Quinolone derivatves against cancer

Abstract

The present invention provides compounds of Formula (I) and pharmaceutically acceptable salts, solvates and prodrugs thereof: Formula (I) wherein RX, X1, X2, X3, X4, Q1, A1, A2, A3, A4, A5 and A6 are as defined in the specification, and antibody-drug conjugates (ADCs) comprising the compounds. The present invention also relates to processes for the preparation of the compounds and ADCs, pharmaceutical compositions containing them and their use in therapy, particularly for use in treating cancers.

Description

[0001] Novel Compounds Field of the Invention The present invention relates to fused tetracyclic heteroaromatic compounds and antibody-drug conjugates (ADCs) comprising the compounds. The present invention also relates to processes for the preparation of the compounds and ADCs, and to pharmaceutical compositions containing them and their use in therapy, particularly for use in treating cancers. Background of the Invention Small molecules have a long history of use in cancer chemotherapy (e.g. cisplatin family and anthracyclines).1One such compound, CX-5461, entered clinical trials for solid tumours with HR-deficiency mutations (NCT02719977)2. The molecule was overall well tolerated, but displayed dose-limiting phototoxicity.2Similarly, photosensitivity had been observed in a previous clinical trial of CX-5461 in patients with hematologic malignancies.3There is a need to provide compounds with improved pharmacological and / or physiological and / or physicochemical properties and / or those that provide a useful alternative to CX-5461. Summary of the Invention A first aspect of the invention provides a compound of Formula (I): Formula (I) wherein: RXis selected from -OH, -SH, -NH2 or a C1-C24 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo and / or -NO2 groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O 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 (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety; X1is N, C-H, C-Hal or C-RX1; X2is N, C-H, C-Hal or C-RX2; X3is N, C-H, C-Hal or C-RX3; and X4is N or C; provided that at least one of X1, X2, X3and X4is N, and that no more than three of X1, X2, X3and X4are N; RX1, RX2and RX3are each independently selected from -OH, -SH, -NH2, -SO2H, -SO3H, -SO2NH2, -NO2, or a C1-C4 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 and / or -NO2 groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O 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 (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety; Q1is O, S, N, N-H, N-RQ1, C-H, C-Hal, or C-RQ2; RQ1is selected from a C1-C4 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 and / or -NO2 groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O 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 (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety, provided that the atom of RQ1that is directly attached to the nitrogen atom of N-RQ1is a carbon atom; RQ2is selected from -OH, -SH, -NH2, -SO2H, -SO3H, -SO2NH2, -NO2, or a C1-C4 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 and / or -NO2 groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O 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 (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety; A1is N, C-H, C-Hal or C-RA1; A2is N, C-H, C-Hal or C-RA2; A3is N, C-H, C-Hal or C-RA3; A4is N, C-H, C-Hal or C-RA4; and A5is N or C; provided that no more than three of A1, A2, A3, A4and A5are N; RA1, RA2, RA3and RA4are each independently selected from -OH, -SH, -NH2, -SO2H, -SO3H, -SO2NH2, -NO2, or a C1-C4 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 and / or -NO2 groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O 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 (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety; A6is N or C; and each Hal is independently selected from a fluoro, chloro, bromo or iodo group. As will be understood, and as indicated by the circles, each of the four rings in the fused tetracyclic ring system of Formula (I) is aromatic. In other words, X1, X2, X3, X4, A1, A2, A3, A4, A5, A6and Q1are selected such that each ring of the fused tetracyclic ring system of Formula (I) is aromatic. 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, O 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, O or S, in its carbon skeleton. Examples of hydrocarbyl groups include alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl and aryl groups / moieties and 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. 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, i-propyl, n-butyl, i-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 C1-C6 alkyl group. An “alkylene” group is similarly defined as a divalent alkyl group. 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. 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-1-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. 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 heteroatoms, e.g. N, O 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), or polycyclic. Typically, a cyclic group is a 3- to 12-membered cyclic group, which means it contains from 3 to 12 ring atoms. More typically, a cyclic group is a 3- to 7-membered monocyclic group, which means it contains from 3 to 7 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. A “heterocyclic” substituent group or a heterocyclic 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, O 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, tetrahydrofuranyl, tetrahydrothiophenyl, pyrazolidinyl, imidazolidinyl, dioxolanyl, oxathiolanyl, piperidinyl, tetrahydropyranyl, thianyl, piperazinyl, dioxanyl, morpholinyl and thiomorpholinyl groups. A “cycloalkyl” substituent group or a cycloalkyl moiety in a substituent group refers to a saturated hydrocarbyl ring containing, for example, from 3 to 7 carbon atoms, examples of which include cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. Unless stated otherwise, a cycloalkyl substituent group or moiety may include monocyclic, bicyclic or polycyclic hydrocarbyl rings. A “cycloalkenyl” substituent group or a cycloalkenyl moiety in a substituent group refers to a non-aromatic unsaturated hydrocarbyl ring having one or more carbon- carbon double bonds and containing, for example, from 3 to 7 carbon atoms, examples of which include cyclopent-1-en-1-yl, cyclohex-1-en-1-yl and cyclohex-1,3- dien-1-yl. Unless stated otherwise, a cycloalkenyl substituent group or moiety may include monocyclic, bicyclic or polycyclic hydrocarbyl rings. 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 heterocycles wherein 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: wherein G = O, S or NH. Unless stated otherwise, where a cyclic group or moiety is stated to be aromatic, such as an aryl or a heteroaryl group, it is to be understood that each ring system within the group or moiety (excluding any ring systems which are part of or formed by optional substituents) is aromatic. Similarly, where a cyclic group or moiety is stated to be non-aromatic, such as a cycloalkyl, cycloalkenyl or non-aromatic heterocyclic group, it is to be understood that each ring system within the group or moiety (excluding any ring systems which are part of or formed by optional substituents) is non-aromatic. 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. As will be appreciated, in an optionally substituted moiety: - each hydrogen atom may optionally be replaced by any specified monovalent substituent; - any two hydrogen atoms attached to the same carbon or nitrogen atom may optionally be replaced by any specified π-bonded substituent; - any sulphur atom may optionally be substituted with one or two of any specified π-bonded substituents; and - 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. 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. Unless stated otherwise, any divalent bridging substituent (e.g. -O-, -S-, -NH-, -CH2-, -CH2-CH2-, etc.) of an optionally substituted group or moiety (e.g. R1) must only be attached to the specified group or moiety and may not be attached to a second group or moiety (e.g. R2), even if the second group or moiety can itself be optionally substituted. 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 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. 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. Unless stated otherwise, any reference to a compound or group is to be considered a reference to all tautomers of that compound or group. Where reference is made to a hydrocarbyl or other group including one or more heteroatoms N, O 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, O or S atom, what is intended is that: C is replaced CH . N .. . is replaced by; –CH2– is replaced by –NH–, –O– or –S–; –CH3 is replaced by –NH2, –OH or –SH; –CH= is replaced by –N=; CH2= is replaced by NH=, O= or S=; or CH≡ is replaced by N≡; 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, O or S in their carbon skeleton. 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. In the context of the present specification, unless otherwise stated, a Cx-Cy group 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-Cy group, 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, O or S, are not to be counted as carbon atoms when calculating the number of carbon atoms in a Cx-Cy group. For example, a morpholinyl group is to be considered a C4 heterocyclic group, not a C6 heterocyclic group. 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 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. As stated in accordance with the first aspect of the invention, RXis selected from -OH, -SH, -NH2 or a C1-C24 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo and / or -NO2 groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O 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 (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety. In one embodiment of the first aspect of the invention, RXis a C1-C24 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight- chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo and / or -NO2 groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O 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 (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety. Typically, the hydrocarbyl group of RXincludes at least one heteroatom independently selected from N, O and S in its carbon skeleton. For example, RXmay be a C1-C24 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo and / or -NO2 groups, wherein the hydrocarbyl group includes one or more heteroatoms each independently selected from N, O and S in its carbon skeleton, wherein any -S- moiety in the hydrocarbyl group may optionally be substituted with one or two groups each independently selected from oxo (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety. Typically in such an embodiment, the hydrocarbyl group is a C1- C12 group. Typically in such an embodiment, the hydrocarbyl group includes no more than five heteroatoms selected from N, O and S in its carbon skeleton. More typically in such an embodiment, the hydrocarbyl group includes no more than four heteroatoms selected from N, O and S in its carbon skeleton. Typically in such an embodiment, the hydrocarbyl group includes no more than three cyclic groups. More typically, the hydrocarbyl group includes no more than two cyclic groups. In one aspect of such an embodiment, the atom of RXthat is directly attached to the remainder of the compound of Formula (I) is a nitrogen, oxygen or sulphur atom, more typically a nitrogen or oxygen atom, and most typically a nitrogen atom. In another aspect of such an embodiment, the atom of RXthat is directly attached to the remainder of the compound of Formula (I) is a carbon atom. For instance, RXmay be a C1-C12 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or two cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo and / or -NO2 groups, wherein the hydrocarbyl group includes one, two, three or four heteroatoms each independently selected from N, O and S in its carbon skeleton, wherein any -S- moiety in the hydrocarbyl group may optionally be substituted with one or two groups each independently selected from oxo (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety. In one embodiment, the hydrocarbyl group of RXincludes at least two heteroatoms each independently selected from N, O and S in its carbon skeleton. For example, RXmay be a C2-C24 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo and / or -NO2 groups, wherein the hydrocarbyl group includes two or more heteroatoms each independently selected from N, O and S in its carbon skeleton, wherein any -S- moiety in the hydrocarbyl group may optionally be substituted with one or two groups each independently selected from oxo (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety, and wherein the atom of RXthat is directly attached to the remainder of the compound of Formula (I) is a nitrogen, oxygen or sulphur atom. Typically in such an embodiment, the hydrocarbyl group is a C2-C12 group. Typically in such an embodiment, the hydrocarbyl group includes two, three, four or five heteroatoms each independently selected from N, O and S in its carbon skeleton. More typically in such an embodiment, the hydrocarbyl group includes two, three or four heteroatoms each independently selected from N, O and S in its carbon skeleton. Typically in such an embodiment, the hydrocarbyl group includes no more than three cyclic groups. More typically, the hydrocarbyl group includes no more than two cyclic groups. Typically in such an embodiment, the atom of RXthat is directly attached to the remainder of the compound of Formula (I) is a nitrogen or oxygen atom. More typically, the atom of RXthat is directly attached to the remainder of the compound of Formula (I) is a nitrogen atom. For instance, RXmay be a C2-C12 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or two cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo and / or -NO2 groups, wherein the hydrocarbyl group includes two, three or four heteroatoms each independently selected from N, O and S in its carbon skeleton, wherein any -S- moiety in the hydrocarbyl group may optionally be substituted with one or two groups each independently selected from oxo (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety. In a further embodiment, RXis a C1-C24 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo and / or -NO2 groups, and wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N and O in its carbon skeleton. Typically in such an embodiment, the hydrocarbyl group of RXincludes at least one heteroatom independently selected from N and O in its carbon skeleton. For example, RXmay be a C1-C24 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo and / or -NO2 groups, wherein the hydrocarbyl group includes one or more heteroatoms each independently selected from N and O in its carbon skeleton. Typically in such an embodiment, the hydrocarbyl group is a C1-C12 group. Typically in such an embodiment, the hydrocarbyl group includes no more than five heteroatoms selected from N and O in its carbon skeleton. More typically in such an embodiment, the hydrocarbyl group includes no more than four heteroatoms selected from N and O in its carbon skeleton. Typically in such an embodiment, the hydrocarbyl group includes no more than three cyclic groups. More typically, the hydrocarbyl group includes no more than two cyclic groups. In one aspect of such an embodiment, the atom of RXthat is directly attached to the remainder of the compound of Formula (I) is a nitrogen or oxygen atom, more typically a nitrogen atom. In another aspect of such an embodiment, the atom of RXthat is directly attached to the remainder of the compound of Formula (I) is a carbon atom. For instance, RXmay be a C1-C12 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or two cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo and / or -NO2 groups, and wherein the hydrocarbyl group includes one, two, three or four heteroatoms each independently selected from N and O in its carbon skeleton. In another embodiment, the hydrocarbyl group of RXincludes at least two heteroatoms each independently selected from N and O in its carbon skeleton. For example, RXmay be a C2-C24 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo and / or -NO2 groups, wherein the hydrocarbyl group includes two or more heteroatoms each independently selected from N and O in its carbon skeleton, and wherein the atom of RXthat is directly attached to the remainder of the compound of Formula (I) is a nitrogen or oxygen atom. Typically in such an embodiment, the hydrocarbyl group is a C2-C12 group. Typically in such an embodiment, the hydrocarbyl group includes two, three, four or five heteroatoms each independently selected from N and O in its carbon skeleton. More typically in such an embodiment, the hydrocarbyl group includes two, three or four heteroatoms each independently selected from N and O in its carbon skeleton. Typically, the hydrocarbyl group includes one nitrogen atom in its carbon skeleton and one, two or three further heteroatoms each independently selected from N and O in its carbon skeleton. Typically in such an embodiment, the hydrocarbyl group includes no more than three cyclic groups. More typically, the hydrocarbyl group includes no more than two cyclic groups. Typically in such an embodiment, the atom of RXthat is directly attached to the remainder of the compound of Formula (I) is a nitrogen atom. For instance, RXmay be a C2-C12 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or two cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo and / or -NO2 groups, wherein the hydrocarbyl group includes two, three or four heteroatoms each independently selected from N and O in its carbon skeleton, and wherein the atom of RXthat is directly attached to the remainder of the compound of Formula (I) is a nitrogen or oxygen atom. In one embodiment, RXis a C1-C24 saturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more fluoro groups and / or one or more oxo (=O) groups, and wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N and O in its carbon skeleton. Typically in such an embodiment, the hydrocarbyl group of RXincludes at least one heteroatom independently selected from N and O in its carbon skeleton. For example, RXmay be selected from a C1-C24 saturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more fluoro groups and / or one or more oxo (=O) groups, and wherein the hydrocarbyl group includes one or more heteroatoms each independently selected from N and O in its carbon skeleton. Typically in such an embodiment, the hydrocarbyl group is a C1-C12 group. Typically in such an embodiment, the hydrocarbyl group includes no more than five heteroatoms selected from N and O in its carbon skeleton. More typically in such an embodiment, the hydrocarbyl group includes no more than four heteroatoms selected from N and O in its carbon skeleton. Typically in such an embodiment, the hydrocarbyl group includes no more than three cyclic groups. More typically, the hydrocarbyl group includes no more than two cyclic groups. Typically in such an embodiment, where the hydrocarbyl group is substituted, it is substituted with one or more fluoro groups and / or one, two or three oxo (=O) groups. More typically, where the hydrocarbyl group is substituted, it is substituted with one or more fluoro groups and / or one or two oxo (=O) groups. In one aspect of such an embodiment, the atom of RXthat is directly attached to the remainder of the compound of Formula (I) is a nitrogen or oxygen atom, more typically a nitrogen atom. In another aspect of such an embodiment, the atom of RXthat is directly attached to the remainder of the compound of Formula (I) is a carbon atom. For instance, RXmay be a C1-C12 saturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or two cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more fluoro groups and / or one or two oxo (=O) groups, and wherein the hydrocarbyl group includes one, two, three or four heteroatoms each independently selected from N and O in its carbon skeleton. In another embodiment, the saturated hydrocarbyl group of RXincludes at least two heteroatoms each independently selected from N and O in its carbon skeleton. For example, RXmay be a C2-C24 saturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more fluoro groups and / or one or more oxo (=O) groups, wherein the hydrocarbyl group includes two or more heteroatoms each independently selected from N and O in its carbon skeleton, and wherein the atom of RXthat is directly attached to the remainder of the compound of Formula (I) is a nitrogen or oxygen atom. Typically in such an embodiment, the hydrocarbyl group is a C2-C12 group. Typically in such an embodiment, the hydrocarbyl group includes two, three, four or five heteroatoms each independently selected from N and O in its carbon skeleton. More typically in such an embodiment, the hydrocarbyl group includes two, three or four heteroatoms each independently selected from N and O in its carbon skeleton. Typically, the hydrocarbyl group includes one nitrogen atom in its carbon skeleton and one, two or three further heteroatoms each independently selected from N and O in its carbon skeleton. Typically in such an embodiment, the hydrocarbyl group includes no more than three cyclic groups. More typically, the hydrocarbyl group includes no more than two cyclic groups. Typically in such an embodiment, where the hydrocarbyl group is substituted, it is substituted with one or more fluoro groups and / or one, two or three oxo (=O) groups. More typically, where the hydrocarbyl group is substituted, it is substituted with one or more fluoro groups and / or one or two oxo (=O) groups. Typically in such an embodiment, the atom of RXthat is directly attached to the remainder of the compound of Formula (I) is a nitrogen atom. For instance, RXmay be a C2-C12 saturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or two cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more fluoro groups and / or one or two oxo (=O) groups, wherein the hydrocarbyl group includes two, three or four heteroatoms each independently selected from N and O in its carbon skeleton, and wherein the atom of RXthat is directly attached to the remainder of the compound of Formula (I) is a nitrogen or oxygen atom. In one embodiment, RXis a C1-C24 saturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more fluoro groups, and wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N and O in its carbon skeleton. Typically in such an embodiment, the hydrocarbyl group of RXincludes at least one heteroatom independently selected from N and O in its carbon skeleton. For example, RXmay be selected from a C1-C24 saturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more fluoro groups, wherein the hydrocarbyl group includes one or more heteroatoms each independently selected from N and O in its carbon skeleton. Typically in such an embodiment, the hydrocarbyl group is a C1-C12 group. Typically in such an embodiment, the hydrocarbyl group includes no more than five heteroatoms selected from N and O in its carbon skeleton. More typically in such an embodiment, the hydrocarbyl group includes no more than four heteroatoms selected from N and O in its carbon skeleton. Typically in such an embodiment, the hydrocarbyl group includes no more than three cyclic groups. More typically, the hydrocarbyl group includes no more than two cyclic groups. In one aspect of such an embodiment, the atom of RXthat is directly attached to the remainder of the compound of Formula (I) is a nitrogen or oxygen atom, more typically a nitrogen atom. In another aspect of such an embodiment, the atom of RXthat is directly attached to the remainder of the compound of Formula (I) is a carbon atom. For instance, RXmay be a C1-C12 saturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or two cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more fluoro groups, and wherein the hydrocarbyl group includes one, two, three or four heteroatoms each independently selected from N and O in its carbon skeleton. In another embodiment, the saturated hydrocarbyl group of RXincludes at least two heteroatoms each independently selected from N and O in its carbon skeleton. For example, RXmay be a C2-C24 saturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more fluoro groups, wherein the hydrocarbyl group includes two or more heteroatoms each independently selected from N and O in its carbon skeleton, and wherein the atom of RXthat is directly attached to the remainder of the compound of Formula (I) is a nitrogen or oxygen atom. Typically in such an embodiment, the hydrocarbyl group is a C2-C12 group. Typically in such an embodiment, the hydrocarbyl group includes two, three, four or five heteroatoms each independently selected from N and O in its carbon skeleton. More typically in such an embodiment, the hydrocarbyl group includes two, three or four heteroatoms each independently selected from N and O in its carbon skeleton. Typically, the hydrocarbyl group includes one nitrogen atom in its carbon skeleton and one, two or three further heteroatoms each independently selected from N and O in its carbon skeleton. Typically in such an embodiment, the hydrocarbyl group includes no more than three cyclic groups. More typically, the hydrocarbyl group includes no more than two cyclic groups. Typically in such an embodiment, the atom of RXthat is directly attached to the remainder of the compound of Formula (I) is a nitrogen atom. For instance, RXmay be a C2-C12 saturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or two cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more fluoro groups, wherein the hydrocarbyl group includes two, three or four heteroatoms each independently selected from N and O in its carbon skeleton, and wherein the atom of RXthat is directly attached to the remainder of the compound of Formula (I) is a nitrogen or oxygen atom. In one embodiment of the first aspect of the invention, -RXis -NR1R2, wherein: R1and R2are each independently selected from hydrogen or a C1-C12 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight- chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo and / or -NO2 groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O 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 (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety; or R1and R2together with the nitrogen atom to which they are attached form a 3- to 12-membered cyclic group, wherein the cyclic group may optionally be substituted with one or more substituents each independently selected from a halo, oxo (=O), -OH, -SH, -NH2, -SO2H, -SO3H, -SO2NH2, -NO2, or a C1-C6 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 and / or -NO2 groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O 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 (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety; provided that the group -NR1R2contains no more than 24 carbon atoms. As will be understood, in such an embodiment the compound is a compound of Formula (II):

[0002] Formula (II) wherein R1, R2, X1-X4, A1-A6and Q1are as defined in accordance with Formula (I). Typically the group -NR1R2contains no more than 18 carbon atoms. More typically, the group -NR1R2contains no more than 12 carbon atoms. In one embodiment of the first aspect of the invention, R1and R2are each independently selected from hydrogen or a C1-C12 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo and / or -NO2 groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O 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 (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety. Typically in such an embodiment, R1and R2are each independently selected from hydrogen or a C1-C8 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include a single cyclic group, wherein the hydrocarbyl group may optionally be substituted with one or more halo and / or -NO2 groups, and wherein the hydrocarbyl group may optionally include one, two, three or four heteroatoms each independently selected from N and O in its carbon skeleton. For example, R1may be a C1-C8 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include a single cyclic group, wherein the hydrocarbyl group may optionally be substituted with one or more halo and / or -NO2 groups, and wherein the hydrocarbyl group may optionally include one, two, three or four heteroatoms each independently selected from N and O in its carbon skeleton, and R2may be selected from hydrogen or a C1-C4 alkyl or C1-C4 haloalkyl group. In a further embodiment, R1is a C1-C8 saturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include a single cyclic group, wherein the hydrocarbyl group may optionally be substituted with one or more fluoro groups and / or a single oxo (=O) group, wherein the hydrocarbyl group optionally includes one or two heteroatoms each independently selected from N and O in its carbon skeleton, and R2is selected from hydrogen or a C1-C3 alkyl or C1-C3 fluoroalkyl group. In one embodiment, R1is selected from a methyl, ethyl, isopropyl or cyclopropyl group, any of which may optionally be fluoro substituted, and R2is selected from hydrogen or a methyl or fluoromethyl group. For example, -NR1R2may have the formula -NMe2. In another embodiment, R1is a C2-C8 saturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include a single cyclic group, wherein the hydrocarbyl group may optionally be substituted with one or more fluoro groups, wherein the hydrocarbyl group includes one or two heteroatoms each independently selected from N and O in its carbon skeleton, and R2is selected from hydrogen or a C1-C3 alkyl or C1-C3 fluoroalkyl group. For example, R1may be selected from a -(C(R101)2)e-X10-R102or -(C(R101)2)e-X10-(C(R101)2)f-X11-R102group, and R2may be selected from hydrogen or a methyl or fluoromethyl group, wherein: X10is selected from O or NR103; X11is selected from O or NR104; e is 2, 3 or 4; f is 2, 3 or 4; each R101is hydrogen; R102is selected from a hydrogen or a methyl, ethyl, isopropyl or cyclopropyl group, any of which may optionally be fluoro substituted; R103is selected from hydrogen or a methyl or fluoromethyl group; and R104is selected from hydrogen or a methyl or fluoromethyl group; or a single R101and R103, or a single R101and R104, or R103and R104, or two R101, together form a -(CH2)2- group; provided that any -(C(R101)2)e-X10-R102or -(C(R101)2)e-X10-(C(R101)2)f-X11-R102group contains no more than 8 carbon atoms. In one aspect of such an embodiment, -NR1R2has a formula selected from:

[0003] In a particular aspect of such an embodiment, R1is a -(C(R101)2)e-NR102R103group, and R2is selected from hydrogen or a methyl or fluoromethyl group, wherein: e is 2, 3 or 4; a single R101and R103, or two R101, together form a -(CH2)2- group; each remaining R101is hydrogen; R102is selected from a methyl, ethyl, isopropyl or cyclopropyl group, any of which may optionally be fluoro substituted; and R103, if not part of a -(CH2)2- group, is selected from hydrogen or a methyl or fluoromethyl group. Thus, in such an aspect, -NR1R2may have a formula selected from: In another embodiment, R1has the formula -L1-R10, wherein L1is a C1-C2 alkylene or C1-C2 fluoroalkylene group, and R10is a 5- or 6-membered heteroaryl group, such as an imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl or isothiazolyl group, and R2is selected from hydrogen or a C1-C3 alkyl or C1-C3 fluoroalkyl group. Typically in such an embodiment, R2is selected from hydrogen or a methyl or fluoromethyl group. In one aspect of such an embodiment, -NR1R2has a formula selected from: . In one embodiment of the first aspect of the invention, R1and R2together with the nitrogen atom to which they are attached form a 3- to 12-membered cyclic group, wherein the cyclic group may optionally be substituted with one or more substituents each independently selected from a halo, oxo (=O), -OH, -SH, -NH2, -SO2H, -SO3H, -SO2NH2, -NO2, or a C1-C6 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 and / or -NO2 groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O 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 (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety, provided that the group -NR1R2contains no more than 24 carbon atoms. As will be understood, where R1and R2together with the nitrogen atom to which they are attached form a 3- to 12-membered cyclic group, the resultant cyclic group is a heterocyclic group. Typically in such an embodiment, R1and R2together with the nitrogen atom to which they are attached form a 4- to 7-membered monocyclic group or a 6- to 12- membered (e.g. 6- to 10-membered) bicyclic group, wherein the monocyclic or the bicyclic group may optionally be substituted with one or more substituents each independently selected from a halo, oxo (=O), -OH, -NH2 or a C1-C6 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, and wherein the hydrocarbyl group may optionally include one or two heteroatoms each independently selected from N and O in its carbon skeleton. Typically where such a monocyclic or bicyclic group is substituted, it is substituted with one or more substituents each independently selected from a fluoro, oxo (=O), -OH, -NH2, or a C1-C4 saturated hydrocarbyl group, wherein the saturated hydrocarbyl group may be straight-chained or branched, or be or include a cyclic group, wherein the saturated hydrocarbyl group may optionally be substituted with one or more fluoro groups and / or a single oxo (=O) group, and wherein the saturated hydrocarbyl group may optionally include a single heteroatom selected from N and O in its carbon skeleton. Where R1and R2together with the nitrogen atom to which they are attached form a 4- to 7-membered monocyclic group, typically the monocyclic group is a saturated monocyclic group. In one embodiment, R1and R2together with the nitrogen atom to which they are attached form a 6- or 7-membered saturated monocyclic group, wherein the saturated monocyclic group includes one further ring heteroatom selected from N and O in its carbon skeleton (such as a piperazinyl, morpholinyl, diazepanyl or oxazepanyl group), and wherein the saturated monocyclic group may optionally be substituted with one or more substituents each independently selected from a fluoro, oxo (=O), -OH, -NH2, or a C1-C4 saturated hydrocarbyl group, wherein the saturated hydrocarbyl group may be straight-chained or branched, or be or include a cyclic group, wherein the saturated hydrocarbyl group may optionally be substituted with one or more fluoro groups and / or a single oxo (=O) group, and wherein the saturated hydrocarbyl group may optionally include a single heteroatom selected from N and O in its carbon skeleton. For example, -NR1R2may have the formula: wherein: n is 1 or 2; m is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; each R11is independently selected from a fluoro, methyl or fluoromethyl group, provided that no more than four R11are selected from a methyl or fluoromethyl group; X12is O or NR12; and R12is hydrogen or a C1-C4 saturated hydrocarbyl group, wherein the saturated hydrocarbyl group may be straight-chained or branched, or be or include a cyclic group, wherein the saturated hydrocarbyl group may optionally be substituted with one or more fluoro groups and / or a single oxo (=O) group, and wherein the saturated hydrocarbyl group may optionally include a single heteroatom selected from N and O in its carbon skeleton. As will be understood, in such an embodiment the compound is a compound of Formula (III):

[0004] Formula (III) wherein X1-X4, A1-A6, Q1, R11, X12, m and n are as defined in accordance with Formula (I). Typically, m is 0. In one embodiment, X12is O. For example, -NR1R2may have the formula: . Typically, X12is NR12. Typically, R12is selected from hydrogen or a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl, fluorocyclopropylmethyl or -CO-R120group, wherein R120is selected from a C1-C3 alkyl, C1-C3 fluoroalkyl, cyclopropyl or fluorocyclopropyl group. More typically, R12is selected from hydrogen or a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl or fluorocyclopropylmethyl group. For example, R12may be selected from hydrogen or a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl or C3-C4 fluorocycloalkyl group. More typically still, R12is selected from hydrogen or a C1-C3 alkyl, C1-C3 fluoroalkyl, cyclopropyl or fluorocyclopropyl group. Yet more typically, R12is selected from hydrogen or a methyl or fluoromethyl group. In one aspect of such an embodiment, -NR1R2has a formula selected from: In another embodiment, R1and R2together with the nitrogen atom to which they are attached form a azetidinyl, pyrrolidinyl, piperidinyl or azepanyl group, wherein the azetidinyl, pyrrolidinyl, piperidinyl or azepanyl group is substituted with a -NR13R14group such that the nitrogen atom of the -NR13R14group is not directly attached to a carbon atom that in turn is directly attached to the ring nitrogen atom of the azetidinyl, pyrrolidinyl, piperidinyl or azepanyl group, wherein R13and R14are each independently selected from hydrogen or a methyl or fluoromethyl group, and wherein the azetidinyl, pyrrolidinyl, piperidinyl or azepanyl group may optionally be further substituted with one or more fluoro groups and / or with one, two, three or four methyl or fluoromethyl groups. Typically in such an embodiment, R1and R2together with the nitrogen atom to which they are attached form a pyrrolidinyl or piperidinyl group, wherein the pyrrolidinyl or piperidinyl group is substituted with a -NR13R14group such that the nitrogen atom of the -NR13R14group is not directly attached to a carbon atom that in turn is directly attached to the ring nitrogen atom of the pyrrolidinyl or piperidinyl group, wherein R13and R14are each independently selected from hydrogen or a methyl or fluoromethyl group. In one aspect of such an embodiment, -NR1R2has the formula: . In yet another embodiment, R1and R2together with the nitrogen atom to which they are attached form a 6- to 12-membered (e.g. 6- to 10-membered) bicyclic group, wherein the bicyclic group may optionally be substituted with one or more substituents each independently selected from a halo, oxo (=O), -OH, -NH2 or a C1-C4 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, and wherein the hydrocarbyl group may optionally include one or two heteroatoms each independently selected from N and O in its carbon skeleton. Without wishing to be bound by theory, it is thought that the compounds of the invention where R1and R2together with the nitrogen atom to which they are attached form a bicyclic group offer particular steric and electronic properties that are advantageous to the pharmacological profile of the molecule. Where R1and R2together with the nitrogen atom to which they are attached form a 6- to 12-membered bicyclic group, typically the bicyclic group is a saturated bicyclic group. For example, R1and R2may together with the nitrogen atom to which they are attached form a 6- to 12-membered (e.g. 6- to 10-membered) saturated bicyclic group, wherein the saturated bicyclic group may optionally be substituted with one or more substituents each independently selected from a fluoro, oxo (=O), -OH, -NH2 or a C1-C4 saturated hydrocarbyl group, wherein the saturated hydrocarbyl group may be straight-chained or branched, or be or include a cyclic group, wherein the saturated hydrocarbyl group may optionally be substituted with one or more fluoro groups and / or a single oxo (=O) group, and wherein the saturated hydrocarbyl group may optionally include a single heteroatom selected from N and O in its carbon skeleton. In one embodiment where R1and R2together with the nitrogen atom to which they are attached form a 6- to 12-membered bicyclic group, R1and R2together with the nitrogen atom to which they are attached form a 8- to 10-membered fused bicyclic group, such that the nitrogen atom of -NR1R2is a ring atom of a first 5- or 6- membered ring of the fused bicyclic group, and the first 5- or 6-membered ring is fused to a second 5- or 6-membered ring of the fused bicyclic group. Typically, the first 5- or 6-membered ring is not aromatic, and the first 5- or 6-membered ring is optionally substituted with one or more substituents each independently selected from a fluoro, oxo (=O), -OH, -NH2, or a C1-C4 saturated hydrocarbyl group, wherein the saturated hydrocarbyl group may be straight-chained or branched, or be or include a cyclic group, wherein the saturated hydrocarbyl group may optionally be substituted with one or more fluoro groups and / or a single oxo (=O) group, and wherein the saturated hydrocarbyl group may optionally include a single heteroatom selected from N and O in its carbon skeleton. In one embodiment, the second 5- or 6-membered ring is aromatic, and the second 5- or 6-membered ring is optionally substituted with one or more substituents each independently selected from a fluoro, chloro, bromo, -OH, -NH2, or a C1-C4 saturated hydrocarbyl group, wherein the saturated hydrocarbyl group may be straight-chained or branched, or be or include a cyclic group, wherein the saturated hydrocarbyl group may optionally be substituted with one or more fluoro groups and / or a single oxo (=O) group, and wherein the saturated hydrocarbyl group may optionally include a single heteroatom selected from N and O in its carbon skeleton. In one aspect of such an embodiment, the first 5- or 6-membered ring is not aromatic and is unsubstituted, and the second 5- or 6-membered ring is an unsubstituted 5- membered heteroaryl ring comprising a NH group. In one aspect of such an embodiment, -NR1R2has the formula: . In another embodiment, the second 5- or 6-membered ring is not aromatic, and the second 5- or 6-membered ring is optionally substituted with one or more substituents each independently selected from a fluoro, oxo (=O), -OH, -NH2, or a C1-C4 saturated hydrocarbyl group, wherein the saturated hydrocarbyl group may be straight-chained or branched, or be or include a cyclic group, wherein the saturated hydrocarbyl group may optionally be substituted with one or more fluoro groups and / or a single oxo (=O) group, and wherein the saturated hydrocarbyl group may optionally include a single heteroatom selected from N and O in its carbon skeleton. Typically in such an embodiment, the first 5- or 6-membered ring is saturated and the second 5- or 6- membered ring is saturated. For example, R1and R2may together with the nitrogen atom to which they are attached form a 8- to 10-membered saturated fused bicyclic group, such that the nitrogen atom of -NR1R2is a ring atom of a first 5- or 6- membered ring of the fused bicyclic group, wherein the first 5- or 6-membered ring is fused to a second 5- or 6-membered ring of the fused bicyclic group, and wherein the fused bicyclic group may optionally substituted with one or more substituents each independently selected from a fluoro, oxo (=O), -OH, -NH2, or a C1-C4 saturated hydrocarbyl group, wherein the saturated hydrocarbyl group may be straight-chained or branched, or be or include a cyclic group, wherein the saturated hydrocarbyl group may optionally be substituted with one or more fluoro groups and / or a single oxo (=O) group, and wherein the saturated hydrocarbyl group may optionally include a single heteroatom selected from N and O in its carbon skeleton. Typically in such an embodiment, the second 5- or 6-membered ring comprises at least one ring nitrogen atom. Typically, said ring nitrogen atom is not directly attached to a sp2hybridised carbon atom. Typically where the second 5- or 6-membered ring comprises at least one ring nitrogen atom, the first 5- or 6-membered ring is saturated and the second 5- or 6-membered ring is saturated. For example, R1and R2may together with the nitrogen atom to which they are attached form a 8- to 10- membered saturated fused bicyclic group, such that the nitrogen atom of -NR1R2is a ring atom of a first 5- or 6-membered ring of the fused bicyclic group, wherein the first 5- or 6-membered ring is fused to a second 5- or 6-membered ring of the fused bicyclic group, wherein the second 5- or 6-membered ring comprises at least one ring nitrogen atom, and wherein the fused bicyclic group may optionally substituted with one or more substituents each independently selected from a fluoro, oxo (=O), -OH, -NH2, or a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl, fluorocyclopropylmethyl or -CO-R121group, wherein each R121is independently selected from a C1-C3 alkyl, C1-C3 fluoroalkyl, cyclopropyl or fluorocyclopropyl group. More typically, where such a fused bicyclic group is substituted, it is substituted with one or more substituents each independently selected from a fluoro, oxo (=O), or a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl, fluorocyclopropylmethyl or -CO-R121group, wherein each R121is independently selected from a C1-C3 alkyl, C1-C3 fluoroalkyl, cyclopropyl or fluorocyclopropyl group. In one embodiment, -NR1R2has the formula: wherein: j is 0, 1, 2 or 3; k is 0, 1, 2 or 3; p is 0, 1, 2 or 3; and q is 0, 1, 2 or 3; provided that: j + k = 2 or 3; p + q = 2 or 3; when j = 0, q is 1, 2 or 3; when k = 0, p is 1, 2 or 3; when p = 0, k is 1, 2 or 3; and when q = 0, j is 1, 2 or 3; and wherein: r is 0, 1 or 2; s is 0, 1 or 2; R15is hydrogen or a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl, fluorocyclopropylmethyl or -CO-R150group, wherein R150is selected from a C1-C3 alkyl, C1-C3 fluoroalkyl, cyclopropyl or fluorocyclopropyl group; and each R16is independently selected from a methyl or fluoromethyl group. As will be understood, in such an embodiment the compound is a compound of Formula (IV): Formula (IV) wherein X1-X4, A1-A6, Q1, R15, R16, j, k, p, q, r and s are as defined in accordance with Formula (I). Typically in such an embodiment, j is 1 or 2 and k is 1 or 2. More typically, j is 1 and k is 1. Typically in such an embodiment, p is 0, 1 or 2 and q is 1 or 2. More typically, p is 1 or 2 and q is 1 or 2. More typically still, p is 1 and q is 1. Typically in such an embodiment, r is 0 and s is 0. Thus, for example, -NR1R2may have the formula: wherein: p is 1 or 2; q is 1 or 2; p + q = 2 or 3; and R15is hydrogen or a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl, fluorocyclopropylmethyl or -CO-R150group, wherein R150is selected from a C1-C3 alkyl, C1-C3 fluoroalkyl, cyclopropyl or fluorocyclopropyl group. Typically in the above embodiments, j + k = 2. More typically, j + k = 2 and p + q = 2. Typically in the above embodiments, R15is hydrogen or a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl or fluorocyclopropylmethyl group. More typically, R15is a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl or fluorocyclopropylmethyl group. More typically still, R15is a methyl, ethyl or cyclopropylmethyl group. For example, -NR1R2may have a formula selected from: . In a further embodiment, -NR1R2has the formula: wherein: r is 0, 1 or 2; s is 0, 1 or 2; t is 1 or 2; and each R16is independently selected from a methyl or fluoromethyl group. As will be understood, in such an embodiment the compound is a compound of Formula (V):

