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WO2025008453A1 - 2-(1h-indol-4-yl)methyl)-isoindoline derivatives as factor b inhibitors - Google Patents

2-(1h-indol-4-yl)methyl)-isoindoline derivatives as factor b inhibitors Download PDF

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Publication number
WO2025008453A1
WO2025008453A1 PCT/EP2024/068846 EP2024068846W WO2025008453A1 WO 2025008453 A1 WO2025008453 A1 WO 2025008453A1 EP 2024068846 W EP2024068846 W EP 2024068846W WO 2025008453 A1 WO2025008453 A1 WO 2025008453A1
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group
groups
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fluoro
independently selected
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French (fr)
Inventor
John Andrew Christopher
Paul Graham Wyatt
Arnaud Cyrille MATHIEU
Thomas William HORNSBY
Martin Edward Cooper
Mark Mills
Klara Abdul HUSSAIN
Christopher Edward Blunt
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Sitala Bio Ltd
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Sitala Bio Ltd
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Priority claimed from GBGB2310221.3A external-priority patent/GB202310221D0/en
Priority claimed from GBGB2316973.3A external-priority patent/GB202316973D0/en
Priority claimed from GBGB2403997.6A external-priority patent/GB202403997D0/en
Application filed by Sitala Bio Ltd filed Critical Sitala Bio Ltd
Publication of WO2025008453A1 publication Critical patent/WO2025008453A1/en
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure

Definitions

  • the present invention relates to compounds possessing an indole moiety linked to an isoindoline moiety, to compounds having similar core structures, and to associated salts, solvates, prodrugs and pharmaceutical compositions.
  • the present invention further relates to methods of synthesising such compounds, and to the use of such compounds in the treatment and prevention of medical disorders and diseases, most especially by Factor B inhibition.
  • Background of the Invention The complement system is a critical part of the innate immune system and serves to help the body fight against infection from pathogens, ultimately leading to inflammation and phagocytic removal of pathogens or foreign particles.
  • the complement system is comprised of multiple proteins, including zymogens which undergo proteolytic cleavage to become activated and facilitate the activation of further zymogens in the cascade.
  • the proteins may be zymogens or proteins without potential for enzymatic activity that change conformation revealing binding sites for other components of the system. These successive enzymatic cleavages lead to a large, amplified response and many regulatory components exist in this system to prevent uncontrolled activation.
  • the complement system can be activated via three pathways: classical, lectin, and alternative.
  • the classical pathway is triggered by antigen:antibody complexes and connects the innate to the adaptive immune system.
  • the lectin pathway is triggered directly by the pathogen when serum protein mannan-binding lectin, collectins or ficolins bind to bacterial or viral mannose-containing carbohydrates.
  • the alternative pathway (also known as the alternate pathway) is initiated by activation of the central complement component, C3, either through spontaneous hydrolysis or enzymatic cleavage.
  • the alternative pathway also serves as a critical amplification loop of all three pathways of complement activation.
  • C3 convertase which cleaves and activates further C3 molecules to promote: 1) opsonization of pathogens so they can be engulfed by phagocytes that recognise key receptors, 2) the recruitment of inflammatory cells by generating chemoattractants at the site of activation, and 3) formation of the C5 convertase resulting in production of C5a and C5b, the latter of which induces direct killing of pathogens by assembling terminal complement components to create membrane attack complex (MAC) pores in the membrane of bacteria or other target cells (Janeway, C. A. Jr.
  • MAC membrane attack complex
  • Factor B can bind to the active forms of C3: C3(H2O) and C3b, generating the proenzyme C3bB (or C3(H2O)B), a target for activation by Factor D.
  • C3(H2O) and C3b Upon cleavage by Factor D, two fragments are generated: Ba and Bb (Schwaeble, W. J., Ali, Y. M., and Sim, R. B., (2020) Chapter 14 - The Roles and Contributions of the Complement System in the Pathophysiology of Autoimmune Diseases, in The Autoimmune Diseases (Sixth Edition) (Rose, N. R., and Mackay, I. R. eds.), Academic Press).
  • C5 convertase cleaves C5 to generate the anaphylatoxin C5a, and C5b which serves as a platform for the formation of the membrane attack complex.
  • Dysregulation of the alternative complement pathway due to genetics or the presence of autoantibodies can lead to many different diseases.
  • Inhibition of Factor B is therefore a key therapeutic target for modulation of the alternative pathway and hence the treatment of numerous diseases, disorders and conditions.
  • Iptacopan LNP023
  • Iptacopan is highly selective for Factor B, showing no inhibition of Factor D or the classical or lectin complement pathways. Also, no significant effects have been observed in a broad assay panel of receptors, ion channels, kinases, and proteases (Schubart, A. et al, Proc. Natl. Acad. Sci. U.S.A.2019, 116, 7926-7931).
  • 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.
  • hydrocarbyl groups include alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl and aryl groups/moieties and combinations of all of these groups/moieties.
  • a hydrocarbyl group is a C1-C20 hydrocarbyl group. More typically a hydrocarbyl group is a C 1 -C 15 hydrocarbyl group. More typically a hydrocarbyl group is a C 1 -C 10 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.
  • alkyl groups/moieties include methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl and n-pentyl groups/moieties.
  • alkyl does not include “cycloalkyl”.
  • an alkyl group is a C 1 -C 12 alkyl group. More typically an alkyl group is a C 1 -C 6 alkyl group.
  • An “alkylene” group is similarly defined as a divalent alkyl group.
  • 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.
  • 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”.
  • an alkenyl group is a C 2 -C 12 alkenyl group. More typically an alkenyl group is a C 2 -C 6 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.
  • an alkynyl group is a C2-C12 alkynyl group.
  • 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.
  • a bicyclic or polycyclic group or moiety is “saturated” it is to be understood that all of the ring systems within the bicyclic or polycyclic group or moiety (excluding any ring systems which are part of or formed by optional substituents) are saturated.
  • 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.
  • 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.
  • non-aromatic heterocyclic groups such as azetinyl, azetidinyl, oxetanyl, thietanyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothiophenyl, pyrazolidinyl, imidazo
  • 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.
  • 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.
  • 5- or 6-membered heteroaryl groups include furanyl, thiophenyl, pyrrolyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, furazanyl, oxadiazolyl, thiadiazolyl, tetrazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl and triazinyl groups.
  • 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.
  • 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 ⁇ -bonded substituent; - any sulphur atom may optionally be substituted with one or two of any specified ⁇ -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.
  • 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.
  • any divalent bridging substituent e.g. -O-, -S-, -NH-, -CH2-, -CH2-CH2-, etc.
  • an optionally substituted group or moiety e.g. R 1
  • R 2 a second group or moiety
  • halo includes fluoro, chloro, bromo and iodo.
  • halo such as a haloalkyl or halomethyl group
  • the group in question is substituted with one or more halo groups independently selected from fluoro, chloro, bromo and iodo.
  • 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.
  • 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.
  • 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.
  • any reference to an element is to be considered a reference to all isotopes of that element.
  • any reference to hydrogen is considered to encompass all isotopes of hydrogen including deuterium and tritium.
  • any reference to a compound or group is to be considered a reference to all tautomers of that compound or group.
  • methoxy, dimethylamino and aminoethyl groups are considered to be hydrocarbyl groups including one or more heteroatoms N, O or S in their carbon skeleton.
  • 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.
  • a Cx-Cy group is defined as a group containing from x to y carbon atoms.
  • a C 1 -C 4 alkyl group is defined as an alkyl group containing from 1 to 4 carbon atoms.
  • optional substituents are not taken into account when calculating the total number of carbon atoms in the parent group substituted with the optional substituents.
  • replacement heteroatoms e.g. N, O or S
  • a morpholinyl group is to be considered a C4 heterocyclic group, not a C6 heterocyclic group.
  • R 2 is selected from hydrogen or a halo group.
  • R 2 is selected from hydrogen or a fluoro, chloro or bromo group. Most typically, R 2 is hydrogen.
  • R 3 is selected from hydrogen or a halo (e.g. fluoro, chloro or bromo), -R 30 , -CN, -CHO, -COR 30 , -CO 2 H or -CO 2 R 30 group, wherein R 30 is selected from a C 1 -C 6 alkyl, C 1 -C 6 fluoroalkyl, C 2 -C 6 alkenyl, C 2 -C 6 fluoroalkenyl or -R 31 group, wherein R 31 is a 3- to 6-membered monocyclic group, wherein the 3- to 6- membered monocyclic group may optionally be substituted with one or more halo (e.g.
  • each R 32 is independently selected from a methyl or a fluoromethyl group, provided that the group R 3 , including any optional substituents, contains no more than 8 carbon atoms.
  • R 3 is selected from hydrogen or a fluoro, chloro, bromo, -R 30 , -CN, -CHO, -COR 30 , -CO2H or -CO2R 30 group, wherein R 30 is selected from a C 1 -C 4 alkyl, C 1 -C 4 fluoroalkyl or -R 31 group, wherein R 31 is selected from a C 3 -C 6 cycloalkyl group, a 4- to 6-membered saturated heterocyclic group, or a phenyl or a 5- or 6-membered heteroaryl group, wherein the C3-C6 cycloalkyl group and the 4- to 6- membered saturated heterocyclic group may optionally be substituted with one or more fluoro groups and/or with one or two groups R 32 , and wherein the phenyl or the 5- or 6- membered heteroaryl group may optionally be substituted with one or more fluoro, chloro and/or bromo groups
  • R 3 is selected from hydrogen or a fluoro, chloro, bromo, -R 30 , -R 31 , -CN, -CHO, -COR 30 , -CO2H or -CO2R 30 group, wherein R 30 is selected from a methyl or fluoromethyl group, and wherein R 31 is a 5-membered heteroaryl group, wherein the 5-membered heteroaryl group may optionally be substituted with one or more fluoro, chloro and/or bromo groups, and/or with one or two groups R 32 .
  • R 3 is selected from hydrogen or a halo (e.g.
  • R 30 is selected from a C 1 -C 4 alkyl, C 3 -C 4 cycloalkyl, C 1 -C 4 fluoroalkyl or C 3 -C 4 fluorocycloalkyl group.
  • R 3 is selected from hydrogen or a fluoro, chloro, bromo -R 30 , -CN, -CHO, -COR 30 , -CO2H or -CO2R 30 group, wherein R 30 is selected from a methyl or fluoromethyl group.
  • R 3 is selected from hydrogen or a halo (e.g. fluoro, chloro or bromo), -CN, C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl or C3-C4 fluorocycloalkyl group.
  • R 3 is selected from hydrogen or a fluoro, chloro, bromo, -CN or methyl group, wherein the methyl group may optionally be fluoro substituted. More typically, R 3 is selected from hydrogen or a fluoro, chloro or bromo group. Most typically, R 3 is hydrogen.
  • the hydrocarbylene group, including any optional substituents contains no more than four carbon atoms.
  • the total number of nitrogen, oxygen and sulphur atoms in any hydrocarbylene group (including any optional substituents) formed by R 3 and R 7 is no more than three. More typically, the total number of nitrogen, oxygen and sulphur atoms in any hydrocarbylene group (including any optional substituents) formed by R 3 and R 7 is no more than two.
  • R 3 and R 7 together form a C 1 -C 4 saturated or unsaturated hydrocarbylene group, wherein the hydrocarbylene group may be straight- chained or branched, or be or include a cyclic group, wherein the hydrocarbylene group may optionally be substituted with one or more fluoro, chloro and/or bromo groups, and wherein the hydrocarbylene group may optionally include one or two heteroatoms each independently selected from N and O in its carbon skeleton, provided that the atom of the hydrocarbylene group that is directly attached to the carbon atom to which R 8 is attached is a carbon atom.
  • R 3 and R 7 together form a hydrocarbylene group
  • the hydrocarbylene group has a chain length of from 1 to 3 atoms. More typically, the hydrocarbylene group has a chain length of 1 or 2 atoms.
  • 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.
  • structure (C) has a chain length between A and B of 3 atoms
  • structure (D) has a chain length between A and B of 5 atoms:
  • R 3 and R 7 together form a hydrocarbylene group
  • R 8 is selected from hydrogen or a fluoro, C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl or C3-C4 fluorocycloalkyl group. More typically, where R 3 and R 7 together form a hydrocarbylene group, R 8 is selected from hydrogen or a fluoro, methyl or fluoromethyl group. More typically still, where R 3 and R 7 together form a hydrocarbylene group, R 8 is hydrogen.
  • R 4 is selected from hydrogen or a fluoro, chloro, bromo, -OH, -NH 2 , -SO 2 NH 2 , -SO 2 -R 40 or -R 40 group, wherein R 40 is selected from a C 1 - C6 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 fluoro, chloro and/or bromo groups, and wherein the hydrocarbyl group may optionally include one, two or three heteroatoms each independently selected from N and O in its carbon skeleton.
  • R 4 is selected from a fluoro, chloro, bromo, -OH, -OR 41 , -N(R 42 )2, -SO2-R 41 , -SO2-N(R 42 )2, -L 4 -OH, -L 4 -OR 41 , -L 4 -N(R 42 )2, -L 4 -SO2-R 41 , -L 4 -SO2-N(R 42 )2, -O-L 4 -OH, -O-L 4 -OR 41 , -O-L 4 -N(R 42 )2, -O-L 4 -SO2-R 41 , -O-L 4 -SO 2 -N(R 42 ) 2 , -NR 43 -L 4 -OH, -NR 43 -L 4 -OR 41 , -NR 43 -L 4 -N(R 42 ) 2 , -NR 43 -L 4 -OH, -NR 43 -L 4 -OR
  • R 4 is selected from a fluoro, chloro, bromo, -OH, -OR 41 , -N(R 42 )2, -SO2-R 41 , -SO2-N(R 42 )2, -L 4 -OH, -L 4 -OR 41 , -L 4 -N(R 42 )2, -L 4 -SO2-R 41 , -L 4 -SO2-N(R 42 )2, -O-L 4 -OH, -O-L 4 -OR 41 , -O-L 4 -N(R 42 )2, -O-L 4 -SO2-R 41 , -O-L 4 -SO 2 -N(R 42 ) 2 , -NR 43 -L 4 -OH, -NR 43 -L 4 -OR 41 , -NR 43 -L 4 -N(R 42 ) 2 , -NR 43 -L 4 -OH, -NR 43 -L 4 -OR
  • R 4 may be a chloro group, or a -R 44 group such as a cyclopropyl group, or a -OR 41 group such as a -OMe or -OCHF2 group.
  • R 4 including any optional substituents, contains no more than 6 carbon atoms.
  • the total number of nitrogen, oxygen and sulphur atoms in R 4 is no more than four. More typically, the total number of nitrogen, oxygen and sulphur atoms in R 4 , including any optional substituents, is no more than three.
  • R 4 is selected from a fluoro, chloro, bromo, -OH, -OR 44 , -N(R 42 )2, -COOH, -COOR 44 , -CON(R 42 )2, -SO2-R 44 , -SO2-N(R 42 )2, -O-L 4 -OH, -O-L 4 -OR 44 , -O-L 4 -N(R 42 )2, -NR 43 -L 4 -OH, -NR 43 -L 4 -OR 44 , -NR 43 -L 4 -N(R 42 )2, or -R 44 group, wherein: each R 42 is independently selected from hydrogen or a -R 44 group; R 43 is selected from hydrogen or a -R 44 group; each R 44 is independently selected from a C 1 -C 4 alkyl or C 3 -C 6 cycloalkyl group, wherein the C1-C4 alkyl or C3-C
  • R 4 is selected from a fluoro, chloro, bromo, -OR 44 , -CON(R 42 ) 2 , -SO 2 -R 44 , -SO 2 -N(R 42 ) 2 , -O-CH 2 -CH 2 -OR 44 , -O-CH 2 -CH 2 -N(R 42 ) 2 , or -R 44 group.
  • R 4 is selected from a fluoro, chloro, bromo, -OR 44 , -CON(R 42 )2, -SO2-R 44 , -O-CH2-CH2-OR 44 , -O-CH2-CH2-N(R 42 )2, or -R 44 group.
  • each R 44 is independently selected from a C1-C4 alkyl or C3-C6 cycloalkyl group, wherein the C1-C4 alkyl or C3-C6 cycloalkyl group may optionally be substituted with one or more fluoro groups.
  • each R 44 is independently selected from a C 1 -C 3 alkyl, cyclopropyl, C 1 -C 3 fluoroalkyl or fluorocyclopropyl group.
  • R 4 is selected from a fluoro, chloro, bromo, -OR 44 -SO 2 -R 44 , -SO 2 -N(R 42 ) 2 , -O-CH 2 -CH 2 -N(R 42 ) 2 , or -R 44 group. More typically still, R 4 is selected from a fluoro, chloro, bromo, -R 44 or -OR 44 group.
  • R 44 is selected from a C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group. Yet more typically, R 4 is selected from a fluoro, chloro, bromo, methyl (Me) or -OMe group, wherein any methyl group may optionally be fluoro substituted. More typically still, R 4 is selected from a methyl (Me) or -OMe group, wherein any methyl group may optionally be fluoro substituted.
  • the hydrocarbylene group, including any optional substituents contains no more than four carbon atoms.
  • the total number of nitrogen, oxygen and sulphur atoms in any hydrocarbylene group (including any optional substituents) formed by R 4 and R 7 is no more than three. More typically, the total number of nitrogen, oxygen and sulphur atoms in any hydrocarbylene group (including any optional substituents) formed by R 4 and R 7 is no more than two.
  • R 4 and R 7 together form a C1-C4 saturated or unsaturated hydrocarbylene group, wherein the hydrocarbylene group may be straight- chained or branched, or be or include a cyclic group, wherein the hydrocarbylene group may optionally be substituted with one or more fluoro, chloro and/or bromo groups, and wherein the hydrocarbylene group may optionally include one or two heteroatoms each independently selected from N and O in its carbon skeleton, provided that the atom of the hydrocarbylene group that is directly attached to the carbon atom to which R 8 is attached is a carbon atom.
  • R 4 and R 7 together form a hydrocarbylene group
  • the hydrocarbylene group has a chain length of from 2 to 4 atoms. More typically, the hydrocarbylene group has a chain length of 2 or 3 atoms. More typically, where R 4 and R 7 together form a hydrocarbylene group, the hydrocarbylene group is selected from -CH 2 -CH 2 -, -CH 2 -O-, -O-CH 2 -, -CH 2 -CH 2 -CH 2 -, -O-CH 2 -CH 2 -, -CH 2 -CH 2 -O- or -CH 2 -O-CH 2 -, provided that the atom of the hydrocarbylene group that is directly attached to the carbon atom to which R 8 is attached is a carbon atom.
  • R 8 is selected from hydrogen or a fluoro, C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl or C3-C4 fluorocycloalkyl group. More typically, where R 4 and R 7 together form a hydrocarbylene group, R 8 is selected from hydrogen or a fluoro, methyl or fluoromethyl group. More typically still, where R 4 and R 7 together form a hydrocarbylene group, R 8 is hydrogen. As stated in accordance with both the first and the second aspects of the invention, R 5 is selected from hydrogen or a halo group.
  • R 5 is selected from hydrogen or a fluoro, chloro or bromo group. More typically, R 5 is selected from hydrogen or a fluoro group. Most typically, R 5 is hydrogen.
  • R 6 is selected from hydrogen or a halo, -R 60 or -OR 60 group, wherein R 60 is selected from a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl or C3-C4 fluorocycloalkyl group. More typically, R 6 is selected from a fluoro, chloro, bromo, -R 60 or -OR 60 group.
  • R 6 is selected from a chloro, bromo, -R 60 or -OR 60 group. Yet more typically, R 6 is selected from a -R 60 or -OR 60 group.
  • R 60 is selected from a C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group.
  • R 6 may be selected from a -R 60 or -OR 60 group, and R 60 may be selected from a C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group.
  • R 60 is selected from a methyl, fluoromethyl, ethyl or fluoroethyl group. More typically still, R 60 is selected from a methyl or fluoromethyl group.
  • R 6 is a chloro, bromo, methyl or a fluoromethyl group. Typically in such an embodiment, R 6 is a methyl or a fluoromethyl group. More typically, R 6 is a methyl group.
  • R 7 and R 8 are each independently selected from hydrogen or a fluoro or a C1-C6 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 fluoro, chloro and/or bromo groups, and wherein the hydrocarbyl group may optionally include one, two or three heteroatoms each independently selected from N and O in its carbon skeleton, provided that the atom of any hydrocarbyl group of R 7 or R 8 that is directly attached to the reminder of the molecule is a carbon atom.
  • R 7 may be selected from hydrogen or a fluoro or a C 1 -C 6 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 fluoro, chloro and/or bromo groups, and wherein the hydrocarbyl group may optionally include one, two or three heteroatoms each independently selected from N and O in its carbon skeleton, provided that the atom of any hydrocarbyl group of R 7 that is directly attached to the reminder of the molecule is a carbon atom, and R 8 may be selected from hydrogen or a fluoro, methyl or fluoromethyl group.
  • R 7 and R 8 are each independently selected from hydrogen or a fluoro, -CN, -COOH, -COOR 71 , -CO-N(R 72 ) 2 , -L 7 -COOH, -L 7 -COOR 71 , -L 7 -CO-N(R 72 ) 2 , -L 7 -OH, -L 7 -OR 71 , -L 7 -N(R 72 )2, -R 73 , -R 74 or -L 7 -R 74 group, wherein: each R 71 is independently selected from a -R 73 or -R 74 group; each R 72 is independently selected from hydrogen or a -R 73 or -R 74 group, or any two R 72 may, together with the nitrogen atom to which they are attached, form a 3- to 6- membered saturated monocyclic heterocyclic group, wherein the 3- to 6-membered saturated monocyclic heterocyclic group may optionally be substitute
  • any R 7 or R 8 group, including any optional substituents contains no more than 10 carbon atoms.
  • R 7 and R 8 are each independently selected from hydrogen or a fluoro, -CN, -COOH, -COOR 71 , -L 7 -COOH, -L 7 -COOR 71 , -L 7 -OH, -L 7 -OR 71 , -L 7 -N(R 72 )2, -R 73 , -R 74 or -L 7 -R 74 group, provided that any R 7 or R 8 group, including any optional substituents, contains no more than 8 carbon atoms, and that each atom of R 7 or R 8 that is directly attached to the reminder of the molecule is a carbon, hydrogen or fluorine atom.
  • R 7 is selected from hydrogen or a fluoro, -CN, -COOH, -COOR 71 , -CO-N(R 72 ) 2 , -L 7 -COOH, -L 7 -COOR 71 , -L 7 -CO-N(R 72 ) 2 -L 7 -OH, -L 7 -OR 71 , -L 7 -N(R 72 ) 2 , -R 73 , -R 74 or -L 7 -R 74 group, provided that R 7 , including any optional substituents, contains no more than 12 carbon atoms, and that the atom of R 7 that is directly attached to the reminder of the molecule is a carbon, hydrogen or fluorine atom, and R 8 is selected from a hydrogen or a fluoro, methyl or fluoromethyl group.
  • R 7 contains no more than 10 carbon atoms. More typically, R 7 is selected from hydrogen or a fluoro, -CN, -COOH, -COOR 71 , -L 7 -COOH, -L 7 -COOR 71 , -L 7 -OH, -L 7 -OR 71 , -L 7 -N(R 72 ) 2 , -R 73 , -R 74 or -L 7 -R 74 group, provided that R 7 , including any optional substituents, contains no more than 8 carbon atoms, and that the atom of R 7 that is directly attached to the reminder of the molecule is a carbon, hydrogen or fluorine atom, and R 8 is selected from a hydrogen or a fluoro, methyl or fluoromethyl group.
  • L 7 may be seen as a straight-chained alkylene group substituted with two R L7 groups, wherein the two R L7 together form a -CH2CH2-, -CH2- or -CF2- group respectively, such that the two R L7 and the carbon atom or atoms to which they are attached together form a cyclopropyl or fluorocyclopropyl group.
  • L 7 may be seen as a straight-chained alkylene group substituted with a single R L7 group, wherein the R L7 and one R 72 group together form a -CH 2 CH 2 - or -CH 2 CH 2 CH 2 - group respectively, such that the R L7 and the R 72 together with the atoms of the -L 7 -N(R 72 )2 group to which they are attached together form a saturated 5- or 6- membered monocyclic heterocyclic group.
  • R 7 is selected from hydrogen or a fluoro, -CN, -COOH, -L 7 -COOH, -L 7 -OH, -L 7 -OR 71 , -L 7 -N(R 72 )2, -R 73 , -R 74 or -L 7 -R 74 group
  • R 8 is selected from a hydrogen or a fluoro, methyl or fluoromethyl group.
  • any R 7 or R 8 group, including any optional substituents contains no more than 6 carbon atoms.
  • the total number of nitrogen, oxygen and sulphur atoms in any R 7 or R 8 group, including any optional substituents is no more than four.
  • R 7 and R 8 are each independently selected from hydrogen or a fluoro, -COOH, -COOR 75 , -CONH2, -CONHR 75 , -CON(R 75 )2, -L 71 -COOH, -L 71 -COOR 75 , -L 71 -CONH2, -L 71 -CONHR 75 , -L 71 -CON(R 75 )2, -L 71 -OH, -L 71 -OR 75 or -R 75 group, wherein: -L 71 - moiety may optionally be fluoro substituted; and each R 75 is independently selected from a C1-C4 alkyl, C2-C4 alkenyl, cyclopropyl, cyclobutyl, C1-C4 fluoroalkyl
  • R 7 is selected from from hydrogen or a fluoro, -COOH, -COOR 75 , -CONH 2 , -CONHR 75 , -CON(R 75 ) 2 , -L 71 -COOH, -L 71 -COOR 75 , -L 71 -CONH2, -L 71 -CONHR 75 , -L 71 -CON(R 75 )2, -L 71 -OH, -L 71 -OR 75 or -R 75 group, and R 8 is selected from a hydrogen or a fluoro, methyl or fluoromethyl group. More typically, R 8 is hydrogen.
  • R 7 is selected from from hydrogen or a fluoro, -COOH, -COOR 75 , -CONH2, -CONHR 75 , -CON(R 75 )2, -L 71 -COOH, -L 71 -COOR 75 , -L 71 -CONH2, -L 71 -CONHR 75 , -L 71 -CON(R 75 )2, -L 71 -OH, -L 71 -OR 75 or -R 75 group
  • R 7 (including any optional substituents) contains no more than 10 carbon atoms.
  • R 7 and R 8 are each independently selected from hydrogen or a fluoro, -COOH, -COOR 75 , -L 71 -COOH, -L 71 -COOR 75 , -L 71 -OH, -L 71 -OR 75 or -R 75 group, wherein: each -L 71 - is independently selected from a , -CHMe-, -CMe2-, -CH2-CH2-, -CH2-CHMe-, -CH2-CMe2-, -CHMe-CH2-, -CHMe-CHMe-, -CHMe-CMe2-, -CMe2-CH2-, -CMe2-CHMe- or -CMe2-CMe2- group, wherein any -L 71 - moiety may optionally be fluoro substituted; and each R 75 is independently selected from a C 1 -C 4 alkyl, C 2 -C 4 alkenyl, cyclopropy
  • R 7 is selected from hydrogen or a fluoro, -COOH, -COOR 75 , -L 71 -COOH, -L 71 -COOR 75 , -L 71 -OH, -L 71 -OR 75 or -R 75 group
  • R 8 is selected from a hydrogen or a fluoro, methyl or fluoromethyl group.
  • each -L 71 - is independently selected from a -CH2-, -CHMe-, -CMe2-, -CH2-CH2-, -CH2-CHMe-, -CH2-CMe2-, -CHMe-CH2-, -CHMe-CHMe-, -CHMe-CMe2-, -CMe2-CH2-, -CMe2-CHMe- or -CMe2-CMe2- group, wherein any -CH2-, -CHMe- or -CMe2- group may optionally be fluoro substituted.
  • each -L 71 - is independently selected from a -CH 2 -, -CHMe-, -CMe 2 -, -CH2-CH2-, -CH2-CHMe-, -CH2-CMe2-, -CHMe-CH2-, -CHMe-CHMe- or -CMe2-CH2- group, wherein any -CH2-, -CHMe- or -CMe2- group may optionally be fluoro substituted.
  • R 7 including any optional substituents contains no more than 6 carbon atoms
  • R 8 is selected from a hydrogen or a fluoro, methyl or fluoromethyl group.
  • R 7 including any optional substituents contains no more than 5 carbon atoms
  • R 8 is selected from a hydrogen or a fluoro, methyl or fluoromethyl group.
  • R 7 and R 8 are each independently selected from hydrogen or a fluoro, -L 71 -COOH, -L 71 -COOR 75 , -L 71 -OH, -L 71 -OR 75 or -R 75 group, wherein: each -L 71 - is independently selected from a -CH2-, -CHMe- or -CMe2- group, wherein any -CH2-, -CHMe- or -CMe2- group may optionally be fluoro substituted; and each R 75 is independently selected from a C 1 -C 3 alkyl, cyclopropyl, C 1 -C 3 fluoroalkyl or fluorocyclopropyl group.
  • R 7 is selected from hydrogen or a fluoro, -L 71 -COOH, -L 71 -COOR 75 , -L 71 -OH, -L 71 -OR 75 or -R 75 group
  • R 8 is selected from a hydrogen or a fluoro, methyl or fluoromethyl group.
  • R 7 is selected from hydrogen or a -L 71 -COOH, -L 71 -COOR 75 or -R 75 group
  • R 8 is hydrogen.
  • R 7 and R 8 are each independently selected from hydrogen or a fluoro, methyl or fluoromethyl group.
  • R 7 may be selected from hydrogen or a fluoro, methyl or fluoromethyl group
  • R 8 may be hydrogen or a fluoro group.
  • at least one of R 7 and R 8 is hydrogen.
  • R 8 is hydrogen.
  • R 7 and R 8 are both hydrogen.
  • -L 78 - is selected from a -CH2-CH2-, -
  • X 10 is N or CR 10
  • X 11 is N or CR 11
  • X 12 is N or CR 12
  • X 13 is N or CR 13 , such that no more than two of X 10 , X 11 , X 12 and X 13 are N.
  • no more than one of X 10 , X 11 , X 12 and X 13 is N.
  • X 11 is CR 11 and X 12 is CR 12
  • X 11 is CR 11 and X 12 is N
  • X 11 is N and X 12 is CR 12 .
  • X 11 is CR 11 and X 12 is CR 12 , or X 11 is N and X 12 is CR 12 .
  • X 10 is N or CR 10
  • X 11 is CR 11
  • X 12 is CR 12 and X 13 is N or CR 13 .
  • no more than one of X 10 and X 13 is N.
  • X 10 is N
  • X 11 is CR 11
  • X 10 is CR 10
  • X 11 is CR 11
  • X 12 is CR 12 and X 13 is CR 13 .
  • each R 10 , R 11 , R 12 and R 13 is independently selected from hydrogen or a halo (e.g. fluoro, chloro or bromo), -OH, -SH, -NH2, -SO2NH2, or a C1-C10 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 (e.g.
  • each R 10 , R 11 , R 12 and R 13 is independently selected from hydrogen or a halo, -OH, -NH2 or a C1-C8 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 groups, and wherein the hydrocarbyl group may optionally include one, two or three heteroatoms each independently selected from N and O in its carbon skeleton.
  • each R 10 , R 11 , R 12 and R 13 is independently selected from hydrogen or a halo, -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.
  • X 11 is CR 11 and X 12 is CR 12
  • X 11 is CR 11 and X 12 is N
  • X 11 is N and X 12 is CR 12
  • one remaining R 10 , R 11 , R 12 or R 13 may be independently selected from hydrogen or a fluoro, chloro or bromo group, or a -R 131 , -OH, -SH, -OR 131 , -SR 131 , -N(R 132 )2, -SO2-R 131 , -SO2-N(R 132 )2, -L 13 -OH, -L 13 -SH, -L 13 -OR 131 , -L 13 -SR 131 , -L 13 -N(R 132 )2, -L 13 -SO2-R 131 , -L 13 -SO2-N(R 132 )2, -O-L 13 -OH, -O-L 13 -SH, -O-L 13 -OR 131 , -O-L 13 -SR 131 , -O-L 13 -N(R 132 )2, -O-L 13 -OH, -
  • the monocyclic group may be saturated or unsaturated.
  • any two R L13 may, together with the atom or atoms to which they are attached, form a phenyl group or a 5- or 6-membered heteroaryl group, wherein phenyl group or the 5- or 6-membered heteroaryl group may optionally be substituted with one or two -OH groups, and/or with one or more fluoro, methyl and/or fluoromethyl groups.
  • any R L13 and any R 131 , or any two R 131 may, together with the atom or atoms to which they are attached, form a 5-membered heteroaryl group, wherein the 5- membered heteroaryl group may optionally be substituted with one or two -OH groups, and/or with one or more fluoro, methyl and/or fluoromethyl groups.
  • any two R L13 and any R 131 , or any three R L13 and any R 131 , or any two R L13 and any two R 131 together with the atoms to which they are attached, form a 6- to 10-membered bicyclic heterocyclic group
  • the 6- to 10-membered bicyclic heterocyclic group may be saturated or unsaturated.
  • any two R L13 and any R 131 may, together with the atoms to which they are attached, form a fused 8- to 10-membered bicyclic heteroaryl group, wherein the fused 8- to 10-membered bicyclic heteroaryl group may optionally be substituted with one or two -OH groups, and/or with one or more fluoro, methyl and/or fluoromethyl groups.
  • R 10 , R 11 , R 12 or R 13 is independently selected from hydrogen or a fluoro, chloro or bromo group, or a -R 131 , -OH, -SH, -OR 131 , -SR 131 , -N(R 132 )2, -SO2-R 131 , -SO2-N(R 132 )2, -L 13 -OH, -L 13 -SH, -L 13 -OR 131 , -L 13 -SR 131 , -L 13 -N(R 132 )2, -L 13 -SO 2 -R 131 , -L 13 -SO 2 -N(R 132 ) 2 , -O-L 13 -OH, -O-L 13 -SH, -O-L 13 -OR 131 , -O-L 13 -SR 131 , -O-L 13 -N(R 132 )2, -O-L 13 -OH
  • said group, including any optional substituents contains no more than 8 carbon atoms.
  • the total number of nitrogen, oxygen and sulphur atoms in said group, including any optional substituents is no more than six. More typically, the total number of nitrogen, oxygen and sulphur atoms in said group, including any optional substituents, is no more than four, or no more than three.
  • X 10 is N or CR 10
  • X 11 is CR 11
  • X 12 is CR 12
  • X 13 is N or CR 13
  • no more than one of X 10 and X 13 is N.
  • the other of R 11 and R 12 is selected from hydrogen or a fluoro, chloro, bromo, -OH, -NH 2 , methyl (Me), ethyl (Et), -OMe, -NHMe, -NMe2, -CH2OH or -CH2NH2 group, wherein any methyl (Me), ethyl (Et) or methylene (-CH2-) group of R 11 or R 12 may optionally be fluoro substituted.
  • one of R 11 and R 12 is selected from a chloro, bromo, fluoromethyl, methoxy, fluoromethoxy, -CH 2 OH or -CN group and the other of R 11 and R 12 is selected from hydrogen or a fluoro, chloro or bromo group. More typically, one of R 11 and R 12 is selected from a chloro, bromo, methoxy, fluoromethoxy or -CN group and the other of R 11 and R 12 is selected from hydrogen or a fluoro, chloro or bromo group. More typically still, one of R 11 and R 12 is a -CN group and the other of R 11 and R 12 is selected from hydrogen or a fluoro, chloro or bromo group.
  • each remaining R 10 , R 11 , R 12 and R 13 is independently selected from hydrogen or a fluoro, chloro, bromo, -OH, -NH 2 , methyl (Me), ethyl (Et), -OMe, -NHMe, -NMe 2 , -CH2OH or -CH2NH2 group, wherein any methyl (Me), ethyl (Et) or methylene (-CH2-) group of R 10 , R 11 , R 12 or R 13 may optionally be fluoro substituted.
  • R 10 , R 11 , R 12 or R 13 is independently selected from hydrogen or a fluoro, chloro, bromo, -OH, -NH 2 , methyl (Me), ethyl (Et), -OMe, -NHMe, -NMe 2 , -CH2OH or -CH2NH2 group, wherein any methyl (Me), ethyl (Et) or methylene (-CH2-) group of R 10 , R 11 , R 12 or R 13 may optionally be fluoro substituted, and each further remaining R 10 , R 11 , R 12 or R 13 is independently selected from hydrogen or a fluoro, chloro or bromo group.
  • R 10 or R 13 may be selected from hydrogen or a fluoro, chloro, bromo, -OH, -NH 2 , methyl (Me), ethyl (Et), -OMe, -NHMe, -NMe 2 , -CH 2 OH or -CH 2 NH 2 group, wherein any methyl (Me), ethyl (Et) or methylene (-CH 2 -) group of R 10 or R 13 may optionally be fluoro substituted, and each remaining R 10 , R 11 , R 12 or R 13 may be independently selected from hydrogen or a fluoro, chloro or bromo group.
  • X 10 is N or CR 10
  • X 11 is CR 11
  • X 12 is CR 12
  • X 13 is N or CR 13
  • no more than one of X 10 and X 13 is N
  • the other of R 11 and R 12 is selected from hydrogen or a fluoro, chloro, bromo, -OH, -NH2, methyl (Me), ethyl (Et), -OMe, -NHMe, -NMe 2 , -CH 2 OH or -CH 2 NH 2 group
  • R 10 and R 13 are each independently selected from hydrogen or a fluoro, chloro, bromo, -OH, -NH2, methyl (Me), ethyl (Et), -OMe, -
  • one of R 10 and R 13 is selected from hydrogen or a fluoro, chloro, bromo, -OH, -NH2, methyl (Me), ethyl (Et), -OMe, -NHMe, -NMe2, -CH2OH or -CH2NH2 group, wherein any methyl (Me), ethyl (Et) or methylene (-CH 2 -) group of R 10 or R 13 may optionally be fluoro substituted, and if present the other of R 10 and R 13 is selected from hydrogen or a fluoro, chloro or bromo group.
  • each R 10 and R 13 is independently selected from hydrogen or a fluoro, chloro or bromo group.
  • X 10 is N or CR 10
  • X 11 is CR 11
  • X 12 is CR 12
  • X 13 is N or CR 13
  • R 10 is selected from hydrogen or a fluoro, chloro, bromo, methyl or fluoromethyl group
  • R 11 is selected from a chloro, bromo, fluoromethyl, methoxy, fluoromethoxy, -CH 2 OH or -CN group
  • R 12 is selected from hydrogen or a fluoro, chloro or bromo group
  • R 13 is selected from hydrogen or a fluoro, chloro, bromo, methyl or fluoromethyl group.
  • X 10 is N or CR 10
  • X 11 is CR 11
  • X 12 is CR 12 and X 13 CR 13
  • R 11 is selected from a chloro, bromo, methoxy, fluoromethoxy, -CH 2 OH or -CN group. More typically, R 11 is selected from a chloro, bromo, methoxy, fluoromethoxy or -CN group. Most typically, R 11 is a -CN group, i.e. X 11 is C-CN.
  • at least one of X 10 , X 12 and X 13 is C-H. More typically, at least two of X 10 , X 12 and X 13 are C-H.
  • X 10 is N, C-H, C-F, C-Cl or C-Br
  • X 11 is C-H, C-F, C-Cl or C-Br
  • X 12 is C-CN and
  • X 13 is N, C-H, C-F, C-Cl or C-Br, provided that no more than one of X 10 and X 13 is N.
  • X 10 is N, C-H, C-F, C-Cl or C-Br
  • X 11 is C-CN
  • X 12 is C-H, C- F, C-Cl or C-Br
  • X 13 is N, C-H, C-F, C-Cl or C-Br, provided that no more than one of X 10 and X 13 is N.
  • each R 14 and R 15 is independently selected from hydrogen or a C1- C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl or C3-C4 fluorocycloalkyl group.
  • R 14 may be hydrogen and R 15 may be selected from hydrogen or a C 1 -C 4 alkyl, C 3 -C 4 cycloalkyl, C 1 -C 4 fluoroalkyl or C 3 -C 4 fluorocycloalkyl group.
  • each R 14 and R 15 is independently selected from hydrogen or a C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group.
  • R 14 may be hydrogen and R 15 may be selected from hydrogen or a C 1 -C 3 alkyl, cyclopropyl, C 1 -C 3 fluoroalkyl or fluorocyclopropyl group.
  • each R 14 and R 15 is independently selected from hydrogen or a methyl or fluoromethyl group.
  • R 14 may be hydrogen and R 15 may be selected from hydrogen or a methyl or fluoromethyl group.
  • R 14 and R 15 are both hydrogen.
  • R 14 and R 15 together with the carbon atom to which they are attached may form a cyclopropyl or a cyclobutyl group, wherein the cyclopropyl or cyclobutyl group may optionally be substituted with one or more fluoro groups.
  • R 16 is selected from hydrogen or a fluoro, -R 160 , -CN, -CHO, -COR 160 , -CO2H or -CO2R 160 group, wherein R 160 is selected from a C1-C4 alkyl, C1-C4 fluoroalkyl or -R 161 group, wherein R 161 is selected from a C3-C6 cycloalkyl group, a 4- to 6- membered saturated heterocyclic group, or a phenyl or a 5- or 6-membered heteroaryl group, wherein the C 3 -C 6 cycloalkyl group and the 4- to 6-membered saturated heterocyclic group may optionally be substituted with one or more fluoro groups and/or with one or two groups R 162 , and wherein the phenyl or the 5- or 6-membered heteroaryl group may optionally be substituted with one or more fluoro, chloro and/or bromo groups, and/or with one
  • R 16 is selected from hydrogen or a fluoro, -R 160 , -R 161 , -CN, -CHO, -COR 160 , -CO 2 H or -CO 2 R 160 group, wherein R 160 is selected from a methyl or fluoromethyl group, and wherein R 161 is a 5-membered heteroaryl group, wherein the 5-membered heteroaryl group may optionally be substituted with one or more fluoro, chloro and/or bromo groups, and/or with one or two groups R 162 .
  • R 17 is selected from hydrogen or a fluoro, C 1 -C 4 alkyl, C 3 - C4 cycloalkyl, C1-C4 fluoroalkyl or C3-C4 fluorocycloalkyl group. More typically, R 17 is selected from hydrogen or a fluoro, C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group. Most typically, R 17 is hydrogen.
  • R 16 is selected from hydrogen or a fluoro, -R 160 , -CN, -CHO, -COR 160 , -CO2H or -CO2R 160 group, wherein R 160 is selected from a C1-C4 alkyl, C 3 -C 4 cycloalkyl, C 1 -C 4 fluoroalkyl or C 3 -C 4 fluorocycloalkyl group, and R 17 is selected from hydrogen or a fluoro, C 1 -C 4 alkyl, C 3 -C 4 cycloalkyl, C 1 -C 4 fluoroalkyl or C 3 - C4 fluorocycloalkyl group.
  • R 17 is selected from hydrogen or a fluoro, C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group.
  • R 16 may be selected from hydrogen or a fluoro, -R 160 , -CN, -CHO, -COR 160 , -CO 2 H or -CO 2 R 160 group, and R 17 may be hydrogen.
  • R 160 is selected from a C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group. More typically in such an aspect, R 160 is selected from a methyl or fluoromethyl group.
  • R 16 is selected from hydrogen or a fluoro, -CN, C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl or C3-C4 fluorocycloalkyl group
  • R 17 is selected from hydrogen or a fluoro, C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl or C3-C4 fluorocycloalkyl group.
  • R 16 may be selected from hydrogen or a fluoro, -CN, C 1 -C 4 alkyl, C 3 -C 4 cycloalkyl, C 1 -C 4 fluoroalkyl or C 3 -C 4 fluorocycloalkyl group, and R 17 may be hydrogen.
  • R 16 is selected from hydrogen or a fluoro, -CN, C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group
  • R 17 is selected from hydrogen or a fluoro, C1-C3 alkyl, cyclopropyl, C 1 -C 3 fluoroalkyl or fluorocyclopropyl group.
  • R 16 may be selected from hydrogen or a fluoro, -CN, C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group
  • R 17 may be hydrogen.
  • each R 16 and R 17 is independently selected from hydrogen or a methyl or fluoromethyl group.
  • R 16 may be selected from hydrogen or a methyl or fluoromethyl group and R 17 may be hydrogen.
  • R 16 and R 17 are both hydrogen.
  • R 16 and R 17 together with the carbon atom to which they are attached may form a cyclopropyl or a cyclobutyl group, wherein the cyclopropyl or cyclobutyl group may optionally be substituted with one or more fluoro groups.
  • R 16 is selected from hydrogen or a fluoro, -CN, C 1 -C 3 alkyl, cyclopropyl, C 1 -C 3 fluoroalkyl or fluorocyclopropyl group
  • R 17 is selected from hydrogen or a fluoro, C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group
  • R 16 and R 17 together with the carbon atom to which they are attached form a cyclopropyl or a cyclobutyl group, wherein the cyclopropyl or cyclobutyl group may optionally be substituted with one or more fluoro groups.
  • the hydrocarbylene group, including any optional substituents contains no more than four carbon atoms.
  • the total number of nitrogen, oxygen and sulphur atoms in any hydrocarbylene group (including any optional substituents) formed by R 17 and R 7 is no more than three. More typically, the total number of nitrogen, oxygen and sulphur atoms in any hydrocarbylene group (including any optional substituents) formed by R 17 and R 7 is no more than two.
  • R 17 and R 7 together form a C1-C4 saturated or unsaturated hydrocarbylene group, wherein the hydrocarbylene group may be straight- chained or branched, or be or include a cyclic group, wherein the hydrocarbylene group may optionally be substituted with one or more halo groups, and wherein the hydrocarbylene group may optionally include one or two heteroatoms each independently selected from N and O in its carbon skeleton, provided that the atom of the hydrocarbylene group that is directly attached to the carbon atom to which R 8 is attached is a carbon atom.
  • R 17 and R 7 together form a hydrocarbylene group typically the hydrocarbylene group has a chain length of from 1 to 3 atoms.
  • R 8 is selected from hydrogen or a fluoro, C 1 -C 4 alkyl, C 3 -C 4 cycloalkyl, C 1 -C 4 fluoroalkyl or C 3 -C 4 fluorocycloalkyl group. More typically, where R 17 and R 7 together form a hydrocarbylene group, R 8 is selected from hydrogen or a fluoro, methyl or fluoromethyl group. More typically still, where R 17 and R 7 together form a hydrocarbylene group, R 8 is hydrogen.
  • R 16 is selected from hydrogen or a fluoro, -CN, C 1 -C 4 alkyl, C 3 -C 4 cycloalkyl, C 1 -C 4 fluoroalkyl or C 3 -C 4 fluorocycloalkyl group. More typically, where R 17 and R 7 together form a hydrocarbylene group, R 16 is selected from hydrogen or a fluoro, -CN, C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group.
  • R 16 is selected from hydrogen or a methyl or fluoromethyl group. Yet more typically, where R 17 and R 7 together form a hydrocarbylene group, R 16 is hydrogen.
  • R 18 and R 19 are each independently selected from hydrogen or a fluoro or a C 1 -C 7 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 fluoro, chloro and/or bromo groups, and wherein the hydrocarbyl group may optionally include one, two or three heteroatoms each independently selected from N and O in its carbon skeleton, provided that the atom of any hydrocarbyl group of R 18 or R 19 that is directly attached to the reminder of the molecule is a carbon atom.
  • R 18 may be selected from hydrogen or a fluoro or a C1-C7 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 fluoro, chloro and/or bromo groups, and wherein the hydrocarbyl group may optionally include one, two or three heteroatoms each independently selected from N and O in its carbon skeleton, provided that the atom of any hydrocarbyl group of R 18 that is directly attached to the reminder of the molecule is a carbon atom, and R 19 may be selected from hydrogen or a fluoro, methyl or fluoromethyl group.
  • R 18 and R 19 are each independently selected from hydrogen or a fluoro, -CN, -COOH, -COOR 181 , -CO-N(R 182 )2, -L 18 -COOH, -L 18 -COOR 181 , -L 18 -CO-N(R 182 ) 2 , -L 18 -OH, -L 18 -OR 181 , -L 18 -N(R 182 ) 2 , -R 183 , -R 184 or -L 18 -R 184 group, wherein: each R 181 is independently selected from a -R 183 or -R 184 group; each R 182 is independently selected from hydrogen or a -R 183 or -R 184 group, or any two R 182 may, together with the nitrogen atom to which they are attached, form a 3- to 6-membered saturated monocyclic heterocyclic group, wherein the 3- to 6- membered saturated monocyclic heterocyclic group
  • any R 18 or R 19 group contains no more than 10 carbon atoms.
  • R 18 and R 19 are each independently selected from hydrogen or a fluoro, -CN, -COOH, -COOR 181 , -L 18 -COOH, -L 18 -COOR 181 , -L 18 -OH, -L 18 -OR 181 , -L 18 -N(R 182 )2, -R 183 , -R 184 or -L 18 -R 184 group, provided that any R 18 or R 19 group, including any optional substituents, contains no more than 8 carbon atoms, and that each atom of R 18 or R 19 that is directly attached to the reminder of the molecule is a carbon, hydrogen or fluorine atom.
  • R 18 is selected from hydrogen or a fluoro, -CN, -COOH, -COOR 181 , -CO-N(R 182 ) 2 , -L 18 -COOH, -L 18 -COOR 181 , -L 18 -CO-N(R 182 ) 2 , -L 18 -OH, -L 18 -OR 181 , -L 18 -N(R 182 )2, -R 183 , -R 184 or -L 18 -R 184 group, provided that R 18 , including any optional substituents, contains no more than 12 carbon atoms, and that the atom of R 18 that is directly attached to the reminder of the molecule is a carbon, hydrogen or fluorine atom, and R 19 is selected from a hydrogen or a fluoro, methyl or fluoromethyl group.
  • R 18 contains no more than 10 carbon atoms. More typically, R 18 is selected from hydrogen or a fluoro, -CN, -COOH, -COOR 181 , -L 18 -COOH, -L 18 -COOR 181 , -L 18 -OH, -L 18 -OR 181 , -L 18 -N(R 182 )2, -R 183 , -R 184 or -L 18 -R 184 group, provided that R 18 , including any optional substituents, contains no more than 8 carbon atoms, and that the atom of R 18 that is directly attached to the reminder of the molecule is a carbon, hydrogen or fluorine atom, and R 19 is selected from a hydrogen or a fluoro, methyl or fluoromethyl group In one aspect of such an embodiment: R 18 and R 19 are each independently selected from hydrogen or a fluoro, -CN, -COOH,
  • R 18 is selected from hydrogen or a fluoro, -CN, -COOH, -L 18 -COOH, -L 18 -OH, -L 18 -OR 181 , -L 18 -N(R 182 )2, -R 183 , -R 184 or -L 18 -R 184 group, and R 19 is selected from a hydrogen or a fluoro, methyl or fluoromethyl group.
  • each L 18 is independently selected from a straight-chained alkylene, alkenylene or alkynylene group, wherein the straight-chained alkylene, alkenylene or alkynylene group optionally includes one or two heteroatoms each independently selected from O and N in its carbon skeleton, wherein the straight-chained alkylene, alkenylene or alkynylene group has a chain length of from 1 to 4 atoms, and wherein the straight- chained alkylene, alkenylene or alkynylene group may
  • any R 18 or R 19 group, including any optional substituents contains no more than 7 carbon atoms.
  • the total number of nitrogen, oxygen and sulphur atoms in any R 18 or R 19 group, including any optional substituents is no more than four. More typically, the total number of nitrogen, oxygen and sulphur atoms in any R 18 or R 19 group, including any optional substituents, is no more than three.
  • R 18 and R 19 are each independently selected from hydrogen or a fluoro or a -R 183 group.
  • each R 183 is independently selected from a C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 fluoroalkyl or C3-C6 fluorocycloalkyl group. More typically, R 18 and R 19 are each independently selected from hydrogen or a fluoro, methyl or fluoromethyl group. In one embodiment, at least one of R 18 and R 19 is hydrogen. In a further embodiment, R 18 and R 19 are both hydrogen.
  • -L 89 - is selected from a -CH
  • R 20 and R 21 are each independently selected from hydrogen or a fluoro group.
  • R 20 and R 21 are both hydrogen.
  • the compound of Formula (I) is not: .
  • a compound of Formula (I) as defined above wherein: R 1 is hydrogen; R 2 is selected from hydrogen or a halo group; R 3 is selected from hydrogen or a halo, -SO2NH2, or a C1-C8 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 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 may optionally be substituted with one or two groups each independently selected from o
  • R 1 is hydrogen
  • R 5 is selected from hydrogen or a halo group
  • R 6 is selected from hydrogen or a halo group
  • R 1 is hydrogen
  • R 2 is selected from hydrogen or a fluoro, chloro or bromo group
  • R 3 is selected from hydrogen or a fluoro, chloro, bromo, -R 30 , -CN, -CHO, -COR 30 , -CO2H or -CO2R 30 group, provided that R 3 , including any optional substituents, contains no more than 8 carbon atoms
  • R 30 is selected from a C 1 -C 6 alkyl, C 1 -C 6 fluoroalkyl, C 2 -C 6 alkenyl, C 2 -C 6 fluoroalkenyl or -R 31 group
  • R 31 is a 3- to 6-membered monocyclic group, wherein the 3- to 6-membered monocyclic group may optionally be substituted with one or more fluoro, chloro and/or bromo groups, and/or with one or two groups
  • R 32 is selected from a C 1 -C 6 alkyl, C 1 -C
  • R 30 is selected from a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl or C3-C4 fluorocycloalkyl group;
  • R 4 is selected from a fluoro, chloro, bromo, -OH, -OR 41 , -N(R 42 )2, -SO2-R 41 , -SO2-N(R 42 )2, -L 4 -OH, -L 4 -OR 41 , -L 4 -N(R 42 )2, -L 4 -SO2-R 41 , -L 4 -SO2-N(R 42 )2, -O-L 4 -OH, -O-L 4 -OR 41 , -O-L 4 -N(R 42 )2, -O-L 4 -OH, -O-L 4 -OR 41 , -O-L 4 -N(R 42 )2, -O-L 4 -SO
  • R 30 is selected from a C 1 -C 4 alkyl, C 3 -C 4 cycloalkyl, C 1 -C 4 fluoroalkyl or C 3 -C 4 fluorocycloalkyl group;
  • R 4 is selected from a fluoro, chloro, bromo, -OH, -OR 41 , -N(R 42 )2, -SO2-R 41 , -SO 2 -N(R 42 ) 2 , -L 4 -OH, -L 4 -OR 41 , -L 4 -N(R 42 ) 2 , -L 4 -SO 2 -R 41 , -L 4 -SO 2 -N(R 42 ) 2 , -O-L 4 -OH, -O-L 4 -OR 41 , -O-L 4 -N(R 42 ) 2 , -O-L 4 -OR 41 , -O-L 4 -N(R 42 ) 2
  • R 1 is hydrogen
  • R 4 is selected from a fluoro, chloro, bromo, -OH, -OR 41 , -N(R 42 ) 2 , -SO 2 -R 41 , -SO2-N(R 42 )2, -L 4 -OH, -L 4 -OR 41 , -L 4 -N(R 42 )2, -L 4 -SO2-R 41 , -L 4 -SO2-N(R 42 )2, -O-L 4 -OH, -O-L 4 -OR 41 , -O-L 4 -N(R 42 )2, -O-L 4 -SO2-R 41 , -O-L 4 -SO2-R 41 , -O-L 4 -SO2-N(R 42 )2, -NR 43 -L 4 -OH, -NR 43 -L 4 -OR 41 , -NR 43 -L 4 -OH, -NR 43 -L 4 -
  • R 4 is selected from a fluoro, chloro, bromo, -OH, -OR 41 , -N(R 42 ) 2 , -SO 2 -R 41 , -SO 2 -N(R 42 ) 2 , -L 4 -OH, -L 4 -OR 41 , -L 4 -N(R 42 ) 2 , -L 4 -SO 2 -R 41 , -L 4 -SO 2 -N(R 42 ) 2 , -O-L 4 -OH, -O-L 4 -OR 41 , -O-L 4 -N(R 42 )2, -O-L 4 -SO2-R 41 , -O-L 4 -SO2-N(R 42 )2, -NR 43 -L 4 -OH, -NR 43 -L 4 -OR 41 , -NR 43 -L 4 -OH, -NR 43 -L 4 -OR 41 , -NR 43
  • R 4 is selected from a fluoro, chloro, bromo, -OH, -OR 41 , -N(R 42 )2, -SO2-R 41 , -SO2-N(R 42 )2, -L 4 -OH, -L 4 -OR 41 , -L 4 -N(R 42 )2, -L 4 -SO2-R 41 , -L 4 -SO2-N(R 42 )2, -O-L 4 -OH, -O-L 4 -OR 41 , -O-L 4 -N(R 42 ) 2 , -O-L 4 -SO 2 -R 41 , -O-L 4 -SO 2 -N(R 42 ) 2 , -NR 43 -L 4 -OH, -NR 43 -L 4 -OR 41 , -NR 43 -L 4 -N(R 42 )2, -NR 43 -L 4 -SO2-
  • R 1 is hydrogen
  • R 2 is selected from hydrogen or a fluoro, chloro or bromo group
  • R 3 is selected from hydrogen or a fluoro, chloro, bromo, -R 30 , -CN, -CHO, -COR 30 , -CO2H or -CO2R 30 group, wherein R 30 is selected from a C1-C4 alkyl, C3-C4 cycloalkyl, C 1 -C 4 fluoroalkyl or C 3 -C 4 fluorocycloalkyl group;
  • R 4 is selected from a fluoro, chloro, bromo, -OH, -OR 41 , -N(R 42 ) 2 , -SO 2 -R 41 , -SO2-N(R 42 )2, -L 4 -OH, -L 4 -OR 41 , -L 4 -N(R 42 )
  • R 3 is selected from hydrogen or a fluoro, chloro, bromo, -CN or methyl group, wherein the methyl group may optionally be fluoro substituted
  • R 7 is selected from hydrogen or a fluoro, -CN, -COOH, -L 7 -COOH, -L 7 -OH, -L 7 -OR 71 , -L 7 -N(R 72 ) 2 , -R 73 , -R 74 or -L 7 -R 74 group, provided that R 7 , including any optional substituents, contains no more than 8 carbon atoms, and that the atom of R 7 that is directly attached to the reminder of the molecule is a carbon, hydrogen or fluorine atom; each R 73 is independently selected from a C 1 -C 4 alkyl or C 3 -C 6 cycloalkyl group, wherein the C 1 -C 4 alkyl or C 3 -C 6 cycloal
  • R 1 is hydrogen
  • R 4 is selected from a fluoro, chloro, bromo, -OH, -OR 41 , -N(R 42 )2, -SO2-R 41 , -SO2-N(R 42 )2, -L 4 -OH, -L 4 -OR 41 , -L 4 -N(R 42 )2, -L 4 -SO2-R 41 , -L 4 -SO2-N(R 42 )2, -O-L 4 -OH, -O-L 4 -OR 41 , -O-L 4 -N(R 42 ) 2 , -O-L 4 -SO 2 -R 41 , -O-L 4 -SO 2 -N(R 42 ) 2 , -NR 43 -L 4 -OH, -NR 43 -L 4 -OR 41 , -NR 43 -L 4 -OH, -NR 43 -L 4 -OR 41 , -NR 43 -
  • R 18 and R 19 are both hydrogen.
