Triazinone derivatives for use in the treatment of inflammation

Abstract

There is provided herein a compound of formula I, wherein R1 and R2 are as defined herein, or a pharmaceutically acceptable salt thereof, for use in the treatment and / or prevention of inflammation.

Description

TRIAZINONE DERIVATIVES FOR USE IN THE TREATMENT OF INFLAMMATIONField of the InventionThe invention relates to a new medical use of known compounds. In particular, the invention relates to the use of positive modulators of Trk receptor signalling in the treatment of inflammation, such as inflammation associated with neurodegenerative disorders.Background of the InventionThe listing or discussion of an apparently prior-published document in this specification should not necessarily be taken as an acknowledgement that the document is part of the state of the art or is common general knowledge.Inflammation is a complex biological response of tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. It is a crucial part of the body's immune response, involving various cellular and molecular processes aimed at removing the harmful microscopic or macroscopic injury and initiating tissue repair. The immune response to an inflammation is generally divided into an innate and adaptive immune response (Bennett et al., Front. Med.

[2018] , 316). While normal acute inflammation is a beneficial and protective response, excessive acute or chronic inflammation(Ibid.) can lead to tissue damage and various diseases, such as autoimmune disorders (Xiang et al., Front. Immunol.

[2023] , 1267091), or exacerbate other disease, including neurodegenerative diseases such as Alzheimer's disease (Heneka et al., Lancet Neurol.

[2015] , 388-405) (Latta, Brothers, and Wilcock, Neuroscience

[2015] , 103-11) (Thakur et al., Inflammation

[2023] , l-17)and Parkinson's disease (Tansey et al., Nat. Rev. Immunol.

[2022] , 657-73).The innate immune system is responsible for the immediate fist-line of defense inflammatory response characterized by the well-known Celsus tetrad of inflammation including the clinical symptoms calor (warmth), rubor (redness), dolor (pain) and tumor (swelling) of inflammation. Neutrophils are among the first responders in the innate immune response, followed by monocytes, which differentiate into macrophages upon entering the inflamed tissue. These immune cells phagocytose pathogens and cellular debris and release additional inflammatory mediators to amplify the inflammatory response. The inflammatory mediators include growth factors, cytokines (including the interleukins, such as interleukin-1 (IL-1) (alpha and beta), IL-4, IL-6,IL-10, IL-11, IL-12, IL-13, interferons (INF) such as INF-gamma, and tumor necrosis factor alpha), chemokines, and eicosanoids, which orchestrate the recruitment of immune cells to the site of inflammation. The adaptive or acquired immune system is the second line of defense and involves, white blood cells such as B- and T- lymphocytes. B-lymphocytes secrete immunoglobulins, including immunoglobulin G (IgG), and cytokines whereas T-lymphocytes orchestrate inflammatory responses via cytokine secretion and interaction with antigen presenting cells.In general, there is a large need for new anti-inflammatory treatments in many therapeutic areas(Kapur, Watson, and Carr, Allergy, Asthma Clin. Immunol.

[2018] , 52) (McCarberg and Gibofsky, Clin. Ther.

[2012] , 1954-63) (Garth, Barnes, and Krick, Int. J. Moi. Sci.

[2018] , 3402) that lack the gastrointestinal side effect like the ulcerogenic properties observed for non-steroidal anti-inflammatory drugs (NSAIDs), the cardiovascular side effects reported for cyclooxygenase-2 (COX-2) selective inhibitors or the side effects observed for corticosteroids including osteoporosis, fluid retention, fatigue, loss of appetite, effects on cognition and problems with changes in mood or other negative neuropsychiatric effects.Neurotrophins are a family of proteins that play essential roles in the development, survival, and function of neurons in the central and peripheral nervous systems. The neurotrophins include nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 / 5 (NT-4 / 5). In addition to their canonical functions in neuronal survival and differentiation, emerging evidence suggests that neurotrophins also participate in the regulation of inflammatory processes (Skaper, Immunology

[2017] , l-15)(Minnone, Benedetti, and Bracci- Laudiero, Int J Mol Sci

[2017] , 18051028) In particular, activation of the TrkA receptor by NGF has been shown to have a pro-inflammatory effect. Neurotrophins exert their effects on inflammation through various mechanisms, including modulation of immune cell function, regulation of cytokine production, and interaction with other inflammatory mediators (Minnone, Benedetti, and Bracci-Laudiero, Int J Mol Sci

[2017] , 18051028)Neuroinflammation , or central inflammation, refers to inflammation that occurs within the central nervous system (CNS), i.e. the brain or spinal cord, and is associated with various neurological disorders, such as Alzheimer's disease (Heneka, Carson, Khoury, Landreth, Brosseron, Feinstein, Jacobs, The Lancet Neurology,

[2015] ), 388-405 (Latta, Brothers, and Wilcock, Neuroscience

[2015] , 103-111) and Parkinson's disease (Tansey, Wallings, Houser, Herrick, Keating, and Joers, Nature Reviews Immunology

[2022] 657-73). In neuroinflammatory conditions, neurotrophins, particularly NGF andBDNF, have been shown to influence the activity of microglia, the resident immune cells of the CNS, as well as infiltrating immune cells. For example, NGF can stimulate the production of pro-inflammatory cytokines by microglia, contributing to neuronal damage in neurodegenerative diseases. It has been shown that both systemic (Holmes and Butchart, Biochem. Soc. Trans.

[2011] , 898-901) (Walker, Ficek, and Westbrook, ACS Chem. Neurosci.

[2019] , 3340-42) and central (Heneka, Carson, Khoury, Landreth, Brosseron, Feinstein, Jacobs, The Lancet Neurology,

[2015] , 388-405) can contribute to Alzheimer's disease. Systemic inflammation or a chronic peripheral inflammation most likely leads to an exaggerated central immune response via proinflammatory cytokines that cross the blood brain barrier (Walker, Ficek, and Westbrook. ACS Chemical Neuroscience,

[2019] 3340-3342.Other central indications in which neurotrophins are believed to have inflammatory effects include myalgic encephalomyelitis / chronic fatigue syndrome (Jonsjb et al., Psychoneuroendocrinology

[2020] , 104578), meningitis (Morichi, Kashiwagi, Takekuma, Hoshika, and Kawashima, International Journal of Neuroscience,

[2012] 17-23) (Tokunaga et al., Pediatric Neurology

[2002] , 102-5) (Kizawa-Ueda et al., Eur Neurol

[2011] , 138-43), autoimmune neuroinflammatory diseases (Wang and Tian, Exp Ther Med

[2021] , 1292), encepahalitis, myelitis and encephalomyelitis (Morichi, Kashiwagi, Takekuma, Hoshika, and Kawashima, International Journal of Neuroscience

[2012] 17-23), (Tokunaga et al., Pediatric Neurology

[2002] , 102-5) (Kizawa-Ueda et al., Eur Neurol

[2011] , 138-43)(Nikpour et al., Acta Neurol Belg

[2024] , 533-42), sequelae of inflammatory diseases of the central nervous system, stroke (Berretta, Tzeng, and Clarkson,

[2014] , vascular dementia, traumatic brain injury (Sims et al., Neural Plast

[2022] , 3889300), cerebral amyloid angiopathy and chronic traumatic encephalopathy.In addition to their role in neuroinflammation, neurotrophins have been implicated in many peripheral inflammatory conditions, such as arthritis (Pecchi et al., Arthritis Res. Ther.

[2014] , R16), asthma (Bonini et al., Proc Natl Acad Sci U S A

[1996] , 10955- 60), cystitis (Hsiang et al., Front Urol

[2022] ; Hsiang, Girard, and Vizzard, Front. Urol.

[2023] , 1089220), , inflammatory skin disorders (Botchkarev et al., Journal of Investigative Dermatology

[2006] , 1719-27; Peters et al.

[2011] , 735-43) (including atopic dermatitis (Weihrauch et al., Int J Mol Sci

[2023] ), psoriasis (Xiang, Zhang, Jiang, Su, and Shi. Frontiers in Immunology,

[0023] 1267091), dermatitis and eczema (Weihrauch et al., Int J Mol Sci

[2023] ),, and pruritis (Ruppenstein et al., Front. Med.

[2021] , 627985)), inflammatory disorders of the peripheral nervous system, inflammatory respiratory disorders (including allergic rhinitis (Bonini, Lambiase,Bonini, Angelucci, Magrini, Manni, and Aloe. Proc Natl Acad Sci USA,

[1996] 10955- 60), allergic airway inflammation (Hahn et al., J Allergy Clin Immunol

[2006] , 787- 94), acute upper and lower respiratory infections diseases (Harford et al., Am J Physiol Lung Cell Mol Physiol, 2021; Othumpangat, Regier, and Piedimonte, Am J Physiol Lung Cell Mol Physiol

[2012] , L1057-66; Othumpangat et al., PLoS One

[2009] , e6444), and chronic lower respiratory diseases including asthma (Bonini, Lambiase, Bonini, Angelucci, Magrini, Manni, and Aloe. Proc Natl Acad Sci USA,

[1996] 10955-60)., inflammatory bowel diseases (Di, Friess, Zhu, Koliopanos, Bley, Di, Innocenti, Zimmermann, and Buehler, Gut

[2000] , 670-79), cystitis and interstitial cystitis Hsiang, Girard, Ratkovits, Campbell, and Vizzard. Front Urol

[2022] 1037511)., systemic lupus erythematosus (Tian et al., Cytokine

[2019] , 154764)' (Bracci-Laudiero et al., NeuroReport

[1993] , 563-65). In these conditions, neurotrophins can influence the function of immune cells, including mast cells, T cells, and macrophages, as well as sensory neurons that innervate the inflamed tissues. For instance, NGF has been shown to promote mast cell activation and degranulation, leading to the release of pro- inflammatory mediators and exacerbation of inflammation in allergic disorders (Marshall, Gomi, Blennerhassett, and Bienenstock, The Journal of Immunology,

[1999] 4271)In summary, neurotrophins play diverse and complex roles in the regulation of inflammation across different tissues and disease states. While neurotrophins such as NGF and BDNF have traditionally been studied for their functions in neuronal development and survival, emerging evidence highlights their involvement in modulating immune responses, cytokine production, and tissue repair processes associated with inflammation.However, the exact effects of neurotrophins on inflammation can be difficult to interpret. As mentioned above, NGF is largely associated with pro-inflammatory effects, through its action on the TrkA receptor, and can be used in induce inflammation in animal models, and BDNF a has also been shown to have pro-inflammatory effects. However, there also some evidence neurotrophins having anti-inflammatory effects in several models such as in microglia (Rizzi et al., Glia

[2018] , 1395-1416; Tiberi, Capsoni, and Cattaneo, Cells

[2022] , 1835), astrocytes (Tiberi et al., Frontiers in Cell and Developmental Biology

