compounds

Abstract

A compound of formula (I), or a salt, solvate or prodrug thereof: Q-L-M (I) wherein Q is a protein binding moiety of formula Q1 or Q2 as defined herein, L is a linker moiety as defined herein; and M is an E3 ubiquitin ligase binding moiety. Also, a pharmaceutical compositions and combinations comprising compounds of formula I and the use of said compounds, compositions and combinations in therapy, particularly in the treatment or prevention of diseases or conditions mediated by RIPK1 kinase.

Description

COMPOUNDSINTRODUCTION

[0001] The present invention relates to bifunctional compounds comprising a protein-binding moiety and an E3 ubiquitin ligase binding moiety. The compounds disclosed herein are useful in a method of targeted protein degradation, in particular the compounds disclosed herein are proteolysis-targeting chimera (PROTAC) protein degraders.

[0002] The protein-binding moiety binds to a protein of interest while the E3 ubiquitin ligase binding moiety recruits and binds an E3 ubiquitin ligase. Simultaneous binding of the protein of interest and ligase by the compounds disclosed herein induces ubiquitylation of the protein of interest and its subsequent degradation by the ubiquitin-proteasome system.

[0003] In one embodiment, the compounds disclosed herein target RIPK1 kinase, and consequently have utility in the treatment or prevention of diseases or conditions mediated by RIPK1 kinase.BACKGROUND OF THE INVENTION

[0004] Receptor-interacting protein kinase-1 (RIPK1) has emerged as a promising therapeutic target for the treatment of various human pathologies, including cancer, neurodegeneration, and autoimmune disorders1-3. Recent studies have shown that RIPK1 plays a crucial role in determining the outcome of cell death in response to various stimuli, including chemotherapy, radiation, and immunotherapy. Additionally, RIPK1 has been found to be involved in the development of resistance to immunotherapy in cancer cells4.

[0005] RIPK1 biology is complex as RIPK1 can positively and negatively regulate cell death and inflammation56, depending on context. While controlled activation of RIPK1 contributes to tissue repair and immune surveillance, chronic deregulated activation of RIPK1 signalling can lead to many immune and autoinflammatory diseases7-12. Blocking RIPK1-induced cell death has been shown to rescue inflammatory-driven pathologies in several models of disease1-3. Aberrant activation of RIPK1, as a consequence of mutations in genes encoding for proteins that negatively regulate RIPK1 such as TBK1, A20 (also known as TNFAIP3), ABIN1 (also known as TNIP1), NEMO, OTULIN and members of the LUBAC complex have been found to trigger RIPK1-mediated autoimmune disorders and autoinflammatory conditions (reviewed in1), including rheumatoid arthritis, psoriasis and dermatitis as well as chronic neurodegenerative conditions such as multiple sclerosis, amyotrophic lateral sclerosis, and Alzheimer’s disease2’1314. As these proteins negatively regulate RIPK1, mutational impairmentor age-related decrease in protein expression or function, has been shown to drive chronic RIPK1 activation, which in turn causes sustained cell death and inflammation. Consistently, targeting RIPK1 kinase activity significantly suppresses the pathology induced by loss of A20 in a mouse model of arthritis1011and inflammatory bowel disease (IBD)15. Similarly, deletion of Nemo in intestinal epithelial cells causes colitis as a consequence of chronic activation of RIPK1. Again, deregulated RIPK1 kinase-mediated cell death is likely the underlying mechanism causing inflammatory disease9. Thus, deregulation of RIPK1 is a common feature in chronic inflammatory disease, indicating RIPK1 as a promising therapeutic target.

[0006] With respect to cancer, targeting RIPK1 using small molecules has the potential to overcome apoptosis resistance and trigger more immunogenic forms of cell death1617, such as necroptosis, to enhance the effectiveness of cancer therapies. Necroptosis is a lytic form of cell death that is often linked to pathogens and, therefore, is highly potent in initiating strong immune responses1819. Additionally, necroptosis can kill apoptosis-resistant tumour cells. Moreover, recent data demonstrate that cancer cells often hijack RIPK1 to promote resistance to immunotherapy by blocking immunogenic forms of cell death4. Importantly, the scaffolding function of RIPK1 contributes to enhanced cell survival and the production of an immunosuppressive chemokine programme, ultimately resulting in decreased infiltration of CD8 and NK cells, and profound resistance to ICB4.

[0007] Although RIPK1 has become a major therapeutic target, its immunosuppressive and pro-survival activity cannot be neutralized by kinase inhibitors alone. This is because RIPK1's ability to promote cell survival and resistance to immunotherapy is not solely dependent on its kinase function but also on its scaffolding activity. Additionally, while kinase inhibitors are highly effective in mice, they only partially suppress RIPK1 -induced cell death in humans, as they are unable to block RIPK1 -induced apoptosis in human cells. Therefore, alternative strategies, such as the use of PROTAC-degraders, that can specifically target RIPK1 scaffolding function may be more effective in treating RIPK1 -driven disease.

[0008] There is a need in the art for alternative and / or improved compounds and alternative / improved methods of specifically targeting and degrading certain proteins, such as RIPK1. For instance, compounds having improved binding specificity to proteins such as RIPK1, and / or having improved pharmacokinetic parameters, such as plasma stability, bioavailability and the like, are desirable in the art.SUMMARY OF THE INVENTION

[0009] In one aspect, the present invention provides a compound of formula I, or a salt, solvate or prodrug thereof as defined herein:Q-L-M (I)

[0010] In a second aspect, the present invention relates to a pharmaceutical composition comprising a compound according to the first aspect, or a pharmaceutically acceptable salt, solvate or prodrug thereof, and one or more pharmaceutically acceptable excipient or carrier.

[0011] In another aspect, the present invention relates to a compound according to the first aspect, or a pharmaceutically acceptable salt, solvate or prodrug thereof, or a pharmaceutical composition according to the second aspect, for use in therapy.

[0012] In another aspect, the present invention relates to a compound according to the first aspect, or a pharmaceutically acceptable salt, solvate or prodrug thereof, or a pharmaceutical composition according to the second aspect, for use in the treatment or prevention of disease or condition mediated by RIPK1.

[0013] In another aspect, the present invention relates to a compound according to the first aspect, or a pharmaceutically acceptable salt, solvate or prodrug thereof, or a pharmaceutical composition according to the second aspect, for use in the treatment or prevention of a proliferative disorder, an inflammatory disease or condition, a neurodegenerative disorder or condition, an autoimmune disorder or condition, or a metabolic disease or condition.

[0014] In another aspect, the present invention relates to a compound according to the first aspect, or a pharmaceutically acceptable salt, solvate or prodrug thereof, or a pharmaceutical composition according to the second aspect, for use in the treatment or prevention of cancer.

[0015] In another aspect, the present invention relates to a method of treating or preventing a disease or condition mediated by RIPK1, said method comprising administering to a subject in need thereof an effective amount of a compound according to the first aspect, or a pharmaceutically acceptable salt, solvate or prodrug thereof, or a pharmaceutical composition according to the second aspect.

[0016] In another aspect, the present invention relates to a method of treating or preventing a proliferative disorder, an inflammatory disease or condition, a neurodegenerative disorder or condition, an autoimmune disorder or condition, or a metabolic disease or condition, said method comprising administering to a subject in need thereof an effective amount of a compound according to the first aspect, or a pharmaceutically acceptable salt, solvate or prodrug thereof, or a pharmaceutical composition according to the second aspect.

[0017] In another aspect, the present invention relates to a method of treating or preventing a cancer, said method comprising administering to a subject in need thereof an effective amount of a compound according to the first aspect, or a pharmaceutically acceptable salt, solvate or prodrug thereof, or a pharmaceutical composition according to the second aspect.

[0018] In another aspect, the present invention relates to a method of degrading a protein in a cell, said method comprising delivering to said cell an effective amount of a compound according to the first aspect, or a pharmaceutically acceptable salt, solvate or prodrug thereof, or a pharmaceutical composition according to the second aspect.

[0019] In another aspect, the present invention relates to a combination of a compound according to the first aspect, or a pharmaceutically acceptable salt, solvate or prodrug thereof, or a pharmaceutical composition according to the second aspect and one or more additional therapeutic agent or treatment.

[0020] Preferred, suitable, and optional features of any one particular aspect of the present invention are also preferred, suitable, and optional features of any other aspect.DETAILED DESCRIPTION OF THE INVENTIONDefinitions

[0021] The compounds and intermediates described herein may be named according to either the IUPAC (International Union for Pure and Applied Chemistry) or CAS (Chemical Abstracts Service) nomenclature systems. It should be understood that unless expressly stated to the contrary, the terms “compounds of Formula I” and the more general term “compounds” refer to and include any and all compounds described by and / or with reference to Formula I. It should also be understood that, unless specified otherwise, these terms encompass all stereoisomers, i.e. cis and trans isomers, as well as optical isomers, i.e. R and S enantiomers, of such compounds and all salts thereof, in substantially pure form and / or any mixtures of the foregoing in any ratio. This understanding extends to sub-formulae of formula I and pharmaceutical compositions and methods of treatment that employ or comprise one or more compounds of the Formula I, either by themselves or in combination with additional agents.

[0022] The various hydrocarbon-containing moieties provided herein may be described using a prefix designating the minimum and maximum number of carbon atoms in the moiety, e.g. “(Ca-b)” or “Ca-Cb” or “(a-b)C”. For example, (Ca-b)alkyl indicates an alkyl moiety having the integer “a” to the integer “b” number of carbon atoms, inclusive. Certain moieties may also be described according to the minimum and maximum number of members with or withoutspecific reference to a particular atom or overall structure. For example, the terms “a to b membered ring” or “having between a to b members” refer to a moiety having the integer “a” to the integer “b” number of atoms, inclusive.

[0023] " About" when used herein in conjunction with a measurable value such as, for example, an amount or a period of time and the like, is meant to encompass reasonable variations of the value, for instance, to allow for experimental error in the measurement of said value.

[0024] As used herein by themselves or in conjunction with another term or terms, "alkyl" and “alkyl group” refer to a branched or unbranched saturated hydrocarbon chain. Unless specified otherwise, alkyl groups typically contain 1-10 carbon atoms, such as 1-6 carbon atoms or 1-4 carbon atoms or 1-3 carbon atoms, and can be substituted or unsubstituted. Representative examples include, but are not limited to, methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, isopropyl, tert-butyl, isobutyl, etc.

[0025] As used herein by themselves or in conjunction with another term or terms, “alkoxy” and “alkoxy group” refer to O-alkyl groups. Representative examples include, but are not limited to, -OMe, -OEt, -O-'Pr and O- Bu. Alkoxy groups can be substituted or unsubstituted unless indicated otherwise.

[0026] As used herein by themselves or in conjunction with another term or terms, “alkylene” and “alkylene group” refer to a branched or unbranched saturated hydrocarbon chain. Unless specified otherwise, alkylene groups typically contain 1-10 carbon atoms, such as 1-6 carbon atoms or 1-3 carbon atoms, and can be substituted or unsubstituted. Representative examples include, but are not limited to, methylene (-CH2-), the ethylene isomers (-CH(CH3)- and -CH2CH2-), the propylene isomers (-CH(CH3)CH2–, -CH(CH2CH3)-, -C(CH3)2-, and -CH2CH2CH2-), etc.

[0027] As used herein by themselves or in conjunction with another term or terms, “alkenyl” and “alkenyl group” refer to a branched or unbranched hydrocarbon chain containing at least one double bond. Unless specified otherwise, alkenyl groups typically contain 2-10 carbon atoms, such as 2-6 carbon atoms or 2-4 carbon atoms, and can be substituted or unsubstituted. Representative examples include, but are not limited to, ethenyl, 3-buten-1-yl, 2-ethenylbutyl, and 3-hexen-1-yl.

[0028] As used herein by themselves or in conjunction with another term or terms, “alkynyl” and “alkynyl group” refer to a branched or unbranched hydrocarbon chain containing at leastone triple bond. Unless specified otherwise, alkynyl groups typically contain 2-10 carbon atoms, such as 2-6 carbon atoms or 2-4 carbon atoms, and can be substituted or unsubstituted. Representative examples include, but are not limited to, ethynyl, 3-butyn-1-yl, propynyl, 2-butyn-1-yl, and 3-pentyn-1-yl.

[0029] As used herein by themselves or in conjunction with another term or terms, “heteroalkyl,” refers to a stable straight or branched chain, or combinations thereof, including at least one carbon atom and at least one heteroatom (e.g., O, N, P, Si, and S), and wherein the nitrogen and sulfur atoms may optionally be oxidized, and the nitrogen heteroatom may optionally be quaternized. The heteroatom(s) may be placed at any interior position of the heteroalkyl group or at the position at which the alkyl group is attached to the remainder of the molecule. A heteroalkyl group is an uncyclized chain. Examples include, but are not limited to: -CH2-CH2-O-CH3, -CH2-CH2-NH-CH3, -CH2-CH2-N(CH3)-CH3, -CH2-S-CH2-CH3, -S(O)-CH3, -CH2-CH2-S(O)2-CH3, -CH=CH-O-CH3, -Si(CH3)3, -CH2-CH=N-OCH3, -CH=CH-N(CH3)-CH3, and polyethylenoxy chains such as -(O(CH2)2)n(OCH2CH3). Up to two or three heteroatoms may be consecutive, such as, for example, -CH2-NH-OCH3 and -CH2-O-Si(CH3)3. A heteroalkyl moiety may include one or more heteroatoms which may be the same or different.

[0030] Similarly, the term “heteroalkylene,” by itself or as part of another substituent, means, unless otherwise stated, a divalent radical derived from heteroalkyl, as exemplified, but not limited by, -CH2-CH2-S-CH2-CH2 - and -CH2-S-CH2-CH2-NH-CH2-. For heteroalkylene groups, heteroatoms can also occupy either or both of the chain termini (e.g., alkyleneoxy, alkylenedioxy, alkyleneamino, alkylenediamino, and the like).

[0031] As used herein by itself or in conjunction with another term or terms, “aromatic” refers to monocyclic and polycyclic ring systems containing 4n+2 pi electrons, where n is an integer. Aromatic should be understood as referring to and including ring systems that contain only carbon atoms (i.e. “aryl”) as well as ring systems that contain at least one heteroatom selected from N, O or S (i.e. “heteroaromatic” or “heteroaryl”). An aromatic ring system can be substituted or unsubstituted.

[0032] As used herein by itself or in conjunction with another term or terms, “non-aromatic” refers to a monocyclic or polycyclic ring system having at least one double bond that is not part of an extended conjugated pi system. As used herein, non-aromatic refers to and includes ring systems that contain only carbon atoms as well as ring systems that contain at least one heteroatom selected from N, O or S. A non-aromatic ring system can be substituted or unsubstituted.

[0033] As used herein by themselves or in conjunction with another term or terms, “aryl” and “aryl group” refer to phenyl and 7-15 membered bicyclic or tricyclic hydrocarbon ring systems, including bridged, spiro, and / or fused ring systems, in which at least one of the rings is aromatic. Aryl groups can be substituted or unsubstituted. Unless specified otherwise, an aryl group may contain 6 ring atoms (i.e., phenyl) or a ring system containing 9 to 15 atoms, such as 9 to 11 ring atoms, or 9 or 10 ring atoms. Representative examples include, but are not limited to, naphthyl, indanyl, 1,2,3,4-tetrahydronaphthalenyl and 6,7,8,9-tetrahydro-5H-benzocycloheptenyl. Suitably an aryl group is phenyl and naphthyl, suitably phenyl.

[0034] As used herein by themselves or in conjunction with another term or terms, “arylalkyl” and “arylalkyl group” refer to an alkyl substituent in which a hydrogen atom is replaced by an aryl group, wherein alkyl group and aryl group are as previously defined, such as, for example, benzyl (C6H5CH2-). Arylalkyl groups can be substituted or unsubstituted.

[0035] As used herein by themselves or in conjunction with another term or terms, “carbocyclic group” and “carbocycle” refer to monocyclic and polycyclic ring systems that contain only carbon atoms in the ring(s), i.e., hydrocarbon ring systems, without regard or reference to aromaticity or degree of unsaturation. Thus, carbocyclic group should be understood as referring to and including ring systems that are fully saturated (such as, for example, a cyclohexyl group), ring systems that are aromatic (such as, for example, a phenyl group), as well as ring systems having fully saturated, aromatic and / or unsaturated portions (such as, for example, cyclohexenyl, 2,3-dihydro-indenyl, and 1,2,3,4-tetrahydronaphthalenyl). The terms carbocyclic and carbocycle further include bridged, fused, and spirocyclic ring systems.

[0036] As used herein by themselves or in conjunction with another term or terms, “cycloalkyl” and “cycloalkyl group” refer to a non-aromatic carbocyclic ring system, that may be monocyclic, bicyclic, or tricyclic, saturated or unsaturated, and may be bridged, spiro, and / or fused. A cycloalkyl group may be substituted or unsubstituted. Unless specified otherwise, a cycloalkyl group typically contains from 3 to 12 ring atoms. In some instances a cycloalkyl group may contain 4 to 10 ring atoms (e.g., 4 ring atoms, 5 ring atoms, 6 ring atoms, 7 ring atoms, etc.). Representative examples include, but are not limited to, cyclopropyl, cyclopropenyl, cyclobutyl, cyclobutenyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, norbornyl, norbornenyl, bicyclo[2.2.1]hexane, bicyclo[2.2.1]heptane, bicyclo[2.2.1]heptene, bicyclo[3.1.1]heptane, bicyclo[3.2.1]octane, bicyclo[2.2.2]octane, bicyclo[3.2.2]nonane, bicyclo[3.3.1]nonane, and bicyclo[3.3.2]decane. Suitably, cycloalkyl groups are selected from cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl groups.

[0037] As used herein by themselves or in conjunction with another term or terms, “cycloalkylalkyl” and “cycloalkylalkyl group” refer to an alkyl substitutent in which a hydrogen atom is replaced by a cycloalkyl group, wherein alkyl group and cycloalkyl group are as previously defined, such as, for example, cyclohexylmethyl (C6H11CH2-). Cycloalkylalkyl groups can be substituted or unsubstituted.

[0038] As used herein by themselves or in conjunction with another term or terms, “haloalkyl” and “haloalkyl group” refer to alkyl groups in which one or more hydrogen atoms are replaced by halogen atoms. Haloalkyl includes both saturated alkyl groups as well as unsaturated alkenyl and alkynyl groups. Representative examples include, but are not limited to, -CF3, -CHF2, -CH2F, -CF2CF3, -CHFCF3, -CH2CF3, -CF2CH3, -CHFCH3, -CF2CF2CF3, -CF2CH2CH3, -CF=CF2, -CCI=CH2, -CBr=CH2, -CI=CH2, -C≡C-CF3, -CHFCH2CH3and -CHFCH2CF3. Haloalkyl groups can be substituted or unsubstituted. Suitably, a haloalkyl group is selected from CHF2and CF3, suitably CF3.

[0039] As used herein by themselves or in conjunction with another term or terms, “haloalkoxy” and “haloalkoxy group” refer to alkoxy groups (i.e. O-alkyl groups) in which one or more hydrogen atoms are replaced by halogen atoms. Haloalkoxy includes both saturated alkoxy groups as well as unsaturated alkenyl and alkynyl groups. Representative examples include, but are not limited to, -OCF3, -OCHF2, -OCH2F, -OCF2CF3, -OCHFCF3, -OCH2CF3, -OCF2CH3, -OCHFCH3, -OCF2CF2CF3, -OCF2CH2CH3, -OCF=CF2, -OCCI=CH2, -OCBr=CH2, -OCHFCH2CH3 and -OCHFCH2CF3. Haloalkoxy groups can be substituted or unsubstituted. Suitably, a haloalkoxy group is selected from -OCHF2and -OCF3, suitably -OCF3.

[0040] As used herein by themselves or in conjunction with another term or terms, “halo” and “halogen” include fluorine, chlorine, bromine and iodine atoms and substituents.

[0041] As used herein by themselves or in conjunction with another term or terms, “heteroaryl” and “heteroaryl group” refer to (a) 5 and 6 membered monocyclic aromatic rings, which contain, in addition to carbon atom(s), at least one heteroatom, such as nitrogen, oxygen or sulfur, and (b) 7 to 15 membered bicyclic and tricyclic rings, which contain, in addition to carbon atom(s), at least one heteroatom, such as nitrogen, oxygen or sulfur, and in which at least one of the rings is aromatic. In some instances, a heteroaryl group can contain two or more heteroatoms, which may be the same or different. Heteroaryl groups can be substituted or unsubstituted, and may be bridged, spiro, and / or fused. In some instances, a heteroaryl group may contain 5, 6, or 8 to 15 ring atoms. In other instances, a heteroaryl group may contain 5 to 10 ring atoms, such as 5, 6, 9, or 10 ring atoms. Representative examples include,but are not limited to, 2,3-dihydrobenzofuranyl, 1,2-dihydroquinolinyl, 3,4-dihydroisoquinolinyl, 1,2,3,4-tetrahydroisoquinolinyl, 1,2,3,4-tetrahydroquinolinyl, benzoxazinyl, benzthiazinyl, chromanyl, furanyl, 2-furanyl, 3-furanyl, imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, oxazolyl, pyridinyl, 2-, 3-, or 4-pyridinyl, pyrimidinyl, 2-, 4-, or 5-pyrimidinyl, pyrazolyl, pyrrolyl, 2- or 3-pyrrolyl, pyrazinyl, pyridazinyl, 3- or 4-pyridazinyl, 2-pyrazinyl, thienyl, 2-thienyl, 3-thienyl, tetrazolyl, thiazolyl, thiadiazolyl, triazinyl, triazolyl, pyridin-2-yl, pyridin-4-yl, pyrimidin-2-yl, pyridazin-4-yl, pyrazin-2-yl, naphthyridinyl, pteridinyl, phthalazinyl, purinyl, alloxazinyl, benzimidazolyl, benzofuranyl, benzofurazanyl, 2H-1-benzopyranyl, benzothiadiazine, benzothiazinyl, benzothiazolyl, benzothiophenyl, benzoxazolyl, cinnolinyl, furopyridinyl, indolinyl, indolizinyl, indolyl, or 2-, 3-, 4-, 5-, 6-, or 7-indolyl, 3H-indolyl, quinazolinyl, quinoxalinyl, isoindolyl, isoquinolinyl, 10-aza-tricyclo[6.3.1.02’7]dodeca-2(7), 3, 5-trienyl, 12-oxa-10-aza-tricyclo[6.3.1,02’7]dodeca-2(7), 3, 5-trienyl, 12-aza-tricyclo[7.2.1.02’7]dodeca- 2(7), 3, 5-trienyl, 10-aza-tricyclo[6.3.2.02’7]trideca-2(7),3,5-trienyl, 2,3,4,5-tetrahydro-1 H-benzo[d]azepinyl, 1,3,4,5-tetrahydro-benzo[d]azepin-2-onyl, 1,3,4,5-tetrahydro-benzo[b]azepin-2-onyl, 2,3,4,5-tetrahydro-benzo[c]azepin-1-onyl, 1,2,3,4-tetrahydro-benzo[e][1,4]diazepin-5-onyl, 2,3,4,5-tetrahydro-1 H-benzo[e][1,4]diazepinyl, 5, 6,8,9-tetrahydro-7-oxa-benzocycloheptenyl, 2,3,4,5-tetrahydro-1 H-benzo[b]azepinyl, 1,2,4,5-tetra hydro- be nzo[e][1,3]diazepin-3-onyl, 3,4-dihydro-2H-benzo[b][1,4]dioxepinyl, 3,4-dihydro-2H-benzo[f][1,4]oxazepin-5-onyl, 6,7,8,9-tetrahydro-5-thia-8-aza-benzocycloheptenyl, 5,5-dioxo-6,7,8,9-tetrahydro-5-thia-8-aza-benzocycloheptenyl, and 2,3,4,5-tetrahydro-benzo[f][1,4]oxazepinyl. Suitably, a heteroaryl is a 5- or 6-membered heteroaryl ring comprising one, two or three heteroatoms selected from N, O or S.

[0042] As used herein by themselves or in conjunction with another term or terms, “heteroarylalkyl” and “heteroarylalkyl group” refer to an alkyl substituent in which a hydrogen atom is replaced by a heteroaryl group, wherein alkyl group and heteroaryl group are as previously defined. Heteroarylalkyl groups can be substituted or unsubstituted. Where carbon numbers are provided, e.g. heteroaryl(Cn-m)alkyl, the range refers to the alkyl group. Suitably, the constituent alkyl group has 1-6 carbons, suitable 1-3 carbons.

[0043] As used herein by themselves or in conjunction with another term or terms, “heterocyclic group” and “heterocycle” refer to monocyclic and polycyclic ring systems that contain carbon atoms and at least one heteroatom selected from nitrogen, oxygen, sulfur or phosphorus in the ring(s), without regard or reference to aromaticity or degree of unsaturation. Thus, a heterocyclic group should be understood as referring to and including ring systems that are fully saturated (such as, for example, a piperidinyl group), ring systems that are aromatic (such as, for example, a pyridinyl group), as well as ring systems having fullysaturated, aromatic and / or unsaturated portions (such as, for example, 1, 2,3,6-tetrahydropyridinyl and 2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-1-yl). The terms heterocyclic and heterocycle further include bridged, fused, and spirocyclic ring systems.

[0044] As used herein by themselves or in conjunction with another term or terms, “heterocycloalkyl” and “heterocycloalkyl group” refer to 3 to 15 membered monocyclic, bicyclic, and tricyclic non-aromatic ring systems, which contain, in addition to carbon atom(s), at least one heteroatom, such as nitrogen, oxygen, sulfur or phosphorus. Heterocycloalkyl groups may be fully saturated or contain unsaturated portions and may be bridged, spiro, and / or fused ring systems. In some instances a heterocycloalkyl group may contain at least two or more heteroatoms, which may be the same or different. Heterocycloalkyl groups can be substituted or unsubstituted. In some instances a heterocycloalkyl group may contain from 3 to 10 ring atoms or from 3 to 7 ring atoms or from 5 to 7 ring atoms, such as 5 ring atoms, 6 ring atoms, or 7 ring atoms. Representative examples include, but are not limited to, tetrahydrofuranyl, pyrrolidinyl, pyrrolinyl, imidazolidinyl, imidazolinyl, pyrazolidinyl, pyrazolinyl, piperidyl, piperazinyl, indolinyl, isoindolinyl, morpholinyl, thiomorpholinyl, homomorpholinyl, homopiperidyl, homopiperazinyl, thiomorpholinyl-5-oxide, thiomorpholinyl-S, S-dioxide, tetrahydropyranyl, piperidinyl, tetrahydrothienyl, homopiperidinyl, homothiomorpholinyl-S, S-dioxide, oxazolidinonyl, dihydropyrazolyl, dihydropyrrolyl, dihydropyrazinyl, dihydropyridinyl, dihydropyrimidinyl, dihydrofuryl, dihydropyranyl, tetrahydrothienyl-5-oxide, tetrahydrothienyl-S, S-dioxide, homothiomorpholinyl-5-oxide, quinuclidinyl, 2-oxa-5-azabicyclo[2.2.1]heptanyl, 8-oxa-3-aza-bicyclo[3.2.1]octanyl, 3,8-diaza-bicyclo[3.2.1]octanyl, 2,5-diaza-bicyclo[2.2.1]heptanyl, 3,8-diaza-bicyclo[3.2.1]octanyl, 3,9-diaza-bicyclo[4.2.1]nonanyl, 2,6-diaza-bicyclo[3.2.2]nonanyl, [1,4]oxaphosphinanyl- 4-oxide, [1,4]azaphosphinanyl- 4-oxide, [1.2]oxaphospholanyl- 2-oxide, phosphinanyl-1-oxide, [1,3]azaphospholidinynl- 3-oxide, [1.3]oxaphospholanyl- 3-oxide, 7-oxabicyclo[2.2.1]heptanyl, 6,8-dihydro-5H-imidazo[1,5-a]pyrazin-7-yl, 6,8-dihydro-5H-imidazo[1,2-a]pyrazin-7-yl, 5,6,8,9-tetrahydro-[1,2,4]triazolo[4, 3-d][1,4]diazepin-7-yl and 6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl. Suitably, a heterocycloalkyl group as defined herein is a monocyclic, bicyclic or spiro heterocyclyl group comprising one, two or three heteroatoms selected from N, O or S.

[0045] As used herein by themselves or in conjunction with another term or terms, “heterocycloalkylalkyl” and “heterocycloalkylalkyl group” refer to an alkyl substituent in which a hydrogen atom is replaced by a heterocycloalkyl group, wherein alkyl group and heterocycloalkyl group are as previously defined, such as, for example, pyrrolidinylmethyl (C4H8NCH2-). Heteroycloalkylalkyl groups can be substituted or unsubstituted. Where carbonnumbers are provided, e.g. heterocycloalkyl(Cn-m)alkyl, the range refers to the alkyl group. Suitably, the constituent alkyl group has 1-6 carbons, suitable 1-3 carbons.

[0046] As used herein, “oxo” refers to a double bond to oxygen, i.e. =0.

[0047] As used herein by itself or in conjunction with another term or terms, “pharmaceutically acceptable” refers to materials that are generally chemically and / or physically compatible with other ingredients (such as, for example, with reference to a formulation), and / or is generally physiologically compatible with the recipient (such as, for example, a subject) thereof.

[0048] As used herein by itself or in conjunction with another term or terms, “pharmaceutical composition” refers to a composition that can be used to treat a disease, condition, or disorder in a subject, including a human.

[0049] As used herein by themselves or in conjunction with another term or terms, “stable” and “chemically stable” refer to a compound that is sufficiently robust to be isolated from a reaction mixture with a useful degree of purity. The present application is directed solely to the preparation of stable compounds. When lists of alternative substituents include members which, owing to valency requirements, chemical stability, or other reasons, cannot be used to substitute a particular group, the list is intended to be read in context to include those members of the list that are suitable for substituting the particular group. For example, when considering the degree of optional substitution of a particular moiety, it should be understood that the number of substituents does not exceed the valency appropriate for that moiety.

[0050] As used herein by themselves or in conjunction with another term or terms, “subject(s)” and “patient(s)”, suitably refer to mammals, in particular humans.

[0051] As used herein by itself or in conjunction with another term or terms, “substituted” indicates that a hydrogen atom on a molecule has been replaced with a different atom or group of atoms and the atom or group of atoms replacing the hydrogen atom is a “substituent.” It should be understood that the terms “substituent”, “substituents”, “moiety”, “moieties”, “group”, or “groups” refer to substituent(s).

[0052] As used herein by themselves or in conjunction with another term or terms, “therapeutic” and “therapeutically effective amount” refer to an amount a compound, composition or medicament that (a) inhibits or causes an improvement in a particular disease, condition or disorder; (b) attenuates, ameliorates or eliminates one or more symptoms of a particular disease, condition or disorder. It should be understood that the terms “therapeutic” and “therapeutically effective” encompass any one of the aforementioned effects (a)-(b), eitheralone or in combination with any of the others (a)-(b). It should be understood that in, for example, a human or other mammal, a therapeutically effective amount can be determined experimentally in a laboratory or clinical setting, or a therapeutically effective amount may be the amount required by the guidelines of the United States Food and Drug Administration (FDA) or equivalent foreign regulatory body, for the particular disease and subject being treated. It should be appreciated that determination of proper dosage forms, dosage amounts, and routes of administration is within the level of ordinary skill in the pharmaceutical and medical arts.

[0053] As used herein whether by themselves or in conjunction with another term or terms, “treating”, “treated” and “treatment”, refer to and include ameliorative, palliative, and curative uses and results. In some embodiments, the terms “treating”, “treated”, and “treatment” refer to curative uses and results as well as uses and results that diminish or reduce the severity of a particular condition, characteristic, symptom, disorder, or disease described herein. For example, treatment can include diminishment of several symptoms of a condition or disorder or complete eradication of said condition or disorder.

[0054] As used herein, the terms “prevent”, “preventative” or “prevention”, refers to diminishing the likelihood, or delaying the onset, of one or more symptoms of a particular disease, condition or disorder described herein. It should be understood that the terms “prevent”, “preventative” or “prevention” are not necessarily used in an absolute sense, but also refers to uses and results where the administration of a compound or composition diminishes the likelihood or seriousness of a condition, symptom, or disease state, and / or delays the onset of a condition, symptom, or disease state for a period of time.

[0055] As used herein, a ’’therapeutic agent” or “therapeutically active agent”, whether used alone or in conjunction with another term or terms, refers to any compound, i.e. a drug, that has been found to be useful in the treatment of a disease, disorder or condition and is not described by Formula I. It should be understood that a therapeutic agent may or may not be approved by the FDA or an equivalent foreign regulatory body.

[0056] A “effective amount” means the amount of a compound that, when administered to a subject or patient for treating a disease, is sufficient to effect such treatment for the disease. The "effective amount" will vary depending on the compound, the disease and its severity and the age, weight, etc., of the subject or patient to be treated.

[0057] A bond terminating in a “” or ” represents that the bond is connected to another atom that is not shown in the structure. A bond terminating inside a cyclic structureand not terminating at an atom of the ring structure represents that the bond may be variably connected to atoms in the ring structure where allowed by valency unless otherwise defined.

[0058] As used herein, the term “moiety” refers a portion or functional group of a molecule. Chemical moieties are often recognized as chemical entities embedded in or appended to a molecule.Compounds

[0059] In one aspect the present disclosure relates to a compound of formula I, or a salt, solvate or prodrug thereof:Q-L-M (I)whereinQ is a protein binding moiety of formula Q1, Q2or Q3:whereR1aand R1bare independently selected from the group consisting of 6 to 15 membered aryl, 5 to 12 membered heteroaryl, 3 to 12 membered heterocycloalkyl, C3-11 cycloalkyl, C1.10alkyl, C2-10 alkenyl and C2-10alkynyl, each of which is optionally substituted with one or more groups Ra1;each Ra1is independently selected from the group consisting of hydroxyl, =0, halogen, CN, C1.6 haloalkyl, Ci-e haloalkoxy, Ci-e alkyl, O-C1.6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, -O-C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, benzyl, 5-6 membered heteroaryl, -C(=O)Rb1,-C(=O)NRd1Re1, -NRd1Re1, -NRd1C(=O)Rb1, -0Rc1, -SRc1, -OC(=O)Rb1,-S(=O)2Rc1and -S(=0)2NRd1Re1, where said Ci-e alkyl, O-C1.6 alkyl, C3-6 cycloalkyl, -O-C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, 5-11 membered heteroaryl, phenyl and benzyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =0, -CN, C1.6 haloalkyl, Ci-e haloalkoxy, C3-6 cycloalkyl, Ci-e alkyl, -O-C1.6 alkyl, phenyl, -C(0)Ci-6alkyl, -C(O)N(H)CI-6alkyl, -C(O)N(CI-6alkyl)2, -CONH2, -C(O)N(H)CI-6alkyl, -C(O)N(CI-6alkyl)2, -N(H)Ci-e alkyl, and -N(Ci-e alkyl)2;where Rb1, Rc1, Rd1and Re1are independently selected from the group consisting of hydrogen, hydroxyl, Ci-e haloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-6 cycloalkyl, C1-6 alkyl, -O-C1.6 alkyl and phenyl, wherein said C1-6 alkyl, -O-C1.6 alkyl, phenyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)Ci-6alkyl, -N(Ci-ealkyl)2, Ci-e haloalkyl, C3-6 cycloalkyl, C6-11aryl, 3-7 membered heterocycloalkyl, Ci-e alkyl and -O-C1.6 alkyl; orRd1and Re1, when attached to the same atom, together with the atom to which they are attached form a 3-7 membered ring, optionally containing one or more heteroatoms selected from O, N and S, and wherein said ring is optionally substituted with one or more Rf1;where each Rf1is independently selected from the group consisting of hydrogen, =0, halogen, -CN, -NH2, -N(H)CI-6 alkyl, -N(Ci-ealkyl)2, Ci-e haloalkyl, C3-6 cycloalkyl, phenyl, 3-7 membered heterocycloalkyl, Ci-e alkyl and -O-C1.6 alkyl;E1is selected from -N(R2)C(=O)-, -C(=O)N(R2a)-, -N(R2)S(=O)2-, -S(=O)2N(R2a)- or -(R2)NC(=O)N(R2a)-;E2is selected from -C(=0)-, -S(=0)2- or -N(R2)C(=O)-;X20is selected from O, S, S(=0), S(=0)2, NH and N(CI-4 alkyl);R2and R2aare independently selected from H, Ci-e alkyl, C3-6cycloalkyl or C3-6 cycloalkyl-CH2-; orR2together with a R7aor R8agroup and the atoms to which they are attached form a 4 to 7 membered heterocycloalkyl ring which is optionally substituted with one or more groups selected from hydroxyl, halogen, =0, -CN, Ci-e haloalkyl, Ci-e haloalkoxy, cyclopropyl, Ci-ealkyl, -O-C1-6 alkyl, -C(O)Ci-6alkyl, -C(O)N(H)Ci-e alkyl, -C(O)N(Ci-e alkyl)2, -CONH2, -C(O)N(H)CI-6alkyl, -C(O)N(Ci-6alkyl)2, -N(H)Ci-e alkyl, and -N(Ci-6alkyl)2;R7a, R7b, R8aand R8bare each independently selected from the group consisting of hydrogen, deuterium, hydroxyl, =0, halogen, CN, Ci-ehaloalkyl, Ci-e haloalkoxy, Ci-e alkyl, O-C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, where said Ci-e alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =0, -CN, C1-6 haloalkyl, Ci-e haloalkoxy, C3-6 cycloalkyl, Ci-e alkyl, -O-C1-6 alkyl, phenyl, -C(0)Ci-6alkyl, -C(O)N(H)Ci-e alkyl, -C(O)N(Ci-e alkyl)2, -CONH2, -C(O)N(H)Ci-e alkyl, -C(O)N(Ci-6alkyl)2,-N(H)Ci-6 alkyl, and -N(Ci-6alkyl)2; orR7aand R8atogether with the carbon atom to which they are attached form a 3-5 membered cycloalkyl or 3-5 membered heterocycloalkyl group, each of which is optionally substituted with one or more groups selected from hydroxyl, halogen, =0, -CN, Ci-ehaloalkyl, C1.6 haloalkoxy, C3-6 cycloalkyl, Ci-ealkyl, -O-C1.6 alkyl, phenyl, -C(0)Ci-6 alkyl, -C(O)N(H)Ci.6 alkyl, -C(O)N(Ci-6alkyl)2,-CONH2, -C(O)N(H)Ci-e alkyl, -C(O)N(Ci-6alkyl)2, -N(H)Ci-e alkyl, and -N(Ci-ealkyl)2; orR7band R8btogether with the carbon atom to which they are attached form a 3-5 membered cycloalkyl or 3-5 membered heterocycloalkyl group, each of which is optionally substituted with one or more groups selected from hydroxyl, halogen, =0, -CN, Ci-ehaloalkyl, C1.6 haloalkoxy, C3-6 cycloalkyl, Ci-ealkyl, -O-C1.6 alkyl, phenyl, -C(0)Ci-6 alkyl, -C(O)N(H)Ci.6 alkyl, -C(O)N(Ci-6alkyl)2,-CONH2, -C(O)N(H)Ci-e alkyl, -C(O)N(Ci-6alkyl)2, -N(H)Ci-e alkyl, and -N(Ci-ealkyl)2;n is an integer of value 0, 1, 2, 3, 4 or 5;B is a cyclic group selected from 5 to 12 membered heteroaryl or C6-11aryl;C is a heterocycle containing at least one nitrogen atom in the ring, wherein the■'k.R R moiety is bonded to ring C via a nitrogen atom in ring C;A is a cyclic group selected from 5 to 15 membered heteroaryl;V is selected from the group consisting of -NH-, -C(O)N(H)-, -N(H)C(O)-, -S(O)(NH)-, -N(H)S(O)-, -S(O)N(H)-, -N(H)S(O)2- and -S(O)2N(H)-;R3and R9are independently selected from the group consisting of hydroxyl, =0, halogen, CN, Ci-ehaloalkyl, Ci-e haloalkoxy, Ci-ealkyl, O-Ci-ealkyl, C2-ealkenyl, C2.6alkynyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, --C(=O)Rb3, -C(=O)ORc3, -C(=O)NRd3Re3, -NRd3Re3, -NRd3C(=O)Rb3,–ORc3, –SRc3, where said Ci-6alkyl,O-C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl and phenyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =0, CN, Ci-ehaloalkyl, Ci-e haloalkoxy, C3-6 cycloalkyl, Ci-e alkyl, O-C1.6 alkyl, -NH2, -N(H)CI-3 alkyl, and -N(Ci-3alkyl)2;where Rb3, Rc3, Rd3and Re3are independently selected from the group consisting of hydrogen, hydroxyl, Ci-e haloalkyl, O-C1.6 haloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-6 cycloalkyl, C1-6 alkyl, -O-C1.6 alkyl and Ce-isaryl, wherein said Ci-e alkyl, -O-C1.6 alkyl, Ce-isaryl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)Ci-ealkyl, -N(Ci-ealkyl)2, Ci-ehaloalkyl, C3-6 cycloalkyl, C6-11aryl, 3-7 membered heterocycloalkyl, Ci-e alkyl and -O-C1-6 alkyl; orRd3and Re3, when attached to the same atom, together with the atom to which they are attached form a 3-7 membered ring, optionally containing one or more heteroatoms selected from O, N and S, and wherein said ring is optionally substituted with one or more Rf3;where each Rf3is independently selected from the group consisting of hydrogen, =0, halogen, -CN, -NH2, -N(H)CI-6 alkyl, -N(CI-6 alkyl)2, Ci-e haloalkyl, C3-6 cycloalkyl, C6-11aryl, 3-7 membered heterocycloalkyl, Ci-e alkyl and -O-C1.6 alkyl;R4is selected from the group consisting of hydroxyl, =0, halogen, -CN, Ci-ehaloalkyl, C1.6 haloalkoxy, Ci-e alkyl, -O-Ci-ealkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, C6-11aryl, 5-11 membered heteroaryl, -C(=O)Rb4, -C(=O)ORc4, -C(=O)NRd4Re4, -NRd4Re4, -NRd4C(=O)Rb4, -NRd4C(=O)ORc4, -NRd4C(=O)NRd4Re4, -NRd4S(=O)2Rb4, -NRd4S(=O)2NRd4Re4, -ORc4, -SRc4, -OC(=O)Rb4, -OC(=O)NRd4Re4, -OC(=O)ORc4, -S(=O)2Rc4, -S(=O)Rc4, -OS(=O)Rc4, -OS(=O)2Rc4, -OS(=O)2ORc4, -S(=O)NRd4Re4, -OS(=O)2NRd4Re4and -S(=O)2NRd4Re4, where said Ci-e alkyl, -O-Ci-6alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, 5-11 membered heteroaryl and C6-11aryl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =0, CN, Ci-e haloalkyl, Ci-e haloalkoxy, C3-6 cycloalkyl, C1-6 alkyl, -O-C1.6 alkyl, phenyl, -NH2, -NHR’, and -NR’R”, where R’ and R” are independently selected from C1-6 alkyl, and where said phenyl is optionally substituted with one or more of hydroxyl, halogen, =0, -CN, Ci-e haloalkyl, Ci-e haloalkoxy, C3-6 cycloalkyl, Ci-e alkyl and -O-C1.6 alkyl;where Rb4, Rc4, Rd4and Re4are independently selected from the group consisting of hydrogen, hydroxyl, Ci-e haloalkyl, -O-C1.6 haloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-6 cycloalkyl, C1-6 alkyl, -O-C1.6 alkyl and Ce-isaryl, wherein said Ci-e alkyl, Ce-isaryl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)Ci-6alkyl, -N(Ci-6alkyl)2, Ci-e haloalkyl, C3-6 cycloalkyl, C6-11aryl, 3-7 membered heterocycloalkyl, Ci-e alkyl and -O-C1.6 alkyl; orRd4and Re4, when attached to the same atom, together with the atom to which they are attached form a 3-7 membered ring, optionally containing one or more heteroatoms selected from O, N and S, and wherein said ring is optionally substituted with one or more Rf4;where each Rf4is independently selected from the group consisting of hydrogen, =0, halogen, -CN, -NH2, -N(H)CI-6 alkyl, -N(CI-6 alkyl)2, C1-6 haloalkyl, C3-6 cycloalkyl, C6-11aryl, 3-7 membered heterocycloalkyl, Ci-e alkyl and -O-C1.6 alkyl;y1, y2, z1 and z2 are integers independently selected from 0, 1, 2, 3 and 4.L is a linker moiety according to formulae L16a, L14c, L14b or L14e:(L16a);where ring J 1 is a 4 to 10 membered heterocycloalkyl ring which may optionally substituted by one or more R26;Z1is absent or a group selected from NH, N(C1-3 alkyl), O or S;n37 and n38 are independently selected from an integer of value 0 to 5; and n36 and n39 are independently selected from an integer of value 0 or 1; andR26at each occurrence is independently selected from the group consisting of hydroxyl, =0, C1.4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1.4 haloalkyl and C3-6 cycloalkyl, each of which may be optionally be substituted with one or more groups selected from C1.4 alkyl, C1.4 alkoxy, C3-6 cycloalkyl, phenyl and hydroxyl;n23 (L14c);where n23 is an integer of value 0 or 1;n24 is an integer of value 0 to 3;n30 is an integer of value 0 or 1;rings G3 and H3 are independently selected from the group consisting of a 4 to 10 membered heterocycloalkyl, a 5 or 6 membered heteroaryl, phenyl and a C3-C10 cycloalkyl, each of which may be optionally substituted by one or more R81;R81at each occurrence is independently selected from the group consisting of hydroxyl, =0, C1.4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1.4 haloalkyl and C3-6 cycloalkyl, each of which may be optionally be substituted with one or more groups selected from C1.4 alkyl, C1.4 alkoxy, C3-6 cycloalkyl, phenyl and hydroxyl; andR12cand R13care independently selected from H, halo, C1.4 alkyl, C3-6 cycloalkyl; or R12cand R13c, together with the carbon atom to which they are attached form a C3-6 cycloalkyl group;R10(L14b);where n20 is a number of value 1 to 5;where n21 and n27 are independently an integer of value 0 or 1;rings G2 and H2 are independently selected from the group consisting of a 4 to 10 membered heterocycloalkyl, a 5 or 6 membered heteroaryl and a C3-C10 cycloalkyl, each of which may be optionally substituted by one or more R80;R80at each occurrence is independently selected from the group consisting of hydroxyl, =0, C1.4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1.4 haloalkyl and C3-6 cycloalkyl, each of which may be optionally be substituted with one or more groups selected from C1.4 alkyl, C1.4 alkoxy, C3-6 cycloalkyl, phenyl and hydroxyl; andR10and R11are independently selected from H, C1.4 alkyl, C3-6 cycloalkyl; or R10and R11, together with the carbon atom to which they are attached form a C3-6 cycloalkyl group;where n50 and n51 are independently an integer of value 0 or 1;n52 and n53 are independently an integer of value 0, 1 or 2;rings G5, H5 and D5 are independently selected from the group consisting of a 4 to 10 membered heterocycloalkyl, a 5 or 6 membered heteroaryl and a C3-C10 cycloalkyl, each of which may be optionally substituted by one or more R8e;R8eat each occurrence is independently selected from the group consisting of hydroxyl, =0, C1.4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1.4 haloalkyl and C3-6 cycloalkyl, each of which may be optionally be substituted with one or more groups selected from C1.4 alkyl, C1.4 alkoxy, C3-6 cycloalkyl, phenyl and hydroxyl; andR10eand R11eare independently selected from H, C1.4 alkyl, C3-6 cycloalkyl; or R10eand R11e, together with the carbon atom to which they are attached form a C3-6 cycloalkyl group.R12eand R13eare independently selected from H, halo, C1.4 alkyl, C3-6 cycloalkyl; or R12eand R13e, together with the carbon atom to which they are attached form a C3-6 cycloalkyl group; andM is an E3 ubiquitin ligase binding moiety.Protein Binding Moiety, Q

[0060] In one embodiment, Q is of formula Q1. In one embodiment, Q1is a RIPK1-binding moiety.