  • R 1 is hydrogen;
  • R 4 is selected from a fluoro, chloro, bromo, -R 44 or -OR 44 group;
  • R 44 is selected from a C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group;
  • R 5 is hydrogen;
  • R 6 is a methyl or a fluoromethyl group;
  • R 7 is selected from hydrogen or a fluoro, -L 71 -COOH, -L 71 -COOR 75 , -L 71 -OH, -L 71 -OR 75 or -R 75 group;
  • -L 71 - is selected from a -CH2-, -CHMe- or -CMe2- group, wherein any -CH2-, -CHMe- or
  • R 18 and R 19 are both hydrogen.
  • the compound of formula (I) or formula (II) has a molecular weight of from 248 to 750 Da.
  • the compound of formula (I) or formula (II) has a molecular weight of from 260 to 600 Da, or from 260 to 500 Da. More typically, the compound of formula (I) or formula (II) has a molecular weight of from 280 to 400 Da.
  • a third aspect of the invention provides a compound selected from the group consisting of:
  • a fourth aspect of the invention provides a pharmaceutically acceptable salt and/or solvate and/or prodrug of any compound of the first, second or third aspect of the invention.
  • the fourth aspect of the invention provides a pharmaceutically acceptable salt and/or solvate of any compound of the first, second or third aspect of the invention.
  • the fourth aspect of the invention may provide (i) a pharmaceutically acceptable salt of any compound of the first, second or third aspect of the invention, or (ii) a pharmaceutically acceptable solvate of any compound of the first, second or third aspect of the invention, or (iii) a pharmaceutically acceptable solvate of a pharmaceutically acceptable salt of any compound of the first, second or third 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.
  • a “salt” of a compound of the present invention includes an acid addition salt.
  • Acid addition salts are preferably pharmaceutically acceptable, non-toxic addition salts with suitable acids, including but not limited to inorganic acids such as hydrohalogenic acids (for example, hydrofluoric, hydrochloric, hydrobromic or hydroiodic acid) or other inorganic acids (for example, nitric, perchloric, sulfuric or phosphoric acid); or organic acids such as organic carboxylic acids (for example, propionic, butyric, glycolic, lactic, mandelic, citric, acetic, benzoic, salicylic, succinic, malic or hydroxysuccinic, tartaric, fumaric, maleic, hydroxymaleic, mucic or galactaric, gluconic, pantothenic or pamoic acid), organic sulfonic acids (for example, methanesulfonic, trifluoromethanesulfonic, ethanesulfonic, 2-hydroxyethanesulfonic, benzenesulfonic, toluene-p-
  • 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.
  • 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.
  • 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.
  • 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.
  • any salt is a pharmaceutically acceptable non-toxic salt.
  • 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.
  • a hydrate e.g. a hemihydrate, monohydrate, dihydrate or trihydrate
  • Such other solvates may be formed with common organic solvents, including but not limited to, alcoholic solvents e.g. methanol, ethanol or isopropanol.
  • the fourth aspect of the invention provides a prodrug of any compound of the first, second or third aspect of the invention.
  • the fourth aspect of the invention may provide a pharmaceutically acceptable salt and/or solvate of such a prodrug.
  • the fourth 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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 1 H 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.
  • 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 to 12 C, 13 C, 1 H, 2 H (D), 14 N, 15 N, 16 O, 17 O, 18 O, 19 F and 127 I, and any radioisotope including, but not limited to 11 C, 14 C, 3 H (T), 13 N, 15 O, 18 F, 123 I, 124 I, 125 I and 131 I.
  • the compounds, salts, solvates and prodrugs of the present invention may be in any polymorphic or amorphous form.
  • Beneficial or desired clinical results include, but are not limited to, the alleviation of symptoms, the prevention of symptoms, the diminishment of extent of disease, the stabilisation (i.e., not worsening) of a condition, the delay or slowing of progression/worsening of a condition/symptom, the amelioration or palliation of a condition/symptom, and remission (whether partial or total), whether detectable or undetectable.
  • the term “palliation”, and variations thereof, as used herein, means that the extent and/or undesirable manifestations of a physiological condition or symptom are lessened and/or time course of the progression is slowed or lengthened, as compared to not administering a compound, salt, solvate, prodrug or pharmaceutical composition of the present invention.
  • prevention 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.
  • prevention includes both the avoidance of occurrence of the disease, disorder or condition, and the delay in onset of the disease, disorder or condition. Any statistically significant (p ⁇ 0.05) avoidance of occurrence, delay in onset or reduction in risk as measured by a controlled clinical trial may be deemed a prevention of the disease, disorder or condition.
  • Subjects amenable to prevention include those at heightened risk of a disease, disorder or condition as identified by genetic or biochemical markers.
  • a seventh aspect of the invention provides the use of a compound of the first, second or third aspect, or a pharmaceutically effective salt, solvate or prodrug of the fourth aspect, in the manufacture of a medicament for the treatment or prevention of a disease, disorder or condition.
  • the treatment or prevention comprises the administration of the compound, salt, solvate, prodrug 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, second or third aspect, or a pharmaceutically acceptable salt, solvate or prodrug of the fourth aspect, or a pharmaceutical composition of the fifth aspect, to thereby treat or prevent the disease, disorder or condition.
  • the complement system is not the primary trigger of disease but acts secondarily to other disease-causing triggers to set up a vicious cycle of inflammation that is propagated by the complement system.
  • inhibition of the complement system can bring about a treatment effect.
  • gain of function Complement C3 and/or Factor B mutations, and/or the loss of function in the regulatory proteins eventuate in uncontrolled C3 activation (Garred, P., Tenner, A. J., and Mollnes, T. E. Pharmacol. Rev.2021, 73, 792-827).
  • common polymorphisms or rare mutations can lead to distinctive phenotypes due to specific impact on function, such as the ability to bind membranes.
  • Some genetic changes result in proteins with altered ability to bind to certain structures (such as glycosaminoglycans or disease-associated epitopes), resulting in tissue-specific diseases.
  • the domain in which the mutation or polymorphism resides can impact disease phenotype.
  • a ninth aspect of the invention provides a compound of the first, second or third aspect of the invention, or a pharmaceutically acceptable salt, solvate or prodrug 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 disease, disorder or condition in an individual, wherein the individual has a germline or somatic mutation in Complement C3 or Factor B, or a germline or somatic mutation in a regulator of the alternate pathway, or a germline or somatic mutation in an enzyme that directly or indirectly causes the production or activation of Factor B.
  • the mutation may be, for example, a gain-of-function or other mutation of Factor B resulting in increased Factor B or C3/C5 convertase activity.
  • the mutation may be a gain-of-function or other mutation of Complement C3 resulting in increased Factor B or C3/C5 convertase activity.
  • the mutation may be a loss of function in a negative regulator (such as Factor H) resulting in increased alternate pathway activity, a gain of function in a positive regulator (such as properdin) resulting in increased alternate pathway activity, or a gain of function in an enzyme that causes the production or activation of Factor B.
  • a negative regulator such as Factor H
  • a gain of function in a positive regulator such as properdin
  • the use comprises the administration of the compound, salt, solvate, prodrug or pharmaceutical composition to the individual.
  • the use may also comprise the diagnosis of an individual having a germline or somatic mutation in (i) Complement C3, (ii) Factor B, (iii) a regulator of the alternate pathway, or (iv) an enzyme that directly or indirectly causes the production or activation of Factor B, wherein the compound, salt, solvate, prodrug or pharmaceutical composition is administered to an individual on the basis of a positive diagnosis for the mutation.
  • identification of the mutation in Complement C3, Factor B, the regulator or the enzyme in the individual may be by any suitable genetic or biochemical means.
  • a tenth aspect of the invention provides the use of a compound of the first, second or third aspect of the invention, or a pharmaceutically acceptable salt, solvate or prodrug of the fourth aspect of the invention, in the manufacture of a medicament for the treatment or prevention of a disease, disorder or condition in an individual, wherein the individual has a germline or somatic mutation in Complement C3 or Factor B, or a germline or somatic mutation in a regulator of the alternate pathway, or a germline or somatic mutation in an enzyme that directly or indirectly causes the production or activation of Factor B.
  • the mutation may be, for example, a gain-of-function or other mutation of Factor B resulting in increased Factor B or C3/C5 convertase activity.
  • the mutation may be a gain-of-function or other mutation of Complement C3 resulting in increased Factor B or C3/C5 convertase activity.
  • the mutation may be a loss of function in a negative regulator (such as Factor H) resulting in increased alternate pathway activity, a gain of function in a positive regulator (such as properdin) resulting in increased alternate pathway activity, or a gain of function in an enzyme that causes the production or activation of Factor B.
  • the treatment or prevention comprises the administration of the compound, salt, solvate, prodrug or medicament to the individual.
  • the treatment or prevention may also comprise the diagnosis of an individual having a germline or somatic mutation in (i) Complement C3, (ii) Factor B, (iii) a regulator of the alternate pathway, or (iv) an enzyme that directly or indirectly causes the production or activation of Factor B, wherein the compound, salt, solvate, prodrug or medicament is administered to an individual on the basis of a positive diagnosis for the mutation.
  • identification of the mutation in Complement C3, Factor B, the regulator or the enzyme in the individual may be by any suitable genetic or biochemical means.
  • An eleventh aspect of the invention provides a method of treatment or prevention of a disease, disorder or condition, the method comprising the steps of diagnosing of an individual having a germline or somatic mutation in (i) Complement C3, (ii) Factor B, (iii) a regulator of the alternate pathway, or (iv) an enzyme that directly or indirectly causes the production or activation of Factor B, and administering an effective amount of a compound of the first, second or third aspect of the invention, or a pharmaceutically acceptable salt, solvate or prodrug of the fourth aspect of the invention, or a pharmaceutical composition of the fifth aspect of the invention, to the positively diagnosed individual, to thereby treat or prevent the disease, disorder or condition.
  • the administration is to a subject in need thereof.
  • the disease, disorder or condition may be a disease, disorder or condition of the immune system, the cardiovascular system, the renal system, the respiratory system, the central nervous system, the reproductive system, the ocular system, the metabolic system, the haematological system, may be a cancer or other malignancy, and/or may be caused by or associated with a pathogen.
  • these general embodiments defined according to broad categories of diseases, disorders and conditions are not mutually exclusive.
  • any particular disease, disorder or condition may be categorized according to more than one of the above general embodiments.
  • a non-limiting example is type I diabetes which is an autoimmune disease and a disease of the endocrine system.
  • the disease, disorder or condition is responsive to Factor B inhibition.
  • Factor B inhibition refers to the complete or partial reduction in the level of activity of Factor B, either unbound or in complex with C3b/C3(H 2 O), and includes, for example, (i) the inhibition of active Factor B or Bb, (ii) the inhibition of latent Factor B (the zymogen) and/or (iii) the inhibition of the conversion of latent Factor B into active Factor B.
  • a number of ocular conditions have been shown to involve Factor B including, in particular, age-related macular degeneration (Schramm, E. C.
  • Factor B has also been implicated in a number of central nervous system conditions including ischemic stroke (Turek-Jakubowska, A. et al, J. Clin. Med.2022, 11, 339; and Elvington, A. et al, J. Immunol.2012, 189(9), 4640-4647), traumatic brain injury (Lindblad, C. et al, Crit. Care 2021, 25, 103; Mallah, K. et al, Acta Neuropathol. Commun.2021, 9(1), 72; and Alawieh, A. et al, J. Neurosci.2018, 38(10), 2519-2532), spinal cord injury (Baldan-Martin, M. et al, Adv.
  • ischemic stroke Turek-Jakubowska, A. et al, J. Clin. Med.2022, 11, 339; and Elvington, A. et al, J. Immunol.2012, 189(9), 4640-4647
  • IDP idiopathic thrombocytopenic purpura
  • PNH paroxysmal nocturnal hemoglobinuria
  • Factor B has been implicated in the pathogenesis of various cancers, including pancreatic cancer (Shimazaki, R. et al, Cell Oncol.2021, 44, 937-950), photocarcinogenesis (Byrne, S. N. et al, Photochem. Photobiol. Sci.2015, 14, 801-806), breast cancer (Suman, S. et al, J. Proteomics 2016, 148, 183-193), gastro-oesophageal cancer (Wu, C.
  • C3 glomerulopathy including dense deposit disease and C3 glomerulonephritis
  • FSGS focal segmental glomerulosclerosis
  • Factor B has been suggested to have a role in a number of metabolic conditions, including diabetes related conditions including, in particular, gestational diabetes (Shen, Y. et al, Gynecol. Endocrinol.2022, 38, 158-163), cardiometabolic disease (Coan, P. M. et al, Hypertension, 2017, 70, 624-633), diabetic macular oedema and diabetic retinopathy as discussed above, diabetic kidney disease (Lu, Q. et al, JCI Insight 2021, 6, e147716), and metabolic disorders including diet-induced steatosis and dyslipidemia (Sadana, P. et al, Int. J. Mol. Sci.2020, 21, 7472).
  • diabetes related conditions including, in particular, gestational diabetes (Shen, Y. et al, Gynecol. Endocrinol.2022, 38, 158-163), cardiometabolic disease (Coan, P. M. et al, Hyper
  • Factor B has been linked to infertility (Sim, Y. J., Ryu, A. R., and Lee, M. Y. Biotechnol. Appl. Biochem.2022, 69, 289-295), inflammation during pregnancy (Livson, S. et al, Front. Immunol.2022, 13, 925630), spontaneous preterm birth (Lynch, A. M. et al, Am. J. Obstet. Gynecol.2008, 199, 354.e1-8), pregnancy loss in antiphospholipid syndrome (Breen, K. A. et al, Thromb. Haemost. 2012, 107(3), 423-429; Salmon, J. E.
  • Factor B has also been linked to several pathogenic diseases, including dengue- associated DHF (dengue hemorrhagic fever) and DSS (dengue shock syndrome) (Cabezas-Falcon, S. et al, J. Gen. Virol.2021, 102, 001547; and Dalrymple, N. A. et al, J. Virol.2012, 86(12), 6408-6415), hyper-inflammatory complications of severe sepsis (Li, D. et al, Crit. Care Med.2016, 44, e289-299; and Zou, L.
  • DHF dengue hemorrhagic fever
  • DSS dengue shock syndrome
  • Nephrol.2020, 31, 829-840 Other diseases, disorders or conditions in which Factor B has been implicated or shown to be involved include: - liver diseases including chronic hepatitis B (Chen, H. et al, Aliment. Pharmacol. Ther.2020, 51, 469-478; Seo, T. Y. et al, BMC Med. Genet.2020, 21(1), 241; and Jiang, D-K. et al, Hepatology, 2015, 62(1), 118-128), acute alcohol-associated hepatitis (Fan, X. et al, Hepatology 2021, 73, 983-997) and large duct biliary obstruction and viral hepatitis (Potter, B. J.
  • any of the diseases, disorders or conditions listed above may be treated or prevented in accordance with the sixth, seventh, eighth, ninth, tenth or eleventh aspect of the present invention.
  • the disease, disorder or condition is selected from: (i) an ocular disease, disorder or condition; (ii) a haematological disease, disorder or condition; (iii) a renal disease, disorder or condition; (iv) a cancer; or (v) an auto-immune disease, disorder or condition.
  • the disease, disorder or condition is selected from: (i) acute kidney injury; (ii) age-related macular degeneration; (iii) airway hyperresponsiveness with inflammation; (iv) Alzheimer’s disease; (v) amyotrophic lateral sclerosis; (vi) ANCA vasculitis; (vii) antiphospholipid syndrome; (viii) aortic stenosis; (ix) atypical hemolytic uremic syndrome; (x) acquired partial lipodystrophy; (xi) acquired thrombotic thrombocytopenic purpura; (xii) bullous pemphigoid; (xiii) C3 glomerulopathy; (xiv) immune complex-mediated membranoproliferative glomerulonephritis (IC- MPGN) (xv) cardiac ischemia and reperfusion; (xvi) cardiac remodelling; (xvii) cardiometabolic disease; (xviii) coeliac disease; (xix) cold agglutinin disease
  • diseases, disorders or conditions which may be responsive to Factor B inhibition and which may be treated or prevented in accordance with sixth, seventh, eighth, ninth, tenth or eleventh aspect of the present invention are listed above.
  • some of the diseases, disorders or conditions mentioned above arise due to mutations in (i) Complement C3, (ii) Factor B, (iii) a direct or indirect regulator of Factor B, or (iv) an enzyme that directly or indirectly causes the production or activation of Factor B.
  • Such mutations may give rise to an increase in alternative pathway activity which may be effectively treated by Factor B inhibition.
  • a twelfth aspect of the invention provides a method of inhibiting Factor B, the method comprising the use of a compound of the first, second or third aspect of the invention, or a pharmaceutically acceptable salt, solvate or prodrug of the fourth aspect of the invention, or a pharmaceutical composition of the fifth aspect of the invention, to inhibit Factor B.
  • the method is performed ex vivo or in vitro, for example in order to analyse the effect on cells of Factor B inhibition.
  • the method is not a method of treatment of the human or animal body.
  • the method is performed in vivo.
  • the method may comprise the step of administering an effective amount of a compound of the first, second or third aspect, or a pharmaceutically acceptable salt, solvate or prodrug of the fourth aspect, or a pharmaceutical composition of the fifth aspect, to thereby inhibit Factor B.
  • the administration is to a subject in need thereof.
  • the method of the twelfth aspect of the invention may be a method of inhibiting Factor B in a non-human animal subject, the method comprising the steps of administering the compound, salt, solvate, prodrug or pharmaceutical composition to the non-human animal subject and optionally subsequently mutilating or sacrificing the non-human animal subject.
  • a method further comprises the step of analysing one or more tissue or fluid samples from the optionally mutilated or sacrificed non-human animal subject.
  • a thirteen aspect of the invention provides a compound of the first, second or third aspect of the invention, or a pharmaceutically acceptable salt, solvate or prodrug of the fourth aspect of the invention, or a pharmaceutical composition of the fifth aspect, for use in the inhibition of Factor B.
  • the use comprises the administration of the compound, salt, solvate, prodrug or pharmaceutical composition to a subject.
  • a fourteenth aspect of the invention provides the use of a compound of the first, second or third aspect of the invention, or a pharmaceutically acceptable salt, solvate or prodrug of the fourth aspect of the invention, in the manufacture of a medicament for the inhibition of Factor B.
  • the inhibition comprises the administration of the compound, salt, solvate, prodrug or medicament to a subject.
  • the subject may be any human or other animal.
  • 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.
  • parenteral including intravenous, subcutaneous, intramuscular, intradermal, intratracheal, intraperitoneal, intraarticular, intracranial and epidural
  • airway (aerosol) airway
  • rectal rectal
  • vaginal, ocular or topical including transdermal, buccal, mucosal, sublingual and topical
  • the compounds, salts, solvates or prodrugs 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.
  • the compounds, salts, solvates or prodrugs of the present invention will generally be provided in a sterile aqueous solution or suspension, buffered to an appropriate pH and isotonicity.
  • Suitable aqueous vehicles include Ringer’s solution and isotonic sodium chloride or glucose.
  • Aqueous suspensions according to the invention may include suspending agents such as cellulose derivatives, sodium alginate, polyvinylpyrrolidone and gum tragacanth, and a wetting agent such as lecithin.
  • Suitable preservatives for aqueous suspensions include ethyl and n-propyl p-hydroxybenzoate.
  • the compounds of the invention may also be presented as liposome formulations.
  • the compounds, salts, solvates or prodrugs of the invention will generally be provided in a form suitable for topical administration, e.g. as eye drops.
  • suitable forms may include ophthalmic solutions, gel-forming solutions, sterile powders for reconstitution, ophthalmic suspensions, ophthalmic ointments, ophthalmic emulsions, ophthalmic gels and ocular inserts.
  • 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.
  • the compounds, salts, solvates or prodrugs of the invention will generally be provided in the form of ointments, cataplasms (poultices), pastes, powders, dressings, creams, plasters or patches.
  • Suitable suspensions and solutions can be used in inhalers for airway (aerosol) administration.
  • the dose of the compounds, salts, solvates or prodrugs of the present invention will, of course, vary with the disease, disorder or condition to be treated or prevented. In general, a suitable dose will be in the range of 0.01 to 500 mg per kilogram body weight of the recipient per day.
  • the desired dose may be presented at an appropriate interval such as once every other day, once a day, twice a day, three times a day or four times a day.
  • the desired dose may be administered in unit dosage form, for example, containing 1 mg to 50 g of active ingredient per unit dosage form.
  • a fifteenth aspect of the invention provides a method of synthesising a compound according to the first aspect of the invention, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, the method comprising the steps of: (i) reacting a compound of Formula (SM-1) with a compound of Formula (SM-2) to produce an intermediate of Formula (It-1): and (ii) deprotecting the intermediate of Formula (It-1) to produce a compound of Formula (I), or a pharmaceutically acceptable salt and/or solvate thereof: wherein: R P is a nitrogen protecting group; R L is a leaving group; and R 1 to R 8 , R 18 to R 21 , and X 10 to X 13 are as defined in accordance with the first aspect of the invention.
  • a sixteenth aspect of the invention provides a method of synthesising a compound according to the second aspect of the invention, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, the method comprising the steps of: (i) reacting a compound of Formula (SM-3) with a compound of Formula (SM-2) to produce an intermediate of Formula (It-2): and (ii) deprotecting the intermediate of Formula (It-2) to produce a compound of Formula (II), or a pharmaceutically acceptable salt and/or solvate thereof: wherein: R P is a nitrogen protecting group; R L is a leaving group; and R 1 , R 4 to R 8 , R 14 to R 21 , and X 10 to X 13 are as defined in accordance with the second aspect of the invention.
  • R P is a nitrogen protecting group. Suitable nitrogen protecting groups may be identified by reference to e.g. Wuts, “Greene’s Protective Groups in Organic Synthesis”, 5 th Ed., 2014.
  • R P is a nitrogen protecting group that is stable under basic conditions. Typically, R P is also stable under weak nucleophilic conditions.
  • R P may be selected from the group consisting of benzyloxycarbonyl (CBz), 4-methoxy-benzyloxycarbonyl, benzyl, t- butoxycarbonyl (Boc), 2-(4-biphenylyl)-isopropoxycarbonyl (Bpoc), triphenylmethyl (Trt) and 2,2,2-trichloroethoxycarbonyl (Troc) protecting groups.
  • R P may be a sulphonyl group, such as a such as a toluenesulphonyl (tosyl or -Ts), methanesulfonyl (mesyl or -Ms), or trifluoromethanesulfonyl (triflyl or -Tf) group.
  • R P is a t- butoxycarbonyl (Boc) or toluenesulphonyl (tosyl or -Ts) group.
  • R L is a leaving group.
  • R L is selected from Cl, Br, I, or a sulfonate leaving group such as a toluenesulfonate (tosylate or -OTs), methanesulfonate (mesylate or -OMs), or trifluoromethanesulfonate (triflate or -OTf) leaving group, or an activated hydroxyl leaving group such as a protonated hydroxyl group, a Vilsmeier reagent (N- (Chloromethylene)-N-methylmethanaminium chloride) activated hydroxyl group, or a phosphonium activated hydroxyl group (e.g.
  • a sulfonate leaving group such as a toluenesulfonate (tosylate or -OTs), methanesulfonate (mesylate or -OMs), or trifluoromethanesulfonate (triflate or -OTf) leaving group, or an activated hydroxyl
  • R L is selected from Cl, Br or I or a Vilsmeier reagent activated hydroxyl group. More typically, R L is selected from Cl or a Vilsmeier reagent activated hydroxyl group. Most typically R L is Cl.
  • a base such as potassium carbonate, sodium bicarbonate, TEA, DIPEA, NaH or DBU, optionally in the presence of a phase transfer reagent such as TBAI.
  • the reaction of step (i) of the fifteenth or sixteenth aspect of the invention occurs in the presence of a dipolar aprotic solvent, such as dimethyl sulfoxide, N,N- dimethylformamide, N,N′-dimethylpropyleneurea, tetrahydrofuran, 1,4-dioxane, acetonitrile, dichloromethane, or N-methyl pyrrolidone.
  • a dipolar aprotic solvent such as dimethyl sulfoxide, N,N- dimethylformamide, N,N′-dimethylpropyleneurea, tetrahydrofuran, 1,4-dioxane, acetonitrile, dichloromethane, or N-methyl pyrrolidone.
  • the solvent is N,N-dimethylformamide, tetrahydrofuran, acetonitrile, dichloromethane or N-methyl pyrrolidone.
  • the solvent is tetrahydro
  • step (ii) of the fifteenth or sixteenth aspect of the invention may occur simultaneously with the reaction of step (i), e.g. via a ‘one-pot’ method, or may occur sequentially.
  • the deprotection conditions will be appropriate to the type of nitrogen protecting group R P used.
  • deprotection may be effected by treatment of the intermediate of Formula (It-1) or (It-2) with: (i) TMS-OTf and 2,6-lutidine, or TMS-OTf and TEA, in a dipolar aprotic solvent, such as dichloromethane; or (ii) a lewis acid, such as AlCl 3 , in a dipolar aprotic solvent, such as dichloromethane; or (iii) a polar protic acid such as HCl, HBr or TFA, in a polar protic solvent such as water and/or methanol.
  • a dipolar aprotic solvent such as dichloromethane
  • a lewis acid such as AlCl 3
  • a polar protic acid such as HCl, HBr or TFA
  • R P is a toluenesulphonyl (tosyl or -Ts) group
  • deprotection may be effected by treatment of the intermediate of Formula (It-1) or (It-2) with TBAF in a dipolar aprotic solvent, such as tetrahydrofuran.
  • the method of the fifteenth aspect of the invention further comprises the step of (iii) converting the compound of Formula (I) into a different compound of Formula (I), or a pharmaceutically acceptable salt and/or solvate thereof.
  • the method of the fifteenth aspect of the invention may further comprise the step (ia) of converting the compound of Formula (It-1) into a different compound of Formula (It-1), or a pharmaceutically acceptable salt and/or solvate thereof, prior to the deprotection step (ii).
  • the method of the sixteenth aspect of the invention further comprises the step of (iii) converting the compound of Formula (II) into a different compound of Formula (II), or a pharmaceutically acceptable salt and/or solvate thereof.
  • the method of the sixteenth aspect of the invention may further comprise the step (ia) of converting the compound of Formula (It-2) into a different compound of Formula (It-2), or a pharmaceutically acceptable salt and/or solvate thereof, prior to the deprotection step (ii).
  • a seventeenth aspect of the invention provides a method of synthesising a compound according to the first aspect of the invention, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, the method comprising the step of: (i) performing a reductive amination on a compound of Formula (SM-4) with a compound of Formula (SM-2) to produce a compound of Formula (P-4) or a pharmaceutically acceptable salt and/or solvate thereof: wherein: R X is selected from hydrogen or R P ; R P is a nitrogen protecting group; and R 2 to R 7 , R 18 to R 21 , and X 10 to X 13 are as defined in accordance with the first aspect of the invention.
  • R X is hydrogen
  • the compound of Formula (P-4) is a compound of Formula (I) of the first aspect of the invention, wherein R 8 is hydrogen.
  • An eighteenth aspect of the invention provides a method of synthesising a compound according to the second aspect of the invention, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, the method comprising the step of: (i) performing a reductive amination on a compound of Formula (SM-5) with a compound of Formula (SM-2) to produce a compound of Formula (P-5) or a pharmaceutically acceptable salt and/or solvate thereof: wherein: R X is selected from hydrogen or R P ; R P is a nitrogen protecting group; and R 4 to R 7 , R 14 to R 21 , and X 10 to X 13 are as defined in accordance with the second aspect of the invention.
  • R X is hydrogen
  • the compound of Formula (P-5) is a compound of Formula (II) of the second aspect of the invention, wherein R 8 is hydrogen.
  • R 7 is hydrogen.
  • R X is R P .
  • R P is a nitrogen protecting group that is stable under basic conditions.
  • R P is also stable under weak nucleophilic conditions.
  • R P may be selected from the group consisting of benzyloxycarbonyl (CBz), 4-methoxy- benzyloxycarbonyl, benzyl, t-butoxycarbonyl (Boc), 2-(4-biphenylyl)- isopropoxycarbonyl (Bpoc), triphenylmethyl (Trt) and 2,2,2-trichloroethoxycarbonyl (Troc) protecting groups.
  • R P is a t- butoxycarbonyl (Boc) group.
  • the reaction of step (i) of the seventeenth or eighteenth aspect of the invention occurs in the presence of a hydride donor, more typically in the presence of a borohydride such as NaHB(OAc)3, NaCNBH3 or NaBH4. Most typically, the reaction of step (i) of the seventeenth or eighteenth aspect of the invention occurs in the presence of NaHB(OAc)3.
  • the reaction of step (i) of the seventeenth or eighteenth aspect of the invention occurs in the presence of an acid such as a carboxylic acid. Typically, the carboxylic acid is acetic acid.
  • the reaction of step (i) of the seventeenth or eighteenth aspect of the invention may occur in the presence of a base, such as TEA, DIPEA or DBU.
  • a base such as TEA, DIPEA or DBU.
  • the base is a trialkylamine such as DIPEA.
  • the reaction of step (i) of the seventeenth or eighteenth aspect of the invention occurs in the presence of a dipolar aprotic solvent, such as dimethyl sulfoxide, N,N-dimethylformamide, N,N′-dimethylpropyleneurea, tetrahydrofuran, 1,4- dioxane, acetonitrile, dichloromethane, or N-methyl pyrrolidone.
  • the solvent is tetrahydrofuran or dichloromethane.
  • R X is a nitrogen protecting group
  • the method of the seventeenth aspect of the invention further comprises the step of (ii) deprotecting the compound of Formula (P-4) to produce a compound of Formula (I), or a pharmaceutically acceptable salt and/or solvate thereof, wherein R 8 is hydrogen.
  • R X is a nitrogen protecting group
  • the method of the eighteenth aspect of the invention further comprises the step of (ii) deprotecting the compound of Formula (P-5) to produce a compound of Formula (II), or a pharmaceutically acceptable salt and/or solvate thereof, wherein R 8 is hydrogen.
  • step (ii) of the seventeenth or eighteenth aspect of the invention may occur simultaneously with the reaction of step (i), e.g. via a ‘one-pot’ method, or may occur sequentially.
  • the deprotection conditions will be appropriate to the type of nitrogen protecting group R P used.
  • R P is a t-butoxycarbonyl (Boc) group
  • deprotection may be effected by treatment of the protected compound of Formula (P-4) or (P-5) with TMS-OTf and 2,6-lutidine in a dipolar aprotic solvent, such as dichloromethane.
  • the method of the seventeenth aspect of the invention further comprises the step of converting the compound of Formula (I), wherein R 8 is hydrogen, into a different compound of Formula (I), or a pharmaceutically acceptable salt and/or solvate thereof.
  • the method of the seventeenth aspect of the invention may further comprise the step of converting the compound of Formula (P-4), wherein R X is a nitrogen protecting group, into a different compound of Formula (P-4), or a pharmaceutically acceptable salt and/or solvate thereof, wherein R X is a nitrogen protecting group, prior to the step of deprotecting the compound of Formula (P-4).
  • the method of the eighteenth aspect of the invention further comprises the step of converting the compound of Formula (II), wherein R 8 is hydrogen, into a different compound of Formula (II), or a pharmaceutically acceptable salt and/or solvate thereof.
  • the method of the eighteenth aspect of the invention may further comprise the step of converting the compound of Formula (P-5), wherein R X is a nitrogen protecting group, into a different compound of Formula (P-5), or a pharmaceutically acceptable salt and/or solvate thereof, wherein R X is a nitrogen protecting group, prior to the step of deprotecting the compound of Formula (P-5).
  • a nineteenth aspect of the invention provides a method of synthesising a compound according to the first aspect of the invention, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, the method comprising the step of: (i) reacting a compound of Formula (SM-6) with a compound of Formula (SM-2) to produce a compound of Formula (P-6) or a pharmaceutically acceptable salt and/or solvate thereof: wherein: R X is selected from hydrogen or R P ; R P is a nitrogen protecting group; R 76 is selected from hydrogen or a fluoro 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 wherein the saturated hydrocarbyl group may optionally include a single heteroatom selected from N and O in its carbon skeleton; R 77 is selected from hydrogen, -
  • a twentieth aspect of the invention provides a method of synthesising a compound according to the second aspect of the invention, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, the method comprising the step of: (i) reacting a compound of Formula (SM-7) with a compound of Formula (SM-2) to produce a compound of Formula (P-7) or a pharmaceutically acceptable salt and/or solvate thereof:
  • Formula (SM-7) Formula (P-7) wherein: R X is selected from hydrogen or R P ; R P is a nitrogen protecting group; R 76 is selected from 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
  • the compound of Formula (P-7) is a compound of Formula (II) of the second aspect of the invention, wherein R 7 is -CH(R 76 )-COR 77 .
  • the group -CH(R 76 )-COR 77 contains no more than 8 carbon atoms.
  • R 76 is selected from hydrogen or a methyl or fluoromethyl group. Typically in such an embodiment, R 76 is hydrogen.
  • the carbon-carbon double bond is configured such that R 76 and R 8 are located trans- across the double bond.
  • R X is R P .
  • R P is a nitrogen protecting group that is stable under basic conditions.
  • R P is also stable under weak nucleophilic conditions.
  • R P may be selected from the group consisting of benzyloxycarbonyl (CBz), 4-methoxy- benzyloxycarbonyl, benzyl, t-butoxycarbonyl (Boc), 2-(4-biphenylyl)- isopropoxycarbonyl (Bpoc), triphenylmethyl (Trt) and 2,2,2-trichloroethoxycarbonyl (Troc) protecting groups.
  • R P may be a sulphonyl group, such as a such as a toluenesulphonyl (tosyl or -Ts), methanesulfonyl (mesyl or -Ms), or trifluoromethanesulfonyl (triflyl or -Tf) group.
  • R P is a toluenesulphonyl (tosyl or -Ts) group.
  • the reaction of step (i) of the nineteenth or twentieth aspect of the invention occurs in the presence of a base.
  • the base is a lithium amide base such as lithium diisopropylamide (LDA), lithium 2,2,6,6-tetramethylpiperidide (Li-TMP) or lithium hexamethyldisilazide (LiHMDS).
  • LDA lithium diisopropylamide
  • Li-TMP lithium 2,2,6,6-tetramethylpiperidide
  • LiHMDS lithium hexamethyldisilazide
  • the base is LDA.
  • the reaction of step (i) of the nineteenth or twentieth aspect of the invention occurs in the presence of a dipolar aprotic solvent, such as dimethyl sulfoxide, N,N- dimethylformamide, N,N′-dimethylpropyleneurea, tetrahydrofuran, 1,4-dioxane, acetonitrile, dichloromethane, or N-methyl pyrrolidone.
  • a dipolar aprotic solvent such as dimethyl sulfoxide, N,N- dimethyl
  • the solvent is tetrahydrofuran.
  • R X is a nitrogen protecting group
  • the method of the nineteenth aspect of the invention further comprises the step of (ii) deprotecting the compound of Formula (P-6) to produce a compound of Formula (I), or a pharmaceutically acceptable salt and/or solvate thereof, wherein R 7 is -CH(R 76 )-COR 77 .
  • the method of the twentieth aspect of the invention further comprises the step of (ii) deprotecting the compound of Formula (P-7) to produce a compound of Formula (II), or a pharmaceutically acceptable salt and/or solvate thereof, wherein R 7 is -CH(R 76 )-COR 77 .
  • the deprotection of step (ii) of the nineteenth or twentieth aspect of the invention may occur simultaneously with the reaction of step (i), e.g. via a ‘one-pot’ method, or may occur sequentially.
  • the deprotection conditions will be appropriate to the type of nitrogen protecting group R P used.
  • R P is a toluenesulphonyl (tosyl or -Ts) group
  • deprotection may be effected by treatment of the compound of Formula (P-6) or (P-7) with TBAF in a dipolar aprotic solvent, such as tetrahydrofuran.
  • the method of the nineteenth aspect of the invention further comprises the step of converting the compound of Formula (I), wherein R 7 is -CH(R 76 )-COR 77 , into a different compound of Formula (I), or a pharmaceutically acceptable salt and/or solvate thereof.
  • the method of the nineteenth aspect of the invention may further comprise the step of converting the compound of Formula (P-6), wherein R X is a nitrogen protecting group, into a different compound of Formula (P-6), or a pharmaceutically acceptable salt and/or solvate thereof, wherein R X is a nitrogen protecting group, prior to the step of deprotecting the compound of Formula (P-6).
  • the method of the twentieth aspect of the invention further comprises the step of converting the compound of Formula (II), wherein R 7 is -CH(R 76 )-COR 77 , into a different compound of Formula (II), or a pharmaceutically acceptable salt and/or solvate thereof.
  • the method of the twentieth aspect of the invention may further comprise the step of converting the compound of Formula (P-7), wherein R X is a nitrogen protecting group, into a different compound of Formula (P-7), or a pharmaceutically acceptable salt and/or solvate thereof, wherein R X is a nitrogen protecting group, prior to the step of deprotecting the compound of Formula (P-7).
  • a twenty-first aspect of the invention provides a method of synthesising a compound according to the second aspect of the invention, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, the method comprising the step of: (i) reducing a compound of Formula (SM-8) to provide a compound of Formula (P-8), or a pharmaceutically acceptable salt and/or solvate thereof: wherein: R X is selected from hydrogen or R P ; R P is a nitrogen protecting group; R 2 to R 8 , R 14 to R 21 and X 10 to X 13 are as defined in accordance with the first and/or second aspect of the invention.
  • R X is hydrogen
  • the compound of Formula (SM-8) is a compound of Formula (I) of the first aspect of the invention
  • the compound of Formula (P-8) is a compound of Formula (II) of the second aspect of the invention
  • at least one of R 14 and R 15 is hydrogen
  • at least one of R 16 and R 17 is hydrogen.
  • R X is R P .
  • R P is a nitrogen protecting group that is stable under basic conditions.
  • R P is also stable under weak nucleophilic conditions.
  • R P may be selected from the group consisting of benzyloxycarbonyl (CBz), 4-methoxy-benzyloxycarbonyl, benzyl, t- butoxycarbonyl (Boc), 2-(4-biphenylyl)-isopropoxycarbonyl (Bpoc), triphenylmethyl (Trt) and 2,2,2-trichloroethoxycarbonyl (Troc) protecting groups.
  • R P is a t-butoxycarbonyl (Boc) group.
  • the reduction of step (i) is performed using a hydride donor (such as NaBH3CN, BH3 or Et3SiH), optionally in the presence of an acid (such as acetic acid or trifluoroacetic acid).
  • a hydride donor such as NaBH3CN, BH3 or Et3SiH
  • an acid such as acetic acid or trifluoroacetic acid.
  • the reduction of step (i) of the twenty-first aspect of the invention occurs in the presence of a dipolar aprotic solvent, such as dimethyl sulfoxide, N,N- dimethylformamide, N,N′-dimethylpropyleneurea, tetrahydrofuran, 1,4-dioxane, acetonitrile, dichloromethane, or N-methyl pyrrolidone.
  • the method of the twenty-first aspect of the invention further comprises the step of (ii) deprotecting the compound of Formula (P-8) to produce a compound of Formula (II), or a pharmaceutically acceptable salt and/or solvate thereof.
  • the deprotection of step (ii) may occur simultaneously with the reaction of step (i), e.g. via a ‘one-pot’ method, or may occur sequentially.
  • the deprotection conditions will be appropriate to the type of nitrogen protecting group R P used.
  • the method of the twenty-first aspect of the invention further comprises the step of converting the compound of Formula (II) into a different compound of Formula (II), or a pharmaceutically acceptable salt and/or solvate thereof.
  • the method of the twenty-first aspect of the invention may further comprise the step of converting the compound of Formula (P-8), wherein R X is a nitrogen protecting group, into a different compound of Formula (P-8), or a pharmaceutically acceptable salt and/or solvate thereof, wherein R X is a nitrogen protecting group, prior to the step of deprotecting the compound of Formula (P-8).
  • a twenty-second aspect of the invention provides a method of synthesising a compound according to the first aspect of the invention, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, the method comprising the step of: (i) reacting a compound of Formula (SM-9) with a compound of Formula (SM-10) to produce a compound of Formula (P-9) or a pharmaceutically acceptable salt and/or solvate thereof: wherein: R X is selected from hydrogen or R P ; R P is a nitrogen protecting group; R L1 is a leaving group; R L2 is a leaving group; and R 2 to R 8 , R 20 , R 21 , and X 10 to X 13 are as defined in accordance with the first aspect of the invention.
  • a twenty-third aspect of the invention provides a method of synthesising a compound according to the second aspect of the invention, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, the method comprising the step of: (i) reacting a compound of Formula (SM-11) with a compound of Formula (SM-10) to produce a compound of Formula (P-10) or a pharmaceutically acceptable salt and/or solvate thereof: wherein: R X is selected from hydrogen or R P ; R P is a nitrogen protecting group; R L1 is a leaving group; R L2 is a leaving group; and R 4 to R 8 , R 14 to R 17 , R 20 , R 21 , and X 10 to X 13 are as defined in accordance with the second aspect of the
  • R X is hydrogen
  • R X is R P .
  • R P is a nitrogen protecting group that is stable under basic conditions.
  • R P is also stable under weak nucleophilic conditions.
  • R P may be selected from the group consisting of benzyloxycarbonyl (CBz), 4-methoxy- benzyloxycarbonyl, benzyl, t-butoxycarbonyl (Boc), 2-(4-biphenylyl)- isopropoxycarbonyl (Bpoc), triphenylmethyl (Trt) and 2,2,2-trichloroethoxycarbonyl (Troc) protecting groups.
  • R P is a t-butoxycarbonyl (Boc) group.
  • R L1 is a leaving group.
  • R L1 is selected from Cl, Br, I, or an alkoxy leaving group such as a C1-C4 alkoxyl group.
  • R L1 is an alkoxy leaving group. More typically, R L1 is a methoxy group.
  • R L2 is a leaving group.
  • R L2 is selected from Cl, Br, I, or a sulfonate leaving group such as a toluenesulfonate (tosylate or -OTs), methanesulfonate (mesylate or -OMs), or trifluoromethanesulfonate (triflate or -OTf) leaving group.
  • R L is selected from Cl, Br or I. More typically, R L is Br.
  • the reaction of step (i) of the twenty-second or twenty-third aspect of the invention occurs in the presence of a base, such as TEA, DIPEA or DBU.
  • the base is a trialkylamine such as TEA.
  • step (i) of the twenty-second or twenty-third aspect of the invention occurs in the presence of a dipolar aprotic solvent, such as dimethyl sulfoxide, N,N-dimethylformamide, N,N′-dimethylpropyleneurea, tetrahydrofuran, 1,4- dioxane, acetonitrile, dichloromethane, or N-methyl pyrrolidone. More typically, the solvent is acetonitrile.
  • a dipolar aprotic solvent such as dimethyl sulfoxide, N,N-dimethylformamide, N,N′-dimethylpropyleneurea, tetrahydrofuran, 1,4- dioxane, acetonitrile, dichloromethane, or N-methyl pyrrolidone. More typically, the solvent is acetonitrile.
  • step (ii) of the twenty-second or twenty-third aspect of the invention may occur simultaneously with the reaction of step (i), e.g. via a ‘one-pot’ method, or may occur sequentially.
  • the deprotection conditions will be appropriate to the type of nitrogen protecting group R P used.
  • R P is a t-butoxycarbonyl (Boc) group
  • deprotection may be effected by treatment of the protected compound of Formula (P-9) or (P-10) with a lewis acid such as AlCl3 in a dipolar aprotic solvent, such as dichloromethane.
  • the method of the twenty-second aspect of the invention may further comprise the step of converting the compound of Formula (P-9), wherein R X is a nitrogen protecting group, into a different compound of Formula (P-9), or a pharmaceutically acceptable salt and/or solvate thereof, wherein R X is a nitrogen protecting group, prior to the step of deprotecting the compound of Formula (P-9).
  • the method of the twenty-third aspect of the invention may further comprise the step of converting the compound of Formula (P-10), wherein R X is a nitrogen protecting group, into a different compound of Formula (P-10), or a pharmaceutically acceptable salt and/or solvate thereof, wherein R X is a nitrogen protecting group, prior to the step of deprotecting the compound of Formula (P-10).
  • Chromatography refers to column chromatography performed using silica or C18 silica and executed under positive pressure (flash chromatography) conditions.
  • LCMS Methods Instruments Waters H-Class with Binary Solvent Pump, Sample Manager with Flow- Through Needle, CMA Column Manager, Photodiode array detector, QDa mass detector (methods A1, A3, B3) or Agilent 1260 with Binary Pump, HiP Sampler, Column Compartment, diodearray detector, G6150 mass selective detector (methods C1, C3); or Shimadzu MS2020 Nexera Series; Shimadzu MS2020 N-Series; or Agilent 1290 Infinity II Series (methods H, I).
  • Methods A1, A3 Column: Waters ACQUITY UPLC CSH C18, 2.1 x 30 mm, 1.7 ⁇ m, at 40 °C; Solvents: A: 0.1% HCO2H in water, B: MeCN; Gradient [time (min)/solvent B in A (%)]: 0.00/2, 0.65/100, 1.00/100 (Method A1) or 0.00/2, 2.50/100, 3.00/100 (Method A3); Flow rate: 1 mL/min (Method A1) or 0.77 mL/min (Method A3); Detection: UV at 210-400 nm, MS by electrospray ionisation.
  • Method B3 Column: Waters ACQUITY UPLC BEH C18, 2.1 x 30 mm, 1.7 ⁇ m, at 40 °C; Solvents: A: 0.1% NH 3 in water, B: MeCN; Gradient [time (min)/solvent B in A (%)]: 0.00/2, 2.50/100, 3.00/100; Flow rate: 0.77 mL/min; Detection: UV at 210-400 nm, MS by electrospray ionisation.
  • Methods C1, C3 Column: Waters Cortecs C18, 30 x 2.1 mm, 2.7 ⁇ m, at 40 °C; Solvents: A: 0.1% HCO2H in water, B: MeCN; Gradient [time (min)/solvent B in A (%)]: 0.00/2, 0.65/100, 1.00/100 (Method C1) or 0.00/2, 2.50/100, 3.00/100 (Method C3); Flow rate: 1 mL/min (Method C1) or 1.35 mL/min (Method C3); Detection: UV at 260 nm +/- 90 nm, MS by electrospray ionisation.
  • Methods D3 Column: Phenomenex Evo C18, 2.1 x 30 mm, 2.6 ⁇ m, at 40 °C; Solvents: A: 0.1% NH 3 in water, B: MeCN; Gradient [time (min)/solvent B in A (%)]: 0.00/2, 2.50/100, 3.00/100; Flow rate: 1.35 mL/min; Detection: UV at 260 nm +/- 90 nm, MS by electrospray ionisation.
  • Method H Column: Agilent Zorbax eclipse plus C18, 50 x 2.1 mm, 1.8 ⁇ m; Solvents: A: 0.1% formic acid in water, B: 0.05% formic acid in MeCN; Gradient [time(min)/solvent B in A (%)]:0.00/5, 0.25/5, 2.50/95, 3.50/95, 3.60/5, 4.00/5; Flow rate 0.8 mL/min; Detection: UV at 210-400 nm, MS by electrospray ionisation and atmospheric pressure chemical ionisation.
  • Method I Column: Phenomenex Kinetex EVO C18, 50 x 3.0 mm, 2.6 ⁇ m; Solvents: A: 5 mM NH4HCO3 in water, B: MeCN; Gradient [time(min)/solvent B in A (%)]: 0.01/5, 0.50/5, 8.00/100, 9.00/100, 9.10/5, 10.00/5; Column temperature 40°C; Flow rate 0.8 mL/min; Detection: UV at 210-400 nm, MS by electrospray ionisation and atmospheric pressure chemical ionisation.
  • Methods P1, P2, P3 and P4 Column: Waters XBridge BEH C18 ODB prep column, 30 mm x 100 mm, 5 ⁇ m; Solvents: A: 0.3% ammonia in water, B: MeCN; Gradient [time (min)/solvent B in A (%)]: 0.00/52.5, 0.50/52.5, 5.50/82.5, 5.60/100, 8.50/100 (Method P1); 0.00/35, 0.50/35, 15.50/65, 15.60/100, 17.50/100 (Method P2); 0.00/25, 0.50/25, 15.50/55, 15.60/100, 17.50/100 (Method P3); 0.00/45, 0.50/45, 10.50/75, 10.60/100, 12.50/100 (Method P4); 0.00/20, 0.50/20, 10.50/50, 10.60/100, 12.50/100 (Method P5); 0.00/27.5, 0.50/27.5, 10.50/57.5, 10.60/
  • Step 2 To a solution of 5-methoxy-7-methyl-1H-indole-4-carbaldehyde (2.80 g, 14.8 mmol) in DMF (60 mL) at 0 °C was added sodium hydride (888 mg, 60 % dispersion in mineral oil, 22.2 mmol) portion wise. The reaction was warmed to rt and stirred for 30 min. The reaction was cooled to 0 °C and 4-methylbenzenesulfonyl chloride (4.23 g, 22.2 mmol) in DMF (5 mL) was added drop-wise, and the reaction was stirred at rt for 14 h before the addition of water (40 mL) at 0 °C.
  • sodium hydride 888 mg, 60 % dispersion in mineral oil, 22.2 mmol
  • Step 2 LDA (2M in THF, 2.43 mL, 4.86 mmol) was added dropwise to a stirred solution of isoindoline-5-carbonitrile hydrochloride (522 mg, 2.89 mmol) in dry THF (10 mL) under N 2 at -70 °C and the reaction was stirred at -70 °C for 15 min.
  • Step 2 A stirred solution of 5-(benzyloxy)-7-methyl-1-tosyl-1H-indole (10.0 g, 25.6 mmol) in EtOH (70 mL), EtOAc (30 mL) and THF (40 mL) was purged with nitrogen for 5 min, followed by the addition of 10% Pd on carbon (5.44 g, 5.11 mmol). The reaction mixture was stirred under an atmosphere of H 2 gas for 24 h at rt. The reaction mixture was filtered through celite, washing the celite with EtOH (50 mL) and ethyl acetate (100 mL), and the combined filtrate was concentrated in vacuo.
  • Step 3 Et 3 N (4.05 mL, 29.1 mmol) was added dropwise to a stirred solution of magnesium chloride (2.37 g, 24.9 mmol) and paraformaldehyde (1.25 g, 41.6 mmol) in THF (25 mL) under N2 and the reaction mixture was then stirred at rt for 10 min.7- Methyl-1-tosyl-1H-indol-5-ol (2.50 g, 8.30 mmol) in THF (10 mL) was added and the reaction mixture was heated at 70 °C for 3 h.
  • reaction mixture was allowed to warm to rt and stirred at rt for 1 h before the addition of 1M aq. HCl (10 mL) and EtOAc (30 mL) and separation of the phases. The aqueous layer was extracted with EtOAc (2 x 15 mL), the combined organic phases were dried over MgSO4, filtered, and concentrated in vacuo.
  • Step 2 Tetrabutylammonium fluoride (1M in THF, 1.00 mL, 1.00 mmol) was added to a solution of 5-(difluoromethoxy)-7-methyl-1-tosyl-1H-indole-4-carbaldehyde (80.0 mg, 0.21 mmol) in THF (1 mL) and the reaction mixture was heated at 65 °C for 90 min. After cooling to rt EtOAc (25 mL) was added and the organic phase was washed with water, saturated sodium bicarbonate, and brine (15 mL of each).
  • Step 2 A mixture of tert-butyl 4-((1,3-dioxoisoindolin-2-yl)methyl)-5-methoxy-7- methyl-1H-indole-1-carboxylate (3.50 g, 95 % purity by LCMS (Method A1), 7.91 mmol) and hydrazine (3.58 mL, 35 % Wt solution in water, 39.5 mmol) in MeOH (40 mL) was stirred at 60 °C for 4 h.
  • Step 2 To a solution of tert-butyl 4-((5-cyanoisoindolin-2-yl)methyl)-5-methoxy-7- methyl-1H-indole-1-carboxylate (264 mg, 84 % pure by LCMS, 0.53 ⁇ mol) in DCM (5 mL) was added 2,6-lutidine (678 ⁇ L, 5.82 mmol) and TMS-OTf (673 ⁇ L, 3.72 mmol). The resulting mixture was stirred at rt for 30 min before dilution with DCM and washing with saturated aq. sodium bicarbonate solution. The phases were separated, the organic phase was dried over Na2SO4, filtered, and concentrated in vacuo.
  • Example 2 2-((5-chloro-7-methyl-1H-indol-4-yl)methyl)isoindoline-5-carbonitrile
  • DIPEA 111 ⁇ L, 0.64 mmol
  • 5-chloro-4- (chloromethyl)-7-methyl-1-tosyl-1H-indole Intermediate 2, 78.0 mg, 0.21 mmol
  • isoindoline-5-carbonitrile hydrochloride (42.1 mg, 0.23 mmol) in MeCN (1 mL) and the reaction stirred for 3 d.
  • Step 2 TBAF (410 ⁇ L, 1M in THF, 410 ⁇ mol) was added to a solution of 2-((5-chloro-7- methyl-1-tosyl-1H-indol-4-yl)methyl)isoindoline-5-carbonitrile (65.0 mg, 137 ⁇ mol) in THF (1 mL) and the reaction heated to 65 °C for 1.5 h. The reaction was diluted with water (20 mL) and extracted with EtOAc (3 x 20 mL). The combined organic phases were dried over MgSO4, filtered and concentrated in vacuo.
  • Example 3 2-(1-(5-methoxy-7-methyl-1H-indol-4-yl)ethyl)isoindoline-5-carbonitrile
  • Step 1 To a solution of tert-butyl 4-(1-hydroxyethyl)-5-methoxy-7-methyl-1H-indole-1- carboxylate (Intermediate 3, 400 mg, 1.31 mmol) in DCM (20 mL) was added N- (chloromethylene)-N-methylmethanaminium chloride (275 mg, 2.15 mmol) and the reaction mixture was stirred at 0 °C for 2 h.
  • N- (chloromethylene)-N-methylmethanaminium chloride 275 mg, 2.15 mmol
  • Step 2 A solution of tert-butyl 4-(1-(5-cyanoisoindolin-2-yl)ethyl)-5-methoxy-7- methyl-1H-indole-1-carboxylate (52.7 mg, 122 ⁇ mol) in DCM (3 mL) was treated with 2,6-lutidine (95 ⁇ L, 820 ⁇ mol) then TMS-OTf (100 ⁇ L, 553 ⁇ mol) at 0 °C for 5 min, then at rt for 5 h. The reaction was concentrated on celite and purified by chromatography on silica gel (40 g cartridge, 0-10% 0.7N ammonia in MeOH/DCM) to afford afford a black residue.
  • silica gel 40 g cartridge, 0-10% 0.7N ammonia in MeOH/DCM
  • Example 4 2-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)isoindoline-5- carbonitrile
  • Step 1 TBAF (1M in THF, 1.45 mL, 1.45 mmol) was added to a solution of 5- cyclopropyl-7-methyl-1-tosyl-1H-indole-4-carbaldehyde (Intermediate 4, 160 mg, 64 % pure by LCMS (Method C1), 290 ⁇ mol) in THF (3 mL) and the reaction heated at 65 °C for 1 h. Water (20 mL) and EtOAc (20 mL) were added and the phases were separated.
  • Step 2 5-Cyclopropyl-7-methyl-1H-indole-4-carbaldehyde (58.0 mg, 256 ⁇ mol) was added to a solution of isoindoline-5-carbonitrile hydrochloride (50.9 mg, 282 ⁇ mol) and DIPEA (54 ⁇ L, 307 ⁇ mol) in DCM (4 mL) and the reaction mixture was stirred at rt for 1 h before addition of STAB (109 mg, 512 ⁇ mol). The reaction was stirred at rt for 3 h before dilution with DCM (20 mL) and 1:1 water/brine (15 mL) and the phases were separated.
  • Example 5 ethyl 3-(5-cyanoisoindolin-2-yl)-3-(5-methoxy-7-methyl-1H-indol-4-yl)- propanoate TBAF (1M in THF, 1.35 mL, 1.35 mmol) was added to a solution of ethyl 3-(5- cyanoisoindolin-2-yl)-3-(5-methoxy-7-methyl-1-tosyl-1H-indol-4-yl)propanoate (Intermediate 6, 200 mg, 73 % pure by LCMS, 0.26 mmol) in THF (10 mL) and the reaction was heated at 65 °C for 12 h.
  • Example 6 2-((5-(difluoromethoxy)-7-methyl-1H-indol-4-yl)methyl)isoindoline-5- carbonitrile 5-(Difluoromethoxy)-7-methyl-1H-indole-4-carbaldehyde (Intermediate 8, 66.0 mg, 60 % pure by 1 H NMR, 176 ⁇ mol) was added to a solution of isoindoline-5-carbonitrile hydrochloride (34.9 mg, 193 ⁇ mol) and DIPEA (37 ⁇ L, 212 ⁇ mol) in DCM (4 mL) and the reaction mixture was stirred at rt for 1 h before the addition of STAB (74.5 mg, 352 ⁇ mol).
  • Example 7 2-((3-fluoro-5-methoxy-7-methyl-1H-indol-4-yl)methyl)isoindoline-5- carbonitrile
  • the title compound was prepared from 3-fluoro-5-methoxy-7-methyl-1H-indole-4- carbaldehyde (Intermediate 9, 50 mg, 81 % pure by LCMS (Method A1), 195 ⁇ mol), isoindoline-5-carbonitrile hydrochloride (38.8 mg, 215 ⁇ mol), DIPEA (41 ⁇ L, 235 ⁇ mol) and STAB (82.9 mg, 391 ⁇ mol) in DCM (2 mL) at rt for 3 h, using the methods of Example 6.
  • Example 8 2-((3-bromo-5-methoxy-7-methyl-1H-indol-4-yl)methyl)isoindoline-5- carbonitrile NBS (29.4 mg, 165 ⁇ mol) was added to a solution of 2-((5-methoxy-7-methyl-1H-indol- 4-yl)methyl)isoindoline-5-carbonitrile (Example 1, 50.0 mg, 1 eq, 158 ⁇ mol) in MeCN (2 mL) and the reaction mixture was stirred at rt for 2 h before the addition of EtOAc (10 mL) and aq. NaHCO3 (10 mL).
