N-substituted 9-aminoacridines and their use in the treatment of cancer

Abstract

There are herein provided compounds of formula (I) or a pharmaceutically-acceptable salt and / or detectably-labelled derivative thereof, wherein X, m, R1, R3, R4, Y and n have meanings as provided in the description. Medical uses thereof are also provided herein.

Description

[0001] N-SUBSTITUTED 9-AMINOACRIDINES AND THEIR USE IN THE TREATMENT OF CANCER

[0002] Field of the Invention

[0003] The present invention relates to novel compounds, compositions comprising such compounds, and the use of such compounds and compositions in medicine. In particular, the present invention relates to the use of such compounds and compositions in methods for the treatment of cancers, which treatment is thought to occur through specific and potent inhibition of MYC: MAX interaction.

[0004] Background of the Invention

[0005] The 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.

[0006] The MYC family of oncogenes, consisting of MYC, MYCN and MYCL (here collectively referred to as "MYC"), encodes basic helix-loop-helix leucine zipper (bHLHZip) transcription factors (Meyer, N. & Penn, L. Z., Nat Rev Cancer, 8, 976-990 (2008)). Through the HLHZip domain, MYC heterodimerizes with the bHLHZip protein MAX, which enables the MYC:MAX complex to bind E-box regulatory DNA elements throughout the genome, thereby controlling transcription of a large group of specific genes. The direct target gene products in turn influences global RIMA and protein synthesis, thereby coordinating multiple fundamental cellular processes, including cell cycle progression, cell growth, apoptosis, senescence, metabolism and stem cell functions. In addition to MAX, MYC interacts with a plethora of other proteins carrying out different functions in gene regulation. Deregulation of expression of MYC family genes / proteins occurs in over half of all human tumors, and can be caused by chromosomal aberrations affecting the MYC loci, such as translocation and gene amplification, or can be due to oncogenic aberrations affecting upstream regulators of MYC. Abnormal MYC expression is often correlated with aggressive disease, resistance to therapy and poor prognosis, and MYC is therefore considered as one of the most important drivers of tumor development. Evidence from mouse models has shown that elimination of MYC using genetic tools often causes complete and irreversible tumor regression with well-tolerated and reversible side effects, suggesting that MYC would be a suitable target for cancer therapy (Soucek, L. et al., Nature, 455, 679-683 (2008)). However, so far there are no specific anti-MYC drugs available in the clinic. Although MYC has previously been considered "undruggable", a number of efforts have been made during recent years to target MYC. MYC expression is sensitive to BET bromodomain inhibitors and to protein translation inhibitors in certain cells. Alternatively, kinases regulating MYC activity and turnover, druggable key downstream MYC target gene products or synthetic lethal interactions involving MYC can be targeted (McKeown, M. R. & Bradner, J. E., Cold Spring Harb Perspect Med, 4, (2014)). However, these approaches are not specific for MYC, are context-dependent, and are presumably bound to fail eventually due to selection of alternative pathways regulating MYC expression and activity in tumor cells.

[0007] While these strategies all target MYC indirectly, several efforts to target the MYC protein directly have also been reported (Fletcher, S. & Prochownik, E. V., Biochim Biophys Acta 1849, 525-543 (2015)). Since MYC is strictly dependent on MAX for binding E-boxes, targeting MYC:MAX or MYC:MAX:DNA interactions are therefore a conceivable approach to target MYC activity (Blackwood, E. M. & Eisenman, R. N., Science 251, 1211-1217 (1991)). This suggests that the MYC: MAX heterodimer could be a potential drug target in vivo. However, targeting protein-protein interactions (PPI) is challenging due to presumed large, flat interactions surfaces lacking pockets amenable for small-molecule binding (Nero et al., 2014). In addition, the monomeric MYC bHLHZip domain is intrinsically disordered, and adopts an o-helical HLHZip fold upon dimerization with MAX (Metallo, 2010; Nair and Burley, 2003). Nevertheless, it has become clear that PPIs often involve "hot spots" engaging a small number, or cluster, of residues where most of the binding energy is localized, and therefore potentially druggable with small molecules (Nero, T. L., Morton, C. J., Holien, J. K., Wielens, J. & Parker, M. W., Nature reviews. Cancer, 14, 248-262 (2014); Zinzalla, G., and Thurston, D.E., Future Med Chem, 1, 65-93 (2009)).

[0008] During recent years there have been several reports of successful targeting of proteinprotein interactions with small molecules, including Nutlin-3a (targeting p53:MDM2) ( Vassilev, L.T. et al., Science, 303, 844-848 (2004)), BET inhibitors such as JQ1 (bromodomains: histones) (Filippakopoulos, P. et al., Nature, 468, 1067-1073 (2010)) and the BH3 mimetic compound Navitoclax / ABT-263 (BCL-2 family protein interactions) (Tse, C. et al., Cancer Res, 68, 3421-3428 (2008)). These compounds, or improved versions, are now in clinical trials, which have encouraged further research on PPIs as drug targets (Arkin, M.R., Tang, Y., and Wells, J. A., Chemistry & biology, 21, 1102-1114 (2014); Nero, T. L., Morton, C. J., Holien, J. K., Wielens, J. & Parker, M. W., Nature reviews. Cancer, 14, 248-262 (2014)). Several research groups have attempted to find compounds targeting the MYC: MAX interaction by screening small-molecule libraries using either FRET, or fluorescence polarization in vitro, or by applying yeast-two-hybrid (Y2H) assays (Fletcher, S. & Prochownik, E. V., Biochim Biophys Acta 1849, 525-543 (2015)). Another approach has been the design of peptidomimetic molecules targeting MYC: MAX PPIs based on the structures of the HLHZip region of MYC or MAX (Giorello, L. et al., Cancer Res, 58, 3654-3659 (1998)). As a result, a number of small molecules have been identified that target the MYC: MAX or MYC:MAX:DNA interaction in vitro and in mammalian cells, and that inhibit MYC-driven tumor cell growth in cell cultures and to some extent in vivo (Fletcher, S. & Prochownik, E. V., Biochim Biophys Acta 1849, 525-543 (2015); McKeown, M. R. 8<. Bradner, J. E., Cold Spring Harb Perspect Med, 4, (2014); Li et al, J Am Chem Soc, 146, 1356-1363 (2024)). Small molecule inhibitors exhibiting anticancer activity in a mouse model have been identified using in silico screening (Han, H. et al., Cancer Cell 36, 483-497 (2019), Zhao, C. et al., J Med Chem, 67, 11751-11768 (2024)). Inhibitors that inhibit MYC activity by covalently binding to cysteines have also been investigated (Boike, L., Cell Chem Biol, 28, 4-13 (2021)).

[0009] Recently, certain azo-containing acridines have been found to interfere with MYC: MAX interaction in cells and in vitro (WO 2019 / 145375).

[0010] Qiu et al., Theranostics, 11, 7658 (2021) describes the compound STOCK2S-26016 as having anticancer properties.

[0011] However, there exists an urgent need to identify and develop new potent and selective direct MYC inhibitors suitable for in vivo applications, such as for the treatment of cancers.

[0012] Detailed Description of the Invention

[0013] It has now been found that certain N-substituted 9-aminoacridines have surprising properties which render such compounds useful in the treatment of cancers.

[0014] By using a cell-based assay, it has now surprisingly been found that these 9-aminoacridines strongly inhibit tumor cell activity in vitro. In particular, the compounds are useful in the treatment of cancers characterised by increased activity of the MYC pathway (i.e. increased MYC activity). Moreover, advantageously, it has now been found that the compounds of the invention are photostable. This is particularly surprising given that it has been found that the compound STOCK2S-26016 for use in the treatment of cancer as described in Qiu et al., Theranostics, 11, 7658 (2021) has low photostability, as shown in the Stability Example (where the STOCK2S-26016 compound is used as reference). The problem of low photostability of this compound was not previously recognised.

[0015] The STOCKS2S-26016 compound refers to the compound of the following structure.

[0016] Compounds of the invention

[0017] In a first aspect of the invention, there is provided a compound of formula I or a pharmaceutically-acceptable salt and / or detectably-labelled derivative thereof, wherein:

[0018] L represents -N(R2)C(O)(CH2)WI-, -N(R2)S(O)qi(CH2)w2- or -C(O)N(R2)(CH2)w3-; wl to w3 each independently represents 0 to 3;

[0019] R1represents C3-12 alkyl, C3-12 alkenyl or C3-12 alkynyl, each optionally substituted by one or more groups independently selected from Gla, C3-10 cycloalkyl optionally substituted by one or more groups independently selected from Glb, heterocyclyl optionally substituted by one or more groups independently selected from Glc, aryl optionally substituted by one or more groups independently selected from Gld, or heteroaryl optionally substituted by one or more groups independently selected from Gle; R2represents H or Ci-6 alkyl optionally substituted by one or more groups independently selected from F, -CN, -OH, -OCi-4 alkyl optionally substituted by one or more F, or =0;

[0020] R3and R4each independently represent H or Ci-6 alkyl optionally substituted by one or more groups independently selected from F, -CN, -OH and -OCi-6 alkyl optionally substituted by one or more F; each X and Y independently represents halo, Ci-6 alkyl optionally substituted by one or more F, -CN, -OH or -OCi-6 alkyl optionally substituted by one or more F; m represents 0, 1, 2, 3 or 4; n represents 0, 1, 2 or 3; ql represents 1 or 2; each Gla, Glband Glcindependently represents halo, Ral, -CN, -Aal-C(O)Rbl, -Abl-C(O)N(Rcl)Rdl, -Acl-C(O)ORel, -Adl-S(O)PRfl, -Ael-S(O)PN(Rgl)Rhl, -A^-SCOJpOR11, -N3, -N(Rjl)Rkl, -OR11, -SRmlor =0; each Gldand Gleindependently represents halo, Ral, -CN, -Aal-C(O)Rbl, -Abl-C(O)N(Rcl)Rdl, -Acl-C(O)ORel, -Adl-S(O)PRfl, -Ael-S(O)PN(Rgl)Rhl, -A^-SCOJpOR11, -N3, -N(Rjl)Rkl, -N02, -OR11or -SRml; each Aalto Aflindependently represents a single bond, -N(Rn1)- or -0-; each Raland Rflindependently represents Ci-6 alkyl, C2-6 alkenyl or C2-6 alkynyl, each optionally substituted by one or more groups independently selected from G2a, C3-10 cycloalkyl optionally substituted by one or more groups independently selected from G2b, heterocyclyl optionally substituted by one or more groups independently selected from G2c, aryl optionally substituted by one or more groups independently selected from G2d, or heteroaryl optionally substituted by one or more groups independently selected from G2e; each Rbl, Rcl, Rdl, Rel, Rgl, Rhl, R'1, Rjl, Rkl, R11, and Rmlindependently represents H or C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl, each optionally substituted by one or more groups independently selected from G2a, C3-10 cycloalkyl optionally substituted by one or more groups independently selected from G2b, heterocyclyl optionally substituted by one or more groups independently selected from G2c, aryl optionally substituted by one or more groups independently selected from G2d, or heteroaryl optionally substituted by one or more groups independently selected from G2e, or alternatively any of RC1and Rdl, Rgland Rhland / or Rjland Rklare linked together to form, together with the nitrogen atom to which they are attached, a 3- to 6-membered ring, which ring optionally contains one further heteroatom and which ring optionally is substituted by one or more groups independently selected from F, C1-3 alkyl optionally substituted by one or more F, or -OC1-3 alkyl optionally substituted by one or more F and =0; each Rnlindependently represents H or C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl, each optionally substituted by one or more groups independently selected from G2a, C3-6 cycloalkyl optionally substituted by one or more groups independently selected from G2bor heterocyclyl optionally substituted by one or more groups independently selected from G2c; each G2a, G2band G2cindependently represents F, Ra2, -ON, -Aa2-C(O)Rb2, -Ab2-C(O)N(Rc2)Rd2, -Ac2-C(O)ORe2, -Ad2-S(O)PRf2, -Ae2-S(O)PN(Rg2)Rh2, -Af2-S(O)PORi2, -N(Rj2)Rk2, -OR12, -SRm2or =0; each G2dand G2eindependently represents halo, Ra2, -ON, -Aa2-C(O)Rb2, -Ab2-C(O)N(Rc2)Rd2, -Ac2-C(O)ORe2, -Ad2-S(O)PRf2, -Ae2-S(O)PN(Rg2)Rh2, -Af2-S(O)PORi2, -N3, -N(Rj2)Rk2, -NO2, -OR12or -SRm2; each Aa2to Af2independently represents a single bond, -N(Rn2)- or -0-; each Ra2and Rf2independently represents C1-6 alkyl optionally substituted by one or more groups independently selected from F, -ON or -OC1-3 alkyl optionally substituted by one or more F; each Rb2, Rc2, Rd2, Re2, Rg2, Rh2, R'2, Rj2, Rk2, R12, Rm2and Rn2independently represents H or C1-6 alkyl optionally substituted by one or more groups independently selected from F, -ON, -OH or -OC1-3 alkyl optionally substituted by one or more F, or alternatively any of Rc2and Rd2, Rg2and Rh2, Rj2and / or Rk2are linked together to form, together with the nitrogen atom to which they are attached, a 3- to 6-membered ring, which ring optionally contains one further heteroatom and which ring optionally is substituted by one or more groups independently selected from F, C1-3 alkyl optionally substituted by one or more F; each p independently represents 1 or 2, which compounds may be referred to herein as the "compounds of the invention".

[0021] 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.

[0022] 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.

[0023] 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.

[0024] Particular acid addition salts that may be mentioned include carboxylate salts (e.g. formate, acetate, trifluoroacetate, propionate, isobutyrate, heptanoate, decanoate, caprate, caprylate, stearate, acrylate, caproate, propiolate, ascorbate, citrate, glucuronate, glutamate, glycolate, a -hydroxy butyrate, 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, hydroxy maleate, hippurate, phthalate or terephthalate salts), halide salts (e.g. chloride, bromide or iodide salts), sulphonate salts (e.g. benzenesulphonate, methyl-, bromo- or chloro- benzenesulphonate, xylenesulphonate, methanesulphonate, ethanesulphonate, propanesulphonate, hydroxy-ethanesulphonate, 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.

[0025] Particular base addition salts that may be mentioned include salts formed 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, tromethamine and lysine) 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.

[0026] More particular pharmaceutically acceptable salts that may be mentioned include hydrochloride salts.

[0027] 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.

[0028] 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.

[0029] Compounds of the invention (and similarly, compounds excluded from the scope of the invention) may contain double bonds and, unless otherwise indicated, may thus exist as E entgegerf) 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 (or within the relevant exclusion).

[0030] For the avoidance of doubt, where a bond is indicated by a wavy line, the skilled person will understand that the substituent bond by that bond may be present in the E or Z configuration. 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).

[0031] 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 various stereoisomers (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.

[0032] 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).

[0033] 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, i.e. polycyclic (e.g. bicyclic or tricyclic), and / or spirocyclic. For example, multicyclic groups that may be mentioned include adamantyl. For the avoidance of doubt, particular alkyl groups that may be mentioned include straight chain (i.e. not branched and / or cyclic) alkyl groups.

[0034] Unless otherwise specified, C2-Z alkenyl 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 three) of carbon atoms, be branched-chain, and / or cyclic (so forming a C4-z cycloalkenyl group). When there is a sufficient number (i.e. a minimum of five) of carbon atoms, such groups may also be part cyclic. For example, part cyclic alkenyl groups (which may also be referred to as "part cycloalkenyl" groups) that may be mentioned include cyclopentenylmethyl and cyclohexenylmethyl. When there is a sufficient number of carbon atoms, such groups may also be multicyclic (e.g. bicyclic or tricyclic) or spirocyclic. For the avoidance of doubt, particular alkenyl groups that may be mentioned include straight chain (i.e. not branched and / or cyclic) alkenyl groups.

[0035] Unless otherwise specified, C2-Z alkynyl 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 four) of carbon atoms, be branched-chain. For the avoidance of doubt, particular alkynyl groups that may be mentioned include straight chain (i.e. not branched and / or cyclic) alkynyl groups.

[0036] For the avoidance of doubt, unless otherwise specified, groups referred to herein as "alkyl", "alkenyl" and / or "alkynyl" will be taken as referring to the highest degree of unsaturation in a bond present in such groups. For example, such a group having a carbon-carbon double bond and, in the same group, a carbon-carbon triple bond will be referred to as "alkynyl". Alternatively, it may be particularly specified that that such groups will comprise only the degree of unsaturation specified (i.e. in one or more bond therein, as appropriate; e.g. in one bond therein).

[0037] For the avoidance of doubt, alkyl, alkenyl and alkynyl groups as described herein may also act as linker groups (i.e. groups joining two or more parts of the compound as described), in which case such groups may be referred to as "alkylene", "alkenylene" and / or "alkynylene" groups, respectively.

[0038] 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).

[0039] As used herein, the term heterocyclyl may refer to non-aromatic monocyclic and polycyclic (e.g. bicyclic) heterocyclic groups (which groups may, where containing a sufficient number of atoms, also be bridged) in which at least one (e.g. one to four) of the atoms in the ring system is other than carbon (i.e. a heteroatom), and in which the total number of atoms in the ring system is between three and twelve (e.g. between five and ten, such as between three and eight; for example, forming a 5- or 6- membered heterocyclyl group). Further, such heterocyclyl groups may be saturated, forming a heterocycloalkyl, or unsaturated containing one or more carbon-carbon or, where possible, carbon-heteroatom or heteroatom-heteroatom double and / or triple bonds, forming for example a C2-Z (e.g. C4-z) heterocycloalkenyl (where z is the upper limit of the range) or a C?-z heterocycloalkynyl group.

[0040] For the avoidance of doubt, the skilled person will understand that heterocyclyl 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 heterocyclyl groups will be well-known to those skilled in the art, such as 7-azabicyclo-[2.2.1]heptanyl,

[0041] 6-azabicyclo[3.1.1]heptanyl, 2-azabicyclo[2.1.1]hexanyl, 6-azabicyclo[3.2.1]-octanyl, 8-azabicyclo[3.2.1]octanyl, aziridinyl, azetidinyl, 2,3-dihydroisothiazolyl, dihydropyranyl, dihydropyridinyl, dihydropyrrolyl (including 2,5-dihydropyrrolyl), dioxolanyl (including 1,3-dioxolanyl), dioxanyl (including 1,3-dioxanyl and 1,4-dioxanyl), dithianyl (including 1,4-dithianyl), dithiolanyl (including 1,3-dithiolanyl), hexahydro- lH-thieno[3,4-cf]imidazole, imidazolidinyl, imidazolinyl, isothiazolidinyl, morpholinyl,

[0042] 7-oxabicyclo[2.2.1]heptanyl, 6-oxabicyclo[3.2.1]-octanyl, oxetanyl, oxiranyl, piperazinyl, piperidinyl, pyranyl, pyrazolidinyl, pyrrolidinonyl, pyrrolidinyl, pyrrolinyl, quinuclidinyl, sulfolanyl, 3-sulfolenyl, tetrahydropyranyl, tetrahydrofuryl, tetra hydropyridinyl (such as 1,2,3,4-tetrahydropyridinyl and 1,2,3,6-tetrahydro- pyridinyl), thietanyl, thiiranyl, thiolanyl, tetrahydrothiopyranyl, thiomorpholinyl, trithianyl (including 1,3,5-trithianyl), tropanyl and the like.

