Compounds

Abstract

A compound of formula (I), or a pharmaceutically acceptable salt or hydrate thereof, is provided, wherein X-Y is -NHSO₂-. A is selected from C₄-C₈ cycloalkyl, bicyclic C₅-C₁₂ cycloalkyl, or a C₄-C₈ cy

Description

The present invention relates to compounds that are capable of modulating ERAP2. The compounds have potential therapeutic applications in the treatment of a variety of disorders, including proliferative, viral, immune and inflammatory disorders. BACKGROUND TO THE INVENTION Endoplasmic Reticulum Aminopeptidase 2 (ERAP2) is a zinc metal loprotease involved in the trimming of antigenic peptides prior to their display by major histocompatibility complex class I (MHC-I). Altered antigen processing and display in cancer cells has the potential to change the immune system recognition and response, so inhibition of ERAP2 may potentially offer new approaches to the treatment of cancer through immunomodulation. ERAP2 is also understood to be an emerging pharmacological target in autoimmunity, in particular, in the control of autoinflammatory diseases, and infectious diseases1. Crystal studies have revealed that the overall domain organisation of ERAP2 is highly similar to that of the recently determined structure of ERAP1 in its closed conformation2. A large internal cavity adjacent to the catalytic site can accommodate large peptide substrates, similar to the closed active form of ERAP1. However, the shape and electrostatic potential distribution in that cavity are distinct compared to the latter, suggesting that ERAP2 may apply distinct pressures in the antigenic peptide repertoire. The ERAP2 structure provides a structural explanation for the different peptide N-terminal specificities between ERAP1 and ERAP2 and suggests that such differences extend throughout the whole peptide sequence. ERAP2 is therefore understood to play a distinct or complementary role in antigen processing, and studies have shown that ERAP2 can complement ERAP1 activity by removing N-terminal amino acids from epitope precursor sequences that ERAP1 process poorly2. Inspired by its potential as a therapeutic target, several studies in recent years have explored the development of small molecule inhibitors of ERAP2. To date, the ERAP2 inhibitor literature is dominated by four types of inhibitor ligands that are all bound at or close to the active site (Orthoanilides e.g. 5K1V; Phosphinic pseudopeptides e.g. 4JBS, 7PFE, 7P7P; Peptidomimetic hydroxamates e.g. 5J6S, 7SHO3; Biarylsulphonamides e.g.6EA44). Despite this detailed understanding of the binding mode, binding pocket architecture and enzyme-inhibitor interactions, the best inhibitors to date are in the 100’s nM to low micromolar range and with poor selectivity against the closely related enzymes ERAP1 and I RAP. Achievement of selectivity may in some instances be even more important than potency, since complete incapacitation of antigenic peptide generation may not be desired therapeutically as opposed to the subtle modulation of a particular epitope’s generation5. Since ERAP1 and ERAP2 are highly homologous, having sequence identity of -50%, the design of inhibitors that demonstrate any degree of selectivity has proved highly challenging. The lack of developable chemotypes is underpinned by the significant obstacles presented by the inhibition of zinc-metalloproteases as an enzyme class. The most rigorously examined family in this theme are the HDAC (histone deacetylase) inhibitors, wherein only two chemotypes have progressed to market despite hundreds of accumulated years of exploration by big pharma. All hydroxamates developed to date are approved with a black box warning due to their mutagenic and clastogenic profiles6. The approved orthoanilides Entinostat, Mocetinostat are promising. This chemotype has been extensively examined by the group of Stratikos (see, e.g., 5K1V)7, but despite extensive work, little progress has been made beyond submicromolar ERAP2 potency and with poorly selective leads. The present invention seeks to provide compounds that are capable of modulating ERAP2. Such compounds have potential therapeutic applications in the treatment of a variety of disorders, including proliferative disorders, immune disorders and inflammatory disorders. STATEMENT OF INVENTION The present invention relates to aryl sulphonamide compounds that are capable of modulating ERAP2. The compounds contain an optionally substituted azetidinyl group that is linked to the sulphonamide -SO2- group via a nitrogen atom. A first aspect of the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt or hydrate thereof, (I) wherein: the group X-Y is -NHSO2-; A is selected from: a C4-C8-cycloalkyl group; a bicyclic Cs-Ci2-cycloalkyl group; and a C4-C8-cycloalkyl group fused to an aryl or heteroaryl group; each of which is optionally substituted by one or more R4 groups; B is a group: (Rs)m wherein the wavy line indicates the point of attachment to Y; Ri is selected from haloalkyl and OR3, R2 is selected from H and halo; R3 is selected from alkyl and benzyl; each R4 is independently selected from alkyl and halo; Rs is at each occurrence independently selected from COOH, (CRiaRiOaNReR?, alkyl, haloalkyl, halo, alkoxy, hydroxyalkyl, cycloalkyl, heteroaryl, and heterocycloalkyl, wherein said cycloalkyl, heteroaryl and heterocycloalkyl are each optionally further substituted by one or more groups selected from alkyl, haloalkyl, NH2 and halo; each Riaand each Rwis independently selected from H, OH, alkyl and hydroxyalkyl; each a is independently 0, 1,2 or 3; R6 and R7 are each independently selected from H, alkyl, SO2-alkyl, haloalkyl and heterocycloalkyl; and m is an integer from 0 to 6. The invention also encompasses enantiomers of compounds of formula (I), and mixtures of enantiomers, including racemic mixtures. Advantageously, the presently claimed compounds are capable of modulating ERAP2, thereby rendering the compounds of therapeutic interest in the treatment of various disorders, for example, in the field of oncology and immuno-oncology. In particular, compounds according to the present invention exhibit excellent potency against ERAP2. A second aspect of the invention relates to a pharmaceutical composition comprising at least one compound as described above and a pharmaceutically acceptable carrier, diluent or excipient. A third aspect of the invention relates to a compound as described above for use in medicine. A fourth aspect of the invention relates to a compound as described above for use in treating or preventing a disorder selected from a proliferative disorder, an immune disorder, a viral disorder, preeclampsia, and an inflammatory disorder. A fifth aspect of the invention relates to the use of a compound as described above in the preparation of a medicament for treating or preventing a disorder selected from a proliferative disorder, an immune disorder, a viral disorder, preeclampsia, and an inflammatory disorder. A sixth aspect of the invention relates to a compound as described above for use in the prevention or treatment of a disorder caused by, associated with or accompanied by any abnormal ERAP2 activity. A seventh aspect of the invention relates to the use of a compound as described above in the preparation of a medicament for the prevention or treatment of a disorder caused by, associated with or accompanied by abnormal ERAP2 activity. An eighth aspect of the invention relates to a method of treating a mammal having a disease state alleviated by modulation of ERAP2, wherein the method comprises administering to a mammal a therapeutically effective amount of a compound as described above. A ninth aspect of the invention relates to a compound as described above for use in treating or preventing a disease state alleviated by modulation of ERAP2. A tenth aspect of the invention relates to the use of a compound as described above in the preparation of a medicament for treating or preventing a disease state alleviated by modulation of ERAP2. An eleventh aspect of the invention relates to a method of treating or preventing a disorder selected from a proliferative disorder, an immune disorder, a viral disorder preeclampsia, and an inflammatory disorder in a subject, wherein the method comprises administering to the subject a therapeutically effective amount of a compound as described above. DETAILED DESCRIPTION The present invention relates to compounds that are capable of modulating ERAP2. “Alkyl” is defined herein as a straight-chain or branched alkyl radical, preferably C1-20 alkyl, more preferably C1-12 alkyl, even more preferably C1-10 alkyl or C1-6 alkyl, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, hexyl. Preferably, the alkyl group is a Ci-4-alkyl group. “Cycloalkyl” is defined herein as a cyclic alkyl ring, preferably, C3-7-cycloalkyl, more preferably Cs-e-cycloalkyl. Preferred examples include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl, or a fused bicyclic ring system such as norbornane. “Halogen” is defined herein as chloro, fluoro, bromo or iodo. Haloalkyl” is defined herein as a straight-chain or branched alkyl radical as defined above, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, hexyl, that is substituted with one or more halogen atoms (that may be the same or different), such as fluorine, chlorine, bromine, and iodine. Preferably, the haloalkyl is a Ci-2ohaloalkyl, more preferably a C1-12 haloalkyl, even more preferably a C1-10 haloalkyl or a C1-6 haloalkyl, or a C1-3 haloalkyl. Preferred examples are CF3 and CHF2, with CF3 being particularly preferred. “Alkoxy” is defined herein as an oxygen atom bonded to an alkyl group as defined above, for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, tertbutoxy, pentoxy and hexoxy. Preferably, the alkoxy is a C1-20 alkoxy, more preferably a C1-12 alkoxy, even more preferably C1-10 alkoxy or a C1-6 alkoxy, or a C1-3 alkoxy. A particularly preferred example is methoxy (-OCH3). “Haloalkyloxy” is defined herein as an alkoxy group as defined above substituted with one or more halogen atoms (that may be the same or different), such as fluorine, chlorine, bromine, and iodine. As used herein, the term “alkenyl” refers to both straight and branched carbon chains which have at least one carbon-carbon double bond. In some embodiments, alkenyl groups may include C2-C12 alkenyl groups. In other embodiments, alkenyl includes C2-C10, C2-C8, C2-C6 or C2-C4 alkenyl groups. In one embodiment of alkenyl, the number of double bonds is 1-3; in another embodiment of alkenyl, the number of double bonds is one. Other ranges of carbon-carbon double bonds and carbon numbers are also contemplated depending on the location of the alkenyl moiety on the molecule. “C2-Cio-alkenyl” groups may include more than one double bond in the chain. As used herein, the term “alkynyl” refers to both straight and branched carbon chains which have at least one carbon-carbon triple bond. In some embodiments, alkynyl groups may include C2-C12 alkynyl groups. In other embodiments, alkynyl includes C2-C10, C2-C8, C2-C6 or C2-C4 alkynyl groups. In one embodiment of alkynyl, the number of triple bonds is 1-3; in another embodiment of alkenyl, the number of triple bonds is one. A particularly preferred alkynyl group is -C=CH. As used herein, the term “polycyclic group” means a group comprising two or more cyclic groups which may be fused, unfused, bridged or spirocyclic. As used herein, the term “aryl” refers to a C6-12 aromatic group, which may be benzocondensed, for example, phenyl or naphthyl. “Heteroaryl” is defined herein as a monocyclic or polycyclic aromatic ring comprising one or more heteroatoms (that may be the same or different), such as oxygen, nitrogen or sulphur. Preferably, the heteroaryl is a monocyclic or bicyclic C2-12 aromatic ring comprising one or more heteroatoms. Examples of suitable heteroaryl groups include thienyl, furanyl, pyrrolyl, pyridinyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, thiadiazolyl etc and benzo derivatives thereof, such as benzofuranyl, benzothienyl, benzimidazolyl, indolyl, isoindolyl, indazolyl etc.; or pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazinyl, tetrazolyl, etc. and benzo derivatives thereof, such as quinolinyl, isoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, naphthyridinyl etc. Particularly preferred heteroaryl groups include 1 / 7-imidazol-5-yl, 1 / 7-imidazol-4-yl, 1 / 7-imidazol-2-yl, 1 / - / -pyrrol-1-yl, 1 / 7-pyrrol-2-yl, 1 / 7-pyrrol-3-yl, 1 / 7-pyrrol-4-yl, 1 / 7-pyrrol-5-yl, 1 / - / -pyrazol-1-yl, 1 / - / -pyrazol-5-yl, 1 / 7-pyrazol-3-yl, 1 / - / -pyrazol-4-yl, oxazol-2-yl, oxazol-4-yl, oxazol-5-yl, 1 / 7-1,2,4-triazol-3-yl, 1 / 7-1,2,4-triazol-5-yl, 1 / 7-1,2,4-triazol-1-yl, 1 / 7-1,2,3-triazol-4-yl, 1 / 7-1,2,3-triazol-5-yl, 1 / 7-1,2,3-triazol-1-yl, thiazol-5-yl, thiazol-4-yl, 1 / 7-1,2,3,4-tetrazol-4-yl, 2 / 7-1,2,3,4-tetrazol-5-yl, oxazol-5-yl, oxazol-4-yl, oxazol-2-yl, isoxazol-3-yl, isoxazol-4-yl, isoxazol-5-yl, isothiazol-3-yl, isothiazol-4-yl, isothiazol-5-yl, pyradizin-3-yl, pyradizin-4-yl, pyrazinyl, 1,3,4-oxadizol-2-yl, 1,3,4-oxadizol-5-yl, 1,2,5-oxadiazol-3-yl, 1,2,5-oxadiazol-4-yl, 1,2,3-oxadiazol-4-yl, 1,2,3-oxadiazol-5-yl, 1,2,4-oxadiazol-3-yl, 1,2,4-oxadiazol-5-yl, isoxazol-5-yl, isoxazol-4-yl and isoxazol-3-yl. “Heterocycloalkyl” refers to a cyclic aliphatic group containing one or more heteroatoms selected from nitrogen, oxygen and sulphur, which is optionally interrupted by one or more -(CO)- groups in the ring and / or which optionally contains one or more double bonds in the ring. The point of attachment can be via a carbon atom or via a heteroatom. Preferably, the heterocycloalkyl group is saturated. Preferably, the heterocycloalkyl group is monocyclic or bicyclic. Preferably, the heterocycloalkyl group is a C3-7-heterocycloalkyl, more preferably a C3-6-heterocycloalkyl. Alternatively, the heterocycloalkyl group is a C4-7-heterocycloalkyl, more preferably a C4-6-heterocycloalkyl. Preferred heterocycloalkyl groups include, but are not limited to, piperazinyl, piperidinyl, morpholinyl, thiomorpholinyl, pyrrolidinyl, tetrahydrofuranyl and tetrahydropyranyl. Where the compound of the invention contains one or more chiral centres, the invention encompasses all enantiomers and diastereomers thereof, as well as mixtures thereof. Racemic mixtures can be used to prepare enantiomerically pure R- and S-forms by separating the enantiomers using standard methods, for example by chemical resolution using optically active acid or by the use of column chromatography or reverse-phase column chromatography using a substantially optically active (or “chiral”) stationary phase as known to those skilled in the art. Racemic mixtures can also be used to prepare enantiomerically enriched mixtures of the S- and R-forms. Mixtures enriched with either the R- or S-enantiomer can also be obtained from the appropriate enantiomerically enriched precursors. In one preferred embodiment of the invention, the compound is in the form of a mixture comprising enantiomers wherein the weightweight ratio is at least approximately 2:1 or greater, preferably at least approximately 5:1 or greater, most preferably at least approximately 10:1 or greater in favour of the enantiomer that displays significant in vitro and / or in vivo activity (the eutomer). In one embodiment, the compound is in the form of a mixture comprising the S-enantiomer and the R-enantiomer, wherein the weightweight ratio of R-enantiomer to S-enantiomer is greater than 1.05:1, more preferably, greater than 2:1, even more preferably greater than 5:1, even more preferably greater than 10:1. In one embodiment, the compound is in the form of a mixture comprising the S-enantiomer and the R-enantiomer, which is substantially enriched with the R-enantiomer. In one embodiment, the compound is in the form of a mixture comprising the S-enantiomer and the R-enantiomer, wherein the weightweight ratio of S-enantiomer to R-enantiomer is greater than 1.05:1, more preferably, greater than 2:1, even more preferably greater than 5:1, even more preferably greater than 10:1. In one embodiment, the compound is in the form of a mixture comprising the S-enantiomer and the R-enantiomer, which is substantially enriched with the S-enantiomer. Compounds of formula (I) One aspect of the invention relates to compounds of formula (I), and pharmaceutically acceptable salts and hydrates thereof: wherein: the group X-Y is -NHSO2-; A is selected from: a C4-C8-cycloalkyl group; a bicyclic Cs-Ci2-cycloalkyl group; and a C4-C8-cycloalkyl group fused to an aryl or heteroaryl group; each of which is optionally substituted by one or more R4 groups; B is a group: wherein the wavy line indicates the point of attachment to Y; Ri is selected from haloalkyl and OR3, R2 is selected from H and halo; R3 is selected from alkyl and benzyl; each R4 is independently selected from alkyl and halo; Rs is at each occurrence independently selected from COOH, (CRiaRiOaNReR?, alkyl, haloalkyl, halo, alkoxy, hydroxyalkyl, cycloalkyl, heteroaryl, and heterocycloalkyl, wherein said cycloalkyl, heteroaryl and heterocycloalkyl are each optionally further substituted by one or more groups selected from alkyl, haloalkyl, NH2 and halo; each Riaand each Rwis independently selected from H, OH, alkyl and hydroxyalkyl; each a is independently 0, 1,2 or 3; Re and R? are each independently selected from H, alkyl, SO2-alkyl, haloalkyl and heterocycloalkyl; and m is an integer from 0 to 6. In one preferred embodiment: the group X-Y is -NHSO2-; A is selected from: a C4-C8-cycloalkyl group; a bicyclic Cs-Ci2-cycloalkyl group; and a C4-C8-cycloalkyl group fused to an aryl or heteroaryl group; each of which is optionally substituted by one or more R4 groups; B is a group: (R5)m wherein the wavy line indicates the point of attachment to Y (i.e. the -SO2- group); Ri is selected from haloalkyl and OR3, R2 is selected from H and halo; R3 is selected from alkyl and benzyl; each R4 is independently selected from alkyl and halo; Rs is at each occurrence independently selected from COOH, NReR?, alkyl, haloalkyl, halo, alkoxy, hydroxyalkyl, heteroaryl, and heterocycloalkyl, wherein said heteroaryl and heterocycloalkyl are each optionally further substituted by one or more groups selected from alkyl, haloalkyl and halo; Re and R? are each independently selected from H, alkyl, haloalkyl and heterocycloalkyl; and m is an integer from 0 to 6. In the compounds of the invention, X-Y is -NHSO2-, i.e. the compounds are of the formula: In one preferred embodiment, Ri is haloalkyl, more preferably CF3. In one preferred embodiment, R2 is H or F, more preferably F. In one preferred embodiment, A is bicyclic Cs-Ci2-cycloalkyl group. The bicyclic group may be a bridged, fused or spirocyclic group. Preferably, in each case, each ring of the bicyclic group is independently a 3-, 4-, 5- or 6-membered ring. Even more preferably, each ring of the bicyclic group is independently a 4-, 5- or 6-membered ring. In one preferred embodiment, A is a spirocyclic group, for example, a bicyclic group in which two cycloalkyl rings are connected through a common atom (a spiro carbon). Preferred bicyclic spirocyclic groups have the following carbocyclic “base” skeletons: spiro[2,3]hexane, spiro[3,3]heptane, spiro[2,4]heptane, spiro[3,4]octane, spiro[2,5]octane, spiro[4,4]nonane, spiro[3,5]nonane, spiro[4,5]decane, spiro[3,6]decane, spiro[5,5]undecane, or spiro[5,6]dodecane. In one preferred embodiment, A is a fused bicyclic Cs-Ci2-cycloalkyl group wherein two cycloalkyl rings share two adjacent atoms. In other words, the rings share one covalent bond, i.e. the bridgehead atoms are adjacent (directly connected). In one preferred embodiment, A is a bridged bicyclic Cs-Ci2-cycloalkyl group wherein two cycloalkyl rings share two non-adjacent atoms, i.e. the bridgehead atoms are separated by at least one carbon atom. In one preferred embodiment, A is a C4-C8-cycloalkyl group fused to an aryl or heteroaryl group. In one preferred embodiment, A is a fused or bridged bicyclic Cs-Cw-cycloalkyl group. In one preferred embodiment, A is a Cs-Cy-cycloalkyl group fused to a phenyl group, or 5 a Cs-Crcycloalkyl group fused to 5- or 6-membered heteroaryl group, wherein said phenyl group and said 5- or 6-membered heteroaryl group are each optionally substituted by one, two or three R4 groups. In one preferred embodiment, A is a C4-C8-cycloalkyl group optionally substituted by one or more R4 groups. 10 In one preferred embodiment, A is selected from: wherein n is 0, 1 or 2. In the above representations, where the A group is bicyclic, the R4 group(s), if present, can be on either or both rings. 