-(CrC6)cycloalkyl, carboxy and -C(O)O-(Ci-C6)alkyl. Most suitably, the substituents are selected from one or more of: fluoro, chloro, bromo, hydroxy, amino, (CrCeJalkyl and (CrCeJalkoxy, wherein alkyl and alkoxy are optionally substituted by one or more chloro. Particularly preferred substituents are: chloro, methyl, ethyl, methoxy and ethoxy.

[0668] As used herein, the term ‘cyano’ refers to a -CN radical. As used herein, the term ‘hydroxyl’ refers to an -OH radical. As used herein, the term ‘amino’ refers to an -NH2group. As used herein, the term “oxo” refers to an “=O” group attached to a carbon atom.

[0669] The term ‘halo’ is used interchangeably with the term ‘halogen’ and refers to a monovalent halogen radical chosen from chloro, bromo, iodo, and fluoro. A ‘halogenated’ compound is one substituted with one or more halo substituent. Particular halo groups are F, Cl and Br; and most particularly are F or Cl. In some preferred embodiments the halo group is F.

[0670] The term ‘CrCe haloalkyl’ refers to a hydrocarbon chain substituted with at least one halogen atom independently chosen at each occurrence, for example fluorine, chlorine, bromine and iodine. The halogen atom may be present at any position on the hydrocarbon chain. Similarly, a C1 -C3 haloalkyl group is linear or branched hydrocarbon chain containing 1 , 2, or 3 carbon atoms substituted with at least one halogen atom. For example, C1-C3 haloalkyl may refer to chloromethyl, fluoromethyl, trifluoromethyl, chloroethyl e.g. 1 -chloroethyl and 2- chloroethyl, trichloroethyl e.g.1 ,2,2-trichloroethyl, 2,2,2-trichloroethyl, fluoroethyl e.g.1 - fluoromethyl and 2- fluoroethyl, trifluoroethyl e.g. 1 ,2,2-trifluoroethyl and 2 ,2 ,2-trifluoroethyl , chloropropyl, trichloropropyl, fluoropropyl, trifluoropropyl.

[0671] ‘Alkylene’ or ‘alkylenyl’ means a difunctional group obtained by removal of a hydrogen atom from an alkyl group as defined above. Non-limiting examples of alkylene include methylene, ethylene and propylene. ‘Lower alkylene’ means an alkylene having from 1 to 6 carbon atoms in the chain, and may be straight or branched. Alkylene groups are optionally substituted. Preferred alkylene groups are -(CR2)n- where n is from 1 to 6, and R is independent selected from H, F, Cl, NH2or wherein R2is =0. More preferably, n is 1 , 2 or 3 and R is H. Most preferable alkylene groups are -(CH2)2- and -CH2-CO-. The term ‘alkenyl’ refers to a monovalent, optionally substituted, unsaturated aliphatic hydrocarbon radical. Therefore, an alkenyl has at least one carbon-carbon double bond (C=C). The number of carbon atoms in the alkenyl group may be indicated, such as from 2 to about 20. For example, a C2-12 alkenyl (or C2-12 alkenyl) refers to an alkenyl group containing 2 to 12 carbon atoms in the structure. Alkenyl groups may be straight (i.e. linear), branched chain, or cyclic. ‘Lower alkenyl’ refers to an alkenyl of 1 to 6 carbon atoms, and may have from 1 to 4 carbon atoms, or 1 to 2 carbon atoms. Representative examples of lower alkenyl radicals include ethenyl, 1 -propenyl, 1 -butenyl, 1 -pentenyl, 1 -hexenyl, isopropenyl, isobutenyl, and the like. Higher alkenyl refers to alkenyls of seven carbons and above, such as 1 -heptenyl, 1 -octenyl, 1 -nonenyl, 1 -decenyl, 1 -dodecenyl, 1 -tetradecenyl, 1 - hexadecenyl, 1 -octadecenyl, 1 -eicosenyl, and the like, along with branched variations thereof. Optional substituents include are described elsewhere.

[0672] ‘Alkenylene’ means a difunctional group obtained by removal of a hydrogen from an alkenyl group that is defined above. Non-limiting examples of alkenylene include -CH=CH-, - C(CH3)=CH-, and -CH=CHCH2-.

[0673] ‘Alkynyl’ and ‘lower alkynyl’ is defined similarly to the term ‘alkenyl’, except that it includes at least one carbon-carbon triple bond.

[0674] Unless defined otherwise, ‘room temperature’ is intended to mean a temperature of from about 16 to 28 °C, typically between about 18 and 25 °C, and more typically between about 18 and 22°C. As used herein, the phrase ‘room temperature’ may be shortened to ‘rt’ or ‘RT’.

[0675] Molecules and Compounds

[0676] Disclosed herein is a compound according to the invention having the structural formula (1 ):

[0677] including any stereoisomer or mixture of stereoisomers including diastereomers and enantiomers, tautomer, isotopic form, pharmaceutically acceptable salt, solvate, prodrug, or pharmaceutically active metabolite thereof, or combinations thereof, wherein:

[0678] Q is O or S;

[0679] X1is selected from C and N;

[0680] X2is selected from CR5and N;

[0681] X3is selected from CR6and N;

[0682] X4is selected from CR7and N;

[0683] X5is selected from C and N; wherein X1, X2, X3, X4and X5are selected so that the ring labelled A is aromatic;

[0684] X6is selected from CR8R9, O and N;

[0685] X7is selected from CR10, CR11R12, O and N; q is 0 or 1 ; wherein when q is 0, X7is O or N; and when X7is O or N and q is 1 , X6is CR8R9;

[0686] L1is a bond, alkylene, haloalkylene, cycloalkylene, or heterocycloalkyl;

[0687] R1is selected from alkyl, cycloalkyl, bicyclic cycloalkyl, heterocycloalkyl, bicyclic heterocycloalkyl, aryl, bicyclic aryl, heteroaryl, bicyclic heteroaryl, aryloxy, and heteroaryloxy, wherein said alkyl, cycloalkyl, bicyclic cycloalkyl, heterocycloalkyl, bicyclic heterocycloalkyl, aryl, bicyclic aryl, heteroaryl, bicyclic heteroaryl, aryloxy and heteroaryloxy are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, NR1aR1 b, alkyl, haloalkyl, alkoxy, haloalkoxy, alkyl-NR1aR1 b, cycloalkyl, heterocycloakyl, aryl, heteroaryl, benzyl, aryloxy, haloaryloxy, heteroaryloxy, C4 alkyl substituted by a heterocycloalkyl;

[0688] R1aand R1 bare each independently selected from H and alkyl;

[0689] R2is selected from H, alkyl and cycloalkyl; or R1, R2and L1and the nitrogen atom to which R2and L1are attached form a heterocycloalkyl, bicyclic heterocycloalkyl, heteroaryl or bicyclic heteroaryl, wherein said heterocycloalkyl, bicyclic heterocycloalkyl, heteroaryl and bicyclic heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, NR1aR1 b, alkyl, haloalkyl, alkoxy, haloalkoxy and alkyl-NR1aR1 b;

[0690] R3is selected from H, OH, CN, NR3aR3b, alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkoxyalkyl, haloalkoxyalkyl, cycloalkoxyalkyl, cycloalkylalkoxy, alkyl-S-alkyl, and alkyl-SO2- alkyl, wherein said alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, alkyl and NR3cR3d;

[0691] R3ais selected from H, alkyl, alkyl-OH, and alkyl-NR3eR3f;

[0692] R3b, R3c, R3d, R3eand R3fare each independently selected from H and alkyl;

[0693] R4is selected from C(O)OH, C(O)NR4aR4b, C(S)NR4aR4band heteroaryl;

[0694] R4aand R4bare each independently selected from H and alkyl;

[0695] R5and R6are each independently selected from H, halogen, OH, CN, alkyl, haloalkyl, alkoxy, alkoxyalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl; or R5and R6together with the carbon atoms to which they are attached form a heterocycle; and

[0696] R7, R8, R9, R10, R11and R12are each independently selected from H, halogen, OH, CN, alkyl, haloalkyl, alkoxy, cycloalkyl, heterocycloalkyl, aryl and heteroaryl.

[0697] In embodiments of the compound of formula (1 ),

[0698] L1is a bond, CrCe alkylene, CrCe haloalkylene, C3-C6 cycloalkylene, or a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[0699] R1is selected from C1-C4 alkyl, C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11 - membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, C9-C10 bicyclic aryl, 5- or 6- membered heteroaryl having one or more ring members selected from N, O, S and SO2, 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, phenoxy, and 5- or 6- membered heteroaryloxy having one or more heteroatoms selected from N, O and S, wherein said alkyl, cycloalkyl, bicyclic cycloalkyl, heterocycloalkyl, bicyclic heterocycloalkyl, phenyl, bicyclic aryl, heteroaryl, bicyclic heteroaryl, phenoxy and heteroaryloxy are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, NR1aR1 b, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkyl-NR1aR1 b, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, benzyl, phenoxy, halophenoxy, 5- or 6- membered heteroaryloxy having one or more heteroatoms selected from N, O and S, and C1-C4 alkyl substituted by a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[0700] R1aand R1 bare each independently selected from H and C1-C4 alkyl;

[0701] R2is selected from H, C1-C4 alkyl and C3-C8 cycloakyl; or R1, R2and L1and the nitrogen atom to which R2and L1are attached form a 3- to 8- membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, 8- to 1 1 -membered bicyclic heterocycloalkyl having one or more heteroatoms selected from N, O and S, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, or 8- to 10-membered bicyclic heteroaryl having one or more heteroatoms selected from N, O and S, wherein said heterocycloalkyl, bicyclic heterocycloalkyl, heteroaryl and bicyclic heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, NR1aR1 b, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy and C1-C4 alkyl-NR1aR1 b;

[0702] R3is selected from H, OH, CN, NR3aR3b, C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, Cr C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, C3-C8 cycloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, C1-C4 alkyl-S-C1-C4 alkyl, and C1-C4 alkyl-SO2- C1-C4 alkyl, wherein said alkyl, cycloalkyl, heterocycloalkyl, phenyl and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, C1-C4 alkyl, and NR3cR3d;

[0703] R3ais selected from H, C1-C4 alkyl, C1-C4 alkyl-OH, and C1-C4 alkyl-NR3eR3f;

[0704] R3b, R3c, R3d, R3eand R3fare each independently selected from H and C1-C4 alkyl;

[0705] R4is selected from C(O)OH, C(O)NR4aR4b, C(S)NR4aR4band 5- or 6-membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0706] R4aand R4bare each independently selected from H and C1-C4 alkyl;

[0707] R5and R6are each independently selected from H, halogen, OH, CN, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 alkoxy-C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S; or R5and R6together with the carbon atoms to which they are attached form a 5- or 6- membered heterocycloalkyl having one or more heteroatoms selected from N, O and S; and R7, R8, R9, R10, R11, and R12are each independently selected from H, halogen, OH, CN, Ci- 04 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S.

[0708] In embodiments of the compound of formula (1 ),

[0709] L1is a bond, CrCe alkylene, CrCe haloalkylene, C3-C6 cycloalkylene, or a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[0710] R1is selected from C1-C4 alkyl, C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11 - membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, C9-C10 bicyclic aryl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, phenoxy, and 5- or 6- membered heteroaryloxy having one or more heteroatoms selected from N, O and S, wherein said alkyl, cycloalkyl, bicyclic cycloalkyl, heterocycloalkyl, bicyclic heterocycloalkyl, phenyl, bicyclic aryl, heteroaryl, bicyclic heteroaryl, phenoxy and heteroaryloxy are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, NR1aR1 b, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkyl-NR1aR1 b, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, benzyl, phenoxy, halophenoxy, 5- or 6- membered heteroaryloxy having one or more heteroatoms selected from N, O and S, and C1-C4 alkyl substituted by a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[0711] R1aand R1 bare each independently selected from H and C1-C4 alkyl;

[0712] R2is selected from H, C1-C4 alkyl and C3-C8 cycloakyl;

[0713] R3is selected from H, OH, CN, NR3aR3b, C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, Cr C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, C3-C8 cycloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, C1-C4 alkyl-S-C1-C4 alkyl, and C1-C4 alkyl-SO2- C1-C4 alkyl, wherein said alkyl, cycloalkyl, heterocycloalkyl, phenyl and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, C1-C4 alkyl, and NR3cR3d; R3ais selected from H, C1-C4 alkyl, C1-C4 alkyl-OH, and C1-C4 alkyl-NR3eR3f;

[0714] R3b, R3c, R3d, R3eand R3fare each independently selected from H and C1-C4 alkyl;

[0715] R4is selected from C(O)OH, C(O)NR4aR4b, C(S)NR4aR4band 5- or 6-membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0716] R4aand R4bare each independently selected from H and C1-C4 alkyl;

[0717] R5and R6are each independently selected from H, halogen, OH, CN, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 alkoxy-C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S; or R5and R6together with the carbon atoms to which they are attached form a 5- or 6- membered heterocycloalkyl having one or more heteroatoms selected from N, O and S; and R7, R8, R9, R10, R11, and R12are each independently selected from H, halogen, OH, CN, Cr C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S.

[0718] In embodiments of the compound of formula (1 ),

[0719] L1is a bond, CrCe alkylene, CrCe haloalkylene, C3-C6 cycloalkylene, or a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[0720] R1is selected from C1-C4 alkyl, C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11 - membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, C9-C10 bicyclic aryl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, phenoxy, and 5- or 6- membered heteroaryloxy having one or more heteroatoms selected from N, O and S, wherein said alkyl, cycloalkyl, bicyclic cycloalkyl, heterocycloalkyl, bicyclic heterocycloalkyl, phenyl, bicyclic aryl, heteroaryl, bicyclic heteroaryl, phenoxy and heteroaryloxy are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, NR1aR1 b, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkyl-NR1aR1 b, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, benzyl, halophenoxy, and C1-C4 alkyl substituted by a 5- or 6- membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[0721] R1aand R1 bare each independently selected from H and C1-C4 alkyl;

[0722] R2is selected from H, C1-C4 alkyl and C3-C8 cycloakyl; R3is selected from H, OH, CN, NR3aR3b, C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C1-C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, C3-C8 cycloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, C1-C4 alkyl-S-C1-C4 alkyl, and C1-C4 alkyl-SO2- C1-C4 alkyl, wherein said alkyl, cycloalkyl, heterocycloalkyl, phenyl and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, C1-C4 alkyl, and NR3cR3d; R3ais selected from H, C1-C4 alkyl, and C1-C4 alkyl-NR3eR3f;

[0723] R3bis selected from H and C1-C4 alkyl;

[0724] R3cis selected from H and C1-C4 alkyl;

[0725] R3dis selected from C1-C4 alkyl;

[0726] R3eand R3fare each independently selected from C1-C4 alkyl;

[0727] R4is selected from C(O)OH, C(O)NR4aR4b, C(S)NR4aR4band 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0728] R4ais selected from H and C1-C4 alkyl;

[0729] R4bis H;

[0730] R5and R6are each independently selected from H, halogen, OH, CN, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 alkoxy-C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S; or R5and R6together with the carbon atoms to which they are attached form a 5- or 6- membered heterocycloalkyl having one or more heteroatoms selected from N, O and S; and R7, R8, R9, R10, R11, and R12are each independently selected from H, halogen, OH, CN, Cr C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S.

[0731] In embodiments of the compound of formula (1 ),

[0732] L1is a bond, CrCe alkylene, CrCe haloalkylene, C3-C6 cycloalkylene, or a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[0733] R1is selected from C1-C4 alkyl, C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11 - membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, and phenoxy, wherein said alkyl, cycloalkyl, heterocycloalkyl, bicyclic cycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, bicyclic heteroaryl, and phenoxy are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, NR1aR1 b, C1-C4 alkyl, C1-C4haloalkyl, C1-C4alkoxy, C1-C4 haloalkoxy, C1-C4 alkyl-NR1aR1 b, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, benzyl, halophenoxy, and C1-C4 alkyl substituted by a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[0734] R1aand R1 bare each independently selected from H and C1-C4 alkyl;

[0735] R2is H;

[0736] R3is selected from H, CN, NR3aR3b, C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C1-C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, C3-C8 cycloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, C1-C4 alkyl-S-C1-C4 alkyl, and C1-C4 alkyl-SC>2-C1-C4 alkyl, wherein said alkyl, cycloalkyl, heterocycloalkyl, phenyl and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, and NR3cR3d;

[0737] R3ais selected from H, C1-C4 alkyl, and C1-C4 alkyl-NR3eR3f;

[0738] R3bis selected from H and C1-C4 alkyl;

[0739] R3cis selected from H and C1-C4 alkyl;

[0740] R3dis selected from C1-C4 alkyl;

[0741] R3eand R3fare each independently selected from C1-C4 alkyl;

[0742] R4is selected from C(O)OH, C(O)NR4aR4b, C(S)NR4aR4band 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0743] R4ais selected from H and C1-C4 alkyl;

[0744] R4bis HR5is selected from H, C1-C4 alkyl, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0745] R6is selected from H, C1-C4 alkyl, C1-C4 alkoxy, and C1-C4 alkoxy-C1-C4 alkyl; and

[0746] R7, R8, R9, R10, R11, and R12are each H.