[0043] Substituents on heterocyclyl groups may, where appropriate, be located on any atom in the ring system including a heteroatom. Further, in the case where the substituent is another cyclic compound, then the cyclic compound may be attached through a single atom on the heterocyclyl group, forming a spirocyclic compound. The point of attachment of heterocyclyl groups may be via any suitable atom in the ring system, including (where appropriate) a further heteroatom (such as a nitrogen atom), or an atom on any fused carbocyclic ring that may be present as part of the ring system. Heterocyclyl groups may also be in the N- or S- oxidised forms, as known to those skilled in the art.

[0044] At each occurrence when mentioned herein, particular heterocyclyl groups that may be mentioned include 3- to 8-membered heterocyclyl groups (e.g. a 4- to 6- membered heterocyclyl group, such as a 5- or 6- membered heterocyclyl group). Certain heterocyclyl groups that may be mentioned include tetra hydrofuranyl (e.g. tetrahydrofuran-2-yl), and tetra hydro pyranyl (e.g. tetrahydro-2H-pyran-4-yl).

[0045] For the avoidance of doubt, references to polycyclic (e.g. bicyclic or tricyclic) groups (for example when employed in the context of heterocyclyl or cycloalkyl groups (e.g. heterocyclyl)) will refer to ring systems wherein at least two scissions would be required to convert such rings into a non-cyclic (i.e. straight or branched) chain, with the minimum number of such scissions corresponding to the number of rings defined (e.g. the term bicyclic may indicate that a minimum of two scissions would be required to convert the rings into a straight chain). For the avoidance of doubt, the term bicyclic (e.g. when employed in the context of alkyl groups) may refer to groups in which the second ring of a two-ring system is formed between two adjacent atoms of the first ring, to groups in which two non-adjacent atoms are linked by an alkyl (which, when linking two moieties, may be referred to as alkylene) group (optionally containing one or more heteroatoms), which later groups may be referred to as bridged, or to groups in which the second ring is attached to a single atom, which latter groups may be referred to as spiro compounds.

[0046] As may be used herein, the term aryl may refer to Ce-i4 (e.g. Ce-io) aromatic groups. Such groups may be monocyclic or bicyclic and, when bicyclic, be either wholly or partly aromatic. Ce-io aryl groups that may be mentioned include phenyl, naphthyl, 1, 2,3,4- tetrahydronaphthyl, indanyl, and the like (e.g. phenyl, naphthyl, and the like). For the avoidance of doubt, the point of attachment of substituents on aryl groups may be via any suitable carbon atom of the ring system.

[0047] 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 or two 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).

[0048] 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.

[0049] 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.

[0050] 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).

[0051] 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[cf]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.

[0052] Particular heteroaryl groups that may be mentioned include furanyl (e.g. furan-2-yl) and pyridinyl (e.g. pyridin-3-yl). For the avoidance of doubt, where a ring is depicted having circle therein, its presence shall indicate that the relevant ring is aromatic. Alternatively, aromatic groups may be depicted as cyclic groups comprising therein a suitable number of double bonds to allow for aromaticity.

[0053] 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 from the 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.

[0054] 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 Ralgroups are present, those Ralgroups may be the same or different. Similarly, where two or more Ra2groups are present and each represent Ci-6 alkyl, the Ci-6 alkyl groups in question (and any substituents thereon) may be the same or different.

[0055] Further for the avoidance of doubt, when it is specified that a substituent is itself optionally substituted by one or more substituents (e.g. R1represents C3-12 alkyl optionally substituted by one or more groups independently selected from Gla), 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).

[0056] 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).

[0057] 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.

[0058] In a particular embodiment of the first aspect of the invention, there is the proviso (A) that the following compounds are excluded:

[0059] (A)

[0060] / V-(9-amino-7-ethoxyacridin-3-yl)benzamide;

[0061] / V-(9-amino-7-ethoxyacridin-3-yl)-3-bromobenzamide;

[0062] / V-(9-amino-7-ethoxyacridin-3-yl)-4-cyanobenzamide; methyl 4-((9-amino-7-ethoxyacridin-3-yl)carbamoyl)benzoate;

[0063] / V-(9-amino-7-ethoxyacridin-3-yl)-2-naphthamide;

[0064] / V-(9-amino-7-ethoxyacridin-3-yl)-4-fluorobenzamide;

[0065] / V-(9-amino-7-ethoxyacridin-3-yl)-3-cyanobenzamide;

[0066] / V-(9-amino-7-ethoxyacridin-3-yl)-3-nitro benzamide;

[0067] / V-(9-amino-7-ethoxyacridin-3-yl)-4-nitro benzamide;

[0068] / V-(9-amino-7-ethoxyacridin-3-yl)-3,5-bis(trifluoromethyl)benzamide; and / V-(9-amino-7-ethoxyacridin-3-yl)furan-2-carboxamide.

[0069] In a particular embodiment of the first aspect of the invention, there is the proviso (B) that the following compounds are excluded:

[0070] (B)

[0071] / V-(9-Amino-7-ethoxyacridin-3-yl)-2-phenylacetamide;

[0072] / V-(9-amino-7-ethoxyacridin-3-yl)-2-bromobenzamide;

[0073] / V-(9-amino-7-ethoxyacridin-3-yl)-4-methylbenzamide; and / V-(9-amino-7-ethoxyacridin-3-yl)-4-methoxybenzamide. In more particular embodiments (i.e. more particular embodiments of the first aspect of the invention), the compound of formula I is not a compound selected from the list consisting of:

[0074] (C)

[0075] In more particular embodiments (i.e. more particular embodiments of the first aspect of the invention), the compound of formula I is not the following compound:

[0076] (D)

[0077] / V-(9-amino-7-ethoxyacridin-3-yl)-4-chlorobenzamide.

[0078] In particular embodiments, the compound of formula I is not a compound referred to at points (A) to (D) above.

[0079] As defined herein, L represents -N(R2)C(O)(CH2)wi-, -N(R2)S(O)qi(CH2)W2-, or -C(O)N(R2)(CH2)W3-.

[0080] The skilled person will understand that each L attaches to the acridine ring via the bond adjacent to N or C, i.e. the left-hand side available bond of L (i.e. the first bond when reading from left to right), and L attached to R1via the bond adjacent to the -(CH2)wi-3- group, i.e. the right-hand side available bond of L. For example, when L represents -N(R2)C(O)(CH2)wi-, the compound of formula I may be drawn as follows: In particular embodiments (i.e. particular embodiments of the first aspect of the invention), L represents -N(R2)C(O)(CH2)wi- or -N(R2)S(O)qi(CH2)W2-.

[0081] In alternative embodiments, L represents -C(O)N(R2)(CH2)w3-.

[0082] In particular embodiments, each wl to w3 independently represents 0 to 2 (i.e. 0, 1 or 2), such as 0 or 1.

[0083] In more particular embodiments, each wl to w3 represent 0.

[0084] In alternative embodiments, each wl to w3 represent 1. For example, wl and / or w2 (e.g. wl) may represent 1.

[0085] As defined herein, ql represents 1 or 2. In particular embodiments, ql represents 2.

[0086] In particular embodiments, R2represents H or C1-3 alkyl optionally substituted by one or more groups independently selected from F, -CN, -OH, -OC1-4 alkyl optionally substituted by one or more F, or =0.

[0087] In more particular embodiments, R2represents H or C1-3 alkyl (e.g. methyl or ethyl) optionally substituted with one or more groups independently selected from F and =0.

[0088] In even more particular embodiments, R2represents H or methyl, e.g. H.

[0089] Thus, in certain embodiments, L represents -NHC(O)-, -N(Ci-3alkyl)C(0)-, -N(Ci-3alkyl)C(O)CH2-, -NHS(O)2-, -N(Ci-3alkyl)S(O)2-, -C(O)NH-, or -C(O)N(Ci-3alkyl)-.

[0090] In more particular embodiments, L represents -NHC(O)-, -NHC(0)CH2-, -NHS(0)2-, - N(Me)S(O)2-, -C(O)NH-, or -C(O)N(Me)-.

[0091] In yet more particular embodiments, L represents -NHC(O)- or -NHC(0)CH2-.

[0092] In particular embodiments, L represents -NHS(0)2- or -N(Me)S(O)2-.

[0093] In particular embodiments, L represents -C(O)NH- or -C(O)N(Me)- (e.g. -C(O)NH-). As defined herein, the compound of formula I is such that R1represents:

[0094] C3-12 alkyl, C3-12 alkenyl or C3-12 alkynyl, each optionally substituted by one or more (e.g. one, two or three, such as one) groups independently selected from Gla,

[0095] C3-10 cycloalkyl optionally substituted by one or more (e.g. one, two or three, such as one) groups independently selected from Glb, heterocyclyl optionally substituted by one or more (e.g. one, two or three, such as one) groups independently selected from Glc, aryl optionally substituted by one or more (e.g. one, two or three, such as one) groups independently selected from Gld, or heteroaryl optionally substituted by one or more (e.g. one, two or three, such as one) groups independently selected from Gle.

[0096] In particular embodiments, the compound of formula I is such that R1represents:

[0097] C3-12 alkyl, C3-12 alkenyl or C3-12 alkynyl, each optionally substituted by one or more (e.g. one, two or three, such as one) groups independently selected from Gla,

[0098] C3-10 cycloalkyl (e.g. C3-6 cycloalkyl) optionally substituted by one or more (e.g. one, two or three, such as one) groups independently selected from Glb, heterocyclyl optionally substituted by one or more (e.g. one, two or three, such as one) groups independently selected from Glc, or aryl optionally substituted by one or more (e.g. one, two or three, such as one) groups independently selected from Gld.

[0099] In particular embodiments, the compound of formula I is such that R1represents:

[0100] C3-12 alkyl, C3-12 alkenyl or C3-12 alkynyl, each optionally substituted by one or more (e.g. one, two or three, such as one) groups independently selected from Gla,

[0101] C3-10 cycloalkyl (e.g. C3-6 cycloalkyl) optionally substituted by one or more (e.g. one, two or three, such as one) groups independently selected from Glb, or aryl optionally substituted by one or more (e.g. one, two or three, such as one) groups independently selected from Gld.

[0102] In particular embodiments, the compound of formula I is such that R1represents:

[0103] C3-10 cycloalkyl (e.g. C3-6 cycloalkyl) optionally substituted by one or more (e.g. one, two or three, such as one) groups independently selected from Glb, heterocyclyl (such as heterocycloalkyl) optionally substituted by one or more (e.g. one, two or three, such as one) groups independently selected from Glc, or aryl optionally substituted by one or more (e.g. one, two or three, such as one) groups independently selected from Gld.

[0104] In more particular embodiments, the compound of formula I is such that R1represents:

[0105] C3-10 cycloalkyl (e.g. C3-6 cycloalkyl) optionally substituted by one or more (e.g. one, two or three, such as one) groups independently selected from Glb,

[0106] C5-6 heterocyclyl (such as C5-6 heterocycloalkyl) optionally substituted by one or more (e.g. one, two or three, such as one) groups independently selected from Glc, or

[0107] Ce-io aryl, each optionally substituted by one or more (e.g. one, two or three, such as one) groups independently selected from Gld.

[0108] In yet more particular embodiments, the compound of formula I is such that R1represents:

[0109] C3-6 or C10 cycloalkyl (such as C3-6 cycloalkyl) optionally substituted by one or more (e.g. one, two or three, such as one) groups independently selected from Glb,

[0110] C5-6 heterocyclyl (such as C5-6 heterocycloalkyl) optionally substituted by one or more (e.g. one, two or three, such as one) groups independently selected from Glc, or

[0111] Ce or C10 aryl, each optionally substituted by one or more (e.g. one, two or three, such as one) groups independently selected from Gld.

[0112] In certain embodiments, the compound of formula I is such that R1represents: cyclopropyl, cyclohexyl or adamantyl, each optionally substituted by one or more (e.g. one, two or three, such as one) groups independently selected from Glb, tetra hydrofuranyl, tetra hydropyranyl or piperidinyl, each optionally substituted by one or more (e.g. one, two or three, such as one) groups independently selected from Glc, or phenyl optionally substituted by one or more (e.g. one, two or three, such as one) groups independently selected from Gld.

[0113] In embodiments wherein R1represents heteroaryl, the heteroaryl represents one or two (particularly, one) ring heteroaryl, optionally substituted with one or more Gle. The skilled person will understand that in such embodiments at least one (or the one) ring of the heteroaryl is an aromatic ring. In certain embodiments, the compound of formula I is such that R1represents C3-10 cycloalkyl (such as C3-8 cycloalkyl, e.g. C3-6 cycloalkyl) optionally substituted by one or more (e.g. one, two or three, such as one) groups independently selected from Glb. In particular such embodiments, R1represents C3-8 cycloalkyl, such as C4-8 cycloalkyl (such as C4-6 cycloalkyl or C5-6 cycloalkyl), optionally substituted by one or more (e.g. one, two or three, such as one) groups independently selected from Glb.

[0114] In certain such embodiments, R1represents cyclohexyl optionally substituted by one or more (e.g. one, two or three, such as one) groups independently selected from Glb.

[0115] In certain embodiments, the compound of formula I is such that R1represents heterocyclyl (such as heterocycloalkyl) optionally substituted by one or more (e.g. one, two or three, such as one) groups independently selected from Glc.

[0116] In certain such embodiments, the compound of formula I is such that R1represents C5-6 heterocyclyl (such as C5-6 heterocycloalkyl) optionally substituted by one or more (e.g. one, two or three, such as one) groups independently selected from Glc.

[0117] In certain embodiments, the compound of formula I is such that R1represents aryl (such as Ce or C10 aryl, e.g. Ce aryl) optionally substituted by one or more (e.g. one, two or three, such as one) groups independently selected from Gld.

[0118] In certain embodiments, the compound of formula I is such that R1represents phenyl optionally substituted by one or more (e.g. one, two or three, such as one) groups independently selected from Gld.

[0119] In certain embodiments, the compound of formula I is such that R1represents heteroaryl (e.g. C5-6 heteroaryl, such as Ce-heteroaryl) optionally substituted by one or more (e.g. one, two or three, such as one) groups independently selected from Gle. In particular such embodiments, R1represents pyridinyl, such as pyridin-3-yl (referring to standard numbering, wherein the nitrogen represents position 1).

[0120] In particular embodiments, the compound of formula I is such that each Gla, Glband Glcindependently represents F, Ral, -Acl-C(O)ORel, -N(Rjl)Rkl, -OR11, or -SRml.

[0121] In more particular embodiments, the compound of formula I is such that each Gla, Glband Glcindependently represents F, Ral, -Acl-C(O)ORel, -N(Rjl)Rkl, or -OR11. In even more particular embodiments, the compound of formula I is such that each Gla, Glband Glcindependently represents F, -Acl-C(O)ORel, -N(Rjl)Rkl, or -OR11.

[0122] For example, the compound of formula I is such that each Gla, Glband Glcindependently represents F, -Acl-C(O)ORel, or -OR11.

[0123] In particular embodiments, the compound of formula I is such that each Gldand Gleindependently represents halo (e.g. F, Cl, Br), Ral, -CN, -Acl-C(O)ORel, -N3, -N(Rjl)Rkl, -NO2, -OR11, or -SRml.

[0124] In particular embodiments, the compound of formula I is such that each Gldand Gleindependently represents halo (e.g. F, Cl, Br), Ral, -CN, -Acl-C(O)ORel, -N(Rjl)Rkl, -NO2, -OR11, or -SRml.

[0125] In more particular embodiments, the compound of formula I is such that each Gldand Gleindependently represents halo (e.g. F, Cl, Br), Ral, -CN, -Acl-C(O)ORel, -N(Rjl)Rkl, -NO2, or -OR11.

[0126] In even more particular embodiments, the compound of formula I is such that each Gldand Gleindependently represents halo (e.g. F, Cl), Ral, -CN, -Acl-C(O)ORel, -N(Rjl)Rkl, or -OR11.

[0127] For example, in certain embodiments, the compound of formula I is such that each Gldand / or Gle(e.g. each Gld) independently represents halo (e.g. F, Cl), Me, -CN, -C(O)OH, -NH2, -NMe2or -OMe.

[0128] In particular embodiments, n represents 0 (i.e. there is no Y substituent present).

[0129] In particular embodiments, R3represents H.

[0130] In particular embodiments, R3and R4each represent H.

[0131] In particular embodiments, one of R3and R4represents H and the other represents methyl.

[0132] In certain embodiments, m represents 0 or 1. In some embodiments, m represents 0.

[0133] In some embodiments, m represents 1.

[0134] In particular embodiments, m represents at least 1 (i.e. at least one X substituent is present), such as m represents 1. In such embodiments, the essential X group may be present in the 7-position of the acridine ring (with m-1, which may be referred to as t, indicating the number of remaining X group(s) that is / are optionally present in other positions). For example, in relation to compounds of formula I wherein the essential L group is in the 3-position, at least one X group may be present in the 7- position.

[0135] The numbering of the acridine ring as used herein is as follows.

[0136] In particular embodiments, the compound of formula I is a compound of formula Ib wherein R1, R3, R4, X, Y, L and n are as defined for compounds of formula I (including all embodiments thereof) and t represents 0, 1, 2 or 3.

[0137] In particular embodiments, t represents 0.

[0138] In particular embodiments, n represents 0.

[0139] Thus, in particular embodiments that may be mentioned, m represents 1 (or t represents 0) and n represents 0.

[0140] For example, in particular embodiments the compound of formula I is a compound of formula Ic wherein R1, R3, R4, X, Y, L and n are as defined for compounds of formula I (including all embodiments thereof).

[0141] In particular embodiments (e.g. of formula la, lb or Ic), each X independently represents halo (e.g. fluoro or chloro, such as fluoro), -OH or -OCi-6 alkyl optionally substituted by one or more F.

[0142] In certain embodiments, at least one X (e.g. where defined, the essential X substituent) represents -OCi-6 alkyl optionally substituted by one or more F, and any remaining X groups, if present, represent fluoro or chloro (e.g. fluoro).

[0143] In particular embodiments: t represents 0; and / or (e.g. and)

[0144] X represents -OH or -OCi-6 alkyl optionally substituted by one or more F.

[0145] In particular embodiments, each X represents -OCi salkyl (e.g. -OC2 alkyl or -OMe, i.e. ethoxy or methoxy) optionally substituted by one or more F.

[0146] For example, in particular embodiments the compound of formula I is a compound of formula Id or le wherein R1, R3, R4, L, X, t, Y and n are as defined for compounds of formula I (including all embodiments thereof).

[0147] As described herein, in the first aspect of the invention there is provided a compound of formula I (including all embodiments thereof, such as compounds of formula la, lb, Ic, Id, and le) or a pharmaceutically-acceptable salt and / or detectably-labelled derivative thereof. For example, in particular embodiments the compound of formula I is a compound of formula Ig or Ih wherein R1, R3, R4, X, Y, L and n are as defined for compounds of formula I (including all embodiments thereof), and t represents 0, 1, 2, or 3.

[0148] For example, in particular embodiments, the compound of formula I is a compound of formula Ig' or Ig" wherein R1, R3, R4, L, X, t, Y and n are as defined for compounds of formula I (including all embodiments thereof).

[0149] In particular embodiments, the compound of formula I is a compound of formula Ih' or

[0150] Ih" wherein R1, R3, R4, L, X, t, Y and n are as defined for compounds of formula I (including all embodiments thereof). For the avoidance of doubt, where compounds of the invention are present as detectably-labelled derivative thereof, such derivatives may also be in the form of a pharmaceutically-acceptable salt.

[0151] In particular embodiments, the compound of the invention is a compound of formula I or a pharmaceutically-acceptable salt thereof.

[0152] In alternative embodiments, the compound of the invention is a detectably-labelled derivative of a compound of formula I, or a pharmaceutically-acceptable salt thereof.