5 In one preferred embodiment, A is: wherein n is 0, 1 or 2. In one preferred embodiment, A is selected from: 10 In one particularly preferred embodiment, A is selected from: In one preferred embodiment, each R4 is independently selected from Me, Et and F. In one preferred embodiment, Ri is CF3, R2 is F or H, X-Y is NHSO2, and A is selected from: In one particularly preferred embodiment, A is selected from: Xe In one preferred embodiment, m is 1 or 2. In one preferred embodiment, Rs is at each occurrence independently selected from (CRiaRib)aNR6R7, alkyl, hydroxyalkyl, heteroaryl, cycloalkyl and heterocycloalkyl, wherein said heteroaryl and heterocycloalkyl are each optionally further substituted by one or more alkyl groups. In one preferred embodiment, each a is independently 0, 1 or 2, more preferably 0 or 1, even more preferably 0. In one preferred embodiment, each Riaand each Ribis independently selected from H, and alkyl, and each a is independently 0 or 1. In one preferred embodiment, Rs is at each occurrence independently selected from NRsR7, alkyl, hydroxyalkyl, heteroaryl and heterocycloalkyl, wherein said heteroaryl and heterocycloalkyl are each optionally further substituted by one or more alkyl groups. In one preferred embodiment, B is: In one preferred embodiment, Rs is selected from (CRiaRib)aNRsR7, CH2OH, heteroaryl, cycloalkyl and heterocycloalkyl wherein said heteroaryl and heterocycloalkyl are optionally substituted by one or more alkyl groups. In one preferred embodiment, Rs is selected from NR6R7, CH2NR6R7, C(Me)2NRsR7, CH2OH, heteroaryl, and heterocycloalkyl wherein said heteroaryl and heterocycloalkyl are optionally substituted by one or more alkyl groups. In one preferred embodiment, R5 is (CRiaRib)aNR6R7. More preferably, R5 is selected from CH2NH2, C(Me)2NH2and NHSO2Me. In one preferred embodiment, R5 is (CRiaRib)aNRsR7and Re and R?are selected from methyl and oxetanyl, preferably wherein either both Re and R7 are methyl or Re is methyl and R7 is oxetanyl. Preferably, a is 0 or 1. In one preferred embodiment, Re and R7each independently selected from H and alkyl, more preferably H and Me. More preferably still, Re and R7are both H. In one preferred embodiment, one of Re and R7 is H and the other is SO2-alkyl. In one preferred embodiment, Rs is selected from cyclopropyl, tetrazolyl, triazolyl, pyrazolyl, imidazolyl, pyridinyl, pyrimidinyl, pyrazinyl, morpholinyl, piperidinyl, piperazinyl, isoxazolyl, 1H-benzo[d]imidazolyl, and pyrrolidinyl, each of which is optionally substituted with one or more groups selected from alkyl and NR6R7. In one preferred embodiment, Rs is selected from tetrazolyl, triazolyl, pyrazolyl, imidazolyl, pyridinyl, pyrimidinyl, pyrazinyl, morpholinyl, piperidinyl, piperazinyl, isoxazolyl, 1H-benzo[d]imidazolyl, and pyrrolidinyl, each of which is optionally substituted with alkyl. In one particularly preferred embodiment, Rs is selected from tetrazolyl, triazolyl, piperazinyl, morpholinyl, imidazolyl, pyrimidinyl, pyrrolidinyl, pyridinyl, and pyrazinyl, each of which is optionally substituted with alkyl. Most preferably, Rs is selected from tetrazolyl, triazolyl, and piperazinyl, each of which is optionally substituted with alkyl. In one particularly preferred embodiment, R5 is a tetrazolyl: optionally substituted with a Me group. In one preferred embodiment, Rs is selected from: each of which is optionally substituted with one or more groups selected from alkyl and 5 NReR?, preferably one or more groups selected from methyl and NH2, more preferably one or more Me groups. In one preferred embodiment, R5 is selected from: each of which is optionally substituted with alkyl, preferably methyl. In one particularly preferred embodiment, Rs is selected from: each of which is optionally substituted with alkyl, preferably methyl. In an even more preferred embodiment, Rs is selected from: each of which is optionally substituted with alkyl, preferably methyl. In one preferred embodiment, R6and R7are selected from methyl and oxetanyl, preferably wherein either both R6 and R7 are methyl or R6 is methyl and R7 is oxetanyl. In one preferred embodiment, the compound of formula (I) is selected from the following. In the structures depicted herein, where the absolute stereochemistry of a bond is known (for example, derived from a bona fide chiral starting material), then the assignment is denoted by (R) or (S) in the conventional manner. Where the absolute configuration is unknown, the bonds are drawn in the plane (flat), and the descriptor adds what is known, for example, “trans racemate”, “trans relative”, “trans diastereomer D1” and the like: Cl h C| xC JL J o 0 (9) J? O. / 21 ^CD °^S / =2 (10) r FX ^F r FX XF F F r J F1 N^ JH h rr^ s^N^N-J V &^00 ?F (11) || ^'N'^ 1 n I J flf A Ji J 0 0 f FAF (12) X c n-n JI N JH H Cn ,nJ h T / b XF (13) N JT F^^ F1 kCj h H rY N A L ^00 XF (14) J F^ F1 r^N l y « H N___N-J | L ^00 XF (15) £ F^ F^ NH H -k N^ ^N-J Y A J°° CF (16) F^ F1 o * H ry^K^ y Joo XF (17) h £ F^^ F1 H fk^OH P.N nJ T / / \\ Joo ^F (18) X F^ F1 ^0 "h ryN^ L / Nx_n-J Y &J 0 0 XF (21) K pX| d 1 H h ryN-rt Y / ¾ jJ O 0 XF (22) J / N-N 1 / N h yY^n / L ,N___N-J Joo XF (23) f F^ F I O< / ZT °'S vf z' (24) F^ FX H H r-r^ V 'NJ J ° ° F'F F (25) x F^^ F' '7 i O. / ZI °^s A ,O (26) F^^ Y z \ o \ z\ ^O w; IZ ° (27) r x F^^ F °yh \IH u Ln. ,nL Y Joo ^F (28) N FX F F Y'NH H ____-N.X M h rY ° ,N^ Y / / ¾ Joo ^F (29) N x F^ F1 0 1 nh H H >.yN. ,Nj Y / / ¾ .Joo XF (30) CM T Z ^Z IZ 0 d';' (31) X\ NH2 h Y / X .N-J 111 A JI A 00 F y F f (32) r FX ^F F b J F I JH h nh2 -NJ Y / ¾ ^00 X (33) b F^ F' oA° 1 NH JH H A 0 0 XF (34) b J F I JH H rv^NH2 I / / ¾ ^00 XF (35) x F^ H / ^X^NH2 k _N. Y / ¾ A 0 0 ^F (36) | J O-NH „ A. _bk „NA (ll^ / / S" Ji J 00 F FTF (37) ^^*b x F^ F I ,H h ry A 0 0 XF (38) and pharmaceutically acceptable salts and hydrates thereof. In one preferred embodiment, the compound of the invention exhibits an IC50 value in the ERAP2 SIINFEKL assay of less than about 10 pM. More preferably, the 5 compound exhibits an IC50 value in the ERAP2 SIINFEKL assay of less than about 5 pM, even more preferably, less than about 1 pM, even more preferably, less than about 0.1 pM, even more preferably, less than about 0.01 pM. Further details of this assay are detailed in the accompanying examples. In one preferred embodiment, the compound of the invention exhibits an IC50 value in the ERAP2 SIINFEKL assay of about 750 nM or less. More preferably, the compound exhibits an IC50 value in the ERAP2 SIINFEKL assay of about 250 nM or less, even more preferably of about 100 nM or less. In one preferred embodiment, the compound of the invention is selected from compounds 1, 3, 4, 9, 10, 11, 12, 13, 14, 16, 21, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37 and 38. In an even more preferred embodiment, the compound of the invention is selected from the following compounds 3, 10, 12, 13, 14, 26, 29, 30, 31, 32, 33, 35, 37 and 38. THERAPEUTIC APPLICATIONS A further aspect of the invention relates to compounds as described herein for use in medicine. The compounds have particular use in the field of oncology and immune oncology, as described in more detail below. Yet another aspect of the invention relates to compounds as described herein for use in treating or preventing a disorder selected from a proliferative disorder, an immune disorder, an inflammatory disorder, preeclampsia and a viral disorder. In a preferred embodiment, the compound of the invention modulates ERAP2. In one embodiment the compound inhibits the activity of ERAP2. In an alternative embodiment the compound increases the activity of ERAP2. In one embodiment the compound of the invention may change the repertoire of presented antigens. One aspect of the invention relates to a compound as described herein for use in treating a proliferative disorder. Preferably, the proliferative disorder is a cancer or leukemia. A cancer may be selected from: basal cell carcinoma, biliary tract cancer; bladder cancer; bone cancer; brain and central nervous system cancer; breast cancer; cancer of the peritoneum; cervical cancer; choriocarcinoma; colon and rectum cancer; connective tissue cancer; cancer of the digestive system; endometrial cancer; esophageal cancer; eye cancer; cancer of the head and neck; gastric cancer (including gastrointestinal cancer); glioblastoma; hepatic carcinoma; hepatoma; intraepithelial neoplasm; kidney or renal cancer; larynx cancer; leukemia; liver cancer; lung cancer (e.g., small-cell lung cancer, non-small cell lung cancer, adenocarcinoma of the lung, and squamous carcinoma of the lung); melanoma; myeloma; neuroblastoma; oral cavity cancer (lip, tongue, mouth, and pharynx); ovarian cancer; pancreatic cancer; prostate cancer; retinoblastoma; rhabdomyosarcoma; rectal cancer; cancer of the respiratory system; salivary gland carcinoma; sarcoma; skin cancer; squamous cell cancer; stomach cancer; testicular cancer; thyroid cancer; uterine or endometrial cancer; cancer of the urinary system; vulval cancer; lymphoma including Hodgkin’s and non-Hodgkin’s lymphoma, as well as B-cell lymphoma (including low grade / follicular non-Hodgkin’s lymphoma (NHL); small lymphocytic (SL) NHL; intermediate grade / follicular NHL; intermediate grade diffuse NHL; high grade immunoblastic NHL; high grade lymphoblastic NHL; high grade small non-cleaved cell NHL; bulky disease NHL; mantle cell lymphoma; AIDS-related lymphoma; and Waldenstrom’s Macroglobulinemia; chronic lymphocytic leukemia (CLL); acute lymphoblastic leukemia (ALL); Hairy cell leukemia; chronic myeloblastic leukemia; as well as other carcinomas and sarcomas; and post-transplant lymphoproliferative disorder (PTLD), as well as abnormal vascular proliferation associated with phakomatoses, edema (such as that associated with brain tumors), and Meigs’ syndrome. In one preferred embodiment, the cancer is bladder cancer. Without wishing to be bound by theory, it is understood that ERAP2 modulators are capable of qualitatively changing the antigen and neoantigen repertoire of cancer cells, as measured using immunopeptidomics and mass spectrometry analysis. For example, the ERAP2 modulator is preferably capable of changing at least 10% of the antigen and neoantigen repertoire of cancer cells, as measured using immunopeptidomics and mass spectrometry analysis. This change is believed to be caused in part by an upregulation in the presentation of certain antigens and neoantigens and also by the presentation of entirely novel antigens and neoantigens. Both changes may lead to an increase in the visibility of the tumour to the immune system, leading to measurable changes in the CD8+ T cell repertoire and CD8+ T cell activation status. This change in CD8+ T cell response may in turn lead to immune-mediated tumour clearance, and can be potentially enhanced by combining with cancer therapeutics such as antibody checkpoint inhibitors (e.g. anti-PD-1). Without wishing to be bound by theory, it is understood that modulators of ERAP2 cause killing of cancer cells by natural killer (NK) cells due to disruption of the interaction between killer cell Ig-like receptors (KIR) or lectin-like receptor CD94-NKG2A on NK cells with classical or non-classical MHC-l-peptide (pMHC-l) complexes on cancer cells. In one preferred embodiment, the disorder is cancer, and the compound increases the visibility of cancer cells to the immune system by altering the repertoire of antigens and neoantigens presented to the immune system. A further aspect of the invention relates to a method of increasing the visibility of cancer cells to the immune system in a subject by altering the repertoire of antigens and neoantigens presented to the immune system, said method comprising administering to the subject a compound of formula (I). In one preferred embodiment, the compound increases the CD8+ T cell response to the cancer cell. In one preferred embodiment, the compound of the invention is for use in the treatment of a disease of uncontrolled cell growth, proliferation and / or survival, an inappropriate cellular immune response, or an inappropriate cellular inflammatory response, particularly in which the uncontrolled cell growth, proliferation and / or survival, inappropriate cellular immune response, or inappropriate cellular inflammatory response is modulated by the ERAP2 pathway. In one preferred embodiment, the disease of uncontrolled cell growth, proliferation and / or survival, inappropriate cellular immune response, or inappropriate cellular inflammatory response is selected from a haematological tumour, a solid tumour and / or metastases thereof. More preferably, the compound is for use in treating a disorder selected from leukaemias and myelodysplastic syndrome, malignant lymphomas, head and neck tumours including brain tumours and brain metastases, tumours of the thorax including non-small cell and small cell lung tumours, gastrointestinal tumours, endocrine tumours, mammary and other gynaecological tumours, urological tumours including renal, bladder and prostate tumours, skin tumours, and sarcomas, and / or metastases thereof. The compound may kill cancer cells, reduce the number of proliferating cells in the cancer and / or reduce the volume or size of a tumour comprising the cancer cells. The compound may reduce the number of metastasising cancer cells. In one embodiment the compound may be used (or is for use) in treating cancer in a subject who has previously had cancer. The compound may be used to reduce the likelihood of the cancer recurring, or the likelihood of further cancer developing. The compound may induce a neoantigen in the recurring or further cancer to which the subject already possesses an existing immune response. As such, the compound may increase or boost an immune response against the cancer. In one embodiment the compound is for use in preventing cancer. The compound may be used for prophylaxis against the development of cancer. That is to say, the compound may stimulate an immune response, such as a vaccine response, against a future cancer. The compound may stimulate in a subject an immune response directed to a neoantigen. Once a cancer develops in the subject, they may be treated again with the compound (or a different compound) to stimulate development of the same neoantigen, thereby eliciting the subject’s pre-existing immune response to said neoantigen to treat or prevent the cancer. The same or a different compound may be used before and after the cancer develops in a subject. In one embodiment the compound may be used for the prevention of cancer. In one embodiment the subject may previously have had cancer, may have a familial history of cancer, may have a high risk for developing cancer, may have a genetic predisposition to developing cancer, or may have been exposed to a carcinogenic agent. In one embodiment the subject may be in remission from cancer. One embodiment provides ex vivo generated antigen-presenting cells, such as dendritic cells (DCs). The antigen-presenting cells may be produced ex vivo to present neo-antigens, such as those generated by a compound according to the present invention. The compound may be used in a method for producing ex vivo an antigen-presenting cell which presents a neo-antigen, and wherein the cell may be used as a vaccine against cancer. The antigen presenting cell such as a dendritic cell may be pulsed or loaded with the neo-antigen or genetically modified (via DNA or RNA transfer) to express one, two or more neo-antigens. Methods of preparing dendritic cell vaccines are known in the art. The neo-antigen may be generated from the subject’s normal tissue in which ERAP2 is modulated with a compound according to the invention. Sources of normal tissue may be fibroblasts or B cells, for example, that can be readily expanded in vitro. Alternatively, RNA from the cancer, total or mRNA enriched poly A+ RNA may be used. Poly A+ RNA can be also amplified to generate sufficient antigen for DC loading and thereby limit the ex vivo culture step. In one embodiment a dendritic cell which has been treated with the compound as described above may be used to treat a subject. The dendritic cell may be contacted with the compound ex vivo, and then the dendritic cell may be administered to the subject. The compound may therefore be used in vitro or in vivo, for example either for in situ treatment or for ex vivo treatment followed by the administration of the treated cells to the subject. Another aspect of the invention relates to a compound as described above for use in treating an immune disorder. In one preferred embodiment, the immune disorder is an autoimmune disorder. Examples of the autoimmune disorders include, but are not limited to: rheumatoid arthritis (RA), myasthenia gravis (MG), multiple sclerosis (MS), systemic lupus erythematosus (SLE), autoimmune thyroiditis (Hashimoto’s thyroiditis), Graves’ disease, inflammatory bowel disease, autoimmune uveoretinitis, polymyositis and certain types of diabetes, systemic vasculitis, polymyositis-dermatomyositis, systemic 29 sclerosis (scleroderma), Sjogren’s Syndrome, ankylosing spondylitis and related spondyloarthropathies, rheumatic fever, hypersensitivity pneumonitis, allergic bronchopulmonary aspergillosis, inorganic dust pneumoconioses, sarcoidosis, autoimmune hemolytic anemia, immunological platelet disorders, cryopathies such as cryofibrinogenemia, psoriasis, Behget’s disease, birdshot chorioretinopathy, autoimmune polyendocrinopathies. Polymorphisms in the ERAP2 gene that impact ERAP2 enzymatic activity are strongly associated with an increased risk of autoimmunity, including the diseases ankylosing spondylitis, psoriasis, inflammatory bowel disease, and birdshot chorioretinopathy8’9’10. Variants of ERAP2 that reduce ERAP2 enzymatic activity are protective against disease, whilst those that reportedly elevate activity are associated with increased disease risk9. This suggests that modulation of ERAP2 activity could be an effective treatment for autoimmune diseases. Thus, in one preferred embodiment, the immune disorder is selected from ankylosing spondylitis, psoriasis, inflammatory bowel disease, and birdshot chorioretinopathy. In one preferred embodiment, the immune disorder is ankylosing spondylitis. Ankylosing spondylitis (AS) is a type of arthritis in which there is long term inflammation of the joints of the spine. Typically, the joints where the spine joins the pelvis are also affected. Occasionally other joints such as the shoulders or hips are involved. Between 0.1% and 1.8% of people are affected and onset is typically in young adults. Although the cause of ankylosing spondylitis is unknown, it involves a combination of genetic and environmental factors. More than 90% of those affected have a specific human leukocyte antigen known as the HLA-B27 antigen11. In addition, certain variants of ERAP2, in conjunction with HLA-B27, are clearly associated with either an elevated or reduced risk of disease, providing evidence of a clear role for modulated antigen presentation in disease12. There is no cure for ankylosing spondylitis and current treatments serve only to improve symptoms and prevent worsening. Medications used to date include NSAIDs, steroids, DMARDs such as sulfasalazine, and biologic agents such as infliximab. In one preferred embodiment, the immune disorder is birdshot chorioretinopathy. Birdshot chorioretinopathy, also known as Birdshot Uveitis or HLA-A29 Uveitis, is a rare form of bilateral posterior uveitis affecting the eye. It causes severe, progressive inflammation of both the choroid and retina. Symptoms include floaters, blurred vision, photopsia (flashing lights in eyes), loss of color vision and nyctalopia. Birdshot chorioretinopathy is thought to be an autoimmune disease. The disease has strong association with the Human leukocyte antigen haplotype (HLA)-A29. This indicates a role for T-lymphocytes in the pathogenesis. Birdshot chorioretinopathy is associated with IL-17, a hallmark cytokine of TH17 cells that play an important role in autoimmunity13’14. A genome-wide association study has ascertained HLA-A29:02 as the primary risk factor and identified that both ERAP1 and ERAP2 are associated with birdshot chorioretinopathy15’16. Genetic variants within the ERAP1 and ERAP2 loci modulate enzyme activity and also mRNA and protein expression. ERAP2 is an aminopeptidase that, together with ERAP1, trims peptides in the endoplasmic reticulum and loads these peptides on HLA molecules for presentation to T cells of the immune system. In one preferred embodiment, the immune disorder is psoriasis. Psoriasis is a chronic skin disease in which skin cells rapidly build up on the surface of the skin forming scales and red patches that are itchy and sometimes painful. The cause is not well-defined but includes both environmental and genetic factors. A large meta-analysis has identified a significant risk allele for psoriasis as resulting in higher ERAP2 expression17. There is no cure for psoriasis and current treatments serve only to improve symptoms and prevent worsening. Medications used in therapy include steroids, methotrexate, sulfasalazine, and biologic agents such as etanercept. In one preferred embodiment, the autoimmune disorder is inflammatory bowel disease (IBD). IBD is a term for a group of inflammatory conditions of the colon and small intestine, with Crohn’s disease and ulcerative colitis being the two major forms of the disease. IBD is characterised by chronic and relapsing