[2023] ) and monocytes (Flugel et al., European Journal of Immunology

[2001] , 11-22).Triazinane-trione compounds with activity as positive modulators of tropomyosin receptor kinase (Trk) receptors, including TrkA, TrkB and TrkC, are described inWO2019 / 162702, WO 2020 / 002950 and WO 2021 / 038241. Positive modulation of these receptors is believed to lead to beneficial effects in a range of disorders. In particular, TrkA and TrkB, and their natural ligands nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are involved in a range of processes in the central nervous system, and upregulation of these signalling pathways is expected to improve cognitive function and have neuroprotective and neurorestorative effects beneficial in the treatment of neurodegenerative and mood disorders. The same signalling pathways have also been associated with glucose metabolism, leading to potential utility in the treatment of disorders such as diabetes, metabolic syndrome and obesity.However, positive modulators of Trk receptors have not previously been described as having anti-inflammatory activity.Detailed Description of the InventionIt has now surprisingly been found that certain triazinane-trione positive modulators TrkA, TrkB and TrkC described in WO2019 / 162702, WO 2020 / 002950 and WO 2021 / 038241 have a range of anti-inflammatory effects in animal models, including reducing levels of the pro-inflammatory mediators interleukin-6 (IL-6) and immunoglobulin G (IgG) in the brains and plasma of aged and APPNL G Fknock-in mice, reducing IgG levels in the plasma and liver of obese mice, reducing the diameter of the knee joint in an arthritis model and reducing NGF-induced inflammation in a mouse model, and thus have properties rendering them useful for the treatment and / or prevention of inflammation.These results suggest a likely effect on inflammation caused by, or otherwise associated with a wide range of indications, including inflammatory disorders, such as arthritis and the inflammation associated with neurodegenerative disorders, such as Alzheimer's disease.The compounds' effects on inflammatory mediators are highly surprising in view of the known pro-inflammatory effects of neurotrophins and Trk (in particular TrkA) receptor signalling.Compounds of the inventionIn a first aspect of the invention, there is provided a compound of formula Ior a pharmaceutically-acceptable salt thereof, wherein:R1is selected from the group consisting of a phenyl group and a benzofuranyl group, which phenyl and benzofuranyl groups are optionally substituted by one or more groups selected from halo, methyl, methoxy and methoxymethyl; andR2is selected from the group consisting of a C1-2 alkyl group, a C1-2 alkoxy group, a Ci- 2 alkoxyCi-2 alkyl group, a C1-2 alkoxy-Ci-2 alkoxy group and -A-R3, whereinA is selected from the group consisting of a direct bond, a C1-2 alkanediyl group, and an -OC1-2 alkanediyl group, which C1-2 alkanediyl and -OC1-2 alkanediyl groups are optionally substituted by one or more groups independently selected from fluoro and =0; andR3represents a 5-membered heteroaryl group selected from the group consisting of pyrazolyl, triazolyl and imidazolyl, which three groups are optionally substituted by one or more groups independently selected from fluoro, C1-2 alkyl and C1-2 fluoroalkyl; or a pyrrolidinyl group, which pyrrolidinyl group is optionally substituted with a =0 group; or a pharmaceutically acceptable salt thereof, for use in the treatment and / or prevention of inflammation.Compounds of formula I (including pharmaceutically acceptable salts) may be referred to herein as the "compounds of the invention".In an alternative first aspect of the invention, there is provided a method of treating and / or preventing inflammation, comprising administering a therapeutically effective amount of a compound of formula I as defined herein, or a pharmaceutically acceptable salt thereof, to a subject in need thereof.In a further alternative first aspect of the invention, there is provided the use of a compound of formula I, or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for the treatment and / or prevention of inflammation.For the avoidance of doubt, the skilled person will understand that references herein to compounds of (particular aspects of) the invention (such as the first aspect of the invention, i.e. referring to compounds of formula I as defined in the first aspect of the invention) will include references to all embodiments and particular features thereof, which embodiments and particular features may be taken in combination to form further embodiments and features of the invention.Unless indicated otherwise, all technical and scientific terms used herein will have their common meaning as understood by one of ordinary skill in the art to which this invention pertains.Pharmaceutically acceptable salts include acid addition salts and base addition salts. Such salts may be formed by conventional means, for example by reaction of a free acid or a free base form of a compound of the invention with one or more equivalents of an appropriate acid or base, optionally in a solvent, or in a medium in which the salt is insoluble, followed by removal of said solvent, or said medium, using standard techniques (e.g. in vacuo, by freeze-drying or by filtration). Salts may also be prepared using techniques known to those skilled in the art, such as by exchanging a counterion of a compound of the invention in the form of a salt with another counter-ion, for example using a suitable ion exchange resin.Particular acid addition salts that may be mentioned include those formed by reaction with corresponding acids, thus protonating the compound of the invention, to form carboxylate salts (e.g. formate, acetate, trifluoroacetate, propionate, isobutyrate, heptanoate, decanoate, caprate, caprylate, stearate, acrylate, caproate, propiolate, ascorbate, citrate, glucuronate, glutamate, glycolate, a-hydroxybutyrate, lactate, tartrate, phenylacetate, mandelate, phenylpropionate, phenylbutyrate, benzoate, chlorobenzoate, methylbenzoate, hydroxybenzoate, methoxybenzoate, dinitrobenzoate, o-acetoxy-benzoate, salicylate, nicotinate, isonicotinate, cinnamate, oxalate, malonate, succinate, suberate, sebacate, fumarate, malate, maleate, hydroxymaleate, hippurate, phthalate or terephthalate salts), hydrogenhalide salts (e.g. hydrochloride, hydrobromide or hydroiodide salts), sulphonate salts (e.g. benzenesulphonate, methyl-, bromo- or chloro-benzenesulphonate, xylenesulphonate,methanesulphonate, ethanesulphonate, propanesulphonate, hydroxyethanesulphonate, 1- or 2- naphthalene-sulphonate or 1,5-naphthalene-disulphonate salts) or sulphate, pyrosulphate, bisulphate, sulphite, bisulphite, phosphate, monohydrogenphosphate, dihydrogenphosphate, metaphosphate, pyrophosphate or nitrate salts, and the like.Particular base addition salts that may be mentioned include salts formed by reaction with corresponding bases, thus removing a proton from compounds of the invention, to form salts with alkali metals (such as Na and K salts), alkaline earth metals (such as Mg and Ca salts), organic bases (such as ethanolamine, diethanolamine, triethanolamine and tromethamine) and inorganic bases (such as ammonia and aluminium hydroxide). More particularly, base addition salts that may be mentioned include Mg, Ca and, most particularly, K and Na salts.For the avoidance of doubt, compounds of the invention may exist as solids, and thus the scope of the invention includes all amorphous, crystalline and part crystalline forms thereof, and may also exist as oils. Where compounds of the invention exist in crystalline and part crystalline forms, such forms may include solvates, which are included in the scope of the invention.For the avoidance of doubt, compounds of the invention may also exist in solution (i.e. in solution in a suitable solvent). For example, compounds of the invention may exist in aqueous solution, in which case compounds of the invention may exist in the form of hydrates thereof.Compounds of the invention may contain double bonds and, unless otherwise indicated, may thus exist as E (entgegen) and Z zusammen) geometric isomers about each individual double bond. Unless otherwise specified, all such isomers and mixtures thereof are included within the scope of the invention.Compounds of the invention may also exhibit tautomerism. All tautomeric forms and mixtures thereof are included within the scope of the invention (particularly those of sufficient stability to allow for isolation thereof).Compounds of the invention may also contain one or more asymmetric carbon atoms and may therefore exhibit optical and / or diastereoisomerism (i.e. existing in enantiomeric or diastereomeric forms). Diastereoisomers may be separated using conventional techniques, e.g. chromatography or fractional crystallisation. The variousstereoisomers (i.e. enantiomers) may be isolated by separation of a racemic or other mixture of the compounds using conventional, e.g. fractional crystallisation or HPLC, techniques. Alternatively the desired enantiomer or diastereoisomer may be obtained from appropriate optically active starting materials under conditions which will not cause racemisation or epimerisation (i.e. a 'chiral pool' method), by reaction of the appropriate starting material with a 'chiral auxiliary' which can subsequently be removed at a suitable stage, by derivatisation (i.e. a resolution, including a dynamic resolution; for example, with a homochiral acid followed by separation of the diastereomeric derivatives by conventional means such as chromatography), or by reaction with an appropriate chiral reagent or chiral catalyst, all of which methods and processes may be performed under conditions known to the skilled person. Unless otherwise specified, all stereoisomers and mixtures thereof are included within the scope of the invention.For the avoidance of doubt, the skilled person will understand that where a particular group is depicted herein as being bound to a ring system via a floating bond (i.e. a bond not shown as being bound to a particular atom within the ring), the relevant group may be bound to any suitable atom within the relevant ring system (i.e. the ring within which the floating bond terminates).Unless otherwise specified, Ci-z alkyl groups (where z is the upper limit of the range) defined herein may be straight-chain or, when there is a sufficient number (i.e. a minimum of two or three, as appropriate) of carbon atoms, be branched-chain, and / or cyclic (so forming a Cs-z cycloalkyl group). When there is a sufficient number (i.e. a minimum of four) of carbon atoms, such groups may also be part cyclic (so forming a C4-z partial cycloalkyl group). For example, cycloalkyl groups that may be mentioned include cyclopropyl, cyclopentyl and cyclohexyl. Similarly, part cyclic alkyl groups (which may also be referred to as "part cycloalkyl" groups) that may be mentioned include cyclopropylmethyl. When there is a sufficient number of carbon atoms, such groups may also be multicyclic (e.g. bicyclic or tricyclic) and / or spirocyclic. For the avoidance of doubt, particular alkyl groups that may be mentioned include straight chain (i.e. not branched and / or cyclic) alkyl groups.Similarly, unless otherwise specified, Ci-z alkoxy groups (-OCi-z alkyl groups) (where z is the upper limit of the range) defined herein may be straight-chain or, when there is a sufficient number (i.e. a minimum of two or three, as appropriate) of carbon atoms, be branched-chain, and / or cyclic (so forming a -OC3-Z cycloalkoxy group). When there is a sufficient number (i.e. a minimum of four) of carbon atoms, such groups may alsobe part cyclic (so forming a -OC4-Zpartial cycloalkoxy group). For example, cycloalkyloxy groups that may be mentioned include cyclopropoxy, cyclopentoxy and cyclohexoxy. Similarly, part cyclic alkoxy groups (which may also be referred to as "part cycloalkoxy" groups) that may be mentioned include cyclopropylmethoxy. When there is a sufficient number of carbon atoms, such groups may also be multicyclic (e.g. bicyclic or tricyclic) and / or spirocyclic. For the avoidance of doubt, particular alkoxy groups that may be mentioned include straight chain (i.e. not branched and / or cyclic) alkoxy groups.For the avoidance of doubt, references to Ci-z alkoxy-Ci-z alkyl groups indicate an alkoxyalkyl group (i.e. -Ci-z alkyl-O-Ci-z alkyl groups) such as methoxymethyl groups. As for alkyl and alkoxy groups, unless otherwise specified such groups may be straightchain, or when there is a sufficient number of carbon atoms, be branched chain, cyclic and / or part cyclic.As used herein, the term 'alkanediyl' refers to a divalent alkyl (i.e. saturated hydrocarbon) group. Unless otherwise indicated, the two groups attached to an alkanediyl group may be attached to any of the carbon atoms of the alkanediyl group (including the same carbon). Examples of alkanediyl groups include methanediyl and ethanediyl.For the avoidance of doubt, as used herein, references to heteroatoms will take their normal meaning as understood by one skilled in the art. Particular heteroatoms that may be mentioned include phosphorus, selenium, tellurium, silicon, boron, oxygen, nitrogen and sulfur (e.g. oxygen, nitrogen and sulfur, such as oxygen and nitrogen).For the avoidance of doubt, the skilled person will understand that aryl groups that may form part of compounds of the invention are those that are chemically obtainable, as known to those skilled in the art. Particular aryl groups that may be mentioned include phenyl and naphthyl, such as phenyl.As may be used herein, references to heteroaryl (with may also be referred to as heteroaromatic) groups may refer to 5- to 14- (e.g. 5- to 10-) membered heteroaromatic groups containing one or more heteroatoms (such as one or more heteroatoms selected from oxygen, nitrogen and / or sulfur). Such heteroaryl groups may comprise one, two, or three rings, of which at least one is aromatic. Substituents on heteroaryl / heteroaromatic groups may, where appropriate, be located on any suitable atom in the ring system, including a heteroatom (e.g. on a suitable N atom).The point of attachment of heteroaryl / heteroaromatic groups may be via any atom in the ring system including (where appropriate) a heteroatom. Bicyclic heteroaryl / heteroaromatic groups may comprise a benzene ring fused to one or more further aromatic or non-aromatic heterocyclic rings, in which instances, the point of attachment of the polycyclic heteroaryl / heteroaromatic group may be via any ring including the benzene ring or the heteroaryl / heteroaromatic or heterocyclyl ring.For the avoidance of doubt, the skilled person will understand that heteroaryl groups that may form part of compounds of the invention are those that are chemically obtainable, as known to those skilled in the art. Various heteroaryl groups will be well- known to those skilled in the art, such as pyridinyl, pyrrolyl, furanyl, thiophenyl, oxadiazolyl, thiadiazolyl, thiazolyl, oxazolyl, pyrazolyl, triazolyl, tetrazolyl, isoxazolyl, isothiazolyl, imidazolyl, imidazopyrimidinyl, imidazothiazolyl, thienothiophenyl, pyrimidinyl, furopyridinyl, indolyl, azaindolyl, pyrazinyl, pyrazolopyrimidinyl, indazolyl, pyrimidinyl, quinolinyl, isoquinolinyl, quinazolinyl, benzofuranyl, benzothiophenyl, benzoimidazolyl, benzoxazolyl, benzothiazolyl, benzotriazolyl and purinyl.For the avoidance of doubt, the oxides of heteroaryl / heteroaromatic groups are also embraced within the scope of the invention (e.g. the / V-oxide).As stated above, heteroaryl includes polycyclic (e.g. bicyclic) groups in which one ring is aromatic (and the other may or may not be aromatic). Hence, other heteroaryl groups that may be mentioned include groups such as benzo[l,3]dioxolyl, benzo[l,4]dioxinyl, dihydrobenzo[d]isothiazole, 3,4-dihydrobenz[l,4]oxazinyl, dihydrobenzothiophenyl, indolinyl, 5H,6H, 7H-pyrrolo[l,2-b]pyrimidinyl, 1, 2,3,4- tetrahydroquinolinyl, thiochromanyl and the like.Particular heteroaryl groups that may be mentioned include pyrazolyl, triazolyl, imidazolyl, and benzofuranyl.As used herein, halo (or a halo group) may be understood to indicate a halogen substituent selected from iodo, bromo, chloro and fluoro. More particular halo groups that may be mentioned include chloro and fluoro groups.The present invention also embraces isotopically-labelled compounds of the present invention which are identical to those recited herein, but for the fact that one or more atoms are replaced by an atom having an atomic mass or mass number different fromthe atomic mass or mass number usually found in nature (or the most abundant one found in nature). All isotopes of any particular atom or element as specified herein are contemplated within the scope of the compounds of the invention. Hence, the compounds of the invention also include deuterated compounds, i.e. compounds of the invention in which one or more hydrogen atoms are replaced by the hydrogen isotope deuterium.For the avoidance of doubt, in cases in which the identity of two or more substituents in a compound of the invention may be the same, the actual identities of the respective substituents are not in any way interdependent. For example, in the situation in which two or more C1-2 alkyl groups are present, those C1-2 alkyl groups may be the same or different.Further for the avoidance of doubt, when it is specified that a substituent is itself optionally substituted by one or more substituents (e.g. a C1-2 alkyl group optionally substituted by one or more groups independently selected from fluoro and =0), these substituents where possible may be positioned on the same or different atoms. Such optional substituents