[0061] In one embodiment, Q is of formula Q3. In one embodiment, Q3is a RIPK1-binding moiety.

[0062] In one embodiment, R1ais selected from the group consisting of 5 to 12 membered heteroaryl, 6 to 15 membered aryl, 3 to 12 membered heterocycloalkyl, C3-11 cycloalkyl and C1.10 alkyl, each of which is optionally substituted with one or more Ra1.

[0063] In one embodiment, R1ais selected from the group consisting of 5 to 9 membered heteroaryl, phenyl, 3 to 9 membered heterocycloalkyl, C3-9 cycloalkyl and C1-6 alkyl, each of which is optionally substituted with one or more Ra1.

[0064] In one embodiment, R1ais selected from the group consisting of 6 to 11 membered aryl, 5 to 9 membered heteroaryl, 3 to 9 membered heterocycloalkyl, C3-9 cycloalkyl and Ci-e alkyl, each of which is optionally substituted with one or more Ra1.

[0065] In one embodiment, R1ais selected from the group consisting of phenyl, 5 to 7 membered heteroaryl, 3 to 7 membered heterocycloalkyl, C3-7 cycloalkyl and C1-6 alkyl, each of which is optionally substituted with one or more Ra1.

[0066] In one embodiment, R1ais selected from the group consisting of phenyl, 5 to 7 membered heteroaryl and 3 to 7 membered heterocycloalkyl, each of which is optionally substituted with one or more Ra1.

[0067] In one embodiment, R1ais selected from the group consisting of phenyl, pyridyl, pyrazinyl, pyrazolyl, piperidinyl, pyrrolidinyl, morpholinyl, tetrahydropyranyl, cyclopropyl and / -propyl, s-butyl, / -butyl, each of which is optionally substituted with one or more Ra1.

[0068] In one embodiment, R1ais selected from the group consisting of phenyl and pyridyl, pyrazolyl, piperidinyl, pyrrolidinyl, morpholinyl, tetrahydropyranyl, / -propyl, s-butyl and / -butyl, each of which is optionally substituted with one or more Ra1.

[0069] In one embodiment, R1ais selected from phenyl and pyridyl, each of which is optionally substituted with one or more Ra1.

[0070] In one embodiment, R1ais selected from the following groups, each of which is optionally substituted with one or more groups Ra1:

[0071] In one embodiment, R1ais selected from the following groups, each of which is optionally substituted with one or more groups Ra1:

[0072] In one embodiment, R1ais selected from the following groups, each of which is optionally substituted with one or more groups Ra1:

[0073] In one embodiment, E1is -N(R2)C(=O)- or -C(=O)N(R2a)-.

[0074] Suitably, E1is -N(R2)C(=O)-. Accordingly, in one embodiment, Q1is of formula Q1i:

[0075] Suitably, E1is -N(R2)C(=O)-. Accordingly, in one embodiment, Q3is of formula Q3i:

[0076] In one embodiment, R2and R2aare independently selected from the group consisting of hydrogen, Ci-e alkyl, C3-6cycloalkyl. Suitably, R2and R2aare independently selected from hydrogen, C1.3 alkyl or cyclopropyl. Suitably, R2and R2aare independently hydrogen or methyl.

[0077] In another embodiment, R2together with a R7aor R8agroup and the atoms to which they are attached form a 4 to 7 membered heterocycloalkyl ring which is optionally substituted with one or more groups selected from hydroxyl, halogen, =0, -CN, Ci-e haloalkyl, Ci-e haloalkoxy, cyclopropyl, Ci-e alkyl, -O-C1.6 alkyl, -C(O)Ci-6 alkyl, –C(O)N(H)C1-6alkyl, –C(O)N(C1-6alkyl)2, –CONH2, –C(O)N(H)C1-6alkyl, –C(O)N(C1-6alkyl)2, –N(H)C1-6alkyl, and –N(C1-6alkyl)2.

[0078] Suitably, R2together with a R7aor R8agroup and the atoms to which they are attached form a 5 or 6 membered heterocycloalkyl ring which is optionally substituted with one or more groups selected from hydroxyl, halogen, =0, -CN, Ci-e haloalkyl, Ci-e haloalkoxy, cyclopropyl, C1.6 alkyl, -O-C1.6 alkyl, -C(O)Ci-6alkyl, -C(O)N(H)CI-6alkyl, -C(O)N(CI-6alkyl)2, -CONH2, -C(O)N(H)CI-6alkyl, -C(O)N(Ci-e alkyl)2, -N(H)Ci-e alkyl, and -N(Ci-e alkyl)2. Suitably, R2together with a R7aor R8agroup and the atoms to which they are attached form a piperidinyl, piperazinyl or morpholinyl ring which is optionally substituted with one or more groups selected from hydroxyl, halogen, =0, -CN, Ci-e haloalkyl, Ci-e haloalkoxy, cyclopropyl, Ci-e alkyl, –O-C1-6alkyl, -C(O)Ci-6alkyl, –C(O)N(H)C1-6alkyl, –C(O)N(C1-6alkyl)2, –CONH2, –C(O)N(H)C1-6alkyl, –C(O)N(C1-6alkyl)2, –N(H)C1-6alkyl, and –N(C1-6alkyl)2.

[0079] In one embodiment, each R7aand R8aare independently selected from the group consisting of hydrogen, hydroxyl, =0, halogen, Ci-e haloalkyl, Ci-e haloalkoxy, Ci-e alkyl, -O-C1.6 alkyl; orR7aand R8atogether with the carbon atom to which they are attached form a 3-5 membered cycloalkyl or 3-5 membered heterocycloalkyl group, each of which is optionally substituted with one or more groups selected from hydroxyl, halogen, =0, CF3 or C1.3 alkyl.

[0080] In one embodiment, each R7aand R8aare independently selected from the group consisting of hydrogen, hydroxyl, =0, fluoro, chloro, CF3, OMe and C1.3 alkyl; orR7aand R8atogether with the carbon atom to which they are attached form a cyclopropyl or oxetanyl group, each of which is optionally substituted with one or more groups selected from hydroxyl, halogen, =0, CF3 or C1.3 alkyl.

[0081] In one embodiment, each R7aand R8aare independently selected from the group consisting of hydrogen, hydroxyl, hydroxymethyl, fluoro and methyl.

[0082] In one embodiment, each R7aand R8aare independently selected from hydrogen, fluoro or methyl, suitably hydrogen or methyl.

[0083] In one embodiment, n is an integer of value 0, 1, 2 or 3. Suitably, n is 0, 1 or 3. Suitably n is 1 or 3.

[0084] In one embodiment, Q is of formula Q1iand n is 3. In one embodiment, Q is of formula Q1iand n is 3 and R1ais phenyl or pyridyl, each of which is optionally substituted with one or more Ra1. In one embodiment, Q is of formula Q1iand n is 3 and R1ais phenyl or pyridyl, each of which is optionally substituted with one or more Ra1; and each R7aand R8aare independently selected from hydrogen, fluoro, methyl and hydroxymethyl. In one embodiment, Q is of formula Q1iand n is 3 and R1ais phenyl or pyridyl, each of which is optionally substituted with one or more Ra1and each R7aand R8aare independently selected from hydrogen, fluoro, methyl and hydroxymethyl; and R2is H or methyl.

[0085] In one embodiment, Q is of formula Q1iand n is 1. In one embodiment, Q is of formula Q1iand n is 1 and R1ais phenyl, pyridyl or piperidinyl, each of which is optionally substituted with one or more Ra1. In one embodiment, Q is of formula Q1iand n is 1 and R1ais phenyl, pyridyl or piperidinyl, each of which is optionally substituted with one or more Ra1; and R7aand R8aare independently selected from hydrogen, methyl and hydroxymethyl. In one embodiment, Q is of formula Q1iand n is 1 and R1ais phenyl, pyridyl or piperidinyl, each of which is optionally substituted with one or more Ra1; and R7aand R8aare independently selected from hydrogen, methyl and hydroxymethyl; and R2is H or methyl.

[0086] In one embodiment, Q is of formula Q1iand n is 1 and R1ais selected from: / ; where the phenyl ring is optionally substituted with one or two fluoro groups and R21is selected from the group consisting of O-CH2-C3-6 cycloalkyl, O-CH2-4 to 7 membered heterocycloalkyl, O-C1.6 alkyl.

[0087] In one embodiment, R21is O-CH2-C3-6 cycloalkyl, O-CH2-5 to 6 membered heterocycloalkyl, O-C1.4 alkyl; suitably R21is selected from O-CH2-C3-6 cycloalkyl, or O-C1.4 alkyl; suitably R21is

[0088] In one embodiment, n is 0. It will be understood that when n is 0 the -C(R7a)(R8a)-moiety is absent and thus the R1agroup is directly connected to E1. Thus, in one embodiment, when n is 0, Q1is of formula Q1ii:

[0089] In one embodiment, Q is of formula Q1iiand E1is -N(R2)C(=O)-. Accordingly, in one embodiment, Q1is of formula Q1iii:

[0090] In one embodiment, Q is of formula Q1iior Q1iiiand R1ais a 5-6 membered heteroaryl, 3 to 7 membered heterocycloalkyl, C3-7 cycloalkyl and C3-6 alkyl, where said heteroaryl, heterocycloalklyl or cycloalkyl is optionally substituted with one or more Ra1; suitably Ra1is selected from phenyl or benzyl, each of which is optionally substituted with one or more groups selected from hydroxyl, halogen, =0, -CN, Ci-e haloalkyl, Ci-e haloalkoxy, C3-6 cycloalkyl, Ci-e alkyl, -O-C1.6 alkyl, phenyl, -C(O)Ci-6alkyl, -C(O)N(H)Ci-e alkyl, -C(O)N(Ci.6alkyl)2,-CONH2, -C(O)N(H)CI-6alkyl, -C(O)N(CI-6alkyl)2, -N(H)CI-6alkyl, and -N(CI-6alkyl)2.

[0091] In one embodiment, Q is of formula Q1iior Q1iiiand R1ais selected from the group consisting of pyrazolyl, triazolyl, piperidinyl, pyrazinyl, morpholinyl and cyclopropyl, each of which is substituted with one or more Ra1group; suitably, Ra1is selected from phenyl or benzyl, each of which is optionally substituted with one or more groups selected from hydroxyl, halogen, =0, -CN, Ci-e haloalkyl, Ci-e haloalkoxy, C3-6 cycloalkyl, Ci-e alkyl, -O-C1.6 alkyl, phenyl, -C(O)Ci-6alkyl, -C(O)N(H)CI-6alkyl, -C(O)N(CI-6alkyl)2, -CONH2, -C(O)N(H)CI-6alkyl, -C(O)N(Ci-6alkyl)2,-N(H)Ci-6 alkyl, and -N(Ci-6alkyl)2.

[0092] In one embodiment, Q is of formula Q1iior Q1iiiand R1ais isopropyl or isobutyl.

[0093] In one embodiment, Q is of formula Q1and selected from the following:each phenyl group is optionally substituted by one or more Ra1.

[0094] In one embodiment, Q is of formula Q1and is selected from the following:where each phenyl or pyridyl group is optionally substituted by one or more Ra1.

[0095] In one embodiment, Q is of formula Q1and is selected from the following:

[0096] In one embodiment, Q is of formula Q1and selected from the following:wherein the phenyl is optionally substituted with one or more groups selected from hydroxyl, halogen, =0, -CN, Ci-e haloalkyl, Ci-e haloalkoxy, C3-6 cycloalkyl, Ci-e alkyl, -O-C1.6 alkyl, phenyl, -C(O)Ci-6alkyl, -C(O)N(H)CI-6alkyl, -C(O)N(CI-6alkyl)2, -CONH2, -C(O)N(H)CI-6alkyl, -C(O)N(Ci-6alkyl)2,-N(H)Ci-6 alkyl, and -N(Ci-6alkyl)2.

[0097] In one embodiment, Q is of formula Q1and is selected from the following:o

[0098] In one embodiment, X20is selected from O, S and S(=O), suitably O or S.

[0099] In one embodiment, Q is of formula Q3or Q3iand R7aand R8aare each independently selected from hydrogen, methyl, hydroxy or fluoro, suitably hydrogen or methyl.

[0100] In one embodiment, Q is of formula Q3andis selected from the following:, wherein the phenyl ring is optionally substituted by one or more Ra1.

[0101] In one embodiment, Q is of formula Q3andis selected from the following:

[0102] In one embodiment, each Ra1is independently selected from the group consisting of hydroxyl, =0, halogen, CN, Ci-ehaloalkyl, Ci-e haloalkoxy, Ci-e alkyl, O-Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, -O-C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, -C(=O)Rb1, -NRd1Re1, -ORc1, where said C1-6 alkyl, O-C1.6 alkyl, C3-6 cycloalkyl, -O-C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl and phenyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =0, -CN, Ci-e haloalkyl, Ci-e haloalkoxy, C3-6 cycloalkyl, Ci-e alkyl, -O-C1-6 alkyl, phenyl, -C(O)Ci-6alkyl, -C(O)N(H)Ci-e alkyl, -C(O)N(Ci-e alkyl)2, -CONH2, - C(O)N(H)CI-6alkyl, -C(O)N(Ci-6alkyl)2, -N(H)Ci-e alkyl, and -N(Ci-6alkyl)2.

[0103] In another embodiment, each Ra1is independently selected from the group consisting of hydroxyl, =0, halogen, CN, Ci-ehaloalkyl, Ci-e haloalkoxy, Ci-e alkyl, O-C1.6 alkyl, C3-6 cycloalkyl, -O-C3-6 cycloalkyl, -C(=O)Rb1, -NRd1Re1, -ORc1, where said Ci-e alkyl, O-C1.6 alkyl, C3-6 cycloalkyl and -O-C3-6 cycloalkyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =0, -CN, Ci-ehaloalkyl, Ci-e haloalkoxy, C3-6 cycloalkyl, Ci-ealkyl, -O-C1-6 alkyl, phenyl, -C(O)Ci-6alkyl, -C(O)N(H)Ci-e alkyl, -C(O)N(Ci.6alkyl)2,-CONH2, -C(O)N(H)CI-6alkyl, -C(O)N(CI-6alkyl)2, -N(H)CI-6alkyl, and -N(CI-6alkyl)2.

[0104] In another embodiment, each Ra1is independently selected from the group consisting of hydroxyl, =0, halogen, CN, CF3, OCF3, C1-6 alkyl, O-C1.6 alkyl, -C(=O)Rb1, -NRd1Re1and -ORc1.

[0105] In another embodiment, each Ra1is independently selected from the group consisting of hydroxyl, =0, halogen, CN, CF3, OCF3, Ci-e alkyl, O-C1.6 alkyl, -C(=O)Me, -NH2, -N(H)Ci.3alkyl and -N(Ci-3alkyl)2.

[0106] In one embodiment, each Rb1is independently selected from hydrogen, C3-6 cycloalkyl or C1-6 alkyl. In another embodiment, each Rb1is independently selected from C3-6 cycloalkyl or C1.4 alkyl.

[0107] In one embodiment, each Rc1is independently selected from the group consisting of hydrogen, Ci-e haloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-6 cycloalkyl, Ci-e alkyl and phenyl, wherein said Ci-e alkyl, phenyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)Ci-ealkyl, -N(Ci-ealkyl)2, Ci-e haloalkyl, C3-6 cycloalkyl, C6-11aryl, 3-7 membered heterocycloalkyl, Ci-e alkyl and -O-C1-6 alkyl.

[0108] In another embodiment, each Rc1is independently selected from the group consisting of hydrogen, Ci-e haloalkyl, C3-6 cycloalkyl and Ci-e alkyl, wherein said Ci-e alkyl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)Ci-ealkyl, - N(Ci-ealkyl)2, Ci-e haloalkyl, C3-6 cycloalkyl, C6-11aryl, 3-7 membered heterocycloalkyl, Ci-e alkyl and -O-C1-6 alkyl. In another embodiment, each Rc1is independently selected from hydrogen or Ci-e alkyl.

[0109] In one embodiment, each Rd1is independently selected from the group consisting of hydrogen, C3-6 cycloalkyl, and Ci-e alkyl, wherein said Ci-e alkyl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, -CN, -NO2, –NH2, -N(H)Ci-ealkyl, - N(Ci-ealkyl)2, Ci-e haloalkyl, C3-6 cycloalkyl, C6-11aryl, 3-7 membered heterocycloalkyl, Ci-e alkyl and -O-C1-6 alkyl. In another embodiment, each Rd1is independently selected from hydrogen or Ci-e alkyl.

[0110] In one embodiment, each Re1is independently selected from the group consisting of hydrogen, Ci-e haloalkyl, 3-7 membered heterocycloalkyl, 5-6 memberedheteroaryl, C3-6 cycloalkyl, Ci-e alkyl and phenyl, wherein said C1-6 alkyl, phenyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)Ci-ealkyl, -N(Ci-ealkyl)2, Ci-ehaloalkyl, C3-6 cycloalkyl, C6-11aryl, 3-7 membered heterocycloalkyl, Ci-e alkyl and -O-C1.6 alkyl.

[0111] In another embodiment, each Re1is independently selected from the group consisting of hydrogen, Ci-ehaloalkyl, C3-6 cycloalkyl and Ci-e alkyl, wherein said Ci-e alkyl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)Ci-ealkyl, -N(Ci-ealkyl)2, Ci-ehaloalkyl, C3-6 cycloalkyl, C6-11aryl, 3-7 membered heterocycloalkyl, Ci-e alkyl and -O-C1.6 alkyl. In another embodiment, each Re1is independently selected from hydrogen or Ci-e alkyl.

[0112] In one embodiment, Rd1and Re1, when attached to the same atom, together with the atom to which they are attached form a 3-7 membered ring, optionally containing one or more heteroatoms selected from O, N and S, and wherein said ring is optionally substituted with one or more Rf1;

[0113] In another embodiment, Rd1and Re1, when attached to the same atom, together with the atom to which they are attached form a 5-7 membered ring, optionally containing one or more heteroatoms selected from O, N and S, and wherein said ring is optionally substituted with one or more Rf1.

[0114] In one embodiment, Rf1is selected from the group consisting of hydrogen, =0, halogen, -CN, -NH2, -N(H)CI-6 alkyl, -N(CI-6 alkyl)2, Ci-e haloalkyl, C3-6 cycloalkyl, Ci-e alkyl and -O-C1-6 alkyl. In another embodiment, Rf1is selected from hydrogen, =0, halogen, -CN, -NH2, -N(H)CI-4 alkyl, -N(Ci-4alkyl)2, Ci.4haloalkyl, C1.4 alkyl and -O-C1.4 alkyl.

[0115] In one embodiment, B is a cyclic group selected from 5 to 12 membered heteroaryl and C6-11aryl. In another embodiment, B is a cyclic group selected from 5 to 6 membered heteroaryl and phenyl.

[0116] In one embodiment, B is a 6-membered heteroaryl ring containing one or more nitrogen atom, or a phenyl group. In another embodiment, B is a pyridine ring or a phenyl group.

[0117] In another embodiment, B is a group of formula BO:X10X16where X9, X10and X16are independently selected from N, CR3oCR³ or CH. Suitably, R3is independently selected from Me, OMe and F.

[0118] In another embodiment, B is a group of formula B1:where X9and X10are independently selected from N, CR3oCR³ or CH.

[0119] In one embodiment, X9is N. In another embodiment, X9isCR³ or CH.

[0120] In one embodiment, X9is N and X10is CH and R2is methyl.

[0121] In one embodiment, B is a group of formula B2:suitably where the dashed line indicates the point of attachment to the group E1and the wavy line indicates the point of attachment to ring A.

[0122] In one embodiment, B is a group of formula B3:suitably where the dashed line indicates the point of attachment to the group E1and the wavy line indicates the point of attachment to ring A.

[0123] In one embodiment, ring B issuitably where the dashed line indicates the point of attachment to the group E1and the wavy line indicates the point of attachment to ring A.

[0124] In one embodiment, ring B issuitably where the dashed line indicates the point of attachment to the group E1and the wavy line indicates the point of attachment to ring A.

[0125] In one embodiment, the wavy line in the example B ring above, B1, B2 or B3 indicates the point of attachment to the adjacent ring A. In another embodiment, the dotted line in B, B1, B2 or B3 indicates the point of attachment to the adjacent ring A.

[0126] In one embodiment, R3is selected from the group consisting of hydroxyl, =0, halogen, CN, Ci-ehaloalkyl, Ci-e haloalkoxy, Ci-ealkyl, O-Ci-ealkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6cycloalkyl, --C(=O)Rb3, -C(=O)ORc3, -C(=O)NRd3Re3, -NRd3Re3, -NRd3C(=O)Rb3,–ORc3, –SRc3, where said Ci-ealkyl, O-C1-6 alkyl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, =0, CN, Ci-e haloalkyl, Ci-e haloalkoxy, C3-6 cycloalkyl, Ci-ealkyl, O-C1.6 alkyl, -NH2, -N(H)CI-3 alkyl, and - N(C1-3 alkyl)2-

[0127] In one embodiment, R3is selected from the group consisting of hydroxyl, =0, halogen, CN, Ci-ehaloalkyl, Ci-e haloalkoxy, Ci-ealkyl, O-Ci-ealkyl, C^alkenyl, C2-6alkynyl, C3-6 cycloalkyl, -NRd3Re3, -ORc3, -SRc3, where said Ci-ealkyl, O-C1-6 alkyl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, =0, CN, Ci-e haloalkyl, Ci-e haloalkoxy, C3-6 cycloalkyl, Ci-ealkyl, O-C1.6 alkyl, -NH2, -N(H)CI-3 alkyl, and -N(Ci-3alkyl)2.

[0128] In one embodiment, R3is selected from the group consisting of hydroxyl, =0, halogen, CN, Ci-ehaloalkyl, Ci-e haloalkoxy, Ci-ealkyl, O-C1.6 alkyl, C2-6 alkenyl, C2-6alkynyl, -NRd3Re3, where said Ci-e alkyl and O-C1.6 alkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, =0, CN, Ci-ehaloalkyl, Ci-e haloalkoxy, C3-6 cycloalkyl, C1-6 alkyl, O-C1-6 alkyl, -NH2, -N(H)CI-3alkyl, and -N(Ci-3alkyl)2.

[0129] In one embodiment, R3is selected from the group consisting of hydroxyl, =0, halogen, CN, Ci-ehaloalkyl, Ci-e haloalkoxy, Ci-ealkyl, O-C1.6 alkyl, C2-6 alkenyl, C2-6alkynyl, -NH2, -N(H)CI-3alkyl, and -N(Ci-3alkyl)2.

[0130] In one embodiment, R3is selected from the group consisting of hydroxyl, =0, halogen, CN, C1.3 haloalkyl, C1.3 haloalkoxy, C1.4 alkyl, O-C1.4 alkyl, -NH2, -N(H)CI-3 alkyl, and -N(Ci-3alkyl)2.

[0131] In one embodiment, R3is selected from the group consisting of hydroxyl, =0, Cl, Br, CN, CF3, OCF2H, OCF3, cyclopropyl, methyl, ethyl, isopropyl, OMe, OEt and OPr.

[0132] In one embodiment, R3is selected from the group consisting of Cl, CF3, OCF2H, OCF3, cyclopropyl, methyl, ethyl, isopropyl, OMe, OEt and OPr.

[0133] In one embodiment, R3is selected from the group consisting of hydroxyl, =0, Cl, CN, CF3, CF2H, OCF3, OCF2H, methyl, ethyl, cyclopropyl, NH2, NHMe, NMe2, OEt, OMe, OPr.

[0134] In one embodiment, R3is selected from the group consisting of hydroxyl, =0, Cl, Br, CN, CF3, OCF3, methyl, ethyl and OMe. In one embodiment, R3is selected from fluoro, methyl, and OMe. In one embodiment, R3is selected from methyl, and OMe.

[0135] In one embodiment, each Rb3is independently selected from hydrogen, C3-6 cycloalkyl or Ci-ealkyl. In another embodiment, each Rb3is independently selected from C3-6 cycloalkyl or C1.4 alkyl.

[0136] In one embodiment, each Rc3is independently selected from the group consisting of hydrogen, Ci-e haloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-6 cycloalkyl, Ci-e alkyl and phenyl, wherein said C1-6 alkyl, phenyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)Ci-ealkyl, -N(Ci-ealkyl)2, Ci-e haloalkyl, C3-6 cycloalkyl, C6-11aryl, 3-7 membered heterocycloalkyl, Ci-e alkyl and -O-C1.6 alkyl.

[0137] In another embodiment, each Rc3is independently selected from the group consisting of hydrogen, Ci-e haloalkyl, C3-6 cycloalkyl and C1-6 alkyl, wherein said Ci-e alkyl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)Ci-ealkyl, -N(Ci-ealkyl)2, Ci-e haloalkyl, C3-6 cycloalkyl, C6-11aryl, 3-7 membered heterocycloalkyl, Ci-e alkyl and -O-C1.6 alkyl. In another embodiment, each Rc3is independently selected from hydrogen or C1-6 alkyl.

[0138] In one embodiment, each Rd3is independently selected from the group consisting of hydrogen, C3-6 cycloalkyl, and Ci-e alkyl, wherein said Ci-e alkyl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)Ci-ealkyl, -N(Ci-ealkyl)2, Ci-e haloalkyl, C3-6 cycloalkyl, C6-11aryl, 3-7 membered heterocycloalkyl, Ci-e alkyl and -O-C1-6 alkyl. In another embodiment, each Rd3is independently selected from hydrogen or Ci-e alkyl.

[0139] In one embodiment, each Re3is independently selected from the group consisting of hydrogen, Ci-e haloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-6 cycloalkyl, Ci-e alkyl and phenyl, wherein said Ci-e alkyl, phenyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)Ci-ealkyl, -N(Ci-ealkyl)2, Ci-e haloalkyl, C3-6 cycloalkyl, C6-11aryl, 3-7 membered heterocycloalkyl, Ci-e alkyl and -O-C1-6 alkyl.

[0140] In another embodiment, each Re3is independently selected from the group consisting of hydrogen, Ci-e haloalkyl, C3-6 cycloalkyl and Ci-e alkyl, wherein said Ci-e alkyl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)Ci-ealkyl, -N(Ci-ealkyl)2, Ci-e haloalkyl, C3-6 cycloalkyl, C6-11aryl, 3-7 membered heterocycloalkyl, Ci-e alkyl and -O-C1-6 alkyl. In another embodiment, each Re3is independently selected from hydrogen or Ci-e alkyl.

[0141] In one embodiment, Rd3and Re3, when attached to the same atom, together with the atom to which they are attached form a 3-7 membered ring, optionally containing one or more heteroatoms selected from O, N and S, and wherein said ring is optionally substituted with one or more Rf3.

[0142] In one embodiment, Rd3and Re3, when attached to the same atom, together with the atom to which they are attached form a 5-7 membered ring, optionally containing one or more heteroatoms selected from O, N and S, and wherein said ring is optionally substituted with one or more Rf3.

[0143] In one embodiment, Rf3is selected from the group consisting of hydrogen, =0, halogen, -CN, -NH2, -N(H)CI-6 alkyl, -N(CI-6 alkyl)2, C1-6 haloalkyl, C3-6 cycloalkyl, Ci-e alkyl and -O-C1.6 alkyl. In another embodiment, Rf3is selected from hydrogen, =0, halogen, -CN, -NH2, -N(H)CI-4 alkyl, -N(Ci-4alkyl)2, C1.4 haloalkyl, C1.4 alkyl and -O-C1.4 alkyl.

[0144] In one embodiment, y1 is an integer selected from 0, 1 and 2. In one embodiment, y1 is 1. In another embodiment, y1 is 0.

[0145] In one embodiment, A is a cyclic group selected from 5 to 12 membered heteroaryl. In another embodiment, A is a 8 to 10 membered fused bicyclic heteroaryl, In another embodiment, A is a 9 or 10 membered fused bicyclic heteroaryl, In another embodiment, A is a 9 or 10 membered fused bicyclic heteroaryl, which suitably contains at least one nitrogen.

[0146] In one embodiment, A is a cyclic group selected from benzothiazolyl, azabenzothiazolyl, benzimidazolyl, aza-benzimidazolyl, imidazopyridinyl, imidazopyridazinyl, imidazopyrazinyl, triazolopyridinyl, pyrazolopyridinyl benzofurazanyl, benzothiadiazinyl, benzothiazinyl, benzoxazolyl, aza-benzoxazolyl, aza-indolyl, cinnolinyl, furopyridinyl, quinazolinyl, quinoxalinyl and isoquinolinyl.

[0147] In one embodiment, A is a cyclic group selected from benzothiazolyl, azabenzothiazolyl, benzimidazolyl, aza-benzimidazolyl, imidazopyridinyl, imidazopyridazinyl, imidazopyrazinyl, benzofurazanyl, benzothiadiazinyl, benzothiazinyl, benzoxazolyl, aza-benzoxazolyl, aza-indolyl, cinnolinyl, furopyridinyl, quinazolinyl, quinoxalinyl and isoquinolinyl.

[0148] In one embodiment, A is a cyclic group selected from benzothiazolyl, azabenzothiazolyl, benzimidazolyl, aza-benzimidazolyl, imidazopyridinyl, imidazopyridazinyl, imidazopyrazinyl, benzoxazolyl, aza-benzoxazolyl, aza-indolyl, cinnolinyl, quinazolinyl, quinoxalinyl and isoquinolinyl.

[0149] In one embodiment, A is a cyclic group selected from benzothiazolyl, azabenzothiazolyl, benzimidazolyl, aza-benzimidazolyl, imidazopyridinyl, imidazopyridazinyl, imidazopyrazinyl, benzoxazolyl, aza-benzoxazolyl, and aza-indolyl.

[0150] In one embodiment, A is a cyclic group selected from benzothiazolyl, azabenzothiazolyl, benzimidazolyl, aza-benzimidazolyl, imidazopyridinyl, imidazopyridazinyl, imidazopyrazinyl, benzoxazolyl, aza-benzoxazolyl, and aza-indolyl.

[0151] In one embodiment, A is a cyclic group selected from benzothiazolyl, azabenzothiazolyl, imidazopyrazinyl (suitably imidazo[1,2-a]pyrazinyl) and imidazopyridinyl (suitably imidazo[1,2-a]pyridinyl) and imidazopyridazinyl (suitably imidazo[1,2-b] pyridazinyl).

[0152] In one embodiment, A is a cyclic group of formula A1wherein X1, X2, X3and X4are independently selected from C, N, CH or CR4; provided that only one of X1, X2, X3and X4is C and forms the point of attachment to ring B or ring C;X5and X6are independently selected from N or C;X7and X8are independently selected from O, S, N, CH, CR4and NR4;with the proviso that at least one of X1, X2, X3, X4, X5, X6, X7and X8must be N.

[0153] In one embodiment, X8is N. In one embodiment, X6is N. In one embodiment, X6and X8are N.

[0154] In one embodiment, X8is N. In one embodiment, X5is N. In one embodiment, X5and X8are N.

[0155] In one embodiment, X7is S oCR³ or CH.

[0156] In one embodiment, X1is N and each of X2, X3and X4are C, CH or CR4; provided that only one of X2, X3and X4is C and forms the point of attachment to ring B or ring C.

[0157] In one embodiment, each of X1, X2, X3and X4are C, CH or CR4; provided that only one of X1, X2, X3and X4is C and forms the point of attachment to ring B or ring C.

[0158] In one embodiment, X2is C and forms the point of attachment to ring B or ring C and X1, X3and X4are independently selected from N, CH or CR4; suitably X1, X3and X4are independently selected from CH or CR4.

[0159] In one embodiment, A is a cyclic group of formula A2wherein X1, X2, X3and X4are independently selected from C, N, CH or CR4;provided that only one of X1, X2, X3and X4is C and forms the point of attachment to ring B or ring C.

[0160] In one embodiment of A2, only one of X1, X2, X3and X4is N. In another embodiment, each of X1, X2, X3and X4is independently selected from C, CH or CR4; provided that only one of X1, X2, X3and X4is C and forms the point of attachment to ring B or ring C.

[0161] In one embodiment, X2is C and forms the point of attachment to ring B or ring C and X1, X3and X4are independently selected from N, CH or CR4; suitably X1, X3and X4are independently selected from CH or CR4.

[0162] In one embodiment, A is a cyclic group of formula A3wherein X11, X12, X13and X14are independently selected from C, N, CH or CR4;provided that only one of X11, X12, X13and X14is C and forms the point of attachment to ring B or ring C.

[0163] In one embodiment, X13is C and forms the point of attachment to ring B or ring C and X11, X12and X14are independently selected from N, CH or CR4. In one such embodiment, X11, X12and X14are independently selected from CH or CR4. In another embodiment, X12is N or CH, and X11and X14are independently selected from CH or CR4.

[0164] In one embodiment, X12is N, and X11and X14are independently selected from CH or CR4.

[0165] In one embodiment, X13is C and forms the point of attachment to ring B or ring C and X14is N. Suitably X11and X12are independently selected from CH or CR4.

[0166] In one embodiment, A is a cyclic group selected from:each of which may be optionally substituted with one or more R4.

[0167] In one embodiment, A is a cyclic group selected from:each of which may be optionally substituted with one or more R4.

[0168] In one embodiment, A is a cyclic group selected from:each of which may be optionally substituted with one or more R4.

[0169] In one embodiment, A is a cyclic group selected from:each of which may be optionally substituted with one or more R4.

[0170] In one embodiment, the wavy line in the examples of ring A above, or subformulae A1 to A3, indicates the point of attachment to the adjacent group V. In another embodiment, the wavy line in the examples of ring A above, or sub-formulae A1 to A3, indicates the point of attachment to the adjacent ring B or ring C.

[0171] In one embodiment, R4is selected from hydroxyl, =0, halogen, CN, Ci-e haloalkyl, Ci-e haloalkoxy, Ci-e alkyl, O-Ci-6 alkyl, C2-6 alkenyl, C^alkynyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, -C(=O)Rb3, -C(=O)ORc4, - C(=O)NRd4Re4, -NRd4Re4, -NRd4C(=O)Rb4,-ORc4, -SRc4, where said Ci-e alkyl, O-Ci-6alkyl, C3.6 cycloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl and phenyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =0, CN, Ci-e haloalkyl, Ci-e haloalkoxy, C3-6 cycloalkyl, C1-6 alkyl, O-C1.6 alkyl, -NH2, -N(H)CI-3 alkyl, and - N(Ci.3alkyl)2.

[0172] In one embodiment, R4is selected from the group consisting of hydroxyl, =0, halogen, CN, Ci-e haloalkyl, Ci-e haloalkoxy, Ci-ealkyl, O-Ci-ealkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6cycloalkyl, -C(=O)Rb4, -C(=O)ORc4, -C(=O)NRd4Re4, -NRd4Re4, -NRd4C(=O)Rb4,-ORc4, - SRc4, where said Ci-ealkyl, O-C1-6 alkyl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, =0, CN, Ci-e haloalkyl, Ci-e haloalkoxy, C3-6 cycloalkyl, Ci-ealkyl, O-C1.6 alkyl, -NH2, -N(H)CI-3 alkyl, and -N(Ci-3alkyl)2.

[0173] In one embodiment, R4is selected from the group consisting of hydroxyl, =0, halogen, CN, Ci-ehaloalkyl, Ci-e haloalkoxy, Ci-ealkyl, O-Ci-ealkyl, C^alkenyl, C2-6alkynyl, C3-6 cycloalkyl, -NRd4Re4, -ORc4, -SRc4, where said Ci-ealkyl, O-C1-6 alkyl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, =0, CN, Ci-e haloalkyl, Ci-e haloalkoxy, C3-6 cycloalkyl, Ci-ealkyl, O-C1.6 alkyl, -NH2, -N(H)CI-3 alkyl, and -N(Ci-3alkyl)2.

[0174] In one embodiment, R4is selected from the group consisting of hydroxyl, =0, halogen, CN, Ci-ehaloalkyl, Ci-e haloalkoxy, Ci-ealkyl, O-C1.6 alkyl, C2-6 alkenyl, C2-6alkynyl, -NRd4Re4, where said Ci-e alkyl and O-C1.6 alkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, =0, CN, Ci-ehaloalkyl, Ci-e haloalkoxy, C3-6 cycloalkyl, C1-6 alkyl, O-C1-6 alkyl, -NH2, -N(H)CI-3alkyl, and -N(Ci-3alkyl)2.

[0175] In one embodiment, R4is selected from the group consisting of hydroxyl, =0, halogen, CN, Ci-ehaloalkyl, Ci-e haloalkoxy, Ci-ealkyl, O-C1.6 alkyl, C2-6 alkenyl, C2-6alkynyl, -NH2, -N(H)CI-3alkyl, and -N(Ci-3alkyl)2.

[0176] In one embodiment, R4is selected from the group consisting of hydroxyl, =0, halogen, CN, C1.3 haloalkyl, C1.3 haloalkoxy, C1.4 alkyl, O-C1.4 alkyl, -NH2, -N(H)CI-3 alkyl, and -N(Ci-3alkyl)2.

[0177] In one embodiment, R4is selected from the group consisting of hydroxyl, =0, Cl, Br, CN, CF3, OCF3, methyl, ethyl and OMe.

[0178] In one embodiment, each Rb4is independently selected from hydrogen, C3-6 cycloalkyl or Ci-ealkyl. In another embodiment, each Rb4is independently selected from C3-6 cycloalkyl or C1.4 alkyl.

[0179] In one embodiment, each Rc4is independently selected from the group consisting of hydrogen, Ci-e haloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-6 cycloalkyl, Ci-ealkyl and phenyl, wherein said Ci-ealkyl, phenyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)Ci-ealkyl, -N(Ci-ealkyl)2, Ci-ehaloalkyl, C3-6 cycloalkyl, C6-11aryl, 3-7 membered heterocycloalkyl, Ci-ealkyl and -O-C1.6 alkyl.

[0180] In one embodiment, each Rc4is independently selected from the group consisting of hydrogen, Ci-ehaloalkyl, C3-6 cycloalkyl and Ci-ealkyl, wherein said Ci-ealkyl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl,halogen, -CN, -NO2, -NH2, -N(H)Ci-6alkyl, -N(Ci-6alkyl)2, Ci-e haloalkyl, C3-6 cycloalkyl, C6-11aryl, 3-7 membered heterocycloalkyl, Ci-e alkyl and -O-C1.6 alkyl. In another embodiment, each Rc4is independently selected from hydrogen or C1-6 alkyl.

[0181] In one embodiment, each Rd4is independently selected from the group consisting of hydrogen, C3-6 cycloalkyl, and Ci-e alkyl, wherein said Ci-e alkyl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)Ci-ealkyl, -N(Ci-ealkyl)2, Ci-e haloalkyl, C3-6 cycloalkyl, C6-11aryl, 3-7 membered heterocycloalkyl, Ci-e alkyl and -O-C1-6 alkyl. In another embodiment, each Rd4is independently selected from hydrogen or Ci-e alkyl

[0182] In one embodiment, each Re4is independently selected from the group consisting of hydrogen, Ci-e haloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-6 cycloalkyl, Ci-e alkyl and phenyl, wherein said Ci-e alkyl, phenyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)Ci-ealkyl, -N(Ci-ealkyl)2, Ci-e haloalkyl, C3-6 cycloalkyl, C6-11aryl, 3-7 membered heterocycloalkyl, Ci-e alkyl and -O-C1-6 alkyl.

[0183] In one embodiment, each Re4is independently selected from the group consisting of hydrogen, Ci-e haloalkyl, C3-6 cycloalkyl and Ci-e alkyl, wherein said Ci-e alkyl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)Ci-ealkyl, -N(Ci-ealkyl)2, Ci-e haloalkyl, C3-6 cycloalkyl, C6-11aryl, 3-7 membered heterocycloalkyl, Ci-e alkyl and -O-C1-6 alkyl. In another embodiment, each Re4is independently selected from hydrogen or Ci-e alkyl.

[0184] In one embodiment, Rd4and Re4, when attached to the same atom, together with the atom to which they are attached form a 3-7 membered ring, optionally containing one or more heteroatoms selected from O, N and S, and wherein said ring is optionally substituted with one or more Rf4.

[0185] In one embodiment, Rd4and Re4, when attached to the same atom, together with the atom to which they are attached form a 5-7 membered ring, optionally containing one or more heteroatoms selected from O, N and S, and wherein said ring is optionally substituted with one or more Rf4.

[0186] In one embodiment, Rf4is selected from the group consisting of hydrogen, =0, halogen, -CN, -NH2, -N(H)CI-6 alkyl, -N(CI-6 alkyl)2, C1-6 haloalkyl, C3-6 cycloalkyl, Ci-e alkyland -O-C1.6 alkyl. In another embodiment, Rf3is selected from hydrogen, =0, halogen, -CN, -NH2, -N(H)CI-4 alkyl, -N(Ci-4alkyl)2, Ci.4haloalkyl, C1.4 alkyl and -O-C1.4 alkyl.

[0187] In one embodiment, z1 is an integer selected from 0, 1 and 2. In another embodiment, z1 is 1. In another embodiment, z1 is 0.

[0188] In one embodiment, V comprises one or more functional groups, which facilitate covalent bonding with the linker moiety L. Examples of suitable functional groups include amino, amido, carbonyl, sulfonyl and sulfonamido for instance.

[0189] In one embodiment, V is selected from the group consisting of -NH-, -C(O)-, -S(O)2-, -C(O)N(H)-, -N(H)C(O)-, -S(O)(NH)-, -N(H)S(O)-, -S(O)N(H)-, -N(H)S(O)2- and -S(O)2N(H)-.

[0190] In one embodiment, V is selected from the group consisting of -NH-, -C(O)-, -C(O)N(H)- and -N(H)C(O)-. In one embodiment, V is selected from the group consisting of -NH-, -C(O)N(H)- and -N(H)C(O)-.

[0191] In one embodiment, V is selected from the group consisting of -NH- or -N(H)C(O)- (i.e. the amide nitrogen atom is bonded to ring A). In another embodiment, V is -NH-.

[0192] In one embodiment, Q is of sub-formula Q1a:whereX1, X3and X4are independently selected from N, CH or CR4;X6is selected from N or C;X7is selected from O, S, N, CH, CR4and NR4;X9and X10are independently selected from N, CR3or CH; andR1a, R7a, R8aand n are as defined in any of the above embodiments.

[0193] In one embodiment, Q is of sub-formula Q1aand X7is N, S oCR³ or CH. In one embodiment, X3and X4are CH. In one embodiment, X1is CH or N.

[0194] In one embodiment, Q is of sub-formula Q1aand X7is CH and X6is N. In one embodiment, Q is of sub-formula Q1aand X7is CH, X6is N and X4is CH. In one embodiment, Q is of sub-formula Q1aand X7is CH, X6is N, X4is CH, X3is CH and X1is N. In one embodiment, Q is of sub-formula Q1aand X7is CH, X6is N, X4is CH, X1is CH and X3is N. In one embodiment, Q is of sub-formula Q1aand X7is CH, X6is N, X4is CH, X1is CH and X3is CH.

[0195] In one embodiment, Q is of sub-formula Q1aand X7is S and X6is C. In one embodiment, Q is of sub-formula Q1aand X7is S, X6is C and X1, X3and X4are CH.

[0196] In one embodiment, X9is CH. In another embodiment, X9is CH and X10is CR3oCR³ or CH.

[0197] In one embodiment, X9is N. In another embodiment, X9is N and X10is CR3oCR³ or CH.

[0198] In one embodiment, X9is N and X10is CH and R2is methyl.

[0199] In one embodiment, R2is hydrogen or methyl.

[0200] In one embodiment, each R7aand R8aare independently selected from the group consisting of hydrogen, hydroxyl, hydroxylmethyl, fluoro and methyl.

[0201] In one embodiment, Q is of sub-formula Q1b:whereX9is selected from N, CR3or CH; andX10is selected from N, CR3or CH;; andR1a, R2, R7a, R8aand n are as defined in any of the above embodiments.

[0202] In one embodiment, X9is CH. In another embodiment, X9is CH and X10is CR3oCR³ or CH.

[0203] In one embodiment, X9is N. In another embodiment, X9is N and X10is CR3oCR³ or CH.

[0204] In one embodiment, X9is N and X10is CH and R2is methyl.

[0205] In one embodiment, R2is hydrogen or methyl.

[0206] In one embodiment, each R7aand R8aare independently selected from the group consisting of hydrogen, hydroxyl, hydroxymethyl, fluoro and methyl.

[0207] In one embodiment, Q is of sub-formula Q1d:whereX9is selected from N, CR3or CH; andX10is selected from N, CR3or CH;; andR1a, R2, R7a, R8aand n are as defined in any of the above embodiments.

[0208] In one embodiment, X9is CH. In another embodiment, X9is CH and X10is CR3oCR³ or CH.

[0209] In one embodiment, X9is N. In another embodiment, X9is N and X10is CR3oCR³ or CH.

[0210] In one embodiment, X9is N and X10is CH and R2is methyl.

[0211] In one embodiment, R2is hydrogen or methyl.

[0212] In one embodiment, each R7aand R8aare independently selected from the group consisting of hydrogen, hydroxyl, hydroxymethyl, fluoro and methyl.

[0213] In one embodiment, Q1is of sub-formula Q1e:whereX9is selected from N, CR3or CH; andX10is selected from N, CR3or CH;X7ais CH or N;X1is selected from N, CH or CR4; andR1a, R2, R7a, R8aand n are as defined in any of the above embodiments.

[0214] In one embodiment of sub-formula Q1e, X9is CH. In another embodiment, X9is CH and X10is CR3oCR³ or CH.

[0215] In one embodiment of sub-formula Q1e, X9is N. In another embodiment, X9is N and X10is CR3oCR³ or CH.

[0216] In one embodiment of sub-formula Q1e, X9is N and X10is CH and R2is methyl.

[0217] In one embodiment of sub-formula Q1e, X10is CH or CR3.

[0218] In one embodiment of sub-formula Q1e, X1is CH.

[0219] In one embodiment of sub-formula Q1e, X7ais selected from N oCR³ or CH.

[0220] In one embodiment of sub-formula Q1e, X1and X7aare CH.

[0221] In one embodiment of sub-formula Q1e, R2is methyl and X10is CH.

[0222] In another embodiment of sub-formula Q1e, R2is H and X10is CR3, suitably R3is methyl or ethyl.