inflammation of the intestine, although the exact cause is unknown. One genome-wide association study has, however, established a connection between ERAP2 expression and IBD18, suggesting that ERAP2 modulators may be effective in treating the condition. In a particularly preferred embodiment, the autoimmune disorder is selected from Crohn’s disease and ulcerative colitis. Another aspect of the invention relates to a compound as described above for use in treating or preventing a viral disorder. Modulators of ERAP2 such as the compounds described herein are capable of changing the antigen repertoire of multiple viruses, which leads to the recognition and destruction of viral infected cells. Accordingly, ERAP2 modulators have potential therapeutic applications in the treatment of viral infection and diseases. ERAP2 has been shown to modulate certain viral antigens, including those from human papilloma virus (HPV), influenza virus, hepatitis C (HCV) and human immunodeficiency virus (HIV)19. The ERAP2 gene has also been identified as a risk factor for death by COVID-198. In one preferred embodiment, the viral disorder is a viral disease or viral infection selected from HIV, HPV, influenza, COVID-19, and HCV. In one preferred embodiment, the viral disorder is HIV. In one preferred embodiment, the viral disorder is influenza. In one preferred embodiment, the viral disorder is HPV. In one preferred embodiment, the viral disorder is HCV. In one preferred embodiment, the viral disorder is COVID-19. Another aspect of the invention relates to a compound as described above for use in the treatment or prevention of preeclampsia. Preeclampsia is a heritable pregnancy disorder with an incidence of around 2-5% that presents with symptoms of new onset hypertension and proteinuria. It has been shown that there is a genetic association between ERAP2 and the development of preeclampsia, although the exact mechanism by which genetic variants of ERAP2 promote this disorder has yet to be fully elucidated9. Another aspect relates to a compound as described herein for use in the prevention or treatment of a disorder caused by, associated with or accompanied by abnormal activity against ERAP2. Another aspect relates to a compound as described herein for use in the prevention or treatment of an ERAP2-associated disease or disorder. Yet another aspect relates to the use of a compound as described herein in the preparation of a medicament for the prevention or treatment of a disorder caused by, associated with or accompanied by any abnormal activity against ERAP2. As used herein the phrase “preparation of a medicament” includes the use of the components of the invention directly as the medicament in addition to their use in any stage of the preparation of such a medicament. Another aspect relates to the use of a compound as described above in the preparation of a medicament for treating or preventing a disorder selected from a proliferative disorder, an immune disorder, a viral disorder, preeclampsia and an inflammatory disorder. Yet another aspect relates to the use of a compound as described herein in the preparation of a medicament for the prevention or treatment of an ERAP2-associated disease or disorder. Another aspect of the invention relates to a method of treating an ERAP2-associated disease or disorder in a subject. The method according to this aspect of the present invention is effected by administering to a subject in need thereof a therapeutically effective amount of a compound of the present invention, as described hereinabove, either perse, or, more preferably, as a part of a pharmaceutical composition, mixed with, for example, a pharmaceutically acceptable carrier, as is detailed hereinafter. Yet another aspect of the invention relates to a method of treating a subject having a disease state alleviated by modulation of ERAP2 wherein the method comprises administering to the subject a therapeutically effective amount of a compound according to the invention. Another aspect relates to a method of treating a disease state alleviated by modulation of ERAP2, wherein the method comprises administering to a subject a therapeutically effective amount of a compound according to the invention. Preferably, the subject is a mammal, more preferably a human. The term “method” refers to manners, means, techniques and procedures for accomplishing a given task including, but not limited to, those manners, means, 33 techniques and procedures either known to, or readily developed from known manners, means, techniques and procedures by practitioners of the chemical, pharmacological, biological, biochemical and medical arts. Herein, the term “treating” includes abrogating, substantially inhibiting, slowing or reversing the progression of a disease or disorder, substantially ameliorating clinical symptoms of a disease or disorder or substantially preventing the appearance of clinical symptoms of a disease or disorder. Herein, the term “preventing” refers to a method for barring an organism from acquiring a disorder or disease in the first place. The term “therapeutically effective amount” refers to that amount of the compound being administered which will relieve to some extent one or more of the symptoms of the disease or disorder being treated. For any compound used in this invention, a therapeutically effective amount, also referred to herein as a therapeutically effective dose, can be estimated initially from cell culture assays. For example, a dose can be formulated in animal models to achieve a circulating concentration range that includes the ICsoor the ICwoas determined in cell culture. Such information can be used to more accurately determine useful doses in humans. Initial dosages can also be estimated from in vivo data. Using these initial guidelines one of ordinary skill in the art could determine an effective dosage in humans. Moreover, toxicity and therapeutic efficacy of the compounds described herein can be determined by standard pharmaceutical procedures in cell cultures or experimental animals, e.g., by determining the LDsoand the ED50. The dose ratio between toxic and therapeutic effect is the therapeutic index and can be expressed as the ratio between LD50 and ED50. Compounds which exhibit high therapeutic indices are preferred. The data obtained from these cell cultures assays and animal studies can be used in formulating a dosage range that is not toxic for use in human. The dosage of such compounds lies preferably within a range of circulating concentrations that include the EDsowith little or no toxicity. The dosage may vary within this range depending upon the dosage form employed and the route of administration utilized. The exact formulation, route of administration and dosage can be chosen by the individual 34 physician in view of the patient’s condition (see, e.g., Fingl etal, 1975, The Pharmacological Basis of Therapeutics, chapter 1, page 1). Dosage amount and interval may be adjusted individually to provide plasma levels of the active compound which are sufficient to maintain therapeutic effect. Usual patient dosages for oral administration range from about 50-2000 mg / kg / day, commonly from about 100-1000 mg / kg / day, preferably from about 150-700 mg / kg / day and most preferably from about 250-500 mg / kg / day. Preferably, therapeutically effective serum levels will be achieved by administering multiple doses each day. In cases of local administration or selective uptake, the effective local concentration of the drug may not be related to plasma concentration. One skilled in the art will be able to optimize therapeutically effective local dosages without undue experimentation. As used herein, “ERAP2-related disease or disorder” refers to a disease or disorder characterized by inappropriate ERAP2 activity, or that responds to modulation of ERAP2 activity. Inappropriate activity refers to either an increase or decrease in ERAP2 activity relative to wildtype ERAP2 (Uniprot ID Q9NZ08), caused by variation in the ERAP2 protein sequence, as measured by enzyme or cellular assays. Inappropriate activity could also be due to overexpression of ERAP2 in diseased tissue compared with healthy adjacent tissue. Preferred diseases or disorders that the compounds described herein may be useful in preventing include proliferative disorders, viral disorders, immune disorders and inflammatory disorders as described hereinbefore. Thus, the present invention further provides use of compounds as defined herein for the manufacture of medicaments for the treatment of diseases where it is desirable to modulate ERAP2. Such diseases include proliferative disorders, viral disorders, immune disorders, preeclampsia and inflammatory disorders as described hereinbefore. In one preferred embodiment, the compound inhibits ERAP2’s digestion of the peptide substrate Glu(EDANS)-Gln-Leu-Glu-[N-Mer-Ser]-lle-lle-Asn-Lys-Glu-Lys(Dabcyl)-Leu. When the above substrate is intact, the Dabcyl group quenches energy emitted from the fluorescent EDANS group, resulting in little to no detectable fluorescence. Once the substrate has been cleaved, however, such quenching is reduced, resulting in detectable fluorescence from the EDANS group. As used herein, this assay is referred to as the “ERAP2 SIINFEKL assay”. The potency of any inhibitor is calculated and expressed as the concentration of the inhibitor required to decrease the enzyme activity of ERAP2 by 50% over its baseline level (i.e. an IC50). In one preferred embodiment, the compound exhibits an IC50 value in the ERAP2 SIINFEKL assay of less than about 10 pM. More preferably, the compound exhibits an IC50 value in the ERAP2 SIINFEKL assay of less than about 5 pM, even more preferably, less than about 1 pM, even more preferably, less than about 0.1 pM, even more preferably, less than about 0.01 pM. In one preferred embodiment, the compound of the invention exhibits an IC50 value in the ERAP2 SIINFEKL assay of about 750 nM or less. More preferably, the compound exhibits an IC50 value in the ERAP2 SIINFEKL assay of about 250 nM or less, even more preferably of about 100 nM or less. In some embodiments, the compounds according to the invention exhibit selectivity for ERAP2. For example, in some embodiments compounds according to the invention exhibit selectivity for modulating ERAP2 over ERAP1. Thus, in certain preferred embodiments, the compound is capable of modulating ERAP2, for example, as measured by the above-described ERAP2 SIINFEKL assay, but does not significantly modulate ERAP1, for example, as measured by the ERAP1 SIINFEKL assay. As used herein, the ERAP1 SIINFEKL assay measures the ability of a compound to inhibit ERAPTs digestion of the substrate peptide Lys(Dabcyl)-Glu-Gln-Leu-Glu-Ser-lle-lle-Asn-Phe-Glu-Lys-Leu-Glu(EDANS). When the above substrate is intact, the Dabcyl group quenches energy emitted from the fluorescent EDANS group, resulting in little to no detectable fluorescence. Once the substrate has been cleaved, however, such quenching is reduced, resulting in detectable fluorescence from the EDANS group. The potency of any inhibitor is calculated and expressed as the concentration of the inhibitor required to decrease the enzyme activity of ERAP1 by 50% over its baseline level (i.e. an IC50). Thus, in preferred embodiments the compound exhibits selective modulatory activity towards ERAP2 compared with ERAP1, based on results obtained from the ERAP2 SIINFEKL assay and ERAP1 SIINFEKL assay described above. PHARMACEUTICAL COMPOSITIONS For use according to the present invention, the compounds or physiologically acceptable salt, ester or other physiologically functional derivative thereof, described herein, may be presented as a pharmaceutical formulation, comprising the compounds or physiologically acceptable salt, ester or other physiologically functional derivative thereof, together with one or more pharmaceutically acceptable carriers therefore and optionally other therapeutic and / or prophylactic ingredients. The carrier(s) must be acceptable in the sense of being compatible with the other ingredients of the formulation and not deleterious to the recipient thereof. The pharmaceutical compositions may be for human or animal usage in human and veterinary medicine. Examples of such suitable excipients for the various different forms of pharmaceutical compositions described herein may be found in the “Handbook of Pharmaceutical Excipients, 2nd Edition, (1994), Edited by A Wade and PJ Weller. The carrier, or, if more than one be present, each of the carriers, must be acceptable in the sense of being compatible with the other ingredients of the formulation and not deleterious to the recipient. Acceptable carriers or diluents for therapeutic use are well known in the pharmaceutical art, and are described, for example, in Remington’s Pharmaceutical Sciences, Mack Publishing Co. (A. R. Gennaro edit. 1985). Examples of suitable carriers include lactose, starch, glucose, methyl cellulose, magnesium stearate, mannitol, sorbitol and the like. Examples of suitable diluents include ethanol, glycerol and water. The choice of pharmaceutical carrier, excipient or diluent can be selected with regard to the intended route of administration and standard pharmaceutical practice. The pharmaceutical compositions may comprise as, or in addition to, the carrier, excipient or diluent any suitable binder(s), lubricant(s), suspending agent(s), coating agent(s), solubilising agent(s), buffer(s), flavouring agent(s), surface active agent(s), thickener(s), preservative(s) (including anti-oxidants) and the like, and substances 37 included for the purpose of rendering the formulation isotonic with the blood of the intended recipient. Examples of suitable binders include starch, gelatin, natural sugars such as glucose, anhydrous lactose, free-flow lactose, beta-lactose, corn sweeteners, natural and synthetic gums, such as acacia, tragacanth or sodium alginate, carboxymethyl cellulose and polyethylene glycol. Examples of suitable lubricants include sodium oleate, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride and the like. Preservatives, stabilizers, dyes and even flavoring agents may be provided in the pharmaceutical composition. Examples of preservatives include sodium benzoate, sorbic acid and esters of p-hydroxybenzoic acid. Antioxidants and suspending agents may be also used. Pharmaceutical formulations include those suitable for oral, topical (including dermal, buccal and sublingual), rectal or parenteral (including subcutaneous, intradermal, intramuscular and intravenous), nasal and pulmonary administration e.g., by inhalation. The formulation may, where appropriate, be conveniently presented in discrete dosage units and may be prepared by any of the methods well known in the art of pharmacy. All methods include the step of bringing into association an active compound with liquid carriers or finely divided solid carriers or both and then, if necessary, shaping the product into the desired formulation. Pharmaceutical formulations suitable for oral administration wherein the carrier is a solid are most preferably presented as unit dose formulations such as boluses, capsules or tablets each containing a predetermined amount of active compound. A tablet may be made by compression or moulding, optionally with one or more accessory ingredients. Compressed tablets may be prepared by compressing in a suitable machine an active compound in a free-flowing form such as a powder or granules optionally mixed with a binder, lubricant, inert diluent, lubricating agent, surface-active agent or dispersing agent. Moulded tablets may be made by moulding an active compound with an inert liquid diluent. Tablets may be optionally coated and, if uncoated, may optionally be scored. Capsules may be prepared by filling an active compound, either alone or in admixture with one or more accessory ingredients, into the capsule shells and then sealing them in the usual manner. Cachets are analogous to capsules wherein an active compound together with any accessory ingredient(s) is sealed in a rice paper envelope. An active compound may also be formulated as dispersible granules, which may for example be suspended in water before administration, or sprinkled on food. The granules may be packaged, e.g., in a sachet. Formulations suitable for oral administration wherein the carrier is a liquid may be presented as a solution or a suspension in an aqueous or non-aqueous liquid, or as an oil-in-water liquid emulsion. Formulations for oral administration include controlled release dosage forms, e.g., tablets wherein an active compound is formulated in an appropriate release -controlling matrix or is coated with a suitable release - controlling film. Such formulations may be particularly convenient for prophylactic use. Pharmaceutical formulations suitable for rectal administration wherein the carrier is a solid are most preferably presented as unit dose suppositories. Suitable carriers include cocoa butter and other materials commonly used in the art. The suppositories may be conveniently formed by admixture of an active compound with the softened or melted carrier(s) followed by chilling and shaping in moulds. Pharmaceutical formulations suitable for parenteral administration include sterile solutions or suspensions of an active compound in aqueous or oleaginous vehicles. Injectable preparations may be adapted for bolus injection or continuous infusion. Such preparations are conveniently presented in unit dose or multi-dose containers which are sealed after introduction of the formulation until required for use. Alternatively, an active compound may be in powder form which is constituted with a suitable vehicle, such as sterile, pyrogen-free water, before use. An active compound may also be formulated as long-acting depot preparations, which may be administered by intramuscular injection or by implantation, e.g., subcutaneously or intramuscularly. Depot preparations may include, for example, suitable polymeric or hydrophobic materials, or ion-exchange resins. Such long-acting formulations are particularly convenient for prophylactic use. Formulations suitable for pulmonary administration via the buccal cavity are presented such that particles containing an active compound and desirably having a diameter in the range of 0.5 to 7 microns are delivered in the bronchial tree of the recipient. As one possibility such formulations are in the form of finely comminuted powders which may conveniently be presented either in a pierceable capsule, suitably of, for example, gelatin, for use in an inhalation device, or alternatively as a self-propelling formulation comprising an active compound, a suitable liquid or gaseous propellant and optionally other ingredients such as a surfactant and / or a solid diluent. Suitable liquid propellants include propane and the chlorofluorocarbons, and suitable gaseous propellants include carbon dioxide. Self-propelling formulations may also be employed wherein an active compound is dispensed in the form of droplets of solution or suspension. Such self-propelling formulations are analogous to those known in the art and may be prepared by established procedures. Suitably they are presented in a container provided with either a manually-operable or automatically functioning valve having the desired spray characteristics; advantageously the valve is of a metered type delivering a fixed volume, for example, 25 to 100 microlitres, upon each operation thereof. As a further possibility an active compound may be in the form of a solution or suspension for use in an atomizer or nebuliser whereby an accelerated airstream or ultrasonic agitation is employed to produce a fine droplet mist for inhalation. Formulations suitable for nasal administration include preparations generally similar to those described above for pulmonary administration. When dispensed such formulations should desirably have a particle diameter in the range 10 to 200 microns to enable retention in the nasal cavity; this may be achieved by, as appropriate, use of a powder of a suitable particle size or choice of an appropriate valve. Other suitable formulations include coarse powders having a particle diameter in the range 20 to 500 microns, for administration by rapid inhalation through the nasal passage from a container held close up to the nose, and nasal drops comprising 0.2 to 5% w / v of an active compound in aqueous or oily solution or suspension. Pharmaceutically acceptable carriers are well known to those skilled in the art and include, but are not limited to, 0.1 M and preferably 0.05 M phosphate buffer or 0.8% 40 saline. Additionally, such pharmaceutically acceptable carriers may be aqueous or non-aqueous solutions, suspensions, and emulsions. Examples of non-aqueous solvents are propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable organic esters such as ethyl oleate. Aqueous carriers include water, alcoholic / aqueous solutions, emulsions or suspensions, including saline and buffered media. Parenteral vehicles include sodium