Protac degraders of mllt1 and / or mllt3

Abstract

The invention relates to a compound which is a Proteolysis Targeting Chimera (PROTAC) or a pharmaceutically acceptable salt thereof, wherein the PROTAC has the structure: M — LINK — U wherein U is an E3 ubiquitin ligase binding moiety, LINK is a moiety that covalently links M and U, and M is an MLLT1 and / or MLLT3 binder of formula (I) wherein: wherein Z1, Z2, Z3, Z4, Y1, Y2, Y3, R1, R2, R8, X, L and Hy are as defined herein, and either R8 is a bond to LINK, or M is bonded to LINK via a C or N atom within group R8 or ring Hy such that a hydrogen atom on the C or N atom within group R8 or ring Hy is replaced with a bond to LINK. The compounds are useful in the treatment of cancer.

Description

[0001] PROTAC DEGRADERS OF MLLT1 AND / OR MLLT3 Field of the Invention The present invention relates to compounds that find use in the treatment of cancer by inducing selective degradation of MLLT1 and / or MLLT3. The invention also provides such compounds per se, pharmaceutical compositions comprising such compounds, and methods of treating cancer by administering such compounds. The processes controlling gene transcription are highly regulated during development and normal homeostasis. Dysregulation of gene transcription is a common driver of cancer with somatic defects in proteins that control gene transcription a frequent occurrence (Cell, 2013, 153, 17; Cell, 2017, 168, 629). Transcriptional elongation is a central step in gene transcription, carried out by the RNA polymerase II (PolII), which itself is kept under tight control by regulatory protein complexes. During development PolII is recruited to sites of the genome proximal to the transcription start site for target genes and is kept in a paused state. Such target genes are often immediate response genes such as heat-shock genes and key developmental genes. Productive elongation is initiated by the coordinated interplay of regulatory protein complexes including the super elongation complex (SEC). The SEC includes multiple proteins with diverse functions including protein phosphorylation, histone reader, histone modification and regulatory activities. Critical to the recruitment of the SEC to target genes are the histone reader proteins MLLT1 (mixed lineage leukaemia translocated to 1, also known as eleven-nineteen leukaemia, ENL) and MLLT3 (mixed lineage leukaemia translocated to 3, also known as AF-9). MLLT1 and 3 contain essential YEATS domains that bind acetylated histones. Mutations in the YEATS domains reduce loading of PolII on to SEC target genes and suppression of gene transcription. (Cell Mol Life Sci 2018, 75, 3931; Nat Rev Mol Cell Biol 2012, 13, 543). Gain-of-function mutations in the MLLT1 Yeats domain have been causally associated with Wilm’s tumor (also known as nephroblastoma) a kidney cancer most commonly observed in children (Nature 2020, 577, 121). Additionally, it has been shown that for certain acute leukaemias MLLT1 represents a critical dependency (Nature 2017, 543, 270). Such leukaemias include mixed-lineage leukaemia (MLL) rearranged leukaemia. MLL rearrangements arise from in frame fusions of the MLL gene with more than 80 different partner genes, many of which are involved in the regulation of transcription elongation including components of the SEC (Front. Pediatr. 5:4. doi: 10.3389 / fped.2017.00004). MLL rearrangements are observed in approximately 10% of all acute leukaemias including a high frequency in infantile ALL where it accounts for 70-80% of all cases (Front. Pediatr. 5:4. doi: 10.3389 / fped.2017.00004). Notably it is reported that patients with MLL rearranged leukaemias have an especially poor prognosis (New Engl J Med 2016, 374, 2209). Target genes for MLL-SEC complexes include potent oncogenes such as BCL-2, Myc and CDK6 along with many other genes implicated in maintaining cancer cell self-renewal, growth and survival, such as the HOX family genes and MEIS1 (Front. Pediatr. 5:4. doi: 10.3389 / fped.2017.00004). Consistent with a role in the regulation of multiple oncogenes, it has been demonstrated that the SEC can play a critical role in the transcriptional addiction of both hematopoietic and solid cancers. For example, data supports potential in non-MLL rearranged leukaemia (Cancer Disc 2022, 12, 2684) and it is reported that with some breast cancer cells, growth and survival is dependent on a SEC mediated transcription of the Myc oncogene (Cell Rep. 2021 Feb 16;34(7):108749. doi: 10.1016 / j.celrep.2021.108749. PMID: 33596420; PMCID: PMC8006859). Taken together the evidence supports MLLT1 as an attractive therapeutic target across acute leukaemias and solid cancers. Proteolysis targeting chimeras (PROTACs) have been proposed as a small molecule- based platform technology capable of inducing proteolysis of a target protein in the body. The PROTAC is a bifunctional compound in which a molecule that binds to a disease-related target protein and an E3 ubiquitin ligase binding moiety are linked by a chemical linker. Theoretically, the PROTAC compound is capable of inducing degradation of the target protein by placing the disease-related target protein near the E3 ubiquitin ligase. Drug discovery efforts have resulted in agents that either bind the YEATS domain to block the MLLT1 and / or MLLT3 protein to histone interaction or that result in degradation of the MLLT1 and / or MLLT3 protein (using a PROTAC approach). In all cases however, the reported activity has been weak (ACS Cent Sci 2021, 7, 815; Cancer Disc 2022, 12, 2684; Angew. Chem. Int. Ed. 2018, 57, 16302). Accordingly, there remains a high need to identify potent modulators of MLLT cell function. Summary of the Invention The inventors have discovered a series of compounds that induce selective degradation of MLLT1 and / or MLLT3. Accordingly, the invention provides a compound which is a Proteolysis Targeting Chimera (PROTAC) or a pharmaceutically acceptable salt thereof, wherein the PROTAC has the structure: wherein U is an E3 ubiquitin ligase binding moiety, LINK is a moiety that covalently links M and U, and M is an MLLT1 and / or MLLT3 binder of formula (I): wherein: one of Z2and Z4is N and the other is C, Z1is N or -C(R4)-, Z3is -C(R4)-, Y1is N or - C(R7)-, Y2is N or -C(R6)-, and Y3is N or -C(R5)-; Hy is a 4- to 7-membered heterocyclyl ring containing X and at least one N atom, wherein: ring Hy is linked to ring A via a C atom within ring Hy, said C atom also being linked to R2; a N atom within ring Hy is substituted by R1; X is a bond, -N(R11)-, O, S, -S(O)2-, -S(O)(NR11)-, or -C(R11)2-; and the rest of ring Hy is unsubstituted or substituted by one or two R3; L is –C(O)N(H)-, wherein the C atom of L is bonded to R8, and the N atom of L is bonded to ring B; R1is H, C1-4cycloalkyl, or C1-4alkyl which is itself unsubstituted or substituted with one C1-4alkoxy or one, two or three halo; R2is H or methyl; each R3is independently selected from C1-4alkyl, C1-4alkoxy, phenyl, a 5- to 6- membered heteroaryl ring and halo, or (i) two R3linked to adjacent C atoms in ring Hy form, together with the C atoms to which they are attached, a C5-6cycloalkyl ring, or (ii) two R3linked to the same C atom in ring Hy form, together with the C atom to which they are attached, a C3-6cycloalkyl ring or a C3-6heterocycloalkyl ring; R4, R6, and R7are independently selected from H, halo, C1-4alkoxy, and C1-4alkyl which is itself unsubstituted or substituted by one, two or three halo; R5is selected from H, halo, C1-4alkoxy, C3-5cycloalkyl and C1-4alkyl which is itself unsubstituted or substituted by one, two or three halo; R8is (i) a bond to LINK or (ii) a group selected from a 6- to 10-membered aryl ring, a 5- to 10-membered heteroaryl ring, a 5- to 10-membered heterocyclyl ring, and a 5- to 6-membered cycloalkyl ring, the group R8being unsubstituted or substituted by one, two or three substituents independently selected from halo, C1-4alkoxy, R10, -(C1-4alkylene)-R10, =O, -CN, and C1-4alkyl which is itself unsubstituted or substituted by one or two R9; each R9is independently selected from halo and C1-4alkoxy; R10is a group selected from a 5- to 6-membered heteroaryl ring, a 3- to 6-membered cycloalkyl ring, a 4- to 6-membered heterocyclyl ring, and a phenyl ring, the group R10being unsubstituted or substituted by one or two substituents independently selected from C1-4alkyl, C1-4alkoxy, and halo; and each R11is independently selected from H, C1-4alkyl, and C1-4cycloalkyl; wherein either R8is (i) a bond to LINK, or R8is a group (ii) and M is bonded to LINK via a C or N atom within group R8or ring Hy (preferably within group R8) such that a hydrogen atom on the C or N atom within group R8or ring Hy is replaced with a bond to LINK. In a preferred embodiment, M is of formula (II):

[0002] wherein: Z1, Z2, Z3, Z4, Y1, Y2, Y3, R1, R2, R8, X and L are as defined above; R3aand R3bare independently selected from H, C1-4alkyl, phenyl, a 5- to 6-membered heteroaryl ring and C1-4alkoxy, or R3aand R3bform, together with the C atom to which they are attached, a C3-6cycloalkyl ring or a C3-6heterocycloalkyl ring, R3cand R3dare independently selected from H, C1-4alkyl, halo, phenyl, a 5- to 6- membered heteroaryl ring and C1-4alkoxy, or R3cand R3dform, together with the C atom to which they are attached, a C3-6cycloalkyl ring or a C3-6heterocycloalkyl ring, with the proviso that when X is NR11, O, or S, then neither R3cnor R3dare halo, or R3aand R3care H, and R3band R3dform, together with the C atoms to which they are attached, a C5-6cycloalkyl ring; wherein at least two of R3a, R3b, R3cand R3dare H and wherein either R8is (i) a bond to LINK, or R8is a group (ii) and M is bonded to LINK via a C or N atom within group R8or ring Hy (preferably within group R8) such that a hydrogen atom on the C or N atom within group R8or ring Hy is replaced with a bond to LINK. In a more preferred embodiment, M is of formula (III):

[0003] wherein: R1is H or C1-4alkyl which is itself unsubstituted or substituted with one C1-4alkoxy or one, two or three halo, preferably with one C1-4alkoxy; R2is H or methyl; R3aand R3bare independently selected from H, C1-4alkyl, and C1-4alkoxy, or R3aand R3bform, together with the C atom to which they are attached, a C3-6cycloalkyl ring, R3cand R3dare independently selected from H, C1-4 alkyl, halo and C1-4 alkoxy, or R3cand R3dform, together with the C atom to which they are attached, a C3-6cycloalkyl ring, with the proviso that when X is O, then neither R3cnor R3dare halo, or R3aand R3care H, and R3band R3dform, together with the C atoms to which they are attached, a C5-6cycloalkyl ring; wherein at least two of R3a, R3b, R3cand R3dare H; X is a bond, -N(Me)-, O or -CH2-; Y1is N or -C(R7)-; R5, R6and R7are independently selected from H, halo, C1-4alkoxy, and C1-4alkyl; R8is (i) a bond to LINK or (ii) a group selected from a 6- to 10-membered aryl ring, a 5- to 10-membered heteroaryl ring, and a 5- to 10-membered heterocyclyl ring, the group R8being unsubstituted or substituted by one, two or three substituents independently selected from halo, C1-4alkoxy, R10, -(C1-4alkylene)-R10, =O, -CN, and C1-4alkyl which is itself unsubstituted or substituted by one or two R9; each R9is independently selected from halo and C1-4alkoxy; and R10is a group selected from a 5- to 6-membered heteroaryl ring, a 3- to 6-membered cycloalkyl ring, a 4- to 6-membered heterocyclyl ring, and a phenyl ring, the group R10 being unsubstituted or substituted by one or two substituents independently selected from C1-4 alkyl, C1-4 alkoxy, and halo; and wherein either R8is (i) a bond to LINK, or R8is a group (ii) and M is bonded to LINK via a C or N atom within group R8or ring Hy (preferably within group R8) such that a hydrogen atom on the C or N atom within group R8or ring Hy is replaced with a bond to LINK. In some embodiments, M is of formula (IIIa): wherein R1, R2, R3a, R3b, R3c, R3d, R5, R6, R8and X are as defined in formula (III). In other embodiments, M is of formula (IIIb): wherein R1, R2, R3a, R3b, R3c, R3d, R5, R6, R7, R8and X are as defined in formula (III). In a particularly preferred embodiment, M is of formula (IV): wherein R8is a group selected from a 6- to 10-membered aryl ring and a 5- to 10- membered heteroaryl ring, the group R8being unsubstituted or substituted by one, two or three substituents independently selected from halo and C1-4alkyl; wherein M is bonded to LINK via a C or N atom within group R8such that a hydrogen atom on the C or N atom within group R8is replaced with LINK. As discussed elsewhere herein, the stereochemistry of the compounds of the invention at the ring Hy is preferably such that the bond from ring Hy to the core ring A is in the “up” position and the bond from ring Hy to R2is the down position. Thus, formula (IV) preferably has the stereochemistry depicted below: In the compounds of the invention, moiety M possesses one N atom in a bridgehead position of the bicyclic heteroaryl ring made up of rings A and B. The present invention also provides a compound as described herein for use in a method of treating cancer in a subject in need thereof. Also provided is a method for treating cancer in a subject, which method comprises administering to said subject an effective amount of a compound as described herein. Further provided is the use of a compound as described herein in the manufacture of a medicament for use in treating cancer in a subject. Brief Description of the Drawings Figure 1: Western blot showing degradation of MLLT1 by compound of Example 595, following procedure described in Example 106. Detailed Description of the Invention Definitions As used herein, a C1-4alkyl group is a linear or branched alkyl group containing from 1 to 4 carbon atoms. A C1-4alkyl group is often a C1-3alkyl group. Examples of C1-4alkyl groups include methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, and tert- butyl. A C1-3alkyl group is typically a C1-2alkyl group. A C1-2alkyl group is methyl or ethyl, typically methyl. For the avoidance of doubt, where multiple alkyl groups are present, the alkyl groups may be the same or different. As used herein, a C1-4alkoxy group is typically a said C1-4alkyl group which is joined to the rest of the molecule via an oxygen atom. Typically, a C1-4alkoxy group is a C1-3alkoxy group. Examples of C1-4alkoxy groups include methoxy, ethoxy, propoxy and butoxy. Typically, a C1-3alkoxy group is a C1-2alkoxy group such as a methoxy or ethoxy group. For the avoidance of doubt, where two alkoxy groups are present, the alkoxy groups may be the same or different. As used herein, a C1-30alkylene group is a linear or branched divalent alkyl group that contains from 1 to 30 carbon atoms. A C1-30alkylene group is sometimes a C1-20alkylene group, and often a C1-10alkylene group. C1-30alkylene groups, C1-20alkylene groups and C1-10alkylene groups are preferably linear. A C1-30alkylene group is sometimes a C1-6alkylene group, typically a C1-4alkylene group or a C1-3alkylene group. Examples of C1-4alkylene groups include methylene, ethylene, n-propylene, iso-propylene, n-butylene, sec-butylene, and tert-butylene. A C1-3 alkylene group is typically a C1-2 alkylene group. A C1-2 alkylene group is methylene or ethylene, typically methylene. For the avoidance of doubt, where multiple alkylene groups are present, the alkylene groups may be the same or different. As used herein, a C2-6alkenylene group is a linear or branched divalent alkenyl group containing from 2 to 6 carbon atoms and having one or more, e.g. one or two, typically one double bonds. Typically a C2-6alkenylene group is a C2-4alkenylene group. Examples of C2-4alkenylene groups include divalent ethenylene, propenylene and butenylene. For the avoidance of doubt, where multiple alkenylene groups are present, the alkenylene groups may be the same or different. An alkyl, alkoxy, alkylene or alkenylene group as used herein may be unsubstituted or substituted. Unless otherwise stated, substituted alkyl, alkoxy, alkylene or alkenylene groups typically carry one or more, e.g. one, two or three e.g. one, or two, e.g. one substituent selected from halo, OH, and unsubstituted C1-4alkoxy. Preferred substituents are halo and C1-4alkoxy unless otherwise stated. The substituents on a substituted alkyl, alkoxy, alkylene or alkenylene group are typically themselves unsubstituted. Where more than one substituent is present, these may be the same or different. As used herein, a halo typically refers to chlorine, fluorine, bromine or iodine, preferably chlorine, bromine or fluorine, more preferably chorine or fluorine, most preferably fluorine unless otherwise stated. A C3-8cycloalkyl ring, is a cyclic hydrocarbon containing from 3 to 8 carbon atoms. A cycloalkyl ring may be saturated or partially unsaturated, but is typically saturated. A C3-8cycloalkyl ring is typically a C3-6cycloalkyl ring. A C5-6partially unsaturated cycloalkyl ring is a cyclic hydrocarbon containing from 5 to 6 carbon atoms and containing 1 or 2, e.g. 1 double bond. C3-6cycloalkyl and C5-6cycloalkyl rings may also be referred to herein as 3- to 6-membered cycloalkyl rings and 5- to 6-membered cycloalkyl rings respectively. A C3-6cycloalkyl ring may be a saturated C3-6cycloalkyl ring. A C3-6cycloalkyl ring may be a C5-6 cycloalkyl ring, in particular a saturated C5-6 cycloalkyl ring. Examples of C3-6cycloalkyl rings are cyclopropyl, cyclobutyl cyclopentyl and cyclohexyl groups. A C3-8cycloalkyl ring may be a C7-8cycloalkyl ring, in particular a saturated C7-8cycloalkyl ring. Examples of C7-8cycloalkyl rings are cycloheptanly, cyclooctanyl, bicyclo[2.2.1]heptanyl and bicyclo[2.2.2]octanyl groups. A 5- to 10-membered heterocyclyl ring is a cyclic group containing from 5 to 10 atoms selected from C, O, N and S in the ring, including at least one heteroatom, and typically one or two heteroatoms unless otherwise stated. The heteroatom or heteroatoms are typically selected from O, N, and S, most typically from S and N, especially N. For example, where the heterocyclyl ring is denoted a nitrogen-containing heterocyclyl group, it contains one nitrogen atom and optionally a further heteroatom selected from O, N and S. A heterocyclyl ring may be saturated or partially unsaturated. A 5- to 10- membered partially unsaturated heterocyclyl ring is a cyclic group containing from 5 to 10 atoms selected from C, O, N and S in the ring and containing 1 or 2, e.g. 1 double bond. Typically, in the compounds described herein, a heterocyclyl ring is saturated unless otherwise specified. A 5- to 10- membered heterocyclyl ring is typically a 4- to 7- membered heterocyclyl ring or a 5- to 6-membered ring. A 4- to 7- membered heterocyclyl ring is typically a monocyclic ring and may be a monocyclic 5- or 6- membered heterocyclyl ring. Alternatively, a 5- to 10- membered heterocyclyl ring may be a 9- or 10- membered fused bicyclic heterocyclyl ring (i.e. a fused heterobicyclic group). In some compounds described herein, a 5- to 10- membered heterocyclyl group is a 4- to 7- membered nitrogen-containing heterocyclyl ring which is unsubstituted or is substituted as described herein. Preferred 4- to 7- membered nitrogen-containing heterocyclyl rings include morpholine, pyrrolidine, piperidine, and piperazine. Examples of 5- and 6- membered saturated heterocyclyl rings include piperazine, piperidine, morpholine, diazinane and pyrrolidine. Diazinane is typically 1,4-diazinane. Examples of 9- and 10- membered bicyclic heterocyclyl rings include azaspiro[4.4]nonane and octahydro-1H-indole. Preferably, the bicyclic heterocyclyl ring comprises 1, 2 or 3, preferably 1 or 2 nitrogen atoms. For the avoidance of doubt, references to a heterocyclyl ring also include fused polycyclic ring systems, including for instance fused bicyclic systems in which a heterocyclyl ring is fused to an aryl group. When the heterocyclyl ring is such a fused heterocyclyl group, preferred examples are fused ring systems wherein a 5- to 6- membered heterocyclyl group is fused to a phenyl group. As used herein, a 6- to 10-membered aryl ring is a substituted or unsubstituted, monocyclic or fused polycyclic aromatic group containing from 6 to 10 carbon atoms in the ring portion. Examples include monocyclic groups such as phenyl and fused bicyclic groups such as naphthyl and indenyl. Phenyl (benzene) is preferred. As used herein, a 5- to 10- membered heteroaryl ring is a substituted or unsubstituted monocyclic or fused polycyclic aromatic group containing from 5 to 10 atoms in the ring portion, including at least one heteroatom, for example 1, 2 or 3 heteroatoms, typically selected from O, S and N. A heteroaryl ring is typically a 5- or 6-membered heteroaryl ring or a 9- or 10- membered heteroaryl ring. Preferably, the heteroaryl ring comprises 1, 2 or 3, preferably 1 or 2 nitrogen atoms. Examples of 5- and 6- membered heteroaryl rings include thiazole, pyrazole, pyrimidine, triazole, 1,2,4-oxadiazole and pyrazine. Examples of 8-, 9- and 10- membered heteroaryl rings include indazole, thieno[2,3-c]pyrazole, imidazo[4,5- b]pyridine, pyrazolo[3,4-b]pyridine, furo[2,3-c]pyridine, indole, benzoxazole, benzothiazole, [1,2,4]triazolo[4,3-a]pyridine, thieno[2,3-d]pyrimidine, 1,2,3- benzotriazole, imidazo[1,5-a]pyridine, imidazo[1,2-a]pyrazine, oxazolo[5,4-b]pyridine, quinoline, naphthyridine, isoquinoline, quinazoline, and quinoxaline. For the avoidance of doubt, references to a heteroaryl ring also include fused polycyclic ring systems, including for instance fused bicyclic systems in which a heteroaryl ring is fused to an aryl group. When the heteroaryl ring is such a fused heteroaryl group, preferred examples are fused ring systems wherein a 5- to 6-membered heteroaryl group is fused to a phenyl group. Indazole is preferred. As used herein, a fused bicyclic group is a group comprising two cyclic moieties sharing a common bond between two atoms. A cycloalkyl, heterocyclyl, aryl or heteroaryl ring may be unsubstituted or substituted as described herein unless otherwise stated. For example, a cycloalkyl, heterocyclyl, aryl or heteroaryl ring may be unsubstituted or substituted with 1, 2 or 3, typically 1 or 2 such as e.g. 1 substituent. Suitable substituents include halo, C1-4alkoxy, R10, -(C1-4alkylene)-R10, =O, -CN, and C1-4alkyl, wherein R10is as defined herein). The substituents on a substituted cycloalkyl, heterocyclyl, aryl or heteroaryl ring are typically themselves unsubstituted, unless otherwise stated. The compounds described herein comprise at least one heterocyclyl ring comprising at least one nitrogen atom. Said nitrogen atom(s) are independently selected from secondary, tertiary and quaternary nitrogen atom(s). A quaternary nitrogen atom is present when the compound comprises a quaternised derivative of one or more monocyclic groups or fused bicyclic groups. As used herein, a quaternised derivative of a moiety such as a cyclic moiety is formed by bonding an additional alkyl group to a nitrogen atom in the moiety such that the valency of the said nitrogen atom increases from 3 to 4 and the nitrogen atom is positively charged. The compounds described herein comprise a heterocyclyl ring identified as ring Hy, which is a 4- to 7-membered heterocyclyl ring. Ring Hy contains X and at least one N atom in the ring portion, wherein X is a bond, -N(R11)-, O, S, -S(O)2-, -S(O)(NR11)-, or - C(R11)2-, and R11is as defined herein. Ring Hy is linked to ring A (as identified in formula (I) above) via a C atom within ring Hy, said C atom also being linked to R2which is as defined herein. A N atom within ring Hy is substituted by R1which is as defined herein. The rest of ring Hy is unsubstituted or substituted by one or two R3(leaving aside the potential substitution of ring Hy by LINK). Each R3is independently selected from C1-4 alkyl, C1-4alkoxy and halo, or (i) two R3linked to adjacent C atoms in ring Hy form, together with the C atoms to which they are attached, a C5-6 cycloalkyl ring, or (ii) two R3linked to the same C atom in ring Hy form, together with the C atom to which they are attached, a C3-6cycloalkyl ring or a C3-6heterocycloalkyl ring, as defined herein. In option (ii), the skilled person would understand that the C atom to which the two R3are attached is a spiro atom (i.e. the common atom that connects the two rings of a spiro compound). As used herein, the terms “monovalent” or “monovalent moiety” are used to describe a chemical group obtainable by removing a hydrogen atom from the corresponding compound. As used herein, the terms “divalent” or “divalent moiety” are used to describe a chemical group obtainable by removing a hydrogen atom from the corresponding monovalent moiety. Thus, as used herein, the terms “divalent” and “divalent moiety” are used to describe a chemical group obtainable by removing two hydrogen atoms from the corresponding compound. In the compounds of the invention, the stereochemistry is not limited. In particular, where moiety M of formula (I) contains one or more chiral centre, the moiety M may be used in enantiomerically or diastereoisomerically pure form, or in the form of a mixture of isomers. Further, for the avoidance of doubt, the compounds of the invention may be used in any tautomeric form. Typically, the agent or substance described herein contains at least 50%, preferably at least 60, 75%, 90% or 95% of a compound which is enantiomerically or diasteriomerically pure. Thus, the compound is preferably substantially optically pure. The moiety M of formula (I) typically contains at least one chiral centre at the carbon atom of ring Hy which is linked to R2and to ring A. Moiety M may be provided in the form of the R-enantiomer at said carbon atom, in the form of the S-enantiomer at said carbon atom, or in the form of a mixture of the two enantiomers. A pure enantiomeric form of either the R- or the S-enantiomer may be preferred. In some embodiments, the R-enantiomer at said carbon atom is preferred, and in particular when R2 is H then the R-enantiomer at said carbon atom is preferred. The preferred stereochemistry at said carbon atom is also depicted by the following illustrative structure of formula (I) where the bond from ring Hy to the core ring A is in the “up” position and the bond from ring Hy to R2is the down position: . This steroechemsitry at the carbon atom of ring Hy which is linked to R2and to ring A, where the bond from ring Hy to the core ring A is in the “up” position and the bond from ring Hy to R2is the down position (as depicted above), is also preferred for the moiety M of formulae (II), (III), (IIIa), (IIIb), (III’), (IIIa’), (IIIb’), (IV) and (IVA). As discussed further herein, where the compounds of the invention contain a chiral centre, and in particular where moiety M contains a chiral centre, the individual stereoisomers may be obtained by chiral synthesis, or by separation of stereoisomers. Stereoisomers may be separated, for example, using chiral chromatography. The individual stereoisomers may be identified using the IUPAC labels R and S as appropriate. Alternatively, the individual stereoisomers may be identified by the order in which they elute, for example the first, second, third or fourth stereisomer respectively, as obtained by separation using chiral chromatography. Where two or more stereocentres are present in a compound or moiety, a combination of IUPAC nomenclature for stereocentres where absolute stereochemistry has been defined, and rate of elution, may be used. For example, where two or more individual stereoisomers are unidentified by IUPAC nomenclature, these stereoisomers may be identified as the fast- and slow-eluting isomers, as obtained by separation using chiral chromatography. Therefore, the stereoisomers at a chiral carbon atom of ring Hy which is linked to R2and to ring A may be defined as the fast-eluting and slow-eluting stereoisomers, as obtained by separation using chiral chromatography. Chiral chromatography is typically reverse phase HPLC. The compounds of the present invention may exist in unsolvated as well as solvated forms with pharmaceutically acceptable solvents such as water, ethanol, and the like, and it is intended that the invention embrace both solvated and unsolvated forms. A compound of the present invention can be converted into a pharmaceutically acceptable salt thereof, and a salt can be converted into the free compound, by conventional methods. For instance, a compound of the present invention can be contacted with a pharmaceutically acceptable acid to form a pharmaceutically acceptable salt. A pharmaceutically acceptable salt is a salt with a pharmaceutically acceptable acid or base. Pharmaceutically acceptable acids include both inorganic acids such as hydrochloric, sulphuric, phosphoric, diphosphoric, hydrobromic or nitric acid and organic acids such as oxalic, citric, fumaric, maleic, malic, ascorbic, succinic, tartaric, benzoic, acetic, methanesulphonic, ethanesulphonic, benzenesulphonic or p-toluenesulphonic acid. Pharmaceutically acceptable bases include alkali metal (e.g. sodium or potassium) and alkali earth metal (e.g. calcium or magnesium) hydroxides and organic bases such as alkyl amines, aralkyl amines and heterocyclic amines. Hydrochloride salts and acetate salts are preferred, in particular hydrochloride salts. Compounds of the Invention The compounds of the invention comprise a binder of MLLT1 and / or MLLT3 (M) that is covalently attached via a linker moiety (LINK) to an E3 ubiquitin ligase binding moiety (U). The inventors have surpisingly discovered that such compounds may have substantially enhanced efficacy compared with a corresponding MLLT1 and / or MLLT3 inhibitor that is not attached to an E3 ubiquitin ligase binding moiety. For example, the antiproliferative effects of the compounds may be substantially enhanced by covalent attachment to the E3 ubiquitin ligase binding moiety. Thus, the invention provides a compound which is a Proteolysis Targeting Chimera (PROTAC) or a pharmaceutically acceptable salt thereof, wherein the PROTAC has the structure: wherein U is an E3 ubiquitin ligase binding moiety, LINK is a moiety that covalently links M and U, and M is an MLLT1 and / or MLLT3 binder of formula (I) as defined herein. In the compounds of the present invention, the MLLT1 and / or MLLT3 binder is covalently attached to the E3 ubiquitin ligase binding moiety via the moiety labelled LINK. LINK is either a single bond or a chemical group that covalently attaches the MLLT1 and / or MLLT3 binder to the E3 ubiquitin ligase binding moiety. The MLLT1 and / or MLLT3 binder is attached to LINK via (i) a single bond at R8, or (ii) a C or N atom within group R8or ring Hy (as described herein) such that a hydrogen atom on the C or N atom within group R8or ring Hy is replaced with a bond to LINK. In case (ii), a hydrogen atom on the C or N atom within group R8or ring Hy is replaced by either a direct single bond to the E3 ubiquitin ligase binding moiety or by a chemical group that covalently attaches the MLLT1 and / or MLLT3 binder to the E3 ubiquitin ligase binding moiety. In case (ii), preferably it is a C or N atom within group R8(as described herein) that is attached to LINK such that a hydrogen atom on the C or N atom within group R8is replaced with a bond to LINK. The description herein discusses the substitution of group R8and ring Hy by various chemical groups aside from LINK. For completeness, the skilled person would readily appreciate that where group R8and / or ring Hy are defined as being unsubstituted, this is intended as a reference to the absence of substituents other than a bond to LINK. Therefore, such a definition retains the option that group R8or ring Hy is attached to LINK via a C or N atom within group R8or ring Hy such that a hydrogen atom on the C or N atom within group R8or ring Hy is replaced with a bond to LINK. Furthermore, the skilled person would readily appreciate that where group R8and / or ring Hy are defined as being substituted by one or more chemical groups (suitable such chemical groups are defined herein), this is intended as a reference to substituents other than a bond to LINK. Therefore, such a definition includes group R8or ring Hy being attached to LINK via a C or N atom within group R8or ring Hy such that a hydrogen atom on the C or N atom within group R8or ring Hy is replaced with a bond to LINK. Therefore, where group R8and / or ring Hy are defined as being unsubstituted or substituted by one or more chemical groups (suitable such chemical groups are defined herein), then one of group R8or ring Hy may also be attached to LINK via a C or N atom within group R8or ring Hy such that a hydrogen atom on the C or N atom within group R8or ring Hy is replaced with a bond to LINK. A bond to LINK may optionally be positioned on a carbon atom which carries a further substituent (where chemically possible). Typically, a carbon or nitrogen atom which is bonded to LINK does not carry a further substituent. For the avoidance of doubt, where group R8and / or ring Hy are defined as being substituted by a hydrogen atom (e.g. where R1, R2, R11, R3a, R3b, R3cand R3dare defined as being a hydrogen atom), then a reference herein to a hydrogen atom within group R8or ring Hy being replaced with a bond to LINK, includes the option that said hydrogen atom (e.g. a hydrogen atom at R1, R2, R11, R3a, R3b, R3cand R3d) is replaced with a bond to LINK. Therefore, where R1, R2, R11, R3a, R3b, R3cand R3dare defined as being a hydrogen atom, then said hydrogen atom may be replaced with a bond to LINK. For the avoidance of doubt, where ring Hy or group R8is substituted, a C or N atom which is bonded to LINK may be within the aryl, heteroaryl, heterocyclyl, or cycloalkyl ring of ring Hy or group R8, or it may be a C or N atom of a substituent on ring Hy or group R8. Preferably, a C or N atom which is bonded to LINK is a C or N atom on the heterocyclyl ring of ring Hy (i.e. directly to the ring and not via a substituent), a C or N atom of the aryl, heteroaryl, heterocyclyl, or cycloalkyl ring of ring Hy or group R8, or the heteroaryl, cycloalkyl, heterocyclyl or a phenyl ring or R10in the case that a group R10is present as, or as part of, a substituent on R8. As the skilled person would readily appreciate, methods for preparation of compounds (in which two discrete chemical entities contribute discrete biological functions to the overall compound) are very well known in the art. A hugely diverse range of techniques for covalently attaching the respective chemical entities, via a vast number of chemical linker moieties, is well established. Such is the ubiquity of these methodologies, that standard text books devoted entirely to this topic have long been available. One such textbook is “Bioconjugate Techniques” (Greg T. Hermanson, Academic Press Inc., 1996), the content of which is herein incorporated by reference in its entirety. MLLT1 and / or MLLT3 binder group M In the compounds of the invention, the MLLT1 and / or MLLT3 binder M is a monovalent moiety of formula (I) as defined herein. In the description that follows, the skilled person will readily understand that M is a monovalent moiety that is bonded to LINK via (i) a single bond at R8, or (ii) a C or N atom within group R8or ring Hy, preferably within group R8, (as described herein) such that a hydrogen atom on the C or N atom within group R8or ring Hy is replaced with a bond to LINK. Thus, in the description that follows, any of the hydrogen atoms on any of the C or N atoms within group R8or ring Hy may be removed to form the point of attachment of the monovalent moiety M to LINK. Typically, in formula (I), ring Hy is a 5- to 6- membered heterocyclyl ring containing X and at least one N atom, for instance one or two N atoms. X is typically a bond, -N(R11)-, O or -C(R11)2-. Preferably, X is a bond, -N(Me)-, O or -CH2-, most preferably X is a bond. In particular, when ring Hy is a 4- or 5-membered heterocyclyl ring, X is most preferably a bond. For example, ring Hy may be selected from a pyrrolidinyl, piperidinyl, morpholinyl or diazinanyl ring. Preferably, ring Hy is a 5-membered heterocyclyl ring containing X and at least one N atom, for instance one N atom. For example, ring Hy may be a pyrrolidinyl ring. Ring Hy is linked to ring A via a C atom within ring Hy, said C atom also being linked to R2. A N atom within ring Hy is substituted by R1. Typically, the N atom of ring Hy which is substituted by R1is adjacent to the C atom of ring Hy that is bonded to ring A. A C or N atom within ring Hy may be bonded to LINK by a hydrogen atom on that C or N atom being replaced by a bond to LINK. Typically, where ring Hy is bonded to LINK, this is via a C atom on Hy. Preferably, the bond to LINK is via (i) a single bond at R8, or (ii) replacement of a hydrogen atom on a C or N within group R8, i.e. the bond to LINK is preferably not via ring Hy. Typically, in formula (I), R1is H, C1-4cycloalkyl, or C1-4alkyl which is itself unsubstituted or substituted with one C1-4alkoxy or one, two or three halo, preferably with one C1-4alkoxy, for example R1may be H or C1-2alkyl which is unsubstituted or substituted with one C1-2alkoxy or one, two or three halo, preferably with one C1-2alkoxy, or R1may be H or C1-2alkyl which is unsubstituted or substituted with one C1-2alkoxy. Preferably, R1is H, methyl, ethyl or methoxyethyl. Most preferably, R1is methyl. In formula (I), R2is H or methyl. Preferably, R2is H. Typically, in formula (I), each R11is independently selected from H and methyl. When X is -N(R11)- or -S(O)(NR11)-, R11is preferably methyl. When X is -C(R11)2-, optionally one R11is replaced with a single bond to LINK and the other R11is H. When X is -C(R11)2-, each R11is preferably H. Aside from groups R1and R2, ring Hy may further be unsubstituted or substituted by one or two R3. Typically, each R3is independently selected from C1-4alkyl, C1-4alkoxy and halo, or (i) two R3linked to adjacent C atoms in ring Hy form, together with the C atoms to which they are attached, a C5-6cycloalkyl ring, or (ii) two R3linked to the same C atom in ring Hy form, together with the C atom to which they are attached, a C3-6cycloalkyl ring. More typically, each R3is independently selected from methyl, ethyl, t-butyl methoxy and fluoro, or (i) two R3linked to adjacent C atoms in ring Hy form, together with the C atoms to which they are attached, a cyclohexyl ring, or (ii) two R3linked to the same C atom in ring Hy form, together with the C atom to which they are attached, a cyclopentyl ring. Preferably, ring Hy is substituted by no R3groups. In another typical emobidment, each R3is independently selected from methyl, ethyl, t- butyl, methoxy and fluoro, or (i) two R3linked to adjacent C atoms in ring Hy form, together with the C atoms to which they are attached, a cyclohexyl ring, or (ii) two R3linked to the same C atom in ring Hy form, together with the C atom to which they are attached, a cyclopropyl ring or a cyclopentyl ring. Preferably, ring Hy is substituted by two R3groups which are both C1-4alkyl, for instance both being methyl, or one R3group which is C1-4alkyl, for instance methyl, ethyl or t-butyl. Typically, therefore, in formula (I), ring Hy is a 5- to 6- membered heterocyclyl ring containing X and at least one N atom, for example a pyrrolidinyl, piperidinyl, morpholinyl or diazinanyl ring; the N atom of ring Hy which is substituted by R1is adjacent to the C atom of ring Hy that is bonded to ring A; R1is H or C1-2 alkyl which is unsubstituted or substituted with one C1-2alkoxy or one, two or three halo, preferably with one C1-2alkoxy; R2is H or methyl; X is a bond, -N(R11)-, O or -C(R11)2-; R11is H or methyl; ring Hy is further unsubstituted or substituted by one or two R3; and each R3is independently selected from C1-4alkyl, C1-4alkoxy and halo, or (i) two R3linked to adjacent C atoms in ring Hy form, together with the C atoms to which they are attached, a C5-6cycloalkyl ring, or (ii) two R3linked to the same C atom in ring Hy form, together with the C atom to which they are attached, a C3-6cycloalkyl ring. Preferably, in formula (I), ring Hy is a pyrrolidinyl ring; the N atom of ring Hy which is substituted by R1is adjacent to the C atom of ring Hy that is bonded to ring A; R1is H, methyl, ethyl or methoxyethyl, more preferably methyl; R2is H; and ring Hy is substituted by no R3groups, i.e. ring Hy is not further substituted and carries substituent R1only. Alternatively, in formula (I), ring Hy is a pyrrolidinyl ring; the N atom of ring Hy which is substituted by R1is adjacent to the C atom of ring Hy that is bonded to ring A; R1is H, methyl, ethyl or methoxyethyl, more preferably methyl; R2is H; and ring Hy is further substituted by two R3groups which are both C1-4alkyl, for instance both being methyl, or one R3group which is C1-4alkyl, for instance methyl, ethyl or t-butyl. Typically, in formula (I), no more than two of Y1, Y2and Y3are N. Preferably, no more than one of Y1, Y2and Y3are N. Most preferably, Y1is N, Y2is -C(R6)-, and Y3is -C(R5)-. Typically, Z2is N, Z4is C, Z1is N, Z3is -C(R4)-, Y1is N or -C(R7)-, Y2is -C(R6)-, and Y3is -C(R5)-. Thus, the bicyclic structure formed by rings A and B has the structure: In one preferred embodiment, Z2is N, Z4is C, Z1is N, Z3is -C(R4)-, Y1is N, Y2is - C(R6)-, and Y3is -C(R5)-, such that the bicyclic structure formed by rings A and B has the structure: In another preferred embodiment, Z2is N, Z4is C, Z1is N, Z3is -C(R4)-, Y1is -C(R7)-, Y2is -C(R6)-, and Y3is -C(R5)- , such that the bicyclic structure formed by rings A and B has the structure:

[0004] Typically, in formula (I), R4, R5, R6, and R7are independently selected from H, halo, C1-4alkoxy, and C1-4alkyl which is itself unsubstituted or substituted by one, two or three halo. Typically, R4, R5, R6, and R7are independently selected from H, halo (e.g. fluoro), methoxy, and methyl. Preferably, either R4, R5, R6, and R7are H, or one of R4, R5, R6, and R7is selected from halo (e.g. fluoro), methoxy, and methyl, and the rest are H. More preferably, R4, R5, R6, and R7are H. In one preferred embodiment, R5, R6, and R7are as defined herein and R4is selected from H and halo. More preferably, R5, R6, and R7are as defined herein and R4is selected from H and fluoro. Most preferably, R5, R6, and R7are as defined herein R4is H. In one preferred embodiment, R5is selected from H, cyclopropyl, C1-4alkoxy, and C1-4alkyl, for example from H, C1-4alkoxy, and C1-4alkyl. More preferably, R5is selected from H, cyclopropyl, methoxy and methyl, for example H, methoxy and methyl. In one preferred embodiment, R6is H. In one preferred embodiment, R7is selected from H and halo. More preferably, R7is selected from H and fluoro. Typically, therefore, in formula (I): - R4is selected from H and halo, and R5, R6, and R7when present are H; - R5is selected from H, cyclopropyl, C1-4alkoxy, and C1-4alkyl, typically from H, C1-4 alkoxy, and C1-4 alkyl, and R4, R6, and R7when present are H; - R7is selected from H and halo, and R4, R5, and R6when present are H; or - R4, R5, R6, and R7are H. Preferably, in formula (I): - R4is selected from H and fluoro, and R5, R6, and R7when present are H; - R5is selected from H, cyclopropyl, methoxy and methyl, typically from H, methoxy and methyl, and R4, R6, and R7when present are H; - R7is selected from H and fluoro, and R4, R5, and R6when present are H; or - R4, R5, R6, and R7are H. In formula (I), L is -C(O)N(H)-, wherein the C atom of L is bonded to R8, and the N atom of L is bonded to ring B In one embodiment, R8is a bond to LINK. In another embodiment, R8is a group selected from a 6- to 10-membered aryl ring, a 5- to 10-membered heteroaryl ring, a 5- to 10-membered heterocyclyl ring, and a 5- to 6- membered cycloalkyl ring, the group R8being unsubstituted or substituted by one, two or three substituents independently selected from halo, C1-4alkoxy, R10, -(C1-4alkylene)- R10, =O, -CN, and C1-4 alkyl which is itself unsubstituted or substituted by one or two R9. R9and R10are as defined herein. Typically, in formula (I), R8is a group selected from a 6- to 10-membered aryl ring, a 5- to 10-membered heteroaryl ring, and a 5- to 6-membered heterocyclyl ring. The aryl, heteroaryl and heterocyclyl rings are as defined herein. For instance, R8may be selected from thiazolyl, pyrazolyl, pyrimidinyl, triazolyl, 1,2,4-oxadiazolyl, pyrazinyl, indazolyl, thieno[2,3-c]pyrazolyl, imidazo[4,5-b]pyridinyl, pyrazolo[3,4-b]pyridinyl, furo[2,3-c]pyridinyl, indolyl, benzoxazolyl, benzothiazolyl, [1,2,4]triazolo[4,3- a]pyridinyl, thieno[2,3-d]pyrimidinyl, 1,2,3-benzotriazolyl, imidazo[1,5-a]pyridinyl, imidazo[1,2-a]pyrazinyl, oxazolo[5,4-b]pyridinyl, quinolinyl, naphthyridinyl, isoquinolinyl, quinazolinyl, and quinoxalinyl. Preferably, R8is a 5- to 10-membered heteroaryl ring preferably containing one, two or three N atoms. Most preferably, R8is an indazolyl group. In some preferred embodiments, R8is a group selected from the following structures. For the avoidance of doubt, the following structures may be unsubstituted or substituted by one, two or three substituents as defined herein. [see below]