[0223] In one embodiment sub-formula Q1e, each R7aand R8aare independently selected from the group consisting of hydrogen, hydroxyl, hydroxymethyl, fluoro and methyl.

[0224] In one embodiment sub-formula Q1e, n is 3, 1 or 0; suitably 3 or 1.

[0225] In one embodiment, Q1eis of formula:

[0226] In one embodiment, Q1is selected from:

[0227] In one embodiment, Q is of formula Q2. In one embodiment, Q2is a RIPK1-binding moiety.

[0228] In one embodiment, R1bis selected from the group consisting of 5 to 12 membered heteroaryl, 6 to 15 membered aryl, 3 to 12 membered heterocycloalkyl, C3-11 cycloalkyl and Ci- 10 alkyl, each of which is optionally substituted with one or more Ra1.

[0229] In one embodiment, R1bis selected from the group consisting of 5 to 9 membered heteroaryl, phenyl, 3 to 9 membered heterocycloalkyl, C3-9 cycloalkyl and C1-6 alkyl, each of which is optionally substituted with one or more Ra1.

[0230] In one embodiment, R1bis selected from the group consisting of 5 to 7 membered heteroaryl, 3 to 7 membered heterocycloalkyl, phenyl, C3-7 cycloalkyl and C1-6 alkyl, each of which is optionally substituted with one or more Ra1.

[0231] In one embodiment, R1bis selected from the group consisting of pyridyl, pyrazinyl, piperidinyl, pyrrolidinyl, morpholinyl, tetrahydropyranyl, phenyl, cyclohexyl, cyclopropyl and branched C1.4 alkyl, each of which is optionally substituted with one or more Ra1.

[0232] In one embodiment, R1bis selected from the group consisting of pyridyl, piperidinyl, cyclohexyl, cyclopropyl and branched C1.4 alkyl, each of which is optionally substituted with one or more Ra1.

[0233] In one embodiment, R1bis selected from the following groups, each of which is optionally substituted with one or more groups Ra1:

[0234] In one embodiment, R1bis selected from the following groups, each of which is optionally substituted with one or more groups Ra1:

[0235] In one embodiment, R1bis selected from the following groups, each of which is optionally substituted with one or more groups Ra1:

[0236] In one embodiment, each R7aand R8aare independently selected from the group consisting of hydrogen, hydroxyl, =0, halogen, Ci-ehaloalkyl, Ci-e haloalkoxy, Ci-e alkyl; orR7aand R8atogether with the carbon atom to which they are attached form a 3-5 membered cycloalkyl or 3-5 membered heterocycloalkyl group, each of which is optionally substituted with one or more groups selected from hydroxyl, halogen, =0, CF3 or C1.3 alkyl.

[0237] In one embodiment, each R7aand R8aare independently selected from the group consisting of hydrogen, hydroxyl, =0, fluoro, chloro, CF3, and C1.3 alkyl; orR7aand R8atogether with the carbon atom to which they are attached form a cyclopropyl or oxetanyl group, each of which is optionally substituted with one or more groups selected from hydroxyl, halogen, =0, CF3 or C1.3 alkyl.

[0238] In one embodiment, each R7aand R8aare independently selected from the group consisting of hydrogen, hydroxyl, hydroxymethyl, fluoro and methyl.

[0239] In one embodiment, R7aand R8aare both hydrogen.

[0240] In one embodiment, n is an integer of value 0, 1, 2 or 3. Suitably, n is 0, 1 or 3. Suitably n is 1 or 3.

[0241] In one embodiment, E2is -C(=O)- or -S(=O)2-.

[0242] Suitably, E2is -C(=O)-. Accordingly in one embodiment Q2is of sub-formula Q2i:

[0244] In one embodiment, Q2is of sub-formula Q2ior Q2iiand R1bis a 5-6 membered heteroaryl group, 3-7 membered heterocycloalkyl group, C3-6 cycloalkyl group or a Ci-e alkyl group, where said heteroaryl, heterocycloalkyl and cycloalkyl are optionally substituted with one or more groups Ra1. Suitably, R1bis a pyridyl group, piperidinyl group, cyclohexyl, cyclopropyl, or a C3-6 alkyl group, where said pyridyl, piperidinyl cyclohexyl and cyclopropyl, are optionally substituted with one or more groups Ra1.

[0245] In one embodiment, Q2is of sub-formula Q2ior Q2iiand R1bis selected from

[0246] In one embodiment, Q2is of sub-formula Q2ior Q2iiand R1bis selected from:

[0247] In one embodiment, Q2is of sub-formula Q2ior Q2iiand R1bis selected from:

[0248] In one embodiment, n is 0. It will be understood that when n is 0 the -C(R7a)(R8a)- moiety is absent and thus the R1bgroup is directly connected to E2. Thus, in one embodiment, when n is 0 and E2is -C(=O)- Q2is of formula Q2iii:

[0249] In one embodiment, Q2is of sub-formula Q2iiiand R1bis a 3-7 membered heterocycloalkyl group, C3-6 cycloalkyl group or a Ci-e alkyl group, where said heterocycloalkyl and cycloalkyl are optionally substituted with one or more groups Ra1.

[0250] In one embodiment, Q2is of sub-formula Q2iiiand R1bis a selected from a 4-7 membered heterocycloalkyl group, C3-6 cycloalkyl group or a C3-6 alkyl group, where said heterocycloalkyl and cycloalkyl are optionally substituted with one or more groups Ra1.

[0251] In one embodiment, Q2is of sub-formula Q2iiiand R1bis a selected from a piperidinyl group, cyclohexyl, cyclopropyl, or a C3-6 alkyl group, where said piperidinyl cyclohexyl and cyclopropyl, are optionally substituted with one or more groups Ra1.

[0252] In one embodiment, Q2is of sub-formula Q2iiiand R1bis a selected from a phenyl or cyclopropyl, or a C3-6 alkyl group, where said phenyl and cyclopropyl, are optionally substituted with one or more groups Ra1.

[0253] In one embodiment, Q2is of sub-formula Q2iiiand R1bis a cyclopropyl or isopropyl group.

[0254] selected from the following:o

[0255] In one embodiment, each Ra1is independently selected from the group consisting of hydroxyl, =0, halogen, CN, Ci-ehaloalkyl, Ci-e haloalkoxy, Ci-e alkyl, O-Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, -O-C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, -C(=O)Rb1, -NRd1Re1, -ORc1, where said C1-6 alkyl, O-C1.6 alkyl, C3-6 cycloalkyl, -O-C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl and phenyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =0, -CN, Ci-e haloalkyl, Ci-e haloalkoxy, C3-6 cycloalkyl, Ci-e alkyl, -O-C1-6 alkyl, phenyl, -C(O)Ci-6alkyl, -C(O)N(H)Ci-e alkyl, -C(O)N(Ci-e alkyl)2, -CONH2, -C(O)N(H)CI-6alkyl, -C(O)N(Ci-6alkyl)2, -N(H)Ci-e alkyl, and -N(Ci-6alkyl)2.

[0256] In another embodiment, each Ra1is independently selected from the group consisting of hydroxyl, =0, halogen, CN, Ci-ehaloalkyl, Ci-e haloalkoxy, Ci-e alkyl, O-C1.6 alkyl, C3-6 cycloalkyl, -O-C3-6 cycloalkyl, -C(=O)Rb1, -NRd1Re1, -ORc1, where said C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl and -O-C3-6 cycloalkyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =0, -CN, Ci-ehaloalkyl, Ci-e haloalkoxy, C3-6 cycloalkyl, Ci-e alkyl, -O-C1-6 alkyl, phenyl, -C(O)Ci-6alkyl, -C(O)N(H)Ci-e alkyl, -C(O)N(Ci-ealkyl)2,-CONH2, -C(O)N(H)CI-6alkyl, -C(O)N(Ci-e alkyl)2, -N(H)Ci-e alkyl, and -N(Ci-e alkyl)2.

[0257] In another embodiment, each Ra1is independently selected from the group consisting of hydroxyl, =0, halogen, CN, CF3, OCF3, Ci-e alkyl, O-C1.6 alkyl, -C(=O)Rb1, -NRd1Re1and -ORc1.

[0258] In another embodiment, each Ra1is independently selected from the group consisting of hydroxyl, =0, halogen, CN, CF3, OCF3, Ci-e alkyl, O-C1.6 alkyl, -C(=O)Me, -NH2, -N(H)Ci-3alkyl and -N(Ci-3alkyl)2.

[0259] In another embodiment, each Ra1is independently selected from the group consisting of halogen, CF3, OCF3, Ci-e alkyl and O-C1.6 alkyl; suitably chloro, fluoro, OCF3, Ci- 4 alkyl and O-C1.4 alkyl.

[0260] In another embodiment, each Ra1is independently selected from the group consisting of hydroxyl, methyl, ethyl and isopropyl.

[0261] In one embodiment, each Rb1is independently selected from hydrogen, C3-6 cycloalkyl or C1-6 alkyl. In another embodiment, each Rb1is independently selected from C3-6 cycloalkyl or C1.4 alkyl.

[0262] In one embodiment, each Rc1is independently selected from the group consisting of hydrogen, Ci-e haloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-6 cycloalkyl, Ci-e alkyl and phenyl, wherein said Ci-e alkyl, phenyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)Ci-ealkyl, -N(Ci-ealkyl)2, Ci-e haloalkyl, C3-6 cycloalkyl, C6-11aryl, 3-7 membered heterocycloalkyl, Ci-e alkyl and -O-C1-6 alkyl.

[0263] In another embodiment, each Rc1is independently selected from the group consisting of hydrogen, Ci-e haloalkyl, C3-6 cycloalkyl and Ci-e alkyl, wherein said Ci-e alkyl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)Ci-ealkyl, -N(Ci-ealkyl)2, Ci-e haloalkyl, C3-6 cycloalkyl, C6-11aryl, 3-7 membered heterocycloalkyl, Ci-e alkyl and -O-C1-6 alkyl. In another embodiment, each Rc1is independently selected from hydrogen or Ci-e alkyl.

[0264] In one embodiment, each Rd1is independently selected from the group consisting of hydrogen, C3-6 cycloalkyl, and Ci-e alkyl, wherein said Ci-e alkyl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)Ci-ealkyl, -N(Ci-ealkyl)2, Ci-e haloalkyl, C3-6 cycloalkyl, C6-11aryl, 3-7 membered heterocycloalkyl, Ci-e alkyl and -O-C1-6 alkyl. In another embodiment, each Rd1is independently selected from hydrogen or Ci-e alkyl.

[0265] In one embodiment, each Re1is independently selected from the group consisting of hydrogen, Ci-e haloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-6 cycloalkyl, Ci-e alkyl and phenyl, wherein said Ci-e alkyl, phenyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)Ci-ealkyl, -N(Ci-ealkyl)2, Ci-e haloalkyl, C3-6 cycloalkyl, C6-11aryl, 3-7 membered heterocycloalkyl, Ci-e alkyl and -O-C1-6 alkyl.

[0266] In another embodiment, each Re1is independently selected from the group consisting of hydrogen, Ci-e haloalkyl, C3-6 cycloalkyl and Ci-e alkyl, wherein said Ci-e alkyl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)Ci-ealkyl, -N(Ci-ealkyl)2, Ci-e haloalkyl, C3-6 cycloalkyl, Ce-naryl, 3-7 membered heterocycloalkyl, Ci-e alkyl and -O-C1.6 alkyl. In another embodiment, each Re1is independently selected from hydrogen or C1-6 alkyl.

[0267] In one embodiment, Rd1and Re1, when attached to the same atom, together with the atom to which they are attached form a 3-7 membered ring, optionally containing one or more heteroatoms selected from O, N and S, and wherein said ring is optionally substituted with one or more Rf1;

[0268] In another embodiment, Rd1and Re1, when attached to the same atom, together with the atom to which they are attached form a 5-7 membered ring, optionally containing one or more heteroatoms selected from O, N and S, and wherein said ring is optionally substituted with one or more Rf1.

[0269] In one embodiment, Rf1is selected from the group consisting of hydrogen, =0, halogen, -CN, -NH2, -N(H)CI-6 alkyl, -N(CI-6 alkyl)2, C1-6 haloalkyl, C3-6 cycloalkyl, Ci-e alkyl and -O-C1.6 alkyl. In another embodiment, Rf1is selected from hydrogen, =0, halogen, -CN, -NH2, -N(H)CI-4 alkyl, -N(Ci-4alkyl)2, C1.4 haloalkyl, C1.4 alkyl and -O-C1.4 alkyl.

[0270] In one embodiment, C is a 5 to 12 membered heterocycle (suitably 5 to 12 membered heterocycloalkyl) containing at least one nitrogen atom in the ring, and wherein theR1 E2R7bR8bmoiety is bonded to ring C via a nitrogen atom in ring C. Consequently, thebonding nitrogen of ring C and the VR7bR8bS moiety combine to give an amide moiety when E2is -C(=O)- for example. Alternatively, when E2is -N(R2)C(=O)-, the bonding nitrogenof ring C and the VR7bR8bS moiety combine to give a urea moiety.

[0271] In another embodiment, C is a 8 to 12 membered heterocycle (suitably 8 to 12 membered heterocycloalkyl) containing at least one nitrogen atom in the ring, and wherein themoiety is bonded to ring C via a nitrogen atom in ring C. In another embodiment, C is a 9 or 10 membered heterocycle (suitably 9 or 10 membered heterocycloalkyl) containing R1A ]. E2at least one nitrogen atom in the ring, and wherein theR7bR8bmoiety is bonded to ring C via a nitrogen atom in ring C.

[0272] In one embodiment, C is a 8 to 11 membered fused bicyclic heterocycle (suitably 8 to 11 membered fused bicyclic heterocycloalkyl) containing at least one nitrogen atom in the R:2ring, and wherein theR moiety is bonded to ring C via a nitrogen atom in ring C. In another embodiment, C is a 9 or 10 membered fused bicyclic heterocycle (suitably 9 or 10 membered fused bicyclic heterocycloalkyl) containing at least one nitrogen atom in the ring, R Eland wherein theR moiety is bonded to ring C via a nitrogen atom in ring C.

[0273] In one embodiment C is of formula C1:\x■25whereR:2the dashed line indicates the point of attachment toR'° R0DX22, X23and X24are independently selected from N, CR9or CH;X25is CH2, CHR9, C(R9)2, NH, NR9, S, S(O), S(O)2or O; andncis an integer selected from 0, 1 or 2.

[0274] In one embodiment, X25is O, CH2or NMe,

[0275] In one embodiment X24is N.

[0276] In one embodiment, X22and X23are CH. In one embodiment, X22and X23are CH and X24is N.

[0277] In one embodiment, ncis an integer selected from 0 or 1.

[0278] In one embodiment, ncis 1 and X25is O, CH2or NMe. In another embodiment, ncis 1 and X25is O, CH2or NMe and X24is N. In another embodiment, ncis 1 and X25is O, CH2or NMe, X22and X23are CH and X24is N.

[0279] In one embodiment, ncis 0 and X25is CH2. In another embodiment, ncis 0 and X25is CH2, and X24is N. In another embodiment, ncis 0 and X25is CH2, X22and X23are CH and X24is N.

[0280] In one embodiment, C is selected from:, each of which may optionally be substituted with R9.

[0281] In another embodiment, C is selected from:, each of which may optionally be substituted with R9.

[0282] In another embodiment, C is selected from:each of which may optionally be substituted with R9.

[0283] In another embodiment, C is selected from:each of which may optionally be substituted with R9.

[0284] In one embodiment, ring C is:which may optionally be substituted with R9.

[0285] In one embodiment, R9is selected from the group consisting of hydroxyl, =0, halogen, CN, Ci-ehaloalkyl, Ci-e haloalkoxy, Ci-ealkyl, O-Ci-ealkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6cycloalkyl, --C(=O)Rb3, -C(=O)ORc3, -C(=O)NRd3Re3, -NRd3Re3, -NRd3C(=O)Rb3,–ORc3, –SRc3, where said Ci-ealkyl, O-C1-6 alkyl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, =0, CN, Ci-e haloalkyl, Ci-e haloalkoxy, C3-6 cycloalkyl, Ci-ealkyl, O-C1.6 alkyl, -NH2, -N(H)CI-3 alkyl, and -N(Ci-3alkyl)2.

[0286] In another embodiment, R9is selected from the group consisting of hydroxyl, =0, halogen, CN, Ci-e haloalkyl, Ci-e haloalkoxy, Ci-e alkyl, O-C1.6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, -NRd3Re3, -ORc3, -SRc3, where said Ci-e alkyl, O-C1.6 alkyl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, =0, CN, Ci-ehaloalkyl, Ci-e haloalkoxy, C3-6 cycloalkyl, Ci-ealkyl, O-C1.6 alkyl, -NH2, -N(H)CI-3 alkyl, and -N(Ci-3alkyl)2.

[0287] In another embodiment, R9is selected from the group consisting of hydroxyl, =0, halogen, CN, Ci-e haloalkyl, Ci-e haloalkoxy, Ci-e alkyl, O-C1.6 alkyl, C2-6 alkenyl, C2-6 alkynyl, -NRd3Re3, where said Ci-ealkyl and O-C1.6 alkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, =0, CN, Ci-e haloalkyl, Ci-e haloalkoxy, C3-6 cycloalkyl, Ci-ealkyl, O-C1.6 alkyl, -NH2, -N(H)CI-3 alkyl, and -N(Ci-3alkyl)2.

[0288] In another embodiment, R9is selected from the group consisting of hydroxyl, =0, halogen, CN, Ci-e haloalkyl, Ci-e haloalkoxy, Ci-e alkyl, O-C1.6 alkyl, C2-6 alkenyl, C2-6 alkynyl, -NH2, -N(H)CI-3alkyl, and -N(Ci-3alkyl)2.

[0289] In another embodiment, R9is selected from the group consisting of hydroxyl, =0, halogen, CN, C1.3 haloalkyl, C1.3 haloalkoxy, C1.4 alkyl, O-C1.4 alkyl, -NH2, -N(H)CI-3 alkyl, and -N(Ci-3alkyl)2.

[0290] In another embodiment, R9is selected from the group consisting of hydroxyl, =0, Cl, Br, CN, CF3, OCF3, methyl, ethyl and OMe.

[0291] In another embodiment, R9is selected from the group consisting of hydroxyl, =0, methyl, ethyl and OMe.

[0292] In one embodiment, y2 is an integer selected from 0, 1 and 2. In another embodiment, y2 is 1. In another embodiment, y2 is 0.

[0293] In one embodiment, z2 is an integer selected from 0, 1 and 2. In another embodiment, z2 is 1. In another embodiment, z2 is 0.

[0294] In one embodiment, A, R4, and V of Q2are independently defined as any of the above-mentioned embodiments of A, R4and V mentioned in respect of Q1.

[0295] In one embodiment, Q2is of sub-formula Q2a:whereX1, X3and X4are independently selected from N, CH or CR4;X6is selected from N or C;X7is selected from O, S, N, CH, CR4and NR4;X25is selected from CH2, CHR9, C(R9)2, NH, NR9, S, S(O), S(O)2or O; andR1a, R7a, R8aand n are independently as defined in any of the above-mentioned embodiments.

[0296] In one embodiment, Q is of sub-formula Q2aand X7is N, S oCR³ or CH. In one embodiment, X3and X4are CH. In one embodiment, X1is CH or N.

[0297] In one embodiment, Q is of sub-formula Q2aand X7is CH and X6is N. In one embodiment, Q is of sub-formula Q2aand X7is CH, X6is N and X4is CH. In one embodiment, Q is of sub-formula Q2aand X7is CH, X6is N, X4is CH, X3is CH and X1is N. In oneembodiment, Q is of sub-formula Q2aand X7is CH, X6is N, X4is CH, X1is CH and X3is N. In one embodiment, Q is of sub-formula Q2aand X7is CH, X6is N, X4is CH, X1is CH and X3is CH.

[0298] In one embodiment, Q is of sub-formula Q2aand X7is S and X6is C. In one embodiment, Q is of sub-formula Q2aand X7is S, X6is C and X1, X3and X4are CH.

[0299] In one embodiment, Q is of sub-formula Q2aandX25is selected from CH2, NH, NMe or O. Suitably, X25is O.

[0300] In one embodiment, Q is of sub-formula Q2a, n is 1, R7band R8bare hydrogen and R1bis a 5-6 membered heteroaryl group, 3-7 membered heterocycloalkyl group, C3-6 cycloalkyl group or a Ci-e alkyl group, where said heteroaryl, heterocycloalkyl and cycloalkyl are optionally substituted with one or more groups Ra1. Suitably, R1bis a pyridyl group, piperidinyl group, cyclohexyl, cyclopropyl, or a C3-6 alkyl group, where said pyridyl, piperidinyl cyclohexyl and cyclopropyl, are optionally substituted with one or more groups Ra1.

[0301] In one embodiment, Q is of sub-formula Q2a, n is 0 and R1bis a selected from a 4-7 membered heterocycloalkyl group, C3-6 cycloalkyl group or a C3-6 alkyl group, where said heterocycloalkyl and cycloalkyl are optionally substituted with one or more groups Ra1. Suitably, R1bis a cyclopropyl or isopropyl group.

[0302] In one embodiment, Q2is of sub-formula Q2e:whereX25is selected from CH2, CHR9, C(R9)2, NH, NR9, S, S(O), S(O)2or O; andR1b, R7b, R8band n are as defined in any of the above-mentioned embodiments.

[0303] In one embodiment, Q is of sub-formula Q2eandX25is selected from CH2, NH, NMe or O. Suitably, X25is O.

[0304] In one embodiment, Q is of sub-formula Q2e, n is 1, R7band R8bare hydrogen and R1bis a 5-6 membered heteroaryl group, 3-7 membered heterocycloalkyl group, C3-6 cycloalkyl group or a Ci-e alkyl group, where said heteroaryl, heterocycloalkyl and cycloalkyl are optionally substituted with one or more groups Ra1. Suitably, R1bis a pyridyl group, piperidinyl group, cyclohexyl, cyclopropyl, or a C3-6 alkyl group, where said pyridyl, piperidinyl cyclohexyl and cyclopropyl, are optionally substituted with one or more groups Ra1.

[0305] In one embodiment, Q is of sub-formula Q2e, n is 0 and R1bis a selected from a 4-7 membered heterocycloalkyl group, C3-6 cycloalkyl group or a C3-6 alkyl group, where said heterocycloalkyl and cycloalkyl are optionally substituted with one or more groups Ra1. Suitably, R1bis a cyclopropyl or isopropyl group.

[0306] In one embodiment, Q2is of sub-formula Q2c:whereX25is selected from CH2, CHR9, C(R9)2, NH, NR9, S, S(O), S(O)2or O; andR1b, R7b, R8band n are as defined in any of the above-mentioned embodiments.

[0307] In one embodiment, Q is of sub-formula Q2candX25is selected from CH2, NH, NMe or O. Suitably, X25is O.

[0308] In one embodiment, Q is of sub-formula Q2c, n is 1, R7band R8bare hydrogen and R1bis a 5-6 membered heteroaryl group, 3-7 membered heterocycloalkyl group, C3-6 cycloalkyl group or a Ci-e alkyl group, where said heteroaryl, heterocycloalkyl and cycloalkyl are optionally substituted with one or more groups Ra1. Suitably, R1bis a pyridyl group, piperidinyl group, cyclohexyl, cyclopropyl, or a C3-6 alkyl group, where said pyridyl, piperidinyl cyclohexyl and cyclopropyl, are optionally substituted with one or more groups Ra1.

[0309] In one embodiment, Q is of sub-formula Q2c, n is 0 and R1bis a selected from a 4-7 membered heterocycloalkyl group, C3-6 cycloalkyl group or a C3-6 alkyl group, where saidheterocycloalkyl and cycloalkyl are optionally substituted with one or more groups Ra1. Suitably, R1bis a cyclopropyl or isopropyl group.

[0310] In another embodiment, Q2is of sub-formula Q2f:X7bis selected from CH or N; andX1is selected from N, CH or CR4;X25is selected from CH2, CHR9, C(R9)2, NH, NR9, S, S(O), S(O)2or O; andR1b, R7b, R8band n are as defined in any of the above-mentioned embodiments.

[0311] In one embodiment of sub-formula Q2f, X25is selected from O, NMe oCR³ or CH.

[0312] In one embodiment of sub-formula Q2f, X7bis selected from N, CH or CR4.

[0313] In one embodiment of sub-formula Q2f, X1is selected from CH.

[0314] In one embodiment of sub-formula Q2f, X1and X7bare CH.

[0315] In one embodiment, Q2iswhere R1b, R7b, R8band n are as defined in any of the above-mentioned embodiments.

[0316] In one embodiment, Q2is selected from the group consisting of:Linker Moiety, L

[0317] The linker moiety serves to connect the protein-targeting moiety, Q, with the E3 ubiquitin ligase binding moiety, M.

[0318] In one embodiment, L is a linker moiety according to formulae L14b:L J n2in27(L14b);where n20 is a number of value 1 to 5;where n21 and n27 are independently an integer of value 0 or 1;rings G2 and H2 are independently selected from the group consisting of a 4 to 10 membered heterocycloalkyl, a 5 or 6 membered heteroaryl and a C3-C10 cycloalkyl, each of which may be optionally substituted by one or more R80;R80at each occurrence is independently selected from the group consisting of hydroxyl, =0, C1.4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1.4 haloalkyl and C3-6 cycloalkyl, each of which may be optionally be substituted with one or more groups selected from C1.4 alkyl, C1.4 alkoxy, C3-6 cycloalkyl, phenyl and hydroxyl; andR10and R11are independently selected from H, C1.4 alkyl, C3-6 cycloalkyl; or R10and R11, together with the carbon atom to which they are attached form a C3-6 cycloalkyl group.

[0319] In one embodiment, rings G2 and H2 are independently selected from the group consisting of a 5 to 10 membered heterocycloalkyl, a 5 or 6 membered heteroaryl and a C3-C10 cycloalkyl, each of which may be optionally substituted by one or more R80.

[0320] In one embodiment, n27 is 1. In another embodiment, n 27 is 0.

[0321] In another embodiment, rings G2 and H2 are independently selected from the group consisting of a 5 to 10 membered heterocycloalkyl, a 5 or 6 membered heteroaryl and a C3-C10 cycloalkyl, each of which may be optionally substituted by one or more R80; and n27 is 1.

[0322] In one embodiment, ring H2 is a 5 or 6 membered heteroaryl which may be optionally substituted by one or more R80.

[0323] In one embodiment, ring H2 is a pyridinyl, pyrimidinyl, pyridazinyl or pyrazinyl ring which may be optionally substituted by one or more R80.

[0324] In one embodiment, L is a linking moiety of formula L14b1:R11n21 (L14b1);

[0325] In one embodiment, ring G2 is selected from the group consisting of a 5 to 10 membered heterocycloalkyl and a C3-C10 cycloalkyl, each of which may be optionally substituted by one or more R80. In another embodiment, ring G2 is a 5 to 9 membered heterocycloalkyl optionally substituted by one or more R80. In another embodiment, ring G2 is a 5 to 9 membered heterocycloalkyl comprising one or two nitrogen atoms, optionally substituted by one or more R80. In another embodiment, ring G2 is a 5 to 8 membered heterocycloalkyl comprising one or two nitrogen atoms, optionally substituted by one or more R80

[0326] In one embodiment, ring G2 is selected from a piperazinyl, piperidinyl, 2,6- diazaspiro[3.3]heptanyl, octahydropyrrolo[3,4-c]pyrrole, 3,6-diazabicyclo[3.1.1]heptane or a 2,5-diazabicyclo[2.2.1]heptane ring, each of which may be optionally substituted by one or more R80.

[0327] In one embodiment, ring G2 is piperazinyl optionally substituted by one or more □ 80

[0328] In one embodiment, n27 is 1.

[0329] In one embodiment, L is a linking moiety of formula L14b2:on21 (L14b2);

[0330] In one embodiment, n20 is a number of value 1, 2 or 3.

[0331] In one embodiment, n21 is 1.

[0332] In one embodiment, n27 is 1.

[0333] In one embodiment, n21 is 1, n20 is 1 and n27 is 0. In another embodiment, n21 is 1, n20 is 1 and n27 is 1.

[0334] In one embodiment, R80, at each occurrence, is independently selected from the group consisting of hydroxyl, =0, C1.4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1.4 haloalkyl and C3-6 cycloalkyl, each of which may be optionally be substituted with one or more groups selected from C1.4 alkyl, C1.4 alkoxy, C3-6 cycloalkyl, phenyl, and hydroxyl.

[0335] In another embodiment, R80, at each occurrence, is independently selected from the group consisting of hydroxyl, =0 and C1.4 alkyl.

[0336] In one embodiment, R10and R11are independently selected from H or C1-3alkyl; or R10and R11, together with the carbon atom to which they are attached, form a cyclopropyl group.

[0337] In one embodiment, R10and R11are independently selected from H or methyl.

[0338] In one embodiment, the linking moiety of formula L14b is selected from the following:o

[0339] In one embodiment, the wavy line indicates the point of attachment to proteinbinding moiety, Q. In another embodiment, the wavy line indicates the point of attachment to E3 ubiquitin ligase binding moiety, M.

[0340] In one embodiment, L is a linking moiety of formula L14c:(L14c);wheren23 is an integer of value 0 or 1;n24 is an integer of value 0 to 3;n30 is an integer of value 0 or 1;rings G3 and H3 are independently selected from the group consisting of a 4 to 10 membered heterocycloalkyl, a 5 or 6 membered heteroaryl, phenyl and a C3-C10 cycloalkyl, each of which may be optionally substituted by one or more R81;R81at each occurrence is independently selected from the group consisting of hydroxyl, =0, C1.4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1.4 haloalkyl and C3-6 cycloalkyl, each of which may be optionally be substituted with one or more groups selected from C1.4 alkyl, C1.4 alkoxy, C3-6 cycloalkyl, phenyl and hydroxyl; andR12cand R13care independently selected from H, halo, C1.4 alkyl, C3-6 cycloalkyl; or R12cand R13c, together with the carbon atom to which they are attached form a C3-6 cycloalkyl group.

[0341] In one embodiment, ring H3 is a 5 or 6 membered heteroaryl which may be optionally substituted by one or more R81.

[0342] In one embodiment, ring H3 is a pyridinyl, pyrimidinyl, pyridazinyl or pyrazinyl ring which may be optionally substituted by one or more R81.

[0343] In one embodiment, ring G3 is selected from the group consisting of a 4 to 10 membered heterocycloalkyl and a C3-C10 cycloalkyl, each of which may be optionally substituted by one or more R81. In another embodiment, ring G3 is a 4 to 9 membered heterocycloalkyl optionally substituted by one or more R81. In another embodiment, ring G3 is a 4 to 9 membered heterocycloalkyl comprising one or two nitrogen atoms, optionally substituted by one or more R8c. In another embodiment, ring G3 is a 4 to 8 membered heterocycloalkyl comprising one or two nitrogen atoms, optionally substituted by one or more R81.

[0344] In one embodiment, G3 is a 6-membered heterocycloalkyl group (suitably piperidinyl or piperazinyl) and H3 is a 6-membered heteroaryl (suitably pyridyl or pyrimidinyl).

[0345] In one embodiment, R12cand R13care independently selected from H and C1.4 alkyl. In another embodiment, R12cand R13care independently selected from H and methyl.

[0346] In one embodiment, one of R12cand R13cis H and the other is methyl. In another embodiment, R12cand R13care both H.

[0347] In one embodiment, n23 is 1.

[0348] In one embodiment, n24 is 1.

[0349] In one embodiment, n23 and n24 are 1. In another embodiment, n23 is 0 and n24 is 2.

[0350] In one embodiment, n30 is 0.

[0351] In one embodiment, R81, at each occurrence, is independently selected from the group consisting of hydroxyl, =0, C1.4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1.4 haloalkyl and C3-6 cycloalkyl, each of which may be optionally be substituted with one or more groups selected from C1.4 alkyl, C1.4 alkoxy, C3-6 cycloalkyl, phenyl, and hydroxyl.

[0352] In another embodiment, R81, at each occurrence, is independently selected from the group consisting of hydroxyl, =0 and C1.4 alkyl.

[0353] In one embodiment, the linking moiety of formula L14c is selected from the following:

[0354] In one embodiment, the wavy line indicates the point of attachment to proteinbinding moiety, Q. In another embodiment, the wavy line indicates the point of attachment to E3 ubiquitin ligase binding moiety, M.

[0355] In one embodiment, L is a linker moiety of formula L16a:(L16a);whereinring J1 is a 4 to 10 membered heterocycloalkyl ring which may optionally substituted by one or more R26;Z1is absent or a group selected from NH, N(C1-3 alkyl), O or S;n37 and n38 are independently selected from an integer of value 0 to 5; and n36 and n39 are independently selected from an integer of value 0 or 1; andR26at each occurrence is independently selected from the group consisting of hydroxyl, =0, C1.4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1.4 haloalkyl and C3-6 cycloalkyl, each of which may be optionally be substituted with one or more groups selected from C1.4 alkyl, C1.4 alkoxy, C3-6 cycloalkyl, phenyl and hydroxyl.

[0356] In one embodiment, ring J1 is a 4 to 9 membered heterocycloalkyl ring, suitably containing one or two nitrogen atoms, optionally substituted by one or more R26. In one embodiment, ring J1 is a 4 to 7 membered heterocycloalkyl ring, suitably containing one or two nitrogen atoms, optionally substituted by one or more R26. In one embodiment, ring J1 is a 5 or 6 membered heterocycloalkyl ring, suitably containing one or two nitrogen atoms, optionally substituted by one or more R26. Suitably, J1 is a piperidinyl or piperazinyl ring, optionally substituted by one or more R26.

[0357] In one embodiment, Z1is absent or a group selected from NH, N(C1-3 alkyl) or O. In another embodiment, Z1is absent or a group selected from O, NH or NMe.

[0358] In one embodiment, n39 is 0. In another embodiment, n36 is 0. In another embodiment, both n39 and n36 are 0. In another embodiment, n36 is 1 and n39 is 0.

[0359] In one embodiment, n37 and n38 are independently selected from 0, 1, 2 or 3. In one embodiment, n37 and n38 are both 1.

[0360] In one embodiment, n36 is 1 and n37 is 1. In another embodiment, n36 is 1, n37 is 1, n 38 is an integer selected from 0, 1, 2 or 3.

[0361] In one embodiment, n39 is 0, n36 is 0, n37 and n38 are each independently an integer selected from 0, 1, 2 or 3. In another embodiment, n39 is 0, n36 is 1, n37 and n38 are each independently an integer selected from 0, 1, 2 or 3.

[0362] In one embodiment, n39 is 0, n36 is 1, n37 and n38 are each 1 and Z1is absent or NMe.

[0363] In one embodiment, n36 is 1, n37 is 1, n 38 and n39 are 0 and Z1is absent.

[0364] In one embodiment, n36 is 1, n37 is 1, n38 and n39 are 1 and Z1is absent.

[0365] In one embodiment, n36 is 0, n37 is 1, n38 and n39 are 1 and Z1is absent.

[0366] In one embodiment, n36 and n 39 are 0, n37 is an integer selected from 1, 2 or 3, n38 is 1 and Z1is absent.

[0367] In one embodiment, R26, at each occurrence, is independently selected from the group consisting of hydroxyl, =0, C1.4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1.4 haloalkyl and C3-6 cycloalkyl, each of which may be optionally be substituted with one or more groups selected from C1.4 alkyl, C1.4 alkoxy, C3-6 cycloalkyl, phenyl, and hydroxyl.

[0368] In another embodiment, R26, at each occurrence, is independently selected from the group consisting of hydroxyl, =0 and C1.4 alkyl.

[0369] In one embodiment, the linking moiety of formula L16a is selected from the following:

[0370] In one embodiment, the wavy line indicates the point of attachment to proteinbinding moiety, Q. In another embodiment, the wavy line indicates the point of attachment to E3 ubiquitin ligase binding moiety, M.

[0371] In one embodiment, L is a linking moiety of formula L14e:

[0372] In one embodiment, ring H5 is a 5 or 6 membered heteroaryl which may be optionally substituted by one or more R8e.

[0373] In one embodiment, ring H5 is a pyridinyl, pyrimidinyl pyridazinyl or pyrazinyl ring which may be optionally substituted by one or more R8e.

[0374] In one embodiment, ring H5 is a 4 to 7 membered heterocycloalkyl which may be optionally substituted by one or more R8e.

[0375] In one embodiment, ring H5 is an azetidinyl, pyrrolidinyl, piperidinyl or piperazinyl ring which may be optionally substituted by one or more R8e.

[0376] In one embodiment, ring D5 is a 5 or 6 membered heteroaryl which may be optionally substituted by one or more R8e. In another embodiment, ring D5 is a 5 membered heteroaryl which may be optionally substituted by one or more R8e

[0377] In one embodiment, ring D5 is an oxazole, isoxazole, pyrazole, imidazole, triazole, thiazole or isothiazole ring which may be optionally substituted by one or more R8e.

[0378] In another embodiment, ring D5 is an oxazole, isoxazole or pyrazole, ring which may be optionally substituted by one or more R8e. In another embodiment, ring D5 is an isoxazole ring which may be optionally substituted by one or more R8e.

[0379] In one embodiment, ring D5 is a 6 membered heteroaryl, suitably selected from pyridyl, pyrimidinyl and pyrazinyl.

[0380] In one embodiment, ring G5 is selected from the group consisting of a 4 to 10 membered heterocycloalkyl and a C3-C10 cycloalkyl, each of which may be optionally substituted by one or more R8e. In another embodiment, ring G5 is a 4 to 9 membered heterocycloalkyl optionally substituted by one or more R8e. In another embodiment, ring G5 is a 4 to 9 membered heterocycloalkyl comprising one or two nitrogen atoms, optionally substituted by one or more R8e. In another embodiment, ring G5 is a 4 to 8 memberedheterocycloalkyl comprising one or two nitrogen atoms, optionally substituted by one or more R8e.

[0381] In one embodiment, ring G5 is a 4 to 7 membered heterocycloalkyl which may be optionally substituted by one or more R8e.

[0382] In one embodiment, ring G5 is an azetidinyl, pyrrolidinyl, piperidinyl or piperazinyl ring which may be optionally substituted by one or more R8e.

[0383] In one embodiment, R12eand R13eare independently selected from H and C1.4 alkyl. In another embodiment, R12eand R13eare independently selected from H and methyl.

[0384] In one embodiment, one of R12eand R13eis H and the other is methyl. In another embodiment, R12eand R13eare both H.

[0385] In one embodiment, n50 is 1. In another embodiment, n51 is 1. In another embodiment, both n50 and n51 are 1. In another embodiment, n51 is 0.

[0386] In one embodiment, n52 is 1. In another embodiment, n53 is 1. In another embodiment, both n52 and n53 are 1. In another embodiment, n51 is 0.

[0387] In one embodiment, n53 is 0 and n51 is 1. In another embodiment, n50 is 1 and n52 is 1. In another embodiment, n50, n51, n52 and n53 are each 1.

[0388] In one embodiment, n50 is 1 and n52 is 1. In another embodiment, n51 is 0 and n53 is 0. In another embodiment, n50 and n52 are 1 and n51 and n53 are 0.

[0389] In one embodiment, R8e, at each occurrence, is independently selected from the group consisting of hydroxyl, =0, C1.4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1.4 haloalkyl and C3-6 cycloalkyl, each of which may be optionally be substituted with one or more groups selected from C1.4 alkyl, C1.4 alkoxy, C3-6 cycloalkyl, phenyl, and hydroxyl.

[0390] In another embodiment, R8e, at each occurrence, is independently selected from the group consisting of hydroxyl, =0 and C1.4 alkyl.

[0391] In one embodiment, R10eand R11eare independently selected from H or C1.3 alkyl; or R10eand R11e, together with the carbon atom to which they are attached, form a cyclopropyl group.

[0392] In one embodiment, R10eand R11eare independently selected from H or methyl.

[0393] In one embodiment, the linking moiety of formula L14e is selected from the following:

[0394] In one embodiment, the wavy line indicates the point of attachment to proteinbinding moiety, Q. In another embodiment, the wavy line indicates the point of attachment to E3 ubiquitin ligase binding moiety, M.

[0395] In one embodiment, the compound of formula I is a compound of sub-formula IGi:(IGi)where R1a, R2, R7a, R8a, n, X1, X3, X4, X6, X7, X9, X10and n20, n21, n27, G2, H2, R10and R11are as defined in any of the above mentioned embodiments (in particular, embodiments of formulae Q1aor L14b); andM is an E3 ubiquitin ligase binding moiety, suitably selected from any of the below mentioned embodiments.

[0396] In one embodiment, the compound of formula I is a compound of sub-formula IGii:where R1a, R2, R7a, R8a, n, X1, X3, X4, X6, X7, X9, X10and n20, n21, n27, G2, R10and R11are as defined in any of the above mentioned embodiments (in particular, embodiments of formulae Q1aor L14b1); andM is an E3 ubiquitin ligase binding moiety, suitably selected from any of the below mentioned embodiments.

[0397] In one embodiment, the compound of formula I is a compound of sub-formula IGiii:where R1a, R2, R7a, R8a, n, X1, X3, X4, X6, X7, X9, X10and n20, n21, n27, R10and R11are as defined in any of the above mentioned embodiments (in particular, embodiments of formulae Q1aor L14b2); andM is an E3 ubiquitin ligase binding moiety, suitably selected from any of the below mentioned embodiments.

[0398] In one embodiment of any of formulae I Gi, I Gii or IGiii, X7is N, S oCR³ or CH. In one embodiment, X3and X4are CH. In one embodiment, X1is CH or N.

[0399] In one embodiment, X7is CH and X6is N. In one embodiment, X7is CH, X6is N and X4is CH. In one embodiment, X7is CH, X6is N, X4is CH, X3is CH and X1is N. In one embodiment, X7is CH, X6is N, X4is CH, X1is CH and X3is N. In one embodiment, X7is CH, X6is N, X4is CH, X1is CH and X3is CH.

[0400] In one embodiment, X7is S and X6is C. In one embodiment, X7is S, X6is C and X1, X3and X4are CH.

[0401] In one embodiment, X9is N. In another embodiment, X9is N and X10is CR3oCR³ or CH.

[0402] In one embodiment, X9is N and X10is CH and R2is methyl.

[0403] In one embodiment, R2is hydrogen or methyl.

[0404] In one embodiment, each R7aand R8aare independently selected from the group consisting of hydrogen, hydroxyl, hydroxymethyl, fluoro and methyl.

[0405] In one embodiment, R1ais selected from the group consisting of phenyl, 5 to 7 membered heteroaryl, 3 to 7 membered heterocycloalkyl, C3-7 cycloalkyl and C1-6 alkyl, each of which is optionally substituted with one or more Ra1.

[0406] In one embodiment, R1ais selected from the group consisting of phenyl, 5 to 7 membered heteroaryl and 3 to 7 membered heterocycloalkyl, each of which is optionally substituted with one or more Ra1.

[0407] In one embodiment, R1ais selected from the group consisting of phenyl, pyridyl, pyrazinyl, pyrazolyl, piperidinyl, pyrrolidinyl, morpholinyl, tetrahydropyranyl, cyclopropyl and / -propyl, s-butyl, / -butyl, each of which is optionally substituted with one or more Ra1.

[0408] In one embodiment, R1ais selected from the following groups, each of which is optionally substituted with one or more groups Ra1:

[0409] In one embodiment, R1ais selected from the following groups, each of which is optionally substituted with one or more groups Ra1:

[0410] In one embodiment, R1ais selected from the following groups, each of which is optionally substituted with one or more groups Ra1:

[0411] In one embodiment, M is of formula M1 as described in any of the below mentioned embodiments.

[0412] In one embodiment, the compound of formula I is a compound of sub-formulawhere R1a, R2, R7a, R8a, n, X1, X3, X4, X6, X7, X9, X10and n23, n24, R12c, R13c, G3 and H3 are as defined in any of the above mentioned embodiments (in particular, embodiments of formulae Q1aor L14c); andM is an E3 ubiquitin ligase binding moiety, suitably selected from any of the below mentioned embodiments.

[0413] In one embodiment, the compound of formula I is a compound of sub-formula IHii:n23 (IHii)where R1a, R2, R7a, R8a, n, X1, X7a, X9, X10and n23, n24, R12c, R13c, G3 and H3 are as defined in any of the above mentioned embodiments (in particular, embodiments of formulae Q1eor L14c); andM is an E3 ubiquitin ligase binding moiety, suitably selected from any of the below mentioned embodiments.

[0414] In one embodiment of formula I Hi, X7is N, S oCR³ or CH. In one embodiment, X3and X4are CH. In one embodiment, X1is CH or N.

[0415] In one embodiment, X7is CH and X6is N. In one embodiment, X7is CH, X6is N and X4is CH. In one embodiment, X7is CH, X6is N, X4is CH, X3is CH and X1is N. In one embodiment, X7is CH, X6is N, X4is CH, X1is CH and X3is N. In one embodiment, X7is CH, X6is N, X4is CH, X1is CH and X3is CH.

[0416] In one embodiment, X7is S and X6is C. In one embodiment, X7is S, X6is C and X1, X3and X4are CH.

[0417] In one embodiment of formula I Hii, X7ais CH. In one embodiment, X1is CH and X7ais CH. In another embodiment, X1is CH and X7ais N.

[0418] In one embodiment of formula IHi or IHii, X9is N. In another embodiment, X9is N and X10is CR3oCR³ or CH.

[0419] In one embodiment of formula IHi or IHii, X9is N and X10is CH and R2is methyl.

[0420] In one embodiment of formula I Hi or IHii, R2is hydrogen or methyl.

[0421] In one embodiment of formula I Hi or IHii, each R7aand R8aare independently selected from the group consisting of hydrogen, hydroxyl, hydroxymethyl, fluoro and methyl.

[0422] In one embodiment of formula I Hi or IHii, G3 is a 6-membered heterocycloalkyl group (suitably piperidinyl or piperazinyl) and H3 is a 6-membered heteroaryl (suitably pyridyl or pyrimidinyl).

[0423] In one embodiment of formula IHi or IHii, n23 and n24 are 1. In another embodiment, n23 is 0 and n24 is 2.

[0424] In one embodiment of formula IHi or IHii, R1ais selected from the group consisting of phenyl, 5 to 7 membered heteroaryl, 3 to 7 membered heterocycloalkyl, C3-7 cycloalkyl and C1-6 alkyl, each of which is optionally substituted with one or more Ra1.

[0425] In one embodiment of formula IHi or IHii, R1ais selected from the group consisting of phenyl, 5 to 7 membered heteroaryl and 3 to 7 membered heterocycloalkyl, each of which is optionally substituted with one or more Ra1.

[0426] In one embodiment of formula IHi or IHii, R1ais selected from the group consisting of phenyl, pyridyl, pyrazinyl, pyrazolyl, piperidinyl, pyrrolidinyl, morpholinyl, tetrahydropyranyl, cyclopropyl and / -propyl, s-butyl, / -butyl, each of which is optionally substituted with one or more Ra1.