chloride solution, Ringer’s dextrose, dextrose and sodium chloride, lactated Ringer’s or fixed oils. Preservatives and other additives may also be present, such as, for example, antimicrobials, antioxidants, chelating agents, inert gases and the like. Formulations suitable for topical formulation may be provided for example as gels, creams or ointments. Such preparations may be applied e.g. to a wound or ulcer either directly spread upon the surface of the wound or ulcer or carried on a suitable support such as a bandage, gauze, mesh or the like which may be applied to and over the area to be treated. Liquid or powder formulations may also be provided which can be sprayed or sprinkled directly onto the site to be treated, e.g. a wound or ulcer. Alternatively, a carrier such as a bandage, gauze, mesh or the like can be sprayed or sprinkle with the formulation and then applied to the site to be treated. According to a further aspect of the invention, there is provided a process for the preparation of a pharmaceutical or veterinary composition as described above, the process comprising bringing the active compound(s) into association with the carrier, for example by admixture. In general, the formulations are prepared by uniformly and intimately bringing into association the active agent with liquid carriers or finely divided solid carriers or both, and then if necessary shaping the product. The invention extends to methods for preparing a pharmaceutical composition comprising bringing a compound as described herein into conjunction or association with a pharmaceutically or veterinarily acceptable carrier or vehicle. SALTS / ESTERS The compounds of the invention can be present as salts or esters, in particular pharmaceutically and veterinarily acceptable salts or esters. Pharmaceutically acceptable salts of the compounds of the invention include suitable acid addition or base salts thereof. A review of suitable pharmaceutical salts may be found in Berge etal, J Pharm Sci, 66, 1-19 (1977). Salts are formed, for example with strong inorganic acids such as mineral acids, e.g. hydrohalic acids such as hydrochloride, hydrobromide and hydroiodide, sulphuric acid, phosphoric acid sulphate, bisulphate, hemisulphate, thiocyanate, persulphate and sulphonic acids; with strong organic carboxylic acids, such as alkanecarboxylic acids of 1 to 4 carbon atoms which are unsubstituted or substituted (e.g., by halogen), such as acetic acid; with saturated or unsaturated dicarboxylic acids, for example oxalic, malonic, succinic, maleic, fumaric, phthalic or tetraphthalic; with hydroxycarboxylic acids, for example ascorbic, glycolic, lactic, malic, tartaric or citric acid; with aminoacids, for example aspartic or glutamic acid; with benzoic acid; or with organic sulfonic acids, such as (Ci-C4)-alkyl- or aryl-sulfonic acids which are unsubstituted or substituted (for example, by a halogen) such as methane- or p-toluene sulfonic acid. Salts which are not pharmaceutically or veterinarily acceptable may still be valuable as intermediates. Preferred salts include, for example, acetate, trifluoroacetate, lactate, gluconate, citrate, tartrate, maleate, malate, pantothenate, adipate, alginate, aspartate, benzoate, butyrate, digluconate, cyclopentanate, glucoheptanate, glycerophosphate, oxalate, heptanoate, hexanoate, fumarate, nicotinate, palmoate, pectinate, 3-phenylpropionate, picrate, pivalate, proprionate, tartrate, lactobionate, pivolate, camphorate, undecanoate and succinate, organic sulphonic acids such as methanesulphonate, ethanesulphonate, 2-hydroxyethane sulphonate, camphorsulphonate, 2-naphthalenesulphonate, benzenesulphonate, p-chlorobenzenesulphonate and p-toluenesulphonate; and inorganic acids such as hydrochloride, hydrobromide, hydroiodide, sulphate, bisulphate, hemisulphate, thiocyanate, persulphate, phosphoric and sulphonic acids. More preferably, the salt is a hydrochloride salt. Esters are formed either using organic acids or alcohols / hydroxides, depending on the functional group being esterified. Organic acids include carboxylic acids, such as alkanecarboxylic acids of 1 to 12 carbon atoms which are unsubstituted or substituted (e.g., by halogen), such as acetic acid; with saturated or unsaturated dicarboxylic acid, for example oxalic, malonic, succinic, maleic, fumaric, phthalic or tetraphthalic; with hydroxycarboxylic acids, for example ascorbic, glycolic, lactic, malic, tartaric or citric acid; with aminoacids, for example aspartic or glutamic acid; with benzoic acid; or with organic sulfonic acids, such as (Ci-C4)-alkyl- or aryl-sulfonic acids which are unsubstituted or substituted (for example, by a halogen) such as methane- or p-toluene sulfonic acid. Suitable hydroxides include inorganic hydroxides, such as sodium hydroxide, potassium hydroxide, calcium hydroxide, aluminium hydroxide. Alcohols include alkanealcohols of 1-12 carbon atoms which may be unsubstituted or substituted, e.g. by a halogen). ENANTIOMERS / TAUTOMERS In all aspects of the present invention previously discussed, the invention includes, where appropriate all enantiomers, diastereoisomers and tautomers of the compounds of the invention. The person skilled in the art will recognise compounds that possess optical properties (one or more chiral carbon atoms) or tautomeric characteristics. The corresponding enantiomers and / or tautomers may be isolated / prepared by methods known in the art. Enantiomers are characterised by the absolute configuration of their chiral centres and described by the R- and S-sequencing rules of Cahn, Ingold and Prelog. Such conventions are well known in the art (e.g. see ‘Advanced Organic Chemistry’, 3rd edition, ed. March, J., John Wiley and Sons, New York, 1985). Compounds of the invention containing a chiral centre may be used as a racemic mixture, an enantiomerically enriched mixture, or the racemic mixture may be separated using well-known techniques and an individual enantiomer may be used alone. STEREO AND GEOMETRIC ISOMERS Some of the compounds of the invention may exist as stereoisomers and / or geometric isomers - e.g. they may possess one or more asymmetric and / or geometric centres and so may exist in two or more stereoisomeric and / or geometric forms. The present invention contemplates the use of all the individual stereoisomers and geometric isomers of those compounds, and mixtures thereof. The terms used in the claims encompass these forms, provided said forms retain the appropriate functional activity (though not necessarily to the same degree). The present invention also includes all suitable isotopic variations of the compound or a pharmaceutically acceptable salt thereof. An isotopic variation of a compound of the present invention or a pharmaceutically acceptable salt thereof is defined as one in which at least one atom is replaced by an atom having the same atomic number but an atomic mass different from the atomic mass usually found in nature. Examples of isotopes that can be incorporated into the agent and pharmaceutically acceptable salts thereof include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulphur, fluorine and chlorine such as 2H, 3H, 13C, 14C, 15N, 170,180,31P, 32P, 35S, 18F and 36CI, respectively. Certain isotopic variations of the agent and pharmaceutically acceptable salts thereof, for example, those in which a radioactive isotope such as 3H or 14C is incorporated, are useful in drug and / or substrate tissue distribution studies. Tritiated, i.e., 3H, and carbon-14, i.e., 14C, isotopes are particularly preferred for their ease of preparation and detectability. Further, substitution with isotopes such as deuterium, i.e., 2H, may afford certain therapeutic advantages resulting from greater metabolic stability, for example, increased in vivo half-life or reduced dosage requirements and hence may be preferred in some circumstances. For example, the invention includes compounds of general formula (I) where any hydrogen atom has been replaced by a deuterium atom. Isotopic variations of the agent of the present invention and pharmaceutically acceptable salts thereof of this invention can generally be prepared by conventional procedures using appropriate isotopic variations of suitable reagents. ATROPISOMERS Some of the compounds of the invention may exist as atropisomers. Atropisomers are stereoisomers arising because of hindered rotation about a single bond, where energy differences due to steric strain or other contributors create a barrier to rotation that is high enough to allow for isolation of individual conformers. The invention encompasses all such atropisomers. PRODRUGS The invention further includes the compounds of the present invention in prodrug form, i.e. covalently bonded compounds which release the active parent drug in vivo. Such prodrugs are generally compounds of the invention wherein one or more appropriate groups have been modified such that the modification may be reversed upon administration to a human or mammalian subject. Reversion is usually performed by an enzyme naturally present in such subject, though it is possible for a second agent to be administered together with such a prodrug in order to perform the reversion in vivo. Examples of such modifications include ester (for example, any of those described above), wherein the reversion may be carried out be an esterase etc. Other such systems will be well known to those skilled in the art. SOLVATES The present invention also includes solvate forms of the compounds of the present invention. The terms used in the claims encompass these forms. Preferably the solvate is a hydrate. POLYMORPHS The invention further relates to the compounds of the present invention in their various crystalline forms, polymorphic forms and (an)hydrous forms. It is well established within the pharmaceutical industry that chemical compounds may be isolated in any of such forms by slightly varying the method of purification and or isolation form the solvents used in the synthetic preparation of such compounds. ADMINISTRATION The pharmaceutical compositions of the present invention may be adapted for rectal, nasal, intrabronchial, topical (including buccal and sublingual), vaginal or parenteral (including subcutaneous, intramuscular, intravenous, intraarterial and intradermal), intraperitoneal or intrathecal administration. Preferably the formulation is an orally administered formulation. The formulations may conveniently be presented in unit dosage form, i.e., in the form of discrete portions containing a unit dose, or a multiple or sub-unit of a unit dose. By way of example, the formulations may be in the form of tablets and sustained release capsules, and may be prepared by any method well known in the art of pharmacy. Formulations for oral administration in the present invention may be presented as: discrete units such as capsules, gellules, drops, cachets, pills or tablets each containing a predetermined amount of the active agent; as a powder or granules; as a solution, emulsion or a suspension of the active agent in an aqueous liquid or a nonaqueous liquid; or as an oil-in-water liquid emulsion or a water-in-oil liquid emulsion; or as a bolus etc. Preferably, these compositions contain from 1 to 250 mg and more preferably from 10-100 mg, of active ingredient per dose. For compositions for oral administration (e.g. tablets and capsules), the term “acceptable carrier” includes vehicles such as common excipients e.g. binding agents, for example syrup, acacia, gelatin, sorbitol, tragacanth, polyvinylpyrrolidone (Povidone), methylcellulose, ethylcellulose, sodium carboxymethylcellulose, hydroxypropyl-methylcellulose, sucrose and starch; fillers and carriers, for example corn starch, gelatin, lactose, sucrose, microcrystalline cellulose, kaolin, mannitol, dicalcium phosphate, sodium chloride and alginic acid; and lubricants such as magnesium stearate, sodium stearate and other metallic stearates, glycerol stearate stearic acid, silicone fluid, talc waxes, oils and colloidal silica. Flavouring agents such as peppermint, oil of wintergreen, cherry flavouring and the like can also be used. It may be desirable to add a colouring agent to make the dosage form readily identifiable. Tablets may also be coated by methods well known in the art. A tablet may be made by compression or moulding, optionally with one or more accessory ingredients. Compressed tablets may be prepared by compressing in a suitable machine the active agent in a free-flowing form such as a powder or granules, optionally mixed with a binder, lubricant, inert diluent, preservative, surface-active or dispersing agent. Moulded tablets may be made by moulding in a suitable machine a mixture of the powdered compound moistened with an inert liquid diluent. The tablets may be optionally be coated or scored and may be formulated so as to provide slow or controlled release of the active agent. Other formulations suitable for oral administration include lozenges comprising the active agent in a flavoured base, usually sucrose and acacia or tragacanth; pastilles comprising the active agent in an inert base such as gelatin and glycerin, or sucrose and acacia; and mouthwashes comprising the active agent in a suitable liquid carrier. Other forms of administration comprise solutions or emulsions which may be injected intravenously, intraarterially, intrathecally, subcutaneously, intradermally, intraperitoneally or intramuscularly, and which are prepared from sterile or sterilisable solutions. Injectable forms typically contain between 10 - 1000 mg, preferably between 10 - 250 mg, of active ingredient per dose. The pharmaceutical compositions of the present invention may also be in form of suppositories, pessaries, suspensions, emulsions, lotions, ointments, creams, gels, sprays, solutions or dusting powders. An alternative means of transdermal administration is by use of a skin patch. For example, the active ingredient can be incorporated into a cream consisting of an aqueous emulsion of polyethylene glycols or liquid paraffin. The active ingredient can also be incorporated, at a concentration of between 1 and 10% by weight, into an ointment consisting of a white wax or white soft paraffin base together with such stabilisers and preservatives as may be required. DOSAGE A person of ordinary skill in the art can easily determine an appropriate dose of one of the instant compositions to administer to a subject without undue experimentation. Typically, a physician will determine the actual dosage which will be most suitable for an individual patient and it will depend on a variety of factors including the activity of the specific compound employed, the metabolic stability and length of action of that compound, the age, body weight, general health, sex, diet, mode and time of administration, rate of excretion, drug combination, the severity of the particular condition, and the individual undergoing therapy. The dosages disclosed herein are exemplary of the average case. There can of course be individual instances where higher or lower dosage ranges are merited, and such are within the scope of this invention. The dosage amount will further be modified according to the mode of administration of the compound. For example, to achieve an “effective amount” for acute therapy, parenteral administration of a compound is typically preferred. An intravenous infusion of the compound in 5% dextrose in water or normal saline, or a similar formulation with suitable excipients, is most effective, although an intramuscular bolus injection is also useful. Typically, the parenteral dose will be about 0.01 to about 100 mg / kg; preferably between 0.1 and 20 mg / kg, in a manner to maintain the concentration of drug in the plasma at a concentration effective to modulate ERAP2. The compounds may be administered one to four times daily at a level to achieve a total daily dose of about 0.4 to about 400 mg / kg / day. The precise amount of an inventive compound which is therapeutically effective, and the route by which such compound is best administered, is readily determined by one of ordinary skill in the art by comparing the blood level of the agent to the concentration required to have a therapeutic effect. The compounds of this invention may also be administered orally to the patient, in a manner such that the concentration of drug is sufficient to achieve one or more of the therapeutic indications disclosed herein. Typically, a pharmaceutical composition containing the compound is administered at an oral dose of between about 0.1 to about 50 mg / kg in a manner consistent with the condition of the patient. Preferably the oral dose would be about 0.5 to about 20 mg / kg. No unacceptable toxicological effects are expected when compounds of the present invention are administered in accordance with the present invention. The compounds of this invention, which may have good bioavailability, may be tested in one of several biological assays to determine the concentration of a compound which is required to have a given pharmacological effect. COMBINATIONS A further aspect of the invention relates to a combination comprising a compound as described herein and one or more additional active agents. In a particularly preferred embodiment, the one or more compounds of the invention are administered in combination with one or more additional active agents, for example, existing drugs available on the market. In such cases, the compounds of the invention may be administered consecutively, simultaneously or sequentially with the one or more other active agents. Drugs in general are more effective when used in combination. In particular, combination therapy is desirable in order to avoid an overlap of major toxicities, mechanism of action and resistance mechanism(s). Furthermore, it is also desirable to administer most drugs at their maximum tolerated doses with minimum time intervals between such doses. The major advantages of combining chemotherapeutic drugs are that it may promote additive or possible synergistic effects through biochemical interactions and also may decrease the emergence of resistance. Beneficial combinations may be suggested by studying the activity of the test compounds with agents known or suspected of being valuable in the treatment of a particular disorder. This procedure can also be used to determine the order of administration of the agents, i.e. before, simultaneously, or after delivery. Such scheduling may be a feature of all the active agents identified herein. In one preferred embodiment, the additional active agent is an immunotherapy agent, more preferably a cancer immunotherapy agent. An “immunotherapy agent” refers to a treatment that uses the subject’s own immune system to fight diseases such as cancer. In one preferred embodiment the compound of the invention inhibits the activity of ERAP2, and the compound is administered in combination with an immunotherapy. The compound may increase the sensitivity of cancer cells to an immunotherapy. The immunotherapy may be mediated by T cells. In one embodiment the compound may increase the number of CD8+ T cells in a tumour. In one embodiment the compound may be used to treat cancers which are weakly responsive or not responsive to immunotherapies. In one preferred embodiment, the additional active agent is a molecule capable of immune checkpoint intervention, a co-stimulatory antibody, a chemotherapy agent, a radiotherapy agent, a targeted therapy agent or an antibody, particularly a monoclonal antibody. In one preferred embodiment, the antibody may be a bispecific antibody, for example a bispecific monoclonal antibody. Bispecific monoclonal antibodies may comprise fusion proteins consisting of two single-chain variable fragments (scFvs) of different antibodies, or amino acid sequences from four different genes, on a single peptide chain. One of the scFvs may bind to T cells via the CD3 receptor, and the other to a tumour cell via a tumour specific molecule. The bispecific antibody may, for example, be selected from: Blinatumomab, Glofitamab, Mosunetuzumab, Solitomab, Talquetamab, and Tebentafusp. These fusion proteins form a link between between T cells and tumor cells. This causes T cells to exert cytotoxic activity on tumor cells by producing proteins like perforin and granzymes which can cause apoptosis of the tumour cell. In one preferred embodiment, the additional active agent is a T cell receptor (TOR) therapy, for example a native or minimally engineered TCR, an engineered TCR, and / or a soluble TCR. In one preferred embodiment, the additional active agent is a bispecific TCR. The TCR may be in the form of a TCR and additional moiety, for example, a bispecific TCR construct comprising a TCR and antibody component or effector molecule. T-cell receptor (TCR)-engineered effector cells may use a naturally occurring (or minimally modified) TCR to develop T-cell-based adoptive T-cell therapy. TCR-based therapy will be known to one of skill in the art, for example as described in Tsimberidou etal. J Hematol Oncol 14, 102 (2021). In