Alkyl amino diacid compounds and radiolabelled variants thereof

Abstract

Novel Compounds The present invention relates to compounds of Formula (I) and to associated salts, solvates, prodrugs and pharmaceutical compositions. The present invention also generally relates to the field of diagnostic and therapeutic compounds. More specifically, the present invention relates to certain radiolabelled compounds, their precursors, and the respective uses. The radiolabelled compounds emit radiation for detection by molecular imaging or for treatment of diseases, disorders, or conditions, most especially cancer.

Description

[0001] Novel Compounds

[0002] Field of the Invention

[0003] The present invention relates generally to the field of diagnostic and therapeutic compounds. In particular, the invention relates to alkyl amino diacid compounds and radiolabelled variants thereof, their synthetic precursors and their use in imaging, diagnosis, and therapy.

[0004] Background of the Invention

[0005] Targeted radionuclide therapies (TRT) have seen great advancement in the last few years and are gaining attention due to both their diagnostic and therapeutic potential for imaging and treating multiple cancer types, including therapy resistant cancer [1], TRTs that carry radionuclides delivering a and P emitters to cancer cells provide a mechanism for DNA damage with potential anti-cancer therapeutic effect [2, 3, 11].

[0006] The cystine-glutamate transporter known as system xc“ is an antiporter that is a membrane protein involved in active transport of two distinct amino acids across the phospholipid membrane of a cell. System xc“ carries cystine into the cell concomitantly as glutamate is passed out of the cell. In recent years, system xc“ has been found to play an important role in tumour growth, progression and multi-drug resistance, and has been found to be upregulated in numerous cancers [4-7], Enhanced expression and activity of system xc“ in tumours presents an opportunity for targeted delivery of radionuclide imaging and therapy [8-10].

[0007] Additionally, delivery of therapeutically effective doses of TRTs has been limited by reduced efficacy and high normal tissue toxicity. Therefore, there is a need for improved methods of delivering radionuclides to cancer cells that would allow tolerable and effective imaging, diagnosis and treatment of cancer patients.

[0008] Summary of the Invention

[0009] A first aspect of the invention provides a compound of Formula (I):

[0010]

[0011] Formula (I)

[0012] or a pharmaceutically acceptable salt, solvate or prodrug thereof, wherein:

[0013] n is 0, 1, 2 or 3;

[0014] m is 1, 2, 3 or 4;

[0015] provided that m+n is 3 or 4;

[0016] when present, R1is hydrogen or C1-C3 alkyl;

[0017] R2is hydrogen or C1-C3 alkyl;

[0018] R3is hydrogen or C1-C3 alkyl;

[0019] A is phenyl, naphthyl or a 5- to 10-membered heteroaryl group;

[0020] L is -O-, -S-, -NR5-, a Ci-Ce straight chained alkylene group, wherein the Ci-Ce straight chained alkylene group optionally includes one, two or three heteroatoms each independently selected from 0, S and NR6in its carbon skeleton, or L is a group -L1-B-L2-, wherein L1and L2are each independently a bond or a C1-C3 straight chained alkylene group, wherein B is a saturated cyclic group selected from a C3-C6 cycloalkyl group, or a 3-, 4-, 5- or 6- membered saturated monocyclic heterocyclic group; wherein L is optionally substituted with one or more substituents independently selected from fluoro, hydroxyl, oxo (=0), C1-C3 alkyl, -O-(Ci-C3 alkyl), -O-(Ci-C3 fluoroalkyl), or C1-C3 fluoroalkyl, and wherein L optionally includes one or more spirocyclic groups, wherein the spirocyclic group is selected from a C3-C5 cycloalkyl group or a C3-C5 saturated heterocyclic group;

[0021] p is 0, 1, or 2;

[0022] R4is halo, -OH, -NH2, -SH, cyano, or a Ci-Cs saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight chained or branched, or be or include a cyclic group, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, 0 and S in its carbon skeleton, and wherein any -S- moiety in the hydrocarbyl group may optionally be substituted with one or two groups each independently selected from oxo (=0) and =NH to form a -SO-, -SO2-, -S( = NH)- or -SO( = NH)-moiety;

[0023] R5is hydrogen, C1-C3 alkyl, or C2-C3 alkylene-OR7;R6is C1-C3 alkyl, or C2-C3 alkylene-OR7;

[0024] R7is hydrogen or methyl; and

[0025] X is iodine, an iodine radioisotope, fluorine, a fluorine radioisotope, or an astatine radioisotope.

[0026] A second aspect of the invention provides a compound of Formula (I) selected from the group described herein, or a pharmaceutically acceptable salt, solvate or prodrug thereof.

[0027] A third aspect of the invention provides a compound of Formula (PI) as described herein, or a pharmaceutically acceptable salt, solvate or prodrug thereof.

[0028] A fourth aspect of the invention provides a process as described herein, for the preparation of a compound of Formula (III) or Formula (IIIA) as described herein, or a pharmaceutically acceptable salt, solvate or prodrug thereof from a compound of Formula (PI) or a pharmaceutically acceptable salt, solvate or prodrug thereof.

[0029] A fifth aspect of the invention provides a pharmaceutical composition comprising a compound, pharmaceutically acceptable salt, solvate or prodrug of the first or second aspect of the invention, and a pharmaceutically acceptable excipient.

[0030] A sixth aspect of the invention provides a kit comprising a compound of the third aspect, or a pharmaceutically acceptable salt, solvate or prodrug thereof and instructions to prepare a compound of Formula (III) or Formula (IIIA).

[0031] A seventh aspect of the invention provides a kit comprising a compound of Formula (III) or Formula (IIIA), or a pharmaceutically acceptable salt, solvate or prodrug thereof or a pharmaceutical composition comprising a compound of Formula (III) or Formula (IIIA) and instructions for use.

[0032] An eight aspect of the invention provides a compound, pharmaceutically acceptable salt, solvate or prodrug of the first or second aspect of the invention, or a pharmaceutical composition of the fifth aspect of the invention, for use in medicine.

[0033] A ninth aspect of the invention provides a compound, pharmaceutically acceptable salt, solvate or prodrug of the first or second aspect of the invention, or a pharmaceutical composition of the fifth aspect of the invention, for use in diagnosis or therapy.A tenth aspect of the invention provides a compound, pharmaceutically acceptable salt, solvate or prodrug of the first or second aspect of the invention, or a pharmaceutical composition of the fifth aspect of the invention, for use in the treatment or prevention of a disease, disorder or condition.

[0034] An eleventh aspect of the invention provides a compound, pharmaceutically acceptable salt, solvate or prodrug of the first or second aspect of the invention, or a pharmaceutical composition of the fifth aspect of the invention, for use in diagnosis.

[0035] A twelfth aspect of the invention provides the use of a compound, pharmaceutically acceptable salt, solvate or prodrug of the first or second aspect of the invention, in the manufacture of a medicament for the diagnosis or treatment or prevention of a disease, disorder or condition.

[0036] A thirteenth aspect of the invention provides a method of diagnosis or treatment or prevention of a disease, disorder or condition, the method comprising the step of administering an effective amount of a compound, pharmaceutically acceptable salt, solvate or prodrug of the first or second aspect of the invention, or a pharmaceutical composition of the fifth aspect of the invention, to thereby diagnose or treat or prevent the disease, disorder or condition.

[0037] A fourteenth aspect of the invention provides a compound of Formula (III), a pharmaceutically acceptable salt, solvate or prodrug thereof, or a pharmaceutical composition comprising the same, for use in diagnosis.

[0038] A fifteenth aspect of the invention provides a compound of Formula (IIIA), a pharmaceutically acceptable salt, solvate or prodrug thereof, or a pharmaceutical composition comprising the same, for use in treating a disease, disorder or condition.

[0039] A sixteenth aspect of the invention provides a method of medical imaging, the method comprising:

[0040] i. administering a compound of Formula (III) or a pharmaceutically acceptable salt, solvate or prodrug thereof or a pharmaceutical composition comprising a compound of Formula (III) described herein to a subject; and

[0041] ii. imaging the subject.

[0042] A seventeenth aspect of the invention provides a method of medical imaging, wherein a compound of Formula (III) or a pharmaceutically acceptable salt, solvate or prodrugthereof, or a pharmaceutical composition comprising a compound of Formula (III) described herein has been administered to a subject, the method comprising imaging the subject.

[0043] An eighteenth aspect of the invention provides a process of preparing a compound of Formula (A) described herein or a salt thereof.

[0044] Brief description of the drawings

[0045] Figure 1 shows the uptake in HBSS of Example 34 into H460 cells.

[0046] Figure 2 shows the uptake in HBSS of Example 35 into H460 cells.

[0047] Figure 3 shows the uptake in HBSS of Example 36 into H460 cells.

[0048] Figure 4 shows the uptake in HBSS of CE2 into H460 cells.

[0049] Figure 5 shows the uptake in HBSS of Example 90 into H460 cells.

[0050] Figure 6 shows the uptake in HBSS of Example 91 into H460 cells.

[0051] Figure 7 shows the uptake in HBSS of Example 89 into H460 cells.

[0052] Figure 8 shows the uptake of Example 34 in competition with natural substrates of system xc“ (xCT).

[0053] Figure 9 shows the uptake of Example 35 in competition with natural substrates of system xc“(xCT).

[0054] Figure 10 shows a representative in vivo PET / CT image of H460 orthotopic lung tumour implantation in nu / nu mice at 120 min using Example 86.

[0055] Figure 11 shows a representative in vivo PET / CT image of H460 subcutaneous tumour implantation in nu / nu mice at 120 min using Example 86.

[0056] Figure 12A shows the UV HPLC chromatogram of Example 10; Figure 12B shows the radio HPLC chromatogram of Example 109.Figure 13 shows the uptake of Example 35 in different cell types.

[0057] Figure 14 shows the uptake of Example 86 in different cell types.

[0058] Figure 15 shows the uptake of Example 35 in cell types with differing levels of expression of system xc“(xCT).

[0059] Figure 16 shows the uptake of Example 86 in cell types with differing levels of expression of system xc“(xCT).

[0060] Figure 17 shows the uptake in HPLM of CE2 into H460 cells.

[0061] Figure 18 shows the uptake in HPLM of Example 35 into H460 cells.

[0062] Figure 19 shows the uptake in HPLM of Example 36 into H460 cells.

[0063] Figure 20 shows the uptake in HPLM of Example 86 into H460 cells.

[0064] Figure 21 shows the uptake in HPLM of Example 90 into H460 cells.

[0065] Figure 22 shows the uptake in HPLM of Example 91 into H460 cells.

[0066] Figure 23 shows the uptake in HPLM of Example 106 into H460 cells.

[0067] Figure 24 shows the uptake in HPLM of Example 107 into H460 cells.

[0068] Figure 25 shows the uptake in HBSS of Example 90 into H460 cells.

[0069] Figure 26 shows the uptake in HBSS of Example 91 into H460 cells.

[0070] Figure 27 shows the uptake in HBSS of Example 92 into H460 cells.

[0071] Figure 28 shows the uptake in HBSS of Example 107 into H460 cells.

[0072] Figure 29 shows the uptake in HBSS of Example 109 in H460 cells.

[0073] Figure 30 shows the cell viability in H460 cells as a percentage of untreated cells following treatment with 20 kBq of Example 109.Detailed description

[0074] A first aspect of the invention provides a compound of Formula (I):

[0075]

[0076] X

[0077] Formula (I)

[0078] or a pharmaceutically acceptable salt, solvate or prodrug thereof, wherein:

[0079] n is 0, 1, 2 or 3;

[0080] m is 1, 2, 3 or 4;

[0081] provided that m+n is 3 or 4;

[0082] when present, R1is hydrogen or C1-C3 alkyl;

[0083] R2is hydrogen or C1-C3 alkyl;

[0084] R3is hydrogen or C1-C3 alkyl;

[0085] L is -O-, -S-, -NR5-, a Ci-Ce straight chained alkylene group, wherein the Ci-Ce straight chained alkylene group optionally includes one, two or three heteroatoms each independently selected from 0, S and NR6in its carbon skeleton, or L is a group -L1-B-L2-, wherein L1and L2are each independently a bond or a C1-C3 straight chained alkylene group, wherein B is a saturated cyclic group selected from a C3-C6 cycloalkyl group, or a 3-, 4-, 5- or 6- membered saturated monocyclic heterocyclic group; wherein L is optionally substituted with one or more substituents independently selected from fluoro, hydroxyl, oxo (=0), C1-C3 alkyl, -0-(Ci-C3 alkyl), -0-(Ci-C3 fluoroalkyl), or C1-C3 fluoroalkyl, and wherein L optionally includes one or more (such as one or two) spirocyclic groups, wherein the spirocyclic group is selected from a C3-C5 cycloalkyl group or a saturated C3-C5 heterocyclic group;

[0086] A is phenyl, naphthyl, or a 5- to 10-membered heteroaryl group;

[0087] p is 0, 1, or 2;

[0088] R4is halo, -OH, -NH2, -SH, cyano, or a Ci-Cs saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight chained or branched, or be or include a cyclic group, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N,0 and S in its carbon skeleton, and wherein any -S- moiety in the hydrocarbyl group may optionally be substituted with one or two groups each independently selected from oxo (=0) and =NH to form a -SO-, -SO2-, -S( = NH)- or -SO( = NH)-moiety;

[0089] R5is hydrogen, C1-C3 alkyl, or C2-C3 alkylene-OR7;

[0090] R6is C1-C3 alkyl, or C2-C3 alkylene-OR7;

[0091] R7is hydrogen or methyl; and

[0092] X is iodine, an iodine radioisotope, fluorine, a fluorine radioisotope, or an astatine radioisotope.

[0093] As stated in accordance with the first aspect, n is 0, 1, 2 or 3. In one embodiment, n is 0 or 1. In one embodiment, n is 0. In one embodiment, n is 1. In one embodiment, n is 2. In one embodiment, n is 3.

[0094] As stated in accordance with the first aspect, m is 1, 2, 3 or 4. In one embodiment, m is 1. In one embodiment, m is 2. In one embodiment, m is 3. In one embodiment, m is 4.

[0095] As stated in accordance with the first aspect, m+n is 3 or 4.

[0096] In one embodiment, m+n is 3. Typically, in this embodiment, n is 0 and m is 3, n is 1 and m is 2, or n is 2 and m is 1. Typically, n is 0 and m is 3, or n is 1 and m is 2. More typically still, n is 0 and m is 3.

[0097] In one embodiment, m+n is 4. Typically, in this embodiment, n is 0 and m is 4, n is 1 and m is 3, n is 2 and m is 2, or n is 3 and m is 1. Typically, n is 0 and m is 4, n is 1 and m is 3, or n is 3 and m is 1. More typically, n is 0 and m is 4, or n is 1 and m is 3. More typically still, n is 0 and m is 4.

[0098] As stated in accordance with the first aspect, when present, each R1is independently hydrogen or C1-C3 alkyl. For the avoidance of doubt, it is noted that when n is 0, the group R1is not present.

[0099] In one embodiment, each R1is independently hydrogen or C1-C2 alkyl. Typically, each R1is independently hydrogen, methyl, or ethyl. More typically, each R1is independently hydrogen or methyl. More typically still, each R1is hydrogen.

[0100] As stated in accordance with the first aspect, each R2is independently hydrogen or Ci-C3alkyl.In one embodiment, each R2is independently hydrogen, methyl, or ethyl. Typically, each R2is independently hydrogen or methyl. In one embodiment, each R2is hyd rogen.

[0101] As stated in accordance with the first aspect, R3is hydrogen or C1-C3 alkyl.

[0102] In one embodiment, R3is hydrogen, methyl or ethyl. Typically, R3is hydrogen or methyl. In one embodiment, R3is hydrogen.

[0103] In one embodiment, each R2is independently hydrogen or methyl, and R3is hydrogen or methyl. In one embodiment, each R2is hydrogen and R3is hydrogen.

[0104] In one embodiment, each R1is independently hydrogen or methyl and R3is hydrogen or methyl. In one embodiment, each R1is hydrogen and R3is hydrogen.

[0105] In one embodiment, each R1is independently hydrogen or methyl, each R2is independently hydrogen or methyl, and R3is hydrogen or methyl. In one embodiment, each R1is hydrogen, each R2is hydrogen, and R3is hydrogen.

[0106] As stated in accordance with the first aspect, L is -O-, -S-, -NR5-, a Ci-Ce straight chained alkylene group, wherein the Ci-Ce straight chained alkylene group optionally includes one, two or three heteroatoms each independently selected from 0, S and NR6in its carbon skeleton, or L is a group -L1-B-L2-, wherein L1and L2are each independently a bond or a C1-C3 straight chained alkylene group, wherein B is a saturated cyclic group selected from a C3-C6 cycloalkyl group, or a 3-, 4-, 5- or 6-membered saturated monocyclic heterocyclic group; wherein L is optionally substituted with one or more substituents independently selected from fluoro, hydroxyl, oxo (=0), C1-C3 alkyl, -0-(Ci-C3 alkyl), -0-(Ci-C3 fluoroalkyl), or C1-C3 fluoroalkyl, and wherein L optionally includes one or more (such as one or two) spirocyclic groups, wherein the spirocyclic group is selected from a C3-C5 cycloalkyl group or a saturated C3-C5 heterocyclic group.

[0107] For the avoidance of doubt, when it is stated that L is a group -L1-B-L2-, it will be understood to mean that -L1and -L2are attached to different atoms of the cyclic group B.

[0108] For the avoidance of doubt, when it is stated that L optionally includes one or more spirocyclic groups, it will be understood to mean that any methylene (-CH2) group in aalkylene chain of L may be substituted by a cyclic group, such that the resultant group H

[0109] is a spirocyclic group, such as X & or

[0110]

[0111] . Thus, for the avoidance of doubt, when a spirocyclic group is described as being, for example, a

[0112] cyclopropyl group, it will be understood to mean the group:.

[0113] As stated in accordance with the first aspect, R5is hydrogen, C1-C3 alkyl, or C2-C3 alkylene-OR7, wherein R7is hydrogen or methyl.

[0114] In one embodiment, R5is hydrogen, methyl, ethyl, propyl, -CH2CH2OH, -CH2CH2CH2OH, -CH2CH2OMe, or -CH2CH2CH2OMe. Typically, R5is hydrogen, methyl, or ethyl. More typically, R5is hydrogen or methyl.

[0115] As stated in accordance with the first aspect, R6is C1-C3 alkyl, or C2-C3 alkylene-OR7. In one embodiment, R6is methyl, ethyl, propyl, -CH2CH2OH, -CH2CH2CH2OH, -CH2CH2OMe, or -CH2CH2CH2OMe. Typically, R6is methyl or ethyl. More typically, R6is methyl.

[0116] In one embodiment, L is a group -L1-B-L2-, wherein L1and L2are each independently a bond or a C1-C3 alkylene group, and wherein B is a saturated cyclic group selected from a C3-C6 cycloalkyl group, or a 3-, 4-, 5- or 6- membered saturated monocyclic heterocyclic group (comprising, for example, one or two heteroatoms independently selected from N, 0 or S in the ring structure), wherein L is optionally substituted. Typically in this embodiment, -L1and -L2are each independently a bond, -CH2- or -CH2CH2-, and B is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxiranyl, aziridinyl, azetidinyl, oxetanyl, thietanyl, pyrrolidinyl, tetra hydrofuranyl, tetrahydrothiophenyl, pyrazolidinyl, dioxolanyl, oxathiolanyl, piperidinyl, tetrahydropyranyl, thianyl, piperazinyl, dioxanyl, morpholinyl, or thiomorpholinyl. Typically, in this embodiment, L is optionally substituted with one or more substituents independently selected from fluoro, hydroxyl, oxo (=0), C1-C3 alkyl, -O-(Ci-C3 alkyl), -O-(Ci-C3 fluoroalkyl), or Ci-C3 fluoroalkyl, and wherein L optionally includes one or more (such as one or two) spirocyclic groups, wherein the spirocyclic group is selected from a C3-C5 cycloalkyl group or a saturated C3-C5 heterocyclic group. Typically, the spirocyclic group is a cyclopropyl, cyclobutyl, cyclopentyl, oxiranyl, aziridinyl, azetidinyl, oxetanyl, thietanyl, pyrrolidinyl, tetra hydrofuranyl, tetrahydrothiophenyl, dioxolanyl, or oxathiolanylgroup. More typically, the spirocyclic group is a cyclopropyl, cyclobutyl, cyclopentyl, oxiranyl, aziridinyl, azetidinyl, or oxetanyl group.

[0117] In one embodiment, -L1and -L2are each independently a bond or -CH2, and B is cyclopropyl, cyclobutyl, azetidinyl, or oxetanyl, each of which is optionally substituted with one or more substituents independently selected from fluoro, hydroxyl, oxo (=0), methyl, ethyl, methoxy, ethoxy, -CF3, CHF2, CH2F, -OCF3, -OCHF2, or -OCH2F.

[0118] Typically in this embodiment, B is cyclopropyl, cyclobutyl, azetidinyl (such as azetidin-1-yl or azetidin-3-yl) or oxetanyl (such as oxetan-2-yl or oxetan-3-yl). Typically, in this embodiment, B is cyclobutyl or azetidinyl.

[0119] In another embodiment, L is -0-, -S-, -NR5-, or a Ci-Ce straight chained alkylene group, wherein the Ci-Ce straight chained alkylene group optionally includes one, two or three heteroatoms each independently selected from 0, S and NR6in its carbon skeleton, and wherein the Ci-Ce straight chained alkylene group may optionally be substituted.

[0120] In one embodiment, L is -0-, -S-, or a Ci-Ce straight chained alkylene group, wherein the Ci-Ce straight chained alkylene group optionally includes one, two or three heteroatoms each independently selected from 0 and S in its carbon skeleton, and wherein the Ci-Ce straight chained alkylene group may optionally be substituted.

[0121] In one embodiment, L is -0-, -S-, or a Ci-Ce straight chained alkylene group, wherein the Ci-Ce straight chained alkylene group optionally includes one or two heteroatoms each independently selected from 0 and S in its carbon skeleton, and wherein the Ci-Ce straight chained alkylene group may optionally be substituted.

[0122] In one embodiment, L is -0-, -S-, or a C1-C4 straight chained alkylene group, wherein the C1-C4 straight chained alkylene group optionally includes one, two or three heteroatoms each independently selected from 0 and S in its carbon skeleton, and wherein the C1-C4 straight chained alkylene group may optionally be substituted.

[0123] In one embodiment, L is -0-, -S-, or a C1-C4 straight chained alkylene group, wherein the C1-C4 straight chained alkylene group optionally includes one or two heteroatoms each independently selected from 0 and S in its carbon skeleton, and wherein the Ci-C4 straight chained alkylene group may optionally be substituted.In one embodiment, L is -O-, -S-, or a C1-C3 straight chained alkylene group, wherein the C1-C3 straight chained alkylene group optionally includes one or two heteroatoms each independently selected from 0 and S in its carbon skeleton, and wherein the Ci-C3 straight chained alkylene group may optionally be substituted.

[0124] In one embodiment, L is -O-, -S-, or a C1-C3 straight chained alkylene group, wherein the C1-C3 straight chained alkylene group is optionally substituted.

[0125] In another embodiment, L is a C2-C3 straight chained alkylene group, wherein the C2-C3 straight chained alkylene group includes one or two heteroatoms each independently selected from 0 and S in its carbon skeleton, and wherein the C2-C3 straight chained alkylene group may optionally be substituted. Typically, in this embodiment, when L is a C2 straight chained alkylene group, the C2 straight chained alkylene group includes one heteroatom independently selected from 0 and S in its carbon skeleton, and when L is a C3 straight chained alkylene group, the C3 straight chained alkylene group includes one or two heteroatoms independently selected from 0 and S in its carbon skeleton.

[0126] The straight chained alkylene group, such as the Ci-Ce, C1-C4, or C1-C3 straight chained alkylene group described above, may optionally be substituted with one or more (such as one, two, three, or four) substituents independently selected from fluoro, hydroxyl, oxo (=0), methyl, ethyl, methoxy, ethoxy, fluoromethyl, fluoroethyl, -O-(fluoromethyl), or -O-(fluoroethyl), and wherein the Ci-Ce, C1-C4, or C1-C3 straight chained alkylene group optionally includes one or more (such as one or two) spirocyclic groups, wherein the spirocyclic group is selected from a C3-C5 cycloalkyl group or a saturated C3-C5 heterocyclic group. Typically, the spirocyclic group is a cyclopropyl, cyclobutyl, cyclopentyl, oxiranyl, aziridinyl, azetidinyl, oxetanyl, thietanyl, pyrrolidinyl, tetra hydrofuranyl, tetrahydrothiophenyl, dioxolanyl, or oxathiolanyl group. More typically, the spirocyclic group is a cyclopropyl, cyclobutyl, oxiranyl, aziridinyl, azetidinyl, or oxetanyl group.

[0127] In one embodiment, the Ci-Ce, C1-C4, or C1-C3 straight chained alkylene group may optionally be substituted with one or two substituents independently selected from fluoro, hydroxyl, oxo (=0), methyl, ethyl, methoxy, ethoxy, fluoromethyl, fluoroethyl, -O-(fluoromethyl), or -O-(fluoroethyl), and wherein the Ci-Ce, C1-C4, or C1-C3 straight chained alkylene group optionally includes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl, cyclobutyl, oxiranyl, aziridinyl, azetidinyl, or oxetanyl group.In one embodiment, the Ci-Ce, C1-C4, or C1-C3 straight chained alkylene group may optionally be substituted with one or two substituents independently selected from fluoro, hydroxyl, oxo (=0), methyl, ethyl, methoxy, -CF3, CHF2, CH2F, -OCF3, -OCHF2, -OCH2F, and wherein the Ci-Ce, C1-C4, or C1-C3 straight chained alkylene group optionally includes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl, cyclobutyl, oxiranyl, aziridinyl, azetidinyl, or oxetanyl group.

[0128] In one embodiment, the Ci-Ce, C1-C4, or C1-C3 straight chained alkylene group may optionally be substituted with one substituent independently selected from fluoro, hydroxyl, methyl, methoxy, -CF3, CHF2, CH2F, -OCF3, -OCHF2, -OCH2F, and wherein the Ci-Ce, C1-C4, or C1-C3 straight chained alkylene group optionally includes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl or cyclobutyl group.

[0129] In one embodiment, L is -0-, -S-, or a Ci-Ce straight chained alkylene group, wherein the Ci-Ce straight chained alkylene group optionally includes one or two heteroatoms each independently selected from 0 and S in its carbon skeleton. In one embodiment, L is -0-, -S-, or a C1-C4 straight chained alkylene group, wherein the C1-C4 straight chained alkylene group optionally includes one or two heteroatoms each independently selected from 0 and S in its carbon skeleton. In one embodiment, L is -0-, -S-, or a C1-C3 straight chained alkylene group, wherein the C1-C3 straight chained alkylene group optionally includes one or two heteroatoms each independently selected from 0 and S in its carbon skeleton.

[0130] In one embodiment, L is -0-, -S-, -NR5-, -CH2-, -CH2CH2-, -CH2CH2CH2-, -CH2CH2CH2CH2-, -CH2CH2CH2CH2CH2-, -CH2CH2CH2CH2CH2CH2-, -CH2O-, -CH2S-, -CH2NR6-, -OCH2-, -OCH2O-, -OCH2S-, -OCH2NR6-, -OCH2CH2-, -OCH2CH2O-, -OCH2CH2S-, -OCH2CH2NR6-, -CH2CH2O-, -CH2CH2S-, -CH2CH2NR6-, -OCH2CH2CH2-, -OCH2CH2CH2O-, -OCH2CH2CH2S-, -OCH2CH2CH2NR6-, -OCH2CH2CH2CH2-, -OCH2CH2CH2CH2CH2-, -OCH2CH2CH2CH2CH2CH2-, -SCH2-, -SCH2O-, -SCH2S-, -SCH2NR6-, -SCH2CH2-, -SCH2CH2S-, -SCH2CH2O-, -SCH2CH2NR6-, -SCH2CH2CH2-, -SCH2CH2CH2O-, -SCH2CH2CH2S-, -SCH2CH2CH2NR5-, -SCH2CH2CH2CH2-, -SCH2CH2CH2CH2CH2-, -SCH2CH2CH2CH2CH2CH2-, -NR6CH2-, -NR6CH2O-, -NR6CH2S-, -NR6CH2NR6-, -NR6CH2CH2-, -NR6CH2CH2NR6-, -NR6CH2CH2O-, -NR6CH2CH2S-, -NR6CH2CH2CH2-, -NR6CH2CH2CH2NR6-, -NR6CH2CH2CH2O-, -NR6CH2CH2CH2S-, -NR6CH2CH2CH2CH2-, -NR6CH2CH2CH2CH2CH2-, -NR6CH2CH2CH2CH2CH2CH2-, -CH2OCH2, -CH2OCH2CH2-, -CH2CH2OCH2-, -CH2CH2CH2O-, -CH2SCH2-, -CH2SCH2CH2-, -CH2CH2SCH2-, -CH2CH2CH2S-, -CH2NR6CH2-, -CH2NR6CH2CH2-, -CH2CH2NR6CH2-, -

[0131]

[0132] CH2CH2CH2NR6, -CH2OCH2CH2CH2-, -CH2CH2OCH2CH2-, -CH2CH2CH2OCH2-,-CH2CH2CH2CH2O-, -CH2SCH2CH2CH2-, -CH2CH2SCH2CH2-, -CH2CH2CH2SCH2-, -CH2CH2CH2CH2S-, -CH2NR6CH2CH2CH2-, -CH2CH2NR6CH2CH2-, -CH2CH2CH2NR6CH2-, -CH2CH2CH2CH2NR6-, -CH2OCH2CH2CH2CH2-, -CH2CH2OCH2CH2CH2-, -CH2CH2CH2OCH2CH2-, -CH2CH2CH2CH2OCH2-, -CH2CH2CH2CH2CH2O-, -CH2SCH2CH2CH2CH2-, -CH2CH2SCH2CH2CH2-, -CH2CH2CH2SCH2CH2-, -CH2CH2CH2CH2SCH2-, -CH2CH2CH2CH2CH2S-, -CH2NR6CH2CH2CH2CH2-, -CH2CH2NR6CH2CH2CH2-, -CH2CH2CH2NR6CH2CH2-, -CH2CH2CH2CH2NR6CH2-, -CH2CH2CH2CH2CH2NR6-, -CH2OCH2CH2CH2CH2CH2-, -CH2CH2OCH2CH2CH2CH2-, -CH2CH2CH2OCH2CH2CH2-, -CH2CH2CH2CH2OCH2CH2-, -CH2CH2CH2CH2CH2OCH2-, -CH2CH2CH2CH2CH2CH2O-, -CH2SCH2CH2CH2CH2CH2-,-CH2CH2SCH2CH2CH2CH2-, -CH2CH2CH2SCH2CH2CH2-, -CH2CH2CH2CH2SCH2CH2-,-CH2CH2CH2CH2CH2SCH2-, -CH2CH2CH2CH2CH2CH2S-, -CH2NRSCH2CH2CH2CH2CH2-, -CH2CH2NRSCH2CH2CH2CH2-, -CH2CH2CH2NRSCH2CH2CH2-, -CH2CH2CH2CH2NRSCH2CH2-, -CH2CH2CH2CH2CH2NR6CH2-, or -CH2CH2CH2CH2CH2CH2NR6-, wherein each is optionally substituted. Typically, in this embodiment, L is optionally substituted with one or two substituents independently selected from fluoro, hydroxyl, methyl, methoxy, -CF3, CHF2, CH2F, -OCF3, -OCHF2, or -OCH2F, and wherein L optionally includes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl, cyclobutyl, oxiranyl, aziridinyl, azetidinyl, or oxetanyl group.

[0133] More typically, in this embodiment, L is optionally substituted with one substituent independently selected from fluoro, hydroxyl, or methyl, and wherein L optionally includes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl or cyclobutyl group.

[0134] In one embodiment, L is -O-, -S-, -CH2-, -CH2CH2-, -CH2CH2CH2-, -CH2CH2CH2CH2-, -CH2CH2CH2CH2CH2-, -CH2CH2CH2CH2CH2CH2-, -CH2O-, -CH2S-, -OCH2-, -OCH2O-, -OCH2S-, -OCH2CH2-, -OCH2CH2O-, -OCH2CH2S-, -CH2CH2O-, -CH2CH2S-, -OCH2CH2CH2-, -OCH2CH2CH2O-, -OCH2CH2CH2S-, -OCH2CH2CH2CH2-, -OCH2CH2CH2CH2CH2-, -OCH2CH2CH2CH2CH2CH2-, -SCH2-, -SCH2O-, -SCH2S-, -SCH2CH2-, -SCH2CH2S-, -SCH2CH2O-, -SCH2CH2CH2-, -SCH2CH2CH2O-, -SCH2CH2CH2S-, -SCH2CH2CH2CH2-, -SCH2CH2CH2CH2CH2-, -SCH2CH2CH2CH2CH2CH2-, -CH2OCH2-, -CH2OCH2CH2-, -CH2CH2OCH2-, -CH2CH2CH2O-, -CH2SCH2-, -CH2SCH2CH2-, -CH2CH2SCH2-, -CH2CH2CH2S-, -CH2OCH2CH2CH2-, -CH2CH2OCH2CH2-, -CH2CH2CH2OCH2-, -CH2CH2CH2CH2O-, -CH2SCH2CH2CH2-, -CH2CH2SCH2CH2-, -CH2CH2CH2SCH2-, -CH2CH2CH2CH2S-, -CH2OCH2CH2CH2CH2-, -CH2CH2OCH2CH2CH2-, -CH2CH2CH2OCH2CH2-, -CH2CH2CH2CH2OCH2-, -CH2CH2CH2CH2CH2O-, -CH2SCH2CH2CH2CH2-, -CH2CH2SCH2CH2CH2-, -CH2CH2CH2SCH2CH2-,-CH2CH2CH2CH2SCH2-, -CH2CH2CH2CH2CH2S-, -CH2OCH2CH2CH2CH2CH2-, -CH2CH2OCH2CH2CH2CH2-, -CH2CH2CH2OCH2CH2CH2-, -CH2CH2CH2CH2OCH2CH2-, -CH2CH2CH2CH2CH2OCH2-, -CH2CH2CH2CH2CH2CH2O-, -CH2SCH2CH2CH2CH2CH2-, -CH2CH2SCH2CH2CH2CH2-, -CH2CH2CH2SCH2CH2CH2-, -CH2CH2CH2CH2SCH2CH2-, -CH2CH2CH2CH2CH2SCH2-, or -CH2CH2CH2CH2CH2CH2S-, wherein each is optionally substituted. Typically, in this embodiment, L is optionally substituted with one substituent independently selected from fluoro, hydroxyl, oxo (=0), methyl, methoxy, -CF3, CHF2, CH2F, -OCF3, -OCHF2, or -OCH2F, and wherein L optionally includes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl or cyclobutyl group. More typically, L is optionally substituted with one substituent independently selected from fluoro, hydroxyl, or methyl, and wherein L optionally includes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl or cyclobutyl group.

[0135] In one embodiment, L is -0-, -S-, -CH2-, -CH2CH2-, -CH2CH2CH2-, -CH2CH2CH2CH2-, -CH2O-, -CH2S-, -OCH2-, -OCH2CH2-, -OCH2CH2O-, -OCH2CH2S-, -CH2CH2O-, -CH2CH2S-, -OCH2CH2CH2-, -OCH2CH2CH2O-, -OCH2CH2CH2S-, -SCH2-, -SCH2CH2-, -SCH2CH2S-, -SCH2CH2O-, -SCH2CH2CH2-, -SCH2CH2CH2O-, -SCH2CH2CH2S-, -CH2OCH2-, -CH2SCH2-, -CH2OCH2CH2-, -CH2CH2OCH2-, -CH2CH2CH2O-, -CH2CH2CH2S-, -CH2SCH2-, -CH2SCH2CH2-, -CH2CH2SCH2-, or -CH2CH2CH2S-, wherein each is optionally substituted. Typically, in this embodiment, L is optionally substituted with one substituent independently selected from fluoro, hydroxyl, oxo (=0), methyl, methoxy, -CF3, CHF2, CH2F, -OCF3, -OCHF2, or -OCH2F, and wherein L optionally includes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl or cyclobutyl group. More typically, L is optionally substituted with one substituent independently selected from fluoro, hydroxyl, or methyl, and wherein L optionally includes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl or cyclobutyl group.

[0136] In one embodiment, L is -0-, -S-, -CH2-, -CH2CH2-, -CH2CH2CH2-, -CH2CH2CH2CH2-, -CH2O-, -CH2S-, -OCH2-, -OCH2CH2-, -OCH2CH2O-, -OCH2CH2S-, -CH2CH2O-, -CH2CH2S-, -OCH2CH2CH2-, -OCH2CH2CH2O-, -OCH2CH2CH2S-, -SCH2-, -SCH2CH2-, -SCH2CH2S-, -SCH2CH2O-, -SCH2CH2CH2-, -SCH2CH2CH2O-, -SCH2CH2CH2S-, -CH2OCH2-, -CH2OCH2CH2-, -CH2CH2OCH2-, -CH2CH2CH2O-, -CH2SCH2-, -CH2SCH2CH2-, -CH2CH2SCH2-, or -CH2CH2CH2S-, wherein each is optionally substituted. Typically, in this embodiment, L is optionally substituted with one substituent independently selected from fluoro, hydroxyl, oxo (=0), methyl, methoxy, -CF3, CHF2, CH2F, -OCF3, -OCHF2, or -OCH2F, and wherein L optionally includes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl or cyclobutyl group. More typically, L is optionallysubstituted with one substituent independently selected from fluoro, hydroxyl, or methyl, and wherein L optionally includes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl or cyclobutyl group.

[0137] In one embodiment, L is -O-, -S-, -CH2-, -CH2S-, -CH2O-, -OCH2-, -CH2CH2-, -CH2CH2CH2-, -CH2CH2CH2CH2-, -OCH2CH2-, -OCH2CH2O-, -OCH2CH2S-, -CH2SCH2-, -CH2CH2O-, -CH2CH2S- -OCH2CH2CH2-, -CH2CH2CH2O-, or -CH2CH2CH2S-.

[0138] In one embodiment, L is -O-, -S-, -CH2-, -CH2S-, -OCH2-, -CH2CH2CH2-, -OCH2CH2O-, -OCH2CH2S-, -CH2CH2O-, -CH2CH2S- -OCH2CH2CH2-, -CH2CH2CH2O-, or -CH2CH2CH2S-. Typically, L is -O-, -CH2-, -OCH2-, -CH2CH2CH2-, or -CH2CH2CH2S-.

[0139] In one embodiment, L is -CH2-.

[0140] As stated in accordance with the first aspect, A is phenyl, naphthyl, or a 5- to 10-membered heteroaryl group.

[0141] In one embodiment, A is phenyl, naphthyl, pyrrolyl, furanyl, thiophenyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, oxadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, indolizinyl, indazolyl, benzimidazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, quinazolinyl, or naphthyridinyl.

[0142] Typically, A is phenyl, naphthyl, or a 6- to 10-membered heteroaryl group.

[0143] In one embodiment, A is phenyl, naphthyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, indolizinyl, indazolyl, benzimidazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, quinazolinyl, or naphthyridinyl. Typically, A is phenyl, pyridinyl, indazolyl, benzimidazolyl, quinolinyl, or isoquinolinyl. More typically, A is phenyl, or indazolyl.

[0144] In one embodiment, A is indazolyl, optionally indazol-l-yl.

[0145] In one embodiment, A is phenyl. Typically, in this embodiment, the group X is in the para or meta position of the phenyl ring. In one embodiment, A is phenyl, and X is in the para position. In another embodiment, A is phenyl, and X is in the meta position.

[0146] As stated in accordance with the first aspect, p is 0, 1 or 2. For the avoidance of doubt, it is noted that when p is 0, the group R4is not present.In one embodiment, p is 0 or 1. In one embodiment, p is 1. In another embodiment, p is 0.

[0147] As stated in accordance with the first aspect, when present, each R4is independently halo, -OH, -NH2, -SH, cyano, or a Ci-Cs saturated or unsaturated hydrocarbyl group which may be straight chained or branched, or be or include a cyclic group, and may optionally be substituted with one or more halo groups, and where the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, 0 and S in its carbon skeleton, and any -S- moiety where present in the hydrocarbyl group may optionally be substituted with one or two groups each independently selected from oxo (=0) and =NH to form a -SO-, -SO2-, -S( = NH)- or -SO( = NH)- moiety.

[0148] In one embodiment, each R4is independently halo, -OH, -NH2, -SH, cyano, or a Ci-Cs saturated or unsaturated hydrocarbyl group which may be straight chained or branched, or be or include a cyclic group, and may optionally be substituted with one or more (such as one, two, three or four) halo groups, and where the hydrocarbyl group may optionally include one or two heteroatoms each independently selected from N, 0 and S in its carbon skeleton, and any -S- moiety when present in the hydrocarbyl group may optionally be substituted with one or two groups each independently selected from oxo (=0) and =NH to form a -SO-, -SO2-, -S( = NH)- or -SO( = NH)- moiety.

[0149] In one embodiment, each R4is independently halo, -OH, -NH2, -SH, cyano, C1-C5 alkyl, -O-(Ci-C5 alkyl), -C3-C5 cycloalkyl, -O(C3-C5 cycloalkyl), C3-C5 heterocycloalkyl, -0(C3-Cs heterocycloalkyl), -NH(Ci-Cs alkyl), -N(Ci-Cs alkyl)2, -NH-S02(CI-CS alkyl), -NH(CO)(Ci-Cs alkyl), or -S(Ci-Cs alkyl), wherein any alkyl group may be optionally substituted by one or more substituents independently selected from halo, OH, OMe, cyclopropyl, or cyclobutyl.

[0150] In one embodiment, each R4is independently fluoro, chloro, bromo, iodo, -OH, -NH2, -SH, cyano, C1-C4 alkyl, -O-(Ci-C4 alkyl), C3-C4 cycloalkyl, -O(C3-C4 cycloalkyl), C3-C4 heterocycloalkyl, -O(C3-C4 heterocycloalkyl), -NH(CI-C4 alkyl), -N(CI-C4 alkyl)2, -NH-SO2(Ci-C4 alkyl), -NH-SO2(CI-C4 haloalkyl), -NH(CO)(CI-C4 alkyl), or -S(Ci-C4 alkyl), wherein any alkyl group may be optionally substituted by one or more substituents selected from fluoro, OH, OMe, cyclopropyl, or cyclobutyl.In one embodiment, each R4is independently fluoro, chloro, bromo, iodo, cyano, C1-C4 alkyl optionally C3-C4 alkyl, -O-(Ci-C4 alkyl) optionally -O-(Cs-C4 alkyl), C3-C4 cycloalkyl, -O(C3-C4 cycloalkyl), C3-C4 heterocycloalkyl, -O(C3-C4 heterocycloalkyl), or -S(Ci-C4 alkyl), wherein any alkyl group may be optionally substituted by one or more substituents selected from fluoro, OH, OMe, cyclopropyl, or cyclobutyl.

[0151] In one embodiment, each R4is independently fluoro, chloro, bromo, iodo, cyano, methyl, ethyl, propyl (such as n-propyl or i-propyl), butyl (such as n-butyl, i-butyl, t-butyl), methoxy, ethoxy, propoxy, butoxy, cyclopropyl, cyclobutyl, -O-cyclopropyl, -O-cyclobutyl, -SMe, or -SEt. Typically, each R4is independently fluoro, iodo, cyano, methyl, ethyl, -OMe, -CH2CHCH3CH3, -OCH2CHCH3CH3, -OCH2CH2CH2CH3, -0-cyclobutyl, -OCH2-cyclobutyl, cyclopropyl, -CH2-cyclopropyl, -O-cyclopropyl, -OCH2-cyclopropyl, or -SMe.

[0152] In one embodiment, each R4is independently fluoro, cyano, methyl -CH2CHCH3CH3, -OCH2CHCH3CH3, -OCH2CH2CH2CH3, -O-cyclobutyl, -OCH2-cyclobutyl, or cyclopropyl.

[0153] In one embodiment, p is 1, and R4is fluoro, cyano, methyl -CH2CHCH3CH3, -0-CH2CHCH3CH3, -OCH2CH2CH2CH3, -O-cyclobutyl, -O-CH2-cyclobutyl, or cyclopropyl. In one embodiment, p is 1, and R4is fluoro, cyano, or methyl. In one embodiment, p is 1, and R4is fluoro.

[0154] In one embodiment, X and R4are different. In one embodiment, when X is127I,125I,124I,123I, or131I, R4is not iodo. In one embodiment, when X is18F or19F, R4is not fluoro.

[0155] As stated in accordance with the first aspect, X is iodine, an iodine radioisotope, fluorine, a fluorine radioisotope, or an astatine radioisotope.

[0156] In one embodiment, X is iodine or fluorine. In one embodiment, X is iodine. In one embodiment, X is fluorine.

[0157] In one embodiment, X is iodine or an iodine radioisotope. In one embodiment, X is fluorine or a fluorine radioisotope. In one embodiment, X is an astatine radioisotope. In one embodiment, X is an iodine radioisotope, a fluorine radioisotope or an astatine radioisotope. In one embodiment, X is an iodine radioisotope or a fluorine radioisotope. In one embodiment, X is an iodine radioisotope. In one embodiment, X is a fluorine radioisotope. In one embodiment, X is an astatine radioisotope.In one embodiment, X is127I,125I,124I,123I,131I,19F,18F, or211At.