[0427] In one embodiment of formula IHi or IHii, R1ais selected from the following groups, each of which is optionally substituted with one or more groups Ra1:

[0428] In one embodiment of formula IHi or IHii, R1ais selected from the following groups, each of which is optionally substituted with one or more groups Ra1:

[0429] In one embodiment of formula IHi or IHii, R1ais selected from the following groups, each of which is optionally substituted with one or more groups Ra1:

[0430] In one embodiment of formula IHi or IHii, M is of formula M6 or M6i as described in any of the below mentioned embodiments.

[0431] In one embodiment, the compound of formula I is a compound of sub-formula(IJ)where R1a, R2, R7a, R8a, n, X1, X3, X4, X6, X7, X9, X10and n36, n37, n38, n39, J1 and Z1are as defined in any of the above mentioned embodiments (in particular, embodiments of formulae Q1aor L16a); andM is an E3 ubiquitin ligase binding moiety, suitably selected from any of the below mentioned embodiments.

[0432] In one embodiment of formulae I J, X7is N, S oCR³ or CH. In one embodiment, X3and X4are CH. In one embodiment, X1is CH or N.

[0433] In one embodiment, X7is CH and X6is N. In one embodiment, X7is CH, X6is N and X4is CH. In one embodiment, X7is CH, X6is N, X4is CH, X3is CH and X1is N. In one embodiment, X7is CH, X6is N, X4is CH, X1is CH and X3is N. In one embodiment, X7is CH, X6is N, X4is CH, X1is CH and X3is CH.

[0434] In one embodiment, X7is S and X6is C. In one embodiment, X7is S, X6is C and X1, X3and X4are CH.

[0435] In one embodiment, X9is N. In another embodiment, X9is N and X10is CR3oCR³ or CH.

[0436] In one embodiment, X9is N and X10is CH and R2is methyl.

[0437] In one embodiment, R2is hydrogen or methyl.

[0438] In one embodiment, each R7aand R8aare independently selected from the group consisting of hydrogen, hydroxyl, hydroxymethyl, fluoro and methyl.

[0439] In one embodiment, J1 is a 6-membered heterocycloalkyl ring, suitably a piperidinyl or piperazinyl ring, optionally substituted by one or more R26.

[0440] In one embodiment, n39 is 0. In another embodiment, n36 is 0. In another embodiment, both n39 and n36 are 0. In another embodiment, n36 is 1 and n39 is 0.

[0441] In one embodiment, n37 and n38 are independently selected from 0, 1, 2 or 3. In one embodiment, n37 and n38 are both 1.

[0442] In one embodiment, n36 is 1 and n37 is 1. In another embodiment, n36 is 1, n37 is 1, n 38 is an integer selected from 0, 1, 2 or 3.

[0443] In one embodiment, n39 is 0, n36 is 0, n37 and n38 are each independently an integer selected from 0, 1, 2 or 3. In another embodiment, n39 is 0, n36 is 1, n37 and n38 are each independently an integer selected from 0, 1, 2 or 3.

[0444] In one embodiment, n39 is 0, n36 is 1, n37 and n38 are each 1 and z is absent or NMe.

[0445] In one embodiment, n36 is 1, n37 is 1, n 38 and n39 are 0 and z is absent.

[0446] In one embodiment, n36 is 1, n37 is 1, n38 and n39 are 1 and z is absent.

[0447] In one embodiment, n36 is 0, n37 is 1, n38 and n39 are 1 and z is absent.

[0448] In one embodiment, R26, at each occurrence, is independently selected from the group consisting of hydroxyl, =0, C1.4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1.4 haloalkyl and C3-6 cycloalkyl, each of which may be optionally be substituted with one or more groups selected from C1.4 alkyl, C1.4 alkoxy, C3-6 cycloalkyl, phenyl, and hydroxyl.

[0449] In another embodiment, R26, at each occurrence, is independently selected from the group consisting of hydroxyl, =0 and C1.4 alkyl.

[0450] In one embodiment, R1ais selected from the group consisting of phenyl, 5 to 7 membered heteroaryl, 3 to 7 membered heterocycloalkyl, C3-7 cycloalkyl and C1-6 alkyl, each of which is optionally substituted with one or more Ra1.

[0451] In one embodiment, R1ais selected from the group consisting of phenyl, 5 to 7 membered heteroaryl and 3 to 7 membered heterocycloalkyl, each of which is optionally substituted with one or more Ra1.

[0452] In one embodiment, R1ais selected from the group consisting of phenyl, pyridyl, pyrazinyl, pyrazolyl, piperidinyl, pyrrolidinyl, morpholinyl, tetrahydropyranyl, cyclopropyl and / -propyl, s-butyl, / -butyl, each of which is optionally substituted with one or more Ra1.

[0453] In one embodiment, R1ais selected from the following groups, each of which is optionally substituted with one or more groups Ra1:

[0454] In one embodiment, R1ais selected from the following groups, each of which is optionally substituted with one or more groups Ra1:

[0455] In one embodiment, R1ais selected from the following groups, each of which is optionally substituted with one or more groups Ra1:

[0456] In one embodiment, M is of formula M1, M6 or M6i as described in any of the below mentioned embodiments.

[0457] In one embodiment, the compound of formula I is a compound of sub-formula IPiii:(IPiii)where R1b, R7b, R8b, n, X25, X1, X3, X4, X6, X7and n20, n21, n27, G2, H2, R10and R11are as defined in any of the above mentioned embodiments (in particular, embodiments of formulae Q2aor L14b); andM is an E3 ubiquitin ligase binding moiety, suitably selected from any of the below mentioned embodiments.

[0458] In one embodiment, the compound of formula I is a compound of sub-formula IPiv:where R1b, R7b, R8b, n, X25, X1, X3, X4, X6, X7and n20, n21, n27, G2, R10and R11are as defined in any of the above mentioned embodiments (in particular, embodiments of formulae Q2aor L14b1); andM is an E3 ubiquitin ligase binding moiety, suitably selected from any of the below mentioned embodiments.

[0459] In one embodiment, the compound of formula I is a compound of sub-formulawhere R1b, R7b, R8b, n, X25, X1, X3, X4, X6, X7and n20, n21, n27, R10and R11are as defined in any of the above mentioned embodiments (in particular, embodiments of formulae Q2aor L14b2); andM is an E3 ubiquitin ligase binding moiety, suitably selected from any of the below mentioned embodiments.

[0460] In one embodiment of any of formulae IPiii, IPiv or IPv, X7is N, S oCR³ or CH. In one embodiment, X3and X4are CH. In one embodiment, X1is CH or N.

[0461] In one embodiment, X7is CH and X6is N. In one embodiment, X7is CH, X6is N and X4is CH. In one embodiment, X7is CH, X6is N, X4is CH, X3is CH and X1is N. In one embodiment, X7is CH, X6is N, X4is CH, X1is CH and X3is N. In one embodiment, X7is CH, X6is N, X4is CH, X1is CH and X3is CH.

[0462] In one embodiment, X7is S and X6is C. In one embodiment, X7is S, X6is C and X1, X3and X4are CH.

[0463] In one embodiment, R7band R8bare independently selected from the group consisting of hydrogen, hydroxyl, hydroxymethyl, fluoro and methyl.

[0464] In one embodiment, X25is selected from CH2, NH, NMe or O. Suitably, X25is O.

[0465] In one embodiment, R1bis a 5-6 membered heteroaryl group, 3-7 membered heterocycloalkyl group, C3-6 cycloalkyl group or a Ci-e alkyl group, where said heteroaryl, heterocycloalkyl and cycloalkyl are optionally substituted with one or more groups Ra1. Suitably, R1bis a pyridyl group, piperidinyl group, cyclohexyl, cyclopropyl, or a C3-6 alkyl group, where said pyridyl, piperidinyl cyclohexyl and cyclopropyl, are optionally substituted with one or more groups Ra1.

[0466] In one embodiment, R1bis selected from the following groups, each of which is optionally substituted with one or more groups Ra1:

[0467] In one embodiment, R1bis selected from the following groups, each of which is optionally substituted with one or more groups Ra1:

[0468] In one embodiment, R1bis selected from the following groups, each of which is optionally substituted with one or more groups Ra1:

[0469] In one embodiment, M is of formula M1 as described in any of the below mentioned embodiments.

[0470] In one embodiment, the compound of formula I is a compound of sub-formula IQi:where R1b, R7b, R8b, n, X25, X1, X3, X4, X6, X7and n23, n24, R12c, R13cG3 and H3 are as defined in any of the above mentioned embodiments (in particular, embodiments of formulae Q2aor L14c); andM is an E3 ubiquitin ligase binding moiety, suitably selected from any of the below mentioned embodiments.

[0471] In one embodiment, the compound of formula I is a compound of sub-formula IQii:where R1b, R7b, R8b, n, X25, X1, X7band n23, n24, R12c, R13cG3 and H3 are as defined in any of the above mentioned embodiments (in particular, embodiments of formulae Q2for L14c); andM is an E3 ubiquitin ligase binding moiety, suitably selected from any of the below mentioned embodiments.

[0472] In one embodiment of formula IQi, X7is N, S oCR³ or CH. In one embodiment, X3and X4are CH. In one embodiment, X1is CH or N.

[0473] In one embodiment of formula IQi, X7is CH and X6is N. In one embodiment, X7is CH, X6is N and X4is CH. In one embodiment, X7is CH, X6is N, X4is CH, X3is CH and X1is N. In one embodiment, X7is CH, X6is N, X4is CH, X1is CH and X3is N. In one embodiment, X7is CH, X6is N, X4is CH, X1is CH and X3is CH.

[0474] In one embodiment of formula IQi, X7is S and X6is C. In one embodiment, X7is S, X6is C and X1, X3and X4are CH.

[0475] In one embodiment of formula IQii, X7bis CH. In one embodiment of formula IQii, X1is CH. In one embodiment, X7bis CH and X1is CH. In another embodiment, X7bis N and X1is CH.

[0476] In one embodiment formula IQi and IQii, R7band R8bare independently selected from the group consisting of hydrogen, hydroxyl, hydroxymethyl, fluoro and methyl.

[0477] In one embodiment formula IQi and IQii, X25is selected from CH2, NH, NMe or O. Suitably, X25is O.

[0478] In one embodiment formula IQi and IQii, R1bis a 5-6 membered heteroaryl group, 3-7 membered heterocycloalkyl group, C3-6 cycloalkyl group or a C1.6 alkyl group, where said heteroaryl, heterocycloalkyl and cycloalkyl are optionally substituted with one or more groups Ra1. Suitably, R1bis a pyridyl group, piperidinyl group, cyclohexyl, cyclopropyl, or a C3-6 alkyl group, where said pyridyl, piperidinyl cyclohexyl and cyclopropyl, are optionally substituted with one or more groups Ra1.

[0479] In one embodiment formula IQi and IQii, R1bis selected from the following groups, each of which is optionally substituted with one or more groups Ra1:

[0480] In one embodiment formula IQi and IQii, R1bis selected from the following groups, each of which is optionally substituted with one or more groups Ra1:

[0481] In one embodiment formula IQi and IQii, R1bis selected from the following groups, each of which is optionally substituted with one or more groups Ra1:

[0482] In one embodiment formula IQi and IQii, G3 is a 6-membered heterocycloalkyl group (suitably piperidinyl or piperazinyl) and H3 is a 6-membered heteroaryl (suitably pyridyl or pyrimidinyl).

[0483] In one embodiment formula IQi and IQii, n23 and n24 are 1. In another embodiment, n23 is 0 and n24 is 2.

[0484] In one embodiment formula IQi and IQii, M is of formula M6 orM6i as described in any of the below mentioned embodiments.

[0485] In one embodiment, the compound of formula I is a compound of sub-formulawhere R1b, R7b, R8b, n, X25, X1, X3, X4, X6, X7and n36, n37, n38, n39, J1 and Z1are as defined in any of the above mentioned embodiments (in particular, embodiments of formulae Q2aor L16a); andM is an E3 ubiquitin ligase binding moiety, suitably selected from any of the below mentioned embodiments.

[0486] In one embodiment of any of formulae IRi, X7is N, S oCR³ or CH. In one embodiment, X3and X4are CH. In one embodiment, X1is CH or N.

[0487] In one embodiment, X7is CH and X6is N. In one embodiment, X7is CH, X6is N and X4is CH. In one embodiment, X7is CH, X6is N, X4is CH, X3is CH and X1is N. In one embodiment, X7is CH, X6is N, X4is CH, X1is CH and X3is N. In one embodiment, X7is CH, X6is N, X4is CH, X1is CH and X3is CH.

[0488] In one embodiment, X7is S and X6is C. In one embodiment, X7is S, X6is C and X1, X3and X4are CH.

[0489] In one embodiment, R7band R8bare independently selected from the group consisting of hydrogen, hydroxyl, hydroxymethyl, fluoro and methyl.

[0490] In one embodiment, X25is selected from CH2, NH, NMe or O. Suitably, X25is O.

[0491] In one embodiment, R1bis a 5-6 membered heteroaryl group, 3-7 membered heterocycloalkyl group, C3-6 cycloalkyl group or a Ci-e alkyl group, where said heteroaryl, heterocycloalkyl and cycloalkyl are optionally substituted with one or more groups Ra1. Suitably, R1bis a pyridyl group, piperidinyl group, cyclohexyl, cyclopropyl, or a C3-6 alkyl group, where said pyridyl, piperidinyl cyclohexyl and cyclopropyl, are optionally substituted with one or more groups Ra1.

[0492] In one embodiment, R1bis selected from the following groups, each of which is optionally substituted with one or more groups Ra1:

[0493] In one embodiment, R1bis selected from the following groups, each of which is optionally substituted with one or more groups Ra1:

[0494] In one embodiment, R1bis selected from the following groups, each of which is optionally substituted with one or more groups Ra1:

[0495] In one embodiment, J1 is a 6-membered heterocycloalkyl ring, suitably a piperidinyl or piperazinyl ring, optionally substituted by one or more R26.

[0496] In one embodiment, n39 is 0. In another embodiment, n36 is 0. In another embodiment, both n39 and n36 are 0. In another embodiment, n36 is 1 and n39 is 0.

[0497] In one embodiment, n37 and n38 are independently selected from 0, 1, 2 or 3. In one embodiment, n37 and n38 are both 1.

[0498] In one embodiment, n36 is 1 and n37 is 1. In another embodiment, n36 is 1, n37 is 1, n 38 is an integer selected from 0, 1, 2 or 3.

[0499] In one embodiment, n39 is 0, n36 is 0, n37 and n38 are each independently an integer selected from 0, 1, 2 or 3. In another embodiment, n39 is 0, n36 is 1, n37 and n38 are each independently an integer selected from 0, 1, 2 or 3.

[0500] In one embodiment, n39 is 0, n36 is 1, n37 and n38 are each 1 and z is absent or NMe.

[0501] In one embodiment, n36 is 1, n37 is 1, n 38 and n39 are 0 and z is absent.

[0502] In one embodiment, n36 is 1, n37 is 1, n38 and n39 are 1 and z is absent.

[0503] In one embodiment, n36 is 0, n37 is 1, n38 and n39 are 1 and z is absent.

[0504] In one embodiment, R26, at each occurrence, is independently selected from the group consisting of hydroxyl, =0, C1.4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1.4 haloalkyl and C3-6 cycloalkyl, each of which may be optionally be substituted with one or more groups selected from Ci-4 alkyl, C1.4 alkoxy, C3-6 cycloalkyl, phenyl, and hydroxyl.

[0505] In another embodiment, R26, at each occurrence, is independently selected from the group consisting of hydroxyl, =0 and C1.4 alkyl.

[0506] In one embodiment, M is of formula M1, M6 or M6i as described in any of the below mentioned embodiments. Suitably M is of formula M6 or M6i.E3 ubiquitin ligase binding moiety, M

[0507] E3 ubiquitin ligase binding moiety, M, is capable of binding to a E3 ubiquitin ligase. In one embodiment, M is an E3 ubiquitin ligase binding moiety capable of binding to von Hippel-Lindau (VHL) E3 ligase.

[0508] In another embodiment, M is a E3 ubiquitin ligase binding moiety of formula M1:whereRM1ais a C2-6 alkyl group which may be optionally substituted with halo, -OH, -O(Ci-4 alkyl), -S(Ci-4alkyl);RM1bis selected from hydrogen or C1-6alkyl which may be optionally substituted with -C(O)N(H)Me, -OH, -NH2, -NH(C1-4alkyl), -N(C1-4alkyl)2, CO2Et and COOH; andRM1cis selected from the group consisting of halo, -NO2, -CN, C2.4alkynyl, -OCF3, 5-6 membered heteroaryl, 5-6 membered heterocycloalkyl and phenyl, where said 5-6membered heteroaryl, 5-6 membered heterocycloalkyl and phenyl are optionally substituted with one or more groups selected from halo and C1.3 alkyl; andwhere the wavy line denotes the point of attachment to L.

[0509] In one embodiment, RM1ais a C3-6 alkyl group.

[0510] In one embodiment, RM1ais an isopropyl or tert-butyl group.

[0511] In one embodiment, RM1bis selected from hydrogen or C1-6alkyl which may be optionally substituted with -C(O)N(H)Me, CO2Et and COOH. In one embodiment, RM1bis selected from hydrogen or methyl.

[0512] In another embodiment, when RM1bis not hydrogen, the substituent is such that the resultant stereochemistry at the chiral carbon is S configuration. In one embodiment, RM1bis (S)-methyl.

[0513] In one embodiment, RM1ais a tert-butyl group and RM1bis selected from hydrogen or methyl, suitably, (S)-methyl.

[0514] In one embodiment, RM1cis a 5-6 membered heteroaryl and phenyl, where said 5-6 membered heteroaryl and phenyl are optionally substituted with one or more groups selected from halo and C1.3 alkyl.

[0515] In another embodiment, RM1cis CN or a 5-6 membered heteroaryl optionally substituted with one or more groups selected from halo and C1.3 alkyl. In another embodiment, RM1cis a 5 membered heteroaryl optionally substituted with one or more groups selected from halo and C1.3 alkyl. Suitably, RM1cis a thiazole or oxazole optionally substituted with one or more groups selected from halo and C1.3 alkyl.

[0516] In another embodiment, RM1cis selected from:

[0517] In one embodiment, the E3 ubiquitin ligase binding moiety of formula M1 is:where RM1bis H or (S)-methyl, and where the wavy line denotes the point of attachment to L.

[0518] In another embodiment, M is a E3 ubiquitin ligase binding moiety of formulawhereRM2ais a C2-6 alkyl group which may be optionally substituted with halo, -OH, -O(Ci-4 alkyl), -S(Ci-4 alkyl);RM2dis selected from:oHRM2bis selected from hydrogen or C1-6alkyl which may be optionally substituted with -C(O)N(H)Me, -OH, -NH2, -NH(C1-4alkyl), -N(C1-4alkyl)2, -CO2Et and COOH; andRM2cis selected from the group consisting of halo, -NO2, -CN, C2.4alkynyl, -OCF3, 5-6 membered heteroaryl, 5-6 membered heterocycloalkyl and phenyl, where said 5-6 membered heteroaryl, 5-6 membered heterocycloalkyl and phenyl are optionally substituted with one or more groups selected from halo and C1.3 alkyl; andwhere the wavy line denotes the point of attachment to L.

[0519] In one embodiment, RM2ais a C3-6 alkyl group, suitably an isopropyl or tert-butyl group.

[0520] In one embodiment, RM2bis selected from hydrogen or Ci-e alkyl which may be optionally substituted with -C(O)N(H)Me, CO2Et and COOH. In another embodiment, RM2bis selected from hydrogen or methyl.

[0521] In another embodiment, when RM2bis not hydrogen, the substituent is such that the resultant stereochemistry at the chiral carbon is S configuration. In one embodiment, RM2bis (S)-methyl.

[0522] In one embodiment, RM2ais a tert-butyl group and RM2bis selected from hydrogen or methyl, suitably, (S)-methyl.

[0523] In one embodiment, RM2cis halo, -CN or a 5-6 membered heteroaryl optionally substituted with one or more groups selected from halo and C1.3 alkyl. In one embodiment,RM2cis -CN or a 5-6 membered heteroaryl optionally substituted with one or more groups selected from halo and C1.3 alkyl. In another embodiment, RM2cis a 5 membered heteroaryl optionally substituted with one or more groups selected from halo and C1.3 alkyl. Suitably, RM2cis a thiazole or oxazole optionally substituted with one or more groups selected from halo and C1.3 alkyl.

[0524] In another embodiment, RM2cis selected from:

[0525] In one embodiment, RM2dis selected from:

[0526] In one embodiment, the E3 ubiquitin ligase binding moiety of formula M2 is:is F or CN, RM2bis hydrogen or methyl (suitably S-methyl), and where the wavy line denotes the point of attachment to L.

[0527] In another embodiment, the E3 ubiquitin ligase binding moiety of formula M2 is:where the wavy line denotes the point of attachment to L.

[0528] In another embodiment, the E3 ubiquitin ligase binding moiety of formula M2where the wavy line denotes the point of attachment to L.

[0529] In another embodiment, M is a E3 ubiquitin ligase binding moiety of formula M3:whereRM3ais a C2-6 alkyl group which may be optionally substituted with halo, -OH, -O(Ci-4 alkyl), -S(Ci-4 alkyl);RM3dis selected from:RM3cis selected from the group consisting of halo, -NO2, -CN, C2-4alkynyl, -OCF3, 5-6 membered heteroaryl, 5-6 membered heterocycloalkyl and phenyl, where said 5-6 membered heteroaryl, 5-6 membered heterocycloalkyl and phenyl are optionally substituted with one or more groups selected from halo and C1.3 alkyl; andwhere the wavy line denotes the point of attachment to L.

[0530] In one embodiment, RM3ais a C3-6 alkyl group, suitably RM3ais an isopropyl or tert-butyl group.

[0531] In one embodiment, RM3dis selected from:

[0532] In one embodiment, RM3cis a 5-6 membered heteroaryl and phenyl, where said 5-6 membered heteroaryl and phenyl are optionally substituted with one or more groups selected from halo and C1.3 alkyl.

[0533] In one embodiment, RM3cis halo, CN or a 5-6 membered heteroaryl optionally substituted with one or more groups selected from halo and C1.3 alkyl. In one embodiment, RM3cis CN or a 5-6 membered heteroaryl optionally substituted with one or more groups selected from halo and C1.3 alkyl. In another embodiment, RM3cis a 5 membered heteroaryl optionally substituted with one or more groups selected from halo and C1.3 alkyl. Suitably, RM3cis a thiazole or oxazole optionally substituted with one or more groups selected from halo and C1.3 alkyl.

[0534] In another embodiment, RM3cis selected from:

[0535] In one embodiment, the E3 ubiquitin ligase binding moiety of formula M3 is:where the wavy line denotes the point of attachment to L.

[0536] In another embodiment, M is a E3 ubiquitin ligase binding moiety of formulawhereRM6ais a C2-6 alkyl group which may be optionally substituted with halo, -OH, -O(Ci-4 alkyl), -S(Ci-4 alkyl);RM6bis selected from hydrogen or C1.6 alkyl which may be optionally substituted with -C(O)N(H)Me, -OH, -NH2, -NH(C1-4alkyl), -N(C1-4alkyl)2, -CO2Et and -COOH; andRM6cis selected from the group consisting of halo, -NO2, -CN, C2-4alkynyl, -OCF3, 5-6 membered heteroaryl, 5-6 membered heterocycloalkyl and phenyl, where said 5-6membered heteroaryl, 5-6 membered heterocycloalkyl and phenyl are optionally substituted with one or more groups selected from halo and C1.3 alkyl;RM6dis a 5 or 6 membered heteroaryl group optionally substituted with one or more groups selected from halo, -O(Ci-3 alkyl) and C1.3 alkyl; andwhere the wavy line denotes the point of attachment to L.

[0537] In another embodiment, M is a E3 ubiquitin ligase binding moiety of formula M6i:(M6i),where RM6a, RM6cand RM6dare as defined above.

[0538] In one embodiment, RM6ais an isopropyl or tert-butyl group, each of which is optionally substituted with halo, -OH, -O(Ci-4 alkyl), -S(Ci-4 alkyl).

[0539] In one embodiment, RM6bis selected from hydrogen or methyl.

[0540] In another embodiment, when RM6bis not hydrogen, the substituent is such that the resultant stereochemistry at the chiral carbon is S configuration. In one embodiment, RM6bis (S)-methyl.

[0541] In one embodiment, RM6ais a tert-butyl or iso-propyl group and RM6bis selected from hydrogen or methyl, suitably, (S)-methyl.

[0542] In one embodiment, RM6cis a 5-6 membered heteroaryl and phenyl, where said 5-6 membered heteroaryl and phenyl are optionally substituted with one or more groups selected from halo and C1.3 alkyl.

[0543] In another embodiment, RM6cis halo, CN or a 5-6 membered heteroaryl optionally substituted with one or more groups selected from halo and C1.3 alkyl. In another embodiment, RM6cis CN or a 5-6 membered heteroaryl optionally substituted with one or more groups selected from halo and C1.3 alkyl. In another embodiment, RM6cis a 5 membered heteroaryl optionally substituted with one or more groups selected from halo and C1.3 alkyl. Suitably, RM6cis a thiazole or oxazole optionally substituted with one or more groups selected from halo and C1.3 alkyl.

[0544] In another embodiment, RM6cis selected from:

[0545] In one embodiment, RM6dis a 5-membered heteroaryl group, suitably selected from triazole, oxazole, isoxazole, pyrazole, imidazole, thiazole and isothiazole, each of which is optionally substituted with one or more groups selected from halo, -O(Ci-3 alkyl) and C1.3 alkyl. In another embodiment, RM6dis a triazole (suitably a 1,2,3-triazole) or an isoxazole group, each of which is optionally substituted with one or more groups selected from halo, -O(C1-3alkyl) and C1-3alkyl.

[0546] In another embodiment, RM6dis selected from:where the wavy line denotes the point of attachment to L.

[0547] In one embodiment, the E3 ubiquitin ligase binding moiety of formula M6 is:where RM6bis H or (S)-methyl, and where the wavy line denotes the point of attachment to L.

[0548] In another embodiment, M is a E3 ubiquitin ligase binding moiety of formulawhereRM7ais a C2-6 alkyl group which may be optionally substituted with halo, -OH, -O(Ci-4 alkyl), -S(Ci-4 alkyl);RM7cis selected from the group consisting of hydrogen, halo, -NO2, -CN, -OCF3, C1-6alkyl, O-C1-6alkyl, C2-4alkynyl and 5-6 membered heteroaryl optionally substituted with one or more groups selected from halo and C1.3 alkyl;RM7dis a 5 or 6 membered heteroaryl group optionally substituted with one or more groups selected from halo, -O(Ci-3 alkyl) and C1.3 alkyl; andRing F7 is a fused 5-7 membered heterocycloalkyl ring or a fused C5-7 cycloalkyl ring;where the wavy line denotes the point of attachment to L.

[0549] In one embodiment of formula M7, ring F7 is a fused 7 membered heterocycloalkyl ring comprising an O or N heteroatom; or a fused C5-7 cycloalkyl ring.

[0550] In one embodiment of formula M7, ring F7 is a fused C5-7 cycloalkyl ring, suitably a fused C7 cycloalkyl ring.

[0551] In another embodiment, M is a E3 ubiquitin ligase binding moiety of formula M7i:whereRM7ais a C2-6 alkyl group which may be optionally substituted with halo, -OH, -O(Ci-4 alkyl), -S(Ci-4alkyl);RM7cis selected from the group consisting of hydrogen, halo, -NO2, -CN, -OCF3, C1-6alkyl, O-C1-6alkyl, C2-4alkynyl and 5-6 membered heteroaryl optionally substituted with one or more groups selected from halo and C1.3 alkyl;RM7dis a 5 or 6 membered heteroaryl group optionally substituted with one or more groups selected from halo, -O(Ci-3 alkyl) and C1.3 alkyl; andn7 is an integer of value 1, 2 or 3;where the wavy line denotes the point of attachment to L.

[0552] In one embodiment of formula M7i, n7 is an integer of value 2 or 3.

[0553] In another embodiment, M is a E3 ubiquitin ligase binding moiety of formula M7ii:(M7ii);whereRM7ais a C2-6 alkyl group which may be optionally substituted with halo, -OH, -O(Ci-4 alkyl), -S(Ci-4 alkyl);RM7cis selected from the group consisting of hydrogen, halo, -NO2, -CN, -OCF3, C1-6alkyl, O-C1-6alkyl, C2-4alkynyl and 5-6 membered heteroaryl optionally substituted with one or more groups selected from halo and C1.3 alkyl;RM7dis a 5 or 6 membered heteroaryl group optionally substituted with one or more groups selected from halo, -O(Ci-3 alkyl) and C1.3 alkyl; andn8 is an integer of value 0 or 1;X70and X71are independently selected from O, CH2, NH and N(CI-4 alkyl) provided that at least one of X70and X71is CH2;where the wavy line denotes the point of attachment to L.

[0554] In one embodiment of formula M7ii, X70is CH2 and X71is selected from O, NH and N(C1-4alkyl). In another embodiment of formula M7ii, X71is CH2and X70is selected from O, NH and N(C1-4alkyl). In another embodiment of formula M7ii, X70and X71are each CH2.

[0555] In one embodiment of formula M7, M7i and M7ii, RM7ais an isopropyl or tertbutyl group, each of which is optionally substituted with halo, -OH, -O(Ci-4 alkyl), -S(Ci-4 alkyl).

[0556] In one embodiment of formula M7, M7i and M7ii, RM7dis a 5-membered heteroaryl group, suitably selected from triazole, oxazole, isoxazole, pyrazole, imidazole, thiazole and isothiazole, each of which is optionally substituted with one or more groups selected from halo, -O(C1-3alkyl) and C1-3alkyl. In another embodiment, RM7dis a triazole (suitably a 1,2,3-triazole) or an isoxazole group, each of which is optionally substituted with one or more groups selected from halo, -O(C1-3alkyl) and C1-3alkyl.

[0557] In another embodiment of formula M7, M7i and M7ii, RM7dis selected from:where the wavy line denotes the point of attachment to L.

[0558] In some embodiments of formula M7, M7i and M7ii, RM7cis selected from the group consisting of hydrogen, halo, -NO2, -CN, methyl, OMe and -OCF3; suitably RM7cis hydrogen, halogen or CN.

[0559] In some embodiments, the E3 ubiquitin ligase binding moiety of formula M7 is:

[0560] In another embodiment, M is a E3 ubiquitin ligase binding moiety of formula M8:whereRM8ais a C2-6 alkyl group which may be optionally substituted with halo, -OH, -O(Ci-4 alkyl), -S(Ci-4 alkyl);RM8bis selected from hydrogen or C1.6 alkyl which may be optionally substituted with -C(O)N(H)Me, -OH, -NH2, -NH(C1-4alkyl), -N(C1-4alkyl)2, -CO2Et and -COOH; andRM8dis a 5 or 6 membered heteroaryl group optionally substituted with one or more groups selected from halo, -O(Ci-3 alkyl) and C1.3 alkyl;RM8eis a 5 or 6 membered heteroaryl, 5 or 6 membered heterocycloalkyl or phenyl group;RM8fis selected from the group consisting of hydrogen, oxo, hydroxyl, Ci-e alkyl, O-C1.6 alkyl, halo, -NO2, -CN, -OCF3, C2-4alkynyl and 5-6 membered heteroaryl optionally substituted with one or more groups selected from halo and C1.3 alkyl; andf1 is an integer of value 0 to 3;where the wavy line denotes the point of attachment to L.

[0561] In another embodiment, M is a E3 ubiquitin ligase binding moiety of formula M8i:where RM8a, RM8b, RM8e, RM8fand f1 are as defined above.

[0562] In one embodiment, RM8ais an isopropyl or tert-butyl group, each of which is optionally substituted with halo, -OH, -O(Ci-4 alkyl), -S(Ci-4 alkyl).

[0563] In one embodiment, RM8bis selected from hydrogen or methyl.

[0564] In another embodiment, when RM8bis not hydrogen, the substituent is such that the resultant stereochemistry at the chiral carbon is S configuration. In one embodiment, RM8bis (S)-methyl.

[0565] In one embodiment, RM8ais a tert-butyl or iso-propyl group and RM8bis selected from hydrogen or methyl, suitably, (S)-methyl.

[0566] In one embodiment, RM8eis a pyrazolyl, imidazolyl or triazolyl group;

[0567] In one embodiment, RM8fis a hydrogen or methyl;

[0568] In one embodiment, f1 is 0, 1 or 2, suitably 0 or 1.

[0569] In one embodiment, RM8dis a 5-membered heteroaryl or heterocycloalkyl group, suitably selected from triazole, oxazole, isoxazole, pyrazole, imidazole, thiazole and isothiazole, each of which is optionally substituted with one or more groups selected from halo, -O(Ci-3alkyl) and C1.3 alkyl. In another embodiment, RM8dis a triazole (suitably a 1,2,3-triazole) or an isoxazole group, each of which is optionally substituted with one or more groups selected from halo, -O(Ci-3 alkyl) and C1.3 alkyl.

[0570] In another embodiment, RM8dis selected from:where the wavy line denotes the point of attachment to L.

[0571] In one embodiment, the E3 ubiquitin ligase binding moiety of formula M8 is:where the wavy line denotes the point of attachment to L.

[0572] In one embodiment, the compound of formula I is a compound of sub-formulaOH (IOi)where n36, n37, n38, n39, J1 and Z1, RM7d, RM7d, RM7a, RM7cand ring F7 are as defined in any of the above mentioned embodiments (in particular embodiments of L16a and M7); andQ is a protein binding moiety of formula Q1, Q2or Q3, suitably selected from any of the above-mentioned embodiments. For example, Q may be selected from the group consisting of formulae Q1i, Q1iiQ1a, Q1b, Q1d, Q1e, Q2i, Q2ii, Q2a, Q2c, Q2e, Q2f, Q3ior an embodiment thereof.

[0573] In one embodiment, the compound of formula I is a compound of sub-formula lOii:OH (lOii)where n23, n24, R12c, R13c, G3 and H3, RM7d, RM7d, RM7a, RM7cand ring F7 are as defined in any of the above mentioned embodiments (in particular embodiments of L14c and M7); andQ is a protein binding moiety of formula Q1, Q2or Q3, suitably selected from any of the above-mentioned embodiments. For example, Q may be selected from the group consisting of formulae Q1i, Q1iiQ1a, Q1b, Q1d, Q1e, Q2i, Q2ii, Q2a, Q2c, Q2e, Q2f, Q3ior an embodiment thereof.

[0574] In one embodiment, the compound of formula I is a compound of sub-formula IPi:where n36, n37, n38, n39, J1 and Z1, RM8d, RM8a, RM8b, RM8e, RM8fand f1 are as defined in any of the above mentioned embodiments (in particular embodiments of L16a and M8); andQ is a protein binding moiety of formula Q1, Q2or Q3, suitably selected from any of the above-mentioned embodiments. For example, Q may be selected from the group consisting of formulae Q1i, Q1iiQ1a, Q1b, Q1d, Q1e, Q2i, Q2ii, Q2a, Q2c, Q2e, Q2f, Q3ior an embodiment thereof.

[0575] In one embodiment, the compound of formula I is a compound of sub-formula IPii:OH (IPii)where n23, n24, R12c, R13c, G3 and H3, RM8d, RM8a, RM8b, RM8e, RM8fand f1 are as defined in any of the above mentioned embodiments (in particular embodiments of L14c and M8); andQ is a protein binding moiety of formula Q1, Q2or Q3, suitably selected from any of the above-mentioned embodiments. For example, Q may be selected from the group consisting of formulae Q1i, Q1iiQ1a, Q1b, Q1d, Q1e, Q2i, Q2ii, Q2a, Q2c, Q2e, Q2f, Q3ior an embodiment thereof.

[0576] In one embodiment, the compound of formula I is a compound of sub-formula ISi:QOH (ISi)where n20, n21, n27, G2, H2, R10, R11, RM1a, RM1band RM1care as defined in any of the above mentioned embodiments (in particular embodiments of L14b and M1); andQ is a protein binding moiety of formula Q1, Q2or Q3, suitably selected from any of the above-mentioned embodiments. For example, Q may be selected from the group consisting of formulae Q1i, Q1iiQ1a, Q1b, Q1d, Q1e, Q2i, Q2ii, Q2a, Q2c, Q2e, Q2f, Q3ior an embodiment thereof.

[0577] In one embodiment, the compound of formula I is a compound of sub-formula ISii:where n20, n21, n27, G2, R10, R11, RM1a, RM1band RM1care as defined in any of the above mentioned embodiments (in particular embodiments of L14b1 and M1); andQ is a protein binding moiety of formula Q1, Q2or Q3, suitably selected from any of the above-mentioned embodiments. For example, Q may be selected from the group consisting of formulae Q1i, Q1iiQ1a, Q1b, Q1d, Q1e, Q2i, Q2ii, Q2a, Q2c, Q2e, Q2f, Q3ior an embodiment thereof.

[0578] In one embodiment, the compound of formula I is a compound of sub-formulaOH (ISiii)where n20, n21, n27, G2, R10, R11, RM1a, RM1band RM1care as defined in any of the above mentioned embodiments (in particular embodiments of L14b2 and M1); andQ is a protein binding moiety of formula Q1, Q2or Q3, suitably selected from any of the above-mentioned embodiments. For example, Q may be selected from the group consisting of formulae Q1i, Q1iiQ1a, Q1b, Q1d, Q1e, Q2i, Q2ii, Q2a, Q2c, Q2e, Q2f, Q3ior an embodiment thereof.

[0579] In one embodiment, the compound of formula I is a compound of sub-formula I Sv:(ISv)where n36, n37, n38, n39, J1 and Z1, RM1a, RM1band RM1care as defined in any of the above mentioned embodiments (in particular embodiments of L16a and M1); andQ is a protein binding moiety of formula Q1, Q2or Q3, suitably selected from any of the above-mentioned embodiments. For example, Q may be selected from the group consisting of formulae Q1i, Q1iiQ1a, Q1b, Q1d, Q1e, Q2i, Q2ii, Q2a, Q2c, Q2e, Q2f, Q3ior an embodiment thereof.

[0580] In one embodiment, of any of the above sub-formulae of compound I, RM1ais an isopropyl or tert-butyl group and RM1bis selected from hydrogen or methyl.

[0581] In another embodiment, RM1cis a 5 membered heteroaryl optionally substituted with one or more groups selected from halo and C1.3 alkyl; and RM1ais an isopropyl or tertbutyl group and RM1bis selected from hydrogen or methyl.

[0582] Suitably, RM1cis a thiazole or oxazole optionally substituted with one or more groups selected from halo and C1.3 alkyl.

[0583] In one embodiment, the compound of formula I is a compound of sub-formulawhere n36, n37, n38, n39, J1 and Z1, RM2a, RM2b, RM2cand RM2dare as defined in any of the above mentioned embodiments (in particular embodiments of L16a and M2); andQ is a protein binding moiety of formula Q1, Q2or Q3, suitably selected from any of the above-mentioned embodiments. For example, Q may be selected from the group consisting of formulae Q1i, Q1iiQ1a, Q1b, Q1d, Q1e, Q2i, Q2ii, Q2a, Q2c, Q2e, Q2f, Q3ior an embodiment thereof.

[0584] In one embodiment, of any of the above-mentioned sub-formulae of formula I, RM2ais an isopropyl or tert-butyl group and RM2bis selected from hydrogen or methyl.

[0585] In another embodiment, RM2cis a 5 membered heteroaryl optionally substituted with one or more groups selected from halo and C1.3 alkyl; and RM2ais an isopropyl or tertbutyl group and RM1bis selected from hydrogen or methyl.

[0586] Suitably, RM2cis a thiazole or oxazole optionally substituted with one or more groups selected from halo and C1.3 alkyl.

[0587] In one embodiment, RM2dis selected from:

[0588] In one embodiment, the compound of formula I is a compound of sub-formula IVi:(IVi)where n36, n37, n38, n39, J1 and Z1, RM3a, RM3cand RM3dare as defined in any of the above mentioned embodiments (in particular embodiments of L16a and M3); andQ is a protein binding moiety of formula Q1, Q2orQ3, suitably selected from any of the above-mentioned embodiments. For example, Q may be selected from the group consisting of formulae Q1i, Q1iiQ1a, Q1b, Q1d, Q1e, Q2i, Q2ii, Q2a, Q2c, Q2e, Q2f, Q3ior an embodiment thereof.

[0589] In one embodiment of formula IVi embodiment, RM3dis selected from:M3cis selected from:

[0590] In one embodiment, the compound of formula I is a compound of sub-formula IWi:OH (IWi)where n36, n37, n38, n39, J1 and Z1, RM6a, RM6b, RM6cand RM6dare as defined in any of the above mentioned embodiments (in particular embodiments of L16a and M6); andQ is a protein binding moiety of formula Q1, Q2or Q3, suitably selected from any of the above-mentioned embodiments. For example, Q may be selected from the group consisting of formulae Q1i, Q1iiQ1a, Q1b, Q1d, Q1e, Q2i, Q2ii, Q2a, Q2c, Q2e, Q2f, Q3ior an embodiment thereof.

[0591] In one embodiment, the compound of formula I is a compound of sub-formula IWii:where n20, n21, n27, G2, H2, R10, R11, RM6a, RM6b, RM6cand RM6dare as defined in any of the above mentioned embodiments (in particular embodiments of L14b and M6); andQ is a protein binding moiety of formula Q1, Q2or Q3, suitably selected from any of the above-mentioned embodiments. For example, Q may be selected from the group consisting of formulae Q1i, Q1iiQ1a, Q1b, Q1d, Q1e, Q2i, Q2ii, Q2a, Q2c, Q2e, Q2f, Q3ior an embodiment thereof.

[0592] In one embodiment, the compound of formula I is a compound of sub-formula IWiii:where n23, n24, R12c, R13cG3 and H3, RM6a, RM6b, RM6cand RM6dare as defined in any of the above mentioned embodiments (in particular embodiments of L14c and M6); andQ is a protein binding moiety of formula Q1, Q2or Q3, suitably selected from any of the above-mentioned embodiments. For example, Q may be selected from the group consisting of formulae Q1i, Q1iiQ1a, Q1b, Q1d, Q1e, Q2i, Q2ii, Q2a, Q2c, Q2e, Q2f, Q3ior an embodiment thereof.

[0593] In one embodiment of the sub-formulae of formula I above, RM6ais an isopropyl or tert-butyl group. In another embodiment, RM6bis selected from hydrogen or methyl.

[0594] In one embodiment of the sub-formulae of formula I above, RM6cis selected from:

[0595] In another embodiment of the sub-formulae of formula I above, RM6dis selected from:where the wavy line denotes the point of attachment to L.

[0596] In one embodiment, the compound of formula I is a compound of sub-formula(lYi);where R1a, R2, R7a, R8a, n, X1, X3, X4, X6, X7, X9, X10, n23, n24, R12c, R13cG3 and H3, RM6a, RM6b, RM6cand RM6dare as defined in any of the above mentioned embodiments (in particular embodiments of Q1a, L14c and M6).

[0597] In one embodiment, the compound of formula I is a compound of sub-formulaOH (IYii);where R1a, R2, R7a, R8a, n, X1, X3, X4, X6, X7, X9, X10, n36, n37, n38, n39, J1 and Z1, RM6a, RM6b, RM6cand RM6dare as defined in any of the above mentioned embodiments (in particular embodiments of Q1a, L16a and M6).

[0598] In one embodiment, the compound of formula I is a compound of sub-formula lYiii:where R1a, R2, R7a, R8a, n, X1, X3, X4, X6, X7, X9, X10, n20, n21, n27, R10, R11, RM1a, RM1band RM1care as defined in any of the above mentioned embodiments (in particular embodiments of Q1a, L14b2 and M1).

[0599] In one embodiment, the compound of formula I is a compound of sub-formula lYiv:where R1a, R2, R7a, R8a, n, X1, X6, X7a, X9, X10, n23, n24, R12c, R13cG3 and H3, RM6a, RM6b, RM6cand RM6dare as defined in any of the above mentioned embodiments (in particular embodiments of Q1e, L14c and M6).

[0600] In one embodiment of formulae I Yi, lYii or lYiii, X7is S and X6is C. In one embodiment, Q is of sub-formula Q1aand X7is S, X6is C and X1, X3and X4are CH.

[0601] In one embodiment of formulae I Yi, lYii or lYiii, X7is CH and X6is N. In one embodiment, X7is CH, X6is N and X4is CH. In one embodiment, X7is CH, X6is N, X4is CH, X3is CH and X1is N. In one embodiment, X7is CH, X6is N, X4is CH, X1is CH and X3is N. In one embodiment, X7is CH, X6is N, X4is CH, X1is CH and X3is CH.

[0602] In one embodiment of formulae lYi, lYii, lYiii or lYiv, In one embodiment, X9is N. In another embodiment, X9is N and X10is CR3oCR³ or CH.

[0603] In one embodiment of formulae lYi, lYii, lYiii or lYiv, X9is CH. In another embodiment, X9is CH and X10is CR3oCR³ or CH.

[0604] In one embodiment of formulae I Yi, lYii, lYiii or lYiv, n36 is 1, n37 is 1, n 38 and n39 are 0 and Z1is absent. In one embodiment, n36 is 1, n37 is 1, n38 and n39 are 1 and Z1is absent. In one embodiment, n36 is 0, n37 is 1, n38 and n39 are 1 and Z1is absent. In one embodiment, n36 and n 39 are 0, n37 is an integer selected from 1, 2 or 3, n38 is 1 and Z1is absent.

[0605] In one embodiment of formulae lYi, lYii, lYiii or lYiv, n21 is 1, n20 is 1 and n27 is 0. In another embodiment, n21 is 1, n20 is 1 and n27 is 1.

[0606] In one embodiment of formulae lYi, lYii, lYiii or lYiv, n23 and n24 are 1. In another embodiment, n23 is 0 and n24 is 2.

[0607] In one embodiment, the compound of formula I is a compound of sub-formulawhere R1b, R7b, R8b, n, X25, X1, X3, X4, X6, X7, n23, n24, R12c, R13c, G3, H3, RM6a, RM6b, RM6cand RM6dare as defined in any of the above mentioned embodiments (in particular embodiments of Q2a, L14c and M6).

[0608] In one embodiment, the compound of formula I is a compound of sub-formulawhere R1b, R7b, R8b, n, X25, X1, X3, X4, X6, X7, n36, n37, n38, n39, J1 and Z1, RM6a, RM6b, RM6cand RM6dare as defined in any of the above mentioned embodiments (in particular embodiments of Q2a, L16a and M6).

[0609] In one embodiment, the compound of formula I is a compound of sub-formula IZiii:RM1bwhere R1b, R7b, R8b, n, X25, X1, X3, X4, X6, X7, n20, n21, n27, R10, R11, RM1a, RM1band RM1care as defined in any of the above mentioned embodiments (in particular embodiments of Q2a, L14b2 and M1).

[0610] In one embodiment, the compound of formula I is a compound of sub-formula

[0611] where R1b, R7b, R8b, n, X25, X1, X6, X7b, n23, n24, R12c, R13c, G3, H3, RM6a, RM6b, RM6cand RM6dare as defined in any of the above mentioned embodiments (in particular embodiments of Q2f, L14c and M6).

[0612] In one embodiment of formulae IZi, IZii or IZiii, X7is S and X6is C. In one embodiment, Q is of sub-formula Q1aand X7is S, X6is C and X1, X3and X4are CH.