one preferred embodiment the additional active agent is a molecule capable of immune checkpoint intervention. Immune checkpoint molecules include CTLA-4, PD-1, VISTA, B7-H2, B7-H3, PD-L1, B7-H4, B7-H6, ICOS, HVEM, PD-L2, CD160, gp49B, PIR-B, KIR family receptors, TIM-1, TIM-3, TIM-4, LAG-3, GITR, 4-IBB, OX-40, BTLA, SIRP, CD47, CD48, 2B4, B7.1, B7.2, ILT-2, ILT-4, TIGIT, HHLA2, IDO, CD39, CD73, A2aR and butyrophilins. Immune checkpoint molecules include both inhibitory and activatory molecules, and interventions may apply to either or both types of molecule. Immune checkpoint inhibitors include, but are not limited to, PD-1 inhibitors, PD-L1 inhibitors, LAG-3 inhibitors, TIM-3 inhibitors, TIGIT inhibitors, BTLA inhibitors and CTLA-4 inhibitors, for example. Co-stimulatory antibodies deliver positive signals through immune-regulatory receptors including but not limited to ICOS, CD137, CD27 OX-40 and GITR. In one highly preferred embodiment, the the additional active agent is an antibody checkpoint inhibitor. Suitable examples of antibody checkpoint inhibitors, include, but are not limited to, anti-PD-1 antibodies, anti-PD-L1 antibodies and anti-CTLA4 antibodies. In one preferred embodiment, the antibody checkpoint inhibitor is an anti-PD-1 antibody, more preferably selected from pembrolizumab, cemiplimab and nivolumab. In one preferred embodiment, the antibody checkpoint inhibitor is an anti-PD-L1 antibody, more preferably selected from atezolizumab, avelumab and durvalumab. In one preferred embodiment, the antibody checkpoint inhibitor is an anti-CTLA4 antibody, more preferably selected from ipilimumab and tremelimumab. In one preferred embodiment the immunotherapy is an anti-cancer vaccine or virus, such as an oncolytic virus. In one preferred embodiment the immunotherapy is a cell-based therapy. In one embodiment the cell-based therapy may be a T cell therapy, such as adoptive T cell therapy, or therapy with CAR-T cells. Adoptive cell-based immunotherapy may include the following: Irradiated autologous or allogeneic tumor cells, tumor lysates or apoptotic tumor cells, antigen-presenting cell-based immunotherapy, dendritic cell-based immunotherapy, adoptive T cell transfer, adoptive CAR T cell therapy, autologous immune enhancement therapy (AIET), cancer vaccines, and / or antigen presenting cells. Such cell-based immunotherapies can be further modified to express one or more gene products to further modulate immune responses, for example expressing cytokines such as GM-CSF, and / or to express tumor-associated antigen (TAA) antigens, such as Mage-1, gp-100, patient-specific neoantigen vaccines, and the like. In a further embodiment, the immunotherapy may comprise non-cell-based immunotherapies. In one embodiment, compositions comprising antigens with or without vaccine-enhancing adjuvants may be used. Such compositions exist in many well-known forms, such as peptide compositions, oncolytic viruses, and recombinant antigen comprising fusion proteins. In an alternative embodiment, immunomodulatory interleukins, such as IL-2, IL-6, IL-7, IL-12, IL-17, IL-23, as well as modulators thereof (e.g., blocking antibodies or more 51 potent or longer lasting forms) may be used. Immunomodulatory cytokines, such as interferons, G-CSF, imiquimod, TNF alpha, and the like, as well as modulators thereof (e.g., blocking antibodies or more potent or longer lasting forms) may also be used. In another embodiment, immunomodulatory chemokines, such as CCL3, CCL26, and CXCL7, and the like, as well as modulators thereof (e.g., blocking antibodies or more potent or longer lasting forms) may be used. In a further embodiment, immunomodulatory molecules targeting immunosuppression, such as STAT3 signaling modulators, FkappaB signaling modulators, and immune checkpoint modulators, may be used. In another embodiment, immunomodulatory drugs, such as immunocytostatic drugs, glucocorticoids, cytostatics, immunophilins and modulators thereof (e.g., rapamycin, a calcineurin inhibitor, tacrolimus, ciclosporin (cyclosporin), pimecrolimus, abetimus, gusperimus, ridaforolimus, everolimus, temsirolimus, zotarolimus, etc.), hydrocortisone (Cortisol), cortisone acetate, prednisone, prednisolone, methylprednisolone, dexamethasone, betamethasone, triamcinolone, beclometasone, fludrocortisone acetate, deoxycorticosterone acetate (doca) aldosterone, a non-glucocorticoid steroid, a pyrimidine synthesis inhibitor, leflunomide, teriflunomide, a folic acid analog, methotrexate, anti-thymocyte globulin, anti-lymphocyte globulin, thalidomide, lenalidomide, pentoxifylline, bupropion, curcumin, catechin, an opioid, an EVIPDH inhibitor, mycophenolic acid, myriocin, fingolimod, an NF-xB inhibitor, raloxifene, drotrecogin alfa, denosumab, an F-xB signaling cascade inhibitor, disulfiram, olmesartan, dithiocarbamate, a proteasome inhibitor, bortezomib, MG132, Prol, PI-0052, curcumin, genistein, resveratrol, parthenolide, thalidomide, lenalidomide, flavopiridol, non-steroidal anti-inflammatory drugs (NSAIDs), arsenic tri oxide, dehydroxymethylepoxyquinomycin (DHMEQ), l3C(indole-3-carbinol) / DIM(di-indolmethane) (13C / DIM), Bay 1 1-7082, luteolin, cell permeable peptide SN-50, IKBa -super repressor overexpression, FKB decoy oligodeoxynucleotide (ODN), or a derivative or analog of any thereto, may be used. In yet another embodiment, immunomodulatory antibodies or protein may be used. For example, antibodies that bind to CD40, Toll-like receptor (TLR), 0X40, GITR, CD27, or to 4-IBB, T-cell bispecific antibodies, an anti-IL-2 receptor antibody, an anti-CD3 antibody, OKT3 (muromonab), otelixizumab, teplizumab, visilizumab, an anti-CD4 antibody, clenoliximab, keliximab, zanolimumab, an anti-CD11a antibody, efalizumab, an anti-CD 18 antibody, erlizumab, rovelizumab, an anti-CD20 antibody, afutuzumab, ocrelizumab, ofatumumab, pascolizumab, rituximab, an anti-CD23 antibody, lumiliximab, an anti-CD40 antibody, teneliximab, toralizumab, an anti-CD40L antibody, ruplizumab, an anti-CD62L antibody, aselizumab, an anti-CD80 antibody, galiximab, an anti-CD147 antibody, gavilimomab, a B-Lymphocyte stimulator (BlyS) inhibiting antibody, belimumab, an CTLA4-lg fusion protein, abatacept, belatacept, an anti-CTLA4 antibody, ipilimumab, tremelimumab, an anti-eotaxin 1 antibody, bertilimumab, an anti-a4-integrin antibody, natalizumab, an anti-IL-6R antibody, tocilizumab, an anti-LFA-1 antibody, odulimomab, an anti-CD25 antibody, basiliximab, daclizumab, inolimomab, an anti-CD5 antibody, zolimomab, an anti-CD2 antibody, siplizumab, nerelimomab, faralimomab, atlizumab, atorolimumab, cedelizumab, dorlimomab aritox, dorlixizumab, fontolizumab, gantenerumab, gomiliximab, lebrilizumab, maslimomab, morolimumab, pexelizumab, reslizumab, rovelizumab, talizumab, telimomab aritox, vapaliximab, vepalimomab, aflibercept, alefacept, rilonacept, an IL-1 receptor antagonist, anakinra, an anti-IL-5 antibody, mepolizumab, an IgE inhibitor, omalizumab, talizumab, an IL12 inhibitor, an IL23 inhibitor, ustekinumab. In one embodiment, the subject may be undergoing or have previously undergone treatment with a chemotherapeutic agent. Examples of chemotherapeutic agents include, but are not limited to, alkylating agents such as thiotepa and CYTOXAN cyclosphosphamide; alkyl sulfonates such as busulfan, improsulfan and piposulfan; aziridines such as benzodopa, carboquone, meturedopa, and uredopa; ethylenimines and methylamelamines including altretamine, triethylenemelamine, trietylenephosphoramide, triethiylenethiophosphoramide and trimethylolomelamine; acetogenins (e.g., bullatacin and bullatacinone); a camptothecin (including the synthetic analogue topotecan); bryostatin; callystatin; CC-1065 (including its adozelesin, carzelesin and bizelesin synthetic analogues); cryptophycins (e.g., cryptophycin 1 and cryptophycin 8); dolastatin; duocarmycin (including the synthetic analogues, KW-2189 and CB 1-TM1); eleutherobin; pancratistatin; a sarcodictyin; spongistatin; nitrogen mustards such as chlorambucil, chlornaphazine, cholophosphamide, estramustine, ifosfamide, mechlorethamine, mechlorethamine oxide hydrochloride, melphalan, novembichin, phenesterine, prednimustine, trofosfamide, uracil mustard; nitrosureas such as carmustine, chlorozotocin, fotemustine, lomustine, nimustine, and ranimnustine; antibiotics such as the enediyne antibiotics (e.g., calicheamicin, especially calicheamicin gammall and calicheamicin omegall (see, e.g., Angew, Chern. Inti. Ed. Engl., 33: 183-186 (1994)); dynemicin, including dynemicin A; bisphosphonates, such as clodronate; an esperamicin; as well as neocarzinostatin chromophore and related chromoprotein enediyne antibiotic chromophores), aclacinomysins, actinomycin, authramycin, azaserine, bleomycins, cactinomycin, carabicin, caminomycin, carzinophilin, chromomycinis, dactinomycin, daunorubicin, detorubicin, 6-diazo-5-oxo-L-norleucine, ADRIAMYCIN doxorubicin (including morpholino- doxorubicin, cyanomorpholino-doxorubicin, 2-pyrrolino-doxorubicin and deoxy doxorubicin), epirubicin, esorubicin, idarubicin, marcellomycin, mitomycins such as mitomycin C, mycophenolic acid, nogalamycin, olivomycins, peplomycin, potfiromycin, puromycin, quelamycin, rodorubicin, streptonigrin, streptozocin, tubercidin, ubenimex, zinostatin, zorubicin; anti-metabolites such as methotrexate and 5-fluorouracil (5-Fll); folic acid analogues such as denopterin, methotrexate, pteropterin, trimetrexate; purine analogs such as fludarabine, 6-mercaptopurine, thiamiprine, thioguanine; pyrimidine analogs such as ancitabine, azacitidine, 6-azauridine, carmofur, cytarabine, dideoxyuridine, doxifluridine, enocitabine, floxuridine; androgens such as calusterone, dromostanolone propionate, epitiostanol, mepitiostane, testolactone; anti-adrenals such as minoglutethimide, mitotane, trilostane; folic acid replenisher such as frolinic acid; aceglatone; aldophosphamide glycoside; aminolevulinic acid; eniluracil; amsacrine; bestrabucil; bisantrene; edatraxate; demecolcine; diaziquone; elformithine; elliptinium acetate; an epothilone; etoglucid; gallium nitrate; hydroxyurea; lentinan; lonidainine; maytansinoids such as maytansine and ansamitocins; mitoguazone; mitoxantrone; mopidanmol; nitraerine; pentostatin; phenamet; pirarubicin; losoxantrone; podophyllinic acid; 2-ethylhydrazide; procarbazine; PSK polysaccharide complex (JHS Natural Products, Eugene, Oreg.); razoxane; rhizoxin; sizofuran; spirogermanium; tenuazonic acid; triaziquone; 2,2’,2”-trichlorotriethylamine; trichothecenes (e.g., T-2 toxin, verracurin A, roridin A and anguidine); urethan; vindesine; dacarbazine; mannomustine; mitobronitol; mitolactol; pipobroman; gacytosine; arabinoside (“Ara-C”); cyclophosphamide; thiotepa; taxoids, e.g., TAXOL paclitaxel (Bristol-Myers Squibb Oncology, Princeton, N.J.), ABRAXANE Cremophor-free, albumin-engineered nanoparticle formulation of paclitaxel (American Pharmaceutical Partners, Schaumberg, 111.), and TAXOTERE doxetaxel (Rhone-Poulenc Rorer, Antony, France); chloranbucil; GEMZAR gemcitabine; 6-thioguanine; mercaptopurine; methotrexate; platinum analogs such as cisplatin, oxaliplatin and carboplatin; vinblastine; platinum; etoposide (VP-16); ifosfamide; mitoxantrone; vincristine; NAVELBINE vinorelbine; novantrone; teniposide; edatrexate; daunomycin; aminopterin; xeloda; ibandronate; irinotecan (Camptosar, CPT-11) (including the treatment regimen of irinotecan with 5-Fll and leucovorin); topoisomerase inhibitor RFS 2000; difluoromethylornithine (DMFO); retinoids such as retinoic acid; capecitabine; combretastatin; leucovorin (LV); oxaliplatin, including the oxaliplatin treatment regimen (FOLFOX); lapatinib (Tykerb); inhibitors of PKC-a, Raf, H-Ras, EGFR (e.g., erlotinib (Tarceva)) and VEGF-A that reduce cell proliferation and pharmaceutically acceptable salts, acids or derivatives of any of the above. In addition, the methods of treatment can further include the use of radiation. In addition, the methods of treatment can further include the use of photodynamic therapy. PROCESS Another aspect of the invention relates to processes for preparing compounds of formula (I) as described herein. In one embododiment, the invention relates to a process for preparing a compound of formula (I) from a compound of formula (II) and a compound of formula (III): Further details of processes according to the invention are set out in the accompanying examples. The present invention is further described by way of the following non-limiting examples. EXAMPLES Where the preparation of starting materials is not described, these are commercially available, known in the literature, or readily obtainable by those skilled in the art using standard procedures. Where it is indicated that compounds were prepared analogously to earlier examples or intermediates, it will be appreciated by the skilled person that the reaction time, number of equivalents of reagents, solvent, concentration and temperature can be modified for each specific reaction and that it may be necessary or desirable to employ different work-up or purification techniques. General Schemes Abbreviations aq: aqueous; DAD: diode array detector; DBU: 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine; DCM: dichloromethane; dioxane: 1,4-dioxane; DIPEA: / V, / V-Diisopropylethylamine; ESI: electrospray ionisation; EtOAc: ethyl acetate; EtOH: ethanol; h: hour(s); HPLC: high performance liquid chromatography; IPA: isopropyl alcohol; LC: liquid chromatography; M: molar, molecular ion; MeCN: acetonitrile; MeOH: methanol; min: minute(s); MS: mass spectrometry; MSD: mass spectrometry detector; m / z: mass to charge ratio; NMR: nuclear magnetic resonance; PDA: photodiode array; ppm: parts per million; SFC: supercritical fluid chromatography; TBME: tert-butyl methyl ether; TIC: total ion current; TFA: trifluoroacetic acid; THF: tetrahydrofuran; RT: room temperature (ca. 20 °C); UV: ultraviolet; UPLC: ultra performance liquid chromatography. Other abbreviations are intended to convey their generally accepted meanings. Scheme 1 (Rs)m cf3 I-5 A. NH H A 0 0 Reagents: (a) Amine, DIPEA, DCM; (b) Zn, NH4CI, THF, water; (c) l-(fluorosulfonyl)-2,3-dimethylimidazol-3-ium trifluoromethanesulfonate, DCM, RT; (d) amine, DBU, MeCN, 50 °C. Aryl halide (1-1) was reacted with the appropriate amine in a nucleophilic substitution reaction, followed by reduction of the resultant nitro-aniline I-2 to primary aniline I-3. This was reacted with the SuFex reagent to afford sulfamoyl fluoride I-4, followed by nucleophilic substitution with the appropriate amine to afford sulfamide I-5. 10 Scheme 2 R' R" 1-6 a, b or c R'\ NH / R" 1-7 15 Reagents: (a) HCI, dioxane, DCM; (b) HCI, IPA; (c) TFA, DCM. Acid mediated deprotection of Boc-protected-amine (1-6) provided the corresponding amine (I-7). General Experimental Conditions All starting materials and solvents were obtained either from commercial sources or prepared according to the literature citation. Reaction mixtures were magnetically stirred, and reactions performed at room temperature (ca. 20 °C) unless otherwise indicated. Column chromatography was performed on an automated flash chromatography system, such as a CombiFlash Rf system or Biotage Isolera Rf system. Normal phase chromatography was performed using pre-packed silica (40 pm) cartridges, running gradients of either EtOAc / isohexane, MeOH / DCM, or (1:3 EtOH / EtOAc) / isohexane, optionally modified with ammonia or acetic acid, unless otherwise indicated, selected on the basis of thin-layer chromatography analysis. Reverse phase chromatography was performed using pre-packed Cis-derivatised silica (40 - 63 pm) cartridges, running gradients of MeCN / water, optionally modified with either ammonium bicarbonate or formic acid, selected on the basis of LC-MS analysis. Preparative HPLC was performed on an automated purification system using one of the following columns: Waters X-select CSH C18 ODB, 130 A, 5 pm, 30 x 100 mm; Waters XBridge BEH C18 ODB prep column, 130A, 5 pm, 30 x 100 mm; Phenomenex Gemini NC-C18, 110 A, 5 pm, 30 x 150 mm. A suitable gradient of MeCN / water modified with either formic acid, ammonia, or ammonium bicarbonate was selected on the basis of LC-MS analysis. 1H NMR spectra were recorded using a Bruker Avance III HD spectrometer at 500 MHz, equipped with a Bruker 5 mm SmartProbe™, or a Bruker Avance 400 MHz spectrometer. Chemical shifts are expressed in parts per million using either the central peaks of the residual protic solvent or an internal standard of tetramethylsilane as references. Peak multiplicities are reported as a combination of s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, br = broad, app = apparent, etc, with coupling constants (J) reported where appropriate. The spectra were recorded at 298 K unless otherwise indicated. Analytical IIPLC-MS experiments to determine retention times and associated mass ions were performed using a Waters ACQUITY UPLC® H-Class system, equipped with Binary Solvent Pump, SM-FTN, CMA, PDA, QDa, running one of the analytical methods described below. Analytical LC-MS experiments to determine retention times and associated mass ions were performed using an Agilent 1260 HPLC system, Quaternery Pump, HiP Sampler, Column Compartment, DAD, G6150 MSD running one of the analytical methods described below. Nomenclature of structures was generated using ‘Structure to Name’ conversion from ChemDraw® Professional 21 (PerkinElmer). Analytical Methods Method 1 - UPLC Acidic 3 min method Column: Waters ACQUITY UPLC®CSH C18, 1.7 pm, 2.1 x 30 mm at 40 °C Detection: UV at 254 nm unless otherwise indicated, MS by electrospray ionisation Solvents: A: 0.1% Formic in water, B: MeCN Gradient: Time %A %B Flow rate (mL / min) 0.00 98 2 0.77 2.50 0 100 0.77 3.00 0 100 0.77 Method 2 - UPLC Basic Method Column: Waters ACQUITY UPLC® BEH C18, 1.7 pm, 2.1 x 30 mm at 40 °C Solvents: A: 0.2% Ammonia in water, B: MeCN Other conditions as Method 1. Method 3 - LCMS Acidic Method Column: Waters Cortecs C18, 30 x 2.1 mm, 2.7pm, at 40 °C Detection: UV at 254 nm unless otherwise indicated, MS by electrospray ionisation Solvents: A: 0.1% formic acid in water, B: MeCN Gradient: Time %A %B Flow rate (mL / min) 0.00 98 2 1.35 2.5 0 100 1.35 3 0 100 1.35 Method 4 - LCMS Basic Method Column: Phenomenex Evo C18, 30 x 2.1 mm, 2.6pm, at 40 °C Solvents: A: 0.2% Ammonia in water, B: MeCN Other conditions as Method 3. General Procedures General Procedure 1: Nucleophilic substitution between amine and aryl halide (I-1) A solution of the aryl halide (1-1) (1 eq) in DCM (20 volumes) was treated with DIPEA (3 eq). The resultant mixture was cooled to 0 °C, then the appropriate amine (1.5 eq) was added dropwise. The mixture was allowed to warm to RT and stir until completion (1 - 24 h). The mixture was partitioned between DCM (15 volumes) and water (20 volumes), then the phases separated. The aqueous phase was extracted with DCM (2 x 6 volumes). The organic phases were combined, dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by chromatography on silica gel to afford the nitro-aniline (I-2). General Procedure 2: Reduction of nitro-aniline (1-2) (a) A rapidly stirred solution of nitro-aniline (1-2) (1 eq) in THF (20 volumes) and water (6 volumes) at 0 °C was treated with NH4CI(s) (7-10 eq), followed by portionwise addition of zinc powder (7-10 eq). The resultant suspension was allowed to warm to RT and stir until completion (2 - 24 h). The mixture was partitioned between EtOAc (12 volumes) and water (20 volumes). The phases were separated, and the organic phase washed with a 1:1 mixture of brine / water (2 x 12 volumes). The aqueous phases were combined and extracted with EtOAc (6 volumes), then the organic phases were combined, dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by chromatography on silica gel to afford the primary aniline (I-3). (b) Prepared according to general procedure 2a, except, after completion, the reaction mixture was cooled to 0 °C. Saturated NaHCO3(aq) (12 volumes) was added, then the reaction mixture was allowed to warm to RT and was worked up and purified. General Procedure 3: Sulfamoyl fluoride formation from primary aniline (1-3) A solution of primary aniline (1-3) (1 eq) in DCM (20 volumes) at 0 °C was treated with 1-(fluorosulfonyl)-2,3-dimethylimidazol-3-ium trifluoromethanesulfonate (1.5 eq) and the resultant mixture was allowed to warm to RT and stir until completion (1 - 24 h). The reaction mixture was concentrated in vacuo onto silica gel and purified by chromatography on silica gel to afford sulfamoyl fluoride (I-4). General Procedure 4: Nucleophilic substitution of sulfamoyl fluoride (1-4) (a) A solution of the appropriate amine (1.5-2 eq) in MeCN (10 volumes) was treated with DBU (5-8 eq). After 15 min, a solution of sulfamoyl fluoride (I-4) (1 eq) in MeCN (10 volumes) was added and the reaction was then stirred at 50 °C until completion (1 - 24 h). The mixture was concentrated in vacuo and the residue partitioned between DCM (30 volumes) and saturated NaHCO3(aq) (30 volumes). The phases were separated, and the organic phase was washed with brine (30 volumes), dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by chromatography on silica gel to afford sulfamide (I-5). (b) Prepared according to general procedure 4a, except the product was purified by reverse phase chromatography on a Cis cartridge. (c) Prepared according to general procedure 4a, except after drying and filtration, the organic phase was concentrated in vacuo onto Celite® and purified by reverse phase chromatography on a Cis cartridge. (d) Prepared according to general procedure 4a, except the product was further purified by reverse phase chromatography on a Cis cartridge. (e) Prepared according to general procedure 4a, except the product was purified by preparative HPLC. (f) A solution of the appropriate amine (1.5-2 eq) in MeCN (15 volumes) was treated with DBU (5-8 eq). After 15 min, a solution of sulfamoyl fluoride (I-4) (1 eq) in MeCN (15 volumes) was added and the reaction was then stirred at 50 °C until completion (1 - 24 h). The residue was partitioned between EtOAc (150 volumes) and 2:1 water / brine (150 volumes). The phases were separated, and the aqueous phase was extracted with EtOAc (150 volumes). The organic phases were combined, dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by chromatography on silica gel to afford sulfamide (1-5). (g) Prepared according to General Procedure 4f, except the product was purified by reverse phase chromatography on a Cis cartridge. General Procedure 5: Boc-deprotection of Boc-protected amine (1-6) A solution of the appropriate Boc-protected amine (1-6) (1 eq) in MeOH (20 volumes) was treated with 4 M HCI in dioxane (10 eq). The reaction mixture was stirred until completion (1 - 24 h), then concentrated in vacuo to afford amine (I-7) as the hydrochloride salt. General Procedure 6: Boc-deprotection of Boc-protected amine (1-6) (a) Prepared according to General Procedure 5, except DCM was used as solvent in place of MeOH. (b) A stirred solution of the appropriate Boc-protected amine (1-6) in DCM (20 volumes) was treated with TFA (10 eq). The resultant mixture was stirred until completion (6-18 h). The mixture was concentrated in vacuo, then the residue dissolved in DCM (400 volumes) and washed with saturated NaHCO3(aq) (400 volumes), dried over MgSO4, filtered, and concentrated in vacuo to afford amine (I-7). (c) Prepared according to General Procedure 5b and then purified by reverse phase chromatography on a Cis cartridge. INTERMEDIATES Intermediate 1a: 5-(Azetidin-3-yl)-2-methyltetrazole hydrochloride / M-Ns IL HCI HN—। Step 1: tert-Butyl 3-(2-methyltetrazol-5-yl)azetidine-1-carboxylate: A suspension of tert-butyl 3-(tetrazol-5-yl)azetidine-1-carboxylate (62 mg, 275 pmol, 99% purity) in DMF (2 mL) was cooled to 0 °C, then treated with NaH (60% in mineral oil) (12 mg 289 pmol). The reaction mixture was stirred at 0 °C for 5 min and then at RT for 1 h. The mixture was cooled to 0 °C and iodomethane (22 pL, 344 pmol) was added. The reaction mixture was stirred at RT for 1 h. The mixture was cooled to 0 °C, then water (10 mL) and TBME (30 mL) were added, the phases separated, and the aqueous phase was further extracted with TBME (2*10 mL). The organic phases were combined, washed with brine (15 mL), then concentrated under in vacuo. The residue was purified by reverse phase chromatography on a 4 g Cis cartridge (5 - 30% (0.1% formic acid in MeCN) I (0.1% formic acid in water)) to afford the title compound (36 mg, 146 pmol, 97% purity) as a colourless oil. 1H NMR (500 MHz, CDCI3) 6 4.37 -4.31 (m, 5H), 4.23 - 4.20 (m, 2H), 4.07 - 4.01 (m, 1H), 1.45 (s, 9H). Step 2: 5-(azetidin-3-yl)-2-methyltetrazole hydrochloride: The title compound (33 mg, 183 pmol, 99% purity) was prepared from the product of Step 1 above (45 mg, 183 pmol, 97% purity) following General Procedure 5. UPLC (Method 1): m / z 140.2 [M+H]+, at 0.14 min. Intermediate 1b: 5-(Azetidin-3-yl)-1 -methyltetrazole hydrochloride HCI HN—1 Step 1: tert-Butyl 3-(1-methyltetrazol-5-yl)azetidine-1-carboxylate: The title compound (25 mg, 100 pmol, 96% purity) was obtained as a colourless oil from the separation performed in Intermediate 1a Step 1.1H NMR (500 MHz, CDCI3) 5 4.44-4.35 (m, 2H), 4.35 - 4.26 (m, 2H), 3.99 (s, 3H), 3.98 - 3.90 (m, 1H), 1.46 (s, 9H). Step 2: 5-(Azetidin-3-yl)-1-methyltetrazole hydrochloride: The title compound (18 mg, 100 pmol, 99% purity) was prepared from the product of Step 1 above (25 mg, 100 pmol, 96% purity) following General Procedure 5. UPLC (Method 1): m / z 140.5 [M+H]+, no mass ion observed [M-Hp, at 0.16 min. Structure / Reference Name / Procedure / Analytical Data C\H h h I % JI o o F y cf3 Intermediate 2 (2-(Cyclohexylamino)-4-fluoro-5-(trifluoromethyl)phenyl)sulfamoyl fluoride (2.80 g, 7.74 mmol, 99% purity) was prepared as a purple solid from 1,5-difluoro-2-nitro-4-(trifluoromethyl)benzene (3.00 g, 13.2 mmol) and cyclohexylamine.following General Procedure 1, 2b and 3a. 1H NMR (500 MHz, CDCI3) 6 7.44 (d, J= 7.1 Hz, 1H), 6.55 (d, J = 12.4 Hz, 1H), 3.34 - 3.20 (m, 1H), 2.08 -1.93 (m, 2H), 1.88-1.73 (m, 2H), 1.71 - 1.58 (m, 1H), 1.51 - 1.22 (m, 6H). One exchangeable proton not observed. 19F NMR (471 MHz, CDCh) 6 -60.05, -109.88. S-F fluorine not observed. h f H T y y o o F cf3 Intermediate 3 (4-Fluoro-2-(((1R,2R)-2-methylcyclohexyl)amino)-5-(trifluoromethyl)phenyl)sulfamoyl fluoride (613 mg, 1.5 mmol, 89% purity) was prepared as a brown oil from 1,5-difluoro-2-nitro-4-(trifluoromethyl)benzene (2.35 g, 10.3 mmol) and (1R,2R)-2-methylcyclohexan-1-amine hydrochloride, sequentially following General Procedure 1, 2a and 3. 1H NMR (400 MHz, CDCI3) 6 7.40 (d, J = 7.3 Hz, 1H), 6.52 (s, 1H), 6.46 (d, J = 13.0 Hz, 1H), 2.89 (td, J = 10.5, 3.9 Hz, 1H), 2.03-1.98 (m, 1H), 1.97-1.75 (m, 3H), 1.76-1.67 (m, 1H), 1.52-1.39 (m, 1H), 1.38-1.21 (m, 2H), 1.19-1.07 (m, 2H), 0.98 (d, J= 6.5 Hz, 3H). 19F NMR (376 MHz, CDCI3) 6 -59.84, -60.71, -110.01. 0>nh h f h T 2 y o o f cf3 Intermediate 4 (4-Fluoro-2-(((1S,2S)-2-methylcyclohexyl)amino)-5-(trifluoromethyl)phenyl)sulfamoyl fluoride (1.22 g, 3.09 mmol, 94% purity) was prepared as a brown oil from 1,5-difluoro-2-nitro-4-(trifluoromethyl)benzene (2.5 g, 11 mmol) and (1S,2S)-2-methylcyclohexan-1-amine hydrochloride, sequentially following General Procedure 1, 2a, and 3. Structure / Reference Name / Procedure / Analytical Data UPLC (Method 1): m / z 373.2 [M+H]+, 371.1 [M-H]’, at 2.13 min. 1H NMR (500 MHz, CDCI3) 6 7.39 (d, J= 7.3 Hz, 1H), 6.59 (s, 1H), 6.44 (d, J = 13.1 Hz, 1H), 2.94 -2.84 (m, 1H), 2.07-2.02 (m, 1H), 1.88-1.82 (m, 1H), 1.82-1.76 (m, 1H), 1.75 - 1.69 (m, 1H), 1.50 - 1.39 (m, 1H), 1.39-1.22 (m, 2H), 1.18-1.08 (m, 2H), 0.98 (d, J = 6.5 Hz, 3H). One exchangeable proton not observed. 19F NMR (471 MHz, CDCI3) 6 -64.57, -114.90. SF fluorine not observed. EXAMPLES Structure / Example Name / Method / Analytical Data O hn-n L jk N H / k N___N-J filT .A. k 00 F F F F Example 1 A / -(2-(cyclohexylamino)-4-fluoro-5-(trifluoromethyl)phenyl)-3-(tetrazol-5-yl)azetidine-1-sulfonamide (300 mg, 641 pmol, 99% purity) was prepared as a tan solid from Intermediate 2 (320 mg, 848 pmol) and tert-butyl 3-(tetrazol-5-yl)azetidine-1-carboxylate, sequentially following General Procedure 5 and 4b. LCMS (Method 3) m / z 464.2 (M+H)+, 462.0 (M-H)-, at 1.62 min; 1H NMR (400 MHz, DMSO) 5 9.20 (s, 1H), 7.38 (d, J= 7.8 Hz, 1H), 6.71 (d, J = 14.1 Hz, 1H), 5.65 -5.58 (m, 1H), 4.24-4.15 (m, 2H), 4.18-4.08 (m, 1H), 4.08-4.01 (m, 2H), 1.89-1.85 (m, 2H), 1.71 -1.66 (m, 2H), 1.64 - 1.55 (m, 1H), 1.45 - 1.29 (m, 2H), 1.25 - 1.11 (m, 3H). One exchangeable proton not observed. One proton is obscured by water peak. 19F NMR (376 MHz, DMSO) 5 -57.78 (d, J = 11.6 Hz), -116.32 (q, J= 11.5 Hz). Structure / Example Name / Method / Analytical Data h-p O. zZI Jw z Z= / A / -(2-(cyclohexylamino)-4-fluoro-5-(trifluoromethyl)phenyl)-3-(pyridin-3-yl)azetidine-1-sulfonamide (72 mg, 145 pmol, 95% purity) was prepared as a light-brown solid from Intermediate 2 (75 mg, 207 pmol) and 3-(azetidin-3-yl)pyridine dihydrochloride, following General Procedure 4b. LCMS (Method 3) m / z no mass ion observed (M+H)+, 471.2 (M-H)-, at 1.52 min; 1H NMR (500 MHz, DMSO) 5 9.18 (s, 1H), 8.57-8.43 (m, 2H), 7.75-7.72 (m, 1H), 7.41 -7.37 (m, 2H), 6.71 (d, J = 14.0 Hz, 1H), 5.72-5.59 (m, 1H), 4.26-4.13 (m, 2H), 3.84 (m, 3H), 3.39-3.33 (m, 1H), 1.90- 1.82 (m, 2H), 1.74-1.63 (m, 2H), 1.62 - 1.54 (m, 1H), 1.42 - 1.30 (m, 2H), 1.29 - 1.22 (m, 1H), 1.22 - 1.10 (m, 2H); 19F NMR (471 MHz, DMSO) 5 -57.74 (d, J= 11.6 Hz), -116.77. r F^ ^F F Example 2 F^ HN'N k N H 1^7^^ k ,N^ ^—J ^00 ^F Example 3 A / -(4-fluoro-2-(((1 / ?,2 / ?)-2-methylcyclohexyl)amino)-5-(trifluoromethyl)phenyl)-3-(tetrazol-5-yl)azetidine-1-sulfonamide (87 mg, 180 pmol, 99% purity) was prepared as a pale pink solid from Intermediate 3 (95 mg, 230 pmol) and tert-butyl 3-(tetrazol-5-yl)azetidine-1-carboxylate, sequentially following General Procedure 5 and 4c. UPLC (Method 1) m / z 477.8 (M+H)+, 476.2 (M-H)-, at 1.76 min; 1H NMR (500 MHz, DMSO) 5 7.35 (d, J = 7.9 Hz, 1H), 6.74 (d, J= 14.3 Hz, 1H), 5.54 (d, J= 8.5 Hz, 1H), 4.24 - 4.04 (m, 5H), 3.08 (m, 1H), 1.90 - 1.82 (m, 1H), 1.77-1.69 (m, 1H), 1.70-1.59 (m, 2H), 1.50-1.39 (m, 1H), 1.41 - 1.30 (m, 1H), 1.28-1.16 (m, 1H), 1.16-1.00 (m, 2H), 0.89 (d, J= 6.5 Hz, 3H). Two exchangeable protons not observed. 19F NMR (471 MHz, DMSO) 5 -57.68 (d, J = 11.5 Hz), -116.24 (q, J = 11.6 Hz). Structure / Example Name / Method / Analytical Data A / -(2-(cyclohexylamino)-4-fluoro-5-(trifluoromethyl)phenyl)-3-(imidazol-1-yl)azetidine-1-sulfonamide (26 mg, 56 pmol, 99% purity) was prepared as a white solid from Intermediate 2 (80 mg, 219 pmol) and 1-(azetidin-3-yl) imidazole hydrochloride, following General Procedure 4e. LCMS (Method 3) m / z 462.0 (M+H)+, 459.8 (M-H)’, at 1.22 min; 1H NMR (500 MHz, DMSO) 6 8.13 (s, 1H), 7.75 (s, 1H), 7.38 (d, J= 7.8 Hz, 1H), 7.30 (d, J= 1.4 Hz, 1H), 6.98 (s, 1H), 6.73 (d, J= 14.0 Hz, 1H), 5.66-5.60 (m, 1H), 5.14-5.07 (m, 1H), 4.28-4.22 (m, 2H), 3.99 (dd, J = 9.0, 5.7 Hz, 2H), 3.43 - 3.35 (m, 1H), 1.94 - 1.85 (m, 2H), 1.73- 1.65 (m, 2H), 1.62 - 1.55 (m, 1H), 1.43-1.32 (m, 2H), 1.24-1.15 (m, 3H); 19F NMR (471 MHz, DMSO) 6 -57.75 (d, J= 11.5 Hz), -116.44. r FX ^F F Example 4 x F1 'JH H L,N-J 1 A o o ^F Example 5 A / -(2-(cyclohexylamino)-4-fluoro-5-(trifluoromethyl)phenyl)-3-(pyrazol-1-yl)azetidine-1-sulfonamide (20 mg, 41 pmol, 95% purity) was prepared as an off-white solid from Intermediate 2 (75 mg, 205 pmol) and 1-(azetidin-3-yl) pyrazole dihydrochloride, following General Procedure 4e. LCMS (Method 3) m / z 462.0 (M+H)+, 459.8 (M-H)-, at 1.82 min; 1H NMR (500 MHz, DMSO) 6 9.24 (s, 1H), 7.80 (d, J= 2.3 Hz, 1H), 7.57 (d, J= 1.8 Hz, 1H), 7.45 (d, J= 7.8 Hz, 1H), 6.72 (d, J= 14.1 Hz, 1H), 6.30 (m, 1H), 5.60 (d, J = 7.8 Hz, 1H), 5.29 - 5.20 (m, 1H), 4.24 (dd, J = 8.2, 6.5 Hz, 2H), 4.19 4.14 (m, 2H), 3.46 - 3.35 (m, 1H), 1.93-1.85 (m, 2H), 1.75 - 1.64 (m, 2H), 1.64 - 1.54 (m, 1H), 1.42- 1.32 (m, 2H), 1.26-1.15 (m, 3H); 19F NMR (471 MHz, DMSO) 6 -57.70 (d, J= 11.6 Hz), -116.29. Structure / Example Name / Method / Analytical Data z^ z \\ / / Z\ Wx izs° A / -(2-(cyclohexylamino)-4-fluoro-5-(trifluoromethyl)phenyl)-3-(pyrazin-2-yl)azetidine-1-sulfonamide (12 mg, 25 pmol, 98% purity) was prepared as a yellow solid from Intermediate 2 (75 mg, 207 pmol) and 2-(azetidin-3-yl)pyrazine, following General Procedure 4a. LCMS (Method 3) m / z 474.2 (M+H)+, 472.2 (M-H)’, at 1.76 min; 1H NMR (500 MHz, DMSO) 6 9.15 (s, 1H), 8.65 (dd, J = 2.6, 1.5 Hz, 1H), 8.60 (d, J = 1.5 Hz, 1H), 8.56 (d, J= 2.6 Hz, 1H), 7.42 (d, J= 7.8 Hz, 1H), 6.70 (d, J = 14.1 Hz, 1H), 5.64-5.58 (m, 1H), 4.15-4.00 (m, 5H), 1.89-1.83 (m, 2H), 1.71 - 1.65 (m, 2H), 1.61 - 1.55 (m, 1H), 1.42-1.31 (m, 2H), 1.23-1.12 (m, 3H). One proton obscured by water peak. 19F NMR (471 MHz, DMSO) 5 -57.76 (d, J = 11.6 Hz), -116.49 (q, J = 11.6 Hz). r ^F F Example 6 r J F1 JH H ^00 ^F Example 7 A / -(2-(cyclohexylamino)-4-fluoro-5-(trifluoromethyl)phenyl)-3-(pyridin-2-yl)azetidine-1-sulfonamide (35 mg, 73 pmol, 99% purity) was prepared as a yellow solid from Intermediate 2 (75 mg, 207 pmol) and 2-(azetidin-3-yl)pyridine dihydrochloride, following General Procedure 4b. LCMS (Method 3) m / z 473.2 (M+H)+, 471.2 (M-H)-, at 1.78 min; 1H NMR (500 MHz, DMSO) 5 9.13 (s, 1H), 8.58 - 8.54 (m, 1H), 7.78 - 7.73 (m, 1H), 7.43 (d, J = 7.8 Hz, 1H), 7.33 - 7.27 (m, 2H), 6.69 (d, J = 14.0 Hz, 1H), 5.61 (d, J= 7.8 Hz, 1H), 4.12-4.05 (m, 4H), 3.94 (p, J= 7.6 Hz, 1H), 3.39-3.33 (m, 1H), 1.90-1.81 (m, 2H), 1.71 - 1.64 (m, 2H), 1.61 - 1.54 (m, 1H), 1.41 -1.31 (m, 2H), 1.23-1.11 (m, 3H). 19F NMR (471 MHz, DMSO) 5 -57.74 (d, J = 11.6 Hz), -116.55 (q, J = 11.6 Hz). Structure / Example Name / Method / Analytical Data A / -(2-(cyclohexylamino)-4-fluoro-5-(trifluoromethyl)phenyl)-3-(piperidin-1-yl)azetidine-1-sulfonamide (25 mg, 51 pmol, 98% purity) was prepared as an off-white solid from Intermediate 2 (75 mg, 207 pmol) and 1-(azetidin-3-yl)piperidine dihydrochloride, following General Procedure 4b. The product was analysed by LCMS (Method 3): m / z 479.2 ((M+H)+, 477.2 (M-H)’ at 1.24 min; 1H NMR (500 MHz, DMSO) 5 7.36 (d, J= 7.8 Hz, 1H), 6.69 (d, J = 14.0 Hz, 1H), 5.66-5.57 (m, 1H), 3.73 (m, 2H), 3.64 (dd, J = 7.8, 6.2 Hz, 2H), 3.44 - 3.36 (m, 1H), 2.98 (p, J = 6.7 Hz, 1H), 2.16 (brs, 4H), 1.95-1.89 (m, 2H), 1.74 - 1.67 (m, 2H), 1.64 - 1.56 (m, 1H), 1.50 - 1.45 (m, 4H), 1.43- 1.32 (m, 4H), 1.29-1.16 (m, 3H). One exchangeable proton not observed. 19F NMR (471 MHz, DMSO) 6-57.72 (d, J= 11.6 Hz), -116.88. r XF F Example 8 r F1 ?H h V A ^00 ^F Example 9 A / -(2-(cyclohexylamino)-4-fluoro-5-(trifluoromethyl)phenyl)-3-(pyrrolidin-1-yl)azetidine-1-sulfonamide (15 mg, 32 pmol, 98% purity) was prepared as an off-white solid from Intermediate 2 (75 mg, 207 pmol) and 1-(azetidin-3-yl)pyrrolidine dihydrochloride, following General Procedure 4b. The product was analysed by LCMS (Method 3): m / z 465.2 ((M+H)+, 463.2 (M-H)- at 1.21 min; 1H NMR (500 MHz, DMSO) 6 7.37 (d, J= 7.8 Hz, 1H), 6.69 (d, J = 14.0 Hz, 1H), 5.60 (d, J= 7.7 Hz, 1H), 3.81 -3.75 (m, 2H), 3.69 (dd, J = 7.9, 5.7 Hz, 2H), 3.47 - 3.38 (m, 1H), 3.24-3.17 (m, 1H), 2.38 (brs, 4H), 1.95-1.89 (m, 2H), 1.74-1.65 (m, 6H), 1.64 - 1.57 (m, 1H), 1.45 -1.33 (m, 2H), 1.28 - 1.17 (m, 3H). One exchangeable proton not observed. 19F NMR (471 MHz, DMSO) 5 -57.76 (d, J= 11.5 Hz), -116.82. Structure / Example Name / Method / Analytical Data A> MH L / N^ ^n-J \ y o o ^F Example 10 A / -(2-(cyclohexylamino)-4-fluoro-5-(trifluoromethyl)phenyl)-3-(4-methyl-1,2,4-triazol-3-yl)azetidine-1-sulfonamide (43 mg, 86 pmol, 95% purity) was prepared as an off-white solid from Intermediate 2 (83 mg, 229 pmol) and 3-(azetidin-3-yl)-4-methyl-1,2,4-triazole, following General Procedure 4c. The product was analysed by LCMS (Method 3): m / z 477.2 (M+H)+ 475.2 (M-H)’ at 1.53 min; 1H NMR (400 MHz, DMSO) 6 9.18 (s, 1H), 8.41 (s, 1H), 7.37 (d, J = 7.8 Hz, 1H), 6.70 (d, J = 14.1 Hz, 1H), 5.63 (d, J= 7.8 Hz, 1H), 4.19-4.09 (m, 4H), 4.07-3.98 (m, 1H), 3.51 (s, 3H), 3.44 - 3.35 (m, 1H), 1.94- 1.82 (m, 2H), 1.74 -1.65 (m, 2H), 1.63 - 1.53 (m, 1H), 1.45 - 1.30 (m, 2H), 1.28-1.12 (m, 3H); 19F NMR (376 MHz, DMSO) 6 -57.75, -116.46. J A m H rA" V A 0 O A Example 11 A / -(2-(cyclohexylamino)-4-fluoro-5-(trifluoromethyl)phenyl)-3-(pyrimidin-5-yl)azetidine-1-sulfonamide (31 mg, 64 pmol, 97% purity) was prepared as an off-white solid from Intermediate 2 (83 mg, 229 pmol) and 5-(azetidin-3-yl)pyrimidine hydrochloride, following General Procedure 4c. The product was analysed by LCMS (Method 3): m / z no mass ion observed (M+H)+ 472.0 (M-H)’ at 1.68 min; 1H NMR (400 MHz, DMSO) 5 9.19 (s, 1H), 9.10 (s, 1H), 8.76 (s, 2H), 7.39 (d, J= 7.9 Hz, 1H), 6.72 (d, J = 14.0 Hz, 1H), 5.64 (d, J= 7.8 Hz, 1H), 4.22-4.18 (m, 2H), 3.95-3.80 (m, 3H), 1.91 - 1.79 (m, 2H), 1.73-1.63 (m, 2H), 1.62-1.51 (m, 1H), 1.44-1.28 (m, 2H), 1.25 - 1.08 (m, 3H). One proton obscured by water peak. 19F NMR (376 MHz, DMSO) 5 -57.80 (d, J = 11.6 Hz), -116.46. Structure / Example Name / Method / Analytical Data jT F^ H h .N-J Y A ^00 XF Example 12 A / -(2-(cyclohexylamino)-4-fluoro-5-(trifluoromethyl)phenyl)-3-(4-methylpiperazin-1-yl)azetidine-1-sulfonamide (25 mg, 48 pmol, 95% purity) was prepared as an off-white solid from Intermediate 2 (83 mg, 229 pmol) and 1-(azetidin-3-yl)-4-methylpiperazine, following General Procedure 4c. The product was analysed by LCMS (Method 3): m / z 494.2 (M+H)+ 492.2 (M-H)’ at 1.22 min; 1H NMR (400 MHz, DMSO) 6 7.33 (d, J= 7.9 Hz, 1H), 6.63 (d, J = 14.0 Hz, 1H), 5.61 (d, J= 7.4 Hz, 1H), 3.71 -3.67 (m, 2H), 3.65 - 3.59 (m, 2H), 3.06 - 2.97 (m, 1H), 2.47 -2.11 (m, 11H), 1.97-1.87 (m, 2H), 1.76-1.65 (m, 2H), 1.64-1.55 (m, 1H), 1.48-1.31 (m, 2H), 1.30-1.13 (m, 3H). One exchangeable proton not observed. One proton obscured by water peak. 19F NMR (376 MHz, DMSO) 5 -57.51 (d, J = 11.5 Hz). One fluorine not observed. Ox X N'N II N CnvnJ h J A "F Example 13 A / -(4-fluoro-2-(((1S,2S)-2-methylcyclohexyl)amino)-5-(trifluoromethyl)phenyl)-3-(tetrazol-5-yl)azetidine-1-sulfonamide (40 mg, 82 pmol, 98% purity) was prepared as a light-pink solid from Intermediate 4 (63 mg, 159 pmol) and tert-butyl 3-(tetrazol-5-yl)azetidine-1-carboxylate, sequentially following General Procedure 5 and 4c. The product was analysed by LCMS (Method 3): m / z 478.2 (M+H)+, 476.0 (M-H)- at 1.69 min; 1H NMR (400 MHz, DMSO) 5 9.20 (s, 1H), 7.35 (d, J= 7.9 Hz, 1H), 6.75 (d, J = 14.3 Hz, 1H), 5.54 (d, J= 8.8 Hz, 1H), 4.28 -4.02 (m, 5H), 3.18-2.99 (m, 1H), 1.90-1.80 (m, 1H), 1.78-1.56 (m, 3H), 1.50 - 1.28 (m, 2H), 1.28 -0.98 (m, 3H), 0.88 (d, J= 6.4 Hz, 3H). One exchangeable proton not observed. Structure / Example Name / Method / Analytical Data ■0 A / -(2-(cyclohexylamino)-4-fluoro-5-(trifluoromethyl)phenyl)-3-(1,2,3-triazol-1-yl)azetidine-1-sulfonamide (8 mg, 17 pmol, 98% purity) was prepared as an off-white solid from Intermediate 2 (75 mg, 207 pmol) and 1-(azetidin-3-yl)-1,2,3-triazole hydrochloride, following General Procedure 4e. The product was analysed by LIPLC (Method 1): m / z 463.2 (M+H)+ 461.2 (M-H)’ at 1.68 min. 1H NMR (400 MHz, DMSO) 5 9.30 (s, 1H), 8.23 (s, 1H), 7.81 (s, 1H), 7.39 (d, J= 7.8 Hz, 1H), 6.73 (d, J = 14.0 Hz, 1H), 5.63 (d, J = 7.8 Hz, 1H), 5.56 - 5.43 (m, 1H), 4.33 - 4.29 (m, 2H), 4.27-4.21 (m, 2H), 1.97-1.81 (m, 2H), 1.75-1.64 (m, 2H), 1.63 - 1.54 (m, 1H), 1.46 - 1.29 (m, 2H), 1.28-1.11 (m, 3H). One proton obscured by solvent peak. 19F NMR (376 MHz, DMSO) 5 -57.68 (d, J= 11.6 Hz), -117.42. r F^ ^F F Example 14 jf r^~N L U JH h k XN-J V & J O O XF Example 15 A / -(2-(cyclohexylamino)-4-fluoro-5-(trifluoromethyl)phenyl)-3-(pyridin-4-yl)azetidine-1-sulfonamide (12 mg, 25 pmol, 99% purity) was prepared as an off-white solid from Intermediate 2 (75 mg, 207 pmol) and 4-(azetidin-3-yl)pyridine dihydrochloride, following General Procedure 4e. The product was analysed by LCMS (Method 3): m / z 473.2 (M+H)+, 471.0 (M-H)- at 1.43 min; 1H NMR (400 MHz, DMSO) 5 9.22 (s, 1H), 8.59 - 8.46 (m, 2H), 7.38 (d, J = 7.8 Hz, 1H), 7.35 - 7.26 (m, 2H), 6.70 (d, J = 14.0 Hz, 1H), 5.63 (d, J= 7.5 Hz, 1H), 4.25-4.11 (m, 2H), 3.83-3.78 (m, 3H), 1.87-1.82 (m, 2H), 1.70-1.64 (m, 2H), 1.62 - 1.52 (m, 1H), 1.45 - 1.26 (m, 2H), 1.21 - 1.10 (m, 3H). One proton obscured by solvent Structure / Example Name / Method / Analytical Data peak. 19F NMR (376 MHz, DMSO) 6 -57.75 (d, J= 11.7 Hz), -116.81. I^^NH u r-~r^N\ III / ,S" o o A / -(2-(cyclohexylamino)-4-fluoro-5-(trifluoromethyl)phenyl)-3-(dimethylamino)azetidine-l-sulfonamide (50 mg, 111 pmol, 97% purity) was prepared as an off-white solid from Intermediate 2 (80 mg, 221 pmol) and N,N-dimethylazetidin-3-amine dihydrochloride, following General Procedure 4b. The product was analysed by LCMS (Method 3): m / z no mass ion observed (M+H)+ 437.2 (M-H)- at 1.19 min; 1H NMR (400 MHz, DMSO) 5 7.39 (d, J =7.9 Hz, 1H), 6.70 (d, J = 14.1 Hz, 1H), 5.63-5.51 (m, 1H), 3.75 (dd, J = 8.1, 7.0 Hz, 2H), 3.65 (dd, J= 8.0, 6.0 Hz, 2H), 3.46-3.37 (m, 1H), 2.98 (p, J= 6.5 Hz, 1H), 2.03 (s, 6H), 1.92 - 1.89 (m, 2H), 1.73- 1.68 (m, 2H), 1.64 - 1.54 (m, 1H), 1.47-1.31 (m, 2H), 1.29-1.17 (m, 3H). One exchangeable proton not observed. r ^F F Example 16 J F1 in H h / ' / if Y A o o XF Example 17 A / -(2-(cyclohexylamino)-4-fluoro-5-(trifluoromethyl)phenyl)-3-(pyrimidin-2-yl)azetidine-1-sulfonamide (45 mg, 94 pmol, 99% purity) was prepared as an off-white solid from Intermediate 2 (80 mg, 221 pmol) and 2-(azetidin-3-yl)pyrimidine hydrochloride, following General Procedure 4b. The product was analysed by LCMS (Method 3): m / z 474.2 (M+H)+, 472.0 (M-H)- at 1.75 min; 1H NMR (400 MHz, DMSO) 5 9.13 (s, 1H), 8.79 (d, J= 4.9 Hz, 2H), 7.43 (t, J = 4.9 Hz, 1H), 7.40 (d, J = 7.9 Hz, 1H), 6.67 (d, J = 14.1 Hz, 1H), 5.62 (d, J= 7.7 Hz, 1H), 4.17-4.09 (m, 4H), 4.06-3.99 (m, 1H), 1.90-1.80 (m, 2H), 1.69 - 1.65 (m, 2H), 1.60 - 1.56 (m, 1H), 1.40 - 1.31 Structure / Example Name / Method / Analytical Data (m, 2H), 1.24 - 1.08 (m, 3H). One proton obscured by solvent peak. N^ / II T 'k o o A / -(2-(cyclohexylamino)-4-fluoro-5-(trifluoromethyl)phenyl)-3-(hydroxymethyl)azetidine-l-sulfonamide (28 mg, 66 pmol, 99% purity) was prepared as an off-white solid from Intermediate 2 (85 mg, 237 pmol) and azetidin-3-ylmethanol