[0158] In one embodiment, X is127I or19F. In one embodiment, X is127I. In one embodiment, X is19F.

[0159] In one embodiment, X is127I,125I,124I,123I or131I. In one embodiment, X is127I,125I, or131I. In one embodiment, X is127I, or125I.

[0160] In one embodiment, X is19F or18F.

[0161] In one embodiment, X is125I,124I,123I,131I,18F, or211At.

[0162] In one embodiment, X is125I,123I,131I, or211At.

[0163] In one embodiment, X is125I,124I,123I,131I, or18F. In one embodiment, X is125I,124I,131I, or18F. In one embodiment, X is124I,131I, or18F.

[0164] In one embodiment, X is124I or18F. In one embodiment, X is124I. In another embodiment, X is18F.

[0165] In one embodiment, X is125I,123I, or131I. In one embodiment, X is125I,131I, or211At. In one embodiment, X is125I or131I. In another embodiment, X is131I or211At.

[0166] In one embodiment, X is125I. In another embodiment, X is131I. In yet another embodiment, X is211At.

[0167] In one embodiment, the compound of Formula (I) is a compound of Formula (lai) -(Ia3) or a pharmaceutically acceptable salt, solvate or prodrug thereof:

[0168]

[0169] (Ia1) (Ia2)X

[0170]

[0171] (Ia3)

[0172] wherein p, R1, R2, R3, R4, R5, R6, R7, A, L, and X are as defined in accordance with Formula (I).

[0173] In another embodiment, the compound of Formula (I) is a compound of Formula (Ia4) - (Ia7) or a pharmaceutically acceptable salt, solvate or prodrug thereof:

[0174]

[0175] (Ia6) (Ia7)

[0176] wherein p, R1, R2, R3, R4, R5, R6, R7, A, L, and X are as defined in accordance with Formula (I).

[0177] Typically, the compound of Formula (I) is a compound of Formula (lai), (Ia2), (Ia4), or (Ia5). In one embodiment, the compound of Formula (I) is a compound of Formula (lai) or (Ia4). In one embodiment, the compound of Formula (I) is a compound of Formula (lai). In one embodiment, the compound of Formula (I) is a compound of Formula (Ia4).The compounds, salts, solvates and prodrugs of the present invention may contain at least one chiral centre. The compounds, salts, solvates and prodrugs may therefore exist in at least two isomeric forms. The present invention encompasses racemic mixtures of the compounds, salts, solvates and prodrugs of the present invention as well as enantiomerically enriched and substantially enantiomerically pure isomers. For the purposes of this invention, a "substantially enantiomerically pure" isomer of a compound comprises less than 5% of other isomers of the same compound, more typically less than 2%, and most typically less than 0.5% by weight.

[0178] In one embodiment, the compound of Formula (I) is a compound of Formula (II) or a pharmaceutically acceptable salt, solvate, or prodrug thereof:

[0179] R1R20

[0180]

[0181] X

[0182] Formula (II)

[0183] wherein n, m, p, R1, R2, R3, R4, R5, R6, R7, A, L, and X are as defined in accordance with Formula (I).

[0184] As would be understood, in the compound of Formula (II), the chiral centre at the amino (-NH2) group is (S).

[0185] In one embodiment, the carbon bearing the -L- group, marked below with an asterisk (*), is a chiral centre and has ( / ?) configuration. In another embodiment, the carbon bearing the -L- group, marked below with an asterisk (*), is a chiral centre and has (S) configuration.

[0186] In one embodiment, the compound of Formula (II) is a compound of Formula (Hal) -(IIa3) or a pharmaceutically acceptable salt, solvate or prodrug thereof:

[0187]

[0188] wherein p, R1, R2, R3, R4, R5, R6, R7, A, L, and X are as defined in accordance with Formula (I).

[0189] In another embodiment, the compound of Formula (II) is a compound of Formula (IIa4) - (IIa7) or a pharmaceutically acceptable salt, solvate or prodrug thereof:

[0190]

[0191] with Formula (I).Typically, the compound of Formula (II) is a compound of Formula (Hal), (IIa2), (IIa4) or (IIa5). In one embodiment, the compound of Formula (II) is a compound of Formula (Hal) or (IIa4). In one embodiment, the compound of Formula (II) is a compound of Formula (Hal). In one embodiment, the compound of Formula (II) is a compound of Formula (IIa4).

[0192] As will be understood, insofar as practical, embodiments directed to one substituent or moiety (such as a given L or X group) may be read in conjunction with embodiments directed to a different substituent or moiety.

[0193] For example, in an exemplary embodiment, there is provided a compound of Formula (I) or Formula (II) as defined above, wherein:

[0194] n is 0, 1, 2 or 3;

[0195] m is 1, 2, 3 or 4;

[0196] provided that m+n is 3 or 4;

[0197] when present, R1is hydrogen;

[0198] R2is hydrogen;

[0199] R3is hydrogen;

[0200] L is -O-, -S-, -NR5-, or a Ci-Ce straight chained alkylene group, wherein the Ci-Ce straight chained alkylene group optionally includes one, two or three heteroatoms each independently selected from 0, S and NR6in its carbon skeleton, wherein the Ci-Ce straight chained alkylene group may optionally be substituted with one or more substituents independently selected from fluoro, hydroxyl, oxo (=0), C1-C3 alkyl, -O-(Ci-C3 alkyl), -O-(Ci-C3 fluoroalkyl), or C1-C3 fluoroalkyl, and wherein the Ci-Ce straight chained alkylene group may include a spirocyclic group, wherein the spirocyclic group is a cyclopropyl, cyclobutyl, oxiranyl, aziridinyl, azetidinyl, or oxetanyl group;

[0201] A is phenyl, naphthyl, or a 6- to 10-membered heteroaryl group;

[0202] p is 0 or 1;

[0203] R4is fluoro, chloro, bromo, iodo, cyano, C1-C4 alkyl optionally C3-C4 alkyl, -0-(C1-C4 alkyl) optionally -O-(C3-C4 alkyl), C3-C4 cycloalkyl, -O(C3-C4 cycloalkyl), C3-C4 heterocycloalkyl, -O(C3-C4 heterocycloalkyl), or -S(Ci-C4 alkyl), wherein any alkyl group may be optionally substituted by one or more substituents selected from fluoro, OH, OMe, cyclopropyl, or cyclobutyl;

[0204] R5is hydrogen or methyl;

[0205] R6is methyl; and

[0206] X is iodine, an iodine radioisotope, fluorine, a fluorine radioisotope, or an astatine radioisotope, optionally wherein X is127I,125I,124I,123I,131I,19F,18F, or211At.In another exemplary embodiment, there is provided a compound of Formula (I) or Formula (II) as defined above, wherein:

[0207] n is 0, 1, 2 or 3;

[0208] m is 1, 2, 3 or 4;

[0209] provided that m+n is 3 or 4;

[0210] when present, R1is hydrogen;

[0211] R2is hydrogen;

[0212] R3is hydrogen;

[0213] L is -O-, -S-, or a Ci-Ce straight chained alkylene group, wherein the Ci-Ce straight chained alkylene group optionally includes one or two heteroatoms each independently selected from 0 and S in its carbon skeleton, wherein the Ci-Ce straight chained alkylene group may optionally be substituted with one or more substituents independently selected from fluoro, hydroxyl, oxo (=0), C1-C3 alkyl,

[0214] -O-(Ci-C3 alkyl), -O-(Ci-C3 fluoroalkyl), or C1-C3 fluoroalkyl, and wherein the Ci-Ce straight chained alkylene group may include a spirocyclic group, wherein the spirocyclic group is a cyclopropyl, cyclobutyl, oxiranyl, aziridinyl, azetidinyl, or oxetanyl group;

[0215] A is phenyl, naphthyl, or a 6- to 10-membered heteroaryl group;

[0216] p is 0 or 1;

[0217] R4is fluoro, chloro, bromo, iodo, cyano, C1-C4 alkyl optionally C3-C4 alkyl, -0-(C1-C4 alkyl) optionally -O-(C3-C4 alkyl), C3-C4 cycloalkyl, -O(C3-C4 cycloalkyl), C3-C4 heterocycloalkyl, -O(C3-C4 heterocycloalkyl), or -S(Ci-C4 alkyl), wherein any alkyl group may be optionally substituted by one or more substituents selected from fluoro, OH, OMe, cyclopropyl, or cyclobutyl; and

[0218] X is iodine, an iodine radioisotope, fluorine, a fluorine radioisotope, or an astatine radioisotope, optionally wherein X is127I,125I,124I,123I,131I,19F,18F, or211At.

[0219] In another exemplary embodiment, there is provided a compound of Formula (I) or Formula (II) as defined above, wherein:

[0220] n is 0 or 1;

[0221] m is 2, 3 or 4;

[0222] provided that m+n is 3 or 4;

[0223] when present, R1is hydrogen;

[0224] R2is hydrogen;

[0225] R3is hydrogen;

[0226] L is -O-, -S-, or a C1-C3 straight chained alkylene group, wherein the C1-C3 straight chained alkylene group optionally includes one or two heteroatoms each independently selected from 0 and S in its carbon skeleton, wherein the C1-C3 straightchained alkylene group is optionally substituted with one or two substituents independently selected from fluoro, hydroxyl, methyl, methoxy, -CF3, CHF2, CH2F, -OCF3, -OCHF2, or -OCH2F, and wherein the C1-C3 straight chained alkylene group optionally includes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl, cyclobutyl, oxiranyl, aziridinyl, azetidinyl, or oxetanyl group;

[0227] A is phenyl, naphthyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, indolizinyl, indazolyl, benzimidazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, quinazolinyl, or naphthyridinyl;

[0228] p is 0 or 1;

[0229] R4is fluoro, iodo, cyano, methyl, ethyl, -OMe, -CH2CHCH3CH3, OCH2CHCH3CH3, -OCH2CH2CH2CH3, -O-cyclobutyl, -OCH2-cyclobutyl, cyclopropyl, -CH2-cyclopropyl, -0-cyclopropyl, -OCH2-cyclopropyl, or -SMe; and

[0230] X is iodine, an iodine radioisotope, fluorine, a fluorine radioisotope, or an astatine radioisotope, optionally wherein X is127I,125I,124I,123I,131I,19F,18F, or211At.

[0231] In another exemplary embodiment, there is provided a compound of Formula (I) or Formula (II) as defined above, wherein:

[0232] n is 0 or 1;

[0233] m is 2, 3 or 4;

[0234] provided that m+n is 3 or 4;

[0235] when present, R1is hydrogen;

[0236] R2is hydrogen;

[0237] R3is hydrogen;

[0238] L is -0-, -S-, or a C1-C3 straight chained alkylene group, wherein the C1-C3 straight chained alkylene group optionally includes one or two heteroatoms each independently selected from 0 and S in its carbon skeleton, wherein the C1-C3 straight chained alkylene group is optionally substituted with one substituent independently selected from fluoro, hydroxyl, or methyl, and wherein the C1-C3 straight chained alkylene group optionally includes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl or cyclobutyl group;

[0239] A is phenyl, pyridinyl, indazolyl, benzimidazolyl, quinolinyl, or isoquinolinyl; p is 0; and

[0240] X is127I,125I,124I,123I,131I,19F,18F, or211At.

[0241] In another exemplary embodiment, there is provided a compound of Formula (I) or Formula (II) as defined above, wherein:

[0242] n is 0 or 1,

[0243] m is 2, 3 or 4;provided that m+n is 3 or 4;

[0244] when present, R1is hydrogen;

[0245] R2is hydrogen;

[0246] R3is hydrogen;

[0247] L is -O-, -S-, or a C1-C3 straight chained alkylene group, wherein the C1-C3 straight chained alkylene group optionally includes one or two heteroatoms each independently selected from 0 and S in its carbon skeleton, wherein the C1-C3 straight chained alkylene group is optionally substituted with one substituent independently selected from fluoro, hydroxyl, or methyl, and wherein the C1-C3 straight chained alkylene group optionally includes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl or cyclobutyl group;

[0248] A is phenyl, pyridinyl, indazolyl, benzimidazolyl, quinolinyl, or isoquinolinyl; P is 1;

[0249] R4is fluoro, iodo, cyano, methyl, ethyl, -OMe, -CH2CHCH3CH3, -OCH2CHCH3CH3, -OCH2CH2CH2CH3, -O-cyclobutyl, -OCH2-cyclobutyl, cyclopropyl, -CH2-cyclopropyl, -O-cyclopropyl, -OCH2-cyclopropyl, or -SMe, optionally wherein R4fluoro; and

[0250] X is127I,125I,124I,123I,131I,19F,18F, or211At.

[0251] In another exemplary embodiment, there is provided a compound of Formula (I) or Formula (II) as defined above, wherein:

[0252] n is 0, or 1;

[0253] m is 2, 3 or 4

[0254] provided that m+n is 3 or 4;

[0255] when present, R1is hydrogen;

[0256] R2is hydrogen;

[0257] R3is hydrogen;

[0258] L is -O-, -S-, -CH2-, -CH2CH2-, -CH2CH2CH2-, -CH2CH2CH2CH2-, -CH2O-, -CH2S-, -OCH2-, -OCH2CH2-, -OCH2CH2O-, -OCH2CH2S-, -CH2CH2O-, -CH2CH2S-, -OCH2CH2CH2-, -OCH2CH2CH2O-, -OCH2CH2CH2S-, -SCH2-, -SCH2CH2-, -SCH2CH2S-, -SCH2CH2O-, -SCH2CH2CH2-, -SCH2CH2CH2O-, -SCH2CH2CH2S-, -CH2OCH2-, -CH2OCH2CH2-, -CH2CH2OCH2-, -CH2CH2CH2O-, -CH2SCH2-, -CH2SCH2CH2-, -CH2CH2SCH2-, or -CH2CH2CH2S-;

[0259] A is phenyl or indazolyl;

[0260] p is 0; and

[0261] X is127I,125I,124I,123I,131I,19F,18F, or211At.In another exemplary embodiment, there is provided a compound of Formula (I) or Formula (II) as defined above, wherein:

[0262] n is 0, 1, 2 or 3;

[0263] m is 1, 2, 3 or 4;

[0264] provided that m+n is 3 or 4;

[0265] when present, R1is hydrogen;

[0266] R2is hydrogen;

[0267] R3is hydrogen;

[0268] L is -O-, -S-, or a Ci-Ce straight chained alkylene group, wherein the Ci-Ce straight chained alkylene group optionally includes one or two heteroatoms each independently selected from 0 and S in its carbon skeleton, wherein the Ci-Ce straight chained alkylene group may optionally be substituted with one or more substituents independently selected from fluoro, hydroxyl, oxo (=0), C1-C3 alkyl,

[0269] -O-(Ci-C3 alkyl), -O-(Ci-C3 fluoroalkyl), or C1-C3 fluoroalkyl, and wherein the Ci-Ce straight chained alkylene group may include a spirocyclic group, wherein the spirocyclic group is a cyclopropyl, cyclobutyl, oxiranyl, aziridinyl, azetidinyl, or oxetanyl group;

[0270] A is phenyl, naphthyl, or a 6- to 10-membered heteroaryl group;

[0271] p is 0 or 1;

[0272] R4is fluoro, chloro, bromo, iodo, cyano, C1-C4 alkyl optionally C3-C4 alkyl, -0-(C1-C4 alkyl) optionally -O-(C3-C4 alkyl), C3-C4 cycloalkyl, -O(C3-C4 cycloalkyl), C3-C4 heterocycloalkyl, -O(C3-C4 heterocycloalkyl), or -S(Ci-C4 alkyl), wherein any alkyl group may be optionally substituted by one or more substituents selected from fluoro, OH, OMe, cyclopropyl, or cyclobutyl; and

[0273] X is127I,125I,124I,123I, or131I.

[0274] In another exemplary embodiment, there is provided a compound of Formula (I) or Formula (II) as defined above, wherein:

[0275] n is 0, 1, 2 or 3;

[0276] m is 1, 2, 3 or 4;

[0277] provided that m+n is 3 or 4;

[0278] when present, R1is hydrogen;

[0279] R2is hydrogen;

[0280] R3is hydrogen;

[0281] L is -O-, -S-, or a Ci-Ce straight chained alkylene group, wherein the Ci-Ce straight chained alkylene group optionally includes one or two heteroatoms each independently selected from 0 and S in its carbon skeleton, wherein the Ci-Ce straight chained alkylene group may optionally be substituted with one or more substituentsindependently selected from fluoro, hydroxyl, oxo (=0), C1-C3 alkyl,

[0282] -0-(Ci-C3 alkyl), -0-(Ci-C3 fluoroalkyl), or C1-C3 fluoroalkyl, and wherein the Ci-Ce straight chained alkylene group may include a spirocyclic group, wherein the spirocyclic group is a cyclopropyl, cyclobutyl, oxiranyl, aziridinyl, azetidinyl, or oxetanyl group;

[0283] A is phenyl, naphthyl, or a 6- to 10-membered heteroaryl group;

[0284] p is 0 or 1;

[0285] R4is fluoro, chloro, bromo, iodo, cyano, C1-C4 alkyl optionally C3-C4 alkyl, -0-(C1-C4 alkyl) optionally -O-(C3-C4 alkyl), C3-C4 cycloalkyl, -O(C3-C4 cycloalkyl), C3-C4 heterocycloalkyl, -O(C3-C4 heterocycloalkyl), or -S(Ci-C4 alkyl), wherein any alkyl group may be optionally substituted by one or more substituents selected from fluoro, OH, OMe, cyclopropyl, or cyclobutyl; and

[0286] X is19F or18F.

[0287] In another exemplary embodiment, there is provided a compound of Formula (I) or Formula (II) as defined above, wherein:

[0288] n is 0, 1, 2 or 3;

[0289] m is 1, 2, 3 or 4;

[0290] provided that m+n is 3 or 4;

[0291] when present, R1is hydrogen;

[0292] R2is hydrogen;

[0293] R3is hydrogen;

[0294] L is -0-, -S-, or a Ci-Ce straight chained alkylene group, wherein the Ci-Ce straight chained alkylene group optionally includes one or two heteroatoms each independently selected from 0 and S in its carbon skeleton, wherein the Ci-Ce straight chained alkylene group may optionally be substituted with one or more substituents independently selected from fluoro, hydroxyl, oxo (=0), C1-C3 alkyl,

[0295] -O-(Ci-C3 alkyl), -O-(Ci-C3 fluoroalkyl), or C1-C3 fluoroalkyl, and wherein the Ci-Ce straight chained alkylene group may include a spirocyclic group, wherein the spirocyclic group is a cyclopropyl, cyclobutyl, oxiranyl, aziridinyl, azetidinyl, or oxetanyl group;

[0296] A is phenyl, naphthyl, or a 6- to 10-membered heteroaryl group;

[0297] p is 0 or 1;

[0298] R4is fluoro, chloro, bromo, iodo, cyano, C1-C4 alkyl optionally C3-C4 alkyl, -0-(C1-C4 alkyl) optionally -O-(C3-C4 alkyl), C3-C4 cycloalkyl, -O(C3-C4 cycloalkyl), C3-C4 heterocycloalkyl, -O(C3-C4 heterocycloalkyl), or -S(Ci-C4 alkyl), wherein any alkyl group may be optionally substituted by one or more substituents selected from fluoro, OH, OMe, cyclopropyl, or cyclobutyl; andX is211At.

[0299] The first aspect further provides a compound of Formula (III):

[0300]

[0301] Formula (III)

[0302] or a pharmaceutically acceptable salt, solvate or prodrug thereof, wherein:

[0303] n is 0, 1, 2 or 3;

[0304] m is 1, 2, 3 or 4;

[0305] provided that m+n is 3 or 4;

[0306] when present, R1is hydrogen or C1-C3 alkyl;

[0307] R2is hydrogen or C1-C3 alkyl;

[0308] R3is hydrogen or C1-C3 alkyl;

[0309] L is -O-, -S-, -NR5-, a Ci-Ce straight chained alkylene group, wherein the Ci-Ce straight chained alkylene group optionally includes one, two or three heteroatoms each independently selected from 0, S and NR6in its carbon skeleton, or L is a group -L1-B-L2-, wherein L1and L2are each independently a bond or a C1-C3 straight chained alkylene group, wherein B is a saturated cyclic group selected from a C3-C6 cycloalkyl group, or a 3-, 4-, 5- or 6- membered saturated monocyclic heterocyclic group; wherein L is optionally substituted with one or more substituents independently selected from fluoro, hydroxyl, oxo (=0), C1-C3 alkyl, -0-(Ci-C3 alkyl), -0-(Ci-C3 fluoroalkyl), or C1-C3 fluoroalkyl, and wherein L optionally includes one or more spirocyclic groups, wherein the spirocyclic group is selected from a C3-C5 cycloalkyl group or a saturated C3-C5 heterocyclic group;

[0310] A is phenyl, naphthyl, or a 5- to 10-membered heteroaryl group;

[0311] p is 0, 1, or 2;

[0312] R4is halo, -OH, -NH2, -SH, cyano, or a Ci-Cs saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight chained or branched, or be or include a cyclic group, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N,0 and S in its carbon skeleton, and wherein any -S- moiety in the hydrocarbyl group may optionally be substituted with one or two groups each independently selected from oxo (=0) and =NH to form a -SO-, -SO2-, -S( = NH)- or -SO( = NH)-moiety;

[0313] R5is hydrogen, C1-C3 alkyl, or C2-C3 alkylene-OR7;

[0314] R6is C1-C3 alkyl, or C2-C3 alkylene-OR7;

[0315] R7is hydrogen, or methyl; and

[0316] X1is125I,124I,123I,131I,18F, or211At.

[0317] In one embodiment, n is 0 or 1. In one embodiment, n is 0. In one embodiment, n is 1. In one embodiment, n is 2. In one embodiment, n is 3.

[0318] In one embodiment, m is 1. In one embodiment, m is 2. In one embodiment, m is 3. In one embodiment, m is 4.

[0319] In one embodiment, m+n is 3. Typically, in this embodiment, n is 0 and m is 3, n is 1 and m is 2, or n is 2 and m is 1. Typically, n is 0 and m is 3, or n is 1 and m is 2. More typically still, n is 0 and m is 3.

[0320] In one embodiment, m+n is 4. Typically, in this embodiment, n is 0 and m is 4, n is 1 and m is 3, n is 2 and m is 2, or n is 3 and m is 1. Typically, n is 0 and m is 4, n is 1 and m is 3, or n is 3 and m is 1. More typically, n is 0 and m is 4, or n is 1 and m is 3. More typically still, n is 0 and m is 4.

[0321] For the avoidance of doubt, it is noted that when n is 0, the group R1is not present.

[0322] In one embodiment, each R1is independently hydrogen or C1-C2 alkyl. Typically, each R1is independently hydrogen, methyl, or ethyl. More typically, each R1is independently hydrogen or methyl. More typically still, each R1is hydrogen.

[0323] In one embodiment, each R2is independently hydrogen, methyl or ethyl. Typically, each R2is independently hydrogen or methyl. In one embodiment, each R2is hyd rogen.

[0324] In one embodiment, R3is hydrogen, methyl, or ethyl. Typically, R3is hydrogen or methyl. In one embodiment, R3is hydrogen.

[0325] In one embodiment, each R2is independently hydrogen or methyl, and R3is hydrogen or methyl. In one embodiment, each R2is hydrogen and R3is hydrogen.In one embodiment, each R1is independently hydrogen or methyl and R3is hydrogen or methyl. In one embodiment, each R1is hydrogen and R3is hydrogen.

[0326] In one embodiment, each R1is independently hydrogen or methyl, each R2is independently hydrogen or methyl, and R3is hydrogen or methyl. In one embodiment, each R1is hydrogen, each R2is hydrogen, and R3is hydrogen.

[0327] For the avoidance of doubt, when it is stated that L is a group -L1-B-L2-, it will be understood to mean that -L1and -L2are attached to different atoms of the cyclic group B.

[0328] For the avoidance of doubt, when it is stated that L optionally includes one or more spirocyclic groups, it will be understood to mean that any methylene (-CH2) group in a alkylene chain of L may be substituted by a cyclic group, such that the resultant group

[0329] is a spirocyclic group, such as X

[0330]

[0331] Xt&orsT. Thus, for the avoidance of doubt, when a spirocyclic group is described as being, for example, a

[0332] cyclopropyl group, it will be understood to mean the group:.

[0333] In one embodiment, R5is hydrogen, methyl, ethyl, propyl, -CH2CH2OH, -CH2CH2CH2OH, -CH2CH2OMe, or -CH₂CH₂CH₂OMe. Typically, R5is hydrogen, methyl, or ethyl. More typically, R5is hydrogen or methyl.

[0334] In one embodiment, R6is methyl, ethyl, propyl, -CH2CH2OH, -CH2CH2CH2OH, -CH2CH2OMe, or -CH₂CH₂CH₂OMe. Typically, R6is methyl or ethyl. More typically, R6is methyl.

[0335] In one embodiment, L is a group -L1-B-L2-, wherein L1and L2are each independently a bond or a C1-C3 alkylene group, and wherein B is a saturated cyclic group selected from a C3-C6 cycloalkyl group, or a 3-, 4-, 5- or 6- membered saturated monocyclic heterocyclic group (comprising, for example, one or two heteroatoms independently selected from N, 0 or S in the ring structure), wherein L is optionally substituted. Typically, in this embodiment, -L1and -L2are each independently a bond, -CH2- or -CH2CH2-, and B is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxiranyl, aziridinyl, azetidinyl, oxetanyl, thietanyl, pyrrolidinyl, tetra hydrofuranyl, tetrahydrothiophenyl, pyrazolidinyl, dioxolanyl, oxathiolanyl, piperidinyl, tetrahydropyranyl, thianyl,pi perazinyl, dioxanyl, morpholinyl, or thiomorpholinyl. Typically, in this embodiment, L is optionally substituted with one or more substituents independently selected from fluoro, hydroxyl, oxo (=0), C1-C3 alkyl, -0-(Ci-C3 alkyl), -0-(Ci-C3 fluoroalkyl), or Ci-C3 fluoroalkyl, and wherein L optionally includes one or more (such as one or two) spirocyclic groups, wherein the spirocyclic group is selected from a C3-C5 cycloalkyl group or a saturated C3-C5 heterocyclic group. Typically, the spirocyclic group is a cyclopropyl, cyclobutyl, cyclopentyl, oxiranyl, aziridinyl, azetidinyl, oxetanyl, thietanyl, pyrrolidinyl, tetra hydrofuranyl, tetrahydrothiophenyl, dioxolanyl, or oxathiolanyl group. More typically, the spirocyclic group is a cyclopropyl, cyclobutyl, cyclopentyl, oxiranyl, aziridinyl, azetidinyl, or oxetanyl group.

[0336] In one embodiment, -L1and -L2are each independently a bond or -CH2, and B is cyclopropyl, cyclobutyl, azetidinyl, or oxetanyl, each of which is optionally substituted with one or more substituents independently selected from fluoro, hydroxyl, oxo (=0), methyl, ethyl, methoxy, ethoxy, -CF3, CHF2, CH2F, -OCF3, -OCHF2, or -OCH2F.

[0337] Typically in this embodiment, B is cyclopropyl, cyclobutyl, azetidinyl (such as azetidin-1-yl or azetidin-3-yl) or oxetanyl (such as oxetan-2-yl or oxetan-3-yl). Typically, in this embodiment, B is cyclobutyl or azetidinyl.

[0338] In another embodiment, L is -0-, -S-, -NR5-, or a Ci-Ce straight chained alkylene group, wherein the Ci-Ce straight chained alkylene group optionally includes one, two or three heteroatoms each independently selected from 0, S and NR6in its carbon skeleton, and wherein the Ci-Ce straight chained alkylene group may optionally be substituted.

[0339] In one embodiment, L is -0-, -S-, or a Ci-Ce straight chained alkylene group, wherein the Ci-Ce straight chained alkylene group optionally includes one, two or three heteroatoms each independently selected from 0 and S in its carbon skeleton, and wherein the Ci-Ce straight chained alkylene group may optionally be substituted.

[0340] In one embodiment, L is -0-, -S-, or a Ci-Ce straight chained alkylene group, wherein the Ci-Ce straight chained alkylene group optionally includes one or two heteroatoms each independently selected from 0 and S in its carbon skeleton, and wherein the Ci-Ce straight chained alkylene group may optionally be substituted.

[0341] In one embodiment, L is -0-, -S-, or a C1-C4 straight chained alkylene group, wherein the C1-C4 straight chained alkylene group optionally includes one, two or three heteroatoms each independently selected from 0 and S in its carbon skeleton, and wherein the C1-C4 straight chained alkylene group may optionally be substituted.In one embodiment, L is -O-, -S-, or a C1-C4 straight chained alkylene group, wherein the C1-C4 straight chained alkylene group optionally includes one or two heteroatoms each independently selected from 0 and S in its carbon skeleton, and wherein the Ci-C4 straight chained alkylene group may optionally be substituted.

[0342] In one embodiment, L is -O-, -S-, or a C1-C3 straight chained alkylene group, wherein the C1-C3 straight chained alkylene group optionally includes one or two heteroatoms each independently selected from 0 and S in its carbon skeleton, and wherein the Ci-C3 straight chained alkylene group may optionally be substituted.

[0343] In one embodiment, L is -O-, -S-, or a C1-C3 straight chained alkylene group, wherein the C1-C3 straight chained alkylene group is optionally substituted.

[0344] In another embodiment, L is a C2-C3 straight chained alkylene group, wherein the C2-C3 straight chained alkylene group includes one or two heteroatoms each independently selected from 0 and S in its carbon skeleton, and wherein the C2-C3 straight chained alkylene group may optionally be substituted. Typically, in this embodiment, when L is a C2 straight chained alkylene group, the C2 straight chained alkylene group includes one heteroatom independently selected from 0 and S in its carbon skeleton, and when L is a C3 straight chained alkylene group, the C3 straight chained alkylene group includes one or two heteroatoms independently selected from 0 and S in its carbon skeleton.

[0345] The straight chained alkylene group, such as the Ci-Ce, C1-C4, or C1-C3 straight chained alkylene group described above, may optionally be substituted with one or more (such as one, two, three, or four) substituents independently selected from fluoro, hydroxyl, oxo (=0), methyl, ethyl, methoxy, ethoxy, fluoromethyl, fluoroethyl, -O-(fluoromethyl), or -O-(fluoroethyl), and wherein the Ci-Ce, C1-C4, or C1-C3 straight chained alkylene group optionally includes one or more (such as one or two) spirocyclic groups, wherein the spirocyclic group is selected from a C3-C5 cycloalkyl group or a saturated C3-C5 heterocyclic group. Typically, the spirocyclic group is a cyclopropyl, cyclobutyl, cyclopentyl, oxiranyl, aziridinyl, azetidinyl, oxetanyl, thietanyl, pyrrolidinyl, tetra hydrofuranyl, tetrahydrothiophenyl, dioxolanyl, or oxathiolanyl group. More typically, the spirocyclic group is a cyclopropyl, cyclobutyl, oxiranyl, aziridinyl, azetidinyl, or oxetanyl group.

[0346] In one embodiment, the Ci-Ce, C1-C4, or C1-C3 straight chained alkylene group may optionally be substituted with one or two substituents independently selected from fluoro, hydroxyl, oxo (=0), methyl, ethyl, methoxy, ethoxy, fluoromethyl, fluoroethyl,-O-(fluoromethyl), or -O-(fluoroethyl), and wherein the Ci-Ce, C1-C4, or C1-C3 straight chained alkylene group optionally includes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl, cyclobutyl, oxiranyl, aziridinyl, azetidinyl, or oxetanyl group.

[0347] In one embodiment, the Ci-Ce, C1-C4, or C1-C3 straight chained alkylene group may optionally be substituted with one or two substituents independently selected from fluoro, hydroxyl, oxo (=0), methyl, ethyl, methoxy, -CF3, CHF2, CH2F, -OCF3, -OCHF2, -OCH2F, and wherein the Ci-Ce, C1-C4, or C1-C3 straight chained alkylene group optionally includes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl, cyclobutyl, oxiranyl, aziridinyl, azetidinyl, or oxetanyl group.

[0348] In one embodiment, the Ci-Ce, C1-C4, or C1-C3 straight chained alkylene group may optionally be substituted with one substituent independently selected from fluoro, hydroxyl, methyl, methoxy, -CF3, CHF2, CH2F, -OCF3, -OCHF2, -OCH2F, and wherein the Ci-Ce, C1-C4, or C1-C3 straight chained alkylene group optionally includes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl, or cyclobutyl group.

[0349] In one embodiment, L is -0-, -S-, -NR5-, -CH2-, -CH2CH2-, -CH2CH2CH2-, -CH2CH2CH2CH2-, -CH2CH2CH2CH2CH2-, -CH2CH2CH2CH2CH2CH2-, -CH2O-, -CH2S-, -CH2NR6-, -OCH2-, -OCH2O-, -OCH2S-, -OCH2NR6-, -OCH2CH2-, -OCH2CH2O-, -OCH2CH2S-, -OCH2CH2NR6-, -CH2CH2O-, -CH2CH2S-, -CH2CH2NR6-, -OCH2CH2CH2-, -OCH2CH2CH2O-, -OCH2CH2CH2S-, -OCH2CH2CH2NR6-, -OCH2CH2CH2CH2-, -OCH2CH2CH2CH2CH2-, -OCH2CH2CH2CH2CH2CH2-, -SCH2-, -SCH2O-, -SCH2S-, -SCH2NR6-, -SCH2CH2-, -SCH2CH2S-, -SCH2CH2O-, -SCH2CH2NR6-, -SCH2CH2CH2-, -SCH2CH2CH2O-, -SCH2CH2CH2S-, -SCH2CH2CH2NR6-, -SCH2CH2CH2CH2-, -SCH2CH2CH2CH2CH2-, -SCH2CH2CH2CH2CH2CH2-, -NR6CH2-, -NR6CH2O-, -NR6CH2S-, -NR6CH2NR6-, -NR6CH2CH2-, -NR6CH2CH2NR6-, -NR6CH2CH2O-, -NR6CH2CH2S-, -NR6CH2CH2CH2-, -NR6CH2CH2CH2NR6-, -NR6CH2CH2CH2O-, -NR6CH2CH2CH2S-, -NR6CH2CH2CH2CH2-, -NR6CH2CH2CH2CH2CH2-, -NR6CH2CH2CH2CH2CH2CH2-, -CH2OCH2, -CH2OCH2CH2-, -CH2CH2OCH2-, -CH2CH2CH2O-, -CH2SCH2-, -CH2SCH2CH2-, -CH2CH2SCH2-, -CH2CH2CH2S-, -CH2NR6CH2-, -CH2NR6CH2CH2-, -CH2CH2NR6CH2-, -CH2CH2CH2NR6, -CH2OCH2CH2CH2-, -CH2CH2OCH2CH2-, -CH2CH2CH2OCH2-, -CH2CH2CH2CH2O-, -CH2SCH2CH2CH2-, -CH2CH2SCH2CH2-, -CH2CH2CH2SCH2-, -CH2CH2CH2CH2S-, -CH2NR6CH2CH2CH2-, -CH2CH2NR6CH2CH2-, -CH2CH2CH2NR6CH2-, -CH2CH2CH2CH2NR5-, -CH2OCH2CH2CH2CH2-, -CH2CH2OCH2CH2CH2-, -CH2CH2CH2OCH2CH2-, -CH2CH2CH2CH2OCH2-, -CH2CH2CH2CH2CH2O-, -CH2SCH2CH2CH2CH2-, -CH2CH2SCH2CH2CH2-, -CH2CH2CH2SCH2CH2-, -

[0350]

[0351] CH2CH2CH2CH2SCH2-, -CH2CH2CH2CH2CH2S-, -CH2NR6CH2CH2CH2CH2-,-CH2CH2NR6CH2CH2CH2-, -CH2CH2CH2NR6CH2CH2-, -CH2CH2CH2CH2NR6CH2-, -CH2CH2CH2CH2CH2NR6-, -CH2OCH2CH2CH2CH2CH2-, -CH2CH2OCH2CH2CH2CH2-, -CH2CH2CH2OCH2CH2CH2-, -CH2CH2CH2CH2OCH2CH2-, -CH2CH2CH2CH2CH2OCH2-, -CH2CH2CH2CH2CH2CH2O-, -CH2SCH2CH2CH2CH2CH2-,-CH2CH2SCH2CH2CH2CH2-, -CH2CH2CH2SCH2CH2CH2-, -CH2CH2CH2CH2SCH2CH2-,-CH2CH2CH2CH2CH2SCH2-, -CH2CH2CH2CH2CH2CH2S-, -CH2NRSCH2CH2CH2CH2CH2-, -CH2CH2NRSCH2CH2CH2CH2-, -CH2CH2CH2NRSCH2CH2CH2-, -CH2CH2CH2CH2NRSCH2CH2-, -CH2CH2CH2CH2CH2NR6CH2-, or -CH2CH2CH2CH2CH2CH2NR6-, wherein each is optionally substituted. Typically, in this embodiment, L is optionally substituted with one or two substituents independently selected from fluoro, hydroxyl, methyl, methoxy, -CF3, CHF2, CH2F, -OCF3, -OCHF2, or -OCH2F, and wherein L optionally includes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl, cyclobutyl, oxiranyl, aziridinyl, azetidinyl, or oxetanyl group. More typically, in this embodiment, L is optionally substituted with one substituent independently selected from fluoro, hydroxyl, or methyl, and wherein L optionally includes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl or cyclobutyl group.

[0352] In one embodiment, L is -O-, -S-, or a Ci-Ce straight chained alkylene group, wherein the Ci-Ce straight chained alkylene group optionally includes one or two heteroatoms each independently selected from 0 and S in its carbon skeleton. In one embodiment, L is -O-, -S-, or a C1-C4 straight chained alkylene group, wherein the C1-C4 straight chained alkylene group optionally includes one or two heteroatoms each independently selected from 0 and S in its carbon skeleton. In one embodiment, L is -O-, -S-, or a C1-C3 straight chained alkylene group, wherein the C1-C3 straight chained alkylene group optionally includes one or two heteroatoms each independently selected from 0 and S in its carbon skeleton.

[0353] In one embodiment, L is -O-, -S-, -CH2-, -CH2CH2-, -CH2CH2CH2-, -CH2CH2CH2CH2-, -CH2CH2CH2CH2CH2-, -CH2CH2CH2CH2CH2CH2-, -CH2O-, -CH2S-, -OCH2-, -OCH2O-, -OCH2S-, -OCH2CH2-, -OCH2CH2O-, -OCH2CH2S-, -CH2CH2O-, -CH2CH2S-, -OCH2CH2CH2-, -OCH2CH2CH2O-, -OCH2CH2CH2S-, -OCH2CH2CH2CH2-, -OCH2CH2CH2CH2CH2-, -OCH2CH2CH2CH2CH2CH2-, -SCH2-, -SCH2O-, -SCH2S-, -SCH2CH2-, -SCH2CH2S-, -SCH2CH2O-, -SCH2CH2CH2-, -SCH2CH2CH2O-, -SCH2CH2CH2S-, -SCH2CH2CH2CH2-, -SCH2CH2CH2CH2CH2-, -SCH2CH2CH2CH2CH2CH2-, -CH2OCH2-, -CH2OCH2CH2-, -CH2CH2OCH2-, -CH2CH2CH2O-, -CH2SCH2-, -CH2SCH2CH2-, -CH2CH2SCH2-, -CH2CH2CH2S-, -CH2OCH2CH2CH2-, -CH2CH2OCH2CH2-, -CH2CH2CH2OCH2-, -CH2CH2CH2CH2O-, -CH2SCH2CH2CH2-, -CH2CH2SCH2CH2-, -CH2CH2CH2SCH2-, -CH2CH2CH2CH2S-, -CH2OCH2CH2CH2CH2-, -CH2CH2OCH2CH2CH2-,-CH2CH2CH2OCH2CH2-, -CH2CH2CH2CH2OCH2-, -CH2CH2CH2CH2CH2O-, -CH2SCH2CH2CH2CH2-, -CH2CH2SCH2CH2CH2-, -CH2CH2CH2SCH2CH2-, -CH2CH2CH2CH2SCH2-, -CH2CH2CH2CH2CH2S-, -CH2OCH2CH2CH2CH2CH2-, -CH2CH2OCH2CH2CH2CH2-, -CH2CH2CH2OCH2CH2CH2-, -CH2CH2CH2CH2OCH2CH2-, -CH2CH2CH2CH2CH2OCH2-, -CH2CH2CH2CH2CH2CH2O-, -CH2SCH2CH2CH2CH2CH2-, -CH2CH2SCH2CH2CH2CH2-, -CH2CH2CH2SCH2CH2CH2-, -CH2CH2CH2CH2SCH2CH2-, -CH2CH2CH2CH2CH2SCH2-, or -CH2CH2CH2CH2CH2CH2S-, wherein each is optionally substituted. Typically, in this embodiment, L is optionally substituted with one substituent independently selected from fluoro, hydroxyl, oxo (=0), methyl, methoxy, -CF3, CHF2, CH2F, -OCF3, -OCHF2, or -OCH2F, and wherein L optionally includes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl or cyclobutyl group. More typically, L is optionally substituted with one substituent independently selected from fluoro, hydroxyl, or methyl, and wherein L optionally includes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl or cyclobutyl group.

[0354] In one embodiment, L is -0-, -S-, -CH2-, -CH2CH2-, -CH2CH2CH2-, -CH2CH2CH2CH2-, -CH2O-, -CH2S-, -OCH2-, -OCH2CH2-, -OCH2CH2O-, -OCH2CH2S-, -CH2CH2O-, -CH2CH2S-, -OCH2CH2CH2-, -OCH2CH2CH2O-, -OCH2CH2CH2S-, -SCH2-, -SCH2CH2-, -SCH2CH2S-, -SCH2CH2O-, -SCH2CH2CH2-, -SCH2CH2CH2O-, -SCH2CH2CH2S-, -CH2OCH2-, -CH2SCH2-, -CH2OCH2CH2-, -CH2CH2OCH2-, -CH2CH2CH2O-, -CH2CH2CH2S-, -CH2SCH2-, -CH2SCH2CH2-, -CH2CH2SCH2-, or -CH2CH2CH2S-, wherein each is optionally substituted. Typically, in this embodiment, L is optionally substituted with one substituent independently selected from fluoro, hydroxyl, oxo (=0), methyl, methoxy, -CF3, CHF2, CH2F, -OCF3, -OCHF2, or -OCH2F, and wherein L optionally includes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl or cyclobutyl group. More typically, L is optionally substituted with one substituent independently selected from fluoro, hydroxyl, or methyl, and wherein L optionally includes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl or cyclobutyl group.

[0355] In one embodiment, L is -0-, -S-, -CH2-, -CH2CH2-, -CH2CH2CH2-, -CH2CH2CH2CH2-, -CH2O-, -CH2S-, -OCH2-, -OCH2CH2-, -OCH2CH2O-, -OCH2CH2S-, -CH2CH2O-, -CH2CH2S-, -OCH2CH2CH2-, -OCH2CH2CH2O-, -OCH2CH2CH2S-, -SCH2-, -SCH2CH2-, -SCH2CH2S-, -SCH2CH2O-, -SCH2CH2CH2-, -SCH2CH2CH2O-, -SCH2CH2CH2S-, -CH2OCH2-, -CH2OCH2CH2-, -CH2CH2OCH2-, -CH2CH2CH2O-, -CH2SCH2-, -CH2SCH2CH2-, -CH2CH2SCH2-, or -CH2CH2CH2S-, wherein each is optionally substituted. Typically, in this embodiment, L is optionally substituted with one substituent independently selected from fluoro, hydroxyl, oxo (=0), methyl, methoxy, -CF3, CHF2, CH2F, -OCF3,-OCHF2, or -OCH2F, and wherein L optionally includes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl or cyclobutyl group. More typically, L is optionally substituted with one substituent independently selected from fluoro, hydroxyl, or methyl, and wherein L optionally includes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl or cyclobutyl group.

[0356] In one embodiment, L is -O-, -S-, -CH2-, -CH2S-, -CH2O-, -OCH2-, -CH2CH2-, -CH2CH2CH2-, -CH2CH2CH2CH2-, -OCH2CH2-, -OCH2CH2O-, -OCH2CH2S-, -CH2SCH2-, -CH2CH2O-, -CH2CH2S- -OCH2CH2CH2-, -CH2CH2CH2O-, or -CH2CH2CH2S-.

[0357] In one embodiment, L is -O-, -S-, -CH2-, -CH2S-, -OCH2-, -CH2CH2CH2-, -OCH2CH2O-, -OCH2CH2S-, -CH2CH2O-, -CH2CH2S- -OCH2CH2CH2-, -CH2CH2CH2O-, or -CH2CH2CH2S-. Typically, L is -O-, -CH2-, -OCH2-, -CH2CH2CH2-, or -CH2CH2CH2S-.

[0358] In one embodiment, L is -CH2-.

[0359] In one embodiment, A is phenyl, naphthyl, pyrrolyl, furanyl, thiophenyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, oxadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, indolizinyl, indazolyl, benzimidazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, quinazolinyl, or naphthyridinyl.

[0360] Typically, A is phenyl, naphthyl, or a 6- to 10-membered heteroaryl group.

[0361] In one embodiment, A is phenyl, naphthyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, indolizinyl, indazolyl, benzimidazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, quinazolinyl, or naphthyridinyl. Typically, A is phenyl, pyridinyl, indazolyl, benzimidazolyl, quinolinyl, or isoquinolinyl. More typically, A is phenyl or indazolyl.