  • Example 9 3-(5-cyanoisoindolin-2-yl)-3-(5-methoxy-7-methyl-1H-indol-4-yl)- propanoic acid LiOH (15.6 mg, 0.65 mmol) was added to a solution of ethyl 3-(5-cyanoisoindolin-2-yl)- 3-(5-methoxy-7-methyl-1H-indol-4-yl)propanoate (Example 5, 40 mg, 0.10 mmol) in THF (2 mL) and water (0.5 mL) and the reaction mixture was stirred at rt for 24 h.
  • Example 10 2-((3-chloro-5-methoxy-7-methyl-1H-indol-4-yl)methyl)isoindoline-5- carbonitrile NCS (37.0 mg, 277 ⁇ mol) was added to a solution of 2-((5-methoxy-7-methyl-1H-indol- 4-yl)methyl)isoindoline-5-carbonitrile (Example 1, 80.0 mg, 252 ⁇ mol) in MeCN (1 mL). After stirring at rt for 1 h, aq. sodium bicarbonate solution (10 mL) and EtOAc (10 mL) were added and the phases were separated.
  • Example 11 2-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-3,3-dimethylisoindoline- 5-carbonitrile
  • Step 1 A mixture of 6-bromo-1,1-dimethylisoindoline hydrochloride (114 mg, 433 ⁇ mol), tert-butyl 4-(chloromethyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate (Intermediate 10, 149 mg, 85 % purity by 1 H NMR, 410 ⁇ mol) and DIPEA (214 ⁇ L, 1.23 mmol) in MeCN (2 mL) was stirred at 60 °C for 4 h.
  • Step 2 A mixture of potassium hexacyanoferrate(II) trihydrate (33.6 mg, 79.5 ⁇ mol), dichloro[bis(2-(diphenylphosphino)phenyl)ether]palladium(II) (Johnson Matthey, catalog number Pd-117, 10.4 mg, 14.5 ⁇ mol) and caesium carbonate (75.1 mg, 230 ⁇ mol) in a vial was degassed and purged with N2 three times.
  • a separate batch of crude material was prepared using the same methods from potassium hexacyanoferrate(II) trihydrate (7.4 mg, 17.5 ⁇ mol), dichloro[bis(2-(diphenylphosphino)phenyl)ether]palladium(II) (Johnson Matthey, catalog number Pd-117, 2.5 mg, 3.5 ⁇ mol), caesium carbonate (14.3 mg, 43.9 ⁇ mol) and tert-butyl 4-((6-bromo-1,1-dimethylisoindolin-2-yl)methyl)-5- methoxy-7-methyl-1H-indole-1-carboxylate (15.8 mg, 94 % purity by 1 H NMR, 29.7 ⁇ mol) in 1,4-dioxane (0.4 mL) and water (0.1 mL) at 90 °C for 2.5 d.
  • Step 3 2,6-Lutidine (53 ⁇ L, 457 ⁇ mol) and trimethylsilyl trifluoromethanesulfonate (69 ⁇ L, 382 ⁇ mol) were added to a solution of tert-butyl 4-((6-cyano-1,1-dimethyl- isoindolin-2-yl)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate (33.0 mg, 95 % purity by LCMS (Method C3), 70 ⁇ mol) in DCM (0.7 mL). After stirring at rt for 1 d the mixture was partitioned between brine (10 mL) and DCM (10 mL).
  • Example 12 2-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-3-oxoisoindoline-5- carbonitrile
  • Step 1 TEA (462 ⁇ L, 3.32 mmol) was added to a solution of tert-butyl 4- (aminomethyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate (Intermediate 11, 338 mg, 95 % purity by 1 H NMR, 1.11 mmol) and methyl 2-(bromomethyl)-5-cyanobenzoate (312 mg, 90 % purity by LCMS (Method C3), 1.11 mmol) in MeCN (5 mL) and the reaction mixture was heated at 80 °C for 1.5 h.
  • Step 2 Aluminum trichloride (135 mg, 1.01 mmol) was added to a solution of tert-butyl 4-((6-cyano-1-oxoisoindolin-2-yl)methyl)-5-methoxy-7-methyl-1H-indole-1- carboxylate (139 mg, 90 % purity by 1 H NMR, 289 ⁇ mol) in anhydrous DCM (3 mL) at 0 °C. The mixture was degassed and purged with N 2 three times before stirring for 3 h whilst warming slowly to rt.
  • Example 13 6-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-oxo-6,7-dihydro-5H- pyrrolo[3,4-b]pyridine-2-carbonitrile
  • Example 13 Step 1 Potassium ferrocyanide trihydrate (424.4 mg, 1.00 mmol) and potassium acetate (247 mg, 2.51 mmol) were added to a solution of tert-butyl 4-((2-chloro-7-oxo- 5,7-dihydro-6H-pyrrolo[3,4-b]pyridin-6-yl)methyl)-5-methoxy-7-methyl-1H-indole-1- carboxylate (Intermediate 12, 370.0 mg, 0.84 mmol) in 1,4-dioxane/water (5:1, 9.6 mL) and the mixture was degassed with nitrogen for 5 min before the addition of BrettPhos Pd G3 (75.9 mg, 0.08 mmol).
  • Step 2 A solution of tert-butyl 4-((2-cyano-7-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]- pyridin-6-yl)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate (350.0 mg, 72 % pure by LCMS (Method C3), 0.58 mmol) in 2,2,2-trifluoroethanol (4 mL) was heated in a microwave reactor at 150 °C for 1 h.
  • Example 14 2-(1-(5-methoxy-7-methyl-1H-indol-4-yl)ethyl)-3-oxoisoindoline-5- carbonitrile
  • Step 1 tert-butyl 4-(1-(6-cyano-1-oxoisoindolin-2-yl)ethyl)-5-methoxy-7-methyl-1H- indole-1-carboxylate was prepared from tert-butyl 4-(1-aminoethyl)-5-methoxy-7- methyl-1H-indole-1-carboxylate (Intermediate 13, 80.0 mg, 95 % pure by 1 H NMR, 0.25 mmol), methyl 2-(bromomethyl)-5-cyanobenzoate (70.5 mg, 90 % purity by LCMS (Method C3), 0.25 mmol) and TEA (104 ⁇ L, 0.75 mmol) in MeCN (2 mL) at 80 °C for 5 h,
  • Step 2 TEA (156 ⁇ L, 1.12 mmol), then TMS-OTf (284 ⁇ L, 1.57 mmol) were added to a solution of tert-butyl 4-(1-(6-cyano-1-oxoisoindolin-2-yl)ethyl)-5-methoxy-7-methyl- 1H-indole-1-carboxylate (100 mg, 0.22 mmol) in DCM (2 mL) at 0 °C. After stirring for 10 min at 0 °C, then for 1.25 h at rt, the reaction mixture was cooled to -10 °C for 15 min and diluted dropwise with DCM (6 mL).
  • glycerol was added to a final concentration of 20 % (v/v), and preparations were stored until use at 4°C.
  • Enzyme assays were performed in 384 well format, in which compounds were prepared as 1:5 serial dilutions (8-point curves) in DMSO and 150 nL of compound was stamped to an assay plate (384-well OptiPlate, Perkin Elmer 6007299) at 100x final assay concentration (FAC). The final assay DMSO concentration was 1% (v/v).
  • the compound preincubation step was initiated by addition of 7.5 ⁇ l biochemical assay buffer containing CVF:Bb complex (5 nM FAC unless stated otherwise), based on input FB concentration and pre-equilibrated to rt) for 30 min at rt. Subsequently, 7.5 ⁇ l biochemical assay buffer containing purified C3 substrate (Complement Technology A113c, to 0.1 ⁇ M FAC) was added and CVF:Bb mediated cleavage was allowed to proceed for 60 min at rt. Reactions were terminated by addition of 3.75 ⁇ l 10x Halt protease inhibitor cocktail (Fisher 78437) in assay buffer, and cooling on ice.
  • CVF:Bb complex 5 nM FAC unless stated otherwise
  • Inhibitor data were normalized to DMSO vehicle, 0 % inhibition) and reference maximum inhibition (10 ⁇ M Iptacopan, 100 % inhibition) plate controls, and compound inhibition curves were fitted to a 4-parameter equation with variable slope to determine IC50 estimates.
  • the results of the factor B biochemical ELISA assay are summarised in Table 1 below as IC 50 values.

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Abstract

The present invention relates to compounds (I) possessing an indole moiety linked to an isoindoline moiety, to compounds having similar core structures, and to associated salts, solvates, prodrugs and pharmaceutical compositions. The present invention further relates to methods of synthesising such compounds, and to the use of such compounds in the treatment and prevention of medical disorders and diseases, most especially by Factor B inhibition.

Description

Novel Compounds Field of the Invention The present invention relates to compounds possessing an indole moiety linked to an isoindoline moiety, to compounds having similar core structures, and to associated salts, solvates, prodrugs and pharmaceutical compositions. The present invention further relates to methods of synthesising such compounds, and to the use of such compounds in the treatment and prevention of medical disorders and diseases, most especially by Factor B inhibition. Background of the Invention The complement system is a critical part of the innate immune system and serves to help the body fight against infection from pathogens, ultimately leading to inflammation and phagocytic removal of pathogens or foreign particles. The complement system is comprised of multiple proteins, including zymogens which undergo proteolytic cleavage to become activated and facilitate the activation of further zymogens in the cascade. The proteins may be zymogens or proteins without potential for enzymatic activity that change conformation revealing binding sites for other components of the system. These successive enzymatic cleavages lead to a large, amplified response and many regulatory components exist in this system to prevent uncontrolled activation. The complement system can be activated via three pathways: classical, lectin, and alternative. The classical pathway is triggered by antigen:antibody complexes and connects the innate to the adaptive immune system. The lectin pathway is triggered directly by the pathogen when serum protein mannan-binding lectin, collectins or ficolins bind to bacterial or viral mannose-containing carbohydrates. The alternative pathway (also known as the alternate pathway) is initiated by activation of the central complement component, C3, either through spontaneous hydrolysis or enzymatic cleavage. The alternative pathway also serves as a critical amplification loop of all three pathways of complement activation. Ultimately, all of these pathways lead to the generation of C3 convertase which cleaves and activates further C3 molecules to promote: 1) opsonization of pathogens so they can be engulfed by phagocytes that recognise key receptors, 2) the recruitment of inflammatory cells by generating chemoattractants at the site of activation, and 3) formation of the C5 convertase resulting in production of C5a and C5b, the latter of which induces direct killing of pathogens by assembling terminal complement components to create membrane attack complex (MAC) pores in the membrane of bacteria or other target cells (Janeway, C. A. Jr. et al, (2001) The complement system and innate immunity, in Immunobiology: The Immune System in Health and Disease, Garland Science, New York). Factor B, a trypsin-like serine protease, is an element of the alternative pathway of the complement cascade. It exists in circulation in its zymogen form until the pathway becomes activated (Schubart, A. et al, Proc. Natl. Acad. Sci. U.S.A.2019, 116, 7926- 7931). Spontaneous steady-state hydrolysis of C3 leads to the formation of C3(H2O). Factor B can bind to the active forms of C3: C3(H2O) and C3b, generating the proenzyme C3bB (or C3(H2O)B), a target for activation by Factor D. Upon cleavage by Factor D, two fragments are generated: Ba and Bb (Schwaeble, W. J., Ali, Y. M., and Sim, R. B., (2020) Chapter 14 - The Roles and Contributions of the Complement System in the Pathophysiology of Autoimmune Diseases, in The Autoimmune Diseases (Sixth Edition) (Rose, N. R., and Mackay, I. R. eds.), Academic Press). Ba is released and Bb, containing a serine protease domain, remains bound to C3(H2O) and C3b, forming the alternative pathway C3 convertases [C3(H2O)Bb and C3bBb]. These trigger the amplification loop by converting C3 to C3a and more C3b. With the addition of yet another C3b to the C3 convertase, the C5 convertase is generated (C3bBbC3b) (Laskowski, J., Thurman, J. M. (2018) Chapter 14 - Factor B, in The Complement FactsBook (Second Edition) (Barnum, S., and Schein, T. eds.), Academic Press). C5 convertase cleaves C5 to generate the anaphylatoxin C5a, and C5b which serves as a platform for the formation of the membrane attack complex. Dysregulation of the alternative complement pathway due to genetics or the presence of autoantibodies can lead to many different diseases. Inhibition of Factor B is therefore a key therapeutic target for modulation of the alternative pathway and hence the treatment of numerous diseases, disorders and conditions. Iptacopan (LNP023), disclosed in Mainolfi et al., J. Med. Chem., 2020, vol.63, pp. 5697-5722, is a known Factor B inhibitor having the following structure: Iptacopan is highly selective for Factor B, showing no inhibition of Factor D or the classical or lectin complement pathways. Also, no significant effects have been observed in a broad assay panel of receptors, ion channels, kinases, and proteases (Schubart, A. et al, Proc. Natl. Acad. Sci. U.S.A.2019, 116, 7926-7931). The drug has recently undergone successful phase III clinical studies in patients suffering from paroxysmal nocturnal hemoglobinuria (PNH) (Novartis Press Release, “Novartis Phase III APPOINT-PNH trial shows investigational oral monotherapy iptacopan improves hemoglobin to near-normal levels, leading to transfusion independence in all treatment-naïve PNH patients”, 26 April 2023). Further indole derivatives stated to have Factor B inhibitory activity are disclosed in WO 2013/164802 A1, US 2013/0296377 A1, WO 2014/143638 A1, WO 2015/009616 A1, WO 2022/028507 A1, WO 2022/028527 A1, WO 2022/143940 A1, WO 2022/143845 A1, WO 2022/155294 A1, WO 2022/218429 A1, WO 2022/256586 A2, WO 2023/278698 A1, WO 2023/020566 A1, WO 2023/072197 A1, WO 2023/139534 A1, WO 2023/187715 A1 and WO 2024/049977 A1. However, there is a need to provide further Factor B inhibitors, especially selective Factor B inhibitors (e.g. versus inhibition of Factor D, classical complement, and/or lectin complement activation). In particular, there 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 known compounds. Summary of the Invention A first aspect of the invention provides a compound of Formula (I): wherein: R1 is hydrogen; R2 is selected from hydrogen or a halo group; R3 is selected from hydrogen or a halo, -SO2NH2, or a C1-C8 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 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 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; R4 is selected from hydrogen or a halo, -OH, -NH2, -SO2NH2, or a C1-C8 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 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 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; R5 is selected from hydrogen or a halo group; R6 is selected from hydrogen or a halo, -R60 or -OR60 group, wherein R60 is selected from a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl or C3-C4 fluorocycloalkyl group; R7 and R8 are each independently selected from hydrogen or a fluoro 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 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 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 any hydrocarbyl group of R7 or R8 that is directly attached to the reminder of the molecule is a carbon atom; or R7 and R8 together with the carbon atom to which they are attached form a 3- to 10-membered cyclic group, such that each ring atom of the cyclic group that is directly attached to the carbon atom to which R7 and R8 are attached is a ring carbon atom, wherein the cyclic 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; or R3 and R7, or R4 and R7, together form a C1-C6 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 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 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 the hydrocarbylene group that is directly attached to the carbon atom to which R8 is attached is a carbon atom; X10 is N or CR10; X11 is N or CR11; X12 is N or CR12; X13 is N or CR13; no more than two of X10, X11, X12 and X13 are N; each R10, R11, R12 and R13 is independently selected from hydrogen or a halo, -OH, -SH, -NH2, -SO2NH2, 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 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 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; R18 and R19 are each independently selected from hydrogen or a fluoro 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 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 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 any hydrocarbyl group of R18 or R19 that is directly attached to the reminder of the molecule is a carbon atom; or R18 and R19 together with the carbon atom to which they are attached form a 3- to 10-membered cyclic group, such that each ring atom of the cyclic group that is directly attached to the carbon atom to which R18 and R19 are attached is a ring carbon atom, wherein the cyclic 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; or R18 and R19 together with the carbon atom to which they are attached form a C=O group; and R20 and R21 are each independently selected from hydrogen or a fluoro group, or R20 and R21 together with the carbon atom to which they are attached form a C=O group. A second aspect of the invention provides compound of Formula (II): wherein: R1 is hydrogen; R4 is selected from hydrogen or a halo, -OH, -NH2, -SO2NH2, or a C1-C8 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 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 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; R5 is selected from hydrogen or a halo group; R6 is selected from hydrogen or a halo, -R60 or -OR60 group, wherein R60 is selected from a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl or C3-C4 fluorocycloalkyl group; R7 and R8 are each independently selected from hydrogen or a fluoro 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 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 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 any hydrocarbyl group of R7 or R8 that is directly attached to the reminder of the molecule is a carbon atom; or R7 and R8 together with the carbon atom to which they are attached form a 3- to 10-membered cyclic group, such that each ring atom of the cyclic group that is directly attached to the carbon atom to which R7 and R8 are attached is a ring carbon atom, wherein the cyclic 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; X10 is N or CR10; X11 is N or CR11; X12 is N or CR12; X13 is N or CR13; no more than two of X10, X11, X12 and X13 are N; each R10, R11, R12 and R13 is independently selected from hydrogen or a halo, -OH, -SH, -NH2, -SO2NH2, 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 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 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; each R14 and R15 is independently selected from hydrogen or a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl or C3-C4 fluorocycloalkyl group, or R14 and R15 together with the carbon atom to which they are attached form a 3- to 6-membered cyclic group, wherein the cyclic group may optionally be substituted with one or more substituents each independently selected from a fluoro, -OH, oxo (=O), methyl or ethyl group, wherein any methyl or ethyl group may optionally be fluoro substituted; R16 is selected from hydrogen or a fluoro, -SO2NH2, or a C1-C8 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 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 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; R17 is selected from hydrogen or a fluoro, C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl or C3-C4 fluorocycloalkyl group; or R16 and R17 together with the carbon atom to which they are attached form a 3- to 6-membered cyclic group, wherein the cyclic group may optionally be substituted with one or more substituents each independently selected from a fluoro, -OH, oxo (=O), methyl or ethyl group, wherein any methyl or ethyl group may optionally be fluoro substituted; or R17 and R7, or R4 and R7, together form a C1-C6 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 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 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 the hydrocarbylene group that is directly attached to the carbon atom to which R8 is attached is a carbon atom; R18 and R19 are each independently selected from hydrogen or a fluoro 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 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 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 any hydrocarbyl group of R18 or R19 that is directly attached to the reminder of the molecule is a carbon atom; or R18 and R19 together with the carbon atom to which they are attached form a 3- to 10-membered cyclic group, such that each ring atom of the cyclic group that is directly attached to the carbon atom to which R18 and R19 are attached is a ring carbon atom, wherein the cyclic 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; or R18 and R19 together with the carbon atom to which they are attached form a C=O group; and R20 and R21 are each independently selected from hydrogen or a fluoro group, or R20 and R21 together with the carbon atom to which they are attached form a C=O group. 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 or moiety is “saturated” it is to be understood that all of the ring systems within the bicyclic or polycyclic group or moiety (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:
Figure imgf000014_0001
wherein G = O, S or NH. Particular examples of 5- or 6-membered heteroaryl groups include furanyl, thiophenyl, pyrrolyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, furazanyl, oxadiazolyl, thiadiazolyl, tetrazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl and triazinyl groups. Unless stated otherwise, where a bicyclic or polycyclic group or moiety is stated to be aromatic, such as an aryl or a heteroaryl group, it is to be understood that all of the ring systems within the bicyclic or polycyclic group or moiety (excluding any ring systems which are part of or formed by optional substituents) are aromatic. Similarly, where a bicyclic or polycyclic 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 all of the ring systems within the bicyclic or polycyclic group or moiety (excluding any ring systems which are part of or formed by optional substituents) are 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, R2 is selected from hydrogen or a halo group. In one embodiment, R2 is selected from hydrogen or a fluoro, chloro or bromo group. Most typically, R2 is hydrogen. As stated in accordance with the first aspect of the invention, R3 is selected from hydrogen or a halo, -SO2NH2, or a C1-C8 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 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 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 R3 and R7 together form a C1-C6 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 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 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 the hydrocarbylene group that is directly attached to the carbon atom to which R8 is attached is a carbon atom. In one embodiment, R3 is selected from hydrogen or a halo, -SO2NH2, or a C1-C8 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 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 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 aspect of such an embodiment, R3 is selected from hydrogen or a halo (e.g. fluoro, chloro or bromo), -R30, -CN, -CHO, -COR30, -CO2H or -CO2R30 group, wherein R30 is selected from a C1-C6 alkyl, C1-C6 fluoroalkyl, C2-C6 alkenyl, C2-C6 fluoroalkenyl or -R31 group, wherein R31 is a 3- to 6-membered monocyclic group, wherein the 3- to 6- membered monocyclic group may optionally be substituted with one or more halo (e.g. fluoro, chloro or bromo) groups, and/or with one or two groups R32, wherein each R32 is independently selected from a methyl or a fluoromethyl group, provided that the group R3, including any optional substituents, contains no more than 8 carbon atoms. Typically in such an embodiment, R3 is selected from hydrogen or a fluoro, chloro, bromo, -R30, -CN, -CHO, -COR30, -CO2H or -CO2R30 group, wherein R30 is selected from a C1-C4 alkyl, C1-C4 fluoroalkyl or -R31 group, wherein R31 is selected from a C3-C6 cycloalkyl group, a 4- to 6-membered saturated heterocyclic group, or a phenyl or a 5- or 6-membered heteroaryl group, wherein the C3-C6 cycloalkyl group and the 4- to 6- membered saturated heterocyclic group may optionally be substituted with one or more fluoro groups and/or with one or two groups R32, and wherein the phenyl or the 5- or 6- membered heteroaryl group may optionally be substituted with one or more fluoro, chloro and/or bromo groups, and/or with one or two groups R32, provided that the group R3, including any optional substituents, contains no more than 8 carbon atoms. More typically in such an embodiment, R3 is selected from hydrogen or a fluoro, chloro, bromo, -R30, -R31, -CN, -CHO, -COR30, -CO2H or -CO2R30 group, wherein R30 is selected from a methyl or fluoromethyl group, and wherein R31 is a 5-membered heteroaryl group, wherein the 5-membered heteroaryl group may optionally be substituted with one or more fluoro, chloro and/or bromo groups, and/or with one or two groups R32. In another aspect of such an embodiment, R3 is selected from hydrogen or a halo (e.g. fluoro, chloro or bromo), -R30, -CN, -CHO, -COR30, -CO2H or -CO2R30 group, wherein R30 is selected from a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl or C3-C4 fluorocycloalkyl group. Typically in such an embodiment, R3 is selected from hydrogen or a fluoro, chloro, bromo -R30, -CN, -CHO, -COR30, -CO2H or -CO2R30 group, wherein R30 is selected from a methyl or fluoromethyl group. In a further aspect of such an embodiment, R3 is selected from hydrogen or a halo (e.g. fluoro, chloro or bromo), -CN, C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl or C3-C4 fluorocycloalkyl group. Typically in such an embodiment, R3 is selected from hydrogen or a fluoro, chloro, bromo, -CN or methyl group, wherein the methyl group may optionally be fluoro substituted. More typically, R3 is selected from hydrogen or a fluoro, chloro or bromo group. Most typically, R3 is hydrogen. In another embodiment of the first aspect of the invention, R3 and R7 together form a C1-C6 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 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 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 the hydrocarbylene group that is directly attached to the carbon atom to which R8 is attached is a carbon atom. Typically, where R3 and R7 together form a hydrocarbylene group, the hydrocarbylene group, including any optional substituents, contains no more than four carbon atoms. Typically, the total number of nitrogen, oxygen and sulphur atoms in any hydrocarbylene group (including any optional substituents) formed by R3 and R7 is no more than three. More typically, the total number of nitrogen, oxygen and sulphur atoms in any hydrocarbylene group (including any optional substituents) formed by R3 and R7 is no more than two. Typically in such an embodiment, R3 and R7 together form a C1-C4 saturated or unsaturated hydrocarbylene group, wherein the hydrocarbylene group may be straight- chained or branched, or be or include a cyclic group, wherein the hydrocarbylene group may optionally be substituted with one or more fluoro, chloro and/or bromo groups, and wherein the hydrocarbylene group may optionally include one or two heteroatoms each independently selected from N and O in its carbon skeleton, provided that the atom of the hydrocarbylene group that is directly attached to the carbon atom to which R8 is attached is a carbon atom. Where R3 and R7 together form a hydrocarbylene group, typically the hydrocarbylene group has a chain length of from 1 to 3 atoms. More typically, the hydrocarbylene group has a chain length of 1 or 2 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:
Figure imgf000021_0001
(C) (D) More typically, where R3 and R7 together form a hydrocarbylene group, the hydrocarbylene group is selected from -CH2-, -CH2-CH2-, -CH=CH-, -CH2-O-, or -O-CH2-, provided that the atom of the hydrocarbylene group that is directly attached to the carbon atom to which R8 is attached is a carbon atom. Typically, where R3 and R7 together form a hydrocarbylene group, R8 is selected from hydrogen or a fluoro, C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl or C3-C4 fluorocycloalkyl group. More typically, where R3 and R7 together form a hydrocarbylene group, R8 is selected from hydrogen or a fluoro, methyl or fluoromethyl group. More typically still, where R3 and R7 together form a hydrocarbylene group, R8 is hydrogen. As stated in accordance with both the first and the second aspects of the invention, R4 is selected from hydrogen or a halo, -OH, -NH2, -SO2NH2, or a C1-C8 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 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 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 R4 and R7 together form a C1-C6 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 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 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 the hydrocarbylene group that is directly attached to the carbon atom to which R8 is attached is a carbon atom. In one embodiment, R4 is selected from hydrogen or a halo, -OH, -NH2, -SO2NH2, or a C1-C8 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 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 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, R4 is selected from hydrogen or a fluoro, chloro, bromo, -OH, -NH2, -SO2NH2, -SO2-R40 or -R40 group, wherein R40 is selected from a C1- C6 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 fluoro, chloro and/or bromo groups, and wherein the hydrocarbyl group may optionally include one, two or three heteroatoms each independently selected from N and O in its carbon skeleton. More typically in such an embodiment, R4 is selected from a fluoro, chloro, bromo, -OH, -OR41, -N(R42)2, -SO2-R41, -SO2-N(R42)2, -L4-OH, -L4-OR41, -L4-N(R42)2, -L4-SO2-R41, -L4-SO2-N(R42)2, -O-L4-OH, -O-L4-OR41, -O-L4-N(R42)2, -O-L4-SO2-R41, -O-L4-SO2-N(R42)2, -NR43-L4-OH, -NR43-L4-OR41, -NR43-L4-N(R42)2, -NR43-L4-SO2-R41, -NR43-L4-SO2-N(R42)2, -SO2-L4-OH, -SO2-L4-OR41, -SO2-L4-N(R42)2, -R44, -R45 or -L4-R45 group, wherein: R41 is selected from a -R44 or -R45 group; each R42 is independently selected from hydrogen or a -R44 or -R45 group, or any two R42 may, together with the nitrogen atom to which they are attached, form a 3- to 6-membered saturated monocyclic heterocyclic group, wherein the 3- to 6-membered saturated monocyclic heterocyclic group may optionally be substituted with one or two oxo (=O) groups and/or with one or more fluoro, methyl and/or fluoromethyl groups; L4 is a straight-chained alkylene group, wherein the straight-chained alkylene group optionally includes one or two heteroatoms each independently selected from O and N in its carbon skeleton, wherein L4 has a chain length of from 1 to 4 atoms, and wherein L4 may optionally be substituted with one or two oxo (=O) groups and/or with one or more groups RL4; each RL4 is independently selected from a fluoro, methyl or fluoromethyl group; or any RL4 and R41, or any RL4 and any R42, may together with the atoms to which they are attached, form a 3- to 6-membered saturated monocyclic heterocyclic group, wherein the 3- to 6-membered saturated monocyclic heterocyclic group may optionally be substituted with one or two oxo (=O) groups and/or with one or more fluoro, methyl and/or fluoromethyl groups; R43 is selected from hydrogen or a -R44 group; each R44 is independently selected from a C1-C4 alkyl or C3-C6 cycloalkyl group, wherein the C1-C4 alkyl or C3-C6 cycloalkyl group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups; and each R45 is independently selected from a phenyl or a 5- or 6-membered heteroaryl group, wherein the phenyl or the 5- or 6-membered heteroaryl group may optionally be substituted with one or more groups each independently selected from fluoro, chloro and bromo, and/or with one or two groups each independently selected from methyl (Me), -CN, -OH, -OMe, -NH2, -NHMe, and -NMe2, wherein any methyl group of R45 may optionally be fluoro substituted; provided that R4, including any optional substituents, contains no more than 8 carbon atoms. In one aspect of such an embodiment, R4 is selected from a fluoro, chloro, bromo, -OH, -OR41, -N(R42)2, -SO2-R41, -SO2-N(R42)2, -L4-OH, -L4-OR41, -L4-N(R42)2, -L4-SO2-R41, -L4-SO2-N(R42)2, -O-L4-OH, -O-L4-OR41, -O-L4-N(R42)2, -O-L4-SO2-R41, -O-L4-SO2-N(R42)2, -NR43-L4-OH, -NR43-L4-OR41, -NR43-L4-N(R42)2, -NR43-L4-SO2-R41, -NR43-L4-SO2-N(R42)2, -R44, -R45 or -L4-R45 group In a further aspect of such an embodiment: R4 is selected from a fluoro, chloro, bromo, -OH, -OR41, -N(R42)2, -SO2-R41, -SO2-N(R42)2, -L4-OH, -L4-OR41, -L4-N(R42)2, -L4-SO2-R41, -L4-SO2-N(R42)2, -O-L4-OH, -O-L4-OR41, -O-L4-N(R42)2, -O-L4-SO2-R41, -O-L4-SO2-N(R42)2, -NR43-L4-OH, -NR43-L4-OR41, -NR43-L4-N(R42)2, -NR43-L4-SO2-R41, -NR43-L4-SO2-N(R42)2, -R44, -R45 or -L4-R45 group; each R42 is independently selected from hydrogen or a -R44 or -R45 group, or any two R42 may, together with the nitrogen atom to which they are attached, form a 3- to 6-membered saturated monocyclic heterocyclic group, wherein the 3- to 6- membered saturated monocyclic heterocyclic group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups; and L4 is a straight-chained alkylene group, wherein the straight-chained alkylene group optionally includes one or two heteroatoms each independently selected from O and N in its carbon skeleton, wherein L4 has a chain length of from 1 to 4 atoms, and wherein L4 may optionally be substituted with one or two oxo (=O) groups and/or with one or more groups RL4, wherein each RL4 is independently selected from a fluoro, methyl or fluoromethyl group; or any RL4 and R41, or any RL4 and any R42, may together with the atoms to which they are attached, form a 3- to 6-membered saturated monocyclic heterocyclic group, wherein the 3- to 6-membered saturated monocyclic heterocyclic group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups. Thus, for example, R4 may be a chloro group, or a -R44 group such as a cyclopropyl group, or a -OR41 group such as a -OMe or -OCHF2 group. Typically, R4, including any optional substituents, contains no more than 6 carbon atoms. Typically, the total number of nitrogen, oxygen and sulphur atoms in R4, including any optional substituents, is no more than four. More typically, the total number of nitrogen, oxygen and sulphur atoms in R4, including any optional substituents, is no more than three. In a more typical embodiment, R4 is selected from a fluoro, chloro, bromo, -OH, -OR44, -N(R42)2, -COOH, -COOR44, -CON(R42)2, -SO2-R44, -SO2-N(R42)2, -O-L4-OH, -O-L4-OR44, -O-L4-N(R42)2, -NR43-L4-OH, -NR43-L4-OR44, -NR43-L4-N(R42)2, or -R44 group, wherein: each R42 is independently selected from hydrogen or a -R44 group; R43 is selected from hydrogen or a -R44 group; each R44 is independently selected from a C1-C4 alkyl or C3-C6 cycloalkyl group, wherein the C1-C4 alkyl or C3-C6 cycloalkyl group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups; and L4 is a -CH2-CH2-, -CH2-CHMe-, -CH2-CMe2-, -CHMe-CH2-, -CHMe-CHMe-, -CHMe-CMe2-, -CMe2-CH2-, -CMe2-CHMe- or -CMe2-CMe2- group, wherein any -CH2-, -CHMe- or -CMe2- group may optionally be fluoro substituted. Typically in such an embodiment, R4 is selected from a fluoro, chloro, bromo, -OR44, -CON(R42)2, -SO2-R44, -SO2-N(R42)2, -O-CH2-CH2-OR44, -O-CH2-CH2-N(R42)2, or -R44 group. More typically in such an embodiment, R4 is selected from a fluoro, chloro, bromo, -OR44, -CON(R42)2, -SO2-R44, -O-CH2-CH2-OR44, -O-CH2-CH2-N(R42)2, or -R44 group. In one embodiment, each R44 is independently selected from a C1-C4 alkyl or C3-C6 cycloalkyl group, wherein the C1-C4 alkyl or C3-C6 cycloalkyl group may optionally be substituted with one or more fluoro groups. More typically, each R44 is independently selected from a C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group. In one aspect of such an embodiment, R4 is selected from a fluoro, chloro, bromo, -OR44 -SO2-R44, -SO2-N(R42)2, -O-CH2-CH2-N(R42)2, or -R44 group. More typically still, R4 is selected from a fluoro, chloro, bromo, -R44 or -OR44 group. Typically in such an embodiment, R44 is selected from a C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group. Yet more typically, R4 is selected from a fluoro, chloro, bromo, methyl (Me) or -OMe group, wherein any methyl group may optionally be fluoro substituted. More typically still, R4 is selected from a methyl (Me) or -OMe group, wherein any methyl group may optionally be fluoro substituted. In another embodiment of either of the first or the second aspects of the invention, R4 and R7 together form a C1-C6 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 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 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 the hydrocarbylene group that is directly attached to the carbon atom to which R8 is attached is a carbon atom. Typically, where R4 and R7 together form a hydrocarbylene group, the hydrocarbylene group, including any optional substituents, contains no more than four carbon atoms. Typically, the total number of nitrogen, oxygen and sulphur atoms in any hydrocarbylene group (including any optional substituents) formed by R4 and R7 is no more than three. More typically, the total number of nitrogen, oxygen and sulphur atoms in any hydrocarbylene group (including any optional substituents) formed by R4 and R7 is no more than two. Typically in such an embodiment, R4 and R7 together form a C1-C4 saturated or unsaturated hydrocarbylene group, wherein the hydrocarbylene group may be straight- chained or branched, or be or include a cyclic group, wherein the hydrocarbylene group may optionally be substituted with one or more fluoro, chloro and/or bromo groups, and wherein the hydrocarbylene group may optionally include one or two heteroatoms each independently selected from N and O in its carbon skeleton, provided that the atom of the hydrocarbylene group that is directly attached to the carbon atom to which R8 is attached is a carbon atom. Where R4 and R7 together form a hydrocarbylene group, typically the hydrocarbylene group has a chain length of from 2 to 4 atoms. More typically, the hydrocarbylene group has a chain length of 2 or 3 atoms. More typically, where R4 and R7 together form a hydrocarbylene group, the hydrocarbylene group is selected from -CH2-CH2-, -CH2-O-, -O-CH2-, -CH2-CH2-CH2-, -O-CH2-CH2-, -CH2-CH2-O- or -CH2-O-CH2-, provided that the atom of the hydrocarbylene group that is directly attached to the carbon atom to which R8 is attached is a carbon atom. Typically, where R4 and R7 together form a hydrocarbylene group, R8 is selected from hydrogen or a fluoro, C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl or C3-C4 fluorocycloalkyl group. More typically, where R4 and R7 together form a hydrocarbylene group, R8 is selected from hydrogen or a fluoro, methyl or fluoromethyl group. More typically still, where R4 and R7 together form a hydrocarbylene group, R8 is hydrogen. As stated in accordance with both the first and the second aspects of the invention, R5 is selected from hydrogen or a halo group. In one embodiment, R5 is selected from hydrogen or a fluoro, chloro or bromo group. More typically, R5 is selected from hydrogen or a fluoro group. Most typically, R5 is hydrogen. As stated in accordance with both the first and the second aspects of the invention, R6 is selected from hydrogen or a halo, -R60 or -OR60 group, wherein R60 is selected from a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl or C3-C4 fluorocycloalkyl group. More typically, R6 is selected from a fluoro, chloro, bromo, -R60 or -OR60 group. More typically still, R6 is selected from a chloro, bromo, -R60 or -OR60 group. Yet more typically, R6 is selected from a -R60 or -OR60 group. In one embodiment, R60 is selected from a C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group. For example, R6 may be selected from a -R60 or -OR60 group, and R60 may be selected from a C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group. Typically, R60 is selected from a methyl, fluoromethyl, ethyl or fluoroethyl group. More typically still, R60 is selected from a methyl or fluoromethyl group. In a further embodiment, R6 is a chloro, bromo, methyl or a fluoromethyl group. Typically in such an embodiment, R6 is a methyl or a fluoromethyl group. More typically, R6 is a methyl group. As stated, in one embodiment of both the first and the second aspects of the invention, R7 and R8 are each independently selected from hydrogen or a fluoro 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 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 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 any hydrocarbyl group of R7 or R8 that is directly attached to the reminder of the molecule is a carbon atom, or R7 and R8 together with the carbon atom to which they are attached form a 3- to 10-membered cyclic group, such that each ring atom of the cyclic group that is directly attached to the carbon atom to which R7 and R8 are attached is a ring carbon atom, wherein the cyclic 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. In one embodiment, R7 and R8 are each independently selected from hydrogen or a fluoro or a C1-C8 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 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 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 any hydrocarbyl group of R7 or R8 that is directly attached to the reminder of the molecule is a carbon atom, or R7 and R8 together with the carbon atom to which they are attached form a 3- to 10-membered cyclic group, such that each ring atom of the cyclic group that is directly attached to the carbon atom to which R7 and R8 are attached is a ring carbon atom, wherein the cyclic 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. In another embodiment, R7 and R8 are each independently selected from hydrogen or a fluoro or a C1-C8 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 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 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 any hydrocarbyl group of R7 or R8 that is directly attached to the reminder of the molecule is a carbon atom. For example, R7 may be selected from hydrogen or a fluoro or a C1-C8 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 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 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 any hydrocarbyl group of R7 that is directly attached to the reminder of the molecule is a carbon atom, and R8 may be selected from hydrogen or a fluoro, C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl or C3-C4 fluorocycloalkyl group. In yet another embodiment, R7 and R8 are each independently selected from hydrogen or a fluoro or a C1-C6 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 fluoro, chloro and/or bromo groups, and wherein the hydrocarbyl group may optionally include one, two or three heteroatoms each independently selected from N and O in its carbon skeleton, provided that the atom of any hydrocarbyl group of R7 or R8 that is directly attached to the reminder of the molecule is a carbon atom. For example, R7 may be selected from hydrogen or a fluoro or a C1-C6 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 fluoro, chloro and/or bromo groups, and wherein the hydrocarbyl group may optionally include one, two or three heteroatoms each independently selected from N and O in its carbon skeleton, provided that the atom of any hydrocarbyl group of R7 that is directly attached to the reminder of the molecule is a carbon atom, and R8 may be selected from hydrogen or a fluoro, methyl or fluoromethyl group. In one embodiment, R7 and R8 are each independently selected from hydrogen or a fluoro, -CN, -COOH, -COOR71, -CO-N(R72)2, -L7-COOH, -L7-COOR71, -L7-CO-N(R72)2, -L7-OH, -L7-OR71, -L7-N(R72)2, -R73, -R74 or -L7-R74 group, wherein: each R71 is independently selected from a -R73 or -R74 group; each R72 is independently selected from hydrogen or a -R73 or -R74 group, or any two R72 may, together with the nitrogen atom to which they are attached, form a 3- to 6- membered saturated monocyclic heterocyclic group, wherein the 3- to 6-membered saturated monocyclic heterocyclic group may optionally be substituted with one or two oxo (=O) groups and/or with one or more fluoro, methyl and/or fluoromethyl groups; each L7 is independently selected from a straight-chained alkylene or alkenylene group, wherein the straight-chained alkylene or alkenylene group optionally includes one or two heteroatoms each independently selected from O and N in its carbon skeleton, wherein L7 has a chain length of from 1 to 4 atoms, and wherein L7 may optionally be substituted with one or two oxo (=O) groups and/or with one or more groups RL7; each RL7 is independently selected from a fluoro, methyl or fluoromethyl group; or any two RL7 may, together with the atom or atoms to which they are attached, form a 3- to 6-membered monocyclic group, wherein the 3- to 6-membered monocyclic group is saturated or monounsaturated, and wherein the 3- to 6-membered monocyclic group may optionally be substituted with one or two oxo (=O) groups and/or with one or more fluoro, methyl and/or fluoromethyl groups; or any RL7 and R71, or any RL7 and any R72, may together with the atoms of the -L7-COOR71, -L7-CO-N(R72)2, -L7-OR71 or -L7-N(R72)2 group to which they are attached, form a 3- to 6-membered monocyclic heterocyclic group, wherein the 3- to 6- membered monocyclic heterocyclic group is saturated or monounsaturated, and wherein the 3- to 6-membered monocyclic heterocyclic group may optionally be substituted with one or two oxo (=O) groups and/or with one or more fluoro, methyl and/or fluoromethyl groups; each R73 is independently selected from a C1-C4 alkyl, C2-C4 alkenyl, C3-C6 cycloalkyl or C5-C6 cycloalkenyl group, wherein the C1-C4 alkyl, C2-C4 alkenyl, C3-C6 cycloalkyl or C5-C6 cycloalkenyl group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups; and each R74 is independently selected from a phenyl or a 5- or 6-membered heteroaryl group, wherein the phenyl or the 5- or 6-membered heteroaryl group may optionally be substituted with one or more groups each independently selected from fluoro, chloro and bromo, and/or with one or two groups each independently selected from methyl (Me), -CN, -OH, -OMe, -NH2, -NHMe, and -NMe2, wherein any methyl group of R74 may optionally be fluoro substituted; provided that any R7 or R8 group, including any optional substituents, contains no more than 12 carbon atoms, and that each atom of R7 or R8 that is directly attached to the reminder of the molecule is a carbon, hydrogen or fluorine atom. Typically in the above embodiment, any R7 or R8 group, including any optional substituents, contains no more than 10 carbon atoms. In one aspect of such an embodiment, R7 and R8 are each independently selected from hydrogen or a fluoro, -CN, -COOH, -COOR71, -L7-COOH, -L7-COOR71, -L7-OH, -L7-OR71, -L7-N(R72)2, -R73, -R74 or -L7-R74 group, provided that any R7 or R8 group, including any optional substituents, contains no more than 8 carbon atoms, and that each atom of R7 or R8 that is directly attached to the reminder of the molecule is a carbon, hydrogen or fluorine atom. More typically, R7 is selected from hydrogen or a fluoro, -CN, -COOH, -COOR71, -CO-N(R72)2, -L7-COOH, -L7-COOR71, -L7-CO-N(R72)2 -L7-OH, -L7-OR71, -L7-N(R72)2, -R73, -R74 or -L7-R74 group, provided that R7, including any optional substituents, contains no more than 12 carbon atoms, and that the atom of R7 that is directly attached to the reminder of the molecule is a carbon, hydrogen or fluorine atom, and R8 is selected from a hydrogen or a fluoro, methyl or fluoromethyl group. Thus, for example, R7 may be hydrogen or a -R73 group such as a methyl, -CF3, ethyl, isopropyl or -CH2CH2CH=CH2 group, or a -COOH group, or a -L7-COOH group such as
Figure imgf000031_0001
Figure imgf000031_0002
group such as a - or -CH2COOEt group, or a -L7-CO-N(R72)2 group such as
Figure imgf000031_0003
group, or a -L7-OH group such group, or a -L7-OR71 group such as a -CH2OMe group, or a -L7-N(R72)2 group such as a
Figure imgf000032_0001
Figure imgf000032_0002
group. Typically in the above embodiments, R7, including any optional substituents, contains no more than 10 carbon atoms. More typically, R7 is selected from hydrogen or a fluoro, -CN, -COOH, -COOR71, -L7-COOH, -L7-COOR71, -L7-OH, -L7-OR71, -L7-N(R72)2, -R73, -R74 or -L7-R74 group, provided that R7, including any optional substituents, contains no more than 8 carbon atoms, and that the atom of R7 that is directly attached to the reminder of the molecule is a carbon, hydrogen or fluorine atom, and R8 is selected from a hydrogen or a fluoro, methyl or fluoromethyl group. As will be understood for example, where R7 is a -L7-COOH group selected from
Figure imgf000032_0003
, , L7 may be seen as a straight-chained alkylene group substituted with two RL7 groups, wherein the two RL7 together form a -CH2CH2-, -CH2- or -CF2- group respectively, such that the two RL7 and the carbon atom or atoms to which they are attached together form a cyclopropyl or fluorocyclopropyl group. Similarly, where R7 is a -L7-N(R72)2 group selected from
Figure imgf000032_0004
or
Figure imgf000032_0005
, L7 may be seen as a straight-chained alkylene group substituted with a single RL7 group, wherein the RL7 and one R72 group together form a -CH2CH2- or -CH2CH2CH2- group respectively, such that the RL7 and the R72 together with the atoms of the -L7-N(R72)2 group to which they are attached together form a saturated 5- or 6- membered monocyclic heterocyclic group. Typically in the above embodiments, each L7 is independently selected from a straight- chained alkylene or alkenylene group, wherein the straight-chained alkylene group optionally includes a single heteroatom selected from O and N in its carbon skeleton, wherein L7 has a chain length of from 1 to 4 atoms, and wherein L7 may optionally be substituted with one or two oxo (=O) groups and/or with one or more groups RL. In one aspect of the above embodiments, each L7 is independently selected from a straight-chained alkylene group, wherein the straight-chained alkylene group optionally includes one or two heteroatoms each independently selected from O and N in its carbon skeleton, wherein L7 has a chain length of from 1 to 4 atoms, and wherein L7 may optionally be substituted with one or two oxo (=O) groups and/or with one or more groups RL7, wherein each RL7 is independently selected from a fluoro, methyl or fluoromethyl group, or wherein any two RL7 may together with the atom or atoms to which they are attached form a 3- to 6-membered saturated monocyclic group, wherein the 3- to 6-membered saturated monocyclic group may optionally be substituted with one or two oxo (=O) groups and/or with one or more fluoro, methyl and/or fluoromethyl groups, or any RL7 and R71, or any RL7 and any R72, may together with the atoms of the -L7-COOR71, -L7-OR71 or -L7-N(R72)2 group to which they are attached, form a 3- to 6-membered saturated monocyclic heterocyclic group, wherein the 3- to 6- membered saturated monocyclic heterocyclic group may optionally be substituted with one or two oxo (=O) groups and/or with one or more fluoro, methyl and/or fluoromethyl groups. In another aspect of the above embodiments: R7 and R8 are each independently selected from hydrogen or a fluoro, -CN, -COOH, -COOR71, -L7-COOH, -L7-COOR71, -L7-OH, -L7-OR71, -L7-N(R72)2, -R73, -R74 or -L7-R74 group; each R72 is independently selected from hydrogen or a -R73 or -R74 group, or any two R72 may, together with the nitrogen atom to which they are attached, form a 3- to 6- membered saturated monocyclic heterocyclic group, wherein the 3- to 6-membered saturated monocyclic heterocyclic group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups; each L7 is independently selected from a straight-chained alkylene group, wherein the straight-chained alkylene group optionally includes one or two heteroatoms each independently selected from O and N in its carbon skeleton, wherein L7 has a chain length of from 1 to 4 atoms, and wherein L7 may optionally be substituted with one or two oxo (=O) groups and/or with one or more groups RL7, wherein each RL7 is independently selected from a fluoro, methyl or fluoromethyl group; or any RL7 and R71, or any RL7 and any R72, may together with the atoms of the -L7-COOR71, -L7-OR71 or -L7-N(R72)2 group to which they are attached, form a 3- to 6- membered saturated monocyclic heterocyclic group, wherein the 3- to 6-membered saturated monocyclic heterocyclic group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups; provided that any R7 or R8 group, including any optional substituents, contains no more than 8 carbon atoms, and that each atom of R7 or R8 that is directly attached to the reminder of the molecule is a carbon, hydrogen or fluorine atom. In yet another aspect of the above embodiments, R7 and R8 are each independently selected from hydrogen or a fluoro, -CN, -COOH, -L7-COOH, -L7-OH, -L7-OR71, -L7-N(R72)2, -R73, -R74 or -L7-R74 group; each R72 is independently selected from hydrogen or a -R73 or -R74 group, or any two R72 may, together with the nitrogen atom to which they are attached, form a 3- to 6- membered saturated monocyclic heterocyclic group, wherein the 3- to 6-membered saturated monocyclic heterocyclic group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups; each L7 is independently selected from a straight-chained alkylene group, wherein the straight-chained alkylene group optionally includes one or two heteroatoms each independently selected from O and N in its carbon skeleton, wherein L7 has a chain length of from 1 to 4 atoms, and wherein L7 may optionally be substituted with one or two oxo (=O) groups and/or with one or more groups RL7, wherein each RL7 is independently selected from a fluoro, methyl or fluoromethyl group; or any RL7 and R71, or any RL7 and any R72, may together with the atoms of the -L7-OR71 or -L7-N(R72)2 group to which they are attached, form a 3- to 6-membered saturated monocyclic heterocyclic group, wherein the 3- to 6-membered saturated monocyclic heterocyclic group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups; and each R73 is independently selected from a C1-C4 alkyl or C3-C6 cycloalkyl group, wherein the C1-C4 alkyl or C3-C6 cycloalkyl group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups; provided that any R7 or R8 group, including any optional substituents, contains no more than 8 carbon atoms, and that each atom of R7 or R8 that is directly attached to the reminder of the molecule is a carbon, hydrogen or fluorine atom. Typically in such an aspect, R7 is selected from hydrogen or a fluoro, -CN, -COOH, -L7-COOH, -L7-OH, -L7-OR71, -L7-N(R72)2, -R73, -R74 or -L7-R74 group, and R8 is selected from a hydrogen or a fluoro, methyl or fluoromethyl group. Typically in the above embodiments, any R7 or R8 group, including any optional substituents, contains no more than 6 carbon atoms. Typically, the total number of nitrogen, oxygen and sulphur atoms in any R7 or R8 group, including any optional substituents, is no more than four. More typically, the total number of nitrogen, oxygen and sulphur atoms in any R7 or R8 group, including any optional substituents, is no more than three. In a further embodiment, R7 and R8 are each independently selected from hydrogen or a fluoro, -COOH, -COOR75, -CONH2, -CONHR75, -CON(R75)2, -L71-COOH, -L71-COOR75, -L71-CONH2, -L71-CONHR75, -L71-CON(R75)2, -L71-OH, -L71-OR75 or -R75 group, wherein:
Figure imgf000035_0001
-L71- moiety may optionally be fluoro substituted; and each R75 is independently selected from a C1-C4 alkyl, C2-C4 alkenyl, cyclopropyl, cyclobutyl, C1-C4 fluoroalkyl, C2-C4 fluoroalkenyl, fluorocyclopropyl or fluorocyclobutyl group, or any two R75 attached to the same nitrogen atom may together with the nitrogen atom to which they are attached form a 4- to 6-membered saturated monocyclic heterocyclic group, such as an azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl or piperazinyl group, wherein the 4- to 6-membered saturated monocyclic heterocyclic group may optionally be substituted with one or more fluoro groups and/or with one or two methyl groups, wherein said methyl groups may optionally be fluoro-substituted; provided that any R7 or R8 group, including any optional substituents, contains no more than 12 carbon atoms. Typically in such an embodiment, R7 is selected from from hydrogen or a fluoro, -COOH, -COOR75, -CONH2, -CONHR75, -CON(R75)2, -L71-COOH, -L71-COOR75, -L71-CONH2, -L71-CONHR75, -L71-CON(R75)2, -L71-OH, -L71-OR75 or -R75 group, and R8 is selected from a hydrogen or a fluoro, methyl or fluoromethyl group. More typically, R8 is hydrogen. Typically, where R7 is selected from from hydrogen or a fluoro, -COOH, -COOR75, -CONH2, -CONHR75, -CON(R75)2, -L71-COOH, -L71-COOR75, -L71-CONH2, -L71-CONHR75, -L71-CON(R75)2, -L71-OH, -L71-OR75 or -R75 group, R7 (including any optional substituents) contains no more than 10 carbon atoms. In a further embodiment, R7 and R8 are each independently selected from hydrogen or a fluoro, -COOH, -COOR75, -L71-COOH, -L71-COOR75, -L71-OH, -L71-OR75 or -R75 group, wherein: each -L71- is independently selected from a
Figure imgf000036_0001