[0153] The skilled person will be aware of numerous means for preparing detectably-labelled derivatives of compounds as described herein. For example, where the compound of the invention is detectably-labelled derivative of a compound of formula I, or a pharmaceutically-acceptable salt thereof, the compound of formula I as defined may be further substituted by (i.e. a H group as present in such compounds may be replaced with) one or more (e.g. one) additional substituent forming a detectable label.

[0154] In particular embodiments, the one or more detectable label will be present as a substituent on a heteroatom, which heteroatom may be present in formula I (including all embodiments thereof) or as part of a substituent as defined for formula I, such as by replacing a H on a hydroxy or amine group.

[0155] In particular, such detectable labels may be present as alternative groups representing: an R3and / or (e.g. or) R4substituent; one or more (e.g. one) substituents on R1and / or L, e.g. as, or as a part of, L, R2, a Gla, a Glb, a Glc, a Gldand / or (e.g. or) Glegroup; one or more (e.g. one) substituent(s) representing an X group, e.g. as, or as a part of, the -OCi-6 alkyl group; and / or (e.g. or) one or more (e.g. one) substituent(s) representing a Y group, e.g. as, or as a part of, the -OCi-6 alkyl group.

[0156] In particular embodiments, the detectable label may be present as an alternative group representing:

[0157] Gla, Glbor Glc(or as part of a Gla, Glbor Glcgroup, e.g. as a Ral, Rbl, Rcl, Rdl, Rel, Rfl, Rgl, Rhl, R'1, Rjl, Rkl, R11, or Rmlgroup); or

[0158] Gldor Gle(or as part of a Gldor Glegroup, e.g. as a Ral, Rbl, Rcl, Rdl, Rel, Rfl, Rgl, Rhl, R'1, Rjl, Rkl, R11, or Rmlgroup); or X, or as the -OCi-6 alkyl group; or

[0159] Y, or as the -OCi-6 alkyl group.

[0160] For example, the detectable label may be present as an alternative group representing, at each instance, one or more (e.g. one) of:

[0161] Rj\ Rkl, R11and Rml.

[0162] For the avoidance of doubt, in particular embodiments there is only one detectable label present in compounds of the invention (e.g. in particular embodiments, one of the above-mentioned groups may alternatively represent a detectable label).

[0163] The skilled person will understand that the term "detectable group", as used herein, will refer to a chemical moiety the presence of which may be identified, and the quantity and, in certain instances, distribution thereof measured, using assays as known to those skilled in the art.

[0164] In alternative embodiments of the first aspect of the invention, the detectable label (or detectable group) may be a radioisotope. In such instances, the skilled person will understand that such radiolabelled compounds may be provided by replacement of one or more (e.g. one) of the atoms forming such compounds with a radioactive isotope thereof (such as by replacement of one or more H with the isotope tritium (T)), which may refer to enrichment of a sample of the compound so that a significant amount (e.g. at least 1%, at least 2%, at least 5% or at least 10% by weight, such as at least 20%, at least 30%, at least 40% or at least 50%, e.g. at least 90%) thereof has the relevant atom replaced with the radioisotope thereof.

[0165] Particular compounds of the invention that may be mentioned include those compounds as described in the examples provided herein, and pharmaceutically acceptable salts thereof. For the avoidance of doubt, where such compounds of the invention include compounds in a particular salt form, compounds of the invention include those compounds in non-salt form and in the form of any pharmaceutically acceptable salt thereof (which may include the salt form present in such examples).

[0166] Thus, particular compounds of the invention that may be mentioned include:

[0167] / V-(9-Amino-7-ethoxyacridin-3-yl)tetrahydrofuran-2-carboxamide;

[0168] / V-(9-Amino-7-ethoxyacridin-3-yl)tetrahydro-2H-pyran-4-carboxamide;

[0169] / V-(9-Amino-7-ethoxyacridin-3-yl)-4-methylbenzenesulfonamide; / V-(9-Amino-7-ethoxyacridin-3-yl)-4-methoxybenzenesulfonamide; and

[0170] / V-(9-Amino-7-ethoxyacridin-3-yl)-4-methoxy-N-methylbenzenesulfonamide, and pharmaceutically acceptable salts and / or detectably-labelled derivatives thereof.

[0171] Certain other compounds of the invention that may be mentioned include:

[0172] / V-(9-Amino-7-ethoxyacridin-3-yl)-2-phenylacetamide, and pharmaceutically acceptable salts and / or detectably-labelled derivatives thereof.

[0173] Certain other compounds of the invention that may be mentioned include:

[0174] / V-(9-Amino-7-ethoxyacridin-3-yl)benzamide;

[0175] / V-(9-Amino-7-ethoxyacridin-3-yl)-3-bromobenzamide;

[0176] / V-(9-Amino-7-ethoxyacridin-3-yl)-4-cyanobenzamide;

[0177] Methyl 4-((9-amino-7-ethoxyacridin-3-yl)carbamoyl)benzoate; and / V-(9-Amino-7-ethoxyacridin-3-yl)furan-2-carboxamide, and pharmaceutically acceptable salts and / or detectably-labelled derivatives thereof.

[0178] Further certain compounds of the invention that may be mentioned include:

[0179] / V-(9-Amino-7-ethoxyacridin-3-yl)-4-azidobenzamide, and pharmaceutically acceptable salts and / or detectably-labelled derivatives thereof.

[0180] Further certain compounds of the invention that may be mentioned include:

[0181] / V-(9-Amino-7-ethoxyacridin-3-yl)nicotinamide;

[0182] / V-(9-Aminoacridin-3-yl)-2-methoxybenzamide;

[0183] / V-(9-Amino-5-ethoxyacridin-3-yl)-2-methoxybenzamide;

[0184] / V-(9-Amino-6-ethoxyacridin-3-yl)-2-methoxybenzamide;

[0185] / V-(9-Amino-7-ethoxyacridin-3-yl)-2-methoxy-N-methylbenzamide;

[0186] / V-(7-Ethoxy-9-(methylamino)acridin-3-yl)-2-methoxybenzamide; and / V-(9-Amino-7-hydroxyacridin-3-yl)benzamide, and pharmaceutically acceptable salts and / or detectably-labelled derivatives thereof. Medical uses

[0187] As indicated herein, the compounds of the invention, and therefore compositions and kits comprising the same, are useful as pharmaceuticals.

[0188] Thus, according to a second aspect of the invention there is provided a compound of the invention, as hereinbefore defined (i.e. a compound as defined in the first aspect of the invention, including all embodiments and particular features thereof), for use as a pharmaceutical (or for use in medicine).

[0189] For the avoidance of doubt, references to compounds of the invention (i.e. compounds as defined in the first aspect of the invention) will include references to compounds of formula I (including all embodiments thereof, such as compounds of formula la to le) and pharmaceutically acceptable salts and detectably-labelled derivatives thereof.

[0190] In particular embodiments of the second aspect of the invention (including all alternatives thereof), there is a proviso that certain compounds are excluded, or that the compound of formula I is not selected from a list of certain compounds, as described in the first aspect of the invention.

[0191] In a more particular embodiment of the second aspect of the invention, there is the proviso (A) that the following compounds are excluded:

[0192] (A)

[0193] / V-(9-amino-7-ethoxyacridin-3-yl)benzamide;

[0194] / V-(9-amino-7-ethoxyacridin-3-yl)-3-bromobenzamide;

[0195] / V-(9-amino-7-ethoxyacridin-3-yl)-4-cyanobenzamide; methyl 4-((9-amino-7-ethoxyacridin-3-yl)carbamoyl)benzoate;

[0196] / V-(9-amino-7-ethoxyacridin-3-yl)-2-naphthamide;

[0197] / V-(9-amino-7-ethoxyacridin-3-yl)-4-fluorobenzamide;

[0198] / V-(9-amino-7-ethoxyacridin-3-yl)-3-cyanobenzamide;

[0199] / V-(9-amino-7-ethoxyacridin-3-yl)-3-nitrobenzamide;

[0200] / V-(9-amino-7-ethoxyacridin-3-yl)-4-nitrobenzamide;

[0201] / V-(9-amino-7-ethoxyacridin-3-yl)-3,5-bis(trifluoromethyl)benzamide; and N-(9-amino-7-ethoxyacridin-3-yl)furan-2-carboxamide, and optionally pharmaceutically acceptable salts thereof.

[0202] In a more particular embodiment of the second aspect of the invention, there is the proviso (D) that the following compound is excluded:

[0203] / V-(9-amino-7-ethoxyacridin-3-yl)-4-chlorobenzamide.

[0204] In particular embodiments of the second aspect of the invention, the compound is a compound of formula I (including all embodiments thereof, such as compounds of formula la, lb, Ic, Id, and le) or a pharmaceutically acceptable salt thereof.

[0205] 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.

[0206] 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.

[0207] 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".

[0208] 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. Compounds may also be useful in medicine as diagnostic agents (particularly compounds comprising datable labels, as described herein).

[0209] As described herein, compounds of the invention may be particularly useful in treating cancers, particularly cancers characterised by increased activity of the MYC pathway.

[0210] Thus, in a third aspect of the invention, there is provided a compound of the invention, as hereinbefore defined, for use in the treatment of cancer.

[0211] In an alternative third aspect of the invention, there is provided a method of treating a cancer comprising administering to a patient in need thereof a therapeutically effective amount of a compound of the invention, as hereinbefore defined.

[0212] In a further alternative third aspect of the invention, there is provided the use of a compound of the invention, as hereinbefore defined, for the manufacture of a medicament for the treatment of a cancer.

[0213] In particular embodiments of the third aspect of the invention, the cancer is a cancer characterised by increased activity of the MYC pathway.

[0214] Therefore, in a particular embodiment, there is provided a compound of the invention as hereinbefore defined, for use in the treatment of a cancer characterised by increased activity of the MYC pathway.

[0215] The skilled person will understand that references to increased activity of the MYC pathway may refer to any instances where cancers have, in a significant number of cells thereof (e.g. at least 10%, such as at least 30%, at least 50%, at least 70%, or at least 90%) biological activity indicative of increased MYC activity when compared to the MYC activity observed in corresponding non-cancerous cells.

[0216] In such instances, the term "increased" may refer to the presence of MYC activity where such activity would not normally occur in corresponding non-cancerous cells, or to an increase in the level of activity when compared to corresponding non-cancerous cells, such as an at least 10% increase (e.g. an at least 50% increase or, more typically, an at least 100% increase). Such increased MYC activity may be observed in samples of such cancerous cells, and thus measured in relation to the given sample as a whole. The skilled person will be aware that increased MYC activity may for instance refer to an increase in the expression of the MYC gene. For the avoidance of doubt, references to the MYC gene may include references to the MYC, MYCN and MYCL oncogenes.

[0217] The skilled person will also be aware that such increased MYC activity may result from a range of oncogenic alterations, such as: increased copy number of the MYC, MYCN or MYCL oncogenes (which may be referred to as "copy number gain" or "gene amplification"); elevated / deregulated expression of MYC, MYCN or MYCL mRNA / protein; and / or increased activity of MYC-family proteins.

[0218] For the avoidance of doubt, references to increased copy number (i.e. gene amplification) of MYC-family (MYC, MYCN, MYCL) genes refer to the presence of additional copies of the relevant MYC gene in the genome of the cancerous cells when compared the corresponding non-cancerous cell-type.

[0219] The skilled person will be aware that copy number can be measured in situ by using techniques such as FISH (fluorescence in situ hybridization), NGS (next generation sequencing), or array-based analysis of copy number variations. The results obtained can be compared to copy number in corresponding normal (i.e. non-cancerous) cells, (e.g. where the cancer is of blood cells, the copy number in non-cancerous blood cells, such as those obtained from the same patient).

[0220] References to increased MYC activity may also refer to elevated MYC-family mRNA levels (overexpression) or to "deregulated" expression (meaning that the gene is expressed in the wrong cell at the wrong time). Expression changes can be caused by gene amplification (increased gene copy number) or, for instance, by altered cell signalling. Determination of whether MYC is overexpressed and / or deregulated may be made by comparison to a control sample. This control sample could be of normal (non-cancerous) cells from the same tissue, of benign tumors from the same tissue and / or of malignant tumours of lower grade. Levels of MYC expression be measured by RNA sequencing, RT-QPCR, microarray analysis, or by in situ hybridization.

[0221] As described herein, references to increased MYC activity may also refer to elevated and / or deregulated MYC-family protein levels. The skilled person will understand that such protein levels can be measured by, for instance, immunohistochemistry, western blot, RPPA (Reverse Phase Protein Array) and / or mass spectrometry. The skilled person will also understand that some tumours with low MYC mRNA might still have high protein levels due to for instance protein stabilization or increased MYC mRNA translation.

[0222] The skilled person will also understand that increased MYC activity may arise due to post-translational modifications and / or altered protein interactions in response to cell signalling, resulting in the activity rather than the level of the MYC proteins being increased. This results in activation (or repression) of MYC target genes, and can be measured using routine techniques, such as expression profiling of mRNA and / or protein by RT-QPCR, microarray analysis, RNA sequencing, western blot, protein arrays, and / or mass spectrometry.

[0223] For the avoidance of doubt, the above-mentioned factors resulting in increased MYC activity also be collectively referred to as "activation of the MYC pathway" or the like.

[0224] In particular embodiments, a cancer is characterised by increased MYC activity when:

[0225] (1) there is an at least 50% increase (such as at least 70%, or at least 90%) in the copy number of a MYC gene in a cancer cell from the patient compared to a corresponding non-cancerous cell from the patient; or

[0226] (2) there is an at least 50% increase (such as at least 70%, or at least 90%) in MYC mRNA or MYC protein levels, in a cancer cell from the patient compared to a corresponding non-cancerous cell from the patient; or

[0227] (3) there is an at least 50% increase (such as at least 70%, or at least 90%) in activity of a MYC pathway in a cancer cell from the patient compared to a corresponding non-cancerous cell from the patient.

[0228] A cancer may also be considered characterised by increased MYC activity when:

[0229] (4) there is deregulated expression of MYC mRNA or MYC protein levels in a cancer cell from the patient compared to a corresponding non-cancerous cell from the patient.

[0230] The skilled person will understand that references to the treatment of a particular condition (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 the treatment of a cancer, the term may refer to achieving a reduction (e.g. at least a 5% reduction, such as at least a 10% or 20% reduction) in the number of cancer cells present and / or the volume of tumor mass (in the case of a solid tumor).

[0231] 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 embodiments, references to a patient will refer to human patients.

[0232] In alternative embodiments, references to a patient may refer to other mammals, such as livestock (e.g. cattle, pigs, sheep, goats, horses, and the like) and / or household pets (e.g. cats, dogs, rabbits, and the like).

[0233] For the avoidance of doubt, the skilled person will understand that such treatment will be performed in a patient (or subject) in need thereof. The need of a patient (or subject) for such treatment may be assessed by those skilled the art using routine techniques.

[0234] As used herein, the terms disease and disorder (and, similarly, the terms condition, illness, medical problem, and the like) may be used interchangeably.

[0235] 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.

[0236] Compounds of the invention may find particular utility in the treatment of cancers known to be frequently characterised by MYC amplification. Thus, in certain embodiments, the cancer is a cancer (or a combination of one or more cancers) selected from the list consisting of:

[0237] Burkitt's lymphoma; ovarian cancer, such as ovarian cancer with BRCA alterations; basal-like / triple negative breast cancer; esophageal squamous cell carcinoma; colon cancer; endometrial cancer; neuroblastoma; lung cancer; medulloblastoma, in particular group 3; pancreatic cancer; head and neck cancer; malignant melanoma; prostate cancer; and hepatocellular carcinomas.

[0238] In particular embodiments, the cancer is neuroblastoma.

[0239] Pharmaceutical compositions

[0240] As 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.

[0241] In a fourth aspect of the invention, there is provided a pharmaceutical composition comprising a compound of the invention as defined herein, and optionally one or more pharmaceutically-acceptable excipient.

[0242] In particular embodiments of the fourth aspect of the invention, there is a proviso that certain compounds are excluded, or that the compound of formula I is not selected from a list of certain compounds, as described in the first or second (e.g. the second) aspect of the invention.

[0243] In particular embodiments of the fourth aspect of the invention, the following compounds are excluded:

[0244] (A)

[0245] / V-(9-amino-7-ethoxyacridin-3-yl)benzamide;

[0246] / V-(9-amino-7-ethoxyacridin-3-yl)-3-bromobenzamide;

[0247] / V-(9-amino-7-ethoxyacridin-3-yl)-4-cyanobenzamide; methyl 4-((9-amino-7-ethoxyacridin-3-yl)carbamoyl)benzoate;

[0248] / V-(9-amino-7-ethoxyacridin-3-yl)-2-naphthamide;

[0249] / V-(9-amino-7-ethoxyacridin-3-yl)-4-fluorobenzamide;

[0250] / V-(9-amino-7-ethoxyacridin-3-yl)-3-cyanobenzamide; / V-(9-amino-7-ethoxyacridin-3-yl)-3-nitro benzamide; / V-(9-amino-7-ethoxyacridin-3-yl)-4-nitro benzamide; / V-(9-amino-7-ethoxyacridin-3-yl)-3,5-bis(trifluoromethyl)benzamide; and / V-(9-amino-7-ethoxyacridin-3-yl)furan-2-carboxamide.

[0251] In a more particular embodiment of the fourth aspect of the invention, there is the proviso (D) that the following compound is excluded:

[0252] / V-(9-amino-7-ethoxyacridin-3-yl)-4-chlorobenzamide.

[0253] 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.

[0254] 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 of the invention) may also apply to pharmaceutical compositions comprising compounds of the invention, as described herein.

[0255] Thus, in a fifth aspect of the invention, there is provided a pharmaceutical composition as defined in the fourth aspect of the invention (including all embodiments thereof) for use in the treatment of a cancer.

[0256] In particular embodiments, there is provided a pharmaceutical composition as defined in the fourth aspect of the invention (including all emboidments thereof) for use in the treatment of a cancer characterised by amplification of MYC (as defined herein, with reference to the third aspect of the invention and all embodiments thereof).

[0257] 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.

[0258] The skilled person will understand that compounds and compositions as described herein will normally be administered orally, intravenously, subcutaneously, intratumorally, buccally, rectally, dermally, nasally, tracheally, bronchially, sublingually, intranasally, topically, transdermally, or 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.

[0259] 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, patches, 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.

[0260] 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.

[0261] 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 of the 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.

[0262] 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.

[0263] 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.

[0264] 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.

[0265] 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. Oral, pulmonary and topical dosages (and subcutaneous dosages, although these dosages may be relatively lower) may range from between about 0.01 pg / kg of body weight per day (pg / kg / day) to about 200 pg / kg / day, preferably about 0.01 to about 10 pg / kg / day, and more preferably about 0.1 to about 5.0 pg / kg / day. 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. In some instances, 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).

[0266] 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.

[0267] 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.

[0268] Combinations and kits-of-parts

[0269] The skilled person will understand that treatment with compounds of the invention may further comprise (i.e. be combined with) further treatment(s) for the same condition. In particular, treatment with compounds of the invention may be combined with means for the treatment of cancers (such as a type of cancer as described herein, e.g. cancers characterised by amplification of MYC), such as treatment with one or more other therapeutic agent that is useful in the in the treatment of such cancers and / or one or more physical method used in the treatment of such cancers (such as treatment through surgery), as known to those skilled in the art.

[0270] As described herein, compounds of the invention may also be combined with one or more other (i.e. different) therapeutic agents (i.e. agents that are not compounds of the invention) that are useful in the treatment of cancers, such as those cancers described herein. Such combination products that provide for the administration of a compound of the invention in conjunction with one or more other therapeutic agent may be presented either as separate formulations, wherein at least one of those formulations comprises a compound of the invention, and at least one comprises the other therapeutic agent, or may be presented (i.e. formulated) as a combined preparation (i.e. presented as a single formulation including a compound of the invention and the one or more other therapeutic agent).