[0005]  A C or N atom within group R8may be bonded to LINK by a hydrogen atom on that C or N atom being replaced by a bond to LINK. Typically, where group R8is bonded to LINK, this is via a C atom on R8. Preferably, a C or N atom within group R8is bonded to LINK such that a hydrogen atom on that C or N atom is replaced by a bond to LINK. Preferably, the C or N atom that is bonded to LINK is a C or N atom of the aryl, heteroaryl, heterocyclyl or cycloalkyl ring of R8or a C or N atom of the heteroaryl, cycloalkyl, heterocyclyl or phenyl ring of R10. More preferably, the C or N atom that is bonded to LINK is a C or N atom of the aryl, heteroaryl, heterocyclyl or cycloalkyl ring of R8. In formula (I), in addition to any bond to LINK (where present) R8is unsubstituted or substituted by one, two or three substituents, for instance one or two substituents. Typically, each substituent is independently selected from halo, C1-4alkoxy, R10, -(CH2)-R10, =O, -CN, and C1-4alkyl which is itself unsubstituted or substituted by one or two groups selected from selected from halo and C1-2alkoxy. More typically, each substituent is independently selected from fluoro, chloro, methoxy, R10, -(CH2)-R10, =O, -CN, and C1-2alkyl which is itself unsubstituted or substituted by one or two groups selected from selected from halo (e.g. fluoro) and methoxy. Preferably, each substituent is independently selected from fluoro, R10and methyl. Most preferably, each substituent is independently selected from fluoro and methyl. R10is as defined herein. Typically, in formula (I), R10is a group selected from a 5- to 6-membered heteroaryl ring, a 3- to 6-membered cycloalkyl ring, a 4- to 5-membered heterocyclyl ring, and a phenyl ring. The cycloalkyl, heteroaryl and heterocyclyl rings are as defined herein. Preferably, R10is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, imidazolyl, oxadiazolyl, oxetanyl, phenyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolidinyl, thiazinyl, thiazolyl and triazolyl, more preferably pyrazolyl. In another embodiment, typically in formula (I), R10is a group selected from a 5- to 6- membered heteroaryl ring, a 3- to 6-membered cycloalkyl ring, a 4- to 6-membered heterocyclyl ring, and a phenyl ring. The cycloalkyl, heteroaryl and heterocyclyl rings are as defined herein. Preferably, R10is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, imidazolyl, oxadiazolyl, oxetanyl, phenyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolidinyl, piperidinyl, thiazinyl, thiazolyl and triazolyl. Typically, in formula (I), in addition to any bond to LINK (where present), R10is unsubstituted or substituted by one or two substituents independently selected from fluoro, methyl and methoxy. Preferably, R10is unsubstituted. Typically, therefore, in formula (I), R8is (i) a bond to LINK or (ii) a group selected from a 6- to 10-membered aryl ring, a 5- to 10-membered heteroaryl ring, and a 5- to 6- membered heterocyclyl ring; the group R8is unsubstituted or substituted by one, two or three substituents, for instance one or two substituents, each independently selected from halo, C1-4 alkoxy, R10, -(CH2)-R10, =O, -CN, and C1-4 alkyl which is itself unsubstituted or substituted by one or two groups selected from selected from halo and C1-2alkoxy; wherein R10is a group selected from a 5- to 6-membered heteroaryl ring, a 3- to 6-membered cycloalkyl ring, a 4- to 5-membered heterocyclyl ring, and a phenyl ring; and R10is unsubstituted or substituted by one or two substituents independently selected from fluoro, methyl and methoxy. Typically, where a C or N atom within group R8is bonded to LINK, the C or N atom that is bonded to LINK is a C or N atom of the aryl, heteroaryl, heterocyclyl or cycloalkyl ring of R8or a C or N atom of the heteroaryl, cycloalkyl, heterocyclyl or phenyl ring of R10. Preferably, in formula (I), R8is phenyl or a 5- to 10-membered heteroaryl ring containing one, two or three N atoms, for example an indazolyl group; the group R8is unsubstituted or substituted by one or two substituents, each independently selected from fluoro, R10and methyl; R10is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, imidazolyl, oxadiazolyl, oxetanyl, phenyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolidinyl, thiazinyl, thiazolyl and triazolyl; and R10is unsubstituted. Preferably, a C or N atom within group R8is bonded to LINK, wherein the C or N atom that is bonded to LINK is a C or N atom of the aryl, heteroaryl, heterocyclyl or cycloalkyl ring of R8. In another typical embodiment of formula (I), R8is (i) a bond to LINK or (ii) a group selected from a 6- to 10-membered aryl ring, a 5- to 10-membered heteroaryl ring, and a 5- to 6-membered heterocyclyl ring; the group R8is unsubstituted or substituted by one, two or three substituents, for instance one or two substituents, each independently selected from halo, C1-4alkoxy, R10, -(CH2)-R10, =O, -CN, and C1-4alkyl which is itself unsubstituted or substituted by one or two groups selected from selected from halo and C1-2alkoxy; wherein R10is a group selected from a 5- to 6-membered heteroaryl ring, a 3- to 6-membered cycloalkyl ring, a 4- to 6-membered heterocyclyl ring, and a phenyl ring; and R10is unsubstituted or substituted by one or two substituents independently selected from fluoro, methyl and methoxy. Preferably, in formula (I), R8is a 5- to 10- membered heteroaryl ring containing one, two or three N atoms, for example an indazolyl group; the group R8is unsubstituted or substituted by one or two substituents, each independently selected from fluoro, R10and methyl; R10is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, imidazolyl, oxadiazolyl, oxetanyl, phenyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolidinyl, piperidinyl, thiazinyl, thiazolyl and triazolyl; and R10is unsubstituted. In a typical embodiment of formula (I), the bicyclic structure formed by rings A and B has the structure: and: Y1is N or -C(R7)-; ring Hy is a 5- to 6- membered heterocyclyl ring containing X and at least one N atom, for example a pyrrolidinyl, piperidinyl, morpholinyl or diazinanyl ring; wherein the N atom of ring Hy which is substituted by R1is adjacent to the C atom of ring Hy that is bonded to ring A; R1is H or C1-2alkyl which is unsubstituted or substituted with one C1-2alkoxy or one, two or three halo, preferably with one C1-2 alkoxy; R2is H or methyl; X is a bond, -N(Me)-, O or -CH2-; ring Hy is further unsubstituted or substituted by one or two R3; wherein each R3is independently selected from C1-4alkyl, C1-4alkoxy and halo, or (i) two R3linked to adjacent C atoms in ring Hy form, together with the C atoms to which they are attached, a C5-6cycloalkyl ring, or (ii) two R3linked to the same C atom in ring Hy form, together with the C atom to which they are attached, a C3-6cycloalkyl ring; R4, R5, R6, and R7are independently selected from H, halo (e.g. fluoro), methoxy, and methyl; the C atom of L is bonded to R8, and the N atom of L is bonded to ring B; R8is (i) a bond to LINK or (ii) a group selected from a 6- to 10-membered aryl ring, a 5- to 10-membered heteroaryl ring, and a 5- to 6-membered heterocyclyl ring; wherein the group R8is unsubstituted or substituted by one, two or three substituents, for instance one or two substituents, each independently selected from halo, C1-4alkoxy, R10, -(CH2)-R10, =O, -CN, and C1-4alkyl which is itself unsubstituted or substituted by one or two groups selected from halo and C1-2alkoxy; and R10is a group selected from a 5- to 6-membered heteroaryl ring, a 3- to 6-membered cycloalkyl ring, a 4- to 5-membered heterocyclyl ring, and a phenyl ring; wherein R10is unsubstituted or substituted by one or two substituents independently selected from fluoro, methyl and methoxy; wherein either R8is (i) a bond to LINK, or R8is a group (ii) and M is bonded to LINK via a C or N atom within group R8or ring Hy, preferably within group R8, such that a hydrogen atom on the C or N atom within group R8or ring Hy is replaced with a bond to LINK. In a preferred embodiment of formula (I), the bicyclic structure formed by rings A and B has the structure:

[0006] and: ring Hy is a pyrrolidinyl ring; wherein the N atom of ring Hy which is substituted by R1is adjacent to the C atom of ring Hy that is bonded to ring A; R1is H, methyl, ethyl or methoxyethyl, more preferably methyl; R2is H; and ring Hy is substituted by no R3groups; either R4, R5, R6, and R7are H, or one of R4, R5, R6, and R7is selected from halo (e.g. fluoro), methoxy, and methyl, and the rest are H; the C atom of L is bonded to R8, and the N atom of L is bonded to ring B; R8is (i) a bond to LINK or (ii) a 5- to 10-membered heteroaryl ring containing one, two or three N atoms, for example an indazolyl group; the group R8is unsubstituted or substituted by one or two substituents, each independently selected from fluoro, R10and methyl; R10is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, imidazolyl, oxadiazolyl, oxetanyl, phenyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolidinyl, thiazinyl, thiazolyl and triazolyl; and R10is unsubstituted; wherein either R8is (i) a bond to LINK, or R8is a group (ii) and M is bonded to LINK via a C or N atom within group R8or ring Hy, preferably within group R8, such that a hydrogen atom on the C or N atom within group R8or ring Hy is replaced with a bond to LINK. In an alternative typical embodiment of formula (I), the bicyclic structure formed by rings A and B has the structure:

[0007] Y1is N or -C(R7)-; ring Hy is a 5- to 6- membered heterocyclyl ring containing X and at least one N atom, for example a pyrrolidinyl, piperidinyl, morpholinyl or diazinanyl ring; wherein the N atom of ring Hy which is substituted by R1is adjacent to the C atom of ring Hy that is bonded to ring A; R1is H or C1-2alkyl which is unsubstituted or substituted with one C1-2alkoxy or one, two or three halo, preferably with one C1-2alkoxy; R2is H or methyl; X is a bond, -N(Me)-, O or -CH2-; ring Hy is further unsubstituted or substituted by one or two R3; wherein each R3is independently selected from C1-4alkyl, C1-4alkoxy and halo, or (i) two R3linked to adjacent C atoms in ring Hy form, together with the C atoms to which they are attached, a C5-6cycloalkyl ring, or (ii) two R3linked to the same C atom in ring Hy form, together with the C atom to which they are attached, a C3-6cycloalkyl ring; R4, R6, and R7are independently selected from H, halo (e.g. fluoro), methoxy, and methyl; R5is selected from H, halo (e.g. fluoro), methoxy, cyclopropyl and methyl; the C atom of L is bonded to R8, and the N atom of L is bonded to ring B; R8is a group selected from a 6- to 10-membered aryl ring, a 5- to 10-membered heteroaryl ring, and a 5- to 6-membered heterocyclyl ring; wherein the group R8is unsubstituted or substituted by one, two or three substituents, for instance one or two substituents, each independently selected from halo, C1-4alkoxy, R10, -(CH2)-R10, =O, - CN, and C1-4alkyl which is itself unsubstituted or substituted by one or two groups selected from halo and C1-2alkoxy; R10is a group selected from a 5- to 6-membered heteroaryl ring, a 3- to 6-membered cycloalkyl ring, a 4- to 6-membered heterocyclyl ring, and a phenyl ring; wherein R10is unsubstituted or substituted by one or two substituents independently selected from fluoro, methyl and methoxy; and wherein M is bonded to LINK via a C or N atom within group R8or ring Hy such that a hydrogen atom on the C or N atom within group R8or ring Hy is replaced with a bond to LINK. In an alternative preferred embodiment of formula (I), the bicyclic structure formed by rings A and B has the structure: and: ring Hy is a pyrrolidinyl ring; wherein the N atom of ring Hy which is substituted by R1is adjacent to the C atom of ring Hy that is bonded to ring A; R1is H, methyl, ethyl or methoxyethyl, more preferably methyl; R2is H; and ring Hy is substituted by two R3groups which are both C1-4alkyl, for instance both being methyl, or one R3group which is C1-4alkyl, for instance methyl, ethyl or t-butyl; either R4, R5, R6, and R7are H, or one of R4, R5, R6, and R7is selected from halo (e.g. fluoro), methoxy, and methyl, and the rest are H; the C atom of L is bonded to R8, and the N atom of L is bonded to ring B; R8is a 5- to 10-membered heteroaryl ring containing one, two or three N atoms, for example an indazolyl group; the group R8is unsubstituted or substituted by one or two substituents, each independently selected from fluoro, R10and methyl; R10is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, imidazolyl, oxadiazolyl, oxetanyl, phenyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolidinyl, piperidinyl, thiazinyl, thiazolyl and triazolyl; R10is unsubstituted; and wherein M is bonded to LINK via a C or N atom within group R8or ring Hy such that a hydrogen atom on the C or N atom within group R8or ring Hy is replaced with a bond to LINK. In a particular embodiment of the compounds of the invention, the MLLT1 and / or MLLT3 binder M is a monovalent moiety of formula (II): wherein: Z1, Z2, Z3, Z4, Y1, Y2, Y3, R1, R2, R8, X and L are as defined above for formula (I); R3aand R3bare independently selected from H, C1-4alkyl, phenyl, a 5- to 6-membered heteroaryl ring and C1-4alkoxy, or R3aand R3bform, together with the C atom to which they are attached, a C3-6cycloalkyl ring or a C3-6heterocycloalkyl ring, R3cand R3dare independently selected from H, C1-4alkyl, halo, phenyl, a 5- to 6- membered heteroaryl ring and C1-4alkoxy, or R3cand R3dform, together with the C atom to which they are attached, a C3-6cycloalkyl ring or a C3-6heterocycloalkyl ring, with the proviso that when X is NR11, O, or S, then neither R3cnor R3dare halo, or R3aand R3care H, and R3band R3dform, together with the C atoms to which they are attached, a C5-6cycloalkyl ring; wherein at least two of R3a, R3b, R3cand R3dare H; wherein either R8is (i) a bond to LINK, or R8is a group (ii) and M is bonded to LINK via a C or N atom within group R8or ring Hy, preferably within group R8, (as described herein) such that a hydrogen atom on the C or N atom within group R8or ring Hy is replaced with a bond to LINK. Typically, in formula (II): R3aand R3bare independently selected from H and methyl; R3cand R3dare independently selected from H, C1-4 alkyl, halo and C1-4 alkoxy, in particular from H, methyl, ethyl, fluoro, methoxy and t-butyl, or R3cand R3dform, together with the C atom to which they are attached, a C5-6cycloalkyl ring (in particular a cyclopentyl ring), with the proviso that when X is NR11, O, or S, then neither R3cnor R3dare fluoro; or R3aand R3care H, and R3band R3dform, together with the C atoms to which they are attached, a C5-6cycloalkyl ring (in particular a cyclohexyl ring); wherein at least two of R3a, R3b, R3cand R3dare H. In an alternative typical embodiment: R3aand R3bare independently selected from H and methyl; R3cand R3dare independently selected from H, C1-4alkyl, halo and C1-4alkoxy, in particular from H, methyl, ethyl, fluoro, methoxy and t-butyl, or R3cand R3dform, together with the C atom to which they are attached, a C3-6 cycloalkyl ring (in particular a cyclopropyl or cyclopentyl ring), with the proviso that when X is NR11, O, or S, then neither R3cnor R3dare fluoro; or R3aand R3care H, and R3band R3dform, together with the C atoms to which they are attached, a C5-6cycloalkyl ring (in particular a cyclohexyl ring); wherein at least two of R3a, R3b, R3cand R3dare H. Optionally, one of R3a, R3b, R3cand R3dis replaced with a single bond to LINK. Preferably, in formula (II), R3a, R3b, R3cand R3dare all H, or one of R3a, R3b, R3cand R3dis methyl, ethyl or t-butyl and the rest are H, or R3cand R3dare methyl and the rest are H. In a typical embodiment of formula (II), the bicyclic structure formed by rings A and B has the structure: and: Y1is N or -C(R7)-; R1is H or C1-2alkyl which is unsubstituted or substituted with one C1-2alkoxy or one, two or three halo, preferably with one C1-2alkoxy; R2is H or methyl; X is a bond, -N(Me)-, O or -CH2-; R3aand R3bare independently selected from H and methyl; R3cand R3dare independently selected from H, C1-4alkyl, halo and C1-4alkoxy, in particular from H, methyl, ethyl, fluoro, methoxy and t-butyl, or R3cand R3dform, together with the C atom to which they are attached, a C5-6cycloalkyl ring (in particular a cyclopentyl ring), with the proviso that when X is NR11, O, or S, then neither R3cnor R3dare fluoro; or R3aand R3care H, and R3band R3dform, together with the C atoms to which they are attached, a C5-6cycloalkyl ring (in particular a cyclohexyl ring); wherein at least two of R3a, R3b, R3cand R3dare H; R4, R5, R6, and R7are independently selected from H, halo (e.g. fluoro), methoxy, and methyl; the C atom of L is bonded to R8, and the N atom of L is bonded to ring B; R8is (i) a bond to LINK or (ii) a group selected from a 6- to 10-membered aryl ring, a 5- to 10-membered heteroaryl ring, and a 5- to 6-membered heterocyclyl ring; wherein the group R8is unsubstituted or substituted by one, two or three substituents, for instance one or two substituents, each independently selected from halo, C1-4alkoxy, R10, -(CH2)-R10, =O, -CN, and C1-4 alkyl which is itself unsubstituted or substituted by one or two groups selected from selected from halo and C1-2alkoxy; and R10is a group selected from a 5- to 6-membered heteroaryl ring, a 3- to 6-membered cycloalkyl ring, a 4- to 5-membered heterocyclyl ring, and a phenyl ring; wherein R10is unsubstituted or substituted by one or two substituents independently selected from fluoro, methyl and methoxy; wherein either R8is (i) a bond to LINK, or R8is a group (ii) and M is bonded to LINK via a C or N atom within group R8or ring Hy, preferably within group R8, such that a hydrogen atom on the C or N atom within group R8or ring Hy is replaced with a bond to LINK. In an alternative typical embodiment of formula (II), the bicyclic structure formed by rings A and B has the structure: and: Y1is N or -C(R7)-; R1is H or C1-2alkyl which is unsubstituted or substituted with one C1-2alkoxy or one, two or three halo, preferably with one C1-2alkoxy; R2is H or methyl; X is a bond, -N(Me)-, O or -CH2-; R3aand R3bare independently selected from H and methyl; R3cand R3dare independently selected from H, C1-4alkyl, halo and C1-4alkoxy, in particular from H, methyl, ethyl, fluoro, methoxy and t-butyl, or R3cand R3dform, together with the C atom to which they are attached, a C3-6cycloalkyl ring (in particular a cyclopropyl or cyclopentyl ring), with the proviso that when X is NR11, O, or S, then neither R3cnor R3dare fluoro; or R3aand R3care H, and R3band R3dform, together with the C atoms to which they are attached, a C5-6cycloalkyl ring (in particular a cyclohexyl ring); wherein at least two of R3a, R3b, R3cand R3dare H; R4, R6, and R7are independently selected from H, halo (e.g. fluoro), methoxy, and methyl; R5is selected from H, halo (e.g. fluoro), methoxy, cyclopropyl and methyl; the C atom of L is bonded to R8, and the N atom of L is bonded to ring B; R8is a group selected from a 6- to 10-membered aryl ring, a 5- to 10-membered heteroaryl ring, and a 5- to 6-membered heterocyclyl ring; wherein the group R8is unsubstituted or substituted by one, two or three substituents, for instance one or two substituents, each independently selected from halo, C1-4alkoxy, R10, -(CH2)-R10, =O, - CN, and C1-4alkyl which is itself unsubstituted or substituted by one or two groups selected from selected from halo and C1-2 alkoxy; R10is a group selected from a 5- to 6-membered heteroaryl ring, a 3- to 6-membered cycloalkyl ring, a 4- to 6-membered heterocyclyl ring, and a phenyl ring; wherein R10is unsubstituted or substituted by one or two substituents independently selected from fluoro, methyl and methoxy; and wherein M is bonded to LINK via a C or N atom within group R8or ring Hy such that a hydrogen atom on the C or N atom within group R8or ring Hy is replaced with a bond to LINK. In a preferred embodiment of formula (II), the bicyclic structure formed by rings A and B has the structure: and: X is absent; R1is H, methyl, ethyl or methoxyethyl, more preferably methyl; R2is H; R3a, R3b, R3cand R3dare all H; either R4, R5, R6, and R7are H, or one of R4, R5, R6, and R7is selected from fluoro, methoxy, and methyl, and the rest are H; the C atom of L is bonded to R8, and the N atom of L is bonded to ring B; R8is a 5- to 10-membered heteroaryl ring containing one, two or three N atoms, for example an indazolyl group; the group R8is unsubstituted or substituted by one or two substituents, each independently selected from fluoro, R10and methyl; R10is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, imidazolyl, oxadiazolyl, oxetanyl, phenyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolidinyl, thiazinyl, thiazolyl and triazolyl; and R10is unsubstituted; and wherein M is bonded to LINK via a C or N atom within group R8or ring Hy, preferably within group R8, such that a hydrogen atom on the C or N atom within group R8or ring Hy is replaced with a bond to LINK. In an alternative preferred embodiment of formula (II), the bicyclic structure formed by rings A and B has the structure: and: X is absent; R1is H, methyl, ethyl or methoxyethyl, more preferably methyl; R2is H; one of R3a, R3b, R3cand R3dis methyl, ethyl or t-butyl, and the rest are H, or R3cand R3dare methyl and the rest are H; either R4, R5, R6, and R7are H, or one of R4, R5, R6, and R7is selected from fluoro, methoxy, and methyl, and the rest are H; the C atom of L is bonded to R8, and the N atom of L is bonded to ring B; R8is a 5- to 10-membered heteroaryl ring containing one, two or three N atoms, for example an indazolyl group; the group R8is unsubstituted or substituted by one or two substituents, each independently selected from fluoro, R10and methyl; R10is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, imidazolyl, oxadiazolyl, oxetanyl, phenyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolidinyl, piperidinyl, thiazinyl, thiazolyl and triazolyl; R10is unsubstituted; and wherein M is bonded to LINK via a C or N atom within group R8or ring Hy such that a hydrogen atom on the C or N atom within group R8or ring Hy is replaced with a bond to LINK. In a further preferred embodiment of formula (II), the bicyclic structure formed by rings A and B has the structure: and: X is absent; R1is H, methyl, ethyl or methoxyethyl, more preferably methyl; R2is H; R3a, R3b, R3cand R3dare all H; either R4, R5, R6, and R7are H, or one of R4, R5, R6, and R7is selected from fluoro, methoxy, and methyl, and the rest are H; the C atom of L is bonded to R8, and the N atom of L is bonded to ring B; and R8is a bond to LINK. In a particularly preferred embodiment of the compounds of the invention, the MLLT1 and / or MLLT3 binder M is a monovalent moiety of formula (III):

[0008] wherein R1, R2, R3a, R3b, R3c, R3d, X, Y1, R5, R6and R8are as defined herein. Typically, in the compounds of formula (III): R1is H or C1-4alkyl which is itself unsubstituted or substituted with C1-4alkoxy; R2is H or methyl; R3aand R3bare independently selected from H, C1-4alkyl, and C1-4alkoxy, or R3aand R3bform, together with the C atom to which they are attached, a C3-6 cycloalkyl ring, R3cand R3dare independently selected from H, C1-4alkyl, halo and C1-4alkoxy, or R3cand R3dform, together with the C atom to which they are attached, a C3-6cycloalkyl ring, with the proviso that when X is O, then neither R3cnor R3dare halo, or R3aand R3care H, and R3band R3dform, together with the C atoms to which they are attached, a C5-6cycloalkyl ring; wherein at least two of R3a, R3b, R3cand R3dare H; X is a bond, -N(Me)-, O or -CH2-; Y1is N or -C(R7)-; R5, R6and R7are independently selected from H, halo C1-4alkoxy, and C1-4alkyl; R8is (i) a bond to LINK or (ii) a group selected from a 6- to 10-membered aryl ring, a 5- to 10-membered heteroaryl ring, and a 5- to 10-membered heterocyclyl ring, the group R8being unsubstituted or substituted by one, two or three substituents independently selected from halo, C1-4alkoxy, R10, -(C1-4alkylene)-R10, =O, -CN, and C1-4alkyl which is itself unsubstituted or substituted by one or two R9; each R9is independently selected from halo and C1-4alkoxy; and R10is a group selected from a 5- to 6-membered heteroaryl ring, a 3- to 6-membered cycloalkyl ring, a 4- to 6-membered heterocyclyl ring, and a phenyl ring, the group R10being unsubstituted or substituted by one or two substituents independently selected from C1-4alkyl, C1-4alkoxy, and halo; wherein either R8is (i) a bond to LINK, or R8is a group (ii) and M is bonded to LINK via a C or N atom within group R8or ring Hy, preferably within group R8, (as described herein) such that a hydrogen atom on the C or N atom within group R8or ring Hy is replaced with a bond to LINK. In some of the particularly preferred embodiments, the MLLT1 and / or MLLT3 binder M is a monovalent moiety of formula (IIIa): wherein R1, R2, R3a, R3b, R3c, R3d, R5, R6, R8and X are as defined in formula (III). In other of the particularly preferred embodiments, the MLLT1 and / or MLLT3 binder M is a monovalent moiety of formula (IIIb):

[0009] wherein R1, R2, R3a, R3b, R3c, R3d, R5, R6, R7, R8and X are as defined in formula (III). Typically, in formula (III), formula (IIIa) and formula (IIIb), R1is H, or C1-4alkyl which is itself unsubstituted or substituted with one C1-4alkoxy or one, two or three halo, preferably with one C1-4alkoxy, for example R1may be H or C1-2alkyl which is unsubstituted or substituted with one C1-2alkoxy or one, two or three halo, preferably with one C1-2alkoxy. Preferably, R1is H, methyl, ethyl or methoxyethyl. Most preferably, R1is methyl. In formula (III), formula (IIIa) and formula (IIIb), R2is H or methyl. Preferably, R2is H. Typically, in formula (III), formula (IIIa) and formula (IIIb), X is a bond, -N(R11)-, O or -C(R11)2-. Preferably, X is a bond, -N(Me)-, O or -CH2-, most preferably X is a bond. Typically, in formula (III), formula (IIIa) and formula (IIIb), each R11is independently selected from H and methyl. When X is -N(R11)- or -S(O)(NR11)-, R11is preferably methyl. When X is -C(R11)2-, one R11is optionally replaced with a single bond to LINK and the other R11is H. When X is -C(R11)2-, each R11is preferably H. Typically, in formula (III), formula (IIIa) and formula (IIIb), R3aand R3bare independently selected from H, C1-4alkyl, halo and C1-4alkoxy, in particular from H and methyl; R3cand R3dare independently selected from H, methyl, ethyl, fluoro, methoxy and t-butyl, or R3cand R3dform, together with the C atom to which they are attached, a C5-6 cycloalkyl ring (in particular a cyclopentyl ring), with the proviso that when X is NR11, O, or S, then neither R3cnor R3dare fluoro; or R3aand R3care H, and R3band R3dform, together with the C atoms to which they are attached, a C5-6cycloalkyl ring (in particular a cyclohexyl ring); wherein at least two of R3a, R3b, R3cand R3dare H. Preferably, in formula (III), formula (IIIa) and formula (IIIb), R3a, R3b, R3cand R3dare all H. Alternatively, one of R3a, R3b, R3cand R3dis methyl, ethyl or t-butyl, and the rest are H, or R3cand R3dare methyl and the rest are H. In all embodiments of formula (III), formula (IIIa) and formula (IIIb) described herein, when X is -N(R11)- or O then neither R3cnor R3dare halo (e.g. fluoro). Typically, in formula (III), formula (IIIa) and formula (IIIb), R5is selected from H, C1-4alkoxy, and C1-4alkyl. Preferably, R5is selected from H, methoxy and methyl. Typically, in formula (III), formula (IIIa) and formula (IIIb), R6is H. Typically, in formula (III) and formula (IIIb), R7is selected from H and halo. Preferably, R7is selected from H and fluoro. Typically, therefore, in formula (III), formula (IIIa) and formula (IIIb): - R5is selected from H, C1-4alkoxy, and C1-4alkyl, and R6and R7when present are H; - R7when present is selected from H and halo, and R5and R6are H; or - R5, R6, and R7when present are H. Preferably, in in formula (III), formula (IIIa) and formula (IIIb): - R5is selected from H, methoxy and methyl, and R6and R7when present are H; - R7when present is selected from H and fluoro, and R5and R6are H; or - R5, R6, and R7when present are H. In one preferred embodiment of formula (III), formula (IIIa) and formula (IIIb), R8is a bond to LINK. In another preferred embodiment of formula (III), formula (IIIa) and formula (IIIb), R8is a group selected from a 6- to 10-membered aryl ring, a 5- to 10-membered heteroaryl ring, and a 5- to 6-membered heterocyclyl ring. The aryl, heteroaryl and heterocyclyl rings are as defined herein. For instance, R8may be selected from thiazolyl, pyrazolyl, pyrimidinyl, triazolyl, 1,2,4-oxadiazolyl, pyrazinyl, indazolyl, thieno[2,3-c]pyrazolyl, imidazo[4,5-b]pyridinyl, pyrazolo[3,4-b]pyridinyl, furo[2,3-c]pyridinyl, indolyl, benzoxazolyl, benzothiazolyl, [1,2,4]triazolo[4,3-a]pyridinyl, thieno[2,3-d]pyrimidinyl, 1,2,3-benzotriazolyl, imidazo[1,5-a]pyridinyl, imidazo[1,2-a]pyrazinyl, oxazolo[5,4- b]pyridinyl, quinolinyl, naphthyridinyl, isoquinolinyl, quinazolinyl, and quinoxalinyl. Preferably, R8is a 5- to 10-membered heteroaryl ring containing one, two or three N atoms. Most preferably, R8is an indazolyl group. Typically, in formula (III), formula (IIIa) and formula (IIIb), R8is a group selected from the following structures. For the avoidance of doubt, the following structures may be unsubstituted or substituted by one, two or three substituents as defined herein. [see below]

[0010] Preferably, R8is an indazolyl group. Typically, in formula (III), formula (IIIa) and formula (IIIb), R8is unsubstituted or substituted by one, two or three substituents, for instance one or two substituents, independently selected from halo, C1-4alkoxy, R10, -(CH2)-R10, =O, -CN, and C1-4alkyl which is itself unsubstituted or substituted by one or two groups selected from selected from halo and C1-2alkoxy. More typically, each substituent is independently selected from fluoro, chloro, methoxy, R10, -(CH2)-R10, =O, -CN, and C1-2alkyl which is itself unsubstituted or substituted by one or two groups selected from selected from halo (e.g. fluoro) and methoxy. Preferably, each substituent is independently selected from fluoro, R10and methyl. Most preferably, each substituent is independently selected from fluoro and methyl. R10is as defined herein. Typically, in formula (III), formula (IIIa) and formula (IIIb), R10is a group selected from a 5- to 6-membered heteroaryl ring, a 3- to 6-membered cycloalkyl ring, a 4- to 5- membered heterocyclyl ring, and a phenyl ring. The aryl, heteroaryl and heterocyclyl rings are as defined herein. Preferably, R10is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, imidazolyl, oxadiazolyl, oxetanyl, phenyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolidinyl, thiazinyl, thiazolyl and triazolyl. Typically, in in formula (III), formula (IIIa) and formula (IIIb), R10is unsubstituted or substituted by one or two substituents independently selected from fluoro, methyl and methoxy. Preferably, R10is unsubstituted. In typical embodiments of formula (III), formula (IIIa) and formula (IIIb): R1is H or C1-2alkyl which is unsubstituted or substituted with one C1-2alkoxy or one, two or three halo, preferably with one C1-2alkoxy; R2is H or methyl; X is a bond, -N(Me)- O or -C(H)2-; R3aand R3bare independently selected from H and methyl; R3cand R3dare independently selected from H, C1-4alkyl, halo and C1-4alkoxy, in particular from H, methyl, ethyl, fluoro, methoxy and t-butyl, or R3cand R3dform, together with the C atom to which they are attached, a C5-6 cycloalkyl ring (in particular a cyclopentyl ring), with the proviso that when X is NR11, O, or S, then neither R3cnor R3dare fluoro; or R3aand R3care H, and R3band R3dform, together with the C atoms to which they are attached, a C5-6cycloalkyl ring (in particular a cyclohexyl ring); wherein at least two of R3a, R3b, R3cand R3dare H; one of the following options applies: (i) R5is selected from H, C1-4alkoxy, and C1-4alkyl, and R6and R7when present are H; or (ii) R7when present is selected from H and halo, and R5and R6are H; or (iii) R5, R6, and R7when present are H; the group R8, where present, is unsubstituted or substituted by one, two or three substituents, for instance one or two substituents, each independently selected from halo, C1-4 alkoxy, R10, -(CH2)-R10, =O, -CN, and C1-4 alkyl which is itself unsubstituted or substituted by one or two groups selected from selected from halo and C1-2alkoxy; and R10is a group selected from a 5- to 6-membered heteroaryl ring, a 3- to 6-membered cycloalkyl ring, a 4- to 5-membered heterocyclyl ring, and a phenyl ring; wherein R10is unsubstituted or substituted by one or two substituents independently selected from fluoro, methyl and methoxy; and R8is (i) a bond to LINK or (ii) a group selected from the following structures:

[0011] wherein either R8is (i) a bond to LINK, or R8is a group (ii) and M is bonded to LINK via a C or N atom within group R8or ring Hy, preferably within group R8, such that a hydrogen atom on the C or N atom within group R8or ring Hy is replaced with a bond to LINK. In preferred embodiments of formula (III), formula (IIIa) and formula (IIIb), X is absent; R1is H, methyl, ethyl or methoxyethyl, more preferably methyl; R2is H; R3a, R3b, R3cand R3dare all H; R5, R6, and R7are H; R8is (i) a bond to LINK or (ii) a 5- to 10-membered heteroaryl ring containing one, two or three N atoms, for example an indazolyl group; the group R8is unsubstituted or substituted by one or two substituents, each independently selected from fluoro, R10and methyl; R10is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, imidazolyl, oxadiazolyl, oxetanyl, phenyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolidinyl, thiazinyl, thiazolyl and triazolyl; and R10is unsubstituted; wherein either R8is (i) a bond to LINK, or R8is a group (ii) and M is bonded to LINK via a C or N atom within group R8or ring Hy, preferably within group R8, such that a hydrogen atom on the C or N atom within group R8or ring Hy is replaced with a bond to LINK. In an alternative particularly preferred embodiment of the compounds of the invention, the MLLT1 and / or MLLT3 binder M is a monovalent moiety of formula (III’): wherein R1, R2, R3a, R3b, R3c, R3d, X, Y1, R5, R6and R8are as defined herein. Typically, in the compounds of formula (III’): R1is H or C1-4alkyl which is itself unsubstituted or substituted with C1-4alkoxy; R2is H or methyl; R3aand R3bare independently selected from H, C1-4alkyl, and C1-4alkoxy, or R3aand R3bform, together with the C atom to which they are attached, a C3-6cycloalkyl ring, R3cand R3dare independently selected from H, C1-4alkyl, halo and C1-4alkoxy, or R3cand R3dform, together with the C atom to which they are attached, a C3-6cycloalkyl ring, with the proviso that when X is O or -N(Me)-, then neither R3cnor R3dare halo, or R3aand R3care H, and R3band R3dform, together with the C atoms to which they are attached, a C5-6 cycloalkyl ring; wherein at least two of R3a, R3b, R3cand R3dare H; X is a bond, -N(Me)-, O or -CH2-; Y1is N or -C(R7)-; R6and R7are independently selected from H, halo C1-4alkoxy, and C1-4alkyl; R5is selected from H, halo C1-4alkoxy, C1-4cycloalkyl and C1-4alkyl; R8is a group selected from a 6- to 10-membered aryl ring, a 5- to 10-membered heteroaryl ring, and a 5- to 10-membered heterocyclyl ring, the group R8being unsubstituted or substituted by one, two or three substituents independently selected from halo, C1-4alkoxy, R10, -(C1-4alkylene)-R10, =O, -CN, and C1-4alkyl which is itself unsubstituted or substituted by one or two R9; each R9is independently selected from halo and C1-4alkoxy; and R10is a group selected from a 5- to 6-membered heteroaryl ring, a 3- to 6-membered cycloalkyl ring, a 4- to 6-membered heterocyclyl ring, and a phenyl ring, the group R10being unsubstituted or substituted by one or two substituents independently selected from C1-4alkyl, C1-4alkoxy, and halo; wherein either R8is (i) a bond to LINK, or R8is a group (ii) and M is bonded to LINK via a C or N atom within group R8or ring Hy (as described herein) such that a hydrogen atom on the C or N atom within group R8or ring Hy is replaced with a bond to LINK. In some of the particularly preferred embodiments, moiety M is of formula (IIIa’):

[0012] wherein R1, R2, R3a, R3b, R3c, R3d, R5, R6, R8and X are as defined in formula (III’). In other of the particularly preferred embodiments, moiety M is of formula (IIIb’): wherein R1, R2, R3a, R3b, R3c, R3d, R5, R6, R7, R8and X are as defined in formula (III’). Typically, in formula (III’), formula (IIIa’) and formula (IIIb’), R1is H, or C1-4alkyl which is itself unsubstituted or substituted with one C1-4alkoxy or one, two or three halo, preferably with one C1-4alkoxy, for example R1may be H or C1-2alkyl which is unsubstituted or substituted with one C1-2alkoxy or one, two or three halo, preferably with one C1-2alkoxy. Preferably, R1is H, methyl, ethyl or methoxyethyl. Most preferably, R1is methyl. In formula (III’), formula (IIIa’) and formula (IIIb’), R2is H or methyl. Preferably, R2is H. Typically, in formula (III’), formula (IIIa’) and formula (IIIb’), X is a bond, -N(R11)-, O or -C(R11)2-. Preferably, X is a bond, -N(Me)-, O or -CH2-, most preferably X is a bond. Typically, in formula (III’), formula (IIIa’) and formula (IIIb’), each R11is independently selected from H and methyl. When X is -N(R11)- or -S(O)(NR11)-, R11is preferably methyl. When X is -C(R11)2-, each R11is preferably H. Typically, in formula (III’), formula (IIIa’) and formula (IIIb’), R3aand R3bare independently selected from H, C1-4alkyl, halo and C1-4alkoxy, in particular from H and methyl; R3cand R3dare independently selected from H, methyl, ethyl, fluoro, methoxy and t-butyl, or R3cand R3dform, together with the C atom to which they are attached, a C3-6cycloalkyl ring (in particular a cyclopropyl or cyclopentyl ring), with the proviso that when X is NR11, O, or S, then neither R3cnor R3dare fluoro; or R3aand R3care H, and R3band R3dform, together with the C atoms to which they are attached, a C5-6cycloalkyl ring (in particular a cyclohexyl ring); wherein at least two of R3a, R3b, R3cand R3dare H. Preferably, in formula (III’), formula (IIIa’) and formula (IIIb’), R3a, R3b, R3cand R3dare all H, or one of R3a, R3b, R3cand R3dis methyl, ethyl or t-butyl and the rest are H, or R3cand R3dare methyl and the rest are H. Typically, in formula (III’), formula (IIIa’) and formula (IIIb’), R5is selected from H, C1-4alkoxy, C1-4cycloalkyl and C1-4alkyl. Preferably, R5is selected from H, methoxy, cyclopropyl and methyl. Typically, in formula (III’), formula (IIIa’) and formula (IIIb’), R6is H. Typically, in formula (III’) and formula (IIIb’), R7is selected from H and halo. Preferably, R7is selected from H and fluoro. Typically, therefore, in formula (III’), formula (IIIa’) and formula (IIIb’): - R5is selected from H, C1-4alkoxy, C1-4cycloalkyl and C1-4alkyl, and R6and R7when present are H; - R7when present is selected from H and halo, and R5and R6are H; or - R5, R6, and R7when present are H. Preferably, in in formula (III’), formula (IIIa’) and formula (IIIb’): - R5is selected from H, methoxy, cyclopropyl and methyl, and R6and R7when present are H; - R7when present is selected from H and fluoro, and R5and R6are H; or - R5, R6, and R7when present are H. Typically, in formula (III’), formula (IIIa’) and formula (IIIb’), R8is a group selected from a 6- to 10-membered aryl ring, a 5- to 10-membered heteroaryl ring, and a 5- to 6- membered heterocyclyl ring. The aryl, heteroaryl and heterocyclyl rings are as defined herein. For instance, R8may be selected from thiazolyl, pyrazolyl, pyrimidinyl, triazolyl, 1,2,4-oxadiazolyl, pyrazinyl, indazolyl, thieno[2,3-c]pyrazolyl, imidazo[4,5- b]pyridinyl, pyrazolo[3,4-b]pyridinyl, furo[2,3-c]pyridinyl, indolyl, benzoxazolyl, benzothiazolyl, [1,2,4]triazolo[4,3-a]pyridinyl, thieno[2,3-d]pyrimidinyl, 1,2,3- benzotriazolyl, imidazo[1,5-a]pyridinyl, imidazo[1,2-a]pyrazinyl, oxazolo[5,4- b]pyridinyl, quinolinyl, naphthyridinyl, isoquinolinyl, quinazolinyl, and quinoxalinyl. . Preferably, R8is a 5- to 10-membered heteroaryl ring containing one, two or three N atoms. Most preferably, R8is an indazolyl group. More typically, in formula (III’), formula (IIIa’) and formula (IIIb’), R8is a group selected from the following structures. For the avoidance of doubt, the following structures may be unsubstituted or substituted by one, two or three substituents as defined herein. [see below]

[0013] Preferably, R8is an indazolyl group. Typically, in formula (III’), formula (IIIa’) and formula (IIIb’), R8is unsubstituted or substituted by one, two or three substituents, for instance one or two substituents, independently selected from halo, C1-4alkoxy, R10, -(CH2)-R10, =O, -CN, and C1-4alkyl which is itself unsubstituted or substituted by one or two groups selected from selected from halo and C1-2alkoxy. More typically, each substituent is independently selected from fluoro, chloro, methoxy, R10, -(CH2)-R10, =O, -CN, and C1-2alkyl which is itself unsubstituted or substituted by one or two groups selected from selected from halo (e.g. fluoro) and methoxy. Preferably, each substituent is independently selected from fluoro, R10and methyl. Most preferably, each substituent is independently selected from fluoro and methyl. R10is as defined herein. Typically, in formula (III’), formula (IIIa’) and formula (IIIb’), R10is a group selected from a 5- to 6-membered heteroaryl ring, a 3- to 6-membered cycloalkyl ring, a 4- to 6- membered heterocyclyl ring, and a phenyl ring. The aryl, heteroaryl and heterocyclyl rings are as defined herein. Preferably, R10is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, imidazolyl, oxadiazolyl, oxetanyl, phenyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolidinyl, piperidinyl, thiazinyl, thiazolyl and triazolyl. Typically, in in formula (III’), formula (IIIa’) and formula (IIIb’), R10is unsubstituted or substituted by one or two substituents independently selected from fluoro, methyl and methoxy. Preferably, R10is unsubstituted. In typical embodiments of formula (III’), formula (IIIa’) and formula (IIIb’): R1is H or C1-2alkyl which is unsubstituted or substituted with one C1-2alkoxy or one, two or three halo, preferably with one C1-2alkoxy; R2is H or methyl; X is a bond, -N(Me)- O or -C(H)2-; R3aand R3bare independently selected from H and methyl; R3cand R3dare independently selected from H, C1-4alkyl, halo and C1-4alkoxy, in particular from H, methyl, ethyl, fluoro, methoxy and t-butyl, or R3cand R3dform, together with the C atom to which they are attached, a C3-6 cycloalkyl ring (in particular a cyclopropyl or cyclopentyl ring), with the proviso that when X is NR11, O, or S, then neither R3cnor R3dare fluoro; or R3aand R3care H, and R3band R3dform, together with the C atoms to which they are attached, a C5-6cycloalkyl ring (in particular a cyclohexyl ring); wherein at least two of R3a, R3b, R3cand R3dare H; one of the following options applies: (i) R5is selected from H, C1-4alkoxy, C1-4cycloalkyl and C1-4alkyl, and R6and R7when present are H; or (ii) R7when present is selected from H and halo, and R5and R6are H; or (iii) R5, R6, and R7when present are H; the group R8is unsubstituted or substituted by one, two or three substituents, for instance one or two substituents, each independently selected from halo, C1-4 alkoxy, R10, -(CH2)-R10, =O, -CN, and C1-4alkyl which is itself unsubstituted or substituted by one or two groups selected from selected from halo and C1-2alkoxy; and R10is a group selected from a 5- to 6-membered heteroaryl ring, a 3- to 6-membered cycloalkyl ring, a 4- to 6-membered heterocyclyl ring, and a phenyl ring; wherein R10is unsubstituted or substituted by one or two substituents independently selected from fluoro, methyl and methoxy; and R8is (i) a bond to LINK or (ii) a group selected from the following structures:

[0014] wherein either R8is (i) a bond to LINK, or R8is a group (ii) and M is bonded to LINK via a C or N atom within group R8or ring Hy such that a hydrogen atom on the C or N atom within group R8or ring Hy is replaced with a bond to LINK. In preferred embodiments of formula (III’), formula (IIIa’) and formula (IIIb’), X is absent; R1is H, methyl, ethyl or methoxyethyl, more preferably methyl; R2is H; R3a, R3b, R3cand R3dare all H, or one of R3a, R3b, R3cand R3dis methyl, ethyl or t-butyl and the rest are H, or R3cand R3dare methyl and the rest are H; R5, R6, and R7are H; R8is (i) a bond to LINK or (ii) phenyl or a 5- to 10-membered heteroaryl ring containing one, two or three N atoms, for example an indazolyl group; the group R8is unsubstituted or substituted by one or two substituents, each independently selected from fluoro, R10and methyl; R10is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, imidazolyl, oxadiazolyl, oxetanyl, phenyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolidinyl, piperidinyl, thiazinyl, thiazolyl and triazolyl; and R10is unsubstituted; wherein either R8is (i) a bond to LINK, or R8is a group (ii) and M is bonded to LINK via a C or N atom within group R8or ring Hy such that a hydrogen atom on the C or N atom within group R8or ring Hy is replaced with a bond to LINK. Particularly preferred MLLT1 and / or MLLT3 binder moieties M are monovalent moieties of the compounds set out below, wherein in each case a hydrogen atom within group R8or ring Hy is removed and forms the position of bonding to LINK: 1-methyl-N-{8-methyl-2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}- 1H-indazole-5-carboxamide; 1,3-dimethyl-N-{8-methyl-2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6- yl}-1H-indazole-6-carboxamide; rel-7-fluoro-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyridin-6-yl}quinoline- 6-carboxamide; N-{2-[(2R,4S)-4-fluoro-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}-1-methyl- 1H-indazole-5-carboxamide; 1,3-dimethyl-N-{2-[(2R)-pyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}-1H-indazole-6- carboxamide; rel-1,3-dimethyl-N-{2-[(2R)-1,4,4-trimethylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6- yl}-1H-indazole-6-carboxamide; rel-1,3-dimethyl-N-{2-[(2R)-1,4,4-trimethylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6- yl}-1H-indazole-6-carboxamide; N-{2-[4-ethyl-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}-1,3-dimethyl-1H- indazole-6-carboxamide; rel-N-{2-[(2R)-1,4-dimethylpiperazin-2-yl]imidazo[1,2-a]pyrazin-6-yl}-1,3-dimethyl- 1H-indazole-6-carboxamide; rel-N-{2-[(2R)-1,4-dimethylpiperazin-2-yl]imidazo[1,2-a]pyrazin-6-yl}-1,3-dimethyl- 1H-indazole-6-carboxamide; rel-7-fluoro-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyridin-6- yl}isoquinoline-6-carboxamide; rel-5-fluoro-1,3-dimethyl-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6- yl}-1H-indazole-6-carboxamide; 1-methyl-N-(2-{2-methyl-2-azaspiro[4.4]nonan-3-yl}imidazo[1,2-a]pyridin-6-yl)-1H- indazole-5-carboxamide; rel-3-ethyl-1-methyl-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}- 1H-indazole-6-carboxamide; rel-3-cyclopropyl-1-methyl-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin- 6-yl}-1H-indazole-6-carboxamide; N-[2-(1,2-dimethylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1-methyl-1H-indazole-5- carboxamide; rel-2-fluoro-4-(2-methyl-1,3-thiazol-5-yl)-N-{2-[(2R)-1-methylpyrrolidin-2- yl]imidazo[1,2-a]pyridin-6-yl}benzamide; rel-1-methyl-N-{2-[(2R)-1-methylpiperidin-2-yl]imidazo[1,2-a]pyridin-6-yl}-1H- indazole-5-carboxamide; rel-1-methyl-N-{2-[(2R)-1-methylpiperidin-2-yl]imidazo[1,2-a]pyridin-6-yl}-1H- indazole-5-carboxamide; 1-methyl-N-{2-[(2S)-1-methyl-octahydro-1H-indol-2-yl]imidazo[1,2-a]pyridin-6-yl}- 1H-indazole-5-carboxamide; 1-methyl-N-{2-[(2R)-1-methyl-octahydro-1H-indol-2-yl]imidazo[1,2-a]pyridin-6-yl}- 1H-indazole-5-carboxamide; rel-2-fluoro-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyridin-6-yl}-5- (pyrazin-2-yl)benzamide; rel-1,3-dimethyl-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}-1H- indazole-6-carboxamide; rel-1,3-dimethyl-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}-1H- indazole-6-carboxamide; rel-1,3-dimethyl-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}-1H- indazole-6-carboxamide; rel-1,3-dimethyl-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}-1H- indazole-6-carboxamide; N-[2-(4-methoxy-1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1-methyl-1H- indazole-5-carboxamide; rel-2-fluoro-5-(2-methyl-1,3-thiazol-5-yl)-N-{2-[(2R)-1-methylpyrrolidin-2- yl]imidazo[1,2-a]pyridin-6-yl}benzamide; N-[2-(1,4-dimethylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1-methyl-1H-indazole-5- carboxamide; rel-2-fluoro-4-(4-methyl-1,3-thiazol-5-yl)-N-{2-[(2R)-1-methylpyrrolidin-2- yl]imidazo[1,2-a]pyridin-6-yl}benzamide; N-[2-(1,5-dimethylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1-methyl-1H-indazole-5- carboxamide; 1-methyl-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyrazin-6-yl]-1H-indazole-5- carboxamide; rel-2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)-N-{2-[(2R)-1-methylpyrrolidin-2- yl]imidazo[1,2-a]pyridin-6-yl}benzamide; rel-2-fluoro-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyridin-6-yl}-4- (pyrimidin-2-yl)benzamide; rel-2-fluoro-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyridin-6-yl}-4- (pyrazin-2-yl)benzamide; 1,3-dimethyl-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1H-thieno[2,3- c]pyrazole-5-carboxamide; 6-methoxy-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1,3- benzothiazole-2-carboxamide; 4-(2-methyl-1,3-thiazol-4-yl)-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6- yl]benzamide; 4-chloro-1,3-dimethyl-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1H- pyrazolo[3,4-b]pyridine-5-carboxamide; 1,3-dimethyl-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1H-indazole-6- carboxamide; N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-6-(1H-pyrazol-1- yl)pyridine-3-carboxamide; N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-4-(1H-1,2,4-triazol-1- yl)benzamide; 2,3-dimethyl-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]quinoxaline-6- carboxamide; N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1,5-naphthyridine-2- carboxamide; 7-chloro-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]quinoline-3- carboxamide; N-[8-methoxy-2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1,3-dimethyl- 1H-indazole-6-carboxamide; N-{2-[1-(2-methoxyethyl)pyrrolidin-2-yl]imidazo[1,2-a]pyridin-6-yl}-1,3-dimethyl-1H- indazole-6-carboxamide; rel-2-fluoro-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyridin-6-yl}-4-(1,3- thiazol-5-yl)benzamide; rel-6-fluoro-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyridin-6- yl}naphthalene-2-carboxamide; rel-6-fluoro-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyridin-6- yl}naphthalene-2-carboxamide; rel-6-fluoro-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyridin-6- yl}naphthalene-2-carboxamide; rel-6-fluoro-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyridin-6- yl}naphthalene-2-carboxamide; rel-2-fluoro-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyridin-6-yl}-4-(1,3- thiazol-5-yl)benzamide; 5-fluoro-1,3-dimethyl-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1H- indazole-6-carboxamide; N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-[1,2,4]triazolo[4,3- a]pyridine-7-carboxamide; 4-chloro-1-methyl-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1H- indazole-5-carboxamide; N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-3H-imidazo[4,5-b]pyridine- 5-carboxamide; N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]imidazo[1,5-a]pyridine-7- carboxamide; N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-4-(1,2,4-oxadiazol-3- yl)benzamide; 3-ethyl-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-[1,2,4]triazolo[4,3- a]pyridine-7-carboxamide; 1,3-dimethyl-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1H- pyrazolo[3,4-b]pyridine-6-carboxamide; N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]imidazo[1,2-a]pyrazine-2- carboxamide; N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]furo[2,3-c]pyridine-2- carboxamide; 1-methyl-N-[2-(4-methylmorpholin-3-yl)imidazo[1,2-a]pyridin-6-yl]-1H-indazole-5- carboxamide; 3-methyl-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-[1,2]oxazolo[5,4- b]pyridine-6-carboxamide; N-[7-fluoro-2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1,3-dimethyl-1H- indazole-6-carboxamide; 4-fluoro-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1H-indole-5- carboxamide; 3-(2-methoxyethyl)-1-methyl-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6- yl]-1H-indazole-5-carboxamide; 3-methyl-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1,2-benzoxazole- 6-carboxamide; N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]quinazoline-7-carboxamide; 2-(4-methoxyphenyl)-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1,3- thiazole-4-carboxamide; N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1,3-benzoxazole-6- carboxamide; N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-2-phenyl-1,3-oxazole-5- carboxamide; 1-cyclohexyl-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1H-1,2,3- benzotriazole-5-carboxamide; 5-methyl-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-4-oxo-1H,4H- thieno[2,3-d]pyrimidine-6-carboxamide; 1-methyl-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-3-(pyrrolidin-3- yl)-1H-indazole-5-carboxamide; N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-3-(1H-pyrazol-1- yl)benzamide; 3-cyclopentyl-1-methyl-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1H- indazole-5-carboxamide; N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-4-[(1H-pyrazol-1- yl)methyl]benzamide; N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1,3-benzothiazole-5- carboxamide; N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-4-(1H-pyrazol-1- yl)benzamide; 6-methoxy-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1H-indole-3- carboxamide; 3-ethyl-1-methyl-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1H- indazole-5-carboxamide; rel-1-methyl-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyridin-6-yl}-1H- indazole-5-carboxamide; rel-1-methyl-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyridin-6-yl}-1H- indazole-5-carboxamide; N-{2-[(rel-2R,4S)-4-methoxy-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}-1- methylindazole-5-carboxamide; N-{2-[(rel-2S,4S)-4-methoxy-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}-1- methylindazole-5-carboxamide; rac-N-[2-(4-tert-butyl-1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyrazin-6-yl]-1,3- dimethylindazole-6-carboxamide; N-{2-[(rel-2R)-1-ethylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}-1,3- dimethylindazole-6-carboxamide; N-{2-[(rel-2S)-1-ethylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}-1,3- dimethylindazole-6-carboxamide; N-(2-((2R, rel-4R)-1,4-dimethylpyrrolidin-2-yl)imidazo[1,2-a]pyrazin-6-yl)-1-methyl- 1H-indazole-5-carboxamide; N-(2-((2R, rel-4S)-1,4-dimethylpyrrolidin-2-yl)imidazo[1,2-a]pyrazin-6-yl)-1-methyl- 1H-indazole-5-carboxamide; 6-fluoro-1-methyl-N-{8-methyl-2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2- a]pyrazin-6-yl}indazole-5-carboxamide; (R)-6-chloro-1-methyl-N-(8-methyl-2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyrazin- 6-yl)-1H-indazole-5-carboxamide; 6-fluoro-3-methyl-N-{8-methyl-2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a] pyrazin-6-yl}imidazo[1,5-a]pyridine-7-carboxamide; 6-fluoro-1,3-dimethyl-N-{8-methyl-2-[(2R)-1-methylpyrrolidin-2-yl] imidazo[1,2- a]pyrazin-6-yl}imidazo[1,5-a]pyridine-7-carboxamide; 1-methyl-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6- yl}pyrazolo[3,4-c]pyridine-5-carboxamide; 6-methoxy-1-methyl-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6- yl}indazole-5-carboxamide; 3-methyl-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}-1,2,3- benzotriazole-5-carboxamide; 1-methyl-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}-3- (piperidin-1-yl)indazole-6-carboxamide; N-[8-cyclopropyl-2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl]-5- fluoro-1,3-dimethyl-indazole-6-carboxamide; N-[8-cyclopropyl-2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl]-1- methyl-indazole-5-carboxamide; 6-fluoro-1-methyl-N-[2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6- yl]indazole-5-carboxamide; 1-methyl-N-[2-[(6R)-5-methyl-5-azaspiro[2.4]heptan-6-yl]imidazo[1,2-a]pyrazin-6- yl]indazole-5-carboxamide; N-{2-[(rel-2R,4R)-4-methoxy-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}-1- methylindazole-5-carboxamide; N-{2-[(rel-2S,4R)-4-methoxy-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}-1- methylindazole-5-carboxamide; N-(2-((2R,4R)-4-fluoro-1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyrazin-6-yl)-1-methyl- 1H-indazole-5-carboxamide. . Particularly preferred MLLT1 and / or MLLT3 binder moieties M are monovalent moieties of the compounds set out below, wherein in each case a hydrogen atom within group R8or ring Hy is removed and forms the position of bonding to LINK: 1-methyl-N-{8-methyl-2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}- 1H-indazole-5-carboxamide; 1,3-dimethyl-N-{8-methyl-2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6- yl}-1H-indazole-6-carboxamide; rel-7-fluoro-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyridin-6-yl}quinoline- 6-carboxamide; N-{2-[(2R,4S)-4-fluoro-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}-1-methyl- 1H-indazole-5-carboxamide; 1,3-dimethyl-N-{2-[(2R)-pyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}-1H-indazole-6- carboxamide; rel-1,3-dimethyl-N-{2-[(2R)-1,4,4-trimethylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6- yl}-1H-indazole-6-carboxamide; rel-1,3-dimethyl-N-{2-[(2R)-1,4,4-trimethylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6- yl}-1H-indazole-6-carboxamide; N-{2-[4-ethyl-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}-1,3-dimethyl-1H- indazole-6-carboxamide; rel-N-{2-[(2R)-1,4-dimethylpiperazin-2-yl]imidazo[1,2-a]pyrazin-6-yl}-1,3-dimethyl- 1H-indazole-6-carboxamide; rel-N-{2-[(2R)-1,4-dimethylpiperazin-2-yl]imidazo[1,2-a]pyrazin-6-yl}-1,3-dimethyl- 1H-indazole-6-carboxamide; rel-7-fluoro-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyridin-6- yl}isoquinoline-6-carboxamide; rel-5-fluoro-1,3-dimethyl-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6- yl}-1H-indazole-6-carboxamide; 1-methyl-N-(2-{2-methyl-2-azaspiro[4.4]nonan-3-yl}imidazo[1,2-a]pyridin-6-yl)-1H- indazole-5-carboxamide; rel-3-ethyl-1-methyl-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}- 1H-indazole-6-carboxamide; rel-3-cyclopropyl-1-methyl-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin- 6-yl}-1H-indazole-6-carboxamide; N-[2-(1,2-dimethylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1-methyl-1H-indazole-5- carboxamide; rel-2-fluoro-4-(2-methyl-1,3-thiazol-5-yl)-N-{2-[(2R)-1-methylpyrrolidin-2- yl]imidazo[1,2-a]pyridin-6-yl}benzamide; rel-1-methyl-N-{2-[(2R)-1-methylpiperidin-2-yl]imidazo[1,2-a]pyridin-6-yl}-1H- indazole-5-carboxamide; rel-1-methyl-N-{2-[(2R)-1-methylpiperidin-2-yl]imidazo[1,2-a]pyridin-6-yl}-1H- indazole-5-carboxamide; 1-methyl-N-{2-[(2S)-1-methyl-octahydro-1H-indol-2-yl]imidazo[1,2-a]pyridin-6-yl}- 1H-indazole-5-carboxamide; 1-methyl-N-{2-[(2R)-1-methyl-octahydro-1H-indol-2-yl]imidazo[1,2-a]pyridin-6-yl}- 1H-indazole-5-carboxamide; rel-2-fluoro-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyridin-6-yl}-5- (pyrazin-2-yl)benzamide; rel-1,3-dimethyl-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}-1H- indazole-6-carboxamide; rel-1,3-dimethyl-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}-1H- indazole-6-carboxamide; rel-1,3-dimethyl-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}-1H- indazole-6-carboxamide; rel-1,3-dimethyl-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}-1H- indazole-6-carboxamide; N-[2-(4-methoxy-1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1-methyl-1H- indazole-5-carboxamide; rel-2-fluoro-5-(2-methyl-1,3-thiazol-5-yl)-N-{2-[(2R)-1-methylpyrrolidin-2- yl]imidazo[1,2-a]pyridin-6-yl}benzamide; N-[2-(1,4-dimethylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1-methyl-1H-indazole-5- carboxamide; rel-2-fluoro-4-(4-methyl-1,3-thiazol-5-yl)-N-{2-[(2R)-1-methylpyrrolidin-2- yl]imidazo[1,2-a]pyridin-6-yl}benzamide; N-[2-(1,5-dimethylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1-methyl-1H-indazole-5- carboxamide; 1-methyl-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyrazin-6-yl]-1H-indazole-5- carboxamide; rel-2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)-N-{2-[(2R)-1-methylpyrrolidin-2- yl]imidazo[1,2-a]pyridin-6-yl}benzamide; rel-2-fluoro-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyridin-6-yl}-4- (pyrimidin-2-yl)benzamide; rel-2-fluoro-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyridin-6-yl}-4- (pyrazin-2-yl)benzamide; 1,3-dimethyl-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1H-thieno[2,3- c]pyrazole-5-carboxamide; 6-methoxy-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1,3- benzothiazole-2-carboxamide; 4-(2-methyl-1,3-thiazol-4-yl)-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6- yl]benzamide; 4-chloro-1,3-dimethyl-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1H- pyrazolo[3,4-b]pyridine-5-carboxamide; 1,3-dimethyl-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1H-indazole-6- carboxamide; N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-6-(1H-pyrazol-1- yl)pyridine-3-carboxamide; N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-4-(1H-1,2,4-triazol-1- yl)benzamide; 2,3-dimethyl-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]quinoxaline-6- carboxamide; N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1,5-naphthyridine-2- carboxamide; 7-chloro-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]quinoline-3- carboxamide; N-[8-methoxy-2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1,3-dimethyl- 1H-indazole-6-carboxamide; N-{2-[1-(2-methoxyethyl)pyrrolidin-2-yl]imidazo[1,2-a]pyridin-6-yl}-1,3-dimethyl-1H- indazole-6-carboxamide; rel-2-fluoro-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyridin-6-yl}-4-(1,3- thiazol-5-yl)benzamide; rel-6-fluoro-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyridin-6- yl}naphthalene-2-carboxamide; rel-6-fluoro-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyridin-6- yl}naphthalene-2-carboxamide; rel-6-fluoro-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyridin-6- yl}naphthalene-2-carboxamide; rel-6-fluoro-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyridin-6- yl}naphthalene-2-carboxamide; rel-2-fluoro-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyridin-6-yl}-4-(1,3- thiazol-5-yl)benzamide; 5-fluoro-1,3-dimethyl-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1H- indazole-6-carboxamide; N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-[1,2,4]triazolo[4,3- a]pyridine-7-carboxamide; 4-chloro-1-methyl-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1H- indazole-5-carboxamide; N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-3H-imidazo[4,5-b]pyridine- 5-carboxamide; N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]imidazo[1,5-a]pyridine-7- carboxamide; N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-4-(1,2,4-oxadiazol-3- yl)benzamide; 3-ethyl-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-[1,2,4]triazolo[4,3- a]pyridine-7-carboxamide; 1,3-dimethyl-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1H- pyrazolo[3,4-b]pyridine-6-carboxamide; N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]imidazo[1,2-a]pyrazine-2- carboxamide; N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]furo[2,3-c]pyridine-2- carboxamide; 1-methyl-N-[2-(4-methylmorpholin-3-yl)imidazo[1,2-a]pyridin-6-yl]-1H-indazole-5- carboxamide; 3-methyl-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-[1,2]oxazolo[5,4- b]pyridine-6-carboxamide; N-[7-fluoro-2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1,3-dimethyl-1H- indazole-6-carboxamide; 4-fluoro-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1H-indole-5- carboxamide; 3-(2-methoxyethyl)-1-methyl-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6- yl]-1H-indazole-5-carboxamide; 3-methyl-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1,2-benzoxazole- 6-carboxamide; N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]quinazoline-7-carboxamide; 2-(4-methoxyphenyl)-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1,3- thiazole-4-carboxamide; N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1,3-benzoxazole-6- carboxamide; N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-2-phenyl-1,3-oxazole-5- carboxamide; 1-cyclohexyl-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1H-1,2,3- benzotriazole-5-carboxamide; 5-methyl-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-4-oxo-1H,4H- thieno[2,3-d]pyrimidine-6-carboxamide; 1-methyl-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-3-(pyrrolidin-3- yl)-1H-indazole-5-carboxamide; N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-3-(1H-pyrazol-1- yl)benzamide; 3-cyclopentyl-1-methyl-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1H- indazole-5-carboxamide; N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-4-[(1H-pyrazol-1- yl)methyl]benzamide; N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1,3-benzothiazole-5- carboxamide; N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-4-(1H-pyrazol-1- yl)benzamide; 6-methoxy-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1H-indole-3- carboxamide; 3-ethyl-1-methyl-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1H- indazole-5-carboxamide; rel-1-methyl-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyridin-6-yl}-1H- indazole-5-carboxamide; rel-1-methyl-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyridin-6-yl}-1H- indazole-5-carboxamide; N-{2-[(rel-2R,4S)-4-methoxy-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}-1- methylindazole-5-carboxamide; N-{2-[(rel-2S,4S)-4-methoxy-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}-1- methylindazole-5-carboxamide; rac-N-[2-(4-tert-butyl-1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyrazin-6-yl]-1,3- dimethylindazole-6-carboxamide. A further preferred MLLT1 and / or MLLT3 binder M is a compound of formula (IVA): wherein R8is a bond to LINK. In a most preferred embodiment of the compounds of the invention, the MLLT1 and / or MLLT3 binder M is a monovalent moiety of formula (IV): wherein R8is a group selected from a 6- to 10-membered aryl ring and a 5- to 10- membered heteroaryl ring, the group R8being unsubstituted or substituted by one, two or three substituents independently selected from halo and C1-4alkyl; wherein M is bonded to LINK via a C or N atom within group R8such that a hydrogen atom on the C or N atom within group R8is replaced with a bond to LINK. Typically, in formula (IV), R8is a group selected from a 6- to 10-membered aryl ring and a 5- to 10-membered heteroaryl ring. The aryl and heteroaryl rings are as defined herein. For instance, R8may be selected from thiazolyl, pyrazolyl, pyrimidinyl, triazolyl, 1,2,4-oxadiazolyl, pyrazinyl, indazolyl, thieno[2,3-c]pyrazolyl, imidazo[4,5- b]pyridinyl, pyrazolo[3,4-b]pyridinyl, furo[2,3-c]pyridinyl, indolyl, benzoxazolyl, benzothiazolyl, [1,2,4]triazolo[4,3-a]pyridinyl, thieno[2,3-d]pyrimidinyl, 1,2,3- benzotriazolyl, imidazo[1,5-a]pyridinyl, imidazo[1,2-a]pyrazinyl, oxazolo[5,4- b]pyridinyl, quinolinyl, naphthyridinyl, isoquinolinyl, quinazolinyl, and quinoxalinyl. More typically, in formula (IV), R8is a group selected from the following structures. For the avoidance of doubt, the following structures may be unsubstituted or substituted by one, two or three substituents as defined herein. [see below]

[0015] Preferably, R8is an indazolyl group or a phenyl group. Typically, in formula (IV), R8is unsubstituted or substituted by one, two or three substituents, for instance one or two substituents, independently selected from halo and C1-4alkyl. Preferably, each substituent is independently selected from fluoro and methyl. In a particularly preferred embodiment, in formula (IV), R8is selected from one of the following structures: wherein: represents the point of attachment of R8to the rest of moiety M; and represents the point of attachment of R8to LINK. For the avoidance of doubt, the group R8is further unsubstituted or substituted as described above. Preferably, the group R8is further unsubstituted or substituted by one or two substituents independently selected from fluorine and methyl. In one embodiment, the group R8is of structure A as defined above. In an alternative embodiment, the group R8is selected from structures B, C and D as defined above. For the avoidance of doubt, R8may be selected from one of structures A, B, C and D in any of formulae (I), (II), (III), (IIIa), (IIIb), (III’), (IIIa’), and (IIIb’). E3 ubiquitin ligase binding moieties The presence of the E3 ubiquitin ligase binding moiety U in the compound of the invention means that the compound is a so-called “PROTAC”. The term PROTAC is an acronym for proteolysis targeting chimera. In general, PROTACs are, as is known in the art, heterobifunctional molecules that comprise two active moieties attached covalently by a linker group. In a PROTAC, the first active moiety (the MLLT1 and / or MLLT3 binder M in the compound of the present invention) binds to a target protein that is intended for degradation (target proteins for the compound of the present invention are MLLT1 and / or MLLT3). The second active moiety (U in the compound of the present invention) is capable of binding to an E3 ubiquitin ligase, thereby inducing selective intracellular proteolysis. Recruitment of the E3 ligase to the target protein results in ubiquitination and subsequent degradation of the target protein by the proteasome. E3 ubiquitin ligase moities are known in the art. Substantially any such moiety can be used. The sole limitation on the moiety is that it be capable of binding to an E3 ubiquitin ligase. Those skilled in the art would appreciate that entirely routine laboratory methods can be used to determine whether a given substance binds to an E3 ubiquitin ligase (including but not limited to any of those disclosed specifically herein). Thus, those skilled in the art would have no difficulty in identifying E3 ubiquitin ligase moieties, nor in establishing whether any existing chemical moiety falls within the bounds of this definition. In certain embodiments, the moiety shows activity or binds to the E3 ubiquitin ligase with an IC50of less than about 200 mM. The IC50can be determined according to any method known in the art, e.g., a fluorescent polarization assay. Merely by way of example of the extensive disclosure in the field concerning PROTACs, and hence E3 ubiquitin ligase binding moieties, reference can be made to Gu et al. (BioEssays 2018, 40, 1700247), Sun et al. (Signal Transduction and Targeted Therapy (2019) 4:64), WO 2020 / 041331, and WO 2019 / 140003, the contents of all of which are herein incorporated by reference in their entireties. Any of the numerous E3 ubiquitin ligase binding moieties disclosed in these documents can be used as an E3 ubiquitin ligase binding moiety in the compounds of the present invention. For the avoidance of doubt, Gu et al. refer to such moieties as ligands to recruit E3 ubiquitin ligase, Sun et al. refer to such moieties as E3 ubiquitin ligase (E3) recruiting ligands, in WO 2020 / 041331 such moieties are referred to as a “ULM” or (small molecule) E3 ubiquitin ligase binding moiety (that binds an E3 ubiquitin ligase) (and noting that the term “ULM” includes each of “ILM”, “CLM”, “VLM” and “MLM”, any of which can be used in the present compounds), and in WO 2019 / 140003 such moieties (labelled “B” in WO 2019 / 140003’s formula (I)) are referred to as a ubiquitin ligase ligand / binder. Further examples of documents disclosing suitable moieties that can be used in the compounds of the present invention are WO2013 / 106643, US2016 / 0045607, WO2014187777, US20140356322 and US 9,249, 153, US2016 / 0058872, US2015 / 0291562 and Winter et al (Science, June 19, 2015, p. 1376), the contents of all of which are herein incorporated by reference in their entireties. Thalidomide, lenalidomide, pomalidomide and analogs thereof are still further examples of suitable moieties. Examples of E3 ubiquitin ligases include von Hippel-Lindau (VHL) and cereblon (CRBN). Preferably the E3 ubiquitin ligase binding moiety (U) is capable of binding to CRBN or VHL. Such moieties are referred to herein as CRBN or VHL E3 ubiquitin ligase binding moieties. In one embodiment, U is a CRBN E3 ubiquitin ligase binding moiety. In another embodiment, U is a VHL E3 ubiquitin ligase binding moiety. In some embodiments, the E3 ubiquitin ligase binding moiety (U) is: (a) a CRBN E3 ubiquitin ligase binding moiety of formula (U1): wherein: RU1is H; Q is selected from -CH(RU6)-, -N(RU6)-, -O-, -C(O)-, -NH-CH(RU6)-, -N=C(RU6)-, or -N=N-; RU6is H or C1-4alkyl; RU2and RU5are each independently selected from H, halogen, C1-4alkyl, NH2, NO2, OH, COOH, CN, CF3, and a single bond to LINK; RU3and RU4are each independently selected from H, halogen, C1-4alkyl, NH2, NO2, OH, COOH, CN, CF3, and a single bond to LINK; wherein one and only one of RU2, RU3, RU4and RU5is a single bond to LINK; (b) a CRBN E3 ubiquitin ligase binding moiety of formula (U4): wherein: RU1’is H; Q’ is N and LUis a single bond, or Q’ is CH and LUis selected from a single bond or -C(O)N(H)-, wherein either (i) the C atom of LUis bonded to phenyl, and the N atom of LUis bonded to Q’; or (ii) the C atom of LUis bonded to Q’, and the N atom of LUis bonded to phenyl; RU12, RU13and RU14are each independently selected from H, halogen, C1-4alkyl, NH2, NO2, OH, COOH, CN, CF3, and a single bond to LINK; wherein one and only one of RU12, RU13and RU14is a single bond to LINK; RU15and RU16are each independently selected from H, halogen, C1-4alkyl, NH2, NO2, OH, COOH, CN and CF3; (c) a CRBN E3 ubiquitin ligase binding moiety of formula (U5):

[0016] wherein: RU17is H; RU18, RU19, RU20and RU21are each independently selected from H, halogen, C1-4alkyl, NH2, NO2, OH, COOH, CN, CF3, and a single bond to LINK; wherein one and only one of RU18, RU19, RU20and RU21is a single bond to LINK; or (d) a VHL E3 ubiquitin ligase binding moiety of formula (U2): wherein: RU7is a group selected from phenyl, a 5- to 6-membered heteroaryl ring, a 5- to 6- membered heterocyclyl ring, and a 5- to 6-membered cycloalkyl ring, the group RU7being unsubstituted or substituted by C1-4alkyl; RU11is H or C1-4alkyl; RU8is selected from C1-4alkyl, phenyl and a 3- to 8-membered cycloalkyl ring; and RU9is a single bond to LINK. In other embodiments, the E3 ubiquitin ligase binding moiety (U) is: (a) a CRBN E3 ubiquitin ligase binding moiety of formula (U1’): wherein: RU1is H; Q is selected from -CH(RU6)-, -N(RU6)-, -O-, -C(O)-, -NH-CH(RU6)-, -N=C(RU6)-, or -N=N-; RU6is H or C1-4alkyl; RU2and RU5are each independently selected from H, halogen, C1-4alkyl, NH2, NO2, OH, COOH, CN, CF3, and a single bond to LINK; RU3and RU4are each independently selected from H, halogen, C1-4alkyl, NH2, NO2, OH, COOH, CN, CF3, and a single bond to LINK; wherein one and only one of RU2, RU3, RU4and RU5is a single bond to LINK; (b) a CRBN E3 ubiquitin ligase binding moiety of formula (U4’):

[0017] wherein: RU1’is H; Q’ is selected from CH and N; RU12, RU13and RU14are each independently selected from H, halogen, C1-4alkyl, NH2, NO2, OH, COOH, CN, CF3, and a single bond to LINK; wherein one and only one of RU12, RU13and RU14is a single bond to LINK; or (c) a VHL E3 ubiquitin ligase binding moiety of formula (U2’): wherein: RU7is a group selected from phenyl, a 5- to 6-membered heteroaryl ring, a 5- to 6- membered heterocyclyl ring, and a 5- to 6-membered cycloalkyl ring, the group RU7being unsubstituted or substituted by C1-4alkyl; RU11is H or C1-4alkyl; RU8is selected from C1-4alkyl, phenyl and a 3- to 8-membered cycloalkyl ring; and RU9is a single bond to LINK. For the avoidance of doubt, in formula (U1) and (U1’), when Q is -NH-CH(RU6)- or - N=C(RU6)-, the N atom of Q is bonded to the phenyl ring in U, and the C atom of Q (not including any C atom that may be in RU6) is bonded to the N atom in U that is adjacent to group Q. Typically, in formula (U1) and (U1’), Q is selected from -CH(RU6)- and -C(O)-. Preferably, Q is selected from -CH2- and -C(O)-. Typically, in formula (U1) and (U1’), RU6is H or methyl. Preferably, RU6is H. Typically, in formula (U1) and (U1’), RU2and RU5are each independently selected from H, fluoro, methyl, NH2, NO2, OH, COOH, CN, CF3, and a single bond to LINK. For example, RU2and RU5may each be independently selected from H, fluoro and a single bond to LINK. Preferably, RU2and RU5are each independently selected from H and a single bond to LINK. Typically, in formula (U1) and (U1’), RU3and RU4are each independently selected from H, fluoro, methyl, NH2, NO2, OH, COOH, CN, CF3and a single bond to LINK. Preferably, RU3and RU4are each independently selected from H and a single bond to LINK. Typically, in formula (U1) and (U1’), two or three of RU2, RU3, RU4and RU5are H. Preferably, three of RU2, RU3, RU4and RU5are H. More preferably, RU2and RU3are H, one of RU4and RU5is a single bond to LINK, and the other of RU4and RU5is H. Typically, therefore, in formula (U1) and (U1’): Q is selected from -CH(RU6)- and -C(O)-; RU6is H or methyl; RU2and RU5are each independently selected from H, fluoro, methyl, NH2, NO2, OH, COOH, CN, CF3, and a single bond to LINK; RU3and RU4are each independently selected from H, fluoro, methyl, NH2, NO2, OH, COOH, CN, CF3 and a single bond to LINK; and two or three of RU2, RU3, RU4and RU5are H. Preferably, in formula (U1) and (U1’): Q is selected from -CH2- and -C(O)-; RU6is H; one of RU2, RU3, RU4and RU5is a single bond to LINK, and the rest are H, for instance wherein RU2and RU3are H, one of RU4and RU5is a single bond to LINK, and the other of RU4and RU5is H. Typically, in formula (U4), Q’ is N and LUis a single bond, or Q’ is CH and LUis - C(O)N(H)-. Preferably, Q’ is N and LUis a single bond. Typically, in formula (U4’), Q’ is selected from CH and N. Preferably, Q’ is N. Typically, in formula (U4), when LUis -C(O)N(H)-, then the C atom of LUis bonded to phenyl, and the N atom of LUis bonded to Q’. Typically, in formula (U4), RU12, RU13and RU14are each independently selected from H, fluoro, methyl, NH2, NO2, OH, COOH, CN, CF3, and a single bond to LINK (wherein one and only one of RU12, RU13and RU14is a single bond to LINK). Preferably, one of RU12, RU13and RU14is a single bond to LINK, one of RU12, RU13and RU14is H and the other of RU12, RU13and RU14is selected from H, fluoro, methyl, NH2, NO2, OH, COOH, CN, CF3, preferably from H, fluoro and methyl. More preferably, one of RU12, RU13and RU14is a single bond to LINK and the other two are H, for instance wherein RU12and RU14are H, and RU13is a single bond to LINK. Typically, in formula (U4’), RU12, RU13and RU14are each independently selected from H, fluoro, methyl, NH2, NO2, OH, COOH, CN, CF3, and a single bond to LINK (wherein one and only one of RU12, RU13and RU14is a single bond to LINK). Preferably, one of RU12, RU13and RU14is a single bond to LINK and the other two are H, for instance wherein RU12and RU14are H, and RU13is a single bond to LINK. Typically, in formula (U4), RU15and RU16are each independently selected from H, fluoro, methyl, NH2, NO2, OH, COOH, CN and CF3. Preferably, RU15and RU16are each independently selected from H, F and Me. In one embodiment of formula (U4), RU15and RU16are H, and two of RU12, RU13and RU14are H. Preferably, RU13, RU14and RU15are H, RU12is a single bond to LINK, and RU16is selected from H, F and Me. Typically, therefore, in formula (U4): Q’ is N and LUis a single bond, or Q’ is CH and LUis -C(O)N(H)-; RU12, RU13and RU14are each independently selected from H, fluoro, methyl, NH2, NO2, OH, COOH, CN, CF3, and a single bond to LINK; and RU15and RU16are each independently selected from H, fluoro, methyl, NH2, NO2, OH, COOH, CN and CF3; wherein one and only one of RU12, RU13and RU14is a single bond to LINK. Preferably, in formula (U4): Q’ is N and LUis a single bond; one of RU12, RU13and RU14is a single bond to LINK and the other two are H, for instance wherein RU12and RU14are H, and RU13is a single bond to LINK, or RU13, RU14and RU15are H, RU12is a single bond to LINK, and RU16is selected from H, F and Me. Typically, therefore, in formula (U4’): Q’ is selected from CH and N; and RU12, RU13and RU14are each independently selected from H, fluoro, methyl, NH2, NO2, OH, COOH, CN, CF3, and a single bond to LINK; wherein one and only one of RU12, RU13and RU14is a single bond to LINK. Preferably, in formula (U4’): Q’ is N; one of RU12, RU13and RU14is a single bond to LINK and the other two are H, for instance wherein RU12and RU14are H, and RU13is a single bond to LINK. Typically, in formula (U5), RU18, RU19, RU20and RU21are each independently selected from H, fluoro, methyl, NH2, NO2, OH, COOH, CN, CF3, and a single bond to LINK (wherein one and only one of RU18, RU19, RU20and RU21is a single bond to LINK). Preferably, one of RU18, RU19, RU20and RU21is a single bond to LINK, one or two, preferably two of RU18, RU19, RU20and RU21are H and the other one or two, preferably one of RU18, RU19, RU20and RU21are selected from H, fluoro, methyl, NH2, NO2, OH, COOH, CN, CF3, preferably from H, fluoro and methyl. More preferably, one of RU18, RU19, RU20and RU21is a single bond to LINK and the other three are H, for instance wherein RU19, RU20and RU21are H, and RU18is a single bond to LINK. Typically, in formula (U2), RU7is a 5- to 6-membered heteroaryl ring. Preferably, RU7is a 5-membered heteroaryl ring containing one S atom and optionally one N atom. Typically, in formula (U2), RU7is unsubstituted or substituted by C1-4alkyl. Preferably, RU7is unsubstituted or substituted by methyl. Typically, in formula (U2), RU11is H or methyl. Preferably, RU11is H. Typically, in formula (U2), RU8is C1-4alkyl or phenyl. Preferably, RU8is t-butyl or phenyl, more preferably t-butyl. Typically, therefore, in formula (U2), RU7is a 5- to 6-membered heteroaryl ring, the group RU7being unsubstituted or substituted by C1-4alkyl, RU11is H or methyl, and RU8is C1-4alkyl or phenyl. Preferably, in formula (U2), RU7is a 5-membered heteroaryl ring containing one S atom and optionally one N atom, the group RU7being unsubstituted or substituted by methyl, RU11is H, and RU8is t-butyl or phenyl, more preferably t-butyl. In a preferred embodiment, the E3 ubiquitin ligase binding moiety (U) is a VHL E3 ubiquitin ligase binding moiety of formula (U3):