, -CHMe-, -CMe2-, -CH2-CH2-, -CH2-CHMe-, -CH2-CMe2-, -CHMe-CH2-, -CHMe-CHMe-, -CHMe-CMe2-, -CMe2-CH2-, -CMe2-CHMe- or -CMe2-CMe2- group, wherein any -L71- moiety may optionally be fluoro substituted; and each R75 is independently selected from a C1-C4 alkyl, C2-C4 alkenyl, cyclopropyl, cyclobutyl, C1-C4 fluoroalkyl, C2-C4 fluoroalkenyl, fluorocyclopropyl or fluorocyclobutyl group. Typically in such an embodiment, R7 is selected from hydrogen or a fluoro, -COOH, -COOR75, -L71-COOH, -L71-COOR75, -L71-OH, -L71-OR75 or -R75 group, and R8 is selected from a hydrogen or a fluoro, methyl or fluoromethyl group. In one aspect of such an embodiment, each -L71- is independently selected from a -CH2-, -CHMe-, -CMe2-, -CH2-CH2-, -CH2-CHMe-, -CH2-CMe2-, -CHMe-CH2-, -CHMe-CHMe-, -CHMe-CMe2-, -CMe2-CH2-, -CMe2-CHMe- or -CMe2-CMe2- group, wherein any -CH2-, -CHMe- or -CMe2- group may optionally be fluoro substituted. More typically, each -L71- is independently selected from a -CH2-, -CHMe-, -CMe2-, -CH2-CH2-, -CH2-CHMe-, -CH2-CMe2-, -CHMe-CH2-, -CHMe-CHMe- or -CMe2-CH2- group, wherein any -CH2-, -CHMe- or -CMe2- group may optionally be fluoro substituted. Typically in such an embodiment, R7 including any optional substituents, contains no more than 6 carbon atoms, and R8 is selected from a hydrogen or a fluoro, methyl or fluoromethyl group. More typically, R7 including any optional substituents, contains no more than 5 carbon atoms, and R8 is selected from a hydrogen or a fluoro, methyl or fluoromethyl group. In another embodiment, R7 and R8 are each independently selected from hydrogen or a fluoro, -L71-COOH, -L71-COOR75, -L71-OH, -L71-OR75 or -R75 group, wherein: each -L71- is independently selected from a -CH2-, -CHMe- or -CMe2- group, wherein any -CH2-, -CHMe- or -CMe2- group may optionally be fluoro substituted; and each R75 is independently selected from a C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group. Typically in such an embodiment, R7 is selected from hydrogen or a fluoro, -L71-COOH, -L71-COOR75, -L71-OH, -L71-OR75 or -R75 group, and R8 is selected from a hydrogen or a fluoro, methyl or fluoromethyl group. More typically in such an embodiment, R7 is selected from hydrogen or a -L71-COOH, -L71-COOR75 or -R75 group, and R8 is hydrogen. In another embodiment, R7 and R8 are each independently selected from hydrogen or a fluoro, methyl or fluoromethyl group. For example, R7 may be selected from hydrogen or a fluoro, methyl or fluoromethyl group, and R8 may be hydrogen or a fluoro group. In one embodiment, at least one of R7 and R8 is hydrogen. Typically, R8 is hydrogen. In a further embodiment, R7 and R8 are both hydrogen. In another embodiment of either of the first or the second aspects of the invention, R7 and R8 together with the carbon atom to which they are attached form a 3- to 10- membered cyclic group, such that each ring atom of the cyclic group that is directly attached to the carbon atom to which R7 and R8 are attached is a ring carbon atom, wherein the cyclic 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. Typically in such an embodiment, R7 and R8 together with the carbon atom to which they are attached form a 3- to 6-membered saturated monocyclic group, such that each ring atom of the saturated monocyclic group that is directly attached to the carbon atom to which R7 and R8 are attached is a ring carbon atom, wherein the saturated monocyclic group may optionally be substituted with one or more fluoro groups and/or one or two substituents each independently selected from oxo (=O), -CN, or a C1-C3 saturated hydrocarbyl group, wherein the saturated hydrocarbyl group may be straight- chained or branched, wherein the saturated hydrocarbyl group may optionally be substituted with one or more fluoro groups, and wherein the saturated hydrocarbyl group may optionally include a single heteroatom selected from N and O in its carbon skeleton. For example, R7 and R8 may together form a group -L78-, wherein -L78- is selected from a -CH2-CH2-, -CH2-CH2-CH2-, -CH2-NH-CH2-, -CH2-O-CH2-, -CH2-CH2-CH2-CH2-, -CH2-CH2-NH-CH2-, -CH2-CH2-O-CH2-, -CH2-NH-CH2-CH2- or -CH2-O-CH2-CH2- group, and wherein -L78- may optionally be substituted with one or more fluoro groups and/or one or two substituents each independently selected from an oxo (=O), -CN, methyl (Me), -OH, -OMe, -NH2, -NHMe or -NMe2 group, wherein any methyl group of a -L78- substituent may optionally be fluoro substituted. As stated in accordance with both the first and the second aspects of the invention, X10 is N or CR10, X11 is N or CR11, X12 is N or CR12 and X13 is N or CR13, such that no more than two of X10, X11, X12 and X13 are N. Typically, no more than one of X10, X11, X12 and X13 is N. Typically, X11 is CR11 and X12 is CR12, or X11 is CR11 and X12 is N, or X11 is N and X12 is CR12. More typically, X11 is CR11 and X12 is CR12, or X11 is N and X12 is CR12. In one embodiment, X10 is N or CR10, X11 is CR11, X12 is CR12 and X13 is N or CR13. Typically in such an embodiment, no more than one of X10 and X13 is N. In one embodiment, X10 is N, X11 is CR11, X12 is CR12 and X13 is CR13. In a further embodiment, X10 is CR10, X11 is CR11, X12 is CR12 and X13 is CR13. As stated, if present each R10, R11, R12 and R13 is independently selected from hydrogen or a halo, -OH, -SH, -NH2, -SO2NH2, 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 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 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, if present each R10, R11, R12 and R13 is independently selected from hydrogen or a halo (e.g. fluoro, chloro or bromo), -OH, -SH, -NH2, -SO2NH2, or a C1-C10 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 (e.g. fluoro, chloro and/or bromo) groups, wherein the hydrocarbyl group may optionally include one, two, three, four, five or six (more typically one, two, three or four) heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein one -S- moiety 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, if present each R10, R11, R12 and R13 is independently selected from hydrogen or a fluoro, chloro, bromo, -OH, -SH, -NH2, -SO2NH2, -CN, or a C1-C8 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 with one or two oxo (=O) groups, and wherein the saturated hydrocarbyl group may optionally include one, two or three heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein one -S- moiety 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 another embodiment, if present each R10, R11, R12 and R13 is independently selected from hydrogen or a halo, -OH, -NH2 or a C1-C8 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 groups, and wherein the hydrocarbyl group may optionally include one, two or three heteroatoms each independently selected from N and O in its carbon skeleton. In one aspect of such an embodiment, R18 and R19 are each independently selected from hydrogen or a fluoro or a C1-C8 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 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 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 any hydrocarbyl group of R18 or R19 that is directly attached to the reminder of the molecule is a carbon atom, or R18 and R19 together with the carbon atom to which they are attached form a 3- to 10-membered cyclic group, such that each ring atom of the cyclic group that is directly attached to the carbon atom to which R18 and R19 are attached is a ring carbon atom, wherein the cyclic 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, or R18 and R19 together with the carbon atom to which they are attached form a C=O group. In one embodiment, if present each R10, R11, R12 and R13 is independently selected from hydrogen or a halo, -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. In another embodiment, if present each R10, R11, R12 and R13 is independently selected from hydrogen or a fluoro, chloro, bromo, -CN, -OH, -NH2 or a C1-C3 saturated hydrocarbyl group, wherein the saturated hydrocarbyl group may be straight-chained or branched, wherein the saturated hydrocarbyl group may optionally be substituted with one or more halo 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 a further embodiment, X11 is CR11 and X12 is CR12, or X11 is CR11 and X12 is N, or X11 is N and X12 is CR12, and one of R11 and R12 is present and selected from a fluoro, chloro, bromo, fluoromethyl, methoxy, fluoromethoxy, -CH2OH, -CN, -COOH, -CONH2 or -C(=NH)NH2 group. In one aspect of such an embodiment, one of R11 and R12 is present and selected from a fluoro, chloro, bromo, fluoromethyl, -CN, -COOH, -CONH2 or -C(=NH)NH2 group. Typically in such an embodiment, one of R11 and R12 is present and selected from a chloro, bromo, fluoromethyl, methoxy, fluoromethoxy, -CH2OH or -CN group. More typically, one of R11 and R12 is present and selected from a chloro, bromo, methoxy, fluoromethoxy or -CN group. Alternately, one of R11 and R12 may be present and selected from a -CN, -COOH, -CONH2 or -C(=NH)NH2 group. Most typically, X11 is C-CN or X12 is C-CN. Typically in such embodiments, one remaining R10, R11, R12 or R13 is independently selected from hydrogen or a halo, -OH, -SH, -NH2, -SO2NH2, 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 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 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 if present each further remaining R10, R11, R12 or R13 is independently selected from hydrogen or a fluoro, chloro or bromo group. For example, one remaining R10, R11, R12 or R13 may be independently selected from hydrogen or a fluoro, chloro or bromo group, or a -R131, -OH, -SH, -OR131, -SR131, -N(R132)2, -SO2-R131, -SO2-N(R132)2, -L13-OH, -L13-SH, -L13-OR131, -L13-SR131, -L13-N(R132)2, -L13-SO2-R131, -L13-SO2-N(R132)2, -O-L13-OH, -O-L13-SH, -O-L13-OR131, -O-L13-SR131, -O-L13-N(R132)2, -O-L13-SO2-R131, -O-L13-SO2-N(R132)2, -S-L13-OH, -S-L13-SH, -S-L13-OR131, -S-L13-SR131, -S-L13-N(R132)2, -S-L13-SO2-R131, -S-L13-SO2-N(R132)2, -NR133-L13-OH, -NR133-L13-SH, -NR133-L13-OR131, -NR133-L13-SR131, -NR133-L13-N(R132)2, -NR133-L13-SO2-R131 or -NR133-L13-SO2-N(R132)2 group, wherein said group, including any optional substituents, contains no more than 12 carbon atoms, and if present each further remaining R10, R11, R12 or R13 may be independently selected from hydrogen or a fluoro, chloro or bromo group, wherein: each R131 is independently selected from a C1-C4 alkyl or C3-C6 cycloalkyl group, wherein the C1-C4 alkyl or C3-C6 cycloalkyl group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups; each R132 is independently selected from hydrogen or a -R131 group; R133 is selected from hydrogen or a -R131 group; L13 is a straight-chained alkylene or alkenylene group, wherein the straight- chained alkylene or alkenylene group optionally includes one, two or three heteroatoms each independently selected from O and N in its carbon skeleton, wherein L13 has a chain length of from 1 to 8 atoms, and wherein L13 may optionally be substituted with one or two groups each independently selected from oxo (=O) and -OH, and/or with one or more groups RL13; each RL13 is independently selected from a fluoro, C1-C3 alkyl, cyclopropyl, C1- C3 fluoroalkyl, fluorocyclopropyl, -CH2OH, -CH2OMe or -CH2O-fluoromethyl group; or any two RL13, or any RL13 and any R131, or any two R131, may, together with the atom or atoms to which they are attached, form a 3- to 7-membered monocyclic group, wherein the 3- to 7-membered monocyclic group may optionally be substituted with one or two groups each independently selected from oxo (=O) and -OH, and/or with one or more fluoro, methyl and/or fluoromethyl groups; or any two RL13 and any R131, or any three RL13 and any R131, or any two RL13 and any two R131, may, together with the atoms to which they are attached, form a 6- to 10- membered bicyclic heterocyclic group, wherein the 6- to 10-membered bicyclic heterocyclic group may optionally be substituted with one or two groups each independently selected from oxo (=O) and -OH, and/or with one or more fluoro, methyl and/or fluoromethyl groups. Where any two RL13, or any RL13 and any R131, or any two R131, together with the atom or atoms to which they are attached, form a 3- to 7-membered monocyclic group, the monocyclic group may be saturated or unsaturated. For example, any two RL13 may, together with the atom or atoms to which they are attached, form a C3-C7 cycloalkyl group or a 3- to 7-membered saturated monocyclic heterocyclic group, wherein the C3-C7 cycloalkyl group or the 3- to 7-membered saturated monocyclic heterocyclic group may optionally be substituted with one or two groups each independently selected from oxo (=O) and -OH, and/or with one or more fluoro, methyl and/or fluoromethyl groups. Similarly, any RL13 and any R131, or any two R131, may, together with the atom or atoms to which they are attached, form a 3- to 7- membered saturated monocyclic heterocyclic group, wherein the 3- to 7-membered saturated monocyclic heterocyclic group may optionally be substituted with one or two groups each independently selected from oxo (=O) and -OH, and/or with one or more fluoro, methyl and/or fluoromethyl groups. Alternately, any two RL13 may, together with the atom or atoms to which they are attached, form a phenyl group or a 5- or 6-membered heteroaryl group, wherein phenyl group or the 5- or 6-membered heteroaryl group may optionally be substituted with one or two -OH groups, and/or with one or more fluoro, methyl and/or fluoromethyl groups. Similarly, any RL13 and any R131, or any two R131, may, together with the atom or atoms to which they are attached, form a 5-membered heteroaryl group, wherein the 5- membered heteroaryl group may optionally be substituted with one or two -OH groups, and/or with one or more fluoro, methyl and/or fluoromethyl groups. Where any two RL13 and any R131, or any three RL13 and any R131, or any two RL13 and any two R131, together with the atoms to which they are attached, form a 6- to 10-membered bicyclic heterocyclic group, the 6- to 10-membered bicyclic heterocyclic group may be saturated or unsaturated. Similarly, the 6- to 10-membered bicyclic heterocyclic group may be a fused 6- to 10-membered bicyclic heterocyclic group, a spiro 6- to 10- membered bicyclic heterocyclic group or a bridged 6- to 10-membered bicyclic heterocyclic group. For example, any two RL13 and any R131 may, together with the atoms to which they are attached, form a saturated fused 8- to 10-membered bicyclic heterocyclic group, wherein the saturated fused 8- to 10-membered bicyclic heterocyclic group may optionally be substituted with one or two groups each independently selected from oxo (=O) and -OH, and/or with one or more fluoro, methyl and/or fluoromethyl groups. Alternately, any two RL13 and any R131 may, together with the atoms to which they are attached, form a fused 8- to 10-membered bicyclic heterocyclic group, wherein the 8- to 10-membered bicyclic heterocyclic group comprises a first ring system that is fused to a second ring system, wherein the first ring system is aromatic and the second ring system is non-aromatic, and wherein the fused 8- to 10-membered bicyclic heterocyclic group may optionally be substituted with one or two groups each independently selected from oxo (=O) and -OH, and/or with one or more fluoro, methyl and/or fluoromethyl groups. Alternately still, any two RL13 and any R131 may, together with the atoms to which they are attached, form a fused 8- to 10-membered bicyclic heteroaryl group, wherein the fused 8- to 10-membered bicyclic heteroaryl group may optionally be substituted with one or two -OH groups, and/or with one or more fluoro, methyl and/or fluoromethyl groups. In another example, any two RL13 and any R131 may, together with the atoms to which they are attached, form a saturated bridged 6- to 8-membered bicyclic heterocyclic group, wherein the saturated bridged 6- to 8-membered bicyclic heterocyclic group may optionally be substituted with one or two groups each independently selected from oxo (=O) and -OH, and/or with one or more fluoro, methyl and/or fluoromethyl groups. In a further example, any three RL13 and any R131 may, together with the atoms to which they are attached, form a saturated fused 8- to 10-membered bicyclic heterocyclic group, wherein the saturated fused 8- to 10-membered bicyclic heterocyclic group may optionally be substituted with one or two groups each independently selected from oxo (=O) and -OH, and/or with one or more fluoro, methyl and/or fluoromethyl groups. Alternately, any three RL13 and any R131 may, together with the atoms to which they are attached, form a fused 8- to 10-membered bicyclic heterocyclic group, wherein the 8- to 10-membered bicyclic heterocyclic group comprises a first ring system that is fused to a second ring system, wherein the first ring system is aromatic and the second ring system is non-aromatic, and wherein the fused 8- to 10-membered bicyclic heterocyclic group may optionally be substituted with one or two groups each independently selected from oxo (=O) and -OH, and/or with one or more fluoro, methyl and/or fluoromethyl groups. Alternately still, any three RL13 and any R131 may, together with the atoms to which they are attached, form a fused 8- to 10-membered bicyclic heteroaryl group, wherein the fused 8- to 10-membered bicyclic heteroaryl group may optionally be substituted with one or two -OH groups, and/or with one or more fluoro, methyl and/or fluoromethyl groups. In one example, any three RL13 and any R131 may, together with the atoms to which they are attached, form a saturated spiro 7- to 10-membered bicyclic heterocyclic group, wherein the saturated spiro 7- to 10-membered bicyclic heterocyclic group may optionally be substituted with one or two groups each independently selected from oxo (=O) and -OH, and/or with one or more fluoro, methyl and/or fluoromethyl groups. In another example, any three RL13 and any R131 may, together with the atoms to which they are attached, form a saturated bridged 6- to 8-membered bicyclic heterocyclic group, wherein the saturated bridged 6- to 8-membered bicyclic heterocyclic group may optionally be substituted with one or two groups each independently selected from oxo (=O) and -OH, and/or with one or more fluoro, methyl and/or fluoromethyl groups. In one example, any two R131 attached to the same nitrogen atom and any two RL13 may, together with the atoms to which they are attached, form a saturated fused 8- to 10- membered bicyclic heterocyclic group, wherein the saturated fused 8- to 10-membered bicyclic heterocyclic group may optionally be substituted with one or two groups each independently selected from oxo (=O) and -OH, and/or with one or more fluoro, methyl and/or fluoromethyl groups. In another example, any two R131 attached to the same nitrogen atom and any two RL13 may, together with the atoms to which they are attached, form a saturated bridged 6- to 8-membered bicyclic heterocyclic group, wherein the saturated bridged 6- to 8- membered bicyclic heterocyclic group may optionally be substituted with one or two groups each independently selected from oxo (=O) and -OH, and/or with one or more fluoro, methyl and/or fluoromethyl groups. In one aspect of any of the above embodiments: L13 is a straight-chained alkylene or alkenylene group, wherein the straight- chained alkylene or alkenylene group optionally includes one or two heteroatoms each independently selected from O and N in its carbon skeleton, wherein L13 has a chain length of from 1 to 8 atoms, and wherein L13 may optionally be substituted with one or two oxo (=O) groups and/or with one or more groups RL13; each RL13 is independently selected from a fluoro, methyl or fluoromethyl group; or any two RL13, or any RL13 and R131, or any two R131, may, together with the atom or atoms to which they are attached, form a 3- to 7-membered monocyclic group, wherein the 3- to 7-membered monocyclic group is saturated or monounsaturated, and wherein the 3- to 7-membered monocyclic group may optionally be substituted with one or two oxo (=O) groups and/or with one or more fluoro, methyl and/or fluoromethyl groups; or any two RL13 and R131 may, together with the atoms to which they are attached, form a 6- to 10-membered bicyclic heterocyclic group, wherein the 6- to 10- membered bicyclic heterocyclic group is saturated or monounsaturated, and wherein the 6- to 10-membered bicyclic heterocyclic group may optionally be substituted with one or two oxo (=O) groups and/or with one or more fluoro, methyl and/or fluoromethyl groups. More typically in such embodiments, one remaining R10, R11, R12 or R13 is independently selected from hydrogen or a fluoro, chloro, bromo, -OH, -SH, -NH2, -SO2NH2, or a C1- C10 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 fluoro, chloro and/or bromo groups, wherein the hydrocarbyl group may optionally include one, two, three, four, five or six (more typically one, two, three or four) heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein one -S- moiety 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 if present each further remaining R10, R11, R12 or R13 is independently selected from hydrogen or a fluoro, chloro or bromo group. More typically still in such embodiments, one of R10 and R13 is present and selected from hydrogen or a fluoro, chloro, bromo, -OH, -SH, -NH2, -SO2NH2, -CN, or a C1-C8 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 with one or two oxo (=O) groups, and wherein the saturated hydrocarbyl group may optionally include one, two or three heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein one -S- moiety 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 if present each further remaining R10, R11, R12 or R13 is independently selected from hydrogen or a fluoro, chloro or bromo group. Typically, where one remaining R10, R11, R12 or R13 is independently selected from hydrogen or a fluoro, chloro or bromo group, or a -R131, -OH, -SH, -OR131, -SR131, -N(R132)2, -SO2-R131, -SO2-N(R132)2, -L13-OH, -L13-SH, -L13-OR131, -L13-SR131, -L13-N(R132)2, -L13-SO2-R131, -L13-SO2-N(R132)2, -O-L13-OH, -O-L13-SH, -O-L13-OR131, -O-L13-SR131, -O-L13-N(R132)2, -O-L13-SO2-R131, -O-L13-SO2-N(R132)2, -S-L13-OH, -S-L13-SH, -S-L13-OR131, -S-L13-SR131, -S-L13-N(R132)2, -S-L13-SO2-R131, -S-L13-SO2-N(R132)2, -NR133-L13-OH, -NR133-L13-SH, -NR133-L13-OR131, -NR133-L13-SR131, -NR133-L13-N(R132)2, -NR133-L13-SO2-R131 or -NR133-L13-SO2-N(R132)2 group, said group, including any optional substituents, contains no more than 10 carbon atoms. More typically said group, including any optional substituents, contains no more than 8 carbon atoms. Typically, the total number of nitrogen, oxygen and sulphur atoms in said group, including any optional substituents, is no more than six. More typically, the total number of nitrogen, oxygen and sulphur atoms in said group, including any optional substituents, is no more than four, or no more than three. In a typical embodiment, where one of R11 and R12 is present and selected from a fluoro, chloro, bromo, fluoromethyl, methoxy, fluoromethoxy, -CH2OH, -CN, -COOH, -CONH2 or -C(=NH)NH2 group, X10 is N or CR10, X11 is CR11, X12 is CR12, X13 is N or CR13, and no more than one of X10 and X13 is N. Typically in such an embodiment, the other of R11 and R12 is selected from hydrogen or a fluoro, chloro, bromo, -OH, -NH2, methyl (Me), ethyl (Et), -OMe, -NHMe, -NMe2, -CH2OH or -CH2NH2 group, wherein any methyl (Me), ethyl (Et) or methylene (-CH2-) group of R11 or R12 may optionally be fluoro substituted. More typically in such an embodiment, one of R11 and R12 is selected from a chloro, bromo, fluoromethyl, methoxy, fluoromethoxy, -CH2OH or -CN group and the other of R11 and R12 is selected from hydrogen or a fluoro, chloro or bromo group. More typically, one of R11 and R12 is selected from a chloro, bromo, methoxy, fluoromethoxy or -CN group and the other of R11 and R12 is selected from hydrogen or a fluoro, chloro or bromo group. More typically still, one of R11 and R12 is a -CN group and the other of R11 and R12 is selected from hydrogen or a fluoro, chloro or bromo group. Typically in such embodiments, one of R10 and R13 is selected from hydrogen or a fluoro, chloro, bromo, -OH, -SH, -NH2, -SO2NH2, or a C1-C10 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 fluoro, chloro and/or bromo groups, wherein the hydrocarbyl group may optionally include one, two, three, four, five or six (more typically one, two, three or four) heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein one -S- moiety 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 if present the other of R10 and R13 is selected from hydrogen or a fluoro, chloro or bromo group. More typically in such embodiments, one of R10 and R13 is selected from hydrogen or a fluoro, chloro, bromo, -OH, -SH, -NH2, -SO2NH2, -CN, or a C1-C8 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 with one or two oxo (=O) groups, and wherein the saturated hydrocarbyl group may optionally include one, two or three heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein one -S- moiety 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 if present the other of R10 and R13 is selected from hydrogen or a fluoro, chloro or bromo group. In one embodiment, where one of R11 and R12 is present and selected from a fluoro, chloro, bromo, fluoromethyl, -CN, -COOH, -CONH2 or -C(=NH)NH2 group, if present each remaining R10, R11, R12 and R13 is independently selected from hydrogen or a fluoro, chloro, bromo, -OH, -NH2, methyl (Me), ethyl (Et), -OMe, -NHMe, -NMe2, -CH2OH or -CH2NH2 group, wherein any methyl (Me), ethyl (Et) or methylene (-CH2-) group of R10, R11, R12 or R13 may optionally be fluoro substituted. More typically, if present one remaining R10, R11, R12 or R13 is independently selected from hydrogen or a fluoro, chloro, bromo, -OH, -NH2, methyl (Me), ethyl (Et), -OMe, -NHMe, -NMe2, -CH2OH or -CH2NH2 group, wherein any methyl (Me), ethyl (Et) or methylene (-CH2-) group of R10, R11, R12 or R13 may optionally be fluoro substituted, and each further remaining R10, R11, R12 or R13 is independently selected from hydrogen or a fluoro, chloro or bromo group. For example, where one of R11 and R12 is present and selected from a fluoro, chloro, bromo, fluoromethyl, -CN, -COOH, -CONH2 or -C(=NH)NH2 group, one of R10 or R13 if present may be selected from hydrogen or a fluoro, chloro, bromo, -OH, -NH2, methyl (Me), ethyl (Et), -OMe, -NHMe, -NMe2, -CH2OH or -CH2NH2 group, wherein any methyl (Me), ethyl (Et) or methylene (-CH2-) group of R10 or R13 may optionally be fluoro substituted, and each remaining R10, R11, R12 or R13 may be independently selected from hydrogen or a fluoro, chloro or bromo group. More typically still, where one of R11 and R12 is present and selected from a fluoro, chloro, bromo, fluoromethyl, -CN, -COOH, -CONH2 or -C(=NH)NH2 group, if present each remaining R10, R11, R12 or R13 is independently selected from hydrogen or a fluoro, chloro or bromo group. In yet another embodiment, X10 is N or CR10, X11 is CR11, X12 is CR12 and X13 is N or CR13, no more than one of X10 and X13 is N, one of R11 and R12 is selected from a fluoro, chloro, bromo, fluoromethyl, -CN, -COOH, -CONH2 or -C(=NH)NH2 group, the other of R11 and R12 is selected from hydrogen or a fluoro, chloro, bromo, -OH, -NH2, methyl (Me), ethyl (Et), -OMe, -NHMe, -NMe2, -CH2OH or -CH2NH2 group, and if present R10 and R13 are each independently selected from hydrogen or a fluoro, chloro, bromo, -OH, -NH2, methyl (Me), ethyl (Et), -OMe, -NHMe, -NMe2, -CH2OH or -CH2NH2 group, wherein any methyl (Me), ethyl (Et) or methylene (-CH2-) group of R10, R11, R12 or R13 may optionally be fluoro substituted. Typically in such an embodiment, one of R11 and R12 is selected from a -CN, -COOH, -CONH2 or -C(=NH)NH2 group and the other of R11 and R12 is selected from hydrogen or a fluoro, chloro or bromo group. More typically, one of R11 and R12 is a -CN group and the other of R11 and R12 is selected from hydrogen or a fluoro, chloro or bromo group. Typically in such an embodiment, one of R10 and R13 is selected from hydrogen or a fluoro, chloro, bromo, -OH, -NH2, methyl (Me), ethyl (Et), -OMe, -NHMe, -NMe2, -CH2OH or -CH2NH2 group, wherein any methyl (Me), ethyl (Et) or methylene (-CH2-) group of R10 or R13 may optionally be fluoro substituted, and if present the other of R10 and R13 is selected from hydrogen or a fluoro, chloro or bromo group. More typically still in such an embodiment, if present each R10 and R13 is independently selected from hydrogen or a fluoro, chloro or bromo group. In a typical embodiment, X10 is N or CR10, X11 is CR11, X12 is CR12 and X13 is N or CR13, no more than one of X10 and X13 is N, R10 is selected from hydrogen or a fluoro, chloro, bromo, methyl or fluoromethyl group, R11 is selected from a chloro, bromo, fluoromethyl, methoxy, fluoromethoxy, -CH2OH or -CN group, R12 is selected from hydrogen or a fluoro, chloro or bromo group, and R13 is selected from hydrogen or a fluoro, chloro, bromo, methyl or fluoromethyl group. Typically in such an embodiment, X10 is N or CR10, X11 is CR11, X12 is CR12 and X13 CR13. Typically in such an embodiment, R11 is selected from a chloro, bromo, methoxy, fluoromethoxy, -CH2OH or -CN group. More typically, R11 is selected from a chloro, bromo, methoxy, fluoromethoxy or -CN group. Most typically, R11 is a -CN group, i.e. X11 is C-CN. Typically, at least one of X10, X12 and X13 is C-H. More typically, at least two of X10, X12 and X13 are C-H. In a further embodiment, X10 is N, C-H, C-F, C-Cl or C-Br, X11 is C-H, C-F, C-Cl or C-Br, X12 is C-CN and X13 is N, C-H, C-F, C-Cl or C-Br, provided that no more than one of X10 and X13 is N. In an alternate embodiment, X10 is N, C-H, C-F, C-Cl or C-Br, X11 is C-CN, X12 is C-H, C- F, C-Cl or C-Br, and X13 is N, C-H, C-F, C-Cl or C-Br, provided that no more than one of X10 and X13 is N. As stated in accordance with the second aspect of the invention, each R14 and R15 is independently selected from hydrogen or a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl or C3-C4 fluorocycloalkyl group, or R14 and R15 together with the carbon atom to which they are attached form a 3- to 6-membered cyclic group, wherein the cyclic group may optionally be substituted with one or more substituents each independently selected from a fluoro, -OH, oxo (=O), methyl or ethyl group, wherein any methyl or ethyl group may optionally be fluoro substituted. In one embodiment, each R14 and R15 is independently selected from hydrogen or a C1- C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl or C3-C4 fluorocycloalkyl group. For example, R14 may be hydrogen and R15 may be selected from hydrogen or a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl or C3-C4 fluorocycloalkyl group. Typically in such an embodiment, each R14 and R15 is independently selected from hydrogen or a C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group. For example, R14 may be hydrogen and R15 may be selected from hydrogen or a C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group. More typically in such an embodiment, each R14 and R15 is independently selected from hydrogen or a methyl or fluoromethyl group. For example, R14 may be hydrogen and R15 may be selected from hydrogen or a methyl or fluoromethyl group. In one embodiment, R14 and R15 are both hydrogen. In another embodiment, R14 and R15 together with the carbon atom to which they are attached form a 3- to 6-membered cyclic group, wherein the cyclic group may optionally be substituted with one or more substituents each independently selected from a fluoro, -OH, oxo (=O), methyl or ethyl group, wherein any methyl or ethyl group may optionally be fluoro substituted. Typically in such an embodiment, R14 and R15 together with the carbon atom to which they are attached form a 3- to 5-membered saturated monocyclic group wherein the saturated monocyclic group may optionally be substituted with one or more fluoro groups and/or one or two substituents each independently selected from oxo (=O) or a methyl or fluoromethyl group. For example, R14 and R15 together with the carbon atom to which they are attached may form a cyclopropyl or a cyclobutyl group, wherein the cyclopropyl or cyclobutyl group may optionally be substituted with one or more fluoro groups. As stated, in one embodiment of the second aspect of the invention, R16 is selected from hydrogen or a fluoro, -SO2NH2, or a C1-C8 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 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 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 R17 is selected from hydrogen or a fluoro, C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl or C3-C4 fluorocycloalkyl group, or R16 and R17 together with the carbon atom to which they are attached form a 3- to 6- membered cyclic group, wherein the cyclic group may optionally be substituted with one or more substituents each independently selected from a fluoro, -OH, oxo (=O), methyl or ethyl group, wherein any methyl or ethyl group may optionally be fluoro substituted. In one embodiment, R16 is selected from hydrogen or a fluoro, -SO2NH2, or a C1-C8 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 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 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 R17 is selected from hydrogen or a fluoro, C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl or C3-C4 fluorocycloalkyl group. In one aspect of such an embodiment, R16 is selected from hydrogen or a fluoro, -R160, -CN, -CHO, -COR160, -CO2H or -CO2R160 group, wherein R160 is selected from a C1-C6 alkyl, C1-C6 fluoroalkyl, C2-C6 alkenyl, C2-C6 fluoroalkenyl or -R161 group, wherein R161 is a 3- to 6-membered monocyclic group, wherein the 3- to 6-membered monocyclic group may optionally be substituted with one or more halo (e.g. fluoro, chloro or bromo) groups and/or with one or two groups R162, wherein each R162 is independently selected from a methyl or a fluoromethyl group, provided that the group R16, including any optional substituents, contains no more than 8 carbon atoms. Typically in such an embodiment, R16 is selected from hydrogen or a fluoro, -R160, -CN, -CHO, -COR160, -CO2H or -CO2R160 group, wherein R160 is selected from a C1-C4 alkyl, C1-C4 fluoroalkyl or -R161 group, wherein R161 is selected from a C3-C6 cycloalkyl group, a 4- to 6- membered saturated heterocyclic group, or a phenyl or a 5- or 6-membered heteroaryl group, wherein the C3-C6 cycloalkyl group and the 4- to 6-membered saturated heterocyclic group may optionally be substituted with one or more fluoro groups and/or with one or two groups R162, and wherein the phenyl or the 5- or 6-membered heteroaryl group may optionally be substituted with one or more fluoro, chloro and/or bromo groups, and/or with one or two groups R162, provided that the group R16, including any optional substituents, contains no more than 8 carbon atoms. More typically in such an embodiment, R16 is selected from hydrogen or a fluoro, -R160, -R161, -CN, -CHO, -COR160, -CO2H or -CO2R160 group, wherein R160 is selected from a methyl or fluoromethyl group, and wherein R161 is a 5-membered heteroaryl group, wherein the 5-membered heteroaryl group may optionally be substituted with one or more fluoro, chloro and/or bromo groups, and/or with one or two groups R162. Typically in the above aspect, R17 is selected from hydrogen or a fluoro, C1-C4 alkyl, C3- C4 cycloalkyl, C1-C4 fluoroalkyl or C3-C4 fluorocycloalkyl group. More typically, R17 is selected from hydrogen or a fluoro, C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group. Most typically, R17 is hydrogen. In one aspect of such an embodiment, R16 is selected from hydrogen or a fluoro, -R160, -CN, -CHO, -COR160, -CO2H or -CO2R160 group, wherein R160 is selected from a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl or C3-C4 fluorocycloalkyl group, and R17 is selected from hydrogen or a fluoro, C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl or C3- C4 fluorocycloalkyl group. Typically in such an aspect, R17 is selected from hydrogen or a fluoro, C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group. For example, R16 may be selected from hydrogen or a fluoro, -R160, -CN, -CHO, -COR160, -CO2H or -CO2R160 group, and R17 may be hydrogen. Typically in such an aspect, R160 is selected from a C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group. More typically in such an aspect, R160 is selected from a methyl or fluoromethyl group. In another aspect of such an embodiment, R16 is selected from hydrogen or a fluoro, -CN, C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl or C3-C4 fluorocycloalkyl group, and R17 is selected from hydrogen or a fluoro, C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl or C3-C4 fluorocycloalkyl group. For example, R16 may be selected from hydrogen or a fluoro, -CN, C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl or C3-C4 fluorocycloalkyl group, and R17 may be hydrogen. Typically in such an embodiment, R16 is selected from hydrogen or a fluoro, -CN, C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group, and R17 is selected from hydrogen or a fluoro, C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group. For example, R16 may be selected from hydrogen or a fluoro, -CN, C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group, and R17 may be hydrogen. More typically in such an embodiment, each R16 and R17 is independently selected from hydrogen or a methyl or fluoromethyl group. For example, R16 may be selected from hydrogen or a methyl or fluoromethyl group and R17 may be hydrogen. In one embodiment, R16 and R17 are both hydrogen. In another embodiment, R16 and R17 together with the carbon atom to which they are attached form a 3- to 6-membered cyclic group, wherein the cyclic group may optionally be substituted with one or more substituents each independently selected from a fluoro, -OH, oxo (=O), methyl or ethyl group, wherein any methyl or ethyl group may optionally be fluoro substituted. Typically in such an embodiment, R16 and R17 together with the carbon atom to which they are attached form a 3- to 5-membered saturated monocyclic group wherein the saturated monocyclic group may optionally be substituted with one or more fluoro groups and/or one or two substituents each independently selected from oxo (=O) or a methyl or fluoromethyl group. For example, R16 and R17 together with the carbon atom to which they are attached may form a cyclopropyl or a cyclobutyl group, wherein the cyclopropyl or cyclobutyl group may optionally be substituted with one or more fluoro groups. In one embodiment of the second aspect of the invention: R16 is selected from hydrogen or a fluoro, -R160, -CN, -CHO, -COR160, -CO2H or -CO2R160 group, wherein R160 is selected from a C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group; and R17 is selected from hydrogen or a fluoro, C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group; or R16 and R17 together with the carbon atom to which they are attached form a 3- to 5-membered saturated monocyclic group wherein the saturated monocyclic group may optionally be substituted with one or more fluoro groups and/or one or two substituents each independently selected from oxo (=O) or a methyl or fluoromethyl group. In another embodiment of the second aspect of the invention: R16 is selected from hydrogen or a fluoro, -CN, C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group; and R17 is selected from hydrogen or a fluoro, C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group; or R16 and R17 together with the carbon atom to which they are attached form a cyclopropyl or a cyclobutyl group, wherein the cyclopropyl or cyclobutyl group may optionally be substituted with one or more fluoro groups. In another embodiment of the second aspect of the invention, R17 and R7 together form a C1-C6 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 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 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 the hydrocarbylene group that is directly attached to the carbon atom to which R8 is attached is a carbon atom. Typically, where R17 and R7 together form a hydrocarbylene group, the hydrocarbylene group, including any optional substituents, contains no more than four carbon atoms. Typically, the total number of nitrogen, oxygen and sulphur atoms in any hydrocarbylene group (including any optional substituents) formed by R17 and R7 is no more than three. More typically, the total number of nitrogen, oxygen and sulphur atoms in any hydrocarbylene group (including any optional substituents) formed by R17 and R7 is no more than two. Typically in such an embodiment, R17 and R7 together form a C1-C4 saturated or unsaturated hydrocarbylene group, wherein the hydrocarbylene group may be straight- chained or branched, or be or include a cyclic group, wherein the hydrocarbylene group may optionally be substituted with one or more halo groups, and wherein the hydrocarbylene group may optionally include one or two heteroatoms each independently selected from N and O in its carbon skeleton, provided that the atom of the hydrocarbylene group that is directly attached to the carbon atom to which R8 is attached is a carbon atom. Where R17 and R7 together form a hydrocarbylene group, typically the hydrocarbylene group has a chain length of from 1 to 3 atoms. More typically, the hydrocarbylene group has a chain length of 1 or 2 atoms. More typically, where R17 and R7 together form a hydrocarbylene group, the hydrocarbylene group is selected from -CH2-, -CH2-CH2-, -CH=CH-, -CH2-O- or -O-CH2-, provided that the atom of the hydrocarbylene group that is directly attached to the carbon atom to which R8 is attached is a carbon atom. Typically, where R17 and R7 together form a hydrocarbylene group, R8 is selected from hydrogen or a fluoro, C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl or C3-C4 fluorocycloalkyl group. More typically, where R17 and R7 together form a hydrocarbylene group, R8 is selected from hydrogen or a fluoro, methyl or fluoromethyl group. More typically still, where R17 and R7 together form a hydrocarbylene group, R8 is hydrogen. Typically, where R17 and R7 together form a hydrocarbylene group, R16 is selected from hydrogen or a fluoro, -CN, C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl or C3-C4 fluorocycloalkyl group. More typically, where R17 and R7 together form a hydrocarbylene group, R16 is selected from hydrogen or a fluoro, -CN, C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group. More typically still, where R17 and R7 together form a hydrocarbylene group, R16 is selected from hydrogen or a methyl or fluoromethyl group. Yet more typically, where R17 and R7 together form a hydrocarbylene group, R16 is hydrogen. As stated in accordance with both the first and the second aspects of the invention, R18 and R19 are each independently selected from hydrogen or a fluoro 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 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 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 any hydrocarbyl group of R18 or R19 that is directly attached to the reminder of the molecule is a carbon atom, or R18 and R19 together with the carbon atom to which they are attached form a 3- to 10-membered cyclic group, such that each ring atom of the cyclic group that is directly attached to the carbon atom to which R18 and R19 are attached is a ring carbon atom, wherein the cyclic 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, or R18 and R19 together with the carbon atom to which they are attached form a C=O group. More typically, R18 and R19 are each independently selected from hydrogen or a fluoro or a C1-C8 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 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 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 any hydrocarbyl group of R18 or R19 that is directly attached to the reminder of the molecule is a carbon atom, or R18 and R19 together with the carbon atom to which they are attached form a 3- to 10-membered cyclic group, such that each ring atom of the cyclic group that is directly attached to the carbon atom to which R18 and R19 are attached is a ring carbon atom, wherein the cyclic 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, or R18 and R19 together with the carbon atom to which they are attached form a C=O group. In one embodiment, R18 and R19 are each independently selected from hydrogen or a fluoro or a C1-C12 (more typically C1-C8) 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 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 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 any hydrocarbyl group of R18 or R19 that is directly attached to the reminder of the molecule is a carbon atom. For example, R18 may be selected from hydrogen or a fluoro or a C1-C12 (more typically C1-C8) 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 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 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 any hydrocarbyl group of R18 that is directly attached to the reminder of the molecule is a carbon atom, and R19 may be selected from hydrogen or a fluoro, C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl or C3- C4 fluorocycloalkyl group. In another embodiment, R18 and R19 are each independently selected from hydrogen or a fluoro or a C1-C7 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 fluoro, chloro and/or bromo groups, and wherein the hydrocarbyl group may optionally include one, two or three heteroatoms each independently selected from N and O in its carbon skeleton, provided that the atom of any hydrocarbyl group of R18 or R19 that is directly attached to the reminder of the molecule is a carbon atom. For example, R18 may be selected from hydrogen or a fluoro or a C1-C7 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 fluoro, chloro and/or bromo groups, and wherein the hydrocarbyl group may optionally include one, two or three heteroatoms each independently selected from N and O in its carbon skeleton, provided that the atom of any hydrocarbyl group of R18 that is directly attached to the reminder of the molecule is a carbon atom, and R19 may be selected from hydrogen or a fluoro, methyl or fluoromethyl group. In one embodiment, R18 and R19 are each independently selected from hydrogen or a fluoro, -CN, -COOH, -COOR181, -CO-N(R182)2, -L18-COOH, -L18-COOR181, -L18-CO-N(R182)2, -L18-OH, -L18-OR181, -L18-N(R182)2, -R183, -R184 or -L18-R184 group, wherein: each R181 is independently selected from a -R183 or -R184 group; each R182 is independently selected from hydrogen or a -R183 or -R184 group, or any two R182 may, together with the nitrogen atom to which they are attached, form a 3- to 6-membered saturated monocyclic heterocyclic group, wherein the 3- to 6- membered saturated monocyclic heterocyclic group may optionally be substituted with one or two oxo (=O) groups and/or with one or more fluoro, methyl and/or fluoromethyl groups; each L18 is independently selected from a straight-chained alkylene, alkenylene or alkynylene group, wherein the straight-chained alkylene, alkenylene or alkynylene group optionally includes one or two heteroatoms each independently selected from O and N in its carbon skeleton, wherein the straight-chained alkylene, alkenylene or alkynylene group has a chain length of from 1 to 4 atoms, and wherein the straight- chained alkylene, alkenylene or alkynylene group may optionally be substituted with one or two oxo (=O) groups and/or with one or more groups RL18; each RL18 is independently selected from a fluoro, methyl or fluoromethyl group; or any two RL18 may together with the atom or atoms to which they are attached form a 3- to 6-membered monocyclic group, wherein the 3- to 6-membered monocyclic group is saturated or monounsaturated, and wherein the 3- to 6-membered monocyclic group may optionally be substituted with one or two oxo (=O) groups and/or with one or more fluoro, methyl and/or fluoromethyl groups; or any RL18 and R181, or any RL18 and any R182, may together with the atoms of the -L18-COOR181, -L18-CO-N(R182)2, -L18-OR181 or -L18-N(R182)2 group to which they are attached, form a 3- to 6-membered monocyclic heterocyclic group, wherein the 3- to 6- membered monocyclic heterocyclic group is saturated or monounsaturated, and wherein the 3- to 6-membered monocyclic heterocyclic group may optionally be substituted with one or two oxo (=O) groups and/or with one or more fluoro, methyl and/or fluoromethyl groups; or L18 is a divalent phenyl or a divalent 5- or 6-membered heteroaryl group, wherein the divalent phenyl or the divalent 5- or 6-membered heteroaryl group may optionally be substituted with one or more groups each independently selected from fluoro, chloro, bromo, methyl and fluoromethyl; each R183 is independently selected from a C1-C4 alkyl, C2-C4 alkenyl, C3-C6 cycloalkyl or C5-C6 cycloalkenyl group, wherein the C1-C4 alkyl, C2-C4 alkenyl, C3-C6 cycloalkyl or C5-C6 cycloalkenyl group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups; and each R184 is independently selected from a phenyl or a 5- or 6-membered heteroaryl group, wherein the phenyl or the 5- or 6-membered heteroaryl group may optionally be substituted with one or more groups each independently selected from fluoro, chloro and bromo, and/or with one or two groups each independently selected from methyl (Me), -CN, -OH, -OMe, -NH2, -NHMe, and -NMe2, wherein the methyl group of R184 may optionally be fluoro substituted; provided that any R18 or R19 group, including any optional substituents, contains no more than 12 carbon atoms, and that each atom of R18 or R19 that is directly attached to the reminder of the molecule is a carbon, hydrogen or fluorine atom. Typically in the above embodiment, any R18 or R19 group, including any optional substituents, contains no more than 10 carbon atoms. In one aspect of such an embodiment, R18 and R19 are each independently selected from hydrogen or a fluoro, -CN, -COOH, -COOR181, -L18-COOH, -L18-COOR181, -L18-OH, -L18-OR181, -L18-N(R182)2, -R183, -R184 or -L18-R184 group, provided that any R18 or R19 group, including any optional substituents, contains no more than 8 carbon atoms, and that each atom of R18 or R19 that is directly attached to the reminder of the molecule is a carbon, hydrogen or fluorine atom. More typically, R18 is selected from hydrogen or a fluoro, -CN, -COOH, -COOR181, -CO-N(R182)2, -L18-COOH, -L18-COOR181, -L18-CO-N(R182)2, -L18-OH, -L18-OR181, -L18-N(R182)2, -R183, -R184 or -L18-R184 group, provided that R18, including any optional substituents, contains no more than 12 carbon atoms, and that the atom of R18 that is directly attached to the reminder of the molecule is a carbon, hydrogen or fluorine atom, and R19 is selected from a hydrogen or a fluoro, methyl or fluoromethyl group. Typically in the above embodiments, R18, including any optional substituents, contains no more than 10 carbon atoms. More typically, R18 is selected from hydrogen or a fluoro, -CN, -COOH, -COOR181, -L18-COOH, -L18-COOR181, -L18-OH, -L18-OR181, -L18-N(R182)2, -R183, -R184 or -L18-R184 group, provided that R18, including any optional substituents, contains no more than 8 carbon atoms, and that the atom of R18 that is directly attached to the reminder of the molecule is a carbon, hydrogen or fluorine atom, and R19 is selected from a hydrogen or a fluoro, methyl or fluoromethyl group In one aspect of such an embodiment: R18 and R19 are each independently selected from hydrogen or a fluoro, -CN, -COOH, -COOR181, -L18-COOH, -L18-COOR181, -L18-OH, -L18-OR181, -L18-N(R182)2, -R183, -R184 or -L18-R184 group; each R182 is independently selected from hydrogen or a -R183 or -R184 group, or any two R182 may, together with the nitrogen atom to which they are attached, form a 3- to 6-membered saturated monocyclic heterocyclic group, wherein the 3- to 6- membered saturated monocyclic heterocyclic group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups; each L18 is independently selected from a straight-chained alkylene, alkenylene or alkynylene group, wherein the straight-chained alkylene, alkenylene or alkynylene group optionally includes one or two heteroatoms each independently selected from O and N in its carbon skeleton, wherein the straight-chained alkylene, alkenylene or alkynylene group has a chain length of from 1 to 4 atoms, and wherein the straight- chained alkylene, alkenylene or alkynylene group may optionally be substituted with one or two oxo (=O) groups and/or with one or more groups RL18, wherein each RL18 is independently selected from a fluoro, methyl or fluoromethyl group; or any RL18 and R181, or any RL18 and any R182, may together with the atoms of the -L18-COOR181, -L18-OR181 or -L18-N(R182)2 group to which they are attached, form a 3- to 6-membered saturated monocyclic heterocyclic group, wherein the 3- to 6-membered saturated monocyclic heterocyclic group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups; or L18 is a divalent phenyl or a divalent 5- or 6-membered heteroaryl group, wherein the divalent phenyl or the divalent 5- or 6-membered heteroaryl group may optionally be substituted with one or more groups each independently selected from fluoro, chloro, bromo, methyl and fluoromethyl; provided that any R18 or R19 group, including any optional substituents, contains no more than 8 carbon atoms, and that each atom of R18 or R19 that is directly attached to the reminder of the molecule is a carbon, hydrogen or fluorine atom. In another aspect of such an embodiment, R18 and R19 are each independently selected from hydrogen or a fluoro, -CN, -COOH, -L18-COOH, -L18-OH, -L18-OR181, -L18-N(R182)2, -R183, -R184 or -L18-R184 group, and each R183 is independently selected from a C1-C4 alkyl or C3-C6 cycloalkyl group, wherein the C1-C4 alkyl or C3-C6 cycloalkyl group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups, provided that any R18 or R19 group, including any optional substituents, contains no more than 8 carbon atoms, and that each atom of R18 or R19 that is directly attached to the reminder of the molecule is a carbon, hydrogen or fluorine atom. Typically in such an aspect, R18 is selected from hydrogen or a fluoro, -CN, -COOH, -L18-COOH, -L18-OH, -L18-OR181, -L18-N(R182)2, -R183, -R184 or -L18-R184 group, and R19 is selected from a hydrogen or a fluoro, methyl or fluoromethyl group. Typically in such an aspect: each R182 is independently selected from hydrogen or a -R183 or -R184 group, or any two R182 may, together with the nitrogen atom to which they are attached, form a 3- to 6-membered saturated monocyclic heterocyclic group, wherein the 3- to 6- membered saturated monocyclic heterocyclic group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups; each L18 is independently selected from a straight-chained alkylene, alkenylene or alkynylene group, wherein the straight-chained alkylene, alkenylene or alkynylene group optionally includes one or two heteroatoms each independently selected from O and N in its carbon skeleton, wherein the straight-chained alkylene, alkenylene or alkynylene group has a chain length of from 1 to 4 atoms, and wherein the straight- chained alkylene, alkenylene or alkynylene group may optionally be substituted with one or two oxo (=O) groups and/or with one or more groups RL18, wherein each RL18 is independently selected from a fluoro, methyl or fluoromethyl group; or any RL18 and R181, or any RL18 and any R182, may together with the atoms of the -L18-COOR181, -L18-OR181 or -L18-N(R182)2 group to which they are attached, form a 3- to 6-membered saturated monocyclic heterocyclic group, wherein the 3- to 6-membered saturated monocyclic heterocyclic group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups; or L18 is a divalent phenyl or a divalent 5- or 6-membered heteroaryl group, wherein the divalent phenyl or the divalent 5- or 6-membered heteroaryl group may optionally be substituted with one or more groups each independently selected from fluoro, chloro, bromo, methyl and fluoromethyl. Typically in the above embodiments, any R18 or R19 group, including any optional substituents, contains no more than 7 carbon atoms. Typically, the total number of nitrogen, oxygen and sulphur atoms in any R18 or R19 group, including any optional substituents, is no more than four. More typically, the total number of nitrogen, oxygen and sulphur atoms in any R18 or R19 group, including any optional substituents, is no more than three. In one aspect of the above embodiments, R18 and R19 are each independently selected from hydrogen or a fluoro or a -R183 group. Typically in such an aspect, each R183 is independently selected from a C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 fluoroalkyl or C3-C6 fluorocycloalkyl group. More typically, R18 and R19 are each independently selected from hydrogen or a fluoro, methyl or fluoromethyl group. In one embodiment, at least one of R18 and R19 is hydrogen. In a further embodiment, R18 and R19 are both hydrogen. In another embodiment, R18 and R19 together with the carbon atom to which they are attached form a 3- to 10-membered cyclic group, such that each ring atom of the cyclic group that is directly attached to the carbon atom to which R18 and R19 are attached is a ring carbon atom, wherein the cyclic 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. Typically in such an embodiment, R18 and R19 together with the carbon atom to which they are attached form a 3- to 6-membered saturated monocyclic group, such that each ring atom of the saturated monocyclic group that is directly attached to the carbon atom to which R18 and R19 are attached is a ring carbon atom, wherein the saturated monocyclic group may optionally be substituted with one or more fluoro groups and/or one or two substituents each independently selected from oxo (=O), -CN, or a C1-C3 saturated hydrocarbyl group, wherein the saturated hydrocarbyl group may be straight- chained or branched, wherein the saturated hydrocarbyl group may optionally be substituted with one or more fluoro groups, and wherein the saturated hydrocarbyl group may optionally include a single heteroatom selected from N and O in its carbon skeleton. For example, R18 and R19 may together form a group -L89-, wherein -L89- is selected from a -CH2-CH2-, -CH2-CH2-CH2-, -CH2-NH-CH2-, -CH2-O-CH2-, -CH2-CH2-CH2-CH2-, -CH2-CH2-NH-CH2-, -CH2-CH2-O-CH2-, -CH2-NH-CH2-CH2- or -CH2-O-CH2-CH2- group, and wherein -L89- may optionally be substituted with one or more fluoro groups and/or one or two substituents each independently selected from an oxo (=O), -CN, methyl (Me), -OH, -OMe, -NH2, -NHMe or -NMe2 group, wherein any methyl group of a -L89- substituent may optionally be fluoro substituted. In a further embodiment, R18 and R19 together with the carbon atom to which they are attached form a C=O group. As stated in accordance with both the first and the second aspects of the invention, R20 and R21 are each independently selected from hydrogen or a fluoro group, or R20 and R21 together with the carbon atom to which they are attached form a C=O group. In one embodiment, R20 and R21 are each independently selected from hydrogen or a fluoro group. In one embodiment, R20 and R21 are both hydrogen. In one embodiment of the first aspect of the invention, the compound of Formula (I) is not:
Figure imgf000064_0001