[0747] In embodiments of the compound of formula (1 ),

[0748] L1is a bond, CrCe alkylene, CrCehaloalkylene, C3-C6 cycloalkylene, or a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[0749] R1selected from:

[0750] C1-C4 haloalkyl; C3-C8 cycloalkyl optionally substituted by one or more substituents independently selected from halogen, OH, CN, NR1aR1 b, C1-C4 alkyl, C1-C4 alkoxy, and C1-C4 haloalkoxy;

[0751] C7-C11 bicyclic cycloalkyl optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, benzyl, C3-C8 cycloalkyl, halophenoxy, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, and C1-C4 alkyl substituted by a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[0752] 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2;

[0753] 8- to 11 -membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, optionally substituted by one or more substituents independently selected from halogen ; phenyl optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkyl-NR1aR1 b, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0754] 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, optionally substituted by one or more substituents independently selected from C1-C4 alkyl and C1-C4 haloalkyl;

[0755] 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, optionally substituted by one or more substitutents independently selected from halogen, C1-C4 alkyl and C1-C4 alkoxy; and phenoxy optionally substituted by one or more C1-C4 alkyl;

[0756] R1aand R1 bare each independently selected from H and C1-C4 alkyl;

[0757] R2is H;

[0758] R3is selected from:

[0759] - H;

[0760] - CN;

[0761] - NR3aR3b;

[0762] C1-C4 alkyl optionally substituted by one of more substituents selected from OH and NR3cR3d;

[0763] C3-C8 cycloalkyl;

[0764] 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, optionally substituted by one or more C1-C4 alkyl; phenyl optionally substituted by one or more halogen; 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0765] C1-C4 alkoxy-C1-C4 alkyl;

[0766] Ci -C4 haloalkoxy-Ci -C4 alkyl ;

[0767] C3-C8cycloalkoxy-C1-C4 alkyl;

[0768] C3-C8 cycloalkyl-C1-C4 alkoxy;

[0769] C1-C4 alkyl-S-C1-C4 alkyl; and

[0770] C1-C4 alkyl-SC>2-C1-C4 alkyl;

[0771] R3ais selected from H, C1-C4 alkyl, and C1-C4 alkyl-NR3eR3f;

[0772] R3bis selected from H and C1-C4 alkyl;

[0773] R3cis selected from H and C1-C4 alkyl;

[0774] R3dis selected from C1-C4 alkyl;

[0775] R3eand R3fare each independently selected from C1-C4 alkyl;

[0776] R4is selected from C(O)OH, C(O)NR4aR4b, C(S)NR4aR4band 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0777] R4ais selected from H and C1-C4 alkyl;

[0778] R4bis H;

[0779] R5is selected from H, C1-C4 alkyl, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0780] R6is selected from H, C1-C4 alkyl, C1-C4 alkoxy, and C1-C4 alkoxy-C1-C4 alkyl; and R7, R8, R9, R10, R11, and R12are each H.

[0781] In embodiments of the compound of formula (1 ),

[0782] L1is a bond, CrCe alkylene, CrCehaloalkylene, C3-C6 cycloalkylene, or a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[0783] R1selected from:

[0784] C1-C4 haloalkyl;

[0785] C3-C8 cycloalkyl optionally substituted by one or more substituents independently selected from halogen, OH, CN, NR1aR1 b, C1-C4 alkyl, C1-C4 alkoxy, and C1-C4 haloalkoxy;

[0786] C7-C11 bicyclic cycloalkyl optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, benzyl, C3-C8 cycloalkyl, halophenoxy, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, and C1-C4 alkyl substituted by a 5- or

[0787] 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S; 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2;

[0788] 8- to 11 -membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, optionally substituted by one or more substituents independently selected from halogen ; phenyl optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkyl-NR1aR1 b, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0789] 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, substituted by one or more substituents independently selected from C1-C4 alkyl and C1-C4 haloalkyl;

[0790] 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, optionally substituted by one or more substitutents independently selected from halogen, C1-C4 alkyl and C1-C4 alkoxy; and phenoxy substituted by one or more C1-C4 alkyl;

[0791] R1aand R1 bare each independently selected from H and C1-C4 alkyl;

[0792] R2is H;

[0793] R3is selected from:

[0794] - H;

[0795] - CN;

[0796] - NR3aR3b;

[0797] C1-C4 alkyl optionally substituted by one or more substituents selected from OH and NR3cR3d;

[0798] C3-C8 cycloalkyl;

[0799] 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, optionally substituted by one or more C1-C4 alkyl; phenyl optionally substituted by one or more halogen;

[0800] 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0801] C1-C4 alkoxy-C1-C4 alkyl;

[0802] Ci -C4 haloalkoxy-Ci -C4 alkyl ;

[0803] C3-C8cycloalkoxy-C1-C4 alkyl;

[0804] C3-C8 cycloalkyl-C1-C4 alkoxy;

[0805] C1-C4 alkyl-S-C1-C4 alkyl; and

[0806] C1-C4 alkyl-SC>2- C1-C4 alkyl;

[0807] R3ais selected from H, C1-C4 alkyl, and C1-C4 alkyl-NR3eR3f;

[0808] R3bis selected from H and C1-C4 alkyl; R3cis selected from H and C1-C4 alkyl;

[0809] R3dis selected from C1-C4 alkyl;

[0810] R3eand R3fare each independently selected from C1-C4 alkyl;

[0811] R4is selected from C(O)OH, C(O)NR4aR4b, C(S)NR4aR4band 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0812] R4ais selected from H and C1-C4 alkyl;

[0813] R4bis H;

[0814] R5is selected from H, C1-C4 alkyl, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0815] R6is selected from H, C1-C4 alkyl, C1-C4 alkoxy, and C1-C4 alkoxy-C1-C4 alkyl; and R7, R8, R9, R10, R11, and R12are each H.

[0816] In embodiments of the compound of formula (1 ),

[0817] L1is a bond, CrCe alkylene, CrCe haloalkylene, or C3-C6 cycloalkylene;

[0818] R1is selected from C1-C4 alkyl, C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11 - membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, and phenoxy, wherein said alkyl, cycloalkyl, heterocycloalkyl, bicyclic cycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, bicyclic heteroaryl, and phenoxy are each optionally substituted by one or more substituents independently selected from halogen, CN, OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkyl-NR1aR1 b, C3-C8 cycloalkyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, benzyl, and C1-C4 alkyl substituted by a 5- or 6- membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[0819] R1aand R1 bare each independently selected from H and C1-C4 alkyl;

[0820] R2is H;

[0821] R3is selected from H, CN, NR3aR3b, C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C1-C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, C3-C8 cycloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, C1-C4 alkyl-S-C1-C4 alkyl, and C1-C4 alkyl-SC>2-C1-C4 alkyl, wherein said alkyl, cycloalkyl, heterocycloalkyl, phenyl and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH and NR3cR3d;

[0822] R3ais selected from H and C1-C4 alkyl;

[0823] R3bis selected from C1-C4 alkyl; R3cis selected from H and C1-C4 alkyl;

[0824] R3dis selected from C1-C4 alkyl;

[0825] R4is selected from C(O)OH, C(O)NR4aR4b, C(S)NR4aR4band 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0826] R4ais selected from H and C1-C4 alkyl;

[0827] R4bis H;

[0828] R5is selected from H, C1-C4 alkyl, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0829] R6is selected from H, C1-C4 alkyl, C1-C4 alkoxy, and C1-C4 alkoxy-C1-C4 alkyl; and

[0830] R7, R8, R9, R10, R11, and R12are each H.

[0831] In embodiments of the compound of formula (1 ),

[0832] L1is a bond, CrCe alkylene, CrCe haloalkylene, or C3-C6 cycloalkylene;

[0833] R1is selected from:

[0834] C1-C4 haloalkyl;

[0835] C3-C8 cycloalkyl optionally substituted by one or more substituents independently selected from halogen, OH, CN, C1-C4 alkyl, C1-C4 alkoxy, and C1-C4 haloalkoxy;

[0836] C7-C11 bicyclic cycloalkyl optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, benzyl, C3-C8 cycloalkyl, and C1-C4 alkyl substituted by a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[0837] 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2;

[0838] 8- to 11 -membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, optionally substituted by one or more substituents independently selected from halogen; phenyl optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkyl-NR1aR1 b, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0839] 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, optionally substituted by one or more substituents independently selected from C1-C4 alkyl and C1-C4 haloalkyl;

[0840] 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, optionally substituted by one or more substituents independently selected halogen, C1-C4 alkyl and C1-C4 alkoxy; and phenoxy optionally substituted by one or more C1-C4 alkyl;

[0841] R1aand R1 bare each independently selected from H and C1-C4 alkyl; R2is H;

[0842] R3is selected from:

[0843] - H;

[0844] - CN;

[0845] - NR3aR3b;

[0846] C1-C4 alkyl optionally substituted by one or more substituents independently selected from OH and NR3cR3d;

[0847] C3-C8 cycloalkyl;

[0848] 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S; phenyl substituted by one or more halogen;

[0849] 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0850] C1-C4 alkoxy-C1-C4 alkyl;

[0851] C3-C8 cycloalkyl-C1-C4 alkoxy;

[0852] C3-C8cycloalkoxy-C1-C4 alkyl;

[0853] Ci -C4 haloalkoxy-Ci -C4 alkyl ;

[0854] C1-C4 alkyl-S-C1-C4 alkyl; and

[0855] C1-C4 alkyl-SO2-C1-C4 alkyl;

[0856] R3ais selected from H and C1-C4 alkyl;

[0857] R3bis selected from C1-C4 alkyl;

[0858] R3cis selected from H and C1-C4 alkyl;

[0859] R3dis selected from C1-C4 alkyl;

[0860] R4is selected from C(O)OH, C(O)NR4aR4b, C(S)NR4aR4band 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0861] R4ais selected from H and C1-C4 alkyl;

[0862] R4bis H;

[0863] R5is selected from H, C1-C4 alkyl, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0864] R6is selected from H, C1-C4 alkyl, C1-C4 alkoxy, and C1-C4 alkoxy-C1-C4 alkyl; and

[0865] R7, R8, R9, R10, R11, and R12are each H.

[0866] In embodiments of the compound of formula (1 ),

[0867] L1is a bond, CrCe alkylene, CrCe haloalkylene, or C3-C6 cycloalkylene;

[0868] R1is selected from:

[0869] C1-C4 haloalkyl; C3-C8 cycloalkyl optionally substituted by one or more substituents independently selected from halogen, OH, CN, C1-C4 alkyl, C1-C4 alkoxy, and C1-C4 haloalkoxy;

[0870] C7-C11 bicyclic cycloalkyl optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, benzyl, C3-C8 cycloalkyl, and C1-C4 alkyl substituted by a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[0871] 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2;

[0872] 8- to 11 -membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, optionally substituted by one or more substituents independently selected from halogen; phenyl optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkyl-NR1aR1 b, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0873] 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, substituted by one or more substituents independently selected from C1-C4 alkyl and C1-C4 haloalkyl;

[0874] 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, optionally substituted by one or more substituents independently selected from halogen, C1-C4 alkyl and C1-C4 alkoxy; and phenoxy substituted by one or more C1-C4 alkyl;

[0875] R1aand R1 bare each independently selected from H and C1-C4 alkyl;

[0876] R2is H;

[0877] R3is selected from:

[0878] - H;

[0879] - CN;

[0880] - NR3aR3b;

[0881] C1-C4 alkyl optionally substituted by one or more substituents independently selected from OH and NR3cR3d;

[0882] C3-C8 cycloalkyl;

[0883] 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S; phenyl substituted by one or more halogen;

[0884] 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0885] C1-C4 alkoxy-C1-C4 alkyl;

[0886] C3-C8 cycloalkyl-C1-C4 alkoxy; C3-C8cycloalkoxy-C1-C4 alkyl;

[0887] Ci -C4 haloalkoxy-Ci -C4 alkyl ;

[0888] C1-C4 alkyl-S-C1-C4 alkyl; and

[0889] C1-C4 alkyl-SC>2-C1-C4 alkyl;

[0890] R3ais selected from H and C1-C4 alkyl;

[0891] R3bis selected from C1-C4 alkyl;

[0892] R3cis selected from H and C1-C4 alkyl;

[0893] R3dis selected from C1-C4 alkyl;

[0894] R4is selected from C(O)OH, C(O)NR4aR4b, C(S)NR4aR4band 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0895] R4ais selected from H and C1-C4 alkyl;

[0896] R4bis H;

[0897] R5is selected from H, C1-C4 alkyl, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0898] R6is selected from H, C1-C4 alkyl, C1-C4 alkoxy, and C1-C4 alkoxy-C1-C4 alkyl; and R7, R8, R9, R10, R11, and R12are each H.

[0899] In embodiments of the compound of formula (1 ),

[0900] L1is a bond, CrCe alkylene, CrCe haloalkylene, or C3-C6 cycloalkylene;

[0901] R1is selected from C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11- membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, and 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, wherein said cycloalkyl, bicyclic cycloalkyl, heterocycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, and bicyclic heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, CN, OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkyl- NR1aR1 b, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0902] R1aand R1 bare each independently selected from H and C1-C4 alkyl;

[0903] R2is H;

[0904] R3is selected from H, CN, NR3aR3b, C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C1-C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, C3-C8 cycloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, C1-C4 alkyl-S-C1-C4 alkyl, and C1-C4 alkyl-SC>2-C1-C4 alkyl, wherein said alkyl, cycloalkyl, heterocycloalkyl, phenyl and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH and NR3cR3d;

[0905] R3ais selected from H and C1-C4 alkyl;

[0906] R3bis selected from C1-C4 alkyl;

[0907] R3cis selected from H and C1-C4 alkyl;

[0908] R3dis selected from C1-C4 alkyl;

[0909] R4is selected from the following groups: wherein indicates the point of attachment to the rest of the compound;

[0910] R5is selected from H and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0911] R6is selected from H, C1-C4 alkyl, C1-C4 alkoxy, and C1-C4 alkoxy-C1-C4 alkyl; and

[0912] R7, R8, R9, R10, R11, and R12are each H.

[0913] In embodiments of the compound of formula (1 ),

[0914] L1is a bond, CrCe alkylene, CrCe haloalkylene, or C3-C6 cycloalkylene;

[0915] R1is selected from:

[0916] C3-C8 cycloalkyl optionally substituted by one or more substituents independently selected from halogen, CN, C1-C4 alkyl, and C1-C4 haloalkoxy;

[0917] C7-C11 bicyclic cycloalkyl optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy;

[0918] 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2;

[0919] 8- to 11 -membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, optionally substituted by one or more substituents independently selected from halogen; phenyl optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkyl-NR1aR1 b, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S; 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, optionally substituted by one or more substituents independently selected from C1-C4 alkyl and C1-C4 haloalkyl; and

[0920] 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, optionally substituted substituted by one or more substituents independently selected from halogen and C1-C4 alkyl;

[0921] R1aand R1 bare each independently selected from H and C1-C4 alkyl;

[0922] R2is H;

[0923] R3is selected from:

[0924] - H;

[0925] - CN;

[0926] - NR3aR3b;

[0927] C1-C4 alkyl optionally substituted by one or more substituents independently selected from OH and NR3cR3d;

[0928] C3-C8 cycloalkyl;

[0929] 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S; phenyl substituted by one or more halogen;

[0930] 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0931] C1-C4 alkoxy-C1-C4 alkyl;

[0932] C3-C8 cycloalkyl-C1-C4 alkoxy;

[0933] C3-C8cycloalkoxy-C1-C4 alkyl;

[0934] Ci -C4 haloalkoxy-Ci -C4 alkyl ;

[0935] C1-C4 alkyl-S-C1-C4 alkyl; and

[0936] C1-C4 alkyl-SO2-C1-C4 alkyl;

[0937] R3ais selected from H and C1-C4 alkyl;

[0938] R3bis selected from C1-C4 alkyl;

[0939] R3cis selected from H and C1-C4 alkyl;

[0940] R3dis selected from C1-C4 alkyl;

[0941] R4is selected from the following groups: wherein indicates the point of attachment to the rest of the compound;

[0942] R5is selected from H and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0943] R6is selected from H, C1-C4 alkyl, C1-C4 alkoxy, and C1-C4 alkoxy-C1-C4 alkyl; and

[0944] R7, R8, R9, R10, R11, and R12are each H.