[0362] In one embodiment, A is indazolyl, optionally indazol-l-yl.

[0363] In one embodiment, A is phenyl. Typically, in this embodiment, the group X1is in the para or meta position of the phenyl ring. In one embodiment, A is phenyl, and X1is in the para position. In another embodiment, A is phenyl, and X1is in the meta position. For the avoidance of doubt, it is noted that when p is 0, the group R4is not present. In one embodiment, p is 0 or 1. In one embodiment, p is 1. In another embodiment, p is 0.In one embodiment, each R4is independently halo, -OH, -NH2, -SH, cyano, or a Ci-Ce saturated or unsaturated hydrocarbyl group which may be straight chained or branched, or be or include a cyclic group, and may optionally be substituted with one or more (such as one, two, three or four) halo groups, and where the hydrocarbyl group may optionally include one or two heteroatoms each independently selected from N, 0 and S in its carbon skeleton, and any -S- moiety when present in the hydrocarbyl group may optionally be substituted with one or two groups each independently selected from oxo (=0) and =NH to form a -SO-, -SO2-, -S( = NH)- or -SO( = NH)- moiety.

[0364] In one embodiment, each R4is independently halo, -OH, -NH2, -SH, cyano, C1-C5 alkyl, -O-(Ci-C5 alkyl), -C3-C5 cycloalkyl, -O(C3-C5 cycloalkyl), C3-C5 heterocycloalkyl, -0(C3-Cs heterocycloalkyl), -NH(Ci-Cs alkyl), -N(Ci-Cs alkyl)2, -NH-S02(CI-CS alkyl), -NH(CO)(Ci-Cs alkyl), or -S(Ci-Cs alkyl), wherein any alkyl group may be optionally substituted by one or more substituents independently selected from halo, OH, OMe, cyclopropyl, or cyclobutyl.

[0365] In one embodiment, each R4is independently fluoro, chloro, bromo, iodo, -OH, -NH2, -SH, cyano, C1-C4 alkyl, -O-(Ci-C4 alkyl), C3-C4 cycloalkyl, -O(C3-C4 cycloalkyl), C3-C4 heterocycloalkyl, -O(C3-C4 heterocycloalkyl), -NH(CI-C4 alkyl), -N(CI-C4 alkyl)2, -NH-SO2(Ci-C4 alkyl), -NH-SO2(CI-C4 haloalkyl), -NH(CO)(CI-C4 alkyl), or -S(Ci-C4 alkyl), wherein any alkyl group may be optionally substituted by one or more substituents selected from fluoro, OH, OMe, cyclopropyl, or cyclobutyl.

[0366] In one embodiment, each R4is independently fluoro, chloro, bromo, iodo, cyano, C1-C4 alkyl optionally C3-C4 alkyl, -O-(Ci-C4 alkyl) optionally -O-(C3-C4 alkyl), C3-C4 cycloalkyl, -O(C3-C4 cycloalkyl), C3-C4 heterocycloalkyl, -O(C3-C4 heterocycloalkyl), or -S(Ci-C4 alkyl), wherein any alkyl group may be optionally substituted by one or more substituents selected from fluoro, OH, OMe, cyclopropyl, or cyclobutyl.

[0367] In one embodiment, each R4is independently fluoro, chloro, bromo, iodo, cyano, methyl, ethyl, propyl (such as n-propyl or i-propyl), butyl (such as n-butyl, i-butyl, t-butyl), methoxy, ethoxy, propoxy, butoxy, cyclopropyl, cyclobutyl, -O-cyclopropyl, -O-cyclobutyl, -SMe, or -SEt. Typically, each R4is independently fluoro, iodo, cyano, methyl, ethyl, -OMe, -CH2CHCH3CH3, -OCH2CHCH3CH3, -OCH2CH2CH2CH3, -0-cyclobutyl, -OCH2-cyclobutyl, cyclopropyl, -CH2-cyclopropyl, -O-cyclopropyl, -OCH2-cyclopropyl, or -SMe.In one embodiment, each R4is independently fluoro, cyano, methyl, -CH2CHCH3CH3, -OCH2CHCH3CH3, -OCH2CH2CH2CH3, -O-cyclobutyl, -OCH2-cyclobutyl, or cyclopropyl.

[0368] In one embodiment, p is 1, and R4is fluoro, -CH2CHCH3CH3, -O-CH2CHCH3CH3, -OCH2CH2CH2CH3, -O-cyclobutyl, -O-CH2-cyclobutyl, or cyclopropyl. In one embodiment, p is 1, and R4is fluoro, cyano, or methyl. In one embodiment, p is 1, and R4is fluoro.

[0369] In one embodiment, X1and R4are different. In one embodiment, when X1is125I,124I,123I, or131I, R4is not iodo. In one embodiment, when X1is18F, R4is not fluoro.

[0370] In one embodiment, X1is125I,123I,131I, or211At.

[0371] In one embodiment, X1is125I,124I,123I,131I, or18F. In one embodiment, X1is125I,124I,123I, or131I. In one embodiment, X1is125I,124I,131I, or18F. In one embodiment, X1is124I,131I, or18F. In one embodiment, X1is125I,131I, or18F. In one embodiment, X1is125I. In one embodiment, X1is131I. In another embodiment, X1is211At.

[0372] In one embodiment, X1is124I or18F. In one embodiment, X1is124I. In another embodiment, X1is18F.

[0373] In one embodiment, X1is125I or18F.

[0374] In one embodiment, the compound of Formula (III) is a compound of Formula (Illa 1) - (IIIa3) or a pharmaceutically acceptable salt, solvate or prodrug thereof:

[0375]

[0376] (lllal) (Illa2)O R1R2O

[0377]

[0378] X1

[0379] (Illa3)

[0380] wherein p, R1, R2, R3, R4, R5, R6, R7, A, L, and X1are as defined in accordance with Formula (III).

[0381] In another embodiment, the compound of Formula (III) is a compound of Formula (IIIa4) - (IIIa7) or a pharmaceutically acceptable salt, solvate or prodrug thereof:

[0382]

[0383] (Illa6) (Illa7)

[0384] wherein p, R1, R2, R3, R4, R5, R6, R7, A, L, and X1are as defined in accordance with Formula (III).

[0385] Typically, the compound of Formula (III) is a compound of Formula (Illa 1), (IIIa2), (IIIa4), or (IIIa5). In one embodiment, the compound of Formula (III) is a compound of Formula (Illa 1) or (IIIa4). In one embodiment, the compound of Formula (III) is a compound of Formula (Illa 1). In one embodiment, the compound of Formula (III) is a compound of Formula (IIIa4).In one embodiment, the compound of Formula (III) is a compound of Formula (III') or a pharmaceutically acceptable salt, solvate, or prodrug thereof:

[0386] R1R20

[0387]

[0388] X1

[0389] Formula (III')

[0390] wherein n, m, p, R1, R2, R3, R4, R5, R6, R7, A, L, and X1are as defined in accordance with Formula (III).

[0391] As would be understood, in the compound of Formula (III'), the chiral centre at the amino (-NH2) group is (S).

[0392] In one embodiment, the carbon bearing the -L- group, marked below with an asterisk (*), is a chiral centre and has ( / ?) configuration. In another embodiment, the carbon bearing the -L- group, marked below with an asterisk (*), is a chiral centre and has (S) configuration.

[0393] In one embodiment, the compound of Formula (III') is a compound of Formula (Illal') - (IIIa3') or a pharmaceutically acceptable salt, solvate or prodrug thereof:

[0394]

[0395] (IIIa1') (Illa2’)

[0396]

[0397] X1

[0398] (Illa3')

[0399] wherein p, R1, R2, R3, R4, R5, R6, R7, A, L, and X1are as defined in accordance with Formula (III).

[0400] In another embodiment, the compound of Formula (III') is a compound of Formula (IIIa4') - (IIIa7') or a pharmaceutically acceptable salt, solvate or prodrug thereof:

[0401]

[0402] wherein p, R1, R2, R3, R4, R5, R6, R7, A, L, and X1are as defined in accordance with Formula (III).

[0403] Typically, the compound of Formula (III') is a compound of Formula (Illal'), (IIIa2'), (IIIa4') or (IIIa5'). In one embodiment, the compound of Formula (III') is a compound of Formula (Illa 1') or (IIIa4'). In one embodiment, the compound of Formula (III') is a compound of Formula (Illal'). In one embodiment, the compound of Formula (III') is a compound of Formula (IIIa4').As will be understood, insofar as practical, embodiments directed to one substituent or moiety (such as a given L or X1group) may be read in conjunction with embodiments directed to a different substituent or moiety.

[0404] For example, in one exemplary embodiment, there is provided a compound of Formula (III) or Formula (III') as defined above, wherein:

[0405] n is 0, 1, 2 or 3;

[0406] m is 1, 2, 3 or 4;

[0407] provided that m+n is 3 or 4;

[0408] when present, R1is hydrogen;

[0409] R2is hydrogen;

[0410] R3is hydrogen;

[0411] L is -O-, -S-, -NR5-, or a Ci-Ce straight chained alkylene group, wherein the Ci-Ce straight chained alkylene group optionally includes one, two or three heteroatoms each independently selected from 0, S and NR6in its carbon skeleton, wherein the Ci-Ce straight chained alkylene group may optionally be substituted with one or more substituents independently selected from fluoro, hydroxyl, oxo (=0), C1-C3 alkyl, -0-(C1-C3 alkyl), -0-(Ci-C3 fluoroalkyl), or C1-C3 fluoroalkyl, and wherein the Ci-Ce straight chained alkylene group may include a spirocyclic group, wherein the spirocyclic group is a cyclopropyl, cyclobutyl, oxiranyl, aziridinyl, azetidinyl, or oxetanyl group;

[0412] A is phenyl, naphthyl, or a 6- to 10-membered heteroaryl group;

[0413] p is 0 or 1;

[0414] R4is fluoro, chloro, bromo, iodo, cyano, C1-C4 alkyl optionally C3-C4 alkyl, -0-(C1-C4 alkyl) optionally -O-(C3-C4 alkyl), C3-C4 cycloalkyl, -O(C3-C4 cycloalkyl), C3-C4 heterocycloalkyl, -O(C3-C4 heterocycloalkyl), or -S(Ci-C4 alkyl), wherein any alkyl group may be optionally substituted by one or more substituents selected from fluoro, OH, OMe, cyclopropyl, or cyclobutyl;

[0415] R5is hydrogen or methyl;

[0416] R6is methyl; and

[0417] X1is125I,124I,123I,131I,18F, or211At.

[0418] In another exemplary embodiment, there is provided a compound of Formula (III) or Formula (IIIA) as defined above, wherein:

[0419] n is 0, 1, 2 or 3;

[0420] m is 1, 2, 3 or 4;

[0421] provided that m+n is 3 or 4;

[0422] when present, R1is hydrogen;R2is hydrogen;

[0423] R3is hydrogen;

[0424] L is -O-, -S-, or a Ci-Ce straight chained alkylene group, wherein the Ci-Ce straight chained alkylene group optionally includes one or two heteroatoms each independently selected from 0 and S in its carbon skeleton, wherein the Ci-Ce straight chained alkylene group may optionally be substituted with one or more substituents independently selected from fluoro, hydroxyl, oxo (=0), C1-C3 alkyl,

[0425] -O-(Ci-C3 alkyl), -O-(Ci-C3 fluoroalkyl), or C1-C3 fluoroalkyl, and wherein the Ci-Ce straight chained alkylene group may include a spirocyclic group, wherein the spirocyclic group is a cyclopropyl, cyclobutyl, oxiranyl, aziridinyl, azetidinyl, or oxetanyl group;

[0426] A is phenyl, naphthyl, or a 6- to 10-membered heteroaryl group;

[0427] p is 0 or 1;

[0428] R4is fluoro, chloro, bromo, iodo, cyano, C1-C4 alkyl optionally C3-C4 alkyl, -0-(C1-C4 alkyl) optionally -O-(C3-C4 alkyl), C3-C4 cycloalkyl, -O(C3-C4 cycloalkyl), C3-C4 heterocycloalkyl, -O(C3-C4 heterocycloalkyl), or -S(Ci-C4 alkyl), wherein any alkyl group may be optionally substituted by one or more substituents selected from fluoro, OH, OMe, cyclopropyl, or cyclobutyl; and

[0429] X1is125I,124I,123I,131I,18F, or211At.

[0430] In another exemplary embodiment, there is provided a compound of Formula (III) or Formula (III') as defined above, wherein:

[0431] n is 0 or 1;

[0432] m is 2, 3 or 4;

[0433] provided that m+n is 3 or 4;

[0434] when present, R1is hydrogen;

[0435] R2is hydrogen;

[0436] R3is hydrogen;

[0437] L is -0-, -S-, or a C1-C3 straight chained alkylene group, wherein the C1-C3 straight chained alkylene group optionally includes one or two heteroatoms each independently selected from 0 and S in its carbon skeleton, wherein the C1-C3 straight chained alkylene group is optionally substituted with one or two substituents independently selected from fluoro, hydroxyl, methyl, methoxy, -CF3, CHF2, CH2F, -OCF3, -OCHF2, or -OCH2F, and wherein the C1-C3 straight chained alkylene group optionally includes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl, cyclobutyl, oxiranyl, aziridinyl, azetidinyl, or oxetanyl group;

[0438] A is phenyl, naphthyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl,isoindolyl, indolizinyl, indazolyl, benzimidazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, quinazolinyl, or naphthyridinyl;

[0439] p is 0 or 1;

[0440] R4is fluoro, iodo, cyano, methyl, ethyl, -OMe, -CH2CHCH3CH3, -OCH2CHCH3CH3, -OCH2CH2CH2CH3, -O-cyclobutyl, -OCH2-cyclobutyl, cyclopropyl, -CH2-cyclopropyl, -O-cyclopropyl, -OCH2-cyclopropyl, or -SMe; and

[0441] X1is125I,124I,123I,131I,18F, or211At.

[0442] In another exemplary embodiment, there is provided a compound of Formula (III) or Formula (III') as defined above, wherein:

[0443] n is 0 or 1;

[0444] m is 2, 3 or 4;

[0445] provided that m+n is 3 or 4;

[0446] when present, R1is hydrogen;

[0447] R2is hydrogen;

[0448] R3is hydrogen;

[0449] L is -O-, -S-, or a C1-C3 straight chained alkylene group, wherein the C1-C3 straight chained alkylene group optionally includes one or two heteroatoms each independently selected from 0 and S in its carbon skeleton, wherein the C1-C3 straight chained alkylene group is optionally substituted with one substituent independently selected from fluoro, hydroxyl, or methyl, and wherein the C1-C3 straight chained alkylene group optionally includes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl or cyclobutyl group;

[0450] A is phenyl, pyridinyl, indazolyl, benzimidazolyl, quinolinyl, or isoquinolinyl; p is 0; and

[0451] X1is125I,124I,123I,131I,18F, or211At.

[0452] In another exemplary embodiment, there is provided a compound of Formula (III) or Formula (III') as defined above, wherein:

[0453] n is 0 or 1;

[0454] m is 2, 3 or 4;

[0455] provided that m+n is 3 or 4;

[0456] when present, R1is hydrogen;

[0457] R2is hydrogen;

[0458] R3is hydrogen;

[0459] L is -O-, -S-, or a C1-C3 straight chained alkylene group, wherein the C1-C3 straight chained alkylene group optionally includes one or two heteroatoms each independently selected from 0 and S in its carbon skeleton, wherein the C1-C3 straightchained alkylene group is optionally substituted with one substituent independently selected from fluoro, hydroxyl, or methyl, and wherein the C1-C3 straight chained alkylene group optionally includes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl or cyclobutyl group;

[0460] A is phenyl, pyridinyl, indazolyl, benzimidazolyl, quinolinyl, or isoquinolinyl; P is 1;

[0461] R4is fluoro, iodo, cyano, methyl, ethyl, -OMe, -CH2CHCH3CH3, -OCH2CHCH3CH3, -OCH2CH2CH2CH3, -O-cyclobutyl, -OCH2-cyclobutyl, cyclopropyl, -CH2-cyclopropyl, -O-cyclopropyl, -OCH2-cyclopropyl, or -SMe, optionally wherein R4fluoro; and

[0462] X1is125I,124I,123I,131I,18F, or211At.

[0463] In another exemplary embodiment, there is provided a compound of Formula (III) or Formula (III') as defined above, wherein:

[0464] n is 0, or 1;

[0465] m is 2, 3 or 4;

[0466] provided that m+n is 3 or 4;

[0467] when present, R1is hydrogen;

[0468] R2is hydrogen;

[0469] R3is hydrogen;

[0470] L is -O-, -S-, -CH2-, -CH2CH2-, -CH2CH2CH2-, -CH2CH2CH2CH2-, -CH2O-, -CH2S-, -OCH2-, -OCH2CH2-, -OCH2CH2O-, -OCH2CH2S-, -CH2CH2O-, -CH2CH2S-, -OCH2CH2CH2-, -OCH2CH2CH2O-, -OCH2CH2CH2S-, -SCH2-, -SCH2CH2-, -SCH2CH2S-, -SCH2CH2O-, -SCH2CH2CH2-, -SCH2CH2CH2O-, -SCH2CH2CH2S-, -CH2OCH2-, -CH2OCH2CH2-, -CH2CH2OCH2-, -CH2CH2CH2O-, -CH2SCH2-, -CH2SCH2CH2-, -CH2CH2SCH2-, or -CH2CH2CH2S-;

[0471] A is phenyl or indazolyl;

[0472] p is 0; and

[0473] X1is125I,124I,123I,131I,18F, or211At.

[0474] In another exemplary embodiment, there is provided a compound of Formula (III) or Formula (IIIA) as defined above, wherein:

[0475] n is 0, 1, 2 or 3;

[0476] m is 1, 2, 3 or 4;

[0477] provided that m+n is 3 or 4;

[0478] when present, R1is hydrogen;

[0479] R2is hydrogen;

[0480] R3is hydrogen;L is -O-, -S-, or a Ci-Ce straight chained alkylene group, wherein the Ci-Ce straight chained alkylene group optionally includes one or two heteroatoms each independently selected from 0 and S in its carbon skeleton, wherein the Ci-Ce straight chained alkylene group may optionally be substituted with one or more substituents independently selected from fluoro, hydroxyl, oxo (=0), C1-C3 alkyl,

[0481] -O-(Ci-C3 alkyl), -O-(Ci-C3 fluoroalkyl), or C1-C3 fluoroalkyl, and wherein the Ci-Ce straight chained alkylene group may include a spirocyclic group, wherein the spirocyclic group is a cyclopropyl, cyclobutyl, oxiranyl, aziridinyl, azetidinyl, or oxetanyl group;

[0482] A is phenyl, naphthyl, or a 6- to 10-membered heteroaryl group;

[0483] p is 0 or 1;

[0484] R4is fluoro, chloro, bromo, iodo, cyano, C1-C4 alkyl optionally C3-C4 alkyl, -0-(C1-C4 alkyl) optionally -O-(C3-C4 alkyl), C3-C4 cycloalkyl, -O(C3-C4 cycloalkyl), C3-C4 heterocycloalkyl, -O(C3-C4 heterocycloalkyl), or -S(Ci-C4 alkyl), wherein any alkyl group may be optionally substituted by one or more substituents selected from fluoro, OH, OMe, cyclopropyl, or cyclobutyl; and

[0485] X1is125I,124I,123I,131I.

[0486] In another exemplary embodiment, there is provided a compound of Formula (III) or Formula (IIIA) as defined above, wherein:

[0487] n is 0, 1, 2 or 3;

[0488] m is 1, 2, 3 or 4;

[0489] provided that m+n is 3 or 4;

[0490] when present, R1is hydrogen;

[0491] R2is hydrogen;

[0492] R3is hydrogen;

[0493] L is -0-, -S-, or a Ci-Ce straight chained alkylene group, wherein the Ci-Ce straight chained alkylene group optionally includes one or two heteroatoms each independently selected from 0 and S in its carbon skeleton, wherein the Ci-Ce straight chained alkylene group may optionally be substituted with one or more substituents independently selected from fluoro, hydroxyl, oxo (=0), C1-C3 alkyl,

[0494] -O-(Ci-C3 alkyl), -O-(Ci-C3 fluoroalkyl), or C1-C3 fluoroalkyl, and wherein the Ci-Ce straight chained alkylene group may include a spirocyclic group, wherein the spirocyclic group is a cyclopropyl, cyclobutyl, oxiranyl, aziridinyl, azetidinyl, or oxetanyl group;

[0495] A is phenyl, naphthyl, or a 6- to 10-membered heteroaryl group;

[0496] p is 0 or 1;

[0497] R4is fluoro, chloro, bromo, iodo, cyano, C1-C4 alkyl optionally C3-C4 alkyl, -0-(C1-C4 alkyl) optionally -O-(C3-C4 alkyl), C3-C4 cycloalkyl, -O(C3-C4 cycloalkyl), C3-C4 heterocycloalkyl, -O(C3-C4 heterocycloalkyl), or -S(Ci-C4 alkyl), wherein any alkyl group may be optionally substituted by one or more substituents selected from fluoro, OH, OMe, cyclopropyl, or cyclobutyl; and

[0498] X1is18F.

[0499] In another exemplary embodiment, there is provided a compound of Formula (III) or Formula (IIIA) as defined above, wherein:

[0500] n is 0, 1, 2 or 3;

[0501] m is 1, 2, 3 or 4;

[0502] provided that m+n is 3 or 4;

[0503] when present, R1is hydrogen;

[0504] R2is hydrogen;

[0505] R3is hydrogen;

[0506] L is -O-, -S-, or a Ci-Ce straight chained alkylene group, wherein the Ci-Ce straight chained alkylene group optionally includes one or two heteroatoms each independently selected from 0 and S in its carbon skeleton, wherein the Ci-Ce straight chained alkylene group may optionally be substituted with one or more substituents independently selected from fluoro, hydroxyl, oxo (=0), C1-C3 alkyl,

[0507] -O-(Ci-C3 alkyl), -O-(Ci-C3 fluoroalkyl), or C1-C3 fluoroalkyl, and wherein the Ci-Ce straight chained alkylene group may include a spirocyclic group, wherein the spirocyclic group is a cyclopropyl, cyclobutyl, oxiranyl, aziridinyl, azetidinyl, or oxetanyl group;

[0508] A is phenyl, naphthyl, or a 6- to 10-membered heteroaryl group;

[0509] p is 0 or 1;

[0510] R4is fluoro, chloro, bromo, iodo, cyano, C1-C4 alkyl optionally C3-C4 alkyl, -0-(C1-C4 alkyl) optionally -O-(C3-C4 alkyl), C3-C4 cycloalkyl, -O(C3-C4 cycloalkyl), C3-C4 heterocycloalkyl, -O(C3-C4 heterocycloalkyl), or -S(Ci-C4 alkyl), wherein any alkyl group may be optionally substituted by one or more substituents selected from fluoro, OH, OMe, cyclopropyl, or cyclobutyl; and

[0511] X1is211At.

[0512] The first aspect further provides a compound of Formula (IIIA):

[0513]

[0514] Formula (IIIA)

[0515] or a pharmaceutically acceptable salt, solvate or prodrug thereof, wherein:

[0516] n is 0, 1, 2 or 3;

[0517] m is 1, 2, 3 or 4;

[0518] provided that m+n is 3 or 4;

[0519] when present, R1is hydrogen or C1-C3 alkyl;

[0520] R2is hydrogen or C1-C3 alkyl;

[0521] R3is hydrogen or C1-C3 alkyl;

[0522] L is -O-, -S-, -NR5-, a Ci-Ce straight chained alkylene group, wherein the Ci-Ce straight chained alkylene group optionally includes one, two or three heteroatoms each independently selected from 0, S and NR6in its carbon skeleton, or L is a group -L1-B-L2-, wherein L1and L2are each independently a bond or a C1-C3 straight chained alkylene group, wherein B is a saturated cyclic group selected from a C3-C6 cycloalkyl group, or a 3-, 4-, 5- or 6- membered saturated monocyclic heterocyclic group; wherein L is optionally substituted with one or more substituents independently selected from fluoro, hydroxyl, oxo (=0), C1-C3 alkyl, -O-(Ci-C3 alkyl), -O-(Ci-C3 fluoroalkyl), or C1-C3 fluoroalkyl, and wherein L optionally includes one or more spirocyclic groups, wherein the spirocyclic group is selected from a C3-C5 cycloalkyl group or a saturated C3-C5 heterocyclic group;

[0523] A is phenyl, naphthyl, or a 5- to 10-membered heteroaryl group;

[0524] p is 0, 1, or 2;

[0525] R4is halo, -OH, -NH2, -SH, cyano, or a Ci-Cs saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight chained or branched, or be or include a cyclic group, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, 0 and S in its carbon skeleton, and wherein any -S- moiety in the hydrocarbyl group may optionally be substituted with one or two groups each independently selected from oxo (=0) and =NH to form a -SO-, -SO2-, -S( = NH)- or -SO( = NH)-moiety;

[0526] R5is hydrogen, C1-C3 alkyl, or C2-C3 alkylene-OR7;R6is C1-C3 alkyl, or C2-C3 alkylene-OR7;

[0527] R7is hydrogen or methyl; and

[0528] X2is125I,123I,131I, or211At.

[0529] In one embodiment, n is 0 or 1. In one embodiment, n is 0. In one embodiment, n is 1. In one embodiment, n is 2. In one embodiment, n is 3.

[0530] In one embodiment, m is 1. In one embodiment, m is 2. In one embodiment, m is 3. In one embodiment, m is 4.

[0531] In one embodiment, m+n is 3. Typically, in this embodiment, n is 0 and m is 3, n is 1 and m is 2, or n is 2 and m is 1. Typically, n is 0 and m is 3, or n is 1 and m is 2. More typically still, n is 0 and m is 3.

[0532] In one embodiment, m+n is 4. Typically, in this embodiment, n is 0 and m is 4, n is 1 and m is 3, n is 2 and m is 2, or n is 3 and m is 1. Typically, n is 0 and m is 4, n is 1 and m is 3, or n is 3 and m is 1. More typically, n is 0 and m is 4, or n is 1 and m is 3. More typically still, n is 0 and m is 4.

[0533] For the avoidance of doubt, it is noted that when n is 0, the group R1is not present.

[0534] In one embodiment, each R1is independently hydrogen or C1-C2 alkyl. Typically, each R1is independently hydrogen, methyl, or ethyl. More typically, each R1is independently hydrogen or methyl. More typically still, each R1is hydrogen.

[0535] In one embodiment, each R2is independently hydrogen, methyl, or ethyl. Typically, each R2is independently hydrogen or methyl. In one embodiment, each R2is hyd rogen.

[0536] In one embodiment, R3is hydrogen, methyl, or ethyl. Typically, R3is hydrogen or methyl. In one embodiment, R3is hydrogen.

[0537] In one embodiment, each R2is independently hydrogen or methyl, and R3is hydrogen or methyl. In one embodiment, each R2is hydrogen and R3is hydrogen.

[0538] In one embodiment, each R1is independently hydrogen or methyl and R3is hydrogen or methyl. In one embodiment, each R1is hydrogen and R3is hydrogen.In one embodiment, each R1is independently hydrogen or methyl, each R2is independently hydrogen or methyl, and R3is hydrogen or methyl. In one embodiment, each R1is hydrogen, each R2is hydrogen, and R3is hydrogen.

[0539] For the avoidance of doubt, when it is stated that L is a group -L1-B-L2-, it will be understood to mean that -L1and -L2are attached to different atoms of the cyclic group B.

[0540] For the avoidance of doubt, when it is stated that L optionally includes one or more spirocyclic groups, it will be understood to mean that any methylene (-CH2) group in a alkylene chain of L may be substituted by a cyclic group, such that the resultant group H

[0541] is a spirocyclic group, such as x x x or x

[0542]

[0543] . Thus, for the avoidance of doubt, when a spirocyclic group is described as being, for example, a

[0544] cyclopropyl group, it will be understood to mean the group:.

[0545] In one embodiment, R5is hydrogen, methyl, ethyl, propyl, -CH2CH2OH, -CH2CH2CH2OH, -CH2CH2OMe, or -CH₂CH₂CH₂OMe. Typically, R5is hydrogen, methyl, or ethyl. More typically, R5is hydrogen or methyl.

[0546] In one embodiment, R6is methyl, ethyl, propyl, -CH2CH2OH, -CH2CH2CH2OH, -CH2CH2OMe, or -CH2CH2CH2OMe. Typically, R6is methyl or ethyl. More typically, R6is methyl.

[0547] In one embodiment, L is a group -L1-B-L2-, wherein L1and L2are each independently a bond or a C1-C3 alkylene group, and wherein B is a saturated cyclic group selected from a C3-C6 cycloalkyl group, or a 3-, 4-, 5- or 6- membered saturated monocyclic heterocyclic group (comprising, for example, one or two heteroatoms independently selected from N, 0 or S in the ring structure), wherein L is optionally substituted. Typically, in this embodiment, -L1and -L2are each independently a bond, -CH2- or -CH2CH2-, and B is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxiranyl, aziridinyl, azetidinyl, oxetanyl, thietanyl, pyrrolidinyl, tetra hydrofuranyl, tetrahydrothiophenyl, pyrazolidinyl, dioxolanyl, oxathiolanyl, piperidinyl, tetrahydropyranyl, thianyl, piperazinyl, dioxanyl, morpholinyl, or thiomorpholinyl. Typically, in this embodiment, L is optionally substituted with one or more substituents independently selected from fluoro, hydroxyl, oxo (=0), C1-C3 alkyl, -O-(Ci-C3 alkyl), -O-(Ci-C3 fluoroalkyl), or Ci-Cs fluoroalkyl, and wherein L optionally includes one or more (such as one or two) spirocyclic groups, wherein the spirocyclic group is selected from a C3-C5 cycloalkyl group or a saturated C3-C5 heterocyclic group. Typically, the spirocyclic group is a cyclopropyl, cyclobutyl, cyclopentyl, oxiranyl, aziridinyl, azetidinyl, oxetanyl, thietanyl, pyrrolidinyl, tetra hydrofuranyl, tetrahydrothiophenyl, dioxolanyl, or oxathiolanyl group. More typically, the spirocyclic group is a cyclopropyl, cyclobutyl, cyclopentyl, oxiranyl, aziridinyl, azetidinyl, or oxetanyl group.

[0548] In one embodiment, -L1and -L2are each independently a bond or -CH2, and B is cyclopropyl, cyclobutyl, azetidinyl, or oxetanyl, each of which is optionally substituted with one or more substituents independently selected from fluoro, hydroxyl, oxo (=0), methyl, ethyl, methoxy, ethoxy, -CF3, CHF2, CH2F, -OCF3, -OCHF2, or -OCH2F.

[0549] Typically in this embodiment, B is cyclopropyl, cyclobutyl, azetidinyl (such as azetidin-1-yl or azetidin-3-yl) or oxetanyl (such as oxetan-2-yl or oxetan-3-yl). Typically, in this embodiment, B is cyclobutyl or azetidinyl.

[0550] In another embodiment, L is -0-, -S-, -NR5-, or a Ci-Ce straight chained alkylene group, wherein the Ci-Ce straight chained alkylene group optionally includes one, two or three heteroatoms each independently selected from 0, S and NR6in its carbon skeleton, and wherein the Ci-Ce straight chained alkylene group may optionally be substituted.

[0551] In one embodiment, L is -0-, -S-, or a Ci-Ce straight chained alkylene group, wherein the Ci-Ce straight chained alkylene group optionally includes one, two or three heteroatoms each independently selected from 0 and S in its carbon skeleton, and wherein the Ci-Ce straight chained alkylene group may optionally be substituted.

[0552] In one embodiment, L is -0-, -S-, or a Ci-Ce straight chained alkylene group, wherein the Ci-Ce straight chained alkylene group optionally includes one or two heteroatoms each independently selected from 0 and S in its carbon skeleton, and wherein the Ci-Ce straight chained alkylene group may optionally be substituted.

[0553] In one embodiment, L is -0-, -S-, or a C1-C4 straight chained alkylene group, wherein the C1-C4 straight chained alkylene group optionally includes one, two or three heteroatoms each independently selected from 0 and S in its carbon skeleton, and wherein the C1-C4 straight chained alkylene group may optionally be substituted.In one embodiment, L is -O-, -S-, or a C1-C4 straight chained alkylene group, wherein the C1-C4 straight chained alkylene group optionally includes one or two heteroatoms each independently selected from 0 and S in its carbon skeleton, and wherein the Ci-C4 straight chained alkylene group may optionally be substituted.

[0554] In one embodiment, L is -O-, -S-, or a C1-C3 straight chained alkylene group, wherein the C1-C3 straight chained alkylene group optionally includes one or two heteroatoms each independently selected from 0 and S in its carbon skeleton, and wherein the Ci-C3 straight chained alkylene group may optionally be substituted.

[0555] In one embodiment, L is -O-, -S-, or a C1-C3 straight chained alkylene group, wherein the C1-C3 straight chained alkylene group is optionally substituted.

[0556] In another embodiment, L is a C2-C3 straight chained alkylene group, wherein the C2-C3 straight chained alkylene group includes one or two heteroatoms each independently selected from 0 and S in its carbon skeleton, and wherein the C2-C3 straight chained alkylene group may optionally be substituted. Typically, in this embodiment, when L is a C2 straight chained alkylene group, the C2 straight chained alkylene group includes one heteroatom independently selected from 0 and S in its carbon skeleton, and when L is a C3 straight chained alkylene group, the C3 straight chained alkylene group includes one or two heteroatoms independently selected from 0 and S in its carbon skeleton.

[0557] The straight chained alkylene group, such as the, Ci-Ce, C1-C4, or C1-C3 straight chained alkylene group described above, may optionally be substituted with one or more (such as one, two, three, or four) substituents independently selected from fluoro, hydroxyl, oxo (=0), methyl, ethyl, methoxy, ethoxy, fluoromethyl, fluoroethyl, -O-(fluoromethyl), or -O-(fluoroethyl), and wherein the Ci-Ce, C1-C4, or C1-C3 straight chained alkylene group optionally includes one or more (such as one or two) spirocyclic groups, wherein the spirocyclic group is selected from a C3-C5 cycloalkyl group or a saturated C3-C5 heterocyclic group. Typically, the spirocyclic group is a cyclopropyl, cyclobutyl, cyclopentyl, oxiranyl, aziridinyl, azetidinyl, oxetanyl, thietanyl, pyrrolidinyl, tetra hydrofuranyl, tetrahydrothiophenyl, dioxolanyl, or oxathiolanyl group. More typically, the spirocyclic group is a cyclopropyl, cyclobutyl, oxiranyl, aziridinyl, azetidinyl, or oxetanyl group.

[0558] In one embodiment, the Ci-Ce, C1-C4, or C1-C3 straight chained alkylene group may optionally be substituted with one or two substituents independently selected fromfluoro, hydroxyl, oxo (=0), methyl, ethyl, methoxy, ethoxy, fluoromethyl, fluoroethyl, -O-(fluoromethyl), or -O-(fluoroethyl), and wherein the Ci-Ce, C1-C4, or C1-C3 straight chained alkylene group optionally includes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl, cyclobutyl, oxiranyl, aziridinyl, azetidinyl, or oxetanyl group.

[0559] In one embodiment, the Ci-Ce, C1-C4, or C1-C3 straight chained alkylene group may optionally be substituted with one or two substituents independently selected from fluoro, hydroxyl, oxo (=0), methyl, ethyl, methoxy, -CF3, CHF2, CH2F, -OCF3, -OCHF2, -OCH2F, and wherein the, Ci-Ce, C1-C4, or C1-C3 straight chained alkylene group optionally includes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl, cyclobutyl, oxiranyl, aziridinyl, azetidinyl, or oxetanyl group.

[0560] In one embodiment, the Ci-Ce, C1-C4, or C1-C3 straight chained alkylene group may optionally be substituted with one substituent independently selected from fluoro, hydroxyl, methyl, methoxy, -CF3, CHF2, CH2F, -OCF3, -OCHF2, -OCH2F, and wherein the Ci-Ce, C1-C4, or C1-C3 straight chained alkylene group optionally includes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl, or cyclobutyl group.

[0561] In one embodiment, L is -0-, -S-, or a Ci-Ce straight chained alkylene group, wherein the Ci-Ce straight chained alkylene group optionally includes one or two heteroatoms each independently selected from 0 and S in its carbon skeleton. In one embodiment, L is -0-, -S-, or a C1-C4 straight chained alkylene group, wherein the C1-C4 straight chained alkylene group optionally includes one or two heteroatoms each independently selected from 0 and S in its carbon skeleton. In one embodiment, L is -0-, -S-, or a C1-C3 straight chained alkylene group, wherein the C1-C3 straight chained alkylene group optionally includes one or two heteroatoms each independently selected from 0 and S in its carbon skeleton.

[0562] In one embodiment, L is -0-, -S-, -NR5-, -CH2-, -CH2CH2-, -CH2CH2CH2-, -CH2CH2CH2CH2-, -CH2CH2CH2CH2CH2-, -CH2CH2CH2CH2CH2CH2-, -CH2O-, -CH2S-, -CH2NR6-, -OCH2-, -OCH2O-, -OCH2S-, -OCH2NR6-, -OCH2CH2-, -OCH2CH2O-, -OCH2CH2S-, -OCH2CH2NR6-, -CH2CH2O-, -CH2CH2S-, -CH2CH2NR6-, -OCH2CH2CH2-, -OCH2CH2CH2O-, -OCH2CH2CH2S-, -OCH2CH2CH2NR6-, -OCH2CH2CH2CH2-, -OCH2CH2CH2CH2CH2-, -OCH2CH2CH2CH2CH2CH2-, -SCH2-, -SCH2O-, -SCH2S-, -SCH2NR6-, -SCH2CH2-, -SCH2CH2S-, -SCH2CH2O-, -SCH2CH2NR6-, -SCH2CH2CH2-, -SCH2CH2CH2O-, -SCH2CH2CH2S-, -SCH2CH2CH2NR6-, -SCH2CH2CH2CH2-, -SCH2CH2CH2CH2CH2-, -SCH2CH2CH2CH2CH2CH2-, -NR6CH2-, -NR6CH2O-, -NR6CH2S-, -

[0563]

[0564] NR6CH2NR6-, -NR6CH2CH2-, -NR6CH2CH2NR6-, -NR6CH2CH2O-, -NR6CH2CH2S-,-NR6CH2CH2CH2-, -NR6CH2CH2CH2NR6-, -NR6CH2CH2CH2O-, -NR6CH2CH2CH2S-, -NR6CH2CH2CH2CH2-, -NR6CH2CH2CH2CH2CH2-, -NR6CH2CH2CH2CH2CH2CH2-, -CH2OCH2, -CH2OCH2CH2-, -CH2CH2OCH2-, -CH2CH2CH2O-, -CH2SCH2-, -CH2SCH2CH2-, -CH2CH2SCH2-, -CH2CH2CH2S-, -CH2NR6CH2-, -CH2NR6CH2CH2-, -CH2CH2NR6CH2-, -CH2CH2CH2NR6, -CH2OCH2CH2CH2-, -CH2CH2OCH2CH2-, -CH2CH2CH2OCH2-, -CH2CH2CH2CH2O-, -CH2SCH2CH2CH2-, -CH2CH2SCH2CH2-, -CH2CH2CH2SCH2-, -CH2CH2CH2CH2S-, -CH2NR6CH2CH2CH2-, -CH2CH2NR6CH2CH2-, -CH2CH2CH2NR6CH2-, -CH2CH2CH2CH2NR6-, -CH2OCH2CH2CH2CH2-, -CH2CH2OCH2CH2CH2-, -CH2CH2CH2OCH2CH2-, -CH2CH2CH2CH2OCH2-, -CH2CH2CH2CH2CH2O-, -CH2SCH2CH2CH2CH2-, -CH2CH2SCH2CH2CH2-, -CH2CH2CH2SCH2CH2-, -CH2CH2CH2CH2SCH2-, -CH2CH2CH2CH2CH2S-, -CH2NR6CH2CH2CH2CH2-, -CH2CH2NR6CH2CH2CH2-, -CH2CH2CH2NR6CH2CH2-, -CH2CH2CH2CH2NR6CH2-, -CH2CH2CH2CH2CH2NR6-, -CH2OCH2CH2CH2CH2CH2-, -CH2CH2OCH2CH2CH2CH2-, -CH2CH2CH2OCH2CH2CH2-, -CH2CH2CH2CH2OCH2CH2-, -CH2CH2CH2CH2CH2OCH2-, -CH2CH2CH2CH2CH2CH2O-, -CH2SCH2CH2CH2CH2CH2-,-CH2CH2SCH2CH2CH2CH2-, -CH2CH2CH2SCH2CH2CH2-, -CH2CH2CH2CH2SCH2CH2-,-CH2CH2CH2CH2CH2SCH2-, -CH2CH2CH2CH2CH2CH2S-, -CH2NRSCH2CH2CH2CH2CH2-, -CH2CH2NRSCH2CH2CH2CH2-, -CH2CH2CH2NRSCH2CH2CH2-, -CH2CH2CH2CH2NRSCH2CH2-, -CH2CH2CH2CH2CH2NR6CH2-, or -CH2CH2CH2CH2CH2CH2NR6-, wherein each is optionally substituted. Typically, in this embodiment, L is optionally substituted with one or two substituents independently selected from fluoro, hydroxyl, methyl, methoxy, -CF3, CHF2, CH2F, -OCF3, -OCHF2, or -OCH2F, and wherein L optionally includes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl, cyclobutyl, oxiranyl, aziridinyl, azetidinyl, or oxetanyl group.

[0565] More typically, in this embodiment, L is optionally substituted with one substituent independently selected from fluoro, hydroxyl, or methyl, and wherein L optionally includes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl or cyclobutyl group.

[0566] In one embodiment, L is -O-, -S-, -CH2-, -CH2CH2-, -CH2CH2CH2-, -CH2CH2CH2CH2-, -CH2CH2CH2CH2CH2-, -CH2CH2CH2CH2CH2CH2-, -CH2O-, -CH2S-, -OCH2-, -OCH2O-, -OCH2S-, -OCH2CH2-, -OCH2CH2O-, -OCH2CH2S-, -CH2CH2O-, -CH2CH2S-, -OCH2CH2CH2-, -OCH2CH2CH2O-, -OCH2CH2CH2S-, -OCH2CH2CH2CH2-, -OCH2CH2CH2CH2CH2-, -OCH2CH2CH2CH2CH2CH2-, -SCH2-, -SCH2O-, -SCH2S-, -SCH2CH2-, -SCH2CH2S-, -SCH2CH2O-, -SCH2CH2CH2-, -SCH2CH2CH2O-, -SCH2CH2CH2S-, -SCH2CH2CH2CH2-, -SCH2CH2CH2CH2CH2-, -SCH2CH2CH2CH2CH2CH2-, -CH2OCH2-, -CH2OCH2CH2-, -CH2CH2OCH2-, -CH2CH2CH2O-, -CH2SCH2-, -CH2SCH2CH2-,-CH2CH2SCH2-, -CH2CH2CH2S-, -CH2OCH2CH2CH2-, -CH2CH2OCH2CH2-, -CH2CH2CH2OCH2-, -CH2CH2CH2CH2O-, -CH2SCH2CH2CH2-, -CH2CH2SCH2CH2-, -CH2CH2CH2SCH2-, -CH2CH2CH2CH2S-, -CH2OCH2CH2CH2CH2-, -CH2CH2OCH2CH2CH2-, -CH2CH2CH2OCH2CH2-, -CH2CH2CH2CH2OCH2-, -CH2CH2CH2CH2CH2O-, -CH2SCH2CH2CH2CH2-, -CH2CH2SCH2CH2CH2-, -CH2CH2CH2SCH2CH2-, -CH2CH2CH2CH2SCH2-, -CH2CH2CH2CH2CH2S-, -CH2OCH2CH2CH2CH2CH2-, -CH2CH2OCH2CH2CH2CH2-, -CH2CH2CH2OCH2CH2CH2-, -CH2CH2CH2CH2OCH2CH2-, -CH2CH2CH2CH2CH2OCH2-, -CH2CH2CH2CH2CH2CH2O-, -CH2SCH2CH2CH2CH2CH2-, -CH2CH2SCH2CH2CH2CH2-, -CH2CH2CH2SCH2CH2CH2-, -CH2CH2CH2CH2SCH2CH2-, -CH2CH2CH2CH2CH2SCH2-, or -CH2CH2CH2CH2CH2CH2S-, wherein each is optionally substituted. Typically, in this embodiment, L is optionally substituted with one substituent independently selected from fluoro, hydroxyl, oxo (=0), methyl, methoxy, -CF3, CHF2, CH2F, -OCF3, -OCHF2, or -OCH2F, and wherein L optionally includes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl or cyclobutyl group. More typically, L is optionally substituted with one substituent independently selected from fluoro, hydroxyl, or methyl, and wherein L optionally includes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl or cyclobutyl group.