may be present in any suitable number thereof (e.g. the relevant group may be substituted with one or more such substituents, such as one such substituent).For the avoidance of doubt, where groups are referred to herein as being optionally substituted it is specifically contemplated that such optional substituents may be not present (i.e. references to such optional substituents may be removed), in which case the optionally substituted group may be referred to as being unsubstituted.Where used herein, a dashed bond (i.e. " - ", or the like) may indicate the position of attachment of the relevant substituent to the core molecule (i.e. the compound of the compound of formula I to which the substituent is attached).For the avoidance of doubt, the skilled person will appreciate that compounds of the invention that are the subject of this invention include those that are obtainable, i.e. those that may be prepared in a stable form. That is, compounds of the invention include those that are sufficiently robust to survive isolation, e.g. from a reaction mixture, to a useful degree of purity.In particular embodiments that may be mentioned, in the compound of formula I, R1represents a phenyl group optionally substituted by one chloro, methyl, methoxy ormethoxymethyl group. More particularly the optional substituent is a methyl, methoxy or methoxymethyl group. Yet more particularly, the optional substituent is a methyl or methoxymethyl group.In further particular embodiments that may be mentioned, the optional substituent (e.g. a methyl or methoxymethyl group) is in the 3- or the 4-position of the phenyl ring relative to the point of attachment of the R1group to the nitrogen atom. In yet further particular embodiments, the optional substituent (e.g. a methyl or methoxymethyl group) is the 3-position of the phenyl ring relative to the point of attachment of the R1group to the nitrogen atom.In further particular embodiments that may me be mentioned, R1represents a phenyl group (i.e. an unsubstituted phenyl group).In further particular embodiments that may be mentioned, R1represents a benzofuranyl group, which benzofuran group is optionally substituted by one or more (e.g. one) methyl groups. In yet further particular embodiments R1representsIn particular embodiments that may be mentioned, R2is selected from the group consisting of a C1-2 alkyl group (e.g. methyl), a methoxymethyl group, a methoxyethoxy group and -A-R3.In further particular embodiments that may be mentioned, R2is selected from the group consisting of a C1-2 alkyl group (e.g. methyl), a methoxymethyl group and a methoxyethoxy group.In further particular embodiments, that may be mentioned, R2represents -A-R3.In particular embodiments that may be mentioned, A is selected from the group consisting of a direct bond, -CH2-, -OCH2- and -OCH2C(O)-. More particularly, A is selected from the group consisting of a direct bond, -CH2- and -OCH2-.In particular embodiments that may be mentioned, R3is selected from a 5-membered heteroaryl group selected from the group consisting of pyrrol-l-yl, pyrazol-l-yl, pyrazol-4-yl, imidazol-l-yl, imidazol-2-yl, imidazol-5-yl and 1,2,4-triazol-l-yl, and apyrrolidin- 1-yl group, wherein each 5-membered heteroaryl group is optionally substituted by one or more fluoro, methyl, or ethyl groups, which latter two groups are optionally substituted by one or more fluoro groups, and the pyrrolidine-l-yl group is optionally substituted by a =0 group.Particular compounds of formula I for use in accordance with the invention that may be mentioned include: l-(3-methyl-4-phenoxyphenyl)-3-phenyl-l, 3, 5-triazinane-2, 4, 6-trionel-(3-methyl-4-phenoxyphenyl)-3-(3-methylphenyl)-l, 3, 5-triazinane-2, 4, 6-trionel-[3-(methoxymethyl)phenyl]-3-(3-methyl-4-phenoxyphenyl)-l,3,5-triazinane-2,4,6-trionel-[3-(methoxymethyl)-4-phenoxyphenyl]-3-(3-methylphenyl)-l,3,5-triazinane-2,4,6-trionel-(2-methyl-l-benzofuran-7-yl)-3-(3-methyl-4-phenoxyphenyl)-l,3,5-triazinane-2, 4, 6-trionel-(l-benzofuran-4-yl)-3-(3-methyl-4-phenoxyphenyl)-l,3,5-triazinane-2, 4, 6-trionel-(l-benzofuran-7-yl)-3-(3-methyl-4-phenoxyphenyl)-l,3,5-triazinane-2, 4, 6-trionel-(3-ethyl-4-phenoxyphenyl)-3-phenyl-l,3,5-triazinane-2, 4, 6-trionel-(3-ethyl-4-phenoxyphenyl)-3-(3-methylphenyl)-l,3,5-triazinane-2, 4, 6-trionel-{4-phenoxy-3-[(lH-pyrazol-l-yl)methyl]phenyl}-3-phenyl-l,3,5-triazinane-2,4,6- trionel-{3-[(lH-imidazol-l-yl)methyl]-4-phenoxyphenyl}-3-phenyl-l,3,5-triazinane-2,4,6- trionel-{4-phenoxy-3-[(lH-l,2,4-triazol-l-yl)methyl]phenyl}-3-phenyl-l,3,5-triazinane-2, 4, 6-trionel-{3-[( lH-imidazol-l-yl)methyl]-4-phenoxyphenyl}-3-(3-methylphenyl)- 1,3,5- triazinane-2, 4, 6-trionel-{3-[( lH-imidazol-2-yl)methoxy]-4-phenoxyphenyl}-3-(3-methylphenyl)- 1,3,5- triazinane-2, 4, 6-trionel-{3-[(4-fluoro-lH-imidazol-l-yl)methyl]-4-phenoxyphenyl}-3-(3-methylphenyl)- 1, 3, 5-triazinane-2, 4, 6-trionel-{3-[(4-fluoro-lH-pyrazol-l-yl)methyl]-4-phenoxyphenyl}-3-phenyl-l,3,5- triazinane-2, 4, 6-trionel-{3-[(4-fluoro-lH-pyrazol-l-yl)methyl]-4-phenoxyphenyl}-3-(3-methylphenyl)-1, 3, 5-triazinane-2, 4, 6-trionel-{3-[(l-ethyl-lH-pyrazol-4-yl)methyl]-4-phenoxyphenyl}-3-phenyl-l,3,5- triazinane-2, 4, 6-trionel-(3-methylphenyl)-3-{4-phenoxy-3-[( IH-pyrazol- l-yl)methyl]phenyl}- 1,3,5- triazinane-2, 4, 6-trionel-{3-[(4-ethyl-lH-pyrazol-l-yl)methyl]-4-phenoxyphenyl}-3-phenyl-l,3,5- triazinane-2, 4, 6-trionel-{3-[(4-ethyl-lH-pyrazol-l-yl)methyl]-4-phenoxyphenyl}-3-(3-methylphenyl)-1, 3, 5-triazinane-2, 4, 6-trionel-(3-{[4-(difluoromethyl)-lH-imidazol-l-yl]methyl}-4-phenoxyphenyl)-3-(3- methylphenyl)-l,3,5-triazinane-2, 4, 6-trionel-[3-(2-methoxyethoxy)-4-phenoxyphenyl]-3-phenyl-l,3,5-triazinane-2, 4, 6-trionel-[3-(2-methoxyethoxy)-4-phenoxyphenyl]-3-(4-methylphenyl)-l,3,5-triazinane-2, 4, 6-trionel-[3-(2-methoxyethoxy)-4-phenoxyphenyl]-3-(3-methylphenyl)-l,3,5-triazinane-2, 4, 6-trionel-[3-(2-methoxyethoxy)-4-phenoxyphenyl]-3-(3-methylphenyl)-l,3,5-triazinane-2, 4, 6-trionel-(4-chlorophenyl)-3-[3-(2-methoxyethoxy)-4-phenoxyphenyl]-l,3,5-triazinane-2, 4, 6-trionel-[3-(2-methoxyethoxy)-4-phenoxyphenyl]-3-(4-methoxyphenyl)-l,3,5-triazinane-2, 4, 6-trionel-[3-(2-methoxyethoxy)-4-phenoxyphenyl]-3-(3-methoxyphenyl)-l,3,5-triazinane-2, 4, 6-trionel-(3-methylphenyl)-3-{3-[(2-oxopyrrolidin-l-yl)methyl]-4-phenoxyphenyl}-l,3,5- triazinane-2, 4, 6-trioneand pharmaceutically acceptable salts thereof.More particular compounds for use in accordance with the invention that may be mentioned include l-(3-methyl-4-phenoxyphenyl)-3-phenyl-l,3,5-triazinane-2, 4, 6-trionel-(3-methyl-4-phenoxyphenyl)-3-(3-methylphenyl)-l, 3, 5-triazinane-2, 4, 6-trionel-[3-(methoxymethyl)phenyl]-3-(3-methyl-4-phenoxyphenyl)-l,3,5-triazinane-2, 4, 6-trionel-[3-(methoxymethyl)-4-phenoxyphenyl]-3-(3-methylphenyl)-l,3,5-triazinane- 2,4,6-trionel-(3-ethyl-4-phenoxyphenyl)-3-(3-methylphenyl)- 1, 3, 5-triazinane-2, 4, 6-trioneand pharmaceutically acceptable salts thereof.A particular compound for use in accordance with the invention is l-(3-methyl-4- phenoxyphenyl)-3-phenyl-l, 3, 5-triazinane-2, 4, 6-trioneor a pharmaceutically acceptable salt thereof.Although compounds of the invention may possess pharmacological activity as such, certain pharmaceutically-acceptable (e.g. "protected") derivatives of compounds of the invention may exist or be prepared which may not possess such activity, but may be administered parenterally or orally and thereafter be metabolised in the body to form compounds of the invention. Such compounds (which may possess some pharmacological activity, provided that such activity is appreciably lower than that of the active compounds to which they are metabolised) may therefore be described as "prodrugs" of compounds of the invention.As used herein, references to prodrugs will include compounds that form a compound of the invention, in an experimentally-detectable amount, within a predetermined time, following enteral or parenteral administration (e.g. oral or parenteral administration).All prodrugs of the compounds of the invention are included within the scope of the invention.Furthermore, certain compounds of the invention may possess no or minimal pharmacological activity as such, but may be administered parenterally or orally, and thereafter be metabolised in the body to form compounds of the invention that possess pharmacological activity as such. Such compounds (which also includes compounds that may possess some pharmacological activity, but that activity is appreciably lower than that of the active compounds of the invention to which they are metabolised), may also be described as "prodrugs".For the avoidance of doubt, compounds of the invention are therefore useful because they possess pharmacological activity, and / or are metabolised in the body following oral or parenteral administration to form compounds that possess pharmacological activity.Medical usesAs described herein, compounds of formula I are useful in the treatment and / or prevention of inflammation. In particular, compounds of formula I are useful in the treatment of inflammation. Yet more particularly, the treatment includes (or is) symptomatic treatment.The skilled person will understand that references to the treatment of a particular condition, such as inflammation, (or, similarly, to treating that condition) will take their normal meanings in the field of medicine. In particular, the terms may refer to achieving a reduction in the severity and / or frequency of occurrence of one or more clinical symptom associated with the condition, as adjudged by a physician attending a patient having or being susceptible to such symptoms. For example, in the case of inflammation, the term may refer to achieving a reduction in inflammation, including achieving a reduction in the clinical symptoms caused by inflammation, such as warmth, redness, pain and swelling. Treatment of inflammation may also include achieving a reduction in proinflammatory markers, such as interleukins (e.g. IL-6, IL- 1b) and immunoglobulins (e.g. immunoglobulin G). Treatment of an inflammatory disorder as described herein may be understood to include achieving a reduction in the inflammation associated with the relevant disorder (for example arthritis).As used herein, the term prevention (and, similarly, preventing) will include references to the prophylaxis of the disease or disorder (and vice-versa). As such, references to prevention may also be references to prophylaxis, and vice versa. In particular, such terms term may refer to achieving a reduction (for example, at least a 10% reduction, such as at least a 20%, 30% or 40% reduction, e.g. at least a 50% reduction) in the likelihood of the patient (or healthy subject) developing the condition (which may be understood as meaning that the condition of the patient changes such that patient is diagnosed by a physician as having, e.g. requiring treatment for, the relevant disease or disorder).As used herein, references to a patient (or to patients) will refer to a living subject being treated, including mammalian (e.g. human) patients. In particular, references to a patient will relate to mammalian patients (including human patients and animals) and more particularly references to patients will refer to human patients.For the avoidance of doubt, the skilled person will understand that such treatment or prevention will be performed in a patient (or subject) in need thereof. The need of a patient (or subject) for such treatment or prevention may be assessed by those skilled the art using routine techniques.As used herein, the terms disease and disorder (and, similarly, the terms condition, illness, medical problem, and the like) may be used interchangeably.As used herein, the term effective amount will refer to an amount of a compound that confers a therapeutic effect on the treated patient. The effect may be observed in a manner that is objective (i.e. measurable by some test or marker) or subjective (i.e. the subject gives an indication of and / or feels an effect). In particular, the effect may be observed (e.g. measured) in a manner that is objective, using appropriate tests as known to those skilled in the art.The skilled person will understand that active ingredients used in the treatment and / or prevention of inflammation may be referred to as anti-inflammatory agents, medicines or medicaments.Accordingly, in a further aspect of the invention, there is provided a compound of formula I, or a pharmaceutically acceptable salt thereof, for use as an anti-inflammatory medicament.In an alternative further aspect, there is provided a compound of formula I, or a pharmaceutically acceptable salt thereof, for use in the manufacture of an antiinflammatory medicament.In the context of the uses and methods described herein, inflammation may be understood to refer to an immune response involving the production of inflammatory mediators, including growth factors, cytokines (including the interleukins, such as interleukin-1 (IL-1) (alpha and beta), IL-2, IL-4, IL-6, IL-10, IL-11, IL-12, IL-13, interferons (INF) such as INF-gamma, and tumor necrosis factor alpha), chemokines, and eicosanoids, which orchestrate the recruitment of immune cells to the site of inflammation. Inflammation may be associated with the classic clinical symptoms of inflammation, warmth, redness, pain and swelling as well as loss of function. However, the term also encompasses inflammation involving the production of inflammatory mediators that does not necessarily involve the classic clinical symptoms of inflammation (for example because the inflammation is internal or if the acute inflammation progress into a chronic state), such inflammation may also be referred to herein as 'inflammatory-like processes'. In another aspect, inflammatory-like processes may be understood to include adaptive responses of the body to cope with physiological situations without an apparent infection or external injury that usually does not involve all or any of the cardinal clinical signs of inflammation. Such situations can include chronic stress, proteopathy such as Alzheimer's disease, neurodegeneration or chronic inflammation. As used herein, inflammation may be understood to include such inflammatory-like (and, similarly, inflammation-like) processes.Inflammation and inflammatory disorders, as discussed herein will be known to the skilled person. In particular, inflammation includes excessive, harmful and / or chronic inflammation that may benefit from medical intervention. Such inflammation and inflammatory disorders are well known to the skilled person (e.g. a physician or scientist with expertise in inflammation).The skilled person will understand that inflammation includes acute, chronic and subacute inflammation. Acute inflammation is part of the body's response to harmful stimuli, such as pathogens, damaged cells and other irritants, involving the production of inflammatory mediators, by the innate and acquired immune system. Acute inflammation is a generally beneficial response, but excessive inflammation can be harmful, and require treatment. Chronic inflammation includes inflammation occurring over several months or years. In some instances, chronic inflammation has anidentifiable cause, such as harmful stimuli, but the cause of long-term inflammation can also be difficult to determine. Chronic inflammation is involved in many chronic disorders, such as autoimmune diseases, neurodegenerative diseases, musculoskeletal diseases, metabolic disorders and gastrointestinal diseases. Sub-acute inflammation is inflammation occurring for an intermediate period of time, such as from 2 to 6 weeks.Accordingly, in particular embodiments that may be mentioned, the inflammation to be treated with the compounds of the invention is acute, chronic or subacute inflammation. Acute inflammation includes particularly harmful or excessive acute inflammation.More particularly, the inflammation is chronic inflammation.In particular embodiments that may be mentioned, the inflammation to be treated with the compounds of the invention peripheral inflammation.Peripheral inflammation may be understood to refer to inflammation occurring outside of the central nervous system, such as in peripheral tissue, the peripheral nervous system and gastrointestinal tract.In further particular embodiments, the inflammation is neuroinflammation.As used herein, neuroinflammation may be understood to refer to inflammation (including inflammatory-like processes) occurring within the central nervous system (CNS), which includes the brain and the spinal cord. Inflammation (including inflammatory-like processes) in the CNS may also be referred to as central inflammation (or central neuroinflammation). Such neuroinflammation (or central inflammation) may be acute or, more particularly, be chronic. As used herein, central inflammation or neuroinflammation or central inflammation may particularly be understood to include to inflammation occurring in the brain.In particular embodiments, the inflammation is peripheral inflammation.In other particular embodiments, the inflammation is central inflammation (or neuroinflammation). In further particular embodiments, the central or neuroinflammation is in the brain (inflammation of the brain).In further particular embodiments, the inflammation is systemic or local. More particularly, the inflammation is systemic inflammation.Inflammation may be associated with a wide range of diseases and disorders and may be induced by a range of different stimuli and biological pathways. As described herein, the compounds of the invention have been found to have a range of anti-inflammatory effects, including reducing inflammation caused by obesity and impaired glucose handling, arthritis, ageing and amyloid pathology, as well as showing an