[0005] Formula (V) wherein X1-X4, A1-A6, Q1, R16, r, s and t are as defined in accordance with Formula (I). Typically in such an embodiment, r is 0 and s is 0. Typically in such an embodiment, t is 1. For example, -NR1R2may have the formula: . In yet another embodiment, -NR1R2has the formula: wherein: j is 0, 1, 2 or 3; and k is 0, 1, 2 or 3; provided that j + k = 2 or 3; and wherein: v is 1 or 2; r is 0, 1 or 2; s is 0, 1 or 2; and each R16is independently selected from a methyl or fluoromethyl group. As will be understood, in such an embodiment the compound is a compound of Formula (VI): Formula (VI) wherein X1-X4, A1-A6, Q1, R16, j, k, r, s and v are as defined in accordance with Formula (I). Typically in such an embodiment, j is 1 or 2 and k is 1 or 2. More typically, j is 1 and k is 1. Typically in such an embodiment, v is 1. Typically in such an embodiment, r is 0 and s is 0. For example, -NR1R2may have the formula: . As will be understood, where a first 5- or 6-membered ring is fused to a second 5- or 6-membered ring across two sp3hybridised ring carbon atoms, e.g. across two ring carbon atoms in a saturated fused bicyclic ring system, the second ring may be fused cis- or trans- to the first ring. For example, -NR1R2may have the formula: . In a further example, -NR1R2may have the formula: . In another embodiment, where R1and R2together with the nitrogen atom to which they are attached form a 6- to 12-membered bicyclic group, R1and R2together with the nitrogen atom to which they are attached form a 6- to 12-membered spiro bicyclic group, such that the nitrogen atom of -NR1R2is a ring atom of a first 4- to 7- membered ring of the spiro bicyclic group, and the first 4 to 7-membered ring shares a spiro ring atom with a second 3- to 7-membered ring of the spiro bicyclic group. Typically, the 6- to 12-membered spiro bicyclic group is unsubstituted or substituted with one or more substituents each independently selected from a fluoro, oxo (=O), -OH, -NH2, or a C1-C4 saturated hydrocarbyl group, wherein the saturated hydrocarbyl group may be straight-chained or branched, or be or include a cyclic group, wherein the saturated hydrocarbyl group may optionally be substituted with one or more fluoro groups and / or a single oxo (=O) group, and wherein the saturated hydrocarbyl group may optionally include a single heteroatom selected from N and O in its carbon skeleton. Typically in such an embodiment, the first 4- to 7-membered ring is saturated and the second 3- to 7-membered ring is saturated. For example, R1and R2may together with the nitrogen atom to which they are attached form a 9- to 11-membered saturated spiro bicyclic group, such that the nitrogen atom of -NR1R2is a ring atom of a first 5- or 6-membered ring of the spiro bicyclic group, and the first 5- or 6-membered ring shares a spiro ring atom with a second 5- or 6-membered ring of the spiro bicyclic group, and wherein the saturated spiro bicyclic group may optionally substituted with one or more substituents each independently selected from a fluoro, oxo (=O), -OH, -NH2, or a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl, fluorocyclopropylmethyl or -CO-R121group, wherein each R121is independently selected from a C1-C3 alkyl, C1-C3 fluoroalkyl, cyclopropyl or fluorocyclopropyl group. Typically in such an embodiment, the second 3- to 7-membered ring is a 4- to 7- membered ring that comprises at least one ring nitrogen or ring oxygen atom. Typically, said ring nitrogen or ring oxygen atom is not directly attached to a sp2hybridised carbon atom. Typically where the second 4- to 7-membered ring comprises at least one ring nitrogen atom or at least one ring oxygen atom, the first 4- to 7- membered ring is saturated and the second 4- to 7-membered ring is saturated. For example, R1and R2may together with the nitrogen atom to which they are attached form a 9- to 11-membered saturated spiro bicyclic group, such that the nitrogen atom of -NR1R2is a ring atom of a first 5- or 6-membered ring of the spiro bicyclic group, and the first 5- or 6-membered ring shares a spiro ring atom with a second 5- or 6- membered ring of the spiro bicyclic group, wherein the second 5- or 6-membered ring comprises at least one ring nitrogen atom or at least one ring oxygen atom, and wherein the saturated spiro bicyclic group may optionally substituted with one or more substituents each independently selected from a fluoro, oxo (=O), -OH, -NH2, or a C1- C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl, fluorocyclopropylmethyl or -CO-R121group, wherein each R121is independently selected from a C1-C3 alkyl, C1-C3 fluoroalkyl, cyclopropyl or fluorocyclopropyl group. More typically, where a saturated spiro bicyclic group is substituted, it is substituted with one or more substituents each independently selected from a fluoro, oxo (=O), or a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl, fluorocyclopropylmethyl or -CO-R121group, wherein each R121is independently selected from a C1-C3 alkyl, C1-C3 fluoroalkyl, cyclopropyl or fluorocyclopropyl group. In one embodiment, -NR1R2has the formula: wherein: X15is O or NR15; j is 0, 1, 2, 3 or 4; k is 0, 1, 2, 3 or 4; p is 0, 1, 2, 3 or 4; and q is 0, 1, 2, 3 or 4; provided that: j + k = 3 or 4; p + q = 3 or 4; when j = 0, q is 1, 2, 3 or 4 and p is 1, 2, 3 or 4; when k = 0, q is 1, 2, 3 or 4 and p is 1, 2, 3 or 4; when p = 0, k is 1, 2, 3 or 4 and j is 1, 2, 3 or 4; and when q = 0, k is 1, 2, 3 or 4 and j is 1, 2, 3 or 4; and wherein: r is 0, 1 or 2; s is 0, 1 or 2; R15is hydrogen or a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl, fluorocyclopropylmethyl or -CO-R150group, wherein R150is selected from a C1-C3 alkyl, C1-C3 fluoroalkyl, cyclopropyl or fluorocyclopropyl group; and each R16is independently selected from a methyl or fluoromethyl group. As will be understood, in such an embodiment the compound is a compound of Formula (VII): Formula (VII) wherein X1-X4, A1-A6, Q1, X15, R16, j, k, p, q, r and s are as defined in accordance with Formula (I). Typically in such an embodiment, j is 1 or 2 and k is 1 or 2. More typically, j is 1 and k is 2. Typically in such an embodiment, p is 0, 1 or 2 and q is 1, 2 or 3. More typically, p is 0, 1 or 2 and q is 2 or 3. More typically still, p is 2 and q is 2. Typically in such an embodiment, r is 0 and s is 0. Typically in such an embodiment, R15is hydrogen or a C1-C4 alkyl, C3-C4 cycloalkyl, C1- C4 fluoroalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl or fluorocyclopropylmethyl group. More typically, R15is hydrogen or a C1-C3 alkyl, C1-C3 fluoroalkyl, cyclopropyl or fluorocyclopropyl group. More typically still, R15is hydrogen or a methyl or fluoromethyl group. Yet more typically, R15is hydrogen or a methyl group. For example, -NR1R2may have a formula selected from: In another embodiment, -NR1R2has the formula: wherein: j is 0, 1, 2, 3 or 4; k is 0, 1, 2, 3 or 4; p is 0, 1, 2 or 3; and q is 0, 1, 2 or 3; provided that: j + k = 3 or 4; p + q = 2 or 3; when j = 0, p is 1, 2 or 3; when k = 0, p is 1, 2 or 3; and when p = 0, j is 1, 2, 3 or 4 and k is 1, 2, 3 or 4; and wherein: r is 0, 1 or 2; s is 0, 1 or 2; R15is hydrogen or a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl or fluorocyclopropylmethyl group; and each R16is independently selected from a methyl or fluoromethyl group. As will be understood, in such an embodiment the compound is a compound of Formula (VIII):

[0006] Formula (VIII) wherein X1-X4, A1-A6, Q1, R15, R16, j, k, p, q, r and s are as defined in accordance with Formula (I). Typically in such an embodiment, j is 1 or 2 and k is 1 or 2. Typically in such an embodiment, p is 1 or 2 and q is 1 or 2. Typically in such an embodiment, r is 0 and s is 0. Typically in such an embodiment, R15is hydrogen or a C1-C3 alkyl, C1-C3 fluoroalkyl, cyclopropyl or fluorocyclopropyl group. More typically, R15is hydrogen or a methyl or fluoromethyl group. More typically still, R15is hydrogen. For example, -NR1R2may have the formula: . In a further embodiment, where R1and R2together with the nitrogen atom to which they are attached form a 6- to 12-membered bicyclic group, R1and R2together with the nitrogen atom to which they are attached form a 7- to 9-membered bridged bicyclic group. Typically, the 7- to 9-membered bridged bicyclic group is unsubstituted or substituted with one or more substituents each independently selected from a fluoro, oxo (=O), -OH, -NH2, or a C1-C4 saturated hydrocarbyl group, wherein the saturated hydrocarbyl group may be straight-chained or branched, or be or include a cyclic group, wherein the saturated hydrocarbyl group may optionally be substituted with one or more fluoro groups and / or a single oxo (=O) group, and wherein the saturated hydrocarbyl group may optionally include a single heteroatom selected from N and O in its carbon skeleton. Typically in such an embodiment, the 7- to 9-membered bridged bicyclic group is saturated. For example, R1and R2may together with the nitrogen atom to which they are attached form a 7- or 8-membered saturated bridged bicyclic group, wherein the saturated bridged bicyclic group may optionally substituted with one or more substituents each independently selected from a fluoro, oxo (=O), -OH, -NH2, or a C1- C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl, fluorocyclopropylmethyl or -CO-R121group, wherein each R121is independently selected from a C1-C3 alkyl, C1-C3 fluoroalkyl, cyclopropyl or fluorocyclopropyl group. Typically in such an embodiment, the 7- to 9-membered bridged bicyclic group comprises a least one further ring nitrogen or ring oxygen atom. Typically, said further ring nitrogen or ring oxygen atom is not directly attached to a sp2hybridised carbon atom. Typically where the 7- to 9-membered bridged bicyclic group comprises a least one further ring nitrogen or ring oxygen atom, the 7- to 9-membered bridged bicyclic group is saturated. For example, R1and R2may together with the nitrogen atom to which they are attached form a 7- or 8-membered saturated bridged bicyclic group, wherein the saturated bridged bicyclic group contains one further ring nitrogen atom, and wherein the saturated bridged bicyclic group may optionally substituted with one or more substituents each independently selected from a fluoro, oxo (=O), -OH, -NH2, or a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl, fluorocyclopropylmethyl or -CO-R121group, wherein each R121is independently selected from a C1-C3 alkyl, C1-C3 fluoroalkyl, cyclopropyl or fluorocyclopropyl group. Typically, where the saturated bridged bicyclic group is substituted, it is substituted with one or more substituents each independently selected from a fluoro, oxo (=O), or a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl, fluorocyclopropylmethyl or -CO-R121group, wherein each R121is independently selected from a C1-C3 alkyl, C1-C3 fluoroalkyl, cyclopropyl or fluorocyclopropyl group. In one embodiment, -NR1R2has the formula: wherein: w is 1 or 2; X15is O or NR15; R15is hydrogen or a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl, fluorocyclopropylmethyl or -CO-R150group, wherein R150is selected from a C1-C3 alkyl, C1-C3 fluoroalkyl, cyclopropyl or fluorocyclopropyl group; one R17and one R18together form a -CH2- or -CH2CH2- group; and each remaining R17and R18is hydrogen. As will be understood, in such an embodiment the compound is a compound of Formula (IX): Formula (IX) wherein X1-X4, A1-A6, Q1, X15, R17, R18and w are as defined in accordance with Formula (I). Typically in such an embodiment, w is 1. Typically in such an embodiment, X15is NR15. Typically in such an embodiment, R15is hydrogen or a C1-C4 alkyl, C3-C4 cycloalkyl, C1- C4 fluoroalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl or fluorocyclopropylmethyl group. More typically, R15is hydrogen or a C1-C3 alkyl, C1-C3 fluoroalkyl, cyclopropyl or fluorocyclopropyl group. More typically still, R15is hydrogen or a methyl or fluoromethyl group. Yet more typically, R15is a methyl or fluoromethyl group. Typically in such an embodiment, one R17and one R18together form a -CH2CH2- group. For example, -NR1R2may have the formula: . In a separate embodiment of the first aspect of the invention, -RXis -OR3, wherein R3is selected from hydrogen or a C1-C12 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo and / or -NO2 groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O 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 (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety. As will be understood, in such an embodiment the compound is a compound of Formula (X): Formula (X) wherein R3, X1-X4, A1-A6and Q1are as defined in accordance with Formula (I). Typically in such an embodiment, R3is C1-C8 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include a single cyclic group, wherein the hydrocarbyl group may optionally be substituted with one or more halo and / or -NO2 groups, and wherein the hydrocarbyl group may optionally include one, two, three or four heteroatoms each independently selected from N and O in its carbon skeleton. In another embodiment, R3is a C2-C8 saturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include a single cyclic group, wherein the hydrocarbyl group may optionally be substituted with one or more fluoro groups, and wherein the hydrocarbyl group includes one or two heteroatoms each independently selected from N and O in its carbon skeleton. For example, R3may be selected from a -(C(R105)2)e-Q10-R106or -(C(R105)2)e-Q10-(C(R105)2)f-Q11-R106group, wherein: Q10is selected from O or NR107; Q11is selected from O or NR108; e is 2, 3 or 4; f is 2, 3 or 4; each R105is hydrogen; R106is selected from a hydrogen or a methyl, ethyl, isopropyl or cyclopropyl group, any of which may optionally be fluoro substituted; R107is selected from hydrogen or a methyl or fluoromethyl group; and R108is selected from hydrogen or a methyl or fluoromethyl group; or a single R105and R107, or a single R105and R108, or R107and R108, or two R105, together form a -(CH2)2- group; provided that any -(C(R105)2)e-Q10-R106or -(C(R105)2)e-Q10-(C(R105)2)f-Q11-R106group contains no more than 8 carbon atoms. In one aspect of such an embodiment, R3is a -(CH2)2-NR106R107group, wherein: R106is selected from a methyl, ethyl, isopropyl or cyclopropyl group, any of which may optionally be fluoro substituted; and R107is selected from hydrogen or a methyl or fluoromethyl group. For example, -OR3may have the formula: . As stated above, in one embodiment of the first aspect of the invention, RXis a C1-C12 saturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or two cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more fluoro groups and / or one or two oxo (=O) groups, and wherein the hydrocarbyl group includes one, two, three or four heteroatoms each independently selected from N and O in its carbon skeleton, provided that the atom of RXthat is directly attached to the remainder of the compound of Formula (I) is a carbon atom. In a further embodiment, Rxis a saturated fused bicyclic heterocyclic group, wherein the fused bicyclic heterocyclic group comprises a first ring system that is directly attached to the remainder of the molecule and a second ring system that is fused to the first ring system, wherein both the first and the second ring system are saturated, wherein the first ring system contains a ring carbon atom that is directly attached to the remainder of the molecule, wherein the saturated fused bicyclic heterocyclic group comprises at least one ring nitrogen atom, and wherein the saturated fused bicyclic heterocyclic group may optionally be substituted with one or more fluoro groups and / or one or two oxo (=O) groups, and / or one or two groups R40, wherein each R40is independently selected from -OH, -NH2, or a C1-C6 saturated hydrocarbyl group, wherein the saturated hydrocarbyl group may be straight-chained or branched, or be or include a single cyclic group, wherein the saturated hydrocarbyl group may optionally be substituted with one or more fluoro groups and / or a single oxo (=O) group, and wherein the saturated hydrocarbyl group may optionally include one or two heteroatoms each independently selected from N and O in its carbon skeleton. Typically in such an embodiment, the fused bicyclic heterocyclic group, including any optional substituents, contains no more than 12 carbon atoms. Typically, the fused bicyclic heterocyclic group, including any optional substituents, contains in total no more than four nitrogen and oxygen atoms. Typically, the second ring system contains a ring nitrogen atom. Typically, the fused bicyclic heterocyclic group contains no more than three ring heteroatoms. More typically, the fused bicyclic heterocyclic group contains no more than two ring heteroatoms. Typically the first ring system is a 4- to 7-membered ring and the second ring system is a 4- to 7-membered ring. More typically, the first ring system is a 5- or 6-membered ring and the second ring system is a 5- or 6-membered ring. Where the saturated fused bicyclic heterocyclic group is substituted, typically it is substituted with one or more fluoro groups and / or one or two groups R40, wherein each R40is independently selected from -OH, -NH2, or a C1-C4 saturated hydrocarbyl group, wherein the saturated hydrocarbyl group may be straight-chained or branched, or be or include a single cyclic group, wherein the saturated hydrocarbyl group may optionally be substituted with one or more fluoro groups and / or a single oxo (=O) group, and wherein the saturated hydrocarbyl group may optionally include a single heteroatom selected from N and O in its carbon skeleton. For example, each R40may be independently selected from a -OH, -NH2, -R41, -CO-R42, -OR41, -NHR41or -N(R41)2 group, wherein each R41is independently selected from a C1-C4 alkyl, C1-C4 fluoroalkyl, C3-C4 cycloalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl or fluorocyclopropylmethyl group, or any two R41attached to the same nitrogen atom may together form a C2-C4 alkylene or a C2-C4 fluoroalkylene group, provided that the group -N(R41)2 contains no more than four carbon atoms, and wherein each R42is independently selected from a C1-C3 alkyl, C1-C3 fluoroalkyl, cyclopropyl or fluorocyclopropyl group. Typically, where the saturated fused bicyclic heterocyclic group is substituted, it is substituted with one or more fluoro groups and / or one or two groups R40, wherein each R40is independently selected from a -NH2, -R41, -CO-R42, -NHR41or -N(R41)2 group, wherein each R41is independently selected from a C1-C4 alkyl, C1-C4 fluoroalkyl, C3-C4 cycloalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl or fluorocyclopropylmethyl group, or any two R41attached to the same nitrogen atom may together form a C2-C4 alkylene or a C2-C4 fluoroalkylene group, provided that the group -N(R41)2 contains no more than four carbon atoms, and wherein each R42is independently selected from a C1-C3 alkyl, C1-C3 fluoroalkyl, cyclopropyl or fluorocyclopropyl group. More typically, where the saturated fused bicyclic heterocyclic group is substituted, it is substituted with one or more fluoro groups and / or a single group selected from -R41or -CO-R42, wherein if present -R41or -CO-R42is directly attached to a ring nitrogen atom of the saturated fused bicyclic heterocyclic group, wherein R41is selected from a C1-C4 alkyl, C1-C4 fluoroalkyl, C3-C4 cycloalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl or fluorocyclopropylmethyl group, and wherein R42is selected from a C1-C3 alkyl, C1-C3 fluoroalkyl, cyclopropyl or fluorocyclopropyl group. In one embodiment, RXhas the formula: wherein: j is 0, 1, 2 or 3; k is 0, 1, 2 or 3; p is 0, 1, 2 or 3; and q is 0, 1, 2 or 3; provided that: j + k = 2 or 3; and p + q = 2 or 3; and wherein: r is 0, 1 or 2; s is 0, 1 or 2; R15is hydrogen or a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl, fluorocyclopropylmethyl or -CO-R150group, wherein R150is selected from a C1-C3 alkyl, C1-C3 fluoroalkyl, cyclopropyl or fluorocyclopropyl group; and each R16is independently selected from a methyl or fluoromethyl group. As will be understood, in such an embodiment the compound is a compound of Formula (XI): wherein X1-X4, A1-A6, Q1, R15, R16, j, k, p, q, r and s are as defined in accordance with Formula (I). Typically in such an embodiment: when j = 0, q is 1, 2 or 3; when k = 0, p is 1, 2 or 3; when p = 0, k is 1, 2 or 3; and when q = 0, j is 1, 2 or 3; Typically in such an embodiment, j is 1 or 2 and k is 1 or 2. Typically in such an embodiment, p is 0, 1 or 2 and q is 1 or 2. More typically, p is 1 or 2 and q is 1 or 2. Typically in such an embodiment, r is 0 and s is 0. Typically in such an embodiment, R15is hydrogen or a C1-C4 alkyl, C3-C4 cycloalkyl, C1- C4 fluoroalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl or fluorocyclopropylmethyl group. More typically, R15is hydrogen or a C1-C3 alkyl, C1-C3 fluoroalkyl, cyclopropyl or fluorocyclopropyl group. For example, RXmay have the formula: . In another embodiment, Rxis a phenyl, naphthyl, a 5- or 6-membered heteroaryl or a bicyclic fused heteroaryl group, wherein the phenyl, naphthyl, 5- or 6-membered heteroaryl or the bicyclic fused heteroaryl group may optionally be substituted with one or more halo groups and / or one or two groups R5, wherein each R5is independently selected from -OH, -NH2, or a C1-C6 saturated hydrocarbyl group, wherein the saturated hydrocarbyl group may be straight-chained or branched, or be or include a single cyclic group, wherein the saturated hydrocarbyl group may optionally be substituted with one or more fluoro groups and / or a single oxo (=O) group, and wherein the saturated hydrocarbyl group may optionally include one or two heteroatoms each independently selected from N and O in its carbon skeleton. Typically in such an embodiment: (i) Rxis a 5- or 6-membered heteroaryl or a bicyclic fused heteroaryl group, wherein the 5- or 6-membered heteroaryl or the bicyclic fused heteroaryl group contains at least one ring nitrogen atom; and / or (ii) the phenyl, naphthyl, 5- or 6-membered heteroaryl or bicyclic fused heteroaryl group is substituted with at least one substituent that comprises a nitrogen atom. For example, Rxmay be a 5- or 6-membered heteroaryl or a bicyclic fused heteroaryl group, wherein the 5- or 6-membered heteroaryl or the bicyclic fused heteroaryl group contains at least one ring nitrogen atom, and wherein the 5- or 6-membered heteroaryl or the bicyclic fused heteroaryl group may optionally be substituted with one or more fluoro, chloro and / or bromo groups, and / or with one or two groups R5, wherein each R5is independently selected from -OH, -NH2, or a C1-C4 saturated hydrocarbyl group, wherein the saturated hydrocarbyl group may be straight-chained or branched, or be or include a single cyclic group, wherein the saturated hydrocarbyl group may optionally be substituted with one or more fluoro groups and / or a single oxo (=O) group, and wherein the saturated hydrocarbyl group may optionally include a single heteroatom selected from N and O in its carbon skeleton. Typically in such an example, each R5is independently selected from a -OH, -NH2, -R51, -CO-R52, -OR51, -NHR51or -N(R51)2 group, wherein each R51is independently selected from a C1-C4 alkyl, C1-C4 fluoroalkyl, C3-C4 cycloalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl or fluorocyclopropylmethyl group, or any two R51attached to the same nitrogen atom may together form a C2-C4 alkylene or a C2-C4 fluoroalkylene group, provided that the group -N(R51)2 contains no more than four carbon atoms, and wherein each R52is independently selected from a C1-C3 alkyl, C1-C3 fluoroalkyl, cyclopropyl or fluorocyclopropyl group. More typically, each R5is independently selected from a -NH2, -R51, -CO-R52, -NHR51or -N(R51)2 group, wherein each R51is independently selected from a C1-C4 alkyl, C1-C4 fluoroalkyl, C3-C4 cycloalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl or fluorocyclopropylmethyl group, or any two R51attached to the same nitrogen atom may together form a C2-C4 alkylene or a C2-C4 fluoroalkylene group, provided that the group -N(R51)2 contains no more than four carbon atoms, and wherein each R52is independently selected from a C1-C3 alkyl, C1-C3 fluoroalkyl, cyclopropyl or fluorocyclopropyl group. More typically still, each R5is independently selected from a -NH2, -R51, -NHR51or -N(R51)2 group, wherein each R51is independently selected from a methyl or fluoromethyl group. In one embodiment, Rxis selected from a 5- or 6-membered heteroaryl or a bicyclic fused heteroaryl group, wherein the ring atoms of the 5- or 6-membered heteroaryl group or the bicyclic fused heteroaryl group are selected from the group consisting of nitrogen and carbon atoms, and wherein the 5- or 6-membered heteroaryl group or the bicyclic fused heteroaryl group may optionally be substituted with one or more fluoro, chloro and / or bromo groups, and / or with a single group R5, wherein R5is selected from a -NH2, -R51, -NHR51or -N(R51)2 group, wherein each R51is independently selected from a methyl or fluoromethyl group. Most typically in such an embodiment, the 5- or 6-membered heteroaryl group or the bicyclic fused heteroaryl group is unsubstituted, i.e. Rxis selected from a 5- or 6-membered heteroaryl or a bicyclic fused heteroaryl group, wherein the ring atoms of the 5- or 6-membered heteroaryl group or the bicyclic fused heteroaryl group are selected from the group consisting of nitrogen and carbon atoms. For example, RXmay may have the formula: In another embodiment, Rxis selected from a phenyl or a 5- or 6-membered heteroaryl group, such as a phenyl or a pyridinyl group, wherein the phenyl or the 5- or 6-membered heteroaryl group is substituted with one or two groups R5, wherein the phenyl or the 5- or 6-membered heteroaryl group is optionally further substituted with one or more fluoro, chloro and / or bromo groups, and wherein each R5is independently selected from -OH, -NH2, or a C1-C6 saturated hydrocarbyl group, wherein the saturated hydrocarbyl group may be straight-chained or branched, or be or include a single cyclic group, wherein the saturated hydrocarbyl group may optionally be substituted with one or more fluoro groups and / or a single oxo (=O) group, and wherein the saturated hydrocarbyl group may optionally include one or two heteroatoms each independently selected from N and O in its carbon skeleton, provided that at least one group R5contains a nitrogen atom. Typically in such an embodiment, the phenyl or the 5- or 6-membered heteroaryl group is substituted with a first substituent selected from a -NH2, -NHR53, -N(R53)2, -CH2-NH2, -CH2-NHR53or -CH2-N(R53)2 group, wherein each R53is independently selected from a C1-C4 alkyl, C1-C4 fluoroalkyl, C3-C4 cycloalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl or fluorocyclopropylmethyl group, or any two R53attached to the same nitrogen atom may together form a C2-C5 alkylene or a C2-C5 fluoroalkylene group, provided that the group -N(R53)2 contains no more than five carbon atoms, and wherein the phenyl or the 5- or 6-membered heteroaryl group may optionally be further substituted with a single methyl or fluoromethyl group and / or with one or more fluoro, chloro and / or bromo groups. Typically, each R53is independently selected from a C1-C3 alkyl, C1-C3 fluoroalkyl, cyclopropyl or fluorocyclopropyl group, or any two R53attached to the same nitrogen atom may together form a C3-C4 alkylene or a C3-C4 fluoroalkylene group, provided that the group -N(R53)2 contains no more than four carbon atoms. In a particular aspect, Rxis selected from a phenyl or a pyridinyl group, wherein the phenyl or the pyridinyl group is substituted with a -NH2, -NHR53, -N(R53)2, -CH2-NH2, -CH2-NHR53or -CH2-N(R53)2 group, wherein each R53is independently selected from a C1-C3 alkyl, C1-C3 fluoroalkyl, cyclopropyl or fluorocyclopropyl group, or any two R53attached to the same nitrogen atom may together form a C3-C4 alkylene or a C3-C4 fluoroalkylene group, provided that the group -N(R53)2 contains no more than four carbon atoms. For example, RXmay may have the formula: As stated in accordance with the first aspect of the invention: X1is N, C-H, C-Hal or C-RX1; X2is N, C-H, C-Hal or C-RX2; X3is N, C-H, C-Hal or C-RX3; and X4is N or C; provided that at least one of X1, X2, X3and X4is N, and that no more than three of X1, X2, X3and X4are N; and RX1, RX2and RX3are each independently selected from -OH, -SH, -NH2, -SO2H, -SO3H, -SO2NH2, -NO2, or a C1-C4 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 and / or -NO2 groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O 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 (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety. Typically, when X4is N, A6is C. Typically, when X4is C, A6is N. As stated, at least one of X1, X2, X3and X4is N. In one embodiment, at least one of X2, X3and X4is N. Typically in such an embodiment, at least one of X2and X3is N. Most typically, X2is N. Without wishing to be bound by theory, it is thought that the compounds of the invention where X2is N offer particular electronic properties that are advantageous to the pharmacological profile of the molecule. Typically, X1is N. For example, where at least one of X2, X3and X4is N, typically X1is also N. Typically, at least one of X1and X2is N. More typically, at least X2is N. More typically still, X1is N and X2is N. Typically, no more than two of X1, X2, X3and X4are N. In one embodiment: X1is N, C-H, C-Hal or C-RX1; X2is N, C-H, C-Hal or C-RX2; X3is N, C-H, C-Hal or C-RX3; and X4is C; provided that at least one of X1, X2and X3is N and that no more than two of X1, X2and X3are N. Typically in such an embodiment, at least one of X2and X3is N. Typically in such an embodiment, at least X1is N. In another embodiment: X1is N, C-H, C-Hal or C-RX1; X2is N, C-H, C-Hal or C-RX2; X3is C-H, C-Hal or C-RX3; and X4is N or C; provided that at least one of X1, X2and X4is N, and that no more than two of X1, X2and X4are N. Typically in such an embodiment, X2is N. In a further embodiment: X1is N, C-H, C-Hal or C-RX1; X2is N, C-H, C-Hal or C-RX2; X3is C-H, C-Hal or C-RX3; and X4is C. provided that at least one of X1and X2is N. In one aspect of such an embodiment, X1is N. Typically in such an embodiment, X2is N. More typically in such an embodiment, X1is N and X2is N. In a further embodiment: X1is N, C-H or C-RX1; X2is N, C-H or C-RX2; X3is N, C-H or C-RX3; and X4is N or C; provided that at least one of X1, X2, X3and X4is N, and that no more than three of X1, X2, X3and X4are N. Typically in such an embodiment, no more than two of X1, X2, X3and X4are N. Typically in such an embodiment, at least one of X2, X3and X4is N. More typically, at least one of X2and X3is N. Most typically, X2is N. In one embodiment: X1is N, C-H or C-RX1; X2is N, C-H or C-RX2; X3is N, C-H or C-RX3; and X4is C; provided that at least one of X1, X2and X3is N and that no more than two of X1, X2and X3are N. Typically in such an embodiment, at least one of X2and X3is N. Typically in such an embodiment, at least X1is N. In another embodiment: X1is N, C-H or C-RX1; X2is N, C-H or C-RX2; X3is C-H or C-RX3; and X4is N or C; provided that at least one of X1, X2and X4is N, and that no more than two of X1, X2and X4are N. In one aspect of such an embodiment, X1is N. Typically in such an embodiment, X2is N. More typically in such an embodiment, X1is N and X2is N. In a further embodiment: X1is N, C-H or C-RX1; X2is N, C-H or C-RX2; X3is C-H or C-RX3; and X4is C; provided that at least one of X1and X2is N. In one aspect of such an embodiment, X1is N. Typically in such an embodiment, X2is N or C-H. More typically, X2is N. More typically still in such an embodiment, X1is N and X2is N. Yet more typically, X1is N, X2is N, and X3is C-H. As stated, RX1, RX2and RX3are each independently selected from -OH, -SH, -NH2, -SO2H, -SO3H, -SO2NH2, -NO2, or a C1-C4 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 and / or -NO2 groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O 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 (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety. In one embodiment of the first aspect of the invention, RX1, RX2and RX3are each independently selected from -OH, -SH, -NH2, -SO2H, -SO3H, -SO2NH2 or a C1-C4 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, and wherein the hydrocarbyl group may optionally include one or two heteroatoms each independently selected from N and O in its carbon skeleton. In another embodiment of the first aspect of the invention, RX1, RX2and RX3are each independently selected from -OH, -SH, -NH2, or a C1-C4 saturated 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, and wherein the hydrocarbyl group may optionally include one or two heteroatoms each independently selected from N, O and S in its carbon skeleton. Typically in such an embodiment, RX1, RX2and RX3are each independently selected from a C1-C4 saturated 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 fluoro groups and / or a single oxo (=O) group, and wherein the hydrocarbyl group may optionally include a single heteroatom selected from N and O in its carbon skeleton. More typically, RX1, RX2and RX3are each independently selected from a C1-C3 saturated 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 fluoro groups, and wherein the hydrocarbyl group may optionally include a single heteroatom selected from N and O in its carbon skeleton. In a further embodiment of the first aspect of the invention, RX2is selected from -OH, -SH, -NH2, or a C1-C4 saturated 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 two heteroatoms each independently selected from N, O and S in its carbon skeleton. Typically in such an embodiment, RX2is a C1-C4 saturated 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 fluoro groups and / or a single oxo (=O) group, and wherein the hydrocarbyl group may optionally include a single heteroatom selected from N and O in its carbon skeleton. More typically, RX2is a C1-C3 saturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include a cyclic group, and wherein the hydrocarbyl group may optionally include a single heteroatom selected from N and O in its carbon skeleton. More typically still in such an embodiment, RX2is a methyl group. In one embodiment, X2is not C-Hal. For example, X2may be N, C-H or C-RX2, wherein RX2is selected from -OH, -SH, -NH2, or a C1-C4 saturated hydrocarbyl group as described above. In one embodiment of the first aspect of the invention, RX1, RX2and RX3are each independently selected from a methyl or fluoromethyl group. In a further embodiment: X1is N, C-H or C-Hal; X2is N, C-H or C-Hal; X3is N, C-H or C-Hal; and X4is C; provided that at least one of X1, X2and X3is N and that no more than two of X1, X2and X3are N. In one aspect of such an embodiment: X1is N or C-H; X2is N or C-H; X3is N or C-H; and X4is C; provided that at least one of X1, X2and X3is N and that no more than two of X1, X2and X3are N. Typically in such an embodiment, at least one of X2and X3is N. Typically in such an embodiment, at least X1is N. In another embodiment: X1is N, C-H or C-Hal; X2is N, C-H or C-Hal; X3is C-H or C-Hal; and X4is C. provided that at least one of X1and X2is N. In one aspect of such an embodiment: X1is N or C-H; X2is N or C-H; X3is C-H; and X4is C. provided that at least one of X1and X2is N. In one aspect of such an embodiment, X1is N. Typically in such an embodiment, X2is N. More typically in such an embodiment, X1is N and X2is N. Yet more typically, X1is N, X2is N, and X3is C-H. As stated in accordance with the first aspect of the invention: Q1is O, S, N, N-H, N-RQ1, C-H, C-Hal, or C-RQ2; RQ1is selected from a C1-C4 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 and / or -NO2 groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O 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 (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety, provided that the atom of RQ1that is directly attached to the nitrogen atom of N-RQ1is a carbon atom; and RQ2is selected from -OH, -SH, -NH2, -SO2H, -SO3H, -SO2NH2, -NO2, or a C1-C4 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 and / or -NO2 groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O 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 (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety. In one embodiment of the first aspect of the invention, RQ1and RQ2are each independently selected from a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl, fluorocyclopropylmethyl or -CO-RQ3group, wherein RQ3is selected from a C1-C3 alkyl, C1-C3 fluoroalkyl, cyclopropyl or fluorocyclopropyl group. More typically, RQ1and RQ2are each independently selected from a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl or fluorocyclopropylmethyl group. More typically still, RQ1and RQ2are each independently selected from a C1-C3 alkyl, C1-C3 fluoroalkyl, cyclopropyl or fluorocyclopropyl group. Yet more typically, RQ1and RQ2are each independently selected from a methyl or fluoromethyl group. Typically, Q1is O, S, N-H, N-RQ1, C-H, C-Hal, or C-RQ2. More typically, Q1is O, S, N-H or N-RQ1. For example, Q1may be O, S or NH, or Q1may be O, S, N-H or N-RQ1, wherein RQ1is selected from a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl, fluorocyclopropylmethyl or -CO-RQ3group, wherein RQ3is selected from a C1-C3 alkyl, C1-C3 fluoroalkyl, cyclopropyl or fluorocyclopropyl group. More typically, Q1is S, N-H or N-RQ1. Typically in such an embodiment, RQ1is a methyl or fluoromethyl group. Yet more typically, Q1is S or N-H. In one embodiment, Q1is S. In another embodiment, Q1is N-H or N-RQ1, wherein RQ1is a methyl or fluoromethyl group. Typically in such an embodiment, Q1is N-H. As stated in accordance with the first aspect of the invention: A1is N, C-H, C-Hal or C-RA1; A2is N, C-H, C-Hal or C-RA2; A3is N, C-H, C-Hal or C-RA3; A4is N, C-H, C-Hal or C-RA4; and A5is N or C; provided that no more than three of A1, A2, A3, A4and A5are N; and RA1, RA2, RA3and RA4are each independently selected from -OH, -SH, -NH2, -SO2H, -SO3H, -SO2NH2, -NO2, or a C1-C4 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 and / or -NO2 groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O 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 (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety. Typically, no more than two of A1, A2, A3, A4and A5are N. More typically, no more than one of A1, A2, A3, A4and A5is N. Typically, when A5is N, X4is N, A6is C and Q1is N, C-H, C-Hal, or C-RQ2. More typically, when A5is N, X4is N, A6is C and Q1is C-H, C-Hal, or C-RQ2. Typically, where Q1is O, S, N-H or N-RQ1, A5is C. In one embodiment, A1is N, C-H, C-Hal or C-RA1; A2is N, C-H, C-Hal or C-RA2; A3is N, C-H, C-Hal or C-RA3; A4is N, C-H, C-Hal or C-RA4; and A5is C; provided that no more than two of A1, A2, A3and A4are N. Typically in such an embodiment, no more than one of A1, A2, A3and A4is N. Typically, where one of A1, A2, A3and A4is N, A2is N or A3is N. More typically, A3is N. In a further embodiment, A1is C-H, C-Hal or C-RA1; A2is C-H, C-Hal or C-RA2; A3is C-H, C-Hal or C-RA3; A4is C-H, C-Hal or C-RA4; and A5is C. Typically in the above embodiments, no more than two of A1, A2, A3and A4are C-RA1, C-RA2, C-RA3or C-RA4. More typically, no more than one of A1, A2, A3and A4is C-RA1, C-RA2, C-RA3or C-RA4. In one embodiment, RA1, RA2, RA3and RA4are each independently selected from -OH, -SH, -NH2, -SO2H, -SO3H, -SO2NH2 or a C1-C4 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, and wherein the hydrocarbyl group may optionally include one or two heteroatoms each independently selected from N and O in its carbon skeleton. More typically, RA1, RA2, RA3and RA4are each independently selected from a C1-C4 saturated 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 fluoro groups and / or a single oxo (=O) group, and wherein the hydrocarbyl group may optionally include a single heteroatom selected from N and O in its carbon skeleton. More typically still, RA1, RA2, RA3and RA4are each independently selected from a methyl, fluoromethyl, methoxy or fluoromethoxy group. Yet more typically, RA1, RA2, RA3and RA4are each independently selected from a methyl or fluoromethyl group. In another embodiment, A1is N, C-H or C-Hal; A2is N, C-H or C-Hal; A3is N, C-H or C-Hal; A4is N, C-H or C-Hal; and A5is C; provided that no more than two of A1, A2, A3and A4are N. Typically in such an embodiment, no more than one of A1, A2, A3and A4is N. Typically, where one of A1, A2, A3and A4is N, A2is N or A3is N. More typically, A3is N. In a further embodiment, A1is C-H or C-Hal; A2is C-H or C-Hal; A3is C-H or C-Hal; A4is C-H or C-Hal; and A5is C. Most typically, A1is C-H, A2is C-H, A3is C-H, A4is C-H and A5is C. As stated in accordance with the first aspect of the invention, A6is N or C. Typically, A6is N. As stated in accordance with the first aspect of the invention, each Hal is independently selected from a fluoro, chloro, bromo or iodo group. Typically, each Hal is independently selected from a fluoro, chloro or bromo group. In one embodiment of the first aspect of the invention, the compound is a compound of Formula (Ia): wherein RX, X1, X2and Q1are as defined in accordance with Formula (I). Typically in such an embodiment, X2is N. Most typically, X1is N and X2is N. In another embodiment of the first aspect of the invention, the compound is a compound of Formula (IIa): Formula (IIa) wherein R1, R2, X1, X2and Q1are as defined in accordance with Formula (II). Typically in such an embodiment, X2is N. Most typically, X1is N and X2is N. In yet another embodiment of the first aspect of the invention, the compound is a compound of Formula (IIIa):