[0567] In one embodiment, L is -0-, -S-, -CH2-, -CH2CH2-, -CH2CH2CH2-, -CH2CH2CH2CH2-, -CH2O-, -CH2S-, -OCH2-, -OCH2CH2-, -OCH2CH2O-, -OCH2CH2S-, -CH2CH2O-, -CH2CH2S-, -OCH2CH2CH2-, -OCH2CH2CH2O-, -OCH2CH2CH2S-, -SCH2-, -SCH2CH2-, -SCH2CH2S-, -SCH2CH2O-, -SCH2CH2CH2-, -SCH2CH2CH2O-, -SCH2CH2CH2S-, -CH2OCH2-, -CH2SCH2-, -CH2OCH2CH2-, -CH2CH2OCH2-, -CH2CH2CH2O-, -CH2CH2CH2S-, -CH2SCH2-, -CH2SCH2CH2-, -CH2CH2SCH2-, or -CH2CH2CH2S-, wherein each is optionally substituted. Typically, in this embodiment, L is optionally substituted with one substituent independently selected from fluoro, hydroxyl, oxo (=0), methyl, methoxy, -CF3, CHF2, CH2F, -OCF3, -OCHF2, or -OCH2F, and wherein L optionally includes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl or cyclobutyl group. More typically, L is optionally substituted with one substituent independently selected from fluoro, hydroxyl, or methyl, and wherein L optionally includes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl or cyclobutyl group.

[0568] In one embodiment, L is -0-, -S-, -CH2-, -CH2CH2-, -CH2CH2CH2-, -CH2CH2CH2CH2-, -CH2O-, -CH2S-, -OCH2-, -OCH2CH2-, -OCH2CH2O-, -OCH2CH2S-, -CH2CH2O-, -CH2CH2S-, -OCH2CH2CH2-, -OCH2CH2CH2O-, -OCH2CH2CH2S-, -SCH2-, -SCH2CH2-, -SCH2CH2S-, -SCH2CH2O-, -SCH2CH2CH2-, -SCH2CH2CH2O-, -SCH2CH2CH2S-, -CH2OCH2-, -CH2OCH2CH2-, -CH2CH2OCH2-, -CH2CH2CH2O-, -CH2SCH2-, -CH2SCH2CH2-,-CH2CH2SCH2-, or -CH2CH2CH2S-, wherein each is optionally substituted. Typically, in this embodiment, L is optionally substituted with one substituent independently selected from fluoro, hydroxyl, oxo (=0), methyl, methoxy, -CF3, CHF2, CH2F, -OCF3, -OCHF2, or -OCH2F, and wherein L optionally includes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl or cyclobutyl group. More typically, L is optionally substituted with one substituent independently selected from fluoro, hydroxyl, or methyl, and wherein L optionally includes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl or cyclobutyl group.

[0569] In one embodiment, L is -0-, -S-, -CH2-, -CH2S-, -CH2O-, -OCH2-, -CH2CH2-, -CH2CH2CH2-, -CH2CH2CH2CH2-, -OCH2CH2-, -OCH2CH2O-, -OCH2CH2S-, -CH2SCH2-, -CH2CH2O-, -CH2CH2S- -OCH2CH2CH2-, -CH2CH2CH2O-, or -CH2CH2CH2S-.

[0570] In one embodiment, L is -0-, -S-, -CH2-, -CH2S-, -OCH2-, -CH2CH2CH2-, -OCH2CH2O-, -OCH2CH2S-, -CH2CH2O-, -CH2CH2S- -OCH2CH2CH2-, -CH2CH2CH2O-, or -CH2CH2CH2S-. Typically, L is -0-, -CH2-, -OCH2-, -CH2CH2CH2-, or -CH2CH2CH2S-.

[0571] In one embodiment, L is -CH2-.

[0572] In one embodiment, A is phenyl, naphthyl, pyrrolyl, furanyl, thiophenyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, oxadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, indolizinyl, indazolyl, benzimidazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, quinazolinyl, or naphthyridinyl.

[0573] Typically, A is phenyl, naphthyl, or a 6- to 10-membered heteroaryl group.

[0574] In one embodiment, A is phenyl, naphthyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, indolizinyl, indazolyl, benzimidazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, quinazolinyl or naphthyridinyl. Typically, A is phenyl, pyridinyl, indazolyl, benzimidazolyl, quinolinyl, or isoquinolinyl. More typically, A is phenyl or indazolyl.

[0575] In one embodiment, A is indazolyl, optionally indazol-l-yl.

[0576] In one embodiment, A is phenyl. Typically, in this embodiment, the group X2is in the para or meta position of the phenyl ring. In one embodiment, A is phenyl, and X2is in the para position. In another embodiment, A is phenyl, and X2is in the meta position. For the avoidance of doubt, it is noted that when p is 0, the group R4is not present.In one embodiment, p is 0 or 1. In one embodiment, p is 1. In another embodiment, p is 0.

[0577] In one embodiment, each R4is independently halo, -OH, -NH2, -SH, cyano, or a Ci-Ce saturated or unsaturated hydrocarbyl group which may be straight chained or branched, or be or include a cyclic group, and may optionally be substituted with one or more (such as one, two, three or four) halo groups, and where the hydrocarbyl group may optionally include one or two heteroatoms each independently selected from N, 0 and S in its carbon skeleton, and any -S- moiety when present in the hydrocarbyl group may optionally be substituted with one or two groups each independently selected from oxo (=0) and =NH to form a -SO-, -SO2-, -S( = NH)- or -SO( = NH)- moiety.

[0578] In one embodiment, each R4is independently halo, -OH, -NH2, -SH, cyano, C1-C5 alkyl, -O-(Ci-C5 alkyl), -C3-C5 cycloalkyl, -O(C3-C5 cycloalkyl), C3-C5 heterocycloalkyl, -0(C3-Cs heterocycloalkyl), -NH(Ci-Cs alkyl), -N(Ci-Cs alkyl)2, -NH-SO2(CI-CS alkyl), -NH(CO)(Ci-Cs alkyl), or -S(Ci-Cs alkyl), wherein any alkyl group may be optionally substituted by one or more substituents independently selected from halo, OH, OMe, cyclopropyl, or cyclobutyl.

[0579] In one embodiment, each R4is independently fluoro, chloro, bromo, iodo, -OH, -NH2, -SH, cyano, C1-C4 alkyl, -O-(Ci-C4 alkyl), C3-C4 cycloalkyl, -O(C3-C4 cycloalkyl), C3-C4 heterocycloalkyl, -O(C3-C4 heterocycloalkyl), -NH(CI-C4 alkyl), -N(CI-C4 alkyl)2, -NH-SO2(Ci-C4 alkyl), -NH-SO2(CI-C4 haloalkyl), -NH(CO)(CI-C4 alkyl), or -S(Ci-C4 alkyl), wherein any alkyl group may be optionally substituted by one or more substituents selected from fluoro, OH, OMe, cyclopropyl, or cyclobutyl.

[0580] In one embodiment, each R4is independently fluoro, chloro, bromo, iodo, cyano, C1-C4 alkyl optionally C3-C4 alkyl, -O-(Ci-C4 alkyl) optionally -O-(C3-C4 alkyl), C3-C4 cycloalkyl, -O(C3-C4 cycloalkyl), C3-C4 heterocycloalkyl, -O(C3-C4 heterocycloalkyl), or -S(Ci-C4 alkyl), wherein any alkyl group may be optionally substituted by one or more substituents selected from fluoro, OH, OMe, cyclopropyl, or cyclobutyl.

[0581] In one embodiment, each R4is independently fluoro, chloro, bromo, iodo, cyano, methyl, ethyl, propyl (such as n-propyl or i-propyl), butyl (such as n-butyl, i-butyl, t-butyl), methoxy, ethoxy, propoxy, butoxy, cyclopropyl, cyclobutyl, -O-cyclopropyl, -O-cyclobutyl, -SMe, or -SEt. Typically, each R4is independently fluoro, iodo, cyano, methyl, ethyl, -OMe, -CH2CHCH3CH3, -OCH2CHCH3CH3, -OCH2CH2CH2CH3, -0-cyclobutyl, -OCH2-cyclobutyl, cyclopropyl, -CH2-cyclopropyl, -O-cyclopropyl, -OCH2-cyclopropyl, or -SMe.

[0582] In one embodiment, each R4is independently fluoro, cyano, methyl, -CH2CHCH3CH3, -OCH2CHCH3CH3, -OCH2CH2CH2CH3, -O-cyclobutyl, -OCH2-cyclobutyl, or cyclopropyl.

[0583] In one embodiment, p is 1, and R4is fluoro, cyano, methyl, -CH2CHCH3CH3, -0-CH2CHCH3CH3, -OCH2CH2CH2CH3, -O-cyclobutyl, -O-CH2-cyclobutyl, or cyclopropyl. In one embodiment, p is 1, and R4is fluoro, cyano or methyl. In one embodiment, p is 1, and R4is fluoro.

[0584] In one embodiment, X2and R4are different. In one embodiment, when X2is125I,123I, or131I, R4is not iodo.

[0585] In one embodiment, X2is125I,123I, or131I. In one embodiment, X2is125I,131I, or211At. In one embodiment, X2is125I or131I. In another embodiment, X2is131I or211At.

[0586] In one embodiment, X2is125I. In another embodiment, X2is131I. In yet another embodiment, X2is211At.

[0587] In one embodiment, the compound of Formula (IIIA) is a compound of Formula (IIIA-al) - (IIIA-a3) or a pharmaceutically acceptable salt, solvate or prodrug thereof:

[0588]

[0589] (IIIA-a1) (IIIA-a2)

[0590]

[0591] X2

[0592] (IIIA-a3)

[0593] wherein p, R1, R2, R3, R4, R5, R6, R7, A, L, and X2are as defined in accordance with Formula (IIIA).

[0594] In another embodiment, the compound of Formula (IIIA) is a compound of Formula (IIIA-a4) - (IIIA-a7) or a pharmaceutically acceptable salt, solvate or prodrug thereof:

[0595] (IIIA-a4) (IIIA-a5)

[0596]

[0597] (IIIA-a6) (IIIA-a7) wherein p, R1, R2, R3, R4, R5, R6, R7, A, L, and X2are as defined in accordance with Formula (IIIA).

[0598] Typically, the compound of Formula (IIIA) is a compound of Formula (IIIA-al), (IIIA-a2), (IIIA-a4), or (IIIA-a5). In one embodiment, the compound of Formula (IIIA) is a compound of Formula (IIIA-al) or (IIIA-a4). In one embodiment, the compound of Formula (IIIA) is a compound of Formula (IIIA-al). In one embodiment, the compound of Formula (IIIA) is a compound of Formula (IIIA-a4).In one embodiment, the compound of Formula (IIIA) is a compound of Formula (IIIA') or a pharmaceutically acceptable salt, solvate, or prodrug thereof:

[0599] R1R2O

[0600] HO OH

[0601]

[0602] Formula (IIIA')

[0603] wherein n, m, p, R1, R2, R3, R4, R5, R6, R7, A, L, and X2are as defined in accordance with Formula (IIIA).

[0604] As would be understood, in the compound of Formula (IIIA'), the chiral centre at the amino (-NH2) group is (S).

[0605] In one embodiment, the carbon bearing the -L- group, marked below with an asterisk (*), is a chiral centre and has ( / ?) configuration. In another embodiment, the carbon bearing the -L- group, marked below with an asterisk (*), is a chiral centre and has (S) configuration.

[0606] In one embodiment, the compound of Formula (IIIA') is a compound of Formula (IIIA-al') - (IIIA-a3') or a pharmaceutically acceptable salt, solvate or prodrug thereof:

[0607] X2

[0608] HO'

[0609] NH2

[0610] TAR4)P

[0611]

[0612] X2

[0613] (IIIA-a1 ') (IIIA-a2')

[0614]

[0615] X2

[0616] (IIIA-a3')

[0617] wherein p, R1, R2, R3, R4, R5, R6, R7, A, L, and X2are as defined in accordance with Formula (IIIA).

[0618] In another embodiment, the compound of Formula (IIIA') is a compound of Formula (IIIA-a4') - (IIIA-a7') or a pharmaceutically acceptable salt, solvate or prodrug thereof:

[0619] (IIIA-a4’) (IIIA-a5’)

[0620] C2r>1 r>1 r->2

[0621]

[0622] (IIIA-a6’) (IIIA-a7')

[0623] wherein p, R1, R2, R3, R4, R5, R6, R7, A, L, and X2are as defined in accordance with Formula (IIIA).

[0624] Typically, the compound of Formula (IIIA') is a compound of Formula (IIIA-al'), (IIIA-a2'), (IIIA-a4') or (IIIA-a5'). In one embodiment, the compound of Formula (IIIA') is a compound of Formula (IIIA-al') or (IIIA-a4'). In one embodiment, the compound of Formula (IIIA') is a compound of Formula (IIIA-al'). In one embodiment, the compound of Formula (IIIA') is a compound of Formula (IIIA-a4').As will be understood, insofar as practical, embodiments directed to one substituent or moiety (such as a given L or X2group) may be read in conjunction with embodiments directed to a different substituent or moiety.

[0625] For example, in one exemplary embodiment, there is provided a compound of Formula (IIIA) or Formula (IIIA') as defined above, wherein:

[0626] n is 0, 1, 2 or 3;

[0627] m is 1, 2, 3 or 4;

[0628] provided that m+n is 3 or 4;

[0629] when present, R1is hydrogen;

[0630] R2is hydrogen;

[0631] R3is hydrogen;

[0632] L is -O-, -S-, -NR5-, or a Ci-Ce straight chained alkylene group, wherein the Ci-Ce straight chained alkylene group optionally includes one, two or three heteroatoms each independently selected from 0, S and NR6in its carbon skeleton, wherein the Ci-Ce straight chained alkylene group may optionally be substituted with one or more substituents independently selected from fluoro, hydroxyl, oxo (=0), C1-C3 alkyl, -0-(C1-C3 alkyl), -0-(Ci-C3 fluoroalkyl), or C1-C3 fluoroalkyl and wherein the Ci-Ce straight chained alkylene group may include a spirocyclic group, wherein the spirocyclic group is a cyclopropyl, cyclobutyl, oxiranyl, aziridinyl, azetidinyl, or oxetanyl group;

[0633] A is phenyl, naphthyl, or a 6- to 10-membered heteroaryl group;

[0634] p is 0 or 1;

[0635] R4is fluoro, chloro, bromo, iodo, cyano, C1-C4 alkyl optionally C3-C4 alkyl, -0-(C1-C4 alkyl) optionally -O-(C3-C4 alkyl), C3-C4 cycloalkyl, -O(C3-C4 cycloalkyl), C3-C4 heterocycloalkyl, -O(C3-C4 heterocycloalkyl), or -S(Ci-C4 alkyl), wherein any alkyl group may be optionally substituted by one or more substituents selected from fluoro, OH, OMe, cyclopropyl, or cyclobutyl;

[0636] R5is hydrogen or methyl;

[0637] R6is methyl; and

[0638] X2is125I,123I,131I, or211At.

[0639] In another exemplary embodiment, there is provided a compound of Formula (IIIA) or Formula (IIIA') as defined above, wherein:

[0640] n is 0, 1, 2 or 3;

[0641] m is 1, 2, 3 or 4;

[0642] provided that m+n is 3 or 4;

[0643] when present, R1is hydrogen;

[0644] R2is hydrogen;R3is hydrogen;

[0645] L is -O-, -S-, or a Ci-Ce straight chained alkylene group, wherein the Ci-Ce straight chained alkylene group optionally includes one or two heteroatoms each independently selected from 0 and S in its carbon skeleton, wherein the Ci-Ce straight chained alkylene group may optionally be substituted with one or more substituents independently selected from fluoro, hydroxyl, oxo (=0), C1-C3 alkyl,

[0646] -O-(Ci-C3 alkyl), -O-(Ci-C3 fluoroalkyl), or C1-C3 fluoroalkyl, and wherein the Ci-Ce straight chained alkylene group may include a spirocyclic group, wherein the spirocyclic group is a cyclopropyl, cyclobutyl, oxiranyl, aziridinyl, azetidinyl, or oxetanyl group;

[0647] A is phenyl, naphthyl, or a 6- to 10-membered heteroaryl group;

[0648] p is 0 or 1;

[0649] R4is fluoro, chloro, bromo, iodo, cyano, C1-C4 alkyl optionally C3-C4 alkyl, -0-(C1-C4 alkyl) optionally -O-(C3-C4 alkyl), C3-C4 cycloalkyl, -O(C3-C4 cycloalkyl), C3-C4 heterocycloalkyl, -O(C3-C4 heterocycloalkyl), or -S(Ci-C4 alkyl), wherein any alkyl group may be optionally substituted by one or more substituents selected from fluoro, OH, OMe, cyclopropyl, or cyclobutyl; and

[0650] X2is125I,123I,131I, or211At.

[0651] In another exemplary embodiment, there is provided a compound of Formula (IIIA) or Formula (IIIA') as defined above, wherein:

[0652] n is 0 or 1;

[0653] m is 2, 3 or 4;

[0654] provided that m+n is 3 or 4;

[0655] when present, R1is hydrogen;

[0656] R2is hydrogen;

[0657] R3is hydrogen;

[0658] L is -0-, -S-, or a C1-C3 straight chained alkylene group, wherein the C1-C3 straight chained alkylene group optionally includes one or two heteroatoms each independently selected from 0 and S in its carbon skeleton, wherein the C1-C3 straight chained alkylene group is optionally substituted with one or two substituents independently selected from fluoro, hydroxyl, methyl, methoxy, -CF3, CHF2, CH2F, -OCF3, -OCHF2, or -OCH2F, and wherein the C1-C3 straight chained alkylene group optionally includes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl, cyclobutyl, oxiranyl, aziridinyl, azetidinyl, or oxetanyl group;

[0659] A is phenyl, naphthyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, indolizinyl, indazolyl, benzimidazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, quinazolinyl, or naphthyridinyl;p is 0 or 1;

[0660] R4is fluoro, iodo, cyano, methyl, ethyl, -OMe, -CH2CHCH3CH3, -OCH2CHCH3CH3, -OCH2CH2CH2CH3, -O-cyclobutyl, -OCH2-cyclobutyl, cyclopropyl, -CH2-cyclopropyl, -O-cyclopropyl, -OCH2-cyclopropyl, or -SMe; and

[0661] X2is125I,123I,131I, or211At.

[0662] In another exemplary embodiment, there is provided a compound of Formula (IIIA) or Formula (IIIA') as defined above, wherein:

[0663] n is 0 or 1;

[0664] m is 2, 3 or 4;

[0665] provided that m+n is 3 or 4;

[0666] when present, R1is hydrogen;

[0667] R2is hydrogen;

[0668] R3is hydrogen;

[0669] L is -O-, -S-, or a C1-C3 straight chained alkylene group, wherein the C1-C3 straight chained alkylene group optionally includes one or two heteroatoms each independently selected from 0 and S in its carbon skeleton, wherein the C1-C3 straight chained alkylene group is optionally substituted with one substituent independently selected from fluoro, hydroxyl, or methyl, and wherein the C1-C3 straight chained alkylene group optionally includes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl or cyclobutyl group;

[0670] A is phenyl, pyridinyl, indazolyl, benzimidazolyl, quinolinyl, or isoquinolinyl; p is 0; and

[0671] X2is125I,123I,131I, or211At.

[0672] In another exemplary embodiment, there is provided a compound of Formula (IIIA) or Formula (IIIA') as defined above, wherein:

[0673] n is 0 or 1,

[0674] m is 2, 3 or 4;

[0675] provided that m+n is 3 or 4;

[0676] when present, R1is hydrogen;

[0677] R2is hydrogen;

[0678] R3is hydrogen;

[0679] L is -O-, -S-, or a C1-C3 straight chained alkylene group, wherein the C1-C3 straight chained alkylene group optionally includes one or two heteroatoms each independently selected from 0 and S in its carbon skeleton, wherein the C1-C3 straight chained alkylene group is optionally substituted with one substituent independently selected from fluoro, hydroxyl, or methyl, and wherein the C1-C3 straight chainedalkylene group optionally includes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl or cyclobutyl group;

[0680] A is phenyl, pyridinyl, indazolyl, benzimidazolyl, quinolinyl, or isoquinolinyl; P is 1;

[0681] R4is fluoro, iodo, cyano, methyl, ethyl, -OMe, -CH2CHCH3CH3, -OCH2CHCH3CH3, -OCH2CH2CH2CH3, -O-cyclobutyl, -OCH2-cyclobutyl, cyclopropyl, -CH2-cyclopropyl, -O-cyclopropyl, -OCH2-cyclopropyl, or -SMe, optionally wherein R4is fluoro; and

[0682] X2is125I,123I,131I, or211At.

[0683] In another exemplary embodiment, there is provided a compound of Formula (IIIA) or Formula (IIIA') as defined above, wherein:

[0684] n is 0, or 1;

[0685] m is 2, 3 or 4;

[0686] provided that m+n is 3 or 4;

[0687] when present, R1is hydrogen;

[0688] R2is hydrogen;

[0689] R3is hydrogen;

[0690] L is -O-, -S-, -CH2-, -CH2CH2-, -CH2CH2CH2-, -CH2CH2CH2CH2-, -CH2O-, -CH2S-, -OCH2-, -OCH2CH2-, -OCH2CH2O-, -OCH2CH2S-, -CH2CH2O-, -CH2CH2S-, -OCH2CH2CH2-, -OCH2CH2CH2O-, -OCH2CH2CH2S-, -SCH2-, -SCH2CH2-, -SCH2CH2S-, -SCH2CH2O-, -SCH2CH2CH2-, -SCH2CH2CH2O-, -SCH2CH2CH2S-, -CH2OCH2-, -CH2OCH2CH2-, -CH2CH2OCH2-, -CH2CH2CH2O-, -CH2SCH2-, -CH2SCH2CH2-, -CH2CH2SCH2-, or -CH2CH2CH2S-;

[0691] A is phenyl or indazolyl;

[0692] p is 0; and

[0693] X2is125I,123I,131I, or211At.

[0694] In another exemplary embodiment, there is provided a compound of Formula (IIIA) or Formula (IIIA') as defined above, wherein:

[0695] n is 0, 1, 2 or 3;

[0696] m is 1, 2, 3 or 4;

[0697] provided that m+n is 3 or 4;

[0698] when present, R1is hydrogen;

[0699] R2is hydrogen;

[0700] R3is hydrogen;

[0701] L is -O-, -S-, or a Ci-Ce straight chained alkylene group, wherein the Ci-Ce straight chained alkylene group optionally includes one or two heteroatoms each independently selected from 0 and S in its carbon skeleton, wherein the Ci-Ce straight chained alkylene group may optionally be substituted with one or more substituents independently selected from fluoro, hydroxyl, oxo (=0), C1-C3 alkyl,

[0702] -O-(Ci-C3 alkyl), -O-(Ci-C3 fluoroalkyl), or C1-C3 fluoroalkyl, and wherein the Ci-Ce straight chained alkylene group may include a spirocyclic group, wherein the spirocyclic group is a cyclopropyl, cyclobutyl, oxiranyl, aziridinyl, azetidinyl, or oxetanyl group;

[0703] A is phenyl, naphthyl, or a 6- to 10-membered heteroaryl group;

[0704] p is 0 or 1;

[0705] R4is fluoro, chloro, bromo, iodo, cyano, C1-C4 alkyl optionally C3-C4 alkyl, -0-(C1-C4 alkyl) optionally -O-(C3-C4 alkyl), C3-C4 cycloalkyl, -O(C3-C4 cycloalkyl), C3-C4 heterocycloalkyl, -O(C3-C4 heterocycloalkyl), or -S(Ci-C4 alkyl), wherein any alkyl group may be optionally substituted by one or more substituents selected from fluoro, OH, OMe, cyclopropyl, or cyclobutyl; and

[0706] X2is125I,123I, or131I.

[0707] In another exemplary embodiment, there is provided a compound of Formula (IIIA) or Formula (IIIA') as defined above, wherein:

[0708] n is 0, 1, 2 or 3;

[0709] m is 1, 2, 3 or 4;

[0710] provided that m+n is 3 or 4;

[0711] when present, R1is hydrogen;

[0712] R2is hydrogen;

[0713] R3is hydrogen;

[0714] L is -O-, -S-, or a Ci-Ce straight chained alkylene group, wherein the Ci-Ce straight chained alkylene group optionally includes one or two heteroatoms each independently selected from 0 and S in its carbon skeleton, wherein the Ci-Ce straight chained alkylene group may optionally be substituted with one or more substituents independently selected from fluoro, hydroxyl, oxo (=0), C1-C3 alkyl,

[0715] -O-(Ci-C3 alkyl), -O-(Ci-C3 fluoroalkyl), or C1-C3 fluoroalkyl, and wherein the Ci-Ce straight chained alkylene group may include a spirocyclic group, wherein the spirocyclic group is a cyclopropyl, cyclobutyl, oxiranyl, aziridinyl, azetidinyl, or oxetanyl group;

[0716] A is phenyl, naphthyl, or a 6- to 10-membered heteroaryl group;

[0717] p is 0 or 1;

[0718] R4is fluoro, chloro, bromo, iodo, cyano, C1-C4 alkyl optionally C3-C4 alkyl, -0-(C1-C4 alkyl) optionally -O-(C3-C4 alkyl), C3-C4 cycloalkyl, -O(C3-C4 cycloalkyl), C3-C4 heterocycloalkyl, -O(C3-C4 heterocycloalkyl), or -S(Ci-C4 alkyl), wherein any alkyl group may be optionally substituted by one or more substituents selected from fluoro, OH, OMe, cyclopropyl, or cyclobutyl; and

[0719] X2is211At.

[0720] The first aspect further provides a compound of Formula (IV):

[0721] R1R2O

[0722]

[0723] X3

[0724] Formula (IV)

[0725] or a pharmaceutically acceptable salt, solvate or prodrug thereof, wherein:

[0726] n is 0, 1, 2 or 3;

[0727] m is 1, 2, 3 or 4;

[0728] provided that m+n is 3 or 4;

[0729] when present, R1is hydrogen or C1-C3 alkyl;

[0730] R2is hydrogen or C1-C3 alkyl;

[0731] R3is hydrogen or C1-C3 alkyl;

[0732] L is -O-, -S-, -NR5-, a Ci-Ce straight chained alkylene group, wherein the Ci-Ce straight chained alkylene group optionally includes one, two or three heteroatoms each independently selected from 0, S and NR6in its carbon skeleton, or L is a group -L1-B-L2-, wherein L1and L2are each independently a bond or a C1-C3 straight chained alkylene group, wherein B is a saturated cyclic group selected from a C3-C6 cycloalkyl group, or a 3-, 4-, 5- or 6- membered saturated monocyclic heterocyclic group; wherein L is optionally substituted with one or more substituents independently selected from fluoro, hydroxyl, oxo (=0), C1-C3 alkyl, -0-(Ci-C3 alkyl), -0-(Ci-C3 fluoroalkyl), or C1-C3 fluoroalkyl, and wherein L optionally includes one or more spirocyclic groups, wherein the spirocyclic group is selected from a C3-C5 cycloalkyl group or a saturated C3-C5 heterocyclic group;

[0733] A is phenyl, naphthyl, or a 5- to 10-membered heteroaryl group;

[0734] p is 0, 1, or 2;

[0735] R4is halo, -OH, -NH2, -SH, cyano, or a Ci-Cs saturated or unsaturatedhydrocarbyl group, wherein the hydrocarbyl group may be straight chained or branched, or be or include a cyclic group, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, 0 and S in its carbon skeleton, and wherein any -S- moiety in the hydrocarbyl group may optionally be substituted with one or two groups each independently selected from oxo (=0) and =NH to form a -SO-, -SO2-, -S( = NH)- or -SO( = NH)-moiety;

[0736] R5is hydrogen, C1-C3 alkyl, or C2-C3 alkylene-OR7;

[0737] R6is C1-C3 alkyl, or C2-C3 alkylene-OR7;

[0738] R7is hydrogen or methyl; and

[0739] X3is127I or19F.

[0740] In one embodiment, X3is127I. In one embodiment, X3is19F.

[0741] Embodiments with respect to n, m, p, R1, R2, R3, R4, R5, R6, R7, L, and A as set out above in conjunction with Formula (I) may also be read in conjunction with Formula (IV).

[0742] The compounds of Formula (IV) may be useful as tool compounds.

[0743] A second aspect of the invention provides a compound selected from the group consisting of:

[0744] 2-amino-7-(4-iodobenzyl)octanedioic acid;

[0745] 2-amino-6-(4-iodobenzyl)heptanedioic acid;

[0746] 2-amino-4-(4-iodobenzyl)heptanedioic acid;

[0747] 2-amino-7-(((4-iodophenyl)thio)methyl)octanedioic acid;

[0748] 2-amino-6-(3-((4-iodophenyl)thio)propyl)heptanedioic acid;

[0749] 2-amino-6-(3-iodobenzyl)heptanedioic acid;

[0750] 2-amino-6-(((4-iodophenyl)thio)methyl)heptanedioic acid;

[0751] 2-a mi no-6-(3-fluoro-4-iodobenzyl) heptanedioic acid;

[0752] 2-amino-6-(3-(5-iodo-lH-indazol-l-yl)propyl)heptanedioic acid;

[0753] 2-amino-7-(3-((4-iodophenyl)thio)propyl)octanedioic acid;

[0754] 2-amino-6-(4-iodobenzyl)octanedioic acid;

[0755] 2-amino-6-((4-iodobenzyl)oxy)heptanedioic acid;

[0756] 2-amino-6-(2-((4-iodophenyl)thio)ethyl)heptanedioic acid;

[0757] 2-amino-5-(4-iodobenzyl)heptanedioic acid;

[0758] 2-amino-4-(4-iodobenzyl)octanedioic acid;

[0759] 2-a mi no-6-(4-iodophenoxy) heptanedioic acid;2-amino-6-(2-((4-iodophenyl)thio)ethoxy)heptanedioic acid;

[0760] 2-amino-6-(4-(iodo-125I)benzyl)heptanedioic acid;

[0761] 2-amino-6-(3-(iodo-125I)benzyl)heptanedioic acid

[0762] 2-a mi no-6-(3-((4-(iodo-125I) phenyl)thio) propyl) heptanedioic acid; 2-amino-6-((4-(iodo-125I)benzyl)oxy)heptanedioic acid;

[0763] 2-amino-7-(3-iodobenzyl)octanedioic acid;

[0764] 2-amino-6-(2-fluoro-4-iodobenzyl)heptanedioic acid;

[0765] 2-amino-6-(3-(4-iodophenoxy)propyl)heptanedioic acid;

[0766] 2-amino-6-(2-(4-iodophenoxy)ethyl)heptanedioic acid;

[0767] 2-amino-6-(3-(4-iodophenyl)propoxy)heptanedioic acid;

[0768] 2-a mi no-6-(2-(4-iodophenoxy)ethoxy) heptanedioic acid;

[0769] 2-a mi no-6-(4-fluorobenzyl) heptanedioic acid;

[0770] 2-amino-6-(2-iodobenzyl)heptanedioic acid;

[0771] 2-a mi no-6-(3-fluorobenzyl) heptanedioic acid;

[0772] 2-amino-6-(4-iodophenethyl)heptanedioic acid;

[0773] 2-amino-7-(4-fluorobenzyl)octanedioic acid;

[0774] 2-amino-7-(3-fluorobenzyl)octanedioic acid;

[0775] 2-a mi no-6-(3-iodophenoxy) heptanedioic acid;

[0776] 2-amino-6-((3-iodobenzyl)oxy)heptanedioic acid;

[0777] 2-amino-6-(3-(3-iodophenyl)propyl)heptanedioic acid;

[0778] 2-amino-6-(3-iodophenethyl)heptanedioic acid;

[0779] 2-a mi no-6-(2-(3-iodophenoxy)ethoxy) heptanedioic acid;

[0780] 2-amino-6-(4-iodophenethoxy)heptanedioic acid;

[0781] 2-amino-6-((4-iodophenoxy)methyl)heptanedioic acid;

[0782] 2-amino-6-(4-(4-iodophenyl)butyl)heptanedioic acid;

[0783] 2-amino-6-(4-(3-iodophenyl)butyl)heptanedioic acid;

[0784] 2-amino-4-(3-iodobenzyl)heptanedioic acid;

[0785] 2-amino-6-(3-(4-iodophenyl)propyl)heptanedioic acid;

[0786] 2-a mi no-6-(2-((4-(iodo-125I)phenyl)thio)ethyl) heptanedioic acid; 2-amino-6-(3-(fluoro-18F)benzyl)heptanedioic acid;

[0787] 2-amino-6-(3-(iodo-131I)benzyl)heptanedioic acid;

[0788] 2-a mi no-6-(3-((4-(iodo-131I) phenyl)thio) propyl) heptanedioic acid; 2-amino-6-(3-(3-(iodo-125I)phenyl)propyl)heptanedioic acid;

[0789] 2-amino-6-(3-(4-(iodo-125I)phenyl)propyl)heptanedioic acid;

[0790] 2-a mi no-6-(4-fluoro-3-iodobenzyl) heptanedioic acid;

[0791] 2-a mi no-6-(3-fluoro-5-iodobenzyl) heptanedioic acid;

[0792] 2-amino-6-((5-iodopyridin-3-yl)methyl)heptanedioic acid;

[0793] 2-amino-6-(4-cyano-3-iodobenzyl)heptanedioic acid;2-amino-6-(2-(3-fluorophenoxy)ethoxy)heptanedioic acid;

[0794] 2-amino-6-(3-iodo-4-methylbenzyl)heptanedioic acid;

[0795] 2-amino-6-(3-(4-(iodo-125I)phenyl) propoxy)heptanedioic acid;

[0796] 2-amino-6-(2-(3-(iodo-125I) phenoxy)ethoxy)heptanedioic acid;

[0797] 2-amino-4-(3-(iodo-125I)benzyl)heptanedioic acid; and

[0798] 2-a mi no-6-(3-(astato-211-At)benzyl) heptanedioic acid;

[0799] and pharmaceutically acceptable salts, solvates or prodrugs of any one thereof.

[0800] In one embodiment, the compound is selected from the group consisting of:

[0801] (2S)-2-amino-7-(4-iodobenzyl)octanedioic acid;

[0802] (2S)-2-amino-6-(4-iodobenzyl)heptanedioic acid;

[0803] (2S)-2-amino-4-(4-iodobenzyl)heptanedioic acid;

[0804] (2S)-2-amino-7-(((4-iodophenyl)thio)methyl)octanedioic acid;

[0805] (2S)-2-amino-6-(3-((4-iodophenyl)thio) propyl) heptanedioic acid;

[0806] (2S)-2-amino-6-(3-iodobenzyl)heptanedioic acid;

[0807] (2S)-2-amino-6-(((4-iodophenyl)thio)methyl) heptanedioic acid;

[0808] (2S)-2-amino-6-(3-fluoro-4-iodobenzyl)heptanedioic acid;

[0809] (2S)-2-amino-6-(3-(5-iodo-lH-indazol-l-yl)propyl)heptanedioic acid; (2S)-2-amino-7-(3-((4-iodophenyl)thio)propyl)octanedioic acid;

[0810] (2S)-2-amino-6-(4-iodobenzyl)octanedioic acid;

[0811] (2S)-2-amino-6-((4-iodobenzyl)oxy)heptanedioic acid compound;

[0812] (2S)-2-amino-6-(2-((4-iodophenyl)thio)ethyl)heptanedioic acid;

[0813] (2S)-2-amino-5-(4-iodobenzyl)heptanedioic acid;

[0814] (2S)-2-amino-4-(4-iodobenzyl)octanedioic acid;

[0815] (2S)-2-a mi no-6-(4-iodophenoxy) heptanedioic acid;

[0816] (2S)-2-amino-6-(2-((4-iodophenyl)thio)ethoxy)heptanedioic acid;

[0817] (2S)-2-amino-6-(4-(iodo-125I)benzyl)heptanedioic acid;

[0818] (2S)-2-a mi no-6-(3-(iodo-125I) benzyl) heptanedioic acid;

[0819] (2S)-2-amino-6-(3-((4-(iodo-125I)phenyl)thio)propyl)heptanedioic acid; (2S)-2-amino-6-((4-(iodo-125I)benzyl)oxy)heptanedioic acid;

[0820] (2S)-2-amino-7-(3-iodobenzyl)octanedioic acid;

[0821] (2S)-2-amino-6-(2-fluoro-4-iodobenzyl)heptanedioic acid;

[0822] (2S)-2-a mi no-6-(3-(4-iodophenoxy)propyl) heptanedioic acid;

[0823] (2S)-2-a mi no-6-(2-(4-iodophenoxy)ethyl) heptanedioic acid;

[0824] (2S)-2-a mi no-6-(3-(4-iodophenyl)propoxy) heptanedioic acid;

[0825] (2S)-2-amino-6-(2-(4-iodophenoxy)ethoxy)heptanedioic acid;

[0826] (2S)-2-amino-6-(4-fluorobenzyl) heptanedioic acid;

[0827] (2S)-2-amino-6-(2-iodobenzyl)heptanedioic acid;(2S)-2-amino-6-(3-fluorobenzyl)heptanedioic acid;

[0828] (2S)-2-amino-6-(4-iodophenethyl)heptanedioic acid;

[0829] (2S)-2-amino-7-(4-fluorobenzyl)octanedioic acid;

[0830] (2S)-2-amino-7-(3-fluorobenzyl)octanedioic acid;

[0831] (2S)-2-a mi no-6-(3-iodophenoxy) heptanedioic acid;

[0832] (2S)-2-amino-6-((3-iodobenzyl)oxy)heptanedioic acid;

[0833] (2S)-2-amino-6-(3-(3-iodophenyl)propyl)heptanedioic acid;

[0834] (2S)-2-amino-6-(3-iodophenethyl)heptanedioic acid;

[0835] (2S)-2-amino-6-(2-(3-iodophenoxy)ethoxy)heptanedioic acid;

[0836] (2S)-2-amino-6-(4-iodophenethoxy) heptanedioic acid;

[0837] (2S)-2-amino-6-((4-iodophenoxy)methyl)heptanedioic acid;

[0838] (2S)-2-amino-6-(4-(4-iodophenyl)butyl)heptanedioic acid;

[0839] (2S)-2-amino-6-(4-(3-iodophenyl)butyl)heptanedioic acid;

[0840] (2S)-2-amino-4-(3-iodobenzyl)heptanedioic acid;

[0841] (2S)-2-amino-6-(3-(4-iodophenyl)propyl)heptanedioic acid;

[0842] (6S)-2-amino-6-(4-iodophenethoxy) heptanedioic acid;

[0843] (2S)-2-amino-6-(2-((4-(iodo-125I)phenyl)thio)ethyl) heptanedioic acid; (2S)-2-amino-6-(3-(fluoro-18F)benzyl)heptanedioic acid;

[0844] (2S)-2-amino-6-(3-(iodo-131I) benzyl) heptanedioic acid;

[0845] (2S)-2-amino-6-(3-((4-(iodo-131I)phenyl)thio)propyl)heptanedioic acid; (2S)-2-a mi no-6-(3-(3-(iodo-125I)phenyl) propyl) heptanedioic acid;

[0846] (2S)-2-a mi no-6-(3-(4-(iodo-125I) phenyl) propyl)heptanedioic acid;

[0847] (2S)-2-amino-6-(4-fluoro-3-iodobenzyl)heptanedioic acid;

[0848] (2S)-2-amino-6-(3-fluoro-5-iodobenzyl)heptanedioic acid;

[0849] (2S)-2-amino-6-((5-iodopyridin-3-yl)methyl) heptanedioic acid;

[0850] (2S)-2-a mi no-6-(4-cyano-3-iodobenzyl) heptanedioic acid;

[0851] (2S)-amino-6-(2-(3-fluorophenoxy)ethoxy)heptanedioic acid;

[0852] (2R)-amino-6-(2-(3-fluorophenoxy)ethoxy)heptanedioic acid;

[0853] (2S)-2-amino-6-(3-iodo-4-methylbenzyl)heptanedioic acid;

[0854] (2S)-2-a mi no-6-(3-(4-(iodo-125I) phenyl) propoxy) heptanedioic acid; (2S)-2-amino-6-(2-(3-(iodo-125I) phenoxy)ethoxy) heptanedioic acid; (2S)-2-amino-4-(3-(iodo-125I)benzyl)heptanedioic acid; and

[0855] (2S)-2-amino-6-(3-(astato-211-At)benzyl)heptanedioic acid;

[0856] and pharmaceutically acceptable salts, solvates or prodrugs of any one thereof.