[0018] V is S or O; W is N or CH; RU10is H or C1-4alkyl; RU11is H or C1-4alkyl; RU8is selected from C1-4alkyl, phenyl and a 3- to 8-membered cycloalkyl ring; and RU9is a single bond to LINK. Typically, in formula (U3), V is S. Typically, in formula (U3), W is N or CH. Preferably, W is N. Typically, in formula (U3), RU10is H or methyl. Preferably, RU10is methyl. Typically, in formula (U3), RU11is H or methyl. Preferably, RU11is H. Typically, in formula (U3), RU8is C1-4alkyl or phenyl. Preferably, RU8is t-butyl or phenyl, more preferably t-butyl. Typically, therefore, in formula (U3), V is S, W is N or CH, RU10is H or methyl, RU11is H or methyl, and RU8is C1-4alkyl or phenyl. Preferably, V is S, W is N, RU10is methyl, RU11is H, RU8is t-butyl or phenyl, more preferably t-butyl. Linkers As discussed herein, in the compounds of the invention, the binder of MLLT1 and / or MLLT3 (M) is covalently attached to an E3 ubiquitin ligase binding moiety (U). This covalent attachment is labelled LINK and may be a direct single bond or a divalent chemical linker group that forms covalent bonds both to the binder of MLLT1 and / or MLLT3 (M), and to the E3 ubiquitin ligase binding moiety (U). Typically, LINK is a divalent chemical linker group that forms covalent bonds both to the binder of MLLT1 and / or MLLT3 (M), and to the E3 ubiquitin ligase binding moiety (U). There is no particular limitation on the nature of LINK in the compounds of the present invention (beyond that the respective active moieties, e.g., U and M, are able to exert their desired function and LINK is capable of covalently attaching them together). Those skilled in the art would recognise that chemical linker groups are routinely used in the construction of bifunctional molecules and would be able routinely to provide appropriate chemical linker groups for attaching particular U and M moieties together. Typically, a chemical linker group for use in the present invention is an organic group. When LINK is a divalent chemical linker group, it may be represented by formula (L): wherein: LINK is attached to M via L1; LINK is attached to U via L3; L1 and L3 are each independently selected from a single bond, -N(R’)-, -C(O)N(R’)-, -O-, -N(R’)C(O)-, -C(O)-, -S(O2)N(R’)-, -N(R’)S(O2)-, -(C1-6alkylene)-, ethynyl, -(C2-6alkenylene)-, a divalent 3- to 6-membered cycloalkyl ring and a divalent 4- to 7- membered heterocyclyl ring; L2 is represented by the formula -(L4)m-; each L4 is independently selected from a divalent 3- to 6-membered cycloalkyl ring, a divalent 4- to 7-membered heterocyclyl ring and a unit of formula: each XLis independently selected from a single bond, -N(R’)-, -O-, -C(O)-, -S-, -SO-, - SO2-, -C(H)=C(H)- and -C(H)≡C(H)-; n is selected from 1 to 4; m is selected from 1 to 30; and each R’ is independently selected from H and C1-4alkyl. In one embodiment, L1 and L3 are each independently selected from a single bond, - N(R’)-, -C(O)N(R’)-, -O-, -N(R’)C(O)-, -C(O)-, -S(O2)N(R’)-, -N(R’)S(O2)-, -(C1-6alkylene)-, -(C2-6 alkenylene)-, a divalent 3- to 6-membered cycloalkyl ring and a divalent 4- to 7-membered heterocyclyl ring; L2 is represented by the formula -(L4)m-; and each L4 is independently selected from a divalent 3- to 6-membered cycloalkyl ring, a divalent 4- to 7-membered heterocyclyl ring and a unit of formula: . When m is not 1 (i.e. when there are two or more L4 groups present), then the XLgroup of any L4 group is not directly bonded to the XLgroup of any other L4 group that is present. Typically, in formula (L), L1 is selected from a single bond, branched or straight-chain - (C1-6alkylene)-, -C(O)N(R’)-, -N(R’)C(O)-, -O-, -S(O2)N(R’)-, -N(R’)S(O2)-, and a divalent 4- to 7-membered heterocyclyl ring. When present, the divalent 4- to 7- membered heterocyclyl ring of L1 typically contains at least one N atom, for instance one or two N atoms. Preferably, when L1 is a divalent 4- to 7-membered heterocyclyl ring, it is a divalent 5- to 6-membered heterocyclyl ring, more preferably a saturated divalent 5- to 6-membered heterocyclyl ring, for instance a divalent moiety of piperidine or diazinane. Preferably, in formula (L), L1 is selected from a single bond, branched or straight-chain -(C1-6alkylene)-, -C(O)N(H)-, -N(H)C(O)-, and a divalent moiety of piperidine or diazinane. Alternatively, L1 is selected from a single bond, - C(O)N(R’)-, -N(R’)C(O)-, -O-, -S(O2)N(R’)-, -N(R’)S(O2)-, and a divalent 4- to 7- membered heterocyclyl ring. When present, the divalent 4- to 7-membered heterocyclyl ring of L1 typically contains at least one N atom, for instance one or two N atoms. Preferably, when L1 is a divalent 4- to 7-membered heterocyclyl ring, it is a divalent 5- to 6-membered heterocyclyl ring, more preferably a saturated divalent 5- to 6- membered heterocyclyl ring, for instance a divalent moiety of piperidine or diazinane. Preferably, in formula (L), L1 is selected from a single bond, -C(O)N(H)-, -N(H)C(O)-, and a divalent moiety of piperidine or diazinane. Preferably, where the group R8within the MLLT1 and / or MLLT3 binder M is (i) a bond to LINK, then L1 within LINK is also a single bond. In this embodiment, L2 within LINK is direcly bonded to the group L within the MLLT1 and / or MLLT3 binder M. Typically, in formula (L), L3 is selected from a single bond, -N(R’)-, -C(O)N(R’)-, -O-, -N(R’)C(O)-, -S(O2)N(R’)-, -N(R’)S(O2)-, ethynyl and a divalent 4- to 7-membered heterocyclyl ring. When present, the divalent 4- to 7-membered heterocyclyl ring of L3 typically contains at least one N atom, for instance one or two N atoms. Preferably, when L3 is a divalent 4- to 7-membered heterocyclyl ring, it is a divalent 5- to 6- membered heterocyclyl ring, more preferably a saturated divalent 5- to 6-membered heterocyclyl ring, for instance a divalent moiety of piperidine or diazinane, preferably 1,4-diazinane. Preferably, in formula (L), L3 is selected from a single bond, -N(H)-, - C(O)N(H)-, -O-, -N(H)C(O)-, ethynyl and a divalent moiety of piperidine or diazinane. Alternatively, L3 is selected from a single bond, -N(R’)-, -C(O)N(R’)-, -O-, - N(R’)C(O)-, -S(O2)N(R’)-, -N(R’)S(O2)-, and a divalent 4- to 7-membered heterocyclyl ring. When present, the divalent 4- to 7-membered heterocyclyl ring of L3 typically contains at least one N atom, for instance one or two N atoms. Preferably, when L3 is a divalent 4- to 7-membered heterocyclyl ring, it is a divalent 5- to 6-membered heterocyclyl ring, more preferably a saturated divalent 5- to 6-membered heterocyclyl ring, for instance a divalent moiety of piperidine or diazinane, preferably 1,4-diazinane. Preferably, in formula (L), L3 is selected from a single bond, -N(H)-, -C(O)N(H)-, -O-, -N(H)C(O)-, and a divalent moiety of piperidine or diazinane. L2 is represented by the formula -(L4)m-. Typically, in formula (L), each L4 is independently selected from a divalent 4- to 7-membered heterocyclyl ring and a unit of described above. Alternatively, each L4 is independently selected from a divalent 4- to 7-membered heterocyclyl ring and a unit of formula Typically, each XLis independently selected from a single bond, -O-, or -S-, - C(H)=C(H)- and -C(H)≡C(H)-, for example a single bond, -O- and -S-, and n is selected from 1 or 2. In one embodiment, each L4 is the same. Alternatively, L2 may comprise two or more blocks, wherein in each block, each L4 is the same. For instance, L2 may be represented by the formula -(L4’)p-(L4’’)q-(L4’’’)r-, wherein L4’, L4’’ and L4’’’ are selected from those moieties described above for L4, and wherein each L4’ is the same, each L4’’ is the same and each L4’’’ is the same. Preferably, L4’, L4’’ and L4’’’ are selected from -CH2-, -CH2CH2O-, -OCH2CH2-, -CH2CH2S- and -SCH2CH2-. More preferably, L4’, L4’’ and L4’’’ are selected from -CH2-, -CH2CH2O- and - OCH2CH2-. p, q and r are integers of from 0 to 30, wherein p+q+r=m. In one embodiment, each L4 unit is the same. For instance, each L4 in formula (L) may be -CH2-, each L4 in formula (L) may be -CH2CH2O-, each L4 in formula (L) may be - OCH2CH2-, each L4 in formula (L) may be -CH2CH2S-, or each L4 in formula (L) may be -SCH2CH2-. More preferably, each L4 in formula (L) is -CH2-, each L4 in formula (L) is -CH2CH2O- or each L4 in formula (L) is -OCH2CH2-. Most preferably, each L4 in formula (L) is -CH2-. Typically, in formula (L), m is selected from 1 to 10. Typically, in formula (L), each R’ is independently selected from H and methyl. Preferably, each R’ is H. When one or more L4 is a divalent 4- to 7-membered heterocyclyl ring, typically only one or two, e.g. one L4 is a divalent 4- to 7-membered heterocyclyl ring. Typically, therefore, none, one or two L4 is a divalent 4- to 7-membered heterocyclyl ring, for example none or one L4 is a divalent 4- to 7-membered heterocyclyl ring. Typically, therefore, in formula (L): L1 is selected from a single bond, branched or straight-chain -(C1-6alkylene)- , -C(O)N(R’)-, -N(R’)C(O)-, -O-, -S(O2)N(R’)-, -N(R’)S(O2)-, and a divalent 4- to 7- membered heterocyclyl ring typically containing at least one N atom, for instance one or two N atoms; L3 is selected from a single bond, -N(R’)-, -C(O)N(R’)-, -O-, -N(R’)C(O)-, -S(O2)N(R’)-, -N(R’)S(O2)-, ethynyl and a divalent 4- to 7-membered heterocyclyl ring typically containing at least one N atom, for instance one or two N atoms; each L4 is independently selected from -CH2-, -CH2CH2O-, -OCH2CH2-, -CH2CH2S-, -SCH2CH2-, and a divalent 4- to 7-membered heterocyclyl ring; m is selected from 1 to 10; and each R’ is independently selected from H and methyl. Alternatively: L1 is selected from a single bond, -C(O)N(R’)-, -N(R’)C(O)-, -O-, -S(O2)N(R’)-, - N(R’)S(O2)-, and a divalent 4- to 7-membered heterocyclyl ring typically containing at least one N atom, for instance one or two N atoms; L3 is selected from a single bond, -N(R’)-, -C(O)N(R’)-, -O-, -N(R’)C(O)-, -S(O2)N(R’)-, -N(R’)S(O2)-, and a divalent 4- to 7-membered heterocyclyl ring typically containing at least one N atom, for instance one or two N atoms; each L4 is independently selected from -CH2-, -CH2CH2O-, -OCH2CH2-, -CH2CH2S-, -SCH2CH2-, and a divalent 4- to 7-membered heterocyclyl ring; m is selected from 1 to 10; and each R’ is independently selected from H and methyl. Preferably, in formula (L): L1 is selected from a single bond, branched or straight-chain -(C1-6alkylene)- , -C(O)N(H)-, -N(H)C(O)-, and a divalent moiety of piperidine or diazinane; L3 is selected from a single bond, -N(H)-, -C(O)N(H)-, -O-, -N(H)C(O)-, ethynyl and a divalent moiety of piperidine or diazinane; each L4 in formula (L) is -CH2-, each L4 in formula (L) is -CH2CH2O-, each L4 in formula (L) is -OCH2CH2-, each L4 in formula (L) is -CH2CH2S-, or each L4 in formula (L) is -SCH2CH2-, with each L4 preferably being -CH2-; m is selected from 1 to 10; and each R’ is H. Alternatively: L1 is selected from a single bond, -C(O)N(H)-, -N(H)C(O)-, and a divalent moiety of piperidine or diazinane; L3 is selected from a single bond, -N(H)-, -C(O)N(H)-, -O-, -N(H)C(O)-, and a divalent moiety of piperidine or diazinane; each L4 in formula (L) is -CH2-, each L4 in formula (L) is -CH2CH2O-, each L4 in formula (L) is -OCH2CH2-, each L4 in formula (L) is -CH2CH2S-, or each L4 in formula (L) is -SCH2CH2-, with each L4 preferably being -CH2-; m is selected from 1 to 10; and each R’ is H. In a typical embodiment, L2 is -(C1-10alkylene)- or -(C1-10alkylene)-C(O)-, preferably - (C1-10alkylene)-. In this embodiment, L1 is preferably selected from a single bond, - C(O)N(H)-, -N(H)C(O)-, and a divalent moiety of piperidine or diazinane. In this embodiment, L3 is preferably selected from a single bond, -N(H)-, -C(O)N(H)-, -O-, - N(H)C(O)-, ethynyl and a divalent moiety of piperidine or diazinane, for example a single bond, -N(H)-, -C(O)N(H)-, -O-, -N(H)C(O)-, and a divalent moiety of piperidine or diazinane. More preferably, L1 and L3 are selected from the following options: - L1 is a single bond and L3 is -N(H)-; - L1 is -C(O)N(H)- or -N(H)C(O)-, and L3 is -C(O)N(H)- or -N(H)C(O)-; - L1 is a divalent moiety of piperidine and L3 is a divalent moiety of diazinane; - L1 is -C(O)N(H)- or -N(H)C(O)-, and L3 is a divalent moiety of diazinane; - L1 is a single bond and L3 is a divalent moiety of diazinane; - L1 is a single bond and L3 is -O-; and - L1 is -C(O)N(H)- or -N(H)C(O)-, and L3 is -O-. In particularly preferred embodiments: - L1 is a divalent moiety of piperidine, L2 is -(C1-6alkylene)- and L3 is a divalent moiety of diazinane; - L1 is a single bond, L2 is -(C1-6alkylene)- and L3 is -N(H)-; - L1 is a single bond, L2 is -(C1-6alkylene)- and L3 is -O-; - L1 is a single bond, L2 is -(C1-6alkylene)- and L3 is a divalent moiety of piperidine or diazinane; or - L1 is a single bond, L2 is -(C1-6alkylene)- and L3 is ethynyl. For the avoidance of doubt, the skilled person would readily appreciate that each of the definitions of moieties U, M and LINK provided herein may be taken together in any combination to arrive at a definition of the compound of the present invention. As examples that are in no way limiting, definitions of moieties U, M and LINK labelled “typically” may be combined to arrive at a definition of a typical compound of the present invention, and definitions of moieties U, M and LINK labelled “preferably” may be combined to arrive at a definition of a preferred compound of the present invention. However, the skilled person would appreciate that a definition labelled “typically” of one moiety may be combined with a definition labelled “preferably” of another moiety to arrive at a definition of a compound of the present invention. In preferred compounds of the present invention, M is of formula (III): wherein: R1is H or C1-4alkyl which is itself unsubstituted or substituted with one C1-4alkoxy or one, two or three halo, preferably with one C1-4 alkoxy; R2is H or methyl; R3aand R3bare independently selected from H, C1-4alkyl, and C1-4alkoxy, or R3aand R3bform, together with the C atom to which they are attached, a C3-6cycloalkyl ring, R3cand R3dare independently selected from H, C1-4alkyl, halo and C1-4alkoxy, or R3cand R3dform, together with the C atom to which they are attached, a C3-6cycloalkyl ring, with the proviso that when X is O, then neither R3cnor R3dare halo, or R3aand R3care H, and R3band R3dform, together with the C atoms to which they are attached, a C5-6cycloalkyl ring; wherein at least two of R3a, R3b, R3cand R3dare H; X is a bond, -N(Me)-, O or -CH2-; Y1is N or -C(R7)-; R5, R6and R7are independently selected from H, halo C1-4alkoxy, and C1-4alkyl; R8is (i) a bond to LINK or (ii) a group selected from a 6- to 10-membered aryl ring, a 5- to 10-membered heteroaryl ring, and a 5- to 10-membered heterocyclyl ring, the group R8being unsubstituted or substituted by one, two or three substituents independently selected from halo, C1-4alkoxy, R10, -(C1-4alkylene)-R10, =O, -CN, and C1-4alkyl which is itself unsubstituted or substituted by one or two R9; each R9is independently selected from halo and C1-4alkoxy; R10is a group selected from a 5- to 6-membered heteroaryl ring, a 3- to 6-membered cycloalkyl ring, a 4- to 6-membered heterocyclyl ring, and a phenyl ring, the group R10being unsubstituted or substituted by one or two substituents independently selected from C1-4alkyl, C1-4alkoxy, and halo; wherein either R8is (i) a bond to LINK, or R8is a group (ii) and M is bonded to LINK via a C or N atom within group R8or ring Hy such that a hydrogen atom on the C or N atom within group R8or ring Hy is replaced with a bond to LINK; and LINK is (a) a single bond, or (b) a chemical linker group represented by formula (L): wherein: LINK is attached to M via L1; LINK is attached to U via L3; when R8is (i) a bond to LINK, then L1 is a single bond and L3 is selected from a single bond, -N(R’)-, -C(O)N(R’)-, -O-, -N(R’)C(O)-, -C(O)-, -S(O2)N(R’)-, -N(R’)S(O2)-, -(C1-6alkylene)-, ethynyl, -(C2-6alkenylene)-, a divalent 3- to 6-membered cycloalkyl ring and a divalent 4- to 7-membered heterocyclyl ring; and when R8is a group (ii), then L1 and L3 are each independently selected from a single bond, -N(R’)-, - C(O)N(R’)-, -O-, -N(R’)C(O)-, -C(O)-, -S(O2)N(R’)-, -N(R’)S(O2)-, -(C1-6alkylene)-, ethynyl, -(C2-6alkenylene)-, a divalent 3- to 6-membered cycloalkyl ring and a divalent 4- to 7-membered heterocyclyl ring; L2 is represented by the formula -(L4)m-; each L4 is independently selected from a divalent 3- to 6-membered cycloalkyl ring, a divalent 4- to 7-membered heterocyclyl ring and a unit of formula: each XLis independently selected from a single bond, -N(R’)-, -O-, -C(O)-, -S-, -SO-, - SO2-, -C(H)=C(H)- and -C(H)≡C(H)-; n is selected from 1 to 4; m is selected from 1 to 30; each R’ is independently selected from H and C1-4alkyl; and U is: (a) a CRBN E3 ubiquitin ligase binding moiety of formula (U1):

[0019] wherein: RU1is H; Q is selected from -CH(RU6)-, -N(RU6)-, -O-, -C(O)-, -NH-CH(RU6)-, -N=C(RU6)-, or -N=N-; RU6is H or C1-4alkyl; RU2and RU5are each independently selected from H, halogen, C1-4alkyl, NH2, NO2, OH, COOH, CN, CF3, and a single bond to LINK; RU3and RU4are each independently selected from H, halogen, C1-4alkyl, NH2, NO2, OH, COOH, CN, CF3, and a single bond to LINK; wherein one and only one of RU2, RU3, RU4and RU5is a single bond to LINK; (b) a CRBN E3 ubiquitin ligase binding moiety of formula (U4): wherein: RU1’is H; Q’ is selected from CH and N; RU12, RU13and RU14are each independently selected from H, halogen, C1-4alkyl, NH2, NO2, OH, COOH, CN, CF3, and a single bond to LINK; wherein one and only one of RU12, RU13and RU14is a single bond to LINK; or (c) a VHL E3 ubiquitin ligase binding moiety of formula (U2): wherein: RU7is a group selected from phenyl, a 5- to 6-membered heteroaryl ring, a 5- to 6- membered heterocyclyl ring, and a 5- to 6-membered cycloalkyl ring, the group RU7being unsubstituted or substituted by C1-4alkyl; RU11is H or C1-4alkyl; RU8is selected from C1-4alkyl, phenyl and a 3- to 8-membered cycloalkyl ring; and RU9is a single bond to LINK. In one preferred aspect of this embodiment, M is of formula (IV): wherein R8is a group selected from a 6- to 10-membered aryl ring and a 5- to 10- membered heteroaryl ring, the group R8being unsubstituted or substituted by one, two or three substituents independently selected from halo and C1-4alkyl; wherein M is bonded to LINK via a C or N atom within group R8such that a hydrogen atom on the C or N atom within group R8is replaced with LINK. In this embodiment, R8is preferably selected from one of the following structures: wherein: represents the point of attachment of R8to the rest of moiety M; represents the point of attachment of R8to LINK; and the group R8is further unsubstituted or substituted by one or two substituents independently selected from fluorine and methyl. In this embodiment, L2 is preferably selected from -(CH2)m-, -(CH2CH2O)m-, - (OCH2CH2)m-, -(CH2CH2S)m-, -(SCH2CH2)m-, and a divalent 4- to 7-membered heterocyclyl ring. In this embodiment, preferably L1 and L3 are each independently selected from a single bond, branched or straight-chain -(C1-6alkylene)-, -N(R’)-, -C(O)N(R’)-, -N(R’)C(O)-, - O-, ethynyl, and a divalent 4- to 7-membered heterocyclyl ring. Preferably in this embodiment, R’ is H and the divalent 4- to 7-membered heterocyclyl ring is piperidine or diazinane. In this embodiment, U is preferably (i) of formula (U1) wherein preferably Q is selected from -CH2- and -C(O)-, RU6is H, one of RU2, RU3, RU4and RU5is a single bond to LINK, and the rest are H, for instance wherein RU2and RU3are H, one of RU4and RU5is a single bond to LINK, and the other of RU4and RU5is H, or (ii) of formula (U3) wherein preferably V is S, W is N, RU10is methyl, RU11is H, and RU8is t-butyl or phenyl, more preferably t-butyl. In a further preferred aspect of this embodiment, M is of formula (IVA): wherein R8is a bond to LINK; L1 is a single bond or branched or straight-chain -(C1-6alkylene)-; L2 is selected from -(CH2)m-, -(CH2CH2O)m-, -(OCH2CH2)m-, -(CH2CH2S)m-, - (SCH2CH2)m-, and a divalent 4- to 7-membered heterocyclyl ring; L3 is selected from a single bond, -N(R’)-, -C(O)N(R’)-, -N(R’)C(O)-, -O-, ethynyl, and a divalent 4- to 7-membered heterocyclyl ring, wherein R’ is preferably H and the divalent 4- to 7-membered heterocyclyl ring is preferably piperidine or diazinane; and U is (i) of formula (U1) wherein Q is selected from -CH2- and -C(O)-, RU6is H, one of RU2, RU3, RU4and RU5is a single bond to LINK, and the rest are H, for instance wherein RU2and RU3are H, one of RU4and RU5is a single bond to LINK, and the other of RU4and RU5is H, or (ii) of formula (U3) wherein V is S, W is N, RU10is methyl, RU11is H, and RU8is t-butyl or phenyl, more preferably t-butyl. Preferably, L1 is a single bond and L3 is selected from a single bond, -N(R’)-, - C(O)N(R’)-, -N(R’)C(O)-, -O-, and a divalent 4- to 7-membered heterocyclyl ring, wherein R’ is preferably H and the divalent 4- to 7-membered heterocyclyl ring is preferably piperidine or diazinane. Preferred compounds of the invention may be selected from: 1-(8-{[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino}octyl)-3-methyl-N-{2- [(rel-2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}indazole-6-carboxamide; 1-(8-{[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino}octyl)-3-methyl-N-{2- [(rel-2S)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}indazole-6-carboxamide; (2S,4R)-1-[(2S)-3,3-dimethyl-2-(11-{[4-({2-[(rel-2R)-1-methylpyrrolidin-2- yl]imidazo[1,2-a]pyrazin-6-yl}carbamoyl)phenyl]formamido}undecanamido)butanoyl]- 4-hydroxy-N-{[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl}pyrrolidine-2-carboxamide; (2S,4R)-1-[(2S)-3,3-dimethyl-2-(11-{[4-({2-[(rel-2S)-1-methylpyrrolidin-2- yl]imidazo[1,2-a]pyrazin-6-yl}carbamoyl)phenyl]formamido}undecanamido)butanoyl]- 4-hydroxy-N-{[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 7-{[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino}-N-{2-[(2R)-1- methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}heptanamide; 3-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-5-yl]piperazin-1- yl}methyl)piperidin-1-yl]-1-methyl-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2- a]pyrazin-6-yl}indazole-5-carboxamide; 3-(4-(2-(4-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)piperazin-1- yl)ethyl)piperidin-1-yl)-1-methyl-N-(2-((R)-1-methylpyrrolidin-2-yl)imidazo[1,2- a]pyrazin-6-yl)-1H-indazole-5-carboxamide 3-(4-(2-(4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperazin-1- yl)ethyl)piperidin-1-yl)-1-methyl-N-(2-((R)-1-methylpyrrolidin-2-yl)imidazo[1,2- a]pyrazin-6-yl)-1H-indazole-5-carboxamide; 1-(8-{[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino}octyl)-5-fluoro-3- methyl-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}indazole-6- carboxamide; 1-(8-{[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]oxy}octyl)-3-methyl-N-{2- [(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}indazole-6-carboxamide; 1-(6-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)amino)hexyl)-3-methyl-N- (2-((R)-1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyrazin-6-yl)-1H-indazole-6- carboxamide; 4-(1-(3-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)propyl)- 1H-pyrazol-4-yl)-N-(2-((R)-1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyrazin-6- yl)benzamide; 4-(1-(3-(1-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)piperidin-4-yl)propyl)-1H- pyrazol-4-yl)-N-(2-((R)-1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyrazin-6- yl)benzamide; 1-(7-(2-(2, 6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl) hept-6-yn-1-yl)-3-methyl-N-(2- ((R)-1-methylpyrrolidin-2-yl) imidazo [1, 2-a] pyrazin-6-yl)-1H-indazole-6- carboxamide; 1-(9-(2-(2, 6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl) non-8-yn-1-yl)-3-methyl-N-(2- ((R)-1-methylpyrrolidin-2-yl) imidazo [1, 2-a] pyrazin-6-yl)-1H-indazole-6- carboxamide; 1-(2-((6-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hex-5-yn-1-yl)oxy)ethyl)-3- methyl-N-(2-((R)-1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyrazin-6-yl)-1H-indazole-6- carboxamide; and the pharmaceutically acceptable salts thereof. Particularly preferred compounds of the invention may be selected from: 1-(8-{[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino}octyl)-3-methyl-N-{2- [(rel-2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}indazole-6-carboxamide; 1-(8-{[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino}octyl)-3-methyl-N-{2- [(rel-2S)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}indazole-6-carboxamide; (2S,4R)-1-[(2S)-3,3-dimethyl-2-(11-{[4-({2-[(rel-2R)-1-methylpyrrolidin-2- yl]imidazo[1,2-a]pyrazin-6-yl}carbamoyl)phenyl]formamido}undecanamido)butanoyl]- 4-hydroxy-N-{[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl}pyrrolidine-2-carboxamide; (2S,4R)-1-[(2S)-3,3-dimethyl-2-(11-{[4-({2-[(rel-2S)-1-methylpyrrolidin-2- yl]imidazo[1,2-a]pyrazin-6-yl}carbamoyl)phenyl]formamido}undecanamido)butanoyl]- 4-hydroxy-N-{[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 7-{[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino}-N-{2-[(2R)-1- methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}heptanamide; and the pharmaceutically acceptable salts thereof. Therapeutic Efficacy The compounds of the present invention are therapeutically useful. The present invention therefore provides compounds as described herein, for use in medicine. The present invention provides compounds as described herein, for use in treating the human or animal body. For the avoidance of doubt, the agent may comprise a compound of the invention in the form of a solvate. Also provided is a pharmaceutical composition comprising a compound of the invention together with a pharmaceutically acceptable carrier or diluent. Typically, the composition contains up to 85 wt% of a compound of the invention. More typically, it contains up to 50 wt% of a compound of the invention. Preferred pharmaceutical compositions are sterile and pyrogen free. Further, when the pharmaceutical compositions provided by the invention contain a compound of the invention which is optically active, the compound of the invention is typically a substantially pure optical isomer. The composition of the invention may be provided as a kit comprising instructions to enable the kit to be used in the methods described herein or details regarding which subjects the method may be used for. As explained above, the compounds of the invention are useful in treating or preventing various disorders. Disorders for treatment using the compounds of the invention may include cancer. In particular, the compounds of the invention are useful for inducing selective degradation of MLLT1 and / or MLLT3. Cancer, e.g. acute lymphoblastic leukemia, acute myeloid leukemia, adrenocortical carcinoma, aids-related lymphoma, primary CNS lymphoma, anal cancer, astrocytomas, brain cancer, basal cell carcinoma, bile duct cancer, bladder cancer, bone cancer (e.g. ewing sarcoma, osteosarcoma and malignant fibrous histiocytoma), breast cancer, bronchial tumors, medulloblastoma and other CNS embryonal tumors, cervical cancer, chronic lymphocytic leukemia, chronic myelogenous leukemia, chronic myeloproliferative neoplasms, colorectal cancer, craniopharyngioma, endometrial cancer, ependymoma, esophageal cancer, esthesioneuroblastoma, ewing sarcoma, extragonadal germ cell tumor, intraocular melanoma, retinoblastoma, fallopian tube cancer, gallbladder cancer, gastric cancer, gastrointestinal carcinoid tumor, gastrointestinal stromal tumors (gist), germ cell tumors, extragonadal germ cell tumors, ovarian germ cell tumors, testicular cancer, gestational trophoblastic disease, hairy cell leukemia, hepatocellular cancer, histiocytosis, langerhans cell, hodgkin lymphoma, hypopharyngeal cancer, intraocular melanoma, islet cell tumors, pancreatic neuroendocrine tumors, kaposi sarcoma, kidney (renal cell) cancer, langerhans cell histiocytosis, laryngeal cancer, leukemia, liver cancer, lung cancer (non-small cell, small cell, pleuropulmonary blastoma, and tracheobronchial tumor), lymphoma, malignant fibrous histiocytoma of bone and osteosarcoma, merkel cell carcinoma, mesothelioma, mouth cancer, multiple endocrine neoplasia syndromes, multiple myeloma / plasma cell neoplasms, mycosis fungoides, myelodysplastic syndromes, myelodysplastic / myeloproliferative neoplasms, myelogenous leukemia, neuroblastoma, non-hodgkin lymphoma, oropharyngeal cancer, osteosarcoma and undifferentiated pleomorphic sarcoma, pancreatic cancer, pancreatic neuroendocrine tumors (islet cell tumors), papillomatosis, paraganglioma, parathyroid cancer, penile cancer, pharyngeal cancer, pheochromocytoma, pituitary tumor, prostate cancer, rectal cancer, retinoblastoma, rhabdomyosarcoma, t-cell lymphoma, testicular cancer, throat cancer, thymoma and thymic carcinoma, thyroid cancer, tracheobronchial tumors and the like is particularly suitable to being treated with the compounds of the invention provided herein. Typically, the compounds of the invention are for use in treating cancers which are transcriptionally addicted cancers, such as breast cancer, acute leukemia, prostate cancer, bladder cancer, cholangiocarcinoma, colon adenocarcinoma, esophageal carcinoma, head and neck squamous cell carcinoma, kidney chromophobe, kidney renal clear cell carcinoma, kidney renal papillary cell carcinoma, liver hepatocellular carcinoma, lung adenocarcinoma, pheochromocytoma and paraganglioma, rectum adenocarcinoma, stomach adenocarcinoma, uterine corpus endometrial carcinoma, cervical squamous cell carcinoma and endocervical adenocarcinoma, lung squamous cell carcinoma and sarcoma (Cell Rep, 2021, 16, 1087). Preferably, the compounds of the invention are for use in treating acute myeloid leukaemia (AML) or acute lymphoblastic leukaemia (ALL), such as mixed-lineage leukaemia (MLL) rearranged acute leukemia (AML and ALL) and NPM1 mutant leukemia. The compounds of the invention may be used as standalone therapeutic agents. Alternatively, they may be used in combination with other active agents such as chemotherapeutic agents, targeted precision medicines or immune oncology agents. For example, they may be used in combination with a Bcl2 targeted drug (for instance venetoclax), FLT3 inhibitor (for instance sorafenib, quizartinib or gilteritinib), EGFR inhibitor (for instance erlotinib, gefitinib, lapatinib or osimertinib), CDK4 / 6 inhibitor (for instance abemaciclib, palbociclib or ribociclib), a chemotherapy (for instance cytarabine, doxorubicin, gemcitabine, cisplatin or paclitaxel) or an immune checkpoint inhibitor (for instance pembrolizumab, nivolumab, durvalumab or cemiplimab). When used to treat a cancer, the compounds of the invention may be used in alleviating, ameliorating or preventing aggravation of the symptoms of the cancer. Typically, treating a cancer may comprise reducing progression of the cancer, e.g. increasing progression free survival (PFS) and / or increasing survival e.g. increasing overall survival (OS). Treating a cancer may comprise preventing or inhibiting growth of a tumour associated with the cancer. Treating a cancer may comprise preventing metastasis of the cancer. Preferably, treating a cancer may comprise reducing the size of a tumour associated with the cancer. As such, the treatment may cause tumour regression in the cancer. Treating a cancer may comprise reducing the number of tumours or lesions present in the patient. When the treatment reduces the size of a tumour associated with the cancer, the size of the tumour is typically reduced from base line by at least 10%. Base line is the size of the tumour at the date treatment with the compound is first started. The size of the tumour is typically as measured in accordance with version 1.1 of the RECIST criteria (for instance as described in Eisenhauer et al, European Journal of Cancer 45 (2009) 228-247). The response to the treatment with the compound may be complete response, partial response or stable disease, in accordance with version 1.1 of the RECIST criteria. Preferably, the response is partial response or complete response. The treatment may achieve progression free survival for at least 60 days, at least 120 days or at least 180 days. The reduction in tumour size may be greater 20%, greater than 30% or greater than 50% reduction relative to base line. The reduction in tumour size may be observed after 30 days of treatment or after 60 days of treatment. In haematological cancers, treating a cancer preferentially may lead to complete remission (CR) of the cancer or it may lead to complete remission with incomplete haematological recovery (CRh) or complete remission but with incomplete platelet recovery (CRp). Additionally, treatment may lead to an increase in duration of remission (DoR), an increase in minimal residual disease (MRD), or an increase in relapse free survival (RFS) (Blood 20071091815 and Leukemia Res 2018, 68, 32). As explained here, the compounds of the invention are useful in treating or preventing various disorders. The present invention therefore provides a compound of the invention for use in medicine. The invention also provides the use of a compound of the invention in the manufacture of a medicament. The invention also provides compositions and products comprising the compounds of the invention. Such compositions and products are also useful in treating or preventing disorders. The present invention therefore provides a composition or product as defined herein for use in medicine. The invention also provides the use of a composition or product of the invention in the manufacture of a medicament. Also provided is a method of treating a subject in need of such treatment, said method comprising administering to the subject a compound of the invention. In some embodiments the subject suffers from or is at risk of suffering from one of the disorders disclosed herein. In one aspect, the subject is a mammal, in particular a human. However, it may be non- human. Preferred non-human animals include, but are not limited to, primates, such as marmosets or monkeys, commercially farmed animals, such as horses, cows, sheep or pigs, and pets, such as dogs, cats, mice, rats, guinea pigs, ferrets, gerbils or hamsters. The subject can be any animal that is capable of being infected by a bacterium. A subject is typically a human patient. The patient may be male or female. The age of the patient is typically at least 18 years, for instance from 30 to 70 years or from 40 to 60 years. Alternatively, the patient may be a child, for instance the patient may be under 18 years of age, or under 12 years of age. In one embodiment, the patient is a child under ten years of age or an infant under two years of age. In one embodiment the invention provides a compound as defined herein for use in treating cancer in paediatric patients. A compound or composition of the invention can be administered to the subject in order to treat one or more symptoms of the disorder. In this embodiment, the subject is typically symptomatic. A therapeutically effective amount of the agent or formulation is administered to such a subject. A therapeutically effective amount is an amount effective to ameliorate one or more symptoms of the disorder. The compound or composition of the invention may be administered in a variety of dosage forms. Thus, it can be administered orally, for example as tablets, troches, lozenges, aqueous or oily suspensions, dispersible powders or granules. The compound or composition of the invention may also be administered parenterally, whether subcutaneously, intravenously, intramuscularly, intrasternally, transdermally or by infusion techniques. The compound or composition may also be administered as a suppository. Preferably, the compound, composition or combination may be administered orally. The compound or composition of the invention is typically formulated for administration with a pharmaceutically acceptable carrier or diluent. For example, solid oral forms may contain, together with the active compound, diluents, e.g. lactose, dextrose, saccharose, cellulose, corn starch or potato starch; lubricants, e.g. silica, talc, stearic acid, magnesium or calcium stearate, and / or polyethylene glycols; binding agents; e.g. starches, arabic gums, gelatin, methylcellulose, carboxymethylcellulose or polyvinyl pyrrolidone; disaggregating agents, e.g. starch, alginic acid, alginates or sodium starch glycolate; effervescing mixtures; dyestuffs; sweeteners; wetting agents, such as lecithin, polysorbates, laurylsulphates; and, in general, non toxic and pharmacologically inactive substances used in pharmaceutical formulations. Such pharmaceutical preparations may be manufactured in known manner, for example, by means of mixing, granulating, tableting, sugar coating, or film coating processes. Liquid dispersions for oral administration may be syrups, emulsions and suspensions. The syrups may contain as carriers, for example, saccharose or saccharose with glycerine and / or mannitol and / or sorbitol. Suspensions and emulsions may contain as carrier, for example a natural gum, agar, sodium alginate, pectin, methylcellulose, carboxymethylcellulose, or polyvinyl alcohol. The suspension or solutions for intramuscular injections or inhalation may contain, together with the active compound, a pharmaceutically acceptable carrier, e.g. sterile water, olive oil, ethyl oleate, glycols, e.g. propylene glycol, and if desired, a suitable amount of lidocaine hydrochloride. Solutions for inhalation, injection or infusion may contain as carrier, for example, sterile water or preferably they may be in the form of sterile, aqueous, isotonic saline solutions. Pharmaceutical compositions suitable for delivery by needleless injection, for example, transdermally, may also be used. A therapeutically effective amount of the compound or composition of the invention is administered to a subject. The dose may be determined according to various parameters, especially according to the compound used; the age, weight and condition of the subject to be treated; the route of administration; and the required regimen. Again, a physician will be able to determine the required route of administration and dosage for any particular subject. A typical daily dose is from about 0.01 to 100 mg per kg, preferably from about 0.1 mg / kg to 50 mg / kg, e.g. from about 1 to 10 mg / kg of body weight, according to the activity of the specific compound, the age, weight and conditions of the subject to be treated, the type and severity of the disease and the frequency and route of administration. Preferably, daily dosage levels are from 5 mg to 2 g. When the compound or composition of the invention is administered to a subject in combination with another active agent, the dose of the other active agent can be determined as described above. The dose may be determined according to various parameters, especially according to the agent used; the age, weight and condition of the subject to be treated; the route of administration; and the required regimen. Again, a physician will be able to determine the required route of administration and dosage for any particular subject. A typical daily dose is from about 0.01 to 100 mg per kg, preferably from about 0.1 mg / kg to 50 mg / kg, e.g. from about 1 to 10 mg / kg of body weight, according to the activity of the specific agent, the age, weight and conditions of the subject to be treated, the type and severity of the disease and the frequency and route of administration. Preferably, daily dosage levels are from 5 mg to 2 g. Synthesis Compounds of the invention can be prepared by the synthetic methods described in the Examples that follow, or by analogy with such methods using appropriate starting materials and methodologies familiar to the skilled chemist. The following examples illustrate the invention. They do not however limit the invention in any way. In this regard, it is important to understand that the particular assay used in the Examples section is designed only to provide an indication of biological activity. There are many assays available to determine biological activity, and a negative result in any one particular assay is therefore not determinative. The invention is defined according to the claims. Examples In the examples which follow below, compounds may be produced in racemic form. Compounds in racemic form are indicated by use of the term rac- in advance of the IUPAC name. In some instances, as indicated, enantiomers and / or diastereomers are separated. In general, the enantiomers and / or diastereomers of the invention can be separated using chiral chromatography. The separated enantiomers and / or diastereomers may be identified in the order in which they elute, for example the first, second, third or fourth eluting isomer respectively, as obtained by separation using chiral chromatography. The isomers may alternatively or additionally be identified using IUPAC naming conventions. Thus, where enantiomers and / or diastereomers have been assigned an absolute stereochemistry, this is indicated as R or S stereochemistry, as appropriate, and by use of a wedge-shaped bond (e.g. the chemical formula. Where enantiomers have been separated but have undefined absolute stereochemistry the term “rel-R” or “rel-S” has been used. In these examples it is understood that the absolute configuration is unknown and the “rel-R” and “rel-S” labels are used merely to distinguish the two enantiomers form one another. The absolute stereochemistry of an enantiomer labelled as “rel-R” may be either R or S. In either case, the corresponding “rel-S” enantiomer has the opposite configuration to the “rel-R” enantiomer. In these examples the use of a rectangular bond (e.g. ) has been used to define the “rel” configuration. Alternatively, where diastereomers have been separated and the absolute configuration is unknown they may be assigned a relative stereochemistry, which denotes the stereochemistry of a first chiral centre with respect to a second chiral centre. Where a relative stereochemistry has been assigned, this is indicated by the term “rel” in the IUPAC name, and by use of a rectangular-shaped bond (e.g. ). Where diastereomers have been separated and the relative and absolute configuration is unknown, the compounds have been labelled by the order in which they elute, for example the first, second, third or fourth eluting isomer respectively, as obtained by separation using chiral chromatography. Temperatures are given in degrees Celsius (°C). The reactants used in the examples below may be obtained from commercial sources or they may be prepared from commercially available starting materials as described herein or by methods known in the art. All the compounds of the invention are synthesized according to the Examples described herein. The progress of the reactions described herein were followed as appropriate by e.g. LC, GC or TLC, and as the skilled person will readily realize, reaction times and temperatures may be adjusted accordingly. NMR spectroscopy: Solids / oils were solubilized in DMSO-d6or MeOH-d4, vortexed vigorously until the solution was clear and transferred to an NMR tube for data acquisition. Liquid-state NMR experiments were recorded using: - 600 MHz (14.1 Tesla) Bruker Avance III NMR spectrometer (600 MHz for1H, 151 MHz for13C) using a triple-resonance1H,15N,13C CP-TCI 5 mm cryoprobe (Bruker Biospin, Germany) - 500 MHz (11.75 Tesla) Bruker Avance I NMR spectrometer (500 MHz for1H, 125 MHz for13C) using a Dual Resonance BBI 5 mm probe (Bruker Biospin, Germany) - 400 MHz (9.4 Tesla) Bruker Avance NEO NMR spectrometer (400 MHz for1H, 100 MHz for13C) using a SEI 5 mm probe (Bruker Biospin, Germany) - 400 MHz (9.4 Tesla) Bruker Avance NEO NMR spectrometer using a PI HR- BBO400S1-BBF / H / D-5.0-Z SP probe (Bruker Biospin, Germany) - 300 MHz Bruker AVANCE III HD NMR spectrometer using a PA BBO 300S1 BBF-H-D-05 Z probe (Bruker Biospin, Germany) - 300 MHz Bruker Avance NEO NMR spectrometer using a PA BBO BBF-H-D- 05 Z (Bruker Biospin, Germany) All the experiments used for the resonance assignment procedure and the elucidation of the products structure (1D1H, 2D1H-1H-COSY, 2D1H-1H-ROESY, 2D1H-13C-HSQC, 2D1H-13C-HMBC) were recorded at 300 K.1H chemical shifts are reported in δ ppm as s (singlet), d (doublet), t (triplet), q (quartet), dd (double doublet), m (multiplet) or br s (broad singlet). UPLC-MS chromatography: UPLC-MS chromatography analysis were recorded using the following apparatus using: - Waters UPLC: Acquity, UV: Acquity PDA, MS: Qda, ELSD - Waters UPLC: Acquity, UV: Acquity TUV, MS: Qda - Waters UPLC: Acquity, UV: Acquity PDA, MS: QDa The apparatus was tested using a CSH C18 Waters column (50 x 2.1 mm), 1.7 µm. It used a combination of the following eluents: H2O + 0.05% TFA (v / v) (solvent A) and MeCN + 0.035% TFA (v / v) (solvent B) and a positive electrospray ES+ as ionization mode. The UV detection was set at 220 and 254 nm. The methods used were the following: - Polar method (1.7 min run): gradient t=02% B, t=0.5 min 2% B, t=1.5 min 98% B, t=1.52 min 2% B, t=1.7 min 2% B - Polar method (3.5 min run): gradient t=02% B, t=1.0 min 2% B, t=2.4 min 98% B, t=3.00 min 98% B, t=3.03 min 2% B, t=3.5 min 2% B - Normal method (1.7 min run): gradient t=02% B, t=1.0 min 98% B, t=1.5 min 98% B, t=1.52 min 2% B, t=1.7 min 2% B - Normal method (3.5 min run): gradient t=02% B, t=2.4 min 98% B, t=3.0 min 98% B, t=3.03 min 2% B, t=3.5 min 2% B Where it is observed mass spectra analysis is reported as [M+H]+for the molecular ion; Someone skilled in the art will also appreciate that isotope patterns may be reported where evident, for example [M+H+2]+represents the isotopic peak of Br if it is present in the molecule; Additionally, some fragmentation ions may be included in the analysis, for example [M+H-tBu]+, [M+H-Boc]+and [M-Cl+MeOH]+. Preparative HPLC method A: Column X-BRIDGE C18 (250*30mm) 5um. Gradient elution is done with 10mM Ammonium Bicarbonate in water (Phase A) and 100% Acetonitrile (Phase B) with gradient Program (B%): 10% B at 0 min hold till 3min, 35%B at 10.0 min, 65% B at 35 min, 99% B at 35.1min hold till 40.0 min, 10%B at 40.1min hold till 45 min. flow rate: 25 mL / min. Abbreviations: In addition to the definitions above, the following abbreviations are used in the Example experimental procedures below. If an abbreviation used herein is not defined, it has its generally accepted meaning: Ac Acetyl AcOH Acetic acid MeCN Acetonitrile BF3.OEt2Boron trifluoride diethyl etherate Boc2O Di-tertbutyl decarbonate Boc tert-butyloxycarbonyl BrettPhos Pd G3 [(2-Di-cyclohexylphosphino-3,6-dimethoxy-2′,4′,6′- triisopropyl- 1,1′-biphenyl)-2-(2′-amino-1,1′-biphenyl)]palladium(II) methanesulfonate CBr4Carbon tetrabromide CHCl3 Chloroform Cs2CO3Cesium carbonate DAST (Diethylamino)sulfur trifluoride DCM Dichloromethane DIPEA Diisopropylethylamine DMF Dimethylformamide DMSO Dimethylsulfoxide DMSO-d6Hexadeuterodimethylsulfoxide DPPA Diphenyl phosphoryl azide EDCl N-Ethyl-N′-(3-dimethylaminopropyl)carbodiimide hydrochloride ee% Enantiomeric excess Et Ethyl EtOAc Ethyl acetate Et3N Triethylamine EtOH Ethanol Et2O Diethylether EPhos Pd G4 Methanesulfonato{Dicyclohexyl[3-(1-methylethoxy)-2',4',6'- tris(1-methylethyl)[1,1'-biphenyl]-2-yl]phosphine}(2'- methylamino-1,1'-biphenyl-2-yl)palladium(II) Et3SiH Triethylsilane GC Gas chromatography GPhos (3-(tert-Butoxy)-2′,6′-diisopropyl-6-methoxy-[1,1′-biphenyl]-2- yl)dicyclohexylphosphane Gphos Pd G6 TES GPhos OAC precatalyst TES Grubbs 2ndgeneration (1,3-Bis(2,4,6-trimethylphenyl)-2- imidazolidinylidene)dichloro(phenylmethylene)(tricyclohexylpho sphine)ruthenium, Benzylidene[1,3-bis(2,4,6-trimethylphenyl)-2- imidazolidinylidene]dichloro(tricyclohexylphosphine)ruthenium, Dichloro[1,3-bis(2,4,6-trimethylphenyl)-2- imidazolidinylidene](benzylidene)(tricyclohexylphosphine)ruthen ium(II) h hour HATU [dimethylamino(triazolo[4,5-b]pyridin-3-yloxy)methylene]- dimethyl-ammonium hexafluorophosphate H2O water Het Heteroaromatic HFIP 1,1,1,3,3,3-Hexafluoro-2-propanol HOBt 1-Hydroxybenzotriazole HPLC High performance liquid chromatography IPA Isopropyl amine iPr2O Isopropyl ether iPrOH Isopropanol iPrOAc Isopropylacetate KI Potassium iodide K3PO4Tripotassium phosphate LC Liquid chromatography LiBEt3H Lithium triethylborohydride LiHMDS Lithium bis(trimethylsilyl)amide LiOH Lithium hydroxide min Minutes Me Methyl MeCN Acetonitrile MeMgBr Methylmagnesium bromide MeOH Methanol MeTHF 2-Methyltetrahydrofuran MgSO4Magnesium sulfate MS Mass spectrometry MtBE Tert-butyl methylether NaH Sodium hydride Na2SO4Sodium sulfate Na2S2O3Sodium thiosulfate NaBH4Sodium borohydride NaBH(OAc)3Sodium triacetoxyborohydride NaBH3CN Sodium cyanoborohydride NBS N-bromosuccinimide NaCl Sodium chloride NaHCO3 Sodium bicarbonate Na2CO3Sodium carbonate NH4Cl Ammonium chloride NH4OAc Ammonium acetate NIS N-Iodosuccinimide NMP N-methyl-2-pyrrolidone NMM N-methylmorpholine N2Nitrogen NaOH Sodium hydroxide Pd(PPh3)4Tetrakis(triphenylphosphine)palladium(0) Pd2(dba)3 Tris(dibenzylideneacetone)dipalladium(0) Pd(dppf)Cl2[1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) Pd / C Palladium on carbon PE Petroleum ether POCl3Phosphorus oxychloride PPh3Triphenylphosphine Rochelle’s salt Potassium sodium tartrate rt room temperature (18 to 22 °C) SOCl2Thionyl chloride STAB Sodium triacetoxyborohydride TBAF Tetrabutylammonium fluoride TBSCl tert-Butyldimethylsilyl chloride tBuLi Tert-butyllithium tBuOH Tert-butanol tBuOK Potassium tert-butoxide TCFH N-[chloro(dimethylamino)methylidene]-N- methylmethanaminium hexafluorophosphate TFA Trifluoroacetic acid TLC Thin layer chromatography THF Tetrahydrofuran TMSCl Chlorotrimethylsilane UPLC Ultra Performance Liquid Chromatography Xantphos 4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene 9-BBN 9-Borabicyclo[3.3.1]nonane Procedures Intermediates 6A and 6B were synthesized following Scheme 1.