[0007] Formula (IIIa) wherein X1, X2, Q1, R11, X12, m and n are as defined in accordance with Formula (III). Typically in such an embodiment, X2is N. Most typically, X1is N and X2is N. In a further embodiment of the first aspect of the invention, the compound is a compound of Formula (IVa): Formula (IVa) wherein X1, X2, Q1, R15, R16, j, k, p, q, r and s are as defined in accordance with Formula (IV). Typically in such an embodiment, X2is N. Most typically, X1is N and X2is N. In one embodiment of the first aspect of the invention, the compound is a compound of Formula (Va): Formula (Va) wherein X1, X2, Q1, R16, r, s and t are as defined in accordance with Formula (V). Typically in such an embodiment, X2is N. Most typically, X1is N and X2is N. In another embodiment of the first aspect of the invention, the compound is a compound of Formula (VIa): wherein X1, X2, Q1, R16, j, k, r, s and v are as defined in accordance with Formula (VI). Typically in such an embodiment, X2is N. Most typically, X1is N and X2is N. In a further embodiment of the first aspect of the invention, the compound is a compound of Formula (VIIa): wherein X1, X2, Q1, X15, R16, j, k, p, q, r and s are as defined in accordance with Formula (VII). Typically in such an embodiment, X2is N. Most typically, X1is N and X2is N. In one embodiment of the first aspect of the invention, the compound is a compound of Formula (VIIIa):

[0008] wherein X1, X2, Q1, R15, R16, j, k, p, q, r and s are as defined in accordance with Formula (VIII). Typically in such an embodiment, X2is N. Most typically, X1is N and X2is N. In another embodiment of the first aspect of the invention, the compound is a compound of Formula (IXa): Formula (IXa) wherein X1, X2, Q1, X15, R17, R18and w are as defined in accordance with Formula (IX). Typically in such an embodiment, X2is N. Most typically, X1is N and X2is N. In a further embodiment of the first aspect of the invention, the compound is a compound of Formula (Xa): Formula (Xa) wherein R3, X1, X2and Q1are as defined in accordance with Formula (X). Typically in such an embodiment, X2is N. Most typically, X1is N and X2is N. In another embodiment of the first aspect of the invention, the compound is a compound of Formula (XIa): Formula (XIa) wherein X1, X2, Q1, R15, R16, j, k, p, q, r and s are as defined in accordance with Formula (XI). Typically in such an embodiment, X2is N. Most typically, X1is N and X2is N. In one embodiment of the first aspect of the invention, the compound is not: . As will be understood, insofar as practical, embodiments directed to one substituent or moiety (such as a given R or X group) may be read in conjunction with embodiments directed to a different substituent or moiety. For example, in a first exemplary embodiment, there is provided a compound of Formula (I) as defined above, wherein: RXis a C1-C12 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or two cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo and / or -NO2 groups, and wherein the hydrocarbyl group includes one, two, three or four heteroatoms each independently selected from N and O in its carbon skeleton; X1is N, C-H, C-Hal or C-RX1; X2is N, C-H, C-Hal or C-RX2; X3is N, C-H, C-Hal or C-RX3; and X4is C; provided that at least one of X1, X2and X3is N and that no more than two of X1, X2and X3are N; RX1, RX2and RX3are each independently selected from -OH, -SH, -NH2, or a C1- C4 saturated 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, and wherein the hydrocarbyl group may optionally include one or two heteroatoms each independently selected from N, O and S in its carbon skeleton; Q1is O, S, N-H or N-RQ1; RQ1is selected from a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl, fluorocyclopropylmethyl or -CO-RQ3group; RQ3is selected from a C1-C3 alkyl, C1-C3 fluoroalkyl, cyclopropyl or fluorocyclopropyl group; A1is N, C-H, C-Hal or C-RA1; A2is N, C-H, C-Hal or C-RA2; A3is N, C-H, C-Hal or C-RA3; A4is N, C-H, C-Hal or C-RA4; A5is C; and RA1, RA2, RA3and RA4are each independently selected from a C1-C4 saturated 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 fluoro groups and / or a single oxo (=O) group, and wherein the hydrocarbyl group may optionally include a single heteroatom selected from N and O in its carbon skeleton; provided that no more than one of A1, A2, A3and A4is N; and provided that no more than two of A1, A2, A3and A4are C-RA1, C-RA2, C-RA3or C-RA4; A6is N; and each Hal is independently selected from a fluoro, chloro or bromo group. In one aspect of the first exemplary embodiment, at least one of X2and X3is N. Typically, X2is N. Typically in accordance with the first exemplary embodiment, Q1is S, or N-H. In one aspect, Q1is NH. In a second exemplary embodiment, there is provided a compound of Formula (II) as defined above, wherein: R1and R2are each independently selected from hydrogen or a C1-C12 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight- chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo and / or -NO2 groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O 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 (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety; or R1and R2together with the nitrogen atom to which they are attached form a 3- to 12-membered cyclic group, wherein the cyclic group may optionally be substituted with one or more substituents each independently selected from a halo, oxo (=O), -OH, -SH, -NH2, -SO2H, -SO3H, -SO2NH2, -NO2, or a C1-C6 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 and / or -NO2 groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O 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 (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety; provided that the group -NR1R2contains no more than 24 carbon atoms; X1is N, C-H, C-Hal or C-RX1; X2is N, C-H, C-Hal or C-RX2; X3is N, C-H, C-Hal or C-RX3; and X4is C; provided that at least one of X1, X2and X3is N and that no more than two of X1, X2and X3are N; RX1, RX2and RX3are each independently selected from -OH, -SH, -NH2, or a C1- C4 saturated 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, and wherein the hydrocarbyl group may optionally include one or two heteroatoms each independently selected from N, O and S in its carbon skeleton; Q1is O, S, N-H or N-RQ1; RQ1is selected from a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl, fluorocyclopropylmethyl or -CO-RQ3group; RQ3is selected from a C1-C3 alkyl, C1-C3 fluoroalkyl, cyclopropyl or fluorocyclopropyl group; A1is N, C-H, C-Hal or C-RA1; A2is N, C-H, C-Hal or C-RA2; A3is N, C-H, C-Hal or C-RA3; A4is N, C-H, C-Hal or C-RA4; A5is C; and RA1, RA2, RA3and RA4are each independently selected from a C1-C4 saturated 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 fluoro groups and / or a single oxo (=O) group, and wherein the hydrocarbyl group may optionally include a single heteroatom selected from N and O in its carbon skeleton; provided that no more than one of A1, A2, A3and A4is N; and provided that no more than two of A1, A2, A3and A4are C-RA1, C-RA2, C-RA3or C-RA4; A6is N; and each Hal is independently selected from a fluoro, chloro or bromo group. In one aspect of the second exemplary embodiment, at least one of X2and X3is N. Typically, X2is N. Typically in accordance with the second exemplary embodiment, Q1is S, or N-H. In one aspect, Q1is NH. Typically in accordance with the second exemplary embodiment: R1is a C1-C8 saturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include a single cyclic group, wherein the hydrocarbyl group may optionally be substituted with one or more fluoro groups and / or a single oxo (=O) group, wherein the hydrocarbyl group optionally includes one or two heteroatoms each independently selected from N and O in its carbon skeleton; and R2is selected from hydrogen or a C1-C3 alkyl or C1-C3 fluoroalkyl group; or R1and R2together with the nitrogen atom to which they are attached form a 4- to 7-membered monocyclic group or a 6- to 12-membered bicyclic group, wherein the monocyclic or the bicyclic group may optionally be substituted with one or more substituents each independently selected from a halo, oxo (=O), -OH, -NH2 or a C1-C6 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, and wherein the hydrocarbyl group may optionally include one or two heteroatoms each independently selected from N and O in its carbon skeleton. In a third exemplary embodiment, there is provided a compound of Formula (X) as defined above, wherein: R3is selected from hydrogen or a C1-C12 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo and / or -NO2 groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O 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 (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety; X1is N, C-H, C-Hal or C-RX1; X2is N, C-H, C-Hal or C-RX2; X3is N, C-H, C-Hal or C-RX3; and X4is C; provided that at least one of X1, X2and X3is N and that no more than two of X1, X2and X3are N; RX1, RX2and RX3are each independently selected from -OH, -SH, -NH2, or a C1- C4 saturated 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, and wherein the hydrocarbyl group may optionally include one or two heteroatoms each independently selected from N, O and S in its carbon skeleton; Q1is O, S, N-H or N-RQ1; RQ1is selected from a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl, fluorocyclopropylmethyl or -CO-RQ3group; RQ3is selected from a C1-C3 alkyl, C1-C3 fluoroalkyl, cyclopropyl or fluorocyclopropyl group; A1is N, C-H, C-Hal or C-RA1; A2is N, C-H, C-Hal or C-RA2; A3is N, C-H, C-Hal or C-RA3; A4is N, C-H, C-Hal or C-RA4; A5is C; and RA1, RA2, RA3and RA4are each independently selected from a C1-C4 saturated 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 fluoro groups and / or a single oxo (=O) group, and wherein the hydrocarbyl group may optionally include a single heteroatom selected from N and O in its carbon skeleton; provided that no more than one of A1, A2, A3and A4is N; and provided that no more than two of A1, A2, A3and A4are C-RA1, C-RA2, C-RA3or C-RA4; A6is N; and each Hal is independently selected from a fluoro, chloro or bromo group. In one aspect of the third exemplary embodiment, at least one of X2and X3is N. Typically, X2is N. Typically in accordance with the third exemplary embodiment, Q1is S, or N-H. In one aspect, Q1is NH. Typically in accordance with the third exemplary embodiment, R3is a C2-C8 saturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include a single cyclic group, wherein the hydrocarbyl group may optionally be substituted with one or more fluoro groups, and wherein the hydrocarbyl group includes one or two heteroatoms each independently selected from N and O in its carbon skeleton. In a fourth exemplary embodiment, there is provided a compound of Formula (I) as defined above, wherein: RXis a C1-C12 saturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or two cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more fluoro groups and / or one or two oxo (=O) groups, and wherein the hydrocarbyl group includes one, two, three or four heteroatoms each independently selected from N and O in its carbon skeleton, provided that the atom of RXthat is directly attached to the remainder of the compound of Formula (I) is a carbon atom; X1is N, C-H, C-Hal or C-RX1; X2is N, C-H, C-Hal or C-RX2; X3is N, C-H, C-Hal or C-RX3; and X4is C; provided that at least one of X1, X2and X3is N and that no more than two of X1, X2and X3are N; RX1, RX2and RX3are each independently selected from -OH, -SH, -NH2, or a C1- C4 saturated 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, and wherein the hydrocarbyl group may optionally include one or two heteroatoms each independently selected from N, O and S in its carbon skeleton; Q1is O, S, N-H or N-RQ1; RQ1is selected from a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl, fluorocyclopropylmethyl or -CO-RQ3group; RQ3is selected from a C1-C3 alkyl, C1-C3 fluoroalkyl, cyclopropyl or fluorocyclopropyl group; A1is N, C-H, C-Hal or C-RA1; A2is N, C-H, C-Hal or C-RA2; A3is N, C-H, C-Hal or C-RA3; A4is N, C-H, C-Hal or C-RA4; A5is C; and RA1, RA2, RA3and RA4are each independently selected from a C1-C4 saturated 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 fluoro groups and / or a single oxo (=O) group, and wherein the hydrocarbyl group may optionally include a single heteroatom selected from N and O in its carbon skeleton; provided that no more than one of A1, A2, A3and A4is N; and provided that no more than two of A1, A2, A3and A4are C-RA1, C-RA2, C-RA3or C-RA4; A6is N; and each Hal is independently selected from a fluoro, chloro or bromo group. In one aspect of the fourth exemplary embodiment, at least one of X2and X3is N. Typically, X2is N. Typically in accordance with the fourth exemplary embodiment, Q1is S, or N-H. In one aspect, Q1is NH. In a fifth exemplary embodiment, there is provided a compound of Formula (I) as defined above, wherein: RXis a phenyl, naphthyl, a 5- or 6-membered heteroaryl or a bicyclic fused heteroaryl group, wherein the phenyl, naphthyl, 5- or 6-membered heteroaryl or the bicyclic fused heteroaryl group may optionally be substituted with one or more halo groups and / or one or two groups R5; each R5is independently selected from -OH, -NH2, or a C1-C6 saturated hydrocarbyl group, wherein the saturated hydrocarbyl group may be straight-chained or branched, or be or include a single cyclic group, wherein the saturated hydrocarbyl group may optionally be substituted with one or more fluoro groups and / or a single oxo (=O) group, and wherein the saturated hydrocarbyl group may optionally include one or two heteroatoms each independently selected from N and O in its carbon skeleton; X1is N, C-H, C-Hal or C-RX1; X2is N, C-H, C-Hal or C-RX2; X3is N, C-H, C-Hal or C-RX3; and X4is C; provided that at least one of X1, X2and X3is N and that no more than two of X1, X2and X3are N; RX1, RX2and RX3are each independently selected from -OH, -SH, -NH2, or a C1- C4 saturated 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, and wherein the hydrocarbyl group may optionally include one or two heteroatoms each independently selected from N, O and S in its carbon skeleton; Q1is O, S, N-H or N-RQ1; RQ1is selected from a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl, fluorocyclopropylmethyl or -CO-RQ3group; RQ3is selected from a C1-C3 alkyl, C1-C3 fluoroalkyl, cyclopropyl or fluorocyclopropyl group; A1is N, C-H, C-Hal or C-RA1; A2is N, C-H, C-Hal or C-RA2; A3is N, C-H, C-Hal or C-RA3; A4is N, C-H, C-Hal or C-RA4; A5is C; and RA1, RA2, RA3and RA4are each independently selected from a C1-C4 saturated 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 fluoro groups and / or a single oxo (=O) group, and wherein the hydrocarbyl group may optionally include a single heteroatom selected from N and O in its carbon skeleton; provided that no more than one of A1, A2, A3and A4is N; and provided that no more than two of A1, A2, A3and A4are C-RA1, C-RA2, C-RA3or C-RA4; A6is N; and each Hal is independently selected from a fluoro, chloro or bromo group. In one aspect of the fifth exemplary embodiment, at least one of X2and X3is N. Typically, X2is N. Typically in accordance with the fifth exemplary embodiment, Q1is S, or N-H. In one aspect, Q1is NH. In a sixth exemplary embodiment, there is provided a compound of Formula (IIa) as defined above, wherein: R1is selected from a methyl, ethyl, isopropyl or cyclopropyl group, any of which may optionally be fluoro substituted; R2is selected from hydrogen or a methyl or fluoromethyl group; X1is N or C-H; and X2is N or C-H; provided that at least one of X1and X2is N; Q1is O, S, N-H or N-RQ1; and RQ1is a methyl or fluoromethyl group. Typically in accordance with the sixth exemplary embodiment, R1is selected from a methyl or fluoromethyl group and R2is selected from a methyl or fluoromethyl group. Typically in accordance with the sixth exemplary embodiment, X2is N. More typically, X1is N and X2is N. Typically in accordance with the sixth exemplary embodiment, Q1is S, or N-H. In one aspect, Q1is NH. In a seventh exemplary embodiment, there is provided a compound of Formula (IIa) as defined above, wherein: R1is selected from a -(C(R101)2)e-X10-R102or -(C(R101)2)e-X10-(C(R101)2)f-X11-R102group, provided that any -(C(R101)2)e-X10-R102or -(C(R101)2)e-X10-(C(R101)2)f-X11-R102group contains no more than 8 carbon atoms; R2is selected from hydrogen or a methyl or fluoromethyl group; X10is selected from O or NR103; X11is selected from O or NR104; e is 2, 3 or 4; f is 2, 3 or 4; each R101is hydrogen; R102is selected from a hydrogen or a methyl, ethyl, isopropyl or cyclopropyl group, any of which may optionally be fluoro substituted; R103is selected from hydrogen or a methyl or fluoromethyl group; and R104is selected from hydrogen or a methyl or fluoromethyl group; or a single R101and R103, or a single R101and R104, or R103and R104, or two R101, together form a -(CH2)2- group; X1is N or C-H; and X2is N or C-H; provided that at least one of X1and X2is N; Q1is O, S, N-H or N-RQ1; and RQ1is a methyl or fluoromethyl group. Typically in accordance with the seventh exemplary embodiment, R1is a -(C(R101)2)e-NR102R103group; R2is selected from hydrogen or a methyl or fluoromethyl group; e is 2, 3 or 4; a single R101and R103, or two R101, together form a -(CH2)2- group; each remaining R101is hydrogen; R102is selected from a methyl, ethyl, isopropyl or cyclopropyl group, any of which may optionally be fluoro substituted; and R103, if not part of a -(CH2)2- group, is selected from hydrogen or a methyl or fluoromethyl group. Typically in accordance with the seventh exemplary embodiment, X2is N. More typically, X1is N and X2is N. Typically in accordance with the seventh exemplary embodiment, Q1is S, or N-H. In one aspect, Q1is NH. In an eighth exemplary embodiment, there is provided a compound of Formula (IIIa) as defined above, wherein: n is 1 or 2; m is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; each R11is independently selected from a fluoro, methyl or fluoromethyl group, provided that no more than four R11are selected from a methyl or fluoromethyl group; X12is O or NR12; R12is selected from hydrogen or a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl, fluorocyclopropylmethyl or -CO-R120group; R120is selected from a C1-C3 alkyl, C1-C3 fluoroalkyl, cyclopropyl or fluorocyclopropyl group; X1is N, C-H or C-Hal; and X2is N, C-H or C-Hal; provided that at least one of X1and X2is N; Q1is O, S, N-H or N-RQ1; RQ1is a methyl or fluoromethyl group; and each Hal is independently selected from a fluoro, chloro or bromo group. Typically in accordance with the eighth exemplary embodiment, X1is N or C-H and X2is N or C-H. More typically, X1is N or C-H and X2is N. More typically still, X1is N and X2is N. Typically in accordance with the eighth exemplary embodiment, Q1is S, or N-H. In one aspect, Q1is NH. In one aspect of the eighth exemplary embodiment, X12is O and m is 0. Typically in such an aspect, n is 1. Typically in accordance with the eighth exemplary embodiment, X12is NR12. Where X12is NR12, typically m is 0. Where X12is NR12, typically R12is selected from hydrogen or a methyl or fluoromethyl group. More typically, R12is selected from hydrogen or a methyl group. Where X12is NR12, typically X1is N or C-H and X2is N. Most typically, X1is N and X2is N. Most typically where X12is NR12, n is 1. Thus, in one aspect of the eighth exemplary embodiment: n is 1; m is 0; X12is NR12; R12is selected from hydrogen or a methyl or fluoromethyl group; X1is N; X2is N; and Q1is S or N-H. Typically in such an aspect, R12is selected from hydrogen or a methyl group. In a ninth exemplary embodiment, there is provided a compound of Formula (IIa) as defined above, wherein: R1and R2together with the nitrogen atom to which they are attached form a azetidinyl, pyrrolidinyl, piperidinyl or azepanyl group, wherein the azetidinyl, pyrrolidinyl, piperidinyl or azepanyl group is substituted with a -NR13R14group such that the nitrogen atom of the -NR13R14group is not directly attached to a carbon atom that in turn is directly attached to the ring nitrogen atom of the azetidinyl, pyrrolidinyl, piperidinyl or azepanyl group, wherein R13and R14are each independently selected from hydrogen or a methyl or fluoromethyl group, and wherein the azetidinyl, pyrrolidinyl, piperidinyl or azepanyl group may optionally be further substituted with one or more fluoro groups and / or with one, two, three or four methyl or fluoromethyl groups; X1is N or C-H; and X2is N or C-H; provided that at least one of X1and X2is N; Q1is O, S, N-H or N-RQ1; and RQ1is a methyl or fluoromethyl group. Typically in accordance with the ninth exemplary embodiment, R1and R2together with the nitrogen atom to which they are attached form a pyrrolidinyl or piperidinyl group, wherein the pyrrolidinyl or piperidinyl group is substituted with a -NR13R14group such that the nitrogen atom of the -NR13R14group is not directly attached to a carbon atom that in turn is directly attached to the ring nitrogen atom of the pyrrolidinyl or piperidinyl group, wherein R13and R14are each independently selected from hydrogen or a methyl or fluoromethyl group. Typically in accordance with the ninth exemplary embodiment, X2is N. More typically, X1is N and X2is N. Typically in accordance with the ninth exemplary embodiment, Q1is S, or N-H. In one aspect, Q1is NH. In a tenth exemplary embodiment, there is provided a compound of Formula (IV) as defined above, wherein: j is 0, 1, 2 or 3; k is 0, 1, 2 or 3; p is 0, 1, 2 or 3; and q is 0, 1, 2 or 3; provided that: j + k = 2 or 3; p + q = 2 or 3; when j = 0, q is 1, 2 or 3; when k = 0, p is 1, 2 or 3; when p = 0, k is 1, 2 or 3; and when q = 0, j is 1, 2 or 3; and wherein: r is 0, 1 or 2; s is 0, 1 or 2; R15is hydrogen or a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl, fluorocyclopropylmethyl or -CO-R150group; R150is selected from a C1-C3 alkyl, C1-C3 fluoroalkyl, cyclopropyl or fluorocyclopropyl group; each R16is independently selected from a methyl or fluoromethyl group; X1is N or C-H; X2is N or C-H; X3is N or C-H; and X4is C; provided that at least one of X1, X2and X3is N, and that no more than two of X1, X2and X3are N; Q1is O, S, N-H or N-RQ1; RQ1is a methyl or fluoromethyl group; A1is C-H or C-Hal; A2is C-H or C-Hal; A3is C-H or C-Hal; A4is C-H or C-Hal; A5is C; and each Hal is independently selected from a fluoro, chloro or bromo group. Typically in accordance with the tenth exemplary embodiment: j is 1 or 2; k is 1 or 2; p is 0, 1 or 2; q is 1 or 2; r is 0; and s is 0. More typically in accordance with the tenth exemplary embodiment: j is 1; k is 1; p is 1 or 2; q is 1 or 2; r is 0; and s is 0. Typically in accordance with the tenth exemplary embodiment, R15is hydrogen or a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl or fluorocyclopropylmethyl group. More typically, R15is a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl or fluorocyclopropylmethyl group. More typically still, R15is a methyl, ethyl or cyclopropylmethyl group. Typically in accordance with the tenth exemplary embodiment, the compound is a compound of Formula (IVa) as defined above, wherein X1, X2, Q1, R15, R16, j, k, p, q, r and s are as defined above. Typically where the compound is a compound of Formula (IVa), X2is N. More typically, X1is N and X2is N. Typically in accordance with the tenth exemplary embodiment, Q1is S, or N-H. In one aspect, Q1is NH. Thus, in one aspect of the tenth exemplary embodiment, there is provided a compound of Formula (IVa) as defined above, wherein: j is 1; k is 1; p is 1 or 2; and q is 1 or 2; provided that p + q = 2 or 3; r is 0; s is 0; R15is a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl or fluorocyclopropylmethyl group; X1is N; X2is N; and Q1is S or N-H. Typically in such an aspect, R15is a methyl, ethyl or cyclopropylmethyl group. In an eleventh exemplary embodiment, there is provided a compound of Formula (Va) as defined above, wherein: r is 0, 1 or 2; s is 0, 1 or 2; t is 1 or 2; each R16is independently selected from a methyl or fluoromethyl group; X1is N or C-H; and X2is N or C-H; provided that at least one of X1and X2is N; Q1is O, S, N-H or N-RQ1; and RQ1is a methyl or fluoromethyl group. Typically in accordance with the eleventh exemplary embodiment, r is 0, s is 0 and t is 1. Typically in accordance with the eleventh exemplary embodiment, X2is N. More typically, X1is N and X2is N. Typically in accordance with the eleventh exemplary embodiment, Q1is S, or N-H. In one aspect, Q1is NH. In a twelfth exemplary embodiment, there is provided a compound of Formula (VIa) as defined above, wherein: j is 0, 1, 2 or 3; and k is 0, 1, 2 or 3; provided that j + k = 2 or 3; v is 1 or 2; r is 0, 1 or 2; s is 0, 1 or 2; each R16is independently selected from a methyl or fluoromethyl group; X1is N or C-H; and X2is N or C-H; provided that at least one of X1and X2is N; Q1is O, S, N-H or N-RQ1; and RQ1is a methyl or fluoromethyl group. Typically in accordance with the twelfth exemplary embodiment, j is 1, k is 1, v is 1, r is 0 and s is 0. Typically in accordance with the twelfth exemplary embodiment, X2is N. More typically, X1is N and X2is N. Typically in accordance with the twelfth exemplary embodiment, Q1is S, or N-H. In one aspect, Q1is NH. In a thirteenth exemplary embodiment, there is provided a compound of Formula (VIIa) as defined above, wherein: X15is O or NR15; j is 0, 1, 2, 3 or 4; k is 0, 1, 2, 3 or 4; p is 0, 1, 2, 3 or 4; and q is 0, 1, 2, 3 or 4; provided that: j + k = 3 or 4; p + q = 3 or 4; when j = 0, q is 1, 2, 3 or 4 and p is 1, 2, 3 or 4; when k = 0, q is 1, 2, 3 or 4 and p is 1, 2, 3 or 4; when p = 0, k is 1, 2, 3 or 4 and j is 1, 2, 3 or 4; and when q = 0, k is 1, 2, 3 or 4 and j is 1, 2, 3 or 4; and wherein: r is 0, 1 or 2; s is 0, 1 or 2; R15is hydrogen or a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl, fluorocyclopropylmethyl or -CO-R150group; R150is selected from a C1-C3 alkyl, C1-C3 fluoroalkyl, cyclopropyl or fluorocyclopropyl group; each R16is independently selected from a methyl or fluoromethyl group; X1is N or C-H; and X2is N or C-H; provided that at least one of X1and X2is N; Q1is O, S, N-H or N-RQ1; and RQ1is a methyl or fluoromethyl group. Typically in accordance with the thirteenth exemplary embodiment: j is 1 or 2; k is 1 or 2; p is 0, 1 or 2; q is 1, 2 or 3; r is 0; and s is 0. More typically in accordance with the thirteenth exemplary embodiment: j is 1; k is 2; p is 2; q is 2; r is 0; and s is 0. Typically in accordance with the thirteenth exemplary embodiment, R15is hydrogen or a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl or fluorocyclopropylmethyl group. More typically, R15is hydrogen or a methyl or fluoromethyl group. Yet more typically, R15is hydrogen or a methyl group. Typically in accordance with the thirteenth exemplary embodiment, X2is N. More typically, X1is N and X2is N. Typically in accordance with the thirteenth exemplary embodiment, Q1is S, or N-H. In one aspect, Q1is NH. Thus, in one aspect of the thirteenth exemplary embodiment, there is provided a compound of Formula (VIIa) as defined above, wherein: X15is O or NR15; j is 1; k is 2; p is 2; q is 2; r is 0; s is 0; R15is hydrogen or a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl or fluorocyclopropylmethyl group; X1is N; X2is N; and Q1is S or N-H. Typically in such an aspect, R15is hydrogen or a methyl group. In a fourteenth exemplary embodiment, there is provided a compound of Formula (VIIIa) as defined above, wherein: j is 0, 1, 2, 3 or 4; k is 0, 1, 2, 3 or 4; p is 0, 1, 2 or 3; and q is 0, 1, 2 or 3; provided that: j + k = 3 or 4; p + q = 2 or 3; when j = 0, p is 1, 2 or 3; when k = 0, p is 1, 2 or 3; and when p = 0, j is 1, 2, 3 or 4 and k is 1, 2, 3 or 4; and wherein: r is 0, 1 or 2; s is 0, 1 or 2; R15is hydrogen or a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl or fluorocyclopropylmethyl group; each R16is independently selected from a methyl or fluoromethyl group; X1is N or C-H; and X2is N or C-H; provided that at least one of X1and X2is N; Q1is O, S, N-H or N-RQ1; and RQ1is a methyl or fluoromethyl group. Typically in accordance with the fourteenth exemplary embodiment: j is 1 or 2; k is 1 or 2; p is 1 or 2; q is 1 or 2; r is 0; and s is 0. More typically in accordance with the fourteenth exemplary embodiment: j is 2; k is 2; p is 1; q is 1; r is 0; and s is 0. Typically in accordance with the fourteenth exemplary embodiment, R15is hydrogen or a methyl or fluoromethyl group. More typically, R15is hydrogen. Typically in accordance with the fourteenth exemplary embodiment, X2is N. More typically, X1is N and X2is N. Typically in accordance with the fourteenth exemplary embodiment, Q1is S, or N-H. In one aspect, Q1is NH. Thus, in one aspect of the fourteenth exemplary embodiment, there is provided a compound of Formula (VIIIa) as defined above, wherein: j is 2; k is 2; p is 1; q is 1; r is 0; s is 0; R15is hydrogen or a methyl or fluoromethyl group; X1is N; X2is N; and Q1is S or N-H. Typically in such an aspect, R15is hydrogen. In a fifteenth exemplary embodiment, there is provided a compound of Formula (IXa) as defined above, wherein: w is 1 or 2; X15is O or NR15; R15is hydrogen or a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl, fluorocyclopropylmethyl or -CO-R150group; R150is selected from a C1-C3 alkyl, C1-C3 fluoroalkyl, cyclopropyl or fluorocyclopropyl group; one R17and one R18together form a -CH2- or -CH2CH2- group; each remaining R17and R18is hydrogen; X1is N or C-H; and X2is N or C-H; provided that at least one of X1and X2is N; Q1is O, S, N-H or N-RQ1; and RQ1is a methyl or fluoromethyl group. Typically in accordance with the fifteenth exemplary embodiment, R15is hydrogen or a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl or fluorocyclopropylmethyl group. More typically, R15is hydrogen or a methyl or fluoromethyl group. Typically in accordance with the fifteenth exemplary embodiment, X2is N. More typically, X1is N and X2is N. Typically in accordance with the fifteenth exemplary embodiment, Q1is S, or N-H. In one aspect, Q1is NH. In a sixteenth exemplary embodiment, there is provided a compound of Formula (Xa) as defined above, wherein: R3is selected from a -(C(R105)2)e-Q10-R106or -(C(R105)2)e-Q10-(C(R105)2)f-Q11-R106group, provided that any -(C(R105)2)e-Q10-R106or -(C(R105)2)e-Q10-(C(R105)2)f-Q11-R106group contains no more than 8 carbon atoms Q10is selected from O or NR107; Q11is selected from O or NR108; e is 2, 3 or 4; f is 2, 3 or 4; each R105is hydrogen; R106is selected from a hydrogen or a methyl, ethyl, isopropyl or cyclopropyl group, any of which may optionally be fluoro substituted; R107is selected from hydrogen or a methyl or fluoromethyl group; and R108is selected from hydrogen or a methyl or fluoromethyl group; or a single R105and R107, or a single R105and R108, or R107and R108, or two R105, together form a -(CH2)2- group; X1is N or C-H; and X2is N or C-H; provided that at least one of X1and X2is N; Q1is O, S, N-H or N-RQ1; and RQ1is a methyl or fluoromethyl group. Typically in accordance with the sixteenth exemplary embodiment, R3is a -(CH2)2-NR106R107group, wherein: R106is selected from a methyl, ethyl, isopropyl or cyclopropyl group, any of which may optionally be fluoro substituted; and R107is selected from hydrogen or a methyl or fluoromethyl group. Typically in accordance with the sixteenth exemplary embodiment, X2is N. More typically, X1is N and X2is N. Typically in accordance with the sixteenth exemplary embodiment, Q1is S, or N-H. In one aspect, Q1is NH. In a seventeenth exemplary embodiment, there is provided a compound of Formula (XIa) as defined above, wherein: j is 0, 1, 2 or 3; k is 0, 1, 2 or 3; p is 0, 1, 2 or 3; and q is 0, 1, 2 or 3; provided that: j + k = 2 or 3; and p + q = 2 or 3; and wherein: r is 0, 1 or 2; s is 0, 1 or 2; R15is hydrogen or a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl, fluorocyclopropylmethyl or -CO-R150group; R150is selected from a C1-C3 alkyl, C1-C3 fluoroalkyl, cyclopropyl or fluorocyclopropyl group; each R16is independently selected from a methyl or fluoromethyl group; X1is N or C-H; and X2is N or C-H; provided that at least one of X1and X2is N; Q1is O, S, N-H or N-RQ1; and RQ1is a methyl or fluoromethyl group. Typically in accordance with the seventeenth exemplary embodiment: j is 1 or 2; k is 1 or 2; p is 1 or 2; q is 1 or 2; r is 0; and s is 0. Typically in accordance with the seventeenth exemplary embodiment, R15is hydrogen or a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl or fluorocyclopropylmethyl group. More typically, R15is hydrogen or a methyl or fluoromethyl group. Typically in accordance with the seventeenth exemplary embodiment, X2is N. More typically, X1is N and X2is N. Typically in accordance with the seventeenth exemplary embodiment, Q1is S, or N-H. In one aspect, Q1is NH. In an eighteenth exemplary embodiment, there is provided a compound of Formula (Ia) as defined above, wherein: Rxis selected from a 5- or 6-membered heteroaryl or a bicyclic fused heteroaryl group, wherein the ring atoms of the 5- or 6-membered heteroaryl group or the bicyclic fused heteroaryl group are selected from the group consisting of nitrogen and carbon atoms, and wherein the 5- or 6-membered heteroaryl group or the bicyclic fused heteroaryl group may optionally be substituted with one or more fluoro, chloro and / or bromo groups, and / or with a single group R5; R5is selected from a -NH2, -R51, -NHR51or -N(R51)2 group; each R51is independently selected from a methyl or fluoromethyl group; X1is N or C-H; and X2is N or C-H; provided that at least one of X1and X2is N; Q1is O, S, N-H or N-RQ1; and RQ1is a methyl or fluoromethyl group. Typically in accordance with the eighteenth exemplary embodiment, the 5- or 6- membered heteroaryl group or the bicyclic fused heteroaryl group is unsubstituted Typically in accordance with the eighteenth exemplary embodiment, X2is N. More typically, X1is N and X2is N. Typically in accordance with the eighteenth exemplary embodiment, Q1is S, or N-H. In one aspect, Q1is NH. In a nineteenth exemplary embodiment, there is provided a compound of Formula (Ia) as defined above, wherein: Rxis selected from a phenyl or a 5- or 6-membered heteroaryl group, wherein the phenyl or the 5- or 6-membered heteroaryl group is substituted with a first substituent selected from a -NH2, -NHR53, -N(R53)2, -CH2-NH2, -CH2-NHR53or -CH2-N(R53)2 group, provided that the group -N(R53)2 contains no more than five carbon atoms, and wherein the phenyl or the 5- or 6-membered heteroaryl group may optionally be further substituted with a single methyl or fluoromethyl group and / or with one or more fluoro, chloro and / or bromo groups; each R53is independently selected from a C1-C4 alkyl, C1-C4 fluoroalkyl, C3-C4 cycloalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl or fluorocyclopropylmethyl group; or any two R53attached to the same nitrogen atom may together form a C2-C5 alkylene or a C2-C5 fluoroalkylene group; X1is N or C-H; and X2is N or C-H; provided that at least one of X1and X2is N; Q1is O, S, N-H or N-RQ1; and RQ1is a methyl or fluoromethyl group. Typically in accordance with the nineteenth exemplary embodiment, Rxis selected from a phenyl or a pyridinyl group, wherein the phenyl or the pyridinyl group is substituted with a -NH2, -NHR53, -N(R53)2, -CH2-NH2, -CH2-NHR53or -CH2-N(R53)2 group, wherein each R53is independently selected from a C1-C3 alkyl, C1-C3 fluoroalkyl, cyclopropyl or fluorocyclopropyl group, or any two R53attached to the same nitrogen atom may together form a C3-C4 alkylene or a C3-C4 fluoroalkylene group, provided that the group -N(R53)2 contains no more than four carbon atoms. Typically in accordance with the nineteenth exemplary embodiment, X2is N. More typically, X1is N and X2is N. Typically in accordance with the nineteenth exemplary embodiment, Q1is S, or N-H. In one aspect, Q1is NH. In one aspect of any of the above embodiments, the compound of the first aspect of the invention has a molecular weight of from 250 to 1000 Da. Typically, the compound of the first aspect of the invention has a molecular weight of from 300 to 750 Da. More typically, the compound of the first aspect of the invention has a molecular weight of from 350 to 600 Da. A second aspect of the invention provides a compound selected from the group consisting of:

[0009]  A third aspect of the invention provides a pharmaceutically acceptable salt and / or solvate and / or prodrug of any compound of the first or second aspect of the invention. In one embodiment, the third aspect of the invention provides a pharmaceutically acceptable salt and / or solvate of any compound of the first or second aspect of the invention. For example, the third aspect of the invention may provide (i) a pharmaceutically acceptable salt of any compound of the first or second aspect of the invention, or (ii) a pharmaceutically acceptable solvate of any compound of the first or second aspect of the invention, or (iii) a pharmaceutically acceptable solvate of a pharmaceutically acceptable salt of any compound of the first or second aspect of the invention. 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, trifluoroacetic, 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-, tri- or 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. 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. 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 mono- potassium salt. 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. The compounds and / or salts 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. In one embodiment, the third aspect of the invention provides a prodrug of any compound of the first or second aspect of the invention. Similarly, the third aspect of the invention may provide a pharmaceutically acceptable salt and / or solvate of such a prodrug. For example, the third aspect of the invention may provide (i) a pharmaceutically acceptable salt of a prodrug, or (ii) a pharmaceutically acceptable solvate of a prodrug, or (iii) a pharmaceutically acceptable solvate of a pharmaceutically acceptable salt of a prodrug. 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. 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. 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. 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. 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 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. 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,18O,19F and127I, and any radioisotope including, but not limited to11C,14C,3H (T),13N,15O,18F,123I,124I,125I and131I. The compounds, salts, solvates and prodrugs of the present invention may be in any polymorphic or amorphous form. A fourth aspect of the invention provides an antibody-drug conjugate comprising a compound of the first or second aspect of the invention, or a pharmaceutically acceptable salt and / or solvate and / or prodrug of the third aspect of the invention. For the avoidance of doubt, it will be understood that the compound, salt, solvate or prodrug needs to lose at least one atom such as a hydrogen atom in order to form the link to the antibody. Typically, the compound, salt, solvate or prodrug of the present invention comprises a a -NH- group, a -NH2 group, a -OH group, or a -SH group, each of which can be used to link the compound, salt, solvate or prodrug to an antibody, with the loss of a hydrogen atom from the -NH-, NH2, -OH or -SH group. For example, the antibody- drug conjugate can have the Formula (I-AB), (II-AB), (III-AB), (IV-AB), (VII-AB), (VIII-AB) or (X-AB): Formula (II-AB)

[0010] Formula (VII-AB)

[0011] Formula (X-AB) wherein LABis a linker, AB is an antibody, and X1-X4, A1-A6, Q1, R2, R11, R16, j, k, m, n, p, q, r and s are as defined in accordance with Formula (I). Typical antibodies that may be used to prepare the antibody-drug conjugate of the fourth aspect of the invention are: ^ Cetuximab ^ Trastuzumab ^ Brentuximab ^ ado-Trastuzumab ^ Polatuzumab ^ Inotuzumab ^ Gemtuzumab ^ Sacituzumab ^ Enfortumab ^ Loncastuximab ^ fam-Trastuzumab ^ Tisotumab ^ Belantamab ^ Mirvetuximab ^ Amivantamab Thus, where the antibody-drug conjugate has the Formula (I-AB), (II-AB), (III-AB), (IV-AB), (VII-AB), (VIII-AB) or (X-AB), the antibody AB may be selected from any of the above. The linker LABis typically a C20-C100 saturated or unsaturated hydrocarbylene group, wherein the hydrocarbylene group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbylene group may optionally be substituted with one or more halo and / or -NO2 groups, wherein the hydrocarbylene group may optionally include one or more heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein any -S- moiety in the hydrocarbylene group may optionally be substituted with one or two groups each independently selected from oxo (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety. More typically, the linker LABis a C30-C70 or C40-C60 partially unsaturated hydrocarbylene group, wherein the hydrocarbylene group may be straight-chained or branched, or be or include one, two, three, four, five or six cyclic groups, wherein the hydrocarbylene group may optionally be substituted with one or more halo groups, wherein the hydrocarbylene group includes from 10 to 30 oxygen atoms, from 5 to 15 nitrogen atoms and from 0 to 5 sulphur atoms in its carbon skeleton, wherein any -S- moiety in the hydrocarbylene group may optionally be substituted with one or two groups each independently selected from oxo (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety. Typically, the linker LABcomprises a maleimide moiety, one or more PEG spacers, optionally a BCN moiety, a valine-citrulline (Val-Cit) dipeptide, and a para- aminobenzyl (PAB) spacer. Typically, the hydrocarbylene group of linker LABhas a chain length of from 20 to 80 atoms. More typically, the hydrocarbylene group has a chain length of from 30 to 70 atoms, or from 40 to 60 atoms. As will be understood, the “chain length” of a hydrocarbylene group refers to the number of atoms of the hydrocarbylene group that are bonded to each other in a continuous chain between the two points of attachment of the hydrocarbylene group to the remainder of the molecule, as measured by the shortest route. By way of example, structure (C) has a chain length between A and B of 3 atoms, whereas structure (D) has a chain length between A and B of 5 atoms: Typical linkers that may be used to link a compound of the first or second aspect of the invention, or a pharmaceutically acceptable salt and / or solvate and / or prodrug of the third aspect of the invention, to an antibody to prepare the antibody-drug conjugate of the fourth aspect of the invention are: ● maleimide-valine-citruline-PABC, including those comprising PEG and / or a BCN-derived moiety ● thioether ● hydrazone and disulfide ● CL2a linker ● maleimide-valine-alanine-PABC ● maleimide tetrapeptide linker (GGFG) ● Maleidocaproic linker ● Sulfo-SPDB disulfide Thus, where the antibody-drug conjugate has the Formula (I-AB), (II-AB), (III-AB), (IV-AB), (VII-AB), (VIII-AB) or (X-AB), the linker LABmay be selected from any of the above. In one embodiment of the fourth aspect of the invention, the antibody-drug conjugate is Cetuximab-mal-vc-4-(1,4-Diazepan-1-yl)-8-oxo-11-thia-1,3,5- triazatetracyclo[8.7.0.0²,⁷.0¹²,¹⁷]heptadeca-2(7),3,5,9,12,14,16-heptaene-9- carboxylic acid or a pharmaceutically acceptable salt and / or solvate thereof. A fifth aspect of the invention provides a pharmaceutical composition comprising a compound of the first or second aspect of the invention, or a pharmaceutically acceptable salt and / or solvate and / or prodrug of the third aspect of the invention, or an antibody-drug conjugate of the fourth aspect of the invention, and a pharmaceutically acceptable excipient. 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. 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. In one embodiment of the fifth aspect of the invention, the pharmaceutical composition comprises a compound of the first aspect of the invention, or a pharmaceutically acceptable salt and / or solvate and / or prodrug thereof, wherein X2is not C-F and wherein RX2is not -NO2. Typically in such an embodiment, Q1is O, S or NH. For example, there may be provided a pharmaceutical composition comprising a compound of the first aspect of the invention, or a pharmaceutically acceptable salt and / or solvate and / or prodrug thereof, wherein X2is C-H or C-RX2, wherein RX2is selected from -OH, -SH, -NH2, or a C1-C4 saturated 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 two heteroatoms each independently selected from N, O and S in its carbon skeleton. Typically in such an embodiment, RX2is a C1-C3 saturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include a cyclic group, and wherein the hydrocarbyl group may optionally include a single heteroatom selected from N and O in its carbon skeleton. Typically in such an embodiment, Q1is O, S or NH. Typically in such an embodiment, X1is N. For example, the compound of the first aspect of the invention, or the pharmaceutically acceptable salt and / or solvate and / or prodrug thereof, may be such that X1is N, X2is C-H, and Q1is O, S or NH. In a further embodiment of the fifth aspect of the invention, the pharmaceutical composition comprises a compound of the first aspect of the invention, or a pharmaceutically acceptable salt and / or solvate and / or prodrug thereof, wherein: X1is N, C-H or C-RX1; X2is N, C-H or C-RX2; X3is N, C-H or C-RX3; and X4is C; provided that at least one of X1, X2and X3is N and that no more than two of X1, X2and X3are N; and wherein RX1, RX2and RX3are each independently selected from -OH, -SH, -NH2, or a C1-C4 saturated 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, and wherein the hydrocarbyl group may optionally include one or two heteroatoms each independently selected from N, O and S in its carbon skeleton. For example, the pharmaceutical composition may comprise a compound of any of the first to fifth exemplary embodiments of the first aspect of the invention, or a pharmaceutically acceptable salt and / or solvate and / or prodrug thereof, wherein: X1is N, C-H or C-RX1; X2is N, C-H or C-RX2; X3is N, C-H or C-RX3; and X4is C. Similarly, the pharmaceutical composition may comprise a compound of the eighth exemplary embodiment of the first aspect of the invention, or a pharmaceutically acceptable salt and / or solvate and / or prodrug thereof, wherein X1is N or C-H and X2is N or C-H. In another embodiment of the fifth aspect of the invention, the pharmaceutical composition comprises a compound of the first aspect of the invention, or a pharmaceutically acceptable salt and / or solvate and / or prodrug thereof, wherein -RXis -OR3. A sixth aspect of the invention provides a compound of the first or second aspect of the invention, or a pharmaceutically acceptable salt and / or solvate and / or prodrug of the third aspect of the invention, or an antibody-drug conjugate of the fourth aspect of the invention, or a pharmaceutical composition of the fifth aspect of the invention, for use in medicine, and / or for use in the treatment or prevention of a disease, disorder or condition. Typically, the use comprises the administration of the compound, salt, solvate, prodrug, antibody-drug conjugate or pharmaceutical composition to a subject. 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, antibody-drug conjugate 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. Typically, the genetic or biochemical markers are appropriate to the disease, disorder or condition under consideration. A seventh aspect of the invention provides the use of a compound of the first or second aspect of the invention, or a pharmaceutically acceptable salt and / or solvate and / or prodrug of the third aspect of the invention, or an antibody-drug conjugate of the fourth aspect of the invention, in the manufacture of a medicament for the treatment or prevention of a disease, disorder or condition. Typically, the treatment or prevention comprises the administration of the compound, salt, solvate, prodrug, antibody-drug conjugate or medicament to a subject. An eighth aspect of the invention provides a method of treatment or prevention of a disease, disorder or condition, the method comprising the step of administering an effective amount of a compound of the first or second aspect of the invention, or a pharmaceutically acceptable salt and / or solvate and / or prodrug of the third aspect of the invention, or an antibody-drug conjugate of the fourth aspect of the invention, or a pharmaceutical composition of the fifth aspect of the invention, to thereby treat or prevent the disease, disorder or condition. Typically, the administration is to a subject in need thereof. In one embodiment of any of the sixth to eighth aspects of the invention, the compound of the first aspect of the invention, or the pharmaceutically acceptable salt and / or solvate and / or prodrug thereof, is a compound of Formula (I), or a pharmaceutically acceptable salt and / or solvate and / or prodrug thereof, wherein X2is not C-F and wherein RX2is not -NO2. Typically in such an embodiment, Q1is O, S or NH. For example, the compound of the first aspect of the invention, or the pharmaceutically acceptable salt and / or solvate and / or prodrug thereof, may be a compound of Formula (I) or a pharmaceutically acceptable salt and / or solvate and / or prodrug thereof, wherein X2is C-H or C-RX2, wherein RX2is selected from -OH, -SH, -NH2, or a C1-C4 saturated 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, and wherein the hydrocarbyl group may optionally include one or two heteroatoms each independently selected from N, O and S in its carbon skeleton. Typically in such an embodiment, RX2is a C1-C3 saturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include a cyclic group, and wherein the hydrocarbyl group may optionally include a single heteroatom selected from N and O in its carbon skeleton. Typically in such an embodiment, Q1is O, S or NH. Typically in such an embodiment, X1is N. For example, the compound of the first aspect of the invention, or the pharmaceutically acceptable salt and / or solvate and / or prodrug thereof, may be such that X1is N, X2is C-H, and Q1is O, S or NH. In a further embodiment of any of the sixth to eighth aspects of the invention, the compound of the first aspect of the invention, or the pharmaceutically acceptable salt and / or solvate and / or prodrug thereof, is a compound of Formula (I), or a pharmaceutically acceptable salt and / or solvate and / or prodrug thereof, wherein: X1is N, C-H or C-RX1; X2is N, C-H or C-RX2; X3is N, C-H or C-RX3; and X4is C; provided that at least one of X1, X2and X3is N and that no more than two of X1, X2and X3are N; and wherein RX1, RX2and RX3are each independently selected from -OH, -SH, -NH2, or a C1-C4 saturated 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, and wherein the hydrocarbyl group may optionally include one or two heteroatoms each independently selected from N, O and S in its carbon skeleton. For example, in accordance with any of the sixth to eighth aspects of the invention, the compound of the first aspect of the invention, or the pharmaceutically acceptable salt and / or solvate and / or prodrug thereof, may be a compound of any of the first to fifth exemplary embodiments of the first aspect of the invention, or a pharmaceutically acceptable salt and / or solvate and / or prodrug thereof, wherein: X1is N, C-H or C-RX1; X2is N, C-H or C-RX2; X3is N, C-H or C-RX3; and X4is C. Similarly, in accordance with any of the sixth to eighth aspects of the invention, the compound of the first aspect of the invention, or the pharmaceutically acceptable salt and / or solvate and / or prodrug thereof, may be a compound of the eighth exemplary embodiment of the first aspect of the invention, or a pharmaceutically acceptable salt and / or solvate and / or prodrug thereof, wherein X1is N or C-H and X2is N or C-H. A ninth aspect of the invention provides a compound of the first or second aspect of the invention, or a pharmaceutically acceptable salt and / or solvate and / or prodrug of the third aspect of the invention, or an antibody-drug conjugate of the fourth aspect of the invention, or a pharmaceutical composition of the fifth aspect of the invention, for use in the treatment or prevention of a cancer. Typically, the use comprises the administration of the compound, salt, solvate, prodrug, antibody-drug conjugate or pharmaceutical composition to a subject. A tenth aspect of the invention provides the use of a compound of the first or second aspect of the invention, or a pharmaceutically acceptable salt and / or solvate and / or prodrug of the third aspect of the invention, or an antibody-drug conjugate of the fourth aspect of the invention, in the manufacture of a medicament for the treatment or prevention of a cancer. Typically, the treatment or prevention comprises the administration of the compound, salt, solvate, prodrug, antibody-drug conjugate or medicament to a subject. An eleventh aspect of the invention provides a method of treatment or prevention of a cancer, the method comprising the step of administering an effective amount of a compound of the first or second aspect of the invention, or a pharmaceutically acceptable salt and / or solvate and / or prodrug of the third aspect of the invention, or an antibody-drug conjugate of the fourth aspect of the invention, or a pharmaceutical composition of the fifth aspect of the invention, to thereby treat or prevent the cancer. Typically, the administration is to a subject in need thereof. The compound of the first or second aspect of the invention, or the pharmaceutically acceptable salt and / or solvate and / or prodrug of the third aspect of the invention, or the antibody-drug conjugate of the fourth aspect of the invention, or the pharmaceutical composition of the fifth aspect of the invention can be combined with other therapeutic agents and treatments, for example, to exploit synergies and enhance the cytotoxic activity in cancer treatment. For example, the compound, salt, solvate, prodrug, antibody-drug conjugate or pharmaceutical composition can used in combination with X-ray radiation; DNA alkylating agents like cisplatin; NU7441, an inhibitor of DNA repair regulating kinase DNA-PK; MK1775, an inhibitor of the cell cycle regulator WEE1 kinase; Pimozide, an inhibitor of the deubiquitinylation enzyme USP1; NSC697923, an inhibitor of ubiquitin conjugating enzyme UBE2N; APR-246, a P53 activator; PARP inhibitors; topoisomerase 1 knockdown; HDAC inhibitors; lysosome inhibitors; and immunomodulators. Unless stated otherwise, in any of the sixth to eleventh 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. 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. Typically, the mode of administration selected is that most appropriate to the disorder, disease or condition to be treated or prevented. For oral administration, the compounds, salts, solvates, prodrugs or antibody-drug conjugates of the present invention will generally be provided in the form of tablets, capsules, hard or soft gelatine capsules, caplets, troches or lozenges, as a powder or granules, or as an aqueous solution, suspension or dispersion. 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. 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. 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. Any form suitable for oral administration may optionally include sweetening agents such as sugar, flavouring agents, colouring agents and / or preservatives. Formulations for rectal administration may be presented as a suppository with a suitable base comprising, for example, cocoa butter or a salicylate. 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. For parenteral use, the compounds, salts, solvates, prodrugs or antibody-drug conjugates 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 of the invention may also be presented as liposome formulations. For ocular administration, the compounds, salts, solvates, prodrugs or antibody-drug conjugates 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 other types 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. For transdermal and other topical administration, the compounds, salts, solvates, prodrugs or antibody-drug conjugates 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. The dose of the compounds, salts, solvates, prodrugs or antibody-drug conjugates 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. All citations are incorporated herein by reference in their entirety. 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. References 1. Silverman, R. B. & Holladay, M. W. The Organic Chemistry of Drug Design and Drug Action. (Elsevier, 2014). doi:10.1016 / C2009-0-64537-2. 2. Hilton, J. et al. Results of the phase I CCTG IND.231 trial of CX-5461 in patients with advanced solid tumors enriched for DNA-repair deficiencies. Nat. Commun. 13, 3607 (2022). 3. Khot, A. et al. First-in-Human RNA Polymerase I Transcription Inhibitor CX-5461 in Patients with Advanced Hematologic Cancers: Results of a Phase I Dose- Escalation Study. Cancer Discov. 9, 1036–1049 (2019). Examples – Compound Synthesis All solvents, reagents and compounds were purchased and used without further purification unless stated otherwise. NMR:1H NMR,13C NMR spectra and 2D NMR spectra were recorded on a Bruker Avance Neo 400 MHz NMR spectrometer at 25°C in CDCl3 / MeOD / DMSO-d6 / DMSO- d6+D2O, respectively, residual undeuterated solvent as internal reference. Chemical shifts (δ) are expressed in ppm and coupling constants (J) are given in Hz. LCMS method: All final compounds were purified to ≥95% purity as determined Shimadzu LC-20AD XR&MS 2020 with UV detection at 220 nm using the following method: Halo C18 column (5.0 μm, 3.0 mm × 30 mm), eluting with binary solvent systems A and B using a 5−95% B over 3.0 minutes gradient elution [A, H2O with 0.04% TFA; B, CH3CN with 0.02% TFA]; flow rate 1.0 mL / min. Mass spectral data were recorded on an Shimadzu LC-20AD XR&MS 2020 with UV detection, ESI. Preparative HPLC method: TFA as buffer: Preparative reversed-phase high pressure liquid chromatography (RP- HPLC) was performed using a Gilson 281 Semi-preparative HPLC system and Phenomenex Luna C18 column (5 μm, 100 mm × 40 mm), eluting with binary solvent systems A and B using a gradient elution [A, H2O with 0.1% TFA; B, CH3CN] with UV detection at 220 nm. HCl as buffer: Preparative reversed-phase high pressure liquid chromatography (RP- HPLC) was performed using a Gilson 281 Semi-preparative HPLC system and Phenomenex Luna C18 column (5 μm, 100 mm × 40 mm), eluting with binary solvent systems A and B using a gradient elution [A, H2O with 0.04% HCl; B, CH3CN] with UV detection at 220 nm. NH4HCO3 as buffer: Preparative reversed-phase high pressure liquid chromatography (RP-HPLC) was performed using a Gilson 281 Semi-preparative HPLC system and Waters Xbridge Prep OBD C18 (10 μm, 150 mm × 40 mm), eluting with binary solvent systems A and B using a gradient elution [A, H2O with 10mM NH4HCO3; B, CH3CN] with UV detection at 220 nm. Synthetic Route 1 Example 1: 4-(4-Methyl-1,4-diazepan-1-yl)-8-oxo-11-thia-1,3,5- triazatetracyclo[8.7.0.0²,⁷.0¹²,¹⁷]heptadeca-2(7),3,5,9,12,14,16-heptaene-9- carboxylic acid 2,4-Dichloropyrimidine-5-carbonyl chloride: A mixture of acid (1.00 g, 5.18 mmol, 1 eq) in SOCl2 (10.00 mL) was stirred at 65°C for 12 h. TLC showed the reaction was completed. The mixture was concentrated in vacuum to give the desired product (1.00 g, 4.73 mmol, 91.28% yield) as a yellow solid. The crude product was used in the next step without further purification. Ethyl 4-chloro-8-oxo-11-thia-1,3,5-triazatetracyclo[8.7.0.0²,⁷.0¹²,¹⁷]- heptadeca-2(7),3,5,9,12,14,16-heptaene-9-carboxylate: To a mixture of acid chloride (0.5 g, 2.26 mmol, 1 eq) and MgCl2 (322.71 mg, 3.39 mmol, 139.10 μL, 1.5 eq) in THF (10.00 mL) was added ethyl 2-(1,3-benzothiazol-2-yl)acetate (621.09 mg, 2.94 mmol, 1.3 eq) and TEA (457.30 mg, 4.52 mmol, 629.02 μL, 2 eq) at -10 °C under N2. The mixture was stirred at 20 °C for 2 h, then to the mixture was added TEA (457.30 mg, 4.52 mmol, 629.02 μL, 2 eq) and the reaction heated to 25 °C and stirred for 10 h. LCMS showed the reaction was complete. The mixture was concentrated and the residue was triturated with MeCN (10 mL). The mixture was filtered and the solid was collected to give the title compound (0.22 g, 0.611 mmol, 27.06% yield) as a yellow solid. The crude product was used in the next step without further purification.1H NMR (400 MHz, CDCl3) δ = 9.63 (s, 1H), 9.37 (br d, J= 8.3 Hz, 1H), 7.75 (br d, J= 7.6 Hz, 1H), 7.64 - 7.56 (m, 1H), 7.54 - 7.45 (m, 1H), 4.50 (q, J= 7.0 Hz, 2H), 1.49 (br t, J= 7.0 Hz, 3H). Ethyl 4-(4-methyl-1,4-diazepan-1-yl)-8-oxo-11-thia-1,3,5-triazatetracyclo- [8.7.0.0²,⁷.0¹²,¹⁷]heptadeca-2(7),3,5,9,12,14,16-heptaene-9-carboxylate: To a mixture of ester (0.17 g, 472.51 μmol, 1 eq) in MeCN (5.00 mL) was added 1- methyl-1,4-diazepane (107.91 mg, 0.946 mmol, 2 eq) at 25 °C under N2. The mixture was stirred at 25 °C for 12 h. LCMS showed the reaction was completed. The mixture was concentrated in vacuum. The residue was triturated with MeCN (20 mL) for 10 min. Then the mixture was filtered and the solid was collected to afford the title compound (0.14 g, 319.99 μmol, 67.72% yield) as a yellow solid. LCMS (ESI+): m / z 438.4 (M+H)+, Rt: 0.466 min. 4-(4-Methyl-1,4-diazepan-1-yl)-8-oxo-11-thia-1,3,5-triazatetracyclo- [8.7.0.0²,⁷.0¹²,¹⁷]heptadeca-2(7),3,5,9,12,14,16-heptaene-9-carboxylic acid: To a solution of ethyl 4-(4-methyl-1,4-diazepan-1-yl)-8-oxo-11-thia-1,3,5- triazatetracyclo[8.7.0.0²,⁷.0¹²,¹⁷]heptadeca-2(7),3,5,9,12,14,16-heptaene-9- carboxylate (0.8 g, 1.83 mmol, 1 eq) in THF (15 mL) and H2O (5 mL) was added LiOH.H2O (230.19 mg, 5.49 mmol, 3 eq), then the mixture was heated to 50 °C and stirred for 2 h. The reaction mixture was filtered. The filtered cake was adjusted to pH 7 with 1 M HCl. Then the filtered cake was triturated with a mixture of 4 M HCl (100 mL), MeOH (10 mL) and MeCN (200 mL) at 25 °C for 30 min, then the mixture was filtered. The filtered cake was collected and lyophilized to give the title compound (Example 1, 0.35 g, 854.78 μmol, 46.75% yield) as a light yellow solid. LCMS (ESI+): m / z 410.3 (M+H) +, Rt: 1.578 min.1H NMR (400 MHz, D2O) δ = 8.73 (br d, J = 4.0 Hz, 1H), 8.31 (d, J = 8.6 Hz, 1H), 7.55 - 7.24 (m, 3H), 4.18 - 3.25 (m, 8H), 3.10 - 2.81 (m, 2H), 2.54 - 2.16 (m, 2H). The following examples were synthesised according to the method outlined in Synthetic Route 1 using commercially available starting materials: 0 z, , 8 4 = - .2 00 O) δ H), Hz, , , , , .64 9 - 6) δ 9.42 9 - - - - - - (br 4.04 H), 2 - (br (m, ) δ.2865 = d, J 7.836 - - (s, .2 00 ) δH), z,,,,,,,, 9 ,7 48 33 03 R + (s, .5 J , ), ), 4 , J 61 - 3 58 R δ 9 ), z, m, m,