[0857] In one embodiment, the compound is selected from the group consisting of:

[0858] (2S,7S)-2-amino-7-(4-iodobenzyl)octanedioic acid;

[0859] (2S,7R)-2-amino-7-(4-iodobenzyl)octanedioic acid;(25.65)-2-amino-6-(4-iodobenzyl)heptanedioic acid;

[0860] (2S,6R)-2-amino-6-(4-iodobenzyl)heptanedioic acid;

[0861] (25.75)-2-amino-7-(((4-iodophenyl)thio)methyl)octanedioic acid;

[0862] (2S,7R)-2-amino-7-(((4-iodophenyl)thio)methyl)octanedioic acid;

[0863] (25.65)-2-amino-6-(3-((4-iodophenyl)thio)propyl)heptanedioic acid; (2S,6R)-2-amino-6-(3-((4-iodophenyl)thio)propyl)heptanedioic acid; (25.65)-2-amino-6-(3-iodobenzyl)heptanedioic acid;

[0864] (2S,6R)-2-amino-6-(3-iodobenzyl)heptanedioic acid;

[0865] (25.65)-2-amino-6-(((4-iodophenyl)thio)methyl)heptanedioic acid;

[0866] (2S,6R)-2-amino-6-(((4-iodophenyl)thio)methyl)heptanedioic acid;

[0867] (25.65)-2-amino-6-(3-fluoro-4-iodobenzyl) heptanedioic acid;

[0868] (2S,6R)-2-a mi no-6-(3-fluoro-4-iodobenzyl) heptanedioic acid;

[0869] (25.65)-2-amino-6-(3-(5-iodo-lH-indazol-l-yl)propyl)heptanedioic acid; (2S,6R)-2-amino-6-(3-(5-iodo-lH-indazol-l-yl)propyl)heptanedioic acid; (25.75)-2-amino-7-(3-((4-iodophenyl)thio)propyl)octanedioic acid;

[0870] (2S,7R)-2-amino-7-(3-((4-iodophenyl)thio)propyl)octanedioic acid;

[0871] (25.65)-2-amino-6-(4-iodobenzyl)octanedioic acid;

[0872] (2S,6R)-2-amino-6-(4-iodobenzyl)octanedioic acid;

[0873] (25.65)-2-amino-6-((4-iodobenzyl)oxy)heptanedioic acid compound; (2S,6R)-2-a mi no-6-((4-iodobenzyl)oxy) heptanedioic acid compound; (25.65)-2-amino-6-(2-((4-iodophenyl)thio)ethyl) heptanedioic acid;

[0874] (2S,6R)-2-amino-6-(2-((4-iodophenyl)thio)ethyl)heptanedioic acid;

[0875] (2S,5S)-2-amino-5-(4-iodobenzyl)heptanedioic acid;

[0876] (2S,5R)-2-amino-5-(4-iodobenzyl)heptanedioic acid;

[0877] (2S,4S)-2-amino-4-(4-iodobenzyl)octanedioic acid;

[0878] (25.65)-2-amino-6-(4-iodophenoxy)heptanedioic acid;

[0879] (2S,6R)-2-a mi no-6-(4-iodophenoxy) heptanedioic acid;

[0880] (25.65)-2-amino-6-(2-((4-iodophenyl)thio)ethoxy) heptanedioic acid; (2S,6R)-2-amino-6-(2-((4-iodophenyl)thio)ethoxy)heptanedioic acid; (25.65)-2-amino-6-(4-(iodo-125I)benzyl)heptanedioic acid;

[0881] (2S,6R)-2-amino-6-(4-(iodo-125I)benzyl) heptanedioic acid;

[0882] (25.65)-2-amino-6-(3-(iodo-125I)benzyl)heptanedioic acid;

[0883] (2S,6R)-2-amino-6-(3-(iodo-125I)benzyl) heptanedioic acid;

[0884] (25.65)-2-amino-6-(3-((4-(iodo-125I)phenyl)thio)propyl)heptanedioic acid; (2S,6R)-2-amino-6-(3-((4-(iodo-125I)phenyl)thio)propyl)heptanedioic acid; (25.65)-2-amino-6-((4-(iodo-125I)benzyl)oxy) heptanedioic acid;

[0885] (2S,6R)-2-amino-6-((4-(iodo-125I)benzyl)oxy)heptanedioic acid;

[0886] (25.75)-2-amino-7-(3-iodobenzyl)octanedioic acid;(2S,7R)-2-amino-7-(3-iodobenzyl)octanedioic acid

[0887] (25.65)-2-amino-6-(2-fluoro-4-iodobenzyl) heptanedioic acid;

[0888] (2S,6R)-2-a mi no-6-(2-fluoro-4-iodobenzyl) heptanedioic acid;

[0889] (25.65)-2-amino-6-(3-(4-iodophenoxy) propyl) heptanedioic acid; (2S,6R)-2-amino-6-(3-(4-iodophenoxy)propyl)heptanedioic acid; (25.65)-2-amino-6-(2-(4-iodophenoxy)ethyl)heptanedioic acid; (2S,6R)-2-amino-6-(2-(4-iodophenoxy)ethyl)heptanedioic acid; (25.65)-2-amino-6-(3-(4-iodophenyl)propoxy) heptanedioic acid; (2S,6R)-2-amino-6-(3-(4-iodophenyl)propoxy)heptanedioic acid; (25.65)-2-amino-6-(2-(4-iodophenoxy)ethoxy)heptanedioic acid; (2S,6R)-2-amino-6-(2-(4-iodophenoxy)ethoxy)heptanedioic acid; (25.65)-2-amino-6-(4-fluorobenzyl)heptanedioic acid;

[0890] (2S,6R)-2-amino-6-(4-fluorobenzyl) heptanedioic acid;

[0891] (25.65)-2-amino-6-(2-iodobenzyl)heptanedioic acid;

[0892] (2S,6R)-2-amino-6-(2-iodobenzyl)heptanedioic acid;

[0893] (25.65)-2-amino-6-(3-fluorobenzyl)heptanedioic acid;

[0894] (2S,6R)-2-amino-6-(3-fluorobenzyl) heptanedioic acid;

[0895] (25.65)-2-a mino-6-(4-iodophenethyl) heptanedioic acid;

[0896] (2S,6R)-2-a mino-6-(4-iodophenethyl) heptanedioic acid;

[0897] (25.75)-2-amino-7-(4-fluorobenzyl)octanedioic acid;

[0898] (2S,7R)-2-amino-7-(4-fluorobenzyl)octanedioic acid;

[0899] (25.75)-2-amino-7-(3-fluorobenzyl)octanedioic acid;

[0900] (2S,7R)-2-amino-7-(3-fluorobenzyl)octanedioic acid;

[0901] (25.65)-2-amino-6-(3-iodophenoxy)heptanedioic acid;

[0902] (2S,6R)-2-amino-6-(3-iodophenoxy) heptanedioic acid;

[0903] (2S,6R)-2-a mi no-6-((3-iodobenzyl)oxy) heptanedioic acid;

[0904] (25.65)-2-amino-6-((3-iodobenzyl)oxy)heptanedioic acid;

[0905] (25.65)-2-amino-6-(3-(3-iodophenyl) propyl) heptanedioic acid; (2S,6R)-2-amino-6-(3-(3-iodophenyl)propyl)heptanedioic acid; (25.65)-2-a mino-6-(3-iodophenethyl) heptanedioic acid;

[0906] (2S,6R)-2-a mino-6-(3-iodophenethyl) heptanedioic acid;

[0907] (25.65)-2-amino-6-(2-(3-iodophenoxy)ethoxy)heptanedioic acid; (2S,6R)-2-amino-6-(2-(3-iodophenoxy)ethoxy)heptanedioic acid; (25.65)-2-amino-6-((4-iodophenoxy)methyl)heptanedioic acid; (2S,6R)-2-amino-6-((4-iodophenoxy)methyl)heptanedioic acid; (25.65)-2-amino-6-(4-(4-iodophenyl)butyl)heptanedioic acid;

[0908] (2S,6R)-2-amino-6-(4-(4-iodophenyl)butyl)heptanedioic acid;

[0909] (25.65)-2-amino-6-(4-(3-iodophenyl)butyl)heptanedioic acid;(2S,6R)-2-amino-6-(4-(3-iodophenyl)butyl)heptanedioic acid;

[0910] (2S,4R)-2-amino-4-(4-iodobenzyl)heptanedioic acid;

[0911] (25.45)-2-amino-4-(4-iodobenzyl)heptanedioic acid;

[0912] (25.45)-2-amino-4-(3-iodobenzyl)heptanedioic acid;

[0913] (2S,4R)-2-amino-4-(3-iodobenzyl)heptanedioic acid;

[0914] (25.65)-2-amino-6-(3-(4-iodophenyl)propyl)heptanedioic acid;

[0915] (2S,6R)-2-amino-6-(3-(4-iodophenyl)propyl)heptanedioic acid;

[0916] (25.65)-2-amino-6-(4-iodophenethoxy) heptanedioic acid;

[0917] (2R,6S)-2-amino-6-(4-iodophenethoxy)heptanedioic acid;

[0918] (2S,6R)-2-amino-6-(4-iodophenethoxy)heptanedioic acid;

[0919] (2R,6R)-2-amino-6-(4-iodophenethoxy) heptanedioic acid;

[0920] (2S,6R)-2-amino-6-(2-((4-(iodo-125I)phenyl)thio)ethyl) heptanedioic acid; (25.65)-2-amino-6-(2-((4-(iodo-125I)phenyl)thio)ethyl) heptanedioic acid; (25.65)-2-amino-6-(3-(fluoro-18F)benzyl)heptanedioic acid;

[0921] (2S,6R)-2-amino-6-(3-(fluoro-18F)benzyl)heptanedioic acid;

[0922] (25.65)-2-amino-6-(3-(iodo-131I) benzyl) heptanedioic acid;

[0923] (2S,6R)-2-amino-6-(3-(iodo-131I)benzyl) heptanedioic acid;

[0924] (25.65)-2-amino-6-(3-((4-(iodo-131I)phenyl)thio)propyl)heptanedioic acid; (2S,6R)-2-amino-6-(3-((4-(iodo-131I)phenyl)thio) propyl)heptanedioic acid; (25.65)-2-amino-6-(3-(3-(iodo-125I)phenyl)propyl)heptanedioic acid; (2S,6R)-2-amino-6-(3-(3-(iodo-125I)phenyl)propyl)heptanedioic acid;

[0925] (25.65)-2-amino-6-(3-(4-(iodo-125I)phenyl)propyl)heptanedioic acid;

[0926] (2S,6R)-2-amino-6-(3-(4-(iodo-125I)phenyl)propyl)heptanedioic acid; (25.65)-2-amino-6-(4-fluoro-3-iodobenzyl) heptanedioic acid;

[0927] (2S,6R)-2-a mi no-6-(4-fluoro-3-iodobenzyl) heptanedioic acid;

[0928] (25.65)-2-amino-6-(3-fluoro-5-iodobenzyl) heptanedioic acid;

[0929] (2S,6R)-2-amino-6-(3-fluoro-5-iodobenzyl) heptanedioic acid;

[0930] (25.65)-2-amino-6-((5-iodopyridin-3-yl) methyl) heptanedioic acid;

[0931] (2S,6R)-2-amino-6-((5-iodopyridin-3-yl)methyl)heptanedioic acid;

[0932] (25.65)-2-amino-6-(4-cyano-3-iodobenzyl) heptanedioic acid;

[0933] (2S,6R)-2-a mino-6-(4-cyano-3-iodobenzyl) heptanedioic acid;

[0934] (2S,6R)-2-amino-6-(2-(3-fluorophenoxy)ethoxy)heptanedioic acid;

[0935] (25.65)-2-amino-6-(2-(3-fluorophenoxy)ethoxy)heptanedioic acid;

[0936] (2R,6R)-2-amino-6-(2-(3-fluorophenoxy)ethoxy)heptanedioic acid;

[0937] (2R,6S)-2-amino-6-(2-(3-fluorophenoxy)ethoxy)heptanedioic acid;

[0938] (25.65)-2-amino-6-(3-iodo-4-methylbenzyl)heptanedioic acid;

[0939] (2S,6R)-2-amino-6-(3-iodo-4-methylbenzyl)heptanedioic acid;

[0940] (25.65)-2-amino-6-(3-(4-(iodo-125I) phenyl) propoxy)heptanedioic acid;(2S,6R)-2-amino-6-(3-(4-(iodo-125I)phenyl) propoxy) heptanedioic acid; (2S,6R)-2-amino-6-(2-(3-(iodo-125I) phenoxy)ethoxy)heptanedioic acid; (25.65)-2-amino-6-(2-(3-(iodo-125I) phenoxy)ethoxy)heptanedioic acid; (2S,4R)-2-amino-4-(3-(iodo-125I)benzyl) heptanedioic acid;

[0941] (25.45)-2-amino-4-(3-(iodo-125I)benzyl)heptanedioic acid;

[0942] (25.65)-2-amino-6-(3-(astato-211-At)benzyl)heptanedioic acid; and (2S,6R)-2-a mi no-6-(3-(astato-211-At) benzyl) heptanedioic acid; and pharmaceutically acceptable salts, solvates or prodrugs of any one thereof.

[0943] In one embodiment, the compound is selected from the group consisting of:

[0944] (2S)-2-amino-7-(4-iodobenzyl)octanedioic acid;

[0945] (2S)-2-amino-6-(4-iodobenzyl)heptanedioic acid;

[0946] (25.45)-2-amino-4-(4-iodobenzyl)heptanedioic acid;

[0947] (2S)-2-amino-7-(((4-iodophenyl)thio)methyl)octanedioic acid;

[0948] (25.65)-2-amino-6-(3-((4-iodophenyl)thio)propyl)heptanedioic acid; (2S,6R)-2-amino-6-(3-((4-iodophenyl)thio)propyl)heptanedioic acid; (2S)-2-amino-6-(3-iodobenzyl)heptanedioic acid;

[0949] (25.65)-2-amino-6-(3-iodobenzyl)heptanedioic acid;

[0950] (2S,6R)-2-amino-6-(3-iodobenzyl)heptanedioic acid;

[0951] (2S)-2-amino-6-(((4-iodophenyl)thio)methyl) heptanedioic acid;

[0952] (2S)-2-amino-6-(3-fluoro-4-iodobenzyl)heptanedioic acid;

[0953] (2S)-2-amino-6-(3-(5-iodo-lH-indazol-l-yl)propyl)heptanedioic acid; (2S)-2-amino-7-(3-((4-iodophenyl)thio)propyl)octanedioic acid;

[0954] (2S)-2-amino-6-(4-iodobenzyl)octanedioic acid;

[0955] (2S)-2-amino-6-((4-iodobenzyl)oxy)heptanedioic acid;

[0956] (2S)-2-amino-6-(2-((4-iodophenyl)thio)ethyl)heptanedioic acid;

[0957] (2S)-2-amino-5-(4-iodobenzyl)heptanedioic acid;

[0958] (25.45)-2-amino-4-(4-iodobenzyl)octanedioic acid;

[0959] (2S)-2-a mi no-6-(4-iodophenoxy) heptanedioic acid;

[0960] (2S)-2-amino-6-(2-((4-iodophenyl)thio)ethoxy)heptanedioic acid;

[0961] (2S)-2-amino-7-(3-iodobenzyl)octanedioic acid;

[0962] (2S)-2-amino-6-(2-fluoro-4-iodobenzyl)heptanedioic acid;

[0963] (2S)-2-a mi no-6-(3-(4-iodophenoxy)propyl) heptanedioic acid;

[0964] (2S)-2-a mi no-6-(2-(4-iodophenoxy)ethyl) heptanedioic acid;

[0965] (2S)-2-a mi no-6-(3-(4-iodophenyl)propoxy) heptanedioic acid;

[0966] (2S)-2-amino-6-(2-(4-iodophenoxy)ethoxy)heptanedioic acid;

[0967] (2S)-2-a mi no-6-(4-(iodo-125I) benzyl) heptanedioic acid;

[0968] (2S)-2-a mi no-6-(3-(iodo-125I) benzyl) heptanedioic acid;(2S)-2-amino-6-(3-((4-(iodo-125I)phenyl)thio)propyl)heptanedioic acid; (2S)-2-amino-6-((4-(iodo-125I)benzyl)oxy)heptanedioic acid;

[0969] (2S)-2-amino-6-(4-fluorobenzyl)heptanedioic acid;

[0970] (2S)-2-amino-6-(2-iodobenzyl)heptanedioic acid;

[0971] (2S)-2-amino-6-(3-fluorobenzyl)heptanedioic acid;

[0972] (2S)-2-amino-6-(4-iodophenethyl)heptanedioic acid;

[0973] (2S)-2-amino-7-(4-fluorobenzyl)octanedioic acid;

[0974] (2S)-2-amino-7-(3-fluorobenzyl)octanedioic acid;

[0975] (2S)-2-a mi no-6-(3-iodophenoxy) heptanedioic acid;

[0976] (2S,6R)-2-amino-6-((3-iodobenzyl)oxy)heptanedioic acid;

[0977] (25.65)-2-amino-6-((3-iodobenzyl)oxy)heptanedioic acid;

[0978] (2S)-2-amino-6-(3-(3-iodophenyl)propyl)heptanedioic acid;

[0979] (2S)-2-amino-6-(3-iodophenethyl)heptanedioic acid;

[0980] (25.65)-2-amino-6-(2-(3-iodophenoxy)ethoxy)heptanedioic acid;

[0981] (2S,6R)-2-amino-6-(2-(3-iodophenoxy)ethoxy)heptanedioic acid;

[0982] 2-amino-6-(4-iodophenethoxy)heptanedioic acid;

[0983] (2S)-2-amino-6-((4-iodophenoxy)methyl)heptanedioic acid;

[0984] (2S)-2-amino-6-(4-(4-iodophenyl)butyl)heptanedioic acid;

[0985] (2S)-2-amino-6-(4-(3-iodophenyl)butyl)heptanedioic acid;

[0986] (2S,4R)-2-amino-4-(4-iodobenzyl)heptanedioic acid;

[0987] (2S,4S)-2-amino-4-(3-iodobenzyl)heptanedioic acid;

[0988] (2S,4R)-2-amino-4-(3-iodobenzyl)heptanedioic acid;

[0989] (2S)-2-amino-6-(3-(4-iodophenyl)propyl)heptanedioic acid;

[0990] (2S)-2-amino-6-(2-((4-(iodo-125I)phenyl)thio)ethyl) heptanedioic acid; (2S)-2-amino-6-(3-(fluoro-18F)benzyl)heptanedioic acid;

[0991] (2S)-2-amino-6-(3-(iodo-131I) benzyl) heptanedioic acid;

[0992] (2S)-2-amino-6-(3-((4-(iodo-131I)phenyl)thio)propyl)heptanedioic acid; (2S)-2-a mi no-6-(3-(3-(iodo-125I)phenyl) propyl) heptanedioic acid;

[0993] (2S)-2-a mi no-6-(3-(4-(iodo-125I) phenyl) propyl)heptanedioic acid;

[0994] (2S)-2-amino-6-(4-fluoro-3-iodobenzyl)heptanedioic acid;

[0995] (2S)-2-amino-6-(3-fluoro-5-iodobenzyl)heptanedioic acid;

[0996] (2S)-2-amino-6-((5-iodopyridin-3-yl)methyl) heptanedioic acid;

[0997] (2S)-2-a mi no-6-(4-cyano-3-iodobenzyl) heptanedioic acid;

[0998] 2-amino-6-(2-(3-fluorophenoxy)ethoxy)heptanedioic acid;

[0999] (2S)-2-amino-6-(3-iodo-4-methylbenzyl)heptanedioic acid;

[1000] (2S)-2-a mi no-6-(3-(4-(iodo-125I) phenyl) propoxy) heptanedioic acid; (2S,6R)-2-amino-6-(2-(3-(iodo-125I) phenoxy)ethoxy)heptanedioic acid; (2S,4R)-2-amino-4-(3-(iodo-125I)benzyl) heptanedioic acid;(25.65)-2-amino-6-(3-(fluoro-18F)benzyl)heptanedioic acid;

[1001] (25.65)-2-amino-6-(3-(iodo-125I)benzyl)heptanedioic acid;

[1002] (25.65)-2-amino-6-(3-(iodo-131I)benzyl)heptanedioic acid; and

[1003] (25.65)-2-amino-6-(3-(astato-211-At)benzyl)heptanedioic acid;

[1004] and pharmaceutically acceptable salts, solvates or prodrugs of any one thereof.

[1005] A third aspect of the invention provides a compound of Formula (PI):

[1006] R1R2O

[1007]

[1008] Y

[1009] Formula (PI)

[1010] or a pharmaceutically acceptable salt, solvate or prodrug thereof, wherein:

[1011] n is 0, 1, 2 or 3;

[1012] m is 1, 2, 3 or 4;

[1013] provided that m+n is 3 or 4;

[1014] when present, R1is hydrogen or C1-C3 alkyl;

[1015] R2is hydrogen or C1-C3 alkyl;

[1016] R3is hydrogen or C1-C3 alkyl;

[1017] L is -O-, -S-, -NR5-, a Ci-Cs straight chained alkylene group, wherein the Ci-Cs straight chained alkylene group optionally includes one, two or three heteroatoms each independently selected from 0, S and NR6in its carbon skeleton, or L is a group -L1-B-L2-, wherein L1and L2are each independently a bond or a C1-C3 straight chained alkylene group, wherein B is a saturated cyclic group selected from a C3-C6 cycloalkyl group, or a 3-, 4-, 5- or 6- membered saturated monocyclic heterocyclic group; wherein L is optionally substituted with one or more substituents independently selected from fluoro, hydroxyl, oxo (=0), C1-C3 alkyl, -0-(Ci-C3 alkyl), -0-(Ci-C3 fluoroalkyl), or C1-C3 fluoroalkyl, and wherein L optionally includes one or more spirocyclic groups, wherein the spirocyclic group is selected from a C3-C5 cycloalkyl group or a saturated C3-C5 heterocyclic group;

[1018] A is phenyl, naphthyl, or a 5- to 10-membered heteroaryl group;

[1019] p is 0, 1, or 2;

[1020] R4is halo, -OH, -NH2, -SH, cyano, or a Ci-Cs saturated or unsaturatedhydrocarbyl group, wherein the hydrocarbyl group may be straight chained or branched, or be or include a cyclic group, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, 0 and S in its carbon skeleton, and wherein any -S- moiety in the hydrocarbyl group may optionally be substituted with one or two groups each independently selected from oxo (=0) and =NH to form a -SO-, -SO2-, -S( = NH)- or -SO( = NH)-moiety;

[1021] R5is hydrogen, C1-C3 alkyl, or C2-C3 alkylene-OR7;

[1022] R6is C1-C3 alkyl, or C2-C3 alkylene-OR7;

[1023] R7is hydrogen or methyl;

[1024] each R8is independently hydrogen or a carboxyl protecting group;

[1025] R9and R10are each independently hydrogen or a nitrogen protecting group; and

[1026] Y is a leaving group.

[1027] The compounds of formula (PI) are synthetic precursors to the compounds of Formula (III) and (IIIA) described herein.

[1028] In one embodiment, n is 0 or 1. In one embodiment, n is 0. In one embodiment, n is 1. In one embodiment, n is 2. In one embodiment, n is 3.

[1029] In one embodiment, m is 1. In one embodiment, m is 2. In one embodiment, m is 3. In one embodiment, m is 4.

[1030] In one embodiment, m+n is 3. Typically, in this embodiment, n is 0 and m is 3, n is 1 and m is 2, or n is 2 and m is 1. Typically, n is 0 and m is 3, or n is 1 and m is 2. More typically still, n is 0 and m is 3.

[1031] In one embodiment, m+n is 4. Typically, in this embodiment, n is 0 and m is 4, n is 1 and m is 3, n is 2 and m is 2, or n is 3 and m is 1. Typically, n is 0 and m is 4, n is 1 and m is 3, or n is 3 and m is 1. More typically, n is 0 and m is 4, or n is 1 and m is 3. More typically still, n is 0 and m is 4.

[1032] For the avoidance of doubt, it is noted that when n is 0, the group R1is not present.

[1033] In one embodiment, each R1is independently hydrogen or C1-C2 alkyl. Typically, each R1is independently hydrogen, methyl, or ethyl. More typically, each R1is independently hydrogen or methyl. More typically still, each R1is hydrogen.In one embodiment, each R2is independently hydrogen, methyl, or ethyl. Typically, each R2is independently hydrogen or methyl. In one embodiment, each R2is hyd rogen.

[1034] In one embodiment, R3is hydrogen, methyl, or ethyl. Typically, R3is hydrogen or methyl. In one embodiment, R3is hydrogen.

[1035] In one embodiment, each R2is independently hydrogen or methyl, and R3is hydrogen or methyl. In one embodiment, each R2is hydrogen and R3is hydrogen.

[1036] In one embodiment, each R1is independently hydrogen or methyl and R3is hydrogen or methyl. In one embodiment, each R1is hydrogen and R3is hydrogen.

[1037] In one embodiment, each R1is independently hydrogen or methyl, each R2is independently hydrogen or methyl, and R3is hydrogen or methyl. In one embodiment, each R1is hydrogen, each R2is hydrogen, and R3is hydrogen.

[1038] For the avoidance of doubt, when it is stated that L is a group -L1-B-L2-, it will be understood to mean that -L1and -L2are attached to different atoms of the cyclic group B.

[1039] For the avoidance of doubt, when it is stated that L optionally includes one or more spirocyclic groups, it will be understood to mean that any methylene (-CH2) group in a alkylene chain of L may be substituted by a cyclic group, such that the resultant group H

[1040] is a spirocyclic group, such as X

[1041]

[1042] X, X X, / , or X X / . Thus, for the avoidance of doubt, when a spirocyclic group is described as being, for example, a

[1043] cyclopropyl group, it will be understood to mean the group:.

[1044] In one embodiment, R5is hydrogen, methyl, ethyl, propyl, -CH2CH2OH, -CH2CH2CH2OH, -CF CFhOMe, or -CH₂CH₂CH₂OMe. Typically, R5is hydrogen, methyl, or ethyl. More typically, R5is hydrogen or methyl.

[1045] In one embodiment, R6is methyl, ethyl, propyl, -CH2CH2OH, -CH2CH2CH2OH, -CF CF OMe, or -CH₂CH₂CH₂OMe. Typically, R6is methyl or ethyl. More typically, R6is methyl.In one embodiment, L is a group -L1-B-L2-, wherein L1and L2are each independently a bond or a C1-C3 alkylene group, and wherein B is a saturated cyclic group selected from a C3-C6 cycloalkyl group, or a 3-, 4-, 5- or 6- membered saturated monocyclic heterocyclic group (comprising, for example, one or two heteroatoms independently selected from N, 0 or S in the ring structure), wherein L is optionally substituted. Typically, in this embodiment, -L1and -L2are each independently a bond, -CH2- or -CH2CH2-, and B is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxiranyl, aziridinyl, azetidinyl, oxetanyl, thietanyl, pyrrolidinyl, tetra hydrofuranyl, tetrahydrothiophenyl, pyrazolidinyl, dioxolanyl, oxathiolanyl, piperidinyl, tetrahydropyranyl, thianyl, piperazinyl, dioxanyl, morpholinyl, or thiomorpholinyl. Typically, in this embodiment, L is optionally substituted with one or more substituents independently selected from fluoro, hydroxyl, oxo (=0), C1-C3 alkyl, -O-(Ci-C3 alkyl), -O-(Ci-C3 fluoroalkyl), or Ci-C3 fluoroalkyl, and wherein L optionally includes one or more (such as one or two) spirocyclic groups, wherein the spirocyclic group is selected from a C3-C5 cycloalkyl group or a saturated C3-C5 heterocyclic group. Typically, the spirocyclic group is a cyclopropyl, cyclobutyl, cyclopentyl, oxiranyl, aziridinyl, azetidinyl, oxetanyl, thietanyl, pyrrolidinyl, tetra hydrofuranyl, tetrahydrothiophenyl, dioxolanyl, or oxathiolanyl group. More typically, the spirocyclic group is a cyclopropyl, cyclobutyl, cyclopentyl, oxiranyl, aziridinyl, azetidinyl, or oxetanyl group.

[1046] In one embodiment, -L1and -L2are each independently a bond or -CH2, and B is cyclopropyl, cyclobutyl, azetidinyl, or oxetanyl, each of which is optionally substituted with one or more substituents independently selected from fluoro, hydroxyl, oxo (=0), methyl, ethyl, methoxy, ethoxy, -CF3, CHF2, CH2F, -OCF3, -OCHF2, or -OCH2F.

[1047] Typically in this embodiment, B is cyclopropyl, cyclobutyl, azetidinyl (such as azetidin-1-yl or azetidin-3-yl) or oxetanyl (such as oxetan-2-yl or oxetan-3-yl). Typically, in this embodiment, B is cyclobutyl or azetidinyl.

[1048] In another embodiment, L is -0-, -S-, -NR5-, or a Ci-Ce straight chained alkylene group, wherein the Ci-Ce straight chained alkylene group optionally includes one, two or three heteroatoms each independently selected from 0, S and NR6in its carbon skeleton, and wherein the Ci-Ce straight chained alkylene group may optionally be substituted.

[1049] In one embodiment, L is -0-, -S-, or a Ci-Ce straight chained alkylene group, wherein the Ci-Ce straight chained alkylene group optionally includes one, two or three heteroatoms each independently selected from 0 and S in its carbon skeleton, and wherein the Ci-Ce straight chained alkylene group may optionally be substituted.In one embodiment, L is -O-, -S-, or a Ci-Ce straight chained alkylene group, wherein the Ci-Ce straight chained alkylene group optionally includes one or two heteroatoms each independently selected from 0 and S in its carbon skeleton, and wherein the Ci-Ce straight chained alkylene group may optionally be substituted.

[1050] In one embodiment, L is -O-, -S-, or a C1-C4 straight chained alkylene group, wherein the C1-C4 straight chained alkylene group optionally includes one, two or three heteroatoms each independently selected from 0 and S in its carbon skeleton, and wherein the C1-C4 straight chained alkylene group may optionally be substituted.

[1051] In one embodiment, L is -O-, -S-, or a C1-C4 straight chained alkylene group, wherein the C1-C4 straight chained alkylene group optionally includes one or two heteroatoms each independently selected from 0 and S in its carbon skeleton, and wherein the Ci-C4 straight chained alkylene group may optionally be substituted.

[1052] In one embodiment, L is -O-, -S-, or a C1-C3 straight chained alkylene group, wherein the C1-C3 straight chained alkylene group optionally includes one or two heteroatoms each independently selected from 0 and S in its carbon skeleton, and wherein the Ci-C3 straight chained alkylene group may optionally be substituted.

[1053] In one embodiment, L is -O-, -S-, or a C1-C3 straight chained alkylene group, wherein the C1-C3 straight chained alkylene group is optionally substituted.

[1054] In another embodiment, L is a C2-C3 straight chained alkylene group, wherein the C2-C3 straight chained alkylene group includes one or two heteroatoms each independently selected from 0 and S in its carbon skeleton, and wherein the C2-C3 straight chained alkylene group may optionally be substituted. Typically, in this embodiment, when L is a C2 straight chained alkylene group, the C2 straight chained alkylene group includes one heteroatom independently selected from 0 and S in its carbon skeleton, and when L is a C3 straight chained alkylene group, the C3 straight chained alkylene group includes one or two heteroatoms independently selected from 0 and S in its carbon skeleton.

[1055] The straight chained alkylene group, such as the Ci-Ce, C1-C4, or C1-C3 straight chained alkylene group described above, may optionally be substituted with one or more (such as one, two, three, or four) substituents independently selected from fluoro, hydroxyl, oxo (=0), methyl, ethyl, methoxy, ethoxy, fluoromethyl, fluoroethyl, -O-(fluoromethyl), or -O-(fluoroethyl), and wherein the Ci-Ce, C1-C4, or C1-C3 straight chained alkylene group optionally includes one or more (such as one or two)spirocyclic groups, wherein the spirocyclic group is selected from a C3-C5 cycloalkyl group or a saturated C3-C5 heterocyclic group. Typically, the spirocyclic group is a cyclopropyl, cyclobutyl, cyclopentyl, oxiranyl, aziridinyl, azetidinyl, oxetanyl, thietanyl, pyrrolidinyl, tetra hydrofuranyl, tetrahydrothiophenyl, dioxolanyl, or oxathiolanyl group. More typically, the spirocyclic group is a cyclopropyl, cyclobutyl, oxiranyl, aziridinyl, azetidinyl, or oxetanyl group.

[1056] In one embodiment, the Ci-Ce, C1-C4, or C1-C3 straight chained alkylene group may optionally be substituted with one or two substituents independently selected from fluoro, hydroxyl, oxo (=0), methyl, ethyl, methoxy, ethoxy, fluoromethyl, fluoroethyl, -O-(fluoromethyl), or -O-(fluoroethyl), and wherein the C1-C12, Ci-Ce, C1-C4, or C1-C3 straight chained alkylene group optionally includes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl, cyclobutyl, oxiranyl, aziridinyl, azetidinyl, or oxetanyl group.

[1057] In one embodiment, the, Ci-Ce, C1-C4, or C1-C3 straight chained alkylene group may optionally be substituted with one or two substituents independently selected from fluoro, hydroxyl, oxo (=0), methyl, ethyl, methoxy, -CF3, CHF2, CH2F, -OCF3, -OCHF2, -OCH2F, and wherein the Ci-Ce, C1-C4, or C1-C3 straight chained alkylene group optionally includes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl, cyclobutyl, oxiranyl, aziridinyl, azetidinyl, or oxetanyl group.

[1058] In one embodiment, the Ci-Ce, C1-C4, or C1-C3 straight chained alkylene group may optionally be substituted with one substituent independently selected from fluoro, hydroxyl, methyl, methoxy, -CF3, CHF2, CH2F, -OCF3, -OCHF2, -OCH2F, and wherein the Ci-Ce, C1-C4, or C1-C3 straight chained alkylene group optionally includes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl, or cyclobutyl group.

[1059] In one embodiment, L is -0-, -S-, or a Ci-Ce straight chained alkylene group, wherein the Ci-Ce straight chained alkylene group optionally includes one or two heteroatoms each independently selected from 0 and S in its carbon skeleton. In one embodiment, L is -0-, -S-, or a C1-C4 straight chained alkylene group, wherein the C1-C4 straight chained alkylene group optionally includes one or two heteroatoms each independently selected from 0 and S in its carbon skeleton. In one embodiment, L is -0-, -S-, or a C1-C3 straight chained alkylene group, wherein the C1-C3 straight chained alkylene group optionally includes one or two heteroatoms each independently selected from 0 and S in its carbon skeleton.In one embodiment, L is -O-, -S-, -NR5-, -CH2-, -CH2CH2-, -CH2CH2CH2-, -CH2CH2CH2CH2-, -CH2CH2CH2CH2CH2-, -CH2CH2CH2CH2CH2CH2-, -CH2O-, -CH2S-, -CH2NR6-, -OCH2-, -OCH2O-, -OCH2S-, -OCH2NR6-, -OCH2CH2-, -OCH2CH2O-, -OCH2CH2S-, -OCH2CH2NR6-, -CH2CH2O-, -CH2CH2S-, -CH2CH2NR6-, -OCH2CH2CH2-, -OCH2CH2CH2O-, -OCH2CH2CH2S-, -OCH2CH2CH2NR6-, -OCH2CH2CH2CH2-, -OCH2CH2CH2CH2CH2-, -OCH2CH2CH2CH2CH2CH2-, -SCH2-, -SCH2O-, -SCH2S-, -SCH2NR6-, -SCH2CH2-, -SCH2CH2S-, -SCH2CH2O-, -SCH2CH2NR6-, -SCH2CH2CH2-, -SCH2CH2CH2O-, -SCH2CH2CH2S-, -SCH2CH2CH2NR5-, -SCH2CH2CH2CH2-, -SCH2CH2CH2CH2CH2-, -SCH2CH2CH2CH2CH2CH2-, -NR6CH2-, -NR6CH2O-, -NR6CH2S-, -NR6CH2NR6-, -NR6CH2CH2-, -NR6CH2CH2NR6-, -NR6CH2CH2O-, -NR6CH2CH2S-, -NR6CH2CH2CH2-, -NR6CH2CH2CH2NR6-, -NR6CH2CH2CH2O-, -NR6CH2CH2CH2S-, -NR6CH2CH2CH2CH2-, -NR6CH2CH2CH2CH2CH2-, -NR6CH2CH2CH2CH2CH2CH2-, -CH2OCH2, -CH2OCH2CH2-, -CH2CH2OCH2-, -CH2CH2CH2O-, -CH2SCH2-, -CH2SCH2CH2-, -CH2CH2SCH2-, -CH2CH2CH2S-, -CH2NR6CH2-, -CH2NR6CH2CH2-, -CH2CH2NR6CH2-, -CH2CH2CH2NR6, -CH2OCH2CH2CH2-, -CH2CH2OCH2CH2-, -CH2CH2CH2OCH2-, -CH2CH2CH2CH2O-, -CH2SCH2CH2CH2-, -CH2CH2SCH2CH2-, -CH2CH2CH2SCH2-, -CH2CH2CH2CH2S-, -CH2NR6CH2CH2CH2-, -CH2CH2NR6CH2CH2-, -CH2CH2CH2NR6CH2-, -CH2CH2CH2CH2NR5-, -CH2OCH2CH2CH2CH2-, -CH2CH2OCH2CH2CH2-, -CH2CH2CH2OCH2CH2-, -CH2CH2CH2CH2OCH2-, -CH2CH2CH2CH2CH2O-, -CH2SCH2CH2CH2CH2-, -CH2CH2SCH2CH2CH2-, -CH2CH2CH2SCH2CH2-, -CH2CH2CH2CH2SCH2-, -CH2CH2CH2CH2CH2S-, -CH2NR6CH2CH2CH2CH2-, -CH2CH2NR6CH2CH2CH2-, -CH2CH2CH2NR6CH2CH2-, -CH2CH2CH2CH2NR6CH2-, -CH2CH2CH2CH2CH2NR6-, -CH2OCH2CH2CH2CH2CH2-, -CH2CH2OCH2CH2CH2CH2-, -CH2CH2CH2OCH2CH2CH2-, -CH2CH2CH2CH2OCH2CH2-, -CH2CH2CH2CH2CH2OCH2-, -CH2CH2CH2CH2CH2CH2O-, -CH2SCH2CH2CH2CH2CH2-,-CH2CH2SCH2CH2CH2CH2-, -CH2CH2CH2SCH2CH2CH2-, -CH2CH2CH2CH2SCH2CH2-,-CH2CH2CH2CH2CH2SCH2-, -CH2CH2CH2CH2CH2CH2S-, -CH2NRSCH2CH2CH2CH2CH2-, -CH2CH2NRSCH2CH2CH2CH2-, -

[1060]

[1061] CH2CH2CH2NRSCH2CH2CH2-, -CH2CH2CH2CH2NRSCH2CH2-, -CH2CH2CH2CH2CH2NR6CH2-, or -CH2CH2CH2CH2CH2CH2N5-, wherein each is optionally substituted. Typically, in this embodiment, L is optionally substituted with one or two substituents independently selected from fluoro, hydroxyl, methyl, methoxy, -CF3, CHF2, CH2F, -OCF3, -OCHF2, or -OCH2F, and wherein L optionally includes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl, cyclobutyl, oxiranyl, aziridinyl, azetidinyl, or oxetanyl group.

[1062] More typically, in this embodiment, L is optionally substituted with one substituent independently selected from fluoro, hydroxyl, or methyl, and wherein L optionallyincludes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl or cyclobutyl group.

[1063] In one embodiment, L is -O-, -S-, -CH2-, -CH2CH2-, -CH2CH2CH2-, -CH2CH2CH2CH2-, -CH2CH2CH2CH2CH2-, -CH2CH2CH2CH2CH2CH2-, -CH2O-, -CH2S-, -OCH2-, -OCH2O-, -OCH2S-, -OCH2CH2-, -OCH2CH2O-, -OCH2CH2S-, -CH2CH2O-, -CH2CH2S-, -OCH2CH2CH2-, -OCH2CH2CH2O-, -OCH2CH2CH2S-, -OCH2CH2CH2CH2-, -OCH2CH2CH2CH2CH2-, -OCH2CH2CH2CH2CH2CH2-, -SCH2-, -SCH2O-, -SCH2S-, -SCH2CH2-, -SCH2CH2S-, -SCH2CH2O-, -SCH2CH2CH2-, -SCH2CH2CH2O-, -SCH2CH2CH2S-, -SCH2CH2CH2CH2-, -SCH2CH2CH2CH2CH2-, -SCH2CH2CH2CH2CH2CH2-, -CH2OCH2-, -CH2OCH2CH2-, -CH2CH2OCH2-, -CH2CH2CH2O-, -CH2SCH2-, -CH2SCH2CH2-, -CH2CH2SCH2-, -CH2CH2CH2S-, -CH2OCH2CH2CH2-, -CH2CH2OCH2CH2-, -CH2CH2CH2OCH2-, -CH2CH2CH2CH2O-, -CH2SCH2CH2CH2-, -CH2CH2SCH2CH2-, -CH2CH2CH2SCH2-, -CH2CH2CH2CH2S-, -CH2OCH2CH2CH2CH2-, -CH2CH2OCH2CH2CH2-, -CH2CH2CH2OCH2CH2-, -CH2CH2CH2CH2OCH2-, -CH2CH2CH2CH2CH2O-, -CH2SCH2CH2CH2CH2-, -CH2CH2SCH2CH2CH2-, -CH2CH2CH2SCH2CH2-, -CH2CH2CH2CH2SCH2-, -CH2CH2CH2CH2CH2S-, -CH2OCH2CH2CH2CH2CH2-, -CH2CH2OCH2CH2CH2CH2-, -CH2CH2CH2OCH2CH2CH2-, -CH2CH2CH2CH2OCH2CH2-, -CH2CH2CH2CH2CH2OCH2-, -CH2CH2CH2CH2CH2CH2O-, -CH2SCH2CH2CH2CH2CH2-, -CH2CH2SCH2CH2CH2CH2-, -CH2CH2CH2SCH2CH2CH2-, -CH2CH2CH2CH2SCH2CH2-, -CH2CH2CH2CH2CH2SCH2-, or -CH2CH2CH2CH2CH2CH2S-, wherein each is optionally substituted. Typically, in this embodiment, L is optionally substituted with one substituent independently selected from fluoro, hydroxyl, oxo (=0), methyl, methoxy, -CF3, CHF2, CH2F, -OCF3, -OCHF2, or -OCH2F, and wherein L optionally includes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl or cyclobutyl group. More typically, L is optionally substituted with one substituent independently selected from fluoro, hydroxyl, or methyl, and wherein L optionally includes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl or cyclobutyl group.

[1064] In one embodiment, L is -0-, -S-, -CH2-, -CH2CH2-, -CH2CH2CH2-, -CH2CH2CH2CH2-, -CH2O-, -CH2S-, -OCH2-, -OCH2CH2-, -OCH2CH2O-, -OCH2CH2S-, -CH2CH2O-, -CH2CH2S-, -OCH2CH2CH2-, -OCH2CH2CH2O-, -OCH2CH2CH2S-, -SCH2-, -SCH2CH2-, -SCH2CH2S-, -SCH2CH2O-, -SCH2CH2CH2-, -SCH2CH2CH2O-, -SCH2CH2CH2S-, -CH2OCH2-, -CH2SCH2-, -CH2OCH2CH2-, -CH2CH2OCH2-, -CH2CH2CH2O-, -CH2CH2CH2S-, -CH2SCH2-, -CH2SCH2CH2-, -CH2CH2SCH2-, or -CH2CH2CH2S-, wherein each is optionally substituted. Typically, in this embodiment, L is optionally substituted with one substituent independently selected from fluoro, hydroxyl, oxo (=0), methyl, methoxy, -CF3, CHF2, CH2F, -OCF3, -OCHF2, or -OCH2F, and wherein L optionallyincludes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl or cyclobutyl group. More typically, L is optionally substituted with one substituent independently selected from fluoro, hydroxyl, or methyl, and wherein L optionally includes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl or cyclobutyl group.

[1065] In one embodiment, L is -O-, -S-, -CH2-, -CH2CH2-, -CH2CH2CH2-, -CH2CH2CH2CH2-, -CH2O-, -CH2S-, -OCH2-, -OCH2CH2-, -OCH2CH2O-, -OCH2CH2S-, -CH2CH2O-, -CH2CH2S-, -OCH2CH2CH2-, -OCH2CH2CH2O-, -OCH2CH2CH2S-, -SCH2-, -SCH2CH2-, -SCH2CH2S-, -SCH2CH2O-, -SCH2CH2CH2-, -SCH2CH2CH2O-, -SCH2CH2CH2S-, -CH2OCH2-, -CH2OCH2CH2-, -CH2CH2OCH2-, -CH2CH2CH2O-, -CH2SCH2-, -CH2SCH2CH2-, -CH2CH2SCH2-, or -CH2CH2CH2S-, wherein each is optionally substituted. Typically, in this embodiment, L is optionally substituted with one substituent independently selected from fluoro, hydroxyl, oxo (=0), methyl, methoxy, -CF3, CHF2, CH2F, -OCF3, -OCHF2, or -OCH2F, and wherein L optionally includes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl or cyclobutyl group. More typically, L is optionally substituted with one substituent independently selected from fluoro, hydroxyl, or methyl, and wherein L optionally includes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl or cyclobutyl group.

[1066] In one embodiment, L is -0-, -S-, -CH2-, -CH2S-, -CH2O-, -OCH2-, -CH2CH2-, -CH2CH2CH2-, -CH2CH2CH2CH2-, -OCH2CH2-, -OCH2CH2O-, -OCH2CH2S-, -CH2SCH2-, -CH2CH2O-, -CH2CH2S- -OCH2CH2CH2-, -CH2CH2CH2O-, or -CH2CH2CH2S-.

[1067] In one embodiment, L is -0-, -S-, -CH2-, -CH2S-, -OCH2-, -CH2CH2CH2-, -OCH2CH2O-, -OCH2CH2S-, -CH2CH2O-, -CH2CH2S- -OCH2CH2CH2-, -CH2CH2CH2O-, or -CH2CH2CH2S-. Typically, L is -0-, -CH2-, -OCH2-, -CH2CH2CH2-, or -CH2CH2CH2S-.

[1068] In one embodiment, L is -CH2-.

[1069] In one embodiment, A is phenyl, naphthyl, pyrrolyl, furanyl, thiophenyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, oxadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, indolizinyl, indazolyl, benzimidazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, quinazolinyl, or naphthyridinyl.

[1070] Typically, A is phenyl, naphthyl, or a 6- to 10-membered heteroaryl group.In one embodiment, A is phenyl, naphthyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, indolizinyl, indazolyl, benzimidazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, quinazolinyl, or naphthyridinyl. Typically, A is phenyl, pyridinyl, indazolyl, benzimidazolyl, quinolinyl, or isoquinolinyl. More typically, A is phenyl or indazolyl.

[1071] In one embodiment, A is indazolyl, optionally indazol-l-yl.

[1072] In one embodiment, A is phenyl. Typically, in this embodiment, the group Y is in the para or meta position of the phenyl ring. In one embodiment, A is phenyl, and Y is in the para position. In another embodiment, A is phenyl, and Y is in the meta position. For the avoidance of doubt, it is noted that when p is 0, the group R4is not present. In one embodiment, p is 0 or 1. In one embodiment, p is 1. In another embodiment, p is 0.

[1073] In one embodiment, each R4is independently halo, -OH, -NH2, -SH, cyano, or a Ci-Ce saturated or unsaturated hydrocarbyl group which may be straight chained or branched, or be or include a cyclic group, and may optionally be substituted with one or more (such as one, two, three or four) halo groups, and where the hydrocarbyl group may optionally include one or two heteroatoms each independently selected from N, 0 and S in its carbon skeleton, and any -S- moiety when present in the hydrocarbyl group may optionally be substituted with one or two groups each independently selected from oxo (=0) and =NH to form a -SO-, -SO2-, -S( = NH)- or -SO( = NH)- moiety.

[1074] In one embodiment, each R4is independently halo, -OH, -NH2, -SH, cyano, C1-C5 alkyl, -O-(Ci-C5 alkyl), -C3-C5 cycloalkyl, -O(C3-C5 cycloalkyl), C3-C5 heterocycloalkyl, -O(C3-Cs heterocycloalkyl), -NH(Ci-Cs alkyl), -N(Ci-Cs alkyl)2, -NH-SO2(CI-CS alkyl), -NH(CO)(Ci-Cs alkyl), or -S(Ci-Cs alkyl), wherein any alkyl group may be optionally substituted by one or more substituents independently selected from halo, OH, OMe, cyclopropyl, or cyclobutyl.

[1075] In one embodiment, each R4is independently fluoro, chloro, bromo, iodo, -OH, -NH2, -SH, cyano, C1-C4 alkyl, -O-(Ci-C4 alkyl), C3-C4 cycloalkyl, -O(C3-C4 cycloalkyl), C3-C4 heterocycloalkyl, -O(C3-C4 heterocycloalkyl), -NH(CI-C4 alkyl), -N(CI-C4 alkyl)2, -NH-SO2(Ci-C4 alkyl), -NH-SO2(CI-C4 haloalkyl), -NH(CO)(CI-C4 alkyl), or -S(Ci-C4 alkyl), wherein any alkyl group may be optionally substituted by one or more substituents selected from fluoro, OH, OMe, cyclopropyl, or cyclobutyl.In one embodiment, each R4is independently fluoro, chloro, bromo, iodo, cyano, C1-C4 alkyl optionally C3-C4 alkyl, -O-(Ci-C4 alkyl) optionally -O-(Cs-C4 alkyl), C3-C4 cycloalkyl, -O(C3-C4 cycloalkyl), C3-C4 heterocycloalkyl, -O(C3-C4 heterocycloalkyl), or -S(Ci-C4 alkyl), wherein any alkyl group may be optionally substituted by one or more substituents selected from fluoro, OH, OMe, cyclopropyl, or cyclobutyl.

[1076] In one embodiment, each R4is independently fluoro, chloro, bromo, iodo, cyano, methyl, ethyl, propyl (such as n-propyl or i-propyl), butyl (such as n-butyl, i-butyl, t-butyl), methoxy, ethoxy, propoxy, butoxy, cyclopropyl, cyclobutyl, -O-cyclopropyl, -O-cyclobutyl, -SMe, or -SEt. Typically, each R4is independently fluoro, iodo, cyano, methyl, ethyl, -OMe, -CH2CHCH3CH3, -OCH2CHCH3CH3, -OCH2CH2CH2CH3, -0-cyclobutyl, -OCH2-cyclobutyl, cyclopropyl, -CH2-cyclopropyl, -O-cyclopropyl, -OCH2-cyclopropyl, or -SMe.