[0020] Scheme 1 Step 1 Intermediate 1: rac-tert-Butyl 2-(2-chloroacetyl)pyrrolidine-1-carboxylate Under dry conditions and argon atmosphere, rac-1‐tert‐butyl 2‐methyl pyrrolidine‐1,2‐ dicarboxylate (CAS: 145681-01-2, 100 g, 0.406 mol) was charged followed by anhydrous THF (860 mL). Then, sodium chloroacetate (124.34 g, 1.01 mol) was added in one portion followed by the dry triethylamine (113 mL, 0.811 mol). While keeping the temperature of the media between 0 and 5°C, a solution of tert-butylmagnesium chloride (1.014 L, 1.01 mol, 1M in THF) was added over 2h. The white suspension was stirred at 2-5°C for 18h. Then, a solution of citric acid (190 g in 570 mL of water) was added over 1h into the reaction mixture while maintaining the temperature between 0- 7°C using an ice bath. The organic layer was washed twice with an aqueous NaHCO3solution (NaHCO3: 25 g, NaCl: 90 g, H2O: 550 mL) and once with brine (NaCl: 100 g, H2O: 400 mL). The organic layer was concentrated under pressure.iPrOAc (300mL) was added to the residue, the organic layer was washed with an aqueous NaHCO3solution (NaHCO3: 5g, NaCl: 18g, H2O: 100mL) and the organic layer was dried over anhydrous MgSO4, filtered, and concentrated under pressure to afford rac-tert-butyl 2- (2-chloroacetyl)pyrrolidine-1-carboxylate (Intermediate 1: 107.7 g, quant.) as a yellow oil which was used in Step 2 without further purification. Mass spec: m / z: 192 [M+H- tBu]+, 148 [M+H-Boc]+;1H NMR (400 MHz, DMSO-d6) δ ppm 4.71 – 4.53 (m, 2H), 4.40 (ddd, J = 11.1, 8.7, 4.8 Hz, 1H), 3.34 (d, J = 7.2 Hz, 2H), 2.24 – 2.05 (m, 1H), 1.93 – 1.66 (m, 3H), 1.35 (d, J = 32.2 Hz, 9H). Step 2 Intermediate 2: rac-tert-Butyl 2-{6-bromoimidazo[1,2-a]pyrazin-2-yl}pyrrolidine- 1-carboxylate In a round bottom flask, 5-bromopyridin-2-amine (CAS: 1072-97-5, 15 g, 86.7 mmol) was dissolved in toluene (75 mL) / MeCN (75 mL). Then, NaHCO3(8.74 g, 0.104 mol) was added, followed by rac-tert-butyl 2-(2-chloroacetyl)pyrrolidine-1-carboxylate (Intermediate 1: 23.34 g, 86.7 mmol) and sodium iodide (1.3 g, 8.67 mmol). The reaction mixture was stirred at 83°C for 18h. After cooling to rt, the mixture was concentrated under reduced pressure. The crude was diluted withiPrOAc (250 mL) and water (250 mL). The layers were filtered, the aqueous and organic layer from the filtrate were separated and the organic layer was dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel using a gradient of acetone in DCM from 0% to 100% to afford rac-tert-Butyl 2-{6-bromoimidazo[1,2-a]pyrazin-2-yl}pyrrolidine-1-carboxylate (Intermediate 2: 14.3 g, 43%) as a white solid. Mass spec: m / z: 366 [M+H]+, 368 [M+H+2]+;1H NMR (400 MHz, DMSO-d6) δ ppm 8.86 (d, J = 14.3 Hz, 1H), 7.67 (d, J = 10.3 Hz, 1H), 7.47 (d, J = 9.5 Hz, 1H), 7.30 (dd, J = 9.5, 2.0 Hz, 1H), 4.91 (d, J = 12.9 Hz, 1H), 3.44 (s, 1H), 3.36 (ddd, J = 10.4, 8.6, 7.2 Hz, 1H), 2.17 (s, 1H), 2.08 – 1.99 (m, 1H), 1.98 – 1.79 (m, 2H), 1.31 (d, J = 74.2 Hz, 9H). Step 3 Intermediate 3: rac-2-{6-Bromoimidazo[1,2-a]pyridin-2-yl}pyrrolidine hydrochloride In a round bottom flask under nitrogen atmosphere, rac-tert-butyl 2-(6- bromoimidazo[1,2-a]pyridin-2-yl)pyrrolidine-1-carboxylate (Intermediate 2: 14.30 g, 37.1 mmol) was solubilized iniPrOAc (75 mL). A solution of hydrogen chloride (74 mL, 0.371 mol, 5M iniPrOAc) was added to the mixture. The mixture was stirred for 2h at rt. A suspension appeared, the reaction mixture was filtered and the solid was washed with isopropanol (3x70 mL), dried under reduced pressure to afford rac-2-{6- Bromoimidazo[1,2-a]pyridin-2-yl}pyrrolidine hydrochloride (Intermediate 3: 10.89 g, 92%) as a brown solid which was used in Step 4 without further purification. Mass spec: m / z: 266 [M+H]+, 268 [M+H+2]+;1H NMR (400 MHz, DMSO-d6) δ ppm 10.13 (s, 1H), 9.17 (s, 1H), 9.07 (dd, J = 2.0, 0.9 Hz, 1H), 8.15 (s, 1H), 7.67 (d, J = 9.5 Hz, 1H), 7.58 (dd, J = 9.5, 1.8 Hz, 1H), 4.84 (p, J = 6.7 Hz, 1H), 3.39 – 3.23 (m, 2H), 2.44 – 2.34 (m, 1H), 2.23 – 2.08 (m, 2H), 2.08 – 1.96 (m, 1H). Step 4 Intermediate 4: rac-2-{6-bromoimidazo[1,2-a]pyridin-2-yl}-1-methylpyrrolidine 6-bromo-2-pyrrolidin-2-yl-imidazo[1,2-a]pyridine hydrochloride (Intermediate 3 (10.20 g, 32.0 mmol) was diluted in MeOH (100 mL), then formaldehyde (37% aq, 4.8 mL, 64.0 mmol) and acetic acid (3.85 g, 64.0 mmol) were added and the mixture was stirred for 1h at rt. Solid supported NaBH3CN (8.01 g, 16.0 mmol – loading 2 mmol / g) was then added and the mixture was stirred at rt for 1.5h. The reaction mixture was filtered, rinsed by MeOH and the filtrate was concentrated under pressure. The residue was diluted with EtOAc and a solution of saturated NaHCO3. The aqueous layer was extracted with EtOAc (5x). The organic layers were combined, dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure to afford rac-2-{6- bromoimidazo[1,2-a]pyridin-2-yl}-1-methylpyrrolidine (Intermediate 4: 7.94 g, 89%) as a yellow oil. Mass spec: m / z: 280 [M+H]+, 282 [M+H+2]+;1H NMR (400 MHz, DMSO-d6) δ ppm 8.82 (d, J = 1.9 Hz, 1H), 7.76 (s, 1H), 7.45 (d, J = 9.5 Hz, 1H), 7.29 (dd, J = 9.5, 2.0 Hz, 1H), 3.33 (d, J = 7.4 Hz, 1H), 3.09 (ddd, J = 10.0, 6.1, 2.5 Hz, 1H), 2.28 (p, J = 8.6 Hz, 1H), 2.21 (s, 3H), 2.19 – 2.11 (m, 1H), 1.88 – 1.70 (m, 3H). Step 5 Intermediate 4A: rac-2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-amine To a solution of rac-2-{6-bromoimidazo[1,2-a]pyridin-2-yl}-1-methylpyrrolidine (Intermediate 4: 2.3 g, 7.06 mmol)) and copper(I) oxide (303 mg; 2.12 mmol)) in DMF (2.8 mL) was added 7.1 M ammonium hydroxide (35 mL, 247 mmol, 25% in H2O). The autoclave reactor was sealed and stirred at 80°C for 18 h (pressure of 3-4 bars observed). The mixture was cooled to rt and DCM / MeOH (9 / 1) and water were added, and the two phases were separated. The aqueous phase was extracted with DCM / MeOH (9 / 1) twice. The combined organic layers were dried over anhydrous MgSO4 and concentrated to dryness to afford 2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-amine (Intermediate 4A: 1.6 g, 82%) as an oil. Mass spec: m / z: 217 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 7.61 (s, 2H), 7.22 (s, 1H), 6.82 (s, 1H), 4.84 (s, 2H), 3.26 (s, 1H), 3.13 – 3.02 (m, 1H), 2.14 (d, J = 46.3 Hz, 5H), 1.79 (s, 3H). Step 6 Intermediate 5A: rel-(2R)-{6-bromoimidazo[1,2-a]pyridin-2-yl}-1- methylpyrrolidine and Intermediate 5B: rel-(2S)-2-{6-bromoimidazo[1,2- a]pyridin-2-yl}-1-methylpyrrolidine rac-2-{6-bromoimidazo[1,2-a]pyridin-2-yl}-1-methylpyrrolidine (Intermediate 4) was separated into the enantiomeric Intermediates 5A and 5B using the following conditions: Novasep Lab LC, column; Chiralcel IA 20µm, 300 x 78mm; Eluent: EtOH + 0.5% IPA; Flow rate: 275 mL / min to provide: Intermediate 5A: rel-(2S)-2-{6-bromoimidazo[1,2-a]pyridin-2-yl}-1- methylpyrrolidine First eluting compound (retention time = 9.5 to 10.5 min): Mass spec: m / z: 280 [M+H]+, 282 [M+H+2]+;1H NMR (400 MHz, DMSO-d6) δ ppm 8.83 (dd, J = 2.1, 0.9 Hz, 1H), 7.75 (s, 1H), 7.45 (dd, J = 9.5, 0.9 Hz, 1H), 7.29 (dd, J = 9.5, 1.9 Hz, 1H), 3.30 (d, J = 7.7 Hz, 1H), 3.08 (ddt, J = 7.9, 6.3, 2.6 Hz, 1H), 2.26 (q, J = 8.7 Hz, 1H), 2.20 (s, 3H), 2.19 – 2.10 (m, 1H), 1.87 – 1.69 (m, 3H). ee = 100%. Intermediate 5B: rel-(2R)-2-{6-bromoimidazo[1,2-a]pyridin-2-yl}-1- methylpyrrolidine Second eluting compound (retention time = 22 to 36 min) Mass spec: m / z: 280 [M+H]+, 282 [M+H+2]+;1H NMR (400 MHz, DMSO-d6) δ ppm 8.83 (dd, J = 2.1, 0.9 Hz, 1H), 7.75 (s, 1H), 7.45 (dd, J = 9.5, 0.9 Hz, 1H), 7.29 (dd, J = 9.5, 1.9 Hz, 1H), 3.30 (d, J = 7.7 Hz, 1H), 3.08 (ddt, J = 7.9, 6.3, 2.6 Hz, 1H), 2.26 (q, J = 8.7 Hz, 1H), 2.20 (s, 3H), 2.19 – 2.10 (m, 1H), 1.87 – 1.69 (m, 3H). ee = 100%. Step 7 Intermediate 6A: rel-2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyridin-6- amine or Intermediate 6B: rel-2-[(2S)-1-methylpyrrolidin-2-yl]imidazo[1,2- a]pyridin-6-amine To a solution of Intermediate 5A or 5B (1 eq) and copper(I) oxide (0.3 eq) in DMF (2.5 M) was added 7.1 M ammonium hydroxide (35 eq, 25% in H2O). The autoclave reactor was sealed and stirred at 80°C for 18 h (pressure of 3-4 bars observed). The mixture was cooled to rt and DCM / MeOH (9 / 1) and water were added, and the two phases were separated. The aqueous phase was extracted with DCM / MeOH (9 / 1) twice. The combined organic layers were dried over anhydrous MgSO4and concentrated to dryness to afford Intermediate 6A or 6B: Intermediate 6A: rel-2-[(2S)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyridin-6- amine Mass spec: m / z: 217 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 7.63 (d, J = 8.7 Hz, 2H), 7.25 (d, J = 9.5 Hz, 1H), 6.81 (dd, J = 9.5, 2.1 Hz, 1H), 4.84 (s, 2H), 3.50 (s, 1H), 3.18 (s, 1H), 2.35 – 2.15 (m, 5H), 1.88 (d, J = 26.2 Hz, 3H). Intermediate 6B: rel-2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyridin-6- amine Mass spec: m / z: 217 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 7.65 – 7.59 (m, 1H), 7.54 (s, 1H), 7.21 (d, J = 9.5 Hz, 1H), 6.77 (dd, J = 9.4, 2.1 Hz, 1H), 4.80 (s, 2H), 3.26 (t, J = 7.9 Hz, 1H), 3.13 – 3.03 (m, 1H), 2.31 – 2.22 (m, 1H), 2.20 (s, 3H), 2.16 – 2.06 (m, 1H), 1.93 – 1.67 (m, 3H). Intermediate 7: rac-2-{6-bromoimidazo[1,2-a]pyridin-2-yl}-1-(2- methoxyethyl)pyrrolidine To a solution of rac-2-{6-bromoimidazo[1,2-a]pyridin-2-yl}pyrrolidine hydrochloride (Intermediate 3; 300 mg, 1.13 mmol) in DMF (4 mL) was added 2-bromoethyl methyl ether (313 mg, 2.25 mmol), tetrabutylammonium iodide Bu4NI (41.6 mg, 0.110 mmol) and DIPEA (583 mg, 4.51 mmol). The mixture was stirred at 80°C for 3h and then quenched with water (5 mL). The mixture was concentrated under reduced pressure. The crude material was purified by reverse phase flash chromatography (C18 Aq) using MeCN / water (84 / 16) as the eluent to provide rac-2-{6-bromoimidazo[1,2-a]pyridin-2- yl}-1-(2-methoxyethyl)pyrrolidine (Intermediate 7: 160 mg 39%) as a light yellow oil. Mass spec: m / z 324 [M+H]+. Intermediate 10 was synthesized following Scheme 2. Scheme 2 Step 1 Intermediate 8: rac-tert-butyl 2-{6-bromo-7-fluoroimidazo[1,2-a]pyridin-2- yl}pyrrolidine-1-carboxylate Using rac-tert-butyl 2-(2-chloroacetyl)pyrrolidine-1-carboxylate (Intermediate 1) as the chloro-ketone and 5-bromo-4-fluoropyridin-2-amine (CAS: 944401-69-8) as the amine and following an analogous procedure to Step 2 of Scheme 1, followed by purification by flash chromatography (eluent: EtOAc / PE, 1 / 4) afforded rac-tert-butyl 2- {6-bromo-7-fluoroimidazo[1,2-a]pyridin-2-yl}pyrrolidine-1-carboxylate (Intermediate 8: 350 mg, 14%) as a yellow oil. Mass spec: m / z: 384 [M+H]+. Step 2 Intermediate 9: rac-2-{6-bromo-7-fluoroimidazo[1,2-a]pyridin-2-yl}pyrrolidine trifluoroacetate A round-bottom flask was charged with rac-tert-butyl 2-{6-bromo-7-fluoroimidazo[1,2- a]pyridin-2-yl}pyrrolidine-1-carboxylate (Intermediate 8: 480 mg, 1.249 mmol), DCM (15 mL) and TFA (3 mL). The reaction was stirred for 2h at rt. The mixture was then concentrated under reduced pressure to provide rac-2-{6-bromo-7-fluoroimidazo[1,2- a]pyridin-2-yl}pyrrolidine trifluoroacetate (Intermediate 9: 380 mg, 96%) as a yellow oil. Mass spec: m / z: 284 [M+H]+. Step 3 Intermediate 10: rac-2-{6-bromo-7-fluoroimidazo[1,2-a]pyridin-2-yl}-1- methylpyrrolidine trifluoroacetate A round-bottom flask was charged with rac-2-{6-bromo-7-fluoroimidazo[1,2-a]pyridin- 2-yl}pyrrolidine trifluoroacetate (Intermediate 9: 380 mg, 1.34 mmol), paraformaldehyde (201 mg, 6.69 mmol), Et3N (406 mg, 4.01 mmol) and MeOH (20 mL). The reaction was stirred for 1h at rt. Then NaBH3CN (252 mg, 4.01 mmol) was added, and the reaction was stirred overnight at 60°C. The reaction was diluted H2O and extracted with EtOAc twice. The combined organic layers were washed with brine, dried over anhydrous Na2SO4,filtered, and concentrated under reduced pressure. The residue was purified by reverse-phase flash chromatography (C18 aq) using a gradient of MeCN in water from 0% to 100% (0.5% TFA) to afford rac-2-{6-bromo-7- fluoroimidazo[1,2-a]pyridin-2-yl}-1-methylpyrrolidine trifluoroacetate (Intermediate 10: 400 mg, 90% as a colorless oil. Mass spec: m / z: 298 [M+H]+. Intermediate 15 was synthesized following Scheme 3.

[0021] Scheme 3 Step 1 Intermediate 11: rac-tert-butyl 2-(2-chloroacetyl)piperidine-1-carboxylate To a solution of rac-1-tert-butyl 2-methyl piperidine-1,2-dicarboxylate (CAS: 167423- 93-0, 1.8 mL, 7.97 mmol), sodium chloroacetate (978 mg, 7.97 mmol) and triethylamine (1.1 mL, 7.97 mmol) in anhydrous THF (18 mL) was added dropwise tert- butylmagnesium chloride (1M in THF 20 mL, 19.9 mmol) at -7°C over 20 min. The reaction mixture was left stirring between 0-5°C for 2h. A solution of citric acid (3.54 g, 18.3 mmol) in water (10 mL) was slowly added to the reaction mixture while maintaining the temperature between 0-5°C. EtOAc was then added to the reaction mixture and the phases were separated. The organic layer was washed twice with a solution of NaHCO3 / NaCl (470 mg of NaHCO3, 1.6 g of NaCl in 10mL H2O) and once with brine. The combined organic layers were dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure to afford rac-tert-butyl 2-(2- chloroacetyl)piperidine-1-carboxylate (Intermediate 11: 1.9 g, 64%) as an orange oil which was used in Step 2 without further purification. Mass spec: m / z: 206 [M- tBu+H]+, 162 [M-Boc+H]+;1H NMR (400 MHz, DMSO-d6) δ ppm 4.76 (dd, J = 6.3, 3.0 Hz, 1H), 4.69 – 4.55 (m, 2H), 3.89 – 3.69 (m, 1H), 3.01 – 2.63 (m, 1H), 2.14 – 2.03 (m, 1H), 1.57 (dtd, J = 17.2, 9.3, 3.9 Hz, 3H), 1.42 – 1.33 (m, 9H), 1.31 – 1.25 (m, 1H), 1.20 – 1.05 (m, 1H). Step 2 Intermediate 12: rac-tert-butyl 2-{6-bromoimidazo[1,2-a]pyridin-2-yl}piperidine- 1-carboxylate To a solution of rac-tert-butyl 2-(2-chloroacetyl)piperidine-1-carboxylate (Intermediate 11: 1.69 g, 4.51 mmol) and 5-bromopyridin-2-amine (780 mg, 4.51 mmol) in toluene (32.5 mL) and MeCN (32.5 mL) was added sodium hydrogen carbonate (454 mg, 5.41 mmol) followed by sodium iodide (68 mg, 0.451 mmol). The reaction mixture was heated at 95°C for 3h. The reaction mixture was concentrated under reduced pressure. The residue was diluted in DCM, filtered and filtrate was concentrated in vacuo. The crude material was purified by flash chromatography on silica gel (120 g) using a gradient of DCM / Acetone (90 / 10) in DCM from 0% to 50% to afford rac-tert-butyl 2- {6-bromoimidazo[1,2-a]pyridin-2-yl}piperidine-1-carboxylate (Intermediate 12: 403 mg, 22%) as an orange oil. Mass spec: m / z: 380 [M+H]+, 382 [M+H+2]+. Step 3 Intermediate 13: rac-2-{6-bromoimidazo[1,2-a]pyridin-2-yl}piperidine hydrochloride To a solution of rac-tert-butyl 2-(6-bromoimidazo[1,2-a]pyridin-2-yl)piperidine-1- carboxylate (Intermediate 12: 400 mg, 0.968 mmol) in 1,4-dioxane (3.23 mL) was added a solution of HCl (3.6 mL, 14.5 mmol, 4N in dioxane). The reaction mixture was stirred at rt for 5h. The reaction mixture was filtered and washed with iPr2O to afford rac-2-{6-bromoimidazo[1,2-a]pyridin-2-yl}piperidine hydrochloride (Intermediate 13: 315 mg, 99%) as a white solid which was used in Step 4 without further purification. Mass spec: m / z: 280 [M+H]+, 282 [M+H+2]+;1H NMR (400 MHz, DMSO-d6) δ ppm 9.39 (s, 1H), 9.13 (d, J = 2.5 Hz, 1H), 8.15 (d, J = 2.3 Hz, 1H), 7.68 (d, J = 9.5 Hz, 1H), 7.63 – 7.56 (m, 1H), 4.49 (t, J = 10.8 Hz, 1H), 3.27 (s, 1H), 3.04 (d, J = 11.8 Hz, 1H), 2.14 (dd, J = 13.6, 3.5 Hz, 1H), 2.03 – 1.59 (m, 5H). Step 4 Intermediate 14: rac-2-{6-bromoimidazo[1,2-a]pyridin-2-yl}-1-methylpiperidine To a solution of rac-2-{6-bromoimidazo[1,2-a]pyridin-2-yl}piperidine hydrochloride (Intermediate 13: 315 mg, 0.967 mmol) in MeOH (6.4 mL) was added formaldehyde (37% aq, 0.13 mL, 1.74 mmol) and acetic acid (0.083 mL, 1.45 mmol). The reaction mixture was stirred at rt for 1.5h before addition of NaBH4(774 mg, 1.93 mmol). The resulting reaction mixture was stirred at rt for 1h. The reaction mixture was filtered through a pad of celite, washed with MeOH and the filtrate was concentrated under reduced pressure. The residue was partitioned between a saturated solution of NaHCO3and EtOAc, the phases were separated, and aqueous phase was extracted with EtOAc twice. The combined organic layers were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to obtain rac-2-{6-bromoimidazo[1,2-a]pyridin-2- yl}-1-methylpiperidine (Intermediate 14: 225 mg, 74%) as a light beige solid which was used in Step 5 without further purification. Mass spec: m / z: 294 [M+H]+, 296 [M+H+2]+;1H NMR (400 MHz, DMSO-d6) δ ppm 8.82 (dd, J = 2.1, 0.8 Hz, 1H), 7.75 (s, 1H), 7.46 (d, J = 9.5 Hz, 1H), 7.29 (dd, J = 9.5, 2.0 Hz, 1H), 3.28 (d, J = 3.1 Hz, 1H), 3.04 (d, J = 10.6 Hz, 1H), 2.91 (d, J = 11.5 Hz, 1H), 2.06 (t, J = 11.2 Hz, 1H), 1.97 (s, 3H), 1.79 – 1.69 (m, 2H), 1.68 – 1.50 (m, 2H), 1.39 – 1.23 (m, 1H). Step 5 Intermediate 15: rac-2-(1-methylpiperidin-2-yl)imidazo[1,2-a]pyridin-6-amine To a solution of rac-2-{6-bromoimidazo[1,2-a]pyridin-2-yl}-1-methylpiperidine (Intermediate 14: 225 mg, 0.711 mmol) in DMF (0.35 mL) was added copper(I) oxide (32 mg, 0.213 mmol) followed by a solution of ammonium hydroxide (3.5 mL, 24.9 mmol, 7.1 M in water). The reaction mixture was heated at 80°C overnight (sealed tube – pressure observed). The reaction mixture was partitioned between H2O and DCM / MeOH (3 / 1), the phases were separated, and the aqueous phase was extracted with DCM / MeOH (3 / 1) twice. The combined organic layers were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to afford rac-2-(1- methylpiperidin-2-yl)imidazo[1,2-a]pyridin-6-amine (Intermediate 15:158 mg, 81%) as a brown oil which was used without further purification. Mass spec: m / z: 231 [M+H]+;1H NMR (400 MHz, DMSO-d6) δ ppm 7.62 (dd, J = 2.2, 0.9 Hz, 1H), 7.52 (s, 1H), 7.21 (d, J = 9.4 Hz, 1H), 6.76 (dd, J = 9.4, 2.1 Hz, 1H), 4.79 (s, 2H), 2.96 – 2.90 (m, 1H), 2.87 (d, J = 3.5 Hz, 1H), 2.03 (td, J = 11.4, 3.3 Hz, 1H), 1.96 (s, 3H), 1.80 – 1.50 (m, 5H), 1.29 (dtd, J = 16.8, 12.3, 4.3 Hz, 1H). Intermediate 21 was synthesized following Scheme 4. Scheme 4 Step 1 Intermediate 16: tert-butyl (2R)-2-[methoxy(methyl)carbamoyl]-octahydro-1H- indole-1-carboxylate To a stirred solution of (2R)-1-(tert-butoxycarbonyl)-octahydroindole-2-carboxylic acid (CAS: 1217525-04-6: 1 g, 3.71 mmol) and N-methyl imidazole (1.52 g, 18.7 mmol) in DMF (10 mL) was added TCFH (1.35 g, 4.82 mmol) at rt. The reaction was stirred at rt for 18h. The reaction mixture was quenched with H2O and extracted with EtOAc three times. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel using DCM / MeOH (9 / 1)] as eluent to afford tert-butyl (2R)-2-[methoxy(methyl)carbamoyl]-octahydro-1H-indole-1- carboxylate (Intermediate 16: 600 mg, 44%) as a white solid. Mass spec: m / z: 313 [M+H]+. Step 2 Intermediate 17: tert-butyl (2R)-2-[methoxy(methyl)carbamoyl]-octahydro-1H- indole-1-carboxylate To a stirred solution of tert-butyl (2R)-2-[methoxy(methyl)carbamoyl]-octahydroindole- 1-carboxylate (Intermediate 16: 600 mg, 1.92 mmol) in THF (6 mL) were added a solution of MeMgBr (3.84mL, 3.84mmol, 1M in THF) dropwise at 0°C under nitrogen atmosphere. The reaction mixture was stirred for 3 days at rt. The reaction was quenched with water and extracted with EtOAc three times. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel using PE / EtOAc (86 / 14) as eluent to afford tert-butyl (2R)-2- [methoxy(methyl)carbamoyl]-octahydro-1H-indole-1-carboxylate (Intermediate 17: 238 mg, 50%) as a colorless oil. Mass spec: m / z: 268 [M+H]+. Step 3 Intermediate 18: tert-butyl (2R)-2-(2-bromoacetyl)-octahydro-1H-indole-1- carboxylate To a stirred solution of tert-butyl (2R)-2-acetyl-octahydroindole-1-carboxylate (Intermediate 17: 200 mg, 0.748 mmol) in THF (3 mL) was added a LiHMDS solution (1.5 mL, 1.496 mmol, 1M in THF) dropwise at -70°C under nitrogen atmosphere. The resulting mixture was stirred at -70°C for 1h. To the above mixture was added TMSCl (162 mg, 1.50 mmol) at -70°C. The resulting mixture was warmed to rt and stirred for 1h. The mixture was cooled to -70°C and a solution of NBS (160 mg, 0.898 mmol) in THF (1 mL) was added dropwise over 1 min at -70°C. The mixture was warmed to rt and was stirred for 2h. The mixture was quenched with a saturated NH4Cl solution. The reaction was extracted three times with EtOAc. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The crude material was purified by flash chromatography on silica gel using PE / EtOAc (92 / 8) as eluent to afford tert-butyl (2R)-2-(2-bromoacetyl)-octahydro-1H-indole-1- carboxylate (Intermediate 18: 168 mg, 64%) as a colorless oil. Mass spec: m / z: 346 [M+H]+. Step 4 Intermediate 19: tert-butyl (2R)-2-{6-bromoimidazo[1,2-a]pyridin-2-yl}- octahydro-1H-indole-1-carboxylate To a stirred solution of tert-butyl (2R)-2-(2-chloroacetyl)-octahydroindole-1- carboxylate (Intermediate 18:168 mg, 0.596 mmol) and 5-bromopyridin-2-amine (124 mg, 0.715 mmol) in Toluene (1 mL) and MeCN (3 mL) were added KI (9.90 mg, 0.06 mmol) and NaHCO3(60 mg, 0.715 mmol) at rt. The resulting mixture was stirred overnight at 100°C. The reaction was diluted with water and extracted with EtOAc three times. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel using PE / EtOAc (81 / 19) to afford tert- butyl (2R)-2-{6-bromoimidazo[1,2-a]pyridin-2-yl}-octahydro-1H-indole-1-carboxylate (Intermediate 19: 110 mg, 73%) as a colorless oil. Mass spec: m / z: 420 [M+H]+. Step 5 Intermediate 20: (2R)-2-{6-bromoimidazo[1,2-a]pyridin-2-yl}-octahydro-1H-indole trifluoroacetate To a stirred solution of tert-butyl (2R)-2-{6-bromoimidazo[1,2-a]pyridin-2-yl}- octahydroindole-1-carboxylate (Intermediate 19:110 mg, 0.262 mmol) in DCM (5 mL) was added TFA (1 mL). The mixture was stirred for 2h at rt. The reaction mixture was concentrated under reduced pressure to afford the title compound (2R)-2-{6- bromoimidazo[1,2-a]pyridin-2-yl}-octahydro-1H-indole trifluoroacetate (Intermediate 20: 80 mg, 95%) as a white solid which was used in Step 6 without further purification. Mass spec: m / z: 320 [M+H]+. Step 6 Intermediate 21: (2R)-2-{6-bromoimidazo[1,2-a]pyridin-2-yl}-1-methyl-octahydro- 1H-indole To a stirred solution of (2R)-2-{6-bromoimidazo[1,2-a]pyridin-2-yl}-octahydro-1H- indole trifluoroacetate (Intermediate 20: 60 mg, 0.187 mmol) in MeOH (3 mL) were added Et3N (0.26 mL, 1.87 mmol) and paraformaldehyde (39 mg, 1.31 mmol) . The resulting mixture was stirred for 1h at rt, then NaBH3CN (35 mg, 0.561 mmol) was added to the mixture which was stirred for 3h at 60°C. The mixture was concentrated under reduced pressure. The crude was purified by reverse-phase flash chromatography (C18 aq) using MeCN / H2O (85 / 15) as eluent to provide (2R)-2-{6-bromoimidazo[1,2- a]pyridin-2-yl}-1-methyl-octahydro-1H-indole (Intermediate 21: 60 mg, quant.) as a colorless oil. Mass spec: m / z: 334 [M+H]+. Intermediate 27 was synthesized following Scheme 5. Scheme 5 Step 1 Intermediate 22: rac-tert-butyl 2-[methoxy(methyl)carbamoyl]-5- methylpyrrolidine-1-carboxylate To a solution of rac-1-(tert-butoxycarbonyl)-5-methylpyrrolidine-2-carboxylic acid (CAS: 1248546-01-1, 1.50 g, 6.54 mmol) and N,O-dimethylhydroxylamine (799 mg, 13.1 mmol) in MeCN (30 mL) were added DIPEA (4.22 g, 32.7 mmol) and HATU (2.98 g, 7.85 mmol). The reaction mixture was stirred at rt overnight and then quenched with water (100 mL). The mixture was extracted three times with EtOAc. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to afford rac-tert-butyl 2-[methoxy(methyl)carbamoyl]-5- methylpyrrolidine-1-carboxylate (Intermediate 22: 1.8 g, 86%) as a colorless oil which was used in Step 2 without further purification. Mass spec: m / z: 173 [M+H-Boc]+. Step 2 Intermediate 23: rac-tert-butyl 2-acetyl-5-methylpyrrolidine-1-carboxylate To a solution of rac-tert-butyl 2-[methoxy(methyl)carbamoyl]-5-methylpyrrolidine-1- carboxylate (Intermediate 22:1.80 g, 5.62 mmol) in THF (40 mL) was added a solution of MeMgBr (1.58 g, 13.2 mmol, 1M in THF). The reaction mixture was stirred at rt for 48h and then quenched with a saturated aqueous NH4Cl solution. The reaction mixture was extracted five times with EtOAc. The combined organic layers were washed brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel using PE / EtOAc (4 / 1) to afford rac-tert-butyl 2-acetyl-5-methylpyrrolidine-1-carboxylate (Intermediate 23: 1.2 g, 76%) as a colorless oil. Mass spec: m / z: 128 [M+H-Boc]+. Step 3 Intermediate 24: rac-tert-butyl 2-(2-bromoacetyl)-3-methylpyrrolidine-1- carboxylate To a solution of rac-tert-butyl 2-acetyl-3-methylpyrrolidine-1-carboxylate (Intermediate 23: 500 mg, 1.76 mmol) in THF (20 mL) at 0°C were added Et3N (890 mg, 8.80 mmol) and TMSOTf (733 mg, 3.30 mmol). The reaction mixture was stirred at rt for 1h and then a solution of NBS (587 mg, 3.300 mmol) in THF (5 mL) was added. The reaction mixture was stirred at rt for 4 h and quenched with water. The reaction mixture was extracted with EtOAc three times. The combined organic layers were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel using PE / EtOAc (3 / 1) to afford rac-tert-butyl 2-(2-bromoacetyl)-3-methylpyrrolidine-1-carboxylate (Intermediate 24: 120 mg, 18%) as a brown oil. Mass spec: m / z: 250 [M+H-t-Bu]+. Step 4 Intermediate 25: rac-tert-butyl 2-{6-bromoimidazo[1,2-a]pyridin-2-yl}-5- methylpyrrolidine-1-carboxylate To a solution of rac-tert-butyl 2-(2-bromoacetyl)-3-methylpyrrolidine-1-carboxylate (Intermediate 24: 100 mg, 0.262 mmol) and 5-bromopyridin-2-amine (56.5 mg, 0.327 mmol) in toluene (1.25 mL) and MeCN (3.75 mL) were added KI (5.42 mg, 0.0330 mmol) and NaHCO3(32.9 mg, 0.392 mmol). The reaction mixture was stirred at 100°C for 3h and then concentrated under reduced pressure. The crude was purified by reverse- phase flash chromatography (C18 aq) using MeCN / H2O (0.05% TFA) (1 / 3) as eluent to provide rac-tert-butyl 2-{6-bromoimidazo[1,2-a]pyridin-2-yl}-5-methylpyrrolidine-1- carboxylate (Intermediate 25: 90 mg, 64%) as a brown solid. Mass spec: m / z: 380 [M+H]+. Step 5 Intermediate 26: rac-2-{6-bromoimidazo[1,2-a]pyridin-2-yl}-5-methylpyrrolidine trifluoroacetate To a solution of rac-tert-butyl 2-{6-bromoimidazo[1,2-a]pyridin-2-yl}-5- methylpyrrolidine-1-carboxylate (Intermediate 25: 90 mg, 0.166 mmol) in DCM (1.5 mL) was added TFA (0.5 mL). The reaction mixture was stirred at rt for 2h and then concentrated under reduced pressure to afford rac-2-{6-bromoimidazo[1,2-a]pyridin-2- yl}-5-methylpyrrolidine trifluoroacetate (Intermediate 26: 80 mg, 97%) as a brown oil. Mass spec: m / z: 270 [M+H]+. Step 6 Intermediate 27: rac-2-{6-bromoimidazo[1,2-a]pyridin-2-yl}-1,3- dimethylpyrrolidine A solution of rac-2-{6-bromoimidazo[1,2-a]pyridin-2-yl}-3-methylpyrrolidine trifluoroacetate (Intermediate 26: 50.0 mg, 0.125 mmol) and paraformaldehyde (42.9 mg, 1.42 mmol) in MeOH (3 mL) was stirred at rt for 1h and then NaBH3CN (33.6 mg, 0.534 mmol) was added. The reaction mixture was stirred at 60°C for 1h and then concentrated under reduced pressure. The crude was purified by reverse-phase flash chromatography (C18 aq) using MeCN / H2O (0.05% TFA) (1 / 3) as eluent to afford rac- 2-{6-bromoimidazo[1,2-a]pyridin-2-yl}-1,3-dimethylpyrrolidine (Intermediate 27: 25 mg, 55%) as a white solid. Mass spec: m / z: 294 [M+H]+. Intermediates 33 was synthesized following Scheme 6.