effect on NGF- induced inflammation. Accordingly, the compounds of the invention (including pharmaceutically acceptable salts thereof) are thought to have utility in the treatment of inflammation induced by a wide range of diseases or disorders.In particular embodiments, the inflammation to be treated and / or prevented with the compounds of the invention comprises inflammation induced and / or driven by NGF.NGF is known to induce inflammation through its effect at the TrkA receptor on both neuronal and non-neuronal cells. This inflammatory process has been reported to be associated with a range of conditions, including arthritis, inflammation of the peripheral nervous system, inflammatory skin diseases, inflammatory respiratory diseases, inflammatory diseases of the digestive system, cystitis and interstitial cystitis, systemic lupus erythematosus, and central indications, including neurodegenerative disorders.Accordingly, in particular embodiments that may be mentioned, the inflammation that may be treated with the compounds of the invention is inflammation associated with a disease or disorder selected from the group consisting of a metabolic disorder, arthritis, an inflammatory disorder of the peripheral nervous system, an inflammatory skin disease, an inflammatory respiratory disease, an inflammatory disease of the digestive system, cystitis, interstitial cystitis, systemic lupus erythematosus (lupus)and a central indication (including neurodegenerative disorders).As used herein, the phrase "associated with" (in the context of inflammation being associated with a particular disease or disorder) may be understood to include inflammation (including inflammatory-like processes) that is caused by, related to, and / or is a consequence of the relevant disease or disorder as well as inflammation (including inflammatory-like processes) that is present in a patient having the relevant disease or disorder and occurring alongside the (other) established symptoms and / or pathology of the disorder. For instance, increased inflammatory processes inAlzheimer's disease (as measured by IL-6) are known to positively correlate to decreased cognitive performance.In particular embodiments, the inflammation is caused by the relevant disease or disorder described herein.In further particular embodiments, the inflammation is related to the relevant disease or disorder described herein.In further particular embodiments, the inflammation is a consequence of the relevant disease or disorder described herein.Metabolic disorders include obesity, insulin resistance and diabetes mellitus (including type 1 and type 2 diabetes). More particular metabolic disorders that may be mentioned are obesity and diabetes. In particular embodiments, the metabolic disorder is obesity. In alternative embodiments, the metabolic disorder is diabetes (including type 1 and type 2 diabetes).As used herein, arthritis includes osteoarthritis (including polyosteoarthritis), rheumatoid arthritis, psoriatic arthritis, reactive arthritis, juvenile idiopathic arthritis, systemic juvenile idiopathic arthritis, spondyloarthritis and post-streptococcal inflammatory arthritis.In particular embodiments, the arthritis is selected from the group consisting of rheumatoid arthritis, psoriatic arthritis and osteoarthritis (including polyosteoarthritis). Yet more particularly, the arthritis is osteoarthritis.Inflammatory disorder of the peripheral nervous system that may be mentioned include inflammatory polyneuropathy (including, particularly, chronic inflammatory demyelinating polyneuropathy) and neuritis. In particular embodiments, the inflammatory disorder of the peripheral nervous system is inflammatory polyneuropathy. In alternative embodiments, the disorder of the peripheral nervous system is neuritis.As used herein, neuritis may be understood to refer to inflammation of a nerve, and, more particularly, to general inflammation of the peripheral nervous system.Inflammatory skin diseases that may be mentioned include psoriasis, dermatitis (including atopic dermatitis (eczema)), and pruritis. In particular embodiments, the inflammatory skin disease is dermatitis or atopic dermatitis.Inflammatory respiratory diseases that may be mentioned include rhinitis (including allergic and chronic rhinitis), allergic airway inflammation, acute upper and lower respiratory infectious diseases and chronic lower respiratory diseases (including asthma). In particular embodiments, the inflammatory respiratory disease is selected from the group consisting of rhinitis (including allergic and chronic rhinitis) and asthma.Acute upper respiratory infections that may be mentioned include common cold, sinusitis, pharyngitis, epiglottitis and laryngotracheitis caused by bacteria or viruses, including influenza virus, respiratory syncytial virus and corona virusAcute lower respiratory infections that may be mentioned include pneumonia, acute bronchitis and bronchiolitis.Inflammatory diseases of the digestive system that may be mentioned include inflammatory bowel disease, which includes ulcerative colitis and Crohn's disease. In particular embodiments, the inflammatory disease of the digestive system is inflammatory bowel disease, including ulcerative colitis and Crohn's disease.As used herein, systemic lupus erythematosus (lupus) includes juvenile lupus.Central indications associated with inflammation that may be mentioned include neurodegenerative disorders (including Alzheimer's disease, Parkinson's disease, Lewy body dementia, frontotemporal lobar degeneration (including frontotemporal dementia), Huntington's disease, motor neuron disease, multiple sclerosis, Charcot- Marie-Tooth disease and amyotrophic lateral sclerosis), myalgic encephalomyelitis / chronic fatigue syndrome, meningitis, autoimmune neuroinflammatory diseases (such as autoimmune encephalitis), tick-borne encephalitis, encephalitis, encephalomyelitis and sequelae of inflammatory diseases of the central nervous system, stroke, transient ischemic attack, vascular dementia, multi-infarct dementia, traumatic brain injury, cerebral amyloid angiopathy and chronic traumatic encephalopathy.In particular embodiments that may be mentioned, the inflammation to be treated and / or prevented with the compounds of the invention is associated with a neurodegenerative disorder.In particular embodiments, the neurodegenerative disorder is a proteopathy (or proteinopathy).As used herein, proteopathy (or proteinopathy) may be understood to refer to a disorder comprising protein misfolding or other conformational irregularities in protein structure. Examples of neurodegenerative proteinopathies include Alzheimer's disease, Parkinson's disease, Lewy body dementia, frontotemporal lobar degeneration (FTLD) (including frontotemporal dementia), amyotrophic lateral sclerosis and prion disease (including Creutzfeldt- Jakob disease)Accordingly, in particular embodiments, the neurodegenerative disease is selected from the group consisting of Alzheimer's disease, Parkinson's disease, Lewy body dementia, frontotemporal lobar degeneration (FTLD) (including frontotemporal dementia), amyotrophic lateral sclerosis and prion disease.In further particular embodiments, the neurodegenerative disorder is selected from the group consisting of Alzheimer's disease, Parkinson's disease, Lewy body dementia, frontotemporal dementia, Huntington's disease, motor neuron disease, multiple sclerosis, Charcot-Marie-Tooth disease and amyotrophic lateral sclerosis.In further particular embodiments, the neurodegenerative disorder is selected from Lewy body dementia, frontotemporal lobar degeneration (including frontotemporal dementia), Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis.Yet more particularly, the neurodegenerative disorder is selected from Alzheimer's disease and Parkinson's disease.Yet more particularly, the neurodegenerative disorder is Alzheimer's disease.As used herein, Alzheimer's disease includes familial and, more particularly, sporadic Alzheimer's disease.In a further aspect of the invention, there is provided a compound of formula I, or a pharmaceutically acceptable salt thereof, for use in the treatment and / or preventionof an inflammatory disease or disorder selected from the group consisting of a metabolic disorder, arthritis an inflammatory disorder of the peripheral nervous system, an inflammatory skin disease, an inflammatory respiratory disease, an inflammatory disease of the digestive system, cystitis, interstitial cystitis, systemic lupus erythematosus and an inflammatory disorder of the central nervous system; wherein the treatment comprises the treatment and / or prevention of the inflammation associated with the inflammatory disease or disorder.In an alternative further aspect of the invention, there is provided a method of treating and / or preventing an inflammatory disease or disorder selected from the group consisting of a metabolic disorder, arthritis, an inflammatory disorder of the peripheral nervous system, an inflammatory skin disease, an inflammatory respiratory disease, an inflammatory disease of the digestive system, cystitis and interstitial cystitis, systemic lupus erythematosus and an inflammatory disorder of the central nervous system, comprising administering a therapeutically effective amount of a compound of formula I, or a pharmaceutically acceptable salt thereof, to a patient in need thereof, wherein the treatment and / or prevention comprises the treatment and / or prevention of the inflammation associated with the inflammatory disease or disorder.In a further alternative aspect of the invention, there is provided the use of a compound of formula I, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for the treatment and / or prevention of an inflammatory disorder selected from the group consisting of a metabolic disorder, arthritis, an inflammatory disorder of the peripheral nervous system, an inflammatory skin disease, an inflammatory respiratory disease, an inflammatory disease of the digestive system, cystitis, interstitial cystitis, systemic lupus erythematosus and an inflammatory disorder of the central nervous system; wherein the treatment and / or prevention comprises treatment and / or prevention of the inflammation associated with the inflammatory disease or disorder.In a further aspect of the invention, there is provided a compound of formula I, or a pharmaceutically acceptable salt thereof, as defined herein, for use in the treatment and / or prevention of an inflammatory disease or disorder selected from an arthritis (including all types of arthritis defined herein) an inflammatory disorder of the peripheral nervous system, an inflammatory skin disease, an inflammatory respiratory disease, an inflammatory disease of the digestive system, cystitis, interstitial cystitis and systemic lupus erythematosus.In an alternative further aspect of the invention, there is provided a method of treating and / or preventing an inflammatory disease or disorder selected from arthritis (including all types of arthritis defined herein), an inflammatory disorder of the peripheral nervous system, an inflammatory skin disease, an inflammatory respiratory disease, an inflammatory disease of the digestive system, cystitis, interstitial cystitis and systemic lupus erythematosus comprising administering a therapeutically effective amount of a compound of formula I, or a pharmaceutically acceptable salt thereof, as defined herein to a patient in need thereof.In an alternative further aspect of the invention, there is provided the use of a compound of formula I, or a pharmaceutically acceptable salt thereof, as defined herein for the manufacture of a medicament for treating and / or preventing an inflammatory treating and / or preventing an inflammatory disease or disorder selected from arthritis (including all types of arthritis defined herein), an inflammatory disorder of the peripheral nervous system, an inflammatory skin disease, an inflammatory respiratory disease, an inflammatory disease of the digestive system cystitis, interstitial cystitis and systemic lupus erythematosus.In particular embodiments of these aspects that may be mentioned, the inflammatory disease or disorder is arthritis, including osteoarthritis (including polyosteoarthritis), rheumatoid arthritis, psoriatic arthritis, reactive arthritis, juvenile idiopathic arthritis, systemic juvenile idiopathic arthritis, spondyloarthritis and post-streptococcal inflammatory arthritis.More particularly, the arthritis is selected from the group consisting of rheumatoid arthritis, osteoarthritis and psoriatic arthritis. Yet more particularly, the arthritis is osteoarthritis.In particular embodiments, the inflammatory disease or disorder is an inflammatory disorder of the peripheral nervous system, optionally selected from inflammatory polyneuropathy (including, particularly, chronic inflammatory demyelinating polyneuropathy) and neuritis. In more particular embodiments, the inflammatory disease of the peripheral nervous system is inflammatory polyneuropathy. In alternative embodiments, the inflammatory disease of the peripheral nervous system is neuritis.In particular embodiments that may be mentioned, the inflammatory disease or disorder is an inflammatory skin disease, optionally selected from psoriasis, dermatitis(including atopic dermatitis (eczema)), and pruritis. In more particular embodiments, the inflammatory skin disease is dermatitis or atopic dermatitis.In further embodiments that may be mentioned, the inflammatory disease or disorder is an inflammatory respiratory disease, optionally wherein the inflammatory respiratory disease is selected from the group consisting of allergic rhinitis, chronic rhinitis, allergic airway inflammation, an acute upper respiratory infectious disease, an acute lower respiratory infectious disease and a chronic lower respiratory disease, optionally wherein the chronic lower respiratory disease is asthma. In particular embodiments, the inflammatory respiratory disease is selected from the group consisting of rhinitis (including allergic and chronic rhinitis) and asthma.In further embodiments that may be mentioned, the inflammatory disease or disorder is an inflammatory disease of the digestive system, optionally wherein the inflammatory disease of the digestive system is an inflammatory bowel disease, selected from ulcerative colitis and Crohn's disease. In particular embodiments, the inflammatory bowel disease is ulcerative colitis. In further particular embodiments, the inflammatory bowel disease is Crohn's disease.In particular embodiments, the inflammatory disease or disorder is cystitis or interstitial cystitis.In particular embodiments, the inflammatory disease or disorder is systemic lupus erythematosus (including juvenile lupus).In particular embodiments of these aspects of the invention (i.e. the use of the compounds of the invention in the treatment of an inflammatory disease or disorder as described herein and methods of treating such inflammatory diseases or disorders with the compounds of the invention), the treatment or prevention of the relevant disorder comprises treating the inflammation associated with (including inflammation caused by, related to and / or occurring as a consequence of) the relevant disorder.The compounds of the invention have been found to reduce inflammatory markers, including, IL-6, IL- 1 b and IgG. Accordingly, in particular embodiments of the uses and methods described herein, the treatment and / or prevention comprises reducing the level of IL-6, IL- 1 b and / or IgG in the patient being treated.In more particular embodiments, the treatment and / or prevention comprises reducing the level of IL-6 in the patient being treated.In more particular embodiments, the treatment and / or prevention comprises reducing the level of IL- 1 b in the patient being treated.In more particular embodiments, the treatment and / or prevention comprises reducing the level of IgG in the patient being treated.As used herein, reducing (the level of) IL-6, IL-lb and / or IgG (and reducing each of these inflammatory markers individually) may be understood to comprise reducing the level of the relevant inflammatory marker(s) either locally or systemically as measured by techniques known to the person skilled in the art, such as, in particular, reducing the level of the relevant marker(s) in the blood of the patient being treated (including whole blood, serum and / or plasma (e.g. plasma)) and / or in the cerebrospinal fluid.Pharmaceutical compositionsAs described herein, compounds of the invention are useful as pharmaceuticals. Such compounds may be administered alone or may be administered by way of known pharmaceutical compositions / formulations.In a further aspect of the invention, there is provided a pharmaceutical composition comprising a compound of the invention as defined herein (including pharmaceutically acceptable salts), and optionally one or more pharmaceutically-acceptable excipient, for use in the treatment and / or prevention of inflammation or an inflammatory disease or disorder as defined herein (including all embodiments as defined herein).As used herein, the term pharmaceutically-acceptable excipients includes references to vehicles, adjuvants, carriers, diluents, pH adjusting and buffering agents, tonicity adjusting agents, stabilizers, wetting agents and the like. In particular, such excipients may include adjuvants, diluents or carriers.In a particular embodiment of this aspect of the invention, the pharmaceutical composition comprises at least one pharmaceutically-acceptable excipient.For the avoidance of doubt, references herein to compounds of invention being for particular uses (and, similarly, to uses and