[0945] In embodiments of the compound of formula (1 ),

[0946] L1is a bond, CrCe alkylene, CrCe haloalkylene, or C3-C6 cycloalkylene;

[0947] R1is selected from:

[0948] C3-C8 cycloalkyl optionally substituted by one or more substituents independently selected from halogen, CN, C1-C4 alkyl, and C1-C4 haloalkoxy;

[0949] C7-C11 bicyclic cycloalkyl optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy;

[0950] 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2;

[0951] 8- to 11 -membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, optionally substituted by one or more substituents independently selected from halogen; phenyl optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkyl-NR1aR1 b, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0952] 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, substituted by one or more substituents independently selected from C1-C4 alkyl and C1-C4 haloalkyl; and

[0953] 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, optionally substituted substituted by one or more substituents independently selected from halogen and C1-C4 alkyl;

[0954] R1aand R1 bare each independently selected from H and C1-C4 alkyl;

[0955] R2is H;

[0956] R3is selected from: - H;

[0957] - CN;

[0958] - NR3aR3b;

[0959] C1-C4 alkyl optionally substituted by one or more substituents independently selected from OH and NR3cR3d;

[0960] C3-C8 cycloalkyl;

[0961] 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S; phenyl substituted by one or more halogen;

[0962] 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0963] C1-C4 alkoxy-C1-C4 alkyl;

[0964] C3-C8 cycloalkyl-C1-C4 alkoxy;

[0965] C3-C8cycloalkoxy-C1-C4 alkyl;

[0966] Ci -C4 haloalkoxy-Ci -C4 alkyl ;

[0967] C1-C4 alkyl-S-C1-C4 alkyl; and

[0968] C1-C4 alkyl-SO2-C1-C4 alkyl;

[0969] R3ais selected from H and C1-C4 alkyl;

[0970] R3bis selected from C1-C4 alkyl;

[0971] R3cis selected from H and C1-C4 alkyl;

[0972] R3dis selected from C1-C4 alkyl;

[0973] R4is selected from the following groups: wherein indicates the point of attachment to the rest of the compound;

[0974] R5is selected from H, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[0975] R6is selected from H, C1-C4 alkyl, C1-C4 alkoxy, and C1-C4 alkoxy-C1-C4 alkyl; and

[0976] R7, R8, R9, R10, R11, and R12are each H.

[0977] In embodiments of the compound of formula (1 ),

[0978] L1is a bond, CrCe alkylene, or C3-C6 cycloalkylene; R1is selected from C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11- membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, and 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, wherein said cycloalkyl, hetercycloalkyl, bicyclic cycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, and bicyclic heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, and C1-C4 haloalkoxy;

[0979] R2is H;

[0980] R3is selected from H, CN, NR3aR3b, C1-C4 alkyl optionally substituted by OH, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C1-C4 alkoxy-C1-C4 alkyl, C3-C8 cycloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl- C1-C4 alkoxy, C1-C4 haloalkoxy-C1-C4 alkyl, C1-C4 alkyl-S-C1-C4 alkyl, and C1-C4 alkyl-SO2- C1-C4 alkyl;

[0981] R3ais H;

[0982] R3bis selected from C1-C4 alkyl;

[0983] R4is selected from the following groups: indicates the point of attachment to the rest of the compound;

[0984] R5is H;

[0985] R6is selected from H and C1-C4 alkyl; and

[0986] R7, R8, R9, R10, R11, and R12are each H.

[0987] In embodiments of the compound of formula (1 ),

[0988] L1is either a bond, CrCe alkylene, or C3-C6 cycloalkylene;

[0989] R1is selected from:

[0990] C3-C8 cycloalkyl optionally substituted by one or more substituents independently selected from halogen, C1-C4 alkyl, and C1-C4 haloalkoxy;

[0991] C7-C11 bicyclic cycloalkyl optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, and C1-C4 alkoxy; 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2;

[0992] 8- to 11 -membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, optionally substituted by one or more substituents independently selected from halogen; phenyl optionally substituted by one or more substituents independently selected from halogen, C1-C4 alkyl and C1-C4 alkoxy;

[0993] 5- or 6- membered heteroaryl having one or more ring members selected from N, O, S and SO2, optionally substituted by one or more substituents independently selected from C1-C4 alkyl and C1-C4 haloalkyl; and

[0994] 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, optionally substituted substituted by one or more substituents independently selected from halogen and C1-C4 alkyl;

[0995] R2is H;

[0996] R3is selected from:

[0997] - H;

[0998] - CN;

[0999] - NR3aR3b;

[1000] C1-C4 alkyl optionally substituted by OH;

[1001] C3-C8 cycloalkyl;

[1002] 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[1003] 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[1004] C1-C4 alkoxy-C1-C4 alkyl;

[1005] C3-C8 cycloalkyl-C1-C4 alkoxy;

[1006] C3-C8cycloalkoxy-C1-C4 alkyl

[1007] Ci -C4 haloalkoxy-Ci -C4 alkyl ;

[1008] C1-C4 alkyl-S-C1-C4 alkyl; and

[1009] C1-C4 alkyl-SO2-C1-C4 alkyl;

[1010] R3ais H;

[1011] R3bis selected from C1-C4 alkyl.

[1012] R4is selected from the following groups: point of attachment to the rest of the compound;

[1013] R5is H;

[1014] R6is selected from H and C1-C4 alkyl; and R7, R8, R9, R10, R11, and R12are each H.

[1015] In embodiments of the compound of formula (1 ),

[1016] L1is either a bond, CrCe alkylene, or C3-C6 cycloalkylene;

[1017] R1is selected from:

[1018] C3-C8 cycloalkyl optionally substituted by one or more substituents independently selected from halogen, C1-C4 alkyl, and C1-C4 haloalkoxy;

[1019] C7-C11 bicyclic cycloalkyl optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, and C1-C4 alkoxy;

[1020] 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2;

[1021] 8- to 11 -membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, optionally substituted by one or more substituents independently selected from halogen; phenyl optionally substituted by one or more substituents independently selected from halogen, C1-C4 alkyl and C1-C4 alkoxy;

[1022] 5- or 6- membered heteroaryl having one or more ring members selected from N, O, S and SO2, substituted by one or more substituents independently selected from Cr C4 alkyl and C1-C4 haloalkyl; and

[1023] 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, optionally substituted substituted by one or more substituents independently selected from halogen and C1-C4 alkyl;

[1024] R2is H;

[1025] R3is selected from:

[1026] - H;

[1027] - CN;

[1028] - NR3aR3b;

[1029] C1-C4 alkyl optionally substituted by OH;

[1030] C3-C8 cycloalkyl; 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[1031] 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[1032] C1-C4 alkoxy-C1-C4 alkyl;

[1033] C3-C8 cycloalkyl-C1-C4 alkoxy;

[1034] C3-C8cycloalkoxy-C1-C4 alkyl;

[1035] Ci -C4 haloalkoxy-Ci -C4 alkyl ;

[1036] C1-C4 alkyl-S-C1-C4 alkyl; and

[1037] C1-C4 alkyl-SC>2-C1-C4 alkyl;

[1038] R3ais H;

[1039] R3bis selected from C1-C4 alkyl.

[1040] R4is selected from the following groups: indicates the point of attachment to the rest of the compound;

[1041] R5is H;

[1042] R6is selected from H and C1-C4 alkyl; and

[1043] R7, R8, R9, R10, R11, and R12are each H.

[1044] In embodiments of the compound of formula (1 ),

[1045] L1is either a bond or CrCe alkylene;

[1046] R1is selected from C3-C8 cycloalkyl, C8-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11- membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, 5- or 6-membered heteroaryl having one or more ring members selected from N, O, S and SO2, and 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, wherein said cycloalkyl, bicyclic cycloalkyl, heterocycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, and bicyclic heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, and C1-C4 haloalkoxy;

[1047] R2is H;

[1048] R3is selected from NR3aR3b, C1-C4 alkyl optionally substituted by one or more substituents independently selected from OH and NR3cR3d, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C3-C8 cycloalkoxy-C1-C4 alkyl, C1-C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, and alkyl-S-C1-C4 alkyl;

[1049] R3ais H;

[1050] R3bis selected from C1-C4 alkyl;

[1051] R4is selected from the following groups: indicates the point of attachment to the rest of the compound;

[1052] R5, R7, R8, R9, R10, R11, and R12are each H; and

[1053] R6is selected from H and C1-C4 alkyl.

[1054] In embodiments of the compound of formula (1 ),

[1055] L1is either a bond or CrCe alkylene;

[1056] R1is selected from:

[1057] C3-C8 cycloalkyl optionally substituted by one or more substituents independently selected from halogen and C1-C4 haloalkoxy;

[1058] C8-C11 bicyclic cycloalkyl optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl and C1-C4 alkoxy;

[1059] 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2;

[1060] 8- to 11 -membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, optionally substituted by one or more substituents independently selected from halogen; phenyl optionally substituted by one or more substituents independently selected from halogen and C1-C4 alkyl;

[1061] 5- or 6- membered heteroaryl having one or more ring members selected from N, O, S and SO2, optionally substituted by one or more substituents independently selected from C1-C4 alkyl and C1-C4 haloalkyl; and

[1062] 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, optionally substituted substituted by one or more substituents independently selected from halogen and C1-C4 alkyl;

[1063] R2is H; R3is selected from:

[1064] - NR3aR3b;

[1065] C1-C4 alkyl optionally substituted by OH;

[1066] C3-C8 cycloalkyl;

[1067] 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[1068] 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[1069] C1-C4 alkoxy-C1-C4 alkyl;

[1070] C3-C8 cycloalkyl-C1-C4 alkoxy;

[1071] C3-C8cycloalkoxy-C1-C4 alkyl;

[1072] C1-C4 haloalkoxy-C1-C4 alkyl; and

[1073] C1-C4 alkyl-S-C1-C4 alkyl;

[1074] R3ais H;

[1075] R3bis selected from C1-C4 alkyl;

[1076] R4is selected from the following groups: indicates the point of attachment to the rest of the compound H;

[1077] R5, R7, R8, R9, R10, R11, and R12are each H; and

[1078] R6is selected from H and C1-C4 alkyl.

[1079] In embodiments of the compound of formula (1 ),

[1080] L1is either a bond or CrCe alkylene;

[1081] R1is selected from:

[1082] C3-C8 cycloalkyl substituted by one or more substituents independently selected from halogen and C1-C4 haloalkoxy;

[1083] C8-C11 bicyclic cycloalkyl optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl and C1-C4 alkoxy;

[1084] 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2;

[1085] 8- to 11 -membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, optionally substituted by one or more substituents independently selected from halogen; phenyl substituted by one or more substituents independently selected from halogen and C1-C4 alkyl;

[1086] 5- or 6- membered heteroaryl having one or more ring members selected from N, O, S and SO2, substituted by one or more substituents independently selected from Cr C4 alkyl and C1-C4 haloalkyl; and

[1087] 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, substituted by one or more substituents independently selected from halogen and C1-C4 alkyl;

[1088] R2is H;

[1089] R3is selected from:

[1090] - NR3aR3b;

[1091] C1-C4 alkyl optionally substituted by OH;

[1092] C3-C8 cycloalkyl;

[1093] 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[1094] 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[1095] C1-C4 alkoxy-C1-C4 alkyl;

[1096] C3-C8 cycloalkyl-C1-C4 alkoxy;

[1097] C3-C8cycloalkoxy-C1-C4 alkyl;

[1098] C1-C4 haloalkoxy-C1-C4 alkyl; and

[1099] C1-C4 alkyl-S-C1-C4 alkyl;

[1100] R3ais H;

[1101] R3bis selected from C1-C4 alkyl;

[1102] R4is selected from the following groups: indicates the point of attachment to the rest of the compound;

[1103] R5, R7, R8, R9, R10, R11, and R12are each H; and

[1104] R6is selected from H and C1-C4 alkyl.

[1105] In embodiments of the compound of formula (1 ),

[1106] In embodiments of the compound of formula (1 ), L1is a bond, CrCe alkylene, CrCe haloalkylene, C3-C6 cycloalkylene, or a 5- or 6-membered heterocycloalkylene having one or more heteroatoms selected from N, O and S.

[1107] In embodiments of the compound of formula (1 ),

[1108] L1is a bond, CrCe alkylene, CrCe haloalkylene, or C3-C6 cycloalkylene.

[1109] In embodiments of the compound of formula (1 ),

[1110] L1is a bond, methylene, ethylidene, 2 ,2 ,2-trifluoroethylidene, and cyclopropylidene.

[1111] In embodiments of the compound of formula (1 ),

[1112] L1is a bond, CrCe alkylene or a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S.

[1113] In embodiments of the compound of formula (1 ),

[1114] L1is either a bond or CrCe alkylene.

[1115] In embodiments of the compound of formula (1 ),

[1116] L1is either a bond or methylene.

[1117] In embodiments of the compound of formula (1 ),

[1118] L1is CrCe alkylene.

[1119] In embodiments of the compound of formula (1 ),

[1120] L1is methylene.

[1121] In embodiments of the compound of formula (1 ),

[1122] L1is a bond.

[1123] In embodiments of the compound of formula (1 ),

[1124] L1is a 5- or 6-membered heterocycloalkylene having one or more heteroatoms selected from N, O and S.

[1125] In embodiments of the compound of formula (1 ),

[1126] R1is selected from C1-C4 alkyl, C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11 - membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, C9-C10 bicyclic aryl, 5- or 6- membered heteroaryl having one or more ring members selected from N, O, S and SO2, 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, phenoxy, and 5- or 6- membered heteroaryloxy having one or more heteroatoms selected from N, O and S, wherein said alkyl, cycloalkyl, bicyclic cycloalkyl, heterocycloalkyl, bicyclic heterocycloalkyl, phenyl, bicyclic aryl, heteroaryl, bicyclic heteroaryl, phenoxy and heteroaryloxy are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, NR1aR1 b, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkyl-NR1aR1 b, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more ring members selected from N, O, S and SO2, benzyl, phenoxy, halophenoxy, 5- or 6- membered heteroaryloxy having one or more heteroatoms selected from N, O and S, and C1-C4 alkyl substituted by a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S; and

[1127] R1aand R1 bare each independently selected from H and C1-C4 alkyl.

[1128] In embodiments of the compound of formula (1 ),

[1129] R1is selected from C1-C4 alkyl, C3-C8 cycloalkyl, C8-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11 - membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, C9-C10 bicyclic aryl, 5- or 6- membered heteroaryl having one or more ring members selected from N, O, S and SO2, 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, phenoxy, and 5- or 6- membered heteroaryloxy having one or more heteroatoms selected from N, O and S, wherein said alkyl, cycloalkyl, bicyclic cycloalkyl, heterocycloalkyl, bicyclic heterocycloalkyl, phenyl, C9-C10 bicyclic aryl, heteroaryl, bicyclic heteroaryl, phenoxy and heteroaryloxy are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, NR1aR1 b, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkyl-NR1aR1 b, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, benzyl, phenoxy, halophenoxy, 5- or 6- membered heteroaryloxy having one or more heteroatoms selected from N, O and S, and C1-C4 alkyl substituted by a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S; and

[1130] R1aand R1 bare each independently selected from H and C1-C4 alkyl.

[1131] In embodiments of the compound of formula (1 ), R1is selected from C1-C4 alkyl, C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11 - membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, 5- or 6- membered heteroaryl having one or more ring members selected from N, O, S and SO2, 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, and phenoxy, wherein said alkyl, cycloalkyl, heterocycloalkyl, bicyclic cycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, bicyclic heteroaryl, and phenoxy are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, NR1aR1 b, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkyl-NR1aR1 b, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, benzyl, phenoxy, halophenoxy, 5- or 6- membered heteroaryloxy having one or more heteroatoms selected from N, O and S, and C1-C4 alkyl substituted by a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S; and R1aand R1 bare each independently selected from H and C1-C4 alkyl.

[1132] In embodiments of the compound of formula (1 ),

[1133] R1is selected from C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11 - membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, 5- or 6- membered heteroaryl having one or more ring members selected from N, O, S and SO2, and 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, wherein said cycloalkyl, heterocycloalkyl, bicyclic cycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, and bicyclic heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, NR1aR1 b, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkyl- NR1aR1 b, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, benzyl, phenoxy, halophenoxy, 5- or 6- membered heteroaryloxy having one or more heteroatoms selected from N, O and S, and C1-C4 alkyl substituted by a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S; and

[1134] R1aand R1 bare each independently selected from H and C1-C4 alkyl.