[0022] Scheme 6 Step 1 Intermediate 28: rac-1-tert-butyl 2-methyl 4-methylidenepyrrolidine-1,2- dicarboxylate A solution of tBuOK (2.77 g, 24.7 mmol) in THF (40 mL) was added to a suspension of methyltriphenylphosphonium bromide (8.81 g, 24.7 mmol) in THF (40 mL) at 0°C. The yellow suspension was stirred at 0°C for 2h before the addition of a solution of 1-tert- butyl 2-methyl 4-oxopyrrolidine-1,2-dicarboxylate (CAS: 362706-26-1, 3.00 g, 12.4 mmol) in THF (40 mL). The reaction mixture was stirred at rt for 3h and then quenched with water. The mixture was diluted with EtOAc and both phases were separated. The aqueous layer was extracted twice with EtOAc. The organic layers were combined, washed with brine dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel using PE / EtOAc (9 / 1) to afford rac-1-tert-butyl 2-methyl 4-methylidenepyrrolidine- 1,2-dicarboxylate (Intermediate 28: 1.70 g, 51%) as colorless oil. Mass spec: m / z: 242 [M+H]+. Step 2 Intermediate 29: rac-1-tert-butyl 2-methyl 4-methylpyrrolidine-1,2-dicarboxylate To a solution of rac-1-tert-butyl 2-methyl 4-methylidenepyrrolidine-1,2-dicarboxylate (Intermediate 28: 1.70 g, 7.34 mmol) in MeOH (40 mL) was added Pd / C (225 mg, 10% in carbon). The mixture was placed under a H2atmosphere (3 atm) and stirred at rt overnight. The solids were filtered out through a celite pad and the filtrate was concentrated under reduced pressure to provide rac-1-tert-butyl 2-methyl 4- methylpyrrolidine-1,2-dicarboxylate (Intermediate 29: 1.70 g, 99%) as colorless oil. Mass spec: m / z: 244 [M+H]+. Step 3 Intermediate 30: rac-tert-butyl 2-(2-chloroacetyl)-4-methylpyrrolidine-1- carboxylate To a solution of rac-1-tert-butyl 2-methyl 4-methylpyrrolidine-1,2-dicarboxylate (Intermediate 29: 1.50 g, 5.55 mmol) and sodium 2-chloroacetate (1.80 g, 15.4 mmol) in THF (40 mL) was added a solution of tert-butylmagnesium chloride (1.80 g, 15.4 mmol, 1M in THF) dropwise at 0°C under N2atmosphere. The reaction mixture was stirred at 0~5 °C for 2h. Then, the mixture was allowed to warm to room temperature and stirred overnight. The reaction was quenched with a citric acid solution and the mixture was extracted three times with EtOAc. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to provide rac-tert-butyl 2-(2-chloroacetyl)-4-methylpyrrolidine-1- carboxylate (Intermediate 30: 1.40 g, 48%) as a yellow oil which was used as such in Step 4. Mass spec: m / z: 262 [M+H]+. Step 4 Intermediate 31: rac-tert-butyl 2-{6-bromoimidazo[1,2-a]pyridin-2-yl}-4- methylpyrrolidine-1-carboxylate To a solution of rac-tert-butyl 2-(2-chloroacetyl)-4-methylpyrrolidine-1-carboxylate (Intermediate 30: 700 mg, 0.670 mmol) and 5-bromopyridin-2-amine (278 mg, 1.61 mmol) in MeCN (4 mL) and toluene (1 mL) were added KI (23.0 mg, 0.134 mmol) and NaHCO3(225 mg, 2.68 mmol). The reaction mixture was stirred at 100°C for 18h and then quenched with water (8 mL). The crude concentrated under reduced pressure. The crude was purified by reverse-phase flash chromatography (C18 aq) using MeCN / H2O (neutral) (65 / 35) as eluent to provide rac-tert-butyl 2-{6-bromoimidazo[1,2-a]pyridin-2- yl}-4-methylpyrrolidine-1-carboxylate (Intermediate 31: 330 mg, 65%) as a yellow oil. Mass spec: m / z: 380 [M+H]+. Step 5 Intermediate 32: rac-2-{6-bromoimidazo[1,2-a]pyridin-2-yl}-4-methylpyrrolidine trifluoroacetate To a solution of rac-tert-butyl 2-{6-bromoimidazo[1,2-a]pyridin-2-yl}-4- methylpyrrolidine-1-carboxylate (Intermediate 31: 330 mg, 0.764 mmol) in DCM (4 mL) was added TFA (1 mL). The reaction mixture was stirred at rt for 2h. The reaction mixture was concentrated under reduced pressure to afford rac-2-{6-bromoimidazo[1,2- a]pyridin-2-yl}-4-methylpyrrolidine trifluoroacetate (Intermediate 32: 220 mg, quant) as a yellow oil which was used in Step 6 without further purification. Mass spec: m / z: 280 [M+H]+. Step 6 Intermediate 33: rac-2-{6-bromoimidazo[1,2-a]pyridin-2-yl}-1,4- dimethylpyrrolidine A solution of rac-tert-butyl 2-{6-bromoimidazo[1,2-a]pyridin-2-yl}-4- methylpyrrolidine-1-carboxylate trifluoroacetate (Intermediate 32: 220 mg, 0.675 mmol), Et3N (238 mg, 2.36 mmol) and paraformaldehyde (70.8 mg, 2.36 mmol) in MeOH (4 mL) was stirred at rt for 1h. NaBH3CN (49.3 mg, 0.785 mmol) was added and the reaction mixture was stirred at 60°C for 1h and then quenched with water. The mixture was concentrated under reduced pressure. The crude was purified by reverse- phase flash chromatography (C18 aq) using MeCN / H2O (neutral) (60 / 40) as eluent to afford rac-2-{6-bromoimidazo[1,2-a]pyridin-2-yl}-1,4-dimethylpyrrolidine (Intermediate 33: 140 mg, 69%) as a yellow oil. Mass spec: m / z: 294 [M+H]+. Intermediate 38 was synthesized following Scheme 7. Scheme 7 Step 1 Intermediate 34: rac-1-tert-butyl 2-methyl 4-methoxypyrrolidine-1,2-dicarboxylate To a solution of rac-1-tert-butyl 2-methyl 4-hydroxypyrrolidine-1,2-dicarboxylate (CAS: 897046-42-3, 4.00 g, 15.5 mmol) in DMF (100 mL) at 0°C was added NaH (0.720 g, 17.9 mmol, 60% in mineral oil). The reaction mixture was stirred at 0°C for 15 min. Iodomethane (3.47 g, 24.5 mmol) was added and the mixture was allowed to warm to rt and stirred for 2h. The reaction mixture was quenched with water and extracted three times with EtOAc. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel using PE / EtOAc (1 / 9) to afford rac-1-tert-butyl 2-methyl 4-methoxypyrrolidine-1,2-dicarboxylate (Intermediate 35: 3.30 g, 82%) as colorless liquid. Mass spec: m / z 260 [M+H]+. Step 2 Intermediate 35: rac-tert-butyl 2-(2-chloroacetyl)-4-methylpyrrolidine-1- carboxylate To a solution of rac-1-tert-butyl 2-methyl 4-methoxypyrrolidine-1,2-dicarboxylate (Intermediate 34:1.50 g, 5.21 mmol), sodium 2-chloroacetate (1.68 g, 14.5 mmol) and Et3N (1.17 g, 11.6 mmol) in THF (30 mL) at 0°C was added dropwise a solution of tert- butylmagnesium chloride (15 mL, 14.5 mmol, 1M in THF). The reaction mixture was stirred at 0~5 °C for 2 h. The mixture was allowed to warm to rt and stirred overnight. The reaction was quenched with a citrate acid aqueous solution and the mixture was extracted with three times with EtOAc. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under vacuum to afford rac-tert-butyl 2-(2-chloroacetyl)-4-methylpyrrolidine-1-carboxylate (Intermediate 35: 1.40 g, 48%) as yellow oil which was used in Step 3 without further purification. Mass spec: m / z 278 [M+H]+. Step 3 Intermediate 36: rac-tert-butyl 2-{6-bromoimidazo[1,2-a]pyridin-2-yl}-4- methoxypyrrolidine-1-carboxylate To a solution of rac-tert-butyl 2-(2-chloroacetyl)-4-methylpyrrolidine-1-carboxylate (Intermediate 35: 800 mg, 1.44 mmol) in MeCN (10 mL) and toluene (4 mL) was added 5-bromopyridin-2-amine (600 mg, 3.46 mmol), KI (100 mg, 0.576 mmol) and NaHCO3(480 mg, 5.76 mmol). The reaction mixture was stirred at 100°C overnight and then quenched with water. The mixture was extracted three times with EtOAc. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel using DCM / MeOH (10 / 1) as eluent to afford rac- tert-butyl 2-{6-bromoimidazo[1,2-a]pyridin-2-yl}-4-methoxypyrrolidine-1-carboxylate (Intermediate 36: 460 mg, 64%) as a brown solid. Mass spec: m / z 396 [M+H]+. Step 4 Intermediate 37: rac-2-{6-bromoimidazo[1,2-a]pyridine-2-yl}-4- methoxypyrrolidine trifluoroacetate To a solution of rac-tert-butyl 2-{6-bromoimidazo[1,2-a]pyridine-2-yl}-4- methoxypyrrolidine-1-carboxylate (Intermediate 36: 360 mg, 0.726 mmol) in DCM (8 mL) was added TFA (2 mL). The reaction mixture was stirred at rt for 2h, then concentrated under reduced pressure to give the rac-2-{6-bromoimidazo[1,2-a]pyridine- 2-yl}-4-methoxypyrrolidine trifluoroacetate (Intermediate 37: 270 mg, quant.) as black oil which was used in Step 5 without further purification. Mass spec: m / z 296 [M+H]+. Step 5 Intermediate 38: rac-2-{6-bromoimidazo[1,2-a]pyridine-2-yl}-4-methoxy-1- methylpyrrolidine A solution of rac-2-{6-bromoimidazo[1,2-a]pyridine-2-yl}-4-methoxypyrrolidine trifluoroacetate (Intermediate 37: 270 mg, 0.730 mmol), Et3N (277 mg, 2.74 mmol) and paraformaldehyde (82.1 mg, 2.74 mmol) in MeOH (5 mL) was stirred at rt for 1h. NaBH3CN (57.3 mg, 0.912 mmol) was added and the reaction mixture was stirred at 60°C for 1h, and then quenched with water. The mixture was concentrated under reduced pressure. The crude was purified by reverse-phase flash chromatography (C18 aq) using CAN / H2O (neutral) (60 / 40) as eluent to afford rac-2-{6-bromoimidazo[1,2- a]pyridine-2-yl}-4-methoxy-1-methylpyrrolidine (Intermediate 38: 120 mg, 50%) as a yellow oil. Mass spec: m / z 312 [M+H]+. General Procedure 1 Intermediate 43 was synthesized following Scheme 8. Intermediate 40 Intermediate 41 NaBH(OAc)3AcOH, H2CO TFA, DCM, rt MeTHF, rt Step 3 Step 4 Intermediate 42Intermediate 43Scheme 8 Step 1 Intermediate 40: tert-butyl (2R)-2-(2-chloroacetyl)pyrrolidine-1-carboxylate To a solution of 1-tert-butyl 2-methyl (2R)-pyrrolidine-1,2-dicarboxylate (CAS: 73323- 65-6: αD+66.7°, C=1 in MeOH; 2.00 g, 8.29 mmol), sodium chloroacetate (2.54 g, 20.7 mmol) and triethylamine (2.3 mL, 16.6 mmol) in THF-anhydrous (18.8 mL) was added dropwise a tert-butylmagnesium chloride solution (1M in THF, 21 mL, 20.7 mmol) at 2-3°C over 20 min. The reaction mixture was stirred between 0-5°C for 2h. A solution of citric acid (3.68 g, 19.1 mmol) in H2O (10.4 mL) was slowly added to the reaction mixture while maintaining the temperature between 0-5°C. EtOAc was added to the reaction mixture, the phases were separated. The organic layer was washed twice with a solution of NaHCO3 / NaCl (470 mg of NaHCO3, 1.6 g of NaCl in 10mL) and once with brine. The combined organic layers were dried over hydrophobic paper and concentrated under reduced pressure to afford tert-butyl (2R)-2-(2- chloroacetyl)pyrrolidine-1-carboxylate (Intermediate 40: 2.05 g, 95%) as a white solid which was used in Step 2 without further purification. Mass spec: m / z: 192 [M+H- tBu]+, 148 [M+H-Boc]+;1H NMR (400 MHz, DMSO-d6) δ ppm 4.71 – 4.53 (m, 2H), 4.40 (ddd, J = 11.1, 8.7, 4.8 Hz, 1H), 3.34 (d, J = 7.2 Hz, 2H), 2.24 – 2.05 (m, 1H), 1.93 – 1.66 (m, 3H), 1.35 (d, J = 32.2 Hz, 9H). Chiral analysis: Chiral purity = 98.6% ee (Column: IC 250x4.65µm; Eluent:5% MeOH+0.5% IPA; Flow rate: 2.4 mL / min; rt = 3.88 min). Step 2 Intermediate 41: tert-butyl (2R)-2-{6-bromoimidazo[1,2-a]pyrazin-2- yl}pyrrolidine-1-carboxylate In a round bottom flask, to a suspension of 5-bromopyrazin-2-amine (CAS: 59489-71-3, 0.92 g, 5.18 mmol) and tert-butyl (2R)-2-(2-chloroacetyl)pyrrolidine-1-carboxylate (Intermediate 40: 2.03 g, 7.77 mmol) in toluene (5.2 mL) and MeCN (5.2 mL) were added NaHCO3(0.52 g, 6.22 mmol) and sodium iodide (1.17 g, 7.77 mmol). The reaction mixture was heated at 80°C overnight. The solvents were removed under reduced pressure and the residue was taken up in EtOAc. The mixture was filtered through a pad of decalite, then the filtrate was washed with a saturated solution of Na2S2O3. The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The crude material was purified by flash chromatography on silica gel using a gradient of EtOAc in heptane from 30% to 100% to afford tert-butyl (2R)-2-{6-bromoimidazo[1,2-a]pyrazin-2-yl}pyrrolidine-1-carboxylate (Intermediate 41: 485 mg, 26%) as a brown solid. Mass spec: m / z: 367 [M+H]+, 369 [M+H+2]+;1H NMR (400 MHz, DMSO-d6) δ ppm 8.92 (d, J = 16.1 Hz, 1H), 8.86 (s, 1H), 7.90 (d, J = 10.1 Hz, 1H), 4.99 (dd, J = 16.0, 7.9 Hz, 1H), 3.46 (ddd, J = 11.5, 7.7, 4.1 Hz, 1H), 3.39 (dt, J = 10.4, 8.1 Hz, 1H), 2.31 – 2.15 (m, 1H), 2.05 (s, 1H), 1.91 (dq, J = 18.0, 6.2 Hz, 2H), 1.30 (s, 9H). Chiral analysis: Chiral purity = 98.8% ee (Column: IA 250 x 4.65 µm; Eluent: 30% (iPrOH+0.5% IPA); Flow rate: 2.4 mL / min; rt = 3.03 min). Intermediate 41A: rac-tert-butyl 2-{6-bromoimidazo[1,2-a]pyrazin-2- yl}pyrrolidine-1-carboxylate Following an analogous procedure to Scheme 8, Step 2, using 5-bromopyrazin-2-amine as the amine (25 g, 0.14 mol) and rac-tert-butyl-2-(2-chloroacetyl)pyrrolidine-1- carboxylate (Intermediate 1: 60 g, 0.206 mol) as the ketone, afforded rac-tert-butyl 2- {6-bromoimidazo[1,2-a]pyrazin-2-yl}pyrrolidine-1-carboxylate (Intermediate 41A: 18.65 g, 36%) as a brown solid. Mass spec: m / z: 367 [M+H]+, 369 [M+H+2]+;1H NMR (400 MHz, DMSO-d6) δ ppm 8.98 – 8.84 (m, 2H), 7.90 (d, J = 9.2 Hz, 1H), 4.99 (dd, J = 15.8, 7.8 Hz, 1H), 3.50 – 3.34 (m, 2H), 2.23 (s, 1H), 2.05 (s, 1H), 1.97 – 1.82 (m, 2H), 1.30 (s, 9H). Intermediate 41B: tert-butyl (2R)-2-(6-bromo-8-methyl-imidazo[1,2-a]pyrazin-2- yl)pyrrolidine-1-carboxylate Following an analogous procedure to Scheme 8, Step 2, using 5-bromo-3- methylpyrazin-2-amine (CAS: 74290-67-8, 0.75 g, 3.90 mmol) as the amine and tert- butyl (2R)-2-(2-chloroacetyl)pyrrolidine-1-carboxylate (Intermediate 40: 1.53 g, 5.86 mmol) as the ketone, afforded tert-butyl (2R)-2-(6-bromo-8-methyl-imidazo[1,2- a]pyrazin-2-yl)pyrrolidine-1-carboxylate (Intermediate 41B: 400 mg, 27%) as an orange solid. Mass spec: m / z: 382 [M+H]+, 384 [M+H+2]+;1H NMR (400 MHz, DMSO-d6) δ ppm 8.75 (d, J = 15.5 Hz, 1H), 7.83 (d, J = 14.6 Hz, 1H), 4.97 (s, 1H), 3.45 (s, 1H), 3.42 – 3.36 (m, 1H), 2.70 (s, 3H), 2.24 (d, J = 13.8 Hz, 1H), 2.05 (dq, J = 12.4, 5.4 Hz, 1H), 1.93 – 1.80 (m, 2H), 1.50 – 1.17 (m, 9H). Intermediate 41C: (rel-2R)-tert-butyl 2-{6-bromoimidazo[1,2-a]pyrazin-2- yl}pyrrolidine-1-carboxylate and Intermediate 41D: (rel-2S)-tert-butyl 2-{6- bromoimidazo[1,2-a]pyrazin-2-yl}pyrrolidine-1-carboxylate rac-tert-Butyl 2-{6-bromoimidazo[1,2-a]pyrazin-2-yl}pyrrolidine-1-carboxylate (Intermediate 41A) was separated by chiral SFC using the following conditions: Column: CHIRAL ART Amylose-C NEO 3x25 cm, 5μm; Mobile Phase A: CO2, Mobile Phase B: MeOH (with 1% 2M NH3in MeOH); Flow rate: 85 mL / min; Gradient: isocratic 40% B. Intermediate 41C: (rel-2R)-tert-butyl 2-{6-bromoimidazo[1,2-a]pyrazin-2- yl}pyrrolidine-1-carboxylate First eluting compound (retention time: 2.7 mins) Mass spec: m / z: 367 [M+H]+, 369 [M+H+2]+;1H NMR (400 MHz, DMSO-d6) δ ppm 8.98 – 8.84 (m, 2H), 7.90 (d, J = 9.2 Hz, 1H), 4.99 (dd, J = 15.8, 7.8 Hz, 1H), 3.50 – 3.34 (m, 2H), 2.23 (s, 1H), 2.05 (s, 1H), 1.97 – 1.82 (m, 2H), 1.30 (s, 9H). Intermediate 41D: (rel-2S)-tert-butyl 2-{6-bromoimidazo[1,2-a]pyrazin-2- yl}pyrrolidine-1-carboxylate Second eluting compound (retention time: 6.57 mins) Mass spec: m / z: 367 [M+H]+, 369 [M+H+2]+;1H NMR (400 MHz, DMSO-d6) δ ppm 8.98 – 8.84 (m, 2H), 7.90 (d, J = 9.2 Hz, 1H), 4.99 (dd, J = 15.8, 7.8 Hz, 1H), 3.50 – 3.34 (m, 2H), 2.23 (s, 1H), 2.05 (s, 1H), 1.97 – 1.82 (m, 2H), 1.30 (s, 9H). Step 3 Intermediate 42: (2R)-2-{6-bromoimidazo[1,2-a]pyrazin-2-yl}pyrrolidine trifluoroacetate Under a nitrogen atmosphere, tert-butyl (2R)-2-(6-bromoimidazo[1,2-a]pyrazin-2- yl)pyrrolidine-1-carboxylate (Intermediate 41: 185 mg, 0.504 mmol) was solubilized in DCM (2.5 mL) and 2,2,2-trifluoroacetic acid (0.39 mL, 5.04 mmol ) was added. The mixture was stirred at rt for 2h. The reaction mixture was concentrated under reduced pressure to afford (2R)-2-{6-bromoimidazo[1,2-a]pyrazin-2-yl}pyrrolidine trifluoroacetate (Intermediate 42: 228 mg, quant.) as a brown oil which were used in Step 4 without further purification. Mass spec: m / z: 267 [M+H]+; 269 [M+H+2]+. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.62 (s, 1H), 9.05 (d, J = 1.4 Hz, 1H), 9.02 – 9.00 (m, 1H), 8.24 (s, 1H), 4.92 (p, J = 6.9 Hz, 1H), 3.33 (dq, J = 8.3, 5.1 Hz, 2H), 2.49 – 2.36 (m, 1H), 2.23 – 1.97 (m, 3H). Chiral analysis: Chiral purity = 98.5% ee (Column: AD 250x4.65µm; Eluent: 40% (EtOH + 0.5% IPA); Flow rate: 2.4 mL / min; rt = 4.74 min). Intermediate 42A: rac-2-{6-bromoimidazo[1,2-a]pyrazin-2-yl}pyrrolidine trifluoroacetate Following an analogous procedure to Scheme 8, Step 3, using rac-tert-butyl 2-(6- bromoimidazo[1,2-a]pyrazin-2-yl)pyrrolidine-1-carboxylate (Intermediate 41A: 21.86 g, 56.5 mmol) as the Boc-protected amine, afforded rac-2-{6-bromoimidazo[1,2- a]pyrazin-2-yl}pyrrolidine trifluoroacetate (Intermediate 42A: 22 g, quant.) as an orange oil. Mass spec: m / z: 267 [M+H]+, 269 [M+H+2]+;1H NMR (400 MHz, DMSO- d6) δ ppm 9.62 (s, 1H), 9.05 (d, J = 1.4 Hz, 1H), 9.02 – 9.00 (m, 1H), 8.24 (s, 1H), 4.92 (p, J = 6.9 Hz, 1H), 3.33 (dq, J = 8.3, 5.1 Hz, 2H), 2.49 – 2.36 (m, 1H), 2.23 – 1.97 (m, 3H). Intermediate 42B: (2R)-2-{6-bromo-8-methylimidazo[1,2-a]pyrazin-2- yl}pyrrolidine trifluoroacetate Following an analogous procedure to Scheme 8, Step 3, starting with tert-butyl (2R)-2- (6-bromo-8-methyl-imidazo[1,2-a]pyrazin-2-yl)pyrrolidine-1-carboxylate (Intermediate 41B: 400 mg, 1.05 mmol), afforded (2R)-2-{6-bromo-8- methylimidazo[1,2-a]pyrazin-2-yl}pyrrolidine trifluoroacetate (Intermediate 42B: 691 mg, quant.) as a red oil. Mass spec: m / z: 281 [M+H]+, 283 [M+H+2]+;1H NMR (400 MHz, DMSO-d6) δ ppm 9.71 (s, 1H), 8.97 (s, 1H), 8.88 (d, J = 0.8 Hz, 1H), 8.20 (s, 1H), 4.88 (p, J = 7.0 Hz, 1H), 3.40 – 3.24 (m, 2H), 2.76 (s, 3H), 2.48 – 2.36 (m, 1H), 2.23 – 1.97 (m, 3H). Step 4 Intermediate 43: (2R)-2-{6-bromoimidazo[1,2-a]pyrazin-2-yl}-1-methylpyrrolidine (2R)-2-{6-bromoimidazo[1,2-a]pyrazin-2-yl}pyrrolidine trifluoroacetate (Intermediate 42: 228 mg, 0.508 mmol) was dissolved in 2-MeTHF (2.5 mL). Formaldehyde (37% aq, 0.076 mL, 1.02 mmol) was added followed by acetic acid (0.058 mL, 1.02 mmol). The reaction mixture was stirred for 20 min, then NaBH(OAc)3(167 mg, 0.763 mmol) was added portion wise (gas evolution). The mixture was stirred for 2h, then cooled to 0 °C and quenched slowly with a saturated solution of NaHCO3. The aqueous layer was extracted with EtOAc three times. The organic layers were combined, washed with brine, dried over anhydrous MgSO4and the solvents were removed under reduced pressure to afford (2R)-2-{6-bromoimidazo[1,2-a]pyrazin-2-yl}-1-methylpyrrolidine (Intermediate 43: 140 mg, 94%) as a yellow oil. m / z: 281 [M+H]+, 283 [M+H+2]+;1H NMR (400 MHz, DMSO-d6) δ ppm 8.91 (d, J = 1.4 Hz, 1H), 8.86 (d, J = 1.2 Hz, 1H), 8.02 (s, 1H), 3.64 (s, 1H), 3.18 (d, J = 9.0 Hz, 1H), 2.46 (d, J = 8.6 Hz, 1H), 2.30 (s, 4H), 1.95 – 1.80 (m, 3H). Chiral analysis: Chiral purity = 98.8% ee (Column: AD 250 x 4.65 µm N°317; Eluent: 25 % (iPrOH + 0.5% IPA); Flow rate: 2.4 mL / min; rt = 6.45 min). Intermediate 43A: rac-2-{6-bromoimidazo[1,2-a]pyrazin-2-yl}-1-methylpyrrolidine Following an analogous procedure to Scheme 8, Step 4, starting with rac-6-bromo-2- pyrrolidin-2-yl-imidazo[1,2-a]pyrazine trifluoroacetate (Intermediate 42A: 19.30 g, 48.1 mmol) as the amine, afforded rac-2-{6-bromoimidazo[1,2-a]pyrazin-2-yl}-1- methylpyrrolidine (Intermediate 43A: 8.13 g, 58%) as a brown oil. Mass spec: m / z: 281 [M+H]+, 283 [M+H+2]+;1H NMR (400 MHz, DMSO-d6) δ ppm 8.91 (d, J = 1.4 Hz, 1H), 8.86 (d, J = 1.2 Hz, 1H), 8.02 (s, 1H), 3.64 (s, 1H), 3.18 (d, J = 9.0 Hz, 1H), 2.46 (d, J = 8.6 Hz, 1H), 2.30 (s, 4H), 1.95 – 1.80 (m, 3H). Intermediate 43B: (2R)-2-{6-bromo-8-methylimidazo[1,2-a]pyrazin-2-yl}-1- methylpyrrolidine Following an analogous procedure to Scheme 8, Step 4, starting with (2R)-2-{6-bromo- 8-methylimidazo[1,2-a]pyrazin-2-yl}pyrrolidine trifluoroacetate (Intermediate 42B: 691 mg, 1.75 mmol) as the amine, afforded (2R)-2-{6-bromo-8-methylimidazo[1,2- a]pyrazin-2-yl}-1-methylpyrrolidine (Intermediate 43B: 313 mg, 59%) as a yellow oil. m / z: 295 [M+H]+, 297 [M+H+2]+;1H NMR (400 MHz, DMSO-d6) δ ppm 8.74 (s, 1H), 7.95 (s, 1H), 3.61 – 3.46 (m, 1H), 3.16 (s, 1H), 2.71 (s, 3H), 2.38 (s, 1H), 2.32 – 2.20 (m, 4H), 1.83 (d, J = 16.7 Hz, 3H). Intermediate 44: (2S)-2-{6-bromoimidazo[1,2-a]pyrazin-2-yl}-1-methylpyrrolidine rac-2-{6-bromoimidazo[1,2-a]pyrazin-2-yl}-1-methylpyrrolidine (Intermediate 43A: 8.13 g, 28 mmol) was purified by chiral chromatography (Column: Chiralpak AD-H 250 x 30 mm, 5 µm; Eluent: CO2 / ( iPrOH + 0.5% IPA) 65 / 35; rt = 2.5 to 3.5 min) to afford (2S)-2-{6-bromoimidazo[1,2-a]pyrazin-2-yl}-1-methylpyrrolidine (Intermediate 44: 3.95 g, 49%). m / z: 281 [M+H]+, 283 [M+H+2]+;1H NMR (400 MHz, DMSO-d6) δ ppm 8.91 (d, J = 1.4 Hz, 1H), 8.86 (d, J = 1.2 Hz, 1H), 8.02 (s, 1H), 3.64 (s, 1H), 3.18 (d, J = 9.0 Hz, 1H), 2.46 (d, J = 8.6 Hz, 1H), 2.30 (s, 4H), 1.95 – 1.80 (m, 3H). Chiral analysis: Column: AD 250 x 4.6, 5 µm; Eluent: CO2 / (iPrOH + 0.5% IPA) 65 / 35; Flow rate: 2.4 mL / min; rt = 2.80 min, first eluting compound. General Procedure 2 Intermediates 47 and 48 were synthesized following Scheme 9. Scheme 9 Step 1 To a vial purged and maintained with an inert atmosphere of nitrogen, were added methyl 3-iodo-1-methyl-1H-indazole-6-carboxylate (CAS: 1041205-25-7, 1 eq), the boronic acid stated below (3 eq), Pd(PPh3)4(0.1 eq) and K3PO4(4 eq) in toluene / H2O (10 / 1) (0.15 M). The resulting mixture was stirred for 16 h at 110 °C. The solids were filtered through a pad of celite. The solution was concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel using a gradient of EtOAc in heptane from 0% to 50% to afford the intermediate detailed below. Intermediate 45: Methyl 3-ethyl-1-methyl-1H-indazole-6-carboxylate Following Scheme 9, Step 1, using ethylboronic acid (CAS: 4433-63-0) as the boronic acid, afforded methyl 3-ethyl-1-methyl-1H-indazole-6-carboxylate (Intermediate 45: 71 mg, 20%) as a colorless oil. Mass spec: m / z: 219 [M+H]+;1H NMR (400 MHz, DMSO-d6) δ ppm 8.21 (s, 1H), 7.85 (d, J = 8.4 Hz, 1H), 7.66 (dd, J = 8.5, 1,4 Hz, 1H), 4.05 (s, 3H), 3.91 (s, 3H), 2.94 (q, J = 7.5 Hz, 2H), 1.31 (t, J = 7.6 Hz, 3H). Intermediate 46: Methyl 3-cyclopropyl-1-methyl-1H-indazole-6-carboxylate Following Scheme 9, Step 1, using cyclopropylboronic acid (CAS: 411235-57-9) as the boronic acid, afforded methyl 3-cyclopropyl-1-methyl-1H-indazole-6-carboxylate (Intermediate 46: 108 mg, 75%) as a pale yellow solid. Mass spec: m / z: 231 [M+H]+;1H NMR (400 MHz, DMSO-d6) δ ppm 8.19 (d, J = 1.4 Hz, 1H), 7.89 (dd, J = 8.4, 2.0 Hz, 1H), 7.65 (dd, J = 8.5, 1.5 Hz, 1H), 4.01 (s, 3H), 3.90 (s, 3H), 2.31 (tt, J = 8.3, 5.1 Hz, 1H), 1.01 (dtd, J = 8.6, 5.1, 2.2 Hz, 2H), 0.97 – 0.91 (m, 2H). Step 2 A suspension of the appropriate intermediate prepared in Scheme 9, Step 1 (1 eq) in ammonium hydroxide (20 eq) was stirred overnight at 50°C in a sealed tube. The reaction mixture was diluted in H2O and the precipitate was filtered to provide the expected products detailed below. Intermediate 47: 3-Ethyl-1-methyl-1H-indazole-6-carboxamide Following Scheme 9, Step 2, using methyl 3-ethyl-1-methyl-1H-indazole-6-carboxylate (Intermediate 45), afforded 3-ethyl-1-methyl-1H-indazole-6-carboxamide (Intermediate 47: 44 mg, 69%) as a white solid. Mass spec: m / z: 204 [M+H]+;1H NMR (400 MHz, DMSO-d6) δ ppm 8.11 (d, J = 1.2 Hz, 1H), 8.03 (d, J = 5.1 Hz, 1H), 7.80 – 7.74 (m, 1H), 7.59 (dd, J = 8.5, 1.4 Hz, 1H), 7.40 (s, 1H), 4.01 (s, 3H), 2.93 (q, J = 7.5 Hz, 2H), 1.31 (t, J = 7.6 Hz, 3H). Intermediate 48: 3-Cyclopropyl-1-methyl-1H-indazole-6-carboxamide Following Scheme 9, Step 2, using afforded methyl 3-cyclopropyl-1-methyl-1H- indazole-6-carboxylate (Intermediate 46) afforded 3-cyclopropyl-1-methyl-1H- indazole-6-carboxamide (Intermediate 48: 33 mg, quant.) as a white solid. Mass spec: m / z: 217 [M+H]+;1H NMR (400 MHz, DMSO-d6) δ ppm 8.09 (s, 1H), 8.02 (s, 1H), 7.81 (d, J = 8.4 Hz, 1H), 7.59 (dd, J = 8.5, 1.4 Hz, 1H), 7.40 (s, 1H), 3.97 (s, 3H), 2.29 (tt, J = 8.3, 5.1 Hz, 1H), 1.05 – 0.90 (m, 4H). Intermediate 49: 1-methyl-1H-indazole-5-carboxamide A stirred solution of 1-methyl-1H-indazole-5-carboxylic acid (CAS: 1176754-31-6, 2.50 g, 14.2 mmol) in anhydrous DCM (125 mL), with a few drops of DMF, was cooled to 0°C before addition of thionyl chloride (1.1 mL, 15.6 mmol). The reaction mixture was stirred 4h at rt until consumption of starting material observed. The mixture was concentrated to dryness and re-dissolved in DCM (110 mL). A solution of NH4OH (11 mL, 71.0 mmol , 25% in water) was added and the mixture was stirred vigorously overnight at rt. Water was added and the mixture was extracted three times with EtOAc. The combined organic layers were dried over a phase separator and concentrated to dryness. The residue was taken up in DCM and the precipitate was filtered, washed with DCM and dried under vaccum at 40°C to afford 1-methyl-1H-indazole-5-carboxamide (Intermediate 49: 1.6 g, 64%) as a beige solid. Mass spec: m / z: 176 [M+H]+;1H NMR (400 MHz, DMSO-d6) δ ppm 8.35 (dd, J = 1.5, 0.7 Hz, 1H), 8.17 (d, J = 0.9 Hz, 1H), 7.98 (s, 1H), 7.93 (dd, J = 8.8, 1.6 Hz, 1H), 7.67 (d, J = 8.8 Hz, 1H), 7.27 (s, 1H), 4.07 (s, 3H). Intermediates 51 and 52 were synthesized following Scheme 10. Scheme 10 Step 1 Intermediate 50: Methyl 1,3-dimethyl-1H-indazole-6-carboxylate To a solution of methyl 4-acetyl-3-fluorobenzoate (CAS: 1059549-72-2, 5.00 g, 24.2 mmol) in NMP (35 mL) was added methylhydrazine (1.5 mL, 29.1 mmol) and the mixture was stirred overnight at 100°C in a sealed tube. The solution was cooled to rt, diluted with H2O (35 mL) and the aqueous layer was extracted with EtOAc (40mL). The organic layer was washed three times with H2O, dried over anhydrous MgSO4, filtered, and concentrated to dryness to afford methyl 1,3-dimethyl-1H-indazole-6- carboxylate (Intermediate 50: 4.3 g, 87%) as an orange oil which was used in Step 2 without further purification. Mass spec: m / z: 205 [M+H]+;1H NMR (400 MHz, DMSO- d6): δ ppm 8.21 (s, 1H), 7.81 (d, J=8.5 Hz, 1H), 7.65 (dd, J=8.5, 1.3 Hz, 1H), 4.03 (s, 3H), 3.90 (s, 3H), 2.50 (s, 3H). Step 2 Intermediate 51: 1,3-dimethyl-1H-indazole-6-carboxylic acid To a solution of methyl 1,3-dimethylindazole-6-carboxylate (Intermediate 50: 4.3 g, 20.0 mmol) in a mixture of THF (50 mL) / MeOH (50 mL) was added a NaOH solution (60 mL, 60.0 mmol, 1M in water) dropwise over 14 min. The resulting mixture was stirred at rt for 45 min. The solvents were removed under reduced pressure and the residue was acidified with a solution of HCl (60 mL, 1N in H2O). The precipitate was filtered, rinsed with H2O (20 mL) and dried under reduced pressure at 40°C overnight to afford 1,3-dimethyl-1H-indazole-6-carboxylic acid (Intermediate 51: 3.85 g, quant.) as a yellow solid. Mass spec: m / z: 191 [M+H]+;1H NMR (400 MHz, DMSO-d6): δ ppm 13.04 (s, 1H), 8.19 (t, J=1.1 Hz, 1H), 7.79 (dd, J=8.3, 0.8 Hz, 1H), 7.65 (dd, J=8.4, 1.3 Hz, 1H), 4.03 (s, 3H), 2.51 (s, 3H). Step 3 Intermediate 52: 1,3-dimethylindazole-6-carboxamide Following the procedure exemplified by Scheme 9, Step 2 (General Procedure 2), using methyl 1,3-dimethyl-1H-indazole-6-carboxylate (Intermediate 50) as the ester, afforded 1,3-dimethylindazole-6-carboxamide (Intermediate 52: 2.15 g, 61%). Mass spec: m / z: 190 [M+H]+;1H NMR (400 MHz, DMSO-d6) δ ppm 8.11 (t, J = 1.1 Hz, 1H), 8.02 (s, 1H), 7.74 (dd, J = 8.4, 0.8 Hz, 1H), 7.60 (dd, J = 8.4, 1.4 Hz, 1H), 7.41 (s, 1H), 4.00 (s, 3H), 2.49 (s, 3H). Intermediate 55 was synthesized following Scheme 11.

[0023] Scheme 11 Step 1 Intermediate 53: 6-bromo-5-fluoro-1,3-dimethyl-1H-indazole To a stirred solution of 1-(4-bromo-2,5-difluorophenyl)ethan-1-one (CAS: 123942-11- 0, 1.00 g, 4.04 mmol) in NMP (8 mL) was added methylhydrazine (0.26 mL, 4.85 mmol) and the mixture was stirred overnight at 120°C. After this time, water was added, and a precipitate was observed. This precipitate was filtered and dried under vacuum to afford 6-bromo-5-fluoro-1,3-dimethyl-1H-indazole (Intermediate 53: 859 mg, 87%) as a white solid. Mass spec: m / z: 243 [M+H]+, 245 [M+H+2]+;1H NMR (400 MHz, DMSO-d6) δ ppm 8.07 (d, J = 5.6 Hz, 1H), 7.72 (d, J = 8.9 Hz, 1H), 3.95 (s, 3H), 2.44 (s, 3H). Step 2 Intermediate 54: 5-fluoro-1,3-dimethyl-1H-indazole-6-carboxylic acid In a sealed tube, to a stirred solution of Xantphos (409 mg, 0.707 mmol), 6-bromo-5- fluoro-1,3-dimethyl-indazole (Intermediate 53: 859 mg, 3.53 mmol), diacetoxypalladium (159 mg, 0.707 mmol), and oxalic acid (477 mg, 5.30 mmol) in DMF (5 mL) were added acetic anhydride (0.49 mL, 5.30 mmol), DIPEA (0.93 mL, 5.30 mmol) and water (0.19 mL, 10.6 mmol). The resulting mixture was heated at 100 °C for 2 h. The mixture was diluted with EtOAc and filtered through decalite. The filtrate was washed with brine, the organic layer was dried with hydrophobic paper and evaporated to dryness. The crude was purified by reverse-phase flash chromatography (50 g aq) using a gradient of MeCN in water from 0% to 100% (neutral) to afford 5- fluoro-1,3-dimethyl-1H-indazole-6-carboxylic acid (Intermediate 54: 264 mg, 27%) as a beige solid. Mass spec: m / z: 209 [M+H]+;1H NMR (400 MHz, DMSO-d6): δ ppm 13.28 (s, 1H), 8.10 (d, J=5.7 Hz, 1H), 7.62 (d, J=11.0 Hz, 1H), 4.02 (s, 3H), 2.47 (s, 3H). Step 3 Intermediate 55: 5-fluoro-1,3-dimethyl-1H-indazole-6-carboxamide A solution of 5-fluoro-1,3-dimethyl-indazole-6-carboxylic acid (Intermediate 54: 244 mg, 1.17 mmol), DIPEA (1.0 mL, 5.86 mmol) and HATU (546 mg, 1.41 mmol) in THF (12 mL) was stirred 30 min at rt in a sealed vial. After this time, NH3gas was injected, and the mixture was stirred overnight at rt. Then, the mixture was diluted with EtOAc and washed with brine. The organic layer was dried with hydrophobic paper and evaporated to dryness. The crude material was purified by flash chromatography on silica gel (12 g) using a gradient of EtOAc / EtOH (3 / 1) in heptane from 0% to 60% to afford 5-fluoro-1,3-dimethyl-1H-indazole-6-carboxamide (Intermediate 55: 230 mg, 94%) as a white solid. Mass spec: m / z: 208 [M+H]+. General procedure 3 Intermediates 61-65 were synthesized following General Procedure 3 in Scheme 12. Scheme 12 Step 1 To a solution of the appropriate boronic acid (1 eq), the appropriate aryl bromide or aryl chloride (R-X; 1 eq) and Na2CO3(3 eq) in 1,4-dioxane / H2O 1 / 1 (0.6 M) was added Pd(PPh3)4(0.1 eq). The reaction mixture was stirred at 80°C overnight. The reaction mixture was cooled to rt, diluted with EtOAc and filtered through a pad of celite. A saturated solution of NaHCO3was added to the filtrate. The aqueous layer was extracted with twice with EtOAc and the organic layer was washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under vacuum. The crude material was purified by flash chromatography on silica gel using a gradient of EtOAc / EtOH (3 / 1) in heptane from 0% to 100% to afford the corresponding Intermediates detailed below. Intermediate 56: Methyl 2-fluoro-4-(2-methyl-1,3-thiazol-5-yl)benzoate Following Step 1 of General Procedure 3 shown in Scheme 12, using 5-bromo-2- methyl-1,3-thiazole (CAS: 57268-16-3) as the aryl bromide (R-X) and [3-fluoro-4- (methoxycarbonyl)phenyl]boronic acid (CAS: 505083-04-5) as the boronic acid, afforded methyl 2-fluoro-4-(2-methyl-1,3-thiazol-5-yl)benzoate (Intermediate 56: 118 mg, 19%) was obtained as a beige solid. Mass spec: m / z: 252 [M+H]+;1H NMR (400 MHz, DMSO-d6) δ ppm 8.28 (s, 1H), 7.92 (t, J = 8.0 Hz, 1H), 7.71 (dd, J = 12.2, 1.8 Hz, 1H), 7.55 (dd, J = 8.2, 1.8 Hz, 1H), 3.86 (s, 3H), 2.71 (s, 3H). Intermediate 57: Methyl 2-fluoro-4-(pyrazin-2-yl)benzoate Following Step 1 of General Procedure 3 shown in Scheme 12, using 2- chloropyrazine (CAS: 14508-49-7) as the aryl chloride (R-X) and [3-fluoro-4- (methoxycarbonyl)phenyl]boronic acid as the boronic acid, afforded methyl 2-fluoro-4- (pyrazin-2-yl)benzoate (Intermediate 57: 91 mg, 40%) as a white solid. Mass spec: m / z: 233 [M+H]+;1H NMR (400 MHz, DMSO-d6) δ ppm 9.40 (d, J = 1.6 Hz, 1H), 8.79 (dd, J = 2.5, 1.5 Hz, 1H), 8.72 (d, J = 2.5 Hz, 1H), 8.15 (d, J = 1.7 Hz, 1H), 8.12 (dd, J = 5.7, 1.5 Hz, 1H), 8.09 – 8.01 (m, 1H), 3.89 (s, 3H). Intermediate 58: Methyl 2-fluoro-4-(1,3-thiazol-5-yl)benzoate Following Step 1 of General Procedure 3 shown in Scheme 12, using 5-bromothiazole (CAS: 3034-55-7) as the aryl-bromide (R-X) and [3-fluoro-4- (methoxycarbonyl)phenyl]boronic acid as the boronic acid, afforded methyl 2-fluoro-4- (1,3-thiazol-5-yl)benzoate (Intermediate 58: 1.2 g, 36%) as a white solid. Mass spec: m / z: 238 [M+H]+. Intermediate 59: Methyl 2-fluoro-5-(2-methyl-1,3-thiazol-5-yl)benzoate Following Step 1 of General Procedure 3 shown in Scheme 12, using 5-bromo-2- methyl-1,3-thiazole (CAS: 57268-16-3) as the aryl-bromide (R-X) and [4-fluoro-3- (methoxycarbonyl)phenyl]boronic acid (CAS: 874219-35-9) as the boronic acid, afforded methyl 2-fluoro-5-(2-methyl-1,3-thiazol-5-yl)benzoate (Intermediate 59: 106 mg, 17%) was obtained as an off-white solid. Mass spec: m / z: 252 [M+H]+;1H NMR (400 MHz, DMSO-d6) δ ppm 8.09 (s, 1H), 8.00 (dd, J = 6.7, 2.5 Hz, 1H), 7.93 (ddd, J = 8.7, 4.5, 2.6 Hz, 1H), 7.44 (dd, J = 10.6, 8.7 Hz, 1H), 3.89 (s, 3H), 2.69 (s, 3H). Intermediate 60: Methyl 2-fluoro-5-(pyrazin-2-yl)benzoate Following Step 1 of General Procedure 3 shown in Scheme 12, using 2- chloropyrazine as the aryl-chloride (R-X) and [4-fluoro-3- (methoxycarbonyl)phenyl]boronic acid, afforded methyl 2-fluoro-5-(pyrazin-2- yl)benzoate (Intermediate 60: 88 mg, 39%) as a white solid. Mass spec: m / z: 233 [M+H]+;1H NMR (400 MHz, DMSO-d6) δ ppm 9.33 (d, J = 1.6 Hz, 1H), 8.75 (dd, J = 2.5, 1.5 Hz, 1H), 8.70 – 8.63 (m, 2H), 8.45 (ddd, J = 8.7, 4.6, 2.5 Hz, 1H), 7.55 (dd, J = 10.7, 8.7 Hz, 1H), 3.91 (s, 3H). Step 2 To a solution of the appropriate ester prepared in Scheme 12, Step 1 (1 eq) in MeOH / THF / H2O 1 / 1 / 1 (0.15 M) was added lithium hydroxide hydrate (2 eq). The reaction mixture was stirred at rt for 18h. The reaction mixture was concentrated under reduced pressure and the residue was diluted with H2O, acidified with citric acid to pH = 4. The resulting precipitate was filtered and dried under vacuum to afford the corresponding Intermediates as detailed below. Intermediate 61: 2-fluoro-4-(2-methyl-1,3-thiazol-5-yl)benzoic acid Following Step 2 of General Procedure 3 shown in Scheme 12, using methyl 2- fluoro-4-(2-methyl-1,3-thiazol-5-yl)benzoate (Intermediate 56) as the ester, afforded 2- fluoro-4-(2-methyl-1,3-thiazol-5-yl)benzoic acid (Intermediate 61: 114 mg, 93%) as a beige solid. Mass spec: m / z: 238 [M+H]+;1H NMR (400 MHz, DMSO-d6) δ ppm 13,17 (s, 1H), 8.26 (s, 1H), 7.90 (t, J = 8.0 Hz, 1H), 7.70 – 7.58 (m, 1H), 7.52 (dd, J = 8.2, 1.8 Hz, 1H), 2.71 (s, 3H). Intermediate 62: 2-fluoro-4-(pyrazin-2-yl)benzoic acid Following Step 2 of General Procedure 3 shown in Scheme 12, using methyl 2- fluoro-4-(pyrazin-2-yl)benzoate (Intermediate 57) as the ester, afforded 2-fluoro-4- (pyrazin-2-yl)benzoic acid (Intermediate 62: 86 mg, 88%) as a white solid. Mass spec: m / z: 219 [M+H]+;1H NMR (400 MHz, DMSO-d6) δ ppm 9.32 (d, J = 1.5 Hz, 1H), 8.75 (dd, J = 2.5, 1.5 Hz, 1H), 8.66 (d, J = 2.5 Hz, 1H), 7.95 (ddt, J = 17.1, 11.6, 1.9 Hz, 2H), 7.88 – 7.78 (m, 1H), 3.37 (s, 2H). Intermediate 63: 2-fluoro-4-(1,3-thiazol-5-yl)benzoic acid Following Step 2 of General Procedure 3 shown in Scheme 12, using methyl 2- fluoro-4-(1,3-thiazol-5-yl)benzoate (Intermediate 58) as the ester, afforded 2-fluoro-4- (1,3-thiazol-5-yl)benzoic acid (Intermediate 63: 353 mg, 83%) as an off-white solid. Mass spec: m / z: 224 [M+H]+;1H NMR (400 MHz, DMSO-d6) δ ppm 13.31 (s, 1H), 9.20 (d, J = 0.9 Hz, 1H), 8.53 (d, J = 0.8 Hz, 1H), 7.92 (t, J = 8.0 Hz, 1H), 7.75 (dd, J = 12.0, 1.8 Hz, 1H), 7.64 – 7.57 (m, 1H). Intermediate 64: 2-fluoro-5-(2-methyl-1,3-thiazol-5-yl)benzoic acid Following Step 2 of General Procedure 3 shown in Scheme 12, using methyl 2- fluoro-5-(2-methyl-1,3-thiazol-5-yl)benzoate (Intermediate 59) as the ester, afforded 2- fluoro-5-(2-methyl-1,3-thiazol-5-yl)benzoic acid (Intermediate 64: 83 mg, 83%) as an off-white solid. Mass spec: m / z: 238 [M+H]+;1H NMR (400 MHz, DMSO-d6) δ ppm 13.28 (s, 1H), 7.89 (s, 1H), 7.80 (dd, J = 6.8, 2.6 Hz, 1H), 7.70 (ddd, J = 8.7, 4.5, 2.6 Hz, 1H), 7.21 (dd, J = 10.6, 8.6 Hz, 1H), 2.50 (s, 3H). Intermediate 65: 2-fluoro-5-(pyrazin-2-yl)benzoic acid Following Step 2 of General Procedure 3 shown in Scheme 12, , using methyl 2- fluoro-5-(pyrazin-2-yl)benzoate (Intermediate 60) as the ester, afforded 2-fluoro-5- (pyrazin-2-yl)benzoic acid (Intermediate 65: 66 mg, 75%) as a white solid. Mass spec: m / z: 219 [M+H]+;1H NMR (400 MHz, DMSO-d6) δ ppm 13.43 (s, 1H), 9.31 (d, J = 1.6 Hz, 1H), 8.74 (dd, J = 2.5, 1.5 Hz, 1H), 8.69 – 8.59 (m, 2H), 8.40 (ddd, J = 8.6, 4.6, 2.5 Hz, 1H), 7.50 (dd, J = 10.6, 8.7 Hz, 1H). General procedure 4 Intermediates 66 and 67 was synthesized following General Procedure 4 in Scheme 13. Scheme 13 Step 1 To a solution of [3-fluoro-4-(methoxycarbonyl)phenyl]boronic acid (CAS: 505083-04- 5; 1 eq), the appropriate aryl-bromide or aryl-chloride (R-X; 1 eq) and Na2CO3(3 eq) in 1,4-dioxane / H2O 1 / 1 (0.6 M) was added Pd(PPh3)4(0.1 eq). The reaction mixture was stirred at 80°C overnight. The reaction mixture was cooled to rt, diluted in CHCl3 / iPrOH [3:1] and filtered through a pad of celite. The solution was then washed twice with brine. The aqueous layer was acidified with a 37% aqueous solution of HCl until a pH = 1-2 was achieved. The aqueous layer was extracted three times with CHCl3 / iPrOH (3 / 1). The combined layers were dried over anhydrous MgSO4, filtered, and concentrated under vacuo to afford the desired products detailed below. Intermediate 66: 2-fluoro-4-(4-methyl-1,3-thiazol-5-yl)benzoic acid Following Step 1 of General Procedure 4 shown in Scheme 13, using 5-bromo-4- methyl-1,3-thiazole (CAS: 111600-83-0) as the aryl-bromide (R-X) and [3-fluoro-4- (methoxycarbonyl)phenyl]boronic acid as the boronic acid, afforded 2-fluoro-4-(4- methyl-1,3-thiazol-5-yl)benzoic acid (Intermediate 66: 190 mg, 64%) as an off-white solid. Mass spec: m / z: 238 [M+H]+. Intermediate 67: 2-fluoro-4-(pyrimidin-2-yl)benzoic acid Following Step 1 of General Procedure 4 shown in Scheme 13, using 2- chloropyrimidine (CAS: 1722-12-9) as the aryl-chloride (R-X) and [3-fluoro-4- (methoxycarbonyl)phenyl]boronic acid as the boronic acid, afforded 2-fluoro-4- (pyrimidin-2-yl)benzoic acid (Intermediate 67: 104 mg, 30%) as a pale yellow solid. Mass spec: m / z: 219 [M+H]+;1H NMR (400 MHz, DMSO-d6) δ ppm 13.40 (s, 1H), 8.99 (d, J = 4.8 Hz, 2H), 8.31 (dd, J = 8.2, 1.6 Hz, 1H), 8.17 (dd, J = 12.2, 1.6 Hz, 1H), 8.04 (t, J = 7.9 Hz, 1H), 7.56 (t, J = 4.9 Hz, 1H). Intermediate 71 was synthesized following Scheme 14. Scheme 14 Step 1 Intermediate 68: N'-(4-bromopyridin-2-yl)propanehydrazide To a solution of 4-bromo-2-diazenylpyridine (CAS: 1019918-39-8, 1.00 g, 5.32 mmol) in DCM (15 mL) was added propanoyl chloride (0.750 g, 8.06 mmol). The reaction was stirred at rt for 2h. The reaction mixture was filtered, and the filter cake was washed with DCM and dried to provide N'-(4-bromopyridin-2-yl)propanehydrazide (Intermediate 68: 1.30 g, 97%) as a white solid. Mass spec: m / z: 244 [M+H]+. Step 2 Intermediate 69: 7-bromo-3-ethyl-[1,2,4]triazolo[4,3-a]pyridine A solution of N'-(4-bromopyridin-2-yl)propanehydrazide (Intermediate 68: 1.30 g, 5.06 mmol) in POCl3(8 mL) was heated to 100°C for 2h. The reaction mixture was concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel using EtOAc / PE (2 / 3) as eluent to afford 7-bromo-3-ethyl- [1,2,4]triazolo[4,3-a]pyridine (Intermediate 69: 1.00 g, 22%) as a yellow solid which was used in step 3 without further purification. Mass spec: m / z: 226 [M+H]+. Step 3 Intermediate 70: methyl 3-ethyl-[1,2,4]triazolo[4,3-a]pyridine-7-carboxylate To a solution of 7-bromo-3-ethyl-[1,2,4]triazolo[4,3-a]pyridine (Intermediate 69: 1.00 g, 1.11 mmol) in MeOH (20 mL) was added Et3N (134 mg, 1.33 mmol) and Pd(dppf)Cl2(32.4 mg, 0.0442 mmol,). The reaction was stirred at 100°C for 16h under CO (30 atm) in a sealed tube and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel using MeOH / DCM (1 / 15) as eluent to provide methyl 3-ethyl-[1,2,4]triazolo[4,3-a]pyridine-7-carboxylate (Intermediate 70: 80.0 mg, 30%) as a yellow solid. Mass spec: m / z: 206 [M+H]+. Step 4 Intermediate 71: 3-ethyl-[1,2,4]triazolo[4,3-a]pyridine-7-carboxylic acid To a solution of methyl 3-ethyl-[1,2,4]triazolo[4,3-a]pyridine-7-carboxylate (Intermediate 70: 80.0 mg, 0.332 mmol) in THF (1 mL) and H2O (1 mL) was added LiOH (46.7 mg, 1.95 mmol). The reaction was stirred at rt for 2h. The resulting mixture was extracted with EtOAc twice. The pH value was adjusted to 3 with HCl 7N solution. Then the mixture was extracted with iPrOH / CHCl3[1:3] three times. The combined organic layers were washed with brine, dried over anhydrous Na2SO4and concentrated under reduced pressure to provide 3-ethyl-[1,2,4]triazolo[4,3-a]pyridine-7-carboxylic acid (Intermediate 71: 65.0 mg, 87%) as a yellow solid which was used in the next step without further purification. Mass spec: m / z: 192 [M+H]+. Intermediate 74 was synthesized following Scheme 15.

