Chlorophyll protein analogs suitable for use in photodynamic therapy (PDT)

Abstract

The present invention relates to chlorophyll protein analogs and pharmaceutically acceptable salts thereof, and to compositions comprising chlorophyll protein analogs and pharmaceutically acceptable salts thereof. The chlorophyll protein analogs and pharmaceutically acceptable salts thereof are suitable for use in photodynamic therapy, cytoluminescence therapy and photodynamic diagnostics, for example for the treatment or detection of tumors or for antiviral therapy. The invention also relates to the use of the chlorophyll protein analogs and pharmaceutically acceptable salts thereof in the manufacture of phototherapeutic or photodiagnostic agents, and to methods of photodynamic therapy, cytoluminescence therapy or photodynamic diagnosis, for example for the treatment or detection of tumors or for antiviral therapy. # imgabs0 #

Description

Technical Field

[0001] The present invention relates to phyllochlorin analogs and pharmaceutically acceptable salts thereof, and to compositions comprising the phyllochlorin analogs and pharmaceutically acceptable salts thereof. The phyllochlorin analogs and pharmaceutically acceptable salts thereof are suitable for use in photodynamic therapy, cellular luminescence therapy and photodynamic diagnosis, for example for treating or detecting tumors or for antiviral therapy. The present invention also relates to the use of the phyllochlorin analogs and pharmaceutically acceptable salts thereof in the manufacture of a light therapeutic agent or a light diagnostic agent, and to methods of photodynamic therapy, cellular luminescence therapy or photodynamic diagnosis, for example for treating or detecting tumors or for antiviral therapy.

[0002] The structure of "phyllochlorin" is shown below:

[0003] Background Art

[0004] Porphyrins and their analogs are known photosensitive chemical compounds that can absorb visible photons and emit them at higher wavelengths. Such unique properties have many applications, and PDT (photodynamic therapy) is one of them.

[0005] Currently, there are two generations of photosensitizers for PDT. The first generation includes hematoporphyrin (blood derivatives), and the second generation is mainly chlorophyll analogs. The later compounds are called chlorins and bacteriochlorins.

[0006] Chlorin e4 has been shown to exhibit good photosensitizing activity. It has been pointed out that chlorin e4 has a protective effect against indomethacin-induced gastric injury in rats and TAA- or CCl4-induced acute liver injury in mice. Therefore, it has been proposed that chlorin e4 may be a promising new drug candidate for anti-gastric ulcer and liver injury protection. WO 2009 / 040411 proposes the use of a zinc complex of chlorin e4 in photodynamic therapy, and WO 2014 / 091241 proposes the use of disodium chlorin e4 in photodynamic therapy.

[0007]

[0008] However, there is a continuing need for better photosensitizers. Compounds with a high singlet oxygen quantum yield and strong photosensitizing ability in organic and aqueous media are needed. Compounds with a high fluorescence quantum yield are also needed. In addition, compounds and / or compositions with higher phototoxicity, lower dark toxicity, good stability, good solubility and / or easy purification are needed. Summary of the Invention

[0009] A first aspect of the present invention provides a compound of formula (I) or a complex of formula (II):

[0010]

[0011] or a pharmaceutically acceptable salt thereof, wherein:

[0012] -R 1 is selected from -CH2OR 2 、-CH2SR 2 、-CH2S(O)R 2 、-CH2S(O)2R 2 、-CH2N(R 2 )2 or -R 2x ;

[0013] -R 2 is independently selected from -H, -C(O)R 4 、-C(O)-OR 4 、-C(O)-SR 4 、-C(O)-N(R 4 )2、-C(S)-OR 4 、-C(S)-SR 4 、-C(S)-N(R 4 )2、-R α -H、-R β 、-R α -R β 、-R α -OH、-R α -OR β 、-R α -SH、-R α -SR β 、-R α -S(O)R β 、-R α -S(O)2R β 、-R α -NH2、-R α -NH(R β )、-R α -N(R β )2、-R α -N3、-R α -X、-R α -[N(R 5 )3]Y、-R α -[P(R 5 )3]Y、-R α -[R 6 Y、-R α -[N(R 5 )2(R 5’ )]、-R α-[P(R 5 )2(R 5’ )] or -R α -[R 6’ ;

[0014] -R 2x is independently selected from -H, -R α -H, -R α -R β , -R α -OH, -R α -OR β , -R α -SH, -R α -SR β , -R α -S(O)R β , -R α -S(O)2R β , -R α -NH2, -R α -NH(R β )), -R α -N(R β )2, -R α -N3, -R α -X, -R α -[N(R 5 )3]Y, -R α -[P(R 5 )3]Y, -R α -[R 6 , -R α -[N(R 5 )2(R 5’ )], -R α -[P(R 5 )2(R 5’ )] or -R α -[R 6’ ;

[0015] -R 4 are each independently selected from -H, -R α -H, -R β , -R α -R β , -R α -OH, -R α -OR β , -R α -SH, -R α -SR β , -R α -S(O)R β , -R α -S(O)2R β, -R α -NH2, -R α -NH(R β ), -R α -N(R β )2, -R α -X, -R α -[N(R 5 )3]Y, -R α -[P(R 5 )3]Y, -R α -[R 6 Y, -R α -[N(R 5 )2(R 5’ )], -R α -[P(R 5 )2(R 5’ )] or -R α -[R 6’ ;

[0016] -R α - Each independently selected from C1-C 42 alkylene, wherein the alkylene may optionally be substituted by one or more (such as one, two, three, four or five) C1-C4 alkyl, C1-C4 haloalkyl or halogen groups, and wherein one or more (such as one, two, three, four, five, six, seven, eight, nine or ten) carbon atoms in the main chain of the alkylene may optionally be replaced by heteroatoms or groups independently selected from O, S, NH or NMe;

[0017] -R β Each independently is a saturated or unsaturated hydrocarbon group, wherein the hydrocarbon group may be straight-chain or branched, or may be or include a cyclic group, wherein the hydrocarbon group may optionally be substituted, and wherein the hydrocarbon group may optionally include one or more (such as one, two, three, four or five) heteroatoms N, O, S, P or Se in its carbon skeleton;

[0018] -R 5 Each independently selected from C1-C4 alkyl, C1-C4 haloalkyl, -(CH2CH2O) n -H, -(CH2CH2O) n -CH3, phenyl or C5-C6 heteroaryl, wherein the phenyl or C5-C6 heteroaryl may optionally be substituted by one or more (such as one, two, three, four or five) C1-C6 alkyl, C1-C6 haloalkyl, -O(C1-C6 alkyl), -O(C1-C6 haloalkyl), halogen, -CO2H, -CO2Z, -CO2NH2, -O-(CH2CH2O) n-H or -O-(CH2CH2O) n substituted by a -CH3 group;

[0019] -R 5’ selected from C1-C4 alkyl, C1-C4 haloalkyl, -(CH2CH2O) n -H, -(CH2CH2O) n -CH3, phenyl or C5-C6 heteroaryl, each of which is substituted by -CO2 - wherein the phenyl or C5-C6 heteroaryl may optionally be further substituted by one or more (such as one, two, three or four) C1-C6 alkyl, C1-C6 haloalkyl, -O(C1-C6 alkyl), -O(C1-C6 haloalkyl), halogen, -CO2H, -CO2Z, -CO2NH2, -O-(CH2CH2O) n -H or -O-(CH2CH2O) n substituted by a -CH3 group;

[0020] -R 6 is optionally substituted by one or more (such as one, two, three, four or five) C1-C6 alkyl, C1-C6 haloalkyl, -O(C1-C6 alkyl), -O(C1-C6 haloalkyl), halogen, -CO2H, -CO2Z, -CO2NH2, -O-(CH2CH2O) n -H or -O-(CH2CH2O) n -[NC5H5] substituted by a -CH3 group;

[0021] -R 6’ is -[NC5H5], which is substituted by -CO2 - and optionally further substituted by one or more (such as one, two, three or four) C1-C6 alkyl, C1-C6 haloalkyl, -O(C1-C6 alkyl), -O(C1-C6 haloalkyl), halogen, -CO2H, -CO2Z, -CO2NH2, -O-(CH2CH2O) n -H or -O-(CH2CH2O) n substituted by a -CH3 group;

[0022] n is 1, 2, 3, 4, 5 or 6;

[0023] X is halogen;

[0024] Y is a counteranion;

[0025] Z is a countercation; and

[0026] M 2+ is a metal cation.

[0027] A second aspect of the present invention provides a compound of formula (I) or a complex of formula (II) according to the first aspect of the present invention, said compound or complex being for use in medicine.

[0028] In the context of the present specification, a "hydrocarbyl" substituent or the hydrocarbyl moiety in a substituent includes only carbon and hydrogen atoms, but does not include any heteroatoms such as N, O, S, P or Se in its carbon skeleton, unless otherwise stated. The hydrocarbyl group / moiety may be saturated or unsaturated (including aromatic), and may be straight-chain or branched, or may be or include a cyclic group, where the cyclic group does not include any heteroatoms such as N, O, S, P or Se in its carbon skeleton, unless otherwise stated. Examples of hydrocarbyl include alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl and aryl groups / moieties and combinations of all of these groups / moieties. Generally, hydrocarbyl is C1-C 60 hydrocarbyl, more usually C1-C 40 hydrocarbyl, more usually C1-C 20 hydrocarbyl. More usually, hydrocarbyl is C1-C 12 hydrocarbyl. More usually, hydrocarbyl is C1-C 10 hydrocarbyl. "Hydrocarbylene" is defined in a similar manner as a divalent hydrocarbyl.

[0029] An "alkyl" substituent or the alkyl moiety in a substituent may be linear (i.e., straight-chained) or branched. Examples of alkyl groups / moieties include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl and n-pentyl groups / moieties. Unless otherwise stated, the term "alkyl" does not include "cycloalkyl". Generally, alkyl is C1-C 12 alkyl. More usually, alkyl is C1-C6 alkyl. "Alkylene" is defined in a similar manner as a divalent alkyl. Generally, alkylene is C1-C 42 alkylene. More usually, alkylene is C1-C 32 alkylene, or C1-C 22 alkylene, or C1-C 12 alkylene.

[0030] An "alkenyl" substituent or the alkenyl moiety in a substituent refers to an unsaturated alkyl group or moiety having one or more carbon-carbon double bonds. Examples of alkenyl groups / moieties include vinyl, propenyl, 1-butenyl, 2-butenyl, 1-pentenyl, 1-hexenyl, 1,3-butadienyl, 1,3-pentadienyl, 1,4-pentadienyl and 1,4-hexadienyl groups / moieties. Unless otherwise stated, the term "alkenyl" does not include "cycloalkenyl". Generally, alkenyl is C2-C 12Alkenyl. More typically, alkenyl is C2-C6 alkenyl. "Alkenylene" is defined in a similar manner as a divalent alkenyl.

[0031] An "alkynyl" substituent or an alkynyl moiety in a substituent refers to an unsaturated alkyl group or moiety having one or more carbon-carbon triple bonds. Examples of alkynyl groups / moieties include ethynyl, propargyl, but-1-ynyl, and but-2-ynyl. Typically, alkynyl is C2-C 12 Alkynyl. More typically, alkynyl is C2-C6 alkynyl. "Alkynylene" is defined in a similar manner as a divalent alkynyl.

[0032] A "cyclic" substituent or a cyclic moiety in a substituent refers to any hydrocarbon ring, where the hydrocarbon ring can be saturated or unsaturated (including aromatic), and may include one or more heteroatoms, such as N, O, S, P, or Se, in its carbon skeleton. Examples of cyclic groups include cycloalkyl, cycloalkenyl, heterocycle, aryl, and heteroaryl as discussed below. The cyclic group can be monocyclic, bicyclic (e.g., bridged, fused, or spiro), or polycyclic. Typically, the cyclic group is a 3- to 12-membered cyclic group, meaning it contains 3 to 12 ring atoms. More typically, the cyclic group is a 3- to 7-membered monocyclic group, meaning it contains 3 to 7 ring atoms.

[0033] A "heterocycle" substituent or a heterocyclic moiety in a substituent refers to a cyclic group or moiety that includes one or more carbon atoms and one or more (such as one, two, three, or four) heteroatoms (e.g., N, O, S, P, or Se) in the ring structure. Examples of heterocyclic groups include heteroaryl and non-aromatic heterocyclic groups as discussed below, such as azetidinyl, azetinyl, tetrahydrofuranyl, pyrrolidinyl, tetrahydrothiophenyl, tetrahydropyranyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, oxetanyl, thietanyl, pyrazolidinyl, imidazolidinyl, dioxolanyl, oxathiolanyl, thianyl, and dioxanyl.

[0034] A "cycloalkyl" substituent or a cycloalkyl moiety in a substituent refers to a saturated hydrocarbon ring containing (for example) 3 to 7 carbon atoms, and examples thereof include cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. Unless otherwise specified, the cycloalkyl substituent or moiety may include a monocyclic, bicyclic, or polycyclic hydrocarbon ring.

[0035] A "cycloalkenyl" substituent or a cycloalkenyl moiety in a substituent refers to a non-aromatic unsaturated hydrocarbon ring having one or more carbon-carbon double bonds and containing (for example) 3 to 7 carbon atoms, and examples thereof include cyclopent-1-en-1-yl, cyclohex-1-en-1-yl, and cyclohex-1,3-dien-1-yl. Unless otherwise specified, the cycloalkenyl substituent or moiety may include a monocyclic, bicyclic, or polycyclic hydrocarbon ring.