. 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: R1 is hydrogen; R2 is selected from hydrogen or a halo group; R3 is selected from hydrogen or a halo, -SO2NH2, or a C1-C8 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 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 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; R4 is selected from hydrogen or a halo, -OH, -NH2, -SO2NH2, or a C1-C8 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 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 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; R5 is selected from hydrogen or a halo group; R6 is selected from hydrogen or a halo, -R60 or -OR60 group, wherein R60 is selected from a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl or C3-C4 fluorocycloalkyl group; R7 and R8 are each independently selected from hydrogen or a fluoro 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 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 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 any hydrocarbyl group of R7 or R8 that is directly attached to the reminder of the molecule is a carbon atom; or R7 and R8 together with the carbon atom to which they are attached form a 3- to 10-membered cyclic group, such that each ring atom of the cyclic group that is directly attached to the carbon atom to which R7 and R8 are attached is a ring carbon atom, wherein the cyclic 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; X10 is N or CR10; X11 is N or CR11; X12 is N or CR12; X13 is N or CR13; no more than two of X10, X11, X12 and X13 are N; each R10, R11, R12 and R13 is independently selected from hydrogen or a halo, -OH, -SH, -NH2, -SO2NH2, 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 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 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; R18 and R19 are each independently selected from hydrogen or a fluoro 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 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 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 any hydrocarbyl group of R18 or R19 that is directly attached to the reminder of the molecule is a carbon atom; or R18 and R19 together with the carbon atom to which they are attached form a 3- to 10-membered cyclic group, such that each ring atom of the cyclic group that is directly attached to the carbon atom to which R18 and R19 are attached is a ring carbon atom, wherein the cyclic 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; or R18 and R19 together with the carbon atom to which they are attached form a C=O group; and R20 and R21 are each independently selected from hydrogen or a fluoro group, or R20 and R21 together with the carbon atom to which they are attached form a C=O group. Typically in such an exemplary embodiment: R7 and R8 are each independently selected from hydrogen or a fluoro or a C1-C8 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 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 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 any hydrocarbyl group of R7 or R8 that is directly attached to the reminder of the molecule is a carbon atom; or R7 and R8 together with the carbon atom to which they are attached form a 3- to 10-membered cyclic group, such that each ring atom of the cyclic group that is directly attached to the carbon atom to which R7 and R8 are attached is a ring carbon atom, wherein the cyclic 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. In one aspect of the first exemplary embodiment: R7 and R8 are each independently selected from hydrogen or a fluoro or a C1-C8 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 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 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 any hydrocarbyl group of R7 or R8 that is directly attached to the reminder of the molecule is a carbon atom; or R7 and R8 together with the carbon atom to which they are attached form a 3- to 10-membered cyclic group, such that each ring atom of the cyclic group that is directly attached to the carbon atom to which R7 and R8 are attached is a ring carbon atom, wherein the cyclic 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; each R10, R11, R12 and R13 is independently selected from hydrogen or a halo, -OH, -NH2 or a C1-C8 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 groups, and wherein the hydrocarbyl group may optionally include one, two or three heteroatoms each independently selected from N and O in its carbon skeleton; and R18 and R19 are each independently selected from hydrogen or a fluoro or a C1-C8 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 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 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 any hydrocarbyl group of R18 or R19 that is directly attached to the reminder of the molecule is a carbon atom; or R18 and R19 together with the carbon atom to which they are attached form a 3- to 10-membered cyclic group, such that each ring atom of the cyclic group that is directly attached to the carbon atom to which R18 and R19 are attached is a ring carbon atom, wherein the cyclic 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; or R18 and R19 together with the carbon atom to which they are attached form a C=O group. In another aspect of the first exemplary embodiment: R7 and R8 are each independently selected from hydrogen or a fluoro or a C1-C8 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 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 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 any hydrocarbyl group of R7 or R8 that is directly attached to the reminder of the molecule is a carbon atom; or R7 and R8 together with the carbon atom to which they are attached form a 3- to 10-membered cyclic group, such that each ring atom of the cyclic group that is directly attached to the carbon atom to which R7 and R8 are attached is a ring carbon atom, wherein the cyclic 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; each R10, R11, R12 and R13 is independently selected from hydrogen or a halo, -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; and R18 and R19 are each independently selected from hydrogen or a fluoro or a C1-C8 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 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 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 any hydrocarbyl group of R18 or R19 that is directly attached to the reminder of the molecule is a carbon atom; or R18 and R19 together with the carbon atom to which they are attached form a 3- to 10-membered cyclic group, such that each ring atom of the cyclic group that is directly attached to the carbon atom to which R18 and R19 are attached is a ring carbon atom, wherein the cyclic 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; or R18 and R19 together with the carbon atom to which they are attached form a C=O group. In a corresponding second exemplary embodiment, there is provided a compound of Formula (II) as defined above, wherein: R1 is hydrogen; R4 is selected from hydrogen or a halo, -OH, -NH2, -SO2NH2, or a C1-C8 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 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 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; R5 is selected from hydrogen or a halo group; R6 is selected from hydrogen or a halo, -R60 or -OR60 group, wherein R60 is selected from a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl or C3-C4 fluorocycloalkyl group; R7 and R8 are each independently selected from hydrogen or a fluoro 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 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 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 any hydrocarbyl group of R7 or R8 that is directly attached to the reminder of the molecule is a carbon atom; or R7 and R8 together with the carbon atom to which they are attached form a 3- to 10-membered cyclic group, such that each ring atom of the cyclic group that is directly attached to the carbon atom to which R7 and R8 are attached is a ring carbon atom, wherein the cyclic 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; X10 is N or CR10; X11 is N or CR11; X12 is N or CR12; X13 is N or CR13; no more than two of X10, X11, X12 and X13 are N; each R10, R11, R12 and R13 is independently selected from hydrogen or a halo, -OH, -SH, -NH2, -SO2NH2, 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 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 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; each R14 and R15 is independently selected from hydrogen or a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl or C3-C4 fluorocycloalkyl group, or R14 and R15 together with the carbon atom to which they are attached form a 3- to 6-membered cyclic group, wherein the cyclic group may optionally be substituted with one or more substituents each independently selected from a fluoro, -OH, oxo (=O), methyl or ethyl group, wherein any methyl or ethyl group may optionally be fluoro substituted; R16 is selected from hydrogen or a fluoro, -SO2NH2, or a C1-C8 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 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 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; R17 is selected from hydrogen or a fluoro, C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl or C3-C4 fluorocycloalkyl group; or R16 and R17 together with the carbon atom to which they are attached form a 3- to 6-membered cyclic group, wherein the cyclic group may optionally be substituted with one or more substituents each independently selected from a fluoro, -OH, oxo (=O), methyl or ethyl group, wherein any methyl or ethyl group may optionally be fluoro substituted; R18 and R19 are each independently selected from hydrogen or a fluoro 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 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 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 any hydrocarbyl group of R18 or R19 that is directly attached to the reminder of the molecule is a carbon atom; or R18 and R19 together with the carbon atom to which they are attached form a 3- to 10-membered cyclic group, such that each ring atom of the cyclic group that is directly attached to the carbon atom to which R18 and R19 are attached is a ring carbon atom, wherein the cyclic 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; or R18 and R19 together with the carbon atom to which they are attached form a C=O group; and R20 and R21 are each independently selected from hydrogen or a fluoro group, or R20 and R21 together with the carbon atom to which they are attached form a C=O group. Typically in such an exemplary embodiment: R7 and R8 are each independently selected from hydrogen or a fluoro or a C1-C8 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 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 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 any hydrocarbyl group of R7 or R8 that is directly attached to the reminder of the molecule is a carbon atom; or R7 and R8 together with the carbon atom to which they are attached form a 3- to 10-membered cyclic group, such that each ring atom of the cyclic group that is directly attached to the carbon atom to which R7 and R8 are attached is a ring carbon atom, wherein the cyclic 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. In one aspect of the second exemplary embodiment: R7 and R8 are each independently selected from hydrogen or a fluoro or a C1-C8 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 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 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 any hydrocarbyl group of R7 or R8 that is directly attached to the reminder of the molecule is a carbon atom; or R7 and R8 together with the carbon atom to which they are attached form a 3- to 10-membered cyclic group, such that each ring atom of the cyclic group that is directly attached to the carbon atom to which R7 and R8 are attached is a ring carbon atom, wherein the cyclic 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; each R10, R11, R12 and R13 is independently selected from hydrogen or a halo, -OH, -NH2 or a C1-C8 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 groups, and wherein the hydrocarbyl group may optionally include one, two or three heteroatoms each independently selected from N and O in its carbon skeleton; and R18 and R19 are each independently selected from hydrogen or a fluoro or a C1-C8 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 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 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 any hydrocarbyl group of R18 or R19 that is directly attached to the reminder of the molecule is a carbon atom; or R18 and R19 together with the carbon atom to which they are attached form a 3- to 10-membered cyclic group, such that each ring atom of the cyclic group that is directly attached to the carbon atom to which R18 and R19 are attached is a ring carbon atom, wherein the cyclic 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; or R18 and R19 together with the carbon atom to which they are attached form a C=O group. In another aspect of the second exemplary embodiment: R7 and R8 are each independently selected from hydrogen or a fluoro or a C1-C8 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 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 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 any hydrocarbyl group of R7 or R8 that is directly attached to the reminder of the molecule is a carbon atom; or R7 and R8 together with the carbon atom to which they are attached form a 3- to 10-membered cyclic group, such that each ring atom of the cyclic group that is directly attached to the carbon atom to which R7 and R8 are attached is a ring carbon atom, wherein the cyclic 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; each R10, R11, R12 and R13 is independently selected from hydrogen or a halo, -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; and R18 and R19 are each independently selected from hydrogen or a fluoro or a C1-C8 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 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 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 any hydrocarbyl group of R18 or R19 that is directly attached to the reminder of the molecule is a carbon atom; or R18 and R19 together with the carbon atom to which they are attached form a 3- to 10-membered cyclic group, such that each ring atom of the cyclic group that is directly attached to the carbon atom to which R18 and R19 are attached is a ring carbon atom, wherein the cyclic 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; or R18 and R19 together with the carbon atom to which they are attached form a C=O group. In a third exemplary embodiment, there is provided a compound of Formula (I) as defined above, wherein: R1 is hydrogen; R2 is selected from hydrogen or a fluoro, chloro or bromo group; R3 is selected from hydrogen or a fluoro, chloro, bromo, -R30, -CN, -CHO, -COR30, -CO2H or -CO2R30 group, provided that R3, including any optional substituents, contains no more than 8 carbon atoms; R30 is selected from a C1-C6 alkyl, C1-C6 fluoroalkyl, C2-C6 alkenyl, C2-C6 fluoroalkenyl or -R31 group; R31 is a 3- to 6-membered monocyclic group, wherein the 3- to 6-membered monocyclic group may optionally be substituted with one or more fluoro, chloro and/or bromo groups, and/or with one or two groups R32; each R32 is independently selected from a methyl or a fluoromethyl group; R4 is selected from a fluoro, chloro, bromo, -OH, -OR41, -N(R42)2, -SO2-R41, -SO2-N(R42)2, -L4-OH, -L4-OR41, -L4-N(R42)2, -L4-SO2-R41, -L4-SO2-N(R42)2, -O-L4-OH, -O-L4-OR41, -O-L4-N(R42)2, -O-L4-SO2-R41, -O-L4-SO2-N(R42)2, -NR43-L4-OH, -NR43-L4-OR41, -NR43-L4-N(R42)2, -NR43-L4-SO2-R41, -NR43-L4-SO2-N(R42)2, -SO2-L4-OH, -SO2-L4-OR41, -SO2-L4-N(R42)2, -R44, -R45 or -L4-R45 group, provided that R4, including any optional substituents, contains no more than 8 carbon atoms; R41 is selected from a -R44 or -R45 group; each R42 is independently selected from hydrogen or a -R44 or -R45 group, or any two R42 may, together with the nitrogen atom to which they are attached, form a 3- to 6-membered saturated monocyclic heterocyclic group, wherein the 3- to 6-membered saturated monocyclic heterocyclic group may optionally be substituted with one or two oxo (=O) groups and/or with one or more fluoro, methyl and/or fluoromethyl groups; L4 is a straight-chained alkylene group, wherein the straight-chained alkylene group optionally includes one or two heteroatoms each independently selected from O and N in its carbon skeleton, wherein L4 has a chain length of from 1 to 4 atoms, and wherein L4 may optionally be substituted with one or two oxo (=O) groups and/or with one or more groups RL4; each RL4 is independently selected from a fluoro, methyl or fluoromethyl group; or any RL4 and R41, or any RL4 and any R42, may together with the atoms to which they are attached, form a 3- to 6-membered saturated monocyclic heterocyclic group, wherein the 3- to 6-membered saturated monocyclic heterocyclic group may optionally be substituted with one or two oxo (=O) groups and/or with one or more fluoro, methyl and/or fluoromethyl groups; R43 is selected from hydrogen or a -R44 group; each R44 is independently selected from a C1-C4 alkyl or C3-C6 cycloalkyl group, wherein the C1-C4 alkyl or C3-C6 cycloalkyl group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups; each R45 is independently selected from a phenyl or a 5- or 6-membered heteroaryl group, wherein the phenyl or the 5- or 6-membered heteroaryl group may optionally be substituted with one or more groups each independently selected from fluoro, chloro and bromo, and/or with one or two groups each independently selected from methyl (Me), -CN, -OH, -OMe, -NH2, -NHMe, and -NMe2, wherein any methyl group of R45 may optionally be fluoro substituted; R5 is selected from hydrogen or a fluoro, chloro or bromo group; R6 is selected from a chloro, bromo, -R60 or -OR60 group; R60 is selected from a C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group; R7 is selected from hydrogen or a fluoro, -CN, -COOH, -COOR71, -CO-N(R72)2, -L7-COOH, -L7-COOR71, -L7-CO-N(R72)2, -L7-OH, -L7-OR71, -L7-N(R72)2, -R73, -R74 or -L7-R74 group, provided that R7, including any optional substituents, contains no more than 10 carbon atoms, and that the atom of R7 that is directly attached to the reminder of the molecule is a carbon, hydrogen or fluorine atom; R71 is selected from a -R73 or -R74 group; each R72 is independently selected from hydrogen or a -R73 or -R74 group, or any two R72 may, together with the nitrogen atom to which they are attached, form a 3- to 6- membered saturated monocyclic heterocyclic group, wherein the 3- to 6-membered saturated monocyclic heterocyclic group may optionally be substituted with one or two oxo (=O) groups and/or with one or more fluoro, methyl and/or fluoromethyl groups; L7 is a straight-chained alkylene or alkenylene group, wherein the straight- chained alkylene or alkenylene group optionally includes one or two heteroatoms each independently selected from O and N in its carbon skeleton, wherein L7 has a chain length of from 1 to 4 atoms, and wherein L7 may optionally be substituted with one or two oxo (=O) groups and/or with one or more groups RL7; each RL7 is independently selected from a fluoro, methyl or fluoromethyl group; or any two RL7 may, together with the atom or atoms to which they are attached, form a 3- to 6-membered monocyclic group, wherein the 3- to 6-membered monocyclic group is saturated or monounsaturated, and wherein the 3- to 6-membered monocyclic group may optionally be substituted with one or two oxo (=O) groups and/or with one or more fluoro, methyl and/or fluoromethyl groups; or any RL7 and R71, or any RL7 and any R72, may together with the atoms of the -L7-COOR71, -L7-CO-N(R72)2, -L7-OR71 or -L7-N(R72)2 group to which they are attached, form a 3- to 6-membered monocyclic heterocyclic group, wherein the 3- to 6- membered monocyclic heterocyclic group is saturated or monounsaturated, and wherein the 3- to 6-membered saturated monocyclic heterocyclic group may optionally be substituted with one or two oxo (=O) groups and/or with one or more fluoro, methyl and/or fluoromethyl groups; each R73 is independently selected from a C1-C4 alkyl, C2-C4 alkenyl, C3-C6 cycloalkyl or C5-C6 cycloalkenyl group, wherein the C1-C4 alkyl, C2-C4 alkenyl, C3-C6 cycloalkyl or C5-C6 cycloalkenyl group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups; each R74 is independently selected from a phenyl or a 5- or 6-membered heteroaryl group, wherein the phenyl or the 5- or 6-membered heteroaryl group may optionally be substituted with one or more groups each independently selected from fluoro, chloro and bromo, and/or with one or two groups each independently selected from methyl (Me), -CN, -OH, -OMe, -NH2, -NHMe, and -NMe2, wherein any methyl group of R74 may optionally be fluoro substituted; and R8 is selected from a hydrogen or a fluoro, methyl or fluoromethyl group; or R7 and R8 together form a group -L78-, wherein -L78- is selected from a -CH2-CH2-, -CH2-CH2-CH2-, -CH2-NH-CH2-, -CH2-O-CH2-, -CH2-CH2-CH2-CH2-, -CH2-CH2-NH-CH2-, -CH2-CH2-O-CH2-, -CH2-NH-CH2-CH2- or -CH2-O-CH2-CH2- group, wherein -L78- may optionally be substituted with one or more fluoro groups and/or one or two substituents each independently selected from an oxo (=O), -CN, methyl (Me), -OH, -OMe, -NH2, -NHMe or -NMe2 group, and wherein any methyl group of a -L78- substituent may optionally be fluoro substituted; X10 is N or CR10; X11 is CR11 and X12 is CR12, or X11 is CR11 and X12 is N, or X11 is N and X12 is CR12; X13 is N or CR13; no more than one of X10, X11, X12 and X13 is N; one of R11 and R12 is present and selected from a fluoro, chloro, bromo, fluoromethyl, methoxy, fluoromethoxy, -CH2OH, -CN, -COOH, -CONH2 or -C(=NH)NH2 group; one remaining R10, R11, R12 or R13 is independently selected from hydrogen or a fluoro, chloro, bromo, -OH, -SH, -NH2, -SO2NH2, or a C1-C10 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 fluoro, chloro and/or bromo groups, wherein the hydrocarbyl group may optionally include one, two, three, four, five or six heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein one -S- moiety 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; if present each further remaining R10, R11, R12 or R13 is independently selected from hydrogen or a fluoro, chloro or bromo group; R18 is selected from hydrogen or a fluoro, -CN, -COOH, -COOR181, -CO-N(R182)2, -L18-COOH, -L18-COOR181, -L18-CO-N(R182)2, -L18-OH, -L18-OR181, -L18-N(R182)2, -R183, -R184 or -L18-R184 group, provided that R18, including any optional substituents, contains no more than 10 carbon atoms, and that the atom of R18 that is directly attached to the reminder of the molecule is a carbon, hydrogen or fluorine atom; and R19 is selected from a hydrogen or a fluoro, methyl or fluoromethyl group; or R18 and R19 together with the carbon atom to which they are attached form a C=O group; R181 is selected from a -R183 or -R184 group; each R182 is independently selected from hydrogen or a -R183 or -R184 group, or any two R182 may, together with the nitrogen atom to which they are attached, form a 3- to 6-membered saturated monocyclic heterocyclic group, wherein the 3- to 6- membered saturated monocyclic heterocyclic group may optionally be substituted with one or two oxo (=O) groups and/or with one or more fluoro, methyl and/or fluoromethyl groups; L18 is a straight-chained alkylene, alkenylene or alkynylene group, wherein the straight-chained alkylene, alkenylene or alkynylene group optionally includes one or two heteroatoms each independently selected from O and N in its carbon skeleton, wherein the straight-chained alkylene, alkenylene or alkynylene group has a chain length of from 1 to 4 atoms, and wherein the straight-chained alkylene, alkenylene or alkynylene group may optionally be substituted with one or two oxo (=O) groups and/or with one or more groups RL18; each RL18 is independently selected from a fluoro, methyl or fluoromethyl group; or any two RL18 may together with the atom or atoms to which they are attached form a 3- to 6-membered monocyclic group, wherein the 3- to 6-membered monocyclic group is saturated or monounsaturated, and wherein the 3- to 6-membered monocyclic group may optionally be substituted with one or two oxo (=O) groups and/or with one or more fluoro, methyl and/or fluoromethyl groups; or any RL18 and R181, or any RL18 and any R182, may together with the atoms of the -L18-COOR181, -L18-CO-N(R182)2, -L18-OR181 or -L18-N(R182)2 group to which they are attached, form a 3- to 6-membered monocyclic heterocyclic group, wherein the 3- to 6- membered monocyclic heterocyclic group is saturated or monounsaturated, and wherein the 3- to 6-membered monocyclic heterocyclic group may optionally be substituted with one or two oxo (=O) groups and/or with one or more fluoro, methyl and/or fluoromethyl groups; or L18 is a divalent phenyl or a divalent 5- or 6-membered heteroaryl group, wherein the divalent phenyl or the divalent 5- or 6-membered heteroaryl group may optionally be substituted with one or more groups each independently selected from fluoro, chloro, bromo, methyl and fluoromethyl; each R183 is independently selected from a C1-C4 alkyl, C2-C4 alkenyl, C3-C6 cycloalkyl or C5-C6 cycloalkenyl group, wherein the C1-C4 alkyl, C2-C4 alkenyl, C3-C6 cycloalkyl or C5-C6 cycloalkenyl group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups; each R184 is independently selected from a phenyl or a 5- or 6-membered heteroaryl group, wherein the phenyl or the 5- or 6-membered heteroaryl group may optionally be substituted with one or more groups each independently selected from fluoro, chloro and bromo, and/or with one or two groups each independently selected from methyl (Me), -CN, -OH, -OMe, -NH2, -NHMe, and -NMe2, wherein the methyl group of R184 may optionally be fluoro substituted; and R20 and R21 are each independently selected from hydrogen or a fluoro group. In one aspect of the third exemplary embodiment: R30 is selected from a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl or C3-C4 fluorocycloalkyl group; R4 is selected from a fluoro, chloro, bromo, -OH, -OR41, -N(R42)2, -SO2-R41, -SO2-N(R42)2, -L4-OH, -L4-OR41, -L4-N(R42)2, -L4-SO2-R41, -L4-SO2-N(R42)2, -O-L4-OH, -O-L4-OR41, -O-L4-N(R42)2, -O-L4-SO2-R41, -O-L4-SO2-N(R42)2, -NR43-L4-OH, -NR43-L4-OR41, -NR43-L4-N(R42)2, -NR43-L4-SO2-R41, -NR43-L4-SO2-N(R42)2, -R44, -R45 or -L4-R45 group, provided that R4, including any optional substituents, contains no more than 8 carbon atoms; R7 is selected from hydrogen or a fluoro, -CN, -COOH, -COOR71, -L7-COOH, -L7-COOR71, -L7-OH, -L7-OR71, -L7-N(R72)2, -R73, -R74 or -L7-R74 group, provided that R7, including any optional substituents, contains no more than 8 carbon atoms, and that the atom of R7 that is directly attached to the reminder of the molecule is a carbon, hydrogen or fluorine atom; and R8 is selected from a hydrogen or a fluoro, methyl or fluoromethyl group; or R7 and R8 together form a group -L78-, wherein -L78- is selected from a -CH2-CH2-, -CH2-CH2-CH2-, -CH2-NH-CH2-, -CH2-O-CH2-, -CH2-CH2-CH2-CH2-, -CH2-CH2-NH-CH2-, -CH2-CH2-O-CH2-, -CH2-NH-CH2-CH2- or -CH2-O-CH2-CH2- group, wherein -L78- may optionally be substituted with one or more fluoro groups and/or one or two substituents each independently selected from an oxo (=O), -CN, methyl (Me), -OH, -OMe, -NH2, -NHMe or -NMe2 group, and wherein any methyl group of a -L78- substituent may optionally be fluoro substituted; one of R11 and R12 is present and selected from a fluoro, chloro, bromo, fluoromethyl, methoxy, fluoromethoxy, -CH2OH, -CN, -COOH, -CONH2 or -C(=NH)NH2 group; one remaining R10, R11, R12 or R13 is independently selected from hydrogen or a fluoro, chloro, bromo, -OH, -SH, -NH2, -SO2NH2, or a C1-C10 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 fluoro, chloro and/or bromo groups, wherein the hydrocarbyl group may optionally include one, two, three or four heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein one -S- moiety 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; if present each further remaining R10, R11, R12 or R13 is independently selected from hydrogen or a fluoro, chloro or bromo group; R18 is selected from hydrogen or a fluoro, -CN, -COOH, -COOR181, -L18-COOH, -L18-COOR181, -L18-OH, -L18-OR181, -L18-N(R182)2, -R183, -R184 or -L18-R184 group, provided that R18, including any optional substituents, contains no more than 8 carbon atoms, and that the atom of R18 that is directly attached to the reminder of the molecule is a carbon, hydrogen or fluorine atom; and R19 is selected from a hydrogen or a fluoro, methyl or fluoromethyl group; or R18 and R19 together with the carbon atom to which they are attached form a C=O group. In a further aspect of the third exemplary embodiment: one of R11 and R12 is present and selected from a fluoro, chloro, bromo, fluoromethyl, methoxy, fluoromethoxy, -CH2OH, -CN, -COOH, -CONH2 or -C(=NH)NH2 group; one remaining R10, R11, R12 or R13 is independently selected from hydrogen or a fluoro, chloro or bromo group, or a -R131, -OH, -SH, -OR131, -SR131, -N(R132)2, -SO2-R131, -SO2-N(R132)2, -L13-OH, -L13-SH, -L13-OR131, -L13-SR131, -L13-N(R132)2, -L13-SO2-R131, -L13-SO2-N(R132)2, -O-L13-OH, -O-L13-SH, -O-L13-OR131, -O-L13-SR131, -O-L13-N(R132)2, -O-L13-SO2-R131, -O-L13-SO2-N(R132)2, -S-L13-OH, -S-L13-SH, -S-L13-OR131, -S-L13-SR131, -S-L13-N(R132)2, -S-L13-SO2-R131, -S-L13-SO2-N(R132)2, -NR133-L13-OH, -NR133-L13-SH, -NR133-L13-OR131, -NR133-L13-SR131, -NR133-L13-N(R132)2, -NR133-L13-SO2-R131 or -NR133-L13-SO2-N(R132)2 group, wherein said group, including any optional substituents, contains no more than 10 carbon atoms, and the total number of nitrogen, oxygen and sulphur atoms in said group, including any optional substituents, is no more than six; each R131 is independently selected from a C1-C4 alkyl or C3-C6 cycloalkyl group, wherein the C1-C4 alkyl or C3-C6 cycloalkyl group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups; each R132 is independently selected from hydrogen or a -R131 group; R133 is selected from hydrogen or a -R131 group; L13 is a straight-chained alkylene or alkenylene group, wherein the straight- chained alkylene or alkenylene group optionally includes one, two or three heteroatoms each independently selected from O and N in its carbon skeleton, wherein L13 has a chain length of from 1 to 8 atoms, and wherein L13 may optionally be substituted with one or two groups each independently selected from oxo (=O) and -OH, and/or with one or more groups RL13; each RL13 is independently selected from a fluoro, C1-C3 alkyl, cyclopropyl, C1- C3 fluoroalkyl, fluorocyclopropyl, -CH2OH, -CH2OMe or -CH2O-fluoromethyl group; or any two RL13, or any RL13 and any R131, or any two R131, may, together with the atom or atoms to which they are attached, form a 3- to 7-membered monocyclic group, wherein the 3- to 7-membered monocyclic group may optionally be substituted with one or two groups each independently selected from oxo (=O) and -OH, and/or with one or more fluoro, methyl and/or fluoromethyl groups; or any two RL13 and any R131, or any three RL13 and any R131, or any two RL13 and any two R131, may, together with the atoms to which they are attached, form a 6- to 10- membered bicyclic heterocyclic group, wherein the 6- to 10-membered bicyclic heterocyclic group may optionally be substituted with one or two groups each independently selected from oxo (=O) and -OH, and/or with one or more fluoro, methyl and/or fluoromethyl groups; and if present each further remaining R10, R11, R12 or R13 is independently selected from hydrogen or a fluoro, chloro or bromo group. In one embodiment of such a further aspect: R30 is selected from a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl or C3-C4 fluorocycloalkyl group; R4 is selected from a fluoro, chloro, bromo, -OH, -OR41, -N(R42)2, -SO2-R41, -SO2-N(R42)2, -L4-OH, -L4-OR41, -L4-N(R42)2, -L4-SO2-R41, -L4-SO2-N(R42)2, -O-L4-OH, -O-L4-OR41, -O-L4-N(R42)2, -O-L4-SO2-R41, -O-L4-SO2-N(R42)2, -NR43-L4-OH, -NR43-L4-OR41, -NR43-L4-N(R42)2, -NR43-L4-SO2-R41, -NR43-L4-SO2-N(R42)2, -R44, -R45 or -L4-R45 group, provided that R4, including any optional substituents, contains no more than 8 carbon atoms; R7 is selected from hydrogen or a fluoro, -CN, -COOH, -COOR71, -L7-COOH, -L7-COOR71, -L7-OH, -L7-OR71, -L7-N(R72)2, -R73, -R74 or -L7-R74 group, provided that R7, including any optional substituents, contains no more than 8 carbon atoms, and that the atom of R7 that is directly attached to the reminder of the molecule is a carbon, hydrogen or fluorine atom; and R8 is selected from a hydrogen or a fluoro, methyl or fluoromethyl group; or R7 and R8 together form a group -L78-, wherein -L78- is selected from a -CH2-CH2-, -CH2-CH2-CH2-, -CH2-NH-CH2-, -CH2-O-CH2-, -CH2-CH2-CH2-CH2-, -CH2-CH2-NH-CH2-, -CH2-CH2-O-CH2-, -CH2-NH-CH2-CH2- or -CH2-O-CH2-CH2- group, wherein -L78- may optionally be substituted with one or more fluoro groups and/or one or two substituents each independently selected from an oxo (=O), -CN, methyl (Me), -OH, -OMe, -NH2, -NHMe or -NMe2 group, and wherein any methyl group of a -L78- substituent may optionally be fluoro substituted; one of R11 and R12 is present and selected from a fluoro, chloro, bromo, fluoromethyl, methoxy, fluoromethoxy, -CH2OH, -CN, -COOH, -CONH2 or -C(=NH)NH2 group; one remaining R10, R11, R12 or R13 is independently selected from hydrogen or a fluoro, chloro or bromo group, or a -R131, -OH, -SH, -OR131, -SR131, -N(R132)2, -SO2-R131, -SO2-N(R132)2, -L13-OH, -L13-SH, -L13-OR131, -L13-SR131, -L13-N(R132)2, -L13-SO2-R131, -L13-SO2-N(R132)2, -O-L13-OH, -O-L13-SH, -O-L13-OR131, -O-L13-SR131, -O-L13-N(R132)2, -O-L13-SO2-R131, -O-L13-SO2-N(R132)2, -S-L13-OH, -S-L13-SH, -S-L13-OR131, -S-L13-SR131, -S-L13-N(R132)2, -S-L13-SO2-R131, -S-L13-SO2-N(R132)2, -NR133-L13-OH, -NR133-L13-SH, -NR133-L13-OR131, -NR133-L13-SR131, -NR133-L13-N(R132)2, -NR133-L13-SO2-R131 or -NR133-L13-SO2-N(R132)2 group, wherein said group, including any optional substituents, contains no more than 10 carbon atoms, and the total number of nitrogen, oxygen and sulphur atoms in said group, including any optional substituents, is no more than four; each R131 is independently selected from a C1-C4 alkyl or C3-C6 cycloalkyl group, wherein the C1-C4 alkyl or C3-C6 cycloalkyl group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups; each R132 is independently selected from hydrogen or a -R131 group; R133 is selected from hydrogen or a -R131 group; L13 is a straight-chained alkylene or alkenylene group, wherein the straight- chained alkylene or alkenylene group optionally includes one or two heteroatoms each independently selected from O and N in its carbon skeleton, wherein L13 has a chain length of from 1 to 8 atoms, and wherein L13 may optionally be substituted with one or two oxo (=O) groups and/or with one or more groups RL13; each RL13 is independently selected from a fluoro, methyl or fluoromethyl group; or any two RL13, or any RL13 and R131, or any two R131, may, together with the atom or atoms to which they are attached, form a 3- to 7-membered monocyclic group, wherein the 3- to 7-membered monocyclic group is saturated or monounsaturated, and wherein the 3- to 7-membered monocyclic group may optionally be substituted with one or two oxo (=O) groups and/or with one or more fluoro, methyl and/or fluoromethyl groups; or any two RL13 and R131 may, together with the atoms to which they are attached, form a 6- to 10-membered bicyclic heterocyclic group, wherein the 6- to 10- membered bicyclic heterocyclic group is saturated or monounsaturated, and wherein the 6- to 10-membered bicyclic heterocyclic group may optionally be substituted with one or two oxo (=O) groups and/or with one or more fluoro, methyl and/or fluoromethyl groups; and if present each further remaining R10, R11, R12 or R13 is independently selected from hydrogen or a fluoro, chloro or bromo group; R18 is selected from hydrogen or a fluoro, -CN, -COOH, -COOR181, -L18-COOH, -L18-COOR181, -L18-OH, -L18-OR181, -L18-N(R182)2, -R183, -R184 or -L18-R184 group, provided that R18, including any optional substituents, contains no more than 8 carbon atoms, and that the atom of R18 that is directly attached to the reminder of the molecule is a carbon, hydrogen or fluorine atom; and R19 is selected from a hydrogen or a fluoro, methyl or fluoromethyl group; or R18 and R19 together with the carbon atom to which they are attached form a C=O group. In a corresponding fourth exemplary embodiment, there is provided a compound of Formula (II) as defined above, wherein: R1 is hydrogen; R4 is selected from a fluoro, chloro, bromo, -OH, -OR41, -N(R42)2, -SO2-R41, -SO2-N(R42)2, -L4-OH, -L4-OR41, -L4-N(R42)2, -L4-SO2-R41, -L4-SO2-N(R42)2, -O-L4-OH, -O-L4-OR41, -O-L4-N(R42)2, -O-L4-SO2-R41, -O-L4-SO2-N(R42)2, -NR43-L4-OH, -NR43-L4-OR41, -NR43-L4-N(R42)2, -NR43-L4-SO2-R41, -NR43-L4-SO2-N(R42)2, -SO2-L4-OH, -SO2-L4-OR41, -SO2-L4-N(R42)2, -R44, -R45 or -L4-R45 group, provided that R4, including any optional substituents, contains no more than 8 carbon atoms; R41 is selected from a -R44 or -R45 group; each R42 is independently selected from hydrogen or a -R44 or -R45 group, or any two R42 may, together with the nitrogen atom to which they are attached, form a 3- to 6-membered saturated monocyclic heterocyclic group, wherein the 3- to 6-membered saturated monocyclic heterocyclic group may optionally be substituted with one or two oxo (=O) groups and/or with one or more fluoro, methyl and/or fluoromethyl groups; L4 is a straight-chained alkylene group, wherein the straight-chained alkylene group optionally includes one or two heteroatoms each independently selected from O and N in its carbon skeleton, wherein L4 has a chain length of from 1 to 4 atoms, and wherein L4 may optionally be substituted with one or two oxo (=O) groups and/or with one or more groups RL4; each RL4 is independently selected from a fluoro, methyl or fluoromethyl group; or any RL4 and R41, or any RL4 and any R42, may together with the atoms to which they are attached, form a 3- to 6-membered saturated monocyclic heterocyclic group, wherein the 3- to 6-membered saturated monocyclic heterocyclic group may optionally be substituted with one or two oxo (=O) groups and/or with one or more fluoro, methyl and/or fluoromethyl groups; R43 is selected from hydrogen or a -R44 group; each R44 is independently selected from a C1-C4 alkyl or C3-C6 cycloalkyl group, wherein the C1-C4 alkyl or C3-C6 cycloalkyl group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups; each R45 is independently selected from a phenyl or a 5- or 6-membered heteroaryl group, wherein the phenyl or the 5- or 6-membered heteroaryl group may optionally be substituted with one or more groups each independently selected from fluoro, chloro and bromo, and/or with one or two groups each independently selected from methyl (Me), -CN, -OH, -OMe, -NH2, -NHMe, and -NMe2, wherein any methyl group of R45 may optionally be fluoro substituted; R5 is selected from hydrogen or a fluoro, chloro or bromo group; R6 is selected from a chloro, bromo, -R60 or -OR60 group; R60 is selected from a C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group; R7 is selected from hydrogen or a fluoro, -CN, -COOH, -COOR71, -CO-N(R72)2, -L7-COOH, -L7-COOR71, -L7-CO-N(R72)2, -L7-OH, -L7-OR71, -L7-N(R72)2, -R73, -R74 or -L7-R74 group, provided that R7, including any optional substituents, contains no more than 10 carbon atoms, and that the atom of R7 that is directly attached to the reminder of the molecule is a carbon, hydrogen or fluorine atom; R71 is selected from a -R73 or -R74 group; each R72 is independently selected from hydrogen or a -R73 or -R74 group, or any two R72 may, together with the nitrogen atom to which they are attached, form a 3- to 6- membered saturated monocyclic heterocyclic group, wherein the 3- to 6-membered saturated monocyclic heterocyclic group may optionally be substituted with one or two oxo (=O) groups and/or with one or more fluoro, methyl and/or fluoromethyl groups; L7 is a straight-chained alkylene or alkenylene group, wherein the straight- chained alkylene or alkenylene group optionally includes one or two heteroatoms each independently selected from O and N in its carbon skeleton, wherein L7 has a chain length of from 1 to 4 atoms, and wherein L7 may optionally be substituted with one or two oxo (=O) groups and/or with one or more groups RL7; each RL7 is independently selected from a fluoro, methyl or fluoromethyl group; or any two RL7 may, together with the atom or atoms to which they are attached, form a 3- to 6-membered monocyclic group, wherein the 3- to 6-membered monocyclic group is saturated or monounsaturated, and wherein the 3- to 6-membered monocyclic group may optionally be substituted with one or two oxo (=O) groups and/or with one or more fluoro, methyl and/or fluoromethyl groups; or any RL7 and R71, or any RL7 and any R72, may together with the atoms of the -L7-COOR71, -L7-CO-N(R72)2, -L7-OR71 or -L7-N(R72)2 group to which they are attached, form a 3- to 6-membered monocyclic heterocyclic group, wherein the 3- to 6- membered monocyclic heterocyclic group is saturated or monounsaturated, and wherein the 3- to 6-membered saturated monocyclic heterocyclic group may optionally be substituted with one or two oxo (=O) groups and/or with one or more fluoro, methyl and/or fluoromethyl groups; each R73 is independently selected from a C1-C4 alkyl, C2-C4 alkenyl, C3-C6 cycloalkyl or C5-C6 cycloalkenyl group, wherein the C1-C4 alkyl, C2-C4 alkenyl, C3-C6 cycloalkyl or C5-C6 cycloalkenyl group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups; each R74 is independently selected from a phenyl or a 5- or 6-membered heteroaryl group, wherein the phenyl or the 5- or 6-membered heteroaryl group may optionally be substituted with one or more groups each independently selected from fluoro, chloro and bromo, and/or with one or two groups each independently selected from methyl (Me), -CN, -OH, -OMe, -NH2, -NHMe, and -NMe2, wherein any methyl group of R74 may optionally be fluoro substituted; and R8 is selected from a hydrogen or a fluoro, methyl or fluoromethyl group; or R7 and R8 together form a group -L78-, wherein -L78- is selected from a -CH2-CH2-, -CH2-CH2-CH2-, -CH2-NH-CH2-, -CH2-O-CH2-, -CH2-CH2-CH2-CH2-, -CH2-CH2-NH-CH2-, -CH2-CH2-O-CH2-, -CH2-NH-CH2-CH2- or -CH2-O-CH2-CH2- group, wherein -L78- may optionally be substituted with one or more fluoro groups and/or one or two substituents each independently selected from an oxo (=O), -CN, methyl (Me), -OH, -OMe, -NH2, -NHMe or -NMe2 group, and wherein any methyl group of a -L78- substituent may optionally be fluoro substituted; X10 is N or CR10; X11 is CR11 and X12 is CR12, or X11 is CR11 and X12 is N, or X11 is N and X12 is CR12; X13 is N or CR13; no more than one of X10, X11, X12 and X13 is N; one of R11 and R12 is present and selected from a fluoro, chloro, bromo, fluoromethyl, methoxy, fluoromethoxy, -CH2OH, -CN, -COOH, -CONH2 or -C(=NH)NH2 group; one remaining R10, R11, R12 or R13 is independently selected from hydrogen or a fluoro, chloro, bromo, -OH, -SH, -NH2, -SO2NH2, or a C1-C10 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 fluoro, chloro and/or bromo groups, wherein the hydrocarbyl group may optionally include one, two, three, four, five or six heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein one -S- moiety 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; if present each further remaining R10, R11, R12 or R13 is independently selected from hydrogen or a fluoro, chloro or bromo group; each R14 and R15 is independently selected from hydrogen or a C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group, or R14 and R15 together with the carbon atom to which they are attached form a cyclopropyl or a cyclobutyl group, wherein the cyclopropyl or cyclobutyl group may optionally be substituted with one or more fluoro groups; R16 is selected from hydrogen or a fluoro, -R160, -CN, -CHO, -COR160, -CO2H or -CO2R160 group, provided that R16, including any optional substituents, contains no more than 8 carbon atoms; R160 is selected from a C1-C6 alkyl, C1-C6 fluoroalkyl, C2-C6 alkenyl, C2-C6 fluoroalkenyl or -R161 group; R161 is a 3- to 6-membered monocyclic group, wherein the 3- to 6-membered monocyclic group may optionally be substituted with one or more fluoro, chloro and/or bromo groups, and/or with one or two groups R162; each R162 is independently selected from a methyl or a fluoromethyl group; and R17 is selected from hydrogen or a fluoro, C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group; or R16 and R17 together with the carbon atom to which they are attached form a 3- to 5-membered saturated monocyclic group, wherein the saturated monocyclic group may optionally be substituted with one or more fluoro groups and/or one or two substituents each independently selected from oxo (=O) or a methyl or fluoromethyl group; R18 is selected from hydrogen or a fluoro, -CN, -COOH, -COOR181, -CO-N(R182)2, -L18-COOH, -L18-COOR181, -L18-CO-N(R182)2, -L18-OH, -L18-OR181, -L18-N(R182)2, -R183, -R184 or -L18-R184 group, provided that R18, including any optional substituents, contains no more than 10 carbon atoms, and that the atom of R18 that is directly attached to the reminder of the molecule is a carbon, hydrogen or fluorine atom; and R19 is selected from a hydrogen or a fluoro, methyl or fluoromethyl group; or R18 and R19 together with the carbon atom to which they are attached form a C=O group; R181 is selected from a -R183 or -R184 group; each R182 is independently selected from hydrogen or a -R183 or -R184 group, or any two R182 may, together with the nitrogen atom to which they are attached, form a 3- to 6-membered saturated monocyclic heterocyclic group, wherein the 3- to 6- membered saturated monocyclic heterocyclic group may optionally be substituted with one or two oxo (=O) groups and/or with one or more fluoro, methyl and/or fluoromethyl groups; L18 is a straight-chained alkylene, alkenylene or alkynylene group, wherein the straight-chained alkylene, alkenylene or alkynylene group optionally includes one or two heteroatoms each independently selected from O and N in its carbon skeleton, wherein the straight-chained alkylene, alkenylene or alkynylene group has a chain length of from 1 to 4 atoms, and wherein the straight-chained alkylene, alkenylene or alkynylene group may optionally be substituted with one or two oxo (=O) groups and/or with one or more groups RL18; each RL18 is independently selected from a fluoro, methyl or fluoromethyl group; or any two RL18 may together with the atom or atoms to which they are attached form a 3- to 6-membered monocyclic group, wherein the 3- to 6-membered monocyclic group is saturated or monounsaturated, and wherein the 3- to 6-membered monocyclic group may optionally be substituted with one or two oxo (=O) groups and/or with one or more fluoro, methyl and/or fluoromethyl groups; or any RL18 and R181, or any RL18 and any R182, may together with the atoms of the -L18-COOR181, -L18-CO-N(R182)2, -L18-OR181 or -L18-N(R182)2 group to which they are attached, form a 3- to 6-membered monocyclic heterocyclic group, wherein the 3- to 6- membered monocyclic heterocyclic group is saturated or monounsaturated, and wherein the 3- to 6-membered monocyclic heterocyclic group may optionally be substituted with one or two oxo (=O) groups and/or with one or more fluoro, methyl and/or fluoromethyl groups; or L18 is a divalent phenyl or a divalent 5- or 6-membered heteroaryl group, wherein the divalent phenyl or the divalent 5- or 6-membered heteroaryl group may optionally be substituted with one or more groups each independently selected from fluoro, chloro, bromo, methyl and fluoromethyl; each R183 is independently selected from a C1-C4 alkyl, C2-C4 alkenyl, C3-C6 cycloalkyl or C5-C6 cycloalkenyl group, wherein the C1-C4 alkyl, C2-C4 alkenyl, C3-C6 cycloalkyl or C5-C6 cycloalkenyl group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups; each R184 is independently selected from a phenyl or a 5- or 6-membered heteroaryl group, wherein the phenyl or the 5- or 6-membered heteroaryl group may optionally be substituted with one or more groups each independently selected from fluoro, chloro and bromo, and/or with one or two groups each independently selected from methyl (Me), -CN, -OH, -OMe, -NH2, -NHMe, and -NMe2, wherein the methyl group of R184 may optionally be fluoro substituted; and R20 and R21 are each independently selected from hydrogen or a fluoro group. In one aspect of the fourth exemplary embodiment: R4 is selected from a fluoro, chloro, bromo, -OH, -OR41, -N(R42)2, -SO2-R41, -SO2-N(R42)2, -L4-OH, -L4-OR41, -L4-N(R42)2, -L4-SO2-R41, -L4-SO2-N(R42)2, -O-L4-OH, -O-L4-OR41, -O-L4-N(R42)2, -O-L4-SO2-R41, -O-L4-SO2-N(R42)2, -NR43-L4-OH, -NR43-L4-OR41, -NR43-L4-N(R42)2, -NR43-L4-SO2-R41, -NR43-L4-SO2-N(R42)2, -R44, -R45 or -L4-R45 group, provided that R4, including any optional substituents, contains no more than 8 carbon atoms; R7 is selected from hydrogen or a fluoro, -CN, -COOH, -COOR71, -L7-COOH, -L7-COOR71, -L7-OH, -L7-OR71, -L7-N(R72)2, -R73, -R74 or -L7-R74 group, provided that R7, including any optional substituents, contains no more than 8 carbon atoms, and that the atom of R7 that is directly attached to the reminder of the molecule is a carbon, hydrogen or fluorine atom; and R8 is selected from a hydrogen or a fluoro, methyl or fluoromethyl group; or R7 and R8 together form a group -L78-, wherein -L78- is selected from a -CH2-CH2-, -CH2-CH2-CH2-, -CH2-NH-CH2-, -CH2-O-CH2-, -CH2-CH2-CH2-CH2-, -CH2-CH2-NH-CH2-, -CH2-CH2-O-CH2-, -CH2-NH-CH2-CH2- or -CH2-O-CH2-CH2- group, wherein -L78- may optionally be substituted with one or more fluoro groups and/or one or two substituents each independently selected from an oxo (=O), -CN, methyl (Me), -OH, -OMe, -NH2, -NHMe or -NMe2 group, and wherein any methyl group of a -L78- substituent may optionally be fluoro substituted; one of R11 and R12 is present and selected from a fluoro, chloro, bromo, fluoromethyl, methoxy, fluoromethoxy, -CH2OH, -CN, -COOH, -CONH2 or -C(=NH)NH2 group; one remaining R10, R11, R12 or R13 is independently selected from hydrogen or a fluoro, chloro, bromo, -OH, -SH, -NH2, -SO2NH2, or a C1-C10 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 fluoro, chloro and/or bromo groups, wherein the hydrocarbyl group may optionally include one, two, three or four heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein one -S- moiety 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; if present each further remaining R10, R11, R12 or R13 is independently selected from hydrogen or a fluoro, chloro or bromo group; R160 is selected from a C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group; R18 is selected from hydrogen or a fluoro, -CN, -COOH, -COOR181, -L18-COOH, -L18-COOR181, -L18-OH, -L18-OR181, -L18-N(R182)2, -R183, -R184 or -L18-R184 group, provided that R18, including any optional substituents, contains no more than 8 carbon atoms, and that the atom of R18 that is directly attached to the reminder of the molecule is a carbon, hydrogen or fluorine atom; and R19 is selected from a hydrogen or a fluoro, methyl or fluoromethyl group; or R18 and R19 together with the carbon atom to which they are attached form a C=O group. In a further aspect of the fourth exemplary embodiment: one of R11 and R12 is present and selected from a fluoro, chloro, bromo, fluoromethyl, methoxy, fluoromethoxy, -CH2OH, -CN, -COOH, -CONH2 or -C(=NH)NH2 group; one remaining R10, R11, R12 or R13 is independently selected from hydrogen or a fluoro, chloro or bromo group, or a -R131, -OH, -SH, -OR131, -SR131, -N(R132)2, -SO2-R131, -SO2-N(R132)2, -L13-OH, -L13-SH, -L13-OR131, -L13-SR131, -L13-N(R132)2, -L13-SO2-R131, -L13-SO2-N(R132)2, -O-L13-OH, -O-L13-SH, -O-L13-OR131, -O-L13-SR131, -O-L13-N(R132)2, -O-L13-SO2-R131, -O-L13-SO2-N(R132)2, -S-L13-OH, -S-L13-SH, -S-L13-OR131, -S-L13-SR131, -S-L13-N(R132)2, -S-L13-SO2-R131, -S-L13-SO2-N(R132)2, -NR133-L13-OH, -NR133-L13-SH, -NR133-L13-OR131, -NR133-L13-SR131, -NR133-L13-N(R132)2, -NR133-L13-SO2-R131 or -NR133-L13-SO2-N(R132)2 group, wherein said group, including any optional substituents, contains no more than 10 carbon atoms, and the total number of nitrogen, oxygen and sulphur atoms in said group, including any optional substituents, is no more than six; each R131 is independently selected from a C1-C4 alkyl or C3-C6 cycloalkyl group, wherein the C1-C4 alkyl or C3-C6 cycloalkyl group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups; each R132 is independently selected from hydrogen or a -R131 group; R133 is selected from hydrogen or a -R131 group; L13 is a straight-chained alkylene or alkenylene group, wherein the straight- chained alkylene or alkenylene group optionally includes one, two or three heteroatoms each independently selected from O and N in its carbon skeleton, wherein L13 has a chain length of from 1 to 8 atoms, and wherein L13 may optionally be substituted with one or two groups each independently selected from oxo (=O) and -OH, and/or with one or more groups RL13; each RL13 is independently selected from a fluoro, C1-C3 alkyl, cyclopropyl, C1- C3 fluoroalkyl, fluorocyclopropyl, -CH2OH, -CH2OMe or -CH2O-fluoromethyl group; or any two RL13, or any RL13 and any R131, or any two R131, may, together with the atom or atoms to which they are attached, form a 3- to 7-membered monocyclic group, wherein the 3- to 7-membered monocyclic group may optionally be substituted with one or two groups each independently selected from oxo (=O) and -OH, and/or with one or more fluoro, methyl and/or fluoromethyl groups; or any two RL13 and any R131, or any three RL13 and any R131, or any two RL13 and any two R131, may, together with the atoms to which they are attached, form a 6- to 10- membered bicyclic heterocyclic group, wherein the 6- to 10-membered bicyclic heterocyclic group may optionally be substituted with one or two groups each independently selected from oxo (=O) and -OH, and/or with one or more fluoro, methyl and/or fluoromethyl groups; and if present each further remaining R10, R11, R12 or R13 is independently selected from hydrogen or a fluoro, chloro or bromo group. In one embodiment of such a further aspect: R4 is selected from a fluoro, chloro, bromo, -OH, -OR41, -N(R42)2, -SO2-R41, -SO2-N(R42)2, -L4-OH, -L4-OR41, -L4-N(R42)2, -L4-SO2-R41, -L4-SO2-N(R42)2, -O-L4-OH, -O-L4-OR41, -O-L4-N(R42)2, -O-L4-SO2-R41, -O-L4-SO2-N(R42)2, -NR43-L4-OH, -NR43-L4-OR41, -NR43-L4-N(R42)2, -NR43-L4-SO2-R41, -NR43-L4-SO2-N(R42)2, -R44, -R45 or -L4-R45 group, provided that R4, including any optional substituents, contains no more than 8 carbon atoms; R7 is selected from hydrogen or a fluoro, -CN, -COOH, -COOR71, -L7-COOH, -L7-COOR71, -L7-OH, -L7-OR71, -L7-N(R72)2, -R73, -R74 or -L7-R74 group, provided that R7, including any optional substituents, contains no more than 8 carbon atoms, and that the atom of R7 that is directly attached to the reminder of the molecule is a carbon, hydrogen or fluorine atom; and R8 is selected from a hydrogen or a fluoro, methyl or fluoromethyl group; or R7 and R8 together form a group -L78-, wherein -L78- is selected from a -CH2-CH2-, -CH2-CH2-CH2-, -CH2-NH-CH2-, -CH2-O-CH2-, -CH2-CH2-CH2-CH2-, -CH2-CH2-NH-CH2-, -CH2-CH2-O-CH2-, -CH2-NH-CH2-CH2- or -CH2-O-CH2-CH2- group, wherein -L78- may optionally be substituted with one or more fluoro groups and/or one or two substituents each independently selected from an oxo (=O), -CN, methyl (Me), -OH, -OMe, -NH2, -NHMe or -NMe2 group, and wherein any methyl group of a -L78- substituent may optionally be fluoro substituted; one of R11 and R12 is present and selected from a fluoro, chloro, bromo, fluoromethyl, methoxy, fluoromethoxy, -CH2OH, -CN, -COOH, -CONH2 or -C(=NH)NH2 group; one remaining R10, R11, R12 or R13 is independently selected from hydrogen or a fluoro, chloro or bromo group, or a -R131, -OH, -SH, -OR131, -SR131, -N(R132)2, -SO2-R131, -SO2-N(R132)2, -L13-OH, -L13-SH, -L13-OR131, -L13-SR131, -L13-N(R132)2, -L13-SO2-R131, -L13-SO2-N(R132)2, -O-L13-OH, -O-L13-SH, -O-L13-OR131, -O-L13-SR131, -O-L13-N(R132)2, -O-L13-SO2-R131, -O-L13-SO2-N(R132)2, -S-L13-OH, -S-L13-SH, -S-L13-OR131, -S-L13-SR131, -S-L13-N(R132)2, -S-L13-SO2-R131, -S-L13-SO2-N(R132)2, -NR133-L13-OH, -NR133-L13-SH, -NR133-L13-OR131, -NR133-L13-SR131, -NR133-L13-N(R132)2, -NR133-L13-SO2-R131 or -NR133-L13-SO2-N(R132)2 group, wherein said group, including any optional substituents, contains no more than 10 carbon atoms, and the total number of nitrogen, oxygen and sulphur atoms in said group, including any optional substituents, is no more than four; each R131 is independently selected from a C1-C4 alkyl or C3-C6 cycloalkyl group, wherein the C1-C4 alkyl or C3-C6 cycloalkyl group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups; each R132 is independently selected from hydrogen or a -R131 group; R133 is selected from hydrogen or a -R131 group; L13 is a straight-chained alkylene or alkenylene group, wherein the straight- chained alkylene or alkenylene group optionally includes one or two heteroatoms each independently selected from O and N in its carbon skeleton, wherein L13 has a chain length of from 1 to 8 atoms, and wherein L13 may optionally be substituted with one or two oxo (=O) groups and/or with one or more groups RL13; each RL13 is independently selected from a fluoro, methyl or fluoromethyl group; or any two RL13, or any RL13 and R131, or any two R131, may, together with the atom or atoms to which they are attached, form a 3- to 7-membered monocyclic group, wherein the 3- to 7-membered monocyclic group is saturated or monounsaturated, and wherein the 3- to 7-membered monocyclic group may optionally be substituted with one or two oxo (=O) groups and/or with one or more fluoro, methyl and/or fluoromethyl groups; or any two RL13 and R131 may, together with the atoms to which they are attached, form a 6- to 10-membered bicyclic heterocyclic group, wherein the 6- to 10- membered bicyclic heterocyclic group is saturated or monounsaturated, and wherein the 6- to 10-membered bicyclic heterocyclic group may optionally be substituted with one or two oxo (=O) groups and/or with one or more fluoro, methyl and/or fluoromethyl groups; and if present each further remaining R10, R11, R12 or R13 is independently selected from hydrogen or a fluoro, chloro or bromo group. In a fifth exemplary embodiment, there is provided a compound of Formula (I) as defined above, wherein: R1 is hydrogen; R2 is selected from hydrogen or a fluoro, chloro or bromo group; R3 is selected from hydrogen or a fluoro, chloro, bromo, -R30, -CN, -CHO, -COR30, -CO2H or -CO2R30 group, wherein R30 is selected from a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl or C3-C4 fluorocycloalkyl group; R4 is selected from a fluoro, chloro, bromo, -OH, -OR41, -N(R42)2, -SO2-R41, -SO2-N(R42)2, -L4-OH, -L4-OR41, -L4-N(R42)2, -L4-SO2-R41, -L4-SO2-N(R42)2, -O-L4-OH, -O-L4-OR41, -O-L4-N(R42)2, -O-L4-SO2-R41, -O-L4-SO2-N(R42)2, -NR43-L4-OH, -NR43-L4-OR41, -NR43-L4-N(R42)2, -NR43-L4-SO2-R41, -NR43-L4-SO2-N(R42)2, -R44, -R45 or -L4-R45 group, provided that R4, including any optional substituents, contains no more than 8 carbon atoms; R41 is selected from a -R44 or -R45 group; each R42 is independently selected from hydrogen or a -R44 or -R45 group, or any two R42 may, together with the nitrogen atom