[0271] Thus, according to a sixth aspect of the invention, there is provided a combination product comprising:

[0272] (I) a compound of the invention, as hereinbefore defined (i.e. in the first aspect of the invention, including all embodiments and particular features thereof); and

[0273] (II) one or more other therapeutic agent that is useful in the treatment of cancer (such as a cancer as described herein), wherein each of components (I) and (II) is formulated in admixture, optionally with one or more a pharmaceutically-acceptable excipient.

[0274] In a seventh aspect of the invention, there is provided a kit-of-parts comprising:

[0275] (a) a pharmaceutical formulation as hereinbefore defined (i.e. in the fifth aspect of the invention); and

[0276] (b) one or more other therapeutic agent that is useful in the treatment of cancer (such as a cancer as described herein), optionally in admixture with one or more pharmaceutically-acceptable excipient, which components (a) and (b) are each provided in a form that is suitable for administration in conjunction (i.e. concomitantly or sequentially) with the other.

[0277] In particular embodiments of the sixth and seventh aspects of the invention, there is a proviso that certain compounds are excluded, or that the compound of formula I is not selected from a list of certain compounds, as described in the first or second (e.g. the second) aspect of the invention.

[0278] In a more particular embodiment of the sixth and seventh aspects of the invention, there is the proviso that the following compounds are excluded:

[0279] (A)

[0280] / V-(9-amino-7-ethoxyacridin-3-yl)benzamide;

[0281] / V-(9-amino-7-ethoxyacridin-3-yl)-3-bromobenzamide; / V-(9-amino-7-ethoxyacridin-3-yl)-4-cyanobenzamide; methyl 4-((9-amino-7-ethoxyacridin-3-yl)carbamoyl)benzoate;

[0282] / V-(9-amino-7-ethoxyacridin-3-yl)-2-naphthamide;

[0283] / V-(9-amino-7-ethoxyacridin-3-yl)-4-fluorobenzamide; / V-(9-amino-7-ethoxyacridin-3-yl)-3-cyanobenzamide; / V-(9-amino-7-ethoxyacridin-3-yl)-3-nitro benzamide; / V-(9-amino-7-ethoxyacridin-3-yl)-4-nitro benzamide;

[0284] / V-(9-amino-7-ethoxyacridin-3-yl)-3,5-bis(trifluoromethyl)benzamide; and / V-(9-amino-7-ethoxyacridin-3-yl)furan-2-carboxamide, and optionally pharmaceutically acceptable salts thereof.

[0285] In a more particular embodiment of the sixth and seventh aspects of the invention, there is the proviso (D) that the following compound is excluded:

[0286] / V-(9-amino-7-ethoxyacridin-3-yl)-4-chlorobenzamide.

[0287] With respect to the kits-of-parts as described herein, by "administration in conjunction with" (and similarly "administered in conjunction with") we include that respective formulations are administered, sequentially, separately or simultaneously, as part of a medical intervention directed towards treatment of the relevant condition.

[0288] Thus, in relation to the present invention, the term "administration in conjunction with" (and similarly "administered in conjunction with") includes that the two active ingredients (i.e. a compound of the invention and a further agent for the treatment of cancer, or compositions comprising the same) are administered (optionally repeatedly) either together, or sufficiently closely in time, to enable a beneficial effect for the patient, that is greater, over the course of the treatment of the relevant condition, than if either agent is administered (optionally repeatedly) alone, in the absence of the other component, over the same course of treatment. Determination of whether a combination provides a greater beneficial effect in respect of, and over the course of, treatment of a particular condition will depend upon the condition to be treated, but may be achieved routinely by the skilled person.

[0289] Further, in the context of the present invention, the term "in conjunction with" includes that one or other of the two formulations may be administered (optionally repeatedly) prior to, after, and / or at the same time as, administration of the other component. When used in this context, the terms "administered simultaneously" and "administered at the same time as" includes instances where the individual doses of the compound of the invention and the additional compound for the treatment of cancer, or pharmaceutically acceptable salts thereof, are administered within 48 hours (e.g. within 24 hours, 12 hours, 6 hours, 3 hours, 2 hours, 1 hour, 45 minutes, 30 minutes, 20 minutes or 10 minutes) of each other.

[0290] Other therapeutic agents useful in the treatment of cancers (such as those cancers as described herein) will be well-known to those skilled in the art. For example, such other therapeutic agents may include therapeutic agents routinely used in the treatment of the relevant cancer type, as will be known to those skilled in the art.

[0291] Preparation of compounds / compositions

[0292] Pharmaceutical compositions / formulations, combination products and kits as described herein may be prepared in accordance with standard and / or accepted pharmaceutical practice.

[0293] 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.

[0294] In further aspects of the invention, there is provided a process for the preparation of a combination product or kit-of-parts as hereinbefore defined, which process comprises bringing into association a compound of the invention, as hereinbefore defined, with the other therapeutic agent that is useful in the treatment of the relevant disease or disorder, and at least one pharmaceutically-acceptable excipient.

[0295] As used herein, references to bringing into association will mean that the two components are rendered suitable for administration in conjunction with each other.

[0296] Thus, in relation to the process for the preparation of a kit-of-parts as hereinbefore defined, by bringing the two components "into association with" each other, we include that the two components of the kit-of-parts may be:

[0297] (i) provided as separate formulations (i.e. independently of one another), which are subsequently brought together for use in conjunction with each other in combination therapy; or (ii) packaged and presented together as separate components of a "combination pack" for use in conjunction with each other in combination therapy.

[0298] Compounds of the invention as described herein may be prepared in accordance with techniques that are well known to those skilled in the art, such as those described in the examples provided hereinafter.

[0299] According to an eighth aspect of the invention there is provided a process for the preparation of a compound of the invention as hereinbefore defined, comprising the step of:

[0300] (i) for compounds wherein L represents -N(R2)C(O)(CH2)wi- or -N(R2)S(O)qi(CH2)w2-, reacting a compound of formula II wherein X, Y, n, m, R2, R3, and R4are as defined herein (i.e. in the first aspect of the invention for compounds of formula I, including all embodiments thereof), with a compound of formula III or IV

[0301] ZC— (CH2)W1-R1LG (in)QrLG-S(O)q1- (CH2)W2-R1(IV)wherein R1, ql, wl and w2 are as defined in herein (i.e. in the first aspect of the invention for compounds of formula I, including all embodiments thereof), and LG is a suitable leaving group as known to those skilled in the art; or

[0302] (ii) for compounds wherein L represents -N(R2)C(O)(CH2)wi- or -N(R2)S(O)qi(CH2)W2-, reacting a compound of formula (V) wherein R3, R4, X, Y, m, n are as defined herein (i.e. in the first aspect of the invention for compounds of formula I, including all embodiments thereof), W is a suitable group which is reactive in a metal-catalysed cross-coupling reaction (e.g. W may be halo, triflate, diazonium, etc.), with a compound of formula (VI) or (VII) wherein R1, R2, wl, w2 and ql are as defined herein (in the first aspect of the invention for compounds of formula I, including all embodiments thereof), in the presence of a suitable metal (e.g. -Pd, Ni, Cu, Ru, Mg, etc) and a suitable ligand.

[0303] (iii) for compounds wherein L represents -C(O)N(R2)(CH2)w3-, reacting a compound of formula (V) wherein R3, R4, X, Y, m, n are as defined herein (i.e. in the first aspect of the invention for compounds of formula I, including all embodiments thereof), W is a suitable group which is reactive in a metal-catalysed cross-coupling reaction (e.g. W may be halo, triflate, diazonium, etc.), in the presence of a formic anhydride (such as acetic formic anhydride), a suitable metal (e.g. -Pd, Ni, Cu, Ru, Mg, etc), a suitable ligand, and optionally in the presence of carbon monoxide, to form a compound of formula (VIII) (VIII), wherein X, Y, m, n, R3and R4are as defined herein (in the first aspect of the invention for compounds of formula I, including all embodiments thereof). The skilled person will understand that the formic anhydride is a compound of formula HC(O)OC(O)R, wherein R is an alkyl group such as methyl. The formic anhydride may be formed from the reaction of a formate anion (e.g. lithium anion) with an anhydride (e.g. acetic anhydride); or (iv) for compounds wherein L represents -C(O)N(R2)(CH2)w3-, reacting a compound of formula (VIII) (VIII), wherein X, Y, m, n, R3and R4are as defined herein (i.e. in the first aspect of the invention for compounds of formula I, including all embodiments thereof), with a compound of formula (IX) to form a compound of formula (I)

[0304] HN-(CH2)W3-R1

[0305] R2(IX) wherein R1, R2and w3 are as defined herein (in the first aspect of the invention for compounds of formula I, including all embodiments thereof); or

[0306] (v) for compounds wherein L represents -C(O)N(R2)(CH2)w3-, reacting a compound of formula (V), in the presence of a suitable metal (e.g. -Pd, Ni, Cu, Ru, Mg, etc), a suitable ligand, and in the presence of carbon monoxide, followed by a reaction with a compound of formula (IX), wherein the compounds of formula (V) and (IX) are as defined in steps (iii) and (iv).

[0307] Compounds of formulae II to IX are either commercially available, are known in the literature, 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.

[0308] 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.

[0309] 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.

[0310] 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.

[0311] 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", 3rd edition, T.W. Greene & P.G.M. Wutz, Wiley-Interscience (1999), the contents of which are incorporated herein by reference.

[0312] Without wishing to be bound by theory, it is believed that compounds of the invention are able to treat cancers, particularly those cancers characterised by increased MYC activity, such as may be due to gene copy number alterations and / or increased expression / activity of MYC (i.e. activation of the MYC pathway), based on their ability to act as potent and specific inhibitors of MYC: MAX interaction, thus inhibiting MYC- dependent tumor cell growth. It is also believed that detectably-labelled derivatives of compounds of the invention may be useful as diagnostic agents and / or as research tools, such as in drug development.

[0313] Compounds of the invention may have the advantage that they may be more efficacious than, be less toxic than, be longer acting than, be more 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.

[0314] In addition, the compounds of the invention are photostable. Therefore, their use as therapeutic agents is advantageous due to increased safety and efficacy compared to an analogous active ingredient that is not photostable.

[0315] As defined herein, a photostable compound refers to a compound which does not produce significant amounts of decomposition products when exposed to solar, UV or visible light, including light from lightbulbs, fluorescent tubes or light-emitting diodes. The change in content, e.g. presence and decomposition products, may be measured by techniques known by the skilled person, such as HPLC.

[0316] As used herein "significant amounts" of decomposition products refer to 20 wt%, such as 15 wt%, 10 wt%, 5 wt%, 3 wt% or 1 wt% (e.g. 1 wt %), when measured with respect to the compound (i.e. the starting compound) being exposed to solar, UV or visible light for 48 hours.

[0317] Examples

[0318] The present invention will be further described by reference to the following examples, which are not intended to limit the scope of the invention.

[0319] Example compounds

[0320] In the event that there is a discrepancy between nomenclature and the structure of compounds as depicted graphically, it is the latter that presides (unless contradicted by any experimental details that may be given and / or unless it is clear from the context). Chemicals and reagents were obtained from commercial suppliers and were used as received unless otherwise stated. All reactions involving moisture sensitive reagents were performed in oven or flame dried glassware under a positive pressure of nitrogen or argon using anhydrous solvents.

[0321] Example 1: N-(9-Amino-7-ethoxyacridin-3-yl)-2-methoxybenzamide trifluoroacetic acid salt

[0322] (a) 7-Ethoxyacridine-3,9-diamine (ethacridine)

[0323] NaHCCh (aq, sat, 100 mL) was added cautiously to a solution of ethacridine lactate (3.50 g, 10.19 mmol) in H2O (60 mL) The mixture was stirred at rt for 18 h and the solids were collected, washed with H2O and dried to give the title compound (2.44 g, 95 %).

[0324] (b) / V-(9-Amino-7-ethoxyacridin-3-yl)-2-methoxybenzamide trifluoroacetic acid salt

[0325] 2-Methoxybenzoyl chloride (337 mg, 0.3 mL, 1.97 mmol) was added to a mixture of ethacridine (250 mg, 0.99 mmol), pyridine (250 mg, 0.99 mmol) and DMF (4 mL) at rt and the mixture was stirred at rt for 18 h. A second portion of 2-methoxybenzoyl chloride (84 mg, 75 pL, 0.49 mmol) was added and the mixture was stirred at rt for 24 h and diluted with EtOAc. The solids were collected and purified by chromatography (C18 column; elution with 5 % MeCN and 0.1 % TFA in H2O to 75 % MeCN and 0.1 % TFA in H2O and then with 99 % MeCN and 0.1 % TFA in H2O) to give the title compound (120 mg, 24 %).

[0326] XH NMR (400 MHz, DMSO-cfe): 6 13.50 (1H, s), 10.81 (1H, s), 9.57 (1H, s), 9.52 (1H, s), 8.68 (1H, d, J = 2.0 Hz), 8.54 (1H, d, J = 9.3 Hz), 7.95 (1H, d, J = 2.4 Hz), 7.78 (1H, d, J = 9.3 Hz), 7.69 - 7.64 (2H, m), 7.60 - 7.54 (2H, m), 7.24 (1H, d, J = 8.2 Hz), 7.11 (1H, td, J = 7.5, 0.8 Hz), 4.20 (2H, q, J = 7.0 Hz), 3.92 (3H, s), 1.43 (3H, t, J = 7.0 Hz).

[0327] Example 2: N-(9-Amino-7-ethoxyacridin-3-yl)benzamide trifluoroacetic acid salt

[0328] The title compound was prepared in accordance with the procedure in Example 1, Step (b) from ethacridine and benzoyl chloride.

[0329] XH NMR (400 MHz, DMSO-cfe): 6 13.51 (1H, s), 10.93 (1H, s), 9.54 (2H, d, J = 9.2 Hz), 8.71 (1H, d, J = 1.8 Hz), 8.56 (1H, d, J = 9.4 Hz), 8.06 - 8.01 (2H, m), 7.96 (1H, d, J = 2.3 Hz), 7.80 (1H, d, J = 9.4 Hz), 7.75 (1H, dd, J = 9.4, 2.0 Hz), 7.70 - 7.65 (2H, m), 7.63 - 7.58 (2H, m), 4.21 (2H, q, J = 7.0 Hz), 1.44 (3H, t, J = 7.0 Hz).

[0330] Example 3: N-(9-Amino-7-ethoxyacridin-3-yl)-4-cyanobenzamide

[0331] 4-Cyanobenzoyl chloride (66 mg, 0.4 mmol) was added to an ice-cooled stirred mixture of ethacridine (25 mg, 0.1 mmol), DMF (1 mL) and pyridine (50 pL). The mixture was stirred for 2 h and the cooling bath was removed. Water was added and the precipitate was collected, treated with hot MeOH and dried to give the title compound (12 mg, 39 %).

[0332] XH NMR (400 MHz, DMSO-cfe): 6 1.43 (t, J=6.94 Hz, 3 H) 4.20 (q, J=7.05 Hz, 2 H) 7.65 (dd, J=9.32, 2.44 Hz, 1 H) 7.74 (dd, J=9.32, 1.94 Hz, 1 H) 7.81 (d, J=9.26 Hz, 1 H) 7.95 (d, J=2.50 Hz, 1 H) 8.07 (d, J=8.50 Hz, 2 H) 8.17 (d, J=1.00 Hz, 2 H) 8.57 (d, J=9.38 Hz, 1 H) 8.65 (d, J=1.88 Hz, 1 H) 9.50 (br. s., 2 H) 11.15 (s, 1 H).

[0333] Example 4: Methyl 4-((9-amino-7-ethoxyacridin-3-yl)carbamoyl)benzoate

[0334] 4-Methoxycarbonylbenzoic acid chloride (10 mg, 0.05 mmol) was added to a mixture of ethacridine (13 mg, 0.05 mmol), pyridine (20 pL, 0.25mmol) and DMF (0.5 mL) at rt. The mixture was heated over night and allowed to come to rt. Water was added and the precipitate was collected, recrystallized from MeCN and then from MeOH and dried to give the title compound (4 mg, 19 %).

[0335] XH NMR (400 MHz, DMSO-cfe): 6 1.45 (t, J=6.94 Hz, 3 H) 3.93 (s, 3 H) 4.23 (q, J=7.00 Hz, 2 H) 7.70 (dd, J=9.19, 2.56 Hz, 1 H) 7.75 (dd, J=9.32, 1.81 Hz, 1 H) 7.82 (d, .7=9.13 Hz, 1 H) 7.98 (d, J=2.25 Hz, 1 H) 8.16 (d, J= 1.75 Hz, 2 H) 8.58 (d, J=9.51 Hz, 1 H) 8.73 (d, .7=1.88 Hz, 1 H) 9.56 (br. s., 1 H) 9.58 (br. s., 1 H) 11.11 (s, 1 H) 13.55 (s, 1 H).

[0336] Example 5: N-(9-Amino-7-ethoxyacridin-3-yl)-3-bromobenzamide

[0337] The title compound was obtained from Molport, Smerla iela 3, Riga, Latvia, LV-1006.

[0338] Example 6: N-(9-Amino-7-ethoxyacridin-3-yl)-2-phenylacetamide trifluoroacetic acid salt A solution of 2-phenylacetyl chloride (366 mg, 0.31 mL, 2.37 mmol) in DMF (0.5 mL) was added dropwise to a stirred mixture of ethacridine (300 mg, 1.18 mmol), pyridine (468 mg, 0.48 mL, 5.92 mmol) and DMF (4 mL) at 0 °C. The mixture was stirred at rt for 2 h and diluted with EtOAc. The solids were collected and purified by chromatography (C18 column; elution from 0.1% TFA in H2O to 0.1% TFA and 95% MeCN in H2O) to give the title compound (170 mg, 30 %).

[0339] XH NMR (400 MHz, DMSO-cfe): 6 13.42 (1H, s), 10.95 (1H, s), 9.53 (1H, s), 9.50 (1H, s), 8.54 - 8.45 (2H, m), 7.95 - 7.9O(1H, m), 7.75 (1H, d, J = 9.3 Hz), 7.67 - 7.60 (1H, m), 7.48 (1H, dd, J = 9.3, 2.1 Hz), 7.41 - 7.32 (4H, m), 7.31 - 7.25 (1H, m), 4.18 (2H, q, J = 6.9 Hz), 3.79 (2H, s), 1.42 (3H, t, J = 6.9 Hz).

[0340] Example 7: N-(9-Amino-7-ethoxyacridin-3-yl)-4-methoxycyclohexane-l - carboxamide trifluoroacetic acid salt

[0341] (a) (trans)-4-Methoxycyclohexane-l-carbonyl chloride

[0342] Oxalyl chloride (361 mg, 0.25 mL, 2.84 mmol) was added dropwise to an ice-cooled stirred mixture of (trans)-4-methoxycyclohexane-l-carboxylic acid (300 mg, 1.90 mmol), DMF (3 drops) and CH2CI2 (10 mL). The solution was stirred at 0 °C for 90 min and used in the following step.

[0343] (b) (trans)-N-(9-Amino-7-ethoxyacridin-3-yl)-4-methoxycyclohexane-l- carboxamide hydrochloride

[0344] A solution of (trans)-4-methoxycyclohexane-l-carbonyl chloride (307 mg, 1.73 mmol) in CH2CI2 (1.5 mL), see Step (a), was added to a stirred mixture of ethacridine (200 mg, 0.79 mmol) in DMF (5 mL) at 0 °C. The mixture was stirred at 0 °C for 30 min and at rt for 16 h. The mixture was concentrated and the residue was dissolved in DMSO (5 mL) and purified by chromatography (C18 column; elution with 0.1 % AcOH and 10 % MeCN in H2O to 0.1 % AcOH and 50 % MeCN in H2O). The obtained material was suspended in MeCN, treated with HCI (4 M in dioxane) and sonicated. The solids were collected, washed with MeCN, suspended in H2O and MeCN, and lyophilized to give the title compound (130 mg, 38 %).