[0036] An "aryl" substituent or the aryl moiety in a substituent refers to an aromatic hydrocarbon radical ring. The term "aryl" includes monocyclic aromatic hydrocarbons and polycyclic fused-ring aromatic hydrocarbons, wherein all fused-ring systems (excluding any ring systems that are part of an optional substituent or formed by an optional substituent) are aromatic. Examples of aryl groups / moieties include phenyl, naphthyl, anthracenyl, and phenanthryl. Unless otherwise specified, the term "aryl" does not include "heteroaryl".

[0037] A "heteroaryl" substituent or the heteroaryl moiety in a substituent refers to an aromatic heterocyclic group or moiety. The term "heteroaryl" includes monocyclic aromatic heterocycles and polycyclic fused-ring aromatic heterocycles, wherein all fused-ring systems (excluding any ring systems that are part of an optional substituent or formed by an optional substituent) are aromatic. Examples of heteroaryl groups / moieties include the following:

[0038]

[0039] wherein G = O, S, or NH.

[0040] For the purposes of this specification, when a combination of multiple moieties is referred to as a group, such as arylalkyl, arylalkenyl, arylalkynyl, alkylaryl, alkenylaryl, or alkynylaryl, the last-mentioned moiety contains the atom through which the group is attached to the remainder of the molecule. An example of arylalkyl is benzyl.

[0041] For the purposes of this specification, in an optionally substituted group or moiety (such as -R β ):

[0042] (i) Each hydrogen atom may optionally be independently replaced by a monovalent substituent selected from the following: halo; -CN; -NO2; -N3; -R x ; -OH; -OR x ; -R y -halo; -R y -CN; -R y -NO2; -R y -N3; -R y -R x ; -R y -OH; -R y -OR x ; -SH; -SR x ; -SOR x ; -SO2H; -SO2R x ; -SO2NH2; -SO2NHR x ; -SO2N(R x )2; -R y -SH; -R y -SR x ; -Ry -SOR x ; -R y -SO2H; -R y -SO2R x ; -R y -SO2NH2; -R y -SO2NHR x ; -R y -SO2N(R x )2; -NH2; -NHR x ; -N(R x )2; -N + (R x )3; -R y -NH2; -R y -NHR x ; -R y -N(R x )2; -R y -N + (R x )3; -CHO; -COR x ; -COOH; -COOR x ; -OCOR x ; -R y -CHO; -R y -COR x ; -R y -COOH; -R y -COOR x ; or -R y -OCOR x ; and / or

[0043] (ii) Any two hydrogen atoms attached to the same carbon atom may optionally be independently substituted by a π-bonded substituent selected from oxo group (=O), =S, =NH or =NR x ; and / or

[0044] (iii) Any two hydrogen atoms attached to the same or different atoms within the same optionally substituted group or moiety may optionally be independently substituted by a bridging substituent selected from -O-, -S-, -NH-, -N(R x )-, -N + (R x )2- or -R y -;

[0045] wherein each -R y- independently selected from alkylene, alkenylene or alkynylene, wherein said alkylene, alkenylene or alkynylene contains 1 to 6 atoms in its main chain, wherein one or more carbon atoms in the main chain of said alkylene, alkenylene or alkynylene may optionally be replaced by one or more heteroatoms N, O or S, and wherein said alkylene, alkenylene or alkynylene may optionally be substituted by one or more halogen groups and / or -R x groups; and

[0046] wherein each -R x is independently selected from C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl or C2-C6 cyclic group, or any two or three -R x connected to the same nitrogen atom may together with the nitrogen atom to which they are attached form a C2-C7 cyclic group, and any -R x may optionally be substituted by one or more C1-C4 alkyl, C1-C4 haloalkyl, -O(C1-C4 alkyl), -O(C1-C4 haloalkyl), halogen group, -OH, -NH2, -CN or oxo group (=O) groups.

[0047] Generally, the substituted group contains 1, 2, 3 or 4 substituents, more usually 1, 2 or 3 substituents, more usually 1 or 2 substituents, and more usually 1 substituent.

[0048] Unless otherwise specified, any divalent bridging substituent of an optionally substituted group or moiety (e.g., -O-, -S-, -NH-, -N(R x )-, -N + (R x )2- or -R y ) must be connected only to the specified group or moiety and may not be connected to a second group or moiety, even if the second group or moiety itself may optionally be substituted.

[0049] The term "halogen group" includes fluorine, chlorine, bromine and iodine.

[0050] Unless otherwise specified, when a group is prefixed with the term "halogen group", such as haloalkyl or halomethyl, it should be understood that the group in question is substituted by one or more halogen groups independently selected from fluorine, chlorine, bromine and iodine. Generally, the maximum number of halogen substituents is limited only by the number of hydrogen atoms available for substitution on the corresponding group without the halogen prefix. For example, halomethyl may contain one, two or three halogen substituents. Haloethyl or halophenyl may contain one, two, three, four or five halogen substituents. Similarly, unless otherwise specified, when a group is prefixed with a specific halogen group, it should be understood that the group in question is substituted by one or more specific halogen groups. For example, the term "fluoromethyl" refers to a methyl group substituted by one, two or three fluorine groups.

[0051] Unless otherwise indicated, when a group is referred to as "halogen-substituted", it is to be understood that the group in question is substituted with one or more halogen atoms independently selected from fluorine, chlorine, bromine, and iodine. Generally, the maximum number of halogen substituents is limited only by the number of hydrogen atoms available for substitution on the group being referred to as halogen-substituted. For example, halogen-substituted methyl may contain one, two, or three halogen substituents. Halogen-substituted ethyl or halogen-substituted phenyl may contain one, two, three, four, or five halogen substituents.

[0052] Unless otherwise indicated, any reference to an element is to be considered a reference to all isotopes of said element. Thus, for example, unless otherwise indicated, any reference to hydrogen is to be considered to encompass all isotopes of hydrogen, including deuterium and tritium.

[0053] Unless otherwise indicated, any reference to a compound or group is to be considered a reference to all tautomers of said compound or group.

[0054] When referring to a hydrocarbyl group or other group that contains one or more heteroatoms N, O, S, P, or Se in its carbon skeleton, or when referring to a hydrocarbyl group or other group in which a carbon atom is replaced by an N, O, S, P, or Se atom, it is intended that:

[0055] is replaced by replaced;

[0056] -CH2- is replaced by -NH-, -PH-, -O-, -S-, or -Se-;

[0057] -CH3 is replaced by -NH2, -PH2, -OH, -SH, or -SeH;

[0058] -CH= is replaced by -N= or -P=;

[0059] CH2= is replaced by NH=, PH=, O=, S=, or Se=; or

[0060] CH≡ is replaced by N≡ or P≡;

[0061] provided that the resulting group contains at least one carbon atom. For example, methoxy, dimethylamino, and aminoethyl are considered to be hydrocarbyl groups that contain one or more heteroatoms N, O, S, P, or Se in their carbon skeletons.

[0062] In the context of this specification, unless otherwise indicated, C x -C yA group is defined as a group containing from x to y carbon atoms. For example, a C1-C4 alkyl group is defined as an alkyl group containing from 1 to 4 carbon atoms. When calculating the total number of carbon atoms in a parent group that is optionally substituted and / or contains optional moieties, the optional substituents and moieties are not taken into account. To avoid doubt, when calculating the number of carbon atoms in a C x -C y group, heteroatoms that replace (such as N, O, S, P or Se) are not counted as carbon atoms. For example, a morpholinyl group is considered a C6 heterocyclic group rather than a C4 heterocyclic group.

[0063] The π electrons of the chlorin ring are delocalized and thus the chlorin ring can be depicted by more than one resonance structure. Resonance structures are different ways of drawing the same compound. Two resonance structures of the chlorin ring are depicted directly below:

[0064]

[0065] Generally, a complex contains a central metal atom or ion called a coordination center and binding molecules or ions called ligands. In this specification, the bond between the coordination center and the ligand is depicted as shown in the complex in the lower left (where the attraction between the anionic ligand and the central metal cation is represented by four dashed lines), but equivalently it can be depicted as shown in the complex in the lower right (where the attraction between the ligand molecule and the central metal atom is represented by two covalent bonds and two dashed lines):

[0066]

[0067] As used herein, -[NC5H5]Y refers to:

[0068]

[0069] In one embodiment of the first or second aspect of the present invention, X is a halogen group selected from fluorine, chlorine, bromine or iodine. In one embodiment, X is chlorine or bromine.

[0070] In one embodiment of the first or second aspect of the present invention, a compound of formula (I) is provided.

[0071] In one embodiment of the first or second aspect of the present invention, Y is a counteranion selected from the following: halides (e.g., fluoride, chloride, bromide or iodide) or other inorganic anions (e.g., bisulfate, hexafluorophosphate (PF6), nitrate, perchlorate, phosphate or sulfate) or organic anions (e.g., acetate, ascorbate, aspartate, benzoate, benzenesulfonate (besylate), bicarbonate, bis(trifluoromethanesulfonyl)imide (TFSI), bitartrate, butyrate, camphorsulfonate (camsylate), carbonate, citrate, caprate, edetate, ethanesulfonate, fumarate, galactonate, glucoheptonate, gluconate, glutamate, glycolate, caproate, β-hydroxybutyrate, 2-hydroxyethanesulfonate, hydroxymaleate, hydroxynaphthoate, hydroxyethylsulfonate, lactate, lactobionate, malate, maleate, mandelate, methanesulfonate, methyl sulfate, mucate, naphthalenesulfonate (naphthalene-2-sulfonate), caprylate, oleate, ornithine, pamoate, pantothenate, polygalacturonate, propionate, propionate, salicylate, stearate, succinate, tartrate, teoclate, tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (BARF), tetrakis(pentafluorophenyl)borate (F5-TPB), tetraphenylborate (TPB), tosylate (p-toluenesulfonate) or trifluoromethanesulfonate).

[0072] In another embodiment of the first or second aspect of the present invention, Y is a counteranion selected from the group consisting of halides (such as fluoride, chloride, bromide or iodide) or other inorganic anions (such as hydrogensulfate, nitrate, perchlorate, phosphate or sulfate) or organic anions (such as acetate, aspartate, benzoate, besylate (benzenesulfonate), butyrate, camsylate (camphorsulfonate), citrate, ethanesulfonate, fumarate, galactonate, gluconate, glutamate, glycolate, 2-hydroxyethanesulfonate, hydroxymaleate, lactate, malate, maleate, mandelate, methanesulfonate, naphthalenesulfonate (naphthalene-2-sulfonate), ornithinate, pamoate, pantothenate, propionate, salicylate, succinate, tartrate, tosylate (p-toluenesulfonate) or trifluoromethanesulfonate). In one embodiment, Y is fluoride, chloride, bromide or iodide. In one embodiment, Y is chloride or bromide.

[0073] In one embodiment of the first or second aspect of the present invention, Z is a countercation selected from inorganic cations (such as lithium, sodium, potassium, magnesium, calcium or ammonium cations) or organic cations (such as amine cations (such as choline or glucosamine cations) or amino acid cations (such as arginine cations)).

[0074] In one embodiment of the first or second aspect of the present invention, M 2+ is a metal cation selected from Zn 2+ , Cu 2+ , Fe 2+ , Pd 2+ or Pt 2+ . In one embodiment, M 2+ is Zn 2+ .

[0075] -R 1 is selected from -CH2OR 2 , -CH2SR 2 , -CH2S(O)R 2 , -CH2S(O)2R 2 , -CH2N(R 2 )2 or -R 2x . In one embodiment, -R 1 is selected from -CH2OR 2 , -CH2SR 2 , -CH2N(R 2 )2 or -R 2xIn one embodiment, -R 1 Selected from -CH2OR 2 、-CH2SR 2 or -CH2N(R 2 )2. In one embodiment, -R 1 Selected from -CH2OR 2 or -CH2SR 2 In one embodiment, -R 1 Yes-CH2OR 2 In one embodiment, -R 1 Yes-R 2x , and -R 2x Yes-R α -X.

[0076] In one embodiment of the first or second aspect of the present invention, -R 2 or -R 2x Selected from -H, -R α -H, -R α -R β , -R α -OH, -R α -OR β , -R α -SH, -R α -SR β , -R α -S(O)R β , -R α -S(O)2R β , -R α -NH2, -R α -NH(R β ),-R α -N(R β )2. -R α -X, -R α -[N(R 5 )3]Y, -R α -[P(R 5 )3]Y, -R α -[R 6 ]Y, -R α -[N(R 5 )2(R 5’ )]、-R α -[P(R 5 )2(R 5’ )] or -R α -[R 6’ In one embodiment, -R 2 or -R 2x Selected from -R α-H, -R α -R β , -R α -OH, -R α -OR β , -R α -SH, -R α -SR β , -R α -S(O)R β , -R α -S(O)2R β , -R α -NH2, -R α -NH(R β ), -R α -N(R β )2, -R α -X, -R α -[N(R 5 )3]Y, -R α -[P(R 5 )3]Y or -R α -[NC5H5]Y. In one embodiment, -R 2 or -R 2x is selected from -R α -OR β , -R α -SR β , -R α -S(O)R β or -R α -S(O)2R β . In one embodiment, -R 2 or -R 2x is selected from -R α -OR β , -R α -SR β , -R α -S(O)R β or -R α -S(O)2R β , and -R β is a glycosyl group. In one embodiment, -R 2 or -R 2x is selected from -R α -OR β or -R α -SR β . In one embodiment, -R 2 or -R 2x is selected from -R α -OR β or -R α -SR β, and -R β is a glycosyl group.