hydrochloride, following General Procedure 4b. The product was analysed by LIPLC (Method 1): m / z 426.3 (M+H)+, 424.2 (M-H)- at 1.69 min; 1H NMR (500 MHz, DMSO) 5 9.02 (s, 1H), 7.36 (d, J= 7.8 Hz, 1H), 6.71 (d, J = 14.0 Hz, 1H), 5.63 (d, J= 7.8 Hz, 1H), 4.79 (app bs, 1H), 3.79 - 3.75 (m, 2H), 3.55 - 3.52 (m, 2H), 3.47 (app d, J = 6.5 Hz, 2H), 3.42 - 3.37 (m, 1H), 2.60 - 2.54 (m, 1H), 1.97- 1.87 (m, 2H), 1.74-1.67 (m, 2H), 1.63 - 1.55 (m, 1H), 1.45 - 1.32 (m, 2H), 1.28 -1.17 (m, 3H).; 19F NMR (471 MHz, DMSO) 5 -57.77 (d, J = 11.4 Hz), -116.68 (q, J= 11.6 Hz). r F^ ^F F Example 18 J l^° m h rrN^ V A ^00 ^F Example 21 A / -(2-(cyclohexylamino)-4-fluoro-5-(trifluoromethyl)phenyl)-3-morpholinoazetidine-1-sulfonamide (65 mg, 130 pmol, 96% purity) was prepared as a light-orange solid from Intermediate 2 (80 mg, 221 pmol) and 4-(azetidin-3-yl)morpholine dihydrochloride, following General Procedure 4b. The product was analysed by LCMS (Method 3): m / z no mass ion observed (M+H)+, 479.2 (M-H)_ at 1.50 min; 1H NMR (500 MHz, DMSO) 6 9.12 (s, 1H), 7.36 (d, J = 7.9 Hz, 1H), 6.71 (d, J = 14.1 Hz, 1H), 5.61 (d, J= 7.8 Hz, 1H), 3.77 - 3.74 (m, 2H), 3.69 - 3.66 (m, 2H), 3.56 (t, J = 4.6 Hz, 4H), 3.44 - 3.35 (m, 1H), 3.10 - 3.02 (m, 1H), 2.25 (m, 4H), 1.97-1.87 (m, 2H), 1.73-1.69 (m, Structure / Example Name / Method / Analytical Data 2H), 1.64 - 1.55 (m, 1H), 1.45 - 1.33 (m, 2H), 1.28 -1.16 (m, 3H); 19F NMR (471 MHz, DMSO) 6 -57.73 (d, J = 11.6 Hz), -116.64. h XN~J t-O [ii A J o o A / -(2-(cyclohexylamino)-4-fluoro-5-(trifluoromethyl)phenyl)-3-(methyl(oxetan-3-yl)amino)azetidine-1-sulfonamide (30 mg, 62 pmol, 99% purity) was prepared as an off-white solid from Intermediate 2 (80 mg, 221 pmol) and / V-methyl-ZV-(oxetan-3-yl)azetidin-3-amine dihydrochloride, following General Procedure 4d. The product was analysed by LIPLC (Method 1): m / z no mass ion observed (M+H)+, 479.2 (M-H)’ at 1.66 min; 1H NMR (500 MHz, DMSO) 6 9.12 (s, 1H), 7.37 (d, J = 7.8 Hz, 1H), 6.70 (d, J = 13.9 Hz, 1H), 5.59 (d, J =7.7 Hz, 1H), 4.47-4.42 (m, 4H), 3.71 -3.62 (m, 5H), 3.26 (t, J = 7.0 Hz, 1H), 2.06 (s, 3H), 1.95 - 1.89 (m, 2H), 1.76-1.65 (m, 2H), 1.63 - 1.53 (m, 1H), 1.45 - 1.34 (m, 2H), 1.28 - 1.18 (m, 3H). One proton obscured by water peak. 19F NMR (471 MHz, DMSO) 6 -57.75 (d, J = 11.5 Hz), -116.60. r F^ ^F F Example 22 F' / N'N JI 'N H ry^N NJ Joo XF Example 23 A / -(2-(cyclohexylamino)-4-fluoro-5-(trifluoromethyl)phenyl)-3-(2-methyltetrazol-5-yl)azetidine-1-sulfonamide (29 mg, 58 pmol, 95% purity) was prepared as an off-white solid from Intermediate 2 (50 mg, 140 pmol) and Intermediate 1a (32 mg, 180 pmol) following General Procedure 4a. The product was analysed by LIPLC (Method 1): m / z 478.3 (M+H)+, 476.3 (M-H); at 1.83 min; 1H NMR (500 MHz, DMSO) 6 9.19 (s, 1H), 7.39 (d, J= 7.8 Hz, 1H), 6.71 (d, J = 14.0 Hz, 1H), 5.61 (d, J= 7.7 Hz, 1H), 4.34 (s, 3H), 4.20 (t, J= 7.1 Hz, 2H), 4.15-4.05 (m, 1H), 4.02 (dd, J = 7.5 Hz, 2H), 3.40 - 3.33 (m, 1H), 1.90 - Structure / Example Name / Method / Analytical Data 1.83 (m, 2H), 1.73- 1.65 (m, 2H), 1.62 - 1.56 (m, 1H), 1.37 (m, 2H), 1.26-1.12 (m, 3H); 19F NMR (471 MHz, DMSO) 6-57.79 (d, J= 11.5 Hz), -116.39 (d, J= 13.9 Hz). °''z z' A / -(2-(cyclohexylamino)-4-fluoro-5-(trifluoromethyl)phenyl)-3-(1-methyltetrazol-5-yl)azetidine-1-sulfonamide (10 mg, 21 pmol, 99% purity) was prepared as an off-white solid from Intermediate 2 (30 mg, 84 pmol) and Intermediate 1b (18 mg, 101 pmol) following General Procedure 4a. The product was analysed by LCMS (Method 1) m / z 478.2 (M+H)+, 476.0 (M-H); at 1.70 min; 1H NMR (500 MHz, DMSO) 6 9.23 (s, 1H), 7.38 (d, J= 7.8 Hz, 1H), 6.71 (d, J = 14.1 Hz, 1H), 5.61 (d, J= 7.8 Hz, 1H), 4.24 - 4.15 (m, 3H), 4.15 - 4.09 (m, 2H), 3.93 (s, 3H), 3.43 -3.34 (m, 1H), 1.94- 1.85 (m, 2H), 1.74-1.66 (m, 2H), 1.63-1.55 (m, 1H), 1.44-1.32 (m, 2H), 1.27-1.15 (m, 3H); 19F NMR (471 MHz, DMSO) 6 -57.72 (d, J = 11.4 Hz), -116.48. r FX ^F F Example 24 X f' H jh P"^ Y 0 0 XF Example 25 A / -(2-(cyclohexylamino)-4-fluoro-5-(trifluoromethyl)phenyl)-3-(methylsulfonamido)azetidine-l-sulfonamide (49 mg, 98 pmol, 98% purity) was prepared as an off-white solid from Intermediate 2 (50 mg, 140 pmol) and / V-(azetidin-3-yl)methanesulfonamide (42 mg, 279 pmol) following General Procedure 4b. UPLC (Method 1): m / z 489.1 (M+H)+, 487.0 (M-H); at 1.70 min. 1H NMR (500 MHz, DMSO) 6 9.15 (s, 1H), 7.89 (d, J= 7.6 Hz, 1H), 7.33 (d, J= 7.8 Hz, 1H), 6.71 (d, J = 14.0 Hz, 1H), 5.61 -5.55 (m, 1H), 4.18-4.07 (m, 1H), 4.01 - 3.94 (m, 2H), 3.79 - 3.72 (m, 2H), 3.44 - 3.33 (m, 1H), 2.90 (s, 3H), 1.95- 1.88 (m, 2H), 1.74 - Structure / Example Name / Method / Analytical Data 1.67 (m, 2H), 1.64 - 1.54 (m, 1H), 1.45 - 1.32 (m, 2H), 1.28-1.15 (m, 3H). 19F NMR (471 MHz, DMSO) 6 -57.73 (d, J= 11.5 Hz), -116.38--116.51 (m). Ol V A / -(2-(cyclohexylamino)-4-fluoro-5- (trifluoromethyl)phenyl)-3-(2-oxooxazolidin-3- Ax7 yl)azetidine-1-sulfonamide (49 mg, 101 pmol, 99% purity) was prepared as an off-white solid from Intermediate 2 (55 mg, 152 pmol, 99% purity) and 3- F F F (azetidin-3-yl)oxazolidin-2-one hydrochloride (54 mg, 304 pmol) following General Procedure 4f. Example 26 LCMS (Method 3): m / z 481.2 [M+H]+, 479.0 [M-H]-, at 1.66 min. 1H NMR (500 MHz, DMSO) 6 9.18 (s, 1H), 7.36 (d, J= 7.8 Hz, 1H), 6.72 (d, J = 14.0 Hz, 1H), 5.71 - 5.50 (m, 1H), 4.59 - 4.43 (m, 1H), 4.38 - 4.22 (m, 2H), 4.08 - 3.97 (m, 2H), 3.95 (t, J = 8.4 Hz, 2H), 3.78 -3.50 (m, 2H), 3.45-3.33 (m, 1H), 1.99-1.86 (m, 2H), 1.74-1.67 (m, 2H), 1.64 - 1.56 (m, 1H), 1.47 - 1.32 (m, 2H), 1.30-1.15 (m, 3H). 19F NMR (471 MHz, DMSO) 6 -57.76 (d, J = 11.6 Hz), -116.36 (q, J = 11.5 Hz). O^-MH A / -(2-(cyclohexylamino)-4-fluoro-5- (trifluoromethyl)phenyl)-3-(2-oxoimidazolidin-1- w' iz X° x / / yl)azetidine-1-sulfonamide (55 mg, 114 pmol, 99% purity) was prepared as an off-white solid from Intermediate 2 (55 mg, 152 pmol, 99% purity) and 1- f^Tf F (azetidin-3-yl)imidazolidin-2-one hydrochloride (54 mg, Example 27 304 pmol) following General Procedure 4f. LCMS (Method 3): m / z 480.2 [M+H]+, 478.2 [M-Hf, at 1.58 min. 1H NMR (500 MHz, DMSO) 6 9.12 (s, 1H), 7.36 (d, J= 7.8 Hz, 1H), 6.72 (d, J = 14.0 Hz, 1H), 6.44 (s, 1H), 5.69 - 5.56 (m, 1H), 4.92 (p, J = 7.4 Hz, 1H), 3.92 - 3.81 (m, 4H), 3.44 - 3.34 (m, 1H), 3.24 (t, J = 5.8 Structure / Example Name / Method / Analytical Data Hz, 2H), 3.08 (td, J = 5.9, 2.5 Hz, 2H), 1.97 - 1.87 (m, 1H), 1.87-1.76 (m, 2H), 1.75 - 1.65 (m, 1H), 1.64 -1.54 (m, 1H), 1.48- 1.29 (m, 2H), 1.29-1.15 (m, 3H). 19F NMR (471 MHz, DMSO) 6 -57.77 (d, J = 11.5 Hz), -116.54. Q vi A8^ A / -(2-(cyclohexylamino)-4-fluoro-5-(trifluoromethyl)phenyl)-3-(2-oxotetrahydropyrimidin-1-yl)azetidine-1-sulfonamide (51 mg, 102 pmol, 99% purity) was prepared as an off-white solid from Intermediate 2 (55 mg, 152 pmol, 99% purity) and 1-(azetidin-3-yl)tetrahydropyrimidin-2-one dihydrochloride following General Procedure 4f. LCMS (Method 3): m / z 494.2 [M+H]+, 492.2 [M-H]-, at 1.61 min. 1H NMR (500 MHz, DMSO) 6 9.14 (s, 1H), 7.36 (d, J= 7.8 Hz, 1H), 6.72 (d, J = 14.0 Hz, 1H), 6.57 (s, 1H), 5.62 (d, J= 7.8 Hz, 1H), 4.48 (p, J= 7.1 Hz, 1H), 4.00 - 3.91 (m, 2H), 3.88 (t, J = 8.3 Hz, 2H), 3.49 -3.34 (m, 3H), 3.30-3.15 (m, 3H), 1.98-1.83 (m, 2H), 1.79-1.64 (m, 2H), 1.64 - 1.55 (m, 1H), 1.46 - 1.31 (m, 2H), 1.31 - 1.15 (m, 3H). One proton obscured by water peak. 19F NMR (471 MHz, DMSO) 5 -57.77 (d, J = 11.6 Hz), -116.46. r ^F F Example 28 N F^^ F1 |^NH H h ryN^o .¾ 0 0 XF Example 29 A / -(2-(cyclohexylamino)-4-fluoro-5-(trifluoromethyl)phenyl)-3-(3-oxopiperazin-1-yl)azetidine-1-sulfonamide (56 mg, 111 pmol, 98% purity) was prepared as an off-white solid from Intermediate 2 (55 mg, 152 pmol, 99% purity) and 4-(azetidin-3-yl)piperazin-2-one dihydrochloride (69 mg, 304 pmol) following General Procedure 4f. LCMS (Method 3): m / z 494.2 [M+H]+, 492.0 [M-Hf, at 1.52 min. 1H NMR (500 MHz, DMSO) 5 9.12 (s, 1H), Structure / Example Name / Method / Analytical Data 7.78 (s, 1H), 7.36 (d, J= 7.8 Hz, 1H), 6.70 (d, J = 14.1 Hz, 1H), 5.60 (d, J= 7.8 Hz, 1H), 3.85-3.76 (m, 2H), 3.76-3.61 (m, 2H), 3.43-3.35 (m, 1H), 3.21 -3.15 (m, 1H), 3.15-3.10 (m, 2H), 2.86 (s, 2H), 2.46 (t, J = 5.5 Hz, 2H), 1.95- 1.83 (m, 2H), 1.78- 1.65 (m, 2H), 1.64-1.54 (m, 1H), 1.46-1.31 (m, 2H), 1.31 - 1.21 (m, 3H). 19F NMR (471 MHz, DMSO) 6 -57.75 (d, J = 11.5 Hz), -116.54 (q, J= 11.5 Hz). 0 L X f NH H A. ,N. fll J! oo F y FTF Example 30 A / -(2-(cyclohexylamino)-4-fluoro-5-(trifluoromethyl)phenyl)-3-(5-oxopyrrolidin-3-yl)azetidine-1-sulfonamide (55 mg, 114 pmol, 99% purity) was prepared as an off-white solid from Intermediate 2 (55 mg, 152 pmol, 99% purity) and tert-butyl 3-(5-oxopyrrolidin-3-yl)azetidine-1-carboxylate (100 mg, 416 pmol), sequentially following General Procedure 5a and 4f. LCMS (Method 3): m / z 479.2 [M+H]+, 477.0 [M-H]-, at 1.56 min. 1H NMR (500 MHz, DMSO) 5 9.08 (s, 1H), 7.52 (s, 1H), 7.35 (d, J= 7.8 Hz, 1H), 6.71 (d, J = 14.0 Hz, 1H), 5.62 (d, J= 7.7 Hz, 1H), 3.92-3.77 (m, 2H), 3.56 - 3.44 (m, 2H), 3.44 - 3.34 (m, 1H), 2.87 - 2.77 (m, 1H), 2.29-2.17 (m, 1H), 1.95-1.86 (m, 2H), 1.86 - 1.75 (m, 1H), 1.75-1.66 (m, 2H), 1.64-1.51 (m, 1H), 1.46-1.30 (m, 2H), 1.27-1.14 (m, 4H). Two protons obscured by water and solvent peaks. 19F NMR (471 MHz, DMSO) 5 -57.76 (d, J = 11.5 Hz), -116.63. Structure / Example Name / Method / Analytical Data NH u ^NH2 AILnJ l|f A J| oo F F^F Example 31 3-Amino-A / -(2-(cyclohexylamino)-4-fluoro-5-(trifluoromethyl)phenyl)azetidine-1 -sulfonamide (30 mg, 72 pmol, 98% purity) was prepared as a pink solid from Intermediate 2 (50 mg, 138 pmol, 99% purity) and tert-butyl azetidin-3-ylcarbamate (48 mg, 276 pmol), sequentially following General Procedure 4a and 6b. UPLC (Method 1): m / z 411.1 (M+H)+, 409.2 (M-H); at 1.11 min. 1H NMR (500 MHz, DMSO) 5 7.32 (d, J =7.9 Hz, 1H), 6.60 (d, J= 14.0 Hz, 1H), 5.64-5.59 (m, 1H), 5.30 (m, 2H), 3.78 (t, J = 7.6 Hz, 2H), 3.61 (p, J = 6.9 Hz, 1H), 3.51 -3.45 (m, 2H), 3.43-3.31 (m, 1H), 1.95 - 1.88 (m, 2H), 1.74-1.66 (m, 2H), 1.63 - 1.56 (m, 1H), 1.45- 1.32 (m, 2H), 1.26-1.15 (m, 3H). One exchangeable proton not observed. 19F NMR (471 MHz, DMSO) 6-57.47 (d, J= 11.8 Hz), -119.03--119.14 (m). nh2 H h liY A Ji A oo f F^F Example 32 2-(Aminomethyl)-A / -(2-(cyclohexylamino)-4-fluoro-5-(trifluoromethyl)phenyl)azetidine-1-sulfonamide (40 mg, 93 pmol, 99% purity) was prepared as an off-white solid from Intermediate 2 (50 mg, 138 pmol, 99% purity) and tert-butyl (azetidin-2-ylmethyl)carbamate hydrochloride (62 mg, 276 pmol), sequentially following General Procedure 4f and 6b. LCMS (Method 3): m / z 425.2 [M+H]+, 423.2 [M-H]-, at 1.26 min. 1H NMR (500 MHz, DMSO) 6 7.38 (s, 3H), 7.25 (d, J= 8.0 Hz, 1H), 6.31 (d, J = 13.8 Hz, 1H), 5.54 (d, J= 8.4 Hz, 1H), 4.15-4.03 (m, 1H), 3.67-3.53 (m, 1H), 3.27 - 3.21 (m, 2H), 2.93 - 2.81 (m, 2H), 2.07 -1.95 (m, 1H), 1.95- 1.84 (m, 3H), 1.76-1.64 (m, 2H), 1.61 - 1.55 (m, 1H), 1.42- 1.32 (m, 2H), 1.30-1.10 Structure / Example Name / Method / Analytical Data (m, 3H). 19F NMR (471 MHz, DMSO) 6 -56.62 (m), -126.54. n / / NHo 3-(Aminomethyl)-A / -(2-(cyclohexylamino)-4-fluoro-5-(trifluoromethyl)phenyl)azetidine-1 -sulfonamide (10 mg, 23 pmol, 98% purity) was prepared as an off-white solid from Intermediate 2 (50 mg, 138 pmol, 99% purity) and tert-butyl (azetidin-3-ylmethyl)carbamate (52 mg, 276 pmol), sequentially following General Procedure 4a and 6c. UPLC (Method 1): m / z 423.1 (M-H)- at 1.13 min. 1H NMR (500 MHz, DMSO) 6 7.29 (d, J =8.0 Hz, 1H), 6.49 (d, J = 13.9 Hz, 1H), 5.63-5.58 (m, 1H), 3.73-3.66 (m, 2H), 3.50 - 3.40 (m, 2H), 3.37 - 3.27 (m, 3H), 2.98 - 2.94 (m, 2H), 2.64 - 2.56 (m, 1H), 1.95 - 1.88 (m, 2H), 1.74-1.65 (m, 2H), 1.63 - 1.56 (m, 1H), 1.45 -1.32 (m, 2H), 1.26 - 1.13 (m, 3H). One exchangeable proton not observed. 19F NMR (471 MHz, DMSO) 5 -57.09 (d, J= 12.0 Hz), -121.83--122.22 (m). r FZ XF F Example 33 r> J F1 o^° 1 NH JH h V A Joo XF Example 34 A / -(2-(cyclohexylamino)-4-fluoro-5-(trifluoromethyl)phenyl)-3-(2-oxooxazolidin-5-yl)azetidine-1-sulfonamide (40 mg, 82 pmol, 99% purity) was prepared as an off-white solid from Intermediate 2 (50 mg, 138 pmol, 99% purity) and 5-(azetidin-3-yl)oxazolidin-2-one hydrochloride (49 mg, 276 pmol) following General Procedure 4f. LCMS (Method 3): m / z 481.2 [M+H]+, 479.0 [M-Hf, at 1.59 min. 1H NMR (500 MHz, DMSO) 5 9.10 (s, 1H), 7.95 (s, 1H), 7.33 (d, J= 7.8 Hz, 1H), 6.71 (d, J = 14.0 Hz, 1H), 5.60 (d, J = 7.8 Hz, 1H), 4.46 - 4.27 (m, 1H), 3.99 - 3.87 (m, 2H), 3.85 - 3.73 (m, 2H), 3.63 - 3.51 (m, 2H), 3.45-3.33 (m, 1H), 2.70-2.56 (m, 1H), 1.97 - 1.87 (m, 2H), 1.76-1.65 (m, 2H), 1.62 - 1.54 (m, Structure / Example Name / Method / Analytical Data 1H), 1.46-1.31 (m, 2H), 1.26-1.12 (m, 3H). 19F NMR (471 MHz, DMSO) 6 -57.75 (d, J = 11.5 Hz), -116.54. F( JH H NH2 Vx J 0 0 ?F Example 35 jrmic acid salt 3-(1-Aminocyclopropyl)-A / -(2-(cyclohexylamino)-4-fluoro-5-(trifluoromethyl)phenyl)azetidine-1-sulfonamide formic acid salt (22 mg, 44 pmol, 98% purity) was prepared as an off-white solid from Intermediate 2 (50 mg, 138 pmol, 99% purity) and tert-butyl (1-(azetidin-3-yl)cyclopropyl)carbamate hydrochloride (69 mg, 276 pmol), sequentially following General Procedure 4a and 6c. UPLC (Method 1): m / z 451.2 (M+H)+, 449.2 (M-H); at 1.17 min. 1H NMR (500 MHz, DMSO) 5 8.18 (s, 1H), 7.32 (d, J= 7.9 Hz, 1H), 6.60 (d, J = 14.0 Hz, 1H), 5.63 - 5.58 (m, 1H), 3.72 - 3.65 (m, 2H), 3.51 - 3.45 (m, 2H), 3.40 - 3.30 (m, 1H), 2.67 - 2.57 (m, 1H), 1.94 -1.87 (m, 2H), 1.73-1.66 (m, 2H), 1.62 - 1.56 (m, 1H), 1.44-1.33 (m, 2H), 1.26-1.15 (m, 3H), 0.59-0.50 (m, 4H). Three exchangeable protons not observed. 19F NMR (471 MHz, DMSO) 5-57.45 (d, J= 11.8 Hz), -118.98--119.14 (m). X F 1 qH H rx^NH2 VX Joo >F Example 36 3-(2-Aminopropan-2-yl)-A / -(2-(cyclohexylamino)-4-fluoro-5-(trifluoromethyl)phenyl)azetidine-1-sulfonamide (3 mg, 6 pmol, 90% purity) was prepared as an off-white solid from Intermediate 2 (50 mg, 138 pmol, 99% purity) and tert-butyl (2-(azetidin-3-yl)propan-2-yl)carbamate hydrochloride (69 mg, 276 pmol), sequentially following General Procedure 4a and 6c. UPLC (Method 1): m / z 453.2 (M+H)+, 450.9 (M-H); at 1.18 min. 1H NMR (500 MHz, MeOD) 5 8.54 - 8.50 (m, 1H), 7.36 (d, J= 7.6 Hz, 1H), 6.52 (d, J= 13.6 Hz, 1H), 4.02 - 3.90 (m, 2H), 3.84 - 3.77 (m, 2H), 3.38 - 3.33 Structure / Example Name / Method / Analytical Data (m, 1H), 2.88-2.80 (m, 1H), 2.05-1.99 (m, 2H), 1.83 - 1.77 (m, 2H), 1.70-1.64 (m, 1H), 1.52-1.41 (m, 2H), 1.37-1.25 (m, 8H), 0.78 - 0.74 (m, 1H). Three exchangeable protons not observed. 19F NMR (471 MHz, MeOD) 5 -60.71 (d, J = 12.1 Hz), -116.87. I^LO,N< / 111 'S' JL X o o A / -(4-fluoro-2-(((1 / ?,2 / ?)-2-methylcyclohexyl)amino)-5-(trifluoromethyl)phenyl)-3-(4-methylpiperazin-1-yl)azetidine-1-sulfonamide (40 mg, 77 pmol, 98% purity) was prepared as an off-white solid from Intermediate 3 (50 mg, 122 pmol, 91% purity) and 1-(azetidin-3-yl)-4-methylpiperazine (38 mg, 244 pmol), following General Procedure 4g. UPLC (Method 1): m / z 507.9 (M+H)+, 506.3 (M-H); at 1.25 min. 1H NMR (500 MHz, DMSO) 5 8.15 (s, 1H), 7.33 (d, J= 7.9 Hz, 1H), 6.71 (d, J = 14.2 Hz, 1H), 5.54 - 5.49 (m, 1H), 3.78 - 3.71 (m, 2H), 3.70 - 3.61 (m, 2H), 3.12 - 3.00 (m, 2H), 2.43 - 2.22 (m, 8H), 2.19 (s, 3H), 1.93-1.87 (m, 1H), 1.78-1.72 (m, 1H), 1.71 -1.60 (m, 2H), 1.51 - 1.42 (m, 1H), 1.41 - 1.32 (m, 1H), 1.28-1.17 (m, 1H), 1.16-1.07 (m, 2H), 0.92 (d, J = 6.4 Hz, 3H). 19F NMR (471 MHz, DMSO) 5 -57.56 (d, J = 11.5 Hz), -117.04--117.25 (m). r FX XF F Example 37 ,x F1 JH h Cy Vx X o 0 XF Example 38 A / -(4-fluoro-2-(((1S,2S)-2-methylcyclohexyl)amino)-5-(trifluoromethyl)phenyl)-3-(4-methylpiperazin-1-yl)azetidine-1-sulfonamide (33 mg, 64 pmol, 98% purity) was prepared as an off-white solid from Intermediate 4 (50 mg, 122 pmol, 91% purity) and 1-(azetidin-3-yl)-4-methylpiperazine (38 mg, 244 pmol), following General Procedure 4g. UPLC (Method 1): m / z 508.3 (M+H)+, 506.3 (M-H); at 1.24 min. 1H NMR (500 MHz, DMSO) 5 8.15 (s, 1H), 7.33 (d, J= 7.9 Hz, 1H), 6.71 (d, J = 14.3 Hz, 1H), 5.54 Structure 1 Example Name 1 Method / Analytical Data - 5.49 (m, 1H), 3.74 (t, J = 7.5 Hz, 2H), 3.70 - 3.61 (m, 2H), 3.13 - 3.00 (m, 2H), 2.45 - 2.22 (m, 8H), 2.19 (s, 3H), 1.93-1.87 (m, 1H), 1.79-1.71 (m, 1H), 1.71 -1.60 (m, 2H), 1.51 - 1.43 (m, 1H), 1.41 - 1.31 (m, 1H), 1.28-1.18 (m, 1H), 1.18-1.05 (m, 2H), 0.92 (d, J = 6.5 Hz, 3H). 19F NMR (471 MHz, DMSO) 5 -57.56 (d, J = 11.6 Hz), -117.04--117.25 (m). Biological Assay 1: ERAP2 SIINFEKL enzyme assay ERAP2 enzyme activity was measured using a 384-well fluorescence assay using the substrate peptide Glu(EDANS)-Gln-Leu-Glu-[N-Mer-Ser]-lle-lle-Asn-Lys-Glu-Lys(Dabcyl)-Leu. Vehicle control (DMSO) and compounds were spotted into each well in a final volume of 250 nL using acoustic dispensing (ECHO550; Labcyte). A 2X solution (7 nM) of human ERAP2 was prepared by diluting the stock enzyme in assay buffer (25 mM Bis-Tris Propane, 0.05% (w / v) HPMC pH 7.75) and 12.5 pl were added to all the wells. The reaction was initiated by adding an equal volume of a 2X solution (6 pM) of peptide substrate in assay buffer. The plate was incubated at 30°C for 90 minutes. Fluorescence intensity was measured on a fluorimeter set at 340 nm for excitation and 490 nm for emission. The activity was calculated for each sample and data fitted to a 4-parameter logistic regression curve to determine the IC50 of each compound. Activity data for compounds according to the invention are shown in Table 1. Biological Assay 2: ERAP1 SIINFEKL enzyme assay ERAP1 enzyme activity was measured using a 384-well fluorescence assay using the substrate peptide Lys(Dabcyl)-Glu-Gln-Leu-Glu-Ser-lle-lle-Asn-Phe-Glu-Lys-Leu-Glu(EDANS). Vehicle control (DMSO) and compounds were spotted into each well in a final volume of 250 nL using acoustic dispensing (ECHO550; Labcyte). A 2X solution (3 nM) of human ERAP1 was prepared by diluting the stock enzyme in assay buffer (25 mM Bis-Tris Propane, 0.05% (w / v) HPMC pH 7.75) and 12.5 pl were added to all the wells. The reaction was initiated by adding an equal volume of a 2X solution (2 pM) 84 of peptide substrate in assay buffer. The plate was incubated at 30°C for 120 minutes. Fluorescence intensity was measured on a fluorimeter set at 340 nm for excitation and 490 nm for emission. The activity was calculated for each sample and data fitted to a 4-parameter logistic regression curve to determine the ICsoof each compound. 5 Various modifications and variations of the described aspects of the invention will be apparent to those skilled in the art without departing from the scope and spirit of the invention. Although the invention has been described in connection with specific preferred embodiments, it should be understood that the invention as claimed should 10 not be unduly limited to such specific embodiments. Indeed, various modifications of the described modes of carrying out the invention which are obvious to those skilled in the relevant fields are intended to be within the scope of the following claims. Table 1: ERAP2 activity of selected compounds according to the invention 1 B 2 C 3 A 4 B 5 C 6 C 7 D 8 D 9 B 10 A 11 B 12 A 13 A 14 A 15 C 16 B 17 C 18 C 21 B 22 C 23 C 24 B 25 B 26 A 27 B 28 B 29 A 30 A 31 A 32 A 33 A 34 B 35 A 36 B 37 A 38 A IC50 in Biological assay 1 vs ERAP2 substrate (Glu(EDANS)-Gln-Leu-Glu-[N-Mer-Ser]-5 lle-lle-Asn-Lys-Glu-Lys(Dabcyl)-Leu); A (<100nM), B (101^ 250nM), C (251^ 750nM), D (>751 nM). IC50 in Biological assay 2 vs ERAP1 substrate (Lys(Dabcyl)-Glu-Gln-Leu-Glu-Ser-lle-lle-Asn-Phe-Glu-Lys-Leu-Glu(EDANS)); All are >100000nM except for the low potency 10 of Example 6 (3.3p.M). REFERENCES [1] L. Medve, "Modulators of hERAP2 discovered by high-throughput screening," Eur J Med Chem, vol. 211, p. 13053, 2021. [2] J. R. Birtley, "The Crystal Structure of Human Endoplasmic Reticulum Aminopeptidase 2 Reveals the Atomic Basis for Distinct Roles in Antigen Processing," Biochemistry, vol. 51, no. 1, pp. 286-295, 2012. [3] V. Camberlein, "Discovery of the First Selective Nanomolar Inhibitors of ERAP2 by Kinetic Target-Guided Synthesis," Angew. Chem. Int. Ed., vol. 61, no. 39, p. e202203560, 2022. [4] R. Arya, "Phenylsulfamoyl Benzoic Acid Inhibitor of ERAP2 with a Novel Mode of Inhibition," ACS Chem. Biol., vol. 17, no. 7, pp. 1756-1768, 2022. [5] A. Papakyriakou, "Novel selective inhibitors of aminopeptidases that generate antigenic peptides," Bioorganic &Medicinal Chemistry Letters, vol. 23, no. 17, pp. 4832-4836, 2013. [6] S. Shen, "Why Hydroxamates May Not Be the Best Histone Deacetylase Inhibitors—What Some May Have Forgotten or Would Rather Forget?," Chem Med Chem, vol. 11, no. 1, pp. 15-21, 2016. [7] A. Mpakali, "Crystal Structures of ERAP2 Complexed with Inhibitors Reveal Pharmacophore Requirements for Optimizing Inhibitor Potency," ACS Medicinal Chemistry Letters, vol. 8, no. 3, pp. 333-337, 2017. [8] B. Mattore, "The emerging multifunctional roles of ERAP1, ERAP2, and I RAP between antigen processing and renin-angiotensin system modulation," Frontiers in Immunology, p. 13:1002375, 2022. [9] F. Paladini, "The multifaceted nature of aminopeptidases ERAP1, ERAP2, and LNPEP: From Evolution to Disease," Frontiers in Immunology, vol. 11, no. July, 2020.