[1135] In embodiments of the compound of formula (1 ), R1is selected from C3-C8 cycloalkyl, C8-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11 - membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, 5- or 6- membered heteroaryl having one or more ring members selected from N, O, S and SO2, and 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, wherein said cycloalkyl, bicyclic cycloalkyl, heterocycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, and bicyclic heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, NR1aR1 b, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, Cr C4 alkyl-NR1aR1 b, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, benzyl, phenoxy, halophenoxy, 5- or 6- membered heteroaryloxy having one or more heteroatoms selected from N, O and S, and C1-C4 alkyl substituted by a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S; and

[1136] R1aand R1 bare each independently selected from H and C1-C4 alkyl.

[1137] In embodiments of the compound of formula (1 ),

[1138] R1is selected from C1-C4 alkyl, C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11 - membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, 5- or 6- membered heteroaryl having one or more ring members selected from N, O, S and SO2, 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, and phenoxy, wherein said alkyl, cycloalkyl, heterocycloalkyl, bicyclic cycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, bicyclic heteroaryl, and phenoxy are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, NR1aR1 b, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkyl-NR1aR1 b, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, benzyl, halophenoxy, and C1-C4 alkyl substituted by a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S; and

[1139] R1aand R1 bare each independently selected from H and C1-C4 alkyl.

[1140] In embodiments of the compound of formula (1 ),

[1141] R1is selected from C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 1 1 - membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, 5- or 6- membered heteroaryl having one or more ring members selected from N, O, S and SO2, and 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, wherein said cycloalkyl, bicyclic cycloalkyl, heterocycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, and bicyclic heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, NR1aR1 b, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, Cr C4 alkyl-NR1aR1 b, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, benzyl, halophenoxy, and C1-C4 alkyl substituted by a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S; and

[1142] R1aand R1 bare each independently selected from H and C1-C4 alkyl.

[1143] In embodiments of the compound of formula (1 ),

[1144] R1is selected from C3-C8 cycloalkyl, C8-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11 - membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, 5- or 6-membered heteroaryl having one or more ring members selected from N, O, S and SO2, and 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, wherein said cycloalkyl, bicyclic cycloalkyl, heterocycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, and bicyclic heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, NR1aR1 b, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, Cr C4 alkyl-NR1aR1 b, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, benzyl, halophenoxy, and C1-C4 alkyl substituted by a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S; and

[1145] R1aand R1 bare each independently selected from H and C1-C4 alkyl.

[1146] In embodiments of the compound of formula (1 ),

[1147] R1is selected from C1-C4 alkyl, C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11 - membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, 5- or 6- membered heteroaryl having one or more ring members selected from N, O, S and SO2, 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, and phenoxy, wherein said alkyl, cycloalkyl, heterocycloalkyl, bicyclic cycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, bicyclic heteroaryl, and phenoxy are each optionally substituted by one or more substituents independently selected from halogen, CN, OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkyl-NR1aR1 b, C3-C8 cycloalkyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, benzyl, and C1-C4 alkyl substituted by a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S; and

[1148] R1aand R1 bare each independently selected from H and C1-C4 alkyl.

[1149] In embodiments of the compound of formula (1 ),

[1150] R1is selected from C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11- membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, 5- or 6- membered heteroaryl having one or more ring members selected from N, O, S and SO2, and 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, wherein said cycloalkyl, bicyclic cycloalkyl, heterocycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, and bicyclic heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, CN, OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkyl- NR1aR1 b, C3-C8 cycloalkyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, benzyl, and C1-C4 alkyl substituted by a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S; and R1aand R1 bare each independently selected from H and C1-C4 alkyl.

[1151] In embodiments of the compound of formula (1 ),

[1152] R1is selected from C3-C8 cycloalkyl, C8-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11- membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, 5- or 6- membered heteroaryl having one or more ring members selected from N, O, S and SO2, and 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, wherein said cycloalkyl, bicyclic cycloalkyl, heterocycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, and bicyclic heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, CN, OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkyl- NR1aR1 b, C3-C8 cycloalkyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, benzyl, and C1-C4 alkyl substituted by a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S; and R1aand R1 bare each independently selected from H and C1-C4 alkyl.

[1153] In embodiments of the compound of formula (1 ),

[1154] R1is selected from C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11- membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, 5- or 6- membered heteroaryl having one or more ring members selected from N, O, S and SO2, and 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, wherein said cycloalkyl, bicyclic cycloalkyl, heterocycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, and bicyclic heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, CN, OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkyl- NR1aR1 b, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S; and

[1155] R1aand R1 bare each independently selected from H and C1-C4 alkyl.

[1156] In embodiments of the compound of formula (1 ),

[1157] R1is selected from C3-C8 cycloalkyl, C8-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11- membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, 5- or 6- membered heteroaryl having one or more ring members selected from N, O, S and SO2, and 8- to 10-membered bicyclic heteroaryl having one or more ring mambers selected from N, O, S and SO2, wherein said cycloalkyl, bicyclic cycloalkyl, heterocycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, and bicyclic heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, CN, OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkyl- NR1aR1 b, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S; and

[1158] R1aand R1 bare each independently selected from H and C1-C4 alkyl.

[1159] In embodiments of the compound of formula (1 ),

[1160] R1is selected from C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11- membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, 5- or 6- membered heteroaryl having one or more ring members selected from N, O, S and SO2, and 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, wherein said cycloalkyl, heterocycloalkyl, bicyclic cycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, and bicyclic heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, and C1-C4 haloalkoxy.

[1161] In embodiments of the compound of formula (1 ),

[1162] R1is selected from C3-C8 cycloalkyl, C8-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11- membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, 5- or 6-membered heteroaryl having one or more ring members selected from N, O, S and SO2, and 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, wherein said cycloalkyl, heterocycloalkyl, bicyclic cycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, and bicyclic heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, and C1-C4 haloalkoxy.

[1163] In embodiments of the compound of formula (1 ),

[1164] R1is selected from:

[1165] C1-C4 haloalkyl;

[1166] C3-C8 cycloalkyl optionally substituted by one or more substituents independently selected from halogen, OH, ON, NR1aR1 b, C1-C4 alkyl, C1-C4 alkoxy, and C1-C4 haloalkoxy;

[1167] C7-C11 bicyclic cycloalkyl optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, benzyl, C3-C8 cycloalkyl, halophenoxy, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, and C1-C4 alkyl substituted by a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[1168] 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2;

[1169] 8- to 11 -membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, optionally substituted by one or more substituents independently selected from halogen ; phenyl optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkyl-NR1aR1 b, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S; 5- or 6- membered heteroaryl having one or more ring members selected from N, O, S and SO2, optionally substituted by one or more substituents independently selected from C1-C4 alkyl and C1-C4 haloalkyl;

[1170] 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, optionally substituted by one or more substitutents independently selected from halogen, C1-C4 alkyl and C1-C4 alkoxy; and phenoxy optionally substituted by one or more C1-C4 alkyl; wherein R1aand R1 bare each independently selected from H and C1-C4 alkyl.

[1171] In embodiments of the compound of formula (1 ),

[1172] R1is selected from:

[1173] C1-C4 haloalkyl;

[1174] C3-C8 cycloalkyl optionally substituted by one or more substituents independently selected from halogen, OH, CN, NR1aR1 b, C1-C4 alkyl, C1-C4 alkoxy, and C1-C4 haloalkoxy;

[1175] C7-C11 bicyclic cycloalkyl optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, benzyl, C3-C8 cycloalkyl, halophenoxy, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, and C1-C4 alkyl substituted by a 5- or

[1176] 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[1177] 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2;

[1178] 8- to 11 -membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, optionally substituted by one or more substituents independently selected from halogen ; phenyl optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkyl-NR1aR1 b, and 5- or 6- membered heteroaryl having one or more ring members selected from N, O, S and SO2 (e.g. having one or more ring members selected from N, O and S) ;

[1179] 5- or 6- membered heteroaryl having one or more ring members selected from N, O, S and SO2, substituted by one or more substituents independently selected from Ci- 04 alkyl and C1-C4 haloalkyl;

[1180] 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, optionally substituted by one or more substitutents independently selected from halogen, C1-C4 alkyl and C1-C4 alkoxy; and phenoxy substituted by one or more C1-C4 alkyl; wherein R1aand R1 bare each independently selected from H and C1-C4 alkyl.

[1181] In embodiments of the compound of formula (1 ),

[1182] R1is selected from:

[1183] C1-C4 haloalkyl;

[1184] C3-C8 cycloalkyl optionally substituted by one or more substituents independently selected from halogen, OH, CN, C1-C4 alkyl, C1-C4 alkoxy, and C1-C4 haloalkoxy;

[1185] C7-C11 bicyclic cycloalkyl optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, benzyl, C3-C8 cycloalkyl, and C1-C4 alkyl substituted by a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[1186] 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2;

[1187] 8- to 11 -membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, optionally substituted by one or more substituents independently selected from halogen; phenyl optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkyl-NR1aR1 b, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[1188] 5- or 6- membered heteroaryl having one or more ring members selected from N, O, S and SO2, optionally substituted by one or more substituents independently selected from C1-C4 alkyl and C1-C4 haloalkyl;

[1189] 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, optionally substituted by one or more substituents independently selected from halogen, C1-C4 alkyl and C1-C4 alkoxy; and phenoxy optionally substituted by one or more C1-C4 alkyl; wherein R1aand R1 bare each independently selected from H and C1-C4 alkyl.

[1190] In embodiments of the compound of formula (1 ),

[1191] R1is selected from:

[1192] C1-C4 haloalkyl;

[1193] C3-C8 cycloalkyl optionally substituted by one or more substituents independently selected from halogen, OH, CN, C1-C4 alkyl, C1-C4 alkoxy, and C1-C4 haloalkoxy;

[1194] C7-C11 bicyclic cycloalkyl optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, benzyl, C3-C8 cycloalkyl, and C1-C4 alkyl substituted by a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S; 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2;

[1195] 8- to 11 -membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, optionally substituted by one or more substituents independently selected from halogen; phenyl optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkyl-NR1aR1 b, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[1196] 5- or 6- membered heteroaryl having one or more ring members selected from N, O, S and SO2, substituted by one or more substituents independently selected from Ci- 04 alkyl and C1-C4 haloalkyl;

[1197] 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, optionally substituted by one or more substituents independently selected from halogen, C1-C4 alkyl and C1-C4 alkoxy; and phenoxy substituted by one or more C1-C4 alkyl; wherein R1aand R1 bare each independently selected from H and C1-C4 alkyl.

[1198] In embodiments of the compound of formula (1 ),

[1199] R1is selected from:

[1200] C3-C8 cycloalkyl optionally substituted by one or more substituents independently selected from halogen, CN, C1-C4 alkyl, and C1-C4 haloalkoxy;

[1201] C7-C11 bicyclic cycloalkyl optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy;

[1202] 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2;

[1203] 8- to 11 -membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, optionally substituted by one or more substituents independently selected from halogen; phenyl optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkyl-NR1aR1 b, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[1204] 5- or 6- membered heteroaryl having one or more ring members selected from N, O, S and SO2, optionally substituted by one or more substituents independently selected from C1-C4 alkyl and C1-C4 haloalkyl; and 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, optionally substituted substituted by one or more substituents independently selected from halogen and C1-C4 alkyl; wherein R1aand R1 bare each independently selected from H and C1-C4 alkyl.

[1205] In embodiments of the compound of formula (1 ),

[1206] R1is selected from:

[1207] C3-C8 cycloalkyl optionally substituted by one or more substituents independently selected from halogen, CN, C1-C4 alkyl, and C1-C4 haloalkoxy;

[1208] C7-C11 bicyclic cycloalkyl optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy;

[1209] 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2;

[1210] 8- to 11 -membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, optionally substituted by one or more substituents independently selected from halogen; phenyl optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkyl-NR1aR1 b, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[1211] 5- or 6- membered heteroaryl having one or more ring members selected from N, O, S and SO2, substituted by one or more substituents independently selected from Ci- 04 alkyl and C1-C4 haloalkyl; and

[1212] 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, optionally substituted substituted by one or more substituents independently selected from halogen and C1-C4 alkyl; wherein R1aand R1 bare each independently selected from H and C1-C4 alkyl.

[1213] In embodiments of the compound of formula (1 ),

[1214] R1is selected from:

[1215] C3-C8 cycloalkyl optionally substituted by one or more substituents independently selected from halogen, C1-C4 alkyl, and C1-C4 haloalkoxy;

[1216] C7-C11 bicyclic cycloalkyl optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, and C1-C4 alkoxy;

[1217] 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2; 8- to 11 -membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, optionally substituted by one or more substituents independently selected from halogen; phenyl optionally substituted by one or more substituents independently selected from halogen, C1-C4 alkyl and C1-C4 alkoxy;

[1218] 5- or 6- membered heteroaryl having one or more ring members selected from N, O, S and SO2, optionally substituted by one or more substituents independently selected from C1-C4 alkyl and C1-C4 haloalkyl; and

[1219] 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, optionally substituted substituted by one or more substituents independently selected from halogen and C1-C4 alkyl.

[1220] In embodiments of the compound of formula (1 ),

[1221] R1is selected from:

[1222] C3-C8 cycloalkyl optionally substituted by one or more substituents independently selected from halogen, C1-C4 alkyl, and C1-C4 haloalkoxy;

[1223] C7-C11 bicyclic cycloalkyl optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, and C1-C4 alkoxy;

[1224] 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2;

[1225] 8- to 11 -membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, optionally substituted by one or more substituents independently selected from halogen; phenyl optionally substituted by one or more substituents independently selected from halogen, C1-C4 alkyl and C1-C4 alkoxy;

[1226] 5- or 6- membered heteroaryl having one or more ring members selected from N, O, S and SO2, substituted by one or more substituents independently selected from Cr C4 alkyl and C1-C4 haloalkyl; and

[1227] 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, optionally substituted substituted by one or more substituents independently selected from halogen and C1-C4 alkyl.

[1228] In embodiments of the compound of formula (1 ),

[1229] R1is selected from:

[1230] C3-C8 cycloalkyl optionally substituted by one or more substituents independently selected from halogen and C1-C4 haloalkoxy; C8-C11 bicyclic cycloalkyl optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl and C1-C4 alkoxy;

[1231] 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2;

[1232] 8- to 11 -membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, optionally substituted by one or more substituents independently selected from halogen; phenyl optionally substituted by one or more substituents independently selected from halogen and C1-C4 alkyl;

[1233] 5- or 6- membered heteroaryl having one or more ring members selected from N, O, S and SO2, optionally substituted by one or more substituents independently selected from C1-C4 alkyl and C1-C4 haloalkyl; and

[1234] 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, optionally substituted substituted by one or more substituents independently selected from halogen and C1-C4 alkyl.

[1235] In embodiments of the compound of formula (1 ),

[1236] R1is selected from:

[1237] C3-C8 cycloalkyl substituted by one or more substituents independently selected from halogen and C1-C4 haloalkoxy;

[1238] C8-C11 bicyclic cycloalkyl optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl and C1-C4 alkoxy;

[1239] 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2;

[1240] 8- to 11 -membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, optionally substituted by one or more substituents independently selected from halogen; phenyl substituted by one or more substituents independently selected from halogen and C1-C4 alkyl;

[1241] 5- or 6- membered heteroaryl having one or more ring members selected from N, O, S and SO2, substituted by one or more substituents independently selected from Cr C4 alkyl and C1-C4 haloalkyl; and

[1242] 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, substituted by one or more substituents independently selected from halogen and C1-C4 alkyl.

[1243] In embodiments of the compound of formula (1 ), R1is selected from the following groups:

[1244] ʼnll

[1245]

[1246] wherein indicates the point of attachment to the rest of the compound.

[1247] In embodiments of the compound of formula (1 ), R1is selected from the following groups:

[1248]

[1249] 

[1250] ZZl

[1251] the compound.

[1252] In embodiments of the compound of formula (1 ), R1is selected from the following groups:

[1253]

[1254]

[1255] SET

[1256] wherein indicates the point of attachment to the rest of the compound.

[1257] In embodiments of the compound of formula (1 ), R1is selected from the following groups:

[1258]

[1259] İ171 Z17I 9171

[1260] of the compound.

[1261] In embodiments of the compound of formula (1 ), R1is selected from the following groups:

[1262] Ķt?T

[1263]

[1264]

[1265] wherein indicates the point of attachment to the rest of the compound.