[0077] In one embodiment of the first or second aspect of the present invention, -R 2 is selected from -C(O)R 4 , -C(O)-OR 4 , -C(O)-SR 4 , -C(O)-N(R 4 )2, -C(S)-OR 4 , -C(S)-SR 4 or -C(S)-N(R 4 )2. In one embodiment, -R 2 is selected from -C(O)R 4 , -C(O)-OR 4 , -C(O)-SR 4 , -C(O)-N(R 4 )2 or -C(S)-N(R 4 )2. In one embodiment, -R 2 is selected from -C(O)R 4 , -C(O)-OR 4 , -C(O)-SR 4 or -C(O)-N(R 4 )2.

[0078] In one embodiment of the first or second aspect of the present invention, -R 2 is -C(O)-N(R 4 )(R 4’ ), where -R 4 is selected from -R α -OR β , -R α -SR β , -R α -S(O)R β or -R α -S(O)2R β , and -R β is a glycosyl group, and -R 4’ is H or C1-C4 alkyl (preferably methyl). In one embodiment, -R 2 is -C(O)-N(R 4 )(R 4’ ), where -R 4 is selected from -R α -OR β or -R α -SR β , and -R β is a glycosyl group, and -R 4’is H or a C1-C4 alkyl group (preferably methyl).

[0079] -R 4' The group means an -R 4 group that is attached to the same atom as another -R 4 group. -R 4 and -R 4’ can be the same or different. Preferably, -R 4 and -R 4’ are different.

[0080] In one embodiment of the first or second aspect of the present invention, -R 2 is -C(O)-N(R 4 )2. In one embodiment, -R 2 is -C(O)-N(C1-C4 alkyl)(R 4 ). In one embodiment, -R 2 is -C(O)-N(CH3)(R 4 ).

[0081] In one embodiment of the first or second aspect of the present invention, each -R α - independently is a C1-C 12 alkylene group, a -(CH2CH2O) m - group, a -(CH2CH2S) m - group, a -(CH2CH2O) m -CH2CH2- group or a -(CH2CH2S) m -CH2CH2- group, all optionally substituted, where m is 1, 2, 3 or 4. In one embodiment, each -R α - independently is a C1-C 12 alkylene group, a -(CH2CH2O) m - group or a -(CH2CH2S) m - group, all optionally substituted, where m is 1, 2, 3 or 4. In one embodiment, each -R α - independently is a C1-C 12 alkylene group or a -(CH2CH2O) m - group, both optionally substituted, where m is 1, 2, 3 or 4. In one embodiment, each -R α - independently is an optionally substituted -(CH2CH2O) m - group, where m is 1, 2, 3 or 4.

[0082] In one embodiment of the first or second aspect of the present invention, each -R α- Independently a C1-C8 alkylene group, or a C1-C6 alkylene group, or a C2-C4 alkylene group, all optionally substituted.

[0083] In one embodiment of the first or second aspect of the present invention, each -R α - Independently unsubstituted or substituted by one or more substituents independently selected from halo, C1-C4 alkyl, or C1-C4 haloalkyl. In one embodiment, each -R α - Independently unsubstituted or substituted by one or two substituents independently selected from halo, C1-C4 alkyl, or C1-C4 haloalkyl. In one embodiment, each -R α - Unsubstituted.

[0084] In one embodiment of the first or second aspect of the present invention, each -R β Independently a saturated or unsaturated hydrocarbon group, wherein the hydrocarbon group may be straight-chain or branched, or may be or include a cyclic group, wherein the hydrocarbon group is optionally substituted, and wherein the hydrocarbon group may optionally include one or more heteroatoms N, O, or S in its carbon skeleton.

[0085] In one embodiment of the first or second aspect of the present invention, at least one -R β Independently a C1-C6 alkyl group, or a C1-C4 alkyl group, or methyl, all optionally substituted. In one embodiment, each -R β Independently a C1-C6 alkyl group, or a C1-C4 alkyl group, or methyl, all optionally substituted.

[0086] In one embodiment of the first or second aspect of the present invention, at least one -R β Independently a glycosyl group. In one embodiment, each -R β Independently a glycosyl group.

[0087] In one embodiment of the first or second aspect of the present invention, each -R β Independently unsubstituted or substituted by one or more substituents independently selected from halo, C1-C4 alkyl, or C1-C4 haloalkyl. In one embodiment, each -R β Independently unsubstituted or substituted by one or two substituents independently selected from halo, C1-C4 alkyl, or C1-C4 haloalkyl. In one embodiment, each -R β Unsubstituted.

[0088] In one embodiment of the first or second aspect of the present invention, each -R 4 Independently selected from -R α -H, -R β 、-Rα -R β 、 -R α -OH, -R α -OR β 、 -R α -SH, -R α -SR β 、 -R α -S(O)R β 、 -R α -S(O)₂R β 、 -R α -NH₂, -R α -NH(R β )、 -R α -N(R β )₂、 -R α -X, -R α -[N(R 5 )₃]Y、 -R α -[P(R 5 )₃]Y or -R α -[NC₅H₅]Y. In one embodiment, each -R 4 is independently selected from -R α -OR β 、 -R α -SR β 、 -R α -S(O)R β or -R α -S(O)₂R β 。 In one embodiment, each -R 4 is independently selected from -R α -OR β 、 -R α -SR β 、 -R α -S(O)R β or -R α -S(O)₂R β , and -R β is a glycosyl group. In one embodiment, each -R 4 is independently selected from -R α -OR β or -R α -SR β 。 In one embodiment, each -R 4 is independently selected from -R α -OR β or -R α -SR β , and -R β is a glycosyl group.

[0089] In one embodiment of the first or second aspect of the present invention, -R 2 、-R 2x or -R 4 at least one of which is independently selected from -R α -OR β 、-R α -SR β 、-R α -S(O)R β or -R α -S(O)2R β and -R β is a glycosyl group. In one embodiment, -R 2 、-R 2x or -R 4 at least one of which is independently selected from -R α -OR β or -R α -SR β and -R β is a glycosyl group.

[0090] For the purposes of the present invention, "glycosyl group" is any group containing at least one monosaccharide subunit, wherein each monosaccharide subunit may optionally be substituted and / or modified. Generally, a glycosyl group consists of one or more monosaccharide subunits, wherein each monosaccharide subunit may optionally be substituted and / or modified.

[0091] Generally, the carbon atom of a single monosaccharide subunit of each glycosyl group is directly (most commonly via a single bond) attached to the remainder of the compound.

[0092] For the purposes of this specification, where it is stated that a first atom or group is "directly attached" to a second atom or group, it is to be understood that the first atom or group is covalently bonded to the second atom or group with no intervening atom or group or groups. For example, for the group -(C=O)N(CH3)2, the carbon atom of each methyl group is directly attached to the nitrogen atom and the carbon atom of the carbonyl group is directly attached to the nitrogen atom, but the carbon atom of the carbonyl group is not directly attached to the carbon atom of either methyl group.

[0093] Generally, each glycosyl group is derived from the corresponding sugar by replacing the hydroxyl group of the sugar with a group defined by the remainder of the compound.

[0094] The single bond between the anomeric carbon of the monosaccharide subunit and the substituent is called a glycosidic bond. The glycosyl group is linked to the anomeric carbon of the monosaccharide subunit through the glycosidic bond. The bond between the saccharidyl group and the rest of the compound can be a glycosidic bond or a non-glycosidic bond. Usually, the bond between the saccharidyl group and the rest of the compound is a glycosidic bond, such that the saccharidyl group is a glycosyl group. When the bond between the saccharidyl group and the rest of the compound is a glycosidic bond, the glycosidic bond can be in the α or β configuration. Usually, such a glycosidic bond is in the β configuration.

[0095] For the purposes of the present invention, when a saccharidyl group "contains x monosaccharide subunits", this means that the saccharidyl group has only x monosaccharide subunits. In contrast, when a saccharidyl group "comprises x monosaccharide subunits", this means that the saccharidyl group has x or more monosaccharide subunits.

[0096] Each saccharidyl group can independently be selected from a monosaccharidyl group, a disaccharidyl group, an oligosaccharidyl group or a polysaccharidyl group. As will be understood, a monosaccharidyl group contains a single monosaccharide subunit. Similarly, a disaccharidyl group contains two monosaccharide subunits. As used herein, an "oligosaccharidyl group" contains from 2 to 9 monosaccharide subunits. Examples of oligosaccharidyl groups include trisaccharidyl groups, tetrasaccharidyl groups, pentasaccharidyl groups, hexasaccharidyl groups, heptasaccharidyl groups, octasaccharidyl groups and nonasaccharidyl groups. As used herein, a "polysaccharidyl group" contains 10 or more monosaccharide subunits (such as 10 - 50, or 10 - 30, or 10 - 20, or 10 - 15 monosaccharide subunits).

[0097] Each monosaccharide subunit within a disaccharidyl group, an oligosaccharidyl group or a polysaccharidyl group can be the same or different. Each monosaccharide subunit within a disaccharidyl group, an oligosaccharidyl group or a polysaccharidyl group can be linked to another monosaccharide subunit within the group via a glycosidic bond or a non-glycosidic bond. Usually, each monosaccharide subunit within a disaccharidyl group, an oligosaccharidyl group or a polysaccharidyl group is linked to another monosaccharide subunit within the group via a glycosidic bond, which can be in the α or β configuration.

[0098] Each oligosaccharidyl group or polysaccharidyl group can be a linear, branched or macrocyclic oligosaccharidyl group or polysaccharidyl group. Usually, each oligosaccharidyl group or polysaccharidyl group is a linear or branched oligosaccharidyl group or polysaccharidyl group.

[0099] In one embodiment, at least one -R β is a monosaccharidyl group or a disaccharidyl group.

[0100] In another embodiment, at least one -R β is a monosaccharidyl group. For example, at least one -R β can be a saccharidyl group containing a single monosaccharide subunit, wherein the monosaccharide subunit can be optionally substituted and / or modified. Usually, at least one -R β is a saccharidyl group containing a single monosaccharide subunit, wherein the monosaccharide subunit can be optionally substituted. More usually, at least one -R βis a glycosyl group containing a single monosaccharide subunit, wherein the monosaccharide subunit is unsubstituted.

[0101] In one embodiment, at least one -R β is an aldosyl group, wherein the aldosyl group may be optionally substituted and / or modified. For example, at least one -R β may be selected from glycerosyl, butyrosyl (such as erythrosyl or threosyl), pentosyl (such as ribosyl, arabinosyl, xylosyl or lyxosyl) or hexosyl (such as allosyl, altrosyl, glucosyl, mannosyl, gulcosyl, idosyl, galactosyl or talosyl), any of which may be optionally substituted and / or modified.

[0102] In another embodiment, at least one -R β is a ketosyl group, wherein the ketosyl group may be optionally substituted and / or modified. For example, at least one -R β may be selected from erythrosyl, pentulosyl (such as ribulosyl or xylulosyl) or hexulosyl (such as psicose, fructosyl, sorbosyl or tagatosyl), any of which may be optionally substituted and / or modified.

[0103] Each monosaccharide subunit may exist in a closed-loop (cyclic) or open-chain (acyclic) form. Generally, each monosaccharide subunit in at least one -R β exists in a closed-loop (cyclic) form. For example, at least one -R β may be a glycosyl group containing a single closed-loop monosaccharide subunit, wherein the monosaccharide subunit may be optionally substituted and / or modified. Generally in such cases, at least one -R β is a pyranosyl or furanosyl group, such as pyranaldosyl, furanaldosyl, pyranoketosyl or furanoketosyl, any of which may be optionally substituted and / or modified. More generally, at least one -R β is a pyranosyl group, such as pyranaldosyl or pyranoketosyl, any of which may be optionally substituted and / or modified.

[0104] In one embodiment, at least one -R β is selected from pyranribosyl, pyranarabinosyl, pyranxylosyl, pyranlyxosyl, allopyranosyl, pyranaltrosyl, pyranglucosyl, pyranmannosyl, pyrangulcosyl, pyranidosyl, pyrangalactosyl or pyrantalosyl, any of which may be optionally substituted and / or modified.

[0105] In another embodiment, at least one -R β is glucosyl, such as pyranglucosyl, wherein the glucosyl or pyranglucosyl may be optionally substituted and / or modified. Generally, at least one -R βis a glucosyl group, wherein the glucosyl group is optionally substituted. More typically, at least one -R β is an unsubstituted glucosyl group.

[0106] Each monosaccharide subunit may exist in the D- or L-configuration. Typically, each monosaccharide subunit exists in the configuration most common in nature.

[0107] In one embodiment, at least one -R β is a D-glucosyl group, such as D-glucopyranosyl, wherein the D-glucosyl group or D-glucopyranosyl may be optionally substituted and / or modified. Typically, at least one -R β is a D-glucosyl group, wherein the D-glucosyl group is optionally substituted. More typically, at least one -R β is an unsubstituted D-glucosyl group.