[10] J. Lopez de Castro, "Intracellular antigen processing by ERAP2: Molecular mechanism and roles in health and disease," Human Immunology, vol. 80, no. 5, pp. 310-317, 2019.

[11] N. Sheehan, "The ramifications of HLA-B27," Journal of the Royal Society of Medicine, vol. 97, no. 1, 2004.

[12] I. G. o. A. S. C. (IGAS), "Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related foci," Nature Genetics, vol. 45, no. 7, pp. 730-738, 2013.

[13] J. Kuiper, ""Interleukin-17 production and T helper 17 cells in peripheral blood mononuclear cells in response to ocular lysate in patients with birdshot chorioretinopathy," Molecular Vision, vol. 19, pp. 2606-14, 2013.

[14] J. Kuiper, "Intraocular interleukin-17 and proinflammatory cytokines in HLA-A29-associated birdshot chorioretinopathy," American Journal of Ophthamology, vol. 152, no. 2, pp. 177-182, 2011.

[15] J. Kuiper, ""A genome-wide association study identifies a functional ERAP2 haplotype associated with birdshot chorioretinopathy," Human Molecular Genetics, vol. 23, no. 22, pp. 6081-6087, 2014.

[16] J. Kuiper, "Functionally distinct ERAP1 and ERAP2 are a hallmark of HLA-A29-(Birdshot) Uveitis," Human Molecular Genetics, 2018.

[17] L. C. Tsoi, "Identification of fifteen new psoriasis susceptibility loci highlights the role of innate immunity," Nature Genetics, vol. 44, no. 12, pp. 1341-1348, 2012.

[18] I. Hulur, "Enrichment of inflammatory bowel disease and colorectal cancer risk variants in colon expression quantitative trait loci," BMC Genomics, vol. 16, no. 138, 2015.

[19] I. Saulle, "An overview on ERAP roles in infections diseases," Cells, vol. 9, 2020.

Claims

1. A compound of formula (I), or a pharmaceutically acceptable salt or hydrate thereof,(I)wherein:the group X-Y is -NHSO2-;A is selected from:a C4-C8-cycloalkyl group;a bicyclic Cs-Ci2-cycloalkyl group; anda C4-C8-cycloalkyl group fused to an aryl or heteroaryl group; each of which is optionally substituted by one or more R4 groups;B is a group:(Rs)mwherein the wavy line indicates the point of attachment to Y;Ri is selected from haloalkyl and OR3,R2 is selected from H and halo;R3 is selected from alkyl and benzyl;each R4 is independently selected from alkyl and halo;Rs is at each occurrence independently selected from COOH, (CRiaRiOaNReR?, alkyl, haloalkyl, halo, alkoxy, hydroxyalkyl, cycloalkyl, heteroaryl, and heterocycloalkyl,wherein said cycloalkyl, heteroaryl and heterocycloalkyl are each optionally further substituted by one or more groups selected from alkyl, haloalkyl, NH2 and halo; each Riaand each Rwis independently selected from H, OH, alkyl and hydroxyalkyl; each a is independently 0, 1,2 or 3;Re and R7 are each independently selected from H, alkyl, SO2-alkyl, haloalkyl and heterocycloalkyl; and m is an integer from 0 to 6.

2. A compound according to claim 1, wherein Ri is haloalkyl, more preferably CF3.

3. A compound according to any preceding claim, wherein R2 is H or F, morepreferably F.

4. A compound according to any preceding claim, wherein A is a fused or bridged bicyclic Cs-Cw-cycloalkyl group.

5. A compound according to any one of claims 1 to 3, wherein A is a C5-C7-cycloalkyl group fused to a phenyl group, or a Cs-Cy-cycloalkyl group fused to 5- or 6-membered heteroaryl group, wherein said phenyl group and said 5- or 6-membered heteroaryl group are each optionally substituted by one, two or three R4 groups.

6. A compound according to any one of claims 1 to 3, wherein A is a C4-C8-cycloalkyl group optionally substituted by one or more R4 groups.

7. A compound according to any one of claims 1 to 3, wherein A is selected from:wherein n is 0, 1 or 2.

8. A compound according to any one of claims 1 to 3 or claim 6 or claim 7, wherein A is:wherein n is 0, 1 or 2.

9. A compound according to any one of claims 1 to 3 or claims 6 to 8, wherein A is selected from:

10. A compound according to any one of claims 1 to 3 or claims 6 to 8, wherein A is selected from:

11. A compound according to claim 10, wherein A is selected from:

12. A compound according to any preceding claim, wherein each R4 isindependently selected from Me, Et and F.

13. A compound according to any preceding claim, wherein Ri is CF3, R2 is F or H, X-Y is NHSO2, and A is selected from:

14. A compound according to any preceding claim, wherein m is 1 or 2.

15. A compound according to any preceding claim, wherein R5 is at eachoccurrence independently selected from NRsR?, alkyl, hydroxyalkyl, heteroaryl, and heterocycloalkyl, wherein said heteroaryl and heterocycloalkyl are each optionally further substituted by one or more alkyl groups.

16. A compound according to any preceding claim, wherein B is:

17. A compound according to any preceding claim, wherein Rs is selected from NR6R7, CH2OH, heteroaryl, and heterocycloalkyl, wherein said heteroaryl and heterocycloalkyl are optionally substituted by one or more alkyl groups.

18. A compound according to any preceding claim, wherein R5 is selected from tetrazolyl, triazolyl, pyrazolyl, imidazolyl, pyridinyl, pyrimidinyl, pyrazinyl, morpholinyl, piperidinyl, piperazinyl, isoxazolyl, 1H-benzo[d]imidazolyl, and pyrrolidinyl, each of which is optionally substituted with alkyl.

19. A compound according to claim 18, wherein Rs is a tetrazolyl:optionally substituted with a Me group.

20. A compound according to claim 18, wherein Rs is selected from:substituted with one or more groups selected from alkyl and NReR?.

21. A compound according to claim 17, wherein Re and R?are selected from methyl and oxetanyl, preferably wherein either both Re and R? are methyl or Re is methyl and R? is oxetanyl.

22. A compound according to any preceding claim which is selected from the following:and enantiomers thereof, and mixtures of enantiomers thereof, including racemic mixtures, and pharmaceutically acceptable salts and solvates thereof.

23. A pharmaceutical composition comprising a compound of formula (I) as defined in any one of claims 1 to 22 admixed with a pharmaceutically acceptable excipient, diluent or carrier, and optionally one or more additional active agents.

24. A compound of formula (I) as defined in any one of claims 1 to 22 or a pharmaceutical composition as defined in claim 23 for use in medicine.

25. A compound of formula (I) as defined in any one of claims 1 to 22 or a pharmaceutical composition as defined in claim 23 for use in treating or preventing a disorder selected from a proliferative disorder, an immune disorder, a viral disorder, preeclampsia and an inflammatory disorder.

26. A compound for use according to claim 25, wherein the compound modulates ERAP2.

27. A compound for use according to claim 25 or claim 26, wherein the disorder is a proliferative disorder, preferably a cancer or leukemia.

28. A compound for use according to any one of claims 25 to 27, wherein the compound kills cancer cells, reduces the number of proliferating cells in the cancer, reduces the volume or size of a tumour comprising the cancer cells, and / or reduces the number of metastasising cancer cells.

29. A compound for use according to claim 25 or claim 26, wherein the compound is for use in preventing cancer, wherein preferably the compound induces a neoantigen to which the subject has an existing immune response.

30. A compound for use according to claim 29, wherein said compound is for use in a subject who has cancer or who is susceptible to developing cancer, wherein the compound stimulates a neo-antigen directed immune response in the subject, and wherein a second compound (which may be the same or different to the first compound), is used subsequently to stimulate the same neo-antigen as the first compound, thereby directing the subject’s immune response against said cancer.

31. A compound for use according to any one of claims 25 to 30, wherein the subject has previously had cancer, has a familial history of cancer, has a high risk for developing cancer, has a genetic predisposition to developing cancer, has been exposed to a carcinogenic agent, and / or is in remission from cancer.

32. An in vitro or in vivo method for producing an antigen-presenting cell which presents a neo-antigen, comprising inducing with a compound of formula (I) as defined in any one of claims 1 to 22 a neo-antigen in said antigen-presenting cell, wherein preferably the antigen-presenting cell is a dendritic cell.

33. An immunogenic composition comprising an antigen-presenting cell obtained or obtainable by the method according to claim 32.

34. An immunogenic composition according to claim 33 for use in treating or preventing cancer in a subject, wherein preferably the immunogenic composition is a vaccine.

35. A compound for use according to any one of claims 25 to 30, wherein said compound is for use in combination with an immunotherapy, wherein preferably the subject has cancer and the compound increases the sensitivity of cancer cells to an immunotherapy.

36. A compound for use according to any one of claims 25 to 30, wherein said compound is for use in combination with a molecule capable of immune checkpoint intervention, a co-stimulatory antibody, a chemotherapy agent, a radiotherapy agent, a targeted therapy agent or an antibody.

37. A compound for use according to claim 36 wherein the molecule capable of immune checkpoint intervention is an antibody checkpoint inhibitor.

38. A compound for use according to claim 37 wherein said antibody checkpoint inhibitor is an anti-PD-1 antibody, an anti-PD-L1 antibody or an anti-CTLA4 antibody.

39. A compound for use according to any one of claims 25 to 30, wherein said compound is for use in combination with T cell receptor (TCR) therapy.

40. A compound for use according to claim 25 or claim 26, wherein the disorder is an immune disorder, and is preferably selected from ankylosing spondylitis, inflammatory bowel disease psoriasis and birdshot chorioretinopathy.

41. A compound for use according to claim 25 or claim 26, wherein the disorder is an inflammatory disorder, more preferably an auto-inflammatory disorder.

42. A compound for use according to claim 25 or claim 26, wherein the viral disorder is an infectious viral disease selected from HIV, HPV, influenza and HCV.

43. A compound for use according to any one of claims 25 to 30, wherein the disorder is cancer, and wherein the compound increases the visibility of cancer cells to the immune system by altering the repertoire of antigens and neoantigens presented to the immune system.

44. A compound for use according to claim 43, wherein the compound increases the CD8+ T cell response to the cancer cell.

45. A combination comprising a compound according to any one of claims 1 to 22 and a further active agent.

46. A combination according to claim 45, wherein the further active agent is a molecule capable of immune checkpoint intervention, a co-stimulatory antibody, a chemotherapy agent, a radiotherapy agent, a targeted therapy agent or an antibody.

47. A combination comprising a compound according to any one of claims 1 to 22 and a T cell receptor (TCR) therapy.T +44(0)30 0300 2000Search report under Section 17 of the Patents Act 1977Application No.: GB2501343.4Claims searched: 1-47Date search completed: 29 June 2026International classificationSubclass and subgroup Valid from A61K31 / 397 01 / 01 / 2006 A61K31 / 4025 01 / 01 / 2006 A61K31 / 41 01 / 01 / 2006 A61K31 / 4155 01 / 01 / 2006 A61K31 / 4178 01 / 01 / 2006 A61K31 / 4192 01 / 01 / 2006 A61K31 / 4196 01 / 01 / 2006 A61K31 / 422 01 / 01 / 2006 A61K31 / 4427 01 / 01 / 2006 A61K31 / 4523 01 / 01 / 2006 A61K31 / 496 01 / 01 / 2006 A61K31 / 497 01 / 01 / 2006 A61K31 / 506 01 / 01 / 2006 A61K31 / 5377 01 / 01 / 2006 A61P29 / 00 01 / 01 / 2006 A61P31 / 12 01 / 01 / 2006 A61P35 / 00 01 / 01 / 2006 A61P35 / 02 01 / 01 / 2006 A61P37 / 00 01 / 01 / 2006 C07C311 / 00 01 / 01 / 2006 C07D205 / 04 01 / 01 / 2006 C07D401 / 04 01 / 01 / 2006 C07D403 / 04 01 / 01 / 2006 C07D405 / 12 01 / 01 / 2006 C07D413 / 04 01 / 01 / 2006Field of searchWorldwide search of patent documents classified in the following areas of the IPC: C07DT +44(0)30 0300 2000Databases used in the preparation of this search report: CAS ONLINE; MARPAT; SEARCH-NPL; SEARCH-PATENTDocuments considered to be relevantPatent literatureCategory Relevant to claims Document of relevance X 33-34 WO 2020 / 225569 A1 (GREY WOLF THERAPEUTICS LTD) - See whole document, particularly page 40 X 33-34 WO 2020 / 104822 A1 (GREY WOLF THERAPEUTICS LTD) - See whole document, particularly page 48 X 33-34 GB 2631426 A (GREY WOLF THERAPEUTICS LTD) - See whole document, particularly pages 19-20 X 33-34 WO 2021 / 094763 A1 (GREY WOLF THERAPEUTICS LTD) - See whole document, particularly page 34 X 33-34 WO 2023 / 007188 A1 (GREY WOLF THERAPEUTICS LTD) - See whole document, particularly page 52Non-patent literature[None]CategoriesLetter or symbol Description X Document indicating lack of novelty or inventive step. Y Document indicating lack of inventive step, if combined with another document of the same category. & Member of the same patent family. A Document indicating technological background. P Document published on or after the priority date but before the filing date of the present application.T +44(0)30 0300 2000Letter or symbol EDescriptionEarlier application published on or after the filing date of the present application.