methods of use relating to compounds ofthe invention) may also apply to pharmaceutical compositions comprising compounds of the invention, as described herein.The skilled person will understand that compounds of the invention may act systemically and / or locally (i.e. at a particular site), and may therefore be administered accordingly using suitable techniques known to those skilled in the art.The skilled person will understand that compounds and compositions as described herein will normally be administered orally, intravenously, subcutaneously, buccally, rectally, dermally, nasally, tracheally, bronchially, sublingually, intranasally, topically, by any other parenteral route or via inhalation, in a pharmaceutically acceptable dosage form.Pharmaceutical compositions as described herein will include compositions in the form of tablets, capsules or elixirs for oral administration, suppositories for rectal administration, sterile solutions or suspensions for parenteral or intramuscular administration, and the like. Alternatively, particularly where such compounds of the invention act locally, pharmaceutical compositions may be formulated for topical administration.Thus, in particular embodiments, the pharmaceutical formulation is provided in a pharmaceutically acceptable dosage form, including tablets or capsules, liquid forms to be taken orally or by injection, suppositories, creams, gels, foams, inhalants (e.g. to be applied intranasally), or forms suitable for topical administration. For the avoidance of doubt, in such embodiments, compounds of the invention may be present as a solid (e.g. a solid dispersion), liquid (e.g. in solution) or in other forms, such as in the form of micelles.For example, in the preparation of pharmaceutical formulations for oral administration, the compound may be mixed with solid, powdered ingredients such as lactose, saccharose, sorbitol, mannitol, starch, amylopectin, cellulose derivatives, gelatin, or another suitable ingredient, as well as with disintegrating agents and lubricating agents such as magnesium stearate, calcium stearate, sodium stearyl fumarate and polyethylene glycol waxes. The mixture may then be processed into granules or compressed into tablets.Soft gelatin capsules may be prepared with capsules containing one or more active compounds (e.g. compounds of the first and, therefore, second and third aspects ofthe invention, and optionally additional therapeutic agents), together with, for example, vegetable oil, fat, or other suitable vehicle for soft gelatin capsules. Similarly, hard gelatine capsules may contain such compound(s) in combination with solid powdered ingredients such as lactose, saccharose, sorbitol, mannitol, potato starch, corn starch, amylopectin, cellulose derivatives or gelatin.Dosage units for rectal administration may be prepared (i) in the form of suppositories which contain the compound(s) mixed with a neutral fat base; (ii) in the form of a gelatin rectal capsule which contains the active substance in a mixture with a vegetable oil, paraffin oil, or other suitable vehicle for gelatin rectal capsules; (iii) in the form of a ready-made micro enema; or (iv) in the form of a dry micro enema formulation to be reconstituted in a suitable solvent just prior to administration.Liquid preparations for oral administration may be prepared in the form of syrups or suspensions, e.g. solutions or suspensions, containing the compound(s) and the remainder of the formulation consisting of sugar or sugar alcohols, and a mixture of ethanol, water, glycerol, propylene glycol and polyethylene glycol. If desired, such liquid preparations may contain colouring agents, flavouring agents, saccharine and carboxymethyl cellulose or other thickening agent. Liquid preparations for oral administration may also be prepared in the form of a dry powder to be reconstituted with a suitable solvent prior to use.Solutions for parenteral administration may be prepared as a solution of the compound(s) in a pharmaceutically acceptable solvent. These solutions may also contain stabilizing ingredients and / or buffering ingredients and are dispensed into unit doses in the form of ampoules or vials. Solutions for parenteral administration may also be prepared as a dry preparation to be reconstituted with a suitable solvent extemporaneously before use.Depending on e.g. potency and physical characteristics of the compound of the invention (i.e. active ingredient), pharmaceutical formulations that may be mentioned include those in which the active ingredient is present in an amount that is at least 1% (or at least 10%, at least 30% or at least 50%) by weight. That is, the ratio of active ingredient to the other components (i.e. the addition of adjuvant, diluent and carrier) of the pharmaceutical composition is at least 1:99 (or at least 10:90, at least 30:70 or at least 50:50) by weight.The skilled person will understand that compounds of the invention may be administered (for example, as formulations as described hereinabove) at varying doses, with suitable doses being readily determined by one of skill in the art. For example, when administered orally, treatment with such compounds may comprise administration of a formulations typically containing between about 0.01 pg to about 2000 mg, for example between about 0.1 pg to about 500 mg, or between 1 pg to about 100 mg (e.g. about 20 pg to about 80 mg), of the active ingredient(s). When administered intravenously, the most preferred doses will range from about 0.001 to about 10 pg / kg / hour during constant rate infusion. Advantageously, treatment may comprise administration of such compounds and compositions in a single daily dose, or the total daily dosage may be administered in divided doses of two, three or four times daily (e.g. twice daily with reference to the doses described herein, such as a dose of 25 mg, 50 mg, 100 mg or 200 mg twice daily).When used herein in relation to a specific value (such as an amount), the term "about" (or similar terms, such as "approximately") will be understood as indicating that such values may vary by up to 10% (particularly, up to 5%, such as up to 1%) of the value defined. It is contemplated that, at each instance, such terms may be replaced with the notation "± 10%", or the like (or by indicating a variance of a specific amount calculated based on the relevant value). It is also contemplated that, at each instance, such terms may be deleted.For the avoidance of doubt, the skilled person (e.g. the physician) will be able to determine the actual dosage which will be most suitable for an individual patient, which is likely to vary with the route of administration, the type and severity of the condition that is to be treated, as well as the species, age, weight, sex, renal function, hepatic function and response of the particular patient to be treated. Although the above- mentioned dosages are exemplary of the average case, there can, of course, be individual instances where higher or lower dosage ranges are merited, and such doses are within the scope of the invention.Preparation of compounds / compositionsPharmaceutical compositions / formulations, combination products and kits as described herein may be prepared in accordance with standard and / or accepted pharmaceutical practice.Thus, in a further aspect of the invention there is provided a process for the preparation of a pharmaceutical composition / formulation, as hereinbefore defined, which process comprises bringing into association a compound of the invention, as hereinbefore defined, with one or more pharmaceutically-acceptable excipient.As used herein, references to bringing into association will mean that the two components are rendered suitable for administration in conjunction with each other.Compounds of the invention as described herein may be prepared in accordance with techniques that are known to those skilled in the art. In particular, synthetic methods for the preparation of compounds of formula I may be found in WO2019 / 162702, WO 2020 / 002950 and WO 2021 / 038241.The compound names used herein where generated using CDD vault from Collaborative Drug Discovery Inc., Burlingame CA, USA or ChemDoodle 8.1.0 from iChemLabs LLC, USA or ACD / ChemSketch 2012 (14.01) from Advanced Chemistry Development (ACD / labs) Ontario, Canada.Compounds of the invention may be obtained following the methods described in the prior art, or may be obtained either by analogy with the processes described herein, or by conventional synthetic procedures, in accordance with standard techniques, from available starting materials using appropriate reagents and reaction conditions. In this respect, the skilled person may refer to inter alia "Comprehensive Organic Synthesis" by B. M. Trost and I. Fleming, Pergamon Press, 1991. Further references that may be employed include "Heterocyclic Chemistry" by J. A. Joule, K. Mills and G. F. Smith, 3rdedition, published by Chapman & Hall, "Comprehensive Heterocyclic Chemistry II" by A. R. Katritzky, C. W. Rees and E. F. V. Scriven, Pergamon Press, 1996 and "science of Synthesis", Volumes 9-17 (Hetarenes and Related Ring Systems), Georg Thieme Verlag, 2006.The skilled person will understand that the substituents as defined herein, and substituents thereon, may be modified one or more times, after or during the processes described above for the preparation of compounds of the invention by way of methods that are well known to those skilled in the art. Examples of such methods include substitutions, reductions, oxidations, dehydrogenations, alkylations, dealkylations, acylations, hydrolyses, esterifications, etherifications, halogenations and nitrations. The precursor groups can be changed to a different such group, or to the groups defined in formula I, at any time during the reaction sequence. The skilled person may also refer to "Comprehensive Organic Functional Group Transformations" by A. R.Katritzky, O. Meth-Cohn and C. W. Rees, Pergamon Press, 1995 and / or "Comprehensive Organic Transformations" by R. C. Larock, Wiley-VCH, 1999.Compounds of the invention may be isolated from their reaction mixtures and, if necessary, purified using conventional techniques as known to those skilled in the art. Thus, processes for preparation of compounds of the invention as described herein may include, as a final step, isolation and optionally purification of the compound of the invention.It will be appreciated by those skilled in the art that, in the processes described above and hereinafter, the functional groups of intermediate compounds may need to be protected by protecting groups. The protection and deprotection of functional groups may take place before or after a reaction in the above-mentioned schemes.Protecting groups may be applied and removed in accordance with techniques that are well-known to those skilled in the art and as described hereinafter. For example, protected compounds / intermediates described herein may be converted chemically to unprotected compounds using standard deprotection techniques. The type of chemistry involved will dictate the need, and type, of protecting groups as well as the sequence for accomplishing the synthesis. The use of protecting groups is fully described in "Protective Groups in Organic Synthesis", 3rdedition, T.W. Greene & P.G.M. Wutz, Wiley-Interscience (1999), the contents of which are incorporated herein by reference.Without wishing to be bound by theory, it is believed that the compounds of the invention (Compounds of formula I, and pharmaceutically acceptable salts thereof, as defined herein) are surprisingly effective in the treatment of inflammation and inflammatory diseases or disorders. In particular, the compounds of the invention have been shown to have a beneficial effect on inflammation associated with obesity, arthritis, aging and neurodegenerative disorders comprising amyloid pathology (e.g. Alzheimer's disease), as well as inflammation caused by nerve growth factor (NGF).Accordingly, the compounds of the invention may be used to treat and / or prevent inflammation arising from a variety of causes and therefore are believed to be able to treat inflammation associated with a wide range of disorders and to be used to treat and / or prevent certain inflammatory disorders. In the course of their use in such treatments (and / or preventions), compounds of the invention may have the advantage that they may be more efficacious than, be less toxic than, be longer acting than, bemore potent than, produce fewer side effects than, be more easily absorbed than, and / or have a better pharmacokinetic profile (e.g. higher oral bioavailability and / or lower clearance) than, and / or have other useful pharmacological, physical, or chemical properties over, compounds known in the prior art, whether for use in the above-stated indications or otherwise. In particular, compounds of the invention may have the advantage that they are more efficacious and / or exhibit advantageous properties in vivo.Brief Description of the FiguresFigure 1 shows the effect of the high fat diet (HFD) and low fat diet (LFD) described in Biological Assay 1 on the bodyweight of mice. The bodyweight of the mice fed the high fat diet gained weight more rapidly than the low fat diet group and from day 23 to the end of the study (day 56), the bodyweight of the mice in the high fat group was significantly higher than those in the low fat group.Figure 2 shows the blood glucose levels of the mice fed the high fat and low fat diets described in Biological Assay 1 at day 29 (Figure 2A) and day 56 (Figure 2B). No significant difference was observed at either time point.Figure 3 shows the glucose and insulin tolerance of the mice fed the high fat and low fat diets described in Biological Assay 1 at 8 weeks. The high fat diet group showed impaired ability to lower blood glucose as well as decreased sensitivity towards insulin at 8 weeks. This is indicated by elevated blood glucose levels after a bolus administration of glucose (Fig 3A) or an insulin injection (Fig 3B).Figure 4 shows the effects of compound #1 (l-(3-methyl-4-phenoxyphenyl)-3-phenyl- 1, 3, 5-triazinane-2, 4, 6-trione) on the total levels of IgG in the plasma (Figure 4A) and liver (Figure 4B) of the mice fed the high fat diet described in Biological Assay 1. Compound #1 significantly decreased the levels of IgG in both plasma and the liver.Figure 5 shows the effect of 3, 10 and 30 mg / kg doses of compound #1 on knee joint diameter at day 7 (Figure 5A) and day 11 (Figure 5B) in the osteoarthritis model described in Biological Assay 2. A reduction in inflammation was evident at day 7 for the 30 mg / kg group (figure 5A) and at all doses (3, 10 and 30 mg / kg) at day 11 (figure 5B).Figure 6 shows the effect of compound #1 on NGF-induced inflammation determined using the assay described in Biological Assay 3. Treatment with 5 mg / kg of compound #1 significantly decreased the paw volume (used as a clinical marker of inflammation) compared to the NGF control group.Figure 7 shows the results of a Western blot analysis of the effects of compound #1 on the levels of IgG in old mice as determined using the assay described in Biological Assay 4. Figures 7A and 7B show that levels of both heavy and light chain IgG were increased in old (aged 20 months at the start of the study) animals compared to 3-4 month old control group and that the levels of the heavy chain and light chain were significantly decreased after a 4 weeks of once daily treatment with a 5 mg / kg dose of compound #1.Figure 8 shows the effect of compound #1 on levels of total IgG in the brain (Figure 8A) and plasma (Figure 8B) of old mice as determined using the assay described in Biological Assay 4. The levels were measured using an ELISA specific for mouse IgG, and again the old mice showed a significant increase in the total IgG compared to the young mice in both the brain and plasma, which was significantly decreased by treatment with compound #1.Figure 9 shows the effect of compound #1 on levels of IL-6 in the brains of old mice as determined following the assay described in Biological Assay 4. The level of IL-6 was significantly higher in the old mice compared to young mice and was significantly decreased by treatment with compound #1.Figure 10 show the effect of compound #1 on the levels of IL-lb in the brains of old mice as determined following the assay described in Biological Assay 4. The level of IL-lb was significantly higher in the old mice compared to the young mice and was significantly decreased by treatment with compound #1.Figure 11 shows the effect of compound #1 on the levels of IL-6 in the brains of APPNL-G-Fknock-in mice as determined using the assay described in Biological Assay 5. The level of IL-6 was increased in the brains of the APPNL G Fknock-in mice compared to wild type mice and was significantly reduced after treatment with 3 mg / kg BID (twice a day) of compound #1 for 30 days.Figure 12 shows the effect of compound #1 on the levels of IgG in the plasma of APPNL-G Fmice. The level of IgG was increased in the plasma of the APPNL G Fknock-in micecompared to wild type mice and was significantly reduced after treatment with 3 mg / kg BID (twice a day) of compound #1 for 30 days.ExamplesThe present invention will be further described by reference to the following examples, which are not intended to limit the scope of the invention.Biological AssaysThe biological activity of the compounds of the invention was assessed using the biological assays discussed in this section.In particular, the compound l-(3-methyl-4-phenoxyphenyl)-3-phenyl-l,3,5- triazinane-2, 4, 6-trionewhich is referred to in this section as compound #1, was tested in the following assays. Compound #1 was administered