[0108] For the purposes of the present invention, in a substituted monosaccharide group or monosaccharide subunit:

[0109] (a) One or more hydroxyl groups of the monosaccharide group or monosaccharide subunit are each independently -H, -F, -Cl, -Br, -I, -CF3, -CCl3, -CBr3, -CI3, -SH, -NH2, -N3, -NH=NH2, -CN, -NO2, -COOH, -R b , -O-R b , -S-R b , -R a -O-R b , -R a -S-R b , -SO-R b , -SO2-R b , -SO2-OR b , -O-SO-R b , -O-SO2-R b , -O-SO2-OR b , -NR b -SO-R b , -NR b -SO2-R b , -NR b -SO2-OR b , -R a -SO-R b , -R a -SO2-R b , -R a -SO2-OR b , -SO-N(R b )2, -SO2-N(R b )2, -O-SO-N(Rb ) 2, -O-SO2-N(R b ) 2, -NR b -SO-N(R b ) 2, -NR b -SO2-N(R b ) 2, -R a -SO-N(R b ) 2, -R a -SO2-N(R b ) 2, -N(R b ) 2, -N(R b ) 3 + , -R a -N(R b ) 2, -R a -N(R b ) 3 + , -P(R b ) 2, -PO(R b ) 2, -OP(R b ) 2, -OPO(R b ) 2, -R a -P(R b ) 2, -R a -PO(R b ) 2, -OSi(R b ) 3, -R a -Si(R b ) 3, -CO-R b , -CO-OR b , -CO-N(R b ) 2, -O-CO-R b , -O-CO-OR b , -O-CO-N(R b ) 2, -NR b -CO-R b , -NR b -CO-OR b , -NR b -CO-N(R b ) 2, -R a -CO-R b , -R a -CO-OR b or -R a -CO-N(R b ) 2 substituted; and / or

[0110] (b) One, two, or three hydrogen atoms directly connected to the carbon atom of a monosaccharide or monosaccharide subunit are each independently selected from -F, -Cl, -Br, -I, -CF3, -CCl3, -CBr3, -CI3, -OH, -SH, -NH2, -N3, -NH=NH2, -CN, -NO2, -COOH, -R b , -O-R b , -S-R b , -R a -O-R b , -R a -S-R b , -SO-R b , -SO2-R b , -SO2-OR b , -O-SO-R b , -O-SO2-R b , -O-SO2-OR b , -NR b -SO-R b , -NR b -SO2-R b , -NR b -SO2-OR b , -R a -SO-R b , -R a -SO2-R b , -R a -SO2-OR b , -SO-N(R b )2, -SO2-N(R b )2, -O-SO-N(R b )2, -O-SO2-N(R b )2, -NR b -SO-N(R b )2, -NR b -SO2-N(R b )2, -R a -SO-N(R b )2, -R a -SO2-N(R b )2, -N(R b )2, -N(R b )3 + , -R a -N(R b )2, -R a -N(R b )3 + , -P(R b )2, -PO(R b)2, -OP(R b )2, -OPO(R b )2, -R a -P(R b )2, -R a -PO(R b )2, -OSi(R b )3, -R a -Si(R b )3, -CO-R b , -CO-OR b , -CO-N(R b )2, -O-CO-R b , -O-CO-OR b , -O-CO-N(R b )2, -NR b -CO-R b , -NR b -CO-OR b , -NR b -CO-N(R b )2, -R a -CO-R b , -R a -CO-OR b or -R a -CO-N(R b )2 substituted; and / or

[0111] (c) One or more hydroxyl groups of a monosaccharide or monosaccharide subunit, together with the hydrogen attached to the same carbon atom as the hydroxyl group, are each independently replaced by =O, =S, =NR b or =N(R b )2 + substituted; and / or

[0112] (d) Any two hydroxyl groups of a monosaccharide or monosaccharide subunit are together replaced by -O-R c -, -S-R c -, -SO-R c -, -SO2-R c -, or -NR b -R c -substituted;

[0113] Wherein:

[0114] Each -R a - is independently a substituted or unsubstituted alkylene, alkenylene or alkynylene group which optionally includes one or more heteroatoms each independently selected from O, N and S in its carbon skeleton and preferably contains 1-10 carbon atoms;

[0115] Each -Rb independently hydrogen, or a substituted or unsubstituted straight-chain, branched-chain or cyclic alkyl, alkenyl, alkynyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, alkylaryl, alkenylaryl or alkynylaryl, which optionally includes in its carbon skeleton one or more heteroatoms each independently selected from O, N and S and preferably contains 1-15 carbon atoms; and

[0116] each -R c - independently is a chemical bond, or a substituted or unsubstituted alkylene, alkenylene or alkynylene, which optionally includes in its carbon skeleton one or more heteroatoms each independently selected from O, N and S and preferably contains 1-10 carbon atoms;

[0117] provided that the monosaccharide group or monosaccharide subunit contains at least one, preferably at least two or at least three -OH, -O-R b , -O-SO-R b , -O-SO2-R b , -O-SO2-OR b , -O-SO-N(R b )2, -O-SO2-N(R b )2, -OP(R b )2, -OPO(R b )2, -OSi(R b )3, -O-CO-R b , -O-CO-OR b , -O-CO-N(R b )2 or -O-R c -.

[0118] Generally, in the substituted monosaccharide group or monosaccharide subunit:

[0119] (a) one or more hydroxyl groups of the monosaccharide group or monosaccharide subunit are each independently -H, -F, -CF3, -SH, -NH2, -N3, -CN, -NO2, -COOH, -R b , -O-R b , -S-R b , -N(R b )2, -OPO(R b )2, -OSi(R b )3, -O-CO-R b , -O-CO-OR b , -O-CO-N(R b )2, -NR b -CO-R b , -NR b -CO-OR b or -NR b-CO-N(R b )2 is replaced; and / or

[0120] (b) One or two hydrogen atoms directly connected to the carbon atom of the monosaccharide group or monosaccharide subunit are each independently replaced by -F, -CF3, -OH, -SH, -NH2, -N3, -CN, -NO2, -COOH, -R b , -O-R b , -S-R b , -N(R b )2, -OPO(R b )2, -OSi(R b )3, -O-CO-R b , -O-CO-OR b , -O-CO-N(R b )2, -NR b -CO-R b , -NR b -CO-OR b or -NR b -CO-N(R b )2 is replaced; and / or

[0121] (c) A hydroxyl group of the monosaccharide group or monosaccharide subunit, together with the hydrogen atom connected to the same carbon atom as the hydroxyl group, is replaced by =O; and / or

[0122] (d) Any two hydroxyl groups of the monosaccharide group or monosaccharide subunit are together replaced by -O-R c - or -NR b -R c -;

[0123] wherein:

[0124] Each -R b is independently hydrogen, or a substituted or unsubstituted straight-chain, branched-chain or cyclic alkyl, alkenyl, alkynyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, alkylaryl, alkenylaryl or alkynylaryl, which optionally includes one, two or three heteroatoms each independently selected from O and N in its carbon skeleton and contains 1-8 carbon atoms; and

[0125] Each -R c - is independently a substituted or unsubstituted alkylene, alkenylene or alkynylene, which optionally includes one, two or three heteroatoms each independently selected from O and N in its carbon skeleton and contains 1-8 carbon atoms;

[0126] Provided that the monosaccharide group or monosaccharide subunit contains at least two, preferably at least three -OH, -O-R b , -OPO(R b )2, -OSi(Rb ) 3, -O-CO-R b , -O-CO-OR b , -O-CO-N(R b )2 or -O-R c -.

[0127] In one embodiment, -R β is a glycosyl group and one or more hydroxyl groups of the glycosyl group are each independently replaced by -O-CO-R b , where each -R b is independently a C1-C4 alkyl group, preferably methyl. In one embodiment, -R β is a glycosyl group and all hydroxyl groups of the glycosyl group are each independently replaced by -O-CO-R b , where each -R b is independently a C1-C4 alkyl group, preferably methyl.

[0128] In the modified monosaccharide unit or monosaccharide subunit:

[0129] (a) The ring of the modified monosaccharide unit or monosaccharide subunit or the ring in the closed-loop form of the modified monosaccharide unit or monosaccharide subunit is partially unsaturated; and / or

[0130] (b) The epoxy group of the modified monosaccharide unit or monosaccharide subunit or the epoxy group in the closed-loop form of the modified monosaccharide unit or monosaccharide subunit is replaced by -S- or -NR d -, where -R d is independently hydrogen, or a substituted or unsubstituted straight-chain, branched-chain or cyclic alkyl, alkenyl, alkynyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, alkylaryl, alkenylaryl or alkynylaryl group, which optionally includes one or more heteroatoms each independently selected from O, N and S in its carbon skeleton and preferably contains 1-15 carbon atoms.

[0131] Alternatively, in the case where the modified monosaccharide subunit forms part of a disaccharide unit, oligosaccharide unit or polysaccharide unit, -R d can be one or more additional monosaccharide subunits that form part of the disaccharide unit, oligosaccharide unit or polysaccharide unit, where any such one or more additional monosaccharide subunits can be optionally replaced and / or modified.

[0132] Generally, in the modified monosaccharide unit or monosaccharide subunit:

[0133] (a) The ring of the modified monosaccharide unit or monosaccharide subunit or the ring in the closed-loop form of the modified monosaccharide unit or monosaccharide subunit contains a single C═C; and / or

[0134] (b) The epoxy group of the modified monosaccharide unit or monosaccharide subunit or the epoxy group in the closed-loop form of the modified monosaccharide unit or monosaccharide subunit is replaced by -NRd -Alternative, where -R d is independently hydrogen, or a substituted or unsubstituted straight-chain, branched-chain or cyclic alkyl, alkenyl, alkynyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, alkylaryl, alkenylaryl or alkynylaryl group, which optionally includes one, two or three heteroatoms each independently selected from O and N in its carbon skeleton and contains 1-8 carbon atoms.

[0135] Typical examples of substituted and / or modified monosaccharide subunits include those corresponding to the following:

[0136] (i) Deoxysugars such as deoxyribose, fucose, fucoidan and rhamnose, in which the hydroxyl group of the monosaccharide or monosaccharide subunit has been replaced by -H;

[0137] (ii) Amino sugars such as glucosamine and galactosamine, in which the hydroxyl group of the monosaccharide or monosaccharide subunit has been replaced by -NH2, most commonly at the 2-position; and

[0138] (iii) Sugar acids containing a -COOH group such as aldonic acids (e.g., gluconic acid), ketonic acids, uronic acids (e.g., glucuronic acid) and aldaric acids (e.g., gularic or galactaric acid).

[0139] In one embodiment of the first or second aspect of the present invention, at least one -R β is a monosaccharide group selected from the following:

[0140]

[0141] Preferably, in a compound or complex according to the first or second aspect of the present invention, at least one -R β is:

[0142]

[0143] In one embodiment of the first or second aspect of the present invention, -R 2 , -R 2x or -R 4 at least one of which is independently selected from -R α -OR β , -R α -SR β , -R α -S(O)R β or -R α -S(O)2R β (preferably selected from -R α -OR β or -R α -SR β ), and -R βSelected from:

[0144]

[0145]

[0146] In one embodiment of the first or second aspect of the present invention, -R 2 , -R 2x or -R 4 is independently selected from at least one of -R α -[N(R 5 )3]Y, -R α -[P(R 5 )3]Y, -R α -[R 6 Y, -R α -[N(R 5 )2(R 5’ )], -R α -[P(R 5 )2(R 5’ )] or -R α -[R 6’ . In one embodiment, -R 2 , -R 2x or -R 4 is independently selected from at least one of -R α -[N(R 5 )3]Y, -R α -[P(R 5 )3]Y or -R α -[R 6 Y. In one embodiment, -R 2 , -R 2x or -R 4 is independently selected from:

[0147]

[0148] In the first or second aspect of the present invention, each -R 5 may be the same or different. In a preferred embodiment, each -R 5 is the same.

[0149] In one embodiment of the first or second aspect of the present invention, each -R 5 is independently unsubstituted or substituted with one or two substituents. In one embodiment, each -R 5 is unsubstituted.

[0150] In one embodiment of the first or second aspect of the present invention, -R 6is unsubstituted or substituted with one or two substituents. In one embodiment, -R 6 is unsubstituted.

[0151] In one embodiment, -R 6 is not substituted with a halogen at the 4-position of the pyridine ring. In one embodiment, -R 6 is not substituted at the 4-position of the pyridine ring. In one embodiment, -R 6 is unsubstituted.

[0152] In one embodiment of the first or second aspect of the present invention, -R 1 comprises 1 to 100 atoms other than hydrogen, preferably 1 to 80 atoms other than hydrogen, preferably 1 to 60 atoms other than hydrogen, preferably 1 to 50 atoms other than hydrogen, and preferably 1 to 45 atoms other than hydrogen.