[1077] In one embodiment, each R4is independently fluoro, cyano, methyl, -CH2CHCH3CH3, -OCH2CHCH3CH3, -OCH2CH2CH2CH3, -O-cyclobutyl, -OCH2-cyclobutyl, or cyclopropyl.

[1078] In one embodiment, p is 1, and R4is fluoro, cyano, methyl, -CH2CHCH3CH3, -0-CH2CHCH3CH3, -OCH2CH2CH2CH3, -O-cyclobutyl, -O-CH2-cyclobutyl, or cyclopropyl. In one embodiment, p is 1, and R4is fluoro, cyano or methyl. In one embodiment, p is 1, and R4is fluoro.

[1079] Each R8is independently hydrogen or a carboxyl protecting group. In one embodiment, each R8is hydrogen.

[1080] In one embodiment, one R8is hydrogen and the other R8is a carboxyl protecting group.

[1081] In one embodiment, each R8is a carboxyl protecting group. Suitable carboxyl protecting groups may be identified by reference to e.g. Wuts, " Greene's Protective Groups in Organic Synthesis", 5thEd., 2014.

[1082] For example, the carboxyl protecting group may be an ester. In one embodiment, each R8is independently methyl, ethyl, propyl (including / so-propyl and n-propyl), butyl (including n-butyl, tert-butyl and sec-butyl) or benzyl.

[1083] In one embodiment, each R8is independently methyl, ethyl, / so-propyl, tert-butyl or benzyl.In one embodiment, each R8is independently methyl, tert-butyl, or benzyl.

[1084] In one embodiment, each R8is independently methyl or tert-butyl. In one embodiment, each R8is independently tert-butyl.

[1085] In one embodiment, one R8is hydrogen and the other R8is tert-butyl.

[1086] R9and R10are each independently hydrogen or a nitrogen protecting group.

[1087] In one embodiment, R9and R10are hydrogen. In one embodiment, one of R9and R10is hydrogen, and the other of R9and R10is a nitrogen protecting group.

[1088] In one embodiment, each R9and R10are independently a nitrogen protecting group.

[1089] Suitable nitrogen protecting groups may be identified by reference to e.g. Wuts, " Greene's Protective Groups in Organic Synthesis", 5thEd., 2014.

[1090] In one embodiment, each R9and R10are independently benzyloxycarbonyl (CBz), 4-methoxy-benzyloxycarbonyl, benzyl, tert-butoxycarbonyl (Boc), 2-(4-biphenylyl)-isopropoxycarbonyl (Bpoc), triphenylmethyl (Trt), or 2,2,2-trichloroethoxycarbonyl (Troc) protecting groups. In another embodiment, each R9and R10are independently a sulfonyl group, such as a toluenesulfonyl (tosyl or -Ts), methanesulfonyl (mesyl or-Ms), or a trifluoromethanesulfonyl (triflyl or -Tf) group.

[1091] In one embodiment, each R9and R10are independently benzyloxycarbonyl (CBz), benzyl, or tert-butoxycarbonyl (Boc) groups.

[1092] In one embodiment, each R9and R10are tert-butoxycarbonyl (Boc) groups.

[1093] In one embodiment, one of R9and R10is hydrogen and the other of R9and R10is a tert-butoxycarbonyl (Boc) group.

[1094] Y is a leaving group. As used herein, the term "leaving group" describes a group suitable to act as such in reactions to halogenate an aryl or heteroaryl ring with one of the halogen radioisotopes described herein (e.g.,18F,123I,124I,125I,131I, and211At). For example, the leaving groups described herein are suitable for use in radiohalogenation reactions, for example, nucleophilic halogenation reactions or electrophilic halogenation reactions. The term leaving group is defined in: IUPAC.Compendium of chemical terminology, 2nd ed. (the "gold book"). Compiled by a. D. Mcnaught and a. Wilkinson. Blackwell scientific publications, Oxford (1997). Online version (2019-) created by s. J. Chalk. ISBN 0-9678550-9-8. https: / / doi.org / 10.1351 / goldbook. The leaving groups described herein are suitable for use, for example, in radioiodination reactions and / or radiofluorination reactions and / or radioastatination reactions. Typical reactions include, for example, nucleophilic aromatic substitution reactions, electrophilic aromatic substitution reactions, and reactions mediated by metals, such as transition metals.

[1095] For example, the leaving group may be a cross coupling leaving group. As used herein, the term "cross coupling" refers to a cross coupling reaction in which two fragments are joined together. Typically, the cross coupling reaction is metal catalysed.

[1096] Suitable leaving groups for the compounds of Formula (Pl) described herein include, for example, boronic esters, boronic acids, sulfonates, trialkylamines, organostannanes, organosilicates, aryliodonium salts, and arylsulfonium salts.

[1097] In one embodiment, Y is selected from a boronic ester, boronic acid, alkylsulfonate, arylsulfonate, trialkylamine, organostannane, organosilicate, aryliodonium salt, and an arylsulfonium salt.

[1098] In one embodiment, Y is selected from a boronic ester, boronic acid, trialkylamine, organostannane, aryliodonium salt, and an arylsulfonium salt.

[1099] In one embodiment, Y is selected from a boronic ester, boronic acid, and an organostannane.

[1100] In one embodiment, Y is selected from a boronic ester or boronic acid. In one embodiment, Y is -B(OH)2, -BPin (boronic acid pinacol ester), -BMIDA (boronic acid MIDA ester) or -BCat (boronic acid catechol ester.

[1101] In one embodiment, Y -BPin (boronic acid pinacol ester). For the avoidance of doubt, the term "-BPin", as used herein, refers to a boronic acid pinacol ester group, which may act as a leaving group. That is, the group:

[1102]

[1103] In one embodiment, Y is an organostannane. In one embodiment, Y is Sn(Ci-Ce alkyl)3. In one embodiment, Y is SnMes or SnBu3. In one embodiment, Y is SnBu3. In one embodiment, Y is a sulfonate.

[1104] In one embodiment, Y is an alkylsulfonate. In one embodiment, Y is mesylate (methanesulfonate) or triflate (trifluoromethanesulfonate).

[1105] In one embodiment, Y is an arylsulfonate. In one embodiment, Y is tosylate (toluenesulfonate).

[1106] In one embodiment, Y is a trialkylamine. In one embodiment, Y is -+NMe3.

[1107] In one embodiment, Y is an aryliodonium salt. In one embodiment, Y is -[Phl]+[D]_, wherein D is BF4, OTs, OTf, OMs, Cl, I, Br, AcO, or CF3C(O)O.

[1108] In one embodiment, Y is -[Phl]+BF4-, -[Phl]+OTs_, or -[Phl]+OTf_. For the avoidance of doubt, the term "-[Phl]+BF4-", as used herein, refers to a phenyliodonium tetrafluoroborate group, which may act as a leaving group. That is, the group:

[1109]

[1110] In one embodiment, Y is an arylsulfonium salt. On one embodiment, Y is -[Ph2S]+TfO_. For the avoidance of doubt, the term "-[Ph2S]+TfO ", as used herein, refers to a diarylsulfonium triflate group, which may act as a leaving group. That is, the group:

[1111] ©

[1112] OTf

[1113] S

[1114]

[1115] In one embodiment, Y is -BPin, -B(OH)2, -[Phl]+BF4-, -[Ph2S]+TfO_, -SnMes, -SnBu3, or -+NMe3.

[1116] In one embodiment, Y is -BPin, -B(OH)2, -SnMes, or -SnBu3. In one embodiment, Y is -BPin, -B(OH)2, or -SnBu3.

[1117] In one embodiment, Y is -BPin or -B(OH)2. In one embodiment, Y is -BPin. In one embodiment, Y is -B(OH)2.In one embodiment, the compound of Formula (PI) is a compound of Formula (Plal) -(PIa3) or a pharmaceutically acceptable salt, solvate or prodrug thereof:

[1118] (Pla1) (Pla2)

[1119]

[1120] (Pla3) wherein p, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, A, L, and Y are as defined in accordance with Formula (PI).

[1121] In another embodiment, the compound of Formula (PI) is a compound of Formula (PIa4) - (PIa7) or a pharmaceutically acceptable salt, solvate or prodrug thereof:

[1122]

[1123] (Pla4) (Pla5)

[1124]

[1125] (Pla6) (Pla7)

[1126] wherein p, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, A, L, and Y are as defined in accordance with Formula (PI).

[1127] Typically, the compound of Formula (PI) is a compound of Formula (Plal), (PIa2), (PIa4), or (PIa5). In one embodiment, the compound of Formula (PI) is a compound of Formula (Plal) or (PIa4). In one embodiment, the compound of Formula (IIIA) is a compound of Formula (Plal). In one embodiment, the compound of Formula (IIIA) is a compound of Formula (PIa4).

[1128] In one embodiment, the compound of Formula (PI) is a compound of Formula (PII):

[1129] R1R2

[1130] R8O

[1131] OR8

[1132] NR9R10

[1133] A

[1134] R4)P

[1135]

[1136] Formula (PII)

[1137] or a pharmaceutically acceptable salt, solvate or prodrug thereof, wherein n, m, p, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, L, A, and Y are as defined in accordance with Formula (PI) above.

[1138] As would be understood, in the compound of Formula (PII), the chiral centre at the amino (-NH2) group is (S).

[1139] In one embodiment, the carbon bearing the -L- group, marked below with an asterisk (*), is a chiral centre and has ( / ?) configuration. In another embodiment, the carbonbearing the -L- group, marked below with an asterisk (*), is a chiral centre and has (S) configuration.

[1140] In one embodiment, the compound of Formula (PII) is a compound of Formula (Pllal) - (PIIa3) or a pharmaceutically acceptable salt, solvate or prodrug thereof:

[1141]

[1142] (Plla3)

[1143] wherein p, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, A, L, and Y are as defined in accordance with Formula (PI).

[1144] In another embodiment, the compound of Formula (PII) is a compound of Formula (PIIa4) - (PIIa7) or a pharmaceutically acceptable salt, solvate or prodrug thereof:

[1145]

[1146] (Plla4) (Plla5)

[1147]

[1148] (Plla6) (Plla7)

[1149] wherein p, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, A, L, and Y are as defined in accordance with Formula (PI).

[1150] Typically, the compound of Formula (PII) is a compound of Formula (Pllal), (PIIa2), (PIIa4), or (PIIa5). In one embodiment, the compound of Formula (PII) is a compound of Formula (Pllal) or (PIIa4). In one embodiment, the compound of Formula (PII) is a compound of Formula (Pllal). In one embodiment, the compound of Formula (PII) is a compound of Formula (PIIa4).

[1151] As will be understood, insofar as practical, embodiments directed to one substituent or moiety (such as a given L or Y group) may be read in conjunction with embodiments directed to a different substituent or moiety.

[1152] For example, in one exemplary embodiment, there is provided a compound of Formula (PI) or Formula (PII) as defined above, wherein:

[1153] n is 0, 1, 2 or 3;

[1154] m is 1, 2, 3 or 4;

[1155] provided that m+n is 3 or 4;

[1156] when present, R1is hydrogen or C1-C3 alkyl;

[1157] R2is hydrogen or C1-C3 alkyl;

[1158] R3is hydrogen or C1-C3 alkyl;

[1159] L is -O-, -S-, a Ci-Ce straight chained alkylene group, wherein the Ci-Ce straight chained alkylene group optionally includes one or two heteroatoms each independently selected from 0 and S in its carbon skeleton; wherein L is optionally substituted with one or more substituents independently selected from fluoro, hydroxyl, oxo (=0), C1-C3 alkyl, -O-(Ci-C3 alkyl), -O-(Ci-C3 fluoroalkyl), or C1-C3 fluoroalkyl, and wherein L optionally includes one or more spirocyclic groups, wherein the spirocyclic group is selected from a C3-C5 cycloalkyl group or a saturated C3-C5 heterocyclic group;

[1160] A is phenyl, naphthyl, or a 5- to 10-membered heteroaryl group;p is 0 or 1;

[1161] R4is fluoro, chloro, bromo, iodo, cyano, methyl, ethyl, propyl (such as n-propyl or i-propyl), butyl (such as n-butyl, i-butyl, t-butyl), methoxy, ethoxy, propoxy, butoxy, cyclopropyl, cyclobutyl, -O-cyclopropyl, -O-cyclobutyl, -SMe, or -SEt;

[1162] each R8is independently hydrogen or a carboxyl protecting group, optionally wherein each R8is independently hydrogen, methyl, ethyl, / so-propyl, tert-butyl or benzyl;

[1163] R9and R10are each independently hydrogen or a nitrogen protecting group, optionally wherein R9and R10are each independently hydrogen, benzyloxycarbonyl (CBz), 4-methoxy-benzyloxycarbonyl, benzyl, tert-butoxycarbonyl (Boc), 2-(4-biphenylyl)-isopropoxycarbonyl (Bpoc), triphenylmethyl (Trt), or 2,2,2-trichloroethoxycarbonyl (Troc); and

[1164] Y is selected from a boronic ester, boronic acid, alkylsulfonate, arylsulfonate, trialkylamine, organostannane, organosilicate, aryliodonium salt, and an arylsulfonium salt, optionally wherein Y is selected from a boronic ester, boronic acid, and an organostannane.

[1165] The compounds of the third aspect are useful in the manufacture of the compounds of Formula (III) and Formula (IIIA) described herein.

[1166] In one embodiment, the third aspect provides a compound selected from the group consisting of:

[1167] di-tert-butyl-2-(bis(tert-butoxycarbonyl)amino)-6-(3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)benzyl)heptanedioate;

[1168] di-tert-butyl-2-(bis(tert-butoxycarbonyl)amino)-6-(4-(4,4,5,5-tetramethyl- 1.3.2-dioxaborolan-2-yl)benzyl)heptanedioate;

[1169] di-tert-butyl-2-[bis(tert-butoxycarbonyl)amino]-6-[3-[4-(4,4,5,5-tetramethyl- 1.3.2-dioxaborolan-2-yl)phenyl]sulfanylpropyl]heptanedioate;

[1170] di-tert-butyl-2-(bis(tert-butoxycarbonyl)amino)-7-(3-((4-(4,4,5,5-tetramethyl- 1.3.2-dioxaborolan-2-yl)phenyl)thio)propyl)octanedioate;

[1171] di-tert-butyl-2-(bis(tert-butoxycarbonyl)amino)-6-(3-(5-(4,4,5,5-tetramethyl- 1.3.2-dioxaborolan-2-yl)-lH-indazol-l-yl)propyl)heptanedioate;

[1172] ditert-butyl-2-[bis(tert-butoxycarbonyl)amino]-6-[[4-(4,4,5,5-tetramethyl- 1.3.2-dioxaborolan-2-yl)phenyl]methoxy] heptanedioate;

[1173] di-tert-butyl-2-(bis(tert-butoxycarbonyl)amino)-7-(4-(4,4,5,5-tetramethyl- 1.3.2-dioxaborolan-2-yl)benzyl)octanedioate;

[1174] ditert-butyl-2-[bis(tert-butoxycarbonyl)amino]-6-[4-(4,4,5,5-tetramethyl- 1.3.2-dioxaborolan-2-yl)phenoxy]heptanedioate;di-tert-butyl-2-(bis(tert-butoxycarbonyl)amino)-6-(3-(4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)phenyl)propyl)heptanedioate;

[1175] di-tert-butyl-2-[bis(tert-butoxycarbonyl)amino]-6-[(3-tributylstannylphenyl)methyl]heptaned ioate;

[1176] di-tert-butyl-2-(bis(tert-butoxycarbonyl)amino)-6-(3-(3-(4,4,5,5-tetramethyl- 1.3.2-dioxaborolan-2-yl)phenyl)propyl)heptanedioate;

[1177] di-tert-butyl-2-(bis(tert-butoxycarbonyl)amino)-6-(3-(4-(4,4,5,5-tetramethyl- 1.3.2-dioxaborolan-2-yl)phenyl)propoxy)heptanedioate;

[1178] di-tert-butyl-2-(bis(tert-butoxycarbonyl)amino)-6-(2-(3-(4,4,5,5-tetramethyl- 1.3.2-dioxaborolan-2-yl)phenoxy)ethoxy) heptanedioate;

[1179] di-tert-butyl 2-(bis(tert-butoxycarbonyl)amino)-4-(3-(4,4,5,5-tetramethyl- 1.3.2-dioxaborolan-2yl) benzyl) heptanedioate;

[1180] 6-(bis(tert-butoxycarbonyl)amino)-7-(tert-butoxy)-7-oxo-2-(3-(4,4,5,5-tetra methyl- 1, 3, 2-dioxaborolan-2-yl)benzyl)heptanoic acid;

[1181] 2-amino-6-(3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)benzyl) heptanedioic acid; and

[1182] 2-amino-6-(3-boronobenzyl)heptanedioic acid;

[1183] and pharmaceutically acceptable salts, solvates or prodrugs of any one thereof.

[1184] In one embodiment, the third aspect provides a compound selected from the group consisting of:

[1185] di-tert-butyl (2S)-2-(bis(tert-butoxycarbonyl)amino)-6-(3-(4,4,5,5-tetra methyl- 1, 3, 2-dioxaborolan-2-yl)benzyl)heptanedioate;

[1186] di-tert-butyl (2S)-2-(bis(tert-butoxycarbonyl)amino)-6-(4-(4,4,5,5-tetra methyl- 1, 3, 2-dioxaborolan-2-yl)benzyl)heptanedioate;

[1187] di-tert-butyl (2S)-2-[bis(tert-butoxycarbonyl)amino]-6-[3-[4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)phenyl]sulfanylpropyl]heptanedioate;

[1188] di-tert-butyl (2S)-2-(bis(tert-butoxycarbonyl)amino)-7-(3-((4-(4,4,5,5-tetra methyl- 1, 3, 2-dioxaborolan-2-yl)phenyl)thio)propyl)octaned ioate;

[1189] di-tert-butyl (2S)-2-(bis(tert-butoxycarbonyl)amino)-6-(3-(5-(4,4,5,5-tetra methyl- 1, 3, 2-dioxaborolan-2-yl)-lH-indazol-l-yl) propyl) heptanedioate;

[1190] di-tert-butyl (2S)-2-[bis(tert-butoxycarbonyl)amino]-6-[[4-(4,4,5,5-tetra methyl- 1, 3, 2-dioxaborolan-2-yl)phenyl] methoxy] heptanedioate;

[1191] di-tert-butyl (2S)-2-(bis(tert-butoxycarbonyl)amino)-7-(4-(4,4,5,5-tetra methyl- 1, 3, 2-dioxaborolan-2-yl)benzyl)octanedioate;

[1192] di-tert-butyl (2S)-2-[bis(tert-butoxycarbonyl)amino]-6-[4-(4,4,5,5-tetra methyl- 1, 3, 2-dioxaborolan-2-yl)phenoxy] heptanedioate;

[1193] di-tert-butyl (2S)-2-(bis(tert-butoxycarbonyl)amino)-6-(3-(4-(4,4,5,5-tetra methyl- 1, 3, 2-dioxaborolan-2-yl)phenyl) propyl) heptanedioate;

[1194] di-tert-butyl (2S)-2-[bis(tert-butoxycarbonyl)amino]-6-[(3-tributylstannylphenyl)methyl]heptaned ioate;

[1195] di-tert-butyl (2S)-2-(bis(tert-butoxycarbonyl)amino)-6-(3-(3-(4,4,5,5-tetra methyl- 1, 3, 2-dioxaborolan-2-yl)phenyl) propyl) heptanedioate;

[1196] di-tert-butyl (2S)-2-(bis(tert-butoxycarbonyl)amino)-6-(3-(4-(4,4,5,5-tetra methyl- 1, 3, 2-d ioxaborolan-2-yl)phenyl) propoxy) hepta ned ioate;

[1197] di-tert-butyl (2S)-2-(bis(tert-butoxycarbonyl)amino)-6-(2-(3-(4,4,5,5-tetra methyl- 1,3, 2-d ioxaborolan-2-yl)phenoxy)ethoxy)hepta ned ioate;

[1198] di-tert-butyl (2S)-2-( bis(tert-butoxycarbonyl)amino)-4-(3-(4,4,5,5-tetra methyl- 1,3, 2-d ioxaborolan-2-yl)benzyl)heptanedioate;

[1199] (2S)-6-(bis(tert-butoxycarbonyl)amino)-7-(tert-butoxy)-7-oxo-2-(3-(4,4,5,5-tetra methyl- 1,3, 2-d ioxaborolan-2-yl)benzyl)heptanoic acid;

[1200] (2S)-2-amino-6-(3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl) benzyl) heptanedioic acid; and

[1201] (2S)-2-amino-6-(3-boronobenzyl)heptanedioic acid;

[1202] and pharmaceutically acceptable salts, solvates or prodrugs of any one thereof.

[1203] In one embodiment, the third aspect provides a compound selected from the group consisting of:

[1204] di-tert-butyl(2S,6S)-2-(bis(tert-butoxycarbonyl)amino)-6-(3-(4,4,5,5-tetra methyl- 1,3, 2-d ioxaborolan-2-yl)benzyl)heptanedioate;

[1205] di-tert-butyl(2S,6R)-2-(bis(tert-butoxycarbonyl)amino)-6-(3-(4,4,5,5-tetra methyl- 1,3, 2-d ioxaborolan-2-yl)benzyl)heptanedioate;

[1206] di-tert-butyl(2S,6S)-2-(bis(tert-butoxycarbonyl)amino)-6-(4-(4,4,5,5-tetra methyl- 1,3, 2-d ioxaborolan-2-yl)benzyl)heptanedioate;

[1207] di-tert-butyl(2S,6R)-2-(bis(tert-butoxycarbonyl)amino)-6-(4-(4,4,5,5-tetra methyl- 1,3, 2-d ioxaborolan-2-yl)benzyl)heptanedioate;

[1208] di-tert-butyl(2S,6S)-2-[bis(tert-butoxycarbonyl)amino]-6-[3-[4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)phenyl]sulfanylpropyl]heptanedioate;

[1209] di-tert-butyl (2S,6R)-2-[bis(tert-butoxycarbonyl)amino]-6-[3-[4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)phenyl]sulfanylpropyl]heptanedioate;

[1210] di-tert-butyl (2S,7S)-2-(bis(tert-butoxycarbonyl)amino)-7-(3-((4-(4,4,5,5-tetra methyl- 1, 3, 2-d ioxaborolan-2-yl)phenyl)thio)propyl)octaned ioate;

[1211] di-tert-butyl (2S,7R)-2-(bis(tert-butoxycarbonyl)amino)-7-(3-((4-(4,4,5,5-tetra methyl- 1, 3, 2-d ioxaborolan-2-yl)phenyl)thio)propyl)octaned ioate;

[1212] di-tert-butyl (2S,6S)-2-(bis(tert-butoxycarbonyl)amino)-6-(3-(5-(4,4,5,5-tetra methyl- 1, 3, 2-d ioxaborolan-2-yl)-lH-indazol-l-yl) propyl) hepta ned ioate;di-tert-butyl (2S,6R)-2-(bis(tert-butoxycarbonyl)amino)-6-(3-(5-(4,4,5,5-tetra methyl- 1, 3, 2-dioxaborolan-2-yl)-lH-indazol-l-yl) propyl) heptanedioate; di-tert-butyl (2S,6S)-2-[bis(tert-butoxycarbonyl)amino]-6-[[4-(4,4,5,5-tetra methyl- 1, 3, 2-dioxaborolan-2-yl)phenyl] methoxy] heptanedioate;

[1213] di-tert-butyl (2S,6R)-2-[bis(tert-butoxycarbonyl)amino]-6-[[4-(4,4,5,5-tetra methyl- 1, 3, 2-dioxaborolan-2-yl)phenyl] methoxy] heptanedioate;

[1214] di-tert-butyl (2S,7S)-2-(bis(tert-butoxycarbonyl)amino)-7-(4-(4,4,5,5-tetra methyl- 1, 3, 2-dioxaborolan-2-yl)benzyl)octanedioate;

[1215] di-tert-butyl (2S,7R)-2-(bis(tert-butoxycarbonyl)amino)-7-(4-(4,4,5,5-tetra methyl- 1, 3, 2-dioxaborolan-2-yl)benzyl)octanedioate;

[1216] di-tert-butyl (2S,6S)-2-[bis(tert-butoxycarbonyl)amino]-6-[4-(4,4,5,5-tetra methyl- 1, 3, 2-dioxaborolan-2-yl)phenoxy] heptanedioate;

[1217] di-tert-butyl (2S,6R)-2-[bis(tert-butoxycarbonyl)amino]-6-[4-(4,4,5,5-tetra methyl- 1, 3, 2-dioxaborolan-2-yl)phenoxy] heptanedioate;

[1218] di-tert-butyl (2S,6S)-2-(bis(tert-butoxycarbonyl)amino)-6-(3-(4-(4,4,5,5-tetra methyl- 1, 3, 2-dioxaborolan-2-yl)phenyl) propyl) heptanedioate;

[1219] di-tert-butyl (2S,6R)-2-(bis(tert-butoxycarbonyl)amino)-6-(3-(4-(4,4,5,5-tetra methyl- 1, 3, 2-dioxaborolan-2-yl)phenyl) propyl) heptanedioate;

[1220] di-tert-butyl (2S,6S)-2-[bis(tert-butoxycarbonyl)amino]-6-[(3-tributylstannylphenyl)methyl]heptaned ioate;

[1221] di-tert-butyl (2S,6R)-2-[bis(tert-butoxycarbonyl)amino]-6-[(3-tributylstannylphenyl)methyl]heptaned ioate;

[1222] di-tert-butyl (2S,6S)-2-(bis(tert-butoxycarbonyl)amino)-6-(3-(3-(4,4,5,5-tetra methyl- 1, 3, 2-dioxaborolan-2-yl)phenyl) propyl) heptanedioate;

[1223] di-tert-butyl (2S,6R)-2-(bis(tert-butoxycarbonyl)amino)-6-(3-(3-(4,4,5,5-tetra methyl- 1, 3, 2-dioxaborolan-2-yl)phenyl) propyl) heptanedioate;

[1224] di-tert-butyl (2S,6S)-2-(bis(tert-butoxycarbonyl)amino)-6-(3-(4-(4,4,5,5-tetra methyl- 1, 3, 2-d ioxaborolan-2-yl)phenyl) propoxy) hepta ned ioate;

[1225] di-tert-butyl (2S,6R)-2-(bis(tert-butoxycarbonyl)amino)-6-(3-(4-(4,4,5,5-tetra methyl- 1,3, 2-d ioxaborolan-2-yl)phenyl) propoxy) hepta ned ioate;

[1226] di-tert-butyl (2S,6R)-2-(bis(tert-butoxycarbonyl)amino)-6-(2-(3-(4,4,5,5-tetra methyl- 1,3, 2-d ioxaborolan-2-yl)phenoxy)ethoxy)hepta ned ioate;

[1227] di-tert-butyl (2S,6S)-2-(bis(tert-butoxycarbonyl)amino)-6-(2-(3-(4,4,5,5-tetra methyl- 1,3, 2-d ioxaborolan-2-yl)phenoxy)ethoxy)hepta ned ioate;

[1228] di-tert-butyl (2S,4R)-2-(bis(tert-butoxycarbonyl)amino)-4-(3-(4,4,5,5-tetra methyl- 1,3, 2-d ioxaborolan-2-yl)benzyl)hepta ned ioate acid;

[1229] di-tert-butyl (2S,4S)-2-(bis(tert-butoxycarbonyl)amino)-4-(3-(4,4,5,5-tetra methyl- 1,3, 2-d ioxaborolan-2-yl)benzyl)hepta ned ioate acid;(2S,6S)-6-(bis(tert-butoxycarbonyl)amino)-7-(tert-butoxy)-7-oxo-2-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)heptanoic acid; (2S,6R)-6-(bis(tert-butoxycarbonyl)amino)-7-(tert-butoxy)-7-oxo-2-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)heptanoic acid; (2S,6S)-2-amino-6-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl) heptanedioic acid; (2S,6R)-2-amino-6-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl) heptanedioic acid; (2S,6S)-2-amino-6-(3-boronobenzyl)heptanedioic acid; and

[1230] (2S,6R)-2-amino-6-(3-boronobenzyl)heptanedioic acid;

[1231] and pharmaceutically acceptable salts, solvates or prodrugs of any one thereof.

[1232] In one embodiment, the third aspect provides a compound selected from the group consisting of:

[1233] di-tert-butyl(2S,6S)-2-(bis(tert-butoxycarbonyl)amino)-6-(3-(4,4,5,5-tetra methyl- 1, 3, 2-dioxaborolan-2-yl)benzyl)heptanedioate;

[1234] di-tert-butyl(2S)-2-(bis(tert-butoxycarbonyl)amino)-6-(4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)benzyl)heptanedioate;

[1235] di-tert-butyl (2S)-2-[bis(tert-butoxycarbonyl)amino]-6-[3-[4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)phenyl]sulfanylpropyl]heptanedioate;

[1236] di-tert-butyl (2S)-2-(bis(tert-butoxycarbonyl)amino)-7-(3-((4-(4,4,5,5-tetra methyl- 1, 3, 2-dioxaborolan-2-yl)phenyl)thio)propyl)octaned ioate;

[1237] di-tert-butyl (2S)-2-(bis(tert-butoxycarbonyl)amino)-6-(3-(5-(4,4,5,5-tetra methyl- 1, 3, 2-dioxaborolan-2-yl)-lH-indazol-l-yl) propyl) heptanedioate;

[1238] di-tert-butyl (2S)-2-[bis(tert-butoxycarbonyl)amino]-6-[[4-(4,4,5,5-tetra methyl- 1, 3, 2-dioxaborolan-2-yl)phenyl] methoxy] heptanedioate;

[1239] di-tert-butyl (2S)-2-(bis(tert-butoxycarbonyl)amino)-7-(4-(4,4,5,5-tetra methyl- 1, 3, 2-dioxaborolan-2-yl)benzyl)octanedioate;

[1240] di-tert-butyl (2S)-2-[bis(tert-butoxycarbonyl)amino]-6-[4-(4,4,5,5-tetra methyl- 1, 3, 2-dioxaborolan-2-yl)phenoxy] heptanedioate;

[1241] di-tert-butyl(2S)-2-(bis(tert-butoxycarbonyl)amino)-6-(3-(4-(4,4,5,5-tetra methyl- 1, 3, 2-dioxaborolan-2-yl)phenyl) propyl) heptanedioate;

[1242] di-tert-butyl (2S)-2-[bis(tert-butoxycarbonyl)amino]-6-[(3-tributylstannylphenyl)methyl]heptaned ioate;

[1243] di-tert-butyl (2S)-2-(bis(tert-butoxycarbonyl)amino)-6-(3-(3-(4,4,5,5-tetra methyl- 1, 3, 2-dioxaborolan-2-yl)phenyl) propyl) heptanedioate;

[1244] di-tert-butyl (2S)-2-(bis(tert-butoxycarbonyl)amino)-6-(3-(4-(4,4,5,5-tetra methyl- 1, 3, 2-d ioxaborolan-2-yl)phenyl) propoxy) hepta ned ioate;di-tert-butyl (2S,6R)-2-(bis(tert-butoxycarbonyl)amino)-6-(2-(3-(4,4,5,5-tetra methyl- 1, 3, 2-dioxaborolan-2-yl)phenoxy)ethoxy)heptaned ioate;

[1245] di-tert-butyl (2S,4R)-2-(bis(tert-butoxycarbonyl)amino)-4-(3-(4,4,5,5-tetra methyl- 1, 3, 2-dioxaborolan-2-yl)benzyl)heptanedioate;

[1246] (2S,6S)-6-(bis(tert-butoxycarbonyl)amino)-7-(tert-butoxy)-7-oxo-2-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)heptanoic acid;

[1247] (2S,6S)-2-amino-6-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl) heptanedioic acid; and

[1248] (2S,6S)-2-amino-6-(3-boronobenzyl)heptanedioic acid;

[1249] and pharmaceutically acceptable salts, solvates or prodrugs of any one thereof.

[1250] A fourth aspect of the invention provides a process for the preparation of a compound of Formula (III) or (IIIA), or a pharmaceutically acceptable salt, solvate or prodrug thereof from a compound of Formula (PI) or a pharmaceutically acceptable salt, solvate or prodrug thereof.

[1251] The compounds of Formula (PI) described herein are useful in the preparation of the compounds of Formula (III) and Formula (IIIA). For example, the compounds of Formula (PI) may undergo a reaction in which the compound of Formula (PI) is reacted with a source of a radioisotope under conditions to replace the group Y, on the compound of Formula (PI) with a radioisotope from the source of radioisotope, and thereafter removing any protecting groups, such that the reaction product is a compound of Formula (III) or (IIIA). Alternatively, any protecting groups may be removed from the compounds of Formula (PI), and thereafter reacted with a source of a radioisotope under conditions to replace the group Y with a radioisotope from the source of radioisotope, such that the reaction product is a compound of Formula (III) or (IIIA).

[1252] In one embodiment of the fourth aspect, the process comprises converting a compound of Formula (PI) into a compound of Formula (III) or (IIIA), the process comprising (i) a radiohalogenation reaction and (ii) a deprotection reaction.

[1253] In one embodiment of the fourth aspect, the process comprises converting a compound of Formula (PI) into a compound of Formula (III) or (IIIA), the process comprising reacting a compound of Formula (PI), or a pharmaceutically acceptable salt, solvate or prodrug thereof with a source of a radioisotope, and thereafter removing any protecting groups, to obtain a compound of Formula (III) or Formula (IIIA) or a pharmaceutically acceptable salt, solvate or prodrug thereof:

[1254]

[1255] Formula (PI) Formula (III) Formula (IIIA)

[1256] wherein n, m, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, X1, X2, Y, L, A and p are defined in the first and third aspect of the present invention.

[1257] In one embodiment of the fourth aspect, the process comprises converting a compound of Formula (PI) into a compound of Formula (III) or (IIIA), the process comprising removing any protecting groups from a compound of Formula (PI), or a pharmaceutically acceptable salt, solvate or prodrug thereof, and thereafter reacting the resulting compound with a source of a radioisotope, to obtain a compound of Formula (III) or Formula (IIIA) or a pharmaceutically acceptable salt, solvate or prodrug thereof:

[1258]

[1259] Formula (PI) Formula (III) Formula (IIIA)

[1260] wherein n, m, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, X1, X2, Y, L, A and p are defined in the first and third aspect of the present invention.

[1261] In one embodiment, the process comprises a radiohalogenation reaction. In one embodiment, the process comprises a nucleophilic radiohalogenation reaction. In one embodiment, the process comprises an electrophilic radiohalogenation reaction. In one embodiment, the process comprises a nucleophilic radioiodination. In one embodiment, the process comprises a nucleophilic radiofluorination reaction. In one embodiment, the process comprises an electrophilic radioastatination reaction.In one embodiment, the process comprises a deprotection reaction. Typically, the radiohalogenation reaction and the deprotection reaction are carried out consecutively. In one embodiment, the process comprises converting a compound of Formula (PI) into a compound of Formula (III) or (IIIA), wherein the process comprises the steps of:

[1262] a) reacting a compound of Formula (PI), or a pharmaceutically acceptable salt, solvate or prodrug thereof with a source of a radioisotope to obtain a compound of Formula (PX) or Formula (PXA) or a pharmaceutically acceptable salt, solvate or prodrug thereof:

[1263]

[1264] Formula (PI) Formula (PX) Formula (PXA)

[1265] and thereafter

[1266] b) removing any protecting groups from the compound of Formula (PX) or (PXA) or a pharmaceutically acceptable salt, solvate or prodrug thereof, to obtain a compound of Formula (III) or Formula (IIIA) or a pharmaceutically acceptable salt, solvate or prodrug thereof:

[1267]

[1268] Formula (PX) Formula (PXA) Formula (III) Formula (IIIA) wherein n, m, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, X1, X2, Y, L, A and p are defined in the first and third aspect of the present invention.

[1269] In one embodiment, the process comprises converting a compound of Formula (PI) into a compound of Formula (III) or (IIIA), wherein the process comprises the steps of:

[1270] a) removing any protecting groups from a compound of Formula (PI), or a pharmaceutically acceptable salt, solvate or prodrug thereof to obtain a compound of Formula (PT) or a pharmaceutically acceptable salt, solvate or prodrug thereof:

[1271]

[1272] Formula (PI) Formula (PI')

[1273] and thereafter

[1274] b) reacting the compound of Formula (PI') or a pharmaceutically acceptable salt, solvate or prodrug thereof, with a source of a radioisotope to obtain a compound of Formula (III) or Formula (IIIA) or a pharmaceutically acceptable salt, solvate or prodrug thereof:

[1275] R1R20R1R2OR1 R2 Q A AM“ir^ ™ " VA ™ A JH2- -01R NH* o <R3NH2A\R4)P A\R4)PYV)P JXX2

[1276]

[1277] Formula (PI ) Formula (III) Formula (IIIA) wherein n, m, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, X1, X2, Y, L, A and p are defined in the first and third aspect of the present invention.

[1278] In one embodiment, the source of the radioisotope is a source of123I,124I,125I,131I,18F or211At.

[1279] In one embodiment, the source of the radioisotope is a source of123I,124I,125I, or131I. In one embodiment, the source of the radioisotope is a source of123I,125I,131I, or211At. In one embodiment, the source of the radioisotope is a source

[1280] of123I,124I,125I,131I, or18F. In one embodiment, the source of the radioisotope is125I,124I,131I, or18F. In one embodiment the source of the radioisotope is a source of124I,131I, or18F. In one embodiment, the source of the radioisotope is a source of124I or18F.

[1281] In one embodiment, the source of the radioisotope is a source of123I,125I, or131I. In one embodiment, the source of the radioisotope is a source of211At,125I, or131I. In one embodiment the source of the radioisotope is a source of125I,131I, or18F. In one embodiment, the source of the radioisotope is a source of125I or131I. In one embodiment, the source of the radioisotope is a source of211At or131I.In one embodiment, the source of the radioisotope is a source of18F. In one embodiment, the source of the radioisotope is a source of123I. In one embodiment, the source of the radioisotope is a source of125I. In one embodiment, the source of the radioisotope is a source of131I. In one embodiment, the source of the radioisotope is a source of211At. In one embodiment, the source of the radioisotope is a source of124I

[1282] Typical sources of iodine and astatine radioisotopes include, for example, salts such as [123I]NaI, [124I]NaI, [125I]NaI, [131I]NaI, or [211At]NaAt. Typical sources of fluorine isotopes include, for example, aqueous [18F]Fluoride (18F ). Astatine-211 may be obtained by dry distillation from a bismuth target.

[1283] Typically, the radiohalogenation reaction is carried out in the presence of a catalyst. In one embodiment, the reaction is carried out in the presence of a copper catalyst. Typically, the copper catalyst is [(OAc)Cu(phen)2]OAc or [Cu(OTf)2(py)4].

[1284] In a specific embodiment of the fourth aspect, the process comprises converting a compound of Formula (PI) into a compound of Formula (III) or (IIIA), wherein the process comprises the steps of:

[1285] a) removing any protecting groups from a compound of Formula (PI), or a pharmaceutically acceptable salt, solvate or prodrug thereof to obtain a compound of Formula (PT) or a pharmaceutically acceptable salt, solvate or prodrug thereof:

[1286] R1R2o R1R2o

[1287]

[1288] Y Y

[1289] Formula (PI) Formula (PI')

[1290] and thereafter

[1291] b) reacting the compound of Formula (PT) or a pharmaceutically acceptable salt, solvate or prodrug thereof, with a source of211At to obtain a compound of Formula (III) or Formula (IIIA) or a pharmaceutically acceptable salt, solvate or prodrug thereof:

[1292]

[1293] wherein n, m, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, Y, L, A and p are defined in the first and third aspect of the present invention and X1and X2are211At.

[1294] In a specific embodiment of the fourth aspect, the process comprises converting a compound of Formula (PIx) into a compound of Formula (Z), wherein the process comprises the steps of:

[1295] a) removing any protecting groups R8, R9and R10from a compound of Formula (PIx), or a pharmaceutically acceptable salt, solvate or prodrug thereof to obtain a compound of Formula (Ply) or a pharmaceutically acceptable salt, solvate or prodrug thereof:

[1296] o o 0 0

[1297] Formula (PIx) Formula (Ply)

[1298]

[1299] and thereafter

[1300] b) reacting the compound of Formula (Ply) or a pharmaceutically acceptable salt, solvate or prodrug thereof, with a source of211At to obtain a compound of Formula (Z) or a pharmaceutically acceptable salt, solvate or prodrug thereof:

[1301]

[1302] Formula (Ply) Formula (Z) wherein each R8is independently hydrogen or a carboxyl protecting group;

[1303] R9and R10are each independently hydrogen or a nitrogen protecting group; and Y is a leaving group.The compounds of the present invention can be used both, in their free base form and their acid addition salt form. For the purposes of this invention, a "salt" of a compound of the present invention includes an acid addition salt. Acid addition salts are preferably pharmaceutically acceptable, non-toxic addition salts with suitable acids, including but not limited to inorganic acids such as hydrohalogenic acids (for example, hydrofluoric, hydrochloric, hydrobromic or hydroiodic acid) or other inorganic acids (for example, nitric, perchloric, sulfuric or phosphoric acid); or organic acids such as organic carboxylic acids (for example, propionic, butyric, glycolic, lactic, mandelic, citric, acetic, benzoic, salicylic, succinic, malic or hydroxysuccinic, tartaric, fumaric, maleic, hydroxymaleic, mucic or galactaric, gluconic, pantothenic or pamoic acid), organic sulfonic acids (for example, methanesulfonic, trifluoromethanesulfonic, ethanesulfonic, 2-hydroxyethanesulfonic, benzenesulfonic, toluene-p-sulfonic, naphthalene-2-sulfonic or camphorsulfonic acid) or amino acids (for example, ornithinic, glutamic or aspartic acid). The acid addition salt may be a mono-, di-, trior multi-acid addition salt. A preferred salt is a hydrohalogenic, sulfuric, phosphoric or organic acid addition salt. A preferred salt is a hydrochloric acid addition salt.

[1304] Where a compound of the invention includes a quaternary ammonium group, typically the compound is used in its salt form. The counter ion to the quaternary ammonium group may be any pharmaceutically acceptable, non-toxic counter ion. Examples of suitable counter ions include the conjugate bases of the protic acids discussed above in relation to acid addition salts.

[1305] The compounds of the present invention can also be used both, in their free acid form and their salt form. For the purposes of this invention, a "salt" of a compound of the present invention includes one formed between a protic acid functionality (such as a carboxylic acid group) of a compound of the present invention and a suitable cation. Suitable cations include, but are not limited to lithium, sodium, potassium, magnesium, calcium and ammonium. The salt may be a mono-, di-, tri- or multi-salt. Preferably the salt is a mono- or di-lithium, sodium, potassium, magnesium, calcium or ammonium salt. More preferably the salt is a mono-sodium salt or a monopotassium salt.

[1306] Preferably any salt is a pharmaceutically acceptable, non-toxic salt. However, in addition to pharmaceutically acceptable salts, other salts are included in the present invention, since they have potential to serve as intermediates in the purification or preparation of other, for example, pharmaceutically acceptable salts, or are useful for identification, characterisation or purification of the free acid or base.In some embodiments of the present invention, therapeutically inactive prodrugs are provided. Prodrugs are compounds which, when administered to a subject such as a human, are converted in whole or in part to a compound of the invention. In most embodiments, the prodrugs are pharmacologically inert chemical derivatives that can be converted in vivo to the active drug molecules to exert a therapeutic effect. Any of the compounds described herein can be administered as a prodrug to increase the activity, bioavailability, or stability of the compound or to otherwise alter the properties of the compound. Typical examples of prodrugs include compounds that have biologically labile protecting groups on a functional moiety of the active compound. Prodrugs include, but are not limited to, compounds that can be oxidized, reduced, aminated, deaminated, hydroxylated, dehydroxylated, hydrolyzed, dehydrolyzed, alkylated, dealkylated, acylated, deacylated, phosphorylated, and / or dephosphorylated to produce the active compound. The present invention also encompasses salts and solvates of such prodrugs as described above.

[1307] The compounds, salts, solvates and prodrugs of the present invention may be anhydrous or in the form of a hydrate (e.g. a hemihydrate, monohydrate, dihydrate or trihydrate) or other solvate. Such other solvates may be formed with common organic solvents, including but not limited to, alcoholic solvents e.g. methanol, ethanol or isopropanol.

[1308] The compounds, salts, solvates and prodrugs of the present invention may be obtained in all grades of purity, for example via conventional techniques such as recrystallisation and / or column chromatography.

[1309] For example, the compounds, salts, solvates and prodrugs of the present invention may be at least 90% pure, at least 95% pure, at least 99% pure, at least 99.5% pure or at least 99.9% pure, as measured by HPLC.

[1310] Alternately, the compounds, salts, solvates and prodrugs of the present invention may be at least 90% pure, at least 95% pure, at least 99% pure, at least 99.5% pure or at least 99.9% pure, as measured by LCMS.

[1311] Alternately still, the compounds, salts, solvates and prodrugs of the present invention may be at least 90% pure, at least 95% pure, at least 99% pure, at least 99.5% pure or at least 99.9% pure, as measured by1H NMR.The compounds, salts, solvates and prodrugs of the present invention may contain any stable isotope including, but not limited to12C,13C,1H,2H (D),14N,15N,16O,17O, and18O, and any radioisotope including, but not limited tonC,14C,3H (T),13N, and15O.