as the free acid (i.e. not as a salt) in the Biological Assays described hereinafter.General ProceduresELISA analysis of inflammatory markersBrains were homogenized in cell lysis buffer (Cell Signaling) including protease and phosphatase inhibitors by 2x5 second using a probe sonicator. The homogenate were left for 5 minutes on ice to ensure complete lysis of the tissue. The resulting lysis mixture was diluted and subsequently transferred to an ELISA plate. The ELISA for IgG (88-50400 Invitrogen), IL-6 (900-T50 PeproTech) and IL-1 b (DY401-05 R&D Systems) was essentially carried out according to the manufacturer's instructions, except for the incubation of cell lysate capture antibody, which was performed overnight at +4°C. Briefly, 96-well Maxisorp plates (NUNC) were coated with 50 mL / well of captureantibody and incubated overnight. Non-specific binding was blocked for 90 min using 5% BSA in tris-buffered saline with 0.3% Triton X-100 (TBS-T) followed by repeated rinsing with TBS-T. Then, 50 mL of samples or standard samples were added to the coated plate and was kept overnight at 4°C. ELISA plates were washed four times followed by an incubation of 2h with 50 mL / well of detection antibody. After repeated washing steps, 50 mL / well of Streptavidin-HRP was added and incubated for 20 min. After washing, 50 mL / well of substrate solution was added and incubated for 25 min. The reaction was stopped by adding 25 mL of stop solution and the absorbance was immediately measured at 450 nm using a SpectraMax iD5 plate reader from Molecular Devices. Unless otherwise mentioned, all incubations were conducted in a shaker at 300 rpm and room temperature. All samples were run in technical duplicates. A standard curve with each protein was included on each ELISA plate and the content of the analyte in samples were calculated using a non-linear regression analysis of the standard curve. One-way ANOVA was used to calculate statistically significant differences.Western blot analysis of immunoglobulin G (IgG)Immunoglobulin G (IgG) levels were evaluated in brain homogenates. Brain homogenates were mixed with 4X concentrated loading buffer and denatured at 95°C for 3 min on a heating block. Proteins were separated on a Novex Bis-Tris 4-12% gel and transferred to a PVDF membrane using an iBIot instrument (Invitrogen). The membrane was blocked using 5% BSA in TBS-T followed by incubation with a goat anti-Mouse IgG unlabeled affinity purified polyclonal antibody (AF007 Bio-Techne)) (dilution 1 : 1000) in TBS-T with 0.1% BSA for at least 60 minutes. Membranes were thereafter washed three times and thereafter incubated with horse-radish peroxidase- coupled secondary donkey anti-goat antibodies for 60 minutes. After washing, western blot detection reagent (Forte, Millipore) was added and immunoreactive proteins were detected by luminescence using C DiGit Blot Scanner and quantified with Image Studio™ Software. (LI-COR Biosciences, Bad Homburg, Germany).Biological Assay 1: Diet-induced obesity and inflammation mouse model30 male C57BL / 6J mice were acquired from Charles River Germany, 5-6 weeks of age at arrival. The animals were allowed to habituate to the maintenance facilities and housed in groups of 5 mice in standard cages. Animals were randomly allocated to three experimental groups. After a week of acclimatization under a rodent diet with 10 Kcal% fat (Low Fat Diet, LFD; DIO-10 kJ% fat (lard) from Ssniff, Germany), mice werefed either the high fat diet (HFD) with 60 Kcal% Fat (DIO-60 kJ% fat (lard) from Ssniff, Germany) (n=20), or the LFD (n=10), matching sucrose content to HFD.All animals remained on the assigned diet for 8 weeks until the termination of the experiment. Compound #1 was administered subcutaneously once daily (5mg / kg, 4ml / kg body weight) to group 3, while vehicle was administered in parallel to group 1 and 2 fed LFD and HFD, respectively. The administration was performed in the morning between 09:00-10:00. Body weight was measured at arrival and three times per week (Monday, Wednesday, and Friday) from the day of the study start and over the course of the 8-week experiment. Blood glucose levels were assessed from nicked tails using a glucometer Contour XT (Bayer). A small incision was made with a scalpel, and then blood was obtained by direct flow or by gently massaging the tail. After wiping the first drop of blood to avoid haemolysis or contamination, 3 ul of blood were drawn on the test strips for glucose determination on the glucometer. Semi-fasted blood glucose (3h fasting) was monitored at day 29. Non-fasted blood glucose levels were monitored on day 56, before the animals were sacrificed.An intraperitoneal glucose tolerance test (IP_GTT) was performed in order to verify the effects on diet on glucose sensitivity. Mice were fasted for 12 h before an intraperitoneal injection of glucose (2 g / kg body weight diluted in 0.9% NaCI). Blood glucose levels were determined using a glucometer Contour XT (Bayer) and plotted as a function of time. A blood sample (3 pl) was drawn from tail vein at 5 different time points: 0 (before i.p. glucose administration), 15, 30, 60 and 120 minutes. The area under the curve (AUC) was calculated using an equation that quantifies the incremental area above the baseline, where only the area above the fasting level for each mouse is considered.To evaluate the response to insulin, mice were injected intraperitoneally with human insulin (Humulin; Eli Lilly) at a dose of 1.0 U / kg body weight in 0.9% NaCI. The rate of fall of blood glucose levels was monitored before (t=0) and at 15, 30, 60 and 90 minutes after insulin injection. For each individual mouse, blood glucose levels were plotted as a function of time. The AUC was calculated as described above for the IP- G l l .The results were analysed using a One-Way and Two-Way analysis of variance (ANOVA). If significant, Tukey's multiple comparison test was performed to assess statistical difference among groups. The level of significance was set at 0.05. All statistics and corresponding graphs were made using Graph Pad Prism.ResultsAs shown in Figure 1, the mice fed the high-fat diet (HFD) gained weight more rapidly than the mice fed the low-fat diet (LFD). Body weight was significantly increased (p<0.01) in the HFD group vs. LFD from day 23 until study completion (Day 56).As shown in Figure 2a and b, the fasting blood glucose levels at day 29 and 56 showed no difference between LFD or HFD. Additionally, baseline blood glucose levels (t=0, before an i.p. bolus of glucose (2 g / kg)) showed no significant differences among the groups for LFD vs HFD (figure 3A).However, the obesogenic high fat diet significantly exacerbated glucose intolerance after 6 weeks compared to LFD group with a p<0.001 at minutes 15, 30 and 60 minutes and impaired insulin sensitivity at about 8 weeks (figure 3a and b). The fact that the impaired glucose tolerance and insulin resistance are not a result of an impaired fasting glucose at day 29 or 56 (figure 2a and b) or baseline blood glucose at t=0 (fig 3) might reveal a state of chronic inflammation in the model, where inflammatory molecules can be the underlying cause for the glucose intolerance in insulin-sensitive tissues.Inflammatory markers were then assessed in the different treatment groups. The level of IgG was found to be significantly elevated in plasma of mice fed a high fat diet whereas treatment with compound #1 in animals fed a high fat diet significantly reduced the levels of IgG as compared to vehicle treated HFD-animals (figure 4A), thus demonstrating that animals fed a high fat diet develop a low-grade chronic inflammation that is reduced on treatment with compound #1.Moreover, inflammatory markers in the liver, which is is constantly exposed to various substances from food intake with inflammatory potential and is a site of complex immunological activity with the ability to produce local Immunoglobulins, were also assessed and, again a significant increase in the levels of IgG was observed in high fat diet mice, which was again reduced by treatment with compound #1 (Figure 4B).These results suggest that the compounds of the invention have the ability to reduce inflammation associated with obesity, impaired glucose handling, insulin resistance and diabetes mellitus.Biological Assay 2: Inflammation in mono-iodoacetate (MIA) induced arthritis in ratsOn day 0 osteoarthritis were induced by intraarticular injection of 2 mg / mL MIA at a dose volume of 50|j L per rat under isoflurane anesthesia to left hind limb. Animals were randomized into twelve groups based on paw withdrawal thresholds (g) on day 3, and treatment was initiated accordingly. Animals of the group (G) 1, vehicle control group was administered with vehicle whereas G2, G3, G4 were administered with the 3, 10 & 30 mg / kg, p.o. of compound #1, respectively. Gil was administered with reference compound Indomethacin 30 mg / kg, p.o. only on day 7 and day 11 and G12 were untreated through the study.Animals were observed for clinical signs to treatment throughout the study. Cage-side observations were made to detect any changes and general activity of the animals. After dose administration, all the animals were observed carefully for treatment related clinical signs, including morbidity and mortality.Knee oedema was used as a measurement of inflammation in the rats by measuring the knee diameter using a digital Vernier caliper (Mitutoyo) on day 3 and 7 and 11 at post 3hr of dosing in ipsilateral limb joints and expressed in mm units. Statistical analysis was conducted using a one-way ANOVA followed by Dunnett's multiple comparison test. Data were considered statistically significant if the P value was less than 0.05.ResultsRepeated once daily dosing of compound #1 at 3, 10 or 30 mg / kg by per oral administration starting at day 3 through day 11 led to significant reduction of knee diameter as a measurement of clinical symptom of inflammation. The reduction in inflammation was evident at day 7 for the 30 mg / kg group (figure 5 A) and at all doses (3, 10 and 30 mg / kg) at day 11 (figure 5B).This suggests that treatment with the compounds of the invention can reduce inflammation associated with arthritis.Biological Assay 3: Model to study NGF-induced inflammation in ratsSprague Dawley rats were 5-6 weeks at arrival to the test facility and 7-8 weeks at the time of the study. The rats were handled and acclimatized to the person performing the study at least 5 days before the study started. On the test day the animals were placed in the test room for at least 1 hour before habituation to the box for 15-20 min. The rats were individually marked and weighed, and the dose was calculated based upon body weight (dose volume lOmL / kg). Compound #1 (5 and lOmg / kg) or vehicle, was administered orally 2h prior to the test. Administration by oral gavage was performed using a syringe with an attached gavage feeding needle. To induce thermal sensitivity, 5 microgram of nerve growth factor (NGF) or vehicle (PBS), was given as an intra plantar injection into the animal's left hind paw (ILP), once per animal with a maximum volume of 30pL. This was carried out 3 hours before the test.As a measurement of paw inflammation, edema / volume (both in ILP and CLP) was measured using a Plethysmometer (electronic volume meter, Ugo Basile®) in connection with sacrifice. Results are expressed in Paw volume (mL).ResultsThe results of the paw volume on the ipsilateral paw are shown in Figure 6. Compound #1 showed a significant anti-inflammatory effect in group treated with 5 mg / kg compared to NGF-control group.This suggests that the compounds of the invention have an anti-inflammatory effect on NGF-induced inflammation. This suggests utility in the treatment of inflammation induced by NGF and in inflammatory disorders involving inflammation caused by NGF and it / or its interactions with the TrkA receptor.Biological Assay 4: Model to study aged-induced inflammation in miceC57BL / 6J mice were 9-10 weeks at arrival and identified by ID numbers (ID no. 1-23). The digits were marked with a permanent marker on their tails. Animals were allowed to age until 20 months old when the study was initiated. The mice were weighed on the first day of study start and every second day (Monday, Wednesday, and Friday). The dose volume was adjusted to the actual bodyweight if the loss or gain in weight was >5g. Body weights and health status were recorded and documented before administration. Compound #1 (5mg / kg) or vehicle was administered subcutaneously once daily (4ml / kg body weight). The administration was performed in the morning between 09:00-12:00. On day 28 the study was terminated, and blood was collected60 min after the last dose. The mice were anesthetized by inhalation of Isoflurane. When adequate depth of anesthesia had been reached, the blood was removed by cardiac puncture. Blood was collected in EDTA microtainer tubes and stored on ice. Plasma was separated within 60 minutes by centrifugation at 3000xG (+4°C) for 10 minutes and stored in -80°C until further analysis.After blood sampling, the animal was euthanized by decapitation and the brain was dissected. Cerebellum was removed and the brain was weighed, put in pre-labelled and pre-weighed foil and immediately snap-frozen on dry ice. The foil was wrapped carefully around the brain once it was frozen and stored in -80°C for further studies. The left hemisphere of the brain was subsequently used for analysis of inflammatory markers. A control group consisting of 3-4 months old animals were used as a comparative cohort representing young animals.ResultsPlasma or brain homogenate of young mice and old mice were used to evaluate levels of inflammation. As can be seen in figure 7A and 7B, the levels of both the light and heavy chain of IgG were increased in brain of old animals as compared to young animals. After once daily treatment for 4 weeks with 5 mg / kg of compound #1 the levels of both light and heavy chain of IgG in brains, were significantly reduced in old animals. This result was validated in brain and plasma (figure 8A and 8B) using an ELISA specific for mouse IgG. Old animals showed a significant increase of total IgG compared to young mice, that was significantly reduced with compound #1 (figure 8). Furthermore, analysis of the levels of the pro-inflammatory cytokines IL-6 and IL- lb in brain homogenates demonstrate increased levels by age and a significant reduction of both cytokines after treatment with compound #1 as can be seen in figures 9 and 10, respectively.The ability of compound #1 to reduce inflammatory markers in plasma and brain tissues, suggests that the compounds of the invention have an effect on both central and peripheral inflammation, arising from ageing, which is implicated in a range of age-related disorders.Biological Assay 5: Model to study amyloid-induced inflammation in APPNL'G'Fknock-in miceAPPNL-G-F knock in mjce express human amyloid precursor protein and provide a model of Alzheimer's pathology. The model has been used to study amyloid beta-induced inflammatory processes.24 female APPNL G Fmice, 10-11 months of age was used in this study. 12 female wildtype C57BL / 6JRJ, 10-11 months of age was used as a control group. The animals were housed in groups of 2-5 mice in IVC standard cages in a temperature- and humidity- controlled room with a 12-hr light / dark cycle (lights on at 6.00 am), with free access to standard lab chow and tap water. For identification of animals, tails were marked with a pen during the study. The animals were weighed three times per week. Animals were administrated with vehicle or 3 mg / kg of Compound #1 by per oral administration, 10 ml / kg, BID at 8:00 ±lh (a.m) and 16:00 ±lh (p.m) for 30 days. Animals were euthanized on day 30 following terminal blood collection and perfusion. Brains were excised and sampled separately.Brains were dissected and cut into left and right hemispheres. Parts of the left brain hemisphere was divided into two of which 2 / 3 were placed on pre-labelled (with animal AC ID) and pre-weighed foil squares (approximately 5 x 5cm) and immediately snap frozen on dry ice. The foil was wrapped carefully around the brain once it was frozen. 1 / 3 of brain was placed into pre-labelled (with animal ID) and pre-weighed Eppendorf tubes and immediately snap frozen on dry ice and stored at -80°C until further processed.ResultsPlasma or brain homogenate of wild type (wt) C57BL / 6JRJ mice, APPNL G Fknock-in mice or APPNL G Fknock-in mice treated with compound #1 were used to characterize the levels of inflammatory markers. As can be seen in figure 11 and 12, the levels IL- 6 and IgG, respectively, were significantly increased in brain homogenate and plasma from APPNL G Fknock-in mice as compared to wild type (Wt) mice. Treatment for 30 days with 3 mg / kg of compound #1 significantly reduced the levels of both IL-6 in brain homogenate and IgG in plasma of compound treated APPNL G Fknock-in mice compared to vehicle treated APPNL G Fknock-in mice.These reduction of inflammatory markers in both plasma and brain homogenate indicate that the compounds of the invention have an effect on both peripheral and central inflammation in an Alzheimer's disease model, suggesting potential utility inthe treatment of inflammation associated with Alzheimer's disease and other neurodegenerative disorders.Overall conclusions from Biological AssaysThe compounds of the invention have been shown to reduce inflammation induced by a range of stimuli and have been shown to reduce inflammatory markers in both brain homogenates and blood plasma, suggesting an effect on both central and peripheral inflammation. 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Claims