[0153] In a particularly preferred embodiment, the first or second aspect of the present invention provides a compound of formula (I) or a complex of formula (II):

[0154]

[0155] or a pharmaceutically acceptable salt thereof, wherein:

[0156] -R 1 is selected from -CH2OR 2 , -CH2SR 2 , -CH2S(O)R 2 , -CH2S(O)2R 2 , -CH2N(R 2 )(R 2’ ) or -R 2x [Preferably, -R 1 is -R 2x ;

[0157] -R 2 and -R 2x are selected from -[(CH2) p Q] r -(CH2) s -[N(R 5 )3]Y, -[(CH2) p Q] r -(CH2) s -[P(R 5 )3]Y, -[(CH2) p Q] r -(CH2) s -[R 6 Y, -[(CH2) p Q]r -(CH2) s -[N(R 5 )2(R 5’ )]、-[(CH2) p Q] r -(CH2) s -[P(R 5 )2(R 5’ )] or -[(CH2) p Q] r -(CH2) s -[R 6’ ;

[0158] -R 2’ is selected from hydrogen or C1-C6 alkyl [preferably, -R 2’ is selected from hydrogen or C1-C3 alkyl; more preferably, -R 2’ is selected from hydrogen or methyl];

[0159] -R 5 are each independently selected from C1-C4 alkyl, C1-C4 haloalkyl, -(CH2CH2O) n -H, -(CH2CH2O) n -CH3, phenyl or C5-C6 heteroaryl, wherein the phenyl or C5-C6 heteroaryl may optionally be substituted by one or more (such as one, two, three, four or five) C1-C6 alkyl, C1-C6 haloalkyl, -O(C1-C6 alkyl), -O(C1-C6 haloalkyl), halogen, -CO2H, -CO2Z, -CO2NH2, -O-(CH2CH2O) n -H or -O-(CH2CH2O) n -CH3 groups;

[0160] -R 5’ is selected from C1-C4 alkyl, C1-C4 haloalkyl, -(CH2CH2O) n -H, -(CH2CH2O) n -CH3, phenyl or C5-C6 heteroaryl, each of which is substituted by -CO2 - and wherein the phenyl or C5-C6 heteroaryl may optionally be further substituted by one or more (such as one, two, three or four) C1-C6 alkyl, C1-C6 haloalkyl, -O(C1-C6 alkyl), -O(C1-C6 haloalkyl), halogen, -CO2H, -CO2Z, -CO2NH2, -O-(CH2CH2O) n -H or -O-(CH2CH2O) n -CH3 groups;

[0161] -R6 is optionally substituted by one or more (such as one, two, three, four or five) C1-C6 alkyl, C1-C6 haloalkyl, -O(C1-C6 alkyl), -O(C1-C6 haloalkyl), halo, -CO2H, -CO2Z, -CO2NH2, -O-(CH2CH2O) n -H or -O-(CH2CH2O) n -CH3 group-substituted -[NC5H5];

[0162] -R 6’ is -[NC5H5], which is substituted by -CO2 - and is optionally further substituted by one or more (such as one, two, three or four) C1-C6 alkyl, C1-C6 haloalkyl, -O(C1-C6 alkyl), -O(C1-C6 haloalkyl), halo, -CO2H, -CO2Z, -CO2NH2, -O-(CH2CH2O) n -H or -O-(CH2CH2O) n -CH3 group;

[0163] Q is O, S, NH or NMe [preferably, Q is O];

[0164] Y is a counteranion;

[0165] Z is a countercation;

[0166] M 2+ is a metal cation;

[0167] n is 1, 2, 3, 4, 5 or 6;

[0168] p is 0, 1, 2, 3 or 4;

[0169] r is 0, 1, 2, 3, 4, 5 or 6; and

[0170] s is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12.

[0171] In a particularly preferred embodiment, the first or second aspect of the present invention provides a compound of formula (I) or a complex of formula (II):

[0172]

[0173] or a pharmaceutically acceptable salt thereof, wherein:

[0174] -R 1 is -R 2x ;

[0175] -R 2xSelected from -[(CH2) p Q] r -(CH2) s -[N(R 5 )3]Y, -[(CH2) p Q] r -(CH2) s -[P(R 5 )3]Y, -[(CH2) p Q] r -(CH2) s -[R 6 Y, -[(CH2) p Q] r -(CH2) s -[N(R 5 )2(R 5’ )], -[(CH2) p Q] r -(CH2) s -[P(R 5 )2(R 5’ )] or -[(CH2) p Q] r -(CH2) s -[R 6’ ;

[0176] -R 5 Each independently selected from C1-C3 alkyl or phenyl, wherein said phenyl may optionally be independently selected from C1-C6 alkyl, -O(C1-C6 alkyl), -CO2H, -CO2Z, -CO2NH2, -O-(CH2CH2O) n -H or -O-(CH2CH2O) n -CH3 one, two, three, four or five substituents;

[0177] -R 5’ Selected from C1-C3 alkyl substituted with -CO2 - or phenyl substituted with -CO2 - wherein said phenyl may optionally be further independently selected from C1-C6 alkyl, -O(C1-C6 alkyl), -CO2H, -CO2Z, -CO2NH2, -O-(CH2CH2O) n -H or -O-(CH2CH2O) n -CH3 one, two, three or four substituents;

[0178] -R 6is optionally independently selected from C1-C6 alkyl, -O(C1-C6 alkyl), -CO2H, -CO2Z, -CO2NH2, -O-(CH2CH2O) n -H or -O-(CH2CH2O) n - [NC5H5] substituted with one, two, three, four or five substituents;

[0179] -R 6’ is -[NC5H5], which is substituted with -CO2 - and optionally further substituted with one, two, three or four substituents independently selected from C1-C6 alkyl, -O(C1-C6 alkyl), -CO2H, -CO2Z, -CO2NH2, -O-(CH2CH2O) n -H or -O-(CH2CH2O) n -CH3;

[0180] Q is O, S, NH or NMe [preferably O];

[0181] Y is a counteranion;

[0182] Z is a countercation;

[0183] M 2+ is a metal cation;

[0184] n is 1, 2, 3, 4, 5 or 6;

[0185] p is 0, 1, 2, 3 or 4;

[0186] r is 0, 1, 2, 3, 4, 5 or 6; and

[0187] s is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12.

[0188] In these two preferred embodiments of the foregoing paragraph, each -R 5 can be the same or different; preferably, each -R 5 is the same.

[0189] In another preferred embodiment of the first or second aspect of the present invention, the compound is a compound of formula (IA), (IB), (IC), (ID), (IE), (IF) or (IG):

[0190]

[0191]

[0192] or a metal cation complex or a pharmaceutically acceptable salt thereof, wherein:

[0193] -R δ selected from C1-C3 alkyl;

[0194] -R ε selected from C1-C6 alkyl, -O(C1-C6 alkyl), -CO2H, -CO2Z, -CO2NH2, -O-(CH2CH2O) n -H or -O-(CH2CH2O) n -CH3;

[0195] Y is a counteranion;

[0196] Z is a countercation;

[0197] n is 1, 2, 3 or 4;

[0198] p is 0, 1, 2, 3 or 4;

[0199] r is 0, 1, 2, 3, 4, 5 or 6;

[0200] s is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12;

[0201] t is 0, 1, 2, 3, 4 or 5; and

[0202] u is 0, 1, 2, 3 and 4.

[0203] The compounds of formulae (IA), (IB), (IC), (ID), (IE), (IF), (IG) according to the first and second aspects of the present invention, and their complexes and salts comprise the moiety -[(CH2) p O] r -(CH2) s -, wherein:

[0204] p is 0, 1, 2, 3 or 4;

[0205] r is 0, 1, 2, 3, 4, 5 or 6; and

[0206] s is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12.

[0207] In one embodiment, p is 2, 3 or 4; r is 1; and s is 2, 3 or 4. In a preferred embodiment, p is 3; r is 1; and s is 3; such that -[(CH2) p O] r -(CH2) s - is -(CH2)3-O-(CH2)3-.

[0208] In another embodiment, p is 2 or 3; r is 2 or 3; and s is 2 or 3. In a preferred embodiment, p is 2; r is 2; and s is 2; such that -[(CH2) p O] r -(CH2) s - is -(CH2CH2O)2-(CH2)2-.

[0209] In another embodiment, r is 0; and s is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12; such that -[(CH2) p O] r -(CH2) s - is -(CH2) 1-12 -.

[0210] Preferably, in the compound or complex according to the first or second aspect of the present invention, the compound or complex is:

[0211]

[0212] wherein

[0213] -R 5 are each independently selected from C1-C4 alkyl, C1-C4 haloalkyl, -(CH2CH2O) n -H, -(CH2CH2O) n -CH3, phenyl or C5-C6 heteroaryl, wherein the phenyl or C5-C6 heteroaryl may optionally be substituted by one or more C1-C4 alkyl, C1-C4 haloalkyl, -O(C1-C4 alkyl), -O(C1-C4 haloalkyl), halogen, -O-(CH2CH2O) n -H or -O-(CH2CH2O) n -CH3 groups;

[0214] -R 8 are each independently selected from C1-C4 alkyl, C1-C4 haloalkyl, -O(C1-C4 alkyl), -O(C1-C4 haloalkyl), halogen, -O-(CH2CH2O) n -H or -O-(CH2CH2O) n -CH3 groups;

[0215] -R 9 are each independently optionally substituted by one or more C1-C4 alkyl, C1-C4 haloalkyl, -O(C1-C4 alkyl), -O(C1-C4 haloalkyl), halogen, -O-(CH2CH2O) n-H or -O-(CH2CH2O) n phenyl substituted with a -CH3 group;

[0216] n is 1, 2, 3 or 4;

[0217] p is 0, 1, 2, 3 or 4;

[0218] q is 0, 1, 2, 3 or 4 (preferably q is 1); and

[0219] Y is a counteranion;

[0220] or a metal cation complex thereof or a pharmaceutically acceptable salt thereof.

[0221] Preferably, in the compound or complex according to the first or second aspect of the present invention, the compound or complex is:

[0222]

[0223]

[0224]

[0225]

[0226]

[0227] or a metal cation complex thereof or a pharmaceutically acceptable salt thereof.

[0228] In one embodiment, the compound or complex according to the first or second aspect of the present invention is in the form of a pharmaceutically acceptable salt. In one embodiment, the compound or complex is in the form of an inorganic salt, such as a lithium salt, sodium salt, potassium salt, magnesium salt, calcium salt or ammonium salt. In one embodiment, the compound or complex is in the form of a sodium salt or a potassium salt. In one embodiment, the compound is in the form of a sodium salt. In another embodiment, the compound or complex is in the form of an organic salt, such as an amine salt (e.g., choline or meglumine salt) or an amino acid salt (e.g., arginine salt).

[0229] The compound or complex according to the first or second aspect of the present invention has at least two chiral centers. The compound or complex according to the first or second aspect of the present invention is preferably substantially enantiomerically pure, which means that, as measured by XRPD or SFC, the compound or complex contains less than 10%, preferably less than 5%, preferably less than 3%, preferably less than 2%, preferably less than 1%, preferably less than 0.5% (all by weight) of other stereoisomers.

[0230] Preferably, the compound or complex according to the first or second aspect of the present invention has an HPLC purity greater than 97%, more preferably greater than 98%, more preferably greater than 99%, more preferably greater than 99.5%, more preferably greater than 99.8%, and most preferably greater than 99.9%. As used herein, the percentage HPLC purity is measured by the area normalization method.

[0231] The third aspect of the present invention provides a composition comprising a compound or complex according to the first or second aspect of the present invention and a pharmaceutically acceptable carrier or diluent.

[0232] In one embodiment, the composition according to the third aspect of the present invention further comprises polyvinylpyrrolidone (PVP). In one embodiment, the composition comprises 0.01%-10% w / w PVP, preferably 0.1%-5% w / w PVP, preferably 0.5%-5% w / w PVP as a percentage of the total weight of the composition. In one embodiment, the PVP is K30.

[0233] In one embodiment, the composition according to the third aspect of the present invention further comprises dimethyl sulfoxide (DMSO). In one embodiment, the composition comprises 0.01%-99% w / w DMSO, preferably 40%-99% w / w DMSO, preferably 65%-99% w / w DMSO as a percentage of the total weight of the composition.

[0234] In one embodiment, the composition according to the third aspect of the present invention further comprises an immune checkpoint inhibitor. In one embodiment, the immune checkpoint inhibitor is an inhibitor of PD-1 (programmed cell death protein 1), PD-L1 (programmed death ligand 1), or CTLA4 (cytotoxic T lymphocyte-associated protein 4). In one embodiment, the immune checkpoint inhibitor is selected from pembrolizumab, nivolumab, cemiplimab, atezolizumab, avelumab, durvalumab, or ipilimumab.

[0235] Preferably, the compound or complex according to the first or second aspect of the present invention and the pharmaceutical composition according to the third aspect of the present invention are suitable for use in photodynamic therapy or cell luminescence therapy.

[0236] Preferably, the compounds or complexes according to the first or second aspect of the present invention and the pharmaceutical composition according to the third aspect of the present invention are suitable for the treatment of atherosclerosis; multiple sclerosis; diabetes; diabetic retinopathy; arthritis; rheumatoid arthritis; fungal, viral, chlamydial, bacterial, nanobacterial or parasitic infectious diseases; HIV; AIDS; sars virus (preferably severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)), Asian (avian) influenza virus, dengue virus, herpes simplex or varicella zoster infection; hepatitis; viral hepatitis; cardiovascular diseases; coronary stenosis; carotid stenosis; intermittent claudication; skin disorders; acne; psoriasis; diseases characterized by excessive proliferation of benign or malignant cells or areas of neovascularization; benign or malignant tumors; early cancer; cervical dysplasia; soft tissue sarcoma; germ cell tumor; retinoblastoma; age-related macular degeneration; lymphoma; Hodgkin lymphoma; head and neck cancer; oral or mouth cancer; or blood cancer, prostate cancer, cervical cancer, uterine cancer, vaginal cancer or other female accessory cancers, breast cancer, nasopharyngeal cancer, tracheal cancer, laryngeal cancer, bronchial cancer, bronchioloalveolar carcinoma, lung cancer, cancer of the hollow organs, esophageal cancer, gastric cancer, cholangiocarcinoma, intestinal cancer, colon cancer, colorectal cancer, rectal cancer, bladder cancer, ureteral cancer, kidney cancer, liver cancer, gallbladder cancer, spleen cancer, brain cancer, lymphatic system cancer, bone cancer, skin cancer or pancreatic cancer.

[0237] Preferably, the compounds or complexes according to the first or second aspect of the present invention and the pharmaceutical composition according to the third aspect of the present invention are suitable for the treatment of diseases characterized by excessive proliferation of benign or malignant cells or areas of neovascularization.