[0345] XH NMR (400 MHz, DMSO-cfe) 6 13.62 (s, 1H), 10.78 (s, 1H), 9.66 (d, J = 17.4 Hz, 2H), 8.58 (d, J = 9.4 Hz, 1H), 8.48 (d, J = 2.0 Hz, 1H), 8.01 (d, J = 2.6 Hz, 1H), 7.82 (d, J = 9.3 Hz, 1H), 7.61 (dd, J = 9.3, 2.6 Hz, 1H), 7.54 (dd, J = 9.4, 2.0 Hz, 1H), 4.19 (q, J = 6.9 Hz, 2H), 3.25 (s, 3H), 3.18 - 3.08 (m, 1H), 2.49 - 2.41 (m, 1H), 2.13 - 2.04 (m, 2H), 1.98 - 1.89 (m, 2H), 1.56 - 1.44 (m, 2H), 1.41 (t, J = 6.9 Hz, 3H), 1.22 - 1.09 (m, 2H).

[0346] Example 8: N-( 9-Amino-7-ethoxyacridin-3-yl)tetrahydrofuran-2-carboxamide acetic acid salt

[0347] (a) Tetrahydrofuran-2-carbonyl chloride

[0348] Oxalyl chloride (1.64 g, 1.13 mL, 12.92 mmol) was added dropwise to a stirred ice- cooled mixture of tetrahydrofuran-2-carboxylic acid (1.00 g, 8.61 mmol), DMF (3 drops) and CH2CI2 (10 mL). The solution was stirred at 0 °C for 90 min and concentrated to give the sub-title compound (1.05 g, 91 %). (b) / V-(9-Amino-7-ethoxyacridin-3-yl)tetrahydrofuran-2-carboxamide

[0349] A solution of tetra hydrofuran-2-carbonyl chloride (191 mg, 1.42 mmol) in CH2CI2 (1 mL) was added to a stirred ice-cooled mixture of ethacridine (180 mg, 0.71 mmol) and pyridine (4 mL). The mixture was stirred at rt for 18 h and concentrated. The residue was purified by chromatography (C18 column; elution with 0.1 % AcOH and 10 % MeCN in H2O to 0.1 % AcOH and 95 % MeCN in H2O) to give the title compound as a mixure with 66 % AcOH (70 mg, 24 %).

[0350] XH NMR (400 MHz, DMSO-de) 6 10.01 (1H, s), 8.39 - 8.32 (2H, m), 8.29 - 7.86 (2H, m), 7.80 - 7.67 (2H, m), 7.59 (1H, dd, J = 9.3, 2.1 Hz), 7.41 (1H, dd, J = 9.3, 2.5 Hz), 4.48 (1H, dd, J = 8.1, 5.7 Hz), 4.18 (2H, q, J = 6.9 Hz), 4.02 (1H, dt, J = 8.1, 6.7 Hz), 3.87 (1H, dt, J = 8.1, 6.7 Hz), 2.29 - 2.19 (1H, m), 2.09 - 2.00 (1H, m), 1.97 - 1.86 (4H, m), 1.42 (3H, t, J = 6.9 Hz).

[0351] Example 9: N-( 9-Amino-7-ethoxyacridin-3-yl)tetrahydro-2H-pyran-4-carboxamide acetic acid salt

[0352] The title compound was prepared from ethacridine and tetrahydro-2H-pyran-4- carboxylic acid in accordance with the procedure in Example 8.

[0353] H NMR (400 MHz, DMSO-de) 6 10.14 (1H, s), 8.28 (1H, d, J = 9.3 Hz), 8.19 (1H, d, J = 2.1 Hz), 7.71 (1H, d, J = 9.3 Hz), 7.65 (1H, d, J = 2.6 Hz), 7.47 (1H, dd, J = 9.3, 2.1 Hz), 7.34 (1H, dd, J = 9.3, 2.6 Hz), 4.18 (2H, q, J = 6.9 Hz), 3.98 - 3.90 (2H, m), 3.39 (2H, td, J = 11.2, 3.3 Hz), 2.73 - 2.63 (1H, m), 1.91 (3H, s), 1.81 - 1.66 (4H, m), 1.43 (3H, t, J = 7.0 Hz).

[0354] Example 10: N-(9-amino-7-ethoxyacridin-3-yl)adamantane-l-carboxamide hydrochloride

[0355] A solution of adamantane-l-carbonyl chloride (470 mg, 2.37 mmol) (prepared from 1-adamantanecarboxylic acid in accordance with the procedure in Example 8, Step (a)) in CH2CI2 (1.5 mL) was added to a stirred ice-cooled mixture of ethacridine (300 mg, 1.18 mmol) and pyridine (9 mL). The suspension was stirred at 0 °C for 30 min, at rt for 1 h and at 90 °C for 1 h. The mixture was concentrated and the residue suspended in EtOAc. The mixture was centrifuged and the solids collected, washed with EtOAc, recrystallized from EtOH and dried to give the title compound (245 mg, 46 %).

[0356] XH NMR (400 MHz, DMSO-de) 6 14.0 - 12.8 (br s, 1H), 9.78 (s, 1H), 9.44 (s, 2H), 8.62 - 8.56 (m, 1H), 8.50 (d, J = 9.2 Hz, 1H), 7.94 - 7.89 (m, 1H), 7.78 (d, J = 9.2 Hz, 1H), 7.67 (d, J = 9.0 Hz, 1H), 7.64 - 7.58 (m, 1H), 4.18 (q, J = 6.9 Hz, 2H), 2.09 - 2.01 (m, 3H), 2.01 - 1.93 (m, 6H), 1.77 - 1.68 (m, 6H), 1.42 (t, J = 6.9 Hz, 3H).

[0357] Example 11 : N-( 9-Amino-7-ethoxyacridin-3-yl)-4-methylbenzenesulfonamide trifluoroacetic acid salt

[0358] Tosyl chloride (150 mg, 0.79 mmol) was added in portions to a stirred mixture of ethacridine (200 mg, 0.79 mmol) and pyridine (3 mL) at rt. The mixture was stirred at rt for 18 h and an additonal portion of tosyl chloride (150 mg, 0.79 mmol) was added and the mixture stirred at rt for 24 h. An additonal portion of tosyl chloride (150 mg, 0.79 mmol) was added and the mixture stirred at rt for 24 h. The mixture was diluted with EtOAc and the solids were collected and suspended in hot EtOAc. The solids were collected and purified by chromatography (C18 column; elution with 0.1 % TFA in H2O to 95 % MeCN and 0.1 % TFA in H2O) to give the title compound (180 mg, 56 %).

[0359] XH NMR (400 MHz, DMSO-cfe): 6 13.40 (1H, s), 11.53 - 11.28 (1H, br s), 9.53 (1H, s), 9.51 (1H, s), 8.44 (1H, d, J = 9.3 Hz), 7.93 - 7.87 (1H, m), 7.86 - 7.81 (2H, m), 7.73 (1H, d, J = 9.2 Hz), 7.67 - 7.59 (1H, m), 7.56 (1H, d, J = 2.2 Hz), 7.40 (2H, d, J = 8.1 Hz), 7.21 (1H, dd, J = 9.3, 2.2 Hz), 4.17 (2H, q, J = 6.9 Hz), 2.32 (3H, s), 1.41 (3H, t, J = 6.9 Hz). Example 12: N-(9-Amino-7-ethoxyacridin-3-yl)-4-methoxybenzenesulfonamide hydrochloride

[0360] 4-Methoxybenzenesulfonyl chloride (245 mg, 1.18 mmol) was added in portions to a stirred mixture of ethacridine (200 mg, 0.79 mmol) and pyridine (5 mL). The mixture was stirred at 50 °C for 18 h and an additonal portion of 4-methoxybenzenesulfonyl chloride (245 mg, 1.18 mmol) was added and the mixture stirred at 50 °C for 18 h and concentrated. The residue was purified by chromatography (C18 column; elution with 0.1 % AcOH and 10 % MeCN in H2O to 0.1 % AcOH and 95 % MeCN in H2O) and the isolated material was treated with HCI (4 M in dioxane, 2 mL) and sonicated for 10 min. The solids were collected and suspended in H2O and lyophilized to give the title compound (45 mg, 13 %).

[0361] XH NMR (400 MHz, DMSO-cfe): 6 13.72 (1H, s), 11.38 (1H, s), 9.75 (1H, s), 9.69 (1H, s), 8.57 (1H, d, J = 9.3 Hz), 8.01 (1H, d, J = 2.6 Hz), 7.95 - 7.89 (2H, m), 7.81 (1H, d, J = 9.3 Hz), 7.65 (1H, d, J = 2.2 Hz), 7.61 (1H, dd, J = 9.3, 2.6 Hz), 7.23 (1H, dd, J = 9.3, 2.2 Hz), 7.13 - 7.07 (2H, m), 4.19 (2H, q, J = 6.9 Hz), 3.78 (3H, s), 1.40 (3H, t, J = 6.9 Hz).

[0362] Example 13: N-(9-Amino-7-ethoxyacridin-3-yl)-4-methoxy-N-methylbenzenesulfon- amide acetic acid salt

[0363] Mel (14 pL, 0.22 mmol) in DMSO (0.45 mL) was added dropwise to a stirred mixture of / V-(9-amino-7-ethoxyacridin-3-yl)-4-methoxybenzenesulfonamide hydrochloride (83 mg, 0.18 mmol), CS2CO3 (118 mg, 0.36 mmol) and DMF (4 mL) at rt. The mixture was stirred at rt for 16 h and concentrated. The residue was purified by chromatography (C18 column; elution with 0.1 % AcOH and 10 % MeCN in H2O to 0.1 % AcOH and 95 % MeCN in H2O) to give the title compound (36 mg, 40 %).

[0364] XH NMR (400 MHz, DMSO-de, ppm) 6 8.28 (1H, d, J = 9.3 Hz), 7.70 (1H, d, J = 9.3 Hz), 7.64 (1H, d, J = 2.7 Hz), 7.50 - 7.45 (2H, m), 7.36 - 7.32 (2H, m), 7.21 (1H, dd, J = 9.3, 2.3 Hz), 7.09 - 7.04 (2H, m), 4.18 (3H, q, J = 6.9 Hz), 3.81 (3H, s), 3.23

[0365] (3H, s), 1.90 (3H, s), 1.42 (3H, t, J = 7.0 Hz).

[0366] Example 14: N-( 9-Amino-7-ethoxyacridin-3-yl)cyclopropanesulfonamide

[0367] Cyclopropanesulfonyl chloride (178 mg, 129 pL, 1.26 mmol) was added dropwise to a stirred mixture of ethacridine (160 mg, 0.63 mmol) and pyridine (5 mL) at rt. The mixture was stirred at 50 °C for 16 h and concentrated. The product was purified by chromatography (C18 column; elution with 0.1 % AcOH and 10 % MeCN in H2O to 0.1 % AcOH and 50 % MeCN in H2O). The fractions containing the desired product were lyophilized to give the title compound as a mixure with 25 % AcOH (130 mg, 49 %).XH NMR (300 MHz, DMSO-de) 6 8.90 - 8.50 (m, 2H), 8.24 - 8.20 (m, 1H), 8.18 (d, J = 9.4 Hz, 1H), 7.82 (d, J = 2.5 Hz, 1H), 7.62 (d, J = 9.2 Hz, 1H), 7.49 (dd, J = 9.2, 2.5 Hz, 1H), 7.28 (d, J = 1.6 Hz, 1H), 6.94 (dd, J = 9.4, 1.6 Hz, 1H), 4.16 (q, J = 6.9 Hz, 2H), 2.62 - 2.52 (m, 2H), 1.90 (s, 0.7H), 1.41 (t, J = 6.9 Hz, 3H), 0.97 - 0.88 (m, 2H), 0.88 - 0.76 (m, 2H).

[0368] Example 15: N-( 9-Amino-7-ethoxyacridin-3-yl)-N-methylcyclopropanesulfonamide acetic acid salt

[0369] Mel (26 pL, 0.41 mmol) in DMSO (0.26 mL) was added dropwise to a stirred mixture of / V-(9-amino-7-ethoxyacridin-3-yl)cyclopropanesulfonamide acetic acid salt (114 mg, 0.27 mmol), CS2CO3 (222 mg, 0.68 mmol) and DMF (5 mL) at rt. The mixture was stirred at rt for 16 h and concentrated. The residue was purified by chromatography (C18 column; elution with 0.1 % AcOH and 10 % MeCN in H2O to 0.1 % AcOH and 95 % MeCN in H2O) to give the title compound as a mixure with 80 % AcOH (71 mg, 60 %).XH NMR (400 MHz, DMSO-cte) 6 8.32 (d, J = 9.3 Hz, 1H), 7.78 (d, J = 2.3 Hz, 1H), 7.74 (d, J = 9.3 Hz, 1H), 7.65 (d, J = 2.7 Hz, 1H), 7.65 - 7.43 (m, 1H), 7.40 - 7.32 (m, 2H), 4.19 (q, J = 7.0 Hz, 2H), 3.40 (s, 3H), 2.81 - 2.73 (m, 1H), 1.89 (s, 2H), 1.43 (d, J = 7.0 Hz, 3H), 1.00 - 0.91 (m, 2H), 0.87 - 0.80 (m, 2H).

[0370] Example 16: 9-Amino-7-ethoxy-N-(2-methoxyphenyl)acridine-3-carboxamide acetic acid salt

[0371] (a) 2-Ethoxy-6-iodoacridin-9-amine hydrogen sulfate

[0372] An ice-cold solution of NaNO? (1.00 g, 14.56 mmol) in H2O (50 mL) was added dropwise over 15 min period to a solution of ethacridine lactate (5.00 g, 14.56 mmol) in H2O (100 mL) at 5 °C immediately followed by the addition of ice-cooled 100 mL of precooled 5% H2SO4 (aq, 5 %, 100 mL) in two portions. The diazonium salt solution was stirred at 5 °C for 25 min and added portionwise to a solution of Nal (4.36 g, 29.12 mmol) in a acetone (60 mL) and H2O (90 mL) over 15 min. The mixture was stirred at 20 °C for 2 h and filtered. The solids were washed with H2O (100 mL) and MeCN (100 mL) and dried over P2O5 to give the sub-title compound (6.20 g, 92 %).

[0373] XH NMR (400 MHz, DMSO-de) 6 14.07 - 12.65 (m, 1H), 9.69 (s, 2H), 8.31 (d, J = 9.0 Hz, 1H), 8.18 (d, J = 1.6 Hz, 1H), 7.91 (d, J = 2.5 Hz, 1H), 7.88 (dd, J = 9.0, 1.6 Hz, 1H), 7.77 (d, J = 9.3 Hz, 1H), 7.69 (dd, J = 9.3, 2.5 Hz, 1H), 4.19 (d, J = 7.0 Hz, 2H), 1.43 (t, J = 7.0 Hz, 3H).

[0374] (b) 9-Amino-7-ethoxyacridine-3-carboxylic acid hydrochloride Diisopropylethylamine (377 mg, 505 pL, 2.92 mmol) and acetic anhydride (298 mg, 276 pL, 2.92 mmol) were added to a solution of HCChLi (208 mg, 4.00 mmol) in DMF (4 mL) and the mixture was stirred at rt for 1 h. A mixture of of 2-ethoxy-6-iodoacridin- 9-amine hydrogen sulfate (500 mg, 1.08 mmol), Pd2(dba)s (30 mg, 0.032 mmol), LiCI (170 mg, 4.00 mmol) and DMF (1.5 mL) was added and the mixture was stirred under CO (5 atm) at 80 °C for 2 h. The mixture was allowed to cool to rt and filtered through Celite, which was washed with DMF (2 mL) and MeCN (15 mL). The filtrate was refridgerated for 16 h and the solids were collected and sonicated with HCI (aq, 1 M). The solids were collected dried in vacuo to give the sub- title compound (250 mg, 73 %).

[0375] 1H NMR (400 MHz, DMSO-de + 2 drops TFA) 6 13.98 (s, 1H), 9.94 - 9.83 (m, 2H), 8.69 (d, J = 9.0 Hz, 1H), 8.43 (d, J = 1.6 Hz, 1H), 8.01 - 7.92 (m, 2H), 7.85 (d, J = 9.3 Hz, 1H), 7.69 (dd, J = 9.3, 2.5 Hz, 1H), 4.19 (d, J = 7.0 Hz, 2H), 1.43 (t, J = 7.0 Hz, 3H).

[0376] (c) 9-Amino-7-ethoxy-N-(2-methoxyphenyl)acridine-3-carboxamide

[0377] Oxalyl chloride (79 mg, 55 pL, 0.63 mmol) was added dropwise to a stirred ice-cooled mixture of 9-amino-7-ethoxyacridine-3-carboxylic acid hydrochloride (133 mg, 0.42 mmol), DMF (3 drops) and CH2CI2 (5 mL). The mixture was stirred at rt for 2 h and cooled to 0 °C. Oxalyl chloride (159 mg, 109 pL, 1.25 mmol) and DMF (3 drops) were added and stirring was continued at 30 °C for 6 h. The mixture was concentrated and the residue was suspended in CH2CI2 (2 mL) and added to a stirred ice-cooled mixture of o-anisidine (128 mg, 117 pL, 1.04 mmol) and pyridine (5 mL). The mixture was stirred at 0 °C for 30 min, at rt for 64 h and concentrated. The residue was purified by chromatography (C18 column; elution with 0.1 % AcOH and 10% MeCN in H2O to 0.1 % AcOH and 95 % MeCN and in H2O) followed by preparative HPLC (XBridge® prep C18 5 pm OBMTMcolumn (30x100 mm), 0.1 % AcOH and 10 % MeCN in H2O to 0.1 % AcOH and 60 % MeCN in H2O) to give the title compound as a mixure with 60 % AcOH (18 mg, 10 %).

[0378] XH NMR (400 MHz, DMSO-de) 6 13.0 - 11.2 (br s, 1H) 9.68 (s, 1H), 8.50 (d, J = 9.0 Hz, 1H), 8.43 (d, J = 1.6 Hz, 1H), 8.2 - 7.8 (br s, 2H), 7.87 - 7.77 (m, 3H), 7.74 (d, J = 2.5 Hz, 1H), 7.44 (dd, J = 9.3, 2.5 Hz, 1H), 7.24 - 7.18 (m, 1H), 7.13 (dd, J = 8.3, 1.4 Hz, 1H), 7.00 (td, J = 7.6, 1.4 Hz, 1H), 4.22 (q, J = 7.0 Hz, 2H), 3.88 (s, 3H), 1.91 (s, 2H), 1.44 (t, J = 7.0 Hz, 3H).

[0379] Example 17: 9-Amino-7-ethoxy-N-(2-methoxyphenyl)-N-methylacridine-3- carboxamide

[0380] The title compound was prepared in accordance with the procedure in Example 16, Step (c) from 9-amino-7-ethoxyacridine-3-carboxylic acid hydrochloride and 2-methoxy- / V-methylaniline.