[1312] The compounds, salts, solvates and prodrugs of the present invention may be in any polymorphic or amorphous form.

[1313] A fifth aspect of the invention provides a pharmaceutical composition comprising a compound, pharmaceutically acceptable salt, solvate or prodrug of the first or second aspect of the invention, and a pharmaceutically acceptable excipient.

[1314] Conventional procedures for the selection and preparation of suitable pharmaceutical formulations are described in, for example, " Aulton's Pharmaceutics - The Design and Manufacture of Medicines", M. E. Aulton and K. M. G. Taylor, Churchill Livingstone Elsevier, 4thEd., 2013.

[1315] Pharmaceutically acceptable excipients including adjuvants, diluents or carriers that may be used in the pharmaceutical compositions of the invention are those conventionally employed in the field of pharmaceutical formulation, and include, but are not limited to, sugars, sugar alcohols, starches, ion exchangers, alumina, aluminium stearate, lecithin, serum proteins such as human serum albumin, buffer substances such as phosphates, glycerine, sorbic acid, potassium sorbate, partial glyceride mixtures of saturated vegetable fatty acids, water, salts or electrolytes such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silica, magnesium trisilicate, polyvinylpyrrolidone, cellulose-based substances, polyethylene glycol, sodium carboxymethylcellulose, polyacrylates, waxes, polyethylene-polyoxypropylene-block polymers, polyethylene glycol and wool fat.

[1316] A sixth aspect of the invention provides a kit comprising a compound of Formula (PI) or a pharmaceutically acceptable salt, solvate or prodrug thereof and instructions to prepare a compound of Formula (III) or Formula (IIIA), or a pharmaceutically acceptable salt, solvate or prodrug thereof.

[1317] A seventh aspect of the invention provides a kit comprising a compound of Formula (III) or Formula (IIIA), or a pharmaceutically acceptable salt, solvate or prodrug thereof, or a pharmaceutical composition comprising a compound of Formula (III) orFormula (IIIA) and instructions for use. In one embodiment, the instructions for use are written instructions on how to administer the compound or composition.

[1318] An eight aspect of the invention provides a compound, pharmaceutically acceptable salt, solvate or prodrug of the first or second aspect of the invention, or a pharmaceutical composition of the fifth aspect of the invention, for use in medicine.

[1319] A ninth aspect of the invention provides a compound, pharmaceutically acceptable salt, solvate or prodrug of the first or second aspect of the invention, or a pharmaceutical composition of the fifth aspect of the invention, for use in diagnosis or therapy. For example, the invention provides a compound of Formula (III) or a pharmaceutically acceptable salt, solvate or prodrug thereof, or a pharmaceutical composition comprising the same, for use in diagnosis or therapy.

[1320] A tenth aspect of the invention provides a compound, pharmaceutically acceptable salt, solvate or prodrug of the first or second aspect of the invention, or a pharmaceutical composition of the fifth aspect of the invention, for use in the treatment or prevention of a disease, disorder or condition. Typically, the use comprises the administration of the compound, pharmaceutically acceptable salt, solvate, prodrug or pharmaceutical composition to a subject. For example, the invention provides a compound of Formula (IIIA) or a pharmaceutically acceptable salt, solvate or prodrug thereof, or a pharmaceutical composition comprising the same, for use in the treatment or prevention of a disease, disorder or condition.

[1321] In one embodiment, a compound of Formula (IIIA) or a pharmaceutically acceptable salt, solvate or prodrug thereof, or a pharmaceutical composition comprising the same, is for use in the treatment or prevention of cancer.

[1322] System xc“ has been found to play an important role in tumour growth, progression, metastasis, and multidrug resistance in multiple types of cancer. In addition, system xc“ has been observed to be overexpressed or upregulated in many cancers which suggests that system xc“ is important for cancer cell survival and tumour development [4-7, 10]. Therefore, the enhanced expression and activity of system xc“ in multiple tumour types allows for the opportunity for targeted delivery of radionuclide imaging and therapy to a wide range of cancers [8-9].

[1323] In one embodiment, the cancer is bladder cancer, brain cancer, breast cancer, estrogen receptor positive (ER+) breast cancer, estrogen receptor negative (ER-)- Ill -breast cancer, invasive ductal breast cancer (IDBC), colon cancer, colorectal cancer, gastric cancer, head and neck cancer, kidney cancer, liver cancer, lung cancer, nonsmall-cell lung cancer (NSCLC), oral cancer, ovarian cancer, pancreatic cancer, prostate cancer, renal cancer, glioma, carcinoma, hepatocellular carcinoma (HCC), prostate carcinoma, squamous cell carcinoma, oesophageal squamous cell carcinoma (ESCC), head and neck squamous cell carcinoma, oral squamous cell carcinoma, tongue squamous cell carcinoma (TSCC), adenocarcinoma, leukaemia, chronic lymphocytic leukaemia (CLL), lymphoma, Burkitt's lymphoma, Kaposi's herpes virus (KSHV) / HIV-associated lymphoma, primary effusion lymphoma (PEL), melanoma, sarcoma, Kaposi's sarcoma (KS), glioblastoma, a solid tumour, a cancer overexpressing system xc“, a cancer upregulating system xc“, or a drug resistant cancer.

[1324] An eleventh aspect of the invention provides a compound, pharmaceutically acceptable salt, solvate or prodrug of the first or second aspect of the invention, or a pharmaceutical composition of the fifth aspect of the invention, for use in diagnosis. Typically, the use comprises the administration of the compound, pharmaceutically acceptable salt, solvate, prodrug or pharmaceutical composition to a subject. For example, the invention provides a compound of Formula (III) or a pharmaceutically acceptable salt, solvate or prodrug thereof, or a pharmaceutical composition comprising the same, for use in diagnosis.

[1325] In one embodiment, a compound of Formula (III) or a pharmaceutically acceptable salt, solvate or prodrug thereof, or a pharmaceutical composition comprising the same, is for use in the diagnosis of cancer.

[1326] In one embodiment, the diagnosis comprises imaging a subject, for example imaging a subject by PET, SPECT, or scintigraphy.

[1327] In one embodiment, the cancer is bladder cancer, brain cancer, breast cancer, estrogen receptor positive (ER+) breast cancer, estrogen receptor negative (ER-) breast cancer, invasive ductal breast cancer (IDBC), colon cancer, colorectal cancer, gastric cancer, head and neck cancer, kidney cancer, liver cancer, lung cancer, nonsmall-cell lung cancer (NSCLC), oral cancer, ovarian cancer, pancreatic cancer, prostate cancer, renal cancer, glioma, carcinoma, hepatocellular carcinoma (HCC), prostate carcinoma, squamous cell carcinoma, oesophageal squamous cell carcinoma (ESCC), head and neck squamous cell carcinoma, oral squamous cell carcinoma, tongue squamous cell carcinoma (TSCC), adenocarcinoma, leukaemia, chroniclymphocytic leukaemia (CLL), lymphoma, Burkitt's lymphoma, Kaposi's herpes virus (KSHV) / HIV-associated lymphoma, primary effusion lymphoma (PEL), melanoma, sarcoma, Kaposi's sarcoma (KS), glioblastoma, a solid tumour, a cancer overexpressing system xc“, a cancer upregulating system xc“, or a drug resistant cancer.

[1328] As would be understood by the skilled person, specific compounds of Formula (III) may be applied when used for imaging and / or diagnosis as opposed to use in treatment. In particular, the identity of the group X1in the compounds of Formula (III) may be varied such that the compounds can be used for imaging and / or diagnosis or can be used in treatment. As would be understood by the skilled person, the compounds of Formula (III) are thus useful in the field of theranostics.

[1329] As used herein, and as would be understood by the skilled person, the concept of "theranostics" refers to the combination of two approaches: diagnosis and treatment. Typically, the concept refers to a radiopharmaceutical agent or a pair of radiopharmaceutical agents containing a radioisotope used for imaging (diagnostics) and / or therapy (therapeutics).

[1330] As would be understood by the skilled person, specific compounds of Formula (III) may also be applied to different diseases, disorders or conditions when used for imaging and / or diagnosis as opposed to use in treatment.

[1331] The term "treatment" as used herein refers equally to curative therapy, and ameliorating or palliative therapy. The term includes obtaining beneficial or desired physiological results, which may or may not be established clinically. Beneficial or desired clinical results include, but are not limited to, the alleviation of symptoms, the prevention of symptoms, the diminishment of extent of disease, the stabilisation (i.e., not worsening) of a condition, the delay or slowing of progression / worsening of a condition / symptom, the amelioration or palliation of a condition / symptom, and remission (whether partial or total), whether detectable or undetectable. The term "palliation", and variations thereof, as used herein, means that the extent and / or undesirable manifestations of a physiological condition or symptom are lessened and / or time course of the progression is slowed or lengthened, as compared to not administering a compound, salt, solvate, prodrug or pharmaceutical composition of the present invention. The term "prevention" as used herein in relation to a disease, disorder or condition, relates to prophylactic or preventative therapy, as well as therapy to reduce the risk of developing the disease, disorder or condition. The term"prevention" includes both the avoidance of occurrence of the disease, disorder or condition, and the delay in onset of the disease, disorder or condition. Any statistically significant (p < 0.05) avoidance of occurrence, delay in onset or reduction in risk as measured by a controlled clinical trial may be deemed a prevention of the disease, disorder or condition. Subjects amenable to prevention include those at heightened risk of a disease, disorder or condition as identified by genetic or biochemical markers. A twelfth aspect of the invention provides the use of a compound, pharmaceutically acceptable salt, solvate or prodrug of the first or second aspect of the invention, in the manufacture of a medicament for the diagnosis or treatment or prevention of a disease, disorder or condition. Typically, the treatment or prevention comprises the administration of the compound, pharmaceutically acceptable salt, solvate, prodrug or medicament to a subject.

[1332] A thirteenth aspect of the invention provides a method of diagnosis or treatment or prevention of a disease, disorder or condition, the method comprising the step of administering an effective amount of a compound, pharmaceutically acceptable salt, solvate or prodrug of the first or second aspect of the invention, or a pharmaceutical composition of the fifth aspect of the invention, to thereby diagnose or treat or prevent the disease, disorder or condition. Typically, the administration is to a subject in need thereof.

[1333] In one embodiment, two or more different compounds of Formula (III) may be administered sequentially. In one embodiment, a first compound of Formula (III) may be administered to a subject, and a second compound of Formula (IIIA) may be administered to the subject. For example, the first compound of Formula (III) may comprise a radioisotope that decays with gamma emission (e.g.125I or123I) or positron emission (e.g.18F), and the second compound of Formula (IIIA) may comprise a radioisotope that decays by alpha emission (e.g.211At) or beta emission (e.g.131I). In this way, the status of the disease, disorder or condition can be determined, and the disease, disorder or condition can be treated. The status of the disease, disorder or condition may be determined after the administration of the compound of Formula (III) by, for example, a method of medical imaging as described herein. The disease, disorder or condition may be treated after the administration of the compound of Formula (IIIA) by, for example, radiotherapy. As would be understood, multiple rounds of administration of compounds of Formula (III) and Formula (IIIA) allows for the status of the disease, disorder or condition to be monitored and the effectiveness of the treatment to be evaluated.The compounds, pharmaceutically acceptable salts, solvates, prodrugs, and pharmaceutical compositions disclosed herein, may be useful in the diagnosis or treatment of cancer.

[1334] In one embodiment, the cancer is bladder cancer, brain cancer, breast cancer, estrogen receptor positive (ER+) breast cancer, estrogen receptor negative (ER-) breast cancer, invasive ductal breast cancer (IDBC), colon cancer, colorectal cancer, gastric cancer, head and neck cancer, kidney cancer, liver cancer, lung cancer, nonsmall-cell lung cancer (NSCLC), oral cancer, ovarian cancer, pancreatic cancer, prostate cancer, renal cancer, glioma, carcinoma, hepatocellular carcinoma (HCC), prostate carcinoma, squamous cell carcinoma, oesophageal squamous cell carcinoma (ESCC), head and neck squamous cell carcinoma, oral squamous cell carcinoma, tongue squamous cell carcinoma (TSCC), adenocarcinoma, leukaemia, chronic lymphocytic leukaemia (CLL), lymphoma, Burkitt's lymphoma, Kaposi's herpes virus (KSHV) / HIV-associated lymphoma, primary effusion lymphoma (PEL), melanoma, sarcoma, Kaposi's sarcoma (KS), glioblastoma, a solid tumour, a cancer overexpressing system xc“, a cancer upregulating system xc“, or a drug resistant cancer.

[1335] In general embodiments of any of the tenth to thirteenth aspects of the invention, the disease, disorder or condition may be a disease, disorder or condition of the immune system, the cardiovascular system, the renal system, the respiratory system, the central nervous system, peripheral nervous system, the reproductive system, the ocular system, the metabolic system, the haematological system, may be a cancer or other malignancy, and / or may be caused by or associated with a pathogen.

[1336] It will be appreciated that these general embodiments defined according to broad categories of diseases, disorders and conditions are not mutually exclusive. In this regard any particular disease, disorder or condition may be categorized according to more than one of the above general embodiments.

[1337] A fourteenth aspect of the invention provides a compound of Formula (III), a pharmaceutically acceptable salt, solvate or prodrug thereof, or a pharmaceutical composition comprising the same, for use in diagnosis.

[1338] In one embodiment, a compound of Formula (III), a pharmaceutically acceptable salt, solvate or prodrug thereof, or a pharmaceutical composition comprising the same, is for use in the diagnosis of cancer.In one embodiment, the cancer is bladder cancer, brain cancer, breast cancer, estrogen receptor positive (ER+) breast cancer, estrogen receptor negative (ER-) breast cancer, invasive ductal breast cancer (IDBC), colon cancer, colorectal cancer, gastric cancer, head and neck cancer, kidney cancer, liver cancer, lung cancer, nonsmall-cell lung cancer (NSCLC), oral cancer, ovarian cancer, pancreatic cancer, prostate cancer, renal cancer, glioma, carcinoma, hepatocellular carcinoma (HCC), prostate carcinoma, squamous cell carcinoma, oesophageal squamous cell carcinoma (ESCC), head and neck squamous cell carcinoma, oral squamous cell carcinoma, tongue squamous cell carcinoma (TSCC), adenocarcinoma, leukaemia, chronic lymphocytic leukaemia (CLL), lymphoma, Burkitt's lymphoma, Kaposi's herpes virus (KSHV) / HIV-associated lymphoma, primary effusion lymphoma (PEL), melanoma, sarcoma, Kaposi's sarcoma (KS), glioblastoma, a solid tumour, a cancer overexpressing system xc“, a cancer upregulating system xc“, or a drug resistant cancer.

[1339] A fifteenth aspect of the invention provides a compound of Formula (IIIA), a pharmaceutically acceptable salt, solvate or prodrug thereof, or a pharmaceutical composition comprising the same, for use in treating a disease, disorder or condition. In one embodiment, a compound of Formula (IIIA), a pharmaceutically acceptable salt, solvate or prodrug thereof, or a pharmaceutical composition comprising the same, is for use in treating cancer.

[1340] In one embodiment, the cancer is bladder cancer, brain cancer, breast cancer, estrogen receptor positive (ER+) breast cancer, estrogen receptor negative (ER-) breast cancer, invasive ductal breast cancer (IDBC), colon cancer, colorectal cancer, gastric cancer, head and neck cancer, kidney cancer, liver cancer, lung cancer, nonsmall-cell lung cancer (NSCLC), oral cancer, ovarian cancer, pancreatic cancer, prostate cancer, renal cancer, glioma, carcinoma, hepatocellular carcinoma (HCC), prostate carcinoma, squamous cell carcinoma, oesophageal squamous cell carcinoma (ESCC), head and neck squamous cell carcinoma, oral squamous cell carcinoma, tongue squamous cell carcinoma (TSCC), adenocarcinoma, leukaemia, chronic lymphocytic leukaemia (CLL), lymphoma, Burkitt's lymphoma, Kaposi's herpes virus (KSHV) / HIV-associated lymphoma, primary effusion lymphoma (PEL), melanoma, sarcoma, Kaposi's sarcoma (KS), glioblastoma, a solid tumour, a cancer overexpressing system xc“, a cancer upregulating system xc“, or a drug resistant cancer.A sixteenth aspect of the invention provides a method of medical imaging, the method comprising:

[1341] i. administering a compound of Formula (III), or a pharmaceutically acceptable salt, solvate or prodrug thereof or a pharmaceutical composition comprising a compound of Formula (III) to a subject; and

[1342] ii. imaging the subject.

[1343] In one embodiment, the compound of Formula (III), or a pharmaceutically acceptable salt, solvate or prodrug thereof or a pharmaceutical composition comprising a compound of Formula (III) is administered to the subject non-invasively. In one embodiment, the compound of Formula (III), or a pharmaceutically acceptable salt, solvate or prodrug thereof or a pharmaceutical composition comprising a compound of Formula (III) is administered intravenously.

[1344] A seventeenth aspect of the invention provides a method of medical imaging, wherein a compound of Formula (III) or a pharmaceutically acceptable salt, solvate or prodrug thereof or a pharmaceutical composition comprising a compound of Formula (III) has been administered to a subject, the method comprising imaging the subject.

[1345] In one embodiment, the imaging of the subject is by PET, SPECT or scintigraphy. In one embodiment, the imaging of the subject is by PET. In one embodiment, the imaging of the subject is by SPECT. In one embodiment, the imaging of the subject is by scintigraphy.

[1346] As used herein, and as would be understood by the skilled person, the term " PET" refers to positron emission tomography, and the term " SPECT" refers to single-photon emission computed tomography. Typical radioisotopes employed in PET imaging include, for example,18F or124I. Typical radioisotopes employed in SPECT imaging include, for example,125I,123I,131I, or211At.

[1347] PET, SPECT, and scintigraphy each rely on the detection and counting of gamma rays or gamma photons. Without wishing to be bound by theory, in some embodiments, the compounds of Formula (III) described herein, upon administration to a subject, accumulate at a target location, for example, a population of cells expressing, overexpressing, or upregulating system xc“ (such as a population of cancerous cells, for example, a tumour) and give rise to emission of gamma photons from that location, for example:

[1348] by positron - electron annilation;by gamma photon decay;

[1349] via electron capture decay; or

[1350] through subsequent decay of a daughter isotope.

[1351] The target cell populations expressing system xc“, at which the compound of Formula (III) has accumulated, can be detected by collection of the emitted gamma photons, for example, through imaging the subject by PET, SPECT, or scintigraphy.

[1352] In one embodiment, the method of medical imaging further comprises the step of introducing a radioisotope on the compound of Formula (III), for example, by suitable reaction with a corresponding compound of Formula (PI).

[1353] Unless stated otherwise, in any of the tenth to seventeenth aspects of the invention, the subject may be any human or other animal. Typically, the subject is a mammal, more typically a human or a domesticated mammal such as a cow, pig, lamb, sheep, goat, horse, cat, dog, rabbit, mouse etc. Most typically, the subject is a human.

[1354] Any of the medicaments employed in the present invention can be administered by oral, parenteral (including intravenous, subcutaneous, intramuscular, intradermal, intratracheal, intraperitoneal, intraarticular, intracranial and epidural), airway (aerosol), rectal, vaginal, ocular or topical (including transdermal, buccal, mucosal, sublingual and topical ocular) administration.

[1355] Typically, the mode of administration selected is that most appropriate to the disorder, disease or condition to be treated or prevented.

[1356] For parenteral use, such as intravenous use, the compounds, salts, solvates or prodrugs of the present invention will generally be provided in a sterile aqueous solution or suspension, buffered to an appropriate pH and isotonicity. Suitable aqueous vehicles include Ringer's solution and isotonic sodium chloride or glucose. Aqueous suspensions according to the invention may include suspending agents such as cellulose derivatives, sodium alginate, polyvinylpyrrolidone and gum tragacanth, and a wetting agent such as lecithin. Suitable preservatives for aqueous suspensions include ethyl and n-propyl p-hydroxybenzoate. The compounds, salts, solvates or prodrugs of the invention may also be presented as liposome formulations.

[1357] For oral administration, the compounds, salts, solvates or prodrugs of the present invention will generally be provided in the form of tablets, capsules, hard or softgelatine capsules, caplets, troches or lozenges, as a powder or granules, or as an aqueous solution, suspension or dispersion.

[1358] Tablets for oral use may include the active ingredient mixed with pharmaceutically acceptable excipients such as inert diluents, disintegrating agents, binding agents, lubricating agents, sweetening agents, flavouring agents, colouring agents and preservatives. Suitable inert diluents include sodium and calcium carbonate, sodium and calcium phosphate, and lactose. Corn starch and alginic acid are suitable disintegrating agents. Binding agents may include starch and gelatine. The lubricating agent, if present, may be magnesium stearate, stearic acid or talc. If desired, the tablets may be coated with a material, such as glyceryl monostearate or glyceryl distearate, to delay absorption in the gastrointestinal tract. Tablets may also be effervescent and / or dissolving tablets.

[1359] Capsules for oral use include hard gelatine capsules in which the active ingredient is mixed with a solid diluent, and soft gelatine capsules wherein the active ingredient is mixed with water or an oil such as peanut oil, liquid paraffin or olive oil.

[1360] Powders or granules for oral use may be provided in sachets or tubs. Aqueous solutions, suspensions or dispersions may be prepared by the addition of water to powders, granules or tablets.

[1361] Any form suitable for oral administration may optionally include sweetening agents such as sugar, flavouring agents, colouring agents and / or preservatives.

[1362] Formulations for rectal administration may be presented as a suppository with a suitable base comprising, for example, cocoa butter or a salicylate.

[1363] Formulations suitable for vaginal administration may be presented as pessaries, tampons, creams, gels, pastes, foams or spray formulations containing in addition to the active ingredient such carriers as are known in the art to be appropriate.

[1364] For ocular administration, the compounds, salts, solvates or prodrugs of the invention will generally be provided in a form suitable for topical administration, e.g. as eye drops. Suitable forms may include ophthalmic solutions, gel-forming solutions, sterile powders for reconstitution, ophthalmic suspensions, ophthalmic ointments, ophthalmic emulsions, ophthalmic gels and ocular inserts. Alternatively, the compounds, salts, solvates or prodrugs of the invention may be provided in a form suitable for othertypes of ocular administration, for example as intraocular preparations (including as irrigating solutions, as intraocular, intravitreal or juxtascleral injection formulations, or as intravitreal implants), as packs or corneal shields, as intracameral, subconjunctival or retrobulbar injection formulations, or as iontophoresis formulations.

[1365] For transdermal and other topical administration, the compounds, salts, solvates or prodrugs of the invention will generally be provided in the form of ointments, cataplasms (poultices), pastes, powders, dressings, creams, plasters or patches. Suitable suspensions and solutions can be used in inhalers for airway (aerosol) administration.

[1366] The dose of the compounds, salts, solvates or prodrugs of the present invention will, of course, vary with the disease, disorder or condition to be treated or prevented. In general, a suitable dose will be in the range of 0.01 to 500 mg per kilogram body weight of the recipient per day. The desired dose may be presented at an appropriate interval such as once every other day, once a day, twice a day, three times a day or four times a day. The desired dose may be administered in unit dosage form, for example, containing 1 mg to 50 g of active ingredient per unit dosage form.

[1367] In the case of the use of a compound described herein for imaging, the dose is in an amount sufficient to provide a signal for medical imaging.

[1368] In the case of the use of a compound described herein for therapy, the dose is an amount sufficient to provide sufficient concentration of the compound to provide a therapeutic benefit. For example, for targeted radiotherapy, the dose of the compound is an amount to provide a sufficient level of ionizing radiation at the desired site. As radioactive compounds, dosage of compounds is typically measured as a dosage of radioactivity, for example, as measured in Curie (Ci) or in Becquerel (Bq). Radioactive dosage also varies based on the radioisotope which is present in the compound.

[1369] It will be appreciated by one of skill in the art that appropriate dosages of the compound of Formula (III) and (IIIA), and compositions comprising the same, can vary from patient to patient. Determining the optimal dosage will generally involve the balancing of the level of therapeutic benefit against any risk or deleterious side effects. Dosage for therapeutic effects may differ from the dosage required for diagnostic effects. The selected dosage level will depend on a variety of factors including the activity of the particular compound of Formula (III) and (IIIA), the route of administration, the time of administration, the rate of excretion of the compound ofFormula (III) and (IIIA), the duration of the treatment, other drugs, compounds, and / or materials used in combination, the severity of the disorder, and the species, sex, age, weight, condition, general health, and prior medical history of the patient. The amount of the compound of Formula (III) and (IIIA) and route of administration will ultimately be at the discretion of the physician, veterinarian, or clinician, although generally the dosage will be selected to achieve local concentrations at the site of action which achieve the desired effect without causing substantial harmful or deleterious side-effects.

[1370] Administration can be affected in one dose, continuously or intermittently (e.g., in divided doses at appropriate intervals) throughout the course of treatment. Methods of determining the most effective means and dosage of administration are well known to those of skill in the art and will vary with the formulation used for therapy, the purpose of the therapy, the target being treated, and the subject being treated. Single or multiple administrations can be carried out with the dose level and pattern being selected by the treating physician, veterinarian, or clinician.

[1371] In the case of the use of a compound of Formula (III) for imaging, the dose is in an amount sufficient to provide a signal for medical imaging.

[1372] In the case of the use of a compound of Formula (IIIA) for therapy, the dose is an amount sufficient to provide sufficient concentration of the compound of Formula (IIIA) to provide a therapeutic benefit. For example, for targeted radiotherapy, the dose of the compound of Formula (IIIA) is an amount to provide a sufficient level of ionizing radiation at the desired site.

[1373] An eighteenth aspect of the invention provides a process of preparing a compound of Formula (A) or a salt thereof, the process comprising:

[1374] (i) converting a compound of Formula (B) or a salt thereof into a compound of Formula (C) or a salt thereof:

[1375] HO O1-2O-R19RCO1-2O-R19R17-N-R18R17-N-R18

[1376]

[1377] r\ Formula (B) Formula (C) wherein, R17and R18are each independently hydrogen or a nitrogen protecting group, R19is a carboxyl protecting group, and Rcis a chiral auxiliary group;(ii) reacting the compound of Formula (C) or a salt thereof with a compound of Formula (E) or a salt thereof to form a compound of Formula (D):

[1378]

[1379] Formula (C) wherein R20is halo, and X3is defined according to the first aspect of the invention;

[1380] (iii) converting the compound of Formula (D) or a salt thereof into a compound of Formula (A) or a salt thereof:

[1381]

[1382] Conveniently, the process of the eighteenth aspect provides a chiral synthesis of the compounds of the present invention.

[1383] R17and R18are each independently hydrogen or a nitrogen protecting group. Suitable nitrogen protecting groups may be identified by reference to e.g. Wuts, " Greene's Protective Groups in Organic Synthesis", 5thEd., 2014.

[1384] In one embodiment, one of R18and R17is hydrogen and the other of R17and R18is a nitrogen protecting group. In another embodiment, R18and R17are each a nitrogen protecting group.

[1385] In one embodiment, the nitrogen protecting group is independently benzyloxycarbonyl (CBz), 4-methoxy-benzyloxycarbonyl, benzyl, tert-butoxycarbonyl (Boc), 2-(4-biphenylyl)-isopropoxycarbonyl (Bpoc), triphenylmethyl (Trt), or 2,2,2-trichloroethoxycarbonyl (Troc) protecting groups. In another embodiment, each R17and R18are independently a sulfonyl group, such as a toluenesulfonyl (tosyl or -Ts), methanesulfonyl (mesyl or-Ms), or a trifluoromethanesulfonyl (triflyl or -Tf) group.In one embodiment, each R17and R18are independently benzyloxycarbonyl (CBz), benzyl, or tert-butoxycarbonyl (Boc) groups.

[1386] In one embodiment, each R17and R18are tert-butoxycarbonyl (Boc) groups.

[1387] In one embodiment, one of R18and R17is hydrogen and the other of R17and R18is a tert-butoxycarbonyl (Boc) group.

[1388] R19is a carboxyl protecting group. Suitable carboxyl protecting groups may be identified by reference to e.g. Wuts, " Greene's Protective Groups in Organic Synthesis", 5thEd., 2014.

[1389] For example, the carboxyl protecting group may be an ester. In one embodiment, R19is methyl, ethyl, propyl (including / so-propyl and n-propyl), butyl (including n-butyl, tert-butyl and sec-butyl) or benzyl.

[1390] In one embodiment, R19is methyl, ethyl, / so-propyl, tert-butyl or benzyl. In one embodiment, R19is methyl, tert-butyl, or benzyl.

[1391] In one embodiment, R19is methyl or tert-butyl. In one embodiment, R19is tert-butyl.

[1392] Rcis a chiral auxiliary group. For the avoidance of doubt, and as would be understood by the skilled person, a chiral auxiliary group will be understood to refer to a stereogenic group or unit that is temporarily incorporated into an organic compound in order to control the stereochemical outcome of the

[1393] synthesis. The chirality present in the auxiliary can bias the stereoselectivity of one or more subsequent reactions.

[1394] Accordingly, in one embodiment, in the compounds of Formula (D) and Formula (A), the carbon bearing the benzyl group, marked with an asterisk (*), is a chiral centre and has (S) configuration. In another embodiment, the carbon bearing the benzyl group, marked with an asterisk (*), is a chiral centre and has (R) configuration. The chirality of the benzyl centre marked with an asterisk (*) is controlled by the chirality present in the chiral auxiliary group (Rc).

[1395] Suitable chiral auxiliary groups (Rc) may be identified by reference to Diaz-Munoz et al., Chirality, 2019, 31, 776-812.

[1396] In one embodiment, Rcis of formula (GIA) or (GIB):R21

[1397]

[1398] (G1A)

[1399] wherein:

[1400] denotes the point of attachment to the carbonyl group on the compound of formula (C) and formula (D);

[1401] R21is S or 0;

[1402] R22is N or 0; and

[1403] R23is / so-propyl, tert-butyl, benzyl (Bn), phenyl, or-CH(Ph)2.

[1404] In one embodiment, R21is 0. In one embodiment, R22is 0. In one embodiment, R23is / so-propyl, benzyl, or phenyl. In one embodiment, R23is benzyl.

[1405] In one embodiment, Rcis of formula (Gl-R) or (Gl-S):

[1406]

[1407]

[1408] (G1-R) (G1-S)

[1409] As would be understood, when Rcis of formula (Gl-R), the carbon bearing the benzyl group, marked with an asterisk (*) in the compounds of Formula (D) and Formula (A), is a chiral centre and has (S) configuration. When Rcis of formula (Gl-S), the carbon bearing the benzyl group, marked with an asterisk (*) in the compounds of Formula (D) and formula (A), is a chiral centre and has ( / ?) configuration.

[1410] In one embodiment, the compound of Formula (D) is a compound of Formula (DA):

[1411]

[1412] X3 (DA)In the compound of Formula (E), R20is halo. In one embodiment, R20is chloro, bromo or iodo. In one embodiment, R20is bromo.

[1413] Step i) may be carried out by reacting a compound of Formula (B) or a salt thereof with a source of a chiral auxiliary group to form a compound of Formula (C).

[1414] In one embodiment, when Rcis of formula (Gl-R) or (Gl-S), the source of the chiral auxiliary group may be a compound of formula (Gl-RA) or (GI-SA):

[1415] o °

[1416] O NH ONH

[1417] \ _ (R) / \ ts; /

[1418]

[1419] zBn Bn

[1420] (G1-RA) (G1-SA)

[1421] The reaction may be a coupling reaction. In one embodiment, the reaction is carried out in the presence of 2,2-dimethylpropanoyl chloride. In one embodiment, the reaction is carried out in a polar aprotic solvent such as THF. In one embodiment, the reaction is carried out at a temperature of about -78 °C to about 20 °C.

[1422] Compounds of Formula (B) may be synthesised by any known method, such as the methods described herein.

[1423] In one embodiment, X3is127I.

[1424] Step (ii) is typically carried out in the presence of a base. In one embodiment, the base is NaHMDS, LiHMDS, or NaH. In one embodiment, the base is NaHMDS. In one embodiment, the reaction is carried out in a polar aprotic solvent such as THF. In one embodiment, the reaction is carried out at a temperature of about -78 °C to about 20 °C.

[1425] Step iii) is typically carried out under oxidative hydrolysis conditions. In one embodiment, step iii) is carried out in the presence of H2O2and a base such as lithium hydroxide or sodium hydroxide. In one embodiment, the reaction is carried out in a polar aprotic solvent such as THF. In one embodiment, the reaction is carried out at a temperature of about 0 °C to about 20 °C.

[1426] The compounds of Formula (A) are stereodefined.The compounds of Formula (A) may be converted into the compounds of Formula (IV) defined herein, using the methods defined herein, for example as outlined in general methods (a) - (o).

[1427] Accordingly, in one embodiment, the process further comprises converting the compound of Formula (A) or a salt thereof into a compound of Formula (IV) or a salt thereof.

[1428] When X3is127I, the compounds of Formula (A) may be converted into the compounds of Formula (PI) described herein, using the methods defined herein, for example as outlined in in general methods (a) - (m).

[1429] Accordingly, in an alternative embodiment, when X3is127I, the process further comprises converting the compound of Formula (A) or a salt thereof into a compound of Formula (PI) or a salt thereof.

[1430] As described herein, the compounds of Formula (PI) may be converted into the compounds of Formula (III) and Formula (IIIA).

[1431] In a specific embodiment, the eighteen aspect provides a process of preparing a compound of Formula (Al) or a salt thereof, the process comprising:

[1432] (i) converting a compound of Formula (Bl) or a salt thereof into a compound of Formula (Cl) or a salt thereof:

[1433]

[1434] (ii) reacting the compound of Formula (Cl) or a salt thereof with a compound of Formula (El) or a salt thereof to form a compound of Formula (DI) or a salt thereof:

[1435]

[1436] Formula (C1)

[1437] Formula (D1) wherein X3is defined according to the first aspect of the invention;

[1438] (iii) converting the compound of Formula (DI) or a salt thereof into a compound of Formula (Al) or a salt thereof:

[1439]

[1440] Formula (D1) Formula (A1)

[1441] The compounds of Formula (Al) are stereodefined.

[1442] When X3is19F, the compound of Formula (Al) is a compound of Formula (Al-F):

[1443]

[1444] Formula (A1-F)

[1445] When X3is127I, the compound of Formula (Al) is a compound of Formula (Al-I):

[1446]

[1447] Formula (A1-I)The compounds of Formula (Al-F) and (Al-I) may be converted into the compounds of Formula (IV) defined herein, using the methods defined herein, for example as outlined in in general methods (a) - (o).

[1448] Accordingly, in one embodiment, the process further comprises converting the compound of Formula (Al) or a salt thereof into a compound of Formula (IV) or a salt thereof.

[1449] The compounds of Formula (Al-I) may be converted into the compounds of Formula (PI) described herein, using the methods defined herein, for example as outlined in general methods (a) - (o).

[1450] Accordingly, in an alternative embodiment, when X3is127I, the process further comprises converting the compound of Formula (Al) or a salt thereof into a compound of Formula (PI) or a salt thereof.

[1451] As described herein, the compounds of Formula (PI) may be converted into the compounds of Formula (III) and Formula (IIIA).

[1452] For the avoidance of doubt, insofar as is practicable any embodiment of a given aspect of the present invention may occur in combination with any other embodiment of the same aspect of the present invention. In addition, insofar as is practicable it is to be understood that any preferred, typical or optional embodiment of any aspect of the present invention should also be considered as a preferred, typical or optional embodiment of any other aspect of the present invention.

[1453] All citations are incorporated herein by reference in their entirety.

[1454] Definitions

[1455] In the context of the present specification, a "hydrocarbyl" substituent group or a hydrocarbyl moiety in a substituent group only includes carbon and hydrogen atoms but, unless stated otherwise, does not include any heteroatoms, such as N, 0 or S, in its carbon skeleton. A hydrocarbyl group / moiety may be saturated or unsaturated (including aromatic), and may be straight-chained or branched, or be or include cyclic groups wherein, unless stated otherwise, the cyclic group does not include any heteroatoms, such as N, 0 or S, in its carbon skeleton. Examples of hydrocarbyl groups include alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl and aryl groups / moietiesand combinations of all of these groups / moieties. Typically, a hydrocarbyl group is a C1-C20 hydrocarbyl group. More typically a hydrocarbyl group is a C1-C15 hydrocarbyl group. More typically a hydrocarbyl group is a C1-C10 hydrocarbyl group. A "hydrocarbylene" group is similarly defined as a divalent hydrocarbyl group.

[1456] An "alkyl" substituent group or an alkyl moiety in a substituent group may be linear (i.e. straight-chained) or branched. Examples of alkyl groups / moieties include methyl, ethyl, n-propyl, / -propyl, n-butyl, / -butyl, t-butyl and n-pentyl groups / moieties. Unless stated otherwise, the term "alkyl" does not include "cycloalkyl". Typically, an alkyl group is a C1-C12 alkyl group. More typically an alkyl group is a Ci-Ce alkyl group. An "alkylene" group is similarly defined as a divalent alkyl group.

[1457] An "alkenyl" substituent group or an alkenyl moiety in a substituent group refers to an unsaturated alkyl group or moiety having one or more carbon-carbon double bonds. Examples of alkenyl groups / moieties include ethenyl, propenyl, 1-butenyl, 2-butenyl, 1-pentenyl, 1-hexenyl, 1,3-butadienyl, 1,3-pentadienyl, 1,4-pentadienyl and 1,4-hexadienyl groups / moieties. Unless stated otherwise, the term "alkenyl" does not include "cycloalkenyl". Typically, an alkenyl group is a C2-C12 alkenyl group. More typically an alkenyl group is a C2-C6 alkenyl group. An "alkenylene" group is similarly defined as a divalent alkenyl group.

[1458] An "alkynyl" substituent group or an alkynyl moiety in a substituent group refers to an unsaturated alkyl group or moiety having one or more carbon-carbon triple bonds. Examples of alkynyl groups / moieties include ethynyl, propargyl, but-l-ynyl and but-2-ynyl groups / moieties. Typically, an alkynyl group is a C2-C12 alkynyl group. More typically an alkynyl group is a C2-C6 alkynyl group. An "alkynylene" group is similarly defined as a divalent alkynyl group.

[1459] A "cyclic" substituent group or a cyclic moiety in a substituent group refers to any hydrocarbyl ring, wherein the hydrocarbyl ring may be saturated or unsaturated (including aromatic) and may include one or more (such as one, two, three or four) heteroatoms, e.g. N, 0 or S, in its carbon skeleton. Examples of cyclic groups include cycloalkyl, cycloalkenyl, heterocyclic, aryl and heteroaryl groups as discussed below. A cyclic group may be monocyclic, bicyclic (e.g. bridged, fused or spiro (including dispiro)), or polycyclic. Typically, a cyclic group is a 3- to 16-membered cyclic group, which means it contains from 3 to 16 ring atoms.For the avoidance of doubt, where it is stated that a bicyclic or polycyclic group is "saturated" it is to be understood that all of the ring systems within the bicyclic or polycyclic group (excluding any ring systems which are part of or formed by optional substituents) are saturated.

[1460] A "heterocyclic" or "heterocyclyl" substituent group or a heterocyclic or heterocyclyl moiety in a substituent group refers to a cyclic group or moiety including one or more carbon atoms and one or more (such as one, two, three or four) heteroatoms, e.g. N, 0 or S, in the ring structure. Examples of heterocyclic groups include heteroaryl groups as discussed below and non-aromatic heterocyclic groups such as azetinyl, azetidinyl, oxetanyl, thietanyl, pyrrolidinyl, tetra hydrofuranyl, tetrahydrothiophenyl, pyrazolidinyl, imidazolidinyl, dioxolanyl, oxathiolanyl, piperidinyl, tetra hydro pyranyl, thianyl, piperazinyl, dioxanyl, morpholinyl and thiomorpholinyl groups.

[1461] A "cycloalkyl" substituent group or a cycloalkyl moiety in a substituent group refers to a saturated hydrocarbyl ring containing, for example, from 3 to 10 carbon atoms, examples of which include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, spiro[2.4]heptanyl, spiro[3.3]heptanyl, spiro[2.5]octanyl, spiro[3.4]octanyl, spiro[4.5]decanyl, and bicyclo[l.l.l]pentanyl. Unless stated otherwise, a cycloalkyl substituent group or moiety may include monocyclic, bicyclic or polycyclic hydrocarbyl rings.

[1462] A "cycloalkenyl" substituent group or a cycloalkenyl moiety in a substituent group refers to a non-aromatic unsaturated hydrocarbyl ring having one or more carboncarbon double bonds and containing, for example, from 3 to 7 carbon atoms, examples of which include cyclopent-l-enyl, cyclohex-l-enyl and cyclohex-1, 3-dienyl. Unless stated otherwise, a cycloalkenyl substituent group or moiety may include monocyclic, bicyclic or polycyclic hydrocarbyl rings.

[1463] An "aryl" substituent group or an aryl moiety in a substituent group refers to an aromatic hydrocarbyl ring. The term "aryl" refers to monocyclic aromatic hydrocarbons and polycyclic fused ring aromatic hydrocarbons wherein all of the fused ring systems (excluding any ring systems which are part of or formed by optional substituents) are aromatic. Examples of aryl groups / moieties include phenyl, naphthyl, anthracenyl and phenanthrenyl. Unless stated otherwise, the term "aryl" does not include "heteroaryl". A "heteroaryl" substituent group or a heteroaryl moiety in a substituent group refers to an aromatic heterocyclic group or moiety. The term "heteroaryl" refers to monocyclic aromatic heterocycles and polycyclic fused ring aromatic heterocycleswherein all of the fused ring systems (excluding any ring systems which are part of or formed by optional substituents) are aromatic. Examples of heteroaryl groups / moieties include the following:

[1464]

[1465] wherein G = 0, S or NH.

[1466] For the purposes of the present specification, where a combination of moieties is referred to as one group, for example, arylalkyl, arylalkenyl, arylalkynyl, alkylaryl, alkenylaryl or alkynylaryl, the last mentioned moiety contains the atom by which the group is attached to the rest of the molecule. An example of an arylalkyl group is benzyl.

[1467] As will be appreciated, in an optionally substituted moiety:

[1468] each hydrogen atom may optionally be replaced by any specified monovalent substituent;

[1469] any two hydrogen atoms attached to the same carbon or nitrogen atom may optionally be replaced by any specified n-bonded substituent;

[1470] any sulphur atom may optionally be substituted with one or two of any specified n-bonded substituents; and

[1471] any two hydrogen atoms attached to the same or different atoms, within the same optionally substituted group or moiety, may optionally be replaced by any specified divalent bridging substituent.

[1472] Typically, a substituted group comprises 1, 2, 3 or 4 substituents, more typically 1, 2 or 3 substituents, more typically 1 or 2 substituents, and more typically 1 substituent.

[1473] Unless stated otherwise, any divalent bridging substituent (e.g. -O-, -S-, -NH-, -CH2-, -CH2-CH2-, etc.) of an optionally substituted group or moiety must only be attached to the specified group or moiety and may not be attached to a second group or moiety, even if the second group or moiety can itself be optionally substituted.

[1474] The term "halo" includes fluoro, chloro, bromo and iodo.Unless stated otherwise, where a group is prefixed by the term "halo", such as a haloalkyl or halomethyl group, it is to be understood that the group in question is substituted with one or more halo groups independently selected from fluoro, chloro, bromo and iodo. Typically, the maximum number of halo substituents is limited only by the number of hydrogen atoms available for substitution on the corresponding group without the halo prefix. For example, a halomethyl group may contain one, two or three halo substituents. A haloethyl or halophenyl group may contain one, two, three, four or five halo substituents. Similarly, unless stated otherwise, where a group is prefixed by a specific halo group, it is to be understood that the group in question is substituted with one or more of the specific halo groups. For example, the term "fluoromethyl" refers to a methyl group substituted with one, two or three fluoro groups. Similarly, unless stated otherwise, where a group is prefixed by the term "monofluoro", it is to be understood that the group in question is substituted with one fluoro group. For example, the term "monofluoromethyl" refers to CH2F and the term "monofluoromethoxy" refers to OCH2F.

[1475] Similarly, unless stated otherwise, where a group is said to be "halo-substituted", it is to be understood that the group in question is substituted with one or more halo groups independently selected from fluoro, chloro, bromo and iodo. Typically, the maximum number of halo substituents is limited only by the number of hydrogen atoms available for substitution on the group said to be halo-substituted. For example, a halo-substituted methyl group may contain one, two or three halo substituents. A halo-substituted ethyl or halo-substituted phenyl group may contain one, two, three, four or five halo substituents.

[1476] Unless stated otherwise, any reference to an element is to be considered a reference to all isotopes of that element. Thus, for example, unless stated otherwise any reference to hydrogen is considered to encompass all isotopes of hydrogen including deuterium and tritium.

[1477] Unless stated otherwise, any reference to a compound or group is to be considered a reference to all tautomers of that compound or group.