[1266] In embodiments of the compound of formula (1 ), R1is selected from the following groups:

[1267]

[1268]

[1269]

[1270]

[1271] of the compound. In embodiments of the compound of formula (1 ), R1is selected from the following groups: Z.91

[1272]

[1273] the point of attachment to the rest of the compound.

[1274] In embodiments of the compound of formula (1 ), R1is selected from the following groups:

[1275]

[1276]

[1277]

[1278]

[1279] In embodiments of the compound of formula (1 ),

[1280] R1is selected from the following groups: of the compound. In embodiments of the compound of formula (1 ), R1is selected from the following groups:

[1281] Z.81

[1282] of the compound.

[1283] In embodiments of the compound of formula (1 ),

[1284] R1, R2and L1and the nitrogen atom to which R2and L1are attached form a heterocycloalkyl, bicyclic heterocycloalkyl, heteroaryl or bicyclic heteroaryl, wherein said heterocycloalkyl, bicyclic heterocycloalkyl, heteroaryl and bicyclic heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, NR1aR1 b, alkyl, haloalkyl, alkoxy, haloalkoxy and alkyl-NR1aR1 b; and

[1285] R1aand R1 bare each independently selected from H and alkyl. In embodiments of the compound of formula (1 ),

[1286] R1, R2and L1and the nitrogen atom to which R2and L1are attached form a 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, 8- to 11 - membered bicyclic heterocycloalkyl having one or more heteroatoms selected from N, O and S, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, or 8- to 10-membered bicyclic heteroaryl having one or more heteroatoms selected from N, O and S, wherein said heterocycloalkyl, bicyclic heterocycloalkyl, heteroaryl and bicyclic heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, NR1aR1 b, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy and C1-C4alkyl-NR1aR1 b; and

[1287] R1aand R1 bare each independently selected from H and C1-C4 alkyl.

[1288] In embodiments of the compound of formula (1 ),

[1289] R1, R2and L1and the nitrogen atom to which R2and L1are attached form a 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, 8- to 11 - membered bicyclic heterocycloalkyl having one or more heteroatoms selected from N, O and S, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, or 8- to 10-membered bicyclic heteroaryl having one or more heteroatoms selected from N, O and S.

[1290] In embodiments of the compound of formula (1 ),

[1291] R1, R2and L1and the nitrogen atom to which R2and L1are attached form a 8- to 11 - membered bicyclic heterocycloalkyl having one or more heteroatoms selected from N, O and S.

[1292] In embodiments of the compound of formula (1 ),

[1293] R1, R2and L1and the nitrogen atom to which R2and L1are attached form the following bicyclic heterocycloalkyl group:

[1294] In embodiments of the compound of formula (1 ), R2is selected from H, C1-C4 alkyl and C3-C8 cycloalkyl. In embodiments of the compound of formula (1 ), R2is selected from H and C1-C4 alkyl.

[1295] In embodiments of the compound of formula (1 ), R2is H.

[1296] In embodiments of the compound of formula (1 ),

[1297] R3is selected from H, OH, CN, NR3aR3b, C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C1-C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, C3-C8 cycloalkoxy-C1-C4 alkyl, C3-C8 cycloalkoxy-C1-C4 alkyl, C1-C4 alkyl-S-C1-C4 alkyl, and C1-C4 alkyl-SO2-C1-C4 alkyl, wherein said alkyl, cycloalkyl, heterocycloalkyl, phenyl and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, C1-C4 alkyl, Cr C4 alkoxy, and NR3cR3d;

[1298] R3ais selected from H, C1-C4 alkyl, C1-C4 alkyl-OH, and C1-C4 alkyl-NR3eR3f;

[1299] R3b, R3c, R3d, R3eand R3fare each independently selected from H and C1-C4 alkyl.

[1300] In embodiments of the compound of formula (1 ),

[1301] R3is selected from H, CN, NR3aR3b, C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C1-C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, C3-C8 cycloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, C1-C4 alkyl-S-C1-C4 alkyl, and C1-C4 alkyl-SC>2-C1-C4 alkyl, wherein said alkyl, cycloalkyl, heterocycloalkyl, phenyl and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, Ci- 04 alkyl, C1-C4 alkoxy, and NR3cR3d;

[1302] R3ais selected from H, C1-C4 alkyl, C1-C4 alkyl-OH, and C1-C4 alkyl-NR3eR3f;

[1303] R3b, R3c, R3d, R3eand R3fare each independently selected from H and C1-C4 alkyl.

[1304] In embodiments of the compound of formula (1 ),

[1305] R3is selected from H, CN, NR3aR3b, C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C1-C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, C3-C8 cycloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, C1-C4 alkyl-S-C1-C4 alkyl, and C1-C4 alkyl-SC>2-C1-C4 alkyl, wherein said alkyl, cycloalkyl, heterocycloalkyl, and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, C1-C4 alkyl, C1-C4 alkoxy, and NR3cR3d;

[1306] R3ais selected from H, C1-C4 alkyl, C1-C4 alkyl-OH, and C1-C4 alkyl-NR3eR3f;

[1307] R3b, R3c, R3d, R3eand R3fare each independently selected from H and C1-C4 alkyl.

[1308] In embodiments of the compound of formula (1 ),

[1309] R3is selected from NR3aR3b, C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C1-C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, C3-C8 cycloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, and C1-C4 alkyl-S-C1-C4 alkyl, wherein said alkyl, cycloalkyl, heterocycloalkyl, and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, C1-C4 alkyl, C1-C4 alkoxy, and NR3cR3d;

[1310] R3ais selected from H, C1-C4 alkyl, C1-C4 alkyl-OH, and C1-C4 alkyl-NR3eR3f;

[1311] R3b, R3c, R3d, R3eand R3fare each independently selected from H and C1-C4 alkyl.

[1312] In embodiments of the compound of formula (1 ),

[1313] R3is selected from H, CN, NR3aR3b, C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C1-C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, C3-C8 cycloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, C1-C4 alkyl-S-C1-C4 alkyl, and C1-C4 alkyl-SC>2-C1-C4 alkyl, wherein said alkyl, cycloalkyl, heterocycloalkyl, phenyl and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, and NR3cR3d;

[1314] R3ais selected from H, C1-C4 alkyl, and C1-C4 alkyl-NR3eR3f;

[1315] R3bis selected from H and C1-C4 alkyl;

[1316] R3cis selected from H and C1-C4 alkyl;

[1317] R3dis selected from C1-C4 alkyl; and

[1318] R3eand R3fare each independently selected from C1-C4 alkyl.

[1319] In embodiments of the compound of formula (1 ),

[1320] R3is selected from H, CN, NR3aR3b, C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C1-C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, C3-C8 cycloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, C1-C4 alkyl-S-C1-C4 alkyl, and C1-C4 alkyl-SC>2-C1-C4 alkyl, wherein said alkyl, cycloalkyl, heterocycloalkyl, and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, and NR3cR3d;

[1321] R3ais selected from H, C1-C4 alkyl, and C1-C4 alkyl-NR3eR3f;

[1322] R3bis selected from H and C1-C4 alkyl;

[1323] R3cis selected from H and C1-C4 alkyl;

[1324] R3dis selected from C1-C4 alkyl; and

[1325] R3eand R3fare each independently selected from C1-C4 alkyl.

[1326] In embodiments of the compound of formula (1 ),

[1327] R3is selected from NR3aR3b, C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C1-C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, C3-C8 cycloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, and C1-C4 alkyl-S-C1-C4 alkyl, wherein said alkyl, cycloalkyl, heterocycloalkyl, and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, and NR3cR3d;

[1328] R3ais selected from H, C1-C4 alkyl, and C1-C4 alkyl-NR3eR3f;

[1329] R3bis selected from H and C1-C4 alkyl;

[1330] R3cis selected from H and C1-C4 alkyl;

[1331] R3dis selected from C1-C4 alkyl; and

[1332] R3eand R3fare each independently selected from C1-C4 alkyl.

[1333] In embodiments of the compound of formula (1 ),

[1334] R3is selected from H, CN, NR3aR3b, C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C1-C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, C3-C8 cycloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, C1-C4 alkyl-S-C1-C4 alkyl, and C1-C4 alkyl-SC>2-C1-C4 alkyl, wherein said alkyl, cycloalkyl, heterocycloalkyl, phenyl and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH and NR3cR3d;

[1335] R3ais selected from H and C1-C4 alkyl;

[1336] R3bis selected from C1-C4 alkyl;

[1337] R3cis selected from H and C1-C4 alkyl; and

[1338] R3dis selected from C1-C4 alkyl.

[1339] In embodiments of the compound of formula (1 ), wherein

[1340] R3is selected from H, CN, NR3aR3b, C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C1-C4 alkoxy-C1-C4 alkyl, C3-C8 cycloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, C1-C4 haloalkoxy-C1-C4 alkyl, C1-C4 alkyl-S-C1-C4 alkyl, and C1-C4 alkyl-SC>2-C1-C4 alkyl, wherein said alkyl, cycloalkyl, heterocycloalkyl, and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH and NR3cR3d;

[1341] R3ais selected from H and C1-C4 alkyl;

[1342] R3bis selected from C1-C4 alkyl;

[1343] R3cis selected from H and C1-C4 alkyl; and

[1344] R3dis selected from C1-C4 alkyl.

[1345] In embodiments of the compound of formula (1 ),

[1346] R3is selected from NR3aR3b, C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C1-C4 alkoxy-C1-C4 alkyl, C3-C8 cycloalkoxy-C1-C4 alkyl, C3-C8cycloalkyl-C1-C4 alkoxy, C1-C4 haloalkoxy-C1-C4 alkyl, and Cr C4 alkyl-S-C1-C4 alkyl, wherein said alkyl, cycloalkyl, heterocycloalkyl, and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH and NR3cR3d;

[1347] R3ais selected from H and C1-C4 alkyl;

[1348] R3bis selected from C1-C4 alkyl;

[1349] R3cis selected from H and C1-C4 alkyl; and

[1350] R3dis selected from C1-C4 alkyl.

[1351] In embodiments of the compound of formula (1 ),

[1352] R3is selected from H, CN, NR3aR3b, C1-C4 alkyl optionally substituted by OH, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C1-C4 alkoxy-C1-C4 alkyl, C3-C8 cycloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl- C1-C4 alkoxy, C1-C4 haloalkoxy-C1-C4 alkyl, C1-C4 alkyl-S-C1-C4 alkyl, and C1-C4 alkyl-SO2- C1-C4 alkyl;

[1353] R3ais H; and

[1354] R3bis selected from C1-C4 alkyl.

[1355] In embodiments of the compound of formula (1 ), R3is selected from NR3aR3b, C1-C4 alkyl substituted by one or more substituents independently selected from OH and NR3cR3d, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C1-C4 alkoxy-C1-C4 alkyl, C3-C8 cycloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, C1-C4 haloalkoxy-C1-C4 alkyl, and C1-C4 alkyl-S-C1-C4 alkyl;

[1356] R3ais H;

[1357] R3bis selected from C1-C4 alkyl.

[1358] In embodiments of the compound of formula (1 ),

[1359] R3is selected from:

[1360] - H;

[1361] - CN;

[1362] - NR3aR3b;

[1363] C1-C4 alkyl optionally substituted by one of more substituents selected from OH and NR3cR3d;

[1364] C3-C8 cycloalkyl;

[1365] 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, optionally substituted by one or more C1-C4 alkyl; phenyl optionally substituted by one or more halogen;

[1366] 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[1367] C1-C4 alkoxy-C1-C4 alkyl;

[1368] Ci -C4 haloalkoxy-Ci -C4 alkyl ;

[1369] C3-C8cycloalkoxy-C1-C4 alkyl;

[1370] C3-C8 cycloalkyl-C1-C4 alkoxy;

[1371] C1-C4 alkyl-S-C1-C4 alkyl; and

[1372] C1-C4 alkyl-SC>2-C1-C4 alkyl; wherein

[1373] R3ais selected from H, C1-C4 alkyl, and C1-C4 alkyl-NR3eR3f;

[1374] R3bis selected from H and C1-C4 alkyl;

[1375] R3cis selected from H and C1-C4 alkyl;

[1376] R3dis selected from C1-C4 alkyl; and

[1377] R3eand R3fare each independently selected from C1-C4 alkyl.

[1378] In embodiments of the compound of formula (1 ),

[1379] R3is selected from: - H;

[1380] - CN;

[1381] - NR3aR3b;

[1382] C1-C4 alkyl optionally substituted by one or more substituents independently selected from OH and NR3cR3d;

[1383] C3-C8 cycloalkyl;

[1384] 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S; phenyl substituted by one or more halogen;

[1385] 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[1386] C1-C4 alkoxy-C1-C4 alkyl;

[1387] C3-C8 cycloalkyl-C1-C4 alkoxy;

[1388] C3-C8cycloalkoxy-C1-C4 alkyl;

[1389] Ci -C4 haloalkoxy-Ci -C4 alkyl ;

[1390] C1-C4 alkyl-S-C1-C4 alkyl; and

[1391] C1-C4 alkyl-SO2-C1-C4 alkyl; wherein

[1392] R3ais selected from H and C1-C4 alkyl;

[1393] R3bis selected from C1-C4 alkyl;

[1394] R3cis selected from H and C1-C4 alkyl; and

[1395] R3dis selected from C1-C4 alkyl.

[1396] In embodiments of the compound of formula (1 ),

[1397] R3is selected from:

[1398] - H;

[1399] - CN;

[1400] - NR3aR3b;

[1401] C1-C4 alkyl optionally substituted by OH;

[1402] C3-C8 cycloalkyl;

[1403] 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[1404] 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[1405] C1-C4 alkoxy-C1-C4 alkyl;

[1406] C3-C8 cycloalkyl-C1-C4 alkoxy;

[1407] C3-C8cycloalkoxy-C1-C4 alkyl; Ci -C4 haloalkoxy-Ci -C4 alkyl ;

[1408] C1-C4 alkyl-S-C1-C4 alkyl; and

[1409] C1-C4 alkyl-SC>2-C1-C4 alkyl; wherein

[1410] R3ais H; and

[1411] R3bis selected from C1-C4 alkyl.

[1412] Clause 89. The compound of any preceding clause, wherein

[1413] R3is selected from:

[1414] - NR3aR3b;

[1415] C1-C4 alkyl optionally substituted by OH;

[1416] C3-C8 cycloalkyl;

[1417] 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[1418] 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[1419] C1-C4 alkoxy-C1-C4 alkyl;

[1420] C3-C8 cycloalkyl-C1-C4 alkoxy;

[1421] C3-C8cycloalkoxy-C1-C4 alkyl;

[1422] C1-C4 haloalkoxy-C1-C4 alkyl; and

[1423] C1-C4 alkyl-S-C1-C4 alkyl; wherein

[1424] R3ais H; and

[1425] R3bis selected from C1-C4 alkyl.

[1426] In embodiments of the compound of formula (1 ),

[1427] R3is selected from C1-C4alkoxy-C1-C4 alkyl.

[1428] In embodiments of the compound of formula (1 ), wherein R3is selected from methoxymethyl.

[1429] In embodiments of the compound of formula (1 ),

[1430] R3is selected from the following groups:

[1431] indicates the point of attachment to the rest of the compound.

[1432] In embodiments of the compound of formula (1 ), R3is selected from the following groups:

[1433] indicates the point of attachment to the rest of the compound. In embodiments of the compound of formula (1 ), R3is selected from the following groups: indicates the point of attachment to the rest of the compound.

[1434] In embodiments of the compound of formula (1 ), R3is selected from the following groups:

[1435]

[1436] In embodiments of the compound of formula (1 ), R4is selected from C(O)OH, C(O)NR4aR4b, C(S)NR4aR4band 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S; and R4aand R4bare each independently selected from H and alkyl.

[1437] In embodiments of the compound of formula (1 ), R4is selected from C(O)NR4aR4band 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S; and

[1438] R4aand R4bare each independently selected from H and alkyl. In embodiments of the compound of formula (1 ),

[1439] R4is selected from C(O)OH, C(O)NR4aR4b, C(S)NR4aR4band 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[1440] R4ais selected from H and C1-C4 alkyl; and R4bis H.

[1441] In embodiments of the compound of formula (1 ),

[1442] R4is selected from C(O)OH, C(O)NR4aR4b, and C(S)NR4aR4b;

[1443] R4ais selected from H and C1-C4 alkyl; and R4bis H.

[1444] In embodiments of the compound of formula (1 ),

[1445] R4is selected from C(O)OH, C(O)NR4aR4band C(S)NR4aR4b; and R4aand R4bare each H.