[0024] Scheme 15 Step 1 Intermediate 72: 1,3-dimethyl-1H-pyrazol-5-amine To a solution of (2Z)-3-aminobut-2-enenitrile (CAS: 1118-61-2, 1 g, 12.1 mmol) in pentan-1-ol (7 mL) was added methyl hydrazine dihydrochloride (2.03 g, 17.1 mmol). The resulting mixture was stirred for 3h at 140°C and cooled to rt. The precipitated solids were collected by filtration and washed with n-hexane (3 x 150 mL) and dried to provide 1,3-dimethyl-1H-pyrazol-5-amine (Intermediate 72: 910 mg, 18%) as a white solid which was used in Step 2 without further purification. Mass spec: m / z: 112 [M+H]+. Step 2 Intermediate 73: ethyl 1,3-dimethyl-1H-pyrazolo[3,4-b]pyridine-6-carboxylate To a solution of 1,3-dimethyl-1H-pyrazol-5-amine (Intermediate 72: 892 mg, 8.02 mmol) in EtOH (5 mL) was added hydrogen chloride solution (5 mL, 4M in 1,4- dioxane). The mixture was stirred at rt for 15 min. Then ethyl (3E)-4-ethoxy-2-oxobut- 3-enoate (1.66 g, 9.63 mmol) was added. The resulting mixture was stirred overnight at 100°C. The mixture was allowed to cool down to rt and quenched with H2O (30 mL). The resulting solution was extracted with DCM (3 x 50 mL) and the organic layers were combined, washed with brine (50 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to provide ethyl 1,3-dimethyl-1H-pyrazolo[3,4- b]pyridine-6-carboxylate (Intermediate 73: 100 mg, 15%) as a brown oil which was used in step 3 without further purification. Mass spec: m / z: 220 [M+H]+. Step 3 Intermediate 74: 1,3-dimethyl-1H-pyrazolo[3,4-b]pyridine-6-carboxylic acid To a solution of ethyl 1,3-dimethylpyrazolo[3,4-b]pyridine-6-carboxylate (Intermediate 73: 90 mg, 0.411 mmol,) in THF (2 mL) / H2O (2 mL) was added LiOH (49.2 mg, 2.05 mmol). The resulting mixture was stirred for 2h at rt. The mixture was acidified to pH = 6 with a 1M HCl solution and extracted three times with CHCl3 / iPrOH (3 / 1). The organic layers were combined, washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to provide 1,3-dimethyl-1H- pyrazolo[3,4-b]pyridine-6-carboxylic acid (Intermediate 74: 40 mg, 40%) as a brown oil which was used without further purification. Mass spec: m / z: 192 [M+H]+. Intermediate 79 was synthesized following Scheme 16. Scheme 16 Step 1 Intermediate 75: Methyl 3-bromo-1-methyl-1H-indazole-5-carboxylate To a solution of methyl 1-methyl-1H-indazole-5-carboxylate (CAS: 1092351-82-0, 4.0 g, 22.16 mmol) in MeCN (150 mL) was added NBS (5.92 g, 33.24 mmol). The reaction mixture was stirred overnight at 80°C. Water was added and extracted with EtOAc three times. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel using EtOAc / PE (3 / 7) as eluent to afford methyl 3-bromo-1-methyl-1H-indazole-5-carboxylate (Intermediate 75: 5.0 g, 76%) as a white solid. Mass spec: m / z: 269 [M+H]+. Step 2 Intermediate 76: Methyl 1-methyl-3-vinyl-1H-indazole-5-carboxylate A round-bottom flask was charged with methyl 3-bromo-1-methyl-1H-indazole-5- carboxylate (Intermediate 75: 1.0 g, 4.15 mmol), 4,4,5,5-tetramethyl-2-vinyl-1,3,2- dioxaborolane (1.01 g, 6.22 mmol), Pd(PPh3)4.DCM adduct (479 mg, 0.42 mmol), K2CO3(1.72 g, 12.44 mmol), 1,4-dioxane (15 mL) and water (3 mL).The reaction mixture was stirred for 3h at 100°C under a nitrogen atmosphere. The mixture was taken up in water and extracted three times with EtOAc. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel using EtOAc / PE (5 / 95) as eluent to afford methyl 1-methyl-3-vinyl-1H-indazole-5- carboxylate (Intermediate 76: 511 mg, 53%) as a yellow solid. Mass spec: m / z: 217 [M+H]+. Step 3 Intermediate 77: Methyl 3-ethyl-1-methylindazole-5-carboxylate A round-bottom flask was charged with methyl 3-ethenyl-1-methylindazole-5- carboxylate (Intermediate 76: 511 mg, 2.55 mmol), Methanol (20 mL) and Pd / C (250 mg, 10% on carbon). The reaction mixture was stirred under an atmosphere of hydrogen (3 atm) for 3h at rt. The solids were filtered, and the organic layer was concentrated under reduced pressure to provide methyl 3-ethyl-1-methylindazole-5-carboxylate (Intermediate 77: 421 mg, 74%) as a white solid. Mass spec: m / z: 219 [M+H]+. Step 4 Intermediate 78: 3-ethyl-1-methylindazole-5-carboxylic acid To a solution of methyl 3-ethyl-1-methylindazole-5-carboxylate (Intermediate 77: 421 mg, 1.93 mmol) in THF (20 mL) and water (5 mL) was added lithium hydroxide (231 mg, 9.65 mmol). The reaction mixture was stirred overnight at 60°C. The pH value of the reaction mixture was adjusted to 5 with a solution of HCl (6 N in water). The resulting solution was extracted three times with DCM. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to afford 3-ethyl-1-methylindazole-5-carboxylic acid (Intermediate 78: 390 mg, 79%) as a white solid which was used in Step 5 without further purification. Mass spec: m / z: 205 [M+H]+. Step 5 Intermediate 79: 3-ethyl-1-methyl-1H-indazole-5-carboxamide A solution of 3-ethyl-1-methylindazole-5-carboxylic acid (Intermediate 78: 200 mg, 0.833 mmol), NH4Cl (225 mg, 4.17 mmol), HATU (475 mg, 1.25 mmol), DIPEA (322 mg, 2.50 mmol) in DMF (5 mL) was stirred overnight at rt. The mixture was concentrated in vacuo. The crude material was purified by reverse-phase flash chromatography (C18) using a MeCN / water (0.5% TFA) (87 / 17) as eluent to afford 3- ethyl-1-methyl-1H-indazole-5-carboxamide (Intermediate 79: 140 mg, 67%) as a white solid. Mass spec: m / z: 204 [M+H]+. Intermediate 82 was synthesized following Scheme 17. Scheme 17 Step 1 Intermediate 80: Methyl 3-(2-hydroxyethyl)-1-methylindazole-5-carboxylate To a solution of methyl 1-methyl-3-vinyl-1H-indazole-5-carboxylate (Intermediate 76: 1.00 g, 4.62 mmol) in THF (20 mL) was added 9-borabicyclo[3.3.1]nonane 9-BBN (37.0 mL, 18.5 mmol) at 0°C. The mixture was stirred at rt for 18h. A NaOH solution (3M in water, 12.3 mL, 37.0 mmol) and H2O2(4.19 g, 37.0 mmol, 30% in water) were added. The reaction mixture was stirred overnight and quenched with a saturated aqueous solution of sodium thiosulfate solution (20 mL). The aqueous layer was extracted with EtOAc three times, and the organic layers were combined, washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to afford methyl 3-(2-hydroxyethyl)-1-methylindazole-5-carboxylate (Intermediate 80: 1.1 g, 90%) as a yellow oil which was used in Step 2 without further purification. Mass spec: m / z 235 [M+H]+. Step 2 Intermediate 81: Methyl 3-(2-methoxyethyl)-1-methylindazole-5-carboxylate To a solution of methyl 3-(2-hydroxyethyl)-1-methylindazole-5-carboxylate (Intermediate 80: 600 mg, 2.56 mmol) in THF (10 mL) was added NaH (79.9 mg, 3.33 mmol, 30% in mineral oil) at 0°C. The mixture was stirred for 30 min, then CH3I (545 mg, 3.84 mmo) was added. The mixture was stirred at rt for 18h, then quenched with water (10 mL). The resulting solution was extracted with EtOAc three times and the organic layers were combined, washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel using EtOAc / PE (2 / 8) as eluent to afford methyl 3- (2-methoxyethyl)-1-methylindazole-5-carboxylate (Intermediate 81: 80 mg, 16%) as a yellow oil. Mass spec: m / z 249 [M+H]+. Step 3 Intermediate 82: 3-(2-methoxyethyl)-1-methylindazole-5-carboxylic acid To a solution of methyl 3-(2-methoxyethyl)-1-methylindazole-5-carboxylate (Intermediate 81: 80.0 mg, 0.32 mmol) in THF (2 mL) was added LiOH (38.6 mg, 1.61 mmol) in water (1 mL). The mixture was stirred at 60°C for 3h. The pH value of the mixture was adjusted to 6 with an aqueous solution of 1M HCl. The resulting solution was extracted with CHCl3 / iPrOH 3 / 1 three times, and the organic layers were combined, washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to afford 3-(2-methoxyethyl)-1-methylindazole-5-carboxylic acid (Intermediate 82: 50 mg, 63%) as a white solid which was used without further purification. Mass spec: m / z 235 [M+H]+. Intermediate 86 was synthesized following Scheme 18.

[0025] Scheme 18 Step 1 Intermediate 83: Methyl 3-(cyclopent-1-en-1-yl)-1-methylindazole-5-carboxylate A solution of methyl 3-bromo-1-methyl-1H-indazole-5-carboxylate (Intermediate 75: 400 mg, 1.418 mmol), 2-(cyclopent-1-en-1-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (319 mg, 1.56 mmol), Pd(PPh3)4(266 mg, 0.230 mmol) and K2CO3(392 mg, 2.84 mmol) in dioxane (15 mL) and water (5 mL) was stirred for 3h at 100°C under nitrogen atmosphere. The reaction was taken in water and extracted with EtOAc three times. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel using EtOAc / PE (3 / 2) as eluent to afford methyl 3- (cyclopent-1-en-1-yl)-1-methylindazole-5-carboxylate (Intermediate 83: 340 mg, 80%) as a yellow solid. Mass spec: m / z: 257 [M+H]+. Step 2 Intermediate 84: Methyl 3-cyclopentyl-1-methylindazole-5-carboxylate A round-bottom flask was charged with methyl 3-(cyclopent-1-en-1-yl)-1- methylindazole-5-carboxylate (Intermediate 83: 330 mg, 1.160 mmol), MeOH (15 mL) and Pd / C (300 mg, 10% on carbon). The reaction was placed under an atmosphere of hydrogen (3 atm). The reaction mixture was stirred under an atmosphere of hydrogen (3 atm) for 3h at rt. The solids were filtered, and the organic layer was concentrated under reduced pressure to provide the title compound methyl 3-cyclopentyl-1-methylindazole- 5-carboxylate (Intermediate 84: 310 mg, 79%) as a yellow oil which was used in Step 3 without further purification. Mass spec: m / z: 259 [M+H]+. Step 3 Intermediate 85: 3-cyclopentyl-1-methylindazole-5-carboxylic acid To a solution of methyl 3-cyclopentyl-1-methylindazole-5-carboxylate (Intermediate 84: 310 mg, 1.02 mmol) in THF (20 mL) and water (5 mL) was added LiOH (98.2 mg, 4.09 mmol). The reaction was stirred for 5h at rt. The pH value of the reaction mixture was adjusted to 5 with a solution of HCl (6mol / L in water). The resulting solution was extracted three times with DCM. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to provide the title compound 3-cyclopentyl-1-methylindazole-5-carboxylic acid (Intermediate 85: 300 mg, 82%) as a white solid which was used in Step 4 without further purification. Mass spec: m / z: 245 [M+H]+. Step 4 Intermediate 86: 3-cyclopentyl-1-methyl-1H-indazole-5-carbonyl chloride To a solution of 3-cyclopentyl-1-methylindazole-5-carboxylic acid (Intermediate 85: 120 mg, 0.393 mmol) in DCM (8 mL) were added DMF (0.05 mL) and oxalyl chloride (100 mg, 0.787 mmol). The reaction mixture was stirred for 2h at rt. The mixture was concentrated under reduced pressure to afford 3-cyclopentyl-1-methyl-1H-indazole-5- carbonyl chloride (Intermediate 86: 60 mg, 37%) as a yellow oil which was used without further purification. Mass spec: m / z: 263 [M+H]+. Intermediate 91 was synthesized following Scheme 19

[0026] Scheme 19 Step 1 Intermediate 87: Methyl 3-[1-(tert-butoxycarbonyl)-2,5-dihydropyrrol-3-yl]-1- methylindazole-5-carboxylate A solution of methyl 3-bromo-1-methylindazole-5-carboxylate (Intermediate 75: 400 mg, 1.42 mmol), tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,5- dihydropyrrole-1-carboxylate (484 mg, 1.56 mmol), Pd(PPh3)4(329 mg, 0.284 mmol) and K2CO3(392 mg, 2.84 mmol) in 1,4-dioxane (15 mL) and water (5 mL) under nitrogen atmosphere. The reaction mixture was stirred for 3h at 100°C. The mixture was diluted with water and extracted with EtOAc three times. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel using EtOAc / PE (1 / 4) as eluent to afford methyl 3-[1-(tert-butoxycarbonyl)-2,5- dihydropyrrol-3-yl]-1-methylindazole-5-carboxylate (Intermediate 87: 410 mg, 70%) as a yellow solid. Mass spec: m / z: 358 [M+H]+. Step 2 Intermediate 88: rac-methyl 3-[1-(tert-butoxycarbonyl)pyrrolidin-3-yl]-1- methylindazole-5-carboxylate To a solution of methyl 3-[1-(tert-butoxycarbonyl)-2,5-dihydropyrrol-3-yl]-1- methylindazole-5-carboxylate (Intermediate 87: 410 mg, 1.05 mmol) in MeOH (30 mL) was added Pd / C (200 mg, 10% on carbon). The mixture was placed under an atmosphere of hydrogen (3 atm) and stirred for 5h at 45°C. The solids were filtered and the filtrate was concentrated under reduced pressure to afford rac-methyl 3-[1-(tert- butoxycarbonyl)pyrrolidin-3-yl]-1-methylindazole-5-carboxylate (Intermediate 88: 350 mg, 72%) as a colorless oil which was used in Step 3 without further purification. Mass spec: m / z: 360 [M+H]+. Step 3 Intermediate 89: rac-3-[1-(tert-butoxycarbonyl)pyrrolidin-3-yl]-1-methylindazole- 5-carboxylic acid To a solution of methyl 3-[1-(tert-butoxycarbonyl)pyrrolidin-3-yl]-1-methylindazole-5- carboxylate (Intermediate 88: 351 mg, 0.831 mmol) in THF (10 mL) and water (3 mL) was added LiOH (99.7 mg, 4.16 mmol). The reaction mixture was stirred overnight at 60°C. The pH of the mixture was then adjusted to 5 by the addition of aqueous solution of HCl (6 N). The aqueous layer was extracted with DCM three times. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to afford rac-3-[1-(tert-butoxycarbonyl)pyrrolidin- 3-yl]-1-methylindazole-5-carboxylic acid (Intermediate 89: 320 mg, 85%) as a white solid which was used in the next step without further purification. Mass spec: m / z: 346 [M+H]+. Step 4 Intermediate 90: rac-tert-butyl 3-(5-carbamoyl-1-methylindazol-3-yl)pyrrolidine- 1-carboxylate To a solution of 3-[1-(tert-butoxycarbonyl)pyrrolidin-3-yl]-1-methylindazole-5- carboxylic acid (Intermediate 89: 290 mg, 0.757 mmol) in DMF (5 mL) were added HATU (431 mg, 1.14 mmol), NH4Cl (162 mg, 3.03 mmol) and DIPEA (293 mg, 2.27 mmol) . The reaction mixture was stirred overnight at rt. The mixture was concentrated under reduced pressure. The crude material was purified by reverse phase flash chromatography (C18 Aq) using MeCN / water (33 / 67) as eluent to rac-tert-butyl 3-(5- carbamoyl-1-methylindazol-3-yl)pyrrolidine-1-carboxylate (Intermediate 90: 150 mg, 49%) as a yellow oil. Mass spec: m / z: 345 [M+H]+. Intermediate 92 was synthesized following Scheme 20. Scheme 20 Step 1 Intermediate 91: ethyl 3-methyl-[1,2]oxazolo[5,4-b]pyridine-6-carboxylate A solution of 3-methyl-1,2-oxazol-5-amine (CAS: 14678-02-5, 400 mg, 4.08 mmol) and ethyl (3E)-4-ethoxy-2-oxobut-3-enoate (CAS: 65260-58-4, 702 mg, 4.08 mmol) in acetic acid was stirred at 120C for 18h, then quenched with water (50 ml). The mixture was extracted with EtOAc three times. The organic layers were combined, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel using EtOAc / PE (13 / 87) as eluent to afford ethyl 3-methyl-[1,2]oxazolo[5,4-b]pyridine-6-carboxylate (Intermediate 91: 324 mg, 31%) as a yellow solid. Mass spec: m / z: 207 [M+H]+. Step 2 Intermediate 92: 3-methyl-[1,2]oxazolo[5,4-b]pyridine-6-carboxylic acid To a solution of ethyl 3-methyl-[1,2]oxazolo[5,4-b]pyridine-6-carboxylate (Intermediate 91: 300 mg, 1.46 mmol) in THF / H2O (4mL / 4mL) was added LiOH (174 mg, 7.27 mmol). The mixture was stirred at rt for 1h. The resulting solution was acidified to pH = 6 with an aqueous 1M HCl solution. The mixture was extracted with EtOAc three times, the organic layers were combined, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to afford 3-methyl-[1,2]oxazolo[5,4- b]pyridine-6-carboxylic acid (Intermediate 92: 45 mg, 18%) as a brown oil. Mass spec: m / z: 179 [M+H]+. Intermediate 95 was synthesized following Scheme 21

[0027] Scheme 21 Step 1 Intermediate 93: Methyl 4-[(Z)-N'-hydroxycarbamimidoyl]benzoate To a solution of methyl 4-cyanobenzoate (CAS: 1129-35-7, 1.00 g, 6.21 mmol) in Ethanol (10 mL) and H2O (1 mL) were added hydroxylamine hydrochloride (0.47 g, 6.83 mmol) and NaHCO3(0.57 g, 6.83 mmol). The mixture was stirred at 80°C for 3h and then quenched with water (10 mL). The resulting solution was extracted with EtOAc three times, and the organic layers were combined, washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to afford methyl 4-[(Z)-N'-hydroxycarbamimidoyl]benzoate (Intermediate 93: 1 g, 74%) as a white solid. Mass spec: m / z 195 [M+H]+. Step 2 Intermediate 94: Methyl 4-(1,2,4-oxadiazol-3-yl)benzoate To a solution of methyl 4-[(Z)-N'-hydroxycarbamimidoyl]benzoate (Intermediate 93: 1.05 g, 5.41 mmol) in trimethyl orthoformate (10 mL) was added BF3.Et2O (40.0 mg, 0.280 mmol). The reaction mixture was heated under microwave conditions for 40 min at 110°C and then quenched with water (10 mL). The aqueous layer was extracted with EtOAc three times, and the organic layers were combined, washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel using EtOAc / PE (1 / 9) as eluent to afford methyl 4-(1,2,4-oxadiazol-3-yl)benzoate (Intermediate 94: 750 mg 76%) as a yellow oil. Mass spec: m / z 205 [M+H]+. Step 3 Intermediate 95: 4-(1,2,4-oxadiazol-3-yl)benzoic acid To a solution of methyl 4-(1,2,4-oxadiazol-3-yl)benzoate (Intermediate 94: 300 mg, 1.47 mmol) in DCM (10 mL) was added BBr3(29.4 mL, 29.4 mmol, 1 M in DCM). The mixture was stirred at rt for 3 days and then quenched with a saturated NaHCO3aqueous solution. The aqueous layer was extracted with EtOAc three times and the organic layers were combined, washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to afford 4-(1,2,4-oxadiazol-3- yl)benzoic acid (Intermediate 95: 160 mg 59%) as a light yellow oil. Mass spec: m / z 191 [M+H]+. Intermediate 97 was synthesized following Scheme 22. Scheme 22 Step 1 Intermediate 96: Methyl 4-chloro-1-methylindazole-5-carboxylate To a solution of 5-bromo-4-chloro-1-methylindazole (CAS: 1785427-70-4, 300 mg, 1.22 mmol) in MeOH (6 mL) were added Pd(dppf)Cl2(358 mg, 0.49 mmol) and Et3N (989 mg, 9.78 mmol). Carbon monoxide (30 atm) was introduced into the autoclave. The solution was then stirred at 100°C for 3 days and then quenched with water (10 mL). Both layers were separated, and the aqueous layer was extracted with EtOAc twice. The organic layers were combined, washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel using EtOAc / PE (18 / 82) as eluent to afford methyl 4- chloro-1-methylindazole-5-carboxylate (Intermediate 96: 80 mg 13%) as a light yellow oil. Mass spec: m / z 225 [M+H]+. Step 2 Intermediate 97: 4-chloro-1-methylindazole-5-carboxylic acid To a solution of methyl 4-chloro-1-methylindazole-5-carboxylate (Intermediate 96: 38.0 mg, 0.170 mmol) in THF (2 mL) was added LiOH (20.3 mg, 0.850 mmol) in H2O (1 mL). The mixture was stirred at 60°C for 3h. The pH was adjusted to 6 with an aqueous solution of HCl (6M). The resulting layers were separated and the aqueous layer was extracted twice with CHCl3 / iPrOH (3 / 1). The organic layers were combined, washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to 4-chloro-1-methylindazole-5-carboxylic acid (Intermediate 97: 30 mg 84%) as a light yellow oil. Mass spec: m / z 211 [M+H]+. General Procedures 5A, 5B and 5C Intermediates 98-107 were prepared using the appropriate General Procedure 5 in Scheme 23. Scheme 23 General procedure 5A To a solution of the appropriate carboxylic acid (1 eq) in DCM (0.25 M) were added SOCl2(2 eq) and DMF (0.5 eq). The reaction mixture was stirred at rt until completion was observed by TLC or LCMS (addition of MeOH into the aliquot to observe the corresponding methyl ester). The mixture was concentrated under vacuo to provide the corresponding acid chloride. General procedure 5B A solution of the appropriate carboxylic acid (1 eq) in SOCl2(0.4 M) was stirred at 80°C until completion was observed by TLC or LCMS (addition of MeOH into the aliquot to observe the corresponding methyl ester). The mixture was concentrated under vacuo to provide the corresponding acid chloride. General procedure 5C To a solution of the carboxylic acid (1 eq) in MeCN (0.15 M) was added SOCl2(2 eq). The reaction mixture was stirred at 80°C until completion was observed by TLC or LCMS (addition of MeOH in the aliquot to observe the corresponding methyl ester). The mixture was concentrated under vacuo to provide the corresponding acid chloride. Intermediate 98: 6-methoxy-1H-indole-3-carbonyl chloride Following General Procedure 5A, using 6-methoxy-1H-indole-3-carboxylic acid (CAS: 90924-43-9) as the carboxylic acid, afforded 6-methoxy-1H-indole-3-carbonyl chloride (Intermediate 98: 120 mg, 99%). Mass spec: m / z: 206 [M-Cl+MeOH]+. Intermediate 99: 4-(pyrazol-1-yl)benzoyl chloride Following General Procedure 5A, using 4-(pyrazol-1-yl)benzoic acid (CAS: 16209- 00-0) as the carboxylic acid, afforded 4-(pyrazol-1-yl)benzoyl chloride (Intermediate 99: 100 mg, 97%) as a brown oil. Mass spec: m / z: 203 [M-Cl+MeOH]+. Intermediate 100: 1,3-benzothiazole-5-carbonyl chloride Following General Procedure 5B, using 1,3-benzothiazole-5-carboxylic acid (CAS: 68867-17-4) as the carboxylic acid, afforded 1,3-benzothiazole-5-carbonyl chloride (Intermediate 100: (160 mg, 92%) as a yellow solid. Mass spec: m / z: 198 [M+H]+. Intermediate 101: 4-(pyrazol-1-ylmethyl)benzoyl chloride Following General Procedure 5A, using 4-(pyrazol-1-ylmethyl)benzoic acid (CAS: 160388-53-4) as the carboxylic acid, afforded 4-(pyrazol-1-ylmethyl)benzoyl chloride (Intermediate 101: 100 mg, 97%) as a brown solid. Mass spec: m / z: 217 [M- Cl+MeOH]+. Intermediate 102: 3-(pyrazol-1-yl)benzoyl chloride Following General Procedure 5A, using 3-(pyrazol-1-yl)benzoic acid (CAS: 264264- 33-7) as the carboxylic acid, afforded 3-(pyrazol-1-yl)benzoyl chloride (Intermediate 102: 100 mg, 97%) as a brown oil. Mass spec: m / z: 203 [M-Cl+MeOH]+. Intermediate 103: 5-methyl-4-oxo-1H-thieno[2,3-d]pyrimidine-6-carbonyl chloride Following General Procedure 5B, using 5-methyl-4-oxo-1H-thieno[2,3-d]pyrimidine- 6-carboxylic acid (CAS: 101667-97-4) as the carboxylic acid, afforded 5-methyl-4-oxo- 1H-thieno[2,3-d]pyrimidine-6-carbonyl chloride (Intermediate 103: 60 mg, 62%) as a light yellow solid. Mass spec: m / z: 229 [M+H]+. Intermediate 104: 1-cyclohexyl-1,2,3-benzotriazole-5-carbonyl chloride Following General Procedure 5A, using 1-cyclohexyl-1,2,3-benzotriazole-5- carboxylic acid (CAS: 691363-11-8) as carboxylic acid, afforded 1-cyclohexyl-1,2,3- benzotriazole-5-carbonyl chloride (Intermediate 104: 70 mg, 98%) as a brown solid. Mass spec: m / z: 260 [M-Cl+MeOH]+. Intermediate 105: 2-phenyl-1,3-oxazole-5-carbonyl chloride Following General Procedure 5C, using 2-phenyl-1,3-oxazole-5-carboxylic acid (CAS: 106833-79-8) as the carboxylic acid, afforded 2-phenyl-1,3-oxazole-5-carbonyl chloride (Intermediate 105: 130 mg, 63%) as a yellow oil. Mass spec: m / z: 208 [M+H]+. Intermediate 106: Quinazoline-7-carbonyl chloride Following General Procedure 5A, using quinazoline-7-carboxylic acid (CAS: 1234616-41-1) as the carboxylic acid, afforded quinazoline-7-carbonyl chloride (Intermediate 106: 60 mg, 98%) as a brown solid. Mass spec: m / z: 189 [M- Cl+MeOH]+. Intermediate 107: 1-methylindazole-5-carbonyl chloride Following General Procedure 5A, using 1-methyl-1H-indazole-5-carboxylic acid (CAS: 1176754-31-6) as the carboxylic acid, afforded 1-methylindazole-5-carbonyl chloride (Intermediate 107: 5.5 g, quant.). Mass spec: m / z: 191 [M-Cl+MeOH]+. Examples 1 to 105 describe compounds which are MLLT1 and / or MLLT3 inhibitors and which may be joined to LINK-U to form a PROTAC of the present invention. Example 1 was synthesized following Scheme 24.

[0028] Scheme 24 Step 1 Intermediate 108: rac-tert-butyl 2-(6-bromo-8-methoxy-imidazo[1,2-pyridine-2- yl)pyrrolidine-1-carboxylate To a stirred solution of 5-bromo-3-methoxypyridin-2-amine (CAS: 42409-58-5, 45 mg, 0.215 mmol) in a 1:1 mixture of dry toluene (200 µL) and dry MeCN (200 µL) were added rac-tert-butyl 2-(2-chloroacetyl)pyrrolidine-1-carboxylate (Intermediate 1: 50 mg, 0.196 mmol) and sodium iodide (3.0 mg, 0.02 mmol). The reaction mixture was stirred at 80°C for 16h. The reaction mixture was concentrated under reduced pressure to give the crude product which was purified by reverse phase flash chromatography (C18 aq) using a gradient of MeCN / water from 0% to 100% to afford rac-tert-butyl 2- (6-bromo-8-methoxy-imidazo[1,2-pyridine-2-yl)pyrrolidine-1-carboxylate (Intermediate 108: 60 mg, 71%) as a yellow oil. Mass spec: m / z 396 [M+H]+, 398 [M+H+2]+;1H NMR (400 MHz, DMSO-d6) δ ppm 8.46 (d, J = 12.6 Hz, 1H), 7.63 (d, J = 8.2 Hz, 1H), 6.76 (d, J = 1.6 Hz, 1H), 4.94 – 4.83 (m, 1H), 3.93 (s, 3H), 3.46 – 3.39 (m, 1H), 2.20 – 2.12 (m, 1H), 2.06 – 2.00 (m, 1H), 1.95 – 1.76 (m, 3H), 1.40 (s, 6H), 1.23 (s, 3H). Step 2 Intermediate 109: rac-tert-butyl 2-[6-[(1,3-dimethylindazole-6-carbonyl)amino]-8- methoxy-imidazo[1,2-a]pyridin-2-yl]pyrrolidine-1-carboxylate To a stirred solution of rac-tert-butyl 2-(6-bromo-8-methoxy-imidazo[1,2-pyridine-2- yl)pyrrolidine-1-carboxylate (Intermediate 108: 250 mg, 0.574 mmol) in anhydrous 1,4-dioxane (0.1 M) were added 1,3-dimethylindazole-6-carboxamide (Intermediate 52: 163 mg, 0.861 mmol) and Cs2CO3(561 mg, 1.72 mmol). The reaction mixture was degassed with argon for 10 min then EPhos Pd G4 (53 mg, 0.0574 mmol) and Dicyclohexyl(3-isopropoxy-2',4',6'-triisopropyl-[1,1'-biphenyl]-2-yl)phosphine (31 mg, 0.057 mmol) were added. The reaction mixture was stirred at 90°C for 16 h. The mixture was cooled to rt and concentrated to dryness to give the crude compound which was purified by reverse-phase flash chromatography (C18 aq) using a gradient of MeCN / water (0.1% AcOH) from 5% to 70% to afford rac-tert-butyl 2-[6-[(1,3- dimethylindazole-6-carbonyl)amino]-8-methoxy-imidazo[1,2-a]pyridin-2- yl]pyrrolidine-1-carboxylate (Intermediate 109: 75 mg, 23%) as a brown solid. Mass spec: m / z 505 [M+H]+;1H NMR (400 MHz, DMSO-d6) δ ppm 10.31 (s, 1H), 8.94 (s, 1H), 8.21 (t, J = 1.1 Hz, 1H), 7.85 (dd, J = 8.4, 0.8 Hz, 1H), 7.76 (d, J = 10.6 Hz, 1H), 7.69 (dd, J = 8.4, 1.4 Hz, 1H), 6.92 (d, J = 1.6 Hz, 1H), 4.90 (d, J = 13.4 Hz, 1H), 4.07 (s, 3H), 3.94 (s, 3H), 3.56 – 3.41 (m, 1H), 3.41 – 3.36 (m, 1H), 2.53 (s, 3H), 2.17 (s, 1H), 2.01 (s, 2H), 1.85 (s, 1H), 1.41 (s, 3H), 1.24 (s, 6H). Step 3 Intermediate 110: rac-N-(8-methoxy-2-pyrrolidin-2-yl-imidazo[1,2-a]pyridin-6-yl)- 1,3-dimethyl-indazole-6-carboxamide trihydrochloride To a stirred solution of rac-tert-butyl 2-[6-[(1,3-dimethylindazole-6-carbonyl)amino]-8- methoxy-imidazo[1,2-a]pyridin-2-yl]pyrrolidine-1-carboxylate (Intermediate 109: 75 mg, 0.134 mmol) in dioxane (2.1 mL) was added dropwise a solution of hydrogen chloride (4N in dioxane, 334 µL, 1.34 mmol). The reaction mixture was stirred at rt for 16 h. Additional hydrogen chloride (4N in dioxane, 334 µL, 1.34 mmol) was added at rt and the reaction mixture was stirred at rt for 72 h. The reaction mixture was concentrated to dryness to afford rac-N-(8-methoxy-2-pyrrolidin-2-yl-imidazo[1,2- a]pyridin-6-yl)-1,3-dimethyl-indazole-6-carboxamide trihydrochloride (Intermediate 110: 75mg, 96%) which was directly used in step 4 without further purification. Mass spec: m / z 405 [M+H]+;1H NMR (400 MHz, DMSO-d6) δ ppm 10.76 (s, 1H), 10.00 (s, 1H), 9.34 – 9.21 (m, 2H), 8.43 – 8.37 (m, 2H), 7.87 (dd, J = 8.5, 0.8 Hz, 1H), 7.73 (dd, J = 8.4, 1.4 Hz, 1H), 7.53 (s, 1H), 4.87 – 4.82 (m, 1H), 4.09 (s, 3H), 4.04 (s, 3H), 3.35 – 3.29 (m, 2H), 2.54 (s, 3H), 2.45 – 2.39 (m, 1H), 2.17 (ddd, J = 17.3, 9.8, 4.6 Hz, 2H), 2.09 – 2.01 (m, 1H). Step 4 Example 1: rac-N-[8-methoxy-2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6- yl]-1,3-dimethyl-indazole-6-carboxamide To a stirred solution of N-(8-methoxy-2-pyrrolidin-2-yl-imidazo[1,2-a]pyridin-6-yl)- 1,3-dimethyl-indazole-6-carboxamide trihydrochloride (Intermediate 110: 75 mg, 0.128 mmol) in MeOH (1.3 mL) were added formaldehyde (37% aq, 48 µL, 0.642 mmol), acetic acid (15 µL, 0.257 mmol) and supported sodium borohydride (103 mg, 0.257 mmol). The reaction mixture was stirred at rt for 16h. Additional supported sodium borohydride (103 mg, 0.257 mmol) was added, and the reaction mixture was stirred at rt for 16h. The reaction mixture was filtered and dried using a phase separator then diluted in anhydrous methanol (1.3 mL). Supported sodium borohydride (103 mg, 0.257 mmol) was added and the reaction mixture was stirred at rt for 16h. The reaction mixture was filtered and dried using a phase separator, washed with MeOH then concentrated to dryness. The crude material was purified by reverse-phase flash chromatography (C18 Aq) using a gradient of MeCN / water (0.1% AcOH) from 0% to 80% to afford rac-N-[8-methoxy-2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6- yl]-1,3-dimethyl-indazole-6-carboxamide (Example 1: 5 mg, 9%) as a white foam. Mass spec: m / z 419 [M+H]+;1H NMR (600 MHz, DMSO-d6): δ ppm 10.29 (s, 1H), 8.93 (d, J = 1.6 Hz, 1H), 8.19-8.22 (m, 1H), 7.82-7.86 (m, 2H), 7.68 (dd, J = 8.4, 1.3 Hz, 1H), 6.90 (d, J = 1.6 Hz, 1H), 4.06 (s, 3H), 3.93 (s, 3H), 3.24-3.28 (m, 1H), 3.06- 3.10 (m, 1H), 2.51-2.54 (m, 3H), 2.09-2.26 (m, 5H), 1.72-1.90 (m, 3H). Example 2 was synthesized following Scheme 25

[0029] Scheme 25 Step 1 Intermediate 111: Ethyl 6-[(1-methylindazole-5-carbonyl)amino]imidazo[1,2- a]pyridine-2-carboxylate To a solution of ethyl 6-aminoimidazo[1,2-a]pyridine-2-carboxylate (CAS: 158980-21- 3,5.00 g, 23.1 mmol) and N-ethyl-N-isopropyl-propan-2-amine (24 mL, 0.139 mol) in DCM (225 mL) was added 1-methylindazole-5-carbonyl chloride (Intermediate 107: 5.41 g, 27.8 mmol). The reaction mixture was stirred for 1h at rt. The mixture was diluted with DCM and washed with water. The resulting solid was filtered to give the title product. The aqueous phase of the filtrate was extracted with DCM, dried with a phase separator and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel using a gradient of MeOH in DCM from 0% to 10% and was combined with the solid obtained previously to afford ethyl 6-[(1- methylindazole-5-carbonyl)amino]imidazo[1,2-a]pyridine-2-carboxylate (Intermediate 111: 5.75 g, 56%) as a beige solid. Mass spec: m / z 364 [M+H]+;1H NMR (400 MHz, DMSO-d6) δ ppm 10.45 (s, 1H), 9.44 (s, 1H), 8.67 (s, 1H), 8.51 (s, 1H), 8.28 (s, 1H), 8.03 (d, J = 8.8 Hz, 1H), 7.80 (d, J = 8.9 Hz, 1H), 7.69 – 7.56 (m, 2H), 4.32 (q, J = 7.1 Hz, 2H), 4.11 (s, 3H), 1.33 (t, J = 7.1 Hz, 3H). Step 2 Intermediate 112: N-[2-(hydroxymethyl)imidazo[1,2-a]pyridin-6-yl]-1-methyl- indazole-5-carboxamide To a solution of ethyl 6-[(1-methylindazole-5-carbonyl)amino]imidazo[1,2-a]pyridine- 2-carboxylate (Intermediate 111: 5.00 g, 13.8 mmol) in anhydrous THF (130 mL) cooled to 0°C was added dropwise a solution of lithium aluminium hydride (2 M in THF, 14 mL, 27.5 mmol). The reaction mixture was stirred for 3h at rt before being quenched with a saturated solution of Rochelle’s salt. The resulting precipitate was filtered and dried under vacuum to afford N-[2-(hydroxymethyl)imidazo[1,2-a]pyridin- 6-yl]-1-methyl-indazole-5-carboxamide (Intermediate 112: 5.0 g, quant) as a brown solid that was used in the next step without any further purification. Mass spec: m / z 322 [M+H]+. Step 3 Intermediate 113: N-[2-(chloromethyl)imidazo[1,2-a]pyridin-6-yl]-1-methyl- indazole-5-carboxamide To a solution of N-[2-(hydroxymethyl)imidazo[1,2-a]pyridin-6-yl]-1-methyl-indazole- 5-carboxamide (Intermediate 112: 5.00 g, 15.2 mmol) in anhydrous DCM (188 mL) cooled to 0°C was added thionyl dichloride (1.4 mL, 19.8 mmol). The mixture was stirred for 16h at rt. Additional thionyl dichloride (1.4 mL, 19.8 mmol) was added and stirring was stirred for another 2h. The observed precipitate was filtered to give the crude product that was purified by flash column chromatography on silica gel using a gradient of MeOH in DCM from 0% to 10% to afford N-[2-(chloromethyl)imidazo[1,2- a]pyridin-6-yl]-1-methyl-indazole-5-carboxamide (Intermediate 113: 1.5 g, 28%) as a yellow solid. Mass spec: m / z 340 [M+H]+. Step 4 Intermediate 114: N-(2-formylimidazo[1,2-a]pyridin-6-yl)-1-methyl-indazole-5- carboxamide A solution of N-[2-(chloromethyl)imidazo[1,2-a]pyridin-6-yl]-1-methyl-indazole-5- carboxamide (Intermediate 113: 2.00 g, 5.89 mmol), triethylamine (0.82 mL, 5.89 mmol) in anhydrous DMSO (29 mL) was stirred at 140°C for 8h. The reaction mixture was diluted with DCM and quenched with a saturated solution of NaHCO3. The resulting white precipitate was dissolved in chloroform / isopropanol (3:1) and organic layer was washed 3 times with a saturated solution of NaHCO3. The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated under vacuum. The crude material was purified by flash chromatography on silica gel using a gradient of MeOH in DCM from 0% to 15% to afford N-(2-formylimidazo[1,2-a]pyridin-6-yl)-1-methyl- indazole-5-carboxamide (Intermediate 114: 222 mg, 12%) as a brown solid. Mass spec: m / z 320 [M+H]+;1H NMR (400 MHz, DMSO-d6) δ ppm 10.50 (s, 1H), 10.00 (s, 1H), 9.52 (dd, J = 2.1, 1.0 Hz, 1H), 8.77 (d, J = 0.7 Hz, 1H), 8.51 (dd, J = 1.7, 0.8 Hz, 1H), 8.28 (d, J = 0.9 Hz, 1H), 8.02 (dd, J = 8.9, 1.7 Hz, 1H), 7.80 (dt, J = 8.9, 0.9 Hz, 1H), 7.72 (dt, J = 9.7, 0.9 Hz, 1H), 7.64 (dd, J = 9.8, 2.0 Hz, 1H), 4.11 (s, 3H). Step 5. Intermediate 115: rac-1-Methyl-N-(2-morpholin-3-ylimidazo[1,2-a]pyridin-6- yl)indazole-5-carboxamide A mixture of N-(2-formylimidazo[1,2-a]pyridin-6-yl)-1-methyl-indazole-5-carboxamide (Intermediate 114: 110 mg, 0.338 mmol), 4Å molecular sieves and [(2- aminoethoxy)methyl]tributylstannane (129 mg, 0.338 mmol) in anhydrous DCM (2 mL) was stirred at rt for 2h. A separate vial was loaded with 2,6-dimethylpyridine (0.040 mL, 0.338 mmol) and copper bis(trifluoromethanesulfonate) (122 mg, 0.338 mmol) in HFIP (1.6 mL). The reaction mixture was stirred at rt for 1h. The pre-formed imine was filtered through a pad of celite, concentrated under reduced pressure then added to the copper salt solution. The mixture was stirred at rt for 16h. Additional [(2- aminoethoxy)methyl]tributylstannane (129 mg, 0.338 mmol) and preformed copperbis(trifluoromethanesulfonate) (122 mg, 0.338 mmol) were added and the reaction mixture was stirred at rt for 16h. The reaction mixture was filtered through a pad of celite, then the filtrate was concentrated to dryness to afford rac-1-Methyl-N- (2-morpholin-3-ylimidazo[1,2-a]pyridin-6-yl)indazole-5-carboxamide (Intermediate 115: 23 mg, 0.061 mmol) used in Step 6 without purification. Mass spec: m / z 377 [M+H]+. Step 6 Example 2: rac-1-methyl-N-[2-(4-methylmorpholin-3-yl)imidazo[1,2-a]pyridin-6- yl]indazole-5-carboxamide A solution of rac-1-methyl-N-(2-morpholin-3-ylimidazo[1,2-a]pyridin-6-yl)indazole-5- carboxamide (Intermediate 115: 23 mg, 0.0611 mmol), acetic acid (0.0035 mL, 0.0611 mmol) and formaldehyde (37% aq, 0.0055 mL, 0.0733 mmol) in MeOH (0.4 mL) was stirred for 1h at rt. Supported NaBH4(24 mg, 0.0611 mmol, loading 2.5 mmol / g) was added and the reaction mixture was stirred for 6h at rt. Additional formaldehyde (37% Aq, 0.0055 mL, 0.0733 mmol) and supported NaBH4(24 mg, 0.0611 mmol, loading 2.5 mmol / g) were added and the mixture was stirred for 4h at rt. The reaction mixture was filtered, and the filtrate was concentrated under vacuum before addition of HCl in dioxane (4N, 5 mL). The solution was concentrated to dryness to give the crude product which was purified by preparative HPLC (column: Fuji Silysia Chromatorex THE C18300 x 50 mm, 10 μm; Eluent: NH4OAc aq 10mM / (MeCN / NH4OAc aq 100mM (90 / 10)) from 80 / 20 to 0 / 100; flow rate: 120 mL / min) to afford rac-1-methyl-N-[2-(4- methylmorpholin-3-yl)imidazo[1,2-a]pyridin-6-yl]indazole-5-carboxamide (Example 2: 2 mg, 9%) as a yellow solid. Mass spec: m / z 391 [M+H]+;1H NMR (600 MHz, DMSO-d6) δ ppm 10.34 (s, 1 H) 9.13 - 9.35 (m, 1 H) 8.49 (dd, J = 1.6, 0.9 Hz, 1 H) 8.26 (d, J = 1.0 Hz, 1 H) 8.02 (dd, J = 8.9, 1.7 Hz, 1 H) 7.92 (s, 1 H) 7.74 - 7.83 (m, 1 H) 7.47 - 7.55 (m, 1 H) 7.44 (dd, J = 9.6, 1.9 Hz, 1 H) 4.10 (s, 3 H) 3.79 - 3.86 (m, 1 H) 3.69 - 3.76 (m, 1 H) 3.58 - 3.67 (m, 1 H) 3.43 - 3.50 (m, 1 H) 3.20 - 3.23 (m, 1 H) 2.75 - 2.82 (m, 1 H) 2.22 - 2.30 (m, 1 H) 2.04 - 2.11 (m, 3 H). Example 3 was synthesized following Scheme 26