[0613] In one embodiment of formulae IZi, IZii or IZiii, X7is CH and X6is N. In one embodiment, X7is CH, X6is N and X4is CH. In one embodiment, X7is CH, X6is N, X4is CH, X3is CH and X1is N. In one embodiment, X7is CH, X6is N, X4is CH, X1is CH and X3is N. In one embodiment, X7is CH, X6is N, X4is CH, X1is CH and X3is CH.

[0614] In one embodiment of formulae IZi, IZii, IZiii or IZiv, X25is selected from CH2, NH, NMe or O. Suitably, X25is O.

[0615] In one embodiment of formulae IZi, IZii, IZiii or IZiv, n36 is 1, n37 is 1, n 38 and n39 are 0 and Z1is absent. In one embodiment, n36 is 1, n37 is 1, n38 and n39 are 1 and Z1is absent. In one embodiment, n36 is 0, n37 is 1, n38 and n39 are 1 and Z1is absent. In one embodiment, n36 and n 39 are 0, n37 is an integer selected from 1, 2 or 3, n38 is 1 and Z1is absent.

[0616] In one embodiment of formulae IZi, IZii, IZiii or IZiv, n21 is 1, n20 is 1 and n27 is 0. In another embodiment, n21 is 1, n20 is 1 and n27 is 1.

[0617] In one embodiment of formulae IZi, IZii, IZiii or IZiv, n23 and n24 are 1. In another embodiment, n23 is 0 and n24 is 2.