[0381] XH NMR (400 MHz, DMSO-cte) 6 8.14 (d, J = 8.9 Hz, 1H), 7.84 - 7.67 (m, 3H), 7.65 - 7.57 (m, 2H), 7.35 (dd, J = 9.3, 2.6 Hz, 1H), 7.28 (dd, J = 7.8, 1.7 Hz, 1H), 7.20 - 7.07 (m, 2H), 6.91 (d, J = 8.3 Hz, 1H), 6.86 - 6.78 (m, 1H), 4.15 (q, J = 6.9 Hz, 2H), 3.71 (s, 3H), 3.28 (s, 3H), 1.40 (t, J = 6.9 Hz, 3H).

[0382] Example 18: N-(Adamantan-l -yl)-9-amino-7-ethoxyacridine-3-carboxamide

[0383] The title compound was prepared in accordance with the procedure in Example 16, Step (c) from 9-amino-7-ethoxyacridine-3-carboxylic acid hydrochloride and 1-adamantanamine

[0384] XH NMR (400 MHz, DMSO-de) 6 14.9 - 12.8 (br s, 1H), 9.53 - 9.09 (m, 1H), 8.62 (d, J = 8.9 Hz, 1H), 8.22 (d, J = 1.6 Hz, 1H), 8.02 (s, 1H), 7.96 (d, J = 2.5 Hz, 1H), 7.89 (d, J = 9.3 Hz, 1H), 7.81 (dd, J = 8.9, 1.6 Hz, 1H), 7.61 (dd, J = 9.3, 2.5 Hz, 1H), 4.22 (q, J = 7.0 Hz, 2H), 2.19 - 2.02 (m, 9H), 1.69 (d, J = 3.2 Hz, 6H), 1.43 (t, J = 7.0 Hz, 3H).

[0385] Example 19: N-(9-Amino-7-ethoxyacridin-3-yl)hexanamide hydrochloride

[0386] The title compound was prepared in accordance with the procedure in Example 7, Step (b) from ethacridine and hexanoyl chloride.

[0387] XH NMR (400 MHz, DMSO-cte) 6 13.59 (s, 1H), 10.80 (s, 1H), 9.66 (d, J = 17.7 Hz, 2H), 8.59 (d, J = 9.3 Hz, 1H), 8.50 (d, J = 2.0 Hz, 1H), 8.02 (d, J = 2.6 Hz, 1H), 7.81 (d, J = 9.3 Hz, 1H), 7.62 (dd, J = 9.3, 2.6 Hz, 1H), 7.52 (dd, J = 9.3, 2.0 Hz, 1H), 4.20 (q, J = 7.0 Hz, 2H), 2.45 (t, J = 7.5 Hz, 2H), 1.70 - 1.58 (m, 2H), 1.41 (t, J = 7.0 Hz, 3H), 1.37 - 1.27 (m, 4H), 0.93 - 0.86 (m, 3H).

[0388] Example 20: N-( 9-Amino-7-ethoxyacridin-3-yl)-3,3-dimethylbutanamide hydrochloride

[0389] A solution of 3,3-dimethylbutanoyl chloride (213 mg, 1.58 mmol) (prepared from 3,3- dimethylbutyric acid in accordance with the procedure in Example 8, Step (a)) in CH2CI2 (1.5 mL) was added to a stirred ice-cooled mixture of ethacridine (200 mg, 0.79 mmol) and pyridine (5 mL). The suspension was stirred at 0 °C for 30 min, at rt for 18 h and at 90 °C for 1 h. The mixture was cooled in an ice-bath and another portion of 3,3- dimethylbutanoyl chloride (213 mg, 1.58 mmol) in CH2CI2 (1 mL) was added and the mixture was stirred at 50 °C for 4 h. The mixture was cooled in an ice-bath and yet another portion of 3,3-dimethylbutanoyl chloride (213 mg, 1.58 mmol) in CH2CI2 (1 mL) was added and the mixture was stirred at 50 °C for 4 h. The mixture was concentrated and the residue dissolved in hot DMSO (5 mL) and allowed to cool to rt and filtered. The solids were collected, washed with MeCN, suspended in H2O and lyophilized to give the title compound (160 mg, 52 %).

[0390] XH NMR (400 MHz, DMSO-de) 6 13.54 (s, 1H), 10.69 (s, 1H), 9.62 (d, J = 15.4 Hz, 2H), 8.60 - 8.54 (m, 2H), 8.01 (d, J = 2.6 Hz, 1H), 7.80 (d, J = 9.2 Hz, 1H), 7.64 (dd, J = 9.2, 2.6 Hz, 1H), 7.50 (dd, J = 9.4, 2.0 Hz, 1H), 4.21 (d, J = 7.0 Hz, 2H), 2.35 (s, 2H), 1.42 (t, J = 7.0 Hz, 3H), 1.06 (s, 9H). Example 21: N-(9-Amino-7-ethoxyacridin-3-yl)-2-(dimethylamino)benzamide acetic acid salt a) 2-(Dimethylamino)benzoyl chloride hydrochloride

[0391] Oxalyl chloride (346 mg, 0.24 mL, 2.72 mmol) was added dropwise to a stirred ice- cooled mixture of 2-(dimethylamino)benzoic acid (300 mg, 1.82 mmol), DMF (1 drop) and CH2CI2 (7 mL). The solution was stirred at 0 °C for 90 min to give the sub-title compound that was used immediately in the next step. b) N-(9-Amino-7-ethoxyacridin-3-yl)-2-(dimethylamino)benzamide acetic acid salt

[0392] A solution of 2-(dimethylamino)benzoyl chloride hydrochloride (290 mg, 1.32 mmol) in CH2CI2 (7 mL) was added to a stirred ice-cooled mixture of ethacridine (200 mg, 0.79 mmol) and pyridine (5 mL). The mixture was stirred at 0 °C for 30 min and at rt for 18 h and concentrated. The residue was suspended in hot DMSO, the solids were collected and purified by chromatography (C18 column; elution with 0.1 % AcOH and 10 % MeCN in H2O to 0.1 % AcOH and 95 % MeCN in H2O) to give the title compound as a mixure with 50 % AcOH (65 mg, 21 %).

[0393] XH NMR (400 MHz, DMSO-de) 6: 11.67 (s, 1H), 8.47 - 8.38 (m, 2H), 8.5 - 7.9 (br s, 2H), 7.80 - 7.71 (m, 3H), 7.57 (dd, J = 9.3, 2.1 Hz, 1H), 7.52 - 7.47 (m, 1H), 7.44 (dd, J = 9.3, 2.5 Hz, 1H), 7.29 - 7.25 (m, 1H), 7.13 (td, J = 7.5, 1.1 Hz, 1H), 4.19 (q, J = 7.0 Hz, 2H), 2.82 (s, 6H), 1.90 (s, 1.6H), 1.43 (d, J = 7.0 Hz, 3H). Example 22: 4-Amino-N-(9-amino-7-ethoxyacridin-3-yl)benzamide hydrochloride

[0394] (a) / V-(9-Amino-7-ethoxyacridin-3-yl)-4-nitrobenzamide hydrochloride

[0395] A solution of 4-nitrobenzoyl chloride (293 mg, 1.58 mmol) in CH2CI2 (1 mL) was added to a stirred ice-cooled mixture of ethacridine (200 mg, 0.79 mmol) and pyridine (5 mL). The mixture was stirred at 0 °C for 30 min and at rt for 48 h. The suspension was cooled to 0 °C and additional amount of 4-nitrobenzoyl chloride (293 mg, 1.58 mmol) in CH2CI2 (1 mL) was added dropwise. The mixture was stirred at 70 °C for 4 h and concentrated. The residue was suspended in hot DMSO, the solids were collected, washed with H2O, then MeCN and dried over P2O5 at 40 °C for 16 h to give sub-title compound (211 mg, 61 %).

[0396] XH NMR (400 MHz, DMSO-de) 6: 13.73 (s, 1H), 11.29 (s, 1H), 9.72 (d, J = 21.5 Hz, 2H), 8.68 - 8.58 (m, 2H), 8.41 - 8.33 (m, 2H), 8.31 - 8.21 (m, 2H), 8.00 (d, J = 2.5 Hz, 1H), 7.84 (d, J = 9.3 Hz, 1H), 7.80 (dd, J = 9.4, 2.0 Hz, 1H), 7.61 (dd, J = 9.3, 2.5 Hz, 1H), 4.18 (q, J = 6.9 Hz, 2H), 1.41 (t, J = 6.9 Hz, 3H).

[0397] (b) 4-Amino- / V-(9-amino-7-ethoxyacridin-3-yl)benzamide hydrochloride A solution of SnCh (277 mg, 1.46 mmol) in HCI (aq, cone, 0.96 mL) was slowly added to a stirred suspension of / V-(9-amino-7-ethoxyacridin-3-yl)-4-nitrobenzamide hydrochloride (80 mg, 0.18 mmol) in acetic acid (6.4 mL). The suspension was stirred at 60 °C for 6 h. Acetone (16 mL) was added and the mixture was stirred vigorously for 15 min. The precipitate was collected, washed with acetone, dissolved in DMSO and purified by chromatography (C18 column; elution with 0.1 % AcOH and 10 % MeCN in H2O to 0.1 % AcOH and 50 % MeCN in H2O) to give the title compound (48 mg, 64 %).XH NMR (400 MHz, DMSO-de) 6: 10.17 (s, 1H), 8.48 (d, J = 2.1 Hz, 1H), 8.40 (d, J = 9.3 Hz, 1H), 8.65 - 8.17 (m, 3H), 7.83 - 7.77 (m, 3H), 7.76 (d, J = 9.3 Hz, 1H), 7.70 (dd, J = 9.3, 2.0 Hz, 1H), 7.47 (dd, J = 9.3, 2.0 Hz, 1H), 6.68 - 6.59 (m, 2H), 5.86 (s, 2H), 4.19 (q, J = 7.0 Hz, 2H), 1.90 (s, 1H), 1.42 (t, J = 7.0 Hz, 3H).

[0398] Example 23: 2-Amino-N-(9-amino-7-ethoxyacridin-3-yl)benzamide hydrochloride

[0399] The title compound was prepared in accordance with the procedure in Example 22, using 2-nitrobenzoyl chloride in Step (a).

[0400] XH NMR (400 MHz, DMSO-de) 6: 10.55 (s, 1H), 9.5 - 8.8 (br s, 1H), 8.60 - 8.46 (m, 2H), 7.93 (d, J = 2.0 Hz, 1H), 7.83 - 7.78 (m, 1H), 7.72 (dd, J = 7.9, 1.3 Hz, 1H), 7.71 (dd, J = 9.3, 2.0 Hz, 1H), 7.58 (dd, J = 9.3, 2.2 Hz, 1H), 7.30 - 7.23 (m, 1H), 6.81 (dd, J = 8.3, 0.9 Hz, 1H), 6.68 - 6.60 (m, 1H), 6.44 (s, 2H), 4.21 (q, J = 6.9 Hz, 2H), 1.43 (t, J = 6.9 Hz, 3H).

[0401] Example 24: N-(9-Amino-7-ethoxyacridin-3-yl)-4-azidobenzamide hydrochloride

[0402] 4-Azidobenzoyl chloride (183 mg, 1.01 mmol) was added to a stirred suspension of ethacridine (170 mg, 0.67 mmol) in pyridine (4 mL) at 0 °C. The mixture was stirred at 0 °C for 30 min and at rt for 72 h. The mixture was filtered and the solids washed with acetonitrile. The solids were suspended in DMSO (7 mL) and purified by chromatography (C18 column; elution from 10 % MeCN and 0.1 % AcOH in H2O to 55 % MeCN and 0.1 % AcOH in H2O). The fractions containing the desired product were combined and HCI (4 M, aq) was added and the mixture was lyophilized to give the title product (94 mg, 32 %).

[0403] XH NMR (400 MHz, DMSO-cfe): 6 13.66 (s, 1H), 10.95 (s, 1H), 9.67 (d, J = 12.2 Hz, 2H), 8.67 (d, J = 1.8 Hz, 1H), 8.62 (d, J = 9.3 Hz, 1H), 8.15 - 8.08 (m, 2H), 8.02 (d, J = 2.2 Hz, 1H), 7.85 (d, J = 9.3 Hz, 1H), 7.80 (dd, J = 9.3, 1.8 Hz, 1H), 7.65 (dd, J = 9.3, 2.2 Hz, 1H), 7.35 - 7.27 (m, 2H), 4.21 (q, J = 6.9 Hz, 2H), 1.42 (t, J = 6.9 Hz, 3H).

[0404] Example 25: N-(9-Amino-7-ethoxyacridin-3-yl)nicotinamide hydrochloride

[0405] A solution of nicotinoyl chloride hydrochloride (253 mg, 1.42 mmol) in CH2CI2 (2 mL) was added dropwise to an ice-cooled stirred mixture of ethacridine (300 mg, 1.18 mmol) and pyridine (4 mL). The mixture was stirred at 0 °C for 30 min and at rt for 48 h. The suspension was cooled to 0 °C and an additional amount of nicotinoyl chloride hydrochloride (253 mg, 1.42 mmol) in CH2CI2 (2 mL) was added dropwise. The mixture was stirred at rt for 16 h and at 70 °C for 16 h and concentrated. The residue was dissolved in hot DMSO (10 mL) and purified by chromatography (C18 column; elution from 10 % MeCN and 0.1 % AcOH in H2O to 50 % MeCN and 0.1 % AcOH in H2O). The fractions containing the desired product were combined and HCI (4 M, aq) was added and the mixture was lyophilized to give the title product (106 mg, 23 %)

[0406] XH NMR (400 MHz, DMSO-de) 6: 13.74 (s, 1H), 11.30 (s, 1H), 9.80 - 9.64 (m, 2H), 9.40 - 9.15 (m, 1H), 8.99 - 8.79 (m, 1H), 8.71 - 8.61 (m, 2H), 8.55 - 8.48 (m, 1H), 8.04 (d, J = 2.4 Hz, 1H), 7.87 (d, J = 9.3 Hz, 1H), 7.82 (dd, J = 9.3, 2.1 Hz, 1H), 7.77 - 7.70 (m, 1H), 7.66 (dd, J = 9.3, 2.4 Hz, 1H), 4.22 (q, J = 6.9 Hz, 2H), 1.43 (t, J = 6.9 Hz, 3H).

[0407] Example 26: N-(9-Aminoacridin-3-yl)-2-methoxybenzamide

[0408] (a) 4-Nitro-2-(phenylamino)benzoic acid

[0409] A mixture of 2-chloro-4-nitrobenzoic acid (1.00 g, 4.96 mmol), aniline (485 mg, 475 pL, 5.21 mmol), Cu (28 mg, 0.45 mmol), Cu?O (28 mg, 0.20 mmol), K2CO3 (686 mg, 4.96 mmol) and 2-ethoxyethanol (5 mL) was stirred at 120 °C for 18 h. MeOH (80 mL) was added and the mixture was filtered through a pad of Celite, which was washed with MeOH (80 mL) and the combined filtrates were concentrated. Na2COs (aq, 5 %, 30 mL) was added to the residue and HCI (aq, 4 M) was added until pH ~6. The precipitate was collected and dissolved in EtOAc which was washed with H2O. The aq layer was extracted with EtOAc and the combined organic phases were dried over Na2SO4 and concentrated. The residue was purified by silica gel chromatography using gradient elution from 0 % to 10 % MeOH in EtOAc to give the sub-title product (525 mg, 41 %).

[0410] (b) 9-Chloro-3-nitroacridine

[0411] A suspension of 4-nitro-2-(phenylamino)benzoic acid (522 mg, 2.02 mmol) in POCI3 (2.4 mL) was stirred at 95 °C for 1.5 h. Excess POCI3 was removed by concentration under reduced pressure and the residue was carefully added to a mixture of NH4OH (aq, cone) and ice. CHCI3 was added and the layers were separated. The aq layer was extracted with CHCI3 and the combined organic phases were washed with a mixture of NH4OH (aq, cone) and H2O and immediately dried with CaCh. The mixture was filtered through a pad of Celite, which was washed with CHCI3. The combined filtrates were concentrated and the residue was dissolved in CHCI3 (20 mL). Petroleum ether (20 mL) was added and the mixture was kept at -20 °C for 18 h. The precipitate was collected, washed with petroleum ether and dried to give the sub-title product (460 mg, 88 %).

[0412] (c) 9-Azido-3-nitroacridine

[0413] Sodium azide (256 mg, 3.94 mmol) was added to a suspension of 9-chloro-3- nitroacridine (510 mg, 1.97 mmol) in DMF (10 mL) at rt. The mixture was stirred at 65 °C for 5 h and water (15 mL) was added. The precipitate was collected, washed with H2O and dried over P2O5 at 30 °C to give the sub-title product (437 mg, 84 %) which was used in the next step without further purification.

[0414] (d) 3-Nitroacridin-9-amine n-BusP (426 mg, 525 pL, 2.10 mmol) was added to a suspension of 9-azido-3- nitroacridine (465 mg, 1.75 mmol) in THF (7 mL) and H2O (0.7 mL) at rt. The mixture was stirred at rt for 1 h, H2O was added and the mixture was extracted with EtOAc. The combined extracts were washed with brine, dried over Na2SC>4, and concentrated. The residue was purified by chromatography to give the sub-title compound (205 mg, 49 %).

[0415] (e) Acridine-3,9-diamine hydrochloride A solution of SnCh (127 mg, 0.67 mmol) in HCI (aq, cone, 0.46 mL) was slowly added to a stirred solution of 3-nitroacridin-9-amine (20 mg, 0.084 mmol) in glacial acetic acid (3 mL) at rt. The mixture was stirred at 60 °C for 18 h and cooled to rt. The solids were collected, washed with acetone and dried over P2O5 at 45 °C to give the sub-title compounde (195 mg, 100 %), which was used in the next step without further purification.

[0416] (f) / V-(9-Aminoacridin-3-yl)-2-methoxybenzamide

[0417] A solution of 2-metoxybenzoylchloride (208 mg, 182 pL, 1.22 mmol) in CH2CI2 (0.6 mL) was added dropwise to a suspension of acridine-3,9-diamine hydrochloride (120 mg, 0.49 mmol) in pyridine (2.7 mL) over 5 min at 0 °C. The mixture was stirred at 0 °C for 30 min and at rt for 18 h and concentrated. The residue was dissolved in hot DMSO (1.6 mL) and purified by chromatography (C18 column; elution from 10 % MeCN and 0.1 % AcOH in H2O to 50 % MeCN and 0.1 % AcOH in H2O). The fractions containing the desired product were combined and lyophilized to give the title product (55 mg, 28 %) as a 3:2 mixture with acetic acid.

[0418] XH NMR (400 MHz, DMSO-de) 6: 10.58 (s, 1H), 9.7 - 8.4 (br s, 1H), 8.55 - 8.49 (m, 3H), 7.84 - 7.75 (m, 2H), 7.68 (dd, J = 7.5, 1.7 Hz, 1H), 7.62 - 7.52 (m, 2H), 7.40 (ddd, J = 8.6, 6.0, 1.7 Hz, 1H), 7.25 - 7.20 (m, 1H), 7.11 (td, J = 7.5, 0.8 Hz, 1H), 3.93 (s, 3H), 1.90 (s, 1.3H).

[0419] Example 27: N-(9-Amino-5-ethoxyacridin-3-yl)-2-methoxybenzamide hydrochloride

[0420] (a) 2-((2-Ethoxyphenyl)amino)-4-nitrobenzoic acid

[0421] A mixture of 2-chloro-4-nitrobenzoic acid (2.00 g, 9.92 mmol), 2-ethoxyaniline (1.43 g, 10.42 mmol), Cu (57 mg, 0.89 mmol), Cu?O (57 mg, 0.40 mmol) and K2CO3 (1.37 g, 9.92 mmol) and 2-ethoxyethanol (10 mL) was heated at 120 °C for 18 h. MeOH (150 mL) was added and the mixture was filtered through a pad of Celite and concentrated. H2O (50 mL) was added to the residue and the pH was adjusted to 9-10 with NaOH (aq, 4 M). The mixture was extracted with EtOAc and the aq phase was acidified with HCI (aq, 4 M) to pH 7. The precipitate was collected, washed with cold H2O and dried over P2O5 at 45 °C to give the sub-title product 1.40 g (47 %).