[1446] In embodiments of the compound of formula (1 ),

[1447] R4is C(O)NR4aR4b; and

[1448] R4aand R4bare each H. In embodiments of the compound of formula (1 ), R4is selected from the following groups: , indicates the point of attachment to the rest of the compound.

[1449] In embodiments of the compound of formula (1 ), R4is selected from the following groups:

[1450]

[1451] In embodiments of the compound of formula (1 ), R4is selected from the following groups: point of attachment to the rest of the compound.

[1452] In embodiments of the compound of formula (1 ),

[1453] R4is indicates the point of attachment to the rest of the compound.

[1454] In embodiments of the compound of formula (1 ),

[1455] R5and R6are each independently selected from H, halogen, OH, CN, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 alkoxy-C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S; or R5and R6together with the carbon atoms to which they are attached form a 5- or 6- membered heterocycle having one or more heteroatoms selected from N, O and S.

[1456] In embodiments of the compound of formula (1 ),

[1457] R5and R6are each independently selected from H, halogen, OH, CN, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 alkoxy-C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S; or R5and R6together with the carbon atoms to which they are attached form a 5- or 6- membered heterocycle having one or more heteroatoms selected from N and O.

[1458] In embodiments of the compound of formula (1 ),

[1459] R5is selected from H, halogen, OH, CN, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 alkoxy-C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S.

[1460] In embodiments of the compound of formula (1 ),

[1461] R5is selected from H, C1-C4 alkyl, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S.

[1462] In embodiments of the compound of formula (1 ),

[1463] R5is selected from H and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S.

[1464] In embodiments of the compound of formula (1 ),

[1465] R5is selected from the following groups: indicates the point of attachment to the rest of the compound.

[1466] In embodiments of the compound of formula (1 ), R5is selected from the following groups: In embodiments of the compound of formula (1 ), R5is H.

[1467] In embodiments of the compound of formula (1 ),

[1468] R6is selected from H, halogen, OH, CN, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 alkoxy-C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S.

[1469] In embodiments of the compound of formula (1 ),

[1470] R6is selected from H, C1-C4 alkyl, C1-C4 alkoxy, and C1-C4 alkoxy-C1-C4 alkyl.

[1471] In embodiments of the compound of formula (1 ), R6is selected from H and C1-C4 alkyl.

[1472] In embodiments of the compound of formula (1 ), R6is selected from the following groups: indicates the point of attachment to the rest of the compound.

[1473] In embodiments of the compound of formula (1 ), R6is H or methyl.

[1474] In embodiments of the compound of formula (1 ), R6is H.

[1475] In embodiments of the compound of formula (1 ),

[1476] R5and R6together with the carbon atoms to which they are attached form a 5- or 6- membered heterocycle having one or more heteroatoms selected from N, O and S.

[1477] In embodiments of the compound of formula (1 ),

[1478] R5and R6together with the carbon atoms to which they are attached form a 5- or 6- membered heterocycle having one or more heteroatoms selected from N and O.

[1479] In embodiments of the compound of formula (1 ), R5and R6together with the carbon atoms to which they are attached form a 5-membered heterocycle containing one O atom.

[1480] In embodiments of the compound of formula (1 ),

[1481] R7, R8, R9, R10, R11, and R12are each H.

[1482] Also disclosed herein is a compound according to the invention having the structural formula

[1483] (2): including any stereoisomer or mixture of stereoisomers including diastereomers and enantiomers, tautomer, isotopic form, pharmaceutically acceptable salt, solvate, prodrug, or pharmaceutically active metabolite thereof, or combinations thereof, wherein:

[1484] X1, X2, X3, X4, and X5are as defined for compounds of formula (1 );

[1485] X7is selected from CR10, O, and N; and q, L1, R1, R2, R3, R4, and R10are as defined in any preceding clause; wherein when q is 0, X7is O or N, and when q is 1 , X7is CR10.

[1486] Also disclosed herein is a compound according to the invention having the structural formula (2a):

[1487] including any stereoisomer or mixture of stereoisomers including diastereomers and enantiomers, tautomer, isotopic form, pharmaceutically acceptable salt, solvate, prodrug, or pharmaceutically active metabolite thereof, or combinations thereof, wherein X1, X5, L1, R1, R2, R3, R4, R5and R6are as defined for compounds of formula (1 ); wherein one of X1and X5is C and the other is N.

[1488] Also disclosed herein is a compound according to the invention having the structural formula

[1489] (2aa):

[1490] including any stereoisomer or mixture of stereoisomers including diastereomers and enantiomers, tautomer, isotopic form, pharmaceutically acceptable salt, solvate, prodrug, or pharmaceutically active metabolite thereof, or combinations thereof, wherein L1, R1, R2, R3, R4, R5and R6are as defined for compounds of formula (1 ).

[1491] Also disclosed herein is a compound according to the invention having the structural formula (2ab): (2ab) including any stereoisomer or mixture of stereoisomers including diastereomers and enantiomers, tautomer, isotopic form, pharmaceutically acceptable salt, solvate, prodrug, or pharmaceutically active metabolite thereof, or combinations thereof, wherein L1, R1, R2, R3, R4, R5and R6are as defined for compounds of formula (1 ).

[1492] Also disclosed herein is a compound according to the invention having the structural formula (2ac): including any stereoisomer or mixture of stereoisomers including diastereomers and enantiomers, tautomer, isotopic form, pharmaceutically acceptable salt, solvate, prodrug, or pharmaceutically active metabolite thereof, or combinations thereof, wherein L1, R1, R2, R3and R4are as defined for compounds of formula (1 ).

[1493] Also disclosed herein is a compound according to the invention having the structural formula (2ad):

[1494]

[1495] Including any stereoisomer or mixture of stereoisomers including diastereomers and enantiomers, tautomer, isotopic form, pharmaceutically acceptable salt, solvate, prodrug, or pharmaceutically active metabolite thereof, or combinations thereof, wherein L1, R1, R2, R3, R4, and R5are as defined for compounds of formula (1 ).

[1496] Also disclosed herein is a compound according to the invention having the structural formula

[1497] (2b): (2b) including any stereoisomer or mixture of stereoisomers including diastereomers and enantiomers, tautomer, isotopic form, pharmaceutically acceptable salt, solvate, prodrug, or pharmaceutically active metabolite thereof, or combinations thereof, wherein q, L1, R1, R2, R3, R4, R5, R6and R10are as defined for compounds of formula (1 ).

[1498] Also disclosed herein is a compound according to the invention having the structural formula (3): including any stereoisomer or mixture of stereoisomers including diastereomers and enantiomers, tautomer, isotopic form, pharmaceutically acceptable salt, solvate, prodrug, or pharmaceutically active metabolite thereof, or combinations thereof, wherein L1, R1, R2, R3, R4and R7are as defined for compounds of formula (1 ).

[1499] Also disclosed herein is a compound according to the invention having the structural formula (4):

[1500] including any stereoisomer or mixture of stereoisomers including diastereomers and enantiomers, tautomer, isotopic form, pharmaceutically acceptable salt, solvate, prodrug, or pharmaceutically active metabolite thereof, or combinations thereof, wherein:

[1501] X1, X2, X3, X4, and X5are as defined in clause 1 ;

[1502] X6is selected from CR8R9and O;

[1503] X7is selected from CR11R12and O; and

[1504] L1, q, R1, R2, R3, R4, R8, R9, R11, and R12are as defined for compounds of formula (1 ); wherein when q is 0, X7is O; and when X7is O and q is 1 , X6is CR8R9.

[1505] Also disclosed herein is a compound according to the invention having the structural formula (4a):

[1506] including any stereoisomer or mixture of stereoisomers including diastereomers and enantiomers, tautomer, isotopic form, pharmaceutically acceptable salt, solvate, prodrug, or pharmaceutically active metabolite thereof, or combinations thereof, wherein:

[1507] L1, q, R1, R2, R3, R4, and R6are as defined for compounds of formula (1 ).

[1508] Also disclosed herein is a compound according to the invention having the structural formula (4b): (4b)

[1509] Including any stereoisomer or mixture of stereoisomers including diastereomers and enantiomers, tautomer, isotopic form, pharmaceutically acceptable salt, solvate, prodrug, or pharmaceutically active metabolite thereof, or combinations thereof, wherein q, L1, R1, R2, R3, R4, R5, R6, R11and R12are as defined for compounds of formula (1 ).

[1510] Also disclosed herein is a compound according to the invention having the structural formula (4c): including any stereoisomer or mixture of stereoisomers including diastereomers and enantiomers, tautomer, isotopic form, pharmaceutically acceptable salt, solvate, prodrug, or pharmaceutically active metabolite thereof, or combinations thereof, wherein q, L1, R1, R2, R3, R4, R5, R6, R8and R9are as defined for compounds of formula (1 ).

[1511] Also disclosed herein is a compound of formula (1 ) which has the structural formula (1 a):

[1512] including any stereoisomer or mixture of stereoisomers including diastereomers and enantiomers, tautomer, isotopic form, pharmaceutically acceptable salt, solvate, prodrug, or pharmaceutically active metabolite thereof, or combinations thereof, wherein:

[1513] Q is O or S;

[1514] X1is selected from C and N;

[1515] X2is selected from CR5and N;

[1516] X3is selected from CR6and N;

[1517] X4is selected from CR7and N;

[1518] X5is selected from C and N; wherein X1, X2, X3, X4and X5are selected so that the ring labelled A is aromatic;

[1519] X6is selected from CR8R9, O and N;

[1520] X7is selected from CR10, CR11R12, O and N; q is 0 or 1 ; wherein when q is 0, X7is O or N; and when X7is O or N and q is 1 , X6is CR8R9;

[1521] L1is a bond, CrCe alkylene, CrCe haloalkylene, C3-C6 cycloalkylene, or a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[1522] R1is selected from C1-C4 alkyl, C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, 8- to 1 1 - membered bicyclic heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, C9-C10 bicyclic aryl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, 8- to 10-membered bicyclic heteroaryl having one or more heteroatoms selected from N, O and S, phenoxy, and 5- or 6- membered heteroaryloxy having one or more heteroatoms selected from N, O and S, wherein said alkyl, cycloalkyl, bicyclic cycloalkyl, heterocycloalkyl, bicyclic heterocycloalkyl, phenyl, bicyclic aryl, heteroaryl, bicyclic heteroaryl, phenoxy and heteroaryloxy are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, NR1aR1 b, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkyl-NR1aR1 b, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, benzyl, phenoxy, halophenoxy, 5- or 6- membered heteroaryloxy having one or more heteroatoms selected from N, O and S, and C1-C4 alkyl substituted by a 5- or 6- membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[1523] R1aand R1 bare each independently selected from H and C1-C4 alkyl;

[1524] R2is selected from H, C1-C4 alkyl and C3-C8 cycloakyl; or R1, R2and L1and the nitrogen atom to which R2and L1are attached form a 3- to 8- membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, 8- to 11 -membered bicyclic heterocycloalkyl having one or more heteroatoms selected from N, O and S, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, or 8- to 10-membered bicyclic heteroaryl having one or more heteroatoms selected from N, O and S, wherein said heterocycloalkyl, bicyclic heterocycloalkyl, heteroaryl and bicyclic heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, NR1aR1 b, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy and C1-C4 alkyl-NR1aR1 b;

[1525] R3is selected from H, OH, CN, NR3aR3b, C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, Cr C4alkoxy-C1-C4 alkyl, C1-C4haloalkoxy-C1-C4alkyl, C3-C8cycloalkoxy-C1-C4alkyl, and C3-C8 cycloalkyl-C1-C4 alkoxy, wherein said alkyl, cycloalkyl, heterocycloalkyl, phenyl and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, C1-C4 alkyl, and NR3cR3d;

[1526] R3ais selected from H, C1-C4 alkyl, C1-C4 alkyl-OH, and C1-C4 alkyl-NR3eR3f;

[1527] R3b, R3c, R3d, R3eand R3fare each independently selected from H and C1-C4 alkyl;

[1528] R4is selected from C(O)OH, C(O)NR4aR4b, C(S)NR4aR4band 5- or 6-membered heteroaryl having one or more heteroatoms selected from N, O and S;

[1529] R4aand R4bare each independently selected from H and C1-C4 alkyl;

[1530] R5and R6are each independently selected from H, halogen, OH, CN, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 alkoxy-C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S; or R5and R6together with the carbon atoms to which they are attached form a 5- or 6- membered heterocycloalkyl having one or more heteroatoms selected from N, O and S; and R7, R8, R9, R10, R11, and R12are each independently selected from H, halogen, OH, CN, Ci- 04 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S.

[1531] In embodiments of the compound of formula (1 a),

[1532] L1is a bond, CrCe alkylene, CrCe haloalkylene, C3-C6 cycloalkylene, or a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[1533] R1is selected from C1-C4 alkyl, C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, 8- to 1 1 - membered bicyclic heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, C9-C10 bicyclic aryl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, 8- to 10-membered bicyclic heteroaryl having one or more heteroatoms selected from N, O and S, phenoxy, and 5- or 6- membered heteroaryloxy having one or more heteroatoms selected from N, O and S, wherein said alkyl, cycloalkyl, bicyclic cycloalkyl, heterocycloalkyl, bicyclic heterocycloalkyl, phenyl, bicyclic aryl, heteroaryl, bicyclic heteroaryl, phenoxy and heteroaryloxy are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, NR1aR1 b, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkyl-NR1aR1 b, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, benzyl, phenoxy, halophenoxy, 5- or 6- membered heteroaryloxy having one or more heteroatoms selected from N, O and S, and C1-C4 alkyl substituted by a 5- or 6- membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[1534] R1aand R1 bare each independently selected from H and C1-C4 alkyl;

[1535] R2is selected from H, C1-C4 alkyl and C3-C8 cycloakyl;

[1536] R3is selected from H, OH, CN, NR3aR3b, C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, Cr C4 alkoxy-C1-C4 alkyl, C1-C4haloalkoxy-C1-C4alkyl, C3-C8cycloalkoxy-C1-C4alkyl, and C3-C8 cycloalkyl-C1-C4 alkoxy, wherein said alkyl, cycloalkyl, heterocycloalkyl, phenyl and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, C1-C4 alkyl, and NR3cR3d; R3ais selected from H, C1-C4 alkyl, C1-C4 alkyl-OH, and C1-C4 alkyl-NR3eR3f;

[1537] R3b, R3c, R3d, R3eand R3fare each independently selected from H and C1-C4 alkyl;

[1538] R4is selected from C(O)OH, C(O)NR4aR4b, C(S)NR4aR4band 5- or 6-membered heteroaryl having one or more heteroatoms selected from N, O and S;

[1539] R4aand R4bare each independently selected from H and C1-C4 alkyl;

[1540] R5and R6are each independently selected from H, halogen, OH, CN, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 alkoxy-C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S; or R5and R6together with the carbon atoms to which they are attached form a 5- or 6- membered heterocycloalkyl having one or more heteroatoms selected from N, O and S; and R7, R8, R9, R10, R11, and R12are each independently selected from H, halogen, OH, CN, Cr C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S.

[1541] In embodiments of the compound of formula (1 a),

[1542] L1is a bond, CrCe alkylene, CrCe haloalkylene, C3-C6 cycloalkylene, or a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[1543] R1is selected from C1-C4 alkyl, C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 8- to 1 1 - membered bicyclic heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, 8- to 10-membered bicyclic heteroaryl having one or more heteroatoms selected from N, O and S, and phenoxy, wherein said alkyl, cycloalkyl, bicyclic cycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, bicyclic heteroaryl, and phenoxy are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, NR1aR1 b, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkyl-NR1aR1 b, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, benzyl, halophenoxy, and C1-C4 alkyl substituted by a 5- or 6- membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[1544] R1aand R1 bare each independently selected from H and C1-C4 alkyl;

[1545] R2is H;

[1546] R3is selected from H, CN, NR3aR3b, C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C1-C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, and C3-C8 cycloalkyl-C1-C4 alkoxy, wherein said alkyl, cycloalkyl, heterocycloalkyl, phenyl and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, and NR3cR3d;

[1547] R3ais selected from H, C1-C4 alkyl, and C1-C4 alkyl-NR3eR3f;

[1548] R3bis selected from H and C1-C4 alkyl;

[1549] R3cis selected from H and C1-C4 alkyl;

[1550] R3dis selected from C1-C4 alkyl;

[1551] R3eand R3fare each independently selected from C1-C4 alkyl;

[1552] R4is selected from C(O)OH, C(O)NR4aR4b, C(S)NR4aR4band 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[1553] R4ais selected from H and C1-C4 alkyl;

[1554] R4bis H;

[1555] R5is selected from H, C1-C4 alkyl, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[1556] R6is selected from H, C1-C4 alkyl, C1-C4 alkoxy, and C1-C4 alkoxy-C1-C4 alkyl; and R7, R8, R9, R10, R11, and R12are each H.