[0618] In one aspect, the present invention relates to a compound of Table 1, or a salt, solvate or prodrug thereof.Table 1Example la: (2S,4R)-4-hydroxy-l-((S)-3- methyl-2-(4-(2-(4-(2-oxo-2-((6-(l-(2- (pyrid in-2-yl)acetyl)-2,3-di hydro-lH- pyrido[2,3-b][l,4]oxazin-7-yl)imidazo[l,2- b]pyridazin-2-yl)amino)ethyl)piperazin-l- yl)pyrimidin-5-yl)-lH-l,2,3-triazol-l- yl)butanoyl)-N-(4-(4-methylthiazol-5- yl)benzyl)pyrrolidine-2-carboxamideExample lb: (2S,4R)-4-hydroxy-l-((S)-3-.0 _ N.methyl-2-(4-(l-(2-oxo-2-((6-(l-(2-(pyridin-2- yl)acetyl)-2,3-dihyd ro-lH-pyrido[2,3- b][l,4]oxazin-7-yl)imidazo[l,2-b]pyridazin-2- 1X n / =\ / s~^ P A / / ^nyl)amino)ethyl)piperidin-4-yl)-lH-l,2,3- l 1HN^C N / ~\ )— < P~N 1 Q n ° Vx -NH 1 triazol-l-yl)butanoyl)-N-(4-(4-methylthiazol- 5-yl)benzyl)pyrrolidine-2-carboxamidel f OH\ \ / / \ V o=z-= ozExample lc: (2S,4R)-4-hydroxy-l-((S)-3- 0 °methyl-2-(4-((4-(2-oxo-2-((6-(l-(2-(pyridin- 2-yl)acetyl)-2,3-dihyd ro-lH-pyrido[2,3- Jb][l,4]oxazin-7-yl)imidazo[l,2-b]pyridazin-2- yl)a mino)ethyl)piperazin-l-yl) methyl)-lH- l,2,3-triazol-l-yl)butanoyl)-N-(4-(4- A^ 0 r°methylth iazol-5-yl)benzyl) pyrrolidine-2- 0^ zzcarboxamideX \ZZ-SExample Id: 5-(2-(2-(4-(5-(l-((S)-l-((2S,4R)- \ / =oz [—4-hydroxy-2-((4-(4-methylthiazol-5- J \ oy l)benzyl)carbamoyl) pyrrol idin-l-yl)-3- r< A z^ methyl-l-oxobutan-2-yl)-lH-l,2,3-triazol-4- f / yl)pyrimidin-2-yl)piperazin-l- yl)acetamido)imidazo[l,2-b]pyridazin-6-yl)- o l-methyl-N-(l-phenylethyl)-lH-indole-3- carboxamideExample le: (2S,4R)-4-hydroxy-l-((S)-3- methyl-2-(4-(l-(2-oxo-2-((6-(l-(2-(pyridin-2- yl)acetyl)-2,3-dihyd ro-lH-pyrido[2,3- Of '\?=Nb][l,4]oxazin-7-yl)imidazo[l,2-a]pyridin-2- / — P— / 0^<NHyl)amino)ethyl)piperidin-4-yl)-lH-l,2,3- triazol-l-yl)butanoyl)-N-(4-(4-methylthiazol- ° QI, oXl-M5-yl)benzyl)pyrrolidine-2-carboxamide N^NP\^N J OHHExample If: (2S,4R)-4-hydroxy-l-((S)-3- methyl-2-(4-(l-(2-((6-(l-(3-methylbutanoyl)- 2,3-dihydro-lH-pyrido[2,3-b][l,4]oxazin-7- yl)imidazo[l,2-a]pyrazin-2-yl)amino)-2- ' ° O^NH oxoethyl)piperidin-4-yl)-lH-l,2,3-triazol-l- V XN=N> t A yl)butanoyl)-N-(4-(4-methylthiazol-5- yl)benzyl)pyrrolidine-2-carboxamide H X" OHExample 2a: (2S,4R)-l-((S)-3,3-dimethyl-2-. O N (2-((2-(4-(2-oxo-2-((6-(l-(2-(pyridin-2- yl)acetyl)-2,3-dihydro-lH-pyrido[2,3- C 1 1 x b][l,4]oxazin-7-yl)benzo[d]thiazol-2- HNX° yl)a mino)ethyl)piperazin-l-yl) pyrimid in-5- yl)oxy)acetamido)butanoyl)-4-hydroxy-N-(4- °Xnsx Q xNx A (4-methylth iazol-5-yl) benzyljpyrrolid ine-2- O O / — \ - / \ V y oz o Z / — \-—carboxamide ( — — N N — — 0 0 AY w ' — ' N= / Exa ' Tmple 2b: (2S,4R)-l-((S)-3,3-dimethy I-2- / I z(2-((2-(4-(2-((6-(l-(5-methylhexanoyl)-2,3- dihydro-lH-pyrido[2,3-b][l,4]oxazin-7- yl)benzo[d]thiazol-2-yl)amino)-2- 0 oxoethyljpi perazin- 1-yl) pyrimidin-5- 0 yl)oxy)acetamido)butanoyl)-4-hydroxy-N-(4- ^ zz(4-methylth iazol-5-yl) benzyljpyrrolid ine-2- Y X carboxamide°oY O o Example 2c: (2S,4R)-l-((S)-2-(2-((2-(4-(2-((6- A p (l-(2-cyclohexylacetyl)-2,3-dihydro-lH- s A X\.0 pyrido[2,3-b][l,4]oxazin-7- HN-4 T yl)benzo[d]thiazol-2-yl)amino)-2- o z XX, X oxoethyljpi perazin- 1-yl) pyrimidin-5-Nr il / NA HNX, yl)oxy)acetamido)-3,3-dimethylbutanoyl)-4- ° 1 ' / N / — \N=\ / — A- hydroxy-N-(4-(4-methylthiazol-5-S~\ N— (\0o ' ' yl)benzyl)pyrrolidine-2-carboxamide UHNAExample 2d: (2S,4R)-l-((S)-3,3-dimethyl-2- (2-((2-(4-(2-((6-(l-(2-(l-methylpiperidin-4- yl)acetyl)-2,3-dihydro-lH-pyrido[2,3- b][l,4]oxazin-7-yl)benzo[d]thiazol-2- yl)amino)-2-oxoethyl)piperazin-l- yl)pyrimidin-5-yl)oxy)acetamido)butanoyl)- 4-hydroxy-N-(4-(4-methylthiazol-5- yl)benzyl)pyrrolidine-2-carboxamideExample 2e: (2S,4R)-l-((S)-2-(2-(4-(2-((7-(3- ((2,2-difluoro-3-(4- A O I fluorophenyl)propyl)carbamoyl)-2-fluoro-4- methylphenyl)-[l,2,4]triazolo[l,5-a]pyridin- 2-yl)amino)ethyl)piperazin-l-yl)acetamido)- o H 0 UN 3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4- ^o=methylth iazol-5-yl)benzyl) pyrrolidine-2- ° -A Q carboxamide oOHExample 2f: (2S,4R)-l-((S)-2-(4-((4-(2-((7-(3- >z_ — ~((2,2-difluoro-3-(4- fluorophenyl)propyl)carbamoyl)-2-fluoro-4- methylphenyl)-[l,2,4]triazolo[l,5-a]pyridin- 2-yl)amino)ethyl)piperazin-l-yl)methyl)-lH- ZXA,0 HN l,2,3-triazol-l-yl)-3-methylbutanoyl)-4- ° )=0hydroxy-N-(4-(4-methylthiazol-5- yl)benzyl)pyrrolidine-2-carboxamide OH X VExample 2g: 5-(2-(2-(4-(5-(2-(((S)-l-((2S,4R)- A J <4-hydroxy-2-((4-(4-methylthiazol-5- / Li]yl)benzyl)carbamoyl) pyrrol idi n-l-yl)-3,3- dimethyl-l-oxobutan-2-yl)amino)-2- ^ 2=ooxoethoxy)pyrimidin-2-yl)piperazin-l- ZIyl)acetamido)imidazo[l,2-b]pyridazin-6-yl)- Al-methyl-N-(l-phenylethyl)-lH-indole-3- bcarboxamideOExample 2h: 5-(2-(2-(4-(5-(2-(((S)-l-((2S,4R)- / <'X4-hydroxy-2-((4-(4-methylthiazol-5- A X o yl)benzyl)carbamoyl) pyrrol idi n-l-yl)-3,3- H o O dimethyl-l-oxobutan-2-yl)amino)-2- T Kt| 1? O= / 0-f > N 0 N $°=\ ] TZ > oHN^O oxoethoxy)pyrimidin-2-yl)piperazin-l- yl)acetamido)imidazo[l,2-b]pyridazin-6-yl)-NL X$0)o1x—, 2-methoxy-N-(3-phenylbutyl) nicotinamide ° A \ Q1OH X OI o Example 2i: N-(2- (cyclopropylmethoxy)benzyl)-5-(2-(2-(4-(5- (2-(((S)-l-((2S,4R)-4-hydroxy-2-((4-(4- methylthiazol-5- yl)benzyl)carbamoyl) pyrrol idi n-l-yl)-3,3- dimethyl-l-oxobutan-2-yl)amino)-2- oxoethoxy)pyrimidin-2-yl)piperazin-l- yl)acetamido)imidazo[l,2-b]pyridazin-6-yl)- 2-methoxynicotinamideExample 3a: (2S,4R)-4-hydroxy-l-((S)-2-(2- ((2-(4-(2-((6-(l-isobutyryl-2,3-dihydro-lH- pyrido[2,3-b][l,4]oxazin-7- yl)benzo[d]thiazol-2-yl)amino)-2- oxoethyljpi perazin- 1-yl) pyrimidin-5- yl)oxy)acetamido)-3,3-dimethylbutanoyl)-N- (4-(4-methylthiazol-5-yl)benzyl) pyrrolid ine- 2-carboxamideExample 3b: (2S,4R)-4-hydroxy-l-((S)-2-(2- N _ ' ((2-(4-(2-((6-(4-isobutyryl-3,4-d ihydro-2 H- <ZJ benzo[b][l,4]oxazin-6-yl)benzo[d]thiazol-2- yl)amino)-2-oxoethyl)piperazin-l- °H « Q. yl)pyrimidin-5-yl)oxy)acetamido)-3,3- dimethylbutanoyl)-N-(4-(4-methylthiazol-5- HZHZr"0H sHV°. N. A yl)benzyl)pyrrolidine-2-carboxamide° Y ' — (1OH Example 3c: (2S,4R)-4-hydroxy-l-((S)-2-(2- ((2-(4-(2-((6-(l-isobutyryl-2,3-dihydro-lH- < Y pyrido[2,3-b][l,4]oxazin-7-yl)imidazo[l,2- a]pyrazin-2-yl)amino)-2-oxoethyl)piperazin- °H HsQ l-yl)pyrimidin-5-yl)oxy)acetamido)-3,3- \ )=\ Y | 1 / dimethylbutanoyl)-N-(4-(4-methylthiazol-5- N= / I 1 H 9 r yl)benzyl)pyrrolidine-2-carboxamide01' A OHExample 3d: (2S,4R)-l-((S)-2-(2-((2-(4-(2-((6- (l-(cyclopropanecarbonyl)-2,3-dihydro-lH- °.pyrido[2,3-b][l,4]oxazin-7- / <1 H 1[ yl)benzo[d]thiazol-2-yl)amino)-2- ( )=\ / = / Y n 'i i / oxoethyljpi perazin- 1-yl) pyrimidin-5- yl)oxy)acetamido)-3,3-dimethylbutanoyl)-4- HXP0„ fv hydroxy-N-(4-(4-methylthiazol-5- ^o-y^NY yl)benzyl)pyrrolidine-2-carboxamide0''Y' OH Example 3e: (2S,4R)-l-((S)-3,3-dimethy 1-2- N _ '(2-((2-(4-(2-((6-(l-(3-methylbutanoyl)-2,3- \ <yXo >—sdihydro-lH-pyrido[2,3-b][l,4]oxazin-7- yl)imidazo[l,2-a]pyrazin-2-yl)amino)-2- oxoethyljpi perazin- 1-yl) pyrimidin-5- < Y\ Z-N ' i Y V i 7 0-< >— V >N0 nHN^0 yl)oxy)acetamido)butanoyl)-4-hydroxy-N-(4- N^ N= / y j H 9 y (4-methylth iazol-5-yl) benzyljpyrrolid ine-2- carboxamide01OH Example 3f: (2S,4R)-l-((S)-3,3-dimethy l-2-(2- ((2-(4-(2-((6-(l-(3-methylbutanoyl)-2,3- \ <zjr dihydro-lH-pyrido[2,3-b][l,4]oxazin-7- / / H L J) yl)benzo[d]thiazol-2-yl)amino)-2- ( / Y Y Y i / oxoethyljpi perazin- 1-yl) pyrimidin-5- yl)oxy)acetamido)butanoyl)-4-hydroxy-N-(4- HX r0YN" I „ fV (4-methylth iazol-5-yl) benzyljpyrrolid ine-2- ^o-Y^NY carboxamide °' OHExample 3g: (2S,4R)-l-((S)-3,3-dimethy I-2- (2-(7-(2-((6-(l-(3-methylbutanoyl)-2,3- <zsX—dihydro-lH-pyrido[2,3-b][l,4]oxazin-7- Q yl)benzo[d]thiazol-2-yl)amino)-2-oxoethyl)- °\ / —2,7-diazaspiro[3.5]nonan-2- 7 —HN^o yl)acetamido)butanoyl)-4-hydroxy-N-((S)-l- H ft r (4-(4-methylthiazol-5-0 / A yfA / ^N V NA.#~\ / ~~N o Ap M i? yl)phenyl)ethyl)pyrrolidine-2-carboxamide S N - - OH HExample 4a: (2S,4R)-l-((S)-2-(4-(2-(4-(2-((6- H N=\ (3-(((R)-3-(4-chlorophenyl)-3- A hyd roxy propyl Jcarbamoy IJ-4- methylphenyl)imidazo[l,2-b]pyridazin-2- yl)amino)-2-oxoethyl)piperazin-l- yl)pyrimidin-5-yl)-lH-l,2,3-triazol-l-yl)-3- methylbutanoyl)-4-hydroxy-N-(4-(4- methylth iazol-5-yl)benzyl) pyrrolidine-2- HO carboxamideExample 4b: (2S,4R)-l-((S)-2-(4-(l-(2-((6-(3- H(((R)-3-(4-chlorophenyl)-3- / =\ PH N-NA \ _ hyd roxy propyl Jcarbamoy I J-4-0 / AOHmethylphenyl)imidazo[l,2-b]pyridazin-2-N=N yl)a mino)-2-oxoethyl)piperidin-4-yl)-lH- l,2,3-triazol-l-yl)-3-methylbutanoyl)-4- hydroxy-N-(4-(4-methylthiazol-5- yl)benzyl)pyrrolidine-2-carboxamideExample 4c: (2S,4R)-l-((S)-2-(4-((4-(2-((6-(3- (((R)-3-(4-chlorophenyl)-3- hydroxypropyl)carbamoyl)-4-CIJJHAJ0<NA Y A methylphenyl)imidazo[l,2-b]pyridazin-2- yl)amino)-2-oxoethyl)piperazin-l-yl)methyl)- rrN 0HN0lH-l,2,3-triazol-l-yl)-3-methylbutanoyl)-4- hydroxy-N-(4-(4-methylthiazol-5- O yl)benzyl)pyrrolidine-2-carboxamideNExample 4d: (2S,4R)-l-((S)-2-(2-((2-(4-(2-((6- (3-(((R)-3-(4-chlorophenyl)-3- < / NJT hyd roxy propyl Jcarbamoy IJ-4- H Q methylphenyl)imidazo[l,2-b]pyridazin-2- - ff \ - (!0yl)amino)-2-oxoethyl)piperazin-l- \=J \= / n j H ft r yl)pyrimidin-5-yl)oxy)acetamido)-3,3-N^oArN NA ° X dimethylbutanoyl)-4-hydroxy-N-(4-(4- \= / YHOHmethylth iazol-5-yl)benzyl) pyrrolidine-2-carboxamideExample 5a: 5-(2-(2-(4-(l-((S)-l-((2S,4R)-4- Hhydroxy-2-((4-(4-methylthiazol-5-. — & |[ if N X \ y l)benzyl)carbamoyl) pyrrol idin-l-yl)-3- V hr0k / kzA / ,sOH methyl-l-oxobutan-2-yl)-lH-l,2,3-triazol-4- o / =<N"N>-NU yl)piperidin-l-yl)acetamido)imidazo[l,2- _ / \0 / b] pyridazin-6-yl)-N-((S)-2-hydroxy-3- phenylpropyl)-N-methylnicotinamide / = / DH YOExample 5b: N-(3-cyclopropy lbutyl)-5-(2-(2- (4-(5-(2-(((S)-l-((2S,4R)-4-hydroxy-2-((4-(4- / <'X methylthiazol-5- ^ / / ° H O yl)benzyl)carbamoyl) pyrrol idi n-l-yl)-3,3- \ N-Nf 7 n y I / dimethyl-l-oxobutan-2-yl)amino)-2- o—(' y — HNOoxoethoxy)pyrimidin-2-yl)piperazin-l- IXvYY yl)acetamido)imidazo[l,2-b]pyridazin-6-yl)- ° A 2-methoxynicotinamide o1OH Example 6a: 5-(2-(2-(4-(5-(2-(((S)-l-((2S,4R)- 4-hydroxy-2-((4-(4-methylthiazol-5- oyl)benzyl)carbamoyl) pyrrol idi n-l-yl)-3,3- X < o>- H QHN— / \ ie h l l o o u a -__ Ndim t y - - x b t n 2-yl)amino)-2- \, — / If |f N | / oxoethoxy)pyrimidin-2-yl)piperazin-l- — ( / \ 0 _ N. „HN.< o o=yl)acetamido)benzo[d]thiazol-6-yl)-N- ^O^f^N^K isopropyl-2-methylnicotinamide1OH Example 6b: 5-(2-(2-(4-(5-(2-(((S)-l-((2S,4R)- O4-hydroxy-2-((4-(4-methylthiazol-5- yl)benzyl)carbamoyl) pyrrol idi n-l-yl)-3,3- —( H r Q dimethyl-l-oxobutan-2-yl)amino)-2- / \ / ii N | J oxoethoxy)pyrimidin-2-yl)piperazin-l- - ( / \ / VN 0 I. _ N _ N. HN _ yl)acetamido)benzo[d]thiazol-6-yl)-N- X*isopropyl-N,2-dimethyl nicotinamide I0\ / = \ -'" Y1OH Example 6c: 5-(2-(2-(4-(5-(2-(((S)-l-((2S,4R)- 4-hydroxy-2-((4-(4-methylthiazol-5- < / NX yl)benzyl)carbamoyl) pyrrol idi n-l-yl)-3,3- HsQ dimethyl-l-oxobutan-2-yl)amino)-2- / \ / Ji N | J oxoethoxy)pyrimidin-2-yl)piperazin-l- V \ 0 L „ HNK NY f H § Y° yl)acetamido)benzo[d]thiazol-6-yl)-N- isopropyl-N-methylnicotinamide' OH Example 7a: N-((S)-3-(3-chlorophenyl)-3- hydroxypropyl)-5-(2-(2-(4-(l-((S)-l-((2S,4R)- 4-hydroxy-2-((4-(4-methylthiazol-5- y l)benzyl)carbamoyl) pyrrol idi n-l-yl)-3- methyl-l-oxobutan-2-yl)-lH-l,2,3-triazol-4- yl)piperidin-l-yl)acetamido)imidazo[l,2- b]pyridazin-6-yl)-2-methoxy nicotinamideExample 7h: N-(3-(4-fluorophenyl)-3- hydroxypropyl)-5-(2-(2-(4-(l-((S)-l-((2S,4R)- r iiNn ilNV \ II J 4-hydroxy-2-((4-(4-methylthiazol-5- L JI H I J] 0 N— \ l(. JF O N / \ yl)benzyl)carbamoyl)pyrrolidin-l-yl)-3-OHN^O methyl-l-oxobutan-2-yl)-lH-l,2,3-triazol-4- yl)piperidin-l-yl)acetamido)imidazo[l,2- b]pyridazin-6-yl)-2-methoxynicotinamideExample 7i: (2S,4R)-l-((2S)-2-(4-(l-(2-((6-(5- (2-benzylmorpholine-4-carbonyl)-6- methoxypyridin-3-yl)imidazo[l,2- b]pyridazin-2-yl)amino)-2- oxoethyl)piperidin-4-yl)-lH-l,2,3-triazol-l- yl)-3-methylbutanoyl)-4-hydroxy-N-(4-(4- methylthiazol-5-yl)benzyl)pyrrolidine-2- carboxamideExample 7j: N-(l-benzyl-lH-pyrazol-4-yl)-5- N^, 0 XXk YY(2-(2-(4-(l-((S)-l-((2S,4R)-4-hydroxy-2-((4- N II N fl \ 1 ^ / 1 (4-methylthiazol-5- H L JJ 0§ O N / \y l)benzyl)carbamoyl) pyrrol idin-l-yl)-3- S oo= —HNN^0 methyl-l-oxobutan-2-yl)-lH-l,2,3-triazol-4- Xyl)piperidin-l-yl)acetamido)imidazo[l,2-N" N'XNQ b]pyridazin-6-yl)-2-methoxy nicotinamideZA OHExample 8a: (2S,4R)-4-hydroxy-l-((S)-3- methyl-2-(4-((4-(2-oxo-2-((6-(l-(2-(pyridin- T l^N2-yl)acetyl)-2,3-dihydro-lH-pyrido[2,3- b][l,4]oxazin-7-yl)imidazo[l,2-a]pyrazin-2- yl)amino)ethyl)piperidin-l-yl)methyl)-lH- l,2,3-triazol-l-yl)butanoyl)-N-(4-(4-,N=\0N X 0 1 N \ \ / ) A Q XA '-N 0 HN methylthiazol-5-yl)benzyl)pyrrolidine-2- ' — N N L y CJ- V carboxamideH\ Z i / ^- 5^t " 0 HOExample 9a: (2S,4R)-4-hydroxy-l-((2S)-3- methyl-2-(4-((5-(2-oxo-2-((6-(l-(2-(pyridin- 2-yl)acetyl)-2,3-dihydro-lH-pyrido[2,3- b][l,4]oxazin-7-yl)imidazo[l,2-b]pyridazin- 2-yl)amino)ethyl)-2,5- N I J |1 HN^ zP AHO- M \ \ diazabicyclo[4.1.0]heptan-2-yl)methyl)-lH- l,2,3-triazol-l-yl)butanoyl)-N-(4-(4- methylthiazol-5-yl)benzyl)pyrrolidine-2-N" N'N" Z^° carboxamideExample 9b: (2S,4R)-l-((S)-2-(4-(4-fluoro-l- (2-oxo-2-((6-(l-(2-(pyridin-2-yl)acetyl)-2,3- dihydro-lH-pyrido[2,3-b][l,4]oxazin-7- r°vNrYiN-# \\ J yl)imidazo[l,2-b]pyridazin-2- r-V X— / HN^>° yl)amino)ethyl)piperidin-4-yl)-lH-l,2,3- triazol-l-yl)-3-methylbutanoyl)-4-hydroxy- O0 / =N> N=NN-(4-(4-methylthiazol-5- OH yl)benzyl)pyrrolidine-2-carboxamide HExample 9c: (2S,4R)-4-hydroxy-l-((2S)-3- methyl-2-(4-((methyl(l-(2-oxo-2-((6-(l-(2- (pyridin-2-yl)acetyl)-2,3-dihydro-lH- pyrido[2,3-b][l,4]oxazin-7-yl)imidazo[l,2- b]pyridazin-2-yl)amino)ethyl)pyrrolidin-3- yl)amino)methyl)-lH-l,2,3-triazol-l- yl)butanoyl)-N-(4-(4-methylthiazol-5- yl)benzyl)pyrrolidine-2-carboxamideExample 10a: (2S,4R)-4-hydroxy-l-((S)-3- methyl-2-(4-(((S)-3-methyl-4-(2-oxo-2-((6- Vs (l-(2-(pyridin-2-yl)acetyl)-2,3-dihydro-lH- pyrido[2,3-b][l,4]oxazin-7-yl)imidazo[l,2- o b]pyridazin-2-yl)amino)ethyl)piperazin-l- O~\ / -0\ J yl)methyl)-lH-l,2,3-triazol-l-yl)butanoyl)- \ HN^ / NA #N-(4-(4-methylthiazol-5- / — \ — \ \ / 0 yl)benzyl)pyrrolidine-2-carboxamide N=< 0 \=NN\=.n wOV / S gH ' Example 10b: (2S,4R)-4-hydroxy-l-((S)-3- A Z.methyl-2-(4-((4-(2-oxo-2-((6-(l-(2-(pyridin- < / =\ P 2-yl)acetyl)-2,3-dihydro-lH-pyrido[2,3-,N—\ ff \ HN— f b][l,4]oxazin-7-yl)imidazo[l,2-b]pyridazin- N=Z 0 \=N!r2-yl)amino)ethyl)-4,7-diazaspiro[2.5]octan- XJ xJx 9 n V'VNP ^OH7-yl)methyl)-lH-l,2,3-triazol-l-yl)butanoyl)- pN-(4-(4-methylthiazol-5- Hyl)benzyl)pyrrolidine-2-carboxamideExample 10c: (2S,4R)-4-hydroxy-l-((2S)-2- (4-((3-(methoxymethyl)-4-(2-oxo-2-((6-(l- \ / _ (2-(pyridin-2-yl)acetyl)-2,3-dihydro-lH- 1IANX'VNH / / T '' zz — ^ pyrido[2,3-b][l,4]oxazin-7-yl)imidazo[l,2- 1 0b]pyridazin-2-yl)amino)ethyl)piperazin-l- 1 II I yl)methyl)-lH-l,2,3-triazol-l-yl)-3- -0 AN methylbutanoyl)-N-(4-(4-methylthiazol-5- yl)benzyl)pyrrolidine-2-carboxamide S-n V^ / H r-sSX / V '-rH^OAN0 1 Example lOd: (2S,4R)-4-hydroxy-l-((S)-3- r^N methyl-2-(4-(((3aR,6aS)-5-(2-oxo-2-((6-(l- (2-(pyridin-2-yl)acetyl)-2,3-dihydro-lH- pyrido[2,3-b][l,4]oxazin-7-yl)imidazo[l,2- N=< 0 AN V / b]pyridazin-2- yl)amino)ethyl)hexahydropyrrolo[3,4- c]pyrrol-2(lH)-yl)methyl)-lH-l,2,3-triazol-l-H-ypp-0yl)butanoyl)-N-(4-(4-methylthiazol-5- yl)benzyl)pyrrolidine-2-carboxamide HOExample lOe: (2S,4R)-4-hydroxy-l-((S)-3- / z--nomethyl-2-(4-((methyl(l-(2-oxo-2-((6-(l-(2- \ z=N / 11 1(pyridin-2-yl)acetyl)-2,3-dihydro-lH- pyrido[2,3-b][l,4]oxazin-7-yl)imidazo[l,2-N=Z Y) HN^J.0 b]pyridazin-2-yl)amino)ethyl)piperidin-4- \\ / ) o;V. 1 N=N z\ yl)amino)methyl)-lH-l,2,3-triazol-l- MNu yl)butanoyl)-N-(4-(4-methylthiazol-5- H ' yl)benzyl)pyrrolidine-2-carboxamideExample 11a: (2S,4R)-l-((S)-2-(4-(l-(2-((6- (3-((l-benzyl-lH-l,2,3-triazol-4- 9 r. yl)carbamoyl)phenyl)imidazo[l,2-N'N 1b]pyridazin-2-yl)amino)-2- ( / P HN^.° oxoethyl)piperidin-4-yl)-lH-l,2,3-triazol-l- HN-f oyl)-3-methylbutanoyl)-4-hydroxy-N-(4-(4- \ _ / v Z^N o \ methylthiazol-5-yl)benzyl)pyrrolidine-2- — N-N 1 n 1 T ) — OH carboxamide HY fAExample lib: (2S,4R)-4-hydroxy-l-((S)-3- / \ \ o=Z- methyl-2-(4-(l-(2-((6-(3-(methyl((S)-3- 5. K '0 / ,vOH phenylbutyl)carbamoyl)phenyl)imidazo[l,2- b]pyridazin-2-yl)amino)-2- oxoethyl)piperidin-4-yl)-lH-l,2,3-triazol-l- * Z Z HNA0yl)butanoyl)-N-(4-(4-methylthiazol-5- yl)benzyl)pyrrolidine-2-carboxamide AO zZIExample 11c: (2S,4R)-4-hydroxy-l-((S)-2-(4- Y(l-(2-((6-(3-(((S)-2-hydroxy-3- phenylpropyl)(methyl)carbamoyl)phenyl)im As,idazo[l,2-b]pyridazin-2-yl)amino)-2- oxoethyl)piperidin-4-yl)-lH-l,2,3-triazol-l- A'yl)-3-methylbutanoyl)-N-(4-(4- methylthiazol-5-yl)benzyl)pyrrolidine-2- / z\ o___ carboxamidevo Example 12a: (2S,4R)-4-hydroxy-l-((S)-3- methyl-2-(4-((6-(2-oxo-2-((6-(l-(2-(pyridin- 2-yl)acetyl)-2,3-dihydro-lH-pyrido[2,3- b][l,4]oxazin-7-yl)imidazo[l,2-b]pyridazin- 2-yl)amino)ethyl)-2,6- diazaspiro[3.3]heptan-2-yl)methyl)-lH- l,2,3-triazol-l-yl)butanoyl)-N-(4-(4- methylthiazol-5-yl)benzyl)pyrrolidine-2- carboxamideExample 13a: (2S,4R)-l-((S)-2-(4-(2-(4-(2- H((6-(3-((2,2-difluoro-3-(4- T n 7 i fluorophenyl)propyl)carbamoyl)-4- \=N J j \ _ methylphenyl)imidazo[l,2-b]pyridazin-2- 0 J,sOH \\ / TA \ N-\ Z—l' yl)amino)-2-oxoethyl)piperazin-l- / \ / N=N \ yl)pyrimidin-5-yl)-lH-l,2,3-triazol-l-yl)-3- methylbutanoyl)-4-hydroxy-N-(4-(4- / =AFmethylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamideExample 13b: 5-(2-(2-(4-(l-((S)-l-((2S,4R)-4-, N=\ N-NA \ hydroxy-2-((4-(4-methylthiazol-5- — ( 0—4. >-<z >=No / ,£> H yl)benzyl)carbamoyl)pyrrolidin-l-yl)-3- methyl-l-oxobutan-2-yl)-lH-l,2,3-triazol-4- yl)piperidin-l-yl)acetamido)imidazo[l,2- HN-AQ b]pyridazin-6-yl)-N-(2-isopropoxybenzyl)-2- 1 fYNmethoxynicotinamideHExample 13c: N-((R)-3-(4-chlorophenyl)-3- r— T n 7 ihydroxypropyl)-5-(2-(2-(4-(5-(l-((S)-l- \=N jf ] \ _ ((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol- 0 r-T J.. OH T N— < Z~~~1 5-yl)benzyl)carbamoyl)pyrrolidin-l-yl)-3- z A Z / N=N y-N \HO NH FN Jmethyl-l-oxobutan-2-yl)-lH-l,2,3-triazol-4- / HNAQyl)pyrimidin-2-yl)piperazin-l- yl)acetamido)imidazo[l,2-b]pyridazin-6-yl)- C X2-methylnicotinamide ciExample 13d: (2S,4R)-l-((S)-2-(4-(2-(4-(2- H((6-(3-(((R)-3-(4-chlorophenyl)-3- T n 7 iZZ 'NJ< 0 hydroxypropyl)carbamoyl)-4- \=N JI J \ _ methylphenyl)imidazo[l,2-b]pyridazin-2- 0 r-C J.'OH \\ \ N-< Z—l- yl)amino)-2-oxoethyl)piperazin-l- W 7 N=N- VN J HQ ^NH 7=Z J yl)pyrimidin-5-yl)-lH-l,2,3-triazol-l-yl)-3- / HNAQ methylbutanoyl)-4-hydroxy-N-((S)-l-(4-(4- methylthiazol-5-yl)phenyl)ethyl)pyrrolidine- 2-carboxamide ci NXX^ Example 13e: N-(l-benzyl-lH-l,2,3-triazol- 4-yl)-5-(2-(2-(4-((l-((S)-l-((2S,4R)-4- N=X 7 'N'Nl lyn- / . \—( / \=N 0 k _ \ ^.'OH hydroxy-2-((4-(4-methylthiazol-5- z \= / y-N | yl)benzyl)carbamoyl)pyrrolidin-l-yl)-3- HN^<0X methyl-l-oxobutan-2-yl)-lH-l,2,3-triazol-4-0o / =\H,NA yl)methyl)piperazin-l- OO-7yl)acetamido)imidazo[l,2-b]pyridazin-6-yl)- 2-methoxynicotinamide 6AHExample 13f: N-(l-benzyl-lH-l,2,3-triazol- N=\ N-N I IT i 14-yl)-5-(2-(2-(4-(5-(l-((S)-l-((2S,4R)-4- 0— Z. > — ( / >=N 0 N / yj7\= / r |i \ hydroxy-2-((4-(4-methylthiazol-5- HN4 7 'OH yl)benzyl)carbamoyl)pyrrolidin-l-yl)-3- Jz A F N -< z-y H0N=N' y-N \ methyl-l-oxobutan-2-yl)-lH-l,2,3-triazol-4- rN'N 0A yl)pyrimidin-2-yl)piperazin-l- A.H / o yl)acetamido)imidazo[l,2-b]pyridazin-6-yl)- O XAY2-methoxynicotinamide sExample 13g: N-(2- (cyclopropylmethoxy)benzyl)-5-(2-(2-(4-(5- N^NH(l-((S)-l-((2S,4R)-4-hydroxy-2-((4-(4- methylthiazol-5- H, J / - / H / i )-NN=N y-NA yl)benzyl)carbamoyl)pyrrolidin-l-yl)-3- methyl-l-oxobutan-2-yl)-lH-l,2,3-triazol-4- \ ) V r~n\ / 0 HNXA 0 r~ NH \=Nyl)pyrimidin-2-yl)piperazin-l- yl)acetamido)imidazo[l,2-b]pyridazin-6- o A ’yl)nicotinamide \=Z N-XHo\ ' T 1 \ / N7 -OH / A r N— < / fNX> N=N' y-Nx J° 1>=O HNAExample 13h: N-(3-cyclopropylbutyl)-5-(2- (2-(4-(5-(l-((S)-l-((2S,4R)-4-hydroxy-2-((4- (4-methylthiazol-5- yl)benzyl)carbamoyl)pyrrolidin-l-yl)-3- <7 Amethyl-l-oxobutan-2-yl)-lH-l,2,3-triazol-4- yl)pyrimidin-2-yl)piperazin-l- yl)acetamido)imidazo[l,2-b]pyridazin-6- yl)nicotinamideOHExample 13i: N-(2-(cyclopropylmethoxy)benzyl)-5-(2-(2-(4-((1- 1 NA ((S)-l-((2S,4R)-4-hydroxy-2-((4-(4- methylthiazol-5- N^ VN 0 O^Hyl)benzyl)carbamoyl)pyrrolidin-l-yl)-3- methyl-l-oxobutan-2-yl)-lH-l,2,3-triazol-4- V 0 N— yl)methyl)piperazin-l- yl)acetamido)imidazo[l,2-b]pyridazin-6-yl)- XON2-methoxynicotinamideOHExample 13j: N-(2- (cyclopropylmethoxy)benzyl)-5-(2-(2-(4-((l- ((S)-l-((2S,4R)-4-hydroxy-2-((4-(4- methylthiazol-5- X X o Z- N N'N° HN yl)benzyl)carbamoyl)pyrrolidin-l-yl)-3- methyl-l-oxobutan-2-yl)-lH-l,2,3-triazol-4- Y r yl)methyl)piperazin-l- XXyl)acetamido)imidazo[l,2-b]pyridazin-6-NHr j X T jN N^S yl)nicotinamideH. — V Y N 'IV N-^0Example 13k: N-(2,2-difluoro-3-(4- \=N J 1 \ _t7 £> H fluorophenyl)propyl)-5-(2-(2-(4-(5-(l-((S)-l- I N-< / T' ((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol- \_ / N=N'' 05-yl)benzyl)carbamoyl)pyrrolidin-l-yl)-3- methyl-l-oxobutan-2-yl)-lH-l,2,3-triazol-4- ^NHHN / yl)pyrimidin-2-yl)piperazin-l- / —TyFyl)acetamido)imidazo[l,2-b]pyridazin-6- yjNA yl)nicotinamide FHExample 131: (2S,4R)-l-((S)-2-(4-(2-(4-(2-((6- zzNYN^N^l(3-((3-(lH-pyrazol-l-yl)propyl)carbamoyl)-0\ 4-methylphenyl)imidazo[l,2-b]pyridazin-2- \=N / ,-'0Hyl)amino)-2-oxoethyl)piperazin-l- °y-Z^C ^XXNyl)pyrimidin-5-yl)-lH-l,2,3-triazol-l-yl)-3-rNH / A0HN^ X-o methylbutanoyl)-4-hydroxy-N-(4-(4- r-N / Z^r methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamideN\Ajd Example 13m: (2S,4R)-N-((S)-3-(4-(2-((6-(3- H J °(((R)-3-(4-chlorophenyl)-3- A N-N^T n 7 i H r\„0H_ / / \=N 00Hhydroxypropyl)carbamoyl)-4- z7 —o methylphenyl)imidazo[l,2-b]pyridazin-2- NHyl)amino)-2-oxoethyl)piperazin-l-yl)-l-(4- (4-methylthiazol-5-yl)phenyl)propyl)-4-H°"'< N= / hydroxy-l-((R)-3-methyl-2-(3- methylisoxazol-5-yl)butanoyl)pyrrolidine-2- Ocarboxamide ClExample 13n: (2S,4R)-N-((S)-3-(4-(2-((6-(3- (((R)-3-(4-chlorophenyl)-3- hydroxypropyl)carbamoyl)-4- IO O I methylphenyl)imidazo[l,2-b]pyridazin-2- yl)amino)-2-oxoethyl)piperazin-l-yl)-l-(4- (4-methylthiazol-5-yl)phenyl)propyl)-4- hydroxy-l-((S)-3-methyl-2-(4-methyl-lH- l,2,3-triazol-l-yl)butanoyl)pyrrolidine-2- u carboxamide 4 1ZT HExample 14a: N-(cyclohexylmethyl)-5-(2-(2- _y / N’YN^N^l0 ^N N (4-(5-(l-((S)-l-((2S,4R)-4-hydroxy-2-((4-(4- >=N' Y',°Hmethylthiazol-5- yl)benzyl)carbamoyl)pyrrolidin-l-yl)-3- methyl-l-oxobutan-2-yl)-lH-l,2,3-triazol-4- yl)pyrimidin-2-yl)piperazin-l- \ / \= ZI o yl)acetamido)imidazo[l,2-b]pyridazin-6-yl)- AK K ° _N\ 2-methoxynicotinamideH V1 < Example 14b: (2S,4R)-4-hydroxy-l-((2S)-3- OI methyl-2-(4-(2-(4-(2-((6-(4-methyl-3-((3- >=N / ,-'0Hphenylbutyl)carbamoyl)phenyl)imidazo[l,2- b]pyridazin-2-yl)amino)-2- ^ N=N'Noxoethyl)piperazin-l-yl)pyrimidin-5-yl)-lH- V / / HN-^0l,2,3-triazol-l-yl)butanoyl)-N-(4-(4- methylthiazol-5-yl)benzyl)pyrrolidine-2- carboxamiden\HExample 14c: (2S,4R)-4-hydroxy-l-((S)-3- 0 Nmethyl-2-(4-(2-(4-(2-((6-(4-methyl-3-((4- / N< / .'0Hmethylpentyl)carbamoyl)phenyl)imidazo[l,2-b]pyridazin-2-yl)amino)-2- / -NH0I oxoethyl)piperazin-l-yl)pyrimidin-5-yl)-lH- l,2,3-triazol-l-yl)butanoyl)-N-(4-(4- 1 / SV-O>methylthiazol-5-yl)benzyl)pyrrolidine-2- carboxamideHExample 14d: 5-(2-(2-(4-(5-(l-((S)-l- N=\ N-N T IT | 1((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-0— Z > / / \=N 0 _ N. / Y |i \5-yl)benzyl)carbamoyl)pyrrolidin-l-yl)-3- methyl-l-oxobutan-2-yl)-lH-l,2,3-triazol-4- yl)pyrimidin-2-yl)piperazin-l- yl)acetamido)imidazo[l,2-b]pyridazin-6-yl)- O0N-(2-isopropoxybenzyl)-2- N methoxynicotinamide MHExample 14e: N-((R)-3-(4-chlorophenyl)-3- (TP 0hydroxypropyl)-5-(2-(2-(4-(5-(l-((S)-l- ((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol- 0, / = \( ' n 1 v' N— \ < / 5-yl)benzyl)carbamoyl)pyrrolidin-l-yl)-3- HO r— NH pN 0 I methyl-l-oxobutan-2-yl)-lH-l,2,3-triazol-4- ' —0yl)pyrimidin-2-yl)piperazin-l- yl)acetamido)imidazo[l,2-b]pyridazin-6-yl)- 2-methoxynicotinamide a 0N\Example 14f: N-(2- H (cyclopropylmethoxy)benzyl)-5-(2-(2-(4-(5- K N=\ N-N7^ / o— Z \ _ ( / \=N 0 _ N.(l-((S)-l-((2S,4R)-4-hydroxy-2-((4-(4- methylthiazol-5-, \ / 0y / N / YN^ 7-Yi \ \ 1 yl)benzyl)carbamoyl)pyrrolidi / 'Y £> H n-l-yl)-3- methyl-l-oxobutan-2-yl)-lH-l,2,3-triazol-4- A yl)pyrimidin-2-yl)piperazin-l- 1 J Y yl)acetamido)imidazo[l,2-b]pyridazin-6-yl)- 2-methoxynicotinamideExample 14g: (2S,4R)-l-((S)-2-(4-(2-(4-(2- H((6-(3-(((R)-3-(4-chlorophenyl)-3- methoxypropyl)carbamoyl)-4-Cl. >=N T J \ methylphenyl)imidazo[l,2-b]pyridazin-2- Z=\ / -OH z \ T r~i-' yl)amino)-2-oxoethyl)piperazin-l- yl)pyrimidin-5-yl)-lH-l,2,3-triazol-l-yl)-3- —Omethylbutanoyl)-4-hydroxy-N-(4-(4- methylthiazol-5-yl)benzyl)pyrrolidine-2- carboxamideExample 14h: N-(2,2-difluoro-3-(4- Hfluorophenyl)propyl)-5-(2-(2-(4-(5-(l-((S)-l- Y((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-05-yl)benzyl)carbamoyl)pyrrolidin-l-yl)-3- / vmethyl-l-oxobutan-2-yl)-lH-l,2,3-triazol-4- / YNVN— o \ ' — / -0Hyl)pyrimidin-2-yl)piperazin-l- yl)acetamido)imidazo[l,2-b]pyridazin-6-yl)- / S / F— 0* II2-methoxynicotinamide F N— \Example 15a: (2S,4R)-4-hydroxy-l-((2S)-3- PH methyl-2-(4-(l-(2-((6-(4-methyl-3-((4,4,4- 0 \ 9 trifluoro-3-hydroxy-3- phenylbutyl)carbamoyl)phenyl)imidazo[l,2-, —? ° HN 0 b]pyridazin-2-yl)amino)-2- oxoethyl)piperidin-4-yl)-lH-l,2,3-triazol-l- yl)butanoyl)-N-(4-(4-methylthiazol-5- POH Y ] 1 NH <\ Jyl)benzyl)pyrrolidine-2-carboxamide F N-\Example 15b: (2S,4R)-l-((2S)-2-(4-(l-(2-((6- \ PH(3-((3-(furan-3-yl)-3- hydroxypropyl)carbamoyl)-4-N" LNmethylphenyl)imidazo[l,2-b]pyridazin-2-, —? ° HN 0 yl)amino)-2-oxoethyl)piperidin-4-yl)-lH- l,2,3-triazol-l-yl)-3-methylbutanoyl)-4- hydroxy-N-(4-(4-methylthiazol-5- OH 0 N"\ yl)benzyl)pyrrolidine-2-carboxamideExample 15c: (2S,4R)-l-((S)-2-(4-(l-(2-((6- \ s0H(3-((2-(4-chlorophenoxy)ethyl)carbamoyl)- 4-methylphenyl)imidazo[l,2-b]pyridazin-2- °HN-^O yl)amino)-2-oxoethyl)piperidin-4-yl)-lH- l,2,3-triazol-l-yl)-3-methylbutanoyl)-4- T H H r |i o N— ' n 7 hydroxy-N-(4-(4-methylthiazol-5- T^^T i X* yl)benzyl)pyrrolidine-2-carboxamide- nh0N-\ Example 15d: (2S,4R)-4-hydroxy-l-((2S)-3- \ PH methyl-2-(4-(l-(2-((6-(4-methyl-3-((l- (pyrazin-2-yl)piperidin-3-N'XN^YN? yl)carbamoyl)phenyl)imidazo[l,2-0HN-XQ b]pyridazin-2-yl)amino)-2- oxoethyl)piperidin-4-yl)-lH-l,2,3-triazol-l- I^II H TX'il |T 1 yl)butanoyl)-N-(4-(4-methylthiazol-5-0N-\ yl)benzyl)pyrrolidine-2-carboxamideExample 15e: (2S,4R)-4-hydroxy-l-((2S)-2- \ PH (4-(l-(2-((6-(3-((2-hydroxy-3-(m- tolyl)propyl)carbamoyl)-4-N'L / Nmethylphenyl)imidazo[l,2-b]pyridazin-2-, —? ° HN 0 yl)amino)-2-oxoethyl)piperidin-4-yl)-lH- l,2,3-triazol-l-yl)-3-methylbutanoyl)-N-(4-?HH 'VTl [C l (4-methylthiazol-5-yl)benzyl)pyrrolidine-2- NH jj0N-\ carboxamideExample 15f: (2S,4R)-l-((2S)-2-(4-(l-(2-((6- \ PH(3-(2-benzylmorpholine-4- carbonyl)phenyl)imidazo[l,2-b]pyridazin-2-N'L / NrNQ yl)amino)-2-oxoethyl)piperidin-4-yl)-lH-, —? ° HN 0 l,2,3-triazol-l-yl)-3-methylbutanoyl)-4- hydroxy-N-(4-(4-methylthiazol-5- II I y— NH \\ II yl)benzyl)pyrrolidine-2-carboxamide 0 N-\Example 15g: (2S,4R)-l-((S)-2-(4-(l-(2-((6- OH (3-(((R)-3-(4-fluorophenyl)-2- hydroxypropyl)(methyl)carbamoyl)phenyl)imidazo[l,2-b]pyridazin-2-yl)amino)-2-, —? ° HN 0 oxoethyl)piperidin-4-yl)-lH-l,2,3-triazol-l- yl)-3-methylbutanoyl)-4-hydroxy-N-(4-(4-?Hi _N„, _ ° ifXr v — / methylthiazol-5-yl)benzyl)pyrrolidine-2- 1 X- NH0N-\ carboxamideExample 15h: (2S,4R)-l-((S)-2-(4-(l-(2-((6- PH (3-((l-benzyl-lH-l,2,3-triazol-4- yl)(methyl)carbamoyl)phenyl)imidazo[l,2-N'L / NrNP b]pyridazin-2-yl)amino)-2-0HN-^O oxoethyl)piperidin-4-yl)-lH-l,2,3-triazol-l- i [^ii fT i yl)-3-methylbutanoyl)-4-hydroxy-N-(4-(4- methylthiazol-5-yl)benzyl)pyrrolidine-2- / Z=—\ N'N 0Jk3“NHN-\carboxamide WOH Example 15i: (2S,4R)-1-((S)-2-(4-((4-(2-((6-(3-((1-benzyl-1H-1,2,3-triazol-4-yl)carbamoyl)phenyl)imidazo[1,2- pb]pyridazin-2-yl)amino)-2- / N'NHN oxoethyl)piperazin-l-yl)methyl)-lH-l,2,3- NN1L / Y triazol-l-yl)-3-methylbutanoyl)-4-hydroxy- N^NH W A >= / N-(4-(4-methylthiazol-5- °' i<irN4 Jk yl)benzyl)pyrrolidine-2-carboxamideExample 15j: (2S,4R)-4-hydroxy-l-((S)-2-(4- ((4-(2-((6-(3-(((S)-2-hydroxy-3-OYVLN-NV(SX phenylpropyl)(methyl)carbamoyl)phenyl)im r o' N— vidazo[l,2-b]pyridazin-2-yl)amino)-2- l *0H( / / oxoethyl)piperazin-l-yl)methyl)-lH-l,2,3- X M AN OHVO triazol-l-yl)-3-methylbutanoyl)-N-(4-(4- O >° methylthiazol-5-yl)benzyl)pyrrolidine-2- carboxamide OH Example 15k: (2S,4R)-l-((S)-2-(4-((4-(2-((6- (3-((2- (cyclopropylmethoxy)benzyl)carbamoyl)phenyl)imidazo[l,2-b]pyridazin-2-yl)amino)-2- oxoethyl)piperazin-l-yl)methyl)-lH-l,2,3- O 0HN\=o triazol-l-yl)-3-methylbutanoyl)-4-hydroxy- N-(4-(4-methylthiazol-5- yl)benzyl)pyrrolidine-2-carboxamide OH OHExample 15l: (2S,4R)-1-((S)-2-(4-((4-(2-((6-(3-((1-benzyl-1H-1,2,3-triazol-4-yl)(methyl)carbamoyl)phenyl)imidazo[1,2- Qb]pyridazin-2-yl)amino)-2- \ N'N UHN oxoethyl)piperazin-l-yl)methyl)-lH-l,2,3- £NN fVtriazol-l-yl)-3-methylbutanoyl)-4-hydroxy- N-(4-(4-methylthiazol-5-N4 A. yl)benzyl)pyrrolidine-2-carboxamideOHExample 15m: 5-(2-(2-(4-((l-((S)-l-((2S,4R)- 4-hydroxy-2-((4-(4-methylthiazol-5- yl)benzyl)carbamoyl)pyrrolidin-l-yl)-3- nM N'NHN methyl-l-oxobutan-2-yl)-lH-l,2,3-triazol-4- \ >'0H\ ) ) yl)methyl)piperazin-l- T °A,N^ < O yl)acetamido)imidazo[l,2-b]pyridazin-6-yl)- M r^VN\_ 'N-((S)-2-hydroxy-3-phenylpropyl)-N-. NM°' riirN NH4k JI JL methylnicotinamide NOHExample 15n: N-(l-benzyl-lH-l,2,3-triazol- 4-yl)-5-(2-(2-(4-((l-((S)-l-((2S,4R)-4- hydroxy-2-((4-(4-methylthiazol-5-N^N" N ° HN>0yl)benzyl)carbamoyl)pyrrolidin-l-yl)-3- methyl-l-oxobutan-2-yl)-lH-l,2,3-triazol-4- NN1 fV yl)methyl)piperazin-l- A S-Z yl)acetamido)imidazo[l,2-b]pyridazin-6- L JIyl)nicotinamide NpH Example 15o: (2S,4R)-l-((2S)-2-(4-((4-(2-((6- (5-(2-benzylmorpholine-4-carbonyl)pyridin- C N'NHN3-yl)imidazo[l,2-b]pyridazin-2-yl)amino)-2- L / 0oxoethyl)piperazin-l-yl)methyl)-lH-l,2,3- I 1triazol-l-yl)-3-methylbutanoyl)-4-hydroxy- N-(4-(4-methylthiazol-5- °' iiN4 jL yl)benzyl)pyrrolidine-2-carboxamide 0 JNH / YZNV / XN / \Example 15p: 5-(2-(2-(4-(5-(l-((S)-l- N— A N-N / IT | 1 / / Xs _ / / \ssN 0((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol- \= / \= / Y *1 \5-yl)benzyl)carbamoyl)pyrrolidin-l-yl)-3- 0= / / .'OH methyl-l-oxobutan-2-yl)-lH-l,2,3-triazol-4- yl)pyrimidin-2-yl)piperazin-l- r0H OHNAOyl)acetamido)imidazo[l,2-b]pyridazin-6-yl)- N-((S)-2-hydroxy-3-phenylpropyl)-N- bmethylnicotinamideHExample 15q: N-(l-benzyl-lH-l,2,3-triazol- N-^ N-N J If 7 1 / / \ _ ( / y=N 04-yl)-5-(2-(2-(4-(5-(l-((S)-l-((2S,4R)-4- \=YY= / Y \ hydroxy-2-((4-(4-methylthiazol-5- 0=< / ,'OH Y N-< / T yl)benzyl)carbamoyl)pyrrolidin-l-yl)-3-N~N methyl-l-oxobutan-2-yl)-lH-l,2,3-triazol-4-,-N-N'Nyl)pyrimidin-2-yl)piperazin-l- yl)acetamido)imidazo[l,2-b]pyridazin-6- Qyl)nicotinamidepH Example 15r: (2S,4R)-l-((2S)-2-(4-((4-(2-((6- (5-(2-benzylmorpholine-4-carbonyl)-6- nmethoxypyridin-3-yl)imidazo[l,2- ^N / bl'N° HN ° b]pyridazin-2-yl)amino)-2- oxoethyl)piperazin-l-yl)methyl)-lH-l,2,3- triazol-l-yl)-3-methylbutanoyl)-4-hydroxy- J 1 A— NH S— / N-(4-(4-methylthiazol-5- A J0 Nyl)benzyl)pyrrolidine-2-carboxamide 1OHExample 16a: (2S,4R)-l-((S)-2-(4-((4-(2-((6- (3-((l-benzyl-lH-l,2,3-triazol-4- yl)carbamoyl)-4-methylphenyl)imidazo[l,2- ob]pyridazin-2-yl)amino)-2- ° HNX° oxoethyl)piperazin-l-yl)methyl)-lH-l,2,3- NN1triazol-l-yl)-3-methylbutanoyl)-4-hydroxy- N^NH YY^VNH 7^N-(4-(4-methylthiazol-5-, N^YNHS-Z yl)benzyl)pyrrolidine-2-carboxamideExample 16b: (2S,4R)-4-hydroxy-l-((S)-2-(4- ((4-(2-((6-(3-(((S)-2-hydroxy-3- phenylpropyl)(methyl)carbamoyl)-4- o=( N=N- y-N 1N—H 01 methylphenyl)imidazo[l,2-b]pyridazin-2- < _HN, A> yl)amino)-2-oxoethyl)piperazin-l- >-0Hyl)methyl)-lH-l,2,3-triazol-l-yl)-3- methylbutanoyl)-N-(4-(4-methylthiazol-5- b -Yyl)benzyl)pyrrolidine-2-carboxamideOH Example 16c: (2S,4R)-l-((2S)-2-(4-((4-(2-((6- (3-((3-cyclopropylbutyl)carbamoyl)-4- methylphenyl)imidazo[l,2-b]pyridazin-2- yl)amino)-2-oxoethyl)piperazin-l- V ° HNX° yl)methyl)-lH-l,2,3-triazol-l-yl)-3- methylbutanoyl)-4-hydroxy-N-(4-(4- AkNH |^V\ °JNJA O- / methylthiazol-5-yl)benzyl)pyrrolidine-2-0TT lTNAcarboxamide JL 1]Example 16d: (2S,4R)-l-((S)-2-(4-((4-(2-((6- (3-((2- (cyclopropylmethoxy)benzyl)carbamoyl)-4- methylphenyl)imidazo[l,2-b]pyridazin-2- yl)amino)-2-oxoethyl)piperazin-l- yl)methyl)-lH-l,2,3-triazol-l-yl)-3- methylbutanoyl)-4-hydroxy-N-(4-(4- methylthiazol-5-yl)benzyl)pyrrolidine-2- carboxamidepH XA o / —Example 16e: (2S,4R)-l-((2S)-2-(4-(2-(4-(2- ((6-(3-((3-NiNrNP cyclopropylbutyl)carbamoyl)phenyl)imidazo[l,2-b]pyridazin-2-yl)amino)-2- A ° oxoethyl)piperazin-l-yl)pyrimidin-5-yl)-lH- l,2,3-triazol-l-yl)-3-methylbutanoyl)-4- A H °Ahydroxy-N-(4-(4-methylthiazol-5- 1 ^— NH yl)benzyl)pyrrolidine-2-carboxamide1oExample 16f: (2S,4R)-l-((S)-2-(4-(2-(4-(2- pH ((6-(3-((l-benzyl-lH-l,2,3-triazol-4- yl)carbamoyl)phenyl)imidazo[l,2- ) — o b]pyridazin-2-yl)amino)-2- oxoethyl)piperazin-l-yl)pyrimidin-5-yl)-lH-N / l,2,3-triazol-l-yl)-3-methylbutanoyl)-4- >=N(l 1 hydroxy-N-(4-(4-methylthiazol-5- ’''O II T H rAl 0 O yl)benzyl)pyrrolidine-2-carboxamide / =< N=NA ° l AA / NHwExample 16g: (2S,4R)-4-hydroxy-l-((S)-2-(4- pH (2-(4-(2-((6-(3-(((S)-2-hydroxy-3- phenylpropyl)(methyl)carbamoyl)phenyl)imN'YNrNQ idazo[l,2-b]pyridazin-2-yl)amino)-2- / A; °HN^O oxoethyl)piperazin-l-yl)pyrimidin-5-yl)-lH- AAN' / l,2,3-triazol-l-yl)-3-methylbutanoyl)-N-(4- [1 J )=Nfi i (4-methylthiazol-5-yl)benzyl)pyrrolidine-2- carboxamideH0i rA] qxo NHExample 16h: (2S,4R)-l-((S)-2-(4-(2-(4-(2- PH((6-(3-((2- (cyclopropylmethoxy)benzyl)carbamoyl)phenyl)imidazo[l,2-b]pyridazin-2-yl)amino)-2- rw" °° oxoethyl)piperazin-l-yl)pyrimidin-5-yl)-lH- l,2,3-triazol-l-yl)-3-methylbutanoyl)-4- Ahydroxy-N-(4-(4-methylthiazol-5- \ T H \ fl 0yl)benzyl)pyrrolidine-2-carboxamide Js. N. Jis Js, N. _ \> — / 1 NHo VW Z A I1z zExample 16i: (2S,4R)-l-((S)-2-(4-(2-(4-(2-((6- (3-((3-(lH-pyrazol-l- yl)propyl)(methyl)carbamoyl)phenyl)imidazo[l,2-b]pyridazin-2-yl)amino)-2- zo=oxoethyl)piperazin-l-yl)pyrimidin-5-yl)-lH- _ / \l,2,3-triazol-l-yl)-3-methylbutanoyl)-4- hydroxy-N-(4-(4-methylthiazol-5- yl)benzyl)pyrrolidine-2-carboxamideExample 16j: (2S,4R)-4-hydroxy-l-((S)-2-(4- (2-(4-(2-((6-(3-(((S)-2-hydroxy-3- phenylpropyl)(methyl)carbamoyl)-4- H °HT ° methylphenyl)imidazo[l,2-b]pyridazin-2- yl)amino)-2-oxoethyl)piperazin-l- yl)pyrimidin-5-yl)-lH-l,2,3-triazol-l-yl)-3- methylbutanoyl)-N-(4-(4-methylthiazol-5- CLXUXV -x v yl)benzyl)pyrrolidine-2-carboxamide r uhExample 16k: (2S,4R)-l-((S)-2-(4-(2-(4-(2- ((6-(3-((2- (cyclopropylmethoxy)benzyl)carbamoyl)-4-N" LNTNQ methylphenyl)imidazo[l,2-b]pyridazin-2- yl)amino)-2-oxoethyl)piperazin-l-0yl)pyrimidin-5-yl)-lH-l,2,3-triazol-l-yl)-3- Amethylbutanoyl)-4-hydroxy-N-(4-(4- I T H T fl omethylthiazol-5-yl)benzyl)pyrrolidine-2- 1 NHcarboxamideExample 161: (2S,4R)-l-((S)-2-(4-(2-(4-(2-((6-N"1J rNP (3-((l-benzyl-lH-l,2,3-triazol-4- / =( ° HN^O yl)carbamoyl)-4-methylphenyl)imidazo[l,2- b]pyridazin-2-yl)amino)-2- oxoethyl)piperazin-l-yl)pyrimidin-5-yl)-lH- H 'V>'jl 0l,2,3-triazol-l-yl)-3-methylbutanoyl)-4- hydroxy-N-(4-(4-methylthiazol-5- _ / ~NAT A r TV-n=n 0 NHyl)benzyl)pyrrolidine-2-carboxamideExample 16m: (2S,4R)-l-((2S)-2-(4-(2-(4-(2- ((6-(3-((3-cyclopropylbutyl)carbamoyl)-4- A -iXX ° HN^O methylphenyl)imidazo[l,2-b]pyridazin-2- yl)amino)-2-oxoethyl)piperazin-l- yl)pyrimidin-5-yl)-lH-l,2,3-triazol-l-yl)-3- VH / \ / O • — f methylbutanoyl)-4-hydroxy-N-(4-(4- methylthiazol-5-yl)benzyl)pyrrolidine-2- carboxamidePHExample 16n: (2S,4R)-l-((S)-2-(4-(2-(4-(2- ((6-(3-(((S)-3-(4-chlorophenyl)-3- hydroxypropyl)carbamoyl)-4-C'Y1 YXX methylphenyl)imidazo[l,2-b]pyridazin-2- X Hyl)amino)-2-oxoethyl)piperazin-l-0X HN- ^ON(j J yl)pyrimidin-5-yl)-lH-l,2,3-triazol-l-yl)-3- methylbutanoyl)-4-hydroxy-N-(4-(4- T H O < 1 methylthiazol-5-yl)benzyl)pyrrolidine-2- carboxamide i X- nhExample 16o: (2S,4R)-l-((S)-2-(4-(2-(4-(2- OH ((6-(3-(((l-(cyclopropylmethyl)-lH-pyrazol- 4-yl)methyl)carbamoyl)-4- methylphenyl)imidazo[l,2-b]pyridazin-2- yl)amino)-2-oxoethyl)piperazin-l- N-N NQ M jQ yl)pyrimidin-5-yl)-lH-l,2,3-triazol-l-yl)-3- Imethylbutanoyl)-4-hydroxy-N-(4-(4- ^NH \ ) I methylthiazol-5-yl)benzyl)pyrrolidine-2-N'carboxamide oPHExample 16p: (2S,4R)-l-((S)-2-(4-(2-(4-(2- ((6-(3-((2-((4- chlorophenyl)thio)ethyl)carbamoyl)-4- y r? methylphenyl)imidazo[l,2-b]pyridazin-2- yl)amino)-2-oxoethyl)piperazin-l- HN^ONf J yl)pyrimidin-5-yl)-lH-l,2,3-triazol-l-yl)-3- methylbutanoyl)-4-hydroxy-N-(4-(4- T H ovN-^X methylthiazol-5-yl)benzyl)pyrrolidine-2- 1 X- NHcarboxamideExample 16q: (2S,4R)-l-((S)-2-(4-(2-(4-(2- \ PH ((6-(3-((2-(4- chlorophenoxy)ethyl)carbamoyl)-4-anmethylphenyl)imidazo[l,2-b]pyridazin-2- / =(0°^NHyl)amino)-2-oxoethyl)piperazin-l- HN^ONf J yl)pyrimidin-5-yl)-lH-l,2,3-triazol-l-yl)-3- methylbutanoyl)-4-hydroxy-N-(4-(4- T H °, O < N I^X methylthiazol-5-yl)benzyl)pyrrolidine-2- i X- NHcarboxamideHzr-N T Tl | 1 / / \s=> 0l^N N\= / H 1 \__ Example 16r: (2S,4R)-l-((S)-2-(4-(2-(4-(2- / / 'OH / =\ V N-\ / Y' ((5-(3-(((R)-3-(4-chlorophenyl)-3- 4 / / N=N y-N' j hydroxypropyl)carbamoyl)-4- / — \01 / =° HN-A methylphenyl)pyrazolo[l,5-a]pyridin-2- HN J0yl)amino)-2-oxoethyl)piperazin-l- >yl)pyrimidin-5-yl)-lH-l,2,3-triazol-l-yl)-3- \ >-OH * N-y methylbutanoyl)-4-hydroxy-N-(4-(4- methylthiazol-5-yl)benzyl)pyrrolidine-2- ( / carboxamide a\ PHExample 17a: (2S,4R)-4-hydroxy-l-((S)-3- 1methyl-2-(4-(l-(2-((6-(l-(2-(5- methylpyridin-2-yl)acetyl)-2,3-dihydro-lH- pyrido[2,3-b][l,4]oxazin-7-yl)imidazo[l,2- b]pyridazin-2-yl)amino)-2- y0^.Kv yu oxoethyl)piperidin-4-yl)-lH-l,2,3-triazol-l- yl)butanoyl)-N-(4-(4-methylthiazol-5- yl)benzyl)pyrrolidine-2-carboxamide XT KT\ PH Example 17b: (2S,4R)-4-hydroxy-l-((S)-3- methyl-2-(4-(2-(4-(2-((6-(l-(2-(4- methylpyridin-2-yl)acetyl)-2,3-dihydro-lH- / =<0 0lHpyrido[2,3-b][l,4]oxazin-7-yl)imidazo[l,2- b]pyridazin-2-yl)amino)-2- \ / N 1 oxoethyl)piperazin-l-yl)pyrimidin-5-yl)-lH- ] 0 '^'Sl,2,3-triazol-l-yl)butanoyl)-N-(4-(4- methylthiazol-5-yl)benzyl)pyrrolidine-2- carboxamide C IT\ PHExample 17c: (2S,4R)-4-hydroxy-l-((S)-3- methyl-2-(4-(l-(2-((6-(l-(2-(6- methylpyridin-2-yl)acetyl)-2,3-dihydro-lH- pyrido[2,3-b][l,4]oxazin-7-yl)imidazo[l,2- r \ °0iHb]pyridazin-2-yl)amino)-2- | 0,. ft 1 oxoethyl)piperidin-4-yl)-lH-l,2,3-triazol-l- yl)butanoyl)-N-(4-(4-methylthiazol-5- rNY jn'n~^nh n^syl)benzyl)pyrrolidine-2-carboxamide\ PH Example 17d: (2S,4R)-l-((S)-2-(4-(l-(2-((6- ( l-(2-(4-(tert-butyl)pyridin-2-yl)acetyl)-2,3- dihydro-lH-pyrido[2,3-b][l,4]oxazin-7- yyT0CANH yl)imidazo[l,2-b]pyridazin-2-yl)amino)-2- oxoethyl)piperidin-4-yl)-lH-l,2,3-triazol-l- | C> t-W. f| 1 yl)-3-methylbutanoyl)-4-hydroxy-N-(4-(4- methylthiazol-5-yl)benzyl)pyrrolidine-2- el ln'"^NHcarboxamidePH Example 17e: (2S,4R)-4-hydroxy-l-((S)-3- methyl-2-(4-(l-(2-((6-(l-(2-(4- methylpyridin-2-yl)acetyl)-2,3-dihydro-lH- pyrido[2,3-b][l,4]oxazin-7-yl)imidazo[l,2-0° JHb]pyridazin-2-yl)amino)-2- 0 > (l 1 oxoethyl)piperidin-4-yl)-lH-l,2,3-triazol-l- yl)butanoyl)-N-(4-(4-methylthiazol-5- yl)benzyl)pyrrolidine-2-carboxamideExample 18a: (2S,4R)-4-hydroxy-l-((S)-3- methyl-2-(4-(2-(4-(2-oxo-2-((6-(l-(4- phenylbutanoyl)-2,3-dihydro-lH- Kf0N=N V pyrido[2,3-b][l,4]oxazin-7-yl)imidazo[l,2- C 0- / H V-Z / =>v.N1!''¥ J ^ / N] b]pyridazin-2-yl)amino)ethyl)piperazin-l- j? O ° yl)pyrimidin-5-yl)-lH-l,2,3-triazol-l- / =\ TA yl)butanoyl)-N-(4-(4-methylthiazol-5-HtpZr0yl)benzyl)pyrrolidine-2-carboxamide. OH Example 18b: (2S,4R)-4-hydroxy-l-((S)-2-(4- (2-(4-(2-((6-(l-isobutyryl-2,3-dihydro-lH- pyrido[2,3-b][l,4]oxazin-7-yl)imidazo[l,2- b]pyridazin-2-yl)amino)-2- oxoethyl)piperazin-l-yl)pyrimidin-5-yl)-lH- kA? l,2,3-triazol-l-yl)-3-methylbutanoyl)-N-(4- il o ^-s(4-methylthiazol-5-yl)benzyl)pyrrolidine-2- ’ t ■,I z zi ^>— NHcarboxamide XLJZ OH Example 18c: (2S,4R)-4-hydroxy-l-((S)-3- methyl-2-(4-(2-(4-(2-((6-(l-(5- methylhexanoyl)-2,3-dihydro-lH- 4Z\ O= "?’ pyrido[2,3-b][l,4]oxazin-7-yl)imidazo[l,2- b]pyridazin-2-yl)amino)-2- o i o A?>=N\ H J oxoethyl)piperazin-l-yl)pyrimidin-5-yl)-lH-1:c0. Js. ( ) N. 1l,2,3-triazol-l-yl)butanoyl)-N-(4-(4- O methylthiazol-5-yl)benzyl)pyrrolidine-2- i ^>— NHcarboxamideExample 18d: (2S,4R)-4-hydroxy-l-((S)-3- \ PH methyl-2-(4-(2-(4-(2-((6-(l-(2- morpholinoacetyl)-2,3-dihydro-lH- pyrido[2,3-b][l,4]oxazin-7-yl)imidazo[l,2- b]pyridazin-2-yl)amino)-2-. r- -H ’ Z" '^K|J >“N\ » J oxoethyl)piperazin-l-yl)pyrimidin-5-yl)-lH- 0. ) N\ 1l,2,3-triazol-l-yl)butanoyl)-N-(4-(4- r il o ^-smethylthiazol-5-yl)benzyl)pyrrolidine-2- 1 NHcarboxamideExample 19a: (2S,4R)-l-((S)-2-(4-(2-(4-(2- ((6-(l-(2-(4-fluorophenyl)acetyl)-2,3- dihydro-lH-pyrido[2,3-b][l,4]oxazin-7- yl)imidazo[l,2-b]pyridazin-2-yl)amino)-2- oxoethyl)piperazin-l-yl)pyrimidin-5-yl)-lH- l,2,3-triazol-l-yl)-3-methylbutanoyl)-4- hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamidexOH Example 19b: (2S,4R)-4-hydroxy-l-((S)-3- methyl-2-(4-(2-(4-(2-oxo-2-((6-(l-(2- AX °X o^NH (pyrimidin-2-yl)acetyl)-2,3-dihydro-lH- pyrido[2,3-b][l,4]oxazin-7-yl)imidazo[l,2- 0 AX b]pyridazin-2-yl)amino)ethyl)piperazin-l- r-Z-M A“NUUOA" °° yl)pyrimidin-5-yl)-lH-l,2,3-triazol-l- xA oxwNCs yl)butanoyl)-N-(4-(4-methylthiazol-5- QM C yl)benzyl)pyrrolidine-2-carboxamide NH _ \ mi XExample 19c: (2S,4R)-4-hydroxy-l-((S)-3- methyl-2-(4-(2-(4-(2-((6-(l-((S)-3-methyl-2- 1z z(l-oxoisoindolin-2-yl)butanoyl)-2,3-dihydro- 1z zAlH-pyrido[2,3-b][l,4]oxazin-7- yl)imidazo[l,2-b]pyridazin-2-yl)amino)-2- oxoethyl)piperazin-l-yl)pyrimidin-5-yl)-lH- l,2,3-triazol-l-yl)butanoyl)-N-(4-(4- methylthiazol-5-yl)benzyl)pyrrolidine-2- carboxamideExample 20a: (2S,4R)-4-hydroxy-l-((S)-3- K / °r _methyl-2-(4-(2-(4-(2-oxo-2-((6-(l-(2- / =° H (f j (pyridin-2-yl)acetyl)-2,3-dihydro-lH- pyrido[2,3-b][l,4]oxazin-7-yl)imidazo[l,2- b]pyridazin-2-yl)amino)ethyl)piperazin-l-NN-N N 0 4 5 ' — > yl)pyrimidin-5-yl)-lH-l,2,3-triazol-l- HN 0Hyl)butanoyl)-N-((S)-6,7,8,9-tetrahydro-5H- benzo[7]annulen-5-yl)pyrrolidine-2- carboxamideN'XExample 20b: (2S,4R)-N-(4-cyanobenzyl)-4-N / =? ° HN 0 hydroxy-l-((S)-3-methyl-2-(4-(2-(4-(2-oxo- 2-((6-(l-(2-(pyridin-2-yl)acetyl)-2,3-dihydro- lH-pyrido[2,3-b][l,4]oxazin-7- o n kyl)imidazo[l,2-b]pyridazin-2- T 4yl)amino)ethyl)piperazin-l-yl)pyrimidin-5- yl)-lH-l,2,3-triazol-l- yl)butanoyl)pyrrolidine-2-carboxamide CExample 20c: (2S,4R)-N-(4-fluorobenzyl)-4- hydroxy-l-((S)-3-methyl-2-(4-(2-(4-(2-oxo- 2-((6-(l-(2-(pyridin-2-yl)acetyl)-2,3-dihydro- lH-pyrido[2,3-b][l,4]oxazin-7- yl)imidazo[l,2-b]pyridazin-2- yl)amino)ethyl)piperazin-l-yl)pyrimidin-5- yl)-lH-l,2,3-triazol-l-yl)butanoyl)pyrrolidine-2-carboxamidePHExample 20d: (2S, 4R)-N-(2-cyano-6, 7,8,9-, NXJ I \ tetrahydro-5H-benzo[7]annulen-5-yl)-4- N 'N' )<N'Y hydroxy-l-((S)-3-methyl-2-(4-(2-(4-(2-oxo- / 0 L2-((6-(l-(2-(pyridin-2-yl)acetyl)-2,3-dihydro- OHi X, lH-pyrido[2,3-b][l,4]oxazin-7- n r-N >-n( / ===Z^N yl)imidazo[l,2-b]pyridazin-2- yl)amino)ethyl)piperazin-l-yl)pyrimidin-5- yl)-lH-l,2,3-triazol-l- yl)butanoyl)pyrrolidine-2-carboxamideExample 20e: (2S,4R)-N-(4-bromobenzyl)-4- hydroxy-l-((S)-3-methyl-2-(4-(2-(4-(2-oxo- / =\ N -N- / x0H2-((6-(l-(2-(pyridin-2-yl)acetyl)-2,3-dihydro-N0lH-pyrido[2,3-b][l,4]oxazin-7- r° / o yl)imidazo[l,2-b]pyridazin-2- yl)amino)ethyl)piperazin-l-yl)pyrimidin-5- f UJ BrAJO--\ ^yl)-lH-l,2,3-triazol-l- N-7Hyl)butanoyl)pyrrolidine-2-carboxamideExample 20f: (2S,4R)-4-hydroxy-l-((S)-3- methyl-2-(4-(2-(4-(2-oxo-2-((6-(l-(2- (pyridin-2-yl)acetyl)-2,3-dihydro-lH- O / oHN'f° pyrido[2,3-b][l,4]oxazin-7-yl)imidazo[l,2- > xxo=b]pyridazin-2-yl)amino)ethyl)piperazin-l- \=0n=N' yl)pyrimidin-5-yl)-lH-l,2,3-triazol-l- Z - L 'r' ~0H\ / =\ JI J / yl)butanoyl)-N-(4- o— <( y — <^\ o <z morpholinobenzyl)pyrrolidine-2- N-N J 1 N Jcarboxamide HbExample 21a: (2S,4R)-4-hydroxy-N-((l- methyl-lH-indazol-6-yl)methyl)-l-((S)-3- CX / 6 „ methyl-2-(4-(2-(4-(2-oxo-2-((6-(l-(2- (pyridin-2-yl)acetyl)-2,3-dihydro-lH- pyrido[2,3-b][l,4]oxazin-7-yl)imidazo[l,2- b x0 Qu o1J ° U\ b]pyridazin-2-yl)amino)ethyl)piperazin-l- o yl)pyrimidin-5-yl)-lH-l,2,3-triazol-l- I JL / z ^ \*z yl)butanoyl)pyrrolidine-2-carboxamide L ' — Example 22a: (2S,4R)-4-hydroxy-l-((2S)-3- PH b z methyl-2-(4-(2-(8-(2-oxo-2-((6-(l-(2- (pyridin-2-yl)acetyl)-2,3-dihydro-lH- pyrido[2,3-b][l,4]oxazin-7-yl)imidazo[l,2- \ ) -1N= / N'NHN b]pyridazin-2-yl)amino)ethyl)octahydro-2H- 1 Y 1 Ax,N^ ) pyrazino[l,2-a]pyrazin-2-yl)pyrimidin-5-yl)- 1 I 1 / NH\ / lH-l,2,3-triazol-l-yl)butanoyl)-N-(4-(4- methylthiazol-5-yl)benzyl)pyrrolidine-2- carboxamide 6Example 22b: (2S,4R)-4-hydroxy-l-((S)-3- methyl-2-(4-(2-(3-(4-(2-oxo-2-((6-(l-(2- (pyridin-2-yl)acetyl)-2,3-dihydro-lH- pyrido[2,3-b][l,4]oxazin-7-yl)imidazo[l,2- b]pyridazin-2-yl)amino)ethyl)piperazin-l- yl)azetidin-l-yl)pyrimidin-5-yl)-lH-l,2,3- triazol-l-yl)butanoyl)-N-(4-(4- methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamideExample 23a: (2S,4R)-4-hydroxy-l-((S)-3- / — \ / °0 NA / methyl-2-(4-(2-(4-(2-((6-(l-(3- methylbutanoyl)-2,3-dihydro-lH- ' N=N' pyrido[2,3-b][l,4]oxazin-7-yl)imidazo[l,2- / =n> C-n b]pyridazin-2-yl)amino)-2- oxoethyl)piperazin-l-yl)pyrimidin-5-yl)-lH- o 1 1 N j / II;0 I Q < l,2,3-triazol-l-yl)butanoyl)-N-(4-(4-O=^\ _ _ r _ NH methylthiazol-5-yl)benzyl)pyrrolidine-2-HN'O— XX —1TIL carboxamide _o J c \J zzr- OH Example 23b: (2S,4R)-4-hydroxy-l-((S)-3- methyl-2-(4-((4-(2-((6-(l-(3- methylbutanoyl)-2,3-dihydro-lH- Xx, \< S)1 / Z N (S) fl V ^^Z I pyrido[2,3-b][l,4]oxazin-7-yl)imidazo[l,2- ZAO) ° b]pyridazin-2-yl)amino)-2- cr z LA O A oxoethyl)piperazin-l-yl)methyl)-lH-l,2,3- A 1 o \\ \ VJ \ triazol-l-yl)butanoyl)-N-(4-(4- methylthiazol-5-yl)benzyl)pyrrolidine-2-N^S q ftcarboxamideExample 23c: (2S,4R)-4-hydroxy-l-((S)-3- methyl-2-(4-((4-(2-oxo-2-((6-(l-(2-(pyridin- h C2-yl)acetyl)-2,3-dihydro-lH-pyrido[2,3- b][l,4]oxazin-7-yl)imidazo[l,2-a]pyrazin-2- yl)amino)ethyl)piperazin-l-yl)methyl)-lH- l,2,3-triazol-l-yl)butanoyl)-N-(4-(4- methylthiazol-5-yl)benzyl)pyrrolidine-2- carboxamideOHExample 23d: (2S,4R)-4-hydroxy-l-((S)-3- A O™ methyl-2-(4-(l-(2-oxo-2-((6-(l-(2-(pyridin-2- oN?N' / NCrNh yl)acetyl)-2,3-dihydro-lH-pyrido[2,3- ^NACCJ ° O^NH b][l,4]oxazin-7-yl)imidazo[l,2-a]pyrazin-2- yl)amino)ethyl)piperidin-4-yl)-lH-l,2,3- o^ / L \ / triazol-l-yl)butanoyl)-N-(4-(4- " I / NJ methylthiazol-5-yl)benzyl)pyrrolidine-2- I ^>— NH L NA, carboxamide. OH Example 23e: (2S,4R)-4-hydroxy-l-((S)-3- methyl-2-(4-(l-(2-((6-(l-(3- methylbutanoyl)-2,3-dihydro-lH- A AXC / ° O^NH pyrido[2,3-b][l,4]oxazin-7-yl)imidazo[l,2- b]pyridazin-2-yl)amino)-2- II 1 °A,NIf 1 oxoethyl)piperidin-4-yl)-lH-l,2,3-triazol-l- yl)butanoyl)-N-(4-(4-methylthiazol-5- AZN NA yl)benzyl)pyrrolidine-2-carboxamideExample 23f: (2S,4R)-4-hydroxy-l-((S)-3- methyl-2-(4-(2-(4-(2-oxo-2-((6-(l-(3- ON(pyrrolidin-l-yl)benzoyl)-2,3-dihydro-lH- pyrido[2,3-b][l,4]oxazin-7-yl)imidazo[l,2- / x X AN\f N^O A >xZ b]pyridazin-2-yl)amino)ethyl)piperazin-l- °xAx ( ) yl)pyrimidin-5-yl)-lH-l,2,3-triazol-l- T H0yl)butanoyl)-N-(4-(4-methylthiazol-5- 1 A- NHyl)benzyl)pyrrolidine-2-carboxamideHOExample 23g: (2R,4S)-4-hydroxy-l-((R)-3- methyl-2-(4-(2-(4-(2-oxo-2-((5-(l-(2- J d(pyridin-2-yl)acetyl)-2,3-dihydro-lH-on < \= / Aj ypyrido[2,3-b][l,4]oxazin-7-yl)pyrazolo[l,5-0HNa]pyridin-2-yl)amino)ethyl)piperazin-l- yl)pyrimidin-5-yl)-lH-l,2,3-triazol-l- >\ A J Oyl)butanoyl)-N-(4-(4-methylthiazol-5-N' A A N Jyl)benzyl)pyrrolidine-2-carboxamide H lAExample 23h: (2S,4R)-4-hydroxy-l-((S)-3-. PHmethyl-2-(4-(2-(4-(2-oxo-2-((6-(l-(2- (pyridin-2-yl)acetyl)-2,3-dihydro-lH- pyrido[2,3-b][l,4]oxazin-7-yl)imidazo[l,2- a]pyrazin-2-yl)amino)ethyl)piperazin-l-. J A n ji J )=N u iyl)pyrimidin-5-yl)-lH-l,2,3-triazol-l- yl)butanoyl)-N-(4-(4-methylthiazol-5- \ ) <\ TII 1 C> N-'X yl)benzyl)pyrrolidine-2-carboxamideExample 23i: (2S,4R)-4-hydroxy-l-((S)-3-HQmethyl-2-(4-(2-(4-(2-((6-(l-(3- / \ / ( _ / N--\_o methylbutanoyl)-2,3-dihydro-lH-0 NAX\ nZ rpyrido[2,3-b][l,4]oxazin-7-yl)imidazo[l,2-0a]pyrazin-2-yl)amino)-2-oxoethyl)piperazin- l-yl)pyrimidin-5-yl)-lH-l,2,3-triazol-l- >=\ jQrNCjN^_ / N~n0|^N Nyl)butanoyl)-N-(4-(4-methylthiazol-5- ' v A N Jyl)benzyl)pyrrolidine-2-carboxamide H NAOH Example 23j: (2S,4R)-4-hydroxy-l-((S)-3- methyl-2-(4-((4-(2-((6-(l-(3- methylbutanoyl)-2,3-dihydro-lH- A rpyrido[2,3-b][l,4]oxazin-7-yl)imidazo[l,2-<s>n v^N A^. O / \ N -'NNo o Ja]pyrazin-2-yl)amino)-2-oxoethyl)piperazin- H 21 A A1\ Vz l-yl)methyl)-lH-l,2,3-triazol-l-yl)butanoyl)- N-(4-(4-methylthiazol-5- yl)benzyl)pyrrolidine-2-carboxamideExample 24a: (2S,4R)-4-hydroxy-l-((S)-3- methyl-2-(4-(2-(4-(2-((6-(l-(2-(5- methylpyridin-2-yl)acetyl)-2,3-dihydro-lH- pyrido[2,3-b][l,4]oxazin-7-yl)imidazo[l,2- / N=\ ° 4 O A ',' " O=<w Wo1(TVs. b]pyridazin-2-yl)amino)-2- / H oxoethyl)piperazin-l-yl)pyrimidin-5-yl)-lH- l,2,3-triazol-l-yl)butanoyl)-N-(4-(4- methylthiazol-5-yl)benzyl)pyrrolidine-2- carboxamideExample 24b: (2S,4R)-4-hydroxy-l-((S)-3- methyl-2-(4-(2-(4-(2-((6-(l-(2-(6- methylpyridin-2-yl)acetyl)-2,3-dihydro-lH- nrpyrido[2,3-b][l,4]oxazin-7-yl)imidazo[l,2- / N=\ ° 4 N-n oNo=X " V / MX JUX b]pyridazin-2-yl)amino)-2- oxoethyl)piperazin-l-yl)pyrimidin-5-yl)-lH- l,2,3-triazol-l-yl)butanoyl)-N-(4-(4-Sx^-Nmethylthiazol-5-yl)benzyl)pyrrolidine-2- carboxamideExample 25a: (2S,4R)-l-((S)-2-(4-(2-(4-(2- ((6-(3-((2-(cyclopropylmethoxy)-5- fluorobenzyl)carbamoyl)-4- methylphenyl)imidazo[l,2-b]pyridazin-2- CT Hyl)amino)-2-oxoethyl)piperazin-l- 1. A A' yl)pyrimidin-5 / -VT N'NA'NH(J z-rjNH V VAA A'-yl)-lH-l,2,3-triazol-l-yl)-3- methylbutanoyl)-4-hydroxy-N-(4-(4- methylthiazol-5-yl)benzyl)pyrrolidine-2- carboxamideExample 26a: (2S,4R)-4-hydroxy-N-((R)-2- N-A / ,-OH hydroxy-l-(4-(4-methylthiazol-5- / rA N y o / yl)phenyl)ethyl)-l-((S)-3-methyl-2-(4-(2-(4- v V""""x\=s0 (2-oxo-2-((6-(l-(2-(pyridin-2-yl)acetyl)-2,3- r-\ o < J dihydro-lH-pyrido[2,3-b][l,4]oxazin-7- yl)imidazo[l,2-b]pyridazin-2- N-7H ^\===\ S-^ yl)amino)ethyl)piperazin-l-yl)pyrimidin-5- yl)-lH-l,2,3-triazol-l- yl)butanoyl)pyrrolidine-2-carboxamideExample 27a: l-((l-((S)-l-((2S,4R)-4- hydroxy-2-((4-(4-methylthiazol-5- NO FL'"''? yl)benzyl)carbamoyl)pyrrolidin-l-yl)-3- methyl-l-oxobutan-2-yl)-lH-l,2,3-triazol-4- ' r v° ° ° iIZ yl)methyl)-N-(6-(l-(2-(pyridin-2-yl)acetyl)- 2,3-dihydro-lH-pyrido[2,3-b][l,4]oxazin-7- I A J r Sr 'tz s-^ yl)imidazo[l,2-a]pyrazin-2-yl)piperidine-4- carboxamide QVz- Example 28a: 7-(2-(2-(4-(5-(l-((S)-l- Z'J Z ((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol- 5-yl)benzyl)carbamoyl)pyrrolidin-l-yl)-3- methyl-l-oxobutan-2-yl)-lH-l,2,3-triazol-4- \ z yl)pyrimidin-2-yl)piperazin-l- yl)acetamido)imidazo[l,2-b]pyridazin-6-yl)- I O 1N-isopropyl-2,3-dihydro-lH-pyrido[2,3- b][l,4]oxazine-l-carboxamide - - T HO o Example 28b: N-((S)-l-(3- I fluorophenyl)ethyl)-7-(2-(2-(4-(5-(l-((S)-l- ((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol- 5-yl)benzyl)carbamoyl)pyrrolidin-l-yl)-3- \ HN— Z A— / ., Nmethyl-l-oxobutan-2-yl)-lH-l,2,3-triazol-4- 7= - L Jl,N~n 0 |^N N yl)pyrimidin-2-yl)piperazin-l- XANAA-A H yl)acetamido)imidazo[l,2-b]pyridazin-6-yl)- 2,3-dihydro-lH-pyrido[2,3-b][l,4]oxazine-l- carboxamideExample 29a: (2S,4R)-l-((S)-2-(4-(2-(4-(2- ((6-(3-((2,2-difluoro-3-(4- fluorophenyl)propyl)carbamoyl)-2-fluoro-4- methylphenyl)imidazo[l,2-b]pyridazin-2- A ° iByl)amino)-2-oxoethyl)piperazin-l- ANO sAA yl)pyrimidin-5-yl)-lH-l,2,3-triazol-l-yl)-3-p( _) <\ T methylbutanoyl)-4-hydroxy-N-(4-(4- Tl 1F\ / FH Tl 1 °> N^\ methylthiazol-5-yl)benzyl)pyrrolidine-2- carboxamide0FExample 29b: (2S,4R)-l-((S)-2-(4-(l-(2-((7- \ PH(3-((2,2-difluoro-3-(4- fluorophenyl)propyl)carbamoyl)-2-fluoro-4- oOANHmethylphenyl)-[l,2,4]triazolo[l,5-a]pyridin- 2-yl)amino)ethyl)piperidin-4-yl)-lH-l,2,3- triazol-l-yl)-3-methylbutanoyl)-4-hydroxy- L il ANH / NN-(4-(4-methylthiazol-5- yl)benzyl)pyrrolidine-2-carboxamideExample 30a: (2S,4R)-l-((S)-2-(4-(2-(4-(2- ((6-(l-(2-(5-chloropyridin-2-yl)acetyl)-2,3- dihydro-lH-pyrido[2,3-b][l,4]oxazin-7- yXyl)imidazo[l,2-b]pyridazin-2-yl)amino)-2- oxoethyl)piperazin-l-yl)pyrimidin-5-yl)-lH- N^N^- — HN-\ l,2,3-triazol-l-yl)-3-methylbutanoyl)-4- Q hydroxy-N-(4-(4-methylthiazol-5- yl)benzyl)pyrrolidine-2-carboxamideExample 31a: (2S,4R)-N-((S)-3-(4-(2-((6-(3- (((R)-3-(4-chlorophenyl)-3- hydroxypropyl)carbamoyl)-4- methylphenyl)imidazo[l,2-b]pyridazin-2- yl)amino)-2-oxoethyl)piperazin-l-yl)-l-(4- A cyanophenyl)propyl)-4-hydroxy-l-((R)-3- methyl-2-(3-methylisoxazol-5- d — fyl)butanoyl)pyrrolidine-2-carboxamideHQExample 32a: (2S,4R)-4-hydroxy-l-((S)-3- methyl-2-(4-(l'-(2-oxo-2-((6-(l-(2-(pyridin- _ / NA^C 2-yl)acetyl)-2,3-dihydro-lH-pyrido[2,3- b][l,4]oxazin-7-yl)imidazo[l,2-b]pyridazin- 2-yl)amino)ethyl)-[l,4'-bipiperidin]-4-yl)- x y F lH-l,2,3-triazol-l-yl)butanoyl)-N-(4-(4- methylthiazol-5-yl)benzyl)pyrrolidine-2- carboxamideExample 33a: (2S,4R)-4-hydroxy-l-((S)-3- methyl-2-(4-((3-(4-(2-oxo-2-((6-(l-(2- (pyridin-2-yl)acetyl)-2,3-dihydro-lH- \ / Av V pyrido[2,3-b][l,4]oxazin-7-yl)imidazo[l,2- M b]pyridazin-2-yl)amino)ethyl)piperazin-l- 0yl)azetidin-l-yl)methyl)-lH-l,2,3-triazol-l- yl)butanoyl)-N-(4-(4-methylthiazol-5- H \.'^0uyl)benzyl)pyrrolidine-2-carboxamideHO