[0012] r J - r J 1 J - d, J ,

[0013] ), H), - + 7.5 J =.47 ). =4

[0014] Synthetic Route 2 Example 6: 4-(4-methyl-1,4-diazepan-1-yl)-8-oxo-1,3,5,11- tetraazatetracyclo[8.7.0.0²,⁷.0¹²,¹⁷]heptadeca-2(7),3,5,9,12,14,16- heptaene-9-carboxylic acid Ethyl 4-chloro-8-oxo-1,3,5,11-tetraazatetracyclo[8.7.0.0²,⁷.0¹²,¹⁷]- heptadeca-2(7),3,5,9,12,14,16-heptaene-9-carboxylate: To a solution of ethyl 2-(1H-benzimidazol-2-yl) acetate (1.56 g, 7.69 mmol, 1 eq) in THF (15 mL) was added MgCl2 (1.09 g, 11.54 mmol, 470.32 μL, 1.5 eq) at 25 °C. Then to the mixture was added a solution of 2,4-dichloropyrimidine-5-carbonyl chloride (2.1 g, 10.0 mmol, 1.3 eq) in THF (10 mL) dropwise at -20 °C. Then DIEA (3.96 g, 80.58 mmol, 5.32 mL, 4 eq) was added at -20 °C. The mixture was stirred at 25 °C for 2 h and then heated to 80 °C and stirred for 2 h. The mixture was concentrated in vacuum. The crude product was triturated with water (50 mL) for 30 min. After filtration, the filter cake was triturated with MeCN (50 mL x 2) for 30 min. After filtration, the filter cake was collected to give the title compound (3.5 g, 6.13 mmol, 93.56% yield, 60% purity) as a yellow solid. LCMS (ESI+): m / z 342.9 (M+H)+, Rt: 0.419 min. Ethyl 4-(4-methyl-1,4-diazepan-1-yl)-8-oxo-1,3,5,11- tetraazatetracyclo[8.7.0.0²,⁷.0¹²,¹⁷]heptadeca-2(7),3,5,9,12,14,16- heptaene-9-carboxylate: To a solution of ethyl 4-chloro-8-oxo-1,3,5,11- tetraazatetracyclo[8.7.0.0²,⁷.0¹²,¹⁷]heptadeca-2(7),3,5,9,12,14,16-heptaene-9- carboxylate (1.5 g, 4.38 mmol, 1 eq) in MeCN (20 mL) was added 1-methyl-1, 4- diazepane (999.50 mg, 8.75 mmol, 1.09 mL, 2 eq) and DIEA (1.70 g, 13.13 mmol, 2.29 mL, 3 eq). The mixture was stirred at 25 °C for 2 h. The mixture was concentrated in vacuum. The residue was purified by prep-HPLC (column: Phenomenex luna C18 100*40mm*5 um;mobile phase: [H2O(0.04% HCl)- ACN];gradient:1%-35% B over 10.0 min) to give the title compound (1.2 g, 2.86 mmol, 65.21% yield, 90% purity) as a yellow solid. LCMS (ESI+): m / z 421.3 (M+H)+, Rt: 1.393 min. 4-(4-Methyl-1,4-diazepan-1-yl)-8-oxo-1,3,5,11-tetraazatetracyclo- [8.7.0.0²,⁷.0¹²,¹⁷]heptadeca-2(7),3,5,9,12,14,16-heptaene-9-carboxylic acid: To a solution of ethyl 4-(4-methyl-1,4-diazepan-1-yl)-8-oxo-1,3,5,11- tetraazatetracyclo[8.7.0.0²,⁷.0¹²,¹⁷]heptadeca-2(7),3,5,9,12,14,16-heptaene-9- carboxylate (100 mg, 237.83 μmol, 1 eq) in THF (0.4 mL) and H2O (0.1 mL) was added LiOH.H2O (19.96 mg, 475.67 μmol, 2 eq). The mixture was stirred at 50 °C for 24 hr. The mixture was filtrated and the filtrate was purified by prep-HPLC (column: Phenomenex luna C18 100*40mm*3 um; mobile phase: [H2O(0.1% TFA)-ACN]; gradient: 1%-30% B over 8.0 min) to give the title compound (Example 6, 37.6 mg, 95.82 μmol, 40.29% yield) as yellow solid. LCMS (ESI+): m / z 393.1 (M+H)+, Rt: 0.279 min.1H NMR (400 MHz, DMSO-d6) δ = 15.71 (d, J = 2.1 Hz, 1H), 13.18 - 12.98 (m, 1H), 10.00 - 9.65 (m, 1H), 9.22 (d, J = 14.1 Hz, 1H), 8.69 - 8.50 (m, 1H), 7.85 - 7.76 (m, 1H), 7.59 - 7.42 (m, 2H), 4.69 - 4.33 (m, 1H), 4.22 - 3.75 (m, 4H), 3.70 - 3.58 (m, 1H), 3.33 - 3.16 (m, 2H), 2.86 (br s, 3H), 2.41 - 2.13 (m, 2H). The following examples were synthesised according to the method outlined in Synthetic Route 2 using commercially available starting materials: 16 (s, .42 3H) Hz, 06 (d, , + ), ), Hz, 2 00 δ z, 9 6, .41 J = .80 J = br Hz, , J d, ), 2 0 δ ), z, Synthetic Route 3 Example 10: 2-(4-methyl-1,4-diazepan-1-yl)-5-oxo-5H-benzo[4',5']oxazolo- [3',2':1,6]pyrido[2,3-d]pyrimidine-6-carboxylic acid 2,4-Dichloropyrimidine-5-carbonyl chloride: A mixture of acid (1.00 g, 5.18 mmol, 1 eq) in SOCl2 (10.00 mL) was stirred at 65°C for 12 h. TLC showed the reaction was completed. The mixture was concentrated in vacuum to give the desired product (1.00 g, 4.73 mmol, 91.28% yield) as a yellow solid. The crude product was used in the next step without further purification. Ethyl 2-chloro-5- oxo-5H-benzo[4',5']oxazolo[3', 2':1, 6]pyrido[2,3- d]- pyrimidine 6-carboxylate: To a solution of ethyl 2-(benzo[d]oxazol-2-yl)acetate (1.42 g, 6.91 mmol, 1 eq) in THF (20 mL) was added MgCl2 (987.21 mg, 10.37 mmol, 425.52 μL, 1.5 eq) at 25 °C. Then to the mixture was added 2, 4-dichloropyrimidine- 5-carbonyl chloride (2.0 g, 9.52 mmol, 83.06% yield, 75% purity) with THF (20 mL) dropwise at -10°C. Then to the mixture was added DIEA (2.68 g, 20.74 mmol, 3.61 mL, 3 eq) dropwise at -25°C. The mixture was stirred at 25°C for 2 h. The mixture was concentrated in vacuo and the residue was triturated with water (50 mL) for 30 min. After filtration, the filter cake was collected triturated with ACN (50 mL) for 30 min. The product was filtered and the filter cake was collected to give the title compound (1.8 g, 5.24 mmol, 84.18% yield) as a yellow solid. LCMS (ESI+): m / z 343.9 (M+H)+, Rt: 0.442 min. Ethyl 2-(4-methyl-1, 4-diazepan-1-yl)-5-oxo-5H-benzo[4',5']oxazolo- [3',2':1,6]pyrido[2,3-d] pyrimidine-6-carboxylate: To a solution of ethyl 2- chloro-5-oxo-5H-benzo[4',5']oxazolo[3',2':1,6]pyrido[2,3-d]pyrimidine- 6-carboxylate (1.8 g, 5.24 mmol, 1 eq) in ACN (20 mL) was added 1-methyl-1,4-diazepane (1.20 g, 10.48 mmol, 1.45 mL, 2 eq). The mixture was stirred at 25°C for 12 hr. The mixture was concentrated in vacuo and the residue was purified by prep-HPLC (column: Phenomenex luna C18 100*40mm*5 µm;mobile phase: [H2O(0.04% HCl)-ACN]; gradient:1%-30% B over 8.0 min) to give the title compound (0.8 g, 1.90 mmol, 36.2% yield) as a yellow solid. LCMS (ESI+): m / z 422.1 (M+H)+, Rt: 0.319 min. 2-(4-Methyl-1,4-diazepan-1-yl)-5-oxo-5H-benzo[4',5']oxazolo[3',2':1,6]- pyrido[2,3-d]pyrimidine-6-carboxylic acid: A solution of ethyl 2-(4-methyl-1, 4- diazepan-1-yl)-5-oxo-5H-benzo[4',5']oxazolo[3',2':1,6]pyrido[2,3-d] pyrimidine-6- carboxylate (500 mg, 1.19 mmol, 1 eq) in TFA (2 mL) and H2O (6 mL) was stirred at 60°C for 12 hr. The mixture was filtered and the filter cake was collected and purified by pre-HPLC (column: Phenomenex luna C18 100*40mm*5 µm; mobile phase: [H2O (0.04% HCl)-ACN]; gradient:1%-25% B over 8.0 min ) to give the title compound (200 mg, 508.39 μmol, 42.85% yield) as a white solid. LCMS (ESI+): m / z 394.2 (M+H)+, Rt: 1.324 min.1H NMR (400 MHz, DMSO-d6+D2O) δ = 9.33 (d, J = 9.1 Hz, 1H), 8.61 - 8.44 (m, 1H), 8.02 - 7.96 (m, 1H), 7.64 (dd, J = 3.1, 5.6 Hz, 2H), 4.73 - 4.32 (m, 1H), 4.20 - 3.88 (m, 3H), 3.85 - 3.62 (m, 1H), 3.47 (br s, 1H), 3.41 - 3.18 (m, 2H), 2.82 (br s, 3H), 2.40 - 2.30 (m, 1H), 2.24 (br d, J = 4.5 Hz, 1H). Synthetic Route 4 Example 11: 2-(5-methylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-5-oxo-5H- benzo[4',5']thiazolo [3',2':1,6]pyrido[2,3-b]pyrazine-6-carboxylic acid 3,5-dichloropyrazine-2-carbonyl chloride: A mixture of 3,5-dichloropyrazine-2- carboxylic acid (10 g, 51.82 mmol, 1 eq) and SOCl2 (100 mL) was stirred at 65 °C for 12 hrs. The reaction mixture was concentrated under reduced pressure to give the title compound (11 g, 49.42 mmol, 95.38% yield, 95% purity) as a brown oil which was directly used in the next step without purification. LCMS (ESI+): m / z 206.9 (M- 4)+, Rt: 0.282 min. Ethyl 2-chloro-5-oxo-5H-benzo[4',5']thiazolo[3',2':1,6]pyrido[2,3-b]- pyrazine-6-carboxylate: To a solution of ethyl 2-(1,3-benzothiazol-2-yl)acetate (5 g, 22.60 mmol, 1 eq) and MgCl2 (3.23 g, 33.89 mmol, 1.39 mL, 1.5 eq) in THF (50 mL) was added 3,5-dichloropyrazine-2-carbonyl chloride (6.21 g, 29.38 mmol, 1.3 eq) and DIEA (11.68 g, 90.39 mmol, 15.74 mL, 4 eq) at 0 °C. The resulting mixture was stirred at 60 °C for 12 hrs. The reaction mixture was concentrated under reduced pressure and the crude product was triturated with H2O (40 mL) and MeCN (30 mL) at 25°C for 30 min to give the title compound (8 g, 20.46 mmol, 90.53% yield, 92% purity) as a green solid. LCMS (ESI+): m / z 359.9 (M+H)+, Rt: 0.401 min.1H NMR (400 MHz, DMSO-d6) δ 9.30 - 9.06 (m, 1H), 8.17 - 8.05 (m, 1H), 7.74 - 7.63 (m, 1H), 7.63 - 7.49 (m, 2H), 4.43 - 4.35 (m, 2H), 1.35 (br t, J = 6.9 Hz, 3H). Ethyl 2-(5-methylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-5-oxo-5H- benzo[4',5']thiazolo[3',2':1,6]pyrido[2,3-b]pyrazine-6-carboxylate: To a solution of ethyl 4-chloro-8-oxo-11-thia-1,3,6-triazatetracyclo[8.7.0.02,7.012,17] heptadeca-2,4,6,9,12(17),13,15-heptaene-9-carboxylate (500 mg, 1.39 mmol, 1 eq) in ACN (5 mL) was added 5-methyl-2,3,3a,4,6,6a-hexahydro-1H-pyrrolo[3,4-c]pyrrole (553.44 mg, 2.78 mmol, 2 eq, 2HCl) and DIEA (359.22 mg, 2.78 mmol, 484.12 μL, 2 eq) at 20 °C. The mixture was stirred at 80 °C for 2 hrs. The reaction mixture was concentrated under reduced pressure and the crude product was triturated with ACN (4 mL) at 20 °C for 30 min to give the title compound (500 mg, 889.83 μmol, 64.03% yield, 80% purity) as a gray solid. LCMS (ESI+): m / z 450.0 (M+H)+, Rt: 0.317 min. 2-(5-methylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-5-oxo-5H-benzo[4',5']- thiazolo [3',2':1,6]pyrido[2,3-b]pyrazine-6-carboxylic acid: To a solution of ethyl 4-(2-methyl-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl)-8-oxo-11-thia- 1,3,6-triazatetracyclo[8.7.0. 02,7.012,17]heptadeca-2,4,6,9,12(17),13,15-heptaene-9- carboxylate (300 mg, 667.37 μmol, 1 eq) in MeOH (1.5 mL) and THF (1.5 mL) was added LiOH.H2O (2 N, 3.00 mL) at 25 °C. The mixture was stirred at 25 °C for 1 hr. The mixture was added to dilute hydrochloric acid to adjust the pH to 5-6. The crude product was triturated with MeOH (0.5 mL) at 20 °C for 30 min to give the title compound (18 mg, 38.76 μmol, 5.81% yield, 98.6% purity, HCl) as a light yellow solid. LCMS (ESI+): m / z 422.1 (M+H)+, Rt: 2.875 min.1H NMR (400 MHz, DMSO- d6+D2O) δ 9.20 (br d, J = 7.0 Hz, 1H), 8.43 (br s, 1H), 8.05 (br d, J = 7.6 Hz, 1H), 7.64 - 7.51 (m, 2H), 4.04 - 3.79 (m, 5H), 3.60 - 3.17 (m, 5H), 2.89 (br s, 3H). Synthetic Route 5 Example 12: 2-(2-Methyl-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl)- 5-oxo-[1,3]benzothiazolo [3,2-a][1,5]naphthyridine-6-carboxylic acid 3,5-Difluoropyridine-2-carbonyl chloride: A mixture of 3,5-difluoropyridine-2- carboxylic acid (5 g, 31.43 mmol, 1 eq) in SOCl2 (81.90 g, 688.41 mmol, 50 mL, 21.90 eq) was stirred at 65°C for 24 h. The reaction mixture was concentrated in vacuo to give the title compound (5.5 g, 30.98 mmol, 98.57% yield) as a white solid. LCMS (ESI+): m / z 174.2 (M-3)+, Rt: 0.256 min. Ethyl 2-fluoro-5-oxo-[1,3]benzothiazolo[3,2-a][1,5]naphthyridine-6- carboxylate: To a solution of ethyl 2-(1,3-benzothiazol-2-yl)acetate (4.76 g, 21.51 mmol, 1 eq) in THF (40 mL) was added MgCl2 (3.07 g, 32.26 mmol, 1.32 mL, 1.5 eq) and 3,5-difluoropyridine-2-carbonyl chloride (4.2 g, 23.66 mmol, 1.1 eq) in THF (10 mL) at -5°C dropwise under N2. TEA (4.35 g, 43.01 mmol, 5.99 mL, 2 eq) was added at -5°C under N2. The resultant mixture was stirred at -5°C for 2 h. TEA (4.30 g, 42.50 mmol, 5.92 mL, 2 eq) was added and the mixture was stirred at 65 °C for 12 h. The reaction mixture was concentrated in vacuo and the crude product was triturated with H2O at 25°C for 20 min, filtered and filter cake was further triturated with MeCN at 25°C for 20 min before being filtered. The filter cake was dried under vacuum to give the title compound (7.1 g, 20.74 mmol, 97.60% yield) as a purple solid. LCMS (ESI+): m / z 343.1 (M+H)+, Rt: 0.410 min. Ethyl 2-(2-methyl-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl)-5-oxo- [1,3] benzothiazolo[3,2-a][1,5]naphthyridine-6-carboxylate: To a solution of ethyl 2-fluoro-5-oxo-[1,3]benzothiazolo[3,2-a][1,5]naphthyridine-6-carboxylate (1.5 g, 4.38 mmol, 1 eq) in MeCN (15 mL) was added DIEA (1.13 g, 8.76 mmol, 1.53 mL, 2 eq) and 5-methyl-2,3,3a,4,6,6a-hexahydro-1H-pyrrolo[3,4-c]pyrrole (663.54 mg, 5.26 mmol, 1.2 eq). The mixture was stirred at 80 °C for 12 h. The reaction mixture was concentrated in vacuo and the crude product was triturated with MeCN (50 mL) at 25°C for 1 h, filtered and the filter cake was dried under vacuum to give the title compound (1.55 g, 3.46 mmol, 78.87% yield) as a yellow solid. LCMS (ESI+): m / z 449.3 (M+H)+, Rt: 0.356 min. 2-(2-Methyl-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl)-5-oxo- [1,3]benzothiazolo [3,2-a][1,5]naphthyridine-6-carboxylic acid: To a solution of ethyl 2-(2-methyl-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl)-5-oxo- [1,3]benzothiazolo[3,2-a][1,5]naphthyridine-6-carboxylate (760 mg, 1.69 mmol, 1 eq) in MeOH (7 mL) and THF (7 mL) and H2O (7 mL) was added LiOH.H2O (711.03 mg, 16.94 mmol, 10 eq). The mixture was stirred at 25°C for 1 h. The reaction mixture was concentrated under reduced pressure and to the mixture was added water (40 mL). The pH was adjusted to pH 1-2 with HCl, the mixture filtered and the filter cake was concentrated in vacuo. The crude product was purified by reversed- phase HPLC (column: CD18-Welch Utimate C18 150*40*7µm; mobile phase: [H2O (0.1%TFA)-ACN]; gradient:0%-29% B over 10.0 min) to give the title compound (340 mg, 628.85 μmol, 37.11% yield, 98.86% purity, TFA) as a yellow solid. LCMS (ESI+): m / z 421.2 (M+H)+, Rt: 1.978 min.1H NMR (400 MHz, DMSO-d6+D2O) δ = 8.38 - 7.92 (m, 3H), 7.65 - 7.28 (m, 3H), 3.95 - 3.85 (m, 1H), 3.81 - 3.59 (m, 5H), 3.49 - 3.38 (m, 2H), 3.33 - 3.19 (m, 1H), 3.06 (br dd, J = 2.2, 4.4 Hz, 1H), 2.89 (s, 3H). Synthetic Route 6 Example 13: 4-(2-Methyl-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl)- 8-oxo-11-oxa-1,3,5-triazatetracyclo[8.7.0.02,7.012,17]heptadeca- 2,4,6,9,12(17),13,15-heptaene-9-carboxylic acid Ethyl 4-chloro-8-oxo-11-oxa-1,3,5-triazatetracyclo[8.7.0.02,7.012,17] heptadeca-2(7),3,5,9,12 (17),13,15-heptaene-9-carboxylate: To a solution of ethyl 2-(1,3-benzoxazol-2-yl)acetate (4.58 g, 22.33 mmol, 1 eq) in THF (100 mL) was added MgCl2 (3.19 g, 33.50 mmol, 1.37 mL, 1.5 eq) at 25°C, then to the mixture was added 2,4-dichloropyrimidine-5-carbonyl chloride (8.5 g, 40.20 mmol, 1.8 eq) with THF (5 mL) dropwise at -25 °C. To the mixture was added DIEA (17.32 g, 134.01 mmol, 23.34 mL, 6 eq) at -25°C, the mixture was stirred at 25°C for 0.5 h. The reaction mixture was concentrated under reduced pressure and the crude product was triturated with water (200 mL) and then filtered and the filter cake was dried under reduce pressure to give the crude product. Then the crude product was triturated with ACN (100 mL) then filtered and the filter cake was dried under reduce pressure to give the title compound (5.7 g, 16.58 mmol, 74.25% yield) as a yellow solid. LCMS (ESI+): Rt: 0.399 min, m / z 343.9 (M+H)+.1H NMR (400 MHz, DMSO-d6) δ = 9.42 (s, 1H), 8.46 (d, J = 7.5 Hz, 1H), 7.89 (d, J = 7.8 Hz, 1H), 7.65 - 7.55 (m, 2H), 4.34 (q, J = 7.1 Hz, 2H), 1.33 (t, J = 7.1 Hz, 3H). Ethyl 4-(2-methyl-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl)-8-oxo- 11-oxa-1,3,5-triazatetracyclo[8.7.0.02,7.012,17]heptadeca- 2,4,6,9,12(17),13,15-heptaene-9-carboxylate: To a solution of ethyl 4-chloro-8- oxo-11-oxa-1,3,5-triazatetracyclo[8.7.0.02,7.012,17]heptadeca-2,4,6,9,12(17),13,15- heptaene-9-carboxylate (5.2 g, 15.13 mmol, 1 eq) and 5-methyl-2,3,3a,4,6,6a- hexahydro-1H-pyrrolo[3,4-c]pyrrole (1.91 g, 15.13 mmol, 1 eq) in ACN (250 mL) was added DIEA (3.91 g, 30.26 mmol, 5.27 mL, 2 eq). The mixture was stirred at 80°C for 12 h. The reaction mixture was filtered and the filter cake was concentrated under reduce pressure. The crude product was triturated with ACN (200 mL) then filtered and the filtrate was dried under reduced pressure to give the title compound (4 g, 9.23 mmol, 61.00% yield) as a yellow solid. LCMS (ESI+): Rt: 0.318 min, m / z 434.2 (M+H)+.1H NMR (400 MHz, DMSO-d6) δ = 9.03 (s, 1H), 8.47 (d, J = 7.9 Hz, 1H), 7.77 (d, J = 7.8 Hz, 1H), 7.55 - 7.46 (m, 2H), 4.29 (q, J = 7.0 Hz, 2H), 4.02 - 3.87 (m, 2H), 3.68 - 3.60 (m, 2H), 3.25 (br d, J = 2.0 Hz, 2H), 3.09 - 2.95 (m, 2H), 2.69 - 2.59 (m, 2H), 2.25 (s, 3H), 1.31 (t, J = 7.1 Hz, 3H). 4-(2-Methyl-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl)-8-oxo-11- oxa-1,3,5-triazatetracyclo[8.7.0.02,7.012,17]heptadeca-2,4,6,9,12(17),13,15- heptaene-9-carboxylic acid: To a solution of ethyl 4-(2-methyl-1,3,3a,4,6,6a- hexahydropyrrolo[3,4-c]pyrrol-5-yl)-8-oxo-11-oxa-1,3,5-triazatetracyclo [8.7.0.02,7.012,17]heptadeca-2,4,6,9,12(17),13,15-heptaene-9-carboxylate (500 mg, 1.15 mmol, 1 eq) was added HCl (4 M, 10.00 mL, 34.68 eq) and stirred at 60°C for 6 h. The reaction mixture was filtered and the filter cake was concentrated under reduce pressure. The crude product was purified by prep-HPLC (column: CD24- WePure Biotech XPT C18 150*25*7µm; mobile phase: [H2O (0.05%HCl)-ACN]; gradient: 0%-28% B over 10.0 min) to give an eluent and the eluent was concentrated under reduce pressure to remove MeCN then lyophilized to give the title compound (24.5 mg, 53.98 μmol, 4.68% yield, 97.36% purity, HCl) as a yellow solid. LCMS (ESI+): Rt: 1.813 min, m / z 406.3 (M+H)+.1H NMR (400 MHz, DMSO-d6+D2O) δ = 9.28 (s, 1H), 8.61 (br d, J = 5.0 Hz, 1H), 7.95 (br d, J = 2.8 Hz, 1H), 7.63 (br d, J = 3.6 Hz, 2H), 4.01 (br d, J = 6.5 Hz, 2H), 3.93 - 3.81 (m, 3H), 3.50 - 3.31 (m, 3H), 3.30 - 3.21 (m, 1H), 3.12 - 2.99 (m, 1H), 2.87 (br d, J = 10.6 Hz, 3H). Synthetic Route 7 Example 31: 2-(5-isopropylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-5-oxo- 5H-benzo[4',5']thiazolo [3',2':1,6]pyrido[2,3-d]pyrimidine-6-carboxylic acid Ethyl 2-(hexahydropyrrolo[3,4-c]pyrrol- 2(1H)-yl)-5-oxo-5H-benzo[4',5']- thiazolo[3',2':1,6]pyrido[2,3-d]pyrimidine-6-carboxylate: A mixture of ethyl 2- (5-(tert-butoxycarbonyl)hexahydropyrrolo[3,4-c]pyrrol-(1H)-yl)-5-oxo-5H-benzo- [4',5']thiazolo[3',2':1,6]pyrido[2,3-d]pyrimidine-6-carboxylate (1 g, 1.87 mmol, 1 eq) in HCl / dioxane (10 mL) was stirred at 25°C for 2 h. The mixture was concentrated in vacuo to give the title compound (0.8 g, 1.84 mmol, 98.39% yield) as a yellow solid. The crude product was directed for the next step without purification. LCMS (ESI+): Rt: 0.338 min, m / z 436.2 (M+H)+. Ethyl 2-(5-isopropylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-5-oxo-5H- benzo[4',5'] thiazolo [3',2':1,6]pyrido[2,3-d]pyrimidine-6-carboxylate: To a solution of ethyl 2-(hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-5-oxo-5H-benzo[4',5']- thiazolo[3',2':1,6]pyrido[2,3-d]pyrimidine-6-carboxylate (0.4 g, 918.49 μmol, 1 eq) in DMF (15 mL) was added acetone (533.45 mg, 9.18 mmol, 675.25 μL, 10 eq) and NaBH(OAc)3 (584.00 mg, 2.76 mmol, 3 eq). The mixture was stirred at 40°C for 12 h. The mixture was concentrated in vacuo and the residue was triturated with ACN and MTBE (50 mL). The precipitate was collected by filtration to give the title compound (0.4 g, 837.56 μmol, 91.19% yield) as a yellow solid. LCMS (ESI+): m / z 478.2 (M+H)+, Rt: 0.360 min. 2-(5-Isopropylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-5-oxo-5H-benzo- [4',5']thiazolo[3',2':1,6]pyrido[2,3-d]pyrimidine-6-carboxylic acid: To a solution of ethyl 2-(5-isopropylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-5-oxo-5H- benzo[4',5']thiazolo [3',2':1,6] pyrido[2,3-d]pyrimidine-6-carboxylate (200 mg, 418.78 μmol, 1 eq) in THF (2 mL) and H2O (0.4 mL) was added LiOH.H2O (35.15 mg, 837.56 μmol, 2 eq). The mixture was stirred at 50°C for 12 h. The mixture was concentrated in vacuo and the residue was purified by prep-HPLC (column: Phenomenex luna C18 100*40mm*5 µm;mobile phase: [H2O(0.04% HCl)-ACN]; gradient:1%-40% B over 8.0 min) to give the title compound (29.3 mg, 65.18 μmol, 15.56% yield, HCl salt) as a yellow solid. LCMS (ESI+): m / z 450.2 (M+H)+, Rt: 1.565 min.1H NMR (400 MHz, D2O) δ = 8.34 (br s, 1H), 8.07 (br d, J = 1.0 Hz, 1H), 7.29 (br d, J = 1.1 Hz, 1H), 7.16 (br s, 2H), 3.94 (br s, 1H), 3.69 (br s, 2H), 3.59 - 3.08 (m, 8H), 1.38 (br s, 6H). The following examples were synthesised according to the method outlined in Synthetic Route 7 using commercially available starting materials:

[0015] Synthetic Route 8 Example 36: 4-(1-Methyl-1,7-diazaspiro[4.4]nonan-7-yl)-8-oxo-11-thia- 1,3,5-triazatetracyclo[8.7.0.02,7.012,17]heptadeca-2,4,6,9,12(17),13,15- heptaene-9-carboxylic acid tert-Butyl 1-methyl-1,7-diazaspiro[4.4]nonane-7-carboxylate: To a solution of tert-butyl 1,7-diazaspiro[4.4]nonane-7-carboxylate (1.5 g, 6.63 mmol, 1 eq) in DCM (15 mL) was added NaBH(OAc)3 (5.62 g, 26.51 mmol, 4 eq) and formaldehyde (1.08 g, 13.26 mmol, 986.91 μL, 37% purity, 2 eq). The mixture was stirred at 25 °C for 2 hrs. The reaction mixture was quenched by the addition of saturated NaHCO3 to pH = 7~8, and then extracted with DCM (3 x 50 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure to give the title compound (1.3 g, 5.35 mmol, 80.79% yield, 100% purity) as a colourless oil which was used in the next step without purification. LCMS (ESI+): m / z 241.1 (M+H)+, Rt: 0.362 min.1H NMR (400 MHz, DMSO-d6) δ 3.42 - 3.36 (m, 1H), 3.23 - 3.13 (m, 2H), 2.92 (d, J = 10.6 Hz, 1H), 2.70 - 2.57 (m, 2H), 2.19 (s, 3H), 1.97 - 1.86 (m, 1H), 1.74 - 1.65 (m, 4H), 1.51 - 1.44 (m, 1H), 1.39 (s, 9H). 1-Methyl-1,7-diazaspiro[4.4]nonane: To a solution of tert-butyl 1-methyl-1,7- diazaspiro[4.4]nonane-7-carboxylate (1.3 g, 5.41 mmol, 1 eq) was added HCl / dioxane (2 N, 13 mL). The mixture was stirred at 25 °C for 2 hr. The reaction mixture was concentrated under reduced pressure to give the title compound (1 g, 4.60 mmol, 85.00% yield, 98.95% purity, 2HCl) as a gray solid which was directly without purification. LCMS (ESI+): m / z 141. (M+H)+, Rt: 0.074 min.1H NMR (400 MHz, DMSO-d6) δ 12.09 - 11.69 (m, 1H), 10.16 - 9.58 (m, 2H), 3.79 - 3.48 (m, 2H), 3.42 - 3.38 (m, 1H), 3.33 - 3.20 (m, 2H), 3.12 (br s, 1H), 2.76 (s, 3H), 2.49 - 2.21 (m, 2H), 2.20 - 1.85 (m, 4H). Ethyl 4-(1-methyl-1,7-diazaspiro[4.4]nonan-7-yl)-8-oxo-11-thia-1,3,5- triazatetracyclo[8.7.0.02,7.012,17]heptadeca-2,4,6,9,12(17),13,15-heptaene-9- carboxylate: To a solution of ethyl 4-chloro-8-oxo-11-thia-1,3,5-triazatetracyclo- [8.7.0.02,7.012,17]heptadeca-2,4,6,9,12(17),13,15-heptaene-9-carboxylate (500 mg, 1.39 mmol, 1 eq) in ACN (5 mL) was added DIEA (359.22 mg, 2.78 mmol, 484.12 μL, 2 eq) and 1-methyl-1,7-diazaspiro[4.4]nonane (592.43 mg, 2.78 mmol, 2 eq, 2HCl). The mixture was stirred at 25 °C for 12 hrs. The reaction mixture was concentrated under reduced pressure to remove solvent. The crude product was triturated with ACN (10 mL) at 25oC for 30 min to give the title compound (500 mg, 1.00 mmol, 72.18% yield, 93.94% purity) as a yellow solid. LCMS (ESI+): m / z 464.1. (M+H)+, Rt: 0.336 min.1H NMR (400 MHz, DMSO-d6) δ 9.27 - 9.16 (m, 1H), 9.04 (d, J = 8.3 Hz, 1H), 7.94 (d, J = 7.5 Hz, 1H), 7.63 - 7.41 (m, 2H), 4.31 (q, J = 7.0 Hz, 2H), 4.13 - 4.01 (m, 1H), 3.94 - 3.82 (m, 1H), 3.77 - 3.65 (m, 2H), 3.17 (br d, J = 8.3 Hz, 1H), 3.01 - 2.93 (m, 1H), 2.67 (br d, J = 10.8 Hz, 3H), 2.15 (br s, 2H), 1.99 (br d, J = 7.6 Hz, 2H), 1.83 - 1.72 (m, 2H), 1.33 (t, J = 7.0 Hz, 3H). 4-(1-Methyl-1,7-diazaspiro[4.4]nonan-7-yl)-8-oxo-11-thia-1,3,5- triazatetracyclo[8.7.0.02,7.012,17]heptadeca-2,4,6,9,12(17),13,15-heptaene-9- carboxylic acid: To a solution of ethyl 4-(1-methyl-1,7-diazaspiro[4.4]nonan-7-yl)-8- oxo-11-thia-1,3,5-triazatetracyclo[8.7.0.02,7.012,17]heptadeca-2,4,6,9,12(17),13,15- heptaene-9-carboxylate (100 mg, 215.73 μmol, 1 eq) in THF (1 mL) and MeOH (1 mL) was added LiOH (2 N, 1 mL, 9.27 eq). The mixture was stirred at 25 °C for 2 hrs. The reaction mixture was quenched by the addition of 1 N HCl to pH = 5~6 at 0 °C, and then the solid was filtered and concentrated under reduced pressure to give a residue. The crude product was triturated with H2O (3 mL) and CAN (3 mL) at 25oC for 30 min to give the title compound (38 mg, 83.64 μmol, 38.77% yield, 95.85% purity, HCl salt) as a yellow solid. LCMS (ESI+): m / z 436.0 (M+H)+, Rt: 2.236 min.1H NMR (400 MHz, D2O) δ = 8.46 - 8.26 (m, 1H), 8.12 - 7.94 (m, 1H), 7.28 (br s, 1H), 7.19 - 6.99 (m, 2H), 3.93 - 3.26 (m, 6H), 3.00 - 2.84 (m, 3H), 2.58 - 2.44 (m, 1H), 2.40 - 2.11 (m, 5H). The following example was synthesised according to the method outlined in Synthetic Route 8 using commercially available starting materials:

[0016] Synthetic Route 9 Example 38: 4-(5-Cyclopropyl-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol- 2-yl)-8-oxo-1,3,5,11-tetrazatetracyclo[8.7.0.02,7.012,17]heptadeca- 2(7),3,5,9,12(17),13,15-heptaene-9-carboxylic acid tert-Butyl 2-cyclopropyl-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5- carboxylate: To a solution of tert-butyl 2,3,3a,4,6,6a-hexahydro-1H-pyrrolo[3,4-c]- pyrrole-5-carboxylate (5 g, 23.55 mmol, 1 eq) and cyclopropylboronic acid (4.05 g, 47.11 mmol, 2 eq) in dichloroethane (50 mL) was added 2-(2-pyridyl)pyridine (3.68 g, 23.55 mmol, 1 eq), Na2CO3 (4.99 g, 47.11 mmol, 2 eq) and Cu(OAc)2 (4.28 g, 23.55 mmol, 1 eq). The mixture was stirred at 70 °C for 12 hrs. The reaction mixture was quenched by the addition of NH3.H2O (1 mL) at 0°C, and then diluted with water (10 mL) and extracted with DCM (3 x 100 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography (SiO2, petroleum ether / ethyl acetate = 0 / 1 to 3 / 1, Rf = 0.55) to give the title compound (2 g, 7.91 mmol, 33.59% yield, 99.81% purity) as a yellow oil. LCMS (ESI+): m / z 253.2 (M+H)+, Rt: 0.334 min.1H NMR (400 MHz, CHLOROFORM-d) δ 3.49 (br s, 2H), 3.20 (br s, 2H), 2.87 (br dd, J = 7.3, 9.0 Hz, 2H), 2.80 - 2.71 (m, 2H), 2.43 (br d, J = 6.6 Hz, 2H), 1.60 - 1.53 (m, 1H), 1.45 (s, 9H), 0.46 - 0.31 (m, 4H). 5-cyclopropyl-2,3,3a,4,6,6a-hexahydro-1H-pyrrolo[3,4-c]pyrrole: To a solution of tert-butyl 2-cyclopropyl-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5- carboxylate (2 g, 7.93 mmol, 1 eq) in DCM (15 mL) was added TFA (5 mL). The mixture was stirred at 25 °C for 2 hrs. The reaction mixture was concentrated under reduced pressure to give the title compound (2 g, 7.51 mmol, 94.78% yield, 100% purity, TFA salt) as a yellow oil which was directly used in the next step without purification. LCMS (ESI+): m / z 153.2 (M+H)+, Rt: 0.076 min.1H NMR (400 MHz, DMSO-d6) δ 9.36 - 9.23 (m, 1H), 3.54 - 2.95 (m, 10H), 2.77 (br d, J = 3.0 Hz, 1H), 0.92 (br s, 2H), 0.84 - 0.77 (m, 2H). Ethyl 4-(5-cyclopropyl-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-2-yl)-8- oxo-1,3,5,11-tetrazatetracyclo[8.7.0.02,7.012,17]heptadeca- 2(7),3,5,9,12(17),13,15-heptaene-9-carboxylate: To a solution of ethyl 4-chloro- 8-oxo-1,3,5,11-tetrazatetracyclo[8.7.0.02,7.012,17]heptadeca-2(7),3,5,9,12(17),13,15- heptaene-9-carboxylate (300 mg, 875.31 μmol, 1 eq) in ACN (3 mL) was added DIEA (339.38 mg, 2.63 mmol, 457.39 μL, 3 eq) and 5-cyclopropyl-2,3,3a,4,6,6a- hexahydro-1H-pyrrolo[3,4-c]pyrrole (349.59 mg, 1.31 mmol, 1.5 eq, TFA). The mixture was stirred at 25 °C for 12 hrs. The reaction mixture was concentrated under reduced pressure and the crude product was triturated with ACN (10 mL) at 25oC for 30 min to give the title compound (400 mg, 692.24 μmol, 79.09% yield, 79.35% purity) as a yellow solid. LCMS (ESI+): m / z 459.1 (M+H)+, Rt: 0.344min.1H NMR (400 MHz, DMSO-d6) δ 9.11 - 8.90 (m, 1H), 8.65 (br d, J = 7.5 Hz, 1H), 7.77 - 7.59 (m, 1H), 7.51 - 7.19 (m, 3H), 4.32 (br d, J = 2.6 Hz, 2H), 4.06 - 3.84 (m, 2H), 3.63 - 3.47 (m, 2H), 3.04 - 2.92 (m, 2H), 2.86 - 2.60 (m, 5H), 1.33 (br s, 3H), 0.42 - 0.34 (m, 2H), 0.29 (br s, 2H). 4-(5-cyclopropyl-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-2-yl)-8-oxo- 1,3,5,11-tetrazatetracyclo[8.7.0.02,7.012,17]heptadeca- 2(7),3,5,9,12(17),13,15-heptaene-9-carboxylic acid: To a solution of ethyl 4-(5- cyclopropyl-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-2-yl)-8-oxo-1,3,5,11- tetrazatetracyclo[8.7.0.02,7.012,17]heptadeca-2(7),3,5,9,12(17),13,15-heptaene-9- carboxylate (100.00 mg, 218.10 μmol, 1 eq) in a mixture of THF (0.5 mL) and MeOH (0.5 mL) was added LiOH (2 M, 1 mL, 9.17 eq). The mixture was stirred at 65 °C for 2 hrs. The reaction mixture was quenched by the addition of 1 N TFA to pH = 6 at 0 °C, and the solid was filtered and concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (TFA condition, column: CD24-XPT C18 150 * 25 * 7 µm; mobile phase: [water (0.1%TFA)-ACN]; gradient: 0%-30% B over 11 min) to give the title compound (33 mg, 58.24 μmol, 26.70% yield, 96.09% purity, TFA salt) as an orange solid. LCMS (ESI+): m / z 431.3 (M+H)+, Rt: 2.202 min.1H NMR (400 MHz, D2O) δ 8.24 - 7.99 (m, 1H), 7.39 - 7.20 (m, 1H), 7.07 - 6.85 (m, 2H), 6.74 (br s, 1H), 4.20 - 3.04 (m, 10H), 2.88 (br s, 1H), 0.94 (br s, 4H). The following example was synthesised according to the method outlined in Synthetic Route 9 using exemplified intermediates: Synthetic Route 10 Example 40: 4-(1-Methyl-3,3a,4,6,7,7a-hexahydro-2H-pyrrolo[3,2-c]pyridin- 5-yl)-8-oxo-11-thia-1,3,5-triazatetracyclo[8.7.0.02,7.012,17]heptadeca- 2,4,6,9,12(17),13,15-heptaene-9-carboxylic acid 1-Methyloctahydro-1H-pyrrolo[3,2-c]pyridine: To a solution of tert-butyl 2,3,3a,4,5,6,7,7a-octahydropyrrolo[3,2-c]pyridine-1-carboxylate (1.5 g, 6.63 mmol, 1 eq) in THF (15 mL) was added LiAlH4 (2.5 M, 7.95 mL, 3 eq) slowly at 0°C. The mixture was heated at 65°C and stirred for 12 hrs. The mixture was quenched with Na2SO4.10H2O and filtered. The filter cake was washed with THF (2 x 10 mL) and the combined filtrate was concentrated to dryness to give the title compound (0.9 g, 5.78 mmol, 87.1% yield, 90% purity) as a yellow oil.1H NMR (400 MHz, METHANOL-d4) 3.14 - 3.00 (m, 1H), 2.78 - 2.77 (m, 1H), 2.84 - 2.75 (m, 1H), 2.68 (td, J = 4.3, 12.5 Hz, 1H), 2.63 - 2.52 (m, 1H), 2.39 - 2.19 (m, 5H), 1.96 - 1.84 (m, 1H), 1.84 - 1.68 (m, 2H), 1.45 - 1.27 (m, 3H). Ethyl 2-(1-methyloctahydro-5H-pyrrolo[3,2-c]pyridin-5-yl)-5-oxo-5H-benzo- [4',5']thiazolo[3',2':1,6]pyrido[2,3-d]pyrimidine-6-carboxylate: To a solution of ethyl 4-chloro-8-oxo-11-thia-1,3,5-triazatetracyclo[8.7.0.02,7.012,17]heptadeca- 2,4,6,9,12(17),13,15-heptaene-9-carboxylate (1 g, 2.50 mmol, 1 eq) and 1-methyl- 2,3,3a,4,5,6,7,7a-octahydropyrrolo[3,2-c]pyridine (385 mg, 2.75 mmol, 1.1 eq) in ACN (10 mL) was added DIEA (646 mg, 5.00 mmol, 871 μL, 2 eq). The mixture was stirred at 25°C for 12 hrs. The mixture was filtered and triturated with ACN (10 mL) at 25°C for 30 min to give the title compound (0.8 g, 1.38 mmol, 55.1%, yield, 80% purity) as a yellow solid. LCMS (ESI+): m / z 464.3 (M+H)+, Rt: 1.212 min. 4-(1-Methyl-3,3a,4,6,7,7a-hexahydro-2H-pyrrolo[3,2-c]pyridin-5-yl)-8-oxo- 11-thia-1,3,5-triazatetracyclo[8.7.0.02,7.012,17]heptadeca- 2,4,6,9,12(17),13,15-heptaene-9-carboxylic acid: To a solution of ethyl 4-(1- methyl-3,3a,4,6,7,7a-hexahydro-2H-pyrrolo[3,2-c]pyridin-5-yl)-8-oxo-11-thia-1,3,5- triazatetracyclo[8.7.0.02,7.012,17]heptadeca-2,4,6,9,12(17),13,15-heptaene-9- carboxylate (0.10 g, 215 μmol, 1 eq) in a mixture of THF (1.00 mL) and MeOH (1.00 mL) was added LiOH (2 N, 1.00 mL, 9.27 eq). The mixture was stirred at 25 °C for 2 hrs. The reaction mixture was concentrated under reduced pressure and to the residue was added water (3.00 mL) and adjusted pH to 5~6. The residue was purified by prep-HPLC (TFA condition, column: CD24-XPT C18 150 * 25 * 7 µm; mobile phase: [water (0.1% TFA) - ACN]; gradient: 10% - 40% B over 10 min) to give the title compound (25.0 mg, 55.5 μmol, 25.7% yield, 96.8% purity, HCl salt) as a yellow solid. LCMS (ESI+): m / z 436.2 (M+H)+, Rt: 2.476 min.1H NMR (400 MHz, DMSO- d6+D2O) δ 9.30 - 9.05 (m, 2H), 8.06 - 7.90 (m, 1H), 7.70 - 7.46 (m, 2H), 4.57 - 4.28 (m, 1H), 3.94 - 3.85 (m, 1H), 3.76 - 3.46 (m, 4H), 3.13 - 3.03 (m, 1H), 2.97 - 2.82 (m, 3H), 2.77 - 2.69 (m, 1H), 2.33 - 1.63 (m, 4H). The following examples were synthesised according to the method outlined in Synthetic Route 10 using commercially available starting materials:

[0017] Synthetic Route 11 Example 44: 2-(2-(tert-butoxycarbonyl)-2,8-diazaspiro[4.5]decan-8-yl)-5- oxo-5H-benzo[4',5']thiazolo[3',2':1,6]pyrido[2,3-d]pyrimidine-6-carboxylic acid To a mixture of ethyl 2-(2-(tert-butoxycarbonyl)-2,8-diazaspiro[4.5]decan-8-yl)-5- oxo-5H-benzo[4',5']thiazolo[3',2':1,6] pyrido[2,3-d]pyrimidine-6-carboxylate (0.2 g, 354.82 μmol, 1 eq) in THF (1 mL) and MeOH (1 mL) was added LiOH.H2O (29.78 mg, 709.64 μmol, 2 eq). The mixture was heated to 50°C and stirred for 12 h. The mixture was filtered and the cake was triturated with MeOH (5 mL) for 10 min. After filtration, the filter cake was triturated with DCM (5 mL) for 10 min and the filter cake was collected to give the title compound (0.15 g, 280.05 μmol, 78.93% yield) as a yellow solid. LCMS (ESI+): Rt: 0.631 min, m / z 536.2 (M+H)+. Example 45: 5-oxo-2-(2,8-diazaspiro[4.5]decan-8-yl)-5H-benzo[4',5']- thiazolo[3',2':1,6]pyrido[2,3-d]pyrimidine-6-carboxylic acid A mixture of 2-(2-(tert-butoxycarbonyl)-2,8-diazaspiro[4.5]decan-8-yl)-5-oxo-5H- benzo[4',5']thiazolo[3',2':1,6]pyrido[2,3-d]pyrimidine-6-carboxylic acid (0.15 g, 280.05 μmol, 1 eq) in HCl / dioxane (2 ml) was stirred at 25°C for 2 h. The mixture was concentrated in vacuo and the filter cake was triturated with DCM (5 mL) for 10 min. The filter cake was collected to give the title compound (80 mg, 140.44 μmol, 50.15% yield, 96.47% purity, TFA salt) as a yellow solid. LCMS (ESI+): Rt: 1.593 min, m / z 436.1 (M+H)+.1H NMR (400 MHz, DMSO-d6+D2O) δ = 9.27 (s, 1H), 9.25 (d, J = 8.5 Hz, 1H), 8.15 (dd, J = 1.1, 7.8 Hz, 1H), 7.67 - 7.62 (m, 1H), 7.61 - 7.56 (m, 1H), 4.18 - 4.09 (m, 1H), 4.06 - 3.86 (m, 3H), 3.35 - 3.30 (m, 2H), 3.12 (s, 2H), 1.95 (t, J = 7.5 Hz, 2H), 1.80 (br s, 2H), 1.74 - 1.67 (m, 2H). The following examples were synthesised according to the method outlined in Synthetic Route 11 using commercially available starting materials:

[0018] Synthetic Route 12 Example 48: 2-(4-methyl-1,4-diazepan-1-yl)-5-oxo-5H-benzo[4,5]thiazolo- [3,2-a][1,8]naphthyridine-6-carboxylic acid Ethyl 2-chloro-5-oxo-[1,3]benzothiazolo[3,2-a][1,8]naphthyridine-6- carboxylate: To a solution of ethyl 2-(1,3-benzothiazol-2-yl)acetate (4 g, 18.08 mmol, 1 eq) and MgCl2 (2.58 g, 27.12 mmol, 1.11 mL, 1.5 eq) in THF (40 mL) was added 2,6-dichloropyridine-3-carbonyl chloride (4.27 g, 19.88 mmol, 1.1 eq) and Et3N (3.66 g, 36.16 mmol, 5.03 mL, 2 eq) at -10°C. The mixture was stirred at 20°C for 2 hrs. To the reaction mixture was added Et3N (3.66 g, 36.16 mmol, 5.03 mL, 2 eq) and the mixture was stirred at 60°C for 12 hrs. The reaction mixture was concentrated under reduced pressure to remove solvent and the crude product was triturated with MeCN (60 mL) at 25°C for 2 h to give the title compound (6 g, 16.05 mmol, 88.81% yield, purity 96%) as a yellow solid. LCMS (ESI+): m / z 358.9 (M+H)+, Rt: 0.523 min. Ethyl 2-(4-methyl-1,4-diazepan-1-yl)-5-oxo-5H-benzo[4,5]thiazolo[3,2-a]- [1,8]naphthyridine-6-carboxylate: A mixture of ethyl 2-chloro-5-oxo-[1,3]- benzothiazolo[3,2-a][1,8]naphthyridine-6-carboxylate (550 mg, 1.53 mmol, 1 eq) and 1-methyl-1,4-diazepane (0.350 g, 3.06 mmol, 0.381 mL, 2 eq) in MeCN (10.00 mL) was stirred at 80°C for 2 h. LCMS showed the reaction was completed. The mixture was concentrated in vacuum. The residue was triturated with MeCN (6.00 mL) for 10 min. Then the mixture was filtered and the solid was collected to afford the title compound (0.54 g, 1.24 mmol, 80.7% yield) as a yellow solid.1H NMR (400 MHz, CHCl3-d) δ = 9.51 (br d, J= 8.4 Hz, 1H), 8.58 (d, J= 9.0 Hz, 1H), 7.73 (d, J= 7.4 Hz, 1H), 7.52 - 7.38 (m, 2H), 6.75 (d, J= 9.1 Hz, 1H), 4.51 (q, J= 7.1 Hz, 2H), 4.07 - 3.76 (m, 4H), 3.32 - 3.24 (m, 4H), 2.45 (s, 3H), 2.07 (quin, J= 5.7 Hz, 2H), 1.50 (t, J= 7.1 Hz, 3H) 2-(4-methyl-1,4-diazepan-1-yl)-5-oxo-5H-benzo[4,5]thiazolo[3,2-a][1,8]- naphthyridine-6-carboxylic acid: To a solution of ethyl 2-(4-methyl-1,4-diazepan- 1-yl)-5-oxo-5H-benzo[4,5] thiazolo[3,2-a][1,8]naphthyridine-6-carboxylate (0.2 g, 458.16 μmol, 1 eq) in THF (5 mL) and H2O (1 mL) and MeOH (1 mL) was added LiOH.H2O (38.45 mg, 916.33 μmol, 2 eq) and the mixture was stirred for 5h at 50°C. The mixture was concentrated in vacuo and the crude product was purified by prep- HPLC (column: Phenomenex Luna C18 100*30mm*5µm; mobile phase: [H2O (0.1% TFA)-ACN]; gradient: 5%-45% B over 8.0 min) to give the title compound (0.05 g, 121.91 μmol, 26.61% yield, 99.59% purity) as a white solid. LCMS (ESI+): m / z 409.2 (M+H)+, Rt: 1.959 min.1H NMR (400 MHz, DMSO-d6+D2O) δ = 9.26 - 9.09 (m, 1H), 8.24 (br d, J = 9.0 Hz, 1H), 7.98 (d, J = 7.8 Hz, 1H), 7.60 (br d, J = 6.8 Hz, 1H), 7.55 - 7.47 (m, 1H), 7.07 (br d, J = 9.0 Hz, 1H), 4.43 - 4.07 (m, 1H), 3.99 - 3.74 (m, 4H), 3.61 - 3.49 (m, 1H), 3.45 - 3.22 (m, 2H), 2.87 (s, 3H), 2.30 (br s, 2H). The following examples were synthesised according to the method outlined in Synthetic Route 12 using commercially available starting materials:

[0019] Synthetic Route 13 Example 51: 4-(1,4-diazepan-1-yl)-8-oxo-1,3,5,11-tetrazatetracyclo- [8.7.0.02,7.012,17]heptadeca-2,4,6,9,12(17),13,15-heptaene-9-carboxylic acid Ethyl 4-(4-tert-butoxycarbonyl-1,4-diazepan-1-yl)-8-oxo-1,3,5,11- tetrazatetracyclo[8.7.0.02,7.012,17]heptadeca-2,4,6,9,12(17),13,15-heptaene- 9-carboxylate: To a solution of ethyl 4-chloro-8-oxo-1,3,5,11-tetrazatetracyclo- [8.7.0.02,7.012,17]heptadeca-2,4,6,9,12(17),13,15-heptaene-9-carboxylate (0.3 g, 875.3 μmol, 1 eq) in ACN (3 mL) was added tert-butyl 1,4-diazepane-1-carboxylate (701.2 mg, 3.50mmol, 690.2 μL, 4 eq) at 25°C. The mixture was stirred at 25°C for 12 hrs. The mixture was filtered and concentrated in vacuo. The residue was triturated with ACN (5 mL) at 25°C for 30 min to give the title compound (0.28 g, 552.7 μmol, 61.3% yield, 86% purity) as a white solid. LCMS (ESI+): Rt: 0.502 min, m / z 507.3 (M+H)+. Ethyl 4-(1,4-diazepan-1-yl)-8-oxo-1,3,5,11-tetrazatetracyclo- [8.7.0.02,7.012,17]heptadeca-2,4,6,9,12(17),13,15-heptaene-9-carboxylate: Ethyl 4-(4-tert-butoxycarbonyl-1,4-diazepan-1-yl)-8-oxo-1,3,5,11-tetrazatetracyclo- [8.7.0. 02,7.012,17]heptadeca-2,4,6,9,12(17),13,15-heptaene-9-carboxylate (0.28 g, 552.7 μmol, 1 eq) was added to HCl / dioxane (2 N, 2.8 mL) and stirred at 25°C for 3 hrs. The reaction mixture was concentrated under reduced pressure to give the title compound (0.2 g, 492.1 μmol, 89.12% yield, 95% purity) as a white solid which was directly in the next step without purification. LCMS (ESI+): Rt: 0.313 min, m / z 407.3 (M+H)+. 4-(1,4-diazepan-1-yl)-8-oxo-1,3,5,11-tetrazatetracyclo[8.7.0.02,7.012,17]- heptadeca-2,4,6,9,12(17),13,15-heptaene-9-carboxylic acid: To a solution of ethyl 4-(1,4-diazepan-1-yl)-8-oxo-1,3,5,11-tetrazatetracyclo[8.7.0.02,7.012,17]- heptadeca-2,4,6,9,12(17),13,15-heptaene-9-carboxylate (0.2 g, 492.1 μmol, 1 eq) in a mixture of H2O (0.4 mL) and EtOH (1.6 mL) was added LiOH.H2O (123.9 mg, 2.9 mmol, 6 eq). The mixture was stirred at 50°C for 12 hrs. The mixture was added to dilute hydrochloric acid to adjust the pH to 5-6, and then filtered to yield the crude product. The residue was purified by prep-HPLC (TFA condition, column: Phenomenex Luna C18 100 * 30 mm * 5 µm; mobile phase: [H2O (0.1% TFA)-ACN]; gradient: 5%- 40% B over 8.0 min) to give the title compound (20.3 mg, 53.27 μmol, 10.83% yield, 99.29% purity, TFA salt) as a white. LCMS (ESI+): Rt: 1.380 min, m / z 379.2 (M+H)+.1H NMR (400 MHz, DMSO -d6+D2O) δ = 9.16 (d, J = 8.5 Hz, 1H), 8.63 - 8.48 (m, 1H), 7.81 - 7.72 (m, 1H), 7.58 - 7.41 (m, 2H), 4.25 - 4.12 (m, 2H), 4.05 (br t, J = 5.8 Hz, 1H), 4.00 (br t, J = 5.8 Hz, 1H), 3.54 - 3.46 (m, 1H), 3.38 - 3.31 (m, 1H), 3.30 - 3.20 (m, 2H), 2.22 (br s, 1H), 2.07 (br s, 1H). Synthetic Route 14 Example 52: 7-methyl-2-(4-methyl-1,4-diazepan-1-yl)-5-oxo-5,7- dihydrobenzo[4',5']imidazo [1',2':1,6] pyrido[2,3-d]pyrimidine-6-carboxylic acid Ethyl 2-chloro-7-methyl-5-oxo-5,7-dihydrobenzo [4',5']imidazo[1',2':1,6]- pyrido[2,3-d]pyrimidine-6-carboxylate: To a solution of ethyl 2-chloro-5-oxo-5,7- dihydrobenzo[4',5']imidazo[1',2':1,6]pyrido[2,3-d]pyrimidine-6-carboxylate (3.0 g, 8.77 mmol, 1 eq) in DMF (30 mL) was added DIEA (3.4 g, 26.31 mmol, 4.58 mL, 3 eq). The mixture was cooled to 0°C and methyl iodide (1.86 g, 13.16 mmol, 817.8 μL, 1.5 eq) was added. The mixture was stirred at 80°C for 12 h. The reaction was quenched by the addition of water (150 mL) and the mixture was stirred for 20 min. The resultant solid was collected by filtration dried to give the title compound (3.0 g, 8.43 mmol, 96.15% yield, 60% purity) as a yellow solid. The crude product was used in the next step directly without further purification. LCMS (ESI+): m / z 357.0 (M+H)+, Rt: 0.444 min. Ethyl 7-methyl-2-(4-methyl-1,4-diazepan-1-yl)-5-oxo-5,7-dihydrobenzo- [4',5']imidazo[1 ':1,6]pyrido[2,3-d]pyrimidine-6-carboxylate: To a solution of ethyl 2-chloro-7-methyl-5-oxo-5,7-dihydrobenzo[4',5']imidazo[1',2':1,6]pyrido[2,3- d]pyrimidine-6-carboxylate (3.4 g, 9.53 mmol, 1 eq) in ACN (35 mL) was added 1- methyl-1,4-diazepane (2.18 g, 19.06 mmol, 2.37 mL, 2 eq) and DIEA (3.70 g, 28.59 mmol, 4.98 mL, 3 eq). The mixture was stirred at 25°C for 12 h. The mixture was concentrated in vacuo and the residue was purified by prep-HPLC (column: Phenomenex luna C18 (250*70mm, 15 µm); mobile phase: [H2O (0.04%HCl)-ACN]; gradient: 20%-50% B over 18.0 min) to give the title compound (600 mg, 1.38 mmol, 14.49% yield) as a yellow solid. LCMS (ESI+): m / z 435.2 (M+H)+, Rt: 0.323 min.1H NMR (400 MHz, DMSO-d6) δ = 11.02 - 10.76 (m, 1H), 9.01 - 8.87 (m, 1H), 8.51 - 8.36 (m, 1H), 7.50 - 7.26 (m, 3H), 4.37 - 4.27 (m, 2H), 4.11 - 3.93 (m, 2H), 3.92 - 3.55 (m, 4H), 3.39 (s, 3H), 3.36 - 3.15 (m, 2H), 2.91 - 2.76 (m, 3H), 2.46 - 2.14 (m, 2H), 1.34 (dt, J = 3.1, 7.0 Hz, 3H). 7-methyl-2-(4-methyl-1,4-diazepan-1-yl)-5-oxo-5,7-dihydrobenzo[4',5']- imidazo[1',2':1,6]pyrido[2,3-d]pyrimidine-6-carboxylic acid: To a solution of ethyl 7-methyl-2-(4-methyl-1,4-diazepan-1-yl)-5-oxo-5,7-dihydrobenzo[4',5']- imidazo[1',2':1,6]pyrido[2, 3-d]pyrimidine-6-carboxylate (300 mg, 690.46 μmol, 1 eq) in THF (4 mL) and H2O (1 mL) was added LiOH.H2O (57.95 mg, 1.38 mmol, 2 eq). The mixture was stirred at 50°C for 2 hr. The mixture was adjusted to pH 7 with 1 M HCl before being filtered. The filter cake was collected and the crude product was purified by prep-HPLC (column: Waters Xbridge Prep OBD C18 150*40mm*10µm; mobile phase: [H2O (10mM NH4HCO3)-ACN]; gradient: 1%-30% B over 8.0 min) to give the title compound (120 mg, 295.25 μmol, 42.76% yield) as a yellow solid. LCMS (ESI+): m / z 407.3 (M+H)+, Rt: 1.367 min.1H NMR (400 MHz, DMSO-d6+D2O) δ = 9.14 (br s, 1H), 8.79 - 8.63 (m, 1H), 7.77 (br d, J = 5.9 Hz, 1H), 7.63 - 7.46 (m, 2H), 4.04 (br s, 1H), 3.96 (br s, 2H), 3.93 - 3.88 (m, 1H), 3.84 (s, 3H), 2.85 (br d, J = 4.3 Hz, 1H), 2.66 (br s, 1H), 2.59 - 2.53 (m, 2H), 2.27 (br d, J = 11.9 Hz, 3H), 2.11 - 2.01 (m, 1H), 1.90 (br d, J = 4.4 Hz, 1H). Synthetic Route 15 Example 53: 2-(5-methylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-5-oxo-5H- benzo[4,5]thiazolo[3,2-a][1,6]naphthyridine-6-carboxylic acid 4,6-Dichloropyridine-3-carbonyl chloride: 4,6-Dichloropyridine-3-carboxylic acid (10 g, 52.0 mmol, 1 eq) in SOCl2 (100 mL) was stirred at 65°C for 12 hrs. The mixture was concentrated under reduced pressure to give the title compound (10 g, 46.4 mmol, 89.4% yield, 98% purity) as a yellow solid which was used without further purification. LCMS (ESI+): m / z 206.0 (M-4)+, Rt: 1.313 min. Ethyl 2-chloro-5-oxo-[1,3]benzothiazolo[3,2-a][1,6]naphthyridine-6- carboxylate: To a solution of ethyl 2-(1,3-benzothiazol-2-yl)acetate (5 g, 22.6 mmol, 1 eq) and MgCl2 (3.23 g, 33.8 mmol, 1.39 mL, 1.5 eq) in ACN (50 mL) was added 4,6- dichloropyridine-3-carbonyl chloride (6.18 g, 29.3 mmol, 1.3 eq) and TEA (9.14 g, 90.2 mmol, 4 eq) slowly at -10°C. The mixture was stirred at 80 °C for 12 hrs. The mixture was concentrated under reduced pressure and the crude product was purified by trituration with water (50 mL) and then ACN (50 mL) at 25°C for 2 hrs to give the title compound (8 g, 19.8 mmol, 87.7% yield, 98% purity) as a light yellow solid. LCMS (ESI+): m / z 359.0 (M+H)+, Rt: 0.394 min.1H NMR (400 MHz, DMSO-d6) δ 9.30 - 9.16 (m, 1H), 8.59 - 8.43 (m, 2H), 8.14 (br d, J = 8.0 Hz, 1H), 7.72 - 7.48 (m, 2H), 4.35 (q, J = 7.1 Hz, 2H), 1.33 (br t, J = 7.1 Hz, 3H). Ethyl 2-(2-methyl-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl)-5-oxo- [1,3]benzothiazolo[3,2-a][1,6]naphthyridine-6-carboxylate: To a solution of ethyl 2-chloro-5-oxo-[1,3]benzothiazolo[3,2-a][1,6]naphthyridine-6-carboxylate (500 mg, 1.39 mmol, 1 eq) and 5-methyl-2,3,3a,4,6,6a-hexahydro-1H-pyrrolo[3,4-c]- pyrrole (193 mg, 1.53 mmol, 1.1 eq) in ACN (5 mL) was added DIEA (540 mg, 4.18 mmol, 728 μL, 3 eq). The mixture was stirred at 80°C for 2 hrs. The reaction mixture was concentrated under reduced pressure and the crude product was triturated with ACN (30 mL) at 25°C for 30 min to give the title (500 mg, 1.00 mmol, 71.9% yield, 90% purity) as a yellow solid. LCMS (ESI+): m / z 449.1 (M+H)+, Rt: 1.140 min.1H NMR (400 MHz, DMSO-d6) δ 8.94 (s, 1H), 8.42 (br d, J = 8.1 Hz, 1H), 8.08 (br d, J = 7.6 Hz, 1H), 7.70 - 7.45 (m, 2H), 7.05 (s, 1H), 4.30 (q, J = 6.9 Hz, 2H), 3.72 - 3.71 (m, 1H), 3.82 - 3.62 (m, 3H), 3.16 (br s, 4H), 3.01 (br s, 2H), 2.60 (br s, 3H), 1.31 (br t, J = 6.9 Hz, 3H). 2-(5-methylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-5-oxo-5H-benzo[4,5]- thiazolo[3,2-a][1,6]naphthyridine-6-carboxylic acid: To a solution of ethyl 2-(2- methyl-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl)-5-oxo-[1,3]benzothiazolo- [3,2-a][1,6]naphthyridine-6-carboxylate (200 mg, 445 μmol, 1 eq) in MeOH (1 mL) and THF (1 mL) was added LiOH.H2O (149 mg, 3.57 mmol, 8 eq). The mixture was stirred at 25°C for 2 hrs. The mixture was concentrated in vacuo and the residue was adjusted to pH=5 with 1N HCl before being filtered. The solids were collected and purified by prep-HPLC (HCl condition, Column: CD06-Waters Xbidge C18 150 * 40 * 10 µm; mobile phase: [water (0.05%HCl)-ACN]; gradient: 0%-27% B over 11 min) to give the title compound (20 mg, 45.4 μmol, 10.2% yield, 95.6% purity) as a yellow solid. LCMS (ESI+): m / z 421.1 (M+H)+, Rt: 2.091 min.1H NMR (400 MHz, DMSO-d6 + D2O) δ 9.11 (s, 1H), 8.59 - 8.48 (m, 1H), 8.17 (d, J = 7.6 Hz, 1H), 7.74 - 7.53 (m, 2H), 7.20 (br s, 1H), 3.95 - 3.75 (m, 4H), 3.62 - 3.61 (m, 1H), 3.66 - 3.58 (m, 1H), 3.45 - 3.45 (m, 1H), 3.45 - 3.45 (m, 1H), 3.57 - 3.16 (m, 2H), 3.15 - 2.94 (m, 1H), 2.85 (br s, 3H). Synthetic Route 16 Example 54: 2-(2-methyl-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl)- 5-oxo-7H-benzimidazolo[1,2-a][1,6]naphthyridine-6-carboxylic acid Ethyl 3-(4,6-dichloro-3-pyridyl)-2-(1,3-dihydrobenzimidazol-2-ylidene)-3- oxo-propanoate: To a mixture of ethyl 2-(1H-benzimidazol-2-yl)acetate (6 g, 29.38 mmol, 1 eq) and MgCl2 (4.20 g, 44.07 mmol, 1.81 mL, 1.5 eq) in THF (100 mL) was added 4,6-dichloropyridine-3-carbonyl chloride (7.11 g, 33.79 mmol, 1.15 eq) and TEA (5.95 g, 58.76 mmol, 8.18 mL, 2 eq) at -5°C under N2. The mixture was stirred at -5°C for 1.5 h. The mixture was concentrated in vacuo and the crude title compound (11 g, crude) was obtained as a yellow liquid. The product was used in the next step without further purification. LCMS (ESI+): m / z 377.8 (M+H)+, Rt: 0.481 min. Ethyl 2-chloro-5-oxo-7H-benzimidazolo[1,2-a][1,6]naphthyridine-6- carboxylate: To a solution of ethyl 3-(4,6-dichloro-3-pyridyl)-2-(1,3- dihydrobenzimidazol-2-ylidene)-3-oxo-propanoate (11 g, 29.08 mmol, 1 eq) in THF (100 mL) was added TEA (5.89 g, 58.17 mmol, 8.10 mL, 2 eq). The mixture was stirred at 80°C for 12h. The reaction mixture was concentrated under reduced pressure to remove solvent. The crude product was triturated with water at 25 °C for 15 min. The crude product was triturated with MeCN at 25°C for 15 min. The title compound (7.6 g, 22.24 mmol, 76.46% yield) was obtained as a yellow solid. LCMS (ESI+): m / z 342.5 (M+H)+, Rt: 0.431 min. 2-(2-methyl-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl)-5-oxo-7H- benzimidazolo[1,2-a][1,6]naphthyridine-6-carboxylic acid: To a solution of ethyl 2-chloro-5-oxo-7H-benzimidazolo[1,2-a][1,6]naphthyridine-6-carboxylate (1 g, 2.93 mmol, 1 eq) and 5-methyl-2,3,3a,4,6,6a-hexahydro-1H-pyrrolo[3,4-c]pyrrole (738.55 mg, 5.85 mmol, 2 eq) in DMF (5 mL) was added DIEA (756.36 mg, 5.85 mmol, 1.02 mL, 2 eq). The mixture was stirred at 110°C for 12 h. To the reaction mixture was added 50 mL water, then the mixture was filtered, and the filter cake was concentrated in vacuo. The residue was purified by prep-HPLC (TFA condition: column: Phenomenex luna C18 100*40mm*3 µm; mobile phase: [H2O (0.1%TFA)-ACN]; gradient: 0%-27% B over 15.0 min). The product was triturated with DMF at 25°C for 30 min to give the title compound (33.1 mg, 61.11 μmol, 19.53% yield, 95.53% purity, TFA salt) as a yellow solid. LCMS (ESI+): m / z 404.2 (M+H)+, Rt: 1.946 min.1H NMR (400 MHz, DMSO-d6) δ = 16.60 - 15.56 (m, 1H), 13.05 (br s, 1H), 10.74 - 10.05 (m, 1H), 9.06 (d, J = 3.0 Hz, 1H), 8.47 - 8.26 (m, 1H), 7.90 (d, J = 7.8 Hz, 1H), 7.69 - 7.37 (m, 2H), 7.16 - 6.93 (m, 1H), 3.96 - 3.83 (m, 3H), 3.82 - 3.57 (m, 4H), 3.24 (br d, J = 2.6 Hz, 2H), 3.08 - 2.93 (m, 1H), 2.86 (br dd, J = 4.4, 11.7 Hz, 1H). Route 17 Example 55: 5-Oxo-2-(pyridin-4-yl)-5H-benzo[4',5']thiazolo[3',2':1,6] pyrido[2,3-d]pyrimidine-6-carboxylic acid Ethyl 5-oxo-2-(pyridin-4-yl)-5H-benzo[4',5']thiazolo[3',2':1,6]pyrido[2,3-d]- pyrimidine-6-carboxylate: To a mixture of ethyl 2-chloro-5-oxo-5H-benzo[4',5']- thiazolo[3',2':1,6]pyrido[2,3-d]pyrimidine-6-carboxylate (0.5 g, 1.39 mmol, 1 eq) in dioxane (10 mL) and H2O (0.5 mL) was added 4-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)pyridine (427.46 mg, 2.08 mmol, 1.5 eq), Cs2CO3 (1.36 g, 4.17 mmol, 3 eq) and Pd(dppf)Cl2 (101.69 mg, 138.97 μmol, 0.1 eq) under N2 protection. The mixture was heated to 90°C and stirred for 2 h. The mixture was concentrated in vacuo. The crude product was purified by chromatography on a silica gel eluting with petroleum ether: ethyl acetate (from 1 / 1 to 0 / 1) to give the title compound (0.28 g, 695.78 μmol, 50.07% yield) as a yellow solid. LCMS (ESI+): m / z 403.2 (M+H)+, Rt: 0.384 min. 5-Oxo-2-(pyridin-4-yl)-5H-benzo[4',5']thiazolo[3',2':1,6]pyrido[2,3-d]- pyrimidine-6-carboxylic acid: To a mixture of ethyl 5-oxo-2-(pyridin-4-yl)-5H- benzo[4',5']thiazolo[3',2':1,6] pyrido[2,3-d]pyrimidine-6-carboxylate (0.1 g, 248.49 μmol, 1 eq) in THF (0.9 mL) and H2O (0.3 mL) was added LiOH.H2O (20.86 mg, 496.99 μmol, 2 eq). The mixture was heated to 50°C and stirred for 12 h. LCMS showed material was consumed, 37% of product was generated (Rt= 0.397, M+1= 375.1). The mixture was concentrated in vacuo. The crude product was purified by prep-HPLC (column: Phenomenex luna C18 100*40mm*5 µm; mobile phase: [H2O (0.1% TFA)-ACN]; gradient:15%-50% B over 8.0 min) to give the title compound (10 mg, 20.48 μmol, 8.24% yield, TFA salt) as yellow solid. LCMS (ESI+): Rt: 1.701 min, m / z 375.1 (M+H)+.1H NMR (400 MHz, DMSO-d6+D2O) δ = 9.97 (s, 1H), 9.73 (d, J = 8.6 Hz, 1H), 8.98 (d, J = 6.0 Hz, 2H), 8.51 (d, J = 6.0 Hz, 2H), 8.30 (d, J = 7.5 Hz, 1H), 7.92 (t, J = 7.4 Hz, 1H), 7.72 (t, J = 7.5 Hz, 1H). The following examples were synthesised according to the method outlined in Synthetic Route 17 using commercially available starting materials:

[0020] Synthetic Route 18 Example 60: 2-(4-((dimethylamino)methyl)phenyl)-5-oxo-5H-benzo[4',5']- thiazolo[3',2':1,6]pyrido[2,3-d]pyrimidine-6-carboxylic acid Ethyl 4-(4-formylphenyl)-8-oxo-11-thia-1,3,5-triazatetracyclo- [8.7.0.02,7.012,17]heptadeca-2,4,6,9,12(17),13,15-heptaene-9-carboxylate: To a solution of ethyl 4-chloro-8-oxo-11-thia-1,3,5-triazatetracyclo[8.7.0.02,7.012,17]- heptadeca-2,4,6,9,12(17),13,15-heptaene-9-carboxylate (1 g, 2.78 mmol, 1 eq) in ultradry dioxane (10 mL) was added (4-formylphenyl)boronic acid (500.09 mg, 3.34 mmol, 1.2 eq), K3PO4 (1.47 g, 6.95 mmol, 2.5 eq) and 1,3-bis[2,6-bis(1-ethylpropyl)- phenyl]-2H-imidazole;3-chloropyridine;dichloropalladium (Pd-PEPPSI-IPent) (220.60 mg, 277.94 μmol, 0.1 eq) under nitrogen. The mixture was stirred at 80 °C for 12 hrs. The reaction mixture was concentrated under reduced pressure and the crude product was triturated with EtOAc (10 mL) and water (10 mL) at 25oC for 30 min to give the title compound (600 mg, 1.06 mmol, 38.15% yield, 75.9% purity) as a faint yellow solid. LCMS (ESI+): m / z 430.0 (M+H)+, Rt: 2.243 min.1H NMR (400 MHz, TFA-d) δ 10.70 (s, 1H), 10.56 - 10.43 (m, 2H), 9.22 (d, J = 8.3 Hz, 2H), 8.70 (d, J = 8.4 Hz, 2H), 8.59 (d, J = 8.0 Hz, 1H), 8.43 (t, J = 8.1 Hz, 1H), 8.36 - 8.27 (m, 1H), 5.26 (q, J = 7.1 Hz, 2H), 2.05 (t, J = 7.1 Hz, 3H). Ethyl 4-[4-[(dimethylamino)methyl]phenyl]-8-oxo-11-thia-1,3,5- triazatetracyclo[8.7.0.02,7.012,17]heptadeca-2,4,6,9,12(17),13,15-heptaene-9- carboxylate: To a solution of ethyl 4-(4-formylphenyl)-8-oxo-11-thia-1,3,5- triazatetracyclo[8.7.0.02,7.012,17]heptadeca-2,4,6,9,12(17),13,15-heptaene-9- carboxylate (400 mg, 931.43 μmol, 1 eq) in DCM (4 mL) was added NaBH(OAc)3 (592.22 mg, 2.79 mmol, 3 eq) and N-methylmethanamine (113.93 mg, 1.40 mmol, 128.01 μL, 1.5 eq, HCl salt). The mixture was stirred at 25 °C for 12 hrs. The reaction mixture was quenched by the addition of saturated NaHCO3 to pH = 7-8, and then extracted with DCM (3 x 5 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure to give the title compound (250 mg, 488.03 μmol, 52.40% yield, 89.51% purity) as an orange solid which was used in the next step without purification. LCMS (ESI+): m / z 459.1 (M+H)+, Rt: 0.077 min.1H NMR (400 MHz, TFA-d) δ 10.59 (s, 1H), 10.38 (d, J = 8.8 Hz, 1H), 9.06 (d, J = 8.3 Hz, 2H), 8.49 (d, J = 7.9 Hz, 1H), 8.39 - 8.31 (m, 1H), 8.25 - 8.19 (m, 1H), 8.13 (d, J = 8.3 Hz, 2H), 5.17 (q, J = 7.2 Hz, 2H), 4.82 (s, 2H), 3.45 - 3.31 (m, 6H), 1.97 (t, J = 7.2 Hz, 3H). 2-(4-((dimethylamino)methyl)phenyl)-5-oxo-5H-benzo[4',5']thiazolo- [3',2':1,6]pyrido[2,3-d]pyrimidine-6-carboxylic acid: To a solution of ethyl 2-(4- ((dimethylamino)methyl)phenyl)-5-oxo-5H-benzo[4',5']thiazolo[3',2':1,6]pyrido[2,3- d]pyrimidine-6-carboxylate (0.10 g, 218 μmol, 1 eq) in a mixture of THF (1.00 mL) and MeOH (1.00 mL) was added LiOH (2 M, 1.00 mL). The mixture was stirred at 25 °C for 2 hrs. The reaction mixture was concentrated under reduced pressure and water (3.00 mL) was added and adjusted pH to 5 – 6 with 1 N HCl. The crude product was triturated with DMF (2.00 mL) at 25oC for 2 hrs and filtered to give the title compound (16.2 mg, 34.9 μmol, 15.91% yield, 96.8% purity, HCl salt) as a yellow solid. LCMS (ESI+): m / z 431.1 (M+H)+, Rt: 2.767 min.1H NMR (400 MHz, DMSO-d6 + D2O) δ = 9.85 (s, 1H), 9.70 (d, J = 8.5 Hz, 1H), 8.65 (d, J = 8.1 Hz, 2H), 8.23 (d, J = 8.1 Hz, 1H), 7.90 - 7.79 (m, 3H), 7.69 (t, J = 7.5 Hz, 1H), 4.43 (s, 2H), 2.81 (s, 6H). Synthetic Route 19 Example 61: 9-Bromo-2-(5-methylhexahydropyrrolo[3,4- c]pyrrol-2(1H)-yl)- 5 oxo-5H-benzo[4',5']thiazolo[3',2':1,6]pyrido[2,3-d]pyrimidine-6-carboxylic acid Ethyl 9-bromo-2-chloro-5-oxo-5H-benzo[4',5']thiazolo[3',2':1,6]pyrido[2,3- d]pyrimidine-6-carboxylate: To a mixture of ethyl 2-(6-bromobenzo[d]thiazol-2- yl)acetate (6 g, 19.99 mmol, 1 eq) in THF (60 mL) was added MgCl2 (2.85 g, 29.98 mmol, 1.23 mL, 1.5 eq), 2,4-dichloropyrimidine-5-carbonyl chloride (5.07 g, 23.99 mmol, 1.2 eq) and DIEA (15.50 g, 119.93 mmol, 20.89 mL, 6 eq) at -20°C. The mixture was warmed to 25°C and stirred for 2 h. The mixture was concentrated in vacuo and the crude product was triturated with MeCN (50 mL) for 30 min. After filtration, the filter cake was collected to give the title compound (5 g, 11.40 mmol, 57.02% yield) as a yellow solid. LCMS (ESI+): Rt: 0.600 min, m / z 440.0 (M+H)+. Ethyl 9-bromo-2-(5-methylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-5-oxo- 5H-benzo[4',5'] thiazolo[3',2':1,6]pyrido[2,3-d]pyrimidine-6-carboxylate: To a mixture of ethyl 9-bromo-2-chloro-5-oxo-5H-benzo[4',5']thiazolo[3',2':1,6]pyrido- [2,3-d]pyrimidine-6-carboxylate (5 g, 11.40 mmol, 1 eq) in MeCN (50 mL) was added DIEA (2.95 g, 22.80 mmol, 3.97 mL, 2 eq) and 5-methyl-2,3,3a,4,6,6a-hexahydro- 1H-pyrrolo[3,4-c]pyrrole (1.73 g, 13.68 mmol, 1.2 eq). The mixture was stirred at 25°C for 2 h. The mixture was concentrated in vacuo and the crude product was triturated with MeCN (50 mL) for 30 min. After filtration, the filter cake was collected to give the title compound (5 g, 9.46 mmol, 83.02% yield) as a yellow solid. LCMS (ESI+): Rt: 0.433 min, m / z 528.0 (M+H)+. 9-Bromo-2-(5-methylhexahydropyrrolo[3,4- c]pyrrol-2(1H)-yl)-5 oxo-5H- benzo[4',5']thiazolo[3',2':1,6]pyrido[2,3-d]pyrimidine-6-carboxylic acid: To a mixture of ethyl 9-bromo-2-(5-methylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-5-oxo- 5H-benzo[4',5']thiazolo[3',2':1,6] pyrido[2,3-d]pyrimidine-6-carboxylate (5 g, 9.46 mmol, 1 eq) in THF (25 mL), MeOH (25 mL) and H2O (5 mL) was added LiOH.H2O (1.19 g, 28.39 mmol, 3 eq). The mixture was heated to 50°C and stirred for 12 h. The mixture was adjusted to pH 3 with 4 M HCl and the resulting solid collected by filtration and purified by prep-HPLC (column: Phenomenex luna c18 250mm*100mm*15µm; mobile phase: [H2O(0.1%TFA)-ACN];gradient:20%-50% B over 20.0 min) to give the title compound (1 g, 2.00 mmol, 21.12% yield) as a yellow solid. LCMS (ESI+): Rt: 0.410 min, m / z 500.1 (M+H)+. Synthetic Route 20 Example 62: 4-(8-tert-butoxycarbonyl-2,8-diazaspiro[4.5]decan-2-yl)-8-oxo- 1,3,5,11-tetrazatetracyclo[8.7.0.02,7.012,17]heptadeca-2,4,6,9,12(17),13,15- heptaene-9-carboxylic acid Ethyl 4-(8-tert-butoxycarbonyl-2,8-diazaspiro[4.5]decan-2-yl)-8-oxo- 1,3,5,11-tetrazatetracyclo[8.7.0.02,7.012,17]heptadeca-2,4,6,9,12(17),13,15- heptaene-9-carboxylate: To a solution of ethyl 4-chloro-8-oxo-1,3,5,11- tetrazatetracyclo[8.7.0.02,7.012,17]heptadeca-2,4,6,9,12(17),13,15-heptaene-9- carboxylate (1 g, 2.92 mmol, 1 eq) and tert-butyl 2,8-diazaspiro[4.5]decane-8- carboxylate (701.24 mg, 2.92 mmol, 1 eq) in ACN (25 mL) was added DIEA (754.18 mg, 5.84 mmol, 1.02 mL, 2 eq), the mixture was stirred at 0°C for 2 h. The reaction mixture was poured into water (30 mL) extracted with dichloromethane (2 x 30 mL), dried over anhydrous sodium sulfate and concentrated under reduce pressure to give the title compound (1.5 g, crude) as a yellow solid. LCMS (ESI+): Rt: 0.505 min, m / z 547.3 (M+H)+. 4-(8-tert-butoxycarbonyl-2,8-diazaspiro[4.5]decan-2-yl)-8-oxo-1,3,5,11- tetrazatetracyclo [8.7.0.02,7.012,17]heptadeca-2,4,6,9,12(17),13,15-heptaene- 9-carboxylic acid: To a solution of ethyl 4-(8-tert-butoxycarbonyl-2,8- diazaspiro[4.5]decan-2-yl)-8-oxo-1,3,5,11-tetrazatetracyclo[8.7.0.02,7.012,17]- heptadeca-2,4,6,9,12(17),13,15-heptaene-9-carboxylate (200 mg, 365.89 μmol, 1 eq) in MeOH (1.5 mL) and THF (1.5 mL) was added LiOH.H2O (2 M, 1.83 mL, 10 eq), the mixture was stirred at 40°C for 12 h. The reaction mixture was concentrated under reduced pressure to give the title compound (160 mg, crude) as a yellow solid. LCMS (ESI+): Rt: 2.785 min, m / z 519.3 (M+H)+. Example 63: 4-(2,8-Diazaspiro[4.5]decan-2-yl)-8-oxo-1,3,5,11- tetrazatetracyclo[8.7.0.02,7.012,17]heptadeca-2,4,6,9,12(17),13,15-heptaene- 9-carboxylic acid To a solution of 4-(8-tert-butoxycarbonyl-2,8-diazaspiro[4.5]decan-2-yl)-8-oxo- 1,3,5,11-tetrazatetracyclo [8.7.0.02,7.012,17]heptadeca-2,4,6,9,12(17),13,15- heptaene-9-carboxylic acid (150 mg, 289.26 μmol, 1 eq) in DCM (2 mL) was added HCl / dioxane (2 M, 2.11 mL, 14.58 eq), the mixture was stirred at 25°C for 0.5 h. The reaction mixture was concentrated under reduced pressure to remove solvent. The crude product was purified by prep-HPLC (column: CD01-Phenomenex luna C18 150*25mm* 10µm; mobile phase: [H2O (0.1%TFA)-ACN]; gradient: 16%-46% B over 11.0 min) to give a eluent and the eluent was concentrated under reduced pressure to remove MeCN then lyophilized to give the title compound (63.5 mg, 119.26 μmol, 41.23% yield, TFA salt) as a white solid. LCMS (ESI+): Rt: 2.159 min, m / z 419.1 (M+H)+.1H NMR (400 MHz, DMSO-d6+D2O) δ = 9.17 - 9.09 (m, 1H), 8.76 - 8.67 (m, 1H), 7.78 (d, J = 8.4 Hz, 1H), 7.57 - 7.41 (m, 2H), 3.88 - 3.76 (m, 4H), 3.14 (s, 4H), 2.10 - 2.01 (m, 2H), 1.87 - 1.75 (m, 4H). Synthetic Route 21 Example 64: 4-(3,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazin-2-yl)-8- oxo-1,3,5,11-tetrazatetracyclo[8.7.0.02,7.012,17]heptadeca- 2,4,6,9,12(17),13,15-heptaene-9-carboxylic acid Ethyl 4-(3,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazin-2-yl)-8-oxo- 1,3,5,11-tetrazatetracyclo[8.7.0.02,7.012,17]heptadeca-2,4,6,9,12(17),13,15- heptaene-9-carboxylate: To a solution of ethyl 4-chloro-8-oxo-1,3,5,11- tetrazatetracyclo[8.7.0.02,7.012,17]heptadeca-2,4,6,9,12(17),13,15-heptaene-9- carboxylate (500 mg, 1.46 mmol, 1 eq) and 1,2,3,4,6,7,8,8a-octahydropyrrolo[1,2-a]- pyrazine (184.11 mg, 1.46 mmol, 1 eq) in ACN (10 mL) was added DIEA (377.09 mg, 2.92 mmol, 508.21 μL, 2 eq), the mixture was stirred at 0°C for 2 h. The reaction mixture was poured into water (20 mL) extracted with dichloromethane (3 x 20 mL), dried over anhydrous sodium sulfate, then concentrated under reduced pressure to give the title compound (500 mg, crude) as a yellow solid. LCMS (ESI+): Rt: 0.306 min, m / z 433.1 (M+H)+. 4-(3,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazin-2-yl)-8-oxo-1,3,5,11- tetrazatetracyclo[8.7.0.02,7.012,17]heptadeca-2,4,6,9,12(17),13,15-heptaene- 9-carboxylic acid: To a solution of ethyl 4-(3,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2- a]pyrazin-2-yl)-8-oxo-1,3,5,11-tetrazatetracyclo[8.7.0.02,7.012,17]heptadeca- 2,4,6,9,12(17),13,15-heptaene-9-carboxylate (150 mg, 346.84 μmol, 1 eq) in MeOH (1.5 mL) and THF (1.5 mL) was added LiOH.H2O (2 M, 1.73 mL, 10 eq), and the mixture was stirred at 40°C for 12 h. The reaction mixture was concentrated under reduced pressure and the crude product was purified by prep-HPLC (column: CD01- Phenomenex luna C18 150*25mm* 10µm; mobile phase: [H2O (0.1%TFA)-ACN]; gradient: 16%-46% B over 11.0 min) to give an eluent and the eluent was concentrated under reduced pressure to remove MeCN, then lyophilized to give the title compound (119.6 mg, 230.69 μmol, 66.51% yield, TFA salt) as a white solid. LCMS (ESI+): Rt: 1.896 min, m / z 405.1 (M+H)+.1H NMR (400 MHz, DMSO-d6+D2O) δ = 9.23 (s, 1H), 8.65 (s, 1H), 7.79 (d, J = 7.4 Hz, 1H), 7.58 - 7.45 (m, 2H), 5.46 - 4.89 (m, 1H), 4.52 - 3.85 (m, 4H), 3.55 - 2.99 (m, 4H), 2.23 - 1.76 (m, 4H). Synthetic Route 22 Example 65: 4-[5-(cyclopropanecarbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo- [3,4-c]pyrrol-2-yl]-8-oxo-11-thia-1,3,5-triazatetracyclo[8.7.0.02,7.012,17]- heptadeca-2,4,6,9,12(17),13,15-heptaene-9-carboxylic acid Ethyl 4-(5-tert-butoxycarbonyl-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol- 2-yl)-8-oxo-11-thia-1,3,5-triazatetracyclo[8.7.0.02,7.012,17]heptadeca- 2,4,6,9,12(17),13,15-heptaene-9-carboxylate: To a solution of ethyl 4-chloro-8- oxo-11-thia-1,3,5-triazatetracyclo [8.7.0.02,7.012,17]heptadeca-2,4,6,9,12(17),13,15- heptaene-9-carboxylate (1 g, 2.78 mmol, 1 eq) and tert-butyl 2,3,3a,4,6,6a- hexahydro-1H-pyrrolo[3,4-c]pyrrole-5-carboxylate (590.04 mg, 2.78 mmol, 1 eq) in ACN (20 mL) was added DIEA (718.44 mg, 5.56 mmol, 968.25 μL, 2 eq) and the mixture was stirred at 80°C for 12 h. The reaction mixture was filtered and the filter cake was concentrated under reduced pressure to give the title compound (1.1 g, crude) as a yellow solid. LCMS (ESI+): Rt: 0.532 min, m / z 536.6 (M+H)+. Ethyl 4-(2,3,3a,4,6,6a-hexahydro-1H-pyrrolo[3,4-c]pyrrol-5-yl)-8-oxo-11- thia-1,3,5-triazatetracyclo[8.7.0.02,7.012,17]heptadeca-2,4,6,9,12(17), 13,15- heptaene-9-carboxylate: To a solution of ethyl 4-(5-tert-butoxycarbonyl- 1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-2-yl)-8-oxo-11-thia-1,3,5- triazatetracyclo[8.7.0.02,7.012,17]heptadeca-2,4,6,9,12(17),13,15-heptaene-9- carboxylate (1 g, 1.87 mmol, 1 eq) in DCM (10 mL) was added HCl / dioxane (2 M, 10 mL), the mixture was stirred at 25°C for 2 h. The reaction mixture was concentrated under reduced pressure to give the title compound (1 g, crude) as a yellow solid. LCMS (ESI+): Rt: 0.389 min, m / z 436.2 (M+H)+. Ethyl 4-[5-(cyclopropanecarbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]- pyrrol-2-yl]-8-oxo-11-thia-1,3,5-triazatetracyclo[8.7.0.02,7.012,17]heptadeca- 2,4,6,9,12(17),13,15-heptaene-9-carboxylate: To a solution of ethyl 4- (2,3,3a,4,6,6a-hexahydro-1H-pyrrolo[3,4-c]pyrrol-5-yl)-8-oxo-11-thia-1,3,5- triazatetracyclo[8.7.0.02,7.012,17]heptadeca-2,4,6,9,12(17),13,15-heptaene-9- carboxylate (1 g, 2.30 mmol, 1 eq) and cyclopropanecarboxylic acid (296.52 mg, 3.44 mmol, 272.54 μL, 1.5 eq) in DMF (20 mL) was added DIEA (1.48 g, 11.48 mmol, 2.00 mL, 5 eq) and HATU (1.31 g, 3.44 mmol, 1.5 eq) and the mixture was stirred at 25°C for 12 h. The reaction mixture was filtered and the filter cake was concentrated under reduced pressure to give the title compound (850 mg, crude) as a grey solid. LCMS (ESI+): Rt: 0.466 min, m / z 504.4 (M+H)+. 4-[5-(cyclopropanecarbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-2- yl]-8-oxo-11-thia-1,3,5-triazatetracyclo[8.7.0.02,7.012,17]heptadeca- 2,4,6,9,12(17),13,15-heptaene-9-carboxylic acid: To a solution of ethyl 4-[5- (cyclopropanecarbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-2-yl]-8-oxo-11- thia-1,3,5-triazatetracyclo[8.7.0.02,7.012,17]heptadeca-2,4,6,9,12(17),13,15-heptaene- 9-carboxylate (400 mg, 794.33 μmol, 1 eq) in THF (4 mL) and MeOH (4 mL) was added LiOH.H2O (2 M, 3.97 mL, 10 eq) and the mixture was stirred at 25°C for 3 h. The reaction mixture was concentrated under reduced pressure and the crude product was purified by prep-HPLC (column: CD24-WePure Biotech XPT C18 150*25*7µm; mobile phase: [H2O (0.1%TFA)-ACN]; gradient: 10%-80% B over 12.0 min) to give an eluent and the eluent was concentrated under reduced pressure to remove MeCN then lyophilized to give the title compound (20 mg, 33.00 μmol, 4.15% yield, 97.26% purity, TFA salt) as a white solid. LCMS (ESI+): Rt: 3.902 min, m / z 476.1 (M+H)+.1H NMR (400 MHz, DMSO-d6+D2O) δ = 9.40 (s, 1H), 9.24 (s, 1H), 8.07 (s, 1H), 7.77 - 7.48 (m, 2H), 4.02 - 3.94 (m, 6H), 3.69 - 3.63 (m, 4H), 1.73 (s, 1H), 0.77 - 0.71 (m, 4H). Synthetic Route 23 Example 66: 4-(2-methyl-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-5- yl)-8-oxo-11-thia-1,3,5-triazatetracyclo[8.7.0.02,7.012,17]heptadeca- 2,4,6,9,12(17),13,15-heptaene-9-carboxylic acid tert-Butyl 5-(trifluoromethylsulfonyloxy)-3,3a,6,6a-tetrahydro-1H- cyclopenta[c]pyrrole-2-carboxylate: To a solution of tert-butyl 5-oxo- 1,3,3a,4,6,6a-hexahydrocyclopenta[c]pyrrole-2-carboxylate (4.5 g, 19.97 mmol, 1 eq) in THF (100 mL) was added LiHMDS (1 M, 25.97 mL, 1.3 eq) at -78°C under N2, and the mixture was stirred at -78°C for 0.5 h, then a solution of 1,1,1-trifluoro-N-phenyl- N-(trifluoromethylsulfonyl)methanesulfonamide (10.00 g, 27.98 mmol, 1.4 eq) in THF (20 mL) was slowly added and stirred at -78°C for 1 h, the mixture was stirred at 25°C for 2 h. The reaction mixture was quenched by the addition of saturated NH4Cl solution 30 mL at 0°C. The reaction mixture was concentrated under reduced pressure and the residue was purified by silica gel chromatography (Petroleum ether / Ethyl acetate=100 / 1 to 1:1) to give the title compound (5 g, 13.99 mmol, 70.05% yield) as a yellow oil. LCMS (ESI+): Rt: 0.528 min, m / z 302.0 (M-56).1H NMR (400 MHz, CHLOROFORM-d) δ = 5.58 (s, 1H), 3.71 (t, J = 9.4 Hz, 1H), 3.58 - 3.49 (m, 1H), 3.45 - 3.34 (m, 2H), 3.16 (s, 1H), 2.99 - 2.84 (m, 2H), 2.40 (d, J = 15.4 Hz, 1H), 1.46 (s, 9H). tert-Butyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,3a,6,6a- tetrahydro-1H-cyclopenta[c]pyrrole-2-carboxylate: To a solution of tert-butyl 5- (trifluoromethylsulfonyloxy)-3,3a,6,6a-tetrahydro-1H-cyclopenta[c]pyrrole-2- carboxylate (5 g, 13.99 mmol, 1 eq) and bis(pinacolato)diboron (BPD) (4.26 g, 16.79 mmol, 1.2 eq) in dioxane (100 mL) was added KOAc (4.12 g, 41.98 mmol, 3 eq), Pd(dppf)Cl2 (307.14 mg, 419.76 μmol, 0.03 eq) and dppf (232.71 mg, 419.76 μmol, 0.03 eq). The suspension was degassed and purged with N2 for 3 times and the reaction was stirred at 80°C for 12 h. The reaction mixture was concentrated under reduced pressure and the residue was purified by silica gel chromatography (Petroleum ether / Ethyl acetate=100 / 1 to 10:1) to give the title compound (4.4 g, 13.12 mmol, 93.80% yield) as a yellow oil. LCMS (ESI+): Rt: 0.530 min, m / z 280.2 (M-56).1H NMR (400 MHz, CHLOROFORM-d) δ = 6.33 (s, 1H), 3.61 (t, J = 9.6 Hz, 1H), 3.54 - 3.42 (m, 2H), 3.38 (tdd, J = 2.5, 5.1, 7.5 Hz, 1H), 2.98 - 2.84 (m, 2H), 2.67 - 2.59 (m, 1H), 2.37 (d, J = 16.5 Hz, 1H), 1.44 (s, 9H), 1.28 (s, 12H). Ethyl 4-(2-tert-butoxycarbonyl-3,3a,6,6a-tetrahydro-1H-cyclopenta[c]pyrrol- 5-yl)-8-oxo-11-thia-1,3,5-triazatetracyclo[8.7.0.02,7.012,17]heptadeca- 2,4,6,9,12(17),13,15-heptaene-9-carboxylate: To a solution of tert-butyl 5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,3a,6,6a-tetrahydro-1H-cyclopenta- [c]pyrrole-2-carboxylate (4.3 g, 12.83 mmol, 1 eq) and ethyl 4-chloro-8-oxo-11-thia- 1,3,5-triazatetracyclo[8.7.0.02,7.012,17]heptadeca-2,4,6,9,12(17), 13,15-heptaene-9- carboxylate (4.61 g, 12.83 mmol, 1 eq) in dioxane (100 mL) and H2O (10 mL) was added Pd(dppf)Cl2 (938.52 mg, 1.28 mmol, 0.1 eq) and Cs2CO3 (12.54 g, 38.48 mmol, 3 eq), and the mixture was stirred at 90°C for 12 h. The reaction mixture was poured into water (100 mL), extracted with dichloromethane (3 x 60 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (Dichloromethane: Methanol=100 / 1 to 3:1) to give the title compound (3.2 g, 6.01 mmol, 46.84% yield) as a yellow solid. LCMS (ESI+): Rt: 0.559 min, m / z 533.1 (M+H).1H NMR (400 MHz, CHLOROFORM-d) δ = 9.77 (s, 1H), 9.60 (d, J = 8.6 Hz, 1H), 7.79 (d, J = 7.8 Hz, 1H), 7.67 - 7.60 (m, 1H), 7.56 - 7.50 (m, 1H), 7.21 (s, 1H), 4.53 (q, J = 7.1 Hz, 2H), 3.68 (dd, J = 1.8, 13.8 Hz, 4H), 3.37 - 3.13 (m, 3H), 3.00 (d, J = 15.1 Hz, 1H), 1.51 (t, J = 7.1 Hz, 3H), 1.45 (s, 9H). Ethyl 4-(2-tert-butoxycarbonyl-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]- pyrrol-5-yl)-8-oxo-11-thia-1,3,5-triazatetracyclo[8.7.0.02,7.012,17]heptadeca- 2,4,6,9,12(17),13,15-heptaene-9-carboxylate: To a solution of ethyl 4-(2-tert- butoxycarbonyl-3,3a,6,6a-tetrahydro-1H-cyclopenta[c]pyrrol-5-yl)-8-oxo-11-thia- 1,3,5-triazatetracyclo[8.7.0.02,7.012,17]heptadeca-2,4,6,9,12(17),13,15-heptaene-9- carboxylate (1.7 g, 3.19 mmol, 1 eq) in DMF (30 mL) and MeOH (15 mL) was added Pd / C (6.79 g, 6.38 mmol, 10% purity, 2 eq). The suspension was degassed and purged with H2 for 3 times and the reaction was stirred at 25°C for 3 h under H2. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography (Dichloromethane: Methanol=100 / 1 to 10:1) to give the title compound (1.1 g, 2.06 mmol, 64.46% yield) as a yellow solid. LCMS (ESI+): Rt: 0.542 min, m / z 535.2 (M+H)+.1H NMR (400 MHz, CHLOROFORM-d) δ = 9.75 (s, 1H), 9.65 (d, J = 8.6 Hz, 1H), 7.78 (d, J = 7.8 Hz, 1H), 7.65 (t, J = 7.9 Hz, 1H), 7.56 - 7.45 (m, 1H), 4.53 (q, J = 7.1 Hz, 2H), 3.82 - 3.72 (m, 1H), 3.59 (d, J = 2.9 Hz, 2H), 3.45 (dd, J = 4.4, 9.8 Hz, 2H), 2.89 (s, 2H), 2.63 - 2.53 (m, 2H), 2.06 (s, 2H), 1.53 - 1.49 (m, 3H), 1.47 (s, 9H). Ethyl 4-(1,2,3,3a,4,5,6,6a-octahydrocyclopenta[c]pyrrol-5-yl)-8-oxo-11-thia- 1,3,5-triazatetracyclo[8.7.0.02,7.012,17]heptadeca-2,4,6,9,12(17),13,15- heptaene-9-carboxylate: To a solution of ethyl 4-(2-tert-butoxycarbonyl- 3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-5-yl)-8-oxo-11-thia-1,3,5- triazatetracyclo[8.7.0.02,7.012,17]heptadeca-2,4,6,9,12(17),13,15-heptaene-9- carboxylate (1.8 g, 3.37 mmol, 1 eq) in DCM (20 mL) was added HCl / dioxane (2 M, 10 mL) and the mixture was stirred at 25°C for 12 h. The reaction mixture was concentrated under reduced pressure to give the title compound (1.6 g, crude, HCl salt) as a yellow solid. LCMS (ESI+): Rt: 0.346 min, m / z 435.1 (M+H)+. Ethyl 4-(2-methyl-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-5-yl)-8- oxo-11-thia-1,3,5-triazatetracyclo[8.7.0.02,7.012,17]heptadeca- 2,4,6,9,12(17),13,15-heptaene-9-carboxylate: To a solution of ethyl 4- (1,2,3,3a,4,5,6,6a-octahydrocyclopenta[c]pyrrol-5-yl)-8-oxo-11-thia-1,3,5- triazatetracyclo[8.7.0.02,7.012,17]heptadeca-2,4,6,9,12(17),13,15-heptaene-9- carboxylate (800 mg, 1.84 mmol, 1 eq, HCl) in DCM (20 mL) was added N- methylmorpholine (NMM) (558.68 mg, 5.52 mmol, 607.26 μL, 3 eq) and the reaction stirred at 25°C for 0.2 h, then (HCHO)n (200 mg) and HOAc (331.69 mg, 5.52 mmol, 316.20 μL, 3 eq) was added and the mixture stirred at 25°C for 1 h. NaBH(OAc)3 (585.32 mg, 2.76 mmol, 1.5 eq) was added and the mixture was stirred at 25°C for 24 h. The reaction mixture was filtered and the filtrate was concentrated under reduce pressure to give the title compound (800 mg, crude) as a yellow oil. LCMS (ESI+): Rt: 0.351 min, m / z 449.1 (M+H)+. 4-(2-methyl-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-5-yl)-8-oxo- 11-thia-1,3,5-triazatetracyclo[8.7.0.02,7.012,17]heptadeca- 2,4,6,9,12(17),13,15-heptaene-9-carboxylic acid: To a solution of ethyl 4-(2- methyl-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-5-yl)-8-oxo-11-thia-1,3,5- triazatetracyclo[8.7.0.02,7.012,17]heptadeca-2,4,6,9,12(17),13,15-heptaene-9- carboxylate (800 mg, 1.78 mmol, 1 eq) in MeOH (8 mL) and THF (8 mL) was added LiOH.H2O (2 M, 8.92 mL, 10 eq) and the mixture was stirred at 25°C for 12 h. The reaction mixture was concentrated under reduced pressure and the crude product was purified by prep-HPLC (column: CD24-WePure Biotech XPT C18 150*25*7µm; mobile phase: [H2O (0.1%TFA)-ACN]; gradient: 10%-40% B over 12.0 min) to give an eluent and the eluent was concentrated under reduced pressure to give the title compound (80.6 mg, 149.59 μmol, 8.39% yield, 99.2% purity, TFA salt) as a white solid. LCMS (ESI+): Rt: 2.600 min, 2.634 min, m / z 421.1 (M+H)+.1H NMR (400 MHz, DMSO- d6+D2O) δ = 9.74 - 9.68 (m, 1H), 9.67 - 9.60 (m, 1H), 8.18 (d, J = 7.9 Hz, 1H), 7.77 (t, J = 7.8 Hz, 1H), 7.69 - 7.61 (m, 1H), 4.09 - 3.92 (m, 1H), 3.74 - 3.60 (m, 1H), 3.56 - 3.41 (m, 1H), 3.36 - 3.11 (m, 2H), 3.05 (s, 1H), 2.93 - 2.79 (m, 4H), 2.65 - 2.56 (m, 1H), 2.23 - 2.14 (m, 2H), 2.08 - 1.83 (m, 1H). Example 67: 4-(1,2,3,3a,4,5,6,6a-octahydrocyclopenta[c]pyrrol-5-yl)-8-oxo- 11-thia-1,3,5-triazatetracyclo[8.7.0.02,7.012,17]heptadeca- 2,4,6,9,12(17),13,15-heptaene-9-carboxylic acid To a solution of ethyl 4-(1,2,3,3a,4,5,6,6a-octahydrocyclopenta[c]pyrrol-5-yl)-8-oxo- 11-thia-1,3,5-triazatetracyclo[8.7.0.02,7.012,17]heptadeca-2,4,6,9,12(17),13,15- heptaene-9-carboxylate (200 mg, 460.29 μmol, 1 eq) in THF (2 mL) and MeOH (2 mL) was added LiOH.H2O (2 M, 2.30 mL, 10 eq) and the mixture was stirred at 25°C for 12 h. The reaction mixture was concentrated under reduced pressure and the crude product was purified by prep-HPLC (column: CD24-WePure Biotech XPT C18 150*25*7µm; mobile phase: [H2O (0.1%TFA)-ACN]; gradient: 10%-40% B over 12.0 min) to give an eluent and the eluent was concentrated under reduce pressure to give the title compound (41.7 mg, 80.12 μmol, 17.41% yield, 100% purity, TFA salt) as a yellow solid. LCMS (ESI+): Rt: 2.577 min, 2.630 min, m / z 407.0 (M+H)+.1H NMR (400 MHz, DMSO-d6+D2O) δ = 9.72 - 9.59 (m, 2H), 8.24 - 8.08 (m, 1H), 7.82 - 7.71 (m, 1H), 7.69 - 7.60 (m, 1H), 3.81 - 3.70 (m, 1H), 3.54 - 3.48 (m, 1H), 3.31 - 3.15 (m, 2H), 3.08 - 2.97 (m, 3H), 2.60 (br s, 1H), 2.32 - 2.23 (m, 1H), 2.22 - 2.15 (m, 1H), 1.94 - 1.83 (m, 1H). Route 24 Example 68: 2-(5-(cyclopropylmethyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)- yl)-5-oxo-5,7-dihydrobenzo [4',5']imidazo[1',2':1,6]pyrido[2,3-d]pyrimidine- 6-carboxylic acid Ethyl 2-(hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-5-oxo-5,7-dihydrobenzo- [4',5']imidazo [1',2':1,6]pyrido[2,3-d]pyrimidine-6-carboxylate: A mixture of ethyl 2-(5-(tert-butoxycarbonyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-5-oxo-5,7- dihydrobenzo[4',5']imidazo[1',2':1,6]pyrido[2,3-d]pyrimidine-6-carboxylate (0.5 g, 964.20 μmol, 1 eq) in HCl / dioxane (5 mL) was stirred at 25°C for 2 h. The reaction mixture was concentrated to give the title compound (0.4 g, 955.91 μmol, 99.14% yield) as a yellow solid. LCMS (ESI+): Rt: 0.344 min, m / z 419.2 (M+H)+. Ethyl 2-(5-(cyclopropylmethyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-5- oxo-5,7-dihydrobenzo[4',5']imidazo[1',2':1,6]pyrido[2,3-d]pyrimidine-6- carboxylate: To a mixture of ethyl 2-(hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-5- oxo-5,7-dihydrobenzo[4',5']imidazo[1',2':1,6]pyrido[2,3-d]pyrimidine-6-carboxylate (0.4 g, 955.89 μmol, 1 eq) in DCE (2 mL) and MeOH (2 mL) was added cyclopropanecarbaldehyde (335.00 mg, 4.76 mmol, 0.34 mL, 5 eq) and NaBH(OAc)3 (607.80 mg, 2.87 mmol, 3 eq). The mixture was heated to 40°C and stirred for 12 h. The mixture was concentrated in vacuo and the crude product was purified by prep- HPLC (column: Phenomenex luna C18 100*40mm*5 um;mobile phase: [H2O(0.04% HCl)-ACN];gradient:5%-45% B over 8.0 min) to give the title compound (0.1 g, 211.62 μmol, 22.14% yield) as a yellow solid. LCMS (ESI+): Rt: 0.401 min, m / z 473.2 (M+H)+. 2-(5-(cyclopropylmethyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-5-oxo- 5,7-dihydrobenzo [4',5']imidazo[1',2':1,6]pyrido[2,3-d]pyrimidine-6- carboxylic acid: To a mixture of ethyl 2-(5-(cyclopropylmethyl)hexahydropyrrolo- [3,4-c]pyrrol-2(1H)-yl)-5-oxo-5,7-dihydrobenzo[4',5'] imidazo[1',2':1,6]pyrido[2,3- d]pyrimidine-6-carboxylate (0.2 g, 392.93 μmol, 1 eq, HCl) in THF (1 mL), MeOH (1 mL) and H2O (0.2 mL) was added LiOH.H2O (98.93 mg, 2.36 mmol, 6 eq). The mixture was heated to 50°C and stirred for 12 h. The mixture was concentrated in vacuo and the crude product was purified by prep-HPLC (column: Phenomenex luna C18 100*40mm*5 µm;mobile phase: [H2O(0.04% HCl)-ACN];gradient:1%-40% B over 8.0 min) to give the title compound (0.1 g, 207.92 μmol, 52.92% yield, HCl) as a yellow solid. LCMS (ESI+): Rt: 1.478 min, m / z 445.4 (M+H)+.1H NMR (400 MHz, DMSO-d6+D2O) δ = 9.15 (d, J = 4.1 Hz, 1H), 8.72 - 8.65 (m, 1H), 7.79 (dd, J = 3.8, 7.8 Hz, 1H), 7.55 - 7.49 (m, 1H), 7.47 - 7.40 (m, 1H), 4.11 - 4.00 (m, 1H), 3.98 - 3.81 (m, 4H), 3.79 - 3.64 (m, 1H), 3.45 (br s, 2H), 3.32 - 3.20 (m, 1H), 3.18 - 3.02 (m, 3H), 1.17 - 0.99 (m, 1H), 0.67 - 0.55 (m, 2H), 0.44 - 0.32 (m, 2H). Synthetic Route 25 Example 69: 4-[2-(dimethylamino)-4-pyridyl]-8-oxo-11-thia-1,3,5- triazatetracyclo[8.7.0.02,7.012,17]heptadeca-2(7),3,5,9,12(17),13,15- heptaene-9-carboxylic acid N,N-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2- amine: To a solution of 4-bromo-N,N-dimethyl-pyridin-2-amine (4 g, 19.89 mmol, 1 eq) and BPD (6.06 g, 23.87 mmol, 1.2 eq) in dioxane (50 mL) was added Pd(dppf)Cl2.CH2Cl2 (1.62 g, 1.99 mmol, 0.1 eq) and Cs2CO3 (16.20 g, 49.74 mmol, 2.5 eq) and the mixture was stirred at 100°C for 12 h. The reaction mixture was concentrated under reduced pressure and the residue was purified by silica gel chromatography (Dichloromethane: Methanol=100 / 1 to 1:1) to give the title compound (1.8 g, 7.25 mmol, 36.46% yield) as a black oil. LCMS (ESI+): Rt: 0.131 min, m / z 167.3 (M-82).1H NMR (400 MHz, DMSO-d6) δ = 8.10 (d, J = 4.8 Hz, 1H), 6.78 (s, 1H), 6.73 (d, J = 4.8 Hz, 1H), 3.01 (s, 6H), 1.29 (s, 6H), 1.07 (s, 6H). Ethyl 4-[2-(dimethylamino)-4-pyridyl]-8-oxo-11-thia-1,3,5-triazatetracyclo- [8.7.0.02,7.012,17]heptadeca-2(7),3,5,9,12(17),13,15-heptaene-9-carboxylate: To a solution of ethyl 4-chloro-8-oxo-11-thia-1,3,5-triazatetracyclo[8.7.0.02,7.012,17]- heptadeca-2,4,6,9,12(17),13,15-heptaene-9-carboxylate (1.15 g, 3.20 mmol, 1 eq) and N,N-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine (793.10 mg, 3.20 mmol, 1 eq) in dioxane (40 mL) and H2O (2 mL) was added Pd(dppf)Cl2 (233.88 mg, 319.63 μmol, 0.1 eq) and Cs2CO3 (3.12 g, 9.59 mmol, 3 eq) and the mixture was stirred at 90°C for 12 h. The reaction mixture was concentrated under reduced pressure and the crude product was triturated with methanol (30 mL) then filtered and the filter cake was dried under reduced pressure to give the title compound (1.1 g, crude) as a brown solid. LCMS (ESI+): Rt: 0.373 min, m / z 446.0 (M+H)+. 4-[2-(dimethylamino)-4-pyridyl]-8-oxo-11-thia-1,3,5-triazatetracyclo- [8.7.0.02,7.012,17]heptadeca-2(7),3,5,9,12(17),13,15-heptaene-9-carboxylic acid: To a solution of ethyl 4-[2-(dimethylamino)-4-pyridyl]-8-oxo-11-thia-1,3,5- triazatetracyclo[8.7.0.02,7.012,17]heptadeca-2(7),3,5,9,12(17),13,15-heptaene-9- carboxylate (600 mg, 1.35 mmol, 1 eq) in THF (6 mL) and MeOH (6 mL) was added LiOH.H2O (2 M, 6.73 mL, 10 eq) and the mixture was stirred at 25°C for 12 h. The reaction mixture was concentrated under reduced pressure and the crude product was purified by prep-HPLC (column: CD24-WePure Biotech XPT C18 150*25*7µm; mobile phase: [H2O (0.1% TFA)-ACN]; gradient: 10%-40% B over 10.0 min) to give a eluent and the eluent was concentrated under reduced pressure to remove MeCN then lyophilized to give the title compound (13.1 mg, 29.57 μmol, 2.20% yield, 94.235% purity) as a yellow solid. LCMS (ESI+): Rt: 1.829 min, m / z 418.3 (M+H)+.1H NMR (400 MHz, TRIFLUOROACETIC ACID-d) δ = 10.64 (s, 1H), 10.17 (d, J = 8.6 Hz, 1H), 8.80 (s, 1H), 8.53 (dd, J = 7.4, 17.5 Hz, 2H), 8.37 (d, J = 7.0 Hz, 1H), 8.33 - 8.27 (m, 1H), 8.24 - 8.18 (m, 1H), 3.88 (s, 6H). Synthetic Route 26 Example 70: 2-morpholino-5-oxo-5H-benzo[4',5']thiazolo[3',2':1,6]pyrido- [2,3-d]pyrimidine-6-carboxylic acid To a solution of ethyl 2-morpholino-5-oxo-5H-benzo[4',5']thiazolo[3',2':1,6]pyrido- [2,3-d]pyrimidine-6-carboxylate (0.3 g, 730.91 μmol, 1 eq) in THF (2 mL), MeOH (2 mL) and H2O (2 mL) was added LiOH.H2O (61.34 mg, 1.46 mmol, 2 eq) at 25°C. The reaction was heated to 50°C and stirred for 12 h. The reaction was filtered and the filtered cake was collected, 100 mg was purified by prep-HPLC (column: Phenomenex Luna C18 100*30mm*5µm;mobile phase: [H2O(0.1% TFA)-ACN];gradient:15%-65% B over 8.0 min) to give the title compound (5.6 mg, 14.64 μmol, 5.60% yield, TFA salt) as a yellow solid. LCMS (ESI+): m / z 383.1 (M+H)+, Rt: 8.526 min.1H NMR (400 MHz, TRIFLUOROACETIC ACID-d) δ = 9.66 (br s, 1H), 9.38 (br d, J = 8.4 Hz, 1H), 7.98 (br d, J = 7.8 Hz, 1H), 7.81 - 7.64 (m, 2H), 4.27 (br s, 4H), 4.13 (br s, 4H). ADC - General experimental All reagents were purchased from Aldrich, MedChemExpress or ChemCruz and were used as received. All reactions were monitored by Liquid chromatography - mass spectrometry (LC-MS) on a Waters Xevo G2-S QToF. Flash chromatographic purifications were carried out using CombiFlash Rf (Teledyne Isco) with a Interchim column (PF-15C18HP-F0025), with H2O-Acetonitrile gradient.1H NMR spectra were recorded at ambient temperature using an internal deuterium lock on Bruker DPX (400 MHz;1H DUL probe) and Bruker Avance III HD (400 MHz; Smart probe). Excess solvents were removed either by rotary evaporation on Buchi Rotavapor R-114 or Genevac EZ-2 Elite. Bioconjugation Small molecules, drugs and fluorophores were removed from antibodies / bioconjugates via Zeba™ Spin Desalting Columns and Plates, 7K and 40K MWCO, 0.5 mL–5 mL, unless otherwise stated. Equivalents of drugs added to antibodies / bioconjugates are reported as 1:1 antibody:drug (i.e. not accounting number of available cysteine residues for reaction). UV-vis spectra were recorded over a range of 220 – 650 nm on a Thermo Scientific™ NanoDrop™ One Microvolume UV-vis spectrophotometer and was used to determine concentration of bioconjugates, and FAR (Fluorophore-to- Antibody Ratio). Sample buffer was used as blank for baseline correction. Final ADC formulations were stored in PBS, pH 7.4, at 4°C. The estimated concentration of Cetuximab conjugates was determined spectrophotometrically at 280 nm by using a molar extinction coefficient, ε, of 210.000 M-1cm-1. Correction factor (CF) for small molecules was calculated. Determination of molecule over antibody ratio, r, follows the formula below: SDS-PAGE gels SDS-PAGE was carried out on pre-cast Bio-Rad 4-15 % GTX mini-Protean acrylamide gels run over 40 min at fixed current of 40 mA. Gels were either visualised under UV light in a SynGene G:BOX (e.g. for visualisation of fluorescent species). Alternatively, gels were washed in H2O and stained in InstantBlue Gel Stain for 1 h and visualised under white light. Samples (7 μL at ~5 μM construct) were mixed with 6x loading buffer (3 μL) and heated at 75 °C for 4 min. Ellman’s assay The Ellman's assay involved combining 2 μL of a 1 mM solution of 5,5’-dithio-bis-(2- nitrobenzoic acid) (Ellman's reagent) in PBS with a bioconjugate sample at a known concentration, in PBS (8 μL). After incubating the solution at 21 °C for 2 minutes, the absorption was recorded at both 280 nm (to determine protein concentration) and 412 nm (for 2-nitro-5-thiobenzoic acid). A reference blank was created using a 1 mM solution of Ellman's reagent in PBS (1 μL), diluted in PBS (4 μL) to serve as a baseline correction. Each sample in PBS was analysed with and without Ellman's reagent, both under identical concentration conditions. The sulfhydryl per protein ratio (SPR) was calculated as follows with ɛ412 = 14150 M-1cm-1: Protein LC-MS Antibodies and their respective conjugates were prepared for analysis by removal of small molecules + buffer exchange into miliQ H2O on ZebaSpinTMcolumns, and were submitted with a concentration of 10-15 µM (1.0 mg×ml-1) for analysis on the Xevo QTOF LC-MS system. 4-10 µL of each sample was injected and separation was achieved using mobile phase A (95% water, 5% MeCN, 0.1% formic acid) and B (5% water, 95% MeCN, 0.1% formic acid) using a gradient elution. Typical conditions were capillary voltage 1.6-2.2 kV, cone voltage 160– 190 V, Trap 40−50 V, Transfer 140 V with backing pressure 3–4 mbar and source temperature of 20 °C. Data acquisition and processing were performed using MassLynx 4.1. The raw data was converted to zero charge mass spectra using a maximum entropy deconvolution algorithm, over the full peak regions as identified via the LC trace. All full antibody samples were deglycosylated with PNGase F enzyme treatment prior to LC-MS analysis. A 2-step protocol was utilised for Cetuximab antibody and respective conjugates to efficiently remove Fab and Fc region N-glycans. ADC Synthetic Route Example ADC-1: Cetuximab-mal-vc-4-(1,4-Diazepan-1-yl)-8-oxo-11-thia- 1,3,5-triazatetracyclo[8.7.0.0²,⁷.0¹²,¹⁷]heptadeca-2(7),3,5,9,12,14,16- heptaene-9-carboxylic acid Intermediate 1: 4-(1,4-Diazepan-1-yl)-8-oxo-11-thia-1,3,5-triazatetracyclo- [8.7.0.0²,⁷.0¹²,¹⁷]heptadeca-2(7),3,5,9,12,14,16-heptaene-9-carboxylic acid (0.028 mmol.1 eq.) and DIPEA (0.028 mmol, 1.1 eq.) were added to a solution of azido- PEG3-Val-Cit-PAB-PNP (20 mg, 0.026 mmol) in DMF (5 mL) under inert atmosphere (argon) and the reaction was stirred at 21 °C for 16 h. After consumption of starting material, solvents were removed in vacuo and crude product was purified via RP flash chromatography to yield intermediate 1. LCMS (ESI+): m / z 1030.4 (M+H)+, Rt: 2.96 min. Intermediate 2: To a solution of native Cetuximab (CTX) (500 μL, 20 μM, 1 eq.) in PBS EDTA (0.5 mm EDTA, pH 7.4) was added TCEP (10 μL, 20 mM in PBS pH = 7.4, 20 eq.) and the reaction mixture incubated at 21 °C for 16 h. The excess reagents were then removed by repeated diafiltration (5x) into fresh buffer using VivaSpin sample concentrators (GE Healthcare, 30,000 MWCO). Following this, analysis by SDS-PAGE and UV / Vis revealed >95% conversion to reduced CTX. Posteriorly, to a solution of reduced CTX (3000 μL, 22 μM, 1 eq.) in PBS EDTA (0.5 mm EDTA, pH 7.4) was added BCN-PEG3-Mal (endo) (80 μL, 20 mM in PBS pH = 7.4, 24 eq.) and the reaction mixture incubated at 21 °C for 16 h. The excess reagents were then removed by SEC ZebaspinTM column, and simultaneously buffer was exchanged to PBS, pH 7.4. Following this, analysis by SDS-PAGE and UV / Vis (Ellman’s assay) revealed >90% conversion to CTX-mal-BCN. Calculated SPR~0. Cetuximab-mal-vc-4-(1,4-Diazepan-1-yl)-8-oxo-11-thia-1,3,5- triazatetracyclo[8.7.0.0²,⁷.0¹²,¹⁷]heptadeca-2(7),3,5,9,12,14,16-heptaene-9- carboxylic acid: To a solution of intermediate 2 (500 μL, 20 μM, 1 eq.) in PBS (pH 7.4) was added intermediate 1 (10 μL, 20 mM in PBS pH = 7.4, 20 eq.) and the reaction mixture incubated at 21 °C for 16 h. The excess reagents were then removed by SEC ZebaspinTM column, and simultaneously buffer was exchanged to PBS, pH 7.4. Following this, analysis by SDS-PAGE and UV / Vis revealed >90% conversion to the title compound, Example ADC-1, DAR > 6. Examples – Biological Studies Cell viability assay Cell culture: Human colorectal adenocarcinoma HCT116 cells (CCL-247, ATCC), HCT116 BRCA2- / -knockout cells (clone 42, Cancer Research UK) as well as colorectal adenocarcinoma DLD-1 cells (CCL-221, Horizon Discovery) and DLD-1 BRCA2- / -knockout cells (HD 105-007, Horizon Discovery) were cultured in RPMI1640, GlutaMAX™ (Gibco) supplemented with 10% heat inactivated fetal bovine serum (ThermoFisher Scientific) at 37 °C in a humidified 5% CO2 atmosphere. Cell Titer Glo a : Antiproliferative effects of compound and ADCs were tested using a CellTiter-Glo® 2.0 cell viability assay (Promega), which determines the number of viable cells in culture by quantifying ATP of metabolically active cells. Cells (500 / well) were seeded on 384-well flat bottom plates in 25 µL of culture medium containing compounds or ADCs a various concentrations. After incubation for 96 hours under normal growth condition, 25 µL of Cell Titer Glo reagent were added to each well, mixed and incubated for 10 min. End-point luminescence was then measured using a PHERAstar Plus (BMG Labtech) and normalized in relation to the average survival of samples treated only with DMSO (100% viability) and wells with no cells added (0% viability). Dose-dependent cell viability was fit using a four-parameter logistic curve in CDD Vault (Collaborative Drug). The 50% inhibitory concentrations (IC50) were determined from three replicates. Human telomerase reverse transcriptase (hTERT)–immortalized primary cells, 184-hTERT-L9 95.22 P53(- / -)and 184-hTERT-L9 83.86 (P53(- / -)BRCA1(- / -)were cultured in MEBM media (Lonza), containing Bullet kit components, minus gentamicin (Lonza), isoprenaline hydrochloride (10 µM), transferrin (5 µg / mL) at 37 °C in a humidified 5% CO2 atmosphere. : The survival and antiproliferative effects of compounds were tested using a colony formation assay which determines the ability of single cells to survive and proliferate into clonal colonies when challenged with compounds. 184- hTERT-L9 95.22 P53(- / -)were seeded at 150 cells / mL and 184-hTERT-L9 83.86 (P53(- / -)BRCA1(- / -)were seeded at 250 cells / mL in supplemented MEBM media into 12-well tissue culture plates and incubated overnight at 37 °C in a humidified 5% CO2 atmosphere. Following overnight incubation cells were dosed with serial diluted compounds or DMSO vehicle and incubated for a further 7 days at 37 °C in a humidified 5% CO2 atmosphere. Colonies were stained with Crystal violet (0.05% w / v) after fixation with 90% methanol. Following plate washing, colonies were counted on the GelCount system (Oxford optronix) and Graphpad prism used to determine IC50 and IC90 values using a 4 parameter sigmoidal curve fit. DMSO vehicle control was used to normalize all data points to 100% Survival fraction for each cell line. The IC50 and IC90 concentrations were determined from two biological replicates. BALB / 3T3 clone A31 Phototoxicity Assay Day 0: Once the cells become >70% confluent in the flask (approx. 3 days), the media will be aspirated and the cell monolayers will be rinsed with 10 mL DPBS. After aspirating the rinse buffer, trypsin will be added to cover the cell monolayer, tilting once or twice. Cell media will be added and pipetted up and down several times to mix and dissociate cell clumps until cells will be separated. Cells will be counted, and 150000 cells / mL of suspension will be prepared. Assay plates will be seeded with BALB / 3T3 clone A31 cells in DMEM media, 15000 cells / well in the 96-well plate, 100 μL / well. Incubate the cells overnight at 37 °C, 10% CO2, relative humidity >90%. Day 1: 1) After allowing for cell attachment overnight, wash the cell with 100 μL HBSS once and is replaced with HBSS. 2) Set the Pico8 digital dispenser to add the test and control articles to the cell assay plates. The top concentration of the working concentration of test article will be started from 100 μM, 3-fold dilution, 8 concentrations. The control article Chlorpromazine will be started from 100 μM, 3-fold dilution, 8 concentrations. The solubility of the compounds and cell status will be observed after the compounds were added into the cell media. 3) The plate 1 and 2 will be incubated in the RT for 1h. Then the plate 2 will be incubated in the dark for 1h. Meanwhile plate1 will be Expose to about 2.4 J / cm2 of UVA irradiation for 40min. After that the test solution will be removed from the plates; the wells will be washed with 150 μL HBSS once and replaced the fresh culture medium. Incubate the cells overnight at 37 °C, 10% CO2, relative humidity >90%. Day 2: 1) Remove the medium, then wash the cells with 100 μL of the pre-warmed HBSS and cultured with 100 μL 50μg / mL Neutral Red (NR) Medium and the cells will be returned to the incubator at 37 °C for an additional 3 hours. 2) Following the 3-hour uptake of the Neutral Red (NR), the medium will be discarded, the wells will be washed with HBSS, and 150 μL extraction buffer (1.0% Glacial Acetic Acid, 50% Ethanol, 49% dH2O) will be added to each well. 3) Shake the microplate gently on a microplate shaker for 2 min and incubated for 15 min in the dark until Neutral Red (NR) have been extracted from the cells and have formed a homogeneous solution. Measure the optical density of the Neutral Red（NR） extract at 540 nm in a spectrophotometer. Save data in an appropriate electronic file format for subsequent analysis. For data analysis, raw data will be exported to Excel for calculation as the equation below. 1. Inhibition%= (1- (Sample / DMSO control) *100 2. The IC50 value was determined from the concentration-response curve with Nonlinear Regression using Sigmoidal dose-response (variable slope) meanwhile transforming X values using X=Log(X) by XL-fit software (Supplier: ID Business Solutions Ltd., Software version: XL fit 5.5.0.5). 3. A Photo-Irritation-Factor (P I F) will be calculated using the following formula: PIF = IC50 (-irradiation) / IC50 (+irradiation). HCT116 - UVA phototoxicity assay The cell line HCT116 (ATCC, cat no. CCL-247) is passaged in RPMI-1640, supplemented with 10% heat Inactivated FBS, in 5% CO2 at 37°C, to a confluence of 70-90%. Media is aspirated, and the cell monolayer washed with 10 mL DPBS. After aspiration of DPBS, cells are detached using trypsin (5 minutes) before media is added to neutralize the trypsin. Cells are mixed in equal volumes of trypan blue (10 µL:10 µL) and viable cells counted. Cells (500 / well) were seeded on 384-well flat bottom plates in 25µL of culture medium containing compounds. Plates were incubated for 30 minutes at 37°C, 5% CO2. Following incubation one replicate plate is irradiated (lid off) with 125 mJ / cm2UVA light for 5 minutes using a Stratalinker crosslinker CL-1000, fitted with UVA (365 nm) bulbs. Following irradiation all plates are incubated for a further 96 hours at 37°C, 5% CO2. After incubation for 96 hours under normal growth condition, 25 µL of Cell Titer Glo reagent were added to each well and agitated at 600 rpm for 2 minutes on a plate shaker, plates are further incubated for 10 min at room temperature. End-point luminescence was then measured using a PHERAstar Plus (BMG Labtech) and normalized in relation to the average survival of samples treated only with DMSO (100% viability) and wells with no cells added (0% viability). Dose-dependent cell viability was fit using a four-parameter logistic curve in CDD Vault (Collaborative Drug). The 50% inhibitory concentrations (IC50) were determined from three replicates. Ratios of IC50s between unirradiated and irradiated replicate plates were determined and used to determine phototoxicity of compounds. Liver Microsome Metabolic Stability Assay (NADPH) Test compounds are incubated at 37°C with liver microsomes (pooled from multiple donors) at 1.0 µM in the presence of NADPH (~1.0 mM) at 0.5 mg / mL microsomal protein. Positive controls include testosterone (3A4 substrate), propafenone (2D6) and diclofenac (2C9). They will be incubated with microsomes in the presence of NADPH. Time samples (0, 5, 15, 30, 45 and 60 minutes) will be removed, immediately mixed with cold acetonitrile containing internal standard (IS). Test compounds incubated with microsomes without NADPH for 60 min are also included. Single point for each test condition (n=1). Samples are analyzed by LC / MS / MS; disappearance of test compound will be assessed based on peak area ratios of analyte / IS (no standard curve). Liver Hepatocyte Assay (NADPH): Test compounds are incubated at 37°C with cryopreserved liver hepatocytes (pooled from multiple donors) at 0.5 × 106cells per mL. The reaction samples will be removed at multiple time points (0, 15, 30, 60, and 90 minutes), and medium control samples without cells at 0 and 90 minutes will be incubated. All samples will be immediately mixed with cold organic solution containing internal standard (IS) to stop the reaction. Samples will be analyzed by LC / MS / MS, and the disappearance of test compound will be assessed based on peak area ratios of analyte / IS (no standard curve). Protein Binding Assay The test compounds or positive control warfarin will be spiked into frozen plasma (commercial vendors, pooled from multiple individuals) at the final concentration of 2 μM. An aliquot of 150 µL of the compound-spiked plasma sample will be added to one side of the chamber in a 96-well equilibrium dialysis plate (HTD dialysis) and an equal volume of dialysis buffer (100 mM sodium phosphate and 150 mM NaCl, 7.4 ± 0.1) will be added to the other side of the chamber. An aliquot of plasma sample will be harvested before the incubation and used as T0 samples for recovery calculation. Triplicate incubations will be performed. The plate will then be incubated in a humidified incubator with 5% CO2 at 37°C for 4 hours. After incubation, 50 µL samples will be taken from the plasma side as well as the buffer side. The plasma sample will be mixed with an equal volume of blank buffer; buffer samples will be mixed with an equal volume of blank plasma. The matrix-matched samples will be quenched with stop solution containing internal standard (IS). Samples are analyzed by LC-MS / MS. Test compound concentrations in plasma and buffer samples will be determined based on peak area ratio of analyte to IS without a standard curve. Cell Titre Glow Data IC50 (µM) values:

[0021] Select human PPB data: Table 3: >95% bound = ’, >75-95% bound = ’, >50-75% bound = ‘+++’, >25-50% bound = ‘++++’, Select human liver microsomes data: Table Select 3T3 Phototoxicity data: Table 5: PIF < 5 = ‘+++’, 5-<10 = ‘++’, ≥10 = ‘+’ HCT116 - UVA phototoxicity assay Table 6: PIF < 5 = ‘+++’, 5-<10 = ‘++’, ≥10 = ‘+’ It will be understood that the present invention has been described above by way of example only. The examples are not intended to limit the scope of the invention. Various modifications and embodiments can be made without departing from the scope and spirit of the invention, which is defined by the following claims only.

Claims

Claims 1. A compound of Formula (I):Formula (I) or a pharmaceutically acceptable salt and / or solvate and / or prodrug thereof; wherein: RXis selected from -OH, -SH, -NH2 or a C1-C24 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo and / or -NO2 groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O 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 (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety; X1is N, C-H, C-Hal or C-RX1; X2is N, C-H, C-Hal or C-RX2; X3is N, C-H, C-Hal or C-RX3; and X4is N or C; provided that at least one of X1, X2, X3and X4is N, and that no more than three of X1, X2, X3and X4are N; RX1, RX2and RX3are each independently selected from -OH, -SH, -NH2, -SO2H, -SO3H, -SO2NH2, -NO2, or a C1-C4 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 and / or -NO2 groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O 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 (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety;Q1is O, S, N, N-H, N-RQ1, C-H, C-Hal, or C-RQ2; RQ1is selected from a C1-C4 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 and / or -NO2 groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O 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 (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety, provided that the atom of RQ1that is directly attached to the nitrogen atom of N-RQ1is a carbon atom; RQ2is selected from -OH, -SH, -NH2, -SO2H, -SO3H, -SO2NH2, -NO2, or a C1-C4 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 and / or -NO2 groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O 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 (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety; A1is N, C-H, C-Hal or C-RA1; A2is N, C-H, C-Hal or C-RA2; A3is N, C-H, C-Hal or C-RA3; A4is N, C-H, C-Hal or C-RA4; and A5is N or C; provided that no more than three of A1, A2, A3, A4and A5are N; RA1, RA2, RA3and RA4are each independently selected from -OH, -SH, -NH2, -SO2H, -SO3H, -SO2NH2, -NO2, or a C1-C4 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 and / or -NO2 groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O 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 (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety; A6is N or C; and each Hal is independently selected from a fluoro, chloro, bromo or iodo group.

2. A compound as claimed in claim 1, or a pharmaceutically acceptable salt and / or solvate and / or prodrug thereof, wherein at least one of X2, X3and X4is N.

3. A compound as claimed in claim 1 or claim 2, or a pharmaceutically acceptable salt and / or solvate and / or prodrug thereof, wherein X2is N.

4. A compound as claimed in any one of claims 1 to 3, wherein RXis a C1-C12 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or two cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo and / or -NO2 groups, and wherein the hydrocarbyl group includes one, two, three or four heteroatoms each independently selected from N and O in its carbon skeleton.

5. A compound as claimed in any one of claims 1 to 4, or a pharmaceutically acceptable salt and / or solvate and / or prodrug thereof, wherein -RXis -NR1R2, wherein: R1and R2are each independently selected from hydrogen or a C1-C12 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight- chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo and / or -NO2 groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O 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 (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety; or R1and R2together with the nitrogen atom to which they are attached form a 3- to 12-membered cyclic group, wherein the cyclic group may optionally be substituted with one or more substituents each independently selected from a halo, oxo (=O), -OH, -SH, -NH2, -SO2H, -SO3H, -SO2NH2, -NO2, or a C1-C6 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 and / or -NO2 groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O 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 (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety; provided that the group -NR1R2contains no more than 24 carbon atoms.

6. A compound as claimed in claim 5, or a pharmaceutically acceptable salt and / or solvate and / or prodrug thereof, wherein R1is a C1-C8 saturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include a single cyclic group, wherein the hydrocarbyl group may optionally be substituted with one or more fluoro groups and / or a single oxo (=O) group, wherein the hydrocarbyl group optionally includes one or two heteroatoms each independently selected from N and O in its carbon skeleton, and R2is selected from hydrogen or a C1-C3 alkyl or C1-C3 fluoroalkyl group.

7. A compound as claimed in claim 5, or a pharmaceutically acceptable salt and / or solvate and / or prodrug thereof, wherein R1and R2together with the nitrogen atom to which they are attached form a 4- to 7-membered monocyclic group or a 6- to 12- membered bicyclic group, wherein the monocyclic or the bicyclic group may optionally be substituted with one or more substituents each independently selected from a halo, oxo (=O), -OH, -NH2 or a C1-C6 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, and wherein the hydrocarbyl group may optionally include one or two heteroatoms each independently selected from N and O in its carbon skeleton.

8. A compound as claimed in claim 7, or a pharmaceutically acceptable salt and / or solvate and / or prodrug thereof, wherein -NR1R2has the formula:wherein: n is 1 or 2; m is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; each R11is independently selected from a fluoro, methyl or fluoromethyl group, provided that no more than four R11are selected from a methyl or fluoromethyl group; X12is O or NR12; and R12is hydrogen or a C1-C4 saturated hydrocarbyl group, wherein the saturated hydrocarbyl group may be straight-chained or branched, or be or include a cyclic group, wherein the saturated hydrocarbyl group may optionally be substituted with one or more fluoro groups and / or a single oxo (=O) group, and wherein the saturated hydrocarbyl group may optionally include a single heteroatom selected from N and O in its carbon skeleton.

9. A compound as claimed in claim 7, or a pharmaceutically acceptable salt and / or solvate and / or prodrug thereof, wherein -NR1R2has the formula:wherein: j is 0, 1, 2 or 3; k is 0, 1, 2 or 3; p is 0, 1, 2 or 3; and q is 0, 1, 2 or 3; provided that: j + k = 2 or 3; p + q = 2 or 3; when j = 0, q is 1, 2 or 3; when k = 0, p is 1, 2 or 3; when p = 0, k is 1, 2 or 3; and when q = 0, j is 1, 2 or 3; and wherein: r is 0, 1 or 2; s is 0, 1 or 2; R15is hydrogen or a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl, fluorocyclopropylmethyl or -CO-R150group; R150is selected from a C1-C3 alkyl, C1-C3 fluoroalkyl, cyclopropyl or fluorocyclopropyl group; and each R16is independently selected from a methyl or fluoromethyl group.

10. A compound as claimed in claim 7, or a pharmaceutically acceptable salt and / or solvate and / or prodrug thereof, wherein -NR1R2has the formula:wherein: X15is O or NR15;j is 0, 1, 2, 3 or 4; k is 0, 1, 2, 3 or 4; p is 0, 1, 2, 3 or 4; and q is 0, 1, 2, 3 or 4; provided that: j + k = 3 or 4; p + q = 3 or 4; when j = 0, q is 1, 2, 3 or 4 and p is 1, 2, 3 or 4; when k = 0, q is 1, 2, 3 or 4 and p is 1, 2, 3 or 4; when p = 0, k is 1, 2, 3 or 4 and j is 1, 2, 3 or 4; and when q = 0, k is 1, 2, 3 or 4 and j is 1, 2, 3 or 4; and wherein: r is 0, 1 or 2; s is 0, 1 or 2; R15is hydrogen or a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl, fluorocyclopropylmethyl or -CO-R150group; R150is selected from a C1-C3 alkyl, C1-C3 fluoroalkyl, cyclopropyl or fluorocyclopropyl group; and each R16is independently selected from a methyl or fluoromethyl group.

11. A compound as claimed in claim 7, or a pharmaceutically acceptable salt and / or solvate and / or prodrug thereof, wherein -NR1R2has the formula:wherein: j is 0, 1, 2, 3 or 4; k is 0, 1, 2, 3 or 4; p is 0, 1, 2 or 3; and q is 0, 1, 2 or 3; provided that: j + k = 3 or 4; p + q = 2 or 3; when j = 0, p is 1, 2 or 3; when k = 0, p is 1, 2 or 3; and when p = 0, j is 1, 2, 3 or 4 and k is 1, 2, 3 or 4;and wherein: r is 0, 1 or 2; s is 0, 1 or 2; R15is hydrogen or a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl or fluorocyclopropylmethyl group; and each R16is independently selected from a methyl or fluoromethyl group.

12. A compound as claimed in any one of claims 1 to 4, or a pharmaceutically acceptable salt and / or solvate and / or prodrug thereof, wherein -RXis -OR3, wherein R3is selected from hydrogen or a C1-C12 saturated or unsaturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or more cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more halo and / or -NO2 groups, wherein the hydrocarbyl group may optionally include one or more heteroatoms each independently selected from N, O 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 (=O) and =NH to form a -SO-, -SO2-, -S(=NH)- or -SO(=NH)- moiety.

13. A compound as claimed in claim 9, or a pharmaceutically acceptable salt and / or solvate and / or prodrug thereof, wherein R3is a C2-C8 saturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include a single cyclic group, wherein the hydrocarbyl group may optionally be substituted with one or more fluoro groups, and wherein the hydrocarbyl group includes one or two heteroatoms each independently selected from N and O in its carbon skeleton.

14. A compound as claimed in any one of claims 1 to 4, or a pharmaceutically acceptable salt and / or solvate and / or prodrug thereof, wherein RXis a C1-C12 saturated hydrocarbyl group, wherein the hydrocarbyl group may be straight-chained or branched, or be or include one or two cyclic groups, wherein the hydrocarbyl group may optionally be substituted with one or more fluoro groups and / or one or two oxo (=O) groups, and wherein the hydrocarbyl group includes one, two, three or four heteroatoms each independently selected from N and O in its carbon skeleton, provided that the atom of RXthat is directly attached to the remainder of the compound of Formula (I) is a carbon atom.

15. A compound as claimed in any one of claims 1 to 4, or a pharmaceutically acceptable salt and / or solvate and / or prodrug thereof, wherein RXis a phenyl, naphthyl, a 5- or 6-membered heteroaryl or a bicyclic fused heteroaryl group, wherein the phenyl, naphthyl, 5- or 6-membered heteroaryl or the bicyclic fused heteroarylgroup may optionally be substituted with one or more halo groups and / or one or two groups R5, wherein each R5is independently selected from -OH, -NH2, or a C1-C6 saturated hydrocarbyl group, wherein the saturated hydrocarbyl group may be straight-chained or branched, or be or include a single cyclic group, wherein the saturated hydrocarbyl group may optionally be substituted with one or more fluoro groups and / or a single oxo (=O) group, and wherein the saturated hydrocarbyl group may optionally include one or two heteroatoms each independently selected from N and O in its carbon skeleton.

16. A compound as claimed in any one of claims 1 to 15, or a pharmaceutically acceptable salt and / or solvate and / or prodrug thereof, wherein: X1is N, C-H, C-Hal or C-RX1; X2is N, C-H, C-Hal or C-RX2; X3is N, C-H, C-Hal or C-RX3; and X4is C; provided that at least one of X1, X2and X3is N and that no more than two of X1, X2and X3are N.

17. A compound as claimed claim 16, or a pharmaceutically acceptable salt and / or solvate and / or prodrug thereof, wherein: X1is N, C-H or C-RX1; X2is N, C-H or C-RX2; X3is N, C-H or C-RX3; and X4is C; provided that at least one of X1, X2and X3is N, and that no more than two of X1, X2and X3are N; and RX1, RX2and RX3are each independently selected from -OH, -SH, -NH2, or a C1- C4 saturated 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, and wherein the hydrocarbyl group may optionally include one or two heteroatoms each independently selected from N, O and S in its carbon skeleton.

18. A compound as claimed in claim 17, or a pharmaceutically acceptable salt and / or solvate and / or prodrug thereof, wherein: X1is N; X2is N; X3is C-H or C-RX3;X4is C; and RX3is a methyl or fluoromethyl group.

19. A compound as claimed in any one of claims 1 to 18, or a pharmaceutically acceptable salt and / or solvate and / or prodrug thereof, wherein Q1is O, S, N-H or N-RQ1, wherein RQ1is selected from a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl, C3-C4 fluorocycloalkyl, cyclopropylmethyl, fluorocyclopropylmethyl or -CO-RQ3group, wherein RQ3is selected from a C1-C3 alkyl, C1-C3 fluoroalkyl, cyclopropyl or fluorocyclopropyl group.

20. A compound as claimed in claim 19, or a pharmaceutically acceptable salt and / or solvate and / or prodrug thereof, wherein Q1is N-H.

21. A compound as claimed in any one of claims 1 to 20, or a pharmaceutically acceptable salt and / or solvate and / or prodrug thereof, wherein: A1is N, C-H, C-Hal or C-RA1; A2is N, C-H, C-Hal or C-RA2; A3is N, C-H, C-Hal or C-RA3; A4is N, C-H, C-Hal or C-RA4; A5is C; and RA1, RA2, RA3and RA4are each independently selected from a C1-C4 saturated 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 fluoro groups and / or a single oxo (=O) group, and wherein the hydrocarbyl group may optionally include a single heteroatom selected from N and O in its carbon skeleton; provided that no more than one of A1, A2, A3and A4is N; and provided that no more than two of A1, A2, A3and A4are C-RA1, C-RA2, C-RA3or C-RA4.

22. A compound as claimed in any one of claims 1 to 21, or a pharmaceutically acceptable salt and / or solvate and / or prodrug thereof, wherein A6is N.

23. A compound as claimed in any one of claims 1 to 22, or a pharmaceutically acceptable salt and / or solvate and / or prodrug thereof, wherein each Hal is independently selected from a fluoro, chloro or bromo group.

24. A compound as claimed in any one of claims 1 to 23, or a pharmaceutically acceptable salt and / or solvate and / or prodrug thereof, wherein the compound is a compound of Formula (Ia):wherein RX, X1, X2and Q1are as defined in accordance with any preceding claim.

25. A compound selected from the group consisting of:or a pharmaceutically acceptable salt and / or solvate and / or prodrug of the selected compound.

26. An antibody-drug conjugate comprising a compound, or a pharmaceutically acceptable salt and / or solvate and / or prodrug thereof, as claimed in any one of claims 1 to 25.

27. A pharmaceutical composition comprising a compound, or a pharmaceutically acceptable salt and / or solvate and / or prodrug thereof, as claimed in any one of claims 1 to 25, or an antibody-drug conjugate as claimed in claim 26, and a pharmaceutically acceptable excipient.

28. A compound, or a pharmaceutically acceptable salt and / or solvate and / or prodrug thereof, as claimed in any one of claims 1 to 25, or an antibody-drug conjugate as claimed in claim 26, or a pharmaceutical composition as claimed in claim 27, for use in medicine 29. A compound, or a pharmaceutically acceptable salt and / or solvate and / or prodrug thereof, as claimed in any one of claims 1 to 25, or an antibody-drug conjugate as claimed in claim 26, or a pharmaceutical composition as claimed in claim 27, for use in treating cancer.

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