to which they are attached, form a 3- to 6-membered saturated monocyclic heterocyclic group, wherein the 3- to 6-membered saturated monocyclic heterocyclic group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups; L4 is a straight-chained alkylene group, wherein the straight-chained alkylene group optionally includes one or two heteroatoms each independently selected from O and N in its carbon skeleton, wherein L4 has a chain length of from 1 to 4 atoms, and wherein L4 may optionally be substituted with one or two oxo (=O) groups and/or with one or more groups RL4, wherein each RL4 is independently selected from a fluoro, methyl or fluoromethyl group, or any RL4 and R41, or any RL4 and any R42, may together with the atoms to which they are attached, form a 3- to 6-membered saturated monocyclic heterocyclic group, wherein the 3- to 6-membered saturated monocyclic heterocyclic group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups; R43 is selected from hydrogen or a -R44 group; each R44 is independently selected from a C1-C4 alkyl or C3-C6 cycloalkyl group, wherein the C1-C4 alkyl or C3-C6 cycloalkyl group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups; each R45 is independently selected from a phenyl or a 5- or 6-membered heteroaryl group, wherein the phenyl or the 5- or 6-membered heteroaryl group may optionally be substituted with one or more groups each independently selected from fluoro, chloro and bromo, and/or with one or two groups each independently selected from methyl (Me), -CN, -OH, -OMe, -NH2, -NHMe, and -NMe2, wherein any methyl group of R45 may optionally be fluoro substituted; R5 is selected from hydrogen or a fluoro, chloro or bromo group; R6 is selected from a -R60 or -OR60 group; R60 is selected from a C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group; R7 is selected from hydrogen or a fluoro, -CN, -COOH, -COOR71, -L7-COOH, -L7-COOR71, -L7-OH, -L7-OR71, -L7-N(R72)2, -R73, -R74 or -L7-R74 group, provided that R7, including any optional substituents, contains no more than 8 carbon atoms, and that the atom of R7 that is directly attached to the reminder of the molecule is a carbon, hydrogen or fluorine atom; R71 is selected from a -R73 or -R74 group; each R72 is independently selected from hydrogen or a -R73 or -R74 group, or any two R72 may, together with the nitrogen atom to which they are attached, form a 3- to 6- membered saturated monocyclic heterocyclic group, wherein the 3- to 6-membered saturated monocyclic heterocyclic group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups; L7 is a straight-chained alkylene group, wherein the straight-chained alkylene group optionally includes one or two heteroatoms each independently selected from O and N in its carbon skeleton, wherein L7 has a chain length of from 1 to 4 atoms, and wherein L7 may optionally be substituted with one or two oxo (=O) groups and/or with one or more groups RL7, wherein each RL7 is independently selected from a fluoro, methyl or fluoromethyl group, or any RL7 and R71, or any RL7 and any R72, may together with the atoms of the -L7-COOR71, -L7-OR71 or -L7-N(R72)2 group to which they are attached, form a 3- to 6-membered saturated monocyclic heterocyclic group, wherein the 3- to 6-membered saturated monocyclic heterocyclic group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups; each R73 is independently selected from a C1-C4 alkyl, C2-C4 alkenyl, C3-C6 cycloalkyl or C5-C6 cycloalkenyl group, wherein the C1-C4 alkyl, C2-C4 alkenyl, C3-C6 cycloalkyl or C5-C6 cycloalkenyl group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups; each R74 is independently selected from a phenyl or a 5- or 6-membered heteroaryl group, wherein the phenyl or the 5- or 6-membered heteroaryl group may optionally be substituted with one or more groups each independently selected from fluoro, chloro and bromo, and/or with one or two groups each independently selected from methyl (Me), -CN, -OH, -OMe, -NH2, -NHMe, and -NMe2, wherein any methyl group of R74 may optionally be fluoro substituted; R8 is selected from a hydrogen or a fluoro, methyl or fluoromethyl group; or R7 and R8 together form a group -L78-, wherein -L78- is selected from a -CH2-CH2-, -CH2-CH2-CH2-, -CH2-NH-CH2-, -CH2-O-CH2-, -CH2-CH2-CH2-CH2-, -CH2-CH2-NH-CH2-, -CH2-CH2-O-CH2-, -CH2-NH-CH2-CH2- or -CH2-O-CH2-CH2- group, wherein -L78- may optionally be substituted with one or more fluoro groups and/or one or two substituents each independently selected from an oxo (=O), -CN, methyl (Me), -OH, -OMe, -NH2, -NHMe or -NMe2 group, and wherein any methyl group of a -L78- substituent may optionally be fluoro substituted; X10 is N or CR10; X11 is CR11 and X12 is CR12, or X11 is CR11 and X12 is N, or X11 is N and X12 is CR12; X13 is N or CR13; no more than one of X10, X11, X12 and X13 is N; one of R11 and R12 is present and selected from a fluoro, chloro, bromo, fluoromethyl, -CN, -COOH, -CONH2 or -C(=NH)NH2 group; if present each remaining R10, R11, R12 and R13 is independently selected from hydrogen or a fluoro, chloro, bromo, -OH, -NH2, methyl (Me), ethyl (Et), -OMe, -NHMe, -NMe2, -CH2OH or -CH2NH2 group, wherein any methyl (Me), ethyl (Et) or methylene (-CH2-) group of R10, R11, R12 or R13 may optionally be fluoro substituted; R18 is selected from hydrogen or a fluoro, -CN, -COOH, -COOR181, -L18-COOH, -L7-COOR181, -L18-OH, -L18-OR181, -L18-N(R182)2, -R183, -R184 or -L18-R184 group, and R19 is selected from a hydrogen or a fluoro, methyl or fluoromethyl group, provided that R18, including any optional substituents, contains no more than 8 carbon atoms, and that the atom of R18 that is directly attached to the reminder of the molecule is a carbon, hydrogen or fluorine atom; or R18 and R19 together with the carbon atom to which they are attached form a C=O group; R181 is selected from a -R183 or -R184 group; each R182 is independently selected from hydrogen or a -R183 or -R184 group, or any two R182 may, together with the nitrogen atom to which they are attached, form a 3- to 6-membered saturated monocyclic heterocyclic group, wherein the 3- to 6- membered saturated monocyclic heterocyclic group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups; L18 is a straight-chained alkylene, alkenylene or alkynylene group, wherein the straight-chained alkylene, alkenylene or alkynylene group optionally includes one or two heteroatoms each independently selected from O and N in its carbon skeleton, wherein the straight-chained alkylene, alkenylene or alkynylene group has a chain length of from 1 to 4 atoms, and wherein the straight-chained alkylene, alkenylene or alkynylene group may optionally be substituted with one or two oxo (=O) groups and/or with one or more groups RL18, wherein each RL18 is independently selected from a fluoro, methyl or fluoromethyl group, or any RL18 and R181, or any RL18 and any R182, may together with the atoms of the -L7-COOR181, -L18-OR181 or -L18-N(R182)2 group to which they are attached, form a 3- to 6-membered saturated monocyclic heterocyclic group, wherein the 3- to 6-membered saturated monocyclic heterocyclic group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups, or L18 is a divalent phenyl or a divalent 5- or 6-membered heteroaryl group, wherein the divalent phenyl or the divalent 5- or 6-membered heteroaryl group may optionally be substituted with one or more groups each independently selected from fluoro, chloro, bromo, methyl and fluoromethyl; each R183 is independently selected from a C1-C4 alkyl, C2-C4 alkenyl, C3-C6 cycloalkyl or C5-C6 cycloalkenyl group, wherein the C1-C4 alkyl, C2-C4 alkenyl, C3-C6 cycloalkyl or C5-C6 cycloalkenyl group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups; each R184 is independently selected from a phenyl or a 5- or 6-membered heteroaryl group, wherein the phenyl or the 5- or 6-membered heteroaryl group may optionally be substituted with one or more groups each independently selected from fluoro, chloro and bromo, and/or with one or two groups each independently selected from methyl (Me), -CN, -OH, -OMe, -NH2, -NHMe, and -NMe2, wherein the methyl group of R184 may optionally be fluoro substituted; and R20 and R21 are each independently selected from hydrogen or a fluoro group. In one aspect of the fifth exemplary embodiment: R3 is selected from hydrogen or a fluoro, chloro, bromo, -CN or methyl group, wherein the methyl group may optionally be fluoro substituted; R7 is selected from hydrogen or a fluoro, -CN, -COOH, -L7-COOH, -L7-OH, -L7-OR71, -L7-N(R72)2, -R73, -R74 or -L7-R74 group, provided that R7, including any optional substituents, contains no more than 8 carbon atoms, and that the atom of R7 that is directly attached to the reminder of the molecule is a carbon, hydrogen or fluorine atom; each R73 is independently selected from a C1-C4 alkyl or C3-C6 cycloalkyl group, wherein the C1-C4 alkyl or C3-C6 cycloalkyl group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups; and R8 is selected from a hydrogen or a fluoro, methyl or fluoromethyl group; or R7 and R8 together form a group -L78-, wherein -L78- is selected from a -CH2-CH2-, -CH2-CH2-CH2-, -CH2-NH-CH2-, -CH2-O-CH2-, -CH2-CH2-CH2-CH2-, -CH2-CH2-NH-CH2-, -CH2-CH2-O-CH2-, -CH2-NH-CH2-CH2- or -CH2-O-CH2-CH2- group, wherein -L78- may optionally be substituted with one or more fluoro groups and/or one or two substituents each independently selected from an oxo (=O), -CN, methyl (Me), -OH, -OMe, -NH2, -NHMe or -NMe2 group, and wherein any methyl group of a -L78- substituent may optionally be fluoro substituted; R18 is selected from hydrogen or a fluoro, -CN, -COOH, -L18-COOH, -L18-OH, -L18-OR181, -L18-N(R182)2, -R183, -R184 or -L18-R184 group, and R19 is selected from a hydrogen or a fluoro, methyl or fluoromethyl group, provided that R18, including any optional substituents, contains no more than 8 carbon atoms, and that the atom of R18 that is directly attached to the reminder of the molecule is a carbon, hydrogen or fluorine atom; or R18 and R19 together with the carbon atom to which they are attached form a C=O group; and each R183 is independently selected from a C1-C4 alkyl or C3-C6 cycloalkyl group, wherein the C1-C4 alkyl or C3-C6 cycloalkyl group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups. In a corresponding sixth exemplary embodiment, there is provided a compound of Formula (II) as defined above, wherein: R1 is hydrogen; R4 is selected from a fluoro, chloro, bromo, -OH, -OR41, -N(R42)2, -SO2-R41, -SO2-N(R42)2, -L4-OH, -L4-OR41, -L4-N(R42)2, -L4-SO2-R41, -L4-SO2-N(R42)2, -O-L4-OH, -O-L4-OR41, -O-L4-N(R42)2, -O-L4-SO2-R41, -O-L4-SO2-N(R42)2, -NR43-L4-OH, -NR43-L4-OR41, -NR43-L4-N(R42)2, -NR43-L4-SO2-R41, -NR43-L4-SO2-N(R42)2, -R44, -R45 or -L4-R45 group, provided that R4, including any optional substituents, contains no more than 8 carbon atoms; R41 is selected from a -R44 or -R45 group; each R42 is independently selected from hydrogen or a -R44 or -R45 group, or any two R42 may, together with the nitrogen atom to which they are attached, form a 3- to 6-membered saturated monocyclic heterocyclic group, wherein the 3- to 6-membered saturated monocyclic heterocyclic group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups; L4 is a straight-chained alkylene group, wherein the straight-chained alkylene group optionally includes one or two heteroatoms each independently selected from O and N in its carbon skeleton, wherein L4 has a chain length of from 1 to 4 atoms, and wherein L4 may optionally be substituted with one or two oxo (=O) groups and/or with one or more groups RL4, wherein each RL4 is independently selected from a fluoro, methyl or fluoromethyl group, or any RL4 and R41, or any RL4 and any R42, may together with the atoms to which they are attached, form a 3- to 6-membered saturated monocyclic heterocyclic group, wherein the 3- to 6-membered saturated monocyclic heterocyclic group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups; R43 is selected from hydrogen or a -R44 group; each R44 is independently selected from a C1-C4 alkyl or C3-C6 cycloalkyl group, wherein the C1-C4 alkyl or C3-C6 cycloalkyl group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups; each R45 is independently selected from a phenyl or a 5- or 6-membered heteroaryl group, wherein the phenyl or the 5- or 6-membered heteroaryl group may optionally be substituted with one or more groups each independently selected from fluoro, chloro and bromo, and/or with one or two groups each independently selected from methyl (Me), -CN, -OH, -OMe, -NH2, -NHMe, and -NMe2, wherein any methyl group of R45 may optionally be fluoro substituted; R5 is selected from hydrogen or a fluoro, chloro or bromo group; R6 is selected from a -R60 or -OR60 group; R60 is selected from a C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group; R7 is selected from hydrogen or a fluoro, -CN, -COOH, -COOR71, -L7-COOH, -L7-COOR71, -L7-OH, -L7-OR71, -L7-N(R72)2, -R73, -R74 or -L7-R74 group, provided that R7, including any optional substituents, contains no more than 8 carbon atoms, and that the atom of R7 that is directly attached to the reminder of the molecule is a carbon, hydrogen or fluorine atom; R71 is selected from a -R73 or -R74 group; each R72 is independently selected from hydrogen or a -R73 or -R74 group, or any two R72 may, together with the nitrogen atom to which they are attached, form a 3- to 6- membered saturated monocyclic heterocyclic group, wherein the 3- to 6-membered saturated monocyclic heterocyclic group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups; L7 is a straight-chained alkylene group, wherein the straight-chained alkylene group optionally includes one or two heteroatoms each independently selected from O and N in its carbon skeleton, wherein L7 has a chain length of from 1 to 4 atoms, and wherein L7 may optionally be substituted with one or two oxo (=O) groups and/or with one or more groups RL7, wherein each RL7 is independently selected from a fluoro, methyl or fluoromethyl group, or any RL7 and R71, or any RL7 and any R72, may together with the atoms of the -L7-COOR71, -L7-OR71 or -L7-N(R72)2 group to which they are attached, form a 3- to 6-membered saturated monocyclic heterocyclic group, wherein the 3- to 6-membered saturated monocyclic heterocyclic group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups; each R73 is independently selected from a C1-C4 alkyl, C2-C4 alkenyl, C3-C6 cycloalkyl or C5-C6 cycloalkenyl group, wherein the C1-C4 alkyl, C2-C4 alkenyl, C3-C6 cycloalkyl or C5-C6 cycloalkenyl group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups; each R74 is independently selected from a phenyl or a 5- or 6-membered heteroaryl group, wherein the phenyl or the 5- or 6-membered heteroaryl group may optionally be substituted with one or more groups each independently selected from fluoro, chloro and bromo, and/or with one or two groups each independently selected from methyl (Me), -CN, -OH, -OMe, -NH2, -NHMe, and -NMe2, wherein any methyl group of R74 may optionally be fluoro substituted; R8 is selected from a hydrogen or a fluoro, methyl or fluoromethyl group; or R7 and R8 together form a group -L78-, wherein -L78- is selected from a -CH2-CH2-, -CH2-CH2-CH2-, -CH2-NH-CH2-, -CH2-O-CH2-, -CH2-CH2-CH2-CH2-, -CH2-CH2-NH-CH2-, -CH2-CH2-O-CH2-, -CH2-NH-CH2-CH2- or -CH2-O-CH2-CH2- group, wherein -L78- may optionally be substituted with one or more fluoro groups and/or one or two substituents each independently selected from an oxo (=O), -CN, methyl (Me), -OH, -OMe, -NH2, -NHMe or -NMe2 group, and wherein any methyl group of a -L78- substituent may optionally be fluoro substituted; X10 is N or CR10; X11 is CR11 and X12 is CR12, or X11 is CR11 and X12 is N, or X11 is N and X12 is CR12; X13 is N or CR13; no more than one of X10, X11, X12 and X13 is N; one of R11 and R12 is present and selected from a fluoro, chloro, bromo, fluoromethyl, -CN, -COOH, -CONH2 or -C(=NH)NH2 group; if present each remaining R10, R11, R12 and R13 is independently selected from hydrogen or a fluoro, chloro, bromo, -OH, -NH2, methyl (Me), ethyl (Et), -OMe, -NHMe, -NMe2, -CH2OH or -CH2NH2 group, wherein any methyl (Me), ethyl (Et) or methylene (-CH2-) group of R10, R11, R12 or R13 may optionally be fluoro substituted; each R14 and R15 is independently selected from hydrogen or a C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group, or R14 and R15 together with the carbon atom to which they are attached form a cyclopropyl or a cyclobutyl group, wherein the cyclopropyl or cyclobutyl group may optionally be substituted with one or more fluoro groups; R16 is selected from hydrogen or a fluoro, -R160, -CN, -CHO, -COR160, -CO2H or -CO2R160 group; R160 is selected from a C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group; and R17 is selected from hydrogen or a fluoro, C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group; or R16 and R17 together with the carbon atom to which they are attached form a 3- to 5-membered saturated monocyclic group wherein the saturated monocyclic group may optionally be substituted with one or more fluoro groups and/or one or two substituents each independently selected from oxo (=O) or a methyl or fluoromethyl group; R18 is selected from hydrogen or a fluoro, -CN, -COOH, -COOR181, -L18-COOH, -L7-COOR181, -L18-OH, -L18-OR181, -L18-N(R182)2, -R183, -R184 or -L18-R184 group, and R19 is selected from a hydrogen or a fluoro, methyl or fluoromethyl group, provided that R18 , including any optional substituents, contains no more than 8 carbon atoms, and that the atom of R18 that is directly attached to the reminder of the molecule is a carbon, hydrogen or fluorine atom; or R18 and R19 together with the carbon atom to which they are attached form a C=O group; R181 is selected from a -R183 or -R184 group; each R182 is independently selected from hydrogen or a -R183 or -R184 group, or any two R182 may, together with the nitrogen atom to which they are attached, form a 3- to 6-membered saturated monocyclic heterocyclic group, wherein the 3- to 6- membered saturated monocyclic heterocyclic group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups; L18 is a straight-chained alkylene, alkenylene or alkynylene group, wherein the straight-chained alkylene, alkenylene or alkynylene group optionally includes one or two heteroatoms each independently selected from O and N in its carbon skeleton, wherein the straight-chained alkylene, alkenylene or alkynylene group has a chain length of from 1 to 4 atoms, and wherein the straight-chained alkylene, alkenylene or alkynylene group may optionally be substituted with one or two oxo (=O) groups and/or with one or more groups RL18, wherein each RL18 is independently selected from a fluoro, methyl or fluoromethyl group, or any RL18 and R181, or any RL18 and any R182, may together with the atoms of the -L7-COOR181, -L18-OR181 or -L18-N(R182)2 group to which they are attached, form a 3- to 6-membered saturated monocyclic heterocyclic group, wherein the 3- to 6-membered saturated monocyclic heterocyclic group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups, or L18 is a divalent phenyl or a divalent 5- or 6-membered heteroaryl group, wherein the divalent phenyl or the divalent 5- or 6-membered heteroaryl group may optionally be substituted with one or more groups each independently selected from fluoro, chloro, bromo, methyl and fluoromethyl; each R183 is independently selected from a C1-C4 alkyl, C2-C4 alkenyl, C3-C6 cycloalkyl or C5-C6 cycloalkenyl group, wherein the C1-C4 alkyl, C2-C4 alkenyl, C3-C6 cycloalkyl or C5-C6 cycloalkenyl group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups; each R184 is independently selected from a phenyl or a 5- or 6-membered heteroaryl group, wherein the phenyl or the 5- or 6-membered heteroaryl group may optionally be substituted with one or more groups each independently selected from fluoro, chloro and bromo, and/or with one or two groups each independently selected from methyl (Me), -CN, -OH, -OMe, -NH2, -NHMe, and -NMe2, wherein the methyl group of R184 may optionally be fluoro substituted; and R20 and R21 are each independently selected from hydrogen or a fluoro group. In one aspect of the sixth exemplary embodiment: R7 is selected from hydrogen or a fluoro, -CN, -COOH, -L7-COOH, -L7-OH, -L7-OR71, -L7-N(R72)2, -R73, -R74 or -L7-R74 group, provided that R7, including any optional substituents, contains no more than 8 carbon atoms, and that the atom of R7 that is directly attached to the reminder of the molecule is a carbon, hydrogen or fluorine atom; each R73 is independently selected from a C1-C4 alkyl or C3-C6 cycloalkyl group, wherein the C1-C4 alkyl or C3-C6 cycloalkyl group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups; R8 is selected from a hydrogen or a fluoro, methyl or fluoromethyl group; or R7 and R8 together form a group -L78-, wherein -L78- is selected from a -CH2-CH2-, -CH2-CH2-CH2-, -CH2-NH-CH2-, -CH2-O-CH2-, -CH2-CH2-CH2-CH2-, -CH2-CH2-NH-CH2-, -CH2-CH2-O-CH2-, -CH2-NH-CH2-CH2- or -CH2-O-CH2-CH2- group, wherein -L78- may optionally be substituted with one or more fluoro groups and/or one or two substituents each independently selected from an oxo (=O), -CN, methyl (Me), -OH, -OMe, -NH2, -NHMe or -NMe2 group, and wherein any methyl group of a -L78- substituent may optionally be fluoro substituted; R16 is selected from hydrogen or a fluoro, -CN, C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group; and R17 is selected from hydrogen or a fluoro, C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group; or R16 and R17 together with the carbon atom to which they are attached form a cyclopropyl or a cyclobutyl group, wherein the cyclopropyl or cyclobutyl group may optionally be substituted with one or more fluoro groups; R18 is selected from hydrogen or a fluoro, -CN, -COOH, -L18-COOH, -L18-OH, -L18-OR181, -L18-N(R182)2, -R183, -R184 or -L18-R184 group, and R19 is selected from a hydrogen or a fluoro, methyl or fluoromethyl group, provided that R18, including any optional substituents, contains no more than 8 carbon atoms, and that the atom of R18 that is directly attached to the reminder of the molecule is a carbon, hydrogen or fluorine atom; or R18 and R19 together with the carbon atom to which they are attached form a C=O group; and each R183 is independently selected from a C1-C4 alkyl or C3-C6 cycloalkyl group, wherein the C1-C4 alkyl or C3-C6 cycloalkyl group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups. In a seventh exemplary embodiment, there is provided a compound of Formula (I) as defined above, wherein: R1 is hydrogen; R2 is hydrogen; R3 is selected from hydrogen or a fluoro, chloro or bromo group; R4 is selected from a fluoro, chloro, bromo, -R44 or -OR44 group; R44 is selected from a C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group; R5 is hydrogen; R6 is a methyl or a fluoromethyl group; R7 is selected from hydrogen or a fluoro, -L71-COOH, -L71-COOR75, -L71-OH, -L71-OR75 or -R75 group; -L71- is selected from a -CH2-, -CHMe- or -CMe2- group, wherein any -CH2-, -CHMe- or -CMe2- group may optionally be fluoro substituted; R75 is selected from a C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group; R8 is selected from a hydrogen or a fluoro, methyl or fluoromethyl group; X10 is N, C-H, C-F, C-Cl or C-Br; X11 is C-CN and X12 is C-H, C-F, C-Cl or C-Br, or X12 is C-CN and X11 is C-H, C-F, C-Cl or C-Br; X13 is N, C-H, C-F, C-Cl or C-Br; no more than one of X10 and X13 is N; R18 and R19 are each independently selected from hydrogen or a fluoro, methyl or fluoromethyl group, or R18 and R19 together with the carbon atom to which they are attached form a C=O group; and R20 and R21 are both hydrogen. In one aspect of the seventh exemplary embodiment, R18 and R19 are both hydrogen. In a corresponding eighth exemplary embodiment, there is provided a compound of Formula (II) as defined above, wherein: R1 is hydrogen; R4 is selected from a fluoro, chloro, bromo, -R44 or -OR44 group; R44 is selected from a C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group; R5 is hydrogen; R6 is a methyl or a fluoromethyl group; R7 is selected from hydrogen or a fluoro, -L71-COOH, -L71-COOR75, -L71-OH, -L71-OR75 or -R75 group; -L71- is selected from a -CH2-, -CHMe- or -CMe2- group, wherein any -CH2-, -CHMe- or -CMe2- group may optionally be fluoro substituted; R75 is selected from a C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group; R8 is selected from a hydrogen or a fluoro, methyl or fluoromethyl group; X10 is N, C-H, C-F, C-Cl or C-Br; X11 is C-CN and X12 is C-H, C-F, C-Cl or C-Br, or X12 is C-CN and X11 is C-H, C-F, C-Cl or C-Br; X13 is N, C-H, C-F, C-Cl or C-Br; no more than one of X10 and X13 is N; R14 and R15 are both hydrogen; R16 and R17 are both hydrogen; R18 and R19 are each independently selected from hydrogen or a fluoro, methyl or fluoromethyl group, or R18 and R19 together with the carbon atom to which they are attached form a C=O group; and R20 and R21 are both hydrogen. In one aspect of the eighth exemplary embodiment, R18 and R19 are both hydrogen. In one aspect of any of the above embodiments, the compound of formula (I) or formula (II) has a molecular weight of from 248 to 750 Da. Typically, the compound of formula (I) or formula (II) has a molecular weight of from 260 to 600 Da, or from 260 to 500 Da. More typically, the compound of formula (I) or formula (II) has a molecular weight of from 280 to 400 Da. A third aspect of the invention provides a compound selected from the group consisting of:
Figure imgf000106_0001
A fourth aspect of the invention provides a pharmaceutically acceptable salt and/or solvate and/or prodrug of any compound of the first, second or third aspect of the invention. In one embodiment, the fourth aspect of the invention provides a pharmaceutically acceptable salt and/or solvate of any compound of the first, second or third aspect of the invention. For example, the fourth aspect of the invention may provide (i) a pharmaceutically acceptable salt of any compound of the first, second or third aspect of the invention, or (ii) a pharmaceutically acceptable solvate of any compound of the first, second or third aspect of the invention, or (iii) a pharmaceutically acceptable solvate of a pharmaceutically acceptable salt of any compound of the first, second or third 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, 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 fourth aspect of the invention provides a prodrug of any compound of the first, second or third aspect of the invention. Similarly, the fourth aspect of the invention may provide a pharmaceutically acceptable salt and/or solvate of such a prodrug. For example, the fourth 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 by 1H 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 to 12C, 13C, 1H, 2H (D), 14N, 15N, 16O, 17O, 18O, 19F and 127I, and any radioisotope including, but not limited to 11C, 14C, 3H (T), 13N, 15O, 18F, 123I, 124I, 125I and 131I. The compounds, salts, solvates and prodrugs of the present invention may be in any polymorphic or amorphous form. A fifth aspect of the invention provides a pharmaceutical composition comprising a compound of the first, second or third aspect of the invention, or a pharmaceutically acceptable salt and/or solvate and/or prodrug 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, 4th Ed., 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. A sixth aspect of the invention provides a compound of the first, second or third aspect of the invention, or a pharmaceutically acceptable salt, solvate or prodrug 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 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 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 and may include for example, inflammatory biomarkers such as C-reactive protein (CRP) and monocyte chemoattractant protein 1 (MCP-1) in the case of inflammation, as well as biomarkers associated with the complement system, such as C5a, terminal complement complex, Factor B, fragments Ba and Bb, Complement C3 fragments C3a and C3b, and downstream degradation products iC3b, C3c and C3d(g). A seventh aspect of the invention provides the use of a compound of the first, second or third aspect, or a pharmaceutically effective salt, solvate or prodrug of the fourth aspect, 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 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, second or third aspect, or a pharmaceutically acceptable salt, solvate or prodrug of the fourth aspect, or a pharmaceutical composition of the fifth aspect, to thereby treat or prevent the disease, disorder or condition. Typically, the administration is to a subject in need thereof. Dysregulation of the alternative complement pathway due to genetics or the presence of autoantibodies can lead to many different diseases. Common polymorphisms in complement proteins or rare mutations can cause dysfunction or dysregulation of the complement system due to over-activation or under-regulation. Autoantibodies can bind to self-cells and drive the complement system such that the capacity of the natural regulators to protect is overwhelmed. In some cases, the cells’ natural defence mechanism, such as shedding of active complexes, can cause symptoms due to loss of critical molecules from the cell surface, such as the acetylcholine receptor. In many diseases, however, the complement system is not the primary trigger of disease but acts secondarily to other disease-causing triggers to set up a vicious cycle of inflammation that is propagated by the complement system. In these diseases, inhibition of the complement system can bring about a treatment effect. In some instances, gain of function Complement C3 and/or Factor B mutations, and/or the loss of function in the regulatory proteins eventuate in uncontrolled C3 activation (Garred, P., Tenner, A. J., and Mollnes, T. E. Pharmacol. Rev.2021, 73, 792-827). In some cases, common polymorphisms or rare mutations can lead to distinctive phenotypes due to specific impact on function, such as the ability to bind membranes. Some genetic changes result in proteins with altered ability to bind to certain structures (such as glycosaminoglycans or disease-associated epitopes), resulting in tissue-specific diseases. The domain in which the mutation or polymorphism resides can impact disease phenotype. Accordingly, a ninth aspect of the invention provides a compound of the first, second or third aspect of the invention, or a pharmaceutically acceptable salt, solvate or prodrug 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 disease, disorder or condition in an individual, wherein the individual has a germline or somatic mutation in Complement C3 or Factor B, or a germline or somatic mutation in a regulator of the alternate pathway, or a germline or somatic mutation in an enzyme that directly or indirectly causes the production or activation of Factor B. The mutation may be, for example, a gain-of-function or other mutation of Factor B resulting in increased Factor B or C3/C5 convertase activity. Alternately, the mutation may be a gain-of-function or other mutation of Complement C3 resulting in increased Factor B or C3/C5 convertase activity. Similarly, the mutation may be a loss of function in a negative regulator (such as Factor H) resulting in increased alternate pathway activity, a gain of function in a positive regulator (such as properdin) resulting in increased alternate pathway activity, or a gain of function in an enzyme that causes the production or activation of Factor B. Such mutations are discussed in Rodriguez de Cordoba, Immunological Reviews, 2023, 313, 71-90, and Kouser et al., Front. Immunol., 2013, 4(93), 1-12. Typically, the use comprises the administration of the compound, salt, solvate, prodrug or pharmaceutical composition to the individual. The use may also comprise the diagnosis of an individual having a germline or somatic mutation in (i) Complement C3, (ii) Factor B, (iii) a regulator of the alternate pathway, or (iv) an enzyme that directly or indirectly causes the production or activation of Factor B, wherein the compound, salt, solvate, prodrug or pharmaceutical composition is administered to an individual on the basis of a positive diagnosis for the mutation. Typically, identification of the mutation in Complement C3, Factor B, the regulator or the enzyme in the individual may be by any suitable genetic or biochemical means. A tenth aspect of the invention provides the use of a compound of the first, second or third aspect of the invention, or a pharmaceutically acceptable salt, solvate or prodrug of the fourth aspect of the invention, in the manufacture of a medicament for the treatment or prevention of a disease, disorder or condition in an individual, wherein the individual has a germline or somatic mutation in Complement C3 or Factor B, or a germline or somatic mutation in a regulator of the alternate pathway, or a germline or somatic mutation in an enzyme that directly or indirectly causes the production or activation of Factor B. The mutation may be, for example, a gain-of-function or other mutation of Factor B resulting in increased Factor B or C3/C5 convertase activity. Alternately, the mutation may be a gain-of-function or other mutation of Complement C3 resulting in increased Factor B or C3/C5 convertase activity. Similarly, the mutation may be a loss of function in a negative regulator (such as Factor H) resulting in increased alternate pathway activity, a gain of function in a positive regulator (such as properdin) resulting in increased alternate pathway activity, or a gain of function in an enzyme that causes the production or activation of Factor B. Typically, the treatment or prevention comprises the administration of the compound, salt, solvate, prodrug or medicament to the individual. The treatment or prevention may also comprise the diagnosis of an individual having a germline or somatic mutation in (i) Complement C3, (ii) Factor B, (iii) a regulator of the alternate pathway, or (iv) an enzyme that directly or indirectly causes the production or activation of Factor B, wherein the compound, salt, solvate, prodrug or medicament is administered to an individual on the basis of a positive diagnosis for the mutation. Typically, identification of the mutation in Complement C3, Factor B, the regulator or the enzyme in the individual may be by any suitable genetic or biochemical means. An eleventh aspect of the invention provides a method of treatment or prevention of a disease, disorder or condition, the method comprising the steps of diagnosing of an individual having a germline or somatic mutation in (i) Complement C3, (ii) Factor B, (iii) a regulator of the alternate pathway, or (iv) an enzyme that directly or indirectly causes the production or activation of Factor B, and administering an effective amount of a compound of the first, second or third aspect of the invention, or a pharmaceutically acceptable salt, solvate or prodrug of the fourth aspect of the invention, or a pharmaceutical composition of the fifth aspect of the invention, to the positively diagnosed individual, to thereby treat or prevent the disease, disorder or condition. Typically, the administration is to a subject in need thereof. In general embodiments of any of the sixth to eleventh aspects of the invention, the disease, disorder or condition may be a disease, disorder or condition of the immune system, the cardiovascular system, the renal system, the respiratory system, the central nervous system, the reproductive system, the ocular system, the metabolic system, the haematological system, may be a cancer or other malignancy, and/or may be caused by or associated with a pathogen. It will be appreciated that these general embodiments defined according to broad categories of diseases, disorders and conditions are not mutually exclusive. In this regard any particular disease, disorder or condition may be categorized according to more than one of the above general embodiments. A non-limiting example is type I diabetes which is an autoimmune disease and a disease of the endocrine system. In one embodiment of the sixth, seventh, eighth, ninth, tenth or eleventh aspect of the invention, the disease, disorder or condition is responsive to Factor B inhibition. As used herein, the term “Factor B inhibition” refers to the complete or partial reduction in the level of activity of Factor B, either unbound or in complex with C3b/C3(H2O), and includes, for example, (i) the inhibition of active Factor B or Bb, (ii) the inhibition of latent Factor B (the zymogen) and/or (iii) the inhibition of the conversion of latent Factor B into active Factor B. A number of ocular conditions have been shown to involve Factor B including, in particular, age-related macular degeneration (Schramm, E. C. et al, Mol. Immunol. 2014, 61, 118-125), retinal detachment (Sweigard, J. H. et al, Sci. Transl. Med.2015, 7, 297ra116-297ra116), Doyne honeycomb retinal dystrophy, also known as malattia leventinese (DHRD/ML) (Crowley, M. A. et al, Hum. Mol. Genet.2023, ddac187), diabetic macular oedema and diabetic retinopathy (Murray, H. et al, Investig. Ophthalmol. Vis. Sci.2018, 59, 5476-5476; Xu et al, Eur. J. Pharmacol.2016,787, 94- 104, Gerl et al, Invest. Opthalmol. Vis. Sci, 2002, 43(4), 1104-1108; Zhang et al, Diabetes 2002, 51(12), 3499-3504; and Murray 'Defining the Role of Complement Factor B of the Alternative Complement Pathway in Diabetic Retinopathy', PhD thesis, University of Sheffield, 2019), retinal ischemia reperfusion (Inafuku, S., Klokman, G., and Connor, K. M. Front. Mol. Neurosci.2018, 11, 278), non-infectious uveitis (Yang, M. et al, Immunol. Res.2016, 64, 610-618; Eskandarpour et al, Am. J. Pathol.2021, 191(2), 320-334, and Tanaka et al, BMC Opthalmol.2014, 14, 83), polypoidal choroidal neovascularization and ocular angiogenesis (Murray, H. et al, Int. J. Mol. Sci.2021, 22, 9580). Factor B has been linked to a number of respiratory conditions and lung diseases including those caused by SARS-CoV-2 (Yan, B. et al, Sci. Immunol.2021, 6, eabg0833), Covid-19 (Fujimura, Y., and Holland, L. Z. Int. J. Hematol.2022, 115, 457- 469), smoke-induced mucosal damage (Davis, K. S. et al, Otolaryngol. Head Neck Surg. 2010, 143, 152-158), airway hyperresponsiveness allergic asthma (Herbert, C. et al, Clin. Sci. (Lond) 2017, 131, 499-509), idiopathic pulmonary fibrosis (Meliconi, R. et al, Clin. Immunol. Immunopathol.1990, 57, 64-73), and airway hyperresponsiveness with inflammation (Taube, C. et al, Proc. Natl. Acad. Sci. U.S.A.2006, 103, 8084-8089). Factor B has also been implicated in a number of central nervous system conditions including ischemic stroke (Turek-Jakubowska, A. et al, J. Clin. Med.2022, 11, 339; and Elvington, A. et al, J. Immunol.2012, 189(9), 4640-4647), traumatic brain injury (Lindblad, C. et al, Crit. Care 2021, 25, 103; Mallah, K. et al, Acta Neuropathol. Commun.2021, 9(1), 72; and Alawieh, A. et al, J. Neurosci.2018, 38(10), 2519-2532), spinal cord injury (Baldan-Martin, M. et al, Adv. Wound Care (New Rochelle) 2020, 9, 277-294; and Qiao, F. et al, Am. J. Pathol.2010, 177(6), 3061-3070), Toxoplasma infection-induced neurological disorders (Shinjyo, N. et al, Front. Immunol.2020, 11, 603924), prion diseases (Chen, C. et al, Med. Microbiol. Immunol.2020, 209, 81-94; and Klein, M. A. et al, Mat. Med.2001, 7(4), 488-492), multiple sclerosis (Solmaz, I. et al, J. Neuroimmunol.2020, 348, 577359; and Linzey, M. et al, Front. Immunol.2022, 13, 924734), amyotrophic lateral sclerosis (Lee, J. D. et al, J. Neuroinflammation 2018, 15, 171), depression (Wang, Q. et al, Psychiatry Research 2019, 272, 404-410; and Reddy, P. V. et al, Clin. Psychopharmacol. Neurosci.2023, 21(2), 313-319), pain (Wåhlén, K. et al, Front. Psychol.2018, 9, 2400), schizophrenia (Mayilyan, K. R., Weinberger, D. R., and Sim, R. B. Drug News Perspect.2008, 21, 200; and Boyajyan, A. et al, Neurochemical Research 2010, 35, 894-898), cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (Unlü, M. et al, Neurosci. Lett.2000, 282, 149-152), lupus cerebritis (Alexander, J. J. et al, Eur. J. Immunol.2007, 37, 1691-1701) and Alzheimer’s disease (Morgan, A. R. et al, Alzheimers Dement.2019, 15, 776-787; and Strohmeyer, R. et al, Brain Res. Mol. Brain Res.2000, 81(1-2), 7-18). Several cardiovascular diseases have been shown to be associated with Factor B, including heart failure (Holt, M. F. et al, Front. Immunol.2021, 12, 800978), cardiac remodelling (Yang, Y. et al, Eur. J. Immunol.2020, 50, 220-233), aortic stenosis (Shahini, N. et al, J. Immunol.2019, 203, 1973-1980), cardiometabolic disease (Coan, P. M. et al, Hypertension 2017, 70, 624-633) and cardiac ischemia and reperfusion (Chun, N. et al, PLOS ONE 2017, 12, e0179450). Factor B has been suggested to play a role in a number of haematological and blood disorders, including idiopathic thrombocytopenic purpura (ITP) (Weitz, I. C. et al, Br. J. Haematol.2023, 203(1), 96-100; and Shindo, R. et al, Immunol. Med.2023, 1-9), paroxysmal nocturnal hemoglobinuria (PNH) (Brodsky, R. A. Blood 2014, 124, 2804- 2811; and Schubart, A. et al, Proc. Natl. Acad. Sci. USA 2019, 116(6), 7926-7931), atypical hemolytic uremic syndrome (Rodríguez de Córdoba, S. et al, Semin. Thromb. Hemost.2014, 40, 422-430; and Goicoechea de Jorge, E. et al, Proc. Natl. Acad. Sci. USA 2007, 104(1), 240-245), transplant-associated thrombotic microangiopathy (Sartain, S. et al, Pediatr. Blood Cancer 2020, 67, e28070), vaso-occlusive crises in sickle cell disease, and delayed hemolytic transfusion reactions (DHTR) in individuals suffering from sickle cell disease (Merle, N. S. et al, Transfus. Clin. Biol.2019, 26(2), 116-124; and Chudwin, D. S. et al, Clin. Immunol. Immunopathol.1994, 71(2), 199- 202). Factor B has been implicated in the pathogenesis of various cancers, including pancreatic cancer (Shimazaki, R. et al, Cell Oncol.2021, 44, 937-950), photocarcinogenesis (Byrne, S. N. et al, Photochem. Photobiol. Sci.2015, 14, 801-806), breast cancer (Suman, S. et al, J. Proteomics 2016, 148, 183-193), gastro-oesophageal cancer (Wu, C. et al, Br. J. Cancer 2015, 113, 220-225), head and neck squamous carcinoma (Ohshiro, K. et al, Int. J. Oncol.2007, 30, 743-749), and adenoma to carcinoma and cutaneous squamous cell carcinoma (Riihilä, P. et al, Am. J. Pathol. 2017, 187, 1186-1197). A number of renal diseases have been shown to be associated with Factor B (Wang, F. M. et al, Front. Genet.2021, 12, 690952), including atypical hemolytic uremic syndrome as discussed above, IgA nephropathy (Zhou, X. J. et al, Clin. J. Am. Soc. Nephrol.2021, 16, 213-224; Rizk, D. V. et al, Kidney Int. Rep.2023, 8(5), 968-979; Poppelaars, F. et al, J. Clin. Med.2021, 10(20), 4715; and Daha, M. R. et al, J. Nephrol. 2016, 29(1), 1-4), membranous nephropathy including primary membranous nephropathy (Couser, W. G. Clin. J. Am. Soc. Nephrol.2017, 12, 983-997; and Novartis Investor Presentation, 'Iptacopan (LNP023) update' 22 June 2021), C3 glomerulopathy (C3G) including dense deposit disease and C3 glomerulonephritis (Barbour, T. D. et al, Nephrol. Dial. Transplant.2013, 28, 1685-1693; Zhang, Y. et al, Clin. J. Am. Soc. Nephrol.2012, 7, 265-274; Pickering, M. C. et al, Kidney Int.2013, 84(6), 1079-1089; Zanchi, C. et al, Mol. Immunol.2023, 161, 25-32; Bomback, A. S. et al, Kidney Int. Rep. 2022, 7(10), 2150-2159; and Novartis Press Release 'Novartis iptacopan meets primary endpoints in Phase II study in rare kidney disease C3 glomerulopathy (C3G)', 4 November 2021), immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) (Iatropoulos, P. et al, J. A. Soc. Nephrol.2018, 29(1), 283-294), thrombotic microangiopathy (TMA)-mediated acute kidney injury (AKI) (Guzzo, G. et al, BMC Nephrol.2021, 22, 252), malignant nephrosclerosis (Zhang, Y. et al, Nephrol. Dial. Transplant.2021, 36, 1222-1233), glomerular sclerosis (Zhang, Y. et al, J. Proteomics 2015, 123, 89-100), renal allograft (Jager, N. M. et al, Front. Immunol.2019, 10, 2528), autosomal dominant polycystic kidney disease (Su, Z. et al, J. Intern. Med.2014, 276, 470-485), acute kidney injury (Laskowski, J. et al, Am. J. Physiol. Renal Physiol.2019, 317, F650-F657), focal segmental glomerulosclerosis (FSGS) (Lenderink, A. M. et al, Am. J. Physiol. Renal Physiol.2007, 293(2), F555- F564; Peng, Y. et al, Front. Pediatr.2023, 11, 1137375; and Turnberg, D. et al, J. Immunol.2006, 177(6), 4094-4102) and postinfectious glomerulonephritis (Sethi, S. et al, Kidney Int., 2013, 83(2), 293-299). Factor B has been suggested to have a role in a number of metabolic conditions, including diabetes related conditions including, in particular, gestational diabetes (Shen, Y. et al, Gynecol. Endocrinol.2022, 38, 158-163), cardiometabolic disease (Coan, P. M. et al, Hypertension, 2017, 70, 624-633), diabetic macular oedema and diabetic retinopathy as discussed above, diabetic kidney disease (Lu, Q. et al, JCI Insight 2021, 6, e147716), and metabolic disorders including diet-induced steatosis and dyslipidemia (Sadana, P. et al, Int. J. Mol. Sci.2020, 21, 7472). Within the reproductive system, Factor B has been linked to infertility (Sim, Y. J., Ryu, A. R., and Lee, M. Y. Biotechnol. Appl. Biochem.2022, 69, 289-295), inflammation during pregnancy (Livson, S. et al, Front. Immunol.2022, 13, 925630), spontaneous preterm birth (Lynch, A. M. et al, Am. J. Obstet. Gynecol.2008, 199, 354.e1-8), pregnancy loss in antiphospholipid syndrome (Breen, K. A. et al, Thromb. Haemost. 2012, 107(3), 423-429; Salmon, J. E. et al, Lupus.2012, 12(7), 535-538; and Salmon, J. E. et al, Curr. Dir. Autoimmun.2004, 7, 133-148), pyelonephritis during pregnancy (Soto, E. et al, J. Matern. Fetal Neonatal Med.2010, 23, 1085-1090), amniotic infection/inflammation (Vaisbuch, E. et al, J. Matern. Fetal Neonatal Med.2009, 22, 905-916) and pre-eclampsia (Jia, K. et al, Med. Sci. Monit.2019, 25, 7087-7093; Lynch, A. M. et al, Am. J. Obstet. Gynecol.2008, 198(4), 385; and Blakey, H. et al, Pregnancy Hypertens.2023, 32, 43-49). Factor B has also been linked to several pathogenic diseases, including dengue- associated DHF (dengue hemorrhagic fever) and DSS (dengue shock syndrome) (Cabezas-Falcon, S. et al, J. Gen. Virol.2021, 102, 001547; and Dalrymple, N. A. et al, J. Virol.2012, 86(12), 6408-6415), hyper-inflammatory complications of severe sepsis (Li, D. et al, Crit. Care Med.2016, 44, e289-299; and Zou, L. et al, J. Immunol.2013, 191(11), 5625-5635), fulminant meningococcal septicemia (Brandtzaeg, P. et al, J. Infect. Dis.1996, 173, 647-655), leprosy caused by Mycobacterium leprae (El Idrissi, N. B. et al, Clin. Exp. Immunol.2016, 184(3), 338-346; and El Idrissi, N. B. et al, Acta Neuropathol.2015, 129(5), 653-667), and postinfectious glomerulonephritis (Chauvet, S. et al, J. Am. Soc. Nephrol.2020, 31, 829-840). Other diseases, disorders or conditions in which Factor B has been implicated or shown to be involved include: - liver diseases including chronic hepatitis B (Chen, H. et al, Aliment. Pharmacol. Ther.2020, 51, 469-478; Seo, T. Y. et al, BMC Med. Genet.2020, 21(1), 241; and Jiang, D-K. et al, Hepatology, 2015, 62(1), 118-128), acute alcohol-associated hepatitis (Fan, X. et al, Hepatology 2021, 73, 983-997) and large duct biliary obstruction and viral hepatitis (Potter, B. J. et al, Digestion 1978, 18, 371-383); - auto-immune conditions including cold agglutinin disease (Berentsen, S. Semin. Hematol.2018, 55, 141-149), ANCA vasculitis (Xiao, H. et al, Am. J. Pathol.2007, 170, 52-64), IgA vasculitis (Demir, S. et al, Diagnostics (Basel) 2023, 13(10), 1729), systemic lupus erythematosus including lupus nephritis (Kono, D. H., Theofilopoulos, A. N. (2011) Chapter 4 - Genetics of Lupus in Mice, in Systemic Lupus Erythematosus (Fifth Edition) (Lahita, R. G. ed.), Academic Press, San Diego; Chen, K. et al, Biomed. Pharmacother.2022, 153, 113433; and Wilson, M. R. et al, Clin. Exp. Immunol.1976, 26(1), 11-20), Sjögren's syndrome (Larssen, E. et al, SAGE Open Med.2019, 7, 2050312119850390), myasthenia gravis (Subías, M. et al, J. Immunology 2014, 193, 5567-5575), acquired thrombotic thrombocytopenic purpura (TTP) (Cao, W. et al, Haematologica 2016, 101, 1319- 1326), neuromyelitis optica (Palace, J. et al, Clinical Trial 2021, 47, 102641), Guillian-Barré syndrome (Campbell, C. I. et al, Brain Commun.2022, 4(6), fcac306l and Halstead, S. K. et al. Brain 2004, 127(9), 2109-2123); and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) (Querol, L. et al, J. Peripher. Nerv. Syst., 2023, 28(2), 276-285); - musculoskeletal disorders and muscle inflammation (Ghafouri, B. et al, BMC Musculoskelet. Disord.2016, 17, 206; and Frenette, J. et al, Am. J. Pathol.2000, 156, 2103-2110), rheumatoid arthritis (Krick, E. H. et al, Clin. Exp. Immunol.1978, 34, 1-9; and Holers, V. M. et al, Front. Immunol., 2018, 9, 1057), and osteoarthritis (Assirelli, E. et al, Front. Immunol.2020, 11, 535010); - inflammatory bowel disease (Shi, D. et al, J. Hum. Genet.2020, 65, 241-249); - primary varicose veins (Shadrina, A. et al, Gene 2018, 659, 93-99); - antiphospholipid syndrome (Breen, K. A. et al, Thromb. Haemost.2012, 107, 423- 429; Kim, M. Y. et al, Ann. Rheum. Dis.2018, 77(4), 549-555; and Picceli, V. F. et al, Lupus, 2016, 25(4), 412-417); - bullous pemphigoid (Nelson, K. C. et al, J. Clin. Invest.2006, 116, 2892-2900); - hemodialysis (Ekdahl, K. N. et al, Immunol. Rev.2023, 313(1), 91-103); - coeliac disease (da Rosa Utiyama, S. R. et al, Int. J. Immunogenet.2005, 32, 307- 314); - burns (Wan, K. C. et al, Burns 1998, 24, 241-244); - hidradenitis suppurativa and pyoderma gangraenosum (Giamarellos-Bourboulis, E. J. et al, Br. J. Dermatol.2020, 183(1), 176-178); - rhabdomyolysis (Boudhabhay, I. et al, Kidney Int.2021, 99(3), 581-597); - nonalcoholic fatty liver disease (NAFLD) including nonalcoholic steatohepatitis (NASH) (Segers, F. M. et al, PLoS One 2014, 9(10), e110053; and Zhao et al, Front. Immunol.2022, 13, 1054159); - Gaucher disease (Pandey, M. K. et al, Nature, 2017, 543(7643), 108-112; and Serfecz, J. C. et al, Int. J. Mol. Sci.2021, 22(18), 9912); and - acquired partial lipodystrophy (Misra, A. et al, Medicine (Baltimore), 2004, 83(1), 18-31, and Sissons, J. G. et al, New England Journal of Medicine, 1976, 294(9), 461-465). Accordingly, any of the diseases, disorders or conditions listed above may be treated or prevented in accordance with the sixth, seventh, eighth, ninth, tenth or eleventh aspect of the present invention. Particular examples of diseases, disorders or conditions which may be responsive to Factor B inhibition and which may be treated or prevented in accordance with the sixth, seventh, eighth, ninth, tenth or eleventh aspect of the present invention include: (i) ocular diseases, disorders or conditions, such as age-related macular degeneration, retinal detachment, Doyne honeycomb retinal dystrophy (also known as malattia leventinese) (DHRD/ML), retinal ischemia reperfusion, non-infectious uveitis, and diabetic retinopathy and diabetic macular oedema; (ii) haematological diseases, disorders or conditions, such as cold agglutinin disease, paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome, transplant-associated thrombotic microangiopathy, vaso- occlusive crises in sickle cell disease, and delayed hemolytic transfusion reactions (DHTR) in individuals suffering from sickle cell disease; (iii) renal diseases, disorders or conditions, such as IgA nephropathy, primary membranous nephropathy, C3 glomerulopathy (C3G) including dense deposit disease and glomerulonephritis, immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN), thrombotic microangiopathy (TMA)-mediated acute kidney injury (AKI), malignant nephrosclerosis, glomerular sclerosis, atypical hemolytic uremic syndrome, focal segmental glomerulosclerosis (FSGS), postinfectious glomerulonephritis, renal allograft, and acute kidney injury; (iv) respiratory diseases, disorders or conditions, such as airway hyperresponsiveness with inflammation, idiopathic pulmonary fibrosis, and those associated with SARS-CoV-2; (v) central nervous system diseases, disorders or conditions, such as Alzheimer’s disease, multiple sclerosis, ischemic stroke, traumatic brain injury, spinal cord injury, amyotrophic lateral sclerosis, schizophrenia, and lupus cerebritis; (vi) cardiovascular diseases, disorders or conditions, such as heart failure, cardiac remodelling, aortic stenosis, cardiometabolic disease and cardiac ischemia and reperfusion; (vii) reproductive diseases, disorders or conditions, such as pre-eclampsia; (viii) metabolic diseases, disorders or conditions, such as complications of type 2 diabetes including diabetic retinopathy and diabetic kidney disease; (ix) cancers such as pancreatic cancer, photocarcinogenesis and cutaneous squamous cell carcinoma; (x) auto-immune diseases, disorders or conditions, such as cold agglutinin disease, ANCA associated vasculitis, systemic lupus erythematosus including lupus nephritis, myasthenia gravis, coeliac disease, neuromyelitis optica, Guillian-Barré syndrome and acquired thrombotic thrombocytopenic purpura (TTP); (xi) musculoskeletal diseases, disorders or conditions, such as rheumatoid arthritis and osteoarthritis; (xii) antiphospholipid syndrome; (xiii) skin diseases, disorders or conditions, such as bullous pemphigoid; (xiv) hemodialysis; and (xv) any disease where an individual has been determined to carry a germline or somatic non-silent mutation in Factor B. More typically, the disease, disorder or condition is selected from: (i) an ocular disease, disorder or condition; (ii) a haematological disease, disorder or condition; (iii) a renal disease, disorder or condition; (iv) a cancer; or (v) an auto-immune disease, disorder or condition. In one embodiment, the disease, disorder or condition is selected from: (i) acute kidney injury; (ii) age-related macular degeneration; (iii) airway hyperresponsiveness with inflammation; (iv) Alzheimer’s disease; (v) amyotrophic lateral sclerosis; (vi) ANCA vasculitis; (vii) antiphospholipid syndrome; (viii) aortic stenosis; (ix) atypical hemolytic uremic syndrome; (x) acquired partial lipodystrophy; (xi) acquired thrombotic thrombocytopenic purpura; (xii) bullous pemphigoid; (xiii) C3 glomerulopathy; (xiv) immune complex-mediated membranoproliferative glomerulonephritis (IC- MPGN) (xv) cardiac ischemia and reperfusion; (xvi) cardiac remodelling; (xvii) cardiometabolic disease; (xviii) coeliac disease; (xix) cold agglutinin disease; (xx) a respiratory condition caused by SARs Cov-2; (xxi) diabetic kidney disease; (xxii) diabetic retinopathy; (xxiii) Doyne honeycomb retinal dystrophy, also known as malattia leventinese (DHRD/ML); (xxiv) focal segmental glomerulosclerosis (FSGS); (xxv) glomerular sclerosis; (xxvi) Guillian-Barré syndrome; (xxvii) heart failure; (xxviii) hemodialysis; (xxix) idiopathic thrombocytopenic purpura (ITP); (xxx) idiopathic pulmonary fibrosis; (xxxi) IgA nephropathy; (xxxii) ischemic stroke; (xxxiii) systemic lupus erythematosus; (xxxiv) lupus nephritis (xxxv) lupus cerebritis; (xxxvi) malignant nephrosclerosis; (xxxvii) multiple sclerosis; (xxxviii) myasthenia gravis; (xxxix) neuromyelitis optica; (xl) non-infectious uveitis; (xli) osteoarthritis; (xlii) pancreatic cancer; (xliii) paroxysmal nocturnal hemoglobinuria (PNH); (xliv) photocarcinogenesis; (xlv) postinfectious glomerulonephritis; (xlvi) pre-eclampsia; (xlvii) membranous nephropathy; (xlviii) renal allograft; (xlix) retinal detachment; (l) retinal ischemia reperfusion; (li) rheumatoid arthritis; (lii) schizophrenia; (liii) a delayed hemolytic transfusion reaction (DHTR) in an individual suffering from sickle cell disease; (liv) a vaso-occlusive crisis in sickle cell disease; (lv) spinal cord injury; (lvi) squamous cell carcinoma; (lvii) thrombotic microangiopathy (TMA)-mediated acute kidney injury (AKI); (lviii) transplant-associated thrombotic microangiopathy; or (lix) traumatic brain injury. Examples of diseases, disorders or conditions which may be responsive to Factor B inhibition and which may be treated or prevented in accordance with sixth, seventh, eighth, ninth, tenth or eleventh aspect of the present invention are listed above. Moreover, some of the diseases, disorders or conditions mentioned above arise due to mutations in (i) Complement C3, (ii) Factor B, (iii) a direct or indirect regulator of Factor B, or (iv) an enzyme that directly or indirectly causes the production or activation of Factor B. Such mutations may give rise to an increase in alternative pathway activity which may be effectively treated by Factor B inhibition. As a result, such diseases, disorders or conditions may be particularly responsive to Factor B inhibition and may be particularly suitable for treatment or prevention in accordance with the sixth, seventh, eighth, ninth, tenth or eleventh aspect of the present invention. Examples of such diseases, disorders or conditions include atypical hemolytic uremic syndrome (aHUS), and age-related macular degeneration (AMD). A twelfth aspect of the invention provides a method of inhibiting Factor B, the method comprising the use of a compound of the first, second or third aspect of the invention, or a pharmaceutically acceptable salt, solvate or prodrug of the fourth aspect of the invention, or a pharmaceutical composition of the fifth aspect of the invention, to inhibit Factor B. In one embodiment of the twelfth aspect of the present invention, the method is performed ex vivo or in vitro, for example in order to analyse the effect on cells of Factor B inhibition. Typically, where the method is performed ex vivo or in vitro, the method is not a method of treatment of the human or animal body. In another embodiment of the twelfth aspect of the present invention, the method is performed in vivo. For example, the method may comprise the step of administering an effective amount of a compound of the first, second or third aspect, or a pharmaceutically acceptable salt, solvate or prodrug of the fourth aspect, or a pharmaceutical composition of the fifth aspect, to thereby inhibit Factor B. Typically, the administration is to a subject in need thereof. Alternately, the method of the twelfth aspect of the invention may be a method of inhibiting Factor B in a non-human animal subject, the method comprising the steps of administering the compound, salt, solvate, prodrug or pharmaceutical composition to the non-human animal subject and optionally subsequently mutilating or sacrificing the non-human animal subject. Typically, such a method further comprises the step of analysing one or more tissue or fluid samples from the optionally mutilated or sacrificed non-human animal subject. A thirteen aspect of the invention provides a compound of the first, second or third aspect of the invention, or a pharmaceutically acceptable salt, solvate or prodrug of the fourth aspect of the invention, or a pharmaceutical composition of the fifth aspect, for use in the inhibition of Factor B. Typically, the use comprises the administration of the compound, salt, solvate, prodrug or pharmaceutical composition to a subject. A fourteenth aspect of the invention provides the use of a compound of the first, second or third aspect of the invention, or a pharmaceutically acceptable salt, solvate or prodrug of the fourth aspect of the invention, in the manufacture of a medicament for the inhibition of Factor B. Typically, the inhibition comprises the administration of the compound, salt, solvate, prodrug or medicament to a subject. Unless stated otherwise, in any of the sixth to fourteenth 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 or prodrugs 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 or prodrugs of the present invention will generally be provided in a sterile aqueous solution or suspension, buffered to an appropriate pH and isotonicity. Suitable aqueous vehicles include Ringer’s solution and isotonic sodium chloride or glucose. Aqueous suspensions according to the invention may include suspending agents such as cellulose derivatives, sodium alginate, polyvinylpyrrolidone and gum tragacanth, and a wetting agent such as lecithin. Suitable preservatives for aqueous suspensions include ethyl and n-propyl p-hydroxybenzoate. The compounds of the invention may also be presented as liposome formulations. For ocular administration, the compounds, salts, solvates or prodrugs of the invention will generally be provided in a form suitable for topical administration, e.g. as eye drops. Suitable forms may include ophthalmic solutions, gel-forming solutions, sterile powders for reconstitution, ophthalmic suspensions, ophthalmic ointments, ophthalmic emulsions, ophthalmic gels and ocular inserts. Alternatively, the compounds, salts, solvates or prodrugs of the invention may be provided in a form suitable for 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 or prodrugs of the invention will generally be provided in the form of ointments, cataplasms (poultices), pastes, powders, dressings, creams, plasters or patches. Suitable suspensions and solutions can be used in inhalers for airway (aerosol) administration. The dose of the compounds, salts, solvates or prodrugs of the present invention will, of course, vary with the disease, disorder or condition to be treated or prevented. In general, a suitable dose will be in the range of 0.01 to 500 mg per kilogram body weight of the recipient per day. The desired dose may be presented at an appropriate interval such as once every other day, once a day, twice a day, three times a day or four times a day. The desired dose may be administered in unit dosage form, for example, containing 1 mg to 50 g of active ingredient per unit dosage form. A fifteenth aspect of the invention provides a method of synthesising a compound according to the first aspect of the invention, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, the method comprising the steps of: (i) reacting a compound of Formula (SM-1) with a compound of Formula (SM-2) to produce an intermediate of Formula (It-1):