[0619] The invention will now be further described by way of the following numbered clauses, which are not claims:1. A compound of formula I, or a salt, solvate or prodrug thereof:Q-L-M (I)whereinQ is a protein binding moiety of formula Q1, Q2or Q3:whereR1aand R1bare independently selected from the group consisting of 6 to 15 membered aryl, 5 to 12 membered heteroaryl, 3 to 12 membered heterocycloalkyl, C3-11 cycloalkyl, C1.10 alkyl, C2-10 alkenyl and C2-10alkynyl, each of which is optionally substituted with one or more groups Ra1;each Ra1is independently selected from the group consisting of hydroxyl, =0, halogen, CN, C1.6 haloalkyl, Ci-e haloalkoxy, Ci-e alkyl, O-C1.6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, -O-C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, benzyl, 5-6 membered heteroaryl, -C(=O)Rb1,-C(=O)NRd1Re1, -NRd1Re1, -NRd1C(=O)Rb1, -ORc1, -SRc1, -OC(=O)Rb1,-S(=O)2Rc1and -S(=O)2NRd1Re1, where said C1-6alkyl, O-C1-6alkyl, C3-6cycloalkyl, -O-C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, 5-11 membered heteroaryl, phenyl and benzyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =O, -CN, C1-6 haloalkyl, C1-6 haloalkoxy, C3-6 cycloalkyl, C1-6 alkyl, -O-C1-6 alkyl, phenyl, -C(O)C1-6alkyl, -C(O)N(H)C1-6alkyl, -C(O)N(C1-6alkyl)2, -CONH2, -C(O)N(H)C1-6alkyl, -C(O)N(C1-6alkyl)2, -N(H)C1-6 alkyl, and -N(C1-6 alkyl)2;where Rb1, Rc1, Rd1and Re1are independently selected from the group consisting of hydrogen, hydroxyl, Ci-e haloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-6 cycloalkyl, C1-6 alkyl, -O-C1.6 alkyl and phenyl, wherein said C1-6 alkyl, -O-C1.6 alkyl, phenyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, -CN, -N02, -NH2, -N(H)Ci-6alkyl, - N(Ci-ealkyl)2, Ci-e haloalkyl, C3-6 cycloalkyl, C6-11aryl, 3-7 membered heterocycloalkyl, Ci-e alkyl and -O-C1.6 alkyl; orRd1and Re1, when attached to the same atom, together with the atom to which they are attached form a 3-7 membered ring, optionally containing one or more heteroatoms selected from O, N and S, and wherein said ring is optionally substituted with one or more Rf1;where each Rf1is independently selected from the group consisting of hydrogen, =O, halogen, -CN, -NH2, -N(H)C1-6 alkyl, -N(C1-6 alkyl)2, C1-6 haloalkyl, C3-6 cycloalkyl, phenyl, 3-7 membered heterocycloalkyl, C1-6 alkyl and -O-C1-6 alkyl;E1is selected from -N(R2)C(=O)-, -C(=O)N(R2a)-, -N(R2)S(=O)2-, -S(=O)2N(R2a)- or -(R2)NC(=O)N(R2a)-;E2is selected from -C(=0)-, -S(=0)2- or -N(R2)C(=O)- (i.e. where the carbonyl is attached to ring C);X20is selected from O, S, S(=0), S(=0)2, NH and N(CI-4 alkyl); R2and R2aare independently selected from H, Ci-e alkyl, C3-6cycloalkyl or C3-6cycloalkyl-CH2-; orR2together with a R7aor R8agroup and the atoms to which they are attached form a 4 to 7 membered heterocycloalkyl ring which is optionally substituted with one or more groups selected from hydroxyl, halogen, =O, -CN, C1-6 haloalkyl, C1-6 haloalkoxy, cyclopropyl, C1-6 alkyl, -O-C1-6 alkyl, -C(O)C1-6alkyl, -C(O)N(H)C1-6alkyl, -C(O)N(C1-6alkyl)2, -CONH2, -C(O)N(H)C1-6alkyl, -C(O)N(C1-6alkyl)2, -N(H)C1-6alkyl, and -N(C1-6alkyl)2;R7a, R7b, R8aand R8bare each independently selected from the group consisting of hydrogen, deuterium, hydroxyl, =O, halogen, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkyl, O-C1-6 alkyl, C2-6alkenyl, C2-6alkynyl, C3-6 cycloalkyl, where said C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, are optionally substituted with one or more groups selected from hydroxyl, halogen,=O, -CN, C1-6 haloalkyl, C1-6 haloalkoxy, C3-6 cycloalkyl, C1-6 alkyl, -O-C1-6 alkyl, phenyl, -C(O)C1-6alkyl, -C(O)N(H)C1-6alkyl, -C(O)N(C1-6alkyl)2, -CONH2, -C(O)N(H)C1-6alkyl, -C(O)N(C1-6alkyl)2,-N(H)C1-6 alkyl, and -N(C1-6alkyl)2; orR7aand R8atogether with the carbon atom to which they are attached form a 3-5 membered cycloalkyl or 3-5 membered heterocycloalkyl group, each of which is optionally substituted with one or more groups selected from hydroxyl, halogen, =O, -CN, C1-6 haloalkyl, C1-6 haloalkoxy, C3-6 cycloalkyl, C1-6 alkyl, -O-C1-6 alkyl, phenyl, -C(O)C1-6 alkyl, -C(O)N(H)C1-6 alkyl, -C(O)N(C1-6alkyl)2,-CONH2, -C(O)N(H)C1-6alkyl, -C(O)N(C1-6alkyl)2, -N(H)C1-6alkyl, and -N(C1-6alkyl)2; orR7band R8btogether with the carbon atom to which they are attached form a 3-5 membered cycloalkyl or 3-5 membered heterocycloalkyl group, each of which is optionally substituted with one or more groups selected from hydroxyl, halogen, =O, -CN, C1-6 haloalkyl, C1-6 haloalkoxy, C3-6 cycloalkyl, C1-6 alkyl, -O-C1-6 alkyl, phenyl, -C(O)C1-6 alkyl, -C(O)N(H)C1-6 alkyl, -C(O)N(Ci-6alkyl)2,-CONH2, -C(O)N(H)CI-6alkyl, -C(O)N(Ci-6alkyl)2, -N(H)CI-6alkyl, and -N(Ci-6alkyl)2;n is an integer of value 0, 1, 2, 3, 4 or 5;B is a cyclic group selected from 5 to 12 membered heteroaryl or C6-11aryl;C is a heterocycle containing at least one nitrogen atom in the ring, wherein theR14>z \nR7bR8bmoiety is bonded to ring C via a nitrogen atom in ring C;A is a cyclic group selected from 5 to 15 membered heteroaryl;V is selected from the group consisting of -NH-, -C(O)N(H)-, -N(H)C(O)-, -S(O)(NH)-, -N(H)S(O)-, -S(O)N(H)-, -N(H)S(O)2- and -S(O)2N(H)-;R3and R9are independently selected from the group consisting of hydroxyl, =0, halogen, CN, Ci-e haloalkyl, Ci-e haloalkoxy, Ci-ealkyl, O-Ci-ealkyl, C2.6alkenyl, C2.6alkynyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, -C(=0)Rb3, -C(=0)0Rc3, -C(=O)NRd3Re3, -NRd3Re3, -NRd3C(=O)Rb3,-ORc3, -SRc3, where said Ci-e alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl and phenyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =0, CN, C1.6 haloalkyl, Ci-e haloalkoxy, C3-6 cycloalkyl, Ci-ealkyl, O-C1-6 alkyl, -NH2, -N(H)CI-3 alkyl, and -N(Ci-3alkyl)2;where Rb3, Rc3, Rd3and Re3are independently selected from the group consisting of hydrogen, hydroxyl, Ci-e haloalkyl, O-C1.6 haloalkyl, 3-7 membered heterocycloalkyl, 5-6membered heteroaryl, C3-6 cycloalkyl, C1-6 alkyl, -O-C1.6 alkyl and Ce-isaryl, wherein said Ci-e alkyl, -O-C1.6 alkyl, Ce-isaryl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)Ci-ealkyl, -N(Ci-ealkyl)2, Ci-e haloalkyl, C3-6 cycloalkyl, C6-11aryl, 3-7 membered heterocycloalkyl, Ci-e alkyl and -O-C1.6 alkyl; orRd3and Re3, when attached to the same atom, together with the atom to which they are attached form a 3-7 membered ring, optionally containing one or more heteroatoms selected from O, N and S, and wherein said ring is optionally substituted with one or more Rf3;where each Rf3is independently selected from the group consisting of hydrogen, =0, halogen, -CN, -NH2, -N(H)CI-6 alkyl, -N(CI-6 alkyl)2, Ci-e haloalkyl, C3-6 cycloalkyl, C6-11aryl, 3-7 membered heterocycloalkyl, Ci-e alkyl and -O-C1.6 alkyl;R4is selected from the group consisting of hydroxyl, =0, halogen, -CN, Ci-e haloalkyl, C1.6 haloalkoxy, C1-6 alkyl, -O-Ci-ealkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, C6-11aryl, 5-11 membered heteroaryl, -C(=0)Rb4, -C(=0)0Rc4, -C(=O)NRd4Re4, -NRd4Re4, -NRd4C(=O)Rb4, -NRd4C(=O)ORc4, -NRd4C(=O)NRd4Re4, -NRd4S(=O)2Rb4, -NRd4S(=O)2NRd4Re4, -ORc4, -SRc4, -0C(=0)Rb4, -OC(=O)NRd4Re4, -0C(=0)0Rc4, -S(=O)2Rc4, -S(=O)Rc4, -OS(=O)Rc4, -OS(=O)2Rc4, -OS(=O)2ORc4, -S(=O)NRd4Re4, -OS(=O)2NRd4Re4and -S(=O)2NRd4Re4, where said Ci-e alkyl, -O-Ci-6alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, 5-11 membered heteroaryl and C6-11aryl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =0, CN, Ci-e haloalkyl, Ci-e haloalkoxy, C3-6 cycloalkyl, C1-6 alkyl, -O-C1.6 alkyl, phenyl, -NH2, -NHR’, and -NR’R”, where R’ and R” are independently selected from C1-6 alkyl, and where said phenyl is optionally substituted with one or more of hydroxyl, halogen, =0, -CN, Ci-e haloalkyl, Ci-e haloalkoxy, C3-6 cycloalkyl, Ci-e alkyl and -O-C1.6 alkyl;where Rb4, Rc4, Rd4and Re4are independently selected from the group consisting of hydrogen, hydroxyl, Ci-e haloalkyl, -O-C1.6 haloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-6 cycloalkyl, C1-6 alkyl, -O-C1.6 alkyl and Ce-isaryl, wherein said Ci-e alkyl, Ce-isaryl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)Ci-ealkyl, -N(Ci-ealkyl)2, Ci-e haloalkyl, C3-6 cycloalkyl, C6-11aryl, 3-7 membered heterocycloalkyl, Ci-e alkyl and -O-C1-6 alkyl; orRd4and Re4, when attached to the same atom, together with the atom to which they are attached form a 3-7 membered ring, optionally containing one or more heteroatoms selected from O, N and S, and wherein said ring is optionally substituted with one or more Rf4;where each Rf4is independently selected from the group consisting of hydrogen, =0, halogen, -CN, -NH2, -N(H)CI-6 alkyl, -N(CI-6 alkyl)2, C1-6 haloalkyl, C3-6 cycloalkyl, C6-11aryl, 3-7 membered heterocycloalkyl, Ci-e alkyl and -O-C1.6 alkyl;y1, y2, z1 and z2 are integers independently selected from 0, 1, 2, 3 and 4.L is a linker moiety according to formulae L16a, L14c, L14b or L14e:(L16a);where ring J 1 is a 4 to 10 membered heterocycloalkyl ring which may optionally substituted by one or more R26;Z1is absent or a group selected from NH, N(C1-3 alkyl), O or S;n37 and n38 are independently selected from an integer of value 0 to 5; and n36 and n39 are independently selected from an integer of value 0 or 1; andR26at each occurrence is independently selected from the group consisting of hydroxyl, =0, C1.4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1.4 haloalkyl and C3-6 cycloalkyl, each of which may be optionally be substituted with one or more groups selected from C1.4 alkyl, C1.4 alkoxy, C3-6 cycloalkyl, phenyl and hydroxyl;(L14c);where n23 is an integer of value 0 or 1;n24 is an integer of value 0 to 3;n30 is an integer of value 0 or 1;rings G3 and H3 are independently selected from the group consisting of a 4 to 10 membered heterocycloalkyl, a 5 or 6 membered heteroaryl, phenyl and a C3-C10 cycloalkyl, each of which may be optionally substituted by one or more R81;R81at each occurrence is independently selected from the group consisting of hydroxyl, =0, C1.4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1.4 haloalkyl and C3-6 cycloalkyl, each of which may be optionally be substituted with one or more groups selected from C1.4 alkyl, C1.4 alkoxy, C3-6 cycloalkyl, phenyl and hydroxyl; andR12cand R13care independently selected from H, halo, C1.4 alkyl, C3-6 cycloalkyl; or R12cand R13c, together with the carbon atom to which they are attached form a C3-6 cycloalkyl group;where n20 is a number of value 1 to 5;where n21 and n27 are independently an integer of value 0 or 1;rings G2 and H2 are independently selected from the group consisting of a 4 to 10 membered heterocycloalkyl, a 5 or 6 membered heteroaryl and a C3-C10 cycloalkyl, each of which may be optionally substituted by one or more R80;R80at each occurrence is independently selected from the group consisting of hydroxyl, =0, C1.4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1.4 haloalkyl and C3-6 cycloalkyl, each of which may be optionally be substituted with one or more groups selected from C1.4 alkyl, C1.4 alkoxy, C3-6 cycloalkyl, phenyl and hydroxyl; andR10and R11are independently selected from H, C1.4 alkyl, C3-6 cycloalkyl; or R10and R11, together with the carbon atom to which they are attached form a C3-6 cycloalkyl group;where n50 and n51 are independently an integer of value 0 or 1;n52 and n53 are independently an integer of value 0, 1 or 2;rings G5, H5 and D5 are independently selected from the group consisting of a 4 to 10 membered heterocycloalkyl, a 5 or 6 membered heteroaryl and a C3-C10 cycloalkyl, each of which may be optionally substituted by one or more R8e;R8eat each occurrence is independently selected from the group consisting of hydroxyl, =0, C1.4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1.4 haloalkyl and C3-6 cycloalkyl, each of which may be optionally be substituted with one or more groups selected from C1.4 alkyl, C1.4 alkoxy, C3-6 cycloalkyl, phenyl and hydroxyl; andR10eand R11eare independently selected from H, C1.4 alkyl, C3-6 cycloalkyl; or R10eand R11e, together with the carbon atom to which they are attached form a C3-6 cycloalkyl group.R12eand R13eare independently selected from H, halo, C1.4 alkyl, C3-6 cycloalkyl; or R12eand R13e, together with the carbon atom to which they are attached form a C3-6 cycloalkyl group; andM is an E3 ubiquitin ligase binding moiety.2. A compound according to clause 1, or a salt, solvate or prodrug thereof, wherein Q is RIPK1 kinase binding moiety.3. A compound according to clause 1 or 2, or a salt, solvate or prodrug thereof, wherein Q is Q1.4. A compound according to clause 1 or 2, or a salt, solvate or prodrug thereof, wherein Q is Q3.5. A compound according to any one of clauses 1 to 4, or a salt, solvate or prodrug thereof, wherein R1ais selected from the group consisting of 5 to 12 membered heteroaryl, 6 to 15 membered aryl, 3 to 12 membered heterocycloalkyl, C3-11 cycloalkyl and C1.10 alkyl, each of which is optionally substituted with one or more Ra1.6. A compound according to any one of clauses 1 to 4, or a salt, solvate or prodrug thereof, wherein R1ais selected from the group consisting of 5 to 9 membered heteroaryl, phenyl, 3 to 9 membered heterocycloalkyl, C3-9 cycloalkyl and Ci-e alkyl, each of which is optionally substituted with one or more Ra1.7. A compound according to any one of clauses 1 to 4, or a salt, solvate or prodrug thereof, wherein R1ais selected from the group consisting of 6 to 15 membered aryl, 5 to 12 membered heteroaryl, 3 to 12 membered heterocycloalkyl, C3-11 cycloalkyl and C1-10 alkyl, each of which is optionally substituted with one or more Ra1.8. A compound according to any one of clauses 1 to 4, or a salt, solvate or prodrug thereof, wherein R1ais selected from the group consisting of 6 to 11 membered aryl, 5 to 9 membered heteroaryl, 3 to 9 membered heterocycloalkyl, C3-9 cycloalkyl and C1-6 alkyl, each of which is optionally substituted with one or more Ra1.9. A compound according to any one of clauses 1 to 4, or a salt, solvate or prodrug thereof, wherein R1ais selected from the group consisting of phenyl, 5 to 7 membered heteroaryl, 3 to 7 membered heterocycloalkyl, C3-7 cycloalkyl and C1-6 alkyl, each of which is optionally substituted with one or more Ra1.10. A compound according to any one of clauses 1 to 4, or a salt, solvate or prodrug thereof, wherein R1ais selected from the group consisting of 6 to 15 membered aryl, 5 to 12 membered heteroaryl and 3 to 12 membered heterocycloalkyl, each of which is optionally substituted with one or more Ra1.11. A compound according to any one of clauses 1 to 4, or a salt, solvate or prodrug thereof, wherein R1ais selected from the group consisting of 6 to 11 membered aryl, 5 to 9 membered heteroaryl and 3 to 9 membered heterocycloalkyl, each of which is optionally substituted with one or more Ra1.12. A compound according to any one of clauses 1 to 4, or a salt, solvate or prodrug thereof, wherein R1ais selected from the group consisting of phenyl, 5 to 7 membered heteroaryl and 3 to 7 membered heterocycloalkyl, each of which is optionally substituted with one or more Ra1.13. A compound according to any one of clauses 1 to 4, or a salt, solvate or prodrug thereof, wherein R1ais selected from the group consisting of phenyl, pyridyl, pyrazinyl, pyrazolyl, piperidinyl, pyrrolidinyl, morpholinyl, tetrahydropyranyl, cyclopropyl and branched C1.4 alkyl, each of which is optionally substituted with one or more Ra1.14. A compound according to any one of clauses 1 to 4, or a salt, solvate or prodrug thereof, wherein R1ais selected from the group consisting of phenyl and pyridyl, pyrazolyl, piperidinyl, pyrrolidinyl, morpholinyl, tetrahydropyranyl and branched C1.4 alkyl, each of which is optionally substituted with one or more Ra1.15. A compound according to any one of clauses 1 to 4, or a salt, solvate or prodrug thereof, wherein R1ais selected from phenyl and pyridyl, each of which is optionally substituted with one or more Ra1.16. A compound according to any one of clauses 1 to 4, or a salt, solvate or prodrug thereof, wherein R1ais selected from the following groups, each of which is optionally substituted with one or more groups Ra1:17. A compound according to any one of clauses 1 to 4, or a salt, solvate or prodrug thereof, wherein R1ais selected from the following groups, each of which is optionally substituted with one or more groups Ra1:18. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein E1is -N(R2)C(=O)- or -C(=O)N(R2a)-.19. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein Q1is of formula Q1i:20. A compound according to any one of clauses 4 to 19, or a salt, solvate or prodrug thereof, wherein Q3is of formula Q3i:21. A compound according to clause 20, or a salt, solvate or prodrug thereof, wherein X20is selected from O, S and S(=O), suitably O or S.22. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein R2is selected from the group consisting of hydrogen, Ci-e alkyl, C3-ecycloalkyl.23. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein R2is hydrogen or methyl.24. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein each R7aand R8aare independently selected from the group consisting of hydrogen, hydroxyl, =0, halogen, Ci-ehaloalkyl, Ci-e haloalkoxy, Ci-e alkyl and -O-C1.6 alkyl; orR7aand R8atogether with the carbon atom to which they are attached form a 3-5 membered cycloalkyl or 3-5 membered heterocycloalkyl group, each of which is optionally substituted with one or more groups selected from hydroxyl, halogen, =0, CF3 or C1.3 alkyl.25. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein each R7aand R8aare independently selected from the group consisting of hydrogen, hydroxyl, =0, fluoro, chloro, CF3, OMe and C1.3 alkyl; orR7aand R8atogether with the carbon atom to which they are attached form a cyclopropyl or oxetanyl group, each of which is optionally substituted with one or more groups selected from hydroxyl, halogen, =0, CF3 or C1.3 alkyl.26. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein each R7aand R8aare independently selected from the group consisting of hydrogen, hydroxyl, fluoro and methyl.27. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein each R7aand R8aare independently hydrogen, fluoro or methyl, suitably hydrogen or methyl.28. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein n is an integer of value 0, 1, 2 or 3.29. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein n is an integer of value 0, 1 or 3.30. A compound according to any one of clauses 1 to 18, or a salt, solvate or prodrug thereof, wherein• E1is -N(R2)C(=O)-, where R2is H or methyl;• n is 3• R1ais phenyl or pyridyl, each of which is optionally substituted with one or more Ra1;and• each R7aand R8aare independently selected from hydrogen, fluoro, methyl and hydroxymethyl.31. A compound according to any one of clauses 1 to 18, or a salt, solvate or prodrug thereof, wherein• E1is -N(R2)C(=O)-, where R2is H or methyl;• n is 1• R1ais phenyl, pyridyl or piperidinyl, each of which is optionally substituted with one or more Ra1; and• R7aand R8aare independently selected from hydrogen, methyl and hydroxymethyl.32. A compound according to any one of clauses 1 to 18, or a salt, solvate or prodrug thereof, whereinE1is -N(R2)C(=O)-, where R2is H or methyl;n is 0; andR1ais isopropyl or isobutyl.33. A compound according to any one of clauses 1 to 4, or a salt, solvate or prodrug thereof, wherein• E1is -N(R2)C(=O)-, where R2is H or methyl;• n is 0 or 1;• R1ais selected from the group consisting of 5-6 membered heteroaryl, 3 to 7 membered heterocycloalkyl and C3-7 cycloalkyl, each of which is substituted with one or more Ra1group • Ra1is selected from phenyl or benzyl, each of which is optionally substituted with one or more groups selected from hydroxyl, halogen, =0, -CN, Ci-e haloalkyl, Ci-e haloalkoxy, C3- 6 cycloalkyl, C1-6 alkyl, -O-Ci-e alkyl, phenyl, -C(0)Ci-6 alkyl, -C(O)N(H)CI-6 alkyl, -C(O)N(CI-6 alkyl)2, -CONH2, -C(O)N(H)CI-6alkyl, -C(O)N(Ci.6alkyl)2, -N(H)Ci-e alkyl, and -N(Ci-6alkyl)2.34. A compound according to any one of clauses 1 to 4, or a salt, solvate or prodrug thereof, wherein• E1is -N(R2)C(=O)-, where R2is H or methyl;• n is 0 or 1;• R1ais selected from the group consisting of pyrazolyl, triazolyl, piperidinyl, pyrazinyl, morpholinyl and cyclopropyl, each of which is substituted with one or more Ra1group• Ra1is selected from phenyl or benzyl, each of which is optionally substituted with one or more groups selected from hydroxyl, halogen, =0, -CN, Ci-e haloalkyl, Ci-e haloalkoxy, C3- 6 cycloalkyl, C1-6 alkyl, -O-Ci-e alkyl, phenyl, -C(0)Ci-6 alkyl, -C(0)N(H)CI-6 alkyl, -C(0)N(CI-6 alkyl)2, -CONH2, -C(O)N(H)CI-6alkyl, -C(O)N(Ci.6alkyl)2, -N(H)Ci-e alkyl, and -N(Ci-6alkyl)2.35. A compound according to any one of clauses 1 to 4, or a salt, solvate or prodrug thereof, wherein• E1is -N(R2)C(=O)-, where R2is H or methyl;• n is 1;R1ais: / ; where the phenyl ring is optionally substituted with one or two fluoro groups and R21is selected from the group consisting of O-CH2-C3-6 cycloalkyl, O-CH2-4 to 7 membered heterocycloalkyl, O-Ci-ealkyl.36. A compound according to clause 35, or a salt, solvate or prodrug thereof, wherein R21is O-CH2-C3-6 cycloalkyl, O-CH2-5 to 6 membered heterocycloalkyl, O-C1.4 alkyl; suitably R21is selected from O-CH2-C3-6 cycloalkyl, or O-C1.4 alkyl.37. A compound according to clause 35 or 36, or a salt, solvate or prodrug thereof, wherein R21is38. A compound according to any one of clauses 1 to 3, or a salt, solvate or prodrug thereof, whereinis selected from the following:where each phenyl group is optionally substituted by one or more Ra1.39. A compound according to any one of clauses 1 to 3, or a salt, solvate or prodrug thereof, whereinis selected from the following:where each phenyl or pyridyl group is optionally substituted by one or more Ra1; orR2is selected from the following:wherein the phenyl is optionally substituted with one or more groups selected from hydroxyl, halogen, =0, -CN, Ci-e haloalkyl, Ci-e haloalkoxy, C3-6 cycloalkyl, Ci-e alkyl, -O-C1.6 alkyl, phenyl, -C(O)Ci-6alkyl, -C(O)N(H)CI-6alkyl, -C(O)N(CI-6alkyl)2, -CONH2, -C(O)N(H)CI-6alkyl, -C(O)N(Ci-6alkyl)2,-N(H)Ci-6 alkyl, and -N(Ci-6alkyl)2.40. A compound according to any one of clauses 1 to 3, or a salt, solvate or prodrug thereof, whereinis selected from the following:o41. A compound according to any one of clauses 1 to 3, or a salt, solvate or prodrug thereof, wherein42. A compound according to clause 4, or a salt, solvate or prodrug thereof, whereinis selected from the following:, wherein the phenyl ring is optionally substituted by one or more Ra1.43. A compound according to clause 4, or a salt, solvate or prodrug thereof, wherein44. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein B is a cyclic group selected from 5 to 12 membered heteroaryl and Ce-ii aryl.45. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein B is a cyclic group selected from 5 to 6 membered heteroaryl and phenyl.46. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein B is a 6-membered heteroaryl ring containing one or more nitrogen atom, or a phenyl group.47. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein B is a pyridyl or a phenyl group.48. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein B is a group of formula BO:where X9, X10and X16are independently selected from N, CR3or CH; suitably where the dashed line indicates the point of attachment to the group E1and the wavy line indicates the point of attachment to ring A.49. A compound according to clause 48, or a salt, solvate or prodrug thereof, wherein X9is N.50. A compound according to clause 48, or a salt, solvate or prodrug thereof, wherein X9is CH.51. A compound according to clause 48 or 49, or a salt, solvate or prodrug thereof, wherein X10and X16are independently selected from CR3oCR³ or CH.52. A compound according to any one of clauses 1 to 48, or a salt, solvate or prodrug thereof, wherein B is a group of formula B2 or B3:suitably where the dashed line indicates the point of attachment to the group E and the wavy line indicates the point of attachment to ring A.53. A compound according to any one of clauses 1 to 48, or a salt, solvate or prodrug thereof, wherein ring B is selected from:suitably where the dashed line indicates the point of attachment to the group E1and the wavy line indicates the point of attachment to ring A.54. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein R3is selected from the group consisting of hydroxyl, =0, halogen, CN, Ci-6 haloalkyl, Ci-e haloalkoxy, Ci-e alkyl, O-Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, --C(=O)Rb3, -C(=O)ORc3, -C(=O)NRd3Re3, -NRd3Re3, -NRd3C(=O)Rb3,–ORc3, –SRc3, where said C1-6 alkyl, O-C1.6 alkyl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, =0, CN, Ci-e haloalkyl, Ci-e haloalkoxy, C3-6 cycloalkyl, C1-6 alkyl, O-C1.6 alkyl, -NH2, -N(H)CI-3 alkyl, and -N(Ci-3alkyl)2.55. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein R3is selected from the group consisting of hydroxyl, =0, halogen, CN, C1.6 haloalkyl, Ci-e haloalkoxy, Ci-e alkyl, O-C1.6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, -NRd3Re3, -0Rc3, -SRc3, where said C1-6 alkyl, O-C1.6 alkyl and C3-6 cycloalkyl areoptionally substituted with one or more groups selected from hydroxyl, halogen, =0, CN, Ci-e haloalkyl, Ci-e haloalkoxy, C3-6 cycloalkyl, C1-6 alkyl, O-C1.6 alkyl, -NH2, -N(H)CI-3 alkyl, and -N(Ci.3alkyl)2.56. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein R3is selected from the group consisting of hydroxyl, =0, halogen, CN, C1.6 haloalkyl, Ci-e haloalkoxy, C1-6 alkyl, O-C1.6 alkyl, C2-6 alkenyl, C^alkynyl, -NRd3Re3, where said Ci-e alkyl and O-C1.6 alkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, =0, CN, Ci-e haloalkyl, Ci-e haloalkoxy, C3-6 cycloalkyl, Ci-e alkyl, O-C1.6 alkyl, -NH2, -N(H)CI-3alkyl, and -N(Ci-3alkyl)2.57. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein R3is selected from the group consisting of hydroxyl, =0, halogen, CN, cyclopropyl, Ci-e haloalkyl, Ci-e haloalkoxy, Ci-e alkyl, O-C1.6 alkyl, C2-6 alkenyl, C^alkynyl, -NH2, -N(H)CI-3alkyl, and -N(Ci-3alkyl)2.58. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein R3is selected from the group consisting of hydroxyl, =0, Cl, Br, CN, CF3, OCF2H, OCF3, cyclopropyl, methyl, ethyl, isopropyl, OMe, OEt and OPr.59. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein R3is selected from the group consisting of F, Cl, CF3, OCF2H, OCF3, cyclopropyl, methyl, ethyl, isopropyl, OMe, OEt and OPr; suitably R3is independently selected from methyl, OMe and F.60. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein each Rb3is independently selected from hydrogen, C3-6 cycloalkyl or Ci-e alkyl.61. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein each Rc3is independently selected from the group consisting of hydrogen, Ci-e haloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-6 cycloalkyl, Ci-e alkyl and phenyl, wherein said Ci-e alkyl, phenyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)Ci-ealkyl, -N(Ci-ealkyl)2, Ci-e haloalkyl, C3-6 cycloalkyl, C6-11aryl, 3-7 membered heterocycloalkyl, Ci-e alkyl and -O-C1.6 alkyl.62. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein each Rc3is independently selected from the group consisting of hydrogen, C1-6 haloalkyl, C3-6 cycloalkyl and C1-6 alkyl, wherein said Ci-e alkyl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)Ci-6alkyl, -N(Ci-ealkyl)2, Ci-e haloalkyl, C3-6 cycloalkyl, C6-11aryl, 3-7 membered heterocycloalkyl, Ci-e alkyl and -O-C1.6 alkyl.63. A compound according to any one of the preceding clauses, each Rd3is independently selected from hydrogen or C1-6 alkyl.64. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein each Re3is independently selected from the group consisting of hydrogen, Ci-e haloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-6 cycloalkyl, Ci-e alkyl and phenyl, wherein said Ci-e alkyl, phenyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)Ci-ealkyl, -N(Ci-ealkyl)2, Ci-e haloalkyl, C3-6 cycloalkyl, C6-11aryl, 3-7 membered heterocycloalkyl, Ci-e alkyl and -O-C1-6 alkyl.65. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein each Re3is independently selected from the group consisting of hydrogen, Ci-e haloalkyl, C3-6 cycloalkyl and Ci-e alkyl, wherein said Ci-e alkyl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)Ci-ealkyl, -N(Ci-ealkyl)2, Ci-e haloalkyl, C3-6 cycloalkyl, C6-11aryl, 3-7 membered heterocycloalkyl, Ci-e alkyl and -O-C1-6 alkyl.66. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein each Re3is independently selected from hydrogen or Ci-e alkyl.67. A compound according to any one of clauses 1 to 62, or a salt, solvate or prodrug thereof, wherein Rd3and Re3, when attached to the same atom, together with the atom to which they are attached form a 3-7 membered ring, optionally containing one or more heteroatoms selected from O, N and S, and wherein said ring is optionally substituted with one or more Rf3.68. A compound according to clause 67, or a salt, solvate or prodrug thereof, wherein Rf3is selected from the group consisting of hydrogen, =0, halogen, -CN, -NH2, -N(H)CI-6 alkyl, — N(Ci-6 alkyl)2, Ci-e haloalkyl, C3-6 cycloalkyl, Ci-e alkyl and -O-C1-6 alkyl. In another embodiment, Rf3is selected from hydrogen, =0, halogen, -CN, -NH2, -N(H)CI-4 alkyl, -N(Ci-4 alkyl)2, C1-4 haloalkyl, C1.4 alkyl and -O-C1-4 alkyl.69. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein y1 is an integer selected from 0, 1 and 2.70. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein y1 is an integer of value 0 or 1.71. A compound according to clause 1 or 2, or a salt, solvate or prodrug thereof, wherein Q is Q2.72. A compound according to any one of clauses 1, 2 and 71, or a salt, solvate or prodrug thereof, wherein R1bis selected from the group consisting of 5 to 12 membered heteroaryl, 6 to 15 membered aryl, 3 to 12 membered heterocycloalkyl, C3-11 cycloalkyl and C1.10 alkyl, each of which is optionally substituted with one or more Ra1.73. A compound according to any one of clauses 1, 2 and 71, or a salt, solvate or prodrug thereof, wherein R1bis selected from the group consisting of 5 to 9 membered heteroaryl, phenyl, 3 to 9 membered heterocycloalkyl, C3-9 cycloalkyl and Ci-e alkyl, each of which is optionally substituted with one or more Ra1.74. A compound according to any one of clauses 1, 2 and 71, or a salt, solvate or prodrug thereof, wherein R1bis selected from the group consisting of 5 to 12 membered heteroaryl, 3 to 12 membered heterocycloalkyl, C3-11 cycloalkyl and Ci- 10 alkyl, each of which is optionally substituted with one or more Ra1.75. A compound according to any one of clauses 1, 2 and 71, or a salt, solvate or prodrug thereof, wherein R1bis selected from the group consisting of 5 to 9 membered heteroaryl, 3 to 9 membered heterocycloalkyl, C3-9 cycloalkyl and Ci-e alkyl, each of which is optionally substituted with one or more Ra1.76. A compound according to any one of clauses 1, 2 and 71, or a salt, solvate or prodrug thereof, wherein R1bis selected from the group consisting of 5 to 7 membered heteroaryl, 3 to 7 membered heterocycloalkyl, C3-7 cycloalkyl and Ci-e alkyl, each of which is optionally substituted with one or more Ra1.77. A compound according to any one of clauses 1, 2 and 71, or a salt, solvate or prodrug thereof, wherein R1bis selected from the group consisting of pyridyl, pyrazinyl, piperidinyl, pyrrolidinyl, morpholinyl, tetrahydropyranyl, cyclohexyl, cyclopropyl and branched C1.4 alkyl, each of which is optionally substituted with one or more Ra1.78. A compound according to any one of clauses 1, 2 and 71, or a salt, solvate or prodrug thereof, wherein R1bis selected from the group consisting of pyridyl, piperidinyl, cyclohexyl,cyclopropyl and branched C1.4 alkyl, each of which is optionally substituted with one or more Ra1.79. A compound according to any one of clauses 1, 2 and 71, or a salt, solvate or prodrug thereof, wherein R1bis selected from the following groups, each of which is optionally substituted with one or more groups Ra1:80. A compound according to any one of clauses 1, 2 and 71 to 79, or a salt, solvate or prodrug thereof, wherein n is an integer of value 0, 1, 2 or 3.81. A compound according to any one of clauses 1, 2 and 71 to 79, or a salt, solvate or prodrug thereof, wherein n is an integer of value 0, 1 or 3.82. A compound according to any one of clauses 1, 2 and 71 to 79, or a salt, solvate or prodrug thereof, wherein n is an integer of value 0 or 1.83. A compound according to any one of clauses 1, 2 and 71 to 82, or a salt, solvate or prodrug thereof, wherein R7band R8bare independently selected from the group consisting of hydrogen, hydroxyl, =0, halogen, Ci-ehaloalkyl, Ci-e haloalkoxy, Ci-e alkyl; orR7aand R8atogether with the carbon atom to which they are attached form a 3-5 membered cycloalkyl or 3-5 membered heterocycloalkyl group, each of which is optionally substituted with one or more groups selected from hydroxyl, halogen, =0, CF3 or C1.3 alkyl.84. A compound according to any one of clauses 1, 2 and 71 to 82, or a salt, solvate or prodrug thereof, wherein R7band R8bare independently selected from the group consisting of hydrogen, hydroxyl, =0, fluoro, chloro, CF3, and C1.3 alkyl; orR7aand R8atogether with the carbon atom to which they are attached form a cyclopropyl or oxetanyl group.85. A compound according to any one of clauses 1, 2 and 71 to 82, or a salt, solvate or prodrug thereof, wherein R7band R8bare independently selected from the group consisting of hydrogen, hydroxyl, hydroxymethyl, fluoro and methyl.86. A compound according to any one of clauses 1, 2 and 71 to 82, or a salt, solvate or prodrug thereof, wherein R7band R8bare hydrogen and n is 1.87. A compound according to any one of clauses 1, 2 and 71 to 86, or a salt, solvate or prodrug thereof, wherein C is a 5 to 12 membered heterocycle containing at least one nitrogen 2atom in the ring, wherein theR / DR‘ moiety is bonded to ring C via a nitrogen atom in ring C.88. A compound according to any one of clauses 1, 2 and 71 to 86, or a salt, solvate or prodrug thereof, wherein C is a 8 to 12 membered heterocycle containing at least one nitrogen 2atom in the ring, and wherein theR / DR' moiety is bonded to ring C via a nitrogen atom in ring C.89. A compound according to any one of clauses 1, 2 and 71 to 86, or a salt, solvate or prodrug thereof, wherein C is a 9 or 10 membered heterocycle containing at least one nitrogen 2atom in the ring, and wherein theR / DR' moiety is bonded to ring C via a nitrogen atom in ring C.90. A compound according to any one of clauses 1, 2 and 71 to 86, or a salt, solvate or prodrug thereof, wherein C is a 9 or 10 membered fused bicyclic heterocycle containing at 2least one nitrogen atom in the ring, and wherein theR / DR' moiety is bonded to ring C via a nitrogen atom in ring C.91. A compound according to any one of clauses 1, 2 and 71 to 90, or a salt, solvate or prodrug thereof, wherein E2is -C(=O)- or -S(=O)2-.92. A compound according to any one of clauses 1, 2 and 71 to 91, or a salt, solvate or prodrug thereof, wherein E2is -C(=O)-.93. A compound according to any one of clauses 1, 2 and 71 to 92, or a salt, solvate or prodrug thereof, wherein C is of formula C1:where0the dashed line indicates the point of attachment toR7bR8bX22, X23and X24are independently selected from N, CR9or CH;X25is CH2, CHR9, C(R9)2, NH, NR9, S, S(O), S(O)2or O; andncis an integer selected from 0, 1 or 2.94. A compound according to clause 93, or a salt, solvate or prodrug thereof, wherein X25is O, CH2or NMe.95. A compound according to clause 93 or 94, or a salt, solvate or prodrug thereof, wherein X24is N.96. A compound according to any one of clauses 93 to 95, or a salt, solvate or prodrug thereof, wherein X22and X23are CH.97. A compound according to any one of clauses 93 to 96, or a salt, solvate or prodrug thereof, wherein ncis an integer selected from 0 or 1.98. A compound according to any one of clauses 1, 2 and 71 to 92, or a salt, solvate or prodrug thereof, wherein C is selected from:, each of which may optionally be substituted with R9.99. A compound according to any one of clauses 1, 2 and 71 to 92, or a salt, solvate or prodrug thereof, wherein C is selected from:, each of which may optionally be substituted with R9.100. A compound according to any one of clauses 1, 2 and 71 to 92, or a salt, solvate or prodrug thereof, wherein C is selected from:each of which may optionally be substituted with R9.101. A compound according to any one of clauses 1, 2 and 71 to 92, or a salt, solvate or prodrug thereof, wherein C is selected from:each of which may optionally be substituted with R9.102. A compound according to any one of clauses 1, 2 and 71 to 92, or a salt, solvate or prodrug thereof, wherein C is:(k / lY Iwhich may optionally be substituted with R9.103. A compound according to any one of clauses 1, 2 and 71 to 102, or a salt, solvate or prodrug thereof, wherein R9is selected from the group consisting of hydroxyl, =0, halogen, CN, Ci-6 haloalkyl, Ci-e haloalkoxy, Ci-e alkyl, O-Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, -NRd3Re3, -ORc3, -SRc3, where said C1-6 alkyl, O-C1.6 alkyl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, =0, CN, Ci-e haloalkyl, Ci-e haloalkoxy, C3-6 cycloalkyl, C1-6 alkyl, O-C1.6 alkyl, -NH2, -N(H)CI-3 alkyl, and -N(Ci.3alkyl)2.104. A compound according to any one of clauses 1, 2 and 71 to 102, or a salt, solvate or prodrug thereof, wherein R9is selected from the group consisting of hydroxyl, =0, halogen, CN, C1.6 haloalkyl, Ci-e haloalkoxy, C1-6 alkyl, O-C1.6 alkyl, C2-6 alkenyl, C2-6 alkynyl, -NRd3Re3, where said Ci-e alkyl and O-C1.6 alkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, =0, CN, Ci-e haloalkyl, Ci-e haloalkoxy, C3-6 cycloalkyl, Ci-e alkyl, O-C1.6 alkyl, -NH2, -N(H)CI-3alkyl, and -N(Ci-3alkyl)2.105. A compound according to any one of clauses 1, 2 and 71 to 102, or a salt, solvate or prodrug thereof, wherein R9is selected from the group consisting of hydroxyl, =0, halogen, CN, C1.6 haloalkyl, Ci-e haloalkoxy, C1-6 alkyl, O-C1.6 alkyl, C2-6 alkenyl, C2-6 alkynyl, -NH2, -N(H)CI-3 alkyl, and -N(Ci-3alkyl)2.106. A compound according to any one of clauses 1, 2 and 71 to 102, or a salt, solvate or prodrug thereof, wherein R9is selected from the group consisting of hydroxyl, =0, halogen,CN, C1.3 haloalkyl, C1.3 haloalkoxy, C1.4 alkyl, O-C1.4 alkyl, -NH2, -N(H)CI-3 alkyl, and -N(C1-3 alkyl)2.107. A compound according to any one of clauses 1, 2 and 71 to 102, or a salt, solvate or prodrug thereof, wherein R9is selected from the group consisting of hydroxyl, =0, Cl, Br, CN, CF3, OCF3, methyl, ethyl and OMe.108. A compound according to any one of clauses 1, 2 and 71 to 102, or a salt, solvate or prodrug thereof, wherein R9is selected from the group consisting of hydroxyl, =0, methyl, ethyl and OMe.109. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein y2 is an integer selected from 0, 1 and 2.110. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein y2 is an integer selected from 0 and 1.111. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein Ra1is independently selected from the group consisting of hydroxyl, =0, halogen, CN, Ci-e haloalkyl, Ci-e haloalkoxy, Ci-e alkyl, O-C1.6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, -O-C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, benzyl, 5-6 membered heteroaryl, -C(=O)Rb1, -NRd1Re1, -ORc1, where said C1-6 alkyl, O-C1.6 alkyl, C3-6 cycloalkyl, -O-C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, phenyl and benzyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =0, -CN, Ci-e haloalkyl, Ci-e haloalkoxy, C3-6 cycloalkyl, Ci-e alkyl, -O-C1.6 alkyl, phenyl, -C(O)Ci-6alkyl, -C(O)N(H)CI-6alkyl, -C(O)N(CI-6alkyl)2, -CONH2, -C(O)N(H)CI-6alkyl, -C(O)N(Ci-6alkyl)2,-N(H)Ci-6 alkyl, and -N(Ci-6alkyl)2.112. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein Ra1is independently selected from the group consisting of hydroxyl, =0, halogen, CN, CF3, OCF3, Ci-6alkyl, O-Ci-6alkyl, -C(=O)Rb1, -NRd1Re1and -ORc1.113. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein Ra1is independently selected from the group consisting of hydroxyl, =0, halogen, CN, CF3, OCF3, Ci-6alkyl, O-Ci-6alkyl, -C(=O)Me, -NH2, -N(H)Ci-3alkyl and -N(Ci.3alkyl)2.114. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein Ra1is independently selected from the group consisting of hydroxyl,=0, halogen, CN, CF3, OCF3, Ci-6alkyl, O-Ci-6alkyl, -C(=O)Me, -NH2, -N(H)Ci-3alkyl and -N(Ci.3alkyl)2.115. A compound according to any one of clauses 1 to 110, or a salt, solvate or prodrug thereof, wherein Ra1is phenyl or benzyl, each of which is optionally substituted with one or more groups selected from hydroxyl, halogen, =0, -CN, Ci-e haloalkyl, Ci-e haloalkoxy, C3.6 cycloalkyl, Ci-e alkyl, -O-Ci-6 alkyl, phenyl, -C(O)Ci-6 alkyl, -C(O)N(H)CI-6 alkyl, -C(O)N(CI-6 alkyl)2, -CONH2, -C(O)N(H)CI-6alkyl, -C(O)N(Ci-6alkyl)2, -N(H)Ci-e alkyl, and -N(Ci-6alkyl)2.116. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein Rb1is independently selected from hydrogen, C3.6 cycloalkyl or Ci-e alkyl.117. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein each Rc1is independently selected from the group consisting of hydrogen, Ci-e haloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3.6 cycloalkyl, Ci-e alkyl and phenyl, wherein said Ci-e alkyl, phenyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl and C3.6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, -CN, -N02, -NH2, -N(H)Ci-ealkyl, -N(Ci-ealkyl)2, Ci-e haloalkyl, C3.6 cycloalkyl, C6-11aryl, 3-7 membered heterocycloalkyl, Ci-e alkyl and -O-Ci-6 alkyl.118. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein each Rc1is independently selected from the group consisting of hydrogen, Ci-e haloalkyl, C3.6 cycloalkyl and Ci-e alkyl, wherein said Ci-e alkyl and C3.6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, -CN, -N02, –NH2, -N(H)Ci-6alkyl, - N(Ci-ealkyl)2, Ci-e haloalkyl, C3.6 cycloalkyl, C6-11aryl, 3-7 membered heterocycloalkyl, Ci-e alkyl and -O-Ci-6 alkyl.119. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein each Rd1is independently selected from the group consisting of hydrogen, C3.6 cycloalkyl, and Ci-e alkyl, wherein said Ci-e alkyl and C3.6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, -CN, -N02, –NH2, -N(H)Ci-6alkyl, — N(Ci-ealkyl)2, Ci-e haloalkyl, C3.6 cycloalkyl, C6-11aryl, 3-7 membered heterocycloalkyl, Ci-e alkyl and -O-Ci-6 alkyl.120. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein each Re1is independently selected from the group consisting of hydrogen, Ci-e haloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3.6cycloalkyl, Ci-e alkyl and phenyl, wherein said Ci-e alkyl, phenyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)Ci-ealkyl, -N(Ci-ealkyl)2, Ci-ehaloalkyl, C3-6 cycloalkyl, C6-11aryl, 3-7 membered heterocycloalkyl, Ci-e alkyl and -O-C1.6 alkyl.121. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein each Re1is independently selected from the group consisting of hydrogen, Ci-ehaloalkyl, C3-6 cycloalkyl and Ci-e alkyl, wherein said Ci-e alkyl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)Ci-ealkyl, -N(Ci-ealkyl)2, Ci-e haloalkyl, C3-6 cycloalkyl, C6-11aryl, 3-7 membered heterocycloalkyl, Ci-e alkyl and -O-C1-6 alkyl.122. A compound according to any one of clauses 1 to 118, or a salt, solvate or prodrug thereof, wherein Rd1and Re1, when attached to the same atom, together with the atom to which they are attached form a 5-7 membered ring, optionally containing one or more heteroatoms selected from O, N and S, and wherein said ring is optionally substituted with one or more Rf1.123. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein Rf1is selected from the group consisting of hydrogen, =0, halogen, -CN, -NH2, -N(H)CI-6 alkyl, -N(Ci-ealkyl)2, Ci-ehaloalkyl, C3-6 cycloalkyl, Ci-e alkyl and -O-C1.6 alkyl.124. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein A is a cyclic group selected from 5 to 12 membered heteroaryl.125. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein A is a 9 or 10 membered fused bicyclic heteroaryl, which suitably contains at least one nitrogen.126. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein A is a cyclic group selected from benzothiazolyl, aza-benzothiazolyl, benzimidazolyl, aza-benzimidazolyl, imidazopyridinyl, imidazopyridazinyl, imidazopyrazinyl, benzofurazanyl, benzothiadiazinyl, benzothiazinyl, benzoxazolyl, aza-benzoxazolyl, aza-indolyl, cinnolinyl, furopyridinyl, quinazolinyl, quinoxalinyl and isoquinolinyl.127. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein A is a cyclic group selected from benzothiazolyl, aza-benzothiazolyl, benzimidazolyl, aza-benzimidazolyl, imidazopyridinyl, imidazopyridazinyl, imidazopyrazinyl,benzoxazolyl, aza-benzoxazolyl, aza-indolyl, cinnolinyl, quinazolinyl, quinoxalinyl and isoquinolinyl.128. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein A is a cyclic group selected from benzothiazolyl, aza-benzothiazolyl, benzimidazolyl, aza-benzimidazolyl, imidazopyridinyl, imidazopyridazinyl, imidazopyrazinyl, benzoxazolyl, aza-benzoxazolyl, and aza-indolyl.129. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein A is a cyclic group selected from benzothiazolyl, aza-benzothiazolyl, benzimidazolyl, aza-benzimidazolyl, imidazopyridinyl, imidazopyridazinyl, imidazopyrazinyl, benzoxazolyl, aza-benzoxazolyl, and aza-indolyl.130. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein A is a cyclic group selected from benzothiazolyl, aza-benzothiazolyl, imidazopyrazinyl (suitably imidazo[1,2-a]pyrazinyl) and imidazopyridinyl (suitably imidazo[1,2-a]pyridinyl) and imidazopyridazinyl (suitably imidazo[1,2-b] pyridazinyl).131. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein A is a cyclic group of formula A1wherein X1, X2, X3and X4are independently selected from C, N, CH or CR4; provided that only one of X1, X2, X3and X4is C and forms the point of attachment to ring B or ring C;X5and X6are independently selected from N or C;X7and X8are independently selected from O, S, N, CH, CR4and NR4;with the proviso that at least one of X1, X2, X3, X4, X5, X6, X7and X8must be N.132. A compound according to clause 131, or a salt, solvate or prodrug thereof, wherein X8is N.133. A compound according to clause 131 or 132, or a salt, solvate or prodrug thereof, wherein X7is S oCR³ or CH.134. A compound according to any one of clauses 131 to 133, or a salt, solvate or prodrug thereof, wherein each of X1, X2, X3and X4are C, CH or CR4; provided that only one of X1, X2, X3and X4is C and forms the point of attachment to ring B or ring C.135. A compound according to any one of clauses 1 to 130, or a salt, solvate or prodrug thereof, wherein A is a cyclic group of formula A2wherein X1, X2, X3and X4are independently selected from C, N, CH or CR4; provided that only one of X1, X2, X3and X4is C and forms the point of attachment to ring B or ring C.136. A compound according to clause 135, or a salt, solvate or prodrug thereof, wherein X2is C and forms the point of attachment to ring B or ring C and X1, X3and X4are independently selected from N, CH or CR4; suitably X1, X3and X4are independently selected CH or CR4.137. A compound according to any one of clauses 1 to 130, or a salt, solvate or prodrug thereof, wherein A is a cyclic group of formula A3wherein X11, X12, X13and X14are independently selected from C, N, CH or CR4;provided that only one of X11, X12, X13and X14is C and forms the point of attachment to ring B or ring C. 138. A compound according to clause 137, or a salt, solvate or prodrug thereof, wherein X13is C and forms the point of attachment to ring B or ring C and X11, X12and X14are independently selected from N, CH or CR4.139. A compound according to clause 137 or 138, or a salt, solvate or prodrug thereof, wherein X12is N or CH, and X11and X14are independently selected from CH or CR4.140. A compound according to clause 137 or 138, or a salt, solvate or prodrug thereof, wherein X11is CH, and X12and X14are independently selected from N, CH or CR4.141. A compound according to any one of clauses 1 to 130, or a salt, solvate or prodrug thereof, wherein A is a cyclic group selected from:each of which may be optionally substituted with one or more R4.142. A compound according to any one of clauses 1 to 130, or a salt, solvate or prodrug thereof, wherein A is a cyclic group selected from:each of which may be optionally substituted with one or more R4.143. A compound according to any one of clauses 1 to 130, or a salt, solvate or prodrugeach of which may be optionally substituted with one or more R4.144. A compound according to any one of clauses 1 to 130, or a salt, solvate or prodrug thereof, wherein A is a cyclic group selected from:each of which may be optionally substituted with one or more R4.145. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein R4is selected from hydroxyl, =0, halogen, CN, Ci-e haloalkyl, Ci-e haloalkoxy, Ci-e alkyl, O-Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, -C(=O)Rb3, -C(=O)ORc4, -C(=O)NRd4Re4, -NRd4Re4, -NRd4C(=O)Rb4,-ORc4, -SRc4, where said Ci-6alkyl, O-Ci-6alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl and phenyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =0, CN, Ci-e haloalkyl, Ci-e haloalkoxy, C3-6 cycloalkyl, C1-6 alkyl, O-C1.6 alkyl, -NH2, -N(H)CI-3 alkyl, and -N(Ci-3alkyl)2.146. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein R4is selected from the group consisting of hydroxyl, =0, halogen, CN, C1.6 haloalkyl, Ci-e haloalkoxy, Ci-e alkyl, O-C1.6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, -C(=O)Rb4, -C(=O)ORc4, -C(=O)NRd4Re4, -NRd4Re4, -NRd4C(=O)Rb4,-ORc4, -SRc4, where said C1-6 alkyl, O-C1.6 alkyl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, =0, CN, Ci-e haloalkyl, Ci-e haloalkoxy, C3-6 cycloalkyl, C1-6 alkyl, O-C1.6 alkyl, -NH2, -N(H)CI-3 alkyl, and -N(Ci-3alkyl)2.147. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein R4is selected from the group consisting of hydroxyl, =0, halogen, CN, Ci-6 haloalkyl, Ci-e haloalkoxy, Ci-e alkyl, O-Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, -NRd4Re4, -ORc4, -SRc4, where said C1-6 alkyl, O-C1.6 alkyl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, =0, CN, Ci-e haloalkyl, Ci-e haloalkoxy, C3-6 cycloalkyl, C1-6 alkyl, O-C1.6 alkyl, -NH2, -N(H)CI-3 alkyl, and -N(Ci.3alkyl)2.148. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein R4is selected from the group consisting of hydroxyl, =0, halogen, CN, C1.6 haloalkyl, Ci-e haloalkoxy, C1-6 alkyl, O-C1.6 alkyl, C2-6 alkenyl, C2-6 alkynyl, -NRd4Re4, where said Ci-e alkyl and O-C1.6 alkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, =0, CN, Ci-e haloalkyl, Ci-e haloalkoxy, C3-6 cycloalkyl, Ci-e alkyl, O-C1.6 alkyl, -NH2, -N(H)CI-3alkyl, and -N(Ci-3alkyl)2.149. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein R4is selected from the group consisting of hydroxyl, =0, halogen, CN, C1.6 haloalkyl, Ci-e haloalkoxy, C1-6 alkyl, O-C1.6 alkyl, C2-6 alkenyl, C2-6 alkynyl, -NH2, -N(H)CI-3 alkyl, and -N(Ci-3alkyl)2.150. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein R4is selected from the group consisting of hydroxyl, =0, halogen, CN, C1.3 haloalkyl, C1.3 haloalkoxy, C1.4 alkyl, O-C1.4 alkyl, -NH2, -N(H)CI-3 alkyl, and -N(C1-3 alkyl)2.151. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein R4is selected from the group consisting of hydroxyl, =0, Cl, Br, CN, CF3, OCF3, methyl, ethyl and OMe.152. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein Rb4is independently selected from hydrogen, C3-6 cycloalkyl or Ci-e alkyl.153. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein each Rc4is independently selected from the group consisting of hydrogen, Ci-e haloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-6 cycloalkyl, Ci-e alkyl and phenyl, wherein said Ci-e alkyl, phenyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)Ci-ealkyl, -N(Ci-6alkyl)2, Ci-ehaloalkyl, C3-6 cycloalkyl, C6-11aryl, 3-7 membered heterocycloalkyl, Ci-e alkyl and -O-C1.6 alkyl.154. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein Rc4is independently selected from the group consisting of hydrogen, C1.6 haloalkyl, C3-6 cycloalkyl and Ci-e alkyl, wherein said Ci-e alkyl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)Ci-6alkyl, -N(Ci-ealkyl)2, Ci-e haloalkyl, C3-6 cycloalkyl, C6-11aryl, 3-7 membered heterocycloalkyl, Ci-e alkyl and -O-C1-6 alkyl.155. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein each Rd4is independently selected from the group consisting of hydrogen, C3-6 cycloalkyl, and Ci-e alkyl, wherein said Ci-e alkyl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)Ci-ealkyl, -N(Ci-ealkyl)2, Ci-e haloalkyl, C3-6 cycloalkyl, C6-11aryl, 3-7 membered heterocycloalkyl, Ci-e alkyl and -O-C1.6 alkyl.156. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein each Re4is independently selected from the group consisting of hydrogen, Ci-e haloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-6 cycloalkyl, Ci-e alkyl and phenyl, wherein said Ci-e alkyl, phenyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)Ci-ealkyl, -N(Ci-ealkyl)2, Ci-ehaloalkyl, C3-6 cycloalkyl, C6-11aryl, 3-7 membered heterocycloalkyl, Ci-e alkyl and -O-C1.6 alkyl.157. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein each Re4is independently selected from the group consisting of hydrogen, Ci-ehaloalkyl, C3-6 cycloalkyl and Ci-e alkyl, wherein said Ci-e alkyl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)Ci-ealkyl, -N(Ci-ealkyl)2, Ci-e haloalkyl, C3-6 cycloalkyl, C6-11aryl, 3-7 membered heterocycloalkyl, Ci-e alkyl and -O-C1.6 alkyl. In another embodiment, each Re4is independently selected from hydrogen or C1-6 alkyl.158. A compound according to any one of clauses 1 to 154, or a salt, solvate or prodrug thereof, wherein Rd4and Re4, when attached to the same atom, together with the atom to which they are attached form a 3-7 membered ring, optionally containing one or more heteroatoms selected from O, N and S, and wherein said ring is optionally substituted with one or more Rf4.159. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein Rf4is selected from the group consisting of hydrogen, =0, halogen, -CN, –NH2, -N(H)CI-6 alkyl, — N(CI-6 alkyl)2, Ci-ehaloalkyl, C3-6 cycloalkyl, Ci-e alkyl and -O-C1.6 alkyl.160. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein z1 is an integer selected from 0, 1 and 2.161. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein z1 is 0 or 1.162. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein z2 is an integer selected from 0, 1 and 2.163. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein z2 is 0 or 1.164. A compound according to any one of clauses 131 to 163, or a salt, solvate or prodrug thereof, wherein the wavy line in A or sub-formulae thereof indicates the point of attachment to the adjacent group V.165. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein V is selected from the group consisting of -NH-, -C(O)-, -S(O)2-, -C(O)N(H)-, -N(H)C(O)-, -S(O)(NH)-, -N(H)S(O)-, -S(O)N(H)-, -N(H)S(O)2- and -S(O)2N(H)-.166. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein V is selected from the group consisting of -NH-, -C(O)-, -C(O)N(H)-and -N(H)C(O)-.167. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein V is selected from the group consisting of -NH-, -C(O)N(H)- and -N(H)C(O)-.168. A compound according to any one of the preceding clauses, or a salt, solvate or prodrug thereof, wherein V is -NH-.169. A compound according to any one of clauses 1 to 3, or a salt, solvate or prodrug thereof, wherein Q is of sub-formula Q1a:whereX1, X3and X4are independently selected from N, CH or CR4;X6is selected from N or C;X7is selected from O, S, N, CH, CR4and NR4;X9and X10are independently selected from N, CR3or CH; andR1a, R7a, R8aand n are as defined in clause 1.170. A compound according to clause 169, or a salt, solvate or prodrug thereof, wherein X7is N, S or CH.171. A compound according to clause 169 or 170, or a salt, solvate or prodrug thereof, wherein X3and X4are CH.172. A compound according to any one of clauses 169 to 171, or a salt, solvate or prodrug thereof, wherein X6is N and X7is CH.173. A compound according to any one of clauses 169 to 171, or a salt, solvate or prodrug thereof, wherein X6is N and X7is N.174. A compound according to any one of clauses 169 to 173, or a salt, solvate or prodrug thereof, wherein X1is N.175. A compound according to any one of clauses 169 to 171, or a salt, solvate or prodrug thereof, wherein X1is N, X6is C and X7is S.176. A compound according to any one of clauses 1 to 3, or a salt, solvate or prodrug thereof, wherein Q is of sub-formula Q1d:whereX9is selected from N, CR3or CH; andX10is selected from N, CR3or CH;; andR1a, R2, R7a, R8aand n are as defined in clause 1.177. A compound according to any one of clauses 1 to 3, or a salt, solvate or prodrug thereof, wherein Q is of sub-formula Q1b:whereX9is selected from N, CR3or CH; andX10is selected from N, CR3or CH;; andR1a, R2, R7a, R8a, E and n are as defined in clause 1.178. A compound according to any one of clauses 1 to 3, or a salt, solvate or prodrug thereof, wherein Q is of sub-formula Q1e:whereX9is selected from N, CR3or CH; andX10is selected from N, CR3or CH;X7ais CH or N;X1is selected from N, CH or CR4; andR1a, R2, R7a, R8aand n are as defined in clause 1.179. A compound according to clause 178, or a salt, solvate or prodrug thereof, wherein X1is CH.180. A compound according to clause 178 or 179, or a salt, solvate or prodrug thereof, wherein X7ais selected from N oCR³ or CH.181. A compound according to any one of clauses 169 to 180, or a salt, solvate or prodrug thereof, wherein X10is CH or CR3.182. A compound according to any one of clauses 169 to 181, or a salt, solvate or prodrug thereof, wherein X9is N oCR³ or CH.183. A compound according to any one of clauses 169 to 182, or a salt, solvate or prodrug thereof, wherein R3is selected from the group consisting of hydroxyl, =0, halogen, CN, cyclopropyl, Ci-e haloalkyl, Ci-e haloalkoxy, Ci-e alkyl, O-Ci-6 alkyl, C2-6 alkenyl, C^alkynyl, -NH2, -N(H)CI-3alkyl, and -N(Ci-3alkyl)2.184. A compound according to any one of clauses 169 to 182, or a salt, solvate or prodrug thereof, wherein R3is selected from the group consisting of hydroxyl, =0, Cl, Br, CN, CF3, OCF2H, OCF3, cyclopropyl, methyl, ethyl, isopropyl, OMe, OEt and OPr.185. A compound according to any one of clauses 169 to 182, or a salt, solvate or prodrug thereof, wherein R3is selected from the group consisting of Cl, CF3, OCF2H, OCF3, cyclopropyl, methyl, ethyl, isopropyl, OMe, OEt and OPr.186. A compound according to any one of clauses 169 to 185, or a salt, solvate or prodrug thereof, wherein R2is selected from the group consisting of hydrogen, C1-6 alkyl, C3-6cycloalkyl.187. A compound according to any one of clauses 169 to 186, or a salt, solvate or prodrug thereof, wherein R2is hydrogen or methyl.188. A compound according to any one of clauses 169 to 187, or a salt, solvate or prodrug thereof, wherein each R7aand R8aare independently selected from the group consisting of hydrogen, hydroxyl, =0, halogen, Ci-ehaloalkyl, Ci-e haloalkoxy, Ci-e alkyl; orR7aand R8atogether with the carbon atom to which they are attached form a 3-5 membered cycloalkyl or 3-5 membered heterocycloalkyl group, each of which is optionally substituted with one or more groups selected from hydroxyl, halogen, =0, CF3 or C1.3 alkyl.189. A compound according to any one of clauses 169 to 187, or a salt, solvate or prodrug thereof, wherein each R7aand R8aare independently selected from the group consisting of hydrogen, hydroxyl, =0, fluoro, chloro, CF3, and C1.3 alkyl; orR7aand R8atogether with the carbon atom to which they are attached form a cyclopropyl or oxetanyl group.190. A compound according to any one of clauses 169 to 187, or a salt, solvate or prodrug thereof, wherein each R7aand R8aare independently selected from the group consisting of hydrogen, hydroxyl, fluoro and methyl.191. A compound according to any one of clauses 169 to 190, or a salt, solvate or prodrug thereof, wherein n is an integer of value 0, 1, 2 or 3.192. A compound according to any one of clauses 169 to 191, or a salt, solvate or prodrug thereof, wherein n is an integer of value 0, 1 or 3.193. A compound according to any one of clauses 169 to 185, or a salt, solvate or prodrug thereof, wherein• R2is H or methyl;• n is 3• R1ais phenyl or pyridyl; and• each R7aand R8aare independently selected from hydrogen, fluoro, methyl and hydroxymethyl.194. A compound according to any one of clauses 169 to 185, or a salt, solvate or prodrug thereof, wherein• R2is H or methyl;• n is 1• R1ais phenyl, pyridyl or piperidinyl; and• R7aand R8aare independently selected from hydrogen, methyl and hydroxymethyl.195. A compound according to any one of clauses 169 to 185, or a salt, solvate or prodrug thereof, wherein• R2is H or methyl;• n is 0; and• R1ais isopropyl or isobutyl.196. A compound according to any one of clauses 169 to 185, or a salt, solvate or prodrug thereof, wherein• R2is H or methyl;• n is 0 or 1;• R1ais selected from the group consisting of 5-6 membered heteroaryl, 3 to 7 membered heterocycloalkyl and C3-7 cycloalkyl, each of which is substituted with one or more Ra1group • Ra1is selected from phenyl or benzyl, each of which is optionally substituted with one or more groups selected from hydroxyl, halogen, =0, -CN, Ci-e haloalkyl, Ci-e haloalkoxy, C3-6 cycloalkyl, Ci-e alkyl, -O-C1-6 alkyl, phenyl, -C(O)Ci-6 alkyl, -C(O)N(H)CI-6 alkyl, -C(O)N(CI-6 alkyl)2, -CONH2, -C(O)N(H)CI-6alkyl, -C(O)N(Ci.6alkyl)2, -N(H)Ci-e alkyl, and -N(Ci-6alkyl)2.197. A compound according to any one of clauses 169 to 185, or a salt, solvate or prodrug thereof, wherein• R2is H or methyl;• n is 0 or 1;• R1ais selected from the group consisting of pyrazolyl, triazolyl, piperidinyl, pyrazinyl, morpholinyl and cyclopropyl, each of which is substituted with one or more Ra1group• Ra1is selected from phenyl or benzyl, each of which is optionally substituted with one or more groups selected from hydroxyl, halogen, =0, -CN, Ci-e haloalkyl, Ci-e haloalkoxy, C3-6 cycloalkyl, Ci-e alkyl, -O-C1-6 alkyl, phenyl, -C(O)Ci-6 alkyl, -C(O)N(H)CI-6 alkyl, -C(O)N(CI-6 alkyl)2, -CONH2, -C(O)N(H)CI-6alkyl, -C(O)N(Ci-6alkyl)2, -N(H)Ci-e alkyl, and -N(Ci-6alkyl)2.198. A compound according to any one of clauses 169 to 185, or a salt, solvate or prodrug thereof, whereinR2is selected from the following:where each phenyl group is optionally substituted by one or more Ra1.199. A compound according to any one of clauses 169 to 185, or a salt, solvate or prodrug thereof, whereinR2is selected from the following:where each phenyl group is optionally substituted by one or more Ra1; orR2is selected from the following:wherein the phenyl is optionally substituted with one or more groups selected from hydroxyl, halogen, =0, -CN, Ci-e haloalkyl, Ci-e haloalkoxy, C3-6 cycloalkyl, Ci-e alkyl, -O-C1.6 alkyl, phenyl, -C(O)Ci-6alkyl, -C(O)N(H)CI-6alkyl, -C(O)N(CI-6alkyl)2, -CONH2, -C(O)N(H)CI-6alkyl, -C(O)N(Ci-6alkyl)2,-N(H)Ci-6 alkyl, and -N(Ci-6alkyl)2.200. A compound according to any one of clauses 169 to 185, or a salt, solvate or prodrug thereof, whereinR2is selected from the following:o201. A compound according to any one of clauses 169 to 185, or a salt, solvate or prodrug thereof, wherein202. A compound according to any one of clauses 1, 2 or 71, or a salt, solvate or prodrug thereof, wherein Q2is of sub-formula Q2a:whereX1, X3and X4are independently selected from N, CH or CR4;X6is selected from N or C;X7is selected from O, S, N, CH, CR4and NR4;X25is selected from CH2, CHR9, C(R9)2, NH, NR9, S, S(O), S(O)2or O; andR1b, R7b, R8band n are as defined in clause 1.203. A compound according to clause 202, or a salt, solvate or prodrug thereof, wherein X7is N, S oCR³ or CH.204. A compound according to clause 202 or 203, or a salt, solvate or prodrug thereof, wherein X3and X4are CH.205. A compound according to any one of clauses 202 to 204, or a salt, solvate or prodrug thereof, wherein X6is N and X7is CH.206. A compound according to any one of clauses 202 to 204, or a salt, solvate or prodrug thereof, wherein X6is N and X7is N.207. A compound according to any one of clauses 202 to 206, or a salt, solvate or prodrug thereof, wherein X1is N.208. A compound according to any one of clauses 202 to 204, or a salt, solvate or prodrug thereof, wherein X1is N, X6is C and X7is S.209. A compound according to any one of clauses 1, 2 or 71, or a salt, solvate or prodrug thereof, wherein Q2is of sub-formula Q2c:whereX25is selected from CH2, CHR9, C(R9)2, NH, NR9, S, S(O), S(O)2or O; andR1b, R7b, R8band n are as defined in clause 1.210. A compound according to any one of clauses 1, 2 or 71, or a salt, solvate or prodrug thereof, wherein Q2is of sub-formula Q2e:whereX25is selected from CH2, CHR9, C(R9)2, NH, NR9, S, S(0), S(0)2or O; andR1b, R7b, R8band n are as defined in clause 1.211. A compound according to any one of clauses 1, 2 or 71, or a salt, solvate or prodrug thereof, wherein Q2is of sub-formula Q2f:X7bis selected from CH or N; andX1is selected from N, CH or CR4;X25is selected from CH2, CHR9, C(R9)2, NH, NR9, S, S(O), S(O)2or O; andR1b, R7b, R8band n are as defined in clause 1.212. A compound according to any one of clauses 211, or a salt, solvate or prodrug thereof, wherein X7bis selected from N oCR³ or CH.213. A compound according to any one of clauses 211 and 212, or a salt, solvate or prodrug thereof, wherein X1is CH.214. A compound according to any one of clauses 202 to 213, or a salt, solvate or prodrug thereof, wherein X25is selected from O, NMe oCR³ or CH.215. A compound according to any one of clauses 202 to 214, or a salt, solvate or prodrug thereof, wherein X25is O.216. A compound according to any one of clauses 202 to 215, or a salt, solvate or prodrug thereof, wherein R9is selected from the group consisting of hydroxyl, =0, Cl, Br, CN, CF3, OCF3, methyl, ethyl and OMe.217. A compound according to any one of clauses 202 to 215, or a salt, solvate or prodrug thereof, wherein R9is selected from the group consisting of hydroxyl, =0, methyl, ethyl and OMe.218. A compound according to any one of clauses 202 to 217, or a salt, solvate or prodrug thereof, wherein R1bis selected from the group consisting of 5 to 12 membered heteroaryl, 6 to 15 membered aryl, 3 to 12 membered heterocycloalkyl, C3-11 cycloalkyl and C1.1...