[1557] In embodiments of the compound of formula (1 a),

[1558] L1is a bond, CrCe alkylene, CrCe haloalkylene, or C3-C6 cycloalkylene;

[1559] R1is selected from C1-C4 alkyl, C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 8- to 11 - membered bicyclic heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, 8- to 10-membered bicyclic heteroaryl having one or more heteroatoms selected from N, O and S, and phenoxy, wherein said alkyl, cycloalkyl, bicyclic cycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, bicyclic heteroaryl, and phenoxy are each optionally substituted by one or more substituents independently selected from halogen, CN, OH, Ci- 04 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkyl-NR1aR1 b, C3-C8 cycloalkyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, benzyl, and C1-C4 alkyl substituted by a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[1560] R1aand R1 bare each independently selected from H and C1-C4 alkyl;

[1561] R2is H;

[1562] R3is selected from H, CN, NR3aR3b, C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C1-C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, and C3-C8 cycloalkyl-C1-C4 alkoxy, wherein said alkyl, cycloalkyl, heterocycloalkyl, phenyl and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH and NR3cR3d;

[1563] R3ais selected from H and C1-C4 alkyl;

[1564] R3bis selected from C1-C4 alkyl;

[1565] R3cis selected from H and C1-C4 alkyl;

[1566] R3dis selected from C1-C4 alkyl;

[1567] R4is selected from C(O)OH, C(O)NR4aR4b, C(S)NR4aR4band 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[1568] R4ais selected from H and C1-C4 alkyl;

[1569] R4bis H ;

[1570] R5is selected from H, C1-C4 alkyl, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[1571] R6is selected from H, C1-C4 alkyl, C1-C4 alkoxy, and C1-C4 alkoxy-C1-C4 alkyl; and R7, R8, R9, R10, R11, and R12are each H.

[1572] In embodiments of the compound of formula (1 a),

[1573] L1is a bond, CrCe alkylene, CrCe haloalkylene, or C3-C6 cycloalkylene;

[1574] R1is selected from C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 8- to 11 -membered bicyclic heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, and 8- to 10-membered bicyclic heteroaryl having one or more heteroatoms selected from N, O and S, wherein said cycloalkyl, bicyclic cycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, and bicyclic heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, CN, OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4alkyl-NR1aR1 b, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[1575] R1aand R1 bare each independently selected from H and C1-C4 alkyl;

[1576] R2is H;

[1577] R3is selected from H, CN, NR3aR3b, C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C1-C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, and C3-C8cycloalkyl-C1-C4 alkoxy, wherein said alkyl, cycloalkyl, heterocycloalkyl, phenyl and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH and NR3cR3d;

[1578] R3ais selected from H and C1-C4 alkyl;

[1579] R3bis selected from C1-C4 alkyl;

[1580] R3cis selected from H and C1-C4 alkyl; R3dis selected from C1-C4 alkyl;

[1581] R4is selected from the following groups: wherein indicates the point of attachment to the rest of the compound;

[1582] R5is selected from H and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[1583] R6is selected from H, C1-C4 alkyl, C1-C4 alkoxy, and C1-C4 alkoxy-C1-C4 alkyl; and R7, R8, R9, R10, R11, and R12are each H.

[1584] In embodiments of the compound of formula (1 a),

[1585] L1is a bond, CrCe alkylene, or CrCe haloalkylene;

[1586] R1is selected from C3-C8cycloalkyl, C7-Cn bicyclic cycloalkyl, 8- to 11 -membered bicyclic heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, and 8- to 10-membered bicyclic heteroaryl having one or more heteroatoms selected from N, O and S, wherein said cycloalkyl, bicyclic cycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, and bicyclic heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, CN, OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4alkyl-NR1aR1 b, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[1587] R1aand R1 bare each independently selected from H and C1-C4 alkyl;

[1588] R2is H;

[1589] R3is selected from H, CN, NR3aR3b, C1-C4 alkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, and C1-C4 alkoxy-C1-C4 alkyl, wherein said alkyl, heterocycloalkyl, phenyl and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen and NR3cR3d;

[1590] R3ais selected from H and C1-C4 alkyl;

[1591] R3bis selected from C1-C4 alkyl;

[1592] R3cis selected from H and C1-C4 alkyl;

[1593] R3dis selected from C1-C4 alkyl;

[1594] R4is C(O)NR4aR4b; R4aand R4bare each H;

[1595] R5is selected from H and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[1596] R6is selected from H, C1-C4 alkyl, C1-C4 alkoxy, and C1-C4 alkoxy-C1-C4 alkyl; and

[1597] R7, R8, R9, R10, R11, and R12are each H.

[1598] In embodiments of the compound of formula (1 a),

[1599] L1is either a bond, CrCe alkylene, or C3-C6 cycloalkylene;

[1600] R1is selected from C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 8- to 11 -membered bicyclic heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, and 8- to 10-membered bicyclic heteroaryl having one or more heteroatoms selected from N, O and S, wherein said cycloalkyl, bicyclic cycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, and bicyclic heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, and C1-C4 haloalkoxy;

[1601] R2is H;

[1602] R3is selected from H, CN, NR3aR3b, C1-C4 alkyl optionally substituted by OH, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C1-C4 alkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy; and C1-C4 haloalkoxy-C1-C4 alkyl;

[1603] R3ais H;

[1604] R3bis selected from C1-C4 alkyl;

[1605] R4is selected from the following groups: indicates the point of attachment to the rest of the compound;

[1606] R5is H;

[1607] R6is selected from H and C1-C4 alkyl; and

[1608] R7, R8, R9, R10, R11, and R12are each H.

[1609] In embodiments of the compound of formula (1 a), L1is either a bond or CrCe alkylene; R1is selected from C3-C8 cycloalkyl, C8-C11 bicyclic cycloalkyl, 8- to 11 -membered bicyclic heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, and 8- to 10-membered bicyclic heteroaryl having one or more heteroatoms selected from N, O and S, wherein said cycloalkyl, bicyclic cycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, and bicyclic heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, and C1-C4 haloalkoxy;

[1610] R2is H;

[1611] R3is selected from H, CN, NR3aR3b, C1-C4 alkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, and C1-C4 alkoxy-C1-C4 alkyl;

[1612] R3ais H;

[1613] R3bis selected from C1-C4 alkyl;

[1614] R4is C(O)NR4aR4b;

[1615] R4aand R4bare each H;

[1616] R5is H;

[1617] R6is selected from H and C1-C4 alkyl; and

[1618] R7, R8, R9, R10, R11, and R12are each H.

[1619] In embodiments of the compound of formula (1 a),

[1620] L1is either a bond or CrCe alkylene;

[1621] R1is selected from C3-C8 cycloalkyl, C8-C11 bicyclic cycloalkyl, 8- to 11 -membered bicyclic heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, and 8- to 10-membered bicyclic heteroaryl having one or more heteroatoms selected from N, O and S, wherein said cycloalkyl, bicyclic cycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, and bicyclic heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, and C1-C4 haloalkoxy;

[1622] R2is H;

[1623] R3is selected from NR3aR3b, C1-C4 alkyl substituted by one or more substituents independently selected from OH and NR3cR3d, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C1-C4 alkoxy-C1-C4 alkyl, and C1-C4 haloalkoxy-C1-C4 alkyl;

[1624] R3ais H; R3bis selected from C1-C4 alkyl;

[1625] R4is selected from the following groups: point of attachment to the rest of the compound ; R5, R6, R7, R8, R9, R10, R11, and R12are each H.

[1626] In embodiments of the compound of formula (1 a),

[1627] L1is either a bond or CrCe alkylene;

[1628] R1is selected from C3-C8 cycloalkyl, C8-C11 bicyclic cycloalkyl, 8- to 1 1 -membered bicyclic heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, wherein said cycloalkyl, bicyclic cycloalkyl, bicyclic heterocycloalkyl, phenyl, and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, and C1-C4 haloalkoxy;

[1629] R2is H;

[1630] R3is selected from NR3aR3b, C1-C4 alkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, and C1-C4 alkoxy-C1-C4alkyl;

[1631] R3ais H;

[1632] R3bis selected from C1-C4 alkyl;

[1633] R4is C(O)NR4aR4b;

[1634] R4aand R4bare each H;

[1635] R5, R6, R7, R8, R9, R10, R11, and R12are each H.

[1636] In embodiments of the compound of formula (1 a), Q is O.

[1637] In embodiments of the compound of formula (1 a), L1is either a bond or CrCe alkylene (e.g. methylene).

[1638] In embodiments of the compound of formula (1 a),

[1639] R1is selected from:

[1640] C3-C8 cycloalkyl optionally substituted by one or more substituents independently selected from halogen and C1-C4 haloalkoxy; C8-C11 bicyclic cycloalkyl optionally substituted by one or more substituents independently selected from halogen and C1-C4 alkoxy;

[1641] 8- to 11 -membered bicyclic heterocycloalkyl having one or more heteroatoms selected from N, O and S, optionally substituted by one or more substituents independently selected from halogen; phenyl optionally substituted by one or more substituents independently selected from halogen and C1-C4 alkyl;

[1642] 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, optionally substituted by one or more substituents independently selected from C1-C4 alkyl and C1-C4 haloalkyl; and

[1643] 8- to 10-membered bicyclic heteroaryl having one or more heteroatoms selected from N, O and S, optionally substituted substituted by one or more substituents independently selected from halogen and C1-C4 alkyl.

[1644] In embodiments of the compound of formula (1 a), R2is H.

[1645] In embodiments of the compound of formula (1 a),

[1646] R3is selected from:

[1647] - NR3aR3b;

[1648] C1-C4 alkyl optionally substituted by OH;

[1649] C3-C8 cycloalkyl;

[1650] 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[1651] 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;

[1652] C1-C4 alkoxy-C1-C4 alkyl;

[1653] C3-C8cycloalkyl-C1-C4 alkoxy; and

[1654] Ci -C4 haloalkoxy-Ci -C4 alkyl ; wherein

[1655] R3ais H; and

[1656] R3bis selected from C1-C4 alkyl.

[1657] In embodiments of the compound of formula (1 a), R3is selected from C1-C4 alkoxy-C1-C4 alkyl.

[1658] In embodiments of the compound of formula (1 a), R4is selected from the following groups: , indicates the point of attachment to the rest of the compound.

[1659] In embodiments of the compound of formula (1 a),

[1660] R4is selected from C(O)OH, C(O)NR4aR4band C(S)NR4aR4b; and R4aand R4bare each H.

[1661] In embodiments of the compound of formula (1 a), R5is selected from the following groups: indicates the point of attachment to the rest of the compound.

[1662] In embodiments of the compound of formula (1 a), R5is H.

[1663] In embodiments of the compound of formula (1 a), R6is H or methyl.

[1664] In embodiments of the compound of formula (1 a), R6is H.

[1665] In embodiments of the compound of formula (1 a), R7, R8, R9, R10, R11, and R12are each H.

[1666] Also disclosed herein is a compound according to the invention having the structural formula (2’a):

[1667] including any stereoisomer or mixture of stereoisomers including diastereomers and enantiomers, tautomer, isotopic form, pharmaceutically acceptable salt, solvate, prodrug, or pharmaceutically active metabolite thereof, or combinations thereof, wherein X1, X5, L1, R1, R2, R3, R4, R5and R6are as defined for compounds of formula (1 a); wherein one of X1and X5is C and the other is N.

[1668] Also disclosed herein is a compound of formula (1 a) having the structural formula (2’aa):

[1669] 121 (2’aa) including any stereoisomer or mixture of stereoisomers including diastereomers and enantiomers, tautomer, isotopic form, pharmaceutically acceptable salt, solvate, prodrug, or pharmaceutically active metabolite thereof, or combinations thereof, wherein L1, R1, R2, R3, R4, R5and R6are as defined for compounds of formula (1 a) .

[1670] Also disclosed herein is a compound of formula (1 a) having the structural formula (2’ab): including any stereoisomer or mixture of stereoisomers including diastereomers and enantiomers, tautomer, isotopic form, pharmaceutically acceptable salt, solvate, prodrug, or pharmaceutically active metabolite thereof, or combinations thereof, wherein L1, R1, R2, R3, R4, R5and R6are as defined for compounds of formula (1 a).

[1671] Also disclosed herein is a compound of formula (1 a) having the structural formula (2’ad):

[1672]

[1673] Including any stereoisomer or mixture of stereoisomers including diastereomers and enantiomers, tautomer, isotopic form, pharmaceutically acceptable salt, solvate, prodrug, or pharmaceutically active metabolite thereof, or combinations thereof, wherein L1, R1, R2, R3, R4, and R5are as defined for compounds of formula (1 a).

[1674] Also disclosed herein is a compound of formula (1 ) which has the structural formula (1 b): including any stereoisomer or mixture of stereoisomers including diastereomers and enantiomers, tautomer, isotopic form, pharmaceutically acceptable salt, solvate, prodrug, or pharmaceutically active metabolite thereof, or combinations thereof, wherein:

[1675] X1is selected from C and N;

[1676] X2is selected from CR5and N;

[1677] X3is selected from CR6and N;

[1678] X4is selected from CR7and N;

[1679] X5is selected from C and N; wherein X1, X2, X3, X4and X5are selected so that the ring labelled A is aromatic;

[1680] X6is selected from CR8R9, O and N;

[1681] X7is selected from CR10, CR11R12, O and N; q is 0 or 1 ; wherein when q is 0, X7is O or N; and when X7is O or N and q is 1 , X6is CR8R9;

[1682] L1is a bond, CrCe alkylene or a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;

[1683] R1is selected from C1-C4 alkyl, C3-C8 cycloalkyl, C8-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, 8- to 11 - membered bicyclic heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, C9-C10 bicyclic aryl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, 8- to 10-membered bicyclic heteroaryl having one or more heteroatoms selected from N, O and S, phenoxy, and 5- or 6- membered heteroaryloxy having one or more heteroatoms selected from N, O and S, wherein said alkyl, cycloalkyl, bicyclic cycloalkyl, heterocycloalkyl, bicyclic heterocycloalkyl, phenyl, bicyclic aryl, heteroaryl, bicyclic heteroaryl, phenoxy and heteroaryloxy are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, NR1aR1 b, C1-C4 alkyl, C1-C4haloalkyl, C1-C4alkoxy, C1-C4haloalkoxy, C1-C4alkyl-NR1aR1 b, Cs-Cscycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, benzyl, phenoxy, halophenoxy and 5- or 6- membered heteroaryloxy having one or more heteroatoms selected from N, O and S;

[1684] R1aand R1 bare each independently selected from H and C1-C4alkyl;

[1685] R2is selected from H, C1-C4 alkyl and C3-C8 cycloakyl; or R1, R2and L1and the nitrogen atom to which R2and L1are attached form a 3- to 8- membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, 8- to 11 -membered bicyclic heterocycloalkyl having one or more heteroatoms selected from N, O and S, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, or 8- to 10-membered bicyclic heteroaryl having one or more heteroatoms selected from N, O and S, wherein said heterocycloalkyl, bicyclic heterocycloalkyl, heteroaryl and bicyclic heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, NR1aR1 b, C1-C4 alkyl, C1-C4haloalkyl, C1-C4alkoxy, Cr C4haloalkoxy and C1-C4alkyl-NR1aR1 b;

[1686] R3is selected from H, OH, CN, NR3aR3b, C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, Cr ...