[0030] Scheme 26 Step 1 Intermediate 116: rac-1-tert-butyl 2-methyl 5-oxo-4-(prop-2-en-1-yl)pyrrolidine- 1,2-dicarboxylate To a solution of rac-1-tert-butyl 2-methyl 5-oxopyrrolidine-1,2-dicarboxylate (CAS: 861657-91-2, 5.00 g, 19.5 mmol) in THF (75 mL) was added a solution of LiHMDS (21.6 mL, 1M in THF, 21.6 mmol) at -78°C. The reaction was stirred at -78°C for 1h and allyl bromide (4.97 g, 41.1mmol) in THF (10 mL) was added. The reaction was stirred at -78°C for 2h and then quenched with a saturated NH4Cl solution (200 mL). The reaction mixture was extracted three times with EtOAc. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated to dryness. The crude material was purified by flash chromatography on silica gel using PE / EtOAc (3 / 1) to afford rac-1-tert-butyl 2-methyl 5-oxo-4-(prop-2-en-1-yl)pyrrolidine- 1,2-dicarboxylate (Intermediate 116: 2.2 g, 30%) as a colorless oil. Mass spec: m / z: 184 [M+H-Boc]+. Step 2 Intermediate 117: rac-1-tert-butyl 2-methyl 5-oxo-4,4-bis(prop-2-en-1- yl)pyrrolidine-1,2-dicarboxylate To a solution of rac-1-tert-butyl 2-methyl 5-oxo-4-(prop-2-en-1-yl)pyrrolidine-1,2- dicarboxylate (Intermediate 116: 1.50 g, 4.50 mmol) in THF (30 mL) was added a solution of LiHMDS (5.56 mL, 1M in THF, 5.56mmol) at -78°C. The reaction was stirred at -78°C for 1h and allyl bromide (1.28 g, 10.6 mmol) in THF (5 mL) was added. The reaction was stirred at -78°C for 2h and quenched with a saturated NH4Cl solution (100 mL). The reaction mixture was extracted three times with EtOAc. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated to dryness. The crude material was purified by flash chromatography on silica gel using PE / EtOAc (3 / 1) to afford rac-1-tert-butyl 2-methyl 5-oxo-4,4-bis(prop- 2-en-1-yl)pyrrolidine-1,2-dicarboxylate (Intermediate 117: 900 mg, 53%) as a colourless oil. Mass spec: m / z: 224 [M+H-Boc]+. Step 3 Intermediate 118: rac-2-tert-butyl 3-methyl 1-oxo-2-azaspiro[4.4]non-7-ene-2,3- dicarboxylate To a solution of rac-1-tert-butyl 2-methyl 5-oxo-4,4-bis(prop-2-en-1-yl)pyrrolidine-1,2- dicarboxylate (Intermediate 117: 900 mg, 2.36 mmol) in DCM (30 mL) was added Grubbs 2ndgeneration catalyst (354 mg, 0.417 mmol). The reaction was stirred at rt overnight. The mixture was filtered, and the filtrate was concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel using PE / EtOAc ( / :1) to afford rac-2-tert-butyl 3-methyl 1-oxo-2-azaspiro[4.4]non-7-ene-2,3- dicarboxylate (Intermediate 118: 700 mg, 85%) as a colourless oil. Mass spec: m / z: 196 [M+H-Boc]+. Step 4 Intermediate 119: rac-2-tert-butyl 3-methyl 1-hydroxy-2-azaspiro[4.4]non-7-ene- 2,3-dicarboxylate To a solution of rac-2-tert-butyl 3-methyl 1-oxo-2-azaspiro[4.4]non-7-ene-2,3- dicarboxylate (Intermediate 118: 500 mg, 1.44 mmol) in THF (13 mL) was added LiBHEt3(179 mg, 1.69 mmol). The reaction was stirred at -78°C for 1h and then quenched with a saturated NaHCO3solution (50 mL). The mixture was extracted three times with EtOAc. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated to dryness to afford rac-2-tert-butyl 3- methyl 1-hydroxy-2-azaspiro[4.4]non-7-ene-2,3-dicarboxylate (Intermediate 119: 500 mg, 93%) as a colorless oil which was used in step 5 without further purification. Mass spec: m / z: 180 [M+H-Boc-OH]+. Step 5 Intermediate 120: rac-2-tert-butyl 3-methyl 2-azaspiro[4.4]non-7-ene-2,3- dicarboxylate To a solution of rac-2-tert-butyl 3-methyl 1-hydroxy-2-azaspiro[4.4]non-7-ene-2,3- dicarboxylate (Intermediate 119: 500 mg, 2.02 mmol) in DCM (20 mL) was added Et3SiH (616 mg, 5.30 mmol). Then the reaction was cooled to -78°C and BF3.Et2O (859 mg, 6.05 mmol) was added. The reaction was allowed to warm to rt over 2h and then quenched with a saturated NaHCO3solution (50 mL). The reaction mixture was extracted three times with EtOAc. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated to dryness to afford rac- 2-tert-butyl 3-methyl 2-azaspiro[4.4]non-7-ene-2,3-dicarboxylate (Intermediate 120: 400 mg, 85%) as a yellow oil which was used in step 6 without further purification. Mass spec: m / z: 226 [M+H-t-Bu]+. Step 6 Intermediate 121: rac-2-tert-butyl 3-methyl 2-azaspiro[4.4]nonane-2,3- dicarboxylate To a solution of rac-2-tert-butyl 3-methyl 2-azaspiro[4.4]non-7-ene-2,3-dicarboxylate (Intermediate 120: 400 mg, 1.14 mmol) in MeOH (10 mL) was added Pd / C (200 mg, 10% in carbon). Hydrogen (3 atm) was introduced and the mixture which was stirred at rt overnight. The mixture was filtered, and the filtrate was concentrated under reduced pressure to afford rac-2-tert-butyl 3-methyl 2-azaspiro[4.4]nonane-2,3-dicarboxylate (Intermediate 121: 350 mg, 88 %) as a brown oil which was used in step 6 without further purification. Mass spec: m / z: 228 [M+H-t-Bu]+. Step 7 Intermediate 122: rac-tert-butyl 3-(2-chloroacetyl)-2-azaspiro[4.4]nonane-2- carboxylate To a solution of rac-2-tert-butyl 3-methyl 2-azaspiro[4.4]nonane-2,3-dicarboxylate (Intermediate 121: 200 mg, 0.568 mmol) in THF (7 mL) was added Et3N (286 mg, 2.82 mmol) and sodium 2-chloroacetate (411 mg, 3.53 mmol). The reaction mixture was cooled to 0°C and tert-butyl(chloro)magnesium (412 mg, 3.53 mmol) was added dropwise under nitrogen atmosphere. The reaction mixture was stirred at 0°C for 2h and then quenched with a saturated NH4Cl solution (50 mL). The mixture was extracted three times with EtOAc. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated to dryness to afford rac-tert-butyl 3- (2-chloroacetyl)-2-azaspiro[4.4]nonane-2-carboxylate (Intermediate 122: 200 mg, 94%) as a colorless oil which was used in step 6 without further purification. Mass spec: m / z: 246 [M+H-t-Bu]+. Step 8 Intermediate 123: rac-tert-butyl 3-{6-bromoimidazo[1,2-a]pyridin-2-yl}-2- azaspiro[4.4]nonane-2-carboxylate To a solution of rac-tert-butyl 3-(2-chloroacetyl)-2-azaspiro[4.4]nonane-2-carboxylate (Intermediate 122: 180 mg, 0.477 mmol) and 5-bromopyridin-2-amine (103 mg, 0.596 mmol) in toluene (1.8 mL) and MeCN (5.4 mL) were added NaHCO3(60.1 mg, 0.715 mmol) and KI (9.90 mg, 0.06 mmol). The reaction was stirred at 100 °C for 16h. The mixture was concentrated under reduced pressure and the resulting crude material was purified by reverse-phase flash chromatography (C18 aq) using MeCN / H2O (2 / 3) to afford rac-tert-butyl 3-{6-bromoimidazo[1,2-a]pyridin-2-yl}-2-azaspiro[4.4]nonane-2- carboxylate (Intermediate 123: 80.0 mg, 32%) as a brown solid. Mass spec: m / z: 420 [M+H]+. Step 9 Intermediate 124: rac-tert-butyl 3-[6-(1-methylindazole-5-amido)imidazo[1,2- a]pyridin-2-yl]-2-azaspiro[4.4]nonane-2-carboxylate To a solution of rac-tert-butyl 3-{6-bromoimidazo[1,2-a]pyridin-2-yl}-2- azaspiro[4.4]nonane-2-carboxylate (Intermediate 123: 75.0 mg, 0.142 mmol) and 1- methylindazole-5-carboxamide (Intermediate 49: 31.3 mg, 0.178 mmol) in dioxane (1.88 mL) were added Cs2CO3(145 mg, 0.445 mmol), Gphos (9.56 mg, 0.0180 mmol) and Gphos Pd G6 TES (16.8 mg, 0.0180 mmol) under nitrogen atmosphere. The reaction was stirred at 100 °C for 2h. The mixture was concentrated under reduced pressure. The crude material was purified by reverse-phase flash chromatography (C18) using MeCN / H2O (1 / 1, 0.05% formic acid) to afford rac-tert-butyl 3-[6-(1- methylindazole-5-amido)imidazo[1,2-a]pyridin-2-yl]-2-azaspiro[4.4]nonane-2- carboxylate (Intermediate 124: 60 mg, 65%) as a brown solid. Mass spec: m / z: 515 [M+H]+. Step 10 Intermediate 125: rac-N-(2-{2-azaspiro[4.4]nonan-3-yl}imidazo[1,2-a]pyridin-6- yl)-1-methylindazole-5-carboxamide trifluoroacetate To a solution of rac-tert-butyl 3-[6-(1-methylindazole-5-amido)imidazo[1,2-a]pyridin-2- yl]-2-azaspiro[4.4]nonane-2-carboxylate (Intermediate 124: 50.0 mg, 0.082 mmol) in DCM (1 mL) was added TFA (0.5 mL). The reaction was stirred at rt for 1h and then concentrated under reduced pressure to afford rac-N-(2-{2-azaspiro[4.4]nonan-3- yl}imidazo[1,2-a]pyridin-6-yl)-1-methylindazole-5-carboxamide trifluoroacetate (Intermediate 125: 40 mg, quant.) as a brown oil which was used in step 11 without further purification. Mass spec: m / z: 415 [M+H]+. Step 11 Example 3: rac-1-methyl-N-(2-{2-methyl-2-azaspiro[4.4]nonan-3-yl}imidazo[1,2- a]pyridin-6-yl)indazole-5-carboxamide A solution of rac-N-(2-{2-azaspiro[4.4]nonan-3-yl}imidazo[1,2-a]pyridin-6-yl)-1- methylindazole-5-carboxamide trifluoroacetate (Intermediate 125: 40.0 mg, 0.0768 mmol) and paraformaldehyde (20.3 mg, 0.672 mmol) in MeOH (2 mL) was stirred at rt for 1h. Then, NaBH3CN (18.2 mg, 0.288 mmol) was added. The reaction solution was stirred at 60°C for 1h. The mixture was concentrated under reduced pressure. The crude material was purified by preparative HPLC (column: Xselect CSH Prep OBD C18, 300 x 50 mm, 5 μm; Eluent: MeCN in H2O (0.1% formic acid) from 5 to 30%; flow rate: 60 mL / min) to afford rac-1-methyl-N-(2-{2-methyl-2-azaspiro[4.4]nonan-3- yl}imidazo[1,2-a]pyridin-6-yl)indazole-5-carboxamide (Example 3: 10.7 mg, 31%) as a white solid. Mass spec: m / z: 429 [M+H]+;1H NMR (300 MHz, MeOH-d4) δ ppm 9.21 (s, 1H), 8.45 (s, 1H), 8.16 (s, 1H), 8.02 (d, J = 8.8 Hz, 1H), 7.83 (s, 1H), 7.67 (d, J = 8.8 Hz, 1H), 7.43 - 7.48 (m, 2H), 4.12 (s, 3H), 3.62 - 3.66 (m, 1H), 3.15 (d, J = 10.0 Hz, 1H), 2.45 (d, J = 9.6 Hz, 1H), 2.37 (s, 3H), 2.21 - 2.26 (m, 1H), 2.02 - 2.08 (m, 1H), 1.70 - 1.85 (m, 8H). Example 4 was synthesized following Scheme 27 Scheme 27 Step 1 Intermediate 126: rac-tert-butyl 2-[methoxy(methyl)carbamoyl]-2- methylpyrrolidine-1-carboxylate To a solution of rac-1-(tert-butoxycarbonyl)-2-methylpyrrolidine-2-carboxylic acid (CAS: 203869-80-1, 2.00 g, 8.72 mmol) in DCM (40 mL) at 0°C were added N, O- dimethylhydroxylamine (0.800 g, 13.0 mmol), EDCI (2.01 g, 10.4 mmol) and NMM (1.06 g, 10.5 mmol). The reaction mixture was stirred at rt for 2h and quenched with water. The aqueous layer was extracted three times with EtOAc and the organic layers were combined, washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to afford rac-tert-butyl 2- [methoxy(methyl)carbamoyl]-2-methylpyrrolidine-1-carboxylate (Intermediate 126: 1.91 g, 80%) as a colorless oil which was used in Step 2 without further purification. Mass spec: m / z 273 [M+H]+. Step 2 Intermediate 127: rac-tert-butyl 2-acetyl-2-methylpyrrolidine-1-carboxylate To a solution of rac-tert-butyl 2-[methoxy(methyl)carbamoyl]-2-methylpyrrolidine-1- carboxylate (Intermediate 126: 1.90 g, 6.98 mmol) in THF (20 mL) at 0°C was added a solution of MeMgBr (17.4 mL, 17.4 mmol, 1M in THF). The reaction mixture was stirred at rt for 48h and then quenched with water. The resulting solution was extracted with EtOAc three times and the organic layers were combined, washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to afford rac- tert-butyl 2-acetyl-2-methylpyrrolidine-1-carboxylate (Intermediate 127: 1.27 g, 72%) as a yellow oil which was used in step 3 without further purification. Mass spec: m / z 228 [M+H]+. Step 3 Intermediate 128: rac-tert-butyl 2-(2-chloroacetyl)-2-methylpyrrolidine-1- carboxylate To a solution of rac-tert-butyl 2-acetyl-2-methylpyrrolidine-1-carboxylate (Intermediate 127: 500 mg, 2.20 mmol) in THF (20 mL) was added a solution of LiHMDS (4.40 mL, 4.40 mmol, 1M in THF) for 1.5h at -78℃ under nitrogen atmosphere, followed by the dropwise addition of TMSCl (478 mg, 4.40 mmol). The reaction mixture was stirred at 0°C for 1h, cooled to -78°C and NCS (441 mg, 3.30 mmol) was added. The reaction mixture was warmed to rt and stirred overnight. The reaction mixture was quenched with water (100 mL). The phases were separated, and the aqueous phase was extracted with EtOAc three times. The combined organic layers were washed with brine (3 x 100 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel using PE / EtOAc (8 / 2) to afford rac-tert-butyl 2-(2- chloroacetyl)-2-methylpyrrolidine-1-carboxylate (Intermediate 128: 500 mg, 87%) as a yellow oil. Mass spec: m / z 262 [M+H]+. Step 4 Intermediate 129: rac-tert-butyl 2-{6-bromoimidazo[1,2-a]pyridin-2-yl}-2- methylpyrrolidine-1-carboxylate To a solution of rac-tert-butyl 2-(2-bromoacetyl)-2-methylpyrrolidine-1-carboxylate (Intermediate 128: 350 mg, 1.14 mmol) in MeCN (3 mL) and toluene (1 mL) were added 5-bromopyridin-2-amine (198 mg, 1.14 mmol), NaHCO3(115 mg, 1.37mmol) and KI (19.0 mg, 0.114 mmol). The reaction mixture was stirred at 100°C for 3h and then quenched with water. The phases were separated, and the aqueous phase was extracted with EtOAc three times. The combined organic layers were combined, washed with brine (3 x 50 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel using PE / EtOAc (8 / 2) to afford rac-tert-butyl 2-{6-bromoimidazo[1,2-a]pyridin-2-yl}- 2-methylpyrrolidine-1-carboxylate (Intermediate 129: 60.0 mg, 14%) as an off-white solid. Mass spec: m / z 380 [M+H]+. Step 5 Intermediate 130: rac-tert-butyl 2-methyl-2-[6-(1-methylindazole-5- amido)imidazo[1,2-a]pyridin-2-yl]pyrrolidine-1-carboxylate To a solution of rac-tert-butyl 2-{6-bromoimidazo[1,2-a]pyridin-2-yl}-2- methylpyrrolidine-1-carboxylate (Intermediate 129: 40.0 mg, 0.142 mmol) and 1- methylindazole-5-carboxamide (Intermediate 49: 27.3 mg, 0.156 mmol) in dioxane were added Cs2CO3(138 mg, 0.426 mmol), Gphos (1.90 mg, 0.004 mmol) and Gphos Pd G6 TES (3.35 mg, 0.004 mmol). The reaction mixture was stirred at 100℃ for 3h under nitrogen atmosphere. The mixture was concentrated under reduced pressure. The crude material was purified by reverse-phase flash chromatography (C18) using MeCN / H2O (75 / 25, 0.05% formic acid) to afford rac-tert-butyl 2-methyl-2-[6-(1- methylindazole-5-amido)imidazo[1,2-a]pyridin-2-yl]pyrrolidine-1-carboxylate (Intermediate 130: 43.0 mg, 86%) as an off-white solid. Mass spec: m / z 389 [M+H]+. Step 6. Intermediate 131: rac-1-methyl-N-[2-(2-methylpyrrolidin-2-yl)imidazo[1,2- a]pyridin-6-yl]indazole-5-carboxamide trifluoroacetate To a solution of rac-tert-butyl 2-methyl-2-[6-(1-methylindazole-5-amido)imidazo[1,2- a]pyridin-2-yl]pyrrolidine-1-carboxylate (Intermediate 130: 40.0 mg, 0.106 mmol) in DCM (0.6 mL) was added TFA (0.2 mL). The reaction mixture was stirred at rt for 2h and then concentrated under reduced pressure to afford rac-1-methyl-N-[2-(2- methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]indazole-5-carboxamide trifluoroacetate (Intermediate 131: 14.0 mg, 95%) as a yellow oil. Mass spec: m / z 280 [M+H]+. Step 7 Example 4: rac-N-[2-(1,2-dimethylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1- methylindazole-5-carboxamide To a solution of rac-1-methyl-N-[2-(2-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6- yl]indazole-5-carboxamide trifluoroacetate (Intermediate 131: 5.0 mg, 0.054 mmol) in MeOH (1 mL) were added Et3N (1 mL) and paraformaldehyde (8.04 mg, 0.270 mmol). The reaction mixture was stirred at rt for 1h. NaBH3CN (10.1 mg, 0.162 mmol) was added. The reaction mixture was stirred at 60°C for 1h and then concentrated under reduced pressure. The residue was purified by preparative HPLC (Column: XBridge Prep OBD C18 Column, 30x150 mm, 5 μm; Eluent: MeCN in water (10mmol / L NH4HCO3+ 0.05% NH4OH) from 30 to 60%; Flow rate: 60 mL / min) to provide rac-N- [2-(1,2-dimethylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1-methylindazole-5- carboxamide (Example 4: 2.4 mg, 4%) as an off-white solid. Mass spec: m / z: 389 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ ppm 10.34 (s, 1H), 9.23 (s,1H), 8.49 (s,1H), 8.26 (s, 1H), 8.00 - 8.03 (m, 1H), 7.86 (s, 1H), 7.77 - 7.79 (m, 1H), 7.50 -7.52 (m, 1H), 7.39 - 7.42 (m, 1H), 4.10 (s, 3H), 2.74 - 2.8...

Claims

CLAIMS 1. A compound which is a Proteolysis Targeting Chimera (PROTAC) or a pharmaceutically acceptable salt thereof, wherein the PROTAC has the structure: wherein U is an E3 ubiquitin ligase binding moiety, LINK is a moiety that covalently links M and U, and M is an MLLT1 and / or MLLT3 binder of formula (I):wherein: one of Z2and Z4is N and the other is C, Z1is N or -C(R4)-, Z3is -C(R4)-, Y1is N or - C(R7)-, Y2is N or -C(R6)-, and Y3is N or -C(R5)-; Hy is a 4- to 7-membered heterocyclyl ring containing X and at least one N atom, wherein: ring Hy is linked to ring A via a C atom within ring Hy, said C atom also being linked to R2; a N atom within ring Hy is substituted by R1; X is a bond, -N(R11)-, O, S, -S(O)2-, -S(O)(NR11)-, or -C(R11)2-; and the rest of ring Hy is unsubstituted or substituted by one or two R3; L is –C(O)N(H)-, wherein the C atom of L is bonded to R8, and the N atom of L is bonded to ring B; R1is H, C1-4cycloalkyl, or C1-4alkyl which is itself unsubstituted or substituted with one C1-4alkoxy or one, two or three halo; R2is H or methyl; each R3is independently selected from C1-4alkyl, C1-4alkoxy, phenyl, a 5- to 6- membered heteroaryl ring and halo, or (i) two R3linked to adjacent C atoms in ring Hy form, together with the C atoms to which they are attached, a C5-6cycloalkyl ring, or (ii) two R3linked to the same C atom in ring Hy form, together with the C atom to which they are attached, a C3-6cycloalkyl ring or a C3-6heterocycloalkyl ring;R4, R6, and R7are independently selected from H, halo, C1-4alkoxy, and C1-4alkyl which is itself unsubstituted or substituted by one, two or three halo; R5is selected from H, halo, C1-4alkoxy, C3-5cycloalkyl and C1-4alkyl which is itself unsubstituted or substituted by one, two or three halo; R8is (i) a bond to LINK or (ii) a group selected from a 6- to 10-membered aryl ring, a 5- to 10-membered heteroaryl ring, a 5- to 10-membered heterocyclyl ring, and a 5- to 6-membered cycloalkyl ring, the group R8being unsubstituted or substituted by one, two or three substituents independently selected from halo, C1-4alkoxy, R10, -(C1-4alkylene)-R10, =O, -CN, and C1-4alkyl which is itself unsubstituted or substituted by one or two R9; each R9is independently selected from halo and C1-4alkoxy; R10is a group selected from a 5- to 6-membered heteroaryl ring, a 3- to 6-membered cycloalkyl ring, a 4- to 6-membered heterocyclyl ring, and a phenyl ring, the group R10being unsubstituted or substituted by one or two substituents independently selected from C1-4alkyl, C1-4alkoxy, and halo; and each R11is independently selected from H, C1-4alkyl, and C1-4cycloalkyl; wherein either R8is (i) a bond to LINK, or R8is a group (ii) and M is bonded to LINK via a C or N atom within group R8such that a hydrogen atom on the C or N atom within group R8is replaced with a bond to LINK.

2. A compound according to claim 1, wherein LINK is (a) a single bond, or (b) a chemical linker group represented by formula (L):wherein: LINK is attached to M via L1; LINK is attached to U via L3; L1 and L3 are each independently selected from a single bond, ethynyl -N(R’)-, - C(O)N(R’)-, -O-, -N(R’)C(O)-, -C(O)-, -S(O2)N(R’)-, -N(R’)S(O2)-, -(C1-6alkylene)-, -(C2-6alkenylene)-, a divalent 3- to 6-membered cycloalkyl ring and a divalent 4- to 7-membered heterocyclyl ring; L2 is represented by the formula -(L4)m-; each L4 is independently selected from a divalent 3- to 6-membered cycloalkyl ring, a divalent 4- to 7-membered heterocyclyl ring and a unit of formula:each XLis independently selected from a single bond, -N(R’)-, -O-, -C(O)-, -S-, -SO-, - SO2-, -C(H)=C(H)- and -C(H)≡C(H)-; n is selected from 1 to 4; m is selected from 1 to 30; and each R’ is independently selected from H and C1-4alkyl.

3. A compound according to claim 1 or 2, wherein U is: (a) a CRBN E3 ubiquitin ligase binding moiety of formula (U1):wherein: RU1is H; Q is selected from -CH(RU6)-, -N(RU6)-, -O-, -C(O)-, -NH-CH(RU6)-, -N=C(RU6)-, or -N=N-; RU6is H or C1-4alkyl;RU2and RU5are each independently selected from H, halogen, C1-4alkyl, NH2, NO2, OH, COOH, CN, CF3, and a single bond to LINK; RU3and RU4are each independently selected from H, halogen, C1-4alkyl, NH2, NO2, OH, COOH, CN, CF3, and a single bond to LINK; wherein one and only one of RU2, RU3, RU4and RU5is a single bond to LINK; (b) a CRBN E3 ubiquitin ligase binding moiety of formula (U4):wherein: RU1’is H; Q’ is N and LUis a single bond, or Q’ is CH and LUis selected from a single bond or -C(O)N(H)-, wherein either (i) the C atom of LUis bonded to phenyl, and the N atom of LUis bonded to Q’; or (ii) the C atom of LUis bonded to Q’, and the N atom of LUis bonded to phenyl; RU12, RU13and RU14are each independently selected from H, halogen, C1-4alkyl, NH2, NO2, OH, COOH, CN, CF3, and a single bond to LINK; wherein one and only one of RU12, RU13and RU14is a single bond to LINK; RU15and RU16are each independently selected from H, halogen, C1-4alkyl, NH2, NO2, OH, COOH, CN and CF3; (c) a CRBN E3 ubiquitin ligase binding moiety of formula (U5):wherein: RU17is H; RU18, RU19, RU20and RU21are each independently selected from H, halogen, C1-4alkyl, NH2, NO2, OH, COOH, CN, CF3, and a single bond to LINK; wherein one and only one of RU18, RU19, RU20and RU21is a single bond to LINK; or (d) a VHL E3 ubiquitin ligase binding moiety of formula (U2):wherein: RU7is a group selected from phenyl, a 5- to 6-membered heteroaryl ring, a 5- to 6- membered heterocyclyl ring, and a 5- to 6-membered cycloalkyl ring, the group RU7being unsubstituted or substituted by C1-4alkyl; RU11is H or C1-4alkyl;RU8is selected from C1-4alkyl, phenyl and a 3- to 8-membered cycloalkyl ring; and RU9is a single bond to LINK.

4. A compound according to any one of the preceding claims, wherein M is of formula (II):wherein: Z1, Z2, Z3, Z4, Y1, Y2, Y3, R1, R2, R8, X and L are as defined in any one of the preceding claims; R3aand R3bare independently selected from H, C1-4alkyl, phenyl, a 5- to 6-membered heteroaryl ring and C1-4alkoxy, or R3aand R3bform, together with the C atom to which they are attached, a C3-6cycloalkyl ring or a C3-6heterocycloalkyl ring, R3cand R3dare independently selected from H, C1-4alkyl, halo, phenyl, a 5- to 6- membered heteroaryl ring and C1-4alkoxy, or R3cand R3dform, together with the C atom to which they are attached, a C3-6cycloalkyl ring or a C3-6heterocycloalkyl ring, with the proviso that when X is NR11, O, or S, then neither R3cnor R3dare halo, or R3aand R3care H, and R3band R3dform, together with the C atoms to which they are attached, a C5-6cycloalkyl ring; wherein at least two of R3a, R3b, R3cand R3dare H; and wherein either R8is (i) a bond to LINK, or R8is a group (ii) and M is bonded to LINK via a C or N atom within group R8such that a hydrogen atom on the C or N atom within group R8is replaced with a bond to LINK.

5. A compound according to any one of claims 1 to 4, wherein M is of formula (III):wherein: R1is H or C1-4alkyl which is itself unsubstituted or substituted with one C1-4alkoxy or one, two or three halo, preferably with one C1-4alkoxy; R2is H or methyl; R3aand R3bare independently selected from H, C1-4alkyl, and C1-4alkoxy, or R3aand R3bform, together with the C atom to which they are attached, a C3-6cycloalkyl ring, R3cand R3dare independently selected from H, C1-4alkyl, halo and C1-4alkoxy, or R3cand R3dform, together with the C atom to which they are attached, a C3-6cycloalkyl ring, with the proviso that when X is O, then neither R3cnor R3dare halo, or R3aand R3care H, and R3band R3dform, together with the C atoms to which they are attached, a C5-6 cycloalkyl ring; wherein at least two of R3a, R3b, R3cand R3dare H; X is a bond, -N(Me)-, O or -CH2-; Y1is N or -C(R7)-; R5, R6and R7are independently selected from H, halo C1-4alkoxy, and C1-4alkyl; R8is (i) a bond to LINK or (ii) a group selected from a 6- to 10-membered aryl ring, a 5- to 10-membered heteroaryl ring, and a 5- to 10-membered heterocyclyl ring, the group R8being unsubstituted or substituted by one, two or three substituents independently selected from halo, C1-4alkoxy, R10, -(C1-4alkylene)-R10, =O, -CN, and C1-4alkyl which is itself unsubstituted or substituted by one or two R9; each R9is independently selected from halo and C1-4 alkoxy;R10is a group selected from a 5- to 6-membered heteroaryl ring, a 3- to 6-membered cycloalkyl ring, a 4- to 6-membered heterocyclyl ring, and a phenyl ring, the group R10being unsubstituted or substituted by one or two substituents independently selected from C1-4alkyl, C1-4alkoxy, and halo; and wherein either R8is (i) a bond to LINK, or R8is a group (ii) and M is bonded to LINK via a C or N atom within group R8such that a hydrogen atom on the C or N atom within group R8is replaced with a bond to LINK.

6. A compound according to any one of claims 1 to 3, wherein M is a monovalent moiety of: 1-methyl-N-{8-methyl-2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}- 1H-indazole-5-carboxamide; 1,3-dimethyl-N-{8-methyl-2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6- yl}-1H-indazole-6-carboxamide; rel-7-fluoro-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyridin-6-yl}quinoline- 6-carboxamide; N-{2-[(2R,4S)-4-fluoro-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}-1-methyl- 1H-indazole-5-carboxamide; 1,3-dimethyl-N-{2-[(2R)-pyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}-1H-indazole-6- carboxamide; rel-1,3-dimethyl-N-{2-[(2R)-1,4,4-trimethylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6- yl}-1H-indazole-6-carboxamide; rel-1,3-dimethyl-N-{2-[(2R)-1,4,4-trimethylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6- yl}-1H-indazole-6-carboxamide; N-{2-[4-ethyl-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}-1,3-dimethyl-1H- indazole-6-carboxamide; rel-N-{2-[(2R)-1,4-dimethylpiperazin-2-yl]imidazo[1,2-a]pyrazin-6-yl}-1,3-dimethyl- 1H-indazole-6-carboxamide; rel-N-{2-[(2R)-1,4-dimethylpiperazin-2-yl]imidazo[1,2-a]pyrazin-6-yl}-1,3-dimethyl- 1H-indazole-6-carboxamide; rel-7-fluoro-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyridin-6- yl}isoquinoline-6-carboxamide;rel-5-fluoro-1,3-dimethyl-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6- yl}-1H-indazole-6-carboxamide; 1-methyl-N-(2-{2-methyl-2-azaspiro[4.4]nonan-3-yl}imidazo[1,2-a]pyridin-6-yl)-1H- indazole-5-carboxamide; rel-3-ethyl-1-methyl-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}- 1H-indazole-6-carboxamide; rel-3-cyclopropyl-1-methyl-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin- 6-yl}-1H-indazole-6-carboxamide; N-[2-(1,2-dimethylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1-methyl-1H-indazole-5- carboxamide; rel-2-fluoro-4-(2-methyl-1,3-thiazol-5-yl)-N-{2-[(2R)-1-methylpyrrolidin-2- yl]imidazo[1,2-a]pyridin-6-yl}benzamide; rel-1-methyl-N-{2-[(2R)-1-methylpiperidin-2-yl]imidazo[1,2-a]pyridin-6-yl}-1H- indazole-5-carboxamide; rel-1-methyl-N-{2-[(2R)-1-methylpiperidin-2-yl]imidazo[1,2-a]pyridin-6-yl}-1H- indazole-5-carboxamide; 1-methyl-N-{2-[(2S)-1-methyl-octahydro-1H-indol-2-yl]imidazo[1,2-a]pyridin-6-yl}- 1H-indazole-5-carboxamide; 1-methyl-N-{2-[(2R)-1-methyl-octahydro-1H-indol-2-yl]imidazo[1,2-a]pyridin-6-yl}- 1H-indazole-5-carboxamide; rel-2-fluoro-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyridin-6-yl}-5- (pyrazin-2-yl)benzamide; rel-1,3-dimethyl-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}-1H- indazole-6-carboxamide; rel-1,3-dimethyl-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}-1H- indazole-6-carboxamide; rel-1,3-dimethyl-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}-1H- indazole-6-carboxamide; rel-1,3-dimethyl-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}-1H- indazole-6-carboxamide; N-[2-(4-methoxy-1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1-methyl-1H- indazole-5-carboxamide;rel-2-fluoro-5-(2-methyl-1,3-thiazol-5-yl)-N-{2-[(2R)-1-methylpyrrolidin-2- yl]imidazo[1,2-a]pyridin-6-yl}benzamide; N-[2-(1,4-dimethylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1-methyl-1H-indazole-5- carboxamide; rel-2-fluoro-4-(4-methyl-1,3-thiazol-5-yl)-N-{2-[(2R)-1-methylpyrrolidin-2- yl]imidazo[1,2-a]pyridin-6-yl}benzamide; N-[2-(1,5-dimethylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1-methyl-1H-indazole-5- carboxamide; 1-methyl-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyrazin-6-yl]-1H-indazole-5- carboxamide; rel-2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)-N-{2-[(2R)-1-methylpyrrolidin-2- yl]imidazo[1,2-a]pyridin-6-yl}benzamide; rel-2-fluoro-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyridin-6-yl}-4- (pyrimidin-2-yl)benzamide; rel-2-fluoro-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyridin-6-yl}-4- (pyrazin-2-yl)benzamide; 1,3-dimethyl-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1H-thieno[2,3- c]pyrazole-5-carboxamide; 6-methoxy-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1,3- benzothiazole-2-carboxamide; 4-(2-methyl-1,3-thiazol-4-yl)-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6- yl]benzamide; 4-chloro-1,3-dimethyl-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1H- pyrazolo[3,4-b]pyridine-5-carboxamide; 1,3-dimethyl-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1H-indazole-6- carboxamide; N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-6-(1H-pyrazol-1- yl)pyridine-3-carboxamide; N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-4-(1H-1,2,4-triazol-1- yl)benzamide; 2,3-dimethyl-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]quinoxaline-6- carboxamide;N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1,5-naphthyridine-2- carboxamide; 7-chloro-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]quinoline-3- carboxamide; N-[8-methoxy-2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1,3-dimethyl- 1H-indazole-6-carboxamide; N-{2-[1-(2-methoxyethyl)pyrrolidin-2-yl]imidazo[1,2-a]pyridin-6-yl}-1,3-dimethyl-1H- indazole-6-carboxamide; rel-2-fluoro-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyridin-6-yl}-4-(1,3- thiazol-5-yl)benzamide; rel-6-fluoro-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyridin-6- yl}naphthalene-2-carboxamide; rel-6-fluoro-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyridin-6- yl}naphthalene-2-carboxamide; rel-6-fluoro-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyridin-6- yl}naphthalene-2-carboxamide; rel-6-fluoro-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyridin-6- yl}naphthalene-2-carboxamide; rel-2-fluoro-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyridin-6-yl}-4-(1,3- thiazol-5-yl)benzamide; 5-fluoro-1,3-dimethyl-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1H- indazole-6-carboxamide; N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-[1,2,4]triazolo[4,3- a]pyridine-7-carboxamide; 4-chloro-1-methyl-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1H- indazole-5-carboxamide; N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-3H-imidazo[4,5-b]pyridine- 5-carboxamide; N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]imidazo[1,5-a]pyridine-7- carboxamide; N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-4-(1,2,4-oxadiazol-3- yl)benzamide;3-ethyl-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-[1,2,4]triazolo[4,3- a]pyridine-7-carboxamide; 1,3-dimethyl-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1H- pyrazolo[3,4-b]pyridine-6-carboxamide; N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]imidazo[1,2-a]pyrazine-2- carboxamide; N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]furo[2,3-c]pyridine-2- carboxamide; 1-methyl-N-[2-(4-methylmorpholin-3-yl)imidazo[1,2-a]pyridin-6-yl]-1H-indazole-5- carboxamide; 3-methyl-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-[1,2]oxazolo[5,4- b]pyridine-6-carboxamide; N-[7-fluoro-2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1,3-dimethyl-1H- indazole-6-carboxamide; 4-fluoro-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1H-indole-5- carboxamide; 3-(2-methoxyethyl)-1-methyl-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6- yl]-1H-indazole-5-carboxamide; 3-methyl-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1,2-benzoxazole- 6-carboxamide; N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]quinazoline-7-carboxamide; 2-(4-methoxyphenyl)-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1,3- thiazole-4-carboxamide; N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1,3-benzoxazole-6- carboxamide; N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-2-phenyl-1,3-oxazole-5- carboxamide; 1-cyclohexyl-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1H-1,2,3- benzotriazole-5-carboxamide; 5-methyl-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-4-oxo-1H,4H- thieno[2,3-d]pyrimidine-6-carboxamide; 1-methyl-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-3-(pyrrolidin-3- yl)-1H-indazole-5-carboxamide;N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-3-(1H-pyrazol-1- yl)benzamide; 3-cyclopentyl-1-methyl-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1H- indazole-5-carboxamide; N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-4-[(1H-pyrazol-1- yl)methyl]benzamide; N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1,3-benzothiazole-5- carboxamide; N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-4-(1H-pyrazol-1- yl)benzamide; 6-methoxy-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1H-indole-3- carboxamide; 3-ethyl-1-methyl-N-[2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyridin-6-yl]-1H- indazole-5-carboxamide; rel-1-methyl-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyridin-6-yl}-1H- indazole-5-carboxamide; rel-1-methyl-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyridin-6-yl}-1H- indazole-5-carboxamide; N-{2-[(rel-2R,4S)-4-methoxy-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}-1- methylindazole-5-carboxamide; N-{2-[(rel-2S,4S)-4-methoxy-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}-1- methylindazole-5-carboxamide; rac-N-[2-(4-tert-butyl-1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyrazin-6-yl]-1,3- dimethylindazole-6-carboxamide; N-{2-[(rel-2R)-1-ethylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}-1,3- dimethylindazole-6-carboxamide; N-{2-[(rel-2S)-1-ethylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}-1,3- dimethylindazole-6-carboxamide; N-(2-((2R, rel-4R)-1,4-dimethylpyrrolidin-2-yl)imidazo[1,2-a]pyrazin-6-yl)-1-methyl- 1H-indazole-5-carboxamide; N-(2-((2R, rel-4S)-1,4-dimethylpyrrolidin-2-yl)imidazo[1,2-a]pyrazin-6-yl)-1-methyl- 1H-indazole-5-carboxamide;6-fluoro-1-methyl-N-{8-methyl-2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2- a]pyrazin-6-yl}indazole-5-carboxamide; (R)-6-chloro-1-methyl-N-(8-methyl-2-(1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyrazin- 6-yl)-1H-indazole-5-carboxamide; 6-fluoro-3-methyl-N-{8-methyl-2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a] pyrazin-6-yl}imidazo[1,5-a]pyridine-7-carboxamide; 6-fluoro-1,3-dimethyl-N-{8-methyl-2-[(2R)-1-methylpyrrolidin-2-yl] imidazo[1,2- a]pyrazin-6-yl}imidazo[1,5-a]pyridine-7-carboxamide; 1-methyl-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6- yl}pyrazolo[3,4-c]pyridine-5-carboxamide; 6-methoxy-1-methyl-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6- yl}indazole-5-carboxamide; 3-methyl-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}-1,2,3- benzotriazole-5-carboxamide; 1-methyl-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}-3- (piperidin-1-yl)indazole-6-carboxamide; N-[8-cyclopropyl-2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl]-5- fluoro-1,3-dimethyl-indazole-6-carboxamide; N-[8-cyclopropyl-2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl]-1- methyl-indazole-5-carboxamide; 6-fluoro-1-methyl-N-[2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6- yl]indazole-5-carboxamide; 1-methyl-N-[2-[(6R)-5-methyl-5-azaspiro[2.4]heptan-6-yl]imidazo[1,2-a]pyrazin-6- yl]indazole-5-carboxamide; N-{2-[(rel-2R,4R)-4-methoxy-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}-1- methylindazole-5-carboxamide; N-{2-[(rel-2S,4R)-4-methoxy-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}-1- methylindazole-5-carboxamide; N-(2-((2R,4R)-4-fluoro-1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyrazin-6-yl)-1-methyl- 1H-indazole-5-carboxamide.

7. A compound according to any one of claims 1 to 3, wherein M is of formula (IV):wherein R8is a group selected from a 6- to 10-membered aryl ring and a 5- to 10- membered heteroaryl ring, the group R8being unsubstituted or substituted by one, two or three substituents independently selected from halo and C1-4alkyl; wherein M is bonded to LINK via a C or N atom within group R8such that a hydrogen atom on the C or N atom within group R8is replaced with LINK.

8. A compound according to claim 7, wherein R8is selected from one of the following structures:wherein: represents the point of attachment of R8to the rest of moiety M; represents the point of attachment of R8to LINK; and the group R8is further unsubstituted or substituted by one or two substituents independently selected from fluorine and methyl.

9. A compound according to any one of claims 1 to 3, wherein M is of formula (IVA):wherein R8is a bond to LINK.

10. A compound according to claim 1 which is selected from: 1-(8-{[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino}octyl)-3-methyl-N-{2- [(rel-2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}indazole-6-carboxamide; 1-(8-{[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino}octyl)-3-methyl-N-{2- [(rel-2S)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}indazole-6-carboxamide; (2S,4R)-1-[(2S)-3,3-dimethyl-2-(11-{[4-({2-[(rel-2R)-1-methylpyrrolidin-2- yl]imidazo[1,2-a]pyrazin-6-yl}carbamoyl)phenyl]formamido}undecanamido)butanoyl]- 4-hydroxy-N-{[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl}pyrrolidine-2-carboxamide; (2S,4R)-1-[(2S)-3,3-dimethyl-2-(11-{[4-({2-[(rel-2S)-1-methylpyrrolidin-2- yl]imidazo[1,2-a]pyrazin-6-yl}carbamoyl)phenyl]formamido}undecanamido)butanoyl]- 4-hydroxy-N-{[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 7-{[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino}-N-{2-[(2R)-1- methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}heptanamide; 3-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-5-yl]piperazin-1- yl}methyl)piperidin-1-yl]-1-methyl-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2- a]pyrazin-6-yl}indazole-5-carboxamide; 3-(4-(2-(4-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)piperazin-1- yl)ethyl)piperidin-1-yl)-1-methyl-N-(2-((R)-1-methylpyrrolidin-2-yl)imidazo[1,2- a]pyrazin-6-yl)-1H-indazole-5-carboxamide 3-(4-(2-(4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperazin-1- yl)ethyl)piperidin-1-yl)-1-methyl-N-(2-((R)-1-methylpyrrolidin-2-yl)imidazo[1,2- a]pyrazin-6-yl)-1H-indazole-5-carboxamide;1-(8-{[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino}octyl)-5-fluoro-3- methyl-N-{2-[(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}indazole-6- carboxamide; 1-(8-{[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]oxy}octyl)-3-methyl-N-{2- [(2R)-1-methylpyrrolidin-2-yl]imidazo[1,2-a]pyrazin-6-yl}indazole-6-carboxamide; 1-(6-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)amino)hexyl)-3-methyl-N- (2-((R)-1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyrazin-6-yl)-1H-indazole-6- carboxamide; 4-(1-(3-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)propyl)- 1H-pyrazol-4-yl)-N-(2-((R)-1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyrazin-6- yl)benzamide; 4-(1-(3-(1-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)piperidin-4-yl)propyl)-1H- pyrazol-4-yl)-N-(2-((R)-1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyrazin-6- yl)benzamide; 1-(7-(2-(2, 6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl) hept-6-yn-1-yl)-3-methyl-N-(2- ((R)-1-methylpyrrolidin-2-yl) imidazo [1, 2-a] pyrazin-6-yl)-1H-indazole-6- carboxamide; 1-(9-(2-(2, 6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl) non-8-yn-1-yl)-3-methyl-N-(2- ((R)-1-methylpyrrolidin-2-yl) imidazo [1, 2-a] pyrazin-6-yl)-1H-indazole-6- carboxamide; 1-(2-((6-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)hex-5-yn-1-yl)oxy)ethyl)-3- methyl-N-(2-((R)-1-methylpyrrolidin-2-yl)imidazo[1,2-a]pyrazin-6-yl)-1H-indazole-6- carboxamide; and the pharmaceutically acceptable salts thereof.

11. A pharmaceutical composition which comprises a compound as defined in any one of claims 1 to 10 and a pharmaceutically acceptable carrier or diluent.

12. A compound as defined in any one of claims 1 to 10 for use in the treatment of the human or animal body by therapy.

13. A compound as defined in any one of claims 1 to 10 for use in the treatment of cancer.

14. The compound for use according to claim 13, wherein the cancer is a transcriptionally addicted cancer, such as breast cancer, acute leukemia, prostate cancer, bladder cancer, cholangiocarcinoma, colon adenocarcinoma, esophageal carcinoma, head and neck squamous cell carcinoma, kidney chromophobe, kidney renal clear cell carcinoma, kidney renal papillary cell carcinoma, liver hepatocellular carcinoma, lung adenocarcinoma, pheochromocytoma and paraganglioma, rectum adenocarcinoma, stomach adenocarcinoma, uterine corpus endometrial carcinoma, cervical squamous cell carcinoma and endocervical adenocarcinoma, lung squamous cell carcinoma, neuroblastoma, midline glioma or sarcoma, preferably neuroblastoma or midline glioma.

15. The compound for use according to claim 13, wherein the cancer is acute myeloid leukaemia (AML), myelodysplastic syndrome (MDS), myeloproliferative neoplasm (MPN) or acute lymphoblastic leukaemia (ALL), for instance wherein the cancer is mixed-lineage leukaemia (MLL), rearranged acute leukemia (AML and ALL) or NPM1 mutant leukemia.

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