Claims

1. CLAIMS1. A compound of formula I, or a salt, solvate or prodrug thereof:Q-L-M (I)whereinQ is a protein binding moiety of formula Q1, Q2or Q3:whereR1aand R1bare independently selected from the group consisting of 6 to 15 membered aryl, 5 to 12 membered heteroaryl, 3 to 12 membered heterocycloalkyl, C3-11 cycloalkyl, C1.10 alkyl, C2-10 alkenyl and C2-10alkynyl, each of which is optionally substituted with one or more groups Ra1;each Ra1is independently selected from the group consisting of hydroxyl, =0, halogen, CN, C1.6 haloalkyl, Ci-e haloalkoxy, Ci-e alkyl, O-C1.6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, -O-C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, benzyl, 5-6 membered heteroaryl, -C(=0)Rb1,-C(=0)NRd1Re1, -NRd1Re1, -NRd1C(=O)Rb1, -0Rc1, -SRc1, -0C(=0)Rb1,-S(=0)2Rc1and -S(=O)2NRd1Re1, where said Ci-e alkyl, O-C1.6 alkyl, C3-6 cycloalkyl,-O-C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, 5-11 membered heteroaryl, phenyl and benzyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =0, -CN, C1.6 haloalkyl, Ci-e haloalkoxy, C3-6 cycloalkyl, Ci-e alkyl, -O-C1.6 alkyl, phenyl, -C(O)Ci-6alkyl, -C(O)N(H)CI-6alkyl, -C(O)N(CI-6alkyl)2, -CONH2, -C(O)N(H)CI-6alkyl, -C(O)N(CI-6alkyl)2, -N(H)Ci-e alkyl, and -N(Ci-e alkyl)2;where Rb1, Rc1, Rd1and Re1are independently selected from the group consisting of hydrogen, hydroxyl, Ci-e haloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-6 cycloalkyl, C1-6 alkyl, -O-C1.6 alkyl and phenyl, wherein said C1-6 alkyl, -O-C1.6 alkyl, phenyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)Ci-6alkyl, -N(Ci-ealkyl)2, Ci-e haloalkyl, C3-6 cycloalkyl, C6-11aryl, 3-7 membered heterocycloalkyl, Ci-e alkyl and -O-C1.6 alkyl; orRd1and Re1, when attached to the same atom, together with the atom to which they are attached form a 3-7 membered ring, optionally containing one or more heteroatoms selected from O, N and S, and wherein said ring is optionally substituted with one or more Rf1;where each Rf1is independently selected from the group consisting of hydrogen, =0, halogen, -CN, -NH2, -N(H)CI-6 alkyl, -N(Ci-ealkyl)2, Ci-e haloalkyl, C3-6 cycloalkyl, phenyl, 3-7 membered heterocycloalkyl, Ci-e alkyl and -O-C1.6 alkyl;E1is selected from -N(R2)C(=O)-, -C(=O)N(R2a)-, -N(R2)S(=O)2-, -S(=O)2N(R2a)- or -(R2)NC(=O)N(R2a)-;E2is selected from -C(=0)-, -S(=0)2- or -N(R2)C(=O)-;X20is selected from O, S, S(=0), S(=0)2, NH and N(CI-4 alkyl);R2and R2aare independently selected from H, Ci-e alkyl, C3-6cycloalkyl or C3-6 cycloalkyl-CH2-; orR2together with a R7aor R8agroup and the atoms to which they are attached form a 4 to 7 membered heterocycloalkyl ring which is optionally substituted with one or more groups selected from hydroxyl, halogen, =O, -CN, C1-6 haloalkyl, C1-6 haloalkoxy, cyclopropyl, C1-6 alkyl, -O-C1-6 alkyl, -C(O)C1-6alkyl, -C(O)N(H)C1-6alkyl, -C(O)N(C1-6alkyl)2, -CONH2, -C(O)N(H)C1-6alkyl, -C(O)N(C1-6alkyl)2, -N(H)C1-6alkyl, and -N(C1-6alkyl)2;R7a, R7b, R8aand R8bare each independently selected from the group consisting of hydrogen, deuterium, hydroxyl, =0, halogen, CN, Ci-e haloalkyl, Ci-e haloalkoxy, Ci-e alkyl, O-C1.6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, where said Ci-e alkyl, O-C1.6 alkyl, C3-6 cycloalkyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =0, -CN, C1.6 haloalkyl, Ci-e haloalkoxy, C3-6 cycloalkyl, Ci-e alkyl, -O-C1.6 alkyl, phenyl, -C(0)Ci-6 alkyl, -C(O)N(H)CI-6alkyl, -C(O)N(CI-6alkyl)2, -CONH2, -C(O)N(H)CI-6alkyl, -C(O)N(Ci-6alkyl)2,-N(H)Ci-6 alkyl, and -N(Ci-6alkyl)2; orR7aand R8atogether with the carbon atom to which they are attached form a 3-5 membered cycloalkyl or 3-5 membered heterocycloalkyl group, each of which is optionally substituted with one or more groups selected from hydroxyl, halogen, =0, -CN, Ci-ehaloalkyl, Ci-6 haloalkoxy, C3-6 cycloalkyl, C1-6 alkyl, -O-C1.6 alkyl, phenyl, -C(O)Ci-6 alkyl, -C(O)N(H)Ci.6 alkyl, -C(O)N(Ci-6alkyl)2,-CONH2, -C(O)N(H)CI-6alkyl, -C(O)N(Ci-6alkyl)2, -N(H)CI-6alkyl, and -N(Ci-ealkyl)2; orR7band R8btogether with the carbon atom to which they are attached form a 3-5 membered cycloalkyl or 3-5 membered heterocycloalkyl group, each of which is optionally substituted with one or more groups selected from hydroxyl, halogen, =0, -CN, Ci-ehaloalkyl, C1-6 haloalkoxy, C3-6 cycloalkyl, Ci-e alkyl, -O-C1-6 alkyl, phenyl, -C(0)Ci-6 alkyl, -C(O)N(H)Ci- 6 alkyl, -C(O)N(Ci-6alkyl)2,-CONH2, -C(O)N(H)Ci-e alkyl, -C(O)N(Ci-6alkyl)2, -N(H)Ci-e alkyl, and -N(Ci-ealkyl)2;n is an integer of value 0, 1, 2, 3, 4 or 5;B is a cyclic group selected from 5 to 12 membered heteroaryl or C6-11aryl;C is a heterocycle containing at least one nitrogen atom in the ring, wherein theR14>Z\nR7bR8bmoiety is bonded to ring C via a nitrogen atom in ring C;A is a cyclic group selected from 5 to 15 membered heteroaryl;V is selected from the group consisting of -NH-, -C(O)N(H)-, -N(H)C(O)-, -S(O)(NH)-, -N(H)S(O)-, -S(O)N(H)-, -N(H)S(O)2- and -S(O)2N(H)-;R3and R9are independently selected from the group consisting of hydroxyl, =0, halogen, CN, Ci-ehaloalkyl, Ci-e haloalkoxy, Ci-ealkyl, O-Ci-ealkyl, C2-ealkenyl, C2-6alkynyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, -C(=0)Rb3, -C(=0)0Rc3, -C(=O)NRd3Re3, -NRd3Re3, -NRd3C(=O)Rb3,-ORc3, -SRc3, where said Ci-e alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl and phenyl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =0, CN, Ci-ehaloalkyl, Ci-e haloalkoxy, C3-6 cycloalkyl, Ci-ealkyl, O-C1.6 alkyl, -NH2, -N(H)CI-3 alkyl, and -N(Ci-3alkyl)2;where Rb3, Rc3, Rd3and Re3are independently selected from the group consisting of hydrogen, hydroxyl, Ci-e haloalkyl, O-C1.6 haloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-6 cycloalkyl, Ci-ealkyl, -O-C1.6 alkyl and Ce-isaryl, wherein said Ci-ealkyl, -O-C1.6 alkyl, Ce-isaryl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)Ci-ealkyl, -N(Ci-ealkyl)2, Ci-e haloalkyl, C3-6 cycloalkyl, C6-11aryl, 3-7 membered heterocycloalkyl, Ci-e alkyl and -O-C1.6 alkyl; orRd3and Re3, when attached to the same atom, together with the atom to which they are attached form a 3-7 membered ring, optionally containing one or more heteroatoms selected from O, N and S, and wherein said ring is optionally substituted with one or more Rf3;where each Rf3is independently selected from the group consisting of hydrogen, =0, halogen, -CN, -NH2, -N(H)CI-6 alkyl, -N(CI-6 alkyl)2, C1-6 haloalkyl, C3-6 cycloalkyl, C6-11aryl, 3-7 membered heterocycloalkyl, Ci-e alkyl and -O-C1.6 alkyl;R4is selected from the group consisting of hydroxyl, =0, halogen, -CN, Ci-e haloalkyl, C1.6 haloalkoxy, C1-6 alkyl, -O-Ci-ealkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, C6-11aryl, 5-11 membered heteroaryl, -C(=0)Rb4, -C(=0)0Rc4, -C(=O)NRd4Re4, -NRd4Re4, -NRd4C(=O)Rb4, -NRd4C(=O)ORc4, -NRd4C(=O)NRd4Re4, -NRd4S(=O)2Rb4, -NRd4S(=O)2NRd4Re4, -ORc4, -SRc4, -0C(=0)Rb4, -OC(=O)NRd4Re4, -0C(=0)0Rc4, -S(=O)2Rc4, -S(=O)Rc4, -OS(=O)Rc4, -OS(=O)2Rc4, -OS(=O)2ORc4, -S(=O)NRd4Re4, -OS(=O)2NRd4Re4and -S(=O)2NRd4Re4, where said Ci-e alkyl, -O-Ci-6alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, 5-11 membered heteroaryl and C6-11aryl, are optionally substituted with one or more groups selected from hydroxyl, halogen, =0, CN, Ci-e haloalkyl, Ci-e haloalkoxy, C3-6 cycloalkyl, C1-6 alkyl, -O-C1.6 alkyl, phenyl, -NH2, -NHR’, and -NR’R”, where R’ and R” are independently selected from C1-6 alkyl, and where said phenyl is optionally substituted with one or more of hydroxyl, halogen, =0, -CN, Ci-e haloalkyl, Ci-e haloalkoxy, C3-6 cycloalkyl, Ci-e alkyl and -O-C1.6 alkyl;where Rb4, Rc4, Rd4and Re4are independently selected from the group consisting of hydrogen, hydroxyl, Ci-e haloalkyl, -O-C1.6 haloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-6 cycloalkyl, C1-6 alkyl, -O-C1.6 alkyl and Ce-isaryl, wherein said Ci-e alkyl, Ce-isaryl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl and C3-6 cycloalkyl are optionally substituted with one or more groups selected from hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)Ci-6alkyl, -N(Ci-ealkyl)2, Ci-e haloalkyl, C3-6 cycloalkyl, C6-11aryl, 3-7 membered heterocycloalkyl, Ci-e alkyl and -O-C1.6 alkyl; orRd4and Re4, when attached to the same atom, together with the atom to which they are attached form a 3-7 membered ring, optionally containing one or more heteroatoms selected from O, N and S, and wherein said ring is optionally substituted with one or more Rf4;where each Rf4is independently selected from the group consisting of hydrogen, =0, halogen, -CN, -NH2, -N(H)CI-6 alkyl, -N(CI-6 alkyl)2, C1-6 haloalkyl, C3-6 cycloalkyl, C6-11aryl, 3-7 membered heterocycloalkyl, Ci-e alkyl and -O-C1.6 alkyl;y1, y2, z1 and z2 are integers independently selected from 0, 1, 2, 3 and 4;L is a linker moiety according to formulae L16a, L14c, L14b or L14e:(L16a);where ring J 1 is a 4 to 10 membered heterocycloalkyl ring which may optionally substituted by one or more R26;Z1is absent or a group selected from NH, N(C1-3 alkyl), O or S;n37 and n38 are independently selected from an integer of value 0 to 5; and n36 and n39 are independently selected from an integer of value 0 or 1; andR26at each occurrence is independently selected from the group consisting of hydroxyl, =0, C1.4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1.4 haloalkyl and C3-6 cycloalkyl, each of which may be optionally be substituted with one or more groups selected from C1.4 alkyl, C1.4 alkoxy, C3-6 cycloalkyl, phenyl and hydroxyl;(L14c);where n23 is an integer of value 0 or 1;n24 is an integer of value 0 to 3;n30 is an integer of value 0 or 1;rings G3 and H3 are independently selected from the group consisting of a 4 to 10 membered heterocycloalkyl, a 5 or 6 membered heteroaryl, phenyl and a C3-C10 cycloalkyl, each of which may be optionally substituted by one or more R81;R81at each occurrence is independently selected from the group consisting of hydroxyl, =0, C1.4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1.4 haloalkyl and C3-6 cycloalkyl, each of which may be optionally be substituted with one or more groups selected from C1.4 alkyl, C1.4 alkoxy, C3-6 cycloalkyl, phenyl and hydroxyl; andR12cand R13care independently selected from H, halo, C1.4 alkyl, C3-6 cycloalkyl; or R12cand R13c, together with the carbon atom to which they are attached form a C3-6 cycloalkyl group;where n20 is a number of value 1 to 5;where n21 and n27 are independently an integer of value 0 or 1;rings G2 and H2 are independently selected from the group consisting of a 4 to 10 membered heterocycloalkyl, a 5 or 6 membered heteroaryl and a C3-C10 cycloalkyl, each of which may be optionally substituted by one or more R80;R80at each occurrence is independently selected from the group consisting of hydroxyl, =0, C1.4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1.4 haloalkyl and C3-6 cycloalkyl, each of which may be optionally be substituted with one or more groups selected from C1.4 alkyl, C1.4 alkoxy, C3-6 cycloalkyl, phenyl and hydroxyl; andR10and R11are independently selected from H, C1.4 alkyl, C3-6 cycloalkyl; or R10and R11, together with the carbon atom to which they are attached form a C3-6 cycloalkyl group;where n50 and n51 are independently an integer of value 0 or 1;n52 and n53 are independently an integer of value 0, 1 or 2;rings G5, H5 and D5 are independently selected from the group consisting of a 4 to 10 membered heterocycloalkyl, a 5 or 6 membered heteroaryl and a C3-C10 cycloalkyl, each of which may be optionally substituted by one or more R8e;R8eat each occurrence is independently selected from the group consisting of hydroxyl, =0, C1.4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1.4 haloalkyl and C3-6 cycloalkyl, each of which may be optionally be substituted with one or more groups selected from C1.4 alkyl, C1.4 alkoxy, C3-6 cycloalkyl, phenyl and hydroxyl;R10eand R11eare independently selected from H, C1.4 alkyl, C3-6 cycloalkyl; or R10eand R11e, together with the carbon atom to which they are attached form a C3-6 cycloalkyl group;R12eand R13eare independently selected from H, halo, C1.4 alkyl, C3-6 cycloalkyl; or R12eand R13e, together with the carbon atom to which they are attached form a C3-6 cycloalkyl group; andM is an E3 ubiquitin ligase binding moiety.

2. A compound according to claim 1, or a salt, solvate or prodrug thereof, wherein Q is of formula Q1and Q1 is of sub-formula Q1i:

3. A compound according to claim 1 or 2, or a salt, solvate or prodrug thereof, wherein Q is of formula Q1and Q1is of sub-formula Q1awhereX1, X3and X4are independently selected from N, CH or CR4;X6is selected from N or C;X7is selected from O, S, N, CH, CR4and NR4;X9and X10are independently selected from N, CR3or CH; andR1a, R7a, R8aand n are as defined in claim 1.

4. A compound according to claim 1 or 2, or a salt, solvate or prodrug thereof, wherein B is selected from:

5. A compound according to claim 1, or a salt, solvate or prodrug thereof, wherein Q is of formula Q2and Q2is of sub-formula Q2i:

6. A compound according to claim 1 or 5, or a salt, solvate or prodrug thereof, wherein Q is of formula Q2and Q2is of sub-formula Q2a:whereX1, X3and X4are independently selected from N, CH or CR4;X6is selected from N or C;X7is selected from O, S, N, CH, CR4and NR4;X25is selected from CH2, CHR9, C(R9)2, NH, NR9, S, S(O), S(O)2or O; andR1a, R7a, R8aand n are as defined in claim 1.

7. A compound according to claim 1 or 5, or a salt, solvate or prodrug thereof, wherein C is:which may optionally be substituted with R9.

8. A compound according to any one of the preceding claims, or a salt, solvate or prodrug thereof, wherein A is a cyclic group selected from:each of which may be optionally substituted with one or more R4.

9. A compound according to any one of the preceding claims, or a salt, solvate or prodrug thereof, wherein V is selected from the group consisting of -NH- and -N(H)C(O)-.

10. A compound according to any one of the preceding claims, or a salt, solvate or prodrug thereof, wherein L is of formula L16a or L14c.

11. A compound according to any one of the preceding claims, or a salt, solvate or prodrug thereof, wherein M is of formula M6:whereRM6ais a C2-6 alkyl group which may be optionally substituted with halo, -OH, -O(Ci-4 alkyl), -S(Ci-4alkyl);RM6bis selected from hydrogen or C1.6 alkyl which may be optionally substituted with -C(O)N(H)Me, -OH, -NH2, -NH(C1-4alkyl), -N(C1-4alkyl)2, -CO2Et and -COOH;RM6cis selected from the group consisting of halo, -NO2, -CN, C2-4alkynyl, -OCF3, 5-6 membered heteroaryl, 5-6 membered heterocycloalkyl and phenyl, where said 5-6 membered heteroaryl, 5-6 membered heterocycloalkyl and phenyl are optionally substituted with one or more groups selected from halo and C1.3 alkyl; andRM6dis a 5 or 6 membered heteroaryl group optionally substituted with one or more groups selected from halo, -O(Ci-3 alkyl) and C1.3 alkyl.

12. A compound or a salt, solvate or prodrug thereof, according to any one of claims 1 to 3, of sub-formula I Yi:where R1a, R2, R7a, R8a, n, X1, X3, X4, X6, X7, X9, X10are as defined in claim 3; n23, n24, R12c, R13c·G3 and H3 are as defined in claim 1; and RM6a, RM6b, RM6cand RM6dare as defined in claim 11.

13. A compound or a salt, solvate or prodrug thereof, according to claim 1, 5 or 6, of subformula IZi:OH (lZi);where R1b, R7b, R8b, n, X25, X1, X3, X4, X6, X7are as defined in claim 6; n23, n24, R12c, R13cG3 and H3 are as defined in claim 1; and RM6a, RM6b, RM6cand RM6dare as defined in claim 11.

14. A compound or a salt, solvate or prodrug thereof, according to any one of claims 1 to 3, of sub-formula I Yii:where R1a, R2, R7a, R8a, n, X1, X3, X4, X6, X7, X9, X10are as defined in claim 3; n36, n37, n38, n39, J1 and Z1are as defined in claim 1; and RM6a, RM6b, RM6cand RM6dare as defined in claim 11.

15. A compound or a salt, solvate or prodrug thereof, according to claim 1, 5 or 6 of subformula IZii:where R1b, R7b, R8b, n, X25, X1, X3, X4, X6, X7are as defined in claim 6; n36, n37, n38, n39, J1 and Z1are as defined in claim 1; and RM6a, RM6b, RM6cand RM6dare as defined in claim 11.

16. A compound or a salt, solvate or prodrug thereof, according to any one of claims 11 to 15, wherein RM6ais an isopropyl.

17. A compound or a salt, solvate or prodrug thereof, according to any one of claims 11 to 16, wherein RM6bis selected from hydrogen or methyl.

18. A compound or a salt, solvate or prodrug thereof, according to any one of claims 11 to 17, wherein RM6dis selected from:

19. A compound or a salt, solvate or prodrug thereof, according to any one of claims 1 to 11 and 14 to 18, wherein J1 is a 4 to 9 membered heterocycloalkyl ring, suitably containing one or two nitrogen atoms, optionally substituted by one or more R26.

20. A compound or a salt, solvate or prodrug thereof, according to any one of claims 1 to 11 and 14 to 19, wherein n39 is 0, n36 is 1, n37 and n38 are each independently an integer selected from 0, 1, 2 or 3.

21. A compound or a salt, solvate or prodrug thereof, according to any one of claims 1 to 11 and 14 to 20, wherein Z1is absent or NMe.

22. A compound or a salt, solvate or prodrug thereof, according to any one of claims 1 to 13 and 16 to 18, wherein G3 is a 6-membered heterocycloalkyl group and H3 is a 6-membered heteroaryl.

23. A compound or a salt, solvate or prodrug thereof, according to any one of claims 1 to 13, 16 to 18 and 22, wherein n23 and n24 are 1.

24. A compound or a salt, solvate or prodrug thereof, according to any one of claims 3, 6, 12 to 23, wherein X7is CH and X6is N.

25. A compound or a salt, solvate or prodrug thereof, according to any one of claims 3, 6, 12 to 23, wherein X7is S and X6is C.

26. A compound or a salt, solvate or prodrug thereof, according to any one of claims 3, 6, 12 to 25, wherein X1is CH or N.

27. A compound or a salt, solvate or prodrug thereof, according to any one of claims 3, 6, 12 to 26, wherein X3and X4are CH.

28. A compound according to any one of claims 1 to 3, 8 to 12, 14, 16 to 27, or a salt, solvate or prodrug thereof, whereinmoiety is selected from the following:o29. A compound according to claim 1, 5 to 11, 13, 15 to 27, or a salt, solvate or prodrug thereof, whereinmoiety is selected from the following:A compound or a salt, solvate or prodrug thereof, selected from any one of the compounds of Table 1.

31. A pharmaceutical composition comprising a compound according to any one of claims 1 to 30, or a pharmaceutically acceptable salt, solvate or prodrug thereof, and one or more pharmaceutically acceptable excipient or carrier.

32. A compound according to any one of clauses 1 to 30, or a pharmaceutically acceptable salt, solvate or prodrug thereof, or a pharmaceutical composition according to clause 31, for use in therapy.

33. A compound according to any one of clauses 1 to 30, or a pharmaceutically acceptable salt, solvate or prodrug thereof, or a pharmaceutical composition according to clause 31, for use in the treatment or prevention of a proliferative disorder, an inflammatory disease or condition, a neurodegenerative disorder or condition, an autoimmune disorder or condition, or a metabolic disease or condition.

34. A compound according to any one of clauses 1 to 30, or a pharmaceutically acceptable salt, solvate or prodrug thereof, or a pharmaceutical composition according to clause 31, for use in the treatment or prevention of a cancer.

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