Claims1. A compound of formula I,wherein:R1is selected from the group consisting of a phenyl group and a benzofuranyl group, which phenyl and benzofuranyl groups are optionally substituted by one or more groups selected from halo, methyl, methoxy and methoxymethyl; andR2is selected from the group consisting of a C1-2 alkyl group, a C1-2 alkoxy group, a Ci- 2 alkoxyCi-2 alkyl group, a C1-2 alkoxy-Ci-2 alkoxy group and -A-R3, whereinA is selected from the group consisting of a direct bond, a C1-2 alkanediyl group, and an -OC1-2 alkanediyl group, which C1-2 alkanediyl and -OC1-2 alkanediyl groups are optionally substituted by one or more groups independently selected from fluoro and =0; andR3represents a 5-membered heteroaryl group selected from the group consisting of pyrazolyl, triazolyl and imidazolyl, which three groups are optionally substituted by one or more groups independently selected from fluoro, C1-2 alkyl and C1-2 fluoroalkyl; or a pyrrolidine group, which pyrrolidine group is optionally substituted with a =0 group; or a pharmaceutically acceptable salt thereof, for use in the treatment and / or prevention of inflammation.

2. A method of treating and / or preventing inflammation, comprising administering a therapeutically effective amount of a compound of formula I, or a pharmaceutically acceptable salt thereof, as defined in Claim 1 to a subject in need thereof.