[0422] (b) 9-Chloro-5-ethoxy-3-nitroacridine

[0423] A suspension of 2-((2-ethoxyphenyl)amino)-4-nitrobenzoic acid (1.00 g, 3.31 mmo) in POCI3 (13.2 mL) was stirred at 95 °C for 1.5 h. Excess POCI3 was removed by concentration under reduced pressure and the residue was carefully added to a mixture of NH4OH (aq, cone, 250 mL) and ice (700 mL). CHCI3 (30 mL) was added and the layers were separated. The aq layer was extracted with CHCI3 and the combined organic phases were washed with a mixture of NH4OH (aq, cone, 100 mL) and H2O (100 mL) and immediately dried with CaCh. The mixture was filtered through a pad of Celite, which was washed with CHCI3. The combined filtrates were concentrated to give the sub-title product (955 mg, 95 %), which was used in the next step without any further purification.

[0424] (c) 9-Azido-5-ethoxy-3-nitroacridine

[0425] Sodium azide (408 mg, 6.28 mmol) was added to a suspension of 9-chloro-5-ethoxy- 3-nitroacridine (950 mg, 3.14 mmol) in DMF (15 mL) at rt. The mixture was stirred at 65 °C for 5 h and H2O was added. The mixture was extracted with EtOAc and the combined organic phases were washed with H2O and brine, dried over Na2SC>4 and concentrated to give the sub-title product (935 mg, 96 %), which was used in the next step without any further purification.

[0426] (d) 5-Ethoxy-3-nitroacridin-9-amine n-BusP (730 mg, 901 pL, 3.61 mmol) was added to a suspension of 9-azido-5-ethoxy- 3-nitroacridine (930 mg, 3.01 mmol) in THF (12 mL) and H2O (1.3 mL) at rt. The solution was stirred at rt for 2 h, H2O was added and the mixture was extracted with EtOAc. The combined extracts were washed with brine, dried over Na2SO4, and concentrated. The residue was purified by chromatography to give the sub-title compound (530 mg, 62 %).

[0427] (e) 5-Ethoxyacridine-3,9-diamine hydrochloride

[0428] The title compound was prepared in accordance with the procedure in Example 26,

[0429] Step (e) from 5-ethoxy-3-nitroacridin-9-amine.

[0430] (f) / V-(9-Amino-5-ethoxyacridin-3-yl)-2-methoxybenzamide

[0431] A solution of 2-metoxybenzoylchloride (147 mg, 128 pL, 0.86 mmol)) in CH2CI2 (0.4 mL) was added dropwise to a suspension of 5-ethoxyacridine-3,9-diamine hydrochloride (100 mg, 0.35 mmol) in pyridine (1.9 mL) at 0 °C. The mixture was stirred at 0 °C for 30 min and at rt for 18 h and concentrated. The residue was dissolved in hot DMSO (1.6 mL) and purified by chromatography (C18 column; elution from 10 % MeCN and 0.01 % HCI in H2O to 50 % MeCN and 0.01 % HCI in H2O). The fractions containing the desired product were combined and lyophilized to give the title product (67 mg, 46 %).

[0432] XH NMR (400 MHz, DMSO-de) 6: 12.55 (s, 1H), 10.79 (s, 1H), 9.92 (s, 1H), 9.83 (s, 1H), 9.15 (d, J = 1.9 Hz, 1H), 8.68 (d, J = 9.3 Hz, 1H), 8.24 - 8.17 (m, 1H), 7.68 (dd, J = 7.5, 1.7 Hz, 1H), 7.60 - 7.51 (m, 3H), 7.51 - 7.45 (m, 1H), 7.27 - 7.21 (m, 1H), 7.12 (td, J = 7.5, 0.8 Hz, 1H), 4.39 (q, J = 6.9 Hz, 2H), 3.93 (s, 3H), 1.55 (t, J = 6.9 Hz, 3H).

[0433] Example 28: N-(9-Amino-6-ethoxyacridin-3-yl)-2-methoxybenzamide hydrochloride

[0434] (a) 2-((3-Ethoxyphenyl)amino)-4-nitrobenzoic acid

[0435] A mixture of 2-chloro-4-nitrobenzoic acid (4.35 g, 21.58 mmol), 3-ethoxyaniline (3.11 g, 3.0 mL, 22.66 mmol), Cu (123 mg, 1.94 mmol), CU2O (123 mg, 0.86 mmol), K2CO3 (2.98 g, 21.58 mmol) and 2-ethoxyethanol (21 mL) was heated at 120 °C for 18 h. MeOH (200 mL) was added and the mixture was filtered through a pad of Celite and concentrated. H2O (100 mL) was added to the residue and the pH was adjusted to 9- 10 with NaOH (aq, 4 M). The mixture was extracted with EtOAc and the combined extracts were washed with brine, HCI (aq, 4 M), brine and dried over Na?SO4 and concentrated to give the sub-title product (3.90 g, 60 %).

[0436] (b) 9-Chloro-3-ethoxy-6-nitroacridine

[0437] The sub-title compound was prepared from 2-((3-ethoxyphenyl)amino)-4-nitrobenzoic acid in accordance with the procedure in Example 27, Step (b) and was purified by chromatography.

[0438] (c) 6-Ehoxyacridine-3,9-diamine hydrochloride

[0439] The sub-title compound was prepared from 9-hloro-3-ethoxy-6-nitroacridine in accordance with the procedures in Example 26, Steps (c) to (e).

[0440] (d) / V-(9-Amino-6-ethoxyacridin-3-yl)-2-methoxybenzamide

[0441] A solution of 2-metoxybenzoylchloride (134 mg, 117 pL, 0.78 mmol)) in CH2CI2 (0.55 mL) was added dropwise to a suspension of 6-ethoxyacridine-3,9-diamine hydrochloride (151 mg, 0.52 mmol) in pyridine (3.2 mL) at 0 °C. The mixture was stirred at 0 °C for 30 min and at rt for 18 h and concentrated. The residue was suspended in hot DMSO (2 mL) and purified by chromatography (C18 column; elution from 10 % MeCN and 0.1 % AcOH in H2O to 50 % MeCN and 0.1 % AcOH in H2O), followed by preparative HPLC (XBridge® prep C18 5 pm OBM™ column (30x100 mm); elution from 10 % MeCN and 0.1 % AcOH in H2O to 50 % MeCN and 0.1 % AcOH in H2O). The fractions containing the desired product were combined and lyophilized to give the title product (20 mg, 9 %).

[0442] XH NMR (400 MHz, DMSO-de) 6: 13.37 (s, 1H), 10.81 (s, 1H), 9.62 (s, 2H), 8.64 - 8.53 (m, 3H), 7.66 (dd, J = 7.5, 1.7 Hz, 1H), 7.60 - 7.53 (m, 2H), 7.26-7.21 (m, 1H), 7.19 - 7.14 (m, 2H), 7.11 (td, J = 7.5, 0.8 Hz, 1H), 4.24 (q, J = 7.0 Hz, 2H), 3.92 (s, 3H), 1.44 (t, J = 7.0 Hz, 3H).

[0443] Example 29: N-( 9-Amino-7-ethoxyacridin-3-yl)-2-methoxy-N-methylbenzamide hydrochloride

[0444] (a) / V-(9-Amino-7-ethoxyacridin-3-yl)-2-methoxybenzamide

[0445] A solution of 2-metoxybenzoylchloride (354 mg, 309 pL, 2.07 mmol) in CH2CI2 (1.25 mL) was added dropwise to a suspension of ethacridine (350 mg, 1.38 mmol) in pyridine (7.2 mL) at 0 °C. The mixture was stirred at 0 °C for 30 min and at rt for 18 h and concentrated. The residue was suspenced in hot DMSO (2 mL) and purified by chromatography (C18 column; elution from 10 % MeCN and 0.1 % AcOH in H2O to 50 % MeCN and 0.1 % AcOH in H2O). The fractions containing the desired product were combined and concentrated. NaHCOs (aq, sat) was added to the residue and the mixture was extracted with EtOAc. The precipitate in aqueous layer was collected by filtration and dried over P2O5 at 35 °C to give the sub-title compound (337 mg, 63 %).

[0446] (b) N-(9-Amino-7-ethoxyacridin-3-yl)-2-methoxy-N-methylbenzamide hydrochloride

[0447] NaOH (35 mg, 0.88 mmol) followed by trimethyl phosphate (75 mg, 62 pL, 0.54 mmol) were added to a solution of / V-(9-amino-7-ethoxyacridin-3-yl)-2-methoxybenzamide (190 mg, 0.49 mmol) in DMSO (2.6 mL). The solution was stirred at 50 °C for 4 h and purified by chromatography (C18 column; elution from 10 % MeCN and 0.1 % AcOH in H2O to 50 % MeCN and 0.1 % AcOH in H2O). The fractions containing the desired product were combined and the pH was adjusted to 11-12 with NaOH (aq, 4 M) The mixture was extracted with EtOAc and the combined organic phases were dried over Na2SO4 and concentrated. The residue was dissolved in DMSO (0.7 mL) and purified by preparative HPLC (XBridge® prep C18 5 pm OBM™ column (30x100 mm); elution from 10 % MeCN and 0.1 % AcOH in H2O to 50 % MeCN and 0.1 % AcOH in H2O). The fractions containing the desired compound were collected, HCI (aq, 4 M.) was added and the mixture was lyophilized to give the title compound (96 mg, 45 %).

[0448] XH NMR (400 MHz, DMSO-de) 6: 13.90 (s, 1H), 9.80 (m, 2H), 8.52 (d, J = 9.3 Hz, 1H), 8.03 (d, J = 2.3 Hz, 1H), 7.86 (d, J = 9.3 Hz, 1H), 7.69 - 7.61 (m, 2H), 7.45 - 7.37 (m, 1H), 7.34 (dd, J = 7.5, 1.6 Hz, 1H), 7.32 - 7.25 (m, 1H), 6.96 - 6.90 (m, 1H), 6.87 (d, J = 8.2 Hz, 1H), 4.21 (q, J = 6.9 Hz, 2H), 3.61 (s, 3H), 3.44 (s, 3H), 1.41 (t, J = 6.9 Hz, 3H).

[0449] Example 30: N-(7-Ethoxy-9-(methylamino )acridin-3-yl)-2-methoxybenzamide hydrochloride

[0450] (a) 2-((4-Ethoxyphenyl)amino)-4-nitrobenzoic acid A mixture of 2-chloro-4-nitrobenzoic acid (3.00 g, 14.88 mmol), 4-ethoxyaniline (2.14 g, 2.0 mL, 15.63 mmol), Cu (85 mg, 1.34 mmol), CU2O (85 mg, 0.60 mmol), K2CO3 (2.06 g, 14.88 mmol) and 2-ethoxyethanol (20 mL) was heated at 100 °C for 18 h. MeOH (150 mL) was added and the mixture was filtered through a pad of Celite and concentrated. H2O (50 mL) was added to the residue and the pH was adjusted to 9 with NaOH (aq, 4 M). The mixture was extracted with EtOAc and the combined extracts were washed with brine, dried over Na2SC>4 and concentrated. The residue was dissolved in Na2COs (aq, 5 %) and the pH was adjusted to 7 by addition of HCI (aq, 4 M). The precipitate was collected, washed with cold H2O and dried over P2O5 at 45 °C to give the sub-title compound (3.55 g, 79 %).

[0451] (b) 9-Chloro-2-ethoxy-3-nitroacridine

[0452] A suspension of 2-((4-ethoxyphenyl)amino)-4-nitrobenzoic acid (3.52 g, 11.64 mmol) in POCI3 (13.6 mL) was stirred at 95 °C for 1.5 h. Excess POCI3 was removed by concentration under reduced pressure and the residue was carefully added to a mixture of NH4OH (aq, cone, 150 ml) and ice (700 mL). CHCI3 (100 mL) was added and the layers were separated. The aq layer was extracted with CHCI3 and the combined organic phases were washed with a mixture of NH4OH (aq, cone, 75 ml) and H2O (75 mL) and immediately dried with CaCh. The mixture was filtered through a pad of Celite, which was washed with CHCI3. The combined filtrates were concentrated and the residue was purified by chromatography to give the sub-title product (2.00 g, 57 %).

[0453] (c) 2-Ethoxy- / V-methyl-6-nitroacridin-9-amine

[0454] A mixture of 9-chloro-2-ethoxy-6-nitroacridine (200 mg, 0.66 mmol) and NH2Me (in THF, 2.0 M, 5.0 mL, 9.91 mmol) was stirred at 50 °C for 18 h. An additional portion of NH2Me (in THF, 2.0 M, 5.0 mL, 9.91 mmol) was added and the mixture was stirred at 50 °C for 22 h. Yet another portion portion of NFhMe (in THF, 2.0 M, 5.0 mL, 9.91 mmol) was added and stirring was continued at 55 °C for 12 h. The mixture was concentrated to give the sub-title product (180 mg, 92 %), which was used in the next step without further purification.

[0455] (d) 7-Ethoxy- / V9-methylacridine-3,9-diamine

[0456] A mixture of 2-ethoxy- / V-methyl-6-nitroacridin-9-amine (200 mg, 0.67 mmol), Fe powder (113 mg, 2.02 mmol), EtOH (920 pL), AcOH (3.7 mL) and H2O (18 pL) was sonicated for 1 h 15 min. The suspension was filtered through a glass filter, which was washed with MeOH-AcOH (1 : 1; 15 mL). The combined filtrates were concentrated to ~ 1 mL and suspended in EtOAc. NaHCCh (aq, sat) was added and the layers were separated. The pH of the aq phase was adjusted to ~ 12 by addition of NaOH (aq, 4 M) and was extracted with EtOAc. The combined extracts were dried over Na?SO4 and concentrated to give the sub-title product (120 mg, 67 %).

[0457] (e) / V-(7-Ethoxy-9-(methylamino)acridin-3-yl)-2-methoxybenzamide hydrochloride

[0458] A solution of 2-metoxybenzoylchloride (152 mg, 133 pL, 0.89 mmol)) in CH2CI2 (0.5 mL) was added dropwise to a suspension of 7-ethoxy- / V9-methylacridine-3,9-diamine (119 mg, 0.45 mmol) in pyridine (3.0 mL) at 0 °C. The mixture was stirred at 0 °C for 30 min and at rt for 16 h and an additional portion of 2-metoxybenzoylchloride (76 mg, 66 pL, 0.45 mmol) was added at 0 °C. The mixture was stirred rt for 16 h and concentrated. The residue was dissolved in hot DMSO and purified by chromatography (C18 column; elution from 10 % MeCN and 0.1 % AcOH in H2O to 40 % MeCN and 0.1 % AcOH in H2O), followed by preparative HPLC (XBridge® prep C18 5 pm OBM™ column (30x 100 mm); elution from 10 % MeCN and 0.1 % AcOH in H2O to 50 % MeCN and 0.1 % AcOH in H2O). The fractions containing the desired product were combined and lyophilized to give the title product (7 mg, 4 %).

[0459] XH NMR (400 MHz, DMSO-de) 6: 13.39 (s, 1H), 10.81 (s, 1H), 9.77 (s, 1H), 8.63 (d, J = 1.9 Hz, 1H), 8.61 (d, J = 9.5 Hz, 1H), 7.99 - 7.94 (m, 1H), 7.78 (d, J = 9.2 Hz, 1H), 7.63 (dd, J = 7.6, 1.8 Hz, 1H), 7.60 (dd, J = 9.2, 2.2 Hz, 1H), 7.58 - 7.53 (m, 1H), 7.51 (dd, J = 9.5, 2.0 Hz, 1H), 7.25 - 7.20 (m, 1H), 7.11 (td, J = 7.5, 0.6 Hz, 1H), 4.22 (q, J = 6.9 Hz, 2H), 3.90 (s, 3H), 3.68 (d, J = 4.7 Hz, 3H), 1.41 (t, J = 6.9 Hz, 3H).

[0460] Example 31: N-(9-Amino-7-hydroxyacridin-3-yl)benzamide trifluoroacetate

[0461] (a) 2-((4-(Benzyloxy)phenyl)amino)-4-nitrobenzoic acid

[0462] A mixture of 2-chloro-4-nitrobenzoic acid (2 g, 10 mmol), 4-benzyloxyaniline hydrochloride (2.3 g, 10 mmol), K2CO3 (2.7 g, 20 mmol), copper powder (126 mg), potassium iodide (82 mg) and DMF (15 mL) was heated at 135 °C for 16 h. The mixture was allowed to cool and poured into HCI (aq, 1 M). The precipitate was collected, washed with H2O and dried to give the sub-title compound (2.7 g, 75 %).

[0463] (b) 2-(Benzyloxy)-9-chloro-6-nitroacridine A solution of 2-((4-(benzyloxy)phenyl)amino)-4-nitrobenzoic acid (1.4 g, 3.8 mmol) in phosphoryl chloride (8 mL) was heated at reflux overnight. After cooling, the mixture was carefully poured into a mixture of NH3 (aq, cone, 100 mL) and crushed ice (200 g). The precipitate was collected, washed with H2O and with MeOH and dried to give the sub-title compound (820 mg, 58 %).

[0464] (c) tert-Butyl (2-(benzyloxy)-6-nitroacridin-9-yl)carbamate

[0465] Amixture of 2-(benzyloxy)-9-chloro-6-nitroacridine (735 mg, 2.0 mmmol), tert-butyl carbamate (283 mg, 2.4 mmol), CS2CO3 (788 mg, 2.4 mmol), Pd(dba)3 (104 mg, 0.05 mmol), Xphos (96 mg, 0.2 mmol) and dioxane (15 ml) was heated at 90 °C for 1 h. The mixture was allowed to cool and concentrated, and the residue was partitioned between EtOAc and H2O. The organic layer was concentrated and the residue was purified by chromatography to give the sub-title compound (520 mg, 58 %)

[0466] (d) tert-Butyl (6-amino-2-(benzyloxy)acridin-9-yl)carbamate

[0467] A slurry of Raney-nickel in water (~12 mg, 0.10 mmol) was added to a stirred solution of tert-butyl (2-(benzyloxy)-6-nitroacridin-9-yl)carbamate (450 mg, 1.00 mmol) in MeOH (30 mL) at rt. NaBH4 (7.6 mg, 0.20 mmol) was added and the mixture was stirred at rt for 1 h and filtered through a pad of Celite. The solids were washed with MeOH and the combined filtrates were concentrated. The residue wa washed with H2O followed by Et20 to give the sub-title compound (370 mg, 88 %). e) tert-Butyl (6-benzamido-2-(benzyloxy)acridin-9-yl)carbamate

[0468] Diisopropylethylamine (117 ul, 0.62 mmol) and HATU (119 mg, 0.31 mmol) was added to a solution of tert-butyl (6-amino-2-(benzyloxy)acridin-9-yl)carbamate (100 mg, 0.24 mmol) and benzoic acid (38 mg, 0.31 mmol) in DMF (5 mL). The mixture was stirred at 65 °C for 12 h and allowed to cool to rt. H2O was added and the precipitate was collected, washed with NaHCCh (aq, sat) and crystalized from EtOH to give the sub-title compound (78 mg, 62%). f) / V-(9-Amino-7-hydroxyacridin-3-yl)benzamide trifluoroacetate

[0469] A mixture of tert-butyl (6-benzamido-2-(benzyloxy)acridin-9-yl)carbamate (30 mg, 0.06 mmol), pyridinium chloride (67 mg, 0.6 mmol) and l-butyl-3-methylimidazolium hexafluorophosphate (100 pL) was heated at 90 °C for 3 h The temperature was increased to 170 °C and additional pyridinium chloride (70 mg) was added. The mixture was heated at 170 °C for 1 h and left to cool to rt. H2O and EtOAc was added and the solid was collected and purified by acidic preparative HPLC to give the title compound.