[1478] Where reference is made to a hydrocarbyl or other group, such as an alkylene group, including one or more heteroatoms N, 0 or S in its carbon skeleton, or where reference is made to a carbon atom of a hydrocarbyl or other group being replaced by an N, 0 or S atom, what is intended is that:- C - - N- - I is replaced b

[1479]

[1480] y I

[1481]

[1482] is replaced by

[1483] -CH2- is replaced by -NH-, -0- or -S-;

[1484] -CH3 is replaced by -NH2, -OH or -SH;

[1485] -CH= is replaced by -N =;

[1486] CH2— is replaced by N

[1487]

[1488] H=, 0= or S=; or

[1489] CH= is replaced by N =;

[1490] provided that the resultant group comprises at least one carbon atom. For example, methoxy, dimethylamino and aminoethyl groups are considered to be hydrocarbyl groups including one or more heteroatoms N, 0 or S in their carbon skeleton.

[1491] Typically, the compounds of the invention contain no more than one quaternary ammonium group. More typically, the compounds of the invention contain no quaternary ammonium groups.

[1492] In the context of the present specification, unless otherwise stated, a Cx-Cygroup is defined as a group containing from x to y carbon atoms. For example, a C1-C4 alkyl group is defined as an alkyl group containing from 1 to 4 carbon atoms. For the purposes of allocating x and y in a Cx-Cygroup, optional substituents are not taken into account when calculating the total number of carbon atoms in the parent group substituted with the optional substituents. For the avoidance of doubt, replacement heteroatoms, e.g. N, 0 or S, are not to be counted as carbon atoms when calculating the number of carbon atoms in a Cx-Cygroup. For example, a morpholinyl group is to be considered a C4 heterocyclic group, not a C6heterocyclic group.

[1493] For the purposes of the present specification, where it is stated that a first atom or group is "directly attached" to a second atom or group it is to be understood that the first atom or group is covalently bonded to the second atom or group with no intervening atom(s) or group(s) being present. So, for example, for the

[1494] group -(C=O)N(CH3)2, the carbon atom of each methyl group is directly attached to the nitrogen atom and the carbon atom of the carbonyl group is directly attached to the nitrogen atom, but the carbon atom of the carbonyl group is not directly attached to the carbon atom of either methyl group.

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[1503] ) Hannah E. Greenwood, Abigail R. Barber, Richard S. Edwards, Will E, Tyrrell, Madeleine E. George, Sofia N. dos Santos, Friedrich Baark, Muhammet Tanc, Erman Khalil, Aimee Falzone, Nathan P. Ward, Janine M. DeBlasi, Laura Torrente, Pritin N. Soni, David R. Pearce, George Firth, Lydia M. Smith, Oskar Vilhelmsson Timmermand, Ariana Huebner, Charles Swanton, Robert E. Hynds, Gina M. DeNicola and Timothy H. Witney. Imaging NRF2 activation in non- small cell lung cancer with positron emission tomography. Nature Communications (2024) 15, 10484.

[1504] 0) Jinyun Liu, Xiaojun Xia, and Peng Huang. xCT: A Critical Molecule That Links Cancer Metabolism to Redox Signaling. Molecular Therapy (2020) 28, 11, 2358.11) Yangmeihui Song, Jianhua Zou, E. Alejandro Castellanos, Naomi Matsuura, John A. Ronald, Adam Shuhendler, Wolfgang A Weber, Assaf A. Gilad, Cristina Muller, Timothy H. Witney, Xiaoyuan Chen. Theranostics - a sure cure for cancer after 100 years?. Theranostics 2024; 14(6): 2464-2488.

[1505] Experimental

[1506] General synthetic methods

[1507] The compounds of the present invention can be prepared by any suitable technique known in the art. Particular methods for forming compounds of the present invention defined herein are shown below and in the accompanying Examples.

[1508] In the description of the synthetic methods described herein and in any referenced synthetic methods that are used to prepare the starting materials, it is to be understood that all proposed reaction conditions, including choice of solvent, reaction atmosphere, reaction temperature, duration of the experiment and workup procedures, can be selected by a person skilled in the art.

[1509] It is understood by one skilled in the art of organic synthesis that the functionality present on various portions of the molecule must be compatible with the reagents and reaction conditions utilised.

[1510] It will be appreciated that during the synthesis of the compounds of the invention in the processes defined herein, or during the synthesis of certain starting materials, it may be desirable to protect certain substituent groups to prevent their undesired reaction. The skilled chemist will appreciate when such protection is required, and how such protecting groups may be put in place and later removed.

[1511] Examples of protecting groups may be found in one of the many general texts on the subject, for example, 'Protective Groups in Organic Synthesis' by Theodora Green (publisher: John Wiley 8i Sons). Protecting groups may be removed by any convenient method described in the literature or known to the skilled chemist as appropriate for the removal of the protecting group in question, such methods being chosen so as to effect removal of the protecting group with the minimum disturbance of groups elsewhere in the molecule. Thus, if reactants include, for example, groups such as amino, carboxy or hydroxy it may be desirable to protect the group in some of the reactions mentioned herein.

[1512] The methodology employed to synthesise a compound of the present invention will vary depending on the nature of n, m R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, L, A, X, X1,X2, X3or any substituent groups associated therewith. Suitable processes for their preparation are described further in the accompanying Examples. It will therefore be understood that different methods may be used to synthesise compounds of the invention, depending on the definition of particular substituents within the compounds, for example the group L. Routine suitable modifications may be made to general methods (a) - (o) in order to synthesis further compounds of the present invention. The resultant compounds of the present invention can be isolated and purified using techniques well known in the art.

[1513] The invention further provides a process for preparing a compound according to the first, second or third aspect, which comprises one or more of the following general methods (a) - (o):

[1514] General Method (a)

[1515] Preparation of a compound of Formula (I), for example a compound scaffold of Formula (lai) or (Ia4), such as a compound of Formula (LVIII), wherein X is iodine or fluorine, and wherein L is typically connected to the backbone chain by a carbon atom, by protection of the amine (-NH2) of the compound of Formula (VI) with a suitable protecting group, to generate a compound of Formula (V), followed by a protection step to generate a compound of Formula (XLVIII), followed by an alkylation with a compound of Formula (XLVII), wherein Z is a suitable leaving group such as a halogen, to generate a compound of Formula (LII) followed by a suitable deprotection step to generate a compound of Formula (LVIII).

[1516] O R2O

[1517] Formula (VI) Formula (V) Formula (XLVIII)

[1518] 7

[1519] O R2O X

[1520] Formula (XLVII) (iii)

[1521] X X

[1522]

[1523] Formula (LII) Formula (LVIII) Typical conditions in General Method (a) above:

[1524] Step (i) comprises protection using, for example, BOC2O in a polar aprotic solvent, in the presence of a base such as DMAP;Step (ii) comprises protection using, for example, BOC2O in a polar protic solvent, or 2-tert-butyl-l,3-diisopropyl-isourea at a temperature around 60 °C;

[1525] Step (Hi) is an alkylation, for example, comprising generating an alkylating agent from the compound of Formula (XLVIII) in the presence of a base such as LDA or LiHMDS at around -78 °C, followed by displacement of the leaving group Z on the compound of Formula (XLVII) via SN2. Typically, Z is bromo. The alkylating agent may be an enolate;

[1526] Step (iv) comprises a suitable deprotection, for example with TFA in DCM at around room temperature, to afford the compound of Formula (LVIII).

[1527] General Method (b)

[1528] Preparation of a compound of Formula (I), for example a compound scaffold of Formula (Ia3) or (Ia6), such as a compound of Formula (LIX), wherein X is iodine or fluorine, and wherein L is typically connected to the backbone chain by a carbon atom, by protection of the amine (-NH2) of the compound of Formula (XVI) with a suitable protecting group to generate a compound of Formula (XV), followed by an alkylation with a compound of Formula (XIV), wherein Z is a suitable leaving group such as a halogen, to generate a compound of Formula (XIII), wherein Hal is a halogen, followed by suitable deprotection and reprotection to generate a compound of Formula (XII), followed by a coupling step, wherein a subsequent deprotection may also be required to generate a compound of Formula (XI), followed by a suitable reduction step to generate a compound of Formula (X), optionally followed by double bond formation to generate a compound of Formula (IX), followed by a cross coupling to generate a compound of Formula (VIII), followed by a suitable reduction step to generate a compound of Formula (VII) or Formula (LIII), optionally followed by suitable diazotization and suitable halide substitution to generate a compound of Formula (LIII), followed by suitable deprotection steps to generate a compound of Formula (LIX).(Hi), (iv) Formula (XVI) Formula (XV)

[1529] Formula (XIII)

[1530]

[1531] Typical conditions in General Method (b) above:

[1532] Step (i) comprises suitable protection using, for example, BOC2O in a polar protic solvent in the presence of a base such as DMAP;

[1533] Step (ii) is an alkylation, for example, comprising generating an alkylating agent from the compound of Formula (XV) in the presence of a base such as LDA or LiHMDS at around -78 °C, followed by displacement of the leaving group Z on the compound of Formula (XIV) via SN2. Typically, Z is bromo. In step (ii), the alkylating agent may be an enolate;

[1534] Step (Hi) comprises suitable deprotection conditions, such as an acid such as TFA in a solvent such as DCM at around room temperature;

[1535] Step (iv) comprises protection using suitable conditions, for example, BOC2O in a polar aprotic solvent, in the presence of a base such as DMAP;Step (v) comprises the formation of an activated group, such as a Weinreb amide, by reacting the compound of Formula (XII) with N, O-dimethylhydroxylamine in the presence of a coupling agent such as HATU and a base such as DIEA, typically at around room temperature;

[1536] Step (vi) comprises suitable protection conditions such as BOC2O in a polar aprotic solvent, in the presence of a base such as DMAP;

[1537] Step (vii) comprises reduction of the Weinreb amide to give the aldehyde, for example, with a reducing agent such as DIBALH;

[1538] Step (viii) comprises an appropriate formation of a double bond, for example using Horner-Wadsworth-Emmons (HWE conditions). Typically, the reaction is carried out in the presence of ethyl 2-(diethoxyphosphoryl)acetate in a base such as t-BuOK in a solvent such as THF;

[1539] Step (ix) comprises a suitable cross coupling, for example, a Buchwald Hartwig cross coupling using benzyl carbamate, a catalyst such as Brettphos Pd-G4 and a base such as cesium carbonate in a polar protic solvent, to insert an amine protected with a suitable protecting group such as Cbz. Typically, Hal is bromo;

[1540] Step (x) comprises a reduction of the double bond in the compound of Formula (VIII) and removal of the protecting group, for example using hydrogen and a Pd catalyst; Step (xi) comprises a suitable SnAr halide substitution, for example, by derivatising the amino group on the compound of Formula (VII) to a leaving group such as a diazonium group using NaNO2and an acid such as TsOH, in the presence of a halide reagent such as KI or HBF4;

[1541] Step (xii) comprises a reduction of the double bond in the compound of Formula (IX) wherein Hal is iodo, for example using hydrogen and Wilkinson's catalyst. Typically, the reaction is carried out in a solvent such as THF and ethanol.

[1542] Step (xiii) comprises an appropriate deprotection, for example with lithium hydroxide in ethanol / water;

[1543] Step (xiv) comprises a further suitable deprotection, for example with TFA in DCM at around room temperature, to afford a compound of Formula (LIX).

[1544] General Method (c)

[1545] Preparation of a compound of Formula (I), for example a compound scaffold of Formula (Ia2) or (Ia5), such as a compound of Formula (LX), wherein X is iodine or fluorine, and wherein L is typically connected to the backbone chain by a carbon atom, by a coupling step, followed by protecting the amine of the compound of Formula (XXVI) with a suitable protecting group, to generate a compound of Formula (XXV), followed by a suitable reduction step to generate a compound of Formula (XXIV),followed by a double bond formation to generate a compound of Formula (XXIII), followed by a suitable reduction step to generate a compound of Formula (XXII), followed by an alkylation with a compound of Formula (XLVII), wherein Z is a suitable leaving group such as a halogen, to generate a compound of Formula (XXI), followed by suitable deprotection and reprotection steps to generate a compound of Formula (XX), followed by acid chloride formation to generate a compound of Formula (XIX), followed by methylation to form a diazoketone of Formula (XVIII), followed by a homologation step to generate a compound of Formula (XVII), followed by suitable deprotection steps to generate a compound of Formula (LX).

[1546] (X)

[1547] Formula (XIX)

[1548] Formula (XVIII)

[1549] (xii), (xiii)

[1550] NH2Formula (LX)

[1551]

[1552] Formula (XVII)

[1553] Typical conditions in General Method (c) above:

[1554] Step (i) comprises formation of an activated group, such as a Weinreb amide, by reacting the compound of Formula (XXVI) with N, O-dimethylhydroxylamine in the presence of a coupling agent such as HATU and a base such as DIEA, typically at around room temperature

[1555] Step (ii) comprises suitable protection using, for example, BOC2O in a polar aprotic solvent, in the presence of a base such as DMAP;Step (iii) comprises reduction of the Weinreb amide of Formula (XXV) to give the aldehyde of Formula (XXIV), for example, using a reducing agent such as DIBALH; Step (iv) comprises formation of a double bond, for example, using HWE conditions. Typically, the reaction is carried out in the presence of tert-butyl 2-(diethoxyphosphoryl)acetate in a base such as t-BuOK in a solvent such as THF;

[1556] Step (v) comprises a reduction of the double bond, for example, using hydrogen and a catalyst such as Ni / Al2O3;

[1557] Step (vi) is an alkylation reaction comprising generating an alkylating agent in the presence of a base, such as LDA or LiHMDS, at a temperature around -78 °C followed by displacement of the leaving group Z on the compound of Formula (XLVII) via SN2. Typically, Z is bromo. In step (vi), the alkylating agent may be an enolate;

[1558] Step (vii) comprises an appropriate deprotection for example with TFA in DCM at around room temperature;

[1559] Step (viii) comprises an appropriate protection using, for example, BOC2O in a polar aprotic solvent, with a base present;

[1560] Step (ix) comprises a formation of an acid chloride, using for example, SOCI2, in a solvent such as DCM in the presence of catalytic DMF;

[1561] Step (x) comprises a methylation using, for example, a methylation reagent such as TMS-diazomethane in a polar aprotic solvent;

[1562] Step (xi) comprises a homologation step, for example, using silver trifluoroacetate in MeCN and MeOH with a base such as TEA;

[1563] Steps (xii) and (xiii) comprises appropriate deprotections to afford a compound of Formula (LX).

[1564] General Method (d)

[1565] Preparation of a compound of Formula (I), for example a compound scaffold of Formula (lai) or (Ia4), such as a compound of Formula (LVIII), wherein X is iodine or fluorine, and wherein L is typically connected to the backbone chain by a carbon atom, by reaction of a compound of Formula (XXXIII), wherein Z is a suitable leaving group such as halo and wherein R11is a suitable protecting group such as a benzyl group, in an alkylation step with a compound of Formula (XLVIII) to generate a compound of Formula (XXXII), followed by a suitable deprotection step to generate a compound of Formula (XXXI), followed by an activation step to generate a compound of Formula (XXX), wherein W is a suitable leaving group such as OTs, bromo or chloro, followed by an SN2 displacement reaction with a compound of Formula (XXIX), wherein Qi is SH, OH or NHR5, to generate a compound of formula (XXVIII), followed by a suitable diazotization and suitable halide substitution to generate a compound of Formula (LII), followed by suitable deprotection steps to generate a compound of Formula (LVIII).O R2O Formula (XXXIII)

[1566] Formula (XXXI) Formula (XLVIII)

[1567] NH2Formula (XXIX)

[1568] (iv) Formula (XXX)

[1569] Formula (XXVIII) Formula (Lil)

[1570] O R20

[1571] X

[1572]

[1573] Formula (LVIII)

[1574] Typical conditions in General Method (d) above:

[1575] Step (i) is an alkylation, for example, comprising generating an alkylating agent from the compound of Formula (XLVIII) in the presence of a base such as LDA or LiHMDS at a temperature around -78 °C, followed by displacement of the leaving group Z on the compound of Formula (XXXIII) via SN2. Typically, the leaving group in the compound of Formula (XXXIII) is chloro. In step (i), the alkylating agent may be an enolate;

[1576] Step (ii) comprises a suitable deprotection, for example when the protecting group R11is benzyl, the deprotection may be carried out using hydrogen and a Pd catalyst such as palladium on carbon;

[1577] Step (iii) comprises suitable formation of a leaving group using, for example, CBr4 in the presence of triphenyl phosphine in a nonpolar aprotic solvent, such as DCM, typically at around room temperature. Typically, W is bromo;

[1578] Step (iv) comprises an alkylation reaction. Typically, the compound of Formula (XXX) is reacted with a base such as K2CO3 in DMF at around room temperature and then in the presence of the compound of Formula (XXIX). For the avoidance of doubt, it will be understood that in the compound of Formula (XXIX), the group Q1may be attached to the ring A, for example an OH group as found in a phenol compound or a SH group as found in a thiophenyl compound, or alternatively the group Q1may be part of the heterocyclic ring system of ring A, for example the NH of an indazolyl group;

[1579] Step (v) comprises a suitable SnAr halide substitution, for example, by derivatising the amino group on the compound of Formula (XXVIII) to a leaving group such as adiazonium group using NaNO2and an acid such as TsOH, in the presence of a halide reagent such as KI or HBF4;

[1580] Step (xii) comprises suitable deprotection to afford a compound of Formula (LVIII).

[1581] General Method (e)

[1582] Preparation of a compound of Formula (I), for example a compound scaffold of Formula (lai) or (Ia4), such as a compound of Formula (LVIII), wherein X is iodine or fluorine, and wherein L is typically connected to the backbone chain by a carbon atom by reaction of a compound of Formula (XLVIII) in an alkylation to afford a compound of Formula (XXXVI), followed by a suitable reduction and oxidation step, the order of which can be reversed to access the homologated target, to generate a compound of Formula (XXXV), followed by an activation step to generate a compound of formula (XXXIV), wherein W is an appropriate leaving group such as OTs, bromo or chloro, followed by a SN2 displacement reaction with a compound of Formula (XLVIIA) or Formula (XLVIIB) wherein Q1is SH, OH or NHR5, optionally followed by a suitable diazotization and suitable halide substitution to generate a compound of Formula (LII), followed by suitable deprotection steps to generate a compound of Formula (LVIII).

[1583] (A) w

[1584]

[1585] Typical conditions in General Method (e) above:

[1586] Step (i) is an alkylation, for example, comprising generating an alkylating agent from the compound of Formula (XLVIII) in the presence of a base such as LDA or LiHMDS at around -78 °C, followed by displacement of the leaving group Z on the compound of Formula (LI) via SN2. Typically, the compound of Formula (LI) is allyl bromide. In step (i), the alkylating agent may be an enolate;

[1587] Step (ii) comprises an oxidation followed by a reduction step or alternatively a reduction followed by an oxidation step, for example, using conditions such as BH3 inTHF, with NaOH and H2O2or O3 followed by a suitable reducing agent such as NaBH4. Step (ii) may be a one pot reaction;

[1588] Step (iii) comprises the formation of a suitable leaving group on the compound of Formula (XXXIV), for example when W is bromo, with appropriate reaction conditions such as CBr4in the presence of triphenyl phosphine in a non-polar aprotic solvent, such as DCM, typically at around room temperature.

[1589] Step (iv) comprises a displacement reaction. Typically, the compound of Formula (XXXIV) is reacted with a base such as NaH in DMF at a temperature of around -20 °C, and then in the presence of a compound of Formula (LVII) or Formula (XXIX). For the avoidance of doubt, it will be understood that in the compounds of Formula (LVII) or Formula (XXIX) the group Q1may be attached to the ring A, for example an OH group as found in a phenol compound or a SH group as found in a thiophenyl compound, or alternatively the group Q1may be part of the heterocyclic ring system of ring A, for example the NH of an indazolyl group.

[1590] Optionally Step (v) comprises a suitable SnAr halide substitution wherein the compound of Formula (XXIX) is used, for example, by derivatising the amino group on the compound of Formula (XXIX) to a leaving group such as a diazonium group using NaNO2 and an acid such as TsOH, in the presence of a halide reagent such as KI or HBF4;

[1591] Step (vi) comprises a suitable deprotection to afford a compound of Formula (LVIII).

[1592] General Method (f)

[1593] Preparation of a compound of Formula (I), for example a compound scaffold of Formula (lai) or (Ia4), such as a compound of Formula (LVIII), wherein X is iodine or fluorine, and wherein L is linked to the backbone chain by an oxygen atom, by reaction of a compound of Formula (XLVIII) in an oxidation reaction, optionally followed by an activation step to generate a compound of Formula (XXXVIII) wherein R12can be H or an appropriate group such that OR12is a leaving group, for example, the group OR12may be OTs, followed by a SN2 displacement reaction with either a compound of Formula (XXXVIIA) wherein Q1is SH, OH or NHR5, or reaction with a compound of Formula (XXXVIIB) wherein Z is a leaving group such as halo, to generate a compound of formula (XLIX), followed by suitable deprotection steps to generate a compound of Formula (LVIII).O R2O Formula (XXXVIIA)

[1594] Formula (XLVIII) Formula (XXXVIII)

[1595] X

[1596] Formula (XXXVIIB)

[1597]

[1598] Typical conditions in General Method (f) above:

[1599] Step (i) comprises an oxidation reaction, such as a Davis oxidation reaction, wherein the compound of Formula (XLVIII) may be reacted with a suitable base such as LDA or LiHMDS at a temperature of around -78 °C, followed by reaction with an oxaziridine such as 3-phenyl-2-(phenylsulfonyl)-l,2-oxaziridine. Typically, the reaction is carried out in a solvent such as THF.

[1600] Step (ii) optionally comprises converting the hydroxyl group on the compound of Formula (XXXVIII) into a leaving group, such as a tosylate. Typically, the reaction is carried out in the presence of an appropriate base such as TEA or DMAP in a solvent such as DCE. As would be understood, in the compound of Formula (XXXVIII) the group OR12may act as a nucleophilic group or act as a leaving group in subsequent reactions, depending on the identity of the group R12. For example, when R12is hydrogen, the group OR12may act as a nucleophile in a subsequent displacement reaction in its deprotonated form. Alternatively, for example, when R12is a group such as tosyl, the group OR12may act as a leaving group in a subsequent displacement reaction.

[1601] Step (iii) comprises an alkylation reaction. When the group OR12is OH, the compound of Formula (XXXVIII) acts as a nucleophile in the alkylation reaction. Accordingly, in the compound of Formula (XXXVIIB), Z is a suitable leaving group, such as bromo. Typically, the reaction is carried out in the presence of a base such as NaH, optionally in the presence of an additive such as TBAI, and typically in a solvent such as DMF. When the group R12is a group such as tosyl, the group OR12can act as a leaving group in the alkylation reaction. Accordingly, in the compound of Formula (XXXVIIA), Q1is typically OH, SH, or NHR5. Typically, the reaction is carried out in the presence of a base such as K2CO3 in a solvent such as DMF.Step (v) comprises suitable deprotection to afford a compound of Formula (LVIII).

[1602] General Method (g)

[1603] Preparation of a compound of Formula (I), such as a compound of Formula (LXI), wherein X is iodine or fluorine, and wherein L is connected to the backbone chain by a heteroatom such as an oxygen atom, a sulfur atom, or a nitrogen atom, typically wherein L is connected to the backbone chain by an oxygen atom, by reaction of a compound of Formula (XXXVIII) wherein R12is hydrogen in an alkylation step to afford a compound of Formula (XLI), followed by a suitable oxidation and reduction step, followed by an activation step to generate a compound of Formula (XL), wherein Q2is a suitable leaving group such as OTs, bromo or chloro, followed by a substitution step with a compound of Formula (XXIX) or Formula (LVII), wherein Q1is SH, OH or NHR5, optionally followed by a suitable diazotization and suitable halide substitution to generate a compound of Formula (LIV), followed by suitable deprotection steps to generate a compound of Formula (LXI).

[1604] Formula (LI)

[1605] (ii), (iii) Formula (XXXVIII)

[1606] NH2R1R2O Formula (XXIX) (iv), (v)

[1607] Formula (XL)

[1608] X

[1609]

[1610] Formula (LVII)

[1611] (Vi)

[1612] Suitable routine modifications may be made to the compound of Formula (XXXVIII) to generate the corresponding SR12compound.

[1613] Typical conditions in General Method (g) above:

[1614] Step (i) comprises an alkylation. Typically, the compound of Formula (XXXVIII) is reacted with a base such as NaH, typically in a solvent such as DMF, optionally in the presence of an additive such as TBAI, followed by reaction with the compound of Formula (LI). Typically, the compound of Formula (LI) is allyl bromide;

[1615] Step (ii) comprises an oxidation followed by reduction step, for example, oxidation with O3 followed by reduction with a suitable reducing agent, such as NaBH4. Step (ii) may be a one pot reaction;Step (iii) comprises formation of a leaving group using appropriate conditions such as tosyl chloride in the presence of an appropriate base such as TEA or DMAP, typically in a solvent such as DCE;

[1616] Step (iv) comprises an alkylation. Typically, the compound of Formula (XXIX) is reacted with the compound of Formula (XL) in the presence of a base such as NaH, optionally in the presence of TBAI and in a solvent such as DMF, or in the presence of a base such as K2CO3 in a solvent such as THF. Typically, in the compound of Formula (XL), the group Q2is OTs;

[1617] Step (v) comprises a suitable SnAr halide substitution, for example, by derivatising the amino group to a leaving group, such as a diazonium group followed by a halide substitution, using t-BuONO in the presence of CH2I2and CuI, and in a solvent such as THF, or a reagent such as HBF4;

[1618] Step (vi) comprises an alkylation. Typically, the compound of Formula (LVII) is reacted with the compound of Formula (XL) in the presence of a base such as NaH, optionally in the presence of TBAI and in a solvent such as DMF, or in the presence of a base such as K2CO3 in a solvent such as THF. Typically, in the compound of Formula (XL), the group Q2is OTs;

[1619] Step (vii) comprises suitable deprotection to afford a compound of Formula (LXI). General Method (h)

[1620] Preparation of a compound of Formula (I), for example a compound scaffold of Formula (Ia3), (Ia6) or (Ia7), such as a compound of Formula (LXII), wherein X is iodine or fluorine, by an olefination reaction on a compound of Formula (XLIV), to generate a compound of Formula (XLIII), followed by olefin metathesis to afford a compound of Formula (XLII), followed by a suitable reduction step to generate a compound of Formula (LV), followed by deprotection steps to generate a compound of Formula (LXII).

[1621] o Formula (LVI) <ii)

[1622] Formula (XLIII) Formula (XLII)

[1623] X

[1624]

[1625] Formula (LXII)Typical conditions in General Method (h) above:

[1626] Step (i) comprises an olefination reaction, for example, a Wittig olefination reaction. Typically, the compound of Formula (XLIV) is reacted with a ylide, typically methylenetriphenylphosphorane in the presence of a base such as potassium tert butoxide and in a solvent such as THF;

[1627] Step (ii) comprises olefin metathesis, for example using an appropriate catalyst such as Grubbs 2ndgeneration catalyst in the presence of a metathesis partner of Formula (LVI) such as ethyl but-3-enoate. Typically, the reaction is carried out in a solvent such as DCM;

[1628] Step (Hi) comprises a reduction, for example using H2 with an appropriate catalyst, for example Wilkinson's catalyst, typically in a solvent such as THF at around room temperature;

[1629] Steps (iv) and (v) comprise suitable deprotection reactions to afford a compound of Formula (LXII).

[1630] General Method (i)

[1631] Preparation o...

Claims

1. Claims1. A compound of Formula (I):XFormula (I)or a pharmaceutically acceptable salt, solvate or prodrug thereof, wherein:n is 0, 1, 2 or 3;m is 1, 2, 3 or 4;provided that m+n is 3 or 4;when present, R1is hydrogen, or C1-C3 alkyl;R2is hydrogen or C1-C3 alkyl;R3is hydrogen or C1-C3 alkyl;L is -O-, -S-, -NR5-, a Ci-Ce straight chained alkylene group, wherein the Ci-Ce straight chained alkylene group optionally includes one, two or three heteroatoms each independently selected from 0, S and NR6in its carbon skeleton, or L is a group -L1-B-L2-, wherein L1and L2are each independently a bond or a C1-C3 straight chained alkylene group, wherein B is a saturated cyclic group selected from a C3-C6 cycloalkyl group, or a 3-, 4-, 5- or 6- membered saturated monocyclic heterocyclic group; wherein L is optionally substituted with one or more substituents independently selected from fluoro, hydroxyl, oxo (=0), C1-C3 alkyl, -O-(Ci-C3 alkyl), -O-(Ci-C3 fluoroalkyl), or C1-C3 fluoroalkyl, and wherein L optionally includes one or more spirocyclic groups, wherein the spirocyclic group is selected from a C3-C5 cycloalkyl group or a saturated C3-C5 heterocyclic group;A is phenyl, naphthyl, or a 5- to 10-membered heteroaryl group;p is 0, 1, or 2;R4is halo, -OH, -NH2, -SH, cyano, or a Ci-Cs saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight chained or branched, or be or include a cyclic group, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N,0 and S in its carbon skeleton, and wherein any -S- moiety in the hydrocarbyl group may optionally be substituted with one or two groups each independently selected from oxo (=0) and =NH to form a -SO-, -SO2-, -S( = NH)- or -SO( = NH)-moiety;R5is hydrogen, C1-C3 alkyl, or C2-C3 alkylene-OR7;R6is C1-C3 alkyl, or C2-C3 alkylene-OR7;R7is hydrogen or methyl;X is iodine, an iodine radioisotope, fluorine, a fluorine radioisotope, or an astatine radioisotope.

2. The compound according to claim 1, wherein X is127I,125I,124I,123I,131I,19F,18F, or211At.

3. The compound according to claim 1 or 2, wherein n is 0 or 1.

4. The compound according to any preceding claim, wherein:when present, each R1is hydrogen;each R2is hydrogen; andR3is hydrogen.

5. The compound according to any one of claims 1-4, wherein L is -O-, -S-, -NR5-, or a Ci-Ce straight chained alkylene group, wherein the Ci-Ce straight chained alkylene group optionally includes one, two or three heteroatoms each independently selected from 0, S and NR6in its carbon skeleton, and wherein the Ci-Ce straight chained alkylene group may optionally be substituted with one or two substituents independently selected from fluoro, hydroxyl, oxo (=0), methyl, ethyl, methoxy, ethoxy, fluoromethyl, fluoroethyl, -O-(fluoromethyl), or -O-(fluoroethyl), and wherein the Ci-Ce straight chained alkylene group optionally includes a spirocyclic group, wherein the spirocyclic group is a cyclopropyl, cyclobutyl, oxiranyl, aziridinyl, azetidinyl, or oxetanyl group.

6. The compound according to one of claims 1-5, wherein A is phenyl, naphthyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, indolizinyl, indazolyl, benzimidazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, quinazolinyl, or naphthyridinyl.

7. The compound according to any one of claims 1-6, wherein p is 0.

8. The compound according to any one of claims 1-6, wherein p is 1, and wherein R4is fluoro, chloro, bromo, iodo, cyano, C1-C4 alkyl optionally C3-C4 alkyl, -O-(Ci-C4alkyl) optionally -O-(C3-C4 alkyl), C3-C4 cycloalkyl, -O(C3-C4 cycloalkyl), C3-C4 heterocycloalkyl, -O(C3-C4 heterocycloalkyl), or -S(Ci-C4 alkyl), wherein any alkyl group may be optionally substituted by one or more substituents selected from fluoro, OH, OMe, cyclopropyl, or cyclobutyl.

9. The compound according to any one of claims 1-8, wherein the compound is of Formula (II):R1R2OFormula (II)or a pharmaceutically acceptable salt, solvate, or prodrug thereof.

10. The compound according to any one of claims 1-8, wherein the compound is of Formula (III):R1R20A )X1Formula (III)or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein X1is125I,124I,123I,131I,18F, or211At.

11. The compound according to any one of claims 1-8, wherein the compound is of Formula (IIIA):or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein X2is125I,123I,131I, or211At.

12. A compound selected from the group consisting of:2-amino-7-(4-iodobenzyl)octanedioic acid;2-amino-6-(4-iodobenzyl)heptanedioic acid;2-amino-4-(4-iodobenzyl)heptanedioic acid;2-amino-7-(((4-iodophenyl)thio)methyl)octanedioic acid;2-a i no-6-(3-((4-iodophenyl)thio)propyl) heptanedioic acid;2-amino-6-(3-iodobenzyl)heptanedioic acid;2-amino-6-(((4-iodophenyl)thio)methyl)heptanedioic acid; 2-amino-6-(3-fluoro-4-iodobenzyl)heptanedioic acid;2-amino-6-(3-(5-iodo-lH-indazol-l-yl)propyl)heptanedioic acid; 2-amino-7-(3-((4-iodophenyl)thio)propyl)octanedioic acid; 2-amino-6-(4-iodobenzyl)octanedioic acid;2-amino-6-((4-iodobenzyl)oxy)heptanedioic acid compound;2-amino-6-(2-((4-iodophenyl)thio)ethyl)heptanedioic acid;2-amino-5-(4-iodobenzyl)heptanedioic acid;2-amino-4-(4-iodobenzyl)octanedioic acid;2-a mi no-6-(4-iodophenoxy) heptanedioic acid;2-a mino-6-(2-((4-iodophenyl)thio)ethoxy) heptanedioic acid;2-amino-6-(4-(iodo-125I)benzyl)heptanedioic acid;2-amino-6-(3-(iodo-125I)benzyl)heptanedioic acid2-amino-6-(3-((4-(iodo-125I)phenyl)thio)propyl)heptanedioic acid; 2-amino-6-((4-(iodo-125I)benzyl)oxy)heptanedioic acid;2-amino-7-(3-iodobenzyl)octanedioic acid;2-amino-6-(2-fluoro-4-iodobenzyl)heptanedioic acid;2-amino-6-(3-(4-iodophenoxy)propyl)heptanedioic acid;2-amino-6-(2-(4-iodophenoxy)ethyl)heptanedioic acid;2-amino-6-(3-(4-iodophenyl)propoxy)heptanedioic acid;2-a mi no-6-(2-(4-iodophenoxy)ethoxy) heptanedioic acid;2-amino-6-(4-fluorobenzyl)heptanedioic acid;2-amino-6-(2-iodobenzyl)heptanedioic acid;2-amino-6-(3-fluorobenzyl)heptanedioic acid;2-amino-6-(4-iodophenethyl)heptanedioic acid;2-amino-7-(4-fluorobenzyl)octanedioic acid;2-amino-7-(3-fluorobenzyl)octanedioic acid;2-a i no-6-(3-iodophenoxy) heptanedioic acid;2-a mi no-6-((3-iodobenzyl)oxy) heptanedioic acid;2-amino-6-(3-(3-iodophenyl)propyl)heptanedioic acid;2-amino-6-(3-iodophenethyl)heptanedioic acid;2-a mi no-6-(2-(3-iodophenoxy)ethoxy) heptanedioic acid;2-amino-6-(4-iodophenethoxy)heptanedioic acid;2-amino-6-((4-iodophenoxy)methyl)heptanedioic acid;2-amino-6-(4-(4-iodophenyl)butyl)heptanedioic acid;2-amino-6-(4-(3-iodophenyl)butyl)heptanedioic acid;2-amino-4-(3-iodobenzyl)heptanedioic acid;2-amino-6-(3-(4-iodophenyl)propyl)heptanedioic acid;2-amino-6-(2-((4-(iodo-125I)phenyl)thio)ethyl)heptanedioic acid; 2-amino-6-(3-(fluoro-18F)benzyl)heptanedioic acid;2-amino-6-(3-(iodo-131I)benzyl)heptanedioic acid;2-amino-6-(3-((4-(iodo-131I)phenyl)thio)propyl)heptanedioic acid; 2-amino-6-((4-(iodo-125I)benzyl)oxy)heptanedioic acid;2-a mi no-6-(3-(3-(iodo-125I)phenyl)propyl) heptanedioic acid;2-a mi no-6-(3-(4-(iodo-125I)phenyl)propyl) heptanedioic acid;2-amino-6-(4-fluoro-3-iodobenzyl)heptanedioic acid;2-amino-6-(3-fluoro-5-iodobenzyl)heptanedioic acid;2-amino-6-((5-iodopyridin-3-yl)methyl)heptanedioic acid;2-amino-6-(4-cyano-3-iodobenzyl)heptanedioic acid;2-a mino-6-(2-(3-fluorophenoxy)ethoxy) heptanedioic acid;2-amino-6-(3-iodo-4-methylbenzyl)heptanedioic acid;2-amino-6-(3-(4-(iodo-125I)phenyl) propoxy)heptanedioic acid; 2-amino-6-(2-(3-(iodo-125I) phenoxy)ethoxy)heptanedioic acid; 2-amino-4-(3-(iodo-125I)benzyl)heptanedioic acid; and2-amino-6-(3-(astato-211-At)benzyl)heptanedioic acid;and pharmaceutically acceptable salts, solvates or prodrugs of any one thereof.

13. A compound of Formula (PI):R1R2OA )■f WYFormula (PI)or a pharmaceutically acceptable salt, solvate or prodrug thereof, wherein:n is 0, 1, 2 or 3;m is 1, 2, 3 or 4;provided that m+n is 3 or 4;when present, R1is hydrogen or C1-C3 alkyl;R2is hydrogen or C1-C3 alkyl;R3is hydrogen or C1-C3 alkyl;L is -O-, -S-, -NR5-, a Ci-Ce straight chained alkylene group, wherein the Ci-Ce straight chained alkylene group optionally includes one, two or three heteroatoms each independently selected from 0, S and NR6in its carbon skeleton, or L is a group -L1-B-L2-, wherein L1and L2are each independently a bond or a C1-C3 straight chained alkylene group, wherein B is a saturated cyclic group selected from a C3-C6 cycloalkyl group, or a 3-, 4-, 5- or 6- membered saturated monocyclic heterocyclic group; wherein L is optionally substituted with one or more substituents independently selected from fluoro, hydroxyl, oxo (=0), C1-C3 alkyl, -O-(Ci-C3 alkyl), -O-(Ci-C3 fluoroalkyl), or C1-C3 fluoroalkyl, and wherein L optionally includes one or more spirocyclic groups, wherein the spirocyclic group is selected from a C3-C5 cycloalkyl group or a saturated C3-C5 heterocyclic group;A is phenyl, naphthyl, or a 5- to 10-membered heteroaryl group;p is 0, 1, or 2;R4is halo, -OH, -NH2, -SH, cyano, or a Ci-Cs saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight chained or branched, or be or include a cyclic group, wherein the hydrocarbyl group may optionally be substituted with one or more halo groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, 0 and S in itscarbon skeleton, and wherein any -S- moiety in the hydrocarbyl group may optionally be substituted with one or two groups each independently selected from oxo (=0) and = NH to form a -SO-, -SO2-, -S( = NH)- or -SO( = NH)-moiety;R5is hydrogen, C1-C3 alkyl, or C2-C3 alkylene-OR7;R6is C1-C3 alkyl, or C2-C3 alkylene-OR7;R7is hydrogen or methyl;each R8is independently hydrogen or a carboxyl protecting group;R9and R10are each independently hydrogen or a nitrogen protecting group; and Y is a leaving group.

14. The compound according to claim 13, wherein Y is selected from a boronic ester, boronic acid, alkylsulfonate, arylsulfonate, trialkylamine, organostannane, organosilicate, aryliodonium salt, and an arylsulfonium salt.

15. The compound according to claim 13 or claim 14, wherein Y is -BPin, -B(OH)2, -SnMes or -SnBu3.

16. The compound according to any one of claims 13-15, wherein the compound is selected from the group consisting of:di-tert-butyl-2-(bis(tert-butoxycarbonyl)amino)-6-(3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)benzyl)heptanedioate;di-tert-butyl-2-(bis(tert-butoxycarbonyl)amino)-6-(4-(4,4,5,5-tetramethyl- 1.3.2-dioxaborolan-2-yl)benzyl)heptanedioate;di-tert-butyl-2-[bis(tert-butoxycarbonyl)amino]-6-[3-[4-(4,4,5,5-tetramethyl- 1.3.2-dioxaborolan-2-yl)phenyl]sulfanylpropyl]heptanedioate;di-tert-butyl-2-(bis(tert-butoxycarbonyl)amino)-7-(3-((4-(4,4,5,5-tetramethyl- 1.3.2-dioxaborolan-2-yl)phenyl)thio)propyl)octanedioate;di-tert-butyl-2-(bis(tert-butoxycarbonyl)amino)-6-(3-(5-(4,4,5,5-tetramethyl- 1.3.2-dioxaborolan-2-yl)-lH-indazol-l-yl)propyl)heptanedioate;ditert-butyl-2-[bis(tert-butoxycarbonyl)amino]-6-[[4-(4,4,5,5-tetramethyl- 1.3.2-dioxaborolan-2-yl)phenyl]methoxy] heptanedioate;di-tert-butyl-2-(bis(tert-butoxycarbonyl)amino)-7-(4-(4,4,5,5-tetramethyl- 1.3.2-dioxaborolan-2-yl)benzyl)octanedioate;ditert-butyl-2-[bis(tert-butoxycarbonyl)amino]-6-[4-(4,4,5,5-tetramethyl- 1.3.2-dioxaborolan-2-yl)phenoxy]heptanedioate;di-tert-butyl-2-(bis(tert-butoxycarbonyl)amino)-6-(3-(4-(4,4,5,5-tetramethyl- 1.3.2-dioxaborolan-2-yl)phenyl)propyl)heptanedioate;di-tert-butyl-2-[bis(tert-butoxycarbonyl)amino]-6-[(3-tributylstannylphenyl)methyl]heptanedioate;di-tert-butyl-2-(bis(tert-butoxycarbonyl)amino)-6-(3-(3-(4,4,5,5-tetramethyl- 1.3.2-dioxaborolan-2-yl)phenyl)propyl)heptanedioate;di-tert-butyl-2-(bis(tert-butoxycarbonyl)amino)-6-(3-(4-(4,4,5,5-tetramethyl- 1.3.2-dioxaborolan-2-yl)phenyl)propoxy)heptanedioate;di-tert-butyl-2-(bis(tert-butoxycarbonyl)amino)-6-(2-(3-(4,4,5,5-tetramethyl- 1.3.2-dioxaborolan-2-yl)phenoxy)ethoxy) heptanedioate;di-tert-butyl 2-(bis(tert-butoxycarbonyl)amino)-4-(3-(4,4,5,5-tetramethyl- 1.3.2-dioxaborolan-2yl) benzyl) heptanedioate;6-(bis(tert-butoxycarbonyl)amino)-7-(tert-butoxy)-7-oxo-2-(3-(4,4,5,5-tetra methyl- 1, 3, 2-dioxaborolan-2-yl)benzyl)heptanoic acid;2-amino-6-(3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)benzyl) heptanedioic acid; and2-amino-6-(3-boronobenzyl)heptanedioic acid;and pharmaceutically acceptable salts, solvates or prodrugs of any one thereof.

17. A process for the preparation of a compound according to claim 10 or claim 11 or a pharmaceutically acceptable salt, solvate or prodrug thereof, wherein the process comprises reacting a compound according to any one of claims 13-16, or a pharmaceutically acceptable salt, solvate or prodrug thereof, with a source of a radioisotope under conditions to replace the group Y on the compound according to any one of claims 13-16 or the pharmaceutically acceptable salt, solvate or prodrug thereof, with a radioisotope from the source of the radioisotope.

18. A pharmaceutical composition comprising a compound according to any one of claims 1-12, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, and a pharmaceutically acceptable excipient.

19. A compound according to any one of claims 1-12, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, or the pharmaceutical composition according to claim 18, for use in medicine.

20. A compound according to claim 10, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, or a pharmaceutical composition comprising the compound according to claim 10, for use in diagnosis.

21. A compound according to claim 10, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, or a pharmaceutical composition comprising the compound according to claim 10, for use in the diagnosis of cancer.

22. A compound according to claim 11, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, or a pharmaceutical composition comprising the compound according to claim 11, for use in treating a disease, disorder or condition.

23. A compound according to claim 11, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, or a pharmaceutical composition comprising the compound according to claim 11, for use in treating cancer.

24. The compound for use according to claim 21 or claim 23, wherein the cancer is bladder cancer, brain cancer, breast cancer, estrogen receptor positive (ER+) breast cancer, estrogen receptor negative (ER-) breast cancer, invasive ductal breast cancer (IDBC), colon cancer, colorectal cancer, gastric cancer, head and neck cancer, kidney cancer, liver cancer, lung cancer, non-small-cell lung cancer (NSCLC), oral cancer, ovarian cancer, pancreatic cancer, prostate cancer, renal cancer, glioma, carcinoma, hepatocellular carcinoma (HCC), prostate carcinoma, squamous cell carcinoma, oesophageal squamous cell carcinoma (ESCC), head and neck squamous cell carcinoma, oral squamous cell carcinoma, tongue squamous cell carcinoma (TSCC), adenocarcinoma, leukaemia, chronic lymphocytic leukaemia (CLL), lymphoma, Burkitt's lymphoma, Kaposi's herpes virus (KSHV) / HIV-associated lymphoma, primary effusion lymphoma (PEL), melanoma, sarcoma, Kaposi's sarcoma (KS), glioblastoma, a solid tumour, a cancer overexpressing system xc“, a cancer upregulating system xc“, or a drug resistant cancer.

25. A method of medical imaging, the method comprising:i. administering a compound according to claim 10, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, or a pharmaceutical composition comprising a compound according to claim 10 to a subject; andii. imaging the subject, optionally wherein the imaging of the subject is by PET, SPECT or scintigraphy.

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