Claims

CLAIMS:

1. A compound of formula (1 ):including any stereoisomer or mixture of stereoisomers including diastereomers and enantiomers, tautomer, isotopic form, pharmaceutically acceptable salt, solvate, prodrug, or pharmaceutically active metabolite thereof, or combinations thereof, wherein:Q is O or S;X1is selected from C and N;X2is selected from CR5and N;X3is selected from CR6and N;X4is selected from CR7and N;X5is selected from C and N; wherein X1, X2, X3, X4and X5are selected so that the ring labelled A is aromatic;X6is selected from CR8R9, O and N;X7is selected from CR10, CR11R12, O and N; q is 0 or 1 ; wherein when q is 0, X7is O or N; and when X7is O or N and q is 1 , X6is CR8R9;L1is a bond, CrCe alkylene, CrCehaloalkylene, C3-C6 cycloalkylene, or a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;R1is selected from C1-C4 alkyl, C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11 - membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, C9-C10 bicyclic aryl, 5- or 6- membered heteroaryl having one or more ring members selected from N, O, S and SO2, 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, phenoxy, and 5- or 6- membered heteroaryloxy having one or more heteroatoms selected from N, O and S, wherein said alkyl, cycloalkyl, bicyclic cycloalkyl, heterocycloalkyl, bicyclic heterocycloalkyl, phenyl, bicyclic aryl, heteroaryl, bicyclic heteroaryl, phenoxy and heteroaryloxy are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, NR1aR1 b, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkyl-NR1aR1 b, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, benzyl, phenoxy, halophenoxy, 5- or 6- membered heteroaryloxy having one or more heteroatoms selected from N, O and S, and C1-C4 alkyl substituted by a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;R1aand R1 bare each independently selected from H and C1-C4 alkyl;R2is selected from H, C1-C4 alkyl and C3-C8 cycloakyl; or R1, R2and L1and the nitrogen atom to which R2and L1are attached form a 3- to 8- membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, 8- to 1 1 -membered bicyclic heterocycloalkyl having one or more heteroatoms selected from N, O and S, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, or 8- to 10-membered bicyclic heteroaryl having one or more heteroatoms selected from N, O and S, wherein said heterocycloalkyl, bicyclic heterocycloalkyl, heteroaryl and bicyclic heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, NR1aR1 b, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy and C1-C4 alkyl-NR1aR1 b;R3is selected from H, OH, CN, NR3aR3b, C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, Cr C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, C3-C8 cycloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, C1-C4 alkyl-S-C1-C4 alkyl, and C1-C4 alkyl-SO2- C1-C4 alkyl, wherein said alkyl, cycloalkyl, heterocycloalkyl, phenyl and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, C1-C4 alkyl, and NR3cR3d;R3ais selected from H, C1-C4 alkyl, C1-C4 alkyl-OH, and C1-C4 alkyl-NR3eR3f;R3b, R3c, R3d, R3eand R3fare each independently selected from H and C1-C4 alkyl;R4is selected from C(O)OH, C(O)NR4aR4b, C(S)NR4aR4band 5- or 6-membered heteroaryl having one or more heteroatoms selected from N, O and S;R4aand R4bare each independently selected from H and C1-C4 alkyl;R5and R6are each independently selected from H, halogen, OH, CN, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 alkoxy-C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S; or R5and R6together with the carbon atoms to which they are attached form a 5- or 6- membered heterocycloalkyl having one or more heteroatoms selected from N, O and S; and R7, R8, R9, R10, R11, and R12are each independently selected from H, halogen, OH, CN, Cr C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S.

2. The compound of claim 1 , whereinL1is a bond, CrCe alkylene, CrCe haloalkylene, C3-C6 cycloalkylene, or a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;R1is selected from C1-C4 alkyl, C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11 - membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, C9-C10 bicyclic aryl, 5- or 6- membered heteroaryl having one or more ring members selected from N, O, S and SO2, 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, phenoxy, and 5- or 6- membered heteroaryloxy having one or more heteroatoms selected from N, O and S, wherein said alkyl, cycloalkyl, bicyclic cycloalkyl, heterocycloalkyl, bicyclic heterocycloalkyl, phenyl, bicyclic aryl, heteroaryl, bicyclic heteroaryl, phenoxy and heteroaryloxy are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, NR1aR1 b, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkyl-NR1aR1 b, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, benzyl, phenoxy, halophenoxy, 5- or 6- membered heteroaryloxy having one or more heteroatoms selected from N, O and S, and C1-C4 alkyl substituted by a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;R1aand R1 bare each independently selected from H and C1-C4 alkyl;R2is selected from H, C1-C4 alkyl and C3-C8 cycloakyl;R3is selected from H, OH, CN, NR3aR3b, C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, Ci- 04 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, C3-C8 cycloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, C1-C4 alkyl-S-C1-C4 alkyl, and C1-C4 alkyl-SO2- C1-C4 alkyl, wherein said alkyl, cycloalkyl, heterocycloalkyl, phenyl and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, C1-C4 alkyl, and NR3cR3d;R3ais selected from H, C1-C4 alkyl, C1-C4 alkyl-OH, and C1-C4 alkyl-NR3eR3f;R3b, R3c, R3d, R3eand R3fare each independently selected from H and C1-C4 alkyl;R4is selected from C(O)OH, C(O)NR4aR4b, C(S)NR4aR4band 5- or 6-membered heteroaryl having one or more heteroatoms selected from N, O and S;R4aand R4bare each independently selected from H and C1-C4 alkyl;R5and R6are each independently selected from H, halogen, OH, CN, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 alkoxy-C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S; or R5and R6together with the carbon atoms to which they are attached form a 5- or 6- membered heterocycloalkyl having one or more heteroatoms selected from N, O and S; and R7, R8, R9, R10, R11, and R12are each independently selected from H, halogen, OH, CN, Cr C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S.

3. The compound of claim 1 or claim 2, whereinL1is a bond, CrCe alkylene, CrCe haloalkylene, C3-C6 cycloalkylene, or a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;R1is selected from C1-C4 alkyl, C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11 - membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, 5- or 6- membered heteroaryl having one or more ring members selected from N, O, S and SO2, 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, and phenoxy, wherein said alkyl, cycloalkyl, heterocycloalkyl, bicyclic cycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, bicyclic heteroaryl, and phenoxy are each optionally substituted by one or more substituents independently selected from halogen, OH, CN, NR1aR1 b, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkyl-NR1aR1 b, C3-C8 cycloalkyl, 3- to 8-memberedheterocycloalkyl having one or more heteroatoms selected from N, O and S, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, benzyl, halophenoxy, and C1-C4 alkyl substituted by a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;R1aand R1 bare each independently selected from H and C1-C4 alkyl;R2is H;R3is selected from H, CN, NR3aR3b, C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C1-C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, C3-C8 cycloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, C1-C4 alkyl-S-C1-C4 alkyl, and C1-C4 alkyl-SC>2-C1-C4 alkyl, wherein said alkyl, cycloalkyl, heterocycloalkyl, phenyl and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, and NR3cR3d;R3ais selected from H, C1-C4 alkyl, and C1-C4 alkyl-NR3eR3f;R3bis selected from H and C1-C4 alkyl;R3cis selected from H and C1-C4 alkyl;R3dis selected from C1-C4 alkyl;R3eand R3fare each independently selected from C1-C4 alkyl;R4is selected from C(O)OH, C(O)NR4aR4b, C(S)NR4aR4band 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;R4ais selected from H and C1-C4 alkyl;R4bis H;R5is selected from H, C1-C4 alkyl, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;R6is selected from H, C1-C4 alkyl, C1-C4 alkoxy, and C1-C4 alkoxy-C1-C4 alkyl; andR7, R8, R9, R10, R11, and R12are each H.

4. The compound of any preceding claim, whereinL1is a bond, CrCe alkylene, CrCe haloalkylene, or C3-C6 cycloalkylene;R1is selected from C1-C4 alkyl, C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11 - membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, 5- or 6- membered heteroaryl having one or more ring members selected from N, O, S and SO2, 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, and phenoxy, wherein said alkyl, cycloalkyl, heterocycloalkyl, bicyclic cycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, bicyclicheteroaryl, and phenoxy are each optionally substituted by one or more substituents independently selected from halogen, CN, OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkyl-NR1aR1 b, C3-C8 cycloalkyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, benzyl, and C1-C4 alkyl substituted by a 5- or 6-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;R1aand R1 bare each independently selected from H and C1-C4 alkyl;R2is H;R3is selected from H, CN, NR3aR3b, C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C1-C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, C3-C8 cycloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, C1-C4 alkyl-S-C1-C4 alkyl, and C1-C4 alkyl-SC>2-C1-C4 alkyl, wherein said alkyl, cycloalkyl, heterocycloalkyl, phenyl and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH and NR3cR3d;R3ais selected from H and C1-C4 alkyl;R3bis selected from C1-C4 alkyl;R3cis selected from H and C1-C4 alkyl;R3dis selected from C1-C4 alkyl;R4is selected from C(O)OH, C(O)NR4aR4b, C(S)NR4aR4band 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;R4ais selected from H and C1-C4 alkyl;R4bis H ;R5is selected from H, C1-C4 alkyl, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;R6is selected from H, C1-C4 alkyl, C1-C4 alkoxy, and C1-C4 alkoxy-C1-C4 alkyl; andR7, R8, R9, R10, R11, and R12are each H.

5. The compound of any preceding claim, whereinL1is a bond, CrCe alkylene, CrCe haloalkylene, or C3-C6 cycloalkylene;R1is selected from C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11- membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, 5- or 6- membered heteroaryl having one or more ring members selected from N, O, S and SO2, and 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, wherein said cycloalkyl, bicyclic cycloalkyl, heterocycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, and bicyclic heteroaryl areeach optionally substituted by one or more substituents independently selected from halogen, CN, OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkyl- NR1aR1 b, and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;R1aand R1 bare each independently selected from H and C1-C4 alkyl;R2is H;R3is selected from H, CN, NR3aR3b, C1-C4 alkyl, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, phenyl, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C1-C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, C3-C8 cycloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, C1-C4 alkyl-S-C1-C4 alkyl, and C1-C4 alkyl-SC>2-C1-C4 alkyl, wherein said alkyl, cycloalkyl, heterocycloalkyl, phenyl and heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH and NR3cR3d;R3ais selected from H and C1-C4 alkyl;R3bis selected from C1-C4 alkyl;R3cis selected from H and C1-C4 alkyl;R3dis selected from C1-C4 alkyl;R4is selected from the following groups:whereinindicates the point of attachment to the rest of the compound;R5is selected from H and 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;R6is selected from H, C1-C4 alkyl, C1-C4 alkoxy, and C1-C4 alkoxy-C1-C4 alkyl; and R7, R8, R9, R10, R11, and R12are each H.

6. The compound of any preceding claim, whereinL1is a bond, CrCe alkylene, or C3-C6 cycloalkylene;R1is selected from C3-C8 cycloalkyl, C7-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11- membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, 5- or 6- membered heteroaryl having one or more ring members selected from N, O, S and SO2, and 8- to 10-membered bicyclic heteroaryl having one or more ringmembers selected from N, O, S and SO2, wherein said cycloalkyl, heterocycloalkyl, bicyclic cycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, and bicyclic heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, and C1-C4 haloalkoxy;R2is H;R3is selected from H, CN, NR3aR3b, C1-C4 alkyl optionally substituted by OH, C3-C8 cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C1-C4 alkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, C1-C4 haloalkoxy- C1-C4 alkyl,, C1-C4 alkyl-S-C1-C4 alkyl, and C1-C4 alkyl-SO2-C1-C4 alkyl;R3ais H;R3bis selected from C1-C4 alkyl;R4is selected from the following groups:indicates the point of attachment to the rest of the compound;R5is H;R6is selected from H and C1-C4 alkyl; andR7, R8, R9, R10, R11, and R12are each H.

7. The compound of any preceding claim, whereinL1is either a bond or CrCe alkylene;R1is selected from C3-C8 cycloalkyl, C8-C11 bicyclic cycloalkyl, 3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2, 8- to 11- membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, phenyl, 5- or 6- membered heteroaryl having one or more ring members selected from N, O, S and SO2, and 8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, wherein said cycloalkyl, bicyclic cycloalkyl, heterocycloalkyl, bicyclic heterocycloalkyl, phenyl, heteroaryl, and bicyclic heteroaryl are each optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, and C1-C4 haloalkoxy;R2is H;R3is selected from NR3aR3b, C1-C4 alkyl optionally substituted by one or more substituents independently selected from OH and NR3cR3d, C3-C8 cycloalkyl, 3- to 8-memberedheterocycloalkyl having one or more heteroatoms selected from N, O and S, 5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S, C3-C8 cycloalkoxy-C1-C4 alkyl, C1-C4 alkoxy-C1-C4 alkyl, C1-C4 haloalkoxy-C1-C4 alkyl, C3-C8 cycloalkyl-C1-C4 alkoxy, and alkyl-S-C1-C4 alkyl;R3ais H;R3bis selected from C1-C4 alkyl;R4is selected from the following groups: pandR6is selected from H and C1-C4 alkyl.

8. The compound of any preceding claim, wherein Q is O.

9. The compound of any preceding claim, wherein L1is either a bond or methylene.

10. The compound of any preceding claim, whereinR1is selected from:C3-C8 cycloalkyl optionally substituted by one or more substituents independently selected from halogen and C1-C4 haloalkoxy;C8-C11 bicyclic cycloalkyl optionally substituted by one or more substituents independently selected from halogen, OH, C1-C4 alkyl and C1-C4 alkoxy;3- to 8-membered heterocycloalkyl having one or more ring members selected from N, O, S and SO2;8- to 11 -membered bicyclic heterocycloalkyl having one or more ring members selected from N, O, S and SO2, optionally substituted by one or more substituents independently selected from halogen ; phenyl optionally substituted by one or more substituents independently selected from halogen and C1-C4 alkyl;5- or 6- membered heteroaryl having one or more ring members selected from N, O, S and SO2, optionally substituted by one or more substituents independently selected from C1-C4 alkyl and C1-C4 haloalkyl; and8- to 10-membered bicyclic heteroaryl having one or more ring members selected from N, O, S and SO2, optionally substituted substituted by one or more substituents independently selected from halogen and C1-C4 alkyl.11 . The compound of any preceding claim, wherein R2is H.

12. The compound of any preceding claim, whereinR3is selected from:- NR3aR3b;C1-C4 alkyl optionally substituted by OH;C3-C8 cycloalkyl;3- to 8-membered heterocycloalkyl having one or more heteroatoms selected from N, O and S;5- or 6- membered heteroaryl having one or more heteroatoms selected from N, O and S;C1-C4 alkoxy-C1-C4 alkyl;C3-C8 cycloalkyl- C1-C4 alkoxy;C3-C8cycloalkoxy-C1-C4 alkyl;C1-C4 haloalkoxy-C1-C4 alkyl; andC1-C4 alkyl-S-C1-C4 alkyl; whereinR3ais H; andR3bis selected from C1-C4 alkyl.

13. The compound of any preceding claim, wherein R3is selected from C1-C4alkoxy-Ci- C4 alkyl.

14. The compound of any one of claims 1 to 3 or 8 to 13, whereinR4is selected from the following groups:compound.

15. A compound of any preceding claim, whereinR5is H.

16. The compound of any preceding claim, wherein R6is H or methyl.

17. A compound according to any preceding claim, wherein R7, R8, R9, R10, R11, and R12are each H.

18. A compound of formula (2a):including any stereoisomer or mixture of stereoisomers including diastereomers and enantiomers, tautomer, isotopic form, pharmaceutically acceptable salt, solvate, prodrug, or pharmaceutically active metabolite thereof, or combinations thereof, wherein X1, X5, L1, R1, R2, R3, R4, R5and R6are as defined in any one of claims 1 to 16; wherein one of X1and X5is C and the other is N.

19. A compound of formula (2aa):including any stereoisomer or mixture of stereoisomers including diastereomers and enantiomers, tautomer, isotopic form, pharmaceutically acceptable salt, solvate, prodrug, or pharmaceutically active metabolite thereof, or combinations thereof, wherein L1, R1, R2, R3, R4, R5and R6are as defined in any one of claims 1 to 16.

20. A compound of formula (2ab):including any stereoisomer or mixture of stereoisomers including diastereomers and enantiomers, tautomer, isotopic form, pharmaceutically acceptable salt, solvate, prodrug, or pharmaceutically active metabolite thereof, or combinations thereof, wherein L1, R1, R2, R3, R4, R5and R6are as defined in any one of claims 1 to 16.

21. A compound of formula (2ad):Including any stereoisomer or mixture of stereoisomers including diastereomers and enantiomers, tautomer, isotopic form, pharmaceutically acceptable salt, solvate, prodrug, or pharmaceutically active metabolite thereof, or combinations thereof, wherein L1, R1, R2, R3, R4, and R5are as defined in any one of claims 1 to 16.

22. The compound of claim 1 , wherein the compound is selected from compounds 1 to 242.

23. The compound of any of claims 1 to 22 for use in medicine.

24. The compound for use of claim 23, wherein the use is in the treatment or prophylaxis of a cancer or proliferative disease or disorder.

25. The compound for use of claim 23, wherein the use is in the treatment or prophylaxis of fibrotic disease or inflammatory disease.

26. A pharmaceutical composition comprising a compound of any of claims 1 to 22, or a stereoisomer or mixture of stereoisomers including diastereomers and enantiomers, tautomer, isotopic form, pharmaceutically acceptable salt, solvate, prodrug, or pharmaceutically active metabolite thereof, or combinations thereof, and at least one pharmaceutically acceptable diluent, excipient or carrier.

27. The pharmaceutical composition of claim 26 for use according to any of claims 23 to 25.

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