3. The use of a compound of formula I, or a pharmaceutically acceptable salt thereof, as defined in Claim 1 for the manufacture of a medicament for the treatment and / or prevention of inflammation.

4. The compound for use, method or use as claimed in any one of Claims 1 to 3, wherein, in the compound of formula I, or pharmaceutically acceptable salt thereof, R1represents a phenyl group optionally substituted by one methyl, methoxy or methoxymethyl group, optionally wherein the optional substituent is a methyl or methoxymethyl group.

5. The compound for use, method or use as claimed in Claim 4, wherein, in the compound of formula I, or pharmaceutically acceptable salt thereof, the optional substituent is in the 3-position of the phenyl ring relative to the point of attachment of the R1group to the nitrogen atom.

6. The compound for use, method or use as claimed in any one of Claims 1 to 3, wherein, in the compound of formula I, or pharmaceutically acceptable salt thereof, R1represents a benzofuranyl group, which benzofuranyl group is optionally substituted by a methyl group, optionally wherein R1represents7. The compound for use, method or use, as claimed in any one of Claims 1 to 6, wherein, in the compound of formula I, or pharmaceutically acceptable salt thereof, A is selected from the group consisting of a direct bond, -CH2- and -OCH2-.

8. The compound fo use, method or use as claimed in any one of Claims 1 to 7, wherein, in the compound of formula I, or pharmaceutically acceptable salt thereof, R3is selected from a 5-membered heteroaryl group selected from the group consisting of pyrrol-l-yl, pyrazol-l-yl, pyrazol-4-yl, imidazol-l-yl, imidazol-2-yl, imidazol-5-yl, and 1,2,4-triazol-l-yl, and a pyrrolidin-l-yl group, wherein each 5-membered heteroaryl group is optionally substituted by one or more fluoro, methyl, or ethyl groups, which latter two groups are optionally substituted by one or more fluoro groups, and the pyrrolidin-l-yl group is optionally substituted by a =0 group.

9. The compound for use, method or use as claimed in Claim 1, wherein the compound of formula I is selected from the group consisting of: l-(3-methyl-4-phenoxyphenyl)-3-phenyl-l, 3, 5-triazinane-2, 4, 6-trionel-(3-methyl-4-phenoxyphenyl)-3-(3-methylphenyl)-l, 3, 5-triazinane-2, 4, 6-trionel-[3-(methoxymethyl)phenyl]-3-(3-methyl-4-phenoxyphenyl)-l,3,5-triazinane- 2,4,6-trionel-[3-(methoxymethyl)-4-phenoxyphenyl]-3-(3-methylphenyl)-l,3,5-triazinane-2, 4, 6-trionel-(2-methyl-l-benzofuran-7-yl)-3-(3-methyl-4-phenoxyphenyl)-l,3,5-triazinane-2, 4, 6-trionel-(l-benzofuran-4-yl)-3-(3-methyl-4-phenoxyphenyl)-l,3,5-triazinane-2, 4, 6-trionel-(l-benzofuran-7-yl)-3-(3-methyl-4-phenoxyphenyl)-l,3,5-triazinane-2, 4, 6-trionel-(3-ethyl-4-phenoxyphenyl)-3-phenyl-l,3,5-triazinane-2, 4, 6-trionel-(3-ethyl-4-phenoxyphenyl)-3-(3-methylphenyl)-l,3,5-triazinane-2, 4, 6-trionel-{4-phenoxy-3-[( IH-pyrazol- l-yl)methyl]phenyl}-3-phenyl- 1,3, 5-triazinane-2, 4,6- trionel-{3-[(lH-imidazol-l-yl)methyl]-4-phenoxyphenyl}-3-phenyl-l,3,5-triazinane-2,4,6- trionel-{4-phenoxy-3-[(lH-l,2,4-triazol-l-yl)methyl]phenyl}-3-phenyl-l,3,5-triazinane-2, 4, 6-trionel-{3-[( lH-imidazol-l-yl)methyl]-4-phenoxyphenyl}-3-(3-methylphenyl)- 1,3,5- triazinane-2, 4, 6-trionel-{3-[( lH-imidazol-2-yl)methoxy]-4-phenoxyphenyl}-3-(3-methylphenyl)- 1,3,5- triazinane-2, 4, 6-trionel-{3-[(4-fluoro-lH-imidazol-l-yl)methyl]-4-phenoxyphenyl}-3-(3-methylphenyl)- l,3,5-triazinane-2, 4, 6-trionel-{3-[(4-fluoro- IH-pyrazol- l-yl)methyl]-4-phenoxyphenyl}-3-phenyl- 1,3,5- triazinane-2, 4, 6-trionel-{3-[(4-fluoro-lH-pyrazol-l-yl)methyl]-4-phenoxyphenyl}-3-(3-methylphenyl)- l,3,5-triazinane-2, 4, 6-trionel-{3-[(l-ethyl-lH-pyrazol-4-yl)methyl]-4-phenoxyphenyl}-3-phenyl-l,3,5- triazinane-2, 4, 6-trionel-(3-methylphenyl)-3-{4-phenoxy-3-[( IH-pyrazol- l-yl)methyl]phenyl}- 1,3,5- triazinane-2, 4, 6-trionel-{3-[(4-ethyl- IH-pyrazol- l-yl)methyl]-4-phenoxyphenyl}-3-phenyl- 1,3,5- triazinane-2, 4, 6-trionel-{3-[(4-ethyl- IH-pyrazol- l-yl)methyl]-4-phenoxyphenyl}-3-(3-methylphenyl)- l,3,5-triazinane-2, 4, 6-trionel-(3-{[4-(difluoromethyl)-lH-imidazol-l-yl]methyl}-4-phenoxyphenyl)-3-(3- methylphenyl)- l,3,5-triazinane-2, 4, 6-trionel-[3-(2-methoxyethoxy)-4-phenoxyphenyl]-3-phenyl-l,3,5-triazinane-2, 4, 6-trionel-[3-(2-methoxyethoxy)-4-phenoxyphenyl]-3-(4-methylphenyl)-l,3,5-triazinane-2, 4, 6-trionel-[3-(2-methoxyethoxy)-4-phenoxyphenyl]-3-(3-methylphenyl)-l,3,5-triazinane-2, 4, 6-trionel-[3-(2-methoxyethoxy)-4-phenoxyphenyl]-3-(3-methylphenyl)-l,3,5-triazinane-2, 4, 6-trionel-(4-chlorophenyl)-3-[3-(2-methoxyethoxy)-4-phenoxyphenyl]-l,3,5-triazinane-2,4,6-trionel-[3-(2-methoxyethoxy)-4-phenoxyphenyl]-3-(4-methoxyphenyl)-l,3,5-triazinane- 2,4,6-trionel-[3-(2-methoxyethoxy)-4-phenoxyphenyl]-3-(3-methoxyphenyl)-l,3,5-triazinane-2, 4, 6-trionel-(3-methylphenyl)-3-{3-[(2-oxopyrrolidin-l-yl)methyl]-4-phenoxyphenyl}-l,3,5- triazinane-2, 4, 6-trioneor a pharmaceutically acceptable salt thereof.

10. The compound for use, method or use as claimed in Claim 9, wherein the compound of formula I is l-(3-methyl-4-phenoxyphenyl)-3-phenyl-l,3,5-triazinane- 2, 4, 6-trioneor a pharmaceutically acceptable salt thereof.

11. The compound for use, method or use as defined in any one of Claims 1 to 10, wherein the inflammation is peripheral inflammation.

12. The compound for use, method or use as defined in any one of Claims 1 to 10, wherein the inflammation is neuroinflammation.

13. The compound for use, method or use as defined in any one of Claims 1 to 12, wherein the inflammation is acute inflammation, sub-acute inflammation or chronic inflammation; optionally wherein the inflammation is chronic inflammation.

14. The compound for use, method or use, as defined in any one of Claims 1 to 12, wherein the inflammation is associated with a disease or disorder selected from the group consisting of a metabolic disorder, arthritis, an inflammatory disorder of the peripheral nervous system, an inflammatory skin disease, an inflammatory respiratory disease, an inflammatory disease of the digestive system, cystitis, interstitial cystitis, systemic lupus erythematosus and an inflammatory disorder of the central nervous system.

15. The compound for use, method or use as claimed in Claim 14, wherein the inflammation is associated with a metabolic disorder, optionally wherein the metabolic disorder is selected from the group consisting of obesity and diabetes.

16. The compound for use, method or use as claimed in Claim 14, wherein the inflammation is associated with arthritis, optionally wherein the arthritis is selected from rheumatoid arthritis, psoriatic arthritis and osteoarthritis.

17. The compound for use, method or use as claimed in Claim 14, wherein the inflammation is associated with an inflammatory disorder of the peripheral nervous system, optionally wherein the inflammatory disorder or the peripheral nervous system is selected from inflammatory polyneuropathy and neuritis.

18. The compound for use, method or use as claimed in Claim 14, wherein the inflammation is associated with an inflammatory skin disease, optionally wherein the inflammatory skin disease is selected from the group consisting of psoriasis, dermatitis and pruritis.

19. The compound for use, method or use as claimed in Claim 14, wherein the inflammation is associated with an inflammatory respiratory disease, optionally wherein the inflammatory respiratory disease is selected from the group consisting of rhinitis, allergic airway inflammation, acute upper and lower respiratory infectious diseases and chronic lower respiratory diseases.

20. The compound for use, method or use as claimed in Claim 14, wherein the inflammation is associated with an inflammatory disease of the digestive system,optionally wherein the inflammatory disease of the digestive system is selected from ulcerative colitis and Crohn's disease.

21. The compound for use, method or use as claimed in Claim 14, wherein the inflammation is associated with systemic lupus erythematosus.

22. The compound for use, method or use as defined in Claim 14, wherein the inflammation is associated with an inflammatory disorder of the central nervous system, optionally wherein the inflammatory disorder or the central nervous system is selected from the group consisting of a neurodegenerative disorder, myalgic encephalomyelitis / chronic fatigue syndrome, meningitis, an autoimmune neuroinflammatory disease, encephalitis, encephalomyelitis, sequelae of inflammatory diseases of the central nervous system, stroke, transient ischemic attack, vascular dementia, multi-infarct dementia, traumatic brain injury, cerebral amyloid angiopathy and chronic traumatic encephalopathy.

23. The compound for use, method or use, as defined in Claim 22, wherein the inflammation is associated with an inflammatory disorder of the central nervous system is a neurodegenerative disorder selected from the group consisting of Alzheimer's disease, Parkinson's disease, Lewy body dementia, frontotemporal lobar degeneration, Huntington's disease, motor neuron disease, multiple sclerosis, Charcot-Marie-Tooth disease and amyotrophic lateral sclerosis.

24. The compound for use, method or use as claimed in Claim 23, wherein the neurodegenerative disorder is selected from Lewy body dementia, frontotemporal lobar degeneration, Parkinson's disease and amyotrophic lateral sclerosis.

25. The compound for use, method or use as claimed in Claim 24, wherein the neurogenerative disorder is selected from Parkinson's disease and Alzheimer's disease optionally wherein the neurodegenerative disorder is Alzheimer's disease.

26. A compound of formula I, or a pharmaceutically acceptable salt thereof, as defined in any one of Claims 1 to 10, for use in the treatment and / or prevention of an inflammatory disease or disorder selected from arthritis, an inflammatory disorder of the peripheral nervous system, an inflammatory skin disease, an inflammatory respiratory disease, an inflammatory disease of the digestive system, cystitis, interstitial cystitis and systemic lupus erythematosus.

27. A method of treating and / or preventing an inflammatory disease or disorder selected from arthritis, an inflammatory disorder of the peripheral nervous system, an inflammatory skin disease, an inflammatory respiratory disease, an inflammatory disease of the digestive system, cystitis, interstitial cystitis and systemic lupus erythematosus comprising administering a therapeutically effective amount of a compound of formula I, or a pharmaceutically acceptable salt thereof, as defined in any one of Claims 1 to 9 to a patient in need thereof.

28. The use of a compound of formula I, or a pharmaceutically acceptable salt thereof, as defined in any one of Claims 1 to 10, for the manufacture of a medicament for treating and / or preventing an inflammatory disease or disorder selected from arthritis, an inflammatory disorder of the peripheral nervous system, an inflammatory skin disease, an inflammatory respiratory disease, cystitis, interstitial cystitis and systemic lupus erythematosus.

29. The compound for use, method or use as claimed in any one of Claims 26 to 28, wherein the inflammatory disease or disorder is arthritis, optionally wherein the arthritis is selected from rheumatoid arthritis, psoriatic arthritis and osteoarthritis.

30. The compound for use, method or use as claimed in any one of Claims 26 to 28, wherein the inflammatory disease or disorder is an inflammatory disorder of the peripheral nervous system, optionally wherein the disease or disorder is selected from inflammatory polyneuropathy and neuritis.

31. The compound for use, method or use as claimed in any one of Claims 26 to 28, wherein the inflammatory disease or disorder is an inflammatory skin disease, optionally wherein the inflammatory skin disease is selected from the group consisting of psoriasis, dermatitis and pruritis.

32. The compound for use, method or use as claimed in any one of Claims 26 to 28, wherein the inflammatory disease or disorder is an inflammatory respiratory disease, optionally wherein the inflammatory respiratory disease is selected from the group consisting of allergic rhinitis, chronic rhinitis, allergic airway inflammation, an acute upper respiratory infectious disease, an acute lower respiratory infectious disease and a chronic lower respiratory disease, optionally wherein the chronic lower respiratory disease is asthma.

33. The compound for use, method or use as claimed in any one of Claims 26 to 28, wherein the inflammatory disease or disorder is an inflammatory disease of the digestive system, optionally wherein the inflammatory disease of the digestive system is selected from ulcerative colitis and Crohn's disease.

34. The compound for use, method or use as claimed in any one of Claims 26 to 28, wherein the inflammatory disease or disorder is selected from cystitis and interstitial cystitis.

35. The compound for use, method or use as claimed in any one of Claims 26 to 28, wherein the inflammatory disease or disorder is systemic lupus erythematosus.

36. The compound for use, method or use as claimed in any one of Claims 1 to 35, wherein the treatment and / or prevention of inflammation or inflammatory disease or disorder comprises reducing the level of IL-6, IL-lb and / or IgG in the patient being treated, optionally wherein the level of IL-6, IL-lb and / or IgG that is reduced is in the blood or in the cerebrospinal fluid.

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