[0238] Preferably, the compounds or complexes according to the first or second aspect of the present invention and the pharmaceutical composition according to the third aspect of the present invention are suitable for the treatment of benign or malignant tumors.

[0239] Preferably, the compounds or complexes according to the first or second aspect of the present invention and the pharmaceutical composition according to the third aspect of the present invention are suitable for the treatment of early cancer; cervical dysplasia; soft tissue sarcoma; germ cell tumor; retinoblastoma; age-related macular degeneration; lymphoma; Hodgkin lymphoma; head and neck cancer; oral or mouth cancer; or blood cancer, prostate cancer, cervical cancer, uterine cancer, vaginal cancer or other female accessory cancers, breast cancer, nasopharyngeal cancer, tracheal cancer, laryngeal cancer, bronchial cancer, bronchioloalveolar carcinoma, lung cancer, cancer of the hollow organs, esophageal cancer, gastric cancer, cholangiocarcinoma, intestinal cancer, colon cancer, colorectal cancer, rectal cancer, bladder cancer, ureteral cancer, kidney cancer, liver cancer, gallbladder cancer, spleen cancer, brain cancer, lymphatic system cancer, bone cancer, skin cancer or pancreatic cancer.

[0240] Preferably, the compound or complex according to the first or second aspect of the present invention and the pharmaceutical composition according to the third aspect of the present invention are suitable for use in photodynamic diagnosis.

[0241] Preferably, the compound or complex according to the first or second aspect of the present invention and the pharmaceutical composition according to the third aspect of the present invention are suitable for detecting atherosclerosis; multiple sclerosis; diabetes; diabetic retinopathy; arthritis; rheumatoid arthritis; fungal, viral, chlamydial, bacterial, nanobacterial or parasitic infectious diseases; HIV; AIDS; sars virus (preferably severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)), Asian (avian) influenza virus, dengue virus, herpes simplex or varicella zoster infection; hepatitis; viral hepatitis; cardiovascular diseases; coronary artery stenosis; carotid artery stenosis; intermittent claudication; skin disorders; acne; psoriasis; diseases characterized by excessive proliferation of benign or malignant cells or by areas of neovascularization; benign or malignant tumors; early cancer; cervical dysplasia; soft tissue sarcoma; germ cell tumor; retinoblastoma; age-related macular degeneration; lymphoma; Hodgkin lymphoma; head and neck cancer; oral or mouth cancer; or blood cancer, prostate cancer, cervical cancer, uterine cancer, vaginal cancer or other female accessory cancers, breast cancer, nasopharyngeal cancer, tracheal cancer, laryngeal cancer, bronchial cancer, bronchioloalveolar carcinoma, lung cancer, cancer of hollow organs, esophageal cancer, gastric cancer, cholangiocarcinoma, intestinal cancer, colon cancer, colorectal cancer, rectal cancer, bladder cancer, ureteral cancer, kidney cancer, liver cancer, gallbladder cancer, spleen cancer, brain cancer, lymphatic system cancer, bone cancer, skin cancer or pancreatic cancer.

[0242] Preferably, the compound or complex according to the first or second aspect of the present invention and the pharmaceutical composition according to the third aspect of the present invention are suitable for detecting areas affected by excessive proliferation of benign or malignant cells or by neovascularization.

[0243] Preferably, the compound or complex according to the first or second aspect of the present invention and the pharmaceutical composition according to the third aspect of the present invention are suitable for detecting benign or malignant tumors.

[0244] Preferably, the compound or complex according to the first or second aspect of the present invention and the pharmaceutical composition according to the third aspect of the present invention are suitable for detecting early cancer; cervical dysplasia; soft tissue sarcoma; germ cell tumor; retinoblastoma; age-related macular degeneration; lymphoma; Hodgkin lymphoma; head and neck cancer; oral or mouth cancer; or blood cancer, prostate cancer, cervical cancer, uterine cancer, vaginal cancer or other female accessory cancers, breast cancer, nasopharyngeal cancer, tracheal cancer, laryngeal cancer, bronchial cancer, bronchioloalveolar carcinoma, lung cancer, cancer of hollow organs, esophageal cancer, gastric cancer, cholangiocarcinoma, intestinal cancer, colon cancer, colorectal cancer, rectal cancer, bladder cancer, ureteral cancer, kidney cancer, liver cancer, gallbladder cancer, spleen cancer, brain cancer, lymphatic system cancer, bone cancer, skin cancer or pancreatic cancer.

[0245] Preferably, the compound or complex according to the first or second aspect of the present invention and the pharmaceutical composition according to the third aspect of the present invention are suitable for fluorescence or phosphorescence detection of the diseases listed above, preferably for fluorescence or phosphorescence detection and quantification of said diseases.

[0246] Preferably, the compound or complex according to the first or second aspect of the present invention and the pharmaceutical composition according to the third aspect of the present invention are adapted to be administered simultaneously with or before the administration of irradiation or sound, preferably adapted to be administered before the administration of irradiation.

[0247] If the compound or complex according to the first or second aspect of the present invention or the pharmaceutical composition according to the third aspect of the present invention is used in photodynamic therapy or cytoluminescence therapy, then they are preferably adapted to be administered 5 to 100 hours before irradiation, preferably 6 to 72 hours before irradiation, preferably 24 to 48 hours before irradiation.

[0248] If the compound or complex according to the first or second aspect of the present invention or the pharmaceutical composition according to the third aspect of the present invention is used in photodynamic diagnosis, then they are preferably adapted to be administered 3 to 60 hours before irradiation, preferably 8 to 40 hours before irradiation.

[0249] Preferably, the irradiation used in photodynamic therapy, cytoluminescence therapy or photodynamic diagnosis is electromagnetic radiation having a wavelength in the range of 500 nm to 1000 nm, preferably 550 nm to 750 nm, preferably 600 nm to 700 nm, preferably 640 nm to 670 nm. The electromagnetic radiation can be administered at about 0.1 - 5 W, preferably at about 1 W for a duration of about 5 - 60 minutes, preferably for a duration of about 15 - 20 minutes. In one embodiment of the present invention, two electromagnetic radiation sources (such as a laser and an LED lamp) are used, both sources being adapted to provide irradiation having a wavelength in the range of 550 nm to 750 nm, preferably 600 nm to 700 nm, preferably 640 nm to 670 nm. In another embodiment of the present invention, the irradiation can be provided by a prostate, anal, vaginal, oral and nasal device for insertion into a body cavity. In another embodiment of the present invention, the irradiation can be provided by interstitial photoactivation, for example, by inserting an optical fiber laser into the lung, liver, lymph node or breast using a fine needle. In another embodiment of the present invention, the irradiation can be provided by endoscopic photoactivation, for example, for delivering light to the lung, stomach, colon, bladder or neck.

[0250] The pharmaceutical composition according to the third aspect of the present invention may be in a form suitable for oral, parenteral (including intravenous, subcutaneous, intramuscular, intradermal, intratracheal, intraperitoneal, intratumoral, intra-articular, intra-abdominal, intracranial and epidural), transdermal, airway (aerosol), rectal, vaginal or topical (including buccal, mucosal and sublingual) administration. The pharmaceutical composition may also be in a form suitable for administration by enema or by injection into a tumor. Preferably, the pharmaceutical composition is in a form suitable for oral, parenteral (such as intravenous, intraperitoneal and intratumoral) or airway administration, preferably in a form suitable for oral or parenteral administration, and preferably in a form suitable for oral administration.

[0251] In a preferred embodiment, the pharmaceutical composition is in a form suitable for oral administration. Preferably, the pharmaceutical composition is provided in the form of tablets, capsules, hard or soft gelatin capsules, cachets, troches or lozenges, in the form of powders or granules, or in the form of aqueous solutions, suspensions or dispersions. More preferably, the pharmaceutical composition is provided in the form of an aqueous solution, suspension or dispersion for oral administration, or alternatively in the form of a lyophilized powder which can be mixed with water before administration to provide an aqueous solution, suspension or dispersion for oral administration. Preferably, the pharmaceutical composition is in a form suitable for providing a compound or complex according to the first or second aspect of the present invention at 0.01 to 10 mg / kg / day, preferably 0.1 to 2 mg / kg / day, preferably about 1 mg / kg / day.

[0252] In another preferred embodiment, the pharmaceutical composition is in a form suitable for parenteral administration. Preferably, the pharmaceutical composition is in a form suitable for intravenous administration. Preferably, the pharmaceutical composition is provided in the form of an aqueous solution for parenteral administration, or alternatively in the form of a lyophilized powder which can be mixed with water before administration to provide an aqueous solution for parenteral administration. Preferably, the pharmaceutical composition is an aqueous solution or suspension having a pH of 6 to 8.5. Preferably, the pharmaceutical composition is in a form suitable for providing a compound or complex according to the first or second aspect of the present invention at 0.01 to 10 mg / kg / day, preferably 0.1 to 2 mg / kg / day, preferably about 1 mg / kg / day.

[0253] In another preferred embodiment, the pharmaceutical composition is in a form suitable for airway administration. Preferably, the pharmaceutical composition is provided in the form of an aqueous solution, suspension or dispersion for airway administration, or alternatively in the form of a lyophilized powder which can be mixed with water before administration to provide an aqueous solution, suspension or dispersion for airway administration. Preferably, the pharmaceutical composition is in a form suitable for providing a compound or complex according to the first or second aspect of the present invention at 0.01 to 10 mg / kg / day, preferably 0.1 to 2 mg / kg / day, preferably about 1 mg / kg / day.

[0254] The fourth aspect of the present invention provides the use of a compound or complex according to the first or second aspect of the present invention in the manufacture of a medicament for treating the following diseases: atherosclerosis; multiple sclerosis; diabetes; diabetic retinopathy; arthritis; rheumatoid arthritis; fungal, viral, chlamydial, bacterial, nanobacterial or parasitic infectious diseases; HIV; AIDS; sars virus (preferably severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)), Asian (avian) influenza virus, dengue virus, herpes simplex or varicella-zoster infection; hepatitis; viral hepatitis; cardiovascular diseases; coronary artery stenosis; carotid artery stenosis; intermittent claudication; skin disorders; acne; psoriasis; diseases characterized by excessive proliferation of benign or malignant cells or areas of new blood vessel formation; benign or malignant tumors; early cancers; cervical dysplasia; soft tissue sarcoma; germ cell tumor; retinoblastoma; age-related macular degeneration; lymphoma; Hodgkin lymphoma; head and neck cancer; oral or mouth cancer; or blood cancer, prostate cancer, cervical cancer, uterine cancer, vaginal cancer or other female accessory cancers, breast cancer, nasopharyngeal cancer, tracheal cancer, laryngeal cancer, bronchial cancer, bronchioloalveolar carcinoma, lung cancer, cancer of the hollow organs, esophageal cancer, gastric cancer, cholangiocarcinoma, intestinal cancer, colon cancer, colorectal cancer, rectal cancer, bladder cancer, ureteral cancer, kidney cancer, liver cancer, gallbladder cancer, spleen cancer, brain cancer, lymphatic system cancer, bone cancer, skin cancer or pancreatic cancer.

[0255] The fourth aspect of the present invention further provides the use of a compound or complex according to the first or second aspect of the present invention in the manufacture of a phototherapeutic agent for photodynamic therapy or cellular luminescence therapy. Preferably, the phototherapeutic agent is suitable for treating atherosclerosis; multiple sclerosis; diabetes; diabetic retinopathy; arthritis; rheumatoid arthritis; fungal, viral, chlamydial, bacterial, nanobacterial or parasitic infectious diseases; HIV; AIDS; sars virus (preferably severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)), Asian (avian) influenza virus, dengue virus, herpes simplex or varicella-zoster infection; hepatitis; viral hepatitis; cardiovascular diseases; coronary artery stenosis; carotid artery stenosis; intermittent claudication; skin disorders; acne; psoriasis; diseases characterized by excessive proliferation of benign or malignant cells or areas of new blood vessel formation; benign or malignant tumors; early cancer; cervical dysplasia; soft tissue sarcoma; germ cell tumor; retinoblastoma; age-related macular degeneration; lymphoma; Hodgkin lymphoma; head and neck cancer; oral or mouth cancer; or blood cancer, prostate cancer, cervical cancer, uterine cancer, vaginal cancer or other female accessory cancers, breast cancer, nasopharyngeal cancer, tracheal cancer, laryngeal cancer, bronchial cancer, bronchioloalveolar carcinoma, lung cancer, cancer of hollow organs, esophageal cancer, gastric cancer, cholangiocarcinoma, intestinal cancer, colon cancer, colorectal cancer, rectal cancer, bladder cancer, ureteral cancer, kidney cancer, liver cancer, gallbladder cancer, spleen cancer, brain cancer, lymphatic system cancer, bone cancer, skin cancer or pancreatic cancer.

[0256] Preferably, the agent or phototherapeutic agent according to the fourth aspect of the present invention is suitable for treating diseases characterized by excessive proliferation of benign or malignant cells or areas of new blood vessel formation.

[0257] Preferably, the agent or phototherapeutic agent according to the fourth aspect of the present invention is suitable for treating benign or malignant tumors.