[0470] 1H NMR (400 MHz, DMSO-c / e) 6: 7.59 - 7.64 (m, 3 H) 7.66 (d, J=7.25 Hz, 1 H) 7.71 (dd, J=9.44, 1.94 Hz, 1 H) 7.76 (d, J=9.13 Hz, 1 H) 7.83 (d, J=2.38 Hz, 1 H) 8.02 (d, J=7.00 Hz, 2 H) 8.54 (d, J=9.38 Hz, 1 H) 8.70 (d, J=1.88 Hz, 1 H) 9.29 - 9.51 (m, 2 H) 10.24 - 10.28 (m, 1 H) 10.90 (s, 1 H) 13.42 (s, 1 H).

[0471] Biological examples

[0472] Biological example 1 : Inhibition of tumor cell activity

[0473] The MYCN-amplified neuroblastoma cell line Kelly was plated in a 96 well plate 48 h pre-treatment. On the day of treatment, compounds from a stock of 10 mM in DMSO were mixed with cell medium (RPMI + 10% FBS) and titrated in 5 concentrations with a dilution factor of 1 : 1, starting at 12.5 uM. Cell medium was exchanged to medium containing compounds. Technical triplicates were used. 24 hours post-treatment, the cell medium was exchanged to a PBS solution with Resazurin (1 : 10000) and incubated for 2 h. The fluorescence of the plate wells was measured in a FluoStar Omega (BMG Labtech). Relative metabolic activity of cells was calculated by comparing to DMSO- treated cells. ICso values were calculated from at least three biological experiments.

[0474] The activity for each compound is denoted with pluses (+) according to their ICso values. If a compound shows ICso values between 1.0 and 3.2 pM, the activity is denoted with + + ++, if it is between 3.3 and 6.4 pM it is denoted with + + + ; if it is between 6.5 and 12.5 it is denoted with + + ; if it higher than 12.5 pM it is denoted with +.

[0475] Biological example 2: Inhibition of tumor cell activity after 72 h

[0476] The MYCN-amplified neuroblastoma cell line Kelly was plated in a 96-well plate 24 h pre-treatment. On the day of treatment, compounds from a stock of 10 mM in DMSO were mixed with cell medium (RPMI + 10% FBS) and titrated in 8 concentrations with a dilution factor of 1: 1, starting at 25 pM. Medium containing compounds was added to the cells. Technical triplicates were used. 72 hours post-treatment, an equal volume of CellTiter-Glo® Reagent was added and luminescence recorded with a SpectraMax instrument. Relative metabolic activity of cells was calculated by comparing to DMSO- treated cells. ICso values were calculated from at least two biological experiments. The activity for each compound is denoted with pluses (+) according to their ICso values. If a compound shows ICso values below 3.2 pM, the activity is denoted with + + ++, if it is between 3.3 and 6.4 pM it is denoted with + + + ; if it is between 6.5 and 12.5 it is denoted with + + ; if it higher than 12.5 pM it is denoted with +.

[0477] Using the assays described in Biological Example 1 and Biological Example 2 the following results were obtained.

[0478] Stability examples

[0479] Stability Example 1 : Stability in solution after 48 h The test compound (1.0 mg) was dissolved in a mixture of 50 % MeCN and 50 % PBS (1 : 1, 5.0 mL, c = 0.2 mg / mL) and kept in a glass vial in the laboratory at ambient light and temperature. The amount of remaining product after 48 h was measured using HPLC (C18 column, eluent system MeCN in 0.1 % H3PO4 aqueous solution). The results are calculated by comparing the heights of the peaks in the HPLC spectra corresponding to the compound in question at time zero with that after 48 h. Using the assay described in Stability Example 1 the following results were obtained. As a reference, 7-ethoxy- / V3-(furan-2-ylmethyl)acridine-3,9-diamine, with the following structure was used. Reference compound nt = not tested

[0480] *expected to be light-sensitive

Claims

1. Claims1. A compound of formula Ior a pharmaceutically-acceptable salt and / or detectably-labelled derivative thereof, wherein:L represents -N(R2)C(O)(CH2)WI-, -N(R2)S(O)qi(CH2)w2- or -C(O)N(R2)(CH2)w3-; wl to w3 each independently represents 0 to 3;R1represents C3-12 alkyl, C3-12 alkenyl or C3-12 alkynyl, each optionally substituted by one or more groups independently selected from Gla, C3-10 cycloalkyl optionally substituted by one or more groups independently selected from Glb, heterocyclyl optionally substituted by one or more groups independently selected from Glc, aryl optionally substituted by one or more groups independently selected from Gld, or heteroaryl optionally substituted by one or more groups independently selected from Gle;R2represents H or Ci-6 alkyl optionally substituted by one or more groups independently selected from F, -ON, -OH, -OCi-4 alkyl optionally substituted by one or more F, or =0;R3and R4each independently represent H or Ci-6 alkyl optionally substituted by one or more groups independently selected from F, -ON, -OH and -OCi-6 alkyl optionally substituted by one or more F; each X and Y independently represents halo, Ci-6 alkyl optionally substituted by one or more F, -CN, -OH or -OCi-6 alkyl optionally substituted by one or more F; m represents 0, 1, 2, 3 or 4; n represents 0, 1, 2 or 3;ql represents 1 or 2; each Gla, Glband Glcindependently represents halo, Ral, -ON, -Aal-C(O)Rbl, -Abl-C(O)N(Rcl)Rdl, -Acl-C(O)ORel, -Adl-S(O)PRfl, -Ael-S(O)PN(Rgl)Rhl, -A^-SCOJpOR11, -N3, -N(Rjl)Rkl, -OR11, -SRmlor =0; each Gldand Gleindependently represents halo, Ral, -ON, -Aal-C(O)Rbl, -Abl-C(O)N(Rcl)Rdl, -Acl-C(O)ORel, -Adl-S(O)PRfl, -Ael-S(O)PN(Rgl)Rhl, -A^-SCOJpOR11, -N3, -N(Rjl)Rkl, -N02, -OR11or -SRml; each Aalto Aflindependently represents a single bond, -N(Rn1)- or -O-; each Raland Rflindependently represents C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl, each optionally substituted by one or more groups independently selected from G2a, C3-10 cycloalkyl optionally substituted by one or more groups independently selected from G2b, heterocyclyl optionally substituted by one or more groups independently selected from G2c, aryl optionally substituted by one or more groups independently selected from G2d, or heteroaryl optionally substituted by one or more groups independently selected from G2e; each Rbl, Rcl, Rdl, Rel, Rgl, Rhl, R'1, Rjl, Rkl, R11, and Rmlindependently represents H or C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl, each optionally substituted by one or more groups independently selected from G2a, C3-10 cycloalkyl optionally substituted by one or more groups independently selected from G2b, heterocyclyl optionally substituted by one or more groups independently selected from G2c, aryl optionally substituted by one or more groups independently selected from G2d, or heteroaryl optionally substituted by one or more groups independently selected from G2e, or alternatively any of RC1and Rdl, Rgland Rhland / or Rjland Rklare linked together to form, together with the nitrogen atom to which they are attached, a 3- to 6-membered ring, which ring optionally contains one further heteroatom and which ring optionally is substituted by one or more groups independently selected from F, C1-3 alkyl optionally substituted by one or more F, or -OCi-3alkyl optionally substituted by one or more F and =0; each Rnlindependently represents H or C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl, each optionally substituted by one or more groups independently selected from G2a, C3-6 cycloalkyl optionally substituted by one or more groups independently selected fromG2bor heterocyclyl optionally substituted by one or more groups independently selected from G2c; each G2a, G2band G2cindependently represents F, Ra2, -ON, -Aa2-C(O)Rb2, -Ab2-C(O)N(Rc2)Rd2, -Ac2-C(O)ORe2, -Ad2-S(O)PRf2, -Ae2-S(O)PN(Rg2)Rh2, -Af2-S(O)PORi2, -N(Rj2)Rk2, -OR12, -SRm2or =0; each G2dand G2eindependently represents halo, Ra2, -ON, -Aa2-C(O)Rb2, -Ab2-C(O)N(Rc2)Rd2, -Ac2-C(O)ORe2, -Ad2-S(O)PRf2, -Ae2-S(O)PN(Rg2)Rh2, -Af2-S(O)PORi2, -N3, -N(Rj2)Rk2, -NO2, -OR12or -SRm2; each Aa2to Af2independently represents a single bond, -N(Rn2)- or -0-; each Ra2and Rf2independently represents C1-6 alkyl optionally substituted by one or more groups independently selected from F, -ON or -OC1-3 alkyl optionally substituted by one or more F; each Rb2, Rc2, Rd2, Re2, Rg2, Rh2, R'2, Rj2, Rk2, R12, Rm2and Rn2independently represents H or C1-6 alkyl optionally substituted by one or more groups independently selected from F, -ON, -OH or -OC1-3 alkyl optionally substituted by one or more F, or alternatively any of Rc2and Rd2, Rg2and Rh2, Rj2and / or Rk2are linked together to form, together with the nitrogen atom to which they are attached, a 3- to 6-membered ring, which ring optionally contains one further heteroatom and which ring optionally is substituted by one or more groups independently selected from F, C1-3 alkyl optionally substituted by one or more F; each p independently represents 1 or 2, wherein the alkyl, alkenyl, and alkynyl groups may be straight-chain or branched- chain; with the provisos (A) and (B) that the following compounds are excluded :(A) / V-(9-amino-7-ethoxyacridin-3-yl)benzamide; / V-(9-amino-7-ethoxyacridin-3-yl)-3-bromobenzamide; / V-(9-amino-7-ethoxyacridin-3-yl)-4-cyanobenzamide; methyl 4-((9-amino-7-ethoxyacridin-3-yl)carbamoyl)benzoate; / V-(9-amino-7-ethoxyacridin-3-yl)-2-naphthamide; / V-(9-amino-7-ethoxyacridin-3-yl)-4-fluorobenzamide; / V-(9-amino-7-ethoxyacridin-3-yl)-3-cyanobenzamide; / V-(9-amino-7-ethoxyacridin-3-yl)-3-nitro benzamide; / V-(9-amino-7-ethoxyacridin-3-yl)-4-nitro benzamide; / V-(9-amino-7-ethoxyacridin-3-yl)-3,5-bis(trifluoromethyl)benzamide; and N-(9-amino-7-ethoxyacridin-3-yl)furan-2-carboxamide.(B) / V-(9-Amino-7-ethoxyacridin-3-yl)-2-phenylacetamide; / V-(9-amino-7-ethoxyacridin-3-yl)-2-bromobenzamide; / V-(9-amino-7-ethoxyacridin-3-yl)-4-methylbenzamide; and / V-(9-amino-7-ethoxyacridin-3-yl)-4-methoxybenzamide.

2. The compound according to Claim 1, wherein the following compound is excluded: / V-(9-amino-7-ethoxyacridin-3-yl)-4-chlorobenzamide.

3. The compound according to Claim 1 or 2, wherein R1is selected from:C3-12 alkyl optionally substituted by one or more groups independently selected fromGla,C3-10 cycloalkyl optionally substituted by one or more groups independently selected from Glb,C5-6 heterocyclyl optionally substituted by one or more groups independently selected from Glc, andCe or C10 aryl, each optionally substituted by one or more groups independently selected from Gld.

4. The compound according to any one of the preceding claims, wherein R1is selected from:C3-10 cycloalkyl optionally substituted by one or more groups independently selected from Glb, andCs-6 heterocycloalkyl optionally substituted by one or more groups independently selected from Glc.

5. The compound according to any one of Claims 1 to 3, wherein R1is selected from:Ce or Cio aryl, each optionally substituted by one or more groups independently selected from Gld.

6. The compound according to Claim 1 or 2, wherein R1represents heteroaryl, such as pyridinyl.

7. The compound according to any one of the preceding claims, wherein each Gla, Glband Glcindependently represents F, Ral, -Acl-C(O)ORel, -N(Rjl)Rkl, -OR11, or -SRml.

8. The compound according to any one of the preceding claims, wherein each Gldand Gleindependently represents halo, Ral, -CN, -Acl-C(O)ORel, -N(Rjl)Rkl, -NO2, - OR11, or -SRml.

9. The compound according to any one of the preceding claims, wherein wl to w3 each independently represent 0 or 1.

10. The compound according to any one of the preceding claims, wherein L represents -N(R2)C(O)-, -N(R2)S(O)qi-, or -C(O)N(R2)-.

11. The compound according to any one of the preceding claims, wherein R2represents H or C1-3 alkyl optionally substituted with one or more groups independently selected from F and =0.

12. The compound according to any one of Claims 1 to 11, wherein n represents 0.

13. The compound according to any one of Claims 1 to 12, wherein R3and R4each represent H.

14. The compound according to any one of Claims 1 to 13, wherein m represents at least 1.

15. The compound according to any one of Claims 1 to 14, wherein m represents 1.

16. The compound according to any one of the preceding claims, wherein the compound of formula I is a compound of formula lbwherein R1, R3, R4, X, Y, L and n are as claimed in any one of the preceding claims, and t represents 0, 1, 2 or 3.

17. The compound according to any one of Claims 1 to 15, wherein the compound of formula I is a compound of formula (Ig) or (Ih)wherein R1, R3, R4, X, Y, L and n are as claimed in any one of the preceding claims, and t represents 0, 1, 2 or 3.

18. The compound according to any one of the preceding claims, wherein each X independently represents F or -OCi-6 alkyl optionally substituted with one or more F.

19. The compound according to any one of Claims 16 to 18, wherein: t represents 0; andX represents -OCi-6 alkyl optionally substituted with one or more F.

20. The compound according to any one of the preceding claims, wherein each X independently represents -OCi salkyl optionally substituted by one or more F.

21. The compound according to any one of the preceding claims, wherein the compound of formula I is a compound of formula lewherein R1, X, Y, L, t and n are as claimed in any one of Claims 1 to 20.

22. A compound of formula I according to any one of Claims 1 to 21 but without the proviso (B), or a pharmaceutically acceptable salt and / or detectably labelled derivative thereof, for use as a pharmaceutical.

23. A compound of formula I according to any one of Claims 1 to 21 but without the provisos, or a pharmaceutically acceptable salt and / or detectably labelled derivative thereof, for use in the treatment of cancer.

24. A method of treating cancer, comprising administering to a patient in need thereof a therapeutically effective amount of a compound of formula I according to any one of Claims 1 to 21 but without the provisos, or a pharmaceutically acceptable salt and / or detectably labelled derivative thereof.

25. The use of a compound of formula I according to any one of Claims 1 to 21 but without the provisos, or a pharmaceutically acceptable salt and / or detectably labelled derivative thereof, for the manufacture of a medicament for the treatment of cancer.

26. The compound for use, method or use according to any one of Claims 23 to 25, wherein the cancer is characterised by increased MYC activity.

27. The compound for use, method or use according to any one of Claims 23 to 26 but without the provisos, wherein the cancer is selected from the list consisting of:Burkitt's lymphoma; ovarian cancer, such as ovarian cancer with BRCA alterations; basel-like breast cancer; esophageal squamous cell carcinoma; colon cancer; endometrial cancer; neuroblastoma;lung cancer; medulloblastoma, such as group 3; pancreatic cancer; malignant melanoma; head and neck cancer; prostate cancer; and hepatocellular carcinomas.

28. A pharmaceutical composition comprising a compound of formula I according to any one of Claims 1 to 21 but without the proviso (B), or a pharmaceutically acceptable salt and / or detectably labelled derivative thereof, and optionally one or more pharmaceutically-acceptable excipient.

29. A pharmaceutical composition according to Claim 28, but without the provisos, for use in the treatment of cancer, such as cancer as defined in any one of Claims 26 or 27.

30. A combination product comprising:(I) a compound of formula I according to any one of Claims 1 to 21 but without the provisos, or a pharmaceutically acceptable salt and / or detectably labelled derivative thereof, and(II) one or more other therapeutic agent that is useful in the treatment of cancer, wherein each of components (I) and (II) is formulated in admixture, optionally with one or more pharmaceutically-acceptable excipient.

31. A kit-of-parts comprising:(a) a pharmaceutical composition ccomprising a compound of formula I according to any one of Claims 1 to 21 but without the provisos, or a pharmaceutically acceptable salt and / or detectably labelled derivative thereof, and optionally one or more pharmaceutically-acceptable excipient and(b) one or more other therapeutic agent that is useful in the treatment of cancer, optionally in admixture with one or more pharmaceutically-acceptable excipient, which components (a) and (b) are each provided in a form that is suitable for administration in conjunction with the other.

32. A process for the preparation of a compound of formula I according to any one of Claims 1 to 21, or a pharmaceutically acceptable salt and / or detectably labelled derivative thereof, comprising the step of:(i) for compounds wherein L represents -N(R2)C(O)(CH2)wi-, -N(R2)S(O)qi(CH2)W2- , reaction of a compound of formula IIwherein X, m, w, R2, R3, R4, Y, and n are as defined in any one of Claims 1 to 21, with a compound of formula III or IVZC— (CH2)W1-R1LG (in) or LG-S(O)qi- (CH2)W2-R1(IV)wherein R1, ql, wl and w2 are as defined in any one of Claims 1 to 21, and LG is a suitable leaving group as known to those skilled in the art.; or(ii) for compounds wherein L represents -N(R2)C(O)(CH2)wi- or -N(R2)S(O)qi(CH2)W2-, reacting a compound of formula (V)wherein R3, R4, X, Y, m, n are as defined in any one of Claims 1 to 21, W is a suitable group which is reactive in a metal-catalysed cross-coupling reaction (e.g. W may be halo, triflate, diazonium, etc.), with a compound of formula (VI) or (VII)wherein R1, R2, wl and w2 are as defined in any one of Claims 1 to 21, in the presence of a suitable metal (e.g. -Pd, Ni, Cu, Ru, Mg, etc) and a suitable ligand; or(iii) for compounds wherein L represents -C(O)N(R2)(CH2)w3-, reacting a compound of formula (V)wherein R3, R4, X, Y, m, n are as defined in any one of Claims 1 to 21, W is a suitable group which is reactive in a metal-catalysed cross-coupling reaction (e.g. W may be halo, triflate, diazonium, etc.), in the presence of a formic anhydride (such as acetic formic anhydride), a suitable metal (e.g. -Pd, Ni, Cu, Ru, Mg, etc), a suitable ligand, and optionally in the presence of carbon monoxide, to form a compound of formula (VIII)wherein X, Y, m, n, R3and R4are as defined in any one of Claims 1 to 21; or(iv) for compounds wherein L represents -C(O)N(R2)(CH2)w3-, reacting a compound of formula (VIII)(VIII), wherein X, Y, m, n, R3and R4are as defined in any one of Claims 1 to 21, with a compound of formula (IX) to form a compound of formula (I)HN— (CH2)W3— R1R2(IX) wherein R1, R2and w3 are as defined in any one of Claims 1 to 21; or(v) for compounds wherein L represents -C(O)N(R2)(CH2)w3-, reacting a compound of formula (V), in the presence of a suitable metal (e.g. -Pd, Ni, Cu, Ru, Mg, etc), a suitable ligand, and in the presence of carbon monoxide, followed by a reaction with a compound of formula (IX), wherein the compounds of formula (V) and (IX) are as defined in steps (iii) and (iv).

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