Figure imgf000128_0001
and (ii) deprotecting the intermediate of Formula (It-1) to produce a compound of Formula (I), or a pharmaceutically acceptable salt and/or solvate thereof:
Figure imgf000128_0002
wherein: RP is a nitrogen protecting group; RL is a leaving group; and R1 to R8, R18 to R21, and X10 to X13 are as defined in accordance with the first aspect of the invention. A sixteenth aspect of the invention provides a method of synthesising a compound according to the second aspect of the invention, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, the method comprising the steps of: (i) reacting a compound of Formula (SM-3) with a compound of Formula (SM-2) to produce an intermediate of Formula (It-2):
Figure imgf000129_0001
and (ii) deprotecting the intermediate of Formula (It-2) to produce a compound of Formula (II), or a pharmaceutically acceptable salt and/or solvate thereof:
Figure imgf000129_0002
wherein: RP is a nitrogen protecting group; RL is a leaving group; and R1, R4 to R8, R14 to R21, and X10 to X13 are as defined in accordance with the second aspect of the invention. As stated in accordance with the fifteenth and sixteenth aspects of the invention, RP is a nitrogen protecting group. Suitable nitrogen protecting groups may be identified by reference to e.g. Wuts, “Greene’s Protective Groups in Organic Synthesis”, 5th Ed., 2014. In one embodiment of the fifteenth or sixteenth aspect of the invention, RP is a nitrogen protecting group that is stable under basic conditions. Typically, RP is also stable under weak nucleophilic conditions. For example, RP may be selected from the group consisting of benzyloxycarbonyl (CBz), 4-methoxy-benzyloxycarbonyl, benzyl, t- butoxycarbonyl (Boc), 2-(4-biphenylyl)-isopropoxycarbonyl (Bpoc), triphenylmethyl (Trt) and 2,2,2-trichloroethoxycarbonyl (Troc) protecting groups. Alternatively, RP may be a sulphonyl group, such as a such as a toluenesulphonyl (tosyl or -Ts), methanesulfonyl (mesyl or -Ms), or trifluoromethanesulfonyl (triflyl or -Tf) group. In one embodiment of the fifteenth or sixteenth aspect of the invention, RP is a t- butoxycarbonyl (Boc) or toluenesulphonyl (tosyl or -Ts) group. As stated, RL is a leaving group. In one embodiment of the fifteenth or sixteenth aspect of the invention, RL is selected from Cl, Br, I, or a sulfonate leaving group such as a toluenesulfonate (tosylate or -OTs), methanesulfonate (mesylate or -OMs), or trifluoromethanesulfonate (triflate or -OTf) leaving group, or an activated hydroxyl leaving group such as a protonated hydroxyl group, a Vilsmeier reagent (N- (Chloromethylene)-N-methylmethanaminium chloride) activated hydroxyl group, or a phosphonium activated hydroxyl group (e.g. generated from Ph3P and di-tert-butyl diazene-1,2-dicarboxylate). Typically, RL is selected from Cl, Br or I or a Vilsmeier reagent activated hydroxyl group. More typically, RL is selected from Cl or a Vilsmeier reagent activated hydroxyl group. Most typically RL is Cl. Typically, unless RL is a protonated hydroxyl group or a phosphonium activated hydroxyl group, the reaction of step (i) of the fifteenth or sixteenth aspect of the invention occurs in the presence of a base, such as potassium carbonate, sodium bicarbonate, TEA, DIPEA, NaH or DBU, optionally in the presence of a phase transfer reagent such as TBAI. Typically, the reaction of step (i) of the fifteenth or sixteenth aspect of the invention occurs in the presence of a dipolar aprotic solvent, such as dimethyl sulfoxide, N,N- dimethylformamide, N,N′-dimethylpropyleneurea, tetrahydrofuran, 1,4-dioxane, acetonitrile, dichloromethane, or N-methyl pyrrolidone. More typically, the solvent is N,N-dimethylformamide, tetrahydrofuran, acetonitrile, dichloromethane or N-methyl pyrrolidone. More typically, the solvent is tetrahydrofuran or acetonitrile. The deprotection of step (ii) of the fifteenth or sixteenth aspect of the invention may occur simultaneously with the reaction of step (i), e.g. via a ‘one-pot’ method, or may occur sequentially. As will be appreciated, the deprotection conditions will be appropriate to the type of nitrogen protecting group RP used. For example, where RP is a t-butoxycarbonyl (Boc) group, deprotection may be effected by treatment of the intermediate of Formula (It-1) or (It-2) with: (i) TMS-OTf and 2,6-lutidine, or TMS-OTf and TEA, in a dipolar aprotic solvent, such as dichloromethane; or (ii) a lewis acid, such as AlCl3, in a dipolar aprotic solvent, such as dichloromethane; or (iii) a polar protic acid such as HCl, HBr or TFA, in a polar protic solvent such as water and/or methanol. Similarly, where RP is a toluenesulphonyl (tosyl or -Ts) group, deprotection may be effected by treatment of the intermediate of Formula (It-1) or (It-2) with TBAF in a dipolar aprotic solvent, such as tetrahydrofuran. Optionally, the method of the fifteenth aspect of the invention further comprises the step of (iii) converting the compound of Formula (I) into a different compound of Formula (I), or a pharmaceutically acceptable salt and/or solvate thereof. Alternately or in addition, the method of the fifteenth aspect of the invention may further comprise the step (ia) of converting the compound of Formula (It-1) into a different compound of Formula (It-1), or a pharmaceutically acceptable salt and/or solvate thereof, prior to the deprotection step (ii). Optionally, the method of the sixteenth aspect of the invention further comprises the step of (iii) converting the compound of Formula (II) into a different compound of Formula (II), or a pharmaceutically acceptable salt and/or solvate thereof. Alternately or in addition, the method of the sixteenth aspect of the invention may further comprise the step (ia) of converting the compound of Formula (It-2) into a different compound of Formula (It-2), or a pharmaceutically acceptable salt and/or solvate thereof, prior to the deprotection step (ii). A seventeenth aspect of the invention provides a method of synthesising a compound according to the first aspect of the invention, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, the method comprising the step of: (i) performing a reductive amination on a compound of Formula (SM-4) with a compound of Formula (SM-2) to produce a compound of Formula (P-4) or a pharmaceutically acceptable salt and/or solvate thereof:
Figure imgf000132_0001
wherein: RX is selected from hydrogen or RP; RP is a nitrogen protecting group; and R2 to R7, R18 to R21, and X10 to X13 are as defined in accordance with the first aspect of the invention. As will be understood, where RX is hydrogen, the compound of Formula (P-4) is a compound of Formula (I) of the first aspect of the invention, wherein R8 is hydrogen. An eighteenth aspect of the invention provides a method of synthesising a compound according to the second aspect of the invention, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, the method comprising the step of: (i) performing a reductive amination on a compound of Formula (SM-5) with a compound of Formula (SM-2) to produce a compound of Formula (P-5) or a pharmaceutically acceptable salt and/or solvate thereof:
Figure imgf000133_0001
wherein: RX is selected from hydrogen or RP; RP is a nitrogen protecting group; and R4 to R7, R14 to R21, and X10 to X13 are as defined in accordance with the second aspect of the invention. As will be understood, where RX is hydrogen, the compound of Formula (P-5) is a compound of Formula (II) of the second aspect of the invention, wherein R8 is hydrogen. In one embodiment of the seventeenth or eighteenth aspect of the invention, R7 is hydrogen. In one embodiment of the seventeenth or eighteenth aspect of the invention, RX is RP. Typically, RP is a nitrogen protecting group that is stable under basic conditions. Typically, RP is also stable under weak nucleophilic conditions. For example, RP may be selected from the group consisting of benzyloxycarbonyl (CBz), 4-methoxy- benzyloxycarbonyl, benzyl, t-butoxycarbonyl (Boc), 2-(4-biphenylyl)- isopropoxycarbonyl (Bpoc), triphenylmethyl (Trt) and 2,2,2-trichloroethoxycarbonyl (Troc) protecting groups. In one embodiment of the seventeenth or eighteenth aspect of the invention, RP is a t- butoxycarbonyl (Boc) group. Typically, the reaction of step (i) of the seventeenth or eighteenth aspect of the invention occurs in the presence of a hydride donor, more typically in the presence of a borohydride such as NaHB(OAc)3, NaCNBH3 or NaBH4. Most typically, the reaction of step (i) of the seventeenth or eighteenth aspect of the invention occurs in the presence of NaHB(OAc)3. Optionally, the reaction of step (i) of the seventeenth or eighteenth aspect of the invention occurs in the presence of an acid such as a carboxylic acid. Typically, the carboxylic acid is acetic acid. Alternatively, the reaction of step (i) of the seventeenth or eighteenth aspect of the invention may occur in the presence of a base, such as TEA, DIPEA or DBU. Typically the base is a trialkylamine such as DIPEA. Typically, the reaction of step (i) of the seventeenth or eighteenth aspect of the invention occurs in the presence of a dipolar aprotic solvent, such as dimethyl sulfoxide, N,N-dimethylformamide, N,N′-dimethylpropyleneurea, tetrahydrofuran, 1,4- dioxane, acetonitrile, dichloromethane, or N-methyl pyrrolidone. More typically, the solvent is tetrahydrofuran or dichloromethane. Where RX is a nitrogen protecting group, optionally the method of the seventeenth aspect of the invention further comprises the step of (ii) deprotecting the compound of Formula (P-4) to produce a compound of Formula (I), or a pharmaceutically acceptable salt and/or solvate thereof, wherein R8 is hydrogen. Similarly, where RX is a nitrogen protecting group, optionally the method of the eighteenth aspect of the invention further comprises the step of (ii) deprotecting the compound of Formula (P-5) to produce a compound of Formula (II), or a pharmaceutically acceptable salt and/or solvate thereof, wherein R8 is hydrogen. The deprotection of step (ii) of the seventeenth or eighteenth aspect of the invention may occur simultaneously with the reaction of step (i), e.g. via a ‘one-pot’ method, or may occur sequentially. As will be appreciated, the deprotection conditions will be appropriate to the type of nitrogen protecting group RP used. For example, where RP is a t-butoxycarbonyl (Boc) group, deprotection may be effected by treatment of the protected compound of Formula (P-4) or (P-5) with TMS-OTf and 2,6-lutidine in a dipolar aprotic solvent, such as dichloromethane. Optionally, the method of the seventeenth aspect of the invention further comprises the step of converting the compound of Formula (I), wherein R8 is hydrogen, into a different compound of Formula (I), or a pharmaceutically acceptable salt and/or solvate thereof. Alternately or in addition, the method of the seventeenth aspect of the invention may further comprise the step of converting the compound of Formula (P-4), wherein RX is a nitrogen protecting group, into a different compound of Formula (P-4), or a pharmaceutically acceptable salt and/or solvate thereof, wherein RX is a nitrogen protecting group, prior to the step of deprotecting the compound of Formula (P-4). Optionally, the method of the eighteenth aspect of the invention further comprises the step of converting the compound of Formula (II), wherein R8 is hydrogen, into a different compound of Formula (II), or a pharmaceutically acceptable salt and/or solvate thereof. Alternately or in addition, the method of the eighteenth aspect of the invention may further comprise the step of converting the compound of Formula (P-5), wherein RX is a nitrogen protecting group, into a different compound of Formula (P-5), or a pharmaceutically acceptable salt and/or solvate thereof, wherein RX is a nitrogen protecting group, prior to the step of deprotecting the compound of Formula (P-5). A nineteenth aspect of the invention provides a method of synthesising a compound according to the first aspect of the invention, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, the method comprising the step of: (i) reacting a compound of Formula (SM-6) with a compound of Formula (SM-2) to produce a compound of Formula (P-6) or a pharmaceutically acceptable salt and/or solvate thereof: wherein: RX is selected from hydrogen or RP; RP is a nitrogen protecting group; R76 is selected from hydrogen or a fluoro 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 wherein the saturated hydrocarbyl group may optionally include a single heteroatom selected from N and O in its carbon skeleton; R77 is selected from hydrogen, -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 wherein the saturated hydrocarbyl group may optionally include a single heteroatom selected from N and O in its carbon skeleton; and R2 to R6, R8, R18 to R21, and X10 to X13 are as defined in accordance with the first aspect of the invention. As will be understood, where RX is hydrogen, the compound of Formula (P-6) is a compound of Formula (I) of the first aspect of the invention, wherein R7 is -CH(R76)-COR77. A twentieth aspect of the invention provides a method of synthesising a compound according to the second aspect of the invention, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, the method comprising the step of: (i) reacting a compound of Formula (SM-7) with a compound of Formula (SM-2) to produce a compound of Formula (P-7) or a pharmaceutically acceptable salt and/or solvate thereof:
Figure imgf000137_0001
Formula (SM-7) Formula (P-7) wherein: RX is selected from hydrogen or RP; RP is a nitrogen protecting group; R76 is selected from 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 wherein the saturated hydrocarbyl group may optionally include a single heteroatom selected from N and O in its carbon skeleton; R77 is selected from hydrogen, -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 wherein the saturated hydrocarbyl group may optionally include a single heteroatom selected from N and O in its carbon skeleton; and R4 to R6, R8, R14 to R21, and X10 to X13 are as defined in accordance with the second aspect of the invention. As will be understood, where RX is hydrogen, the compound of Formula (P-7) is a compound of Formula (II) of the second aspect of the invention, wherein R7 is -CH(R76)-COR77. Typically in accordance with the nineteenth and twentieth aspects of the invention, the group -CH(R76)-COR77 contains no more than 8 carbon atoms. In one embodiment of the nineteenth or twentieth aspect of the invention, R76 is selected from hydrogen or a methyl or fluoromethyl group. Typically in such an embodiment, R76 is hydrogen. In one embodiment of the nineteenth or twentieth aspect of the invention, R77 is a -OR79 group, wherein R79 is a C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group. Typically in such an embodiment, R77 is -OEt. Typically in accordance with the nineteenth and twentieth aspects of the invention, R8 is hydrogen. In the compounds of Formula (SM-6) and (SM-7), the carbon-carbon double bond in the -C(R8)=C(R76)-COR77 group may be configured such that R76 and R8 are located cis- or trans- across the double bond. Typically, the carbon-carbon double bond is configured such that R76 and R8 are located trans- across the double bond. In one embodiment of the nineteenth or twentieth aspect of the invention, RX is RP. Typically, RP is a nitrogen protecting group that is stable under basic conditions. Typically, RP is also stable under weak nucleophilic conditions. For example, RP may be selected from the group consisting of benzyloxycarbonyl (CBz), 4-methoxy- benzyloxycarbonyl, benzyl, t-butoxycarbonyl (Boc), 2-(4-biphenylyl)- isopropoxycarbonyl (Bpoc), triphenylmethyl (Trt) and 2,2,2-trichloroethoxycarbonyl (Troc) protecting groups. Alternatively, RP may be a sulphonyl group, such as a such as a toluenesulphonyl (tosyl or -Ts), methanesulfonyl (mesyl or -Ms), or trifluoromethanesulfonyl (triflyl or -Tf) group. In one embodiment of the nineteenth or twentieth aspect of the invention, RP is a toluenesulphonyl (tosyl or -Ts) group. Typically, the reaction of step (i) of the nineteenth or twentieth aspect of the invention occurs in the presence of a base. Typically, the base is a lithium amide base such as lithium diisopropylamide (LDA), lithium 2,2,6,6-tetramethylpiperidide (Li-TMP) or lithium hexamethyldisilazide (LiHMDS). Most typically, the base is LDA. Typically, the reaction of step (i) of the nineteenth or twentieth aspect of the invention occurs in the presence of a dipolar aprotic solvent, such as dimethyl sulfoxide, N,N- dimethylformamide, N,N′-dimethylpropyleneurea, tetrahydrofuran, 1,4-dioxane, acetonitrile, dichloromethane, or N-methyl pyrrolidone. More typically, the solvent is tetrahydrofuran. Where RX is a nitrogen protecting group, optionally the method of the nineteenth aspect of the invention further comprises the step of (ii) deprotecting the compound of Formula (P-6) to produce a compound of Formula (I), or a pharmaceutically acceptable salt and/or solvate thereof, wherein R7 is -CH(R76)-COR77. Similarly, where RX is a nitrogen protecting group, optionally the method of the twentieth aspect of the invention further comprises the step of (ii) deprotecting the compound of Formula (P-7) to produce a compound of Formula (II), or a pharmaceutically acceptable salt and/or solvate thereof, wherein R7 is -CH(R76)-COR77. The deprotection of step (ii) of the nineteenth or twentieth aspect of the invention may occur simultaneously with the reaction of step (i), e.g. via a ‘one-pot’ method, or may occur sequentially. As will be appreciated, the deprotection conditions will be appropriate to the type of nitrogen protecting group RP used. For example, where RP is a toluenesulphonyl (tosyl or -Ts) group, deprotection may be effected by treatment of the compound of Formula (P-6) or (P-7) with TBAF in a dipolar aprotic solvent, such as tetrahydrofuran. Optionally, the method of the nineteenth aspect of the invention further comprises the step of converting the compound of Formula (I), wherein R7 is -CH(R76)-COR77, into a different compound of Formula (I), or a pharmaceutically acceptable salt and/or solvate thereof. Alternately or in addition, the method of the nineteenth aspect of the invention may further comprise the step of converting the compound of Formula (P-6), wherein RX is a nitrogen protecting group, into a different compound of Formula (P-6), or a pharmaceutically acceptable salt and/or solvate thereof, wherein RX is a nitrogen protecting group, prior to the step of deprotecting the compound of Formula (P-6). Optionally, the method of the twentieth aspect of the invention further comprises the step of converting the compound of Formula (II), wherein R7 is -CH(R76)-COR77, into a different compound of Formula (II), or a pharmaceutically acceptable salt and/or solvate thereof. Alternately or in addition, the method of the twentieth aspect of the invention may further comprise the step of converting the compound of Formula (P-7), wherein RX is a nitrogen protecting group, into a different compound of Formula (P-7), or a pharmaceutically acceptable salt and/or solvate thereof, wherein RX is a nitrogen protecting group, prior to the step of deprotecting the compound of Formula (P-7). A twenty-first aspect of the invention provides a method of synthesising a compound according to the second aspect of the invention, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, the method comprising the step of: (i) reducing a compound of Formula (SM-8) to provide a compound of Formula (P-8), or a pharmaceutically acceptable salt and/or solvate thereof:
Figure imgf000140_0001
wherein: RX is selected from hydrogen or RP; RP is a nitrogen protecting group; R2 to R8, R14 to R21 and X10 to X13 are as defined in accordance with the first and/or second aspect of the invention. As will be understood, where RX is hydrogen, the compound of Formula (SM-8) is a compound of Formula (I) of the first aspect of the invention, and the compound of Formula (P-8) is a compound of Formula (II) of the second aspect of the invention Typically in accordance with the twenty-first aspect of the invention, at least one of R14 and R15 is hydrogen, and at least one of R16 and R17 is hydrogen. In one embodiment of the twenty-first aspect of the invention, RX is RP. Typically, RP is a nitrogen protecting group that is stable under basic conditions. Typically, RP is also stable under weak nucleophilic conditions. For example, RP may be selected from the group consisting of benzyloxycarbonyl (CBz), 4-methoxy-benzyloxycarbonyl, benzyl, t- butoxycarbonyl (Boc), 2-(4-biphenylyl)-isopropoxycarbonyl (Bpoc), triphenylmethyl (Trt) and 2,2,2-trichloroethoxycarbonyl (Troc) protecting groups. In one embodiment of the twenty-first aspect of the invention, RP is a t-butoxycarbonyl (Boc) group. In one embodiment of the twenty-first aspect of the invention, the reduction of step (i) is performed using a hydride donor (such as NaBH3CN, BH3 or Et3SiH), optionally in the presence of an acid (such as acetic acid or trifluoroacetic acid). Typically, the reduction of step (i) of the twenty-first aspect of the invention occurs in the presence of a dipolar aprotic solvent, such as dimethyl sulfoxide, N,N- dimethylformamide, N,N′-dimethylpropyleneurea, tetrahydrofuran, 1,4-dioxane, acetonitrile, dichloromethane, or N-methyl pyrrolidone. Where RX is a nitrogen protecting group, optionally the method of the twenty-first aspect of the invention further comprises the step of (ii) deprotecting the compound of Formula (P-8) to produce a compound of Formula (II), or a pharmaceutically acceptable salt and/or solvate thereof. The deprotection of step (ii) may occur simultaneously with the reaction of step (i), e.g. via a ‘one-pot’ method, or may occur sequentially. As will be appreciated, the deprotection conditions will be appropriate to the type of nitrogen protecting group RP used. For example, where RP is a t-butoxycarbonyl (Boc) group, deprotection may be effected by treatment of the protected compound of Formula (P-8) with TMS-OTf and 2,6-lutidine in a dipolar aprotic solvent, such as dichloromethane. Optionally, the method of the twenty-first aspect of the invention further comprises the step of converting the compound of Formula (II) into a different compound of Formula (II), or a pharmaceutically acceptable salt and/or solvate thereof. Alternately or in addition, the method of the twenty-first aspect of the invention may further comprise the step of converting the compound of Formula (P-8), wherein RX is a nitrogen protecting group, into a different compound of Formula (P-8), or a pharmaceutically acceptable salt and/or solvate thereof, wherein RX is a nitrogen protecting group, prior to the step of deprotecting the compound of Formula (P-8). A twenty-second aspect of the invention provides a method of synthesising a compound according to the first aspect of the invention, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, the method comprising the step of: (i) reacting a compound of Formula (SM-9) with a compound of Formula (SM-10) to produce a compound of Formula (P-9) or a pharmaceutically acceptable salt and/or solvate thereof:
Figure imgf000142_0001
wherein: RX is selected from hydrogen or RP; RP is a nitrogen protecting group; RL1 is a leaving group; RL2 is a leaving group; and R2 to R8, R20, R21, and X10 to X13 are as defined in accordance with the first aspect of the invention. As will be understood, where RX is hydrogen, the compound of Formula (P-9) is a compound of Formula (I) of the first aspect of the invention, wherein R18 and R19 together with the carbon atom to which they are attached form a C=O group. A twenty-third aspect of the invention provides a method of synthesising a compound according to the second aspect of the invention, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, the method comprising the step of: (i) reacting a compound of Formula (SM-11) with a compound of Formula (SM-10) to produce a compound of Formula (P-10) or a pharmaceutically acceptable salt and/or solvate thereof:
Figure imgf000143_0001
wherein: RX is selected from hydrogen or RP; RP is a nitrogen protecting group; RL1 is a leaving group; RL2 is a leaving group; and R4 to R8, R14 to R17, R20, R21, and X10 to X13 are as defined in accordance with the second aspect of the invention. As will be understood, where RX is hydrogen, the compound of Formula (P-10) is a compound of Formula (II) of the second aspect of the invention, wherein R18 and R19 together with the carbon atom to which they are attached form a C=O group. In one embodiment of the twenty-second or twenty-third aspect of the invention, RX is RP. Typically, RP is a nitrogen protecting group that is stable under basic conditions. Typically, RP is also stable under weak nucleophilic conditions. For example, RP may be selected from the group consisting of benzyloxycarbonyl (CBz), 4-methoxy- benzyloxycarbonyl, benzyl, t-butoxycarbonyl (Boc), 2-(4-biphenylyl)- isopropoxycarbonyl (Bpoc), triphenylmethyl (Trt) and 2,2,2-trichloroethoxycarbonyl (Troc) protecting groups. In one embodiment of the twenty-second or twenty-third aspect of the invention, RP is a t-butoxycarbonyl (Boc) group. As stated, RL1 is a leaving group. In one embodiment of the twenty-second or twenty- third aspect of the invention, RL1 is selected from Cl, Br, I, or an alkoxy leaving group such as a C1-C4 alkoxyl group. Typically, RL1 is an alkoxy leaving group. More typically, RL1 is a methoxy group. As stated, RL2 is a leaving group. In one embodiment of the twenty-second or twenty- third aspect of the invention, RL2 is selected from Cl, Br, I, or a sulfonate leaving group such as a toluenesulfonate (tosylate or -OTs), methanesulfonate (mesylate or -OMs), or trifluoromethanesulfonate (triflate or -OTf) leaving group. Typically, RL is selected from Cl, Br or I. More typically, RL is Br. Typically, the reaction of step (i) of the twenty-second or twenty-third aspect of the invention occurs in the presence of a base, such as TEA, DIPEA or DBU. Typically the base is a trialkylamine such as TEA. Typically, the reaction of step (i) of the twenty-second or twenty-third aspect of the invention occurs in the presence of a dipolar aprotic solvent, such as dimethyl sulfoxide, N,N-dimethylformamide, N,N′-dimethylpropyleneurea, tetrahydrofuran, 1,4- dioxane, acetonitrile, dichloromethane, or N-methyl pyrrolidone. More typically, the solvent is acetonitrile. Where RX is RP, optionally the method of the twenty-second aspect of the invention further comprises the step of (ii) deprotecting the compound of Formula (P-9) to produce a compound of Formula (I), or a pharmaceutically acceptable salt and/or solvate thereof, wherein R18 and R19 together with the carbon atom to which they are attached form a C=O group. Similarly, where RX is RP, optionally the method of the twenty-third aspect of the invention further comprises the step of (ii) deprotecting the compound of Formula (P-10) to produce a compound of Formula (II), or a pharmaceutically acceptable salt and/or solvate thereof, wherein R18 and R19 together with the carbon atom to which they are attached form a C=O group. The deprotection of step (ii) of the twenty-second or twenty-third aspect of the invention may occur simultaneously with the reaction of step (i), e.g. via a ‘one-pot’ method, or may occur sequentially. As will be appreciated, the deprotection conditions will be appropriate to the type of nitrogen protecting group RP used. For example, where RP is a t-butoxycarbonyl (Boc) group, deprotection may be effected by treatment of the protected compound of Formula (P-9) or (P-10) with a lewis acid such as AlCl3 in a dipolar aprotic solvent, such as dichloromethane. Optionally, the method of the twenty-second aspect of the invention further comprises the step of converting the compound of Formula (I), wherein R18 and R19 together with the carbon atom to which they are attached form a C=O group, into a different compound of Formula (I), or a pharmaceutically acceptable salt and/or solvate thereof. Alternately or in addition, the method of the twenty-second aspect of the invention may further comprise the step of converting the compound of Formula (P-9), wherein RX is a nitrogen protecting group, into a different compound of Formula (P-9), or a pharmaceutically acceptable salt and/or solvate thereof, wherein RX is a nitrogen protecting group, prior to the step of deprotecting the compound of Formula (P-9). Optionally, the method of the twenty-third aspect of the invention further comprises the step of converting the compound of Formula (II), wherein R18 and R19 together with the carbon atom to which they are attached form a C=O group, into a different compound of Formula (II), or a pharmaceutically acceptable salt and/or solvate thereof. Alternately or in addition, the method of the twenty-third aspect of the invention may further comprise the step of converting the compound of Formula (P-10), wherein RX is a nitrogen protecting group, into a different compound of Formula (P-10), or a pharmaceutically acceptable salt and/or solvate thereof, wherein RX is a nitrogen protecting group, prior to the step of deprotecting the compound of Formula (P-10). 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. Examples - Compound Synthesis All solvents, reagents and compounds were purchased and used without further purification unless stated otherwise. Experimental Methods Room temperature (rt) refers to approximately 20-27°C.1H NMR spectra were typically recorded at 400 or 500 MHz at room temperature unless otherwise specified. Chemical shift values are expressed in parts per million (ppm), i.e. (δ)-values, and were referenced relative to the solvent resonance. Standard abbreviations, or their combinations, are used for the multiplicity of the NMR signals, for example: s=singlet, br=broad, d=doublet, t=triplet, q=quartet, quin=quintet or p=pentet, h=heptet, dd=doublet of doublets, dt=doublet of triplets, m=multiplet. Coupling constants are listed as J values, measured in Hz. LCMS data are given in the format: retention time (in minutes), mass ion, electrospray mode (positive or negative). Chromatography refers to column chromatography performed using silica or C18 silica and executed under positive pressure (flash chromatography) conditions. LCMS Methods Instruments: Waters H-Class with Binary Solvent Pump, Sample Manager with Flow- Through Needle, CMA Column Manager, Photodiode array detector, QDa mass detector (methods A1, A3, B3) or Agilent 1260 with Binary Pump, HiP Sampler, Column Compartment, diodearray detector, G6150 mass selective detector (methods C1, C3); or Shimadzu MS2020 Nexera Series; Shimadzu MS2020 N-Series; or Agilent 1290 Infinity II Series (methods H, I). Methods A1, A3: Column: Waters ACQUITY UPLC CSH C18, 2.1 x 30 mm, 1.7 µm, at 40 °C; Solvents: A: 0.1% HCO2H in water, B: MeCN; Gradient [time (min)/solvent B in A (%)]: 0.00/2, 0.65/100, 1.00/100 (Method A1) or 0.00/2, 2.50/100, 3.00/100 (Method A3); Flow rate: 1 mL/min (Method A1) or 0.77 mL/min (Method A3); Detection: UV at 210-400 nm, MS by electrospray ionisation. Method B3: Column: Waters ACQUITY UPLC BEH C18, 2.1 x 30 mm, 1.7 µm, at 40 °C; Solvents: A: 0.1% NH3 in water, B: MeCN; Gradient [time (min)/solvent B in A (%)]: 0.00/2, 2.50/100, 3.00/100; Flow rate: 0.77 mL/min; Detection: UV at 210-400 nm, MS by electrospray ionisation. Methods C1, C3: Column: Waters Cortecs C18, 30 x 2.1 mm, 2.7 μm, at 40 °C; Solvents: A: 0.1% HCO2H in water, B: MeCN; Gradient [time (min)/solvent B in A (%)]: 0.00/2, 0.65/100, 1.00/100 (Method C1) or 0.00/2, 2.50/100, 3.00/100 (Method C3); Flow rate: 1 mL/min (Method C1) or 1.35 mL/min (Method C3); Detection: UV at 260 nm +/- 90 nm, MS by electrospray ionisation. Methods D3: Column: Phenomenex Evo C18, 2.1 x 30 mm, 2.6 μm, at 40 °C; Solvents: A: 0.1% NH3 in water, B: MeCN; Gradient [time (min)/solvent B in A (%)]: 0.00/2, 2.50/100, 3.00/100; Flow rate: 1.35 mL/min; Detection: UV at 260 nm +/- 90 nm, MS by electrospray ionisation. Method H: Column: Agilent Zorbax eclipse plus C18, 50 x 2.1 mm, 1.8 µm; Solvents: A: 0.1% formic acid in water, B: 0.05% formic acid in MeCN; Gradient [time(min)/solvent B in A (%)]:0.00/5, 0.25/5, 2.50/95, 3.50/95, 3.60/5, 4.00/5; Flow rate 0.8 mL/min; Detection: UV at 210-400 nm, MS by electrospray ionisation and atmospheric pressure chemical ionisation. Method I: Column: Phenomenex Kinetex EVO C18, 50 x 3.0 mm, 2.6 µm; Solvents: A: 5 mM NH4HCO3 in water, B: MeCN; Gradient [time(min)/solvent B in A (%)]: 0.01/5, 0.50/5, 8.00/100, 9.00/100, 9.10/5, 10.00/5; Column temperature 40°C; Flow rate 0.8 mL/min; Detection: UV at 210-400 nm, MS by electrospray ionisation and atmospheric pressure chemical ionisation. Preparative HPLC Methods Instruments: Waters 2767 Sample Manager, Waters 2545 Binary Gradient Module, Waters Systems Fluidics Organiser, Waters 515 ACD pump, Waters 515 Makeup pump, Waters 2998 Photodiode Array Detector, Waters QDa. Methods P1, P2, P3 and P4: Column: Waters XBridge BEH C18 ODB prep column, 30 mm x 100 mm, 5 µm; Solvents: A: 0.3% ammonia in water, B: MeCN; Gradient [time (min)/solvent B in A (%)]: 0.00/52.5, 0.50/52.5, 5.50/82.5, 5.60/100, 8.50/100 (Method P1); 0.00/35, 0.50/35, 15.50/65, 15.60/100, 17.50/100 (Method P2); 0.00/25, 0.50/25, 15.50/55, 15.60/100, 17.50/100 (Method P3); 0.00/45, 0.50/45, 10.50/75, 10.60/100, 12.50/100 (Method P4); 0.00/20, 0.50/20, 10.50/50, 10.60/100, 12.50/100 (Method P5); 0.00/27.5, 0.50/27.5, 10.50/57.5, 10.60/100, 12.50/100 (Method P6); Flow rate: 40 mL/min with an at-column dilution pump giving 2 mL/min MeOH over the entire method; Detection: UV across 210-400 nm with PDA, QDA and ELS detection; samples dissolved in DMSO and filtered before purification. Abbreviations AcOH acetic acid aq. aqueous Boc tert-butoxycarbonyl BrettPhos Pd G3 [(2-di-cyclohexylphosphino-3,6-dimethoxy-2′,4′,6′- triisopropyl-1,1′-biphenyl)-2-(2′-amino-1,1′- biphenyl)]palladium(II) methanesulfonate (CAS # 1470372-59-8) d day(s) DCM dichloromethane DIAD diisopropyl azodicarboxylate DIPEA N,N-diisopropylethylamine DMF N,N-dimethylformamide DMSO dimethylsulfoxide ELS evaporative light scattering EtOAc ethyl acetate EtOH ethanol FAC final assay concentration g gas h hour(s) LCMS liquid chromatography mass spectrometry LDA lithium diisopropylamide MTBE tert-butyl methyl ether MeCN acetonitrile MeOH methanol MHz megahertz min minute(s) MW molecular weight m/z mass-to-charge ratio NBS N-bromosuccinimide NCS N-chlorosuccinimide NMR nuclear magnetic resonance (spectroscopy) PDA photodiode array QDA quadrupole mass detector Rt retention time rt room temperature s second(s) SCX strong cation exchange STAB sodium triacetoxyborohydride TBAF tetra-n-butylammonium fluoride TEA triethylamine Tf triflyl, also called trifluoromethanesulfonyl THF tetrahydrofuran TMS trimethylsilyl TMS-OTf trimethylsilyl trifluoromethanesulfonate Ts tosyl, also called toluenesulfonyl Wt weight Synthesis of Intermediates Intermediate 1: (5-chloro-7-methyl-1-tosyl-1H-indol-4-yl)methanol The title compound (CAS # 1481633-49-1) may be synthesized by methods reported in the literature (see e.g. Adams, C. M. et al, WO 2015/009616 A1, page 79). Intermediate 2: 5-chloro-4-(chloromethyl)-7-methyl-1-tosyl-1H-indole
Figure imgf000150_0001
The title compound (CAS # 1644667-09-3) may be synthesized by methods reported in the literature (see e.g. Adams, C. et al, WO 2015/009616 A1, page 82). Intermediate 3: tert-butyl 4-(1-hydroxyethyl)-5-methoxy-7-methyl-1H-indole-1- carboxylate
Figure imgf000150_0002
The title compound (CAS # 2924563-90-4) may be synthesized by methods reported in the literature (see e.g. Zhu, H. Y. et al, WO 2023/072197 A1, pages 48-49). Intermediate 4: 5-cyclopropyl-7-methyl-1-tosyl-1H-indole-4-carbaldehyde
Figure imgf000150_0003
The title compound (CAS # 1481633-54-8) may be synthesized by methods reported in the literature (see e.g. Adams, C. M. et al, WO 2013/164802 A1, page 188). Intermediate 5: 5-methoxy-7-methyl-1-tosyl-1H-indole-4-carbaldehyde
Figure imgf000151_0001
Step 1: tert-butyl 4-formyl-5-methoxy-7-methyl-1H-indole-1-carboxylate (5.00 g, 17.3 mmol) was suspended in MeOH (40 mL) and aq. sodium hydroxide (2M, 17.3 mL, 34.6 mmol) was added. The reaction mixture was stirred at 60 °C for 2 h before concentration in vacuo and addition of EtOAc (150 mL) and water (100 mL). The phases were separated and the aqueous phase was extracted with EtOAc (50 mL). The combined organic phases were diluted with DCM to give a homogenous clear solution which was dried over Na2SO4, filtered and concentrated in vacuo. Purification by chromatography on silica gel (120 g cartridge, 0-100% EtOAc/isohexane) yielded 5- methoxy-7-methyl-1H-indole-4-carbaldehyde (2.85 g, 95 % pure by LCMS (Method B3), 14.3 mmol, 83 % yield) as a pale yellow solid; LCMS: Rt = 0.98 (Method B3); m/z 189.8 (M+H)+ (ES+); 1H NMR: (500 MHz, DMSO-d6) δ 11.38 (s, 1H), 10.53 (d, J=1.2 Hz, 1H), 7.50 (td, J=2.8, 1.3 Hz, 1H), 7.06 (dd, J=2.9, 1.8 Hz, 1H), 6.84 (s, 1H), 3.90 (s, 3H), 2.55 (d, J=1.0 Hz, 3H). Step 2: To a solution of 5-methoxy-7-methyl-1H-indole-4-carbaldehyde (2.80 g, 14.8 mmol) in DMF (60 mL) at 0 °C was added sodium hydride (888 mg, 60 % dispersion in mineral oil, 22.2 mmol) portion wise. The reaction was warmed to rt and stirred for 30 min. The reaction was cooled to 0 °C and 4-methylbenzenesulfonyl chloride (4.23 g, 22.2 mmol) in DMF (5 mL) was added drop-wise, and the reaction was stirred at rt for 14 h before the addition of water (40 mL) at 0 °C. After stirring for 30 min the resulting precipitate was collected by filtration, rinsed with water (200 mL), tert-butyl methyl ether (150 mL) and iso-hexane (150 mL), then dried in vacuo to yield 5-methoxy-7- methyl-1-tosyl-1H-indole-4-carbaldehyde (Intermediate 5, 3.52 g, 10.3 mmol, 66 % yield) as a pale white solid; LCMS: Rt = 0.66 (Method C1); m/z 344.2 (M+H)+ (ES+); 1H NMR: (500 MHz, DMSO-d6) δ 10.48 (s, 1H), 8.00 (d, J=3.8 Hz, 1H), 7.61 (d, J=6.6 Hz, 2H), 7.50 (d, J=3.8 Hz, 1H), 7.39 (d, J=6.6 Hz, 2H), 7.00 (s, 1H), 3.90 (s, 3H), 2.58 (s, 3H), 2.34 (s, 3H). Intermediate 6: ethyl 3-(5-cyanoisoindolin-2-yl)-3-(5-methoxy-7-methyl-1-tosyl-1H- indol-4-yl)propanoate
Figure imgf000152_0001
Step 1: NaH (874 mg, 60% Wt dispersion in mineral oil, 21.8 mmol) was added to a solution of ethyl 2-(diethoxyphosphoryl)acetate (2.08 mL, 10.5 mmol) in dry THF (30 mL) under N2 at 0 °C. After stirring for 10 mins at 0 °C a solution of 5-methoxy-7- methyl-1-tosyl-1H-indole-4-carbaldehyde (Intermediate 5, 3.00 g, 8.74 mmol) in THF (2 mL) was added slowly and the reaction mixture was stirred at rt for 12 h before quenching with water (10 mL). EtOAc (100 mL) and water (100 mL) were added and the phases were separated. The organic phase was extracted with EtOAc (2 x 100 mL), the combined organic phases were dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by chromatography on silica gel (12 g cartridge, 0-50% EtOAc/isohexane) to yield ethyl (E)-3-(5-methoxy-7-methyl-1-tosyl-1H-indol-4- yl)acrylate (1.10 g, 76 % pure by LCMS (Method A3), 2.02 mmol, 23 % yield) as a pale yellow oil; LCMS: Rt = 2.05 (Method A3); m/z 414.2 (M+H)+ (ES+). Step 2: LDA (2M in THF, 2.43 mL, 4.86 mmol) was added dropwise to a stirred solution of isoindoline-5-carbonitrile hydrochloride (522 mg, 2.89 mmol) in dry THF (10 mL) under N2 at -70 °C and the reaction was stirred at -70 °C for 15 min. A solution of ethyl (E)-3-(5-methoxy-7-methyl-1-tosyl-1H-indol-4-yl)acrylate (1.10 g, 76 pure % by LCMS, 2.02 mmol) in THF (5 mL) was then added dropwise and the reaction was stirred at -70 °C for 1 h then at rt for 4 h. The reaction was quenched by the addition of saturated aqueous NH4Cl solution with cooling and the reaction mixture was further diluted with water (50 mL) and EtOAc (50 mL). The phases were separated and the aqueous phase was extracted with EtOAc (2 x 50 mL). The combined organic phases were dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by chromatography on silica gel (12 g cartridge, 0-100% EtOAc/isohexane) to yield ethyl 3-(5-cyanoisoindolin-2-yl)-3-(5-methoxy-7-methyl-1-tosyl-1H-indol-4- yl)propanoate (Intermediate 6, 160 mg, 73 pure % by LCMS (Method C3), 0.21 mmol, 11 % yield) as a pale brown gum; LCMS: Rt = 1.31 (Method C3); m/z 556.0 (M- H)- (ES-). Intermediate 7: 5-hydroxy-7-methyl-1-tosyl-1H-indole-4-carbaldehyde
Figure imgf000153_0001
Step 1: Sodium hydride (2.02 g, 60% dispersion in mineral oil, 50.5 mmol) was added to a stirred solution of 5-(benzyloxy)-7-methyl-1H-indole (10.0 g, 42.1 mmol) in DMF (100 mL) at 0 °C. The reaction mixture was stirred for 1 h before the addition of 4- methylbenzenesulfonyl chloride (10.4 g, 54.6 mmol). The reaction mixture was stirred at rt for 16 h, quenched with ice-cold water (500 mL), and extracted with ethyl acetate (3 x 100 mL). The combined organic phases were dried over Na2SO4 and concentrated in vacuo. Purification by chromatography on silica gel eluting with 0-50% EtOAc in hexanes yielded 5-(benzyloxy)-7-methyl-1-tosyl-1H-indole (10.0 g, 25.6 mmol, 61 % yield) as an off-white solid; LCMS: Rt = 2.76 (Method H); m/z 392.1 (M+H)+ (ES+). Step 2: A stirred solution of 5-(benzyloxy)-7-methyl-1-tosyl-1H-indole (10.0 g, 25.6 mmol) in EtOH (70 mL), EtOAc (30 mL) and THF (40 mL) was purged with nitrogen for 5 min, followed by the addition of 10% Pd on carbon (5.44 g, 5.11 mmol). The reaction mixture was stirred under an atmosphere of H2 gas for 24 h at rt. The reaction mixture was filtered through celite, washing the celite with EtOH (50 mL) and ethyl acetate (100 mL), and the combined filtrate was concentrated in vacuo. Purification by chromatography on silica gel eluting with 0-50% EtOAc in hexanes yielded 7-methyl-1- tosyl-1H-indol-5-ol (4.00 g, 13.3 mmol, 52 % yield) as a green solid; LCMS: Rt = 2.14 (Method H); m/z 302.1 (M+H)+ (ES+); 1H NMR: (400 MHz, DMSO-d6) δ 9.29 (s, 1H), 7.68 (d, J=3.6 Hz, 1H), 7.55 (d, J=8.4 Hz, 2H), 7.36 (d, J=8.0 Hz, 2H), 6.71 (t, J=7.2 Hz, 2H), 6.53 (s, 1H), 2.43 (s, 3H), 2.32 (s, 3H). Step 3: Et3N (4.05 mL, 29.1 mmol) was added dropwise to a stirred solution of magnesium chloride (2.37 g, 24.9 mmol) and paraformaldehyde (1.25 g, 41.6 mmol) in THF (25 mL) under N2 and the reaction mixture was then stirred at rt for 10 min.7- Methyl-1-tosyl-1H-indol-5-ol (2.50 g, 8.30 mmol) in THF (10 mL) was added and the reaction mixture was heated at 70 °C for 3 h. After cooling to 0 °C the reaction mixture was quenched with 2N HCl (10 mL), the pH was adjusted to 2, and the reaction mixture was stirred for 30 min. The resulting solid was isolated by filtration, dried in vacuo, and washed with MTBE (2 x 15 mL) to yield 5-hydroxy-7-methyl-1-tosyl-1H-indole-4- carbaldehyde (Intermediate 7, 1.70 g, 5.16 mmol, 62 % yield) as an off-white solid; LCMS: Rt = 4.77 (Method I); m/z 330.1 (M+H)+ (ES+); 1H NMR: (400 MHz, DMSO- d6) δ 10.75 (s, 1H), 10.43 (s, 1H), 7.95 (d, J=3.6 Hz, 1H), 7.61-7.59 (m, 2H), 7.47 (d, J=4.0 Hz, 1H), 7.39 (d, J=8.0 Hz, 2H), 6.70 (s, 1H), 2.49 (s, 3H), 2.34 (s, 3H). Intermediate 8: 5-(difluoromethoxy)-7-methyl-1H-indole-4-carbaldehyde
Figure imgf000154_0001
Step 1: KOH (1.15 g, 20.5 mmol) was added to a solution of 5-hydroxy-7-methyl-1-tosyl- 1H-indole-4-carbaldehyde (Intermediate 7, 450 mg, 1.37 mmol) in MeCN (1 mL) and water (1 mL) at 0 °C. The reaction was stirred for approximately 3 min until all the base had dissolved and then diethyl (bromodifluoromethyl)phosphonate (485 μL, 2.73 mmol) was added. The reaction mixture was allowed to warm to rt and stirred at rt for 1 h before the addition of 1M aq. HCl (10 mL) and EtOAc (30 mL) and separation of the phases. The aqueous layer was extracted with EtOAc (2 x 15 mL), the combined organic phases were dried over MgSO4, filtered, and concentrated in vacuo. Purification by chromatography on silica gel eluting with 0-100% EtOAc/isohexane yielded 5- (difluoromethoxy)-7-methyl-1-tosyl-1H-indole-4-carbaldehyde (142 mg, 0.37 mmol, 27 % yield) as a colourless oil; LCMS: Rt = 0.73 (Method C1); m/z 380.2 (M+H)+ (ES+); 1H NMR: (500 MHz, DMSO-d6) δ 10.40 (s, 1H), 8.16 (d, J=3.8 Hz, 1H), 7.68 (d, J=1.8 Hz, 1H), 7.67 (d, J=1.9 Hz, 1H), 7.57 (d, J=3.8 Hz, 1H), 7.44 (s, 1H), 7.42 (s, 1H), 7.31 (t, J=73.7 Hz, 1H), 7.13 (s, 1H), 2.57 (s, 3H), 2.36 (s, 3H). Step 2: Tetrabutylammonium fluoride (1M in THF, 1.00 mL, 1.00 mmol) was added to a solution of 5-(difluoromethoxy)-7-methyl-1-tosyl-1H-indole-4-carbaldehyde (80.0 mg, 0.21 mmol) in THF (1 mL) and the reaction mixture was heated at 65 °C for 90 min. After cooling to rt EtOAc (25 mL) was added and the organic phase was washed with water, saturated sodium bicarbonate, and brine (15 mL of each). The organic phase was dried over Na2SO4, filtered, and concentrated in vacuo to yield 5- (difluoromethoxy)-7-methyl-1H-indole-4-carbaldehyde (Intermediate 8, 68.0 mg, 60 % pure by 1H NMR, 0.18 mmol) as a yellow gum which was used without further purification; LCMS: Rt = 0.59 (Method C1); m/z 224.0 (M-H)- (ES-); 1H NMR: (500 MHz, DMSO-d6) δ 11.72 (s, 1H), 10.45 (s, 1H), 7.65 (t, J=2.8 Hz, 1H), 7.26 (t, J=74.5 Hz, 1H), 7.15 (dd, J=3.0, 1.9 Hz, 1H), 6.94 (s, 1H), 2.58 (s, 3H). Intermediate 9: 3-fluoro-5-methoxy-7-methyl-1H-indole-4-carbaldehyde
Figure imgf000155_0001
1-(Chloromethyl)-4-fluoro-1,4-diazabicyclo[2.2.2]octane-1,4-diium tetrafluoroborate (3.65 g, 10.3 mmol) was added portion wise to a solution of 5-methoxy-7-methyl-1H- indole-4-carbaldehyde (Intermediate 5, Step 1 product, 1.50 g, 1 Eq, 7.93 mmol) in MeCN (30 mL) and pyridine (10 mL) at 0 ºC. After stirring at rt for 12 h further 1- (chloromethyl)-4-fluoro-1,4-diazabicyclo[2.2.2]octane-1,4-diium tetrafluoroborate (3.65 g, 10.3 mmol) was added and the reaction mixture was stirred at 0 ºC for 4 h. EtOAc (50 mL) was added and the organic phase was washed with water (3 x 50 mL) and brine (3 x 50 mL), dried over Na2SO4 and concentrated in vacuo. Purification by chromatography on silica gel (24 g cartridge, 0-100% EtOAc/isohexane) yielded 3- fluoro-5-methoxy-7-methyl-1H-indole-4-carbaldehyde (Intermediate 9, 100 mg, 81 % pure by LCMS (Method A1), 0.39 mmol, 5 % yield) as a yellow solid; LCMS: Rt = 0.45 (Method A1); m/z 208.2 (M+H)+ (ES+); 1H NMR: (500 MHz, CDCl3) δ 10.68 (s, 1H), 7.15 (t, J=2.9 Hz, 1H), 6.76 (s, 1H), 3.95 (s, 3H), 2.52 (s, 3H), one exchangeable proton not observed. Intermediate 10: tert-butyl 4-(chloromethyl)-5-methoxy-7-methyl-1H-indole-1- carboxylate The title compound (CAS # 2797067-18-4) may be synthesized by methods reported in the literature (see e.g. Wiles, J. A. et al, WO 2022/155294 A1, pages 41-42). Intermediate 11: tert-butyl 4-(aminomethyl)-5-methoxy-7-methyl-1H-indole-1- carboxylate
Figure imgf000156_0001
Step 1: Triphenylphosphine (1.34 g, 5.10 mmol), DIAD (1.06 mL, 5.44 mmol) and isoindoline-1,3-dione (600 mg, 4.08 mmol) were added to a solution of tert-butyl 4- (hydroxymethyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate (1.00 g, 3.40 mmol) in THF (15 mL). After stirring for 3 h at rt the mixture was concentrated in vacuo. Purification by chromatography on silica gel (24 g cartridge, 0-50% EtOAc/isohexane) yielded tert-butyl 4-((1,3-dioxoisoindolin-2-yl)methyl)-5-methoxy-7-methyl-1H-indole- 1-carboxylate (1.01 g, 96 % purity by LCMS (Method A1), 2.3 mmol, 68 % yield) as a white solid; LCMS: Rt = 0.74 (Method A1); m/z 421.2 (M+H)+ (ES+); 1H NMR: (500 MHz, CDCl3) δ 7.82-7.74 (m, 2H), 7.65 (dd, J=5.4, 3.0 Hz, 2H), 7.51 (d, J=3.8 Hz, 1H), 6.79 (d, J=3.8 Hz, 1H), 6.72 (s, 1H), 5.08 (s, 2H), 3.89 (s, 3H), 2.59 (s, 3H), 1.60 (s, 9H). Step 2: A mixture of tert-butyl 4-((1,3-dioxoisoindolin-2-yl)methyl)-5-methoxy-7- methyl-1H-indole-1-carboxylate (3.50 g, 95 % purity by LCMS (Method A1), 7.91 mmol) and hydrazine (3.58 mL, 35 % Wt solution in water, 39.5 mmol) in MeOH (40 mL) was stirred at 60 °C for 4 h. After concentration in vacuo, purification by chromatography on silica gel (40 g cartridge, 0-10% (0.7 M Ammonia/MeOH)/DCM) yielded tert-butyl 4-(aminomethyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate (Intermediate 11, 1.30 g, 95 % purity by 1H NMR, 4.25 mmol, 54 % yield) as a light brown gum; 1H NMR: (500 MHz, CDCl3) δ 7.55-7.45 (m, 1H), 6.73 (s, 1H), 6.61-6.55 (m, 1H), 3.99 (s, 2H), 3.88 (s, 3H), 2.62 (s, 3H), 1.62 (s, 9H), two exchangeable protons not observed. Intermediate 12: tert-butyl 4-((2-chloro-7-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]- pyridin-6-yl)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate
Figure imgf000157_0001
A mixture of TEA (0.68 mL, 4.88 mmol), tert-butyl 4-(aminomethyl)-5-methoxy-7- methyl-1H-indole-1-carboxylate (Intermediate 11, 425 mg, 1.46 mmol) and methyl 3- (bromomethyl)-6-chloropicolinate (430 mg, 1.63 mmol) in MeCN (10 mL) was heated at 80 °C for 5 h. After cooling to rt, DCM (30 mL) and water (50 mL) were added, the phases were separated, and the aqueous phase was extracted with DCM (30 mL). The combined organic phases were dried over sodium sulfate and concentrated in vacuo. Purification by chromatography on silica gel (24 g cartridge, 0-10% MeOH/DCM) yielded tert-butyl 4-((2-chloro-7-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridin-6-yl)- methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate (Intermediate 12, 534 mg, 97 % pure by LCMS (Method C3), 1.17 mmol, 80 % yield) as a white solid; LCMS: Rt = 1.85 (Method C3); m/z 442.2 (M+H)+ (ES+). Intermediate 13: tert-butyl 4-(1-aminoethyl)-5-methoxy-7-methyl-1H-indole-1- carboxylate
Figure imgf000157_0002
The title compound was prepared in two steps from triphenylphosphine (1.26 g, 4.80 mmol), DIAD (998 μL, 5.07 mmol), isoindoline-1,3-dione (567 mg, 3.85 mmol) and tert-butyl 4-(1-hydroxyethyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate (Intermediate 3, 1.00 g, 3.27 mmol) in THF (15 mL) at rt for 12 h; then hydrazine in water (0.55 mL, 35 % Wt, 6.07 mmol) in MeOH (15 mL) at 60 °C for 14 h, using the methods of Intermediate 11. After completion of step 2 the crude product was purified by chromatography on silica gel (80 g cartridge, 0-10% (0.7 M Ammonia/MeOH)/DCM) to yield tert-butyl 4-(1-aminoethyl)-5-methoxy-7-methyl-1H- indole-1-carboxylate (Intermediate 13, 345 mg, 95 % pure by 1H NMR, 1.08 mmol, 33 % yield over two steps) as a colourless gum; LCMS: Rt = 1.09 (Method C3); m/z 305.2 (M+H)+ (ES+); 1H NMR: (500 MHz, DMSO-d6) δ 7.54 (d, J=3.8 Hz, 1H), 6.98 (d, J=3.8 Hz, 1H), 6.81 (s, 1H), 4.52 (q, J=6.8 Hz, 1H), 3.81 (s, 3H), 2.48 (s, 3H), 1.57 (s, 9H), 1.33 (d, J=6.7 Hz, 3H), two exchangeable protons not observed. Synthesis of Examples Example 1: 2-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)isoindoline-5-carbonitrile
Figure imgf000158_0001
Step 1: To a mixture of tert-butyl 4-formyl-5-methoxy-7-methyl-1H-indole-1- carboxylate (176 mg, 0.61 mmol) and isoindoline-5-carbonitrile hydrochloride (100 mg, 0.55 mmol) in THF (5 mL) was added STAB (176 mg, 0.83 mmol). The resulting mixture was stirred at rt for 90 min then acetic acid (200 uL) was added. The reaction mixture was poured onto an SCX cartridge, washed with MeOH then eluted with a solution of 0.7N ammonia in MeOH. The eluent was concentrated in vacuo to yield tert-butyl 4-((5-cyanoisoindolin-2-yl)methyl)-5-methoxy-7-methyl-1H-indole-1- carboxylate (264 mg, 84 % pure by LCMS (Method D3), 0.53 μmol, 96 % yield) as a beige solid; LCMS: Rt = 2.07 (Method D3); m/z no ionisation observed. Step 2: To a solution of tert-butyl 4-((5-cyanoisoindolin-2-yl)methyl)-5-methoxy-7- methyl-1H-indole-1-carboxylate (264 mg, 84 % pure by LCMS, 0.53 μmol) in DCM (5 mL) was added 2,6-lutidine (678 μL, 5.82 mmol) and TMS-OTf (673 μL, 3.72 mmol). The resulting mixture was stirred at rt for 30 min before dilution with DCM and washing with saturated aq. sodium bicarbonate solution. The phases were separated, the organic phase was dried over Na2SO4, filtered, and concentrated in vacuo. Purification by reverse phase chromatography on a 12 g C18 cartridge eluting with 5- 100% MeCN in 10 mM aqueous ammonium bicarbonate yielded 2-((5-methoxy-7- methyl-1H-indol-4-yl)methyl)isoindoline-5-carbonitrile (Example 1, 51.0 mg, 0.16 mmol, 30 % yield) as a beige solid; LCMS: Rt = 0.78 (Method C3); m/z 318.2 (M+H)+ (ES+); 1H NMR: (500 MHz, DMSO-d6) δ 10.87 (s, 1H), 7.65 (s, 1H), 7.62 (dd, J=7.7, 1.5 Hz, 1H), 7.39 (d, J=7.8 Hz, 1H), 7.27 (t, J=2.8 Hz, 1H), 6.73 (s, 1H), 6.53 (dd, J=3.1, 1.9 Hz, 1H), 4.06 (s, 2H), 3.89 (s, 2H), 3.85 (s, 2H), 3.78 (s, 3H), 2.46 (s, 3H). Example 2: 2-((5-chloro-7-methyl-1H-indol-4-yl)methyl)isoindoline-5-carbonitrile
Figure imgf000159_0001
Step 1: DIPEA (111 μL, 0.64 mmol) was added to a solution of 5-chloro-4- (chloromethyl)-7-methyl-1-tosyl-1H-indole (Intermediate 2, 78.0 mg, 0.21 mmol) and isoindoline-5-carbonitrile hydrochloride (42.1 mg, 0.23 mmol) in MeCN (1 mL) and the reaction stirred for 3 d. Water (5 mL) was added and the resulting precipitate collected by filtration, washed with water (2 x 5 mL) and dried in a desiccator to yield 2- ((5-chloro-7-methyl-1-tosyl-1H-indol-4-yl)methyl)isoindoline-5-carbonitrile (85.0 mg, 0.18 mmol, 84 % yield) as an off white powder; LCMS: Rt = 1.49 (Method A3); m/z 476.1 (M+H)+ (ES+). Step 2: TBAF (410 μL, 1M in THF, 410 μmol) was added to a solution of 2-((5-chloro-7- methyl-1-tosyl-1H-indol-4-yl)methyl)isoindoline-5-carbonitrile (65.0 mg, 137 μmol) in THF (1 mL) and the reaction heated to 65 °C for 1.5 h. The reaction was diluted with water (20 mL) and extracted with EtOAc (3 x 20 mL). The combined organic phases were dried over MgSO4, filtered and concentrated in vacuo. The crude product was purified by chromatography on silica gel (12 g cartridge, 0-50% EtOAc/isohexane) to yield 2-((5-chloro-7-methyl-1H-indol-4-yl)methyl)isoindoline-5-carbonitrile (Example 2, 37.0 mg, 0.11 mmol, 84 % yield) as a yellow solid; LCMS: Rt = 0.80 (Method A3); m/z 322.15 (M+H)+ (ES+); 1H NMR: (500 MHz, DMSO-d6) δ 11.26 (s, 1H), 7.67 (s, 1H), 7.65-7.62 (m, 1H), 7.42 (d, J=7.8 Hz, 1H), 7.38 (t, J=2.8 Hz, 1H), 6.95 (s, 1H), 6.68 (dd, J=3.1, 1.8 Hz, 1H), 4.19 (s, 2H), 3.94 (s, 2H), 3.89 (s, 2H), 2.47-2.43 (m, 3H). Example 3: 2-(1-(5-methoxy-7-methyl-1H-indol-4-yl)ethyl)isoindoline-5-carbonitrile
Figure imgf000160_0001
Step 1: To a solution of tert-butyl 4-(1-hydroxyethyl)-5-methoxy-7-methyl-1H-indole-1- carboxylate (Intermediate 3, 400 mg, 1.31 mmol) in DCM (20 mL) was added N- (chloromethylene)-N-methylmethanaminium chloride (275 mg, 2.15 mmol) and the reaction mixture was stirred at 0 °C for 2 h. Isoindoline-5-carbonitrile hydrochloride (250 mg, 1.39 mmol) and DIPEA (500 μL, 2.87 mmol) was dissolved in MeCN (30 mL) and this solution was slowly added to the reaction at 0 °C and stirred for 15 min, then at rt for 30 min. DIPEA (395 μL, 2.27 mmol) was added and the reaction mixture was stirred for 1.5 h at 20°C before dilution with 1M aq. citric acid (100 mL) and extraction with EtOAc (2 x 100 mL). The combined organic phases were washed with brine (100 mL), dried using Na2SO4 and concentrated in vacuo. Purification by chromatography on silica gel (40 g cartridge, 0-100% EtOAc/isohexane then 0-10% 0.7N ammonia in MeOH/DCM) yielded tert-butyl 4-(1-(5-cyanoisoindolin-2-yl)ethyl)-5-methoxy-7- methyl-1H-indole-1-carboxylate (353 mg, 0.82 mmol, 62 % yield) as a black oil; LCMS: Rt = 1.16 (Method C3); m/z 430.2 (M-H)- (ES-). Step 2: A solution of tert-butyl 4-(1-(5-cyanoisoindolin-2-yl)ethyl)-5-methoxy-7- methyl-1H-indole-1-carboxylate (52.7 mg, 122 μmol) in DCM (3 mL) was treated with 2,6-lutidine (95 μL, 820 μmol) then TMS-OTf (100 μL, 553 μmol) at 0 °C for 5 min, then at rt for 5 h. The reaction was concentrated on celite and purified by chromatography on silica gel (40 g cartridge, 0-10% 0.7N ammonia in MeOH/DCM) to afford afford a black residue. Further purification by prep-HPLC (Method P1) yielded 2-(1-(5-methoxy-7-methyl-1H-indol-4-yl)ethyl)isoindoline-5-carbonitrile (Example 3, 4.2 mg, 13 μmol, 10 % yield) as a brown solid; LCMS: Rt = 0.70 (Method C3); m/z 330.2 (M-H)- (ES-); 1H NMR: (500 MHz, MeOD) δ 7.55-7.47 (m, 2H), 7.31 (d, J=7.7 Hz, 1H), 7.17 (d, J=3.1 Hz, 1H), 6.80 (d, J=3.1 Hz, 1H), 6.74 (s, 1H), 4.48 (q, J=6.7 Hz, 1H), 4.04 (t, J=13.9 Hz, 2H), 3.87-3.70 (m, 5H), 2.49 (s, 3H), 1.57 (d, J=6.7 Hz, 3H), one exchangeable proton not observed. Example 4: 2-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)isoindoline-5- carbonitrile