[0258] Preferably, the agent or phototherapeutic agent according to the fourth aspect of the present invention is suitable for treating early cancer; cervical dysplasia; soft tissue sarcoma; germ cell tumor; retinoblastoma; age-related macular degeneration; lymphoma; Hodgkin lymphoma; head and neck cancer; oral or mouth cancer; or blood cancer, prostate cancer, cervical cancer, uterine cancer, vaginal cancer or other female accessory cancers, breast cancer, nasopharyngeal cancer, tracheal cancer, laryngeal cancer, bronchial cancer, bronchioloalveolar carcinoma, lung cancer, cancer of hollow organs, esophageal cancer, gastric cancer, cholangiocarcinoma, intestinal cancer, colon cancer, colorectal cancer, rectal cancer, bladder cancer, ureteral cancer, kidney cancer, liver cancer, gallbladder cancer, spleen cancer, brain cancer, lymphatic system cancer, bone cancer, skin cancer or pancreatic cancer.

[0259] The fourth aspect of the present invention further provides the use of a compound or complex according to the first or second aspect of the present invention in the manufacture of a photodiagnostic agent for photodynamic diagnosis.

[0260] Preferably, the photo-diagnostic agent of the fourth aspect of the present invention is suitable for detecting atherosclerosis; multiple sclerosis; diabetes; diabetic retinopathy; arthritis; rheumatoid arthritis; fungal, viral, chlamydial, bacterial, nanobacterial or parasitic infectious diseases; HIV; AIDS; sars virus (preferably severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)), Asian (avian) influenza virus, dengue virus, herpes simplex or varicella-zoster infection; hepatitis; viral hepatitis; cardiovascular diseases; coronary artery stenosis; carotid artery stenosis; intermittent claudication; skin disorders; acne; psoriasis; diseases characterized by excessive proliferation of benign or malignant cells or regions of neovascularization; benign or malignant tumors; early cancer; cervical dysplasia; soft tissue sarcoma; germ cell tumor; retinoblastoma; age-related macular degeneration; lymphoma; Hodgkin lymphoma; head and neck cancer; oral or mouth cancer; or blood cancer, prostate cancer, cervical cancer, uterine cancer, vaginal cancer or other female accessory cancers, breast cancer, nasopharyngeal cancer, tracheal cancer, laryngeal cancer, bronchial cancer, bronchioloalveolar carcinoma, lung cancer, cancer of hollow organs, esophageal cancer, gastric cancer, cholangiocarcinoma, intestinal cancer, colon cancer, colorectal cancer, rectal cancer, bladder cancer, ureteral cancer, kidney cancer, liver cancer, gallbladder cancer, spleen cancer, brain cancer, lymphatic system cancer, bone cancer, skin cancer or pancreatic cancer.

[0261] Preferably, the photo-diagnostic agent of the fourth aspect of the present invention is suitable for detecting regions affected by excessive proliferation of benign or malignant cells or neovascularization.

[0262] Preferably, the photo-diagnostic agent of the fourth aspect of the present invention is suitable for detecting benign or malignant tumors.

[0263] Preferably, the photo-diagnostic agent of the fourth aspect of the present invention is suitable for detecting early cancer; cervical dysplasia; soft tissue sarcoma; germ cell tumor; retinoblastoma; age-related macular degeneration; lymphoma; Hodgkin lymphoma; head and neck cancer; oral or mouth cancer; or blood cancer, prostate cancer, cervical cancer, uterine cancer, vaginal cancer or other female accessory cancers, breast cancer, nasopharyngeal cancer, tracheal cancer, laryngeal cancer, bronchial cancer, bronchioloalveolar carcinoma, lung cancer, cancer of hollow organs, esophageal cancer, gastric cancer, cholangiocarcinoma, intestinal cancer, colon cancer, colorectal cancer, rectal cancer, bladder cancer, ureteral cancer, kidney cancer, liver cancer, gallbladder cancer, spleen cancer, brain cancer, lymphatic system cancer, bone cancer, skin cancer or pancreatic cancer.

[0264] Preferably, the photo-diagnostic agent of the fourth aspect of the present invention is suitable for fluorescent or phosphorescent detection of the disease, preferably fluorescent or phosphorescent detection and quantification of the disease.

[0265] Preferably, the medicament, photo-therapeutic agent or photo-diagnostic agent is suitable for administration simultaneously with or before the administration of irradiation or sound, preferably suitable for administration before the administration of irradiation.

[0266] If a pharmaceutical or a photo-therapeutic agent is used in photodynamic therapy or in cell luminescence therapy, it is preferably adapted to be administered 5 to 100 hours before irradiation, preferably 6 to 72 hours before irradiation, preferably 24 to 48 hours before irradiation.

[0267] If a photo-diagnostic agent is used in photodynamic diagnosis, it is preferably adapted to be administered 3 to 60 hours before irradiation, preferably 8 to 40 hours before irradiation.

[0268] Preferably, the irradiation used in photodynamic therapy, cell luminescence therapy or photodynamic diagnosis is electromagnetic radiation having a wavelength in the range of 500 nm to 1000 nm, preferably 550 nm to 750 nm, preferably 600 nm to 700 nm, preferably 640 nm to 670 nm. The electromagnetic radiation can be administered at about 0.1 - 5 W, preferably at about 1 W for a duration of about 5 - 60 minutes, preferably for a duration of about 15 - 20 minutes. In one embodiment of the invention, two electromagnetic radiation sources (e.g., a laser and an LED lamp) are used, both sources being adapted to provide irradiation having a wavelength in the range of 550 nm to 750 nm, preferably 600 nm to 700 nm, preferably 640 nm to 670 nm. In another embodiment of the invention, the irradiation can be provided by a prostate, anal, vaginal, oral and nasal device for insertion into a body cavity. In another embodiment of the invention, the irradiation can be provided by interstitial photoactivation, for example using a thin needle to insert a fiber laser into the lung, liver, lymph node or breast. In another embodiment of the invention, the irradiation can be provided by endoscopic photoactivation, for example for delivering light to the lung, stomach, colon, bladder or neck.

[0269] The fifth aspect of the present invention provides a method for treating atherosclerosis; multiple sclerosis; diabetes; diabetic retinopathy; arthritis; rheumatoid arthritis; fungal, viral, chlamydial, bacterial, nanobacterial or parasitic infectious diseases; HIV; AIDS; sars virus (preferably severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)), Asian (avian) influenza virus, dengue virus, herpes simplex or varicella-zoster infection; hepatitis; viral hepatitis; cardiovascular diseases; coronary artery stenosis; carotid artery stenosis; intermittent claudication; skin disorders; acne; psoriasis; diseases characterized by excessive proliferation of benign or malignant cells or areas of new blood vessel formation; benign or malignant tumors; early cancer; cervical dysplasia; soft tissue sarcoma; germ cell tumor; retinoblastoma; age-related macular degeneration; lymphoma; Hodgkin lymphoma; head and neck cancer; oral or mouth cancer; or blood cancer, prostate cancer, cervical cancer, uterine cancer, vaginal cancer or other female accessory cancers, breast cancer, nasopharyngeal cancer, tracheal cancer, laryngeal cancer, bronchial cancer, bronchioloalveolar carcinoma, lung cancer, cancer of hollow organs, esophageal cancer, gastric cancer, cholangiocarcinoma, intestinal cancer, colon cancer, colorectal cancer, rectal cancer, bladder cancer, ureteral cancer, kidney cancer, liver cancer, gallbladder cancer, spleen cancer, brain cancer, lymphatic system cancer, bone cancer, skin cancer or pancreatic cancer; the method comprising administering to a human or animal in need thereof a therapeutically effective amount of a compound or complex according to the first or second aspect of the present invention.

[0270] The fifth aspect of the present invention also provides a method for photodynamic therapy or cell luminescence therapy of human or animal diseases, the method comprising administering to a human or animal in need thereof a therapeutically effective amount of a compound or complex according to the first or second aspect of the present invention. Preferably, the human or animal disease is atherosclerosis; multiple sclerosis; diabetes; diabetic retinopathy; arthritis; rheumatoid arthritis; fungal, viral, chlamydial, bacterial, nanobacterial or parasitic infectious diseases; HIV; AIDS; sars virus (preferably severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)), Asian (avian) influenza virus, dengue virus, herpes simplex or varicella-zoster infection; hepatitis; viral hepatitis; cardiovascular diseases; coronary artery stenosis; carotid artery stenosis; intermittent claudication; skin disorders; acne; psoriasis; diseases characterized by excessive proliferation of benign or malignant cells or areas of neovascularization; benign or malignant tumors; early cancer; cervical dysplasia; soft tissue sarcoma; germ cell tumor; retinoblastoma; age-related macular degeneration; lymphoma; Hodgkin lymphoma; head and neck cancer; oral or mouth cancer; or blood cancer, prostate cancer, cervical cancer, uterine cancer, vaginal cancer or other female accessory cancers, breast cancer, nasopharyngeal cancer, tracheal cancer, laryngeal cancer, bronchial cancer, bronchioloalveolar carcinoma, lung cancer, cancer of hollow organs, esophageal cancer, gastric cancer, cholangiocarcinoma, intestinal cancer, colon cancer, colorectal cancer, rectal cancer, bladder cancer, ureteral cancer, kidney cancer, liver cancer, gallbladder cancer, spleen cancer, brain cancer, lymphatic system cancer, bone cancer, skin cancer or pancreatic cancer.

[0271] Preferably, the method of the fifth aspect of the present invention is a method for treating excessive proliferation of benign or malignant cells or areas of neovascularization.

[0272] Preferably, the method of the fifth aspect of the present invention is a method for treating benign or malignant tumors.

[0273] Preferably, the method of the fifth aspect of the present invention is a method for treating early cancer; cervical dysplasia; soft tissue sarcoma; germ cell tumor; retinoblastoma; age-related macular degeneration; lymphoma; Hodgkin lymphoma; head and neck cancer; oral or mouth cancer; or blood cancer, prostate cancer, cervical cancer, uterine cancer, vaginal cancer or other female accessory cancers, breast cancer, nasopharyngeal cancer, tracheal cancer, laryngeal cancer, bronchial cancer, bronchioloalveolar carcinoma, lung cancer, cancer of hollow organs, esophageal cancer, gastric cancer, cholangiocarcinoma, intestinal cancer, colon cancer, colorectal cancer, rectal cancer, bladder cancer, ureteral cancer, kidney cancer, liver cancer, gallbladder cancer, spleen cancer, brain cancer, lymphatic system cancer, bone cancer, skin cancer or pancreatic cancer.

[0274] The fifth aspect of the present invention also provides a method for photodynamic diagnosis of human or animal diseases, which method comprises administering to a human or animal a diagnostically effective amount of a compound or complex according to the first or second aspect of the present invention. Preferably, the human or animal disease is atherosclerosis; multiple sclerosis; diabetes; diabetic retinopathy; arthritis; rheumatoid arthritis; fungal, viral, chlamydial, bacterial, nanobacterial or parasitic infectious diseases; HIV; AIDS; sars virus (preferably severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)), Asian (avian) influenza virus, dengue virus, herpes simplex or varicella-zoster infection; hepatitis; viral hepatitis; cardiovascular disease; coronary artery stenosis; carotid artery stenosis; intermittent claudication; skin disorders; acne; psoriasis; diseases characterized by excessive proliferation of benign or malignant cells or areas of neovascularization; benign or malignant tumors; early cancer; cervical dysplasia; soft tissue sarcoma; germ cell tumor; retinoblastoma; age-related macular degeneration; lymphoma; Hodgkin lymphoma; head and neck cancer; oral or mouth cancer; or blood cancer, prostate cancer, cervical cancer, uterine cancer, vaginal cancer or other female accessory cancers, breast cancer, nasopharyngeal cancer, tracheal cancer, laryngeal cancer, bronchial cancer, bronchioloalveolar carcinoma, lung cancer, cancer of hollow organs, esophageal cancer, gastric cancer, cholangiocarcinoma, intestinal cancer, colon cancer, colorectal cancer, rectal cancer, bladder cancer, ureteral cancer, kidney cancer, liver cancer, gallbladder cancer, spleen cancer, brain cancer, lymphatic system cancer, bone cancer, skin cancer or pancreatic cancer. Preferably, the human or animal disease is characterized by excessive proliferation of benign or malignant cells or areas of neovascularization. Preferably, the human or animal disease is a benign or malignant tumor. Preferably, the human or animal disease is early cancer; cervical dysplasia; soft tissue sarcoma; germ cell tumor; retinoblastoma; age-related macular degeneration; lymphoma; Hodgkin lymphoma; head and neck cancer; oral or mouth cancer; or blood cancer, prostate cancer, cervical cancer, uterine cancer, vaginal cancer or other female accessory cancers, breast cancer, nasopharyngeal cancer, tracheal cancer, laryngeal cancer, bronchial cancer, bronchioloalveolar carcinoma, lung cancer, cancer of hollow organs, esophageal cancer, gastric cancer, cholangiocarcinoma, intestinal cancer, colon cancer, colorectal cancer, rectal cancer, bladder cancer, ureteral cancer, kidney cancer, liver cancer, gallbladder cancer, spleen cancer, brain cancer, lymphatic system cancer, bone cancer, skin cancer or pancreatic cancer. Preferably, the method of photodynamic diagnosis is suitable for fluorescence or phosphorescence detection of the disease, preferably suitable for fluorescence or phosphorescence detection and quantification of the disease.

[0275] In any method of the fifth aspect of the present invention, the human or animal is preferably further subjected to irradiation or sound simultaneously with or after administration of the compound or complex according to the first or second aspect of the present invention. Preferably, the human or animal is irradiated after administration of the compound or complex according to the first or second aspect of the present invention.

[0276] If the method is a method of photodynamic therapy or a method of cellular luminescence therapy, it is preferably carried out by irradiating a human or animal 5 to 100 hours, preferably 6 to 72 hours, preferably 24 to 48 hours after administration of the compound or complex according to the first or second aspect of the present invention.