Figure imgf000161_0001
Step 1: TBAF (1M in THF, 1.45 mL, 1.45 mmol) was added to a solution of 5- cyclopropyl-7-methyl-1-tosyl-1H-indole-4-carbaldehyde (Intermediate 4, 160 mg, 64 % pure by LCMS (Method C1), 290 μmol) in THF (3 mL) and the reaction heated at 65 °C for 1 h. Water (20 mL) and EtOAc (20 mL) were added and the phases were separated. The aqueous phase was extracted with EtOAc (2 x 20 mL), the combined organic phases were washed with saturated aq. sodium bicarbonate solution (20 mL) and brine (20 mL), dried over MgSO4, filtered, and concentrated in vacuo. The crude product was purified by chromatography on silica gel (24 g cartridge, 0-50% EtOAc/isohexane) to yield 5-cyclopropyl-7-methyl-1H-indole-4-carbaldehyde (60.0 mg, 88 % pure by LCMS, 0.26 mmol, 91 % yield) as a yellow solid; LCMS: Rt = 1.38 (Method A3); m/z 200.1 (M+H)+ (ES+); 1H NMR: (500 MHz, DMSO-d6) δ 11.40 (s, 1H), 10.90 (s, 1H), 7.51 (t, J=2.7 Hz, 1H), 7.12 (dd, J=3.1, 1.9 Hz, 1H), 6.76 (s, 1H), 2.69- 2.61 (m, 1H), 2.49 (s, 3H), 1.05-0.98 (m, 2H), 0.77 (qd, J=5.0, 2.0 Hz, 2H). Step 2: 5-Cyclopropyl-7-methyl-1H-indole-4-carbaldehyde (58.0 mg, 256 μmol) was added to a solution of isoindoline-5-carbonitrile hydrochloride (50.9 mg, 282 μmol) and DIPEA (54 μL, 307 μmol) in DCM (4 mL) and the reaction mixture was stirred at rt for 1 h before addition of STAB (109 mg, 512 μmol). The reaction was stirred at rt for 3 h before dilution with DCM (20 mL) and 1:1 water/brine (15 mL) and the phases were separated. The aqueous phase was extracted with DCM (20 mL) and the combined organic phases were filtered through a phase separator and concentrated onto Celite. The crude product was purified by reverse phase chromatography on a 12 g C18 cartridge eluting with 5-60% MeCN in 10 mM aqueous ammonium bicarbonate to yield 2-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)isoindoline-5-carbonitrile (Example 4, 55.0 mg, 0.17 mmol, 66 % yield) as a white solid; LCMS: Rt = 1.79 (Method B3); m/z 325.8 (M-H)- (ES-); 1H NMR: (500 MHz, DMSO-d6) δ 10.89 (s, 1H), 7.67 (s, 1H), 7.65- 7.61 (m, 1H), 7.41 (d, J=7.8 Hz, 1H), 7.26 (dd, J=2.8, 2.8 Hz, 1H), 6.60 (d, J=2.5 Hz, 1H), 6.51 (s, 1H), 4.23 (s, 2H), 3.91 (s, 2H), 3.87 (s, 2H), 2.40 (s, 3H), 2.30 (ddd, J=13.8, 8.5, 5.3 Hz, 1H), 0.87 (dt, J=9.1, 3.1 Hz, 2H), 0.63-0.56 (m, 2H). Example 5: ethyl 3-(5-cyanoisoindolin-2-yl)-3-(5-methoxy-7-methyl-1H-indol-4-yl)- propanoate
Figure imgf000162_0001
TBAF (1M in THF, 1.35 mL, 1.35 mmol) was added to a solution of ethyl 3-(5- cyanoisoindolin-2-yl)-3-(5-methoxy-7-methyl-1-tosyl-1H-indol-4-yl)propanoate (Intermediate 6, 200 mg, 73 % pure by LCMS, 0.26 mmol) in THF (10 mL) and the reaction was heated at 65 °C for 12 h. After cooling to rt, water (50 mL) was added and the phases were separated. The aqueous phase was extracted with EtOAc (3 x 50 mL), the combined organic phases layers were dried over Na2SO4, filtered and concentrated in vacuo. Purification by chromatography on silica gel (4 g cartridge, 0-50% EtOAc/isohexane) yielded ethyl 3-(5-cyanoisoindolin-2-yl)-3-(5-methoxy-7-methyl-1H- indol-4-yl)propanoate (Example 5, 80 mg, 0.20 mmol, 77 % yield) as a pale orange solid; LCMS: Rt = 0.85 (Method A3); m/z 402.0 (M-H)- (ES-); 1H NMR: (500 MHz, DMSO-d6) δ 10.88 (s, 1H), 7.67-7.58 (m, 2H), 7.38 (d, J=7.8 Hz, 1H), 7.24 (t, J=2.9 Hz, 1H), 6.72 (s, 1H), 6.62 (dd, J=3.1, 1.9 Hz, 1H), 4.83 (dd, J=7.9, 6.1 Hz, 1H), 3.96 (d, J=14.2 Hz, 1H), 3.89 (ddt, J=10.8, 6.5, 3.8 Hz, 3H), 3.76 (d, J=0.9 Hz, 3H), 3.75-3.66 (m, 2H), 3.10 (dd, J=14.4, 6.0 Hz, 1H), 2.90 (dd, J=14.5, 7.9 Hz, 1H), 2.44 (s, 3H), 1.01 (td, J=7.1, 1.0 Hz, 3H). Example 6: 2-((5-(difluoromethoxy)-7-methyl-1H-indol-4-yl)methyl)isoindoline-5- carbonitrile
Figure imgf000163_0001
5-(Difluoromethoxy)-7-methyl-1H-indole-4-carbaldehyde (Intermediate 8, 66.0 mg, 60 % pure by 1H NMR, 176 μmol) was added to a solution of isoindoline-5-carbonitrile hydrochloride (34.9 mg, 193 μmol) and DIPEA (37 μL, 212 μmol) in DCM (4 mL) and the reaction mixture was stirred at rt for 1 h before the addition of STAB (74.5 mg, 352 μmol). After stirring at rt for 3 h, DCM (20 mL) and 1:1 water/brine (15 mL) were added and the phases were separated. The aqueous phase was extracted with DCM (20 mL) and the combined organic phases were filtered and concentrated onto celite. Purification by reverse phase chromatography on a 12 g C18 cartridge eluting with 5- 100% (0.1 % formic acid in MeCN) in (0.1 % formic acid in water) yielded 2-((5- (difluoromethoxy)-7-methyl-1H-indol-4-yl)methyl)isoindoline-5-carbonitrile (Example 6, 12.5 mg, 88 % pure by LCMS, 31 μmol, 18 % yield) as a colourless solid; LCMS: Rt = 0.80 (Method A3); m/z 354.2 (M+H)+ (ES+); 1H NMR: (500 MHz, DMSO-d6) δ 11.26 (s, 1H), 7.69 (s, 1H), 7.65 (d, J=7.7 Hz, 1H), 7.45-7.39 (m, 2H), 6.99 (t, J =75.3 Hz, 1H), 6.80 (s, 1H), 6.72 (s, 1H), 4.17-4.13 (m, 2H), 3.96-3.92 (m, 4H), 2.48 (s, 3H). Example 7: 2-((3-fluoro-5-methoxy-7-methyl-1H-indol-4-yl)methyl)isoindoline-5- carbonitrile
Figure imgf000163_0002
The title compound was prepared from 3-fluoro-5-methoxy-7-methyl-1H-indole-4- carbaldehyde (Intermediate 9, 50 mg, 81 % pure by LCMS (Method A1), 195 µmol), isoindoline-5-carbonitrile hydrochloride (38.8 mg, 215 μmol), DIPEA (41 μL, 235 μmol) and STAB (82.9 mg, 391 μmol) in DCM (2 mL) at rt for 3 h, using the methods of Example 6. Purification by reverse phase column chromatography on a 12g Flash C18 cartridge, eluting with 0-70% MeCN in 10 mM aq. ammonium bicarbonate, yielded 2- ((3-fluoro-5-methoxy-7-methyl-1H-indol-4-yl)methyl)isoindoline-5-carbonitrile (Example 7, 4.0 mg, 12 µmol, 6 % yield) as a light brown solid; LCMS: Rt = 1.60 (Method B3); m/z 336.2 (M+H)+ (ES+); 1H NMR: (500 MHz, CD3OD) δ 7.52 (dd, J=9.4, 1.6 Hz, 2H), 7.38-7.32 (m, 1H), 7.07 (d, J=2.5 Hz, 1H), 6.82 (s, 1H), 4.27 (d, J=1.1 Hz, 2H), 4.05 (s, 2H), 4.03 (s, 2H), 3.87 (s, 3H), 2.46 (d, J=0.8 Hz, 3H), one exchangeable proton was not observed. Example 8: 2-((3-bromo-5-methoxy-7-methyl-1H-indol-4-yl)methyl)isoindoline-5- carbonitrile
Figure imgf000164_0001
NBS (29.4 mg, 165 μmol) was added to a solution of 2-((5-methoxy-7-methyl-1H-indol- 4-yl)methyl)isoindoline-5-carbonitrile (Example 1, 50.0 mg, 1 eq, 158 μmol) in MeCN (2 mL) and the reaction mixture was stirred at rt for 2 h before the addition of EtOAc (10 mL) and aq. NaHCO3 (10 mL). The phases were separated and the aqueous phase was extracted with EtOAc (2 x 10 mL). The combined organic phases were concentrated in vacuo and purified by chromatography on silica gel (4 g cartridge, 0-100% EtOAc/isohexane) to yield 2-((3-bromo-5-methoxy-7-methyl-1H-indol-4- yl)methyl)isoindoline-5-carbonitrile (Example 8, 20.0 mg, 84 % pure by LCMS (Method B3), 42 μmol, 38 % yield) as a pale brown solid; LCMS: Rt = 1.71 (Method B3); m/z 394.5, 396.1 (M-H)- (ES-); 1H NMR: (400 MHz, DMSO-d6) δ 11.30 (s, 1H), 7.66 (s, 1H), 7.62 (d, J=7.8 Hz, 1H), 7.45 (d, J=2.8 Hz, 1H), 7.41 (d, J=7.8 Hz, 1H), 6.85 (s, 1H), 4.31 (s, 2H), 3.94 (s, 2H), 3.90 (s, 2H), 3.80 (s, 3H), 2.45 (s, 3H). Example 9: 3-(5-cyanoisoindolin-2-yl)-3-(5-methoxy-7-methyl-1H-indol-4-yl)- propanoic acid
Figure imgf000165_0001
LiOH (15.6 mg, 0.65 mmol) was added to a solution of ethyl 3-(5-cyanoisoindolin-2-yl)- 3-(5-methoxy-7-methyl-1H-indol-4-yl)propanoate (Example 5, 40 mg, 0.10 mmol) in THF (2 mL) and water (0.5 mL) and the reaction mixture was stirred at rt for 24 h. Concentration in vacuo yielded 3-(5-cyanoisoindolin-2-yl)-3-(5-methoxy-7-methyl-1H- indol-4-yl)propanoic acid (Example 9, 33 mg, 81 % pure by LCMS, 0.07 mmol, 75 % yield) as a brown solid; LCMS: Rt = 0.70 (Method A3); m/z 374.0 (M-H)- (ES-); 1H NMR: (500 MHz, DMSO-d6) δ 10.74 (s, 1H), 7.60-7.55 (m, 2H), 7.33 (d, J=7.7 Hz, 1H), 7.16 (d, J=3.1 Hz, 1H), 6.67-6.62 (m, 2H), 4.93 (dd, J=8.6, 3.5 Hz, 1H), 3.93 (d, J=14.8 Hz, 1H), 3.85 (d, J=13.8 Hz, 1H), 3.81-3.69 (m, 5H), 2.78 (d, J=9.8 Hz, 1H), 2.42 (s, 3H), 2.18 (d, J=15.2 Hz, 1H), one exchangeable proton not observed. Example 10: 2-((3-chloro-5-methoxy-7-methyl-1H-indol-4-yl)methyl)isoindoline-5- carbonitrile
Figure imgf000165_0002
NCS (37.0 mg, 277 μmol) was added to a solution of 2-((5-methoxy-7-methyl-1H-indol- 4-yl)methyl)isoindoline-5-carbonitrile (Example 1, 80.0 mg, 252 μmol) in MeCN (1 mL). After stirring at rt for 1 h, aq. sodium bicarbonate solution (10 mL) and EtOAc (10 mL) were added and the phases were separated. The aqueous layer was extracted with EtOAc (2 x 10 mL) and the combined organic phases were concentrated in vacuo. Purification by prep-HPLC (Method P2) yielded 2-((3-chloro-5-methoxy-7-methyl-1H- indol-4-yl)methyl)isoindoline-5-carbonitrile (Example 10, 15.2 mg, 95 % purity by LCMS (Method C3), 41 μmol, 17 % yield) as a light brown solid; LCMS: Rt = 0.97 (Method C3); m/z 350.2 (M-H)- (ES-); 1H NMR: (400 MHz, DMSO-d6) δ 11.18 (s, 1H), 7.66 (s, 1H), 7.62 (d, J=8.0 Hz, 1H), 7.43-7.38 (m, 2H), 6.84 (s, 1H), 4.28 (s, 2H), 3.92 (s, 2H), 3.89 (s, 2H), 3.80 (s, 3H), 2.44 (d, J=0.8 Hz, 3H). Example 11: 2-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-3,3-dimethylisoindoline- 5-carbonitrile
Figure imgf000166_0001
Step 1: A mixture of 6-bromo-1,1-dimethylisoindoline hydrochloride (114 mg, 433 μmol), tert-butyl 4-(chloromethyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate (Intermediate 10, 149 mg, 85 % purity by 1H NMR, 410 μmol) and DIPEA (214 μL, 1.23 mmol) in MeCN (2 mL) was stirred at 60 °C for 4 h. After cooling to rt and concentration in vacuo onto silica, purification by chromatography on silica gel (12 g cartridge, 0-50% EtOAc/isohexane) yielded tert-butyl 4-((6-bromo-1,1-dimethyl- isoindolin-2-yl)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate (138 mg, 94 % purity by 1H NMR, 0.26 mmol, 63 % yield) as a colourless oil which solidified to a white solid on standing; LCMS: Rt = 2.57 (Method D3); m/z 499.2, 501.0 (M+H)+ (ES+); 1H NMR: (500 MHz, DMSO-d6) δ 7.55 (d, J=3.7 Hz, 1H), 7.44 (d, J=1.9 Hz, 1H), 7.29 (dd, J=7.9, 1.9 Hz, 1H), 7.06 (d, J=8.0 Hz, 1H), 6.86 (s, 1H), 6.78 (d, J=3.8 Hz, 1H), 3.95 (s, 2H), 3.83 (s, 3H), 3.58 (s, 2H), 2.53 (s, 3H), 1.57 (s, 9H), 1.38 (s, 6H). Step 2: A mixture of potassium hexacyanoferrate(II) trihydrate (33.6 mg, 79.5 μmol), dichloro[bis(2-(diphenylphosphino)phenyl)ether]palladium(II) (Johnson Matthey, catalog number Pd-117, 10.4 mg, 14.5 μmol) and caesium carbonate (75.1 mg, 230 μmol) in a vial was degassed and purged with N2 three times. A solution of tert-butyl 4- ((6-bromo-1,1-dimethylisoindolin-2-yl)methyl)-5-methoxy-7-methyl-1H-indole-1- carboxylate (80.6 mg, 94 % purity by 1H NMR, 152 μmol) in 1,4-dioxane (1.25 mL) and water (0.25 mL) was added and the purging repeated. The mixture was then stirred at 90 °C for 1 d. After cooling to rt further dichloro[bis(2-(diphenylphosphino)phenyl) ether]palladium(II) (Johnson Matthey, catalog number Pd-117, 10.4 mg, 14.5 μmol), potassium hexacyanoferrate(II) trihydrate (34.4 mg, 93.4 μmol) and caesium carbonate (25.0 mg, 76.7 μmol) were added. The vial was degassed and purged with N2 three times, heated at 90 °C for 2 d, then cooled to rt. A separate batch of crude material was prepared using the same methods from potassium hexacyanoferrate(II) trihydrate (7.4 mg, 17.5 μmol), dichloro[bis(2-(diphenylphosphino)phenyl)ether]palladium(II) (Johnson Matthey, catalog number Pd-117, 2.5 mg, 3.5 μmol), caesium carbonate (14.3 mg, 43.9 μmol) and tert-butyl 4-((6-bromo-1,1-dimethylisoindolin-2-yl)methyl)-5- methoxy-7-methyl-1H-indole-1-carboxylate (15.8 mg, 94 % purity by 1H NMR, 29.7 μmol) in 1,4-dioxane (0.4 mL) and water (0.1 mL) at 90 °C for 2.5 d. The two crude reaction mixtures were combined and partitioned between saturated aq. sodium bicarbonate (30 mL) and EtOAc (30 mL). The phases were separated and the organic phase was washed with brine (30 mL), dried over magnesium sulfate and concentrated in vacuo onto silica. Purification by chromatography on silica gel (12 g cartridge, 0-50% EtOAc/isohexane) yielded tert-butyl 4-((6-cyano-1,1-dimethylisoindolin-2-yl)methyl)- 5-methoxy-7-methyl-1H-indole-1-carboxylate (34.7 mg, 95 % purity by LCMS (Method C3), 74 μmol, 41 % yield) as a clear oil which solidified to a white solid on standing; LCMS: Rt = 1.38 (Method C3); m/z 446.4 (M+H)+ (ES+); 1H NMR: (500 MHz, DMSO- d6) δ 7.76 (s, 1H), 7.60 (dd, J=7.7, 1.5 Hz, 1H), 7.56 (d, J=3.7 Hz, 1H), 7.32 (d, J=7.8 Hz, 1H), 6.87 (s, 1H), 6.78 (d, J=3.8 Hz, 1H), 3.97 (s, 2H), 3.83 (s, 3H), 3.69 (s, 2H), 2.53 (s, 3H), 1.57 (s, 9H), 1.41 (s, 6H). Step 3: 2,6-Lutidine (53 μL, 457 μmol) and trimethylsilyl trifluoromethanesulfonate (69 μL, 382 μmol) were added to a solution of tert-butyl 4-((6-cyano-1,1-dimethyl- isoindolin-2-yl)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate (33.0 mg, 95 % purity by LCMS (Method C3), 70 μmol) in DCM (0.7 mL). After stirring at rt for 1 d the mixture was partitioned between brine (10 mL) and DCM (10 mL). The organic phase was dried over magnesium sulfate and concentrated in vacuo onto celite. Purification by reverse phase chromatography on a 4 g Flash C18 cartridge, eluting with 35-70% MeCN/10 mM ammonium bicarbonate, followed by prep-HPLC (Method P3, then Method P4) yielded 2-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-3,3-dimethyl- isoindoline-5-carbonitrile (Example 11, 1.2 mg, 95 % purity by 1H NMR, 3.3 μmol, 5 % yield) as a clear orange glass; LCMS: Rt = 0.85 (Method C3); m/z 346.2 (M+H)+ (ES+); 1H NMR: (500 MHz, CD3OD) δ 7.57 (d, J=1.3 Hz, 1H), 7.50 (dd, J=7.7, 1.5 Hz, 1H), 7.27 (d, J=7.7 Hz, 1H), 7.23 (d, J=3.1 Hz, 1H), 6.75 (s, 1H), 6.60 (d, J=3.1 Hz, 1H), 4.10 (s, 2H), 3.92 (s, 2H), 3.86 (s, 3H), 2.49 (d, J=0.8 Hz, 3H), 1.51 (s, 6H), one exchangeable proton not observed. Example 12: 2-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-3-oxoisoindoline-5- carbonitrile
Figure imgf000168_0001
Step 1: TEA (462 μL, 3.32 mmol) was added to a solution of tert-butyl 4- (aminomethyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate (Intermediate 11, 338 mg, 95 % purity by 1H NMR, 1.11 mmol) and methyl 2-(bromomethyl)-5-cyanobenzoate (312 mg, 90 % purity by LCMS (Method C3), 1.11 mmol) in MeCN (5 mL) and the reaction mixture was heated at 80 °C for 1.5 h. After cooling to rt the mixture was partitioned between EtOAc (50 mL) and brine (50 mL). The organic phase was dried over magnesium sulfate and concentrated in vacuo onto silica. Purification by chromatography on silica gel (12 g cartridge, 0-60% EtOAc/isohexane) yielded tert- butyl 4-((6-cyano-1-oxoisoindolin-2-yl)methyl)-5-methoxy-7-methyl-1H-indole-1- carboxylate (226 mg, 90 % purity by 1H NMR, 0.47 mmol, 43 % yield) as an off-white solid; LCMS: Rt = 1.87 (Method C3); m/z 432.2 (M+H)+ (ES+); 1H NMR: (500 MHz, DMSO-d6) δ 8.14 (s, 1H), 7.99 (dd, J=7.9, 1.5 Hz, 1H), 7.71 (d, J=7.9 Hz, 1H), 7.61 (d, J=3.8 Hz, 1H), 6.93 (s, 1H), 6.81 (d, J=3.8 Hz, 1H), 4.91 (s, 2H), 4.30 (s, 2H), 3.88 (s, 3H), 2.53 (s, 3H), 1.56 (s, 9H). Step 2: Aluminum trichloride (135 mg, 1.01 mmol) was added to a solution of tert-butyl 4-((6-cyano-1-oxoisoindolin-2-yl)methyl)-5-methoxy-7-methyl-1H-indole-1- carboxylate (139 mg, 90 % purity by 1H NMR, 289 μmol) in anhydrous DCM (3 mL) at 0 °C. The mixture was degassed and purged with N2 three times before stirring for 3 h whilst warming slowly to rt. A separate batch of crude material was prepared using the same methods from tert-butyl 4-((6-cyano-1-oxoisoindolin-2-yl)methyl)-5-methoxy-7- methyl-1H-indole-1-carboxylate (11.1 mg, 90 % purity by 1H NMR, 23.2 μmol) and aluminum trichloride (12.0 mg, 3.89 Eq, 90 μmol) in anhydrous DCM (0.3 mL) at 0 °C, slowly warming to rt over 3 h. The combined reaction mixtures were diluted with EtOAc (75 mL), saturated aq. sodium bicarbonate solution (50 mL) was added and the phases were separated. The organic phase was washed with brine (50 mL), dried over magnesium sulfate, and concentrated in vacuo onto silica. Purification by chromatography on silica gel (12 g cartridge, 0-50% EtOAc/isohexane) yielded 2-((5- methoxy-7-methyl-1H-indol-4-yl)methyl)-3-oxoisoindoline-5-carbonitrile (Example 12, 71.9 mg, 95 % purity by 1H NMR, 0.21 mmol, 66 % yield) as an off-white solid; LCMS: Rt = 1.33 (Method C3); m/z 330.2 (M-H)- (ES-); 1H NMR: (500 MHz, DMSO- d6) δ 10.98 (s, 1H), 8.14 (s, 1H), 7.98 (dd, J=7.9, 1.6 Hz, 1H), 7.69 (d, J=7.9 Hz, 1H), 7.26 (t, J=2.8 Hz, 1H), 6.78 (s , 1H), 6.47 (dd, J=3.1, 1.9 Hz, 1H), 4.94 (s, 2H), 4.24 (s, 2H), 3.83 (s, 3H), 2.45 (s, 3H). Example 13: 6-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-oxo-6,7-dihydro-5H- pyrrolo[3,4-b]pyridine-2-carbonitrile
Figure imgf000169_0001
Intermediate 12 Example 13 Step 1: Potassium ferrocyanide trihydrate (424.4 mg, 1.00 mmol) and potassium acetate (247 mg, 2.51 mmol) were added to a solution of tert-butyl 4-((2-chloro-7-oxo- 5,7-dihydro-6H-pyrrolo[3,4-b]pyridin-6-yl)methyl)-5-methoxy-7-methyl-1H-indole-1- carboxylate (Intermediate 12, 370.0 mg, 0.84 mmol) in 1,4-dioxane/water (5:1, 9.6 mL) and the mixture was degassed with nitrogen for 5 min before the addition of BrettPhos Pd G3 (75.9 mg, 0.08 mmol). After heating at 80 °C for 5 h the reaction mixture was cooled to rt, EtOAc (50 mL) and water (100 mL) were added and the phases were separated. The aqueous phase was extracted with EtOAc (50 mL) and the combined organic phases were dried over sodium sulfate and concentrated in vacuo. Purification by chromatography on silica gel (24 g cartridge, 0-10% MeOH/DCM) yielded tert-butyl 4-((2-cyano-7-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridin-6-yl)- methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate (358 mg, 72 % pure by LCMS (Method C3), 0.60 mmol, 71 % yield) as an off white solid; LCMS: Rt = 1.76 (Method C3); m/z 431.2 (M-H)- (ES-). Step 2: A solution of tert-butyl 4-((2-cyano-7-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]- pyridin-6-yl)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate (350.0 mg, 72 % pure by LCMS (Method C3), 0.58 mmol) in 2,2,2-trifluoroethanol (4 mL) was heated in a microwave reactor at 150 °C for 1 h. After cooling to rt and concentration in vacuo, purification by preparative HPLC (Method P5) yielded 6-((5-methoxy-7-methyl-1H- indol-4-yl)methyl)-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine-2-carbonitrile (Example 13, 55.2 mg, 0.17 mmol, 28 % yield) as an off white solid; LCMS: Rt = 1.17 (Method C3); m/z 331.2 (M-H)- (ES-); 1H NMR: (500 MHz, DMSO-d6) δ 11.00 (s, 1H), 8.18 (d, J=8.0 Hz, 1H), 8.13 (dd, J=7.9, 1.2 Hz, 1H), 7.28 (d, J=2.8 Hz, 1H), 6.79 (s, 1H), 6.47 (dd, J=3.2, 1.7 Hz, 1H), 4.98 (s, 2H), 4.27 (s, 2H), 3.83 (d, J=1.2 Hz, 3H), 2.46 (s, 3H). Example 14: 2-(1-(5-methoxy-7-methyl-1H-indol-4-yl)ethyl)-3-oxoisoindoline-5- carbonitrile
Figure imgf000170_0001
Step 1: tert-butyl 4-(1-(6-cyano-1-oxoisoindolin-2-yl)ethyl)-5-methoxy-7-methyl-1H- indole-1-carboxylate was prepared from tert-butyl 4-(1-aminoethyl)-5-methoxy-7- methyl-1H-indole-1-carboxylate (Intermediate 13, 80.0 mg, 95 % pure by 1H NMR, 0.25 mmol), methyl 2-(bromomethyl)-5-cyanobenzoate (70.5 mg, 90 % purity by LCMS (Method C3), 0.25 mmol) and TEA (104 μL, 0.75 mmol) in MeCN (2 mL) at 80 °C for 5 h, using the methods of Example 12, Step 1. Following completion of the reaction DCM (30 mL) and water (30 mL) were added, and the phases were separated. The organic phase was concentrated in vacuo onto silica and purified by chromatography on silica gel (4 g cartridge, 0-70% EtOAc/isohexane) to yield tert-butyl 4-(1-(6-cyano-1- oxoisoindolin-2-yl)ethyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate (100 mg, 0.22 mmol, 90 % yield) as a pale yellow gel; LCMS: Rt = 1.95 (Method C3); m/z 444.2 (M-H)- (ES-). Step 2: TEA (156 μL, 1.12 mmol), then TMS-OTf (284 μL, 1.57 mmol) were added to a solution of tert-butyl 4-(1-(6-cyano-1-oxoisoindolin-2-yl)ethyl)-5-methoxy-7-methyl- 1H-indole-1-carboxylate (100 mg, 0.22 mmol) in DCM (2 mL) at 0 °C. After stirring for 10 min at 0 °C, then for 1.25 h at rt, the reaction mixture was cooled to -10 °C for 15 min and diluted dropwise with DCM (6 mL). After stirring for 5 min at -10 °C, TEA (1 mL) was added dropwise followed by slow addition of saturated aq. sodium bicarbonate solution (20 mL). The mixture was stirred at 0 °C for 10 min, warmed to rt, and the phases were separated. The organic phase washed with saturated aq. sodium bicarbonate solution (20 mL), dried over sodium sulfate and concentrated in vacuo. Purification by prep-HPLC (Method P6) yielded 2-(1-(5-methoxy-7-methyl-1H-indol-4- yl)ethyl)-3-oxoisoindoline-5-carbonitrile (Example 14, 7.30 mg, 95 % pure by 1H NMR, 20 μmol, 9 % yield) as a white solid; LCMS: Rt = 1.39 (Method C3); m/z 344.0 (M-H)- (ES-); 1H NMR: (400 MHz, DMSO-d6) δ 10.98 (s, 1H), 8.13-8.03 (m, 1H), 7.99 (dd, J=7.9, 1.6 Hz, 1H), 7.75 (dd, J=7.9, 0.8 Hz, 1H), 7.30 (t, J=2.8 Hz, 1H), 6.76 (s, 1H), 6.58 (dd, J=3.1, 1.8 Hz, 1H), 5.98 (q, J=7.2 Hz, 1H), 4.75 (d, J=19.3 Hz, 1H), 4.21 (d, J=19.3 Hz, 1H), 3.78 (s, 3H), 2.44 (d, J=0.9 Hz, 3H), 1.75 (d, J=7.3 Hz, 3H). Examples – Biological Studies Factor B Biochemical ELISA assay Compound inhibition of Factor B (FB) enzymatic activity was assessed in a biochemical ELISA format, which measured the cleavage of C3 substrate to C3a by activated cobra venom factor (CVF) : Bb complex. CVF:Bb was first prepared by incubation of 1 µM serum purified Factor B (Quidel A408), 1 µM CVF (Quidel A600), and 300 nM Factor D (Quidel A409) in biochemical assay buffer (phosphate buffered saline containing 10 mM MgCl2 and 0.05 % w/v CHAPS; pH7.4) for 3 h at rt. Following completion of the reaction, glycerol was added to a final concentration of 20 % (v/v), and preparations were stored until use at 4°C. Enzyme assays were performed in 384 well format, in which compounds were prepared as 1:5 serial dilutions (8-point curves) in DMSO and 150 nL of compound was stamped to an assay plate (384-well OptiPlate, Perkin Elmer 6007299) at 100x final assay concentration (FAC). The final assay DMSO concentration was 1% (v/v). The compound preincubation step was initiated by addition of 7.5 µl biochemical assay buffer containing CVF:Bb complex (5 nM FAC unless stated otherwise), based on input FB concentration and pre-equilibrated to rt) for 30 min at rt. Subsequently, 7.5 µl biochemical assay buffer containing purified C3 substrate (Complement Technology A113c, to 0.1 µM FAC) was added and CVF:Bb mediated cleavage was allowed to proceed for 60 min at rt. Reactions were terminated by addition of 3.75 µl 10x Halt protease inhibitor cocktail (Fisher 78437) in assay buffer, and cooling on ice. Following 5 min incubation, samples (1:100 dilution) were transferred to a 96 well ELISA format for detection of human C3a (Invitrogen 15517925) and processed according to the manufacturer’s instructions. Binding of anti C3a biotin / Streptavidin-horse radish peroxidase (HRP) was quantified using the chromogen HRP substrate 3,3',5,5'-tetramethylbenzidine added for 7 - 10 min, followed by addition of stop solution and measurement of absorbance at 450 nm (BMG Clariostar). C3a concentration was interpolated from the absorbance data with reference to a C3a standard curve (ng / mL). Inhibitor data were normalized to DMSO vehicle, 0 % inhibition) and reference maximum inhibition (10 µM Iptacopan, 100 % inhibition) plate controls, and compound inhibition curves were fitted to a 4-parameter equation with variable slope to determine IC50 estimates. The results of the factor B biochemical ELISA assay are summarised in Table 1 below as IC50 values. Example No Factor B Example No Factor B Biochemical IC50 Biochemical IC50 1† ++ 9 ++ 2† ++ 10 +++ 3† +++ 11 ++++ 4 ++ 12 ++++ 6 +++ 13 ++++ 7 ++ 14 ++++ 8 +++ Table 1: Factor B Biochemical inhibitory potency (IC50 < 500 nM = ‘++++’, 500 nM-<1 µM = ‘+++’, 1-<3 µM = ‘++’, ≥3 µM = ‘+’. † Assay based on 20 nM FAC CVF:Bb complex.

Claims

Claims 1. A compound of Formula (I):
Figure imgf000173_0001
Formula (I) or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof; wherein: R1 is hydrogen; R2 is selected from hydrogen or a halo group; R3 is selected from hydrogen or a halo, -SO2NH2, or a C1-C8 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 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 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; R4 is selected from hydrogen or a halo, -OH, -NH2, -SO2NH2, or a C1-C8 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 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 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; R5 is selected from hydrogen or a halo group; R6 is selected from hydrogen or a halo, -R60 or -OR60 group, wherein R60 is selected from a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl or C3-C4 fluorocycloalkyl group; R7 and R8 are each independently selected from hydrogen or a fluoro 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 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 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 any hydrocarbyl group of R7 or R8 that is directly attached to the reminder of the molecule is a carbon atom; or R7 and R8 together with the carbon atom to which they are attached form a 3- to 10-membered cyclic group, such that each ring atom of the cyclic group that is directly attached to the carbon atom to which R7 and R8 are attached is a ring carbon atom, wherein the cyclic 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; or R3 and R7, or R4 and R7, together form a C1-C6 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 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 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 the hydrocarbylene group that is directly attached to the carbon atom to which R8 is attached is a carbon atom; X10 is N or CR10; X11 is N or CR11; X12 is N or CR12; X13 is N or CR13; no more than two of X10, X11, X12 and X13 are N; each R10, R11, R12 and R13 is independently selected from hydrogen or a halo, -OH, -SH, -NH2, -SO2NH2, 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 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 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; R18 and R19 are each independently selected from hydrogen or a fluoro 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 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 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 any hydrocarbyl group of R18 or R19 that is directly attached to the reminder of the molecule is a carbon atom; or R18 and R19 together with the carbon atom to which they are attached form a 3- to 10-membered cyclic group, such that each ring atom of the cyclic group that is directly attached to the carbon atom to which R18 and R19 are attached is a ring carbon atom, wherein the cyclic 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; or R18 and R19 together with the carbon atom to which they are attached form a C=O group; and R20 and R21 are each independently selected from hydrogen or a fluoro group, or R20 and R21 together with the carbon atom to which they are attached form a C=O group.
2. A compound as claimed in claim 1, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, wherein R2 is selected from hydrogen or a fluoro, chloro or bromo group.
3. A compound as claimed in claim 1 or claim 2, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, wherein R3 is selected from hydrogen or a fluoro, chloro, bromo, -R30, -CN, -CHO, -COR30, -CO2H or -CO2R30 group, wherein R30 is selected from a C1-C6 alkyl, C1-C6 fluoroalkyl, C2-C6 alkenyl, C2-C6 fluoroalkenyl or -R31 group, wherein R31 is a 3- to 6-membered monocyclic group, wherein the 3- to 6- membered monocyclic group may optionally be substituted with one or more fluoro, chloro and/or bromo groups, and/or with one or two groups R32, wherein each R32 is independently selected from a methyl or a fluoromethyl group, provided that the group R3, including any optional substituents, contains no more than 8 carbon atoms.
4. A compound of Formula (II):
Figure imgf000176_0001
Formula (II) or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof; wherein: R1 is hydrogen; R4 is selected from hydrogen or a halo, -OH, -NH2, -SO2NH2, or a C1-C8 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 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 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; R5 is selected from hydrogen or a halo group; R6 is selected from hydrogen or a halo, -R60 or -OR60 group, wherein R60 is selected from a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl or C3-C4 fluorocycloalkyl group; R7 and R8 are each independently selected from hydrogen or a fluoro 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 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 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 any hydrocarbyl group of R7 or R8 that is directly attached to the reminder of the molecule is a carbon atom; or R7 and R8 together with the carbon atom to which they are attached form a 3- to 10-membered cyclic group, such that each ring atom of the cyclic group that is directly attached to the carbon atom to which R7 and R8 are attached is a ring carbon atom, wherein the cyclic 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; X10 is N or CR10; X11 is N or CR11; X12 is N or CR12; X13 is N or CR13; no more than two of X10, X11, X12 and X13 are N; each R10, R11, R12 and R13 is independently selected from hydrogen or a halo, -OH, -SH, -NH2, -SO2NH2, 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 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 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; each R14 and R15 is independently selected from hydrogen or a C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl or C3-C4 fluorocycloalkyl group, or R14 and R15 together with the carbon atom to which they are attached form a 3- to 6-membered cyclic group, wherein the cyclic group may optionally be substituted with one or more substituents each independently selected from a fluoro, -OH, oxo (=O), methyl or ethyl group, wherein any methyl or ethyl group may optionally be fluoro substituted; R16 is selected from hydrogen or a fluoro, -SO2NH2, or a C1-C8 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 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 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; R17 is selected from hydrogen or a fluoro, C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 fluoroalkyl or C3-C4 fluorocycloalkyl group; or R16 and R17 together with the carbon atom to which they are attached form a 3- to 6-membered cyclic group, wherein the cyclic group may optionally be substituted with one or more substituents each independently selected from a fluoro, -OH, oxo (=O), methyl or ethyl group, wherein any methyl or ethyl group may optionally be fluoro substituted; or R17 and R7, or R4 and R7, together form a C1-C6 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 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 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 the hydrocarbylene group that is directly attached to the carbon atom to which R8 is attached is a carbon atom; R18 and R19 are each independently selected from hydrogen or a fluoro 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 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 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 any hydrocarbyl group of R18 or R19 that is directly attached to the reminder of the molecule is a carbon atom; or R18 and R19 together with the carbon atom to which they are attached form a 3- to 10-membered cyclic group, such that each ring atom of the cyclic group that is directly attached to the carbon atom to which R18 and R19 are attached is a ring carbon atom, wherein the cyclic 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; or R18 and R19 together with the carbon atom to which they are attached form a C=O group; and R20 and R21 are each independently selected from hydrogen or a fluoro group, or R20 and R21 together with the carbon atom to which they are attached form a C=O group.
5. A compound as claimed in claim 4, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, wherein each R14 and R15 is independently selected from hydrogen or a C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group, or R14 and R15 together with the carbon atom to which they are attached form a cyclopropyl or a cyclobutyl group, wherein the cyclopropyl or cyclobutyl group may optionally be substituted with one or more fluoro groups.
6. A compound as claimed in claim 4 or claim 5, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, wherein: R16 is selected from hydrogen or a fluoro, -R160, -CN, -CHO, -COR160, -CO2H or -CO2R160 group, provided that R16, including any optional substituents, contains no more than 8 carbon atoms; R160 is selected from a C1-C6 alkyl, C1-C6 fluoroalkyl, C2-C6 alkenyl, C2-C6 fluoroalkenyl or -R161 group; R161 is a 3- to 6-membered monocyclic group, wherein the 3- to 6-membered monocyclic group may optionally be substituted with one or more fluoro, chloro and/or bromo groups, and/or with one or two groups R162; each R162 is independently selected from a methyl or a fluoromethyl group; and R17 is selected from hydrogen or a fluoro, C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group; or R16 and R17 together with the carbon atom to which they are attached form a 3- to 5-membered saturated monocyclic group wherein the saturated monocyclic group may optionally be substituted with one or more fluoro groups and/or one or two substituents each independently selected from oxo (=O) or a methyl or fluoromethyl group.
7. A compound as claimed in any one of claims 1 to 6, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, wherein: R4 is selected from a fluoro, chloro, bromo, -OH, -OR41, -N(R42)2, -SO2-R41, -SO2-N(R42)2, -L4-OH, -L4-OR41, -L4-N(R42)2, -L4-SO2-R41, -L4-SO2-N(R42)2, -O-L4-OH, -O-L4-OR41, -O-L4-N(R42)2, -O-L4-SO2-R41, -O-L4-SO2-N(R42)2, -NR43-L4-OH, -NR43-L4-OR41, -NR43-L4-N(R42)2, -NR43-L4-SO2-R41, -NR43-L4-SO2-N(R42)2, -SO2-L4-OH, -SO2-L4-OR41, -SO2-L4-N(R42)2, -R44, -R45 or -L4-R45 group, provided that R4, including any optional substituents, contains no more than 8 carbon atoms; R41 is selected from a -R44 or -R45 group; each R42 is independently selected from hydrogen or a -R44 or -R45 group, or any two R42 may, together with the nitrogen atom to which they are attached, form a 3- to 6-membered saturated monocyclic heterocyclic group, wherein the 3- to 6-membered saturated monocyclic heterocyclic group may optionally be substituted with one or two oxo (=O) groups and/or with one or more fluoro, methyl and/or fluoromethyl groups; L4 is a straight-chained alkylene group, wherein the straight-chained alkylene group optionally includes one or two heteroatoms each independently selected from O and N in its carbon skeleton, wherein L4 has a chain length of from 1 to 4 atoms, and wherein L4 may optionally be substituted with one or two oxo (=O) groups and/or with one or more groups RL4; each RL4 is independently selected from a fluoro, methyl or fluoromethyl group; or any RL4 and R41, or any RL4 and any R42, may together with the atoms to which they are attached, form a 3- to 6-membered saturated monocyclic heterocyclic group, wherein the 3- to 6-membered saturated monocyclic heterocyclic group may optionally be substituted with one or two oxo (=O) groups and/or with one or more fluoro, methyl and/or fluoromethyl groups; R43 is selected from hydrogen or a -R44 group; each R44 is independently selected from a C1-C4 alkyl or C3-C6 cycloalkyl group, wherein the C1-C4 alkyl or C3-C6 cycloalkyl group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups; and each R45 is independently selected from a phenyl or a 5- or 6-membered heteroaryl group, wherein the phenyl or the 5- or 6-membered heteroaryl group may optionally be substituted with one or more groups each independently selected from fluoro, chloro and bromo, and/or with one or two groups each independently selected from methyl (Me), -CN, -OH, -OMe, -NH2, -NHMe, and -NMe2, wherein any methyl group of R45 may optionally be fluoro substituted.
8. A compound as claimed in any one of claims 1 to 7, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, wherein R5 is selected from hydrogen or a fluoro, chloro or bromo group.
9. A compound as claimed in any one of claims 1 to 8, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, wherein: R6 is selected from a chloro, bromo, -R60 or -OR60 group; and R60 is selected from a C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group.
10. A compound as claimed in any one of claims 1 to 9, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, wherein: R7 is selected from hydrogen or a fluoro, -CN, -COOH, -COOR71, -CO-N(R72)2, -L7-COOH, -L7-COOR71, -L7-CO-N(R72)2, -L7-OH, -L7-OR71, -L7-N(R72)2, -R73, -R74 or -L7-R74 group, provided that R7, including any optional substituents, contains no more than 12 carbon atoms, and that the atom of R7 that is directly attached to the reminder of the molecule is a carbon, hydrogen or fluorine atom; R71 is selected from a -R73 or -R74 group; each R72 is independently selected from hydrogen or a -R73 or -R74 group, or any two R72 may, together with the nitrogen atom to which they are attached, form a 3- to 6- membered saturated monocyclic heterocyclic group, wherein the 3- to 6-membered saturated monocyclic heterocyclic group may optionally be substituted with one or two oxo (=O) groups and/or with one or more fluoro, methyl and/or fluoromethyl groups; L7 is a straight-chained alkylene or alkenylene group, wherein the straight- chained alkylene or alkenylene group optionally includes one or two heteroatoms each independently selected from O and N in its carbon skeleton, wherein L7 has a chain length of from 1 to 4 atoms, and wherein L7 may optionally be substituted with one or two oxo (=O) groups and/or with one or more groups RL7; each RL7 is independently selected from a fluoro, methyl or fluoromethyl group; or any two RL7 may, together with the atom or atoms to which they are attached, form a 3- to 6-membered monocyclic group, wherein the 3- to 6-membered monocyclic group is saturated or monounsaturated, and wherein the 3- to 6-membered monocyclic group may optionally be substituted with one or two oxo (=O) groups and/or with one or more fluoro, methyl and/or fluoromethyl groups; or any RL7 and R71, or any RL7 and any R72, may together with the atoms of the -L7-COOR71, -L7-CO-N(R72)2, -L7-OR71 or -L7-N(R72)2 group to which they are attached, form a 3- to 6-membered monocyclic heterocyclic group, wherein the 3- to 6- membered monocyclic heterocyclic group is saturated or monounsaturated, and wherein the 3- to 6-membered saturated monocyclic heterocyclic group may optionally be substituted with one or two oxo (=O) groups and/or with one or more fluoro, methyl and/or fluoromethyl groups; each R73 is independently selected from a C1-C4 alkyl, C2-C4 alkenyl, C3-C6 cycloalkyl or C5-C6 cycloalkenyl group, wherein the C1-C4 alkyl, C2-C4 alkenyl, C3-C6 cycloalkyl or C5-C6 cycloalkenyl group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups; each R74 is independently selected from a phenyl or a 5- or 6-membered heteroaryl group, wherein the phenyl or the 5- or 6-membered heteroaryl group may optionally be substituted with one or more groups each independently selected from fluoro, chloro and bromo, and/or with one or two groups each independently selected from methyl (Me), -CN, -OH, -OMe, -NH2, -NHMe, and -NMe2, wherein any methyl group of R74 may optionally be fluoro substituted; and R8 is selected from a hydrogen or a fluoro, methyl or fluoromethyl group; or R7 and R8 together form a group -L78-, wherein -L78- is selected from a -CH2-CH2-, -CH2-CH2-CH2-, -CH2-NH-CH2-, -CH2-O-CH2-, -CH2-CH2-CH2-CH2-, -CH2-CH2-NH-CH2-, -CH2-CH2-O-CH2-, -CH2-NH-CH2-CH2- or -CH2-O-CH2-CH2- group, wherein -L78- may optionally be substituted with one or more fluoro groups and/or one or two substituents each independently selected from an oxo (=O), -CN, methyl (Me), -OH, -OMe, -NH2, -NHMe or -NMe2 group, and wherein any methyl group of a -L78- substituent may optionally be fluoro substituted.
11. A compound as claimed in any one of claims 1 to 10, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, wherein: X10 is N or CR10; X11 is CR11 and X12 is CR12, or X11 is CR11 and X12 is N, or X11 is N and X12 is CR12; X13 is N or CR13; and no more than one of X10, X11, X12 and X13 is N.
12. A compound as claimed in any one of claims 1 to 11, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, wherein: one of R11 and R12 is present and selected from a fluoro, chloro, bromo, fluoromethyl, methoxy, fluoromethoxy, -CH2OH, -CN, -COOH, -CONH2 or -C(=NH)NH2 group; and one remaining R10, R11, R12 or R13 is independently selected from hydrogen or a fluoro, chloro, bromo, -OH, -SH, -NH2, -SO2NH2, or a C1-C10 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 fluoro, chloro and/or bromo groups, wherein the hydrocarbyl group may optionally include one, two, three, four, five or six heteroatoms each independently selected from N, O and S in its carbon skeleton, and wherein one -S- moiety 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 if present each further remaining R10, R11, R12 or R13 is independently selected from hydrogen or a fluoro, chloro or bromo group.
13. A compound as claimed in any one of claims 1 to 12, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, wherein: R18 is selected from hydrogen or a fluoro, -CN, -COOH, -COOR181, -CO-N(R182)2, -L18-COOH, -L18-COOR181, -L18-CO-N(R182)2, -L18-OH, -L18-OR181, -L18-N(R182)2, -R183, -R184 or -L18-R184 group, provided that R18, including any optional substituents, contains no more than 12 carbon atoms, and that the atom of R18 that is directly attached to the reminder of the molecule is a carbon, hydrogen or fluorine atom; and R19 is selected from a hydrogen or a fluoro, methyl or fluoromethyl group; or R18 and R19 together with the carbon atom to which they are attached form a C=O group; R181 is selected from a -R183 or -R184 group; each R182 is independently selected from hydrogen or a -R183 or -R184 group, or any two R182 may, together with the nitrogen atom to which they are attached, form a 3- to 6-membered saturated monocyclic heterocyclic group, wherein the 3- to 6- membered saturated monocyclic heterocyclic group may optionally be substituted with one or two oxo (=O) groups and/or with one or more fluoro, methyl and/or fluoromethyl groups; L18 is a straight-chained alkylene, alkenylene or alkynylene group, wherein the straight-chained alkylene, alkenylene or alkynylene group optionally includes one or two heteroatoms each independently selected from O and N in its carbon skeleton, wherein the straight-chained alkylene, alkenylene or alkynylene group has a chain length of from 1 to 4 atoms, and wherein the straight-chained alkylene, alkenylene or alkynylene group may optionally be substituted with one or two oxo (=O) groups and/or with one or more groups RL18; each RL18 is independently selected from a fluoro, methyl or fluoromethyl group; or any two RL18 may together with the atom or atoms to which they are attached form a 3- to 6-membered monocyclic group, wherein the 3- to 6-membered monocyclic group is saturated or monounsaturated, and wherein the 3- to 6-membered monocyclic group may optionally be substituted with one or two oxo (=O) groups and/or with one or more fluoro, methyl and/or fluoromethyl groups; or any RL18 and R181, or any RL18 and any R182, may together with the atoms of the -L18-COOR181, -L18-CO-N(R182)2, -L18-OR181 or -L18-N(R182)2 group to which they are attached, form a 3- to 6-membered monocyclic heterocyclic group, wherein the 3- to 6- membered monocyclic heterocyclic group is saturated or monounsaturated, and wherein the 3- to 6-membered monocyclic heterocyclic group may optionally be substituted with one or two oxo (=O) groups and/or with one or more fluoro, methyl and/or fluoromethyl groups; or L18 is a divalent phenyl or a divalent 5- or 6-membered heteroaryl group, wherein the divalent phenyl or the divalent 5- or 6-membered heteroaryl group may optionally be substituted with one or more groups each independently selected from fluoro, chloro, bromo, methyl and fluoromethyl; each R183 is independently selected from a C1-C4 alkyl, C2-C4 alkenyl, C3-C6 cycloalkyl or C5-C6 cycloalkenyl group, wherein the C1-C4 alkyl, C2-C4 alkenyl, C3-C6 cycloalkyl or C5-C6 cycloalkenyl group may optionally be substituted with one or more fluoro groups and/or one or two oxo (=O) groups; and each R184 is independently selected from a phenyl or a 5- or 6-membered heteroaryl group, wherein the phenyl or the 5- or 6-membered heteroaryl group may optionally be substituted with one or more groups each independently selected from fluoro, chloro and bromo, and/or with one or two groups each independently selected from methyl (Me), -CN, -OH, -OMe, -NH2, -NHMe, and -NMe2, wherein the methyl group of R184 may optionally be fluoro substituted.
14. A compound as claimed in any one of claims 1 to 13, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, wherein R20 and R21 are each independently selected from hydrogen or a fluoro group.
15. A compound as claimed in claim 1, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, wherein: R1 is hydrogen; R2 is hydrogen; R3 is selected from hydrogen or a fluoro, chloro or bromo group; R4 is selected from a fluoro, chloro, bromo, -R44 or -OR44 group; R44 is selected from a C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group; R5 is hydrogen; R6 is a methyl or a fluoromethyl group; R7 is selected from hydrogen or a fluoro, -L71-COOH, -L71-COOR75, -L71-OH, -L71-OR75 or -R75 group; -L71- is selected from a -CH2-, -CHMe- or -CMe2- group, wherein any -CH2-, -CHMe- or -CMe2- group may optionally be fluoro substituted; R75 is selected from a C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group; R8 is selected from a hydrogen or a fluoro, methyl or fluoromethyl group;
Figure imgf000186_0001
no more than one of X10 and X13 is N; R18 and R19 are each independently selected from hydrogen or a fluoro, methyl or fluoromethyl group, or R18 and R19 together with the carbon atom to which they are attached form a C=O group; and R20 and R21 are both hydrogen.
16. A compound as claimed in claim 4, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, wherein: R1 is hydrogen; R4 is selected from a fluoro, chloro, bromo, -R44 or -OR44 group; R44 is selected from a C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group; R5 is hydrogen; R6 is a methyl or a fluoromethyl group; R7 is selected from hydrogen or a fluoro, -L71-COOH, -L71-COOR75, -L71-OH, -L71-OR75 or -R75 group; -L71- is selected from a -CH2-, -CHMe- or -CMe2- group, wherein any -CH2-, -CHMe- or -CMe2- group may optionally be fluoro substituted; R75 is selected from a C1-C3 alkyl, cyclopropyl, C1-C3 fluoroalkyl or fluorocyclopropyl group; R8 is selected from a hydrogen or a fluoro, methyl or fluoromethyl group; X10 is N, C-H, C-F, C-Cl or C-Br;
Figure imgf000186_0002
no more than one of X10 and X13 is N; R14 and R15 are both hydrogen; R16 and R17 are both hydrogen; R18 and R19 are each independently selected from hydrogen or a fluoro, methyl or fluoromethyl group, or R18 and R19 together with the carbon atom to which they are attached form a C=O group; and R20 and R21 are both hydrogen. A compound selected from the group consisting of:
Figure imgf000187_0001
or a pharmaceutically acceptable salt and/or solvate and/or prodrug of the selected compound. 18. 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 17, and a pharmaceutically acceptable excipient. 19. A compound, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, as claimed in any one of claims 1 to 17, or a pharmaceutical composition as claimed in claim 18, for use in medicine. 20. A compound, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, as claimed in any one of claims 1 to 17, or a pharmaceutical composition as claimed in claim 18, for use in the treatment or prevention of a disease, disorder or condition, wherein the disease, disorder or condition is responsive to Factor B inhibition. 21. A compound, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, or a pharmaceutical composition, as claimed in claim 19 or claim 20, for use in the treatment or prevention of a disease, disorder or condition, wherein the disease, disorder or condition is selected from: (i) an ocular disease, disorder or condition; (ii) a haematological disease, disorder or condition; (iii) a renal disease, disorder or condition; (iv) a respiratory disease, disorder or condition; (v) a central nervous system disease, disorder or condition; (vi) a cardiovascular disease, disorder or condition; (vii) a reproductive disease, disorder or condition; (viii) a metabolic disease, disorder or condition; (ix) a cancer; (x) an auto-immune disease, disorder or condition; (xi) a musculoskeletal disease, disorder or condition; (xii) antiphospholipid syndrome; (xiii) a skin disease, disorder or condition; (xiv) hemodialysis; or (xv) any disease where an individual has been determined to carry a germline or somatic non-silent mutation in Factor B. 22. A compound, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, or a pharmaceutical composition, as claimed in claim 19 or claim 20, for use in the treatment or prevention of a disease, disorder or condition, wherein the disease, disorder or condition is selected from: (i) acute kidney injury; (ii) age-related macular degeneration; (iii) airway hyperresponsiveness with inflammation; (iv) Alzheimer’s disease; (v) amyotrophic lateral sclerosis; (vi) ANCA vasculitis; (vii) antiphospholipid syndrome; (viii) aortic stenosis; (ix) atypical hemolytic uremic syndrome; (x) acquired partial lipodystrophy; (xi) acquired thrombotic thrombocytopenic purpura; (xii) bullous pemphigoid; (xiii) C3 glomerulopathy; (xiv) immune complex-mediated membranoproliferative glomerulonephritis (IC- MPGN) (xv) cardiac ischemia and reperfusion; (xvi) cardiac remodelling; (xvii) cardiometabolic disease; (xviii) coeliac disease; (xix) cold agglutinin disease; (xx) a respiratory condition caused by SARs Cov-2; (xxi) diabetic kidney disease; (xxii) diabetic retinopathy; (xxiii) Doyne honeycomb retinal dystrophy, also known as malattia leventinese (DHRD/ML); (xxiv) focal segmental glomerulosclerosis (FSGS); (xxv) glomerular sclerosis; (xxvi) Guillian-Barré syndrome; (xxvii) heart failure; (xxviii) hemodialysis; (xxix) idiopathic thrombocytopenic purpura (ITP); (xxx) idiopathic pulmonary fibrosis; (xxxi) IgA nephropathy; (xxxii) ischemic stroke; (xxxiii) systemic lupus erythematosus; (xxxiv) lupus nephritis (xxxv) lupus cerebritis; (xxxvi) malignant nephrosclerosis; (xxxvii) multiple sclerosis; (xxxviii) myasthenia gravis; (xxxix) neuromyelitis optica; (xl) non-infectious uveitis; (xli) osteoarthritis; (xlii) pancreatic cancer; (xliii) paroxysmal nocturnal hemoglobinuria (PNH); (xliv) photocarcinogenesis; (xlv) postinfectious glomerulonephritis; (xlvi) pre-eclampsia; (xlvii) membranous nephropathy; (xlviii) renal allograft; (xlix) retinal detachment; (l) retinal ischemia reperfusion; (li) rheumatoid arthritis; (lii) schizophrenia; (liii) a delayed hemolytic transfusion reaction (DHTR) in an individual suffering from sickle cell disease; (liv) a vaso-occlusive crisis in sickle cell disease; (lv) spinal cord injury; (lvi) squamous cell carcinoma; (lvii) thrombotic microangiopathy (TMA)-mediated acute kidney injury (AKI); (lviii) transplant-associated thrombotic microangiopathy; or (lix) traumatic brain injury. 23. A method of inhibiting Factor B, the method comprising the use of a compound, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, as claimed in any one of claims 1 to 17, or a pharmaceutical composition as claimed in claim 18, to inhibit Factor B. 24. A method of synthesising a compound, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, as claimed in claim 1, the method comprising the steps of: (i) reacting a compound of Formula (SM-1) with a compound of Formula (SM-2) to produce an intermediate of Formula (It-1):
Figure imgf000191_0001
and (ii) deprotecting the intermediate of Formula (It-1) to produce a compound of Formula (I), or a pharmaceutically acceptable salt and/or solvate thereof:
Figure imgf000191_0002
wherein: RP is a nitrogen protecting group; RL is a leaving group; and R1 to R8, R18 to R21, and X10 to X13 are as defined in accordance with claim 1. 25. A method of synthesising a compound, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, as claimed in claim 4, the method comprising the steps of: (i) reacting a compound of Formula (SM-3) with a compound of Formula (SM-2) to produce an intermediate of Formula (It-2):
Figure imgf000192_0001
and (ii) deprotecting the intermediate of Formula (It-2) to produce a compound of Formula (II), or a pharmaceutically acceptable salt and/or solvate thereof:
Figure imgf000192_0002
wherein: RP is a nitrogen protecting group; RL is a leaving group; and R1, R4 to R8, R14 to R21, and X10 to X13 are as defined in accordance with claim 4. 26. A method of synthesising a compound, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, as claimed in claim 1, the method comprising the step of: (i) performing a reductive amination on a compound of Formula (SM-4) with a compound of Formula (SM-2) to produce a compound of Formula (P-4) or a pharmaceutically acceptable salt and/or solvate thereof:
Figure imgf000193_0001
wherein: RX is selected from hydrogen or RP; RP is a nitrogen protecting group; and R2 to R7, R18 to R21, and X10 to X13 are as defined in accordance with claim 1. 27. A method of synthesising a compound, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, as claimed in claim 4, the method comprising the step of: (i) performing a reductive amination on a compound of Formula (SM-5) with a compound of Formula (SM-2) to produce a compound of Formula (P-5) or a pharmaceutically acceptable salt and/or solvate thereof: wherein: RX is selected from hydrogen or RP; RP is a nitrogen protecting group; and R4 to R7, R14 to R21, and X10 to X13 are as defined in accordance with claim 4. 28. A method of synthesising a compound, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, as claimed in claim 1, the method comprising the step of: (i) reacting a compound of Formula (SM-6) with a compound of Formula (SM-2) to produce a compound of Formula (P-6) or a pharmaceutically acceptable salt and/or solvate thereof:
Figure imgf000194_0001
wherein: RX is selected from hydrogen or RP; RP is a nitrogen protecting group; R76 is selected from hydrogen or a fluoro 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 wherein the saturated hydrocarbyl group may optionally include a single heteroatom selected from N and O in its carbon skeleton; R77 is selected from hydrogen, -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 wherein the saturated hydrocarbyl group may optionally include a single heteroatom selected from N and O in its carbon skeleton; and R2 to R6, R8, R18 to R21, and X10 to X13 are as defined in accordance with claim 1. 29. A method of synthesising a compound, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, as claimed in claim 4, the method comprising the step of: (i) reacting a compound of Formula (SM-7) with a compound of Formula (SM-2) to produce a compound of Formula (P-7) or a pharmaceutically acceptable salt and/or solvate thereof:
Figure imgf000195_0001
Formula (SM-7) Formula (P-7) wherein: RX is selected from hydrogen or RP; RP is a nitrogen protecting group; R76 is selected from 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 wherein the saturated hydrocarbyl group may optionally include a single heteroatom selected from N and O in its carbon skeleton; R77 is selected from hydrogen, -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 wherein the saturated hydrocarbyl group may optionally include a single heteroatom selected from N and O in its carbon skeleton; and R4 to R6, R8, R14 to R21, and X10 to X13 are as defined in accordance with claim 4. 30. A method of synthesising a compound, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, as claimed in claim 4, the method comprising the step of: (i) reducing a compound of Formula (SM-8) to provide a compound of Formula (P-8), or a pharmaceutically acceptable salt and/or solvate thereof:
Figure imgf000196_0001
wherein: RX is selected from hydrogen or RP; RP is a nitrogen protecting group; R2 to R8, R18 to R21 and X10 to X13 are as defined in accordance with claim 1; and R14 to R17 are as defined in accordance with claim 4. 31. A method of synthesising a compound, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, as claimed in claim 1, the method comprising the step of: (i) reacting a compound of Formula (SM-9) with a compound of Formula (SM-10) to produce a compound of Formula (P-9) or a pharmaceutically acceptable salt and/or solvate thereof:
Figure imgf000197_0001
wherein: RX is selected from hydrogen or RP; RP is a nitrogen protecting group; RL1 is a leaving group; RL2 is a leaving group; and R2 to R8, R20, R21, and X10 to X13 are as defined in accordance with claim 1. 32. A method of synthesising a compound, or a pharmaceutically acceptable salt and/or solvate and/or prodrug thereof, as claimed in claim 4, the method comprising the step of: (i) reacting a compound of Formula (SM-11) with a compound of Formula (SM-10) to produce a compound of Formula (P-10) or a pharmaceutically acceptable salt and/or solvate thereof: wherein: RX is selected from hydrogen or RP; RP is a nitrogen protecting group; RL1 is a leaving group; RL2 is a leaving group; and R4 to R8, R14 to R17, R20, R21, and X10 to X13 are as defined in accordance with claim 4.
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