[0277] If the method is a method of photodynamic diagnosis, it is preferably carried out by irradiating a human or animal 3 to 60 hours, preferably 8 to 40 hours after administration of the compound or complex according to the first or second aspect of the present invention.

[0278] Preferably, the irradiation is electromagnetic radiation having a wavelength in the range of 500 nm to 1000 nm, preferably 550 nm to 750 nm, preferably 600 nm to 700 nm, preferably 640 nm to 670 nm. The electromagnetic radiation can be applied at about 0.1 - 5 W, preferably at about 1 W for about 5 - 60 minutes, preferably for about 15 - 20 minutes. In one embodiment of the present invention, two electromagnetic radiation sources (such as a laser and an LED lamp) are used, both sources being adapted to provide irradiation having a wavelength in the range of 550 nm to 750 nm, preferably 600 nm to 700 nm, preferably 640 nm to 670 nm. In another embodiment of the present invention, the irradiation can be provided by a device for inserting into body cavities such as the prostate, anus, vagina, mouth and nose. In another embodiment of the present invention, the irradiation can be provided by interstitial photoactivation, for example, using a fine needle to insert a fiber laser into the lung, liver, lymph node or breast. In another embodiment of the present invention, the irradiation can be provided by endoscopic photoactivation, for example, for delivering light to the lung, stomach, colon, bladder or neck.

[0279] In any method according to the fifth aspect of the present invention, preferably the human or animal is a human.

[0280] The sixth aspect of the present invention provides a pharmaceutical combination or a kit, the pharmaceutical combination or the kit comprising:

[0281] (a) a compound or complex according to the first or second aspect of the present invention; and

[0282] (b) an immune checkpoint inhibitor.

[0283] In one embodiment, the immune checkpoint inhibitor is an inhibitor of PD-1 (programmed cell death protein 1), PD-L1 (programmed death ligand 1) or CTLA4 (cytotoxic T lymphocyte-associated protein 4). In one embodiment, the immune checkpoint inhibitor is selected from pembrolizumab, nivolumab, cemiplimab, atezolizumab, avelumab, durvalumab or ipilimumab.

[0284] Preferably, the combination or kit of the sixth aspect is for treating a disease, disorder or condition which responds to PD-1, PD-L1 or CTLA4 inhibition. Preferably, the combination or kit of the sixth aspect is for treating cancer. In one embodiment, the cancer is melanoma, lung cancer (such as non-small cell lung cancer), renal cancer, bladder cancer, head and neck cancer or Hodgkin's lymphoma.

[0285] The sixth aspect also provides the use of the combination or kit of the sixth aspect of the present invention in the manufacture of a medicament for treating a disease, disorder or condition which responds to PD-1, PD-L1 or CTLA4 inhibition. The sixth aspect also provides the use of the combination or kit of the sixth aspect of the present invention in the manufacture of a medicament for treating cancer. In one embodiment, the cancer is melanoma, lung cancer (such as non-small cell lung cancer), renal cancer, bladder cancer, head and neck cancer or Hodgkin's lymphoma.

[0286] The sixth aspect of the present invention also provides a method for treating a disease, disorder or condition which responds to PD-1, PD-L1 or CTLA4 inhibition, the method comprising administering to a human or animal in need thereof a therapeutically effective amount of the combination or kit of the sixth aspect of the present invention. The sixth aspect of the present invention also provides a method for treating cancer, the method comprising administering to a human or animal in need thereof a therapeutically effective amount of the combination or kit of the sixth aspect of the present invention. In one embodiment, the cancer is melanoma, lung cancer (such as non-small cell lung cancer), renal cancer, bladder cancer, head and neck cancer or Hodgkin's lymphoma.

[0287] For the combination or kit of the sixth aspect of the present invention, the compound or complex and the immune checkpoint inhibitor according to the first or second aspect of the present invention can be provided together in a pharmaceutical composition or separately in two pharmaceutical compositions. If provided in two pharmaceutical compositions, these can be administered simultaneously or at different times.

[0288] Preferably, the combination or kit of the sixth aspect is suitable for administration simultaneously with or before administration of irradiation or sound, preferably suitable for administration before administration of irradiation. In one embodiment, the combination or kit of the sixth aspect is suitable for administration 5 to 100 hours before irradiation, preferably 6 to 72 hours before irradiation, preferably 24 to 48 hours before irradiation.

[0289] Preferably, the irradiation used in photodynamic therapy or cellular luminescence therapy is electromagnetic radiation having a wavelength in the range of 500 nm to 1000 nm, preferably 550 nm to 750 nm, preferably 600 nm to 700 nm, preferably 640 nm to 670 nm. The electromagnetic radiation can be applied at about 0.1 - 5 W, preferably at about 1 W for about 5 - 60 minutes, preferably for about 15 - 20 minutes. In one embodiment of the present invention, two electromagnetic radiation sources (e.g., a laser and an LED lamp) are used, both sources being adapted to provide irradiation having a wavelength in the range of 550 nm to 750 nm, preferably 600 nm to 700 nm, preferably 640 nm to 670 nm. In another embodiment of the present invention, the irradiation can be provided by a prostate, anal, vaginal, oral, and nasal device for insertion into a body cavity. In another embodiment of the present invention, the irradiation can be provided by interstitial photoactivation, for example, using a fine needle to insert a fiber laser into the lung, liver, lymph node, or breast. In another embodiment of the present invention, the irradiation can be provided by endoscopic photoactivation, for example, for delivering light to the lung, stomach, colon, bladder, or neck.

[0290] To avoid doubt, within the scope of practicability, any embodiment of a given aspect of the present invention can be combined with any other embodiment of the same aspect of the present invention. Additionally, within the scope of practicability, it should be understood that any preferred or optional embodiment of any aspect of the present invention should also be regarded as a preferred or optional embodiment of any other aspect of the present invention.

[0291] Synthesis experimental details

[0292] Synthesis of Synthesis Example 1 – 3 - ((7S,8S)-18 - ethyl - 2,5,8,12,17 - pentamethyl - 13 - vinyl - 7H,8H - porphyrin - 7 - yl)propan - 1 - ol (also known as chlorophyllin 3 - hydroxypropyl) (Compound 1)

[0293]

[0294] Synthesis of chlorophyllin methyl ester

[0295]

[0296] Add chlorophyllin (2.40 g, 4.72 mmol, 1 equivalent), potassium carbonate (0.78 g, 5.66 mmol, 1.2 equivalents), DMF (30 mL), and a small stir bar to a single - neck 100 mL RBF. Place the flask under nitrogen and stir at 300 rpm. Then add methyl iodide (382 μL, 6.13 mmol, 1.3 equivalents) and stir the flask at room temperature. HPLC analysis was performed after 2 hours and after stirring throughout the weekend, and the completion of the reaction was confirmed. Dilute the solution with DCM (30 mL) and pass through a (Filter at 1 cm depth) until no more color elutes. Remove the solvent under reduced pressure to give approximately 4 g of a blue solid. Dissolve the crude material in EtOAc (125 mL) and wash with water (2 × 100 mL), dry (Na2SO4) and concentrate under reduced pressure to give the crude product as a dark blue / green solid (2.7 g). Purify the crude material by column chromatography (silica, 4 × 23 cm, gradient solvent from DCM to 3% MeOH / DCM) to give methyl chlorophyll protein as a dark blue / green solid (1.60 g, 64.8%).

[0297] 1 1H NMR (400 MHz, CDCl3) δ -2.22 (br, 1H), -2.10 (br, 1H), 1.72 - 1.80 (m, 6H), 2.20 - 2.10 (m, 1H), 2.10 - 2.00 (m, 1H), 2.48 - 2.62 (m, 2H), 3.38 (s, 3H), 3.53 (s, 3H), 3.58 (s, 3H), 3.64 (s, 3H), 3.84 (q, 2H), 3.98 (s, 3H), 4.50 (q, 1H), 4.56 (d, 1H), 6.13 (dd, 1H), 6.37 (dd, 1H), 8.16 (dd, 1H), 8.83 (br s, 2H), 9.71 (br s, 2H).

[0298] Reduced to 3-((7S,8S)-18-ethyl-2,5,8,12,17-pentamethyl-13-ethenyl-7H,8H-porphyrin-7- yl)propan-1-ol

[0299]

[0300] To a 2-necked 500 mL RBF, add lithium aluminum hydride (670 mg, 16.8 mmol, 5 eq) and THF (200 mL). Stir the solution (350 rpm) and cool it for 10 minutes using an ice / water bath under nitrogen. Add chlorophyllin methyl ester (1.75 g, 3.35 mmol, 1 eq) in portions over 5 minutes. After 30 minutes, add lithium aluminum hydride (670 mg, 16.8 mmol, 5 eq) again and continue stirring for 90 minutes, during which the reaction mixture is allowed to warm slightly. TLC analysis shows completion of the reaction. Cool the flask (ice / water bath) and add water (1.3 mL), then add 4 M NaOH (1.3 mL). After stirring for 10 minutes, add water (4.0 mL) and warm the solution to room temperature and stir for 15 minutes. Add sodium sulfate and stir the mixture for 10 minutes, then filter and wash with DCM until no more color elutes. Then remove the solvent under reduced pressure to obtain approximately 2.3 g of crude product (still containing some solvent). HPLC analysis at this stage indicates a crude product purity of 97.3%. Purify the crude material by column chromatography (silica, 4 × 11 cm, 2%-4% MeOH / DCM) to obtain Compound 1 (1.60 g, 97%) as a dark blue / green solid (HPLC purity: 97.6%).

[0301] 1 H NMR (400 MHz, CDCl3) δ 9.72 (m, 2H), 8.88 (s, 1H), 8.84 (m, 1H), 8.16 (dd, 1H), 6.48 (dd, 1H), 6.14 (dd, 1H), 4.51 (m, 2H), 3.94 (s, 3H), 3.85 (q, 2H), 3.63 (s, 3H), 3.60 - 3.50 (m, 5H), 3.38 (s, 3H), 2.21 - 2.612 (m, 1H), 1.85 - 1.72 (m, 8H), 1.52 - 1.40 (m, 2H), 1.12 - 1.05 (m, 1H), -2.10 (br, 1H), -2.22 (br, 1H).

[0302] Synthesis of 3-((7S,8S)-18-Ethyl-2,5,8,12,17-pentamethyl-13-vinyl-7H,8H-porphyrin-7-yl)propyl Acetate (Compound 2) - Synthesis Example 2

[0303]

[0304] Chlorophyll protein 3 - hydroxypropyl (Compound 1) (100 mg, 0.202 mmol, 1 equiv), pyridine (0.7 mL), acetic anhydride (0.2 mL, 2.11 mmol, 10 equiv), and DMAP (0.5 mg) were added to a single - necked 25 mL RBF. The solution was stirred at 30 °C for 1 h. Analysis by TLC and HPLC indicated completion of the reaction. Ethyl acetate (10 mL) and water (5 mL) were added and the mixture was stirred vigorously for 10 min. The layers were separated and the ethyl acetate layer was washed with 0.5 M HCl (3 x 5 mL), saturated NaHCO3 (3 x 5 mL), dried (Na2SO4), and concentrated to give Compound 2 as a dark green flaky solid, which was used without further purification (78 mg, 72%) (HPLC purity: 98.8%).

[0305] 1 H NMR (400 MHz, CDCl3) δ 9.72 (m, 2H), 8.86 (s, 1H), 8.84 (m, 1H), 8.16 (dd, 1H), 6.48 (dd, 1H), 6.13 (dd, 1H), 4.52 (m, 2H), 4.06 (t, 2H), 3.95 (s, 3H), 3.85 (q, 2H), 3.65 (s, 3H), 3.54 (s, 3H), 3.37 (s, 3H), 2.21 - 2.13 (m, 1H), 1.96 (s, 3H), 1.95 - 1.80 (m, 2H), 1.80 - 1.72 (m, 6H), 1.62 - 1.50 (m, 2H), - 2.10 (br, 1H), - 2.22 (br, 1H).

[0306] Synthesis of Synthesis Example 3 - (7S,8S)-8-(3 - chloropropyl)-17 - ethyl - 3,7,10,13,18 - pentamethyl - 2 - vinyl - 7H,8H - porphyrin (also known as chlorophyll protein 3 - chloropropyl) (Compound 3)

[0307]

[0308] Charge a single-necked 25 mL RBF with chlorophyll protein 3-hydroxypropyl (Compound 1) (0.50 g, 1.01 mmol, 1 equiv), dichloroethane (4 mL), and thionyl chloride (200 mg, 1.68 mmol, 1.65 equiv). Cool the resulting solution using an ice / water bath and stir (350 rpm) under a nitrogen atmosphere. Add DMF (1 drop), then stir the mixture at room temperature for 1 h, then stir for an additional 1 h at 40 °C, at which point HPLC analysis shows the reaction is complete. Then cool the reaction mixture using an ice / water bath and add pH 7 phosphate buffer (10 mL). Extract the mixture with DCM (2 x 15 mL), dry (Na2SO4), and concentrate under reduced pressure to obtain the crude chloride. Perform column chromatography using 1% MeOH / DCM (3 x 10 cm silica) to obtain Compound 3 as a dark blue / green solid (450 mg, 87%).

[0309] 1 1H NMR (400 MHz, CDCl3) δ 9.71 (m, 2H), 8.85 (s, 1H), 8.84 (m, 1H), 8.17 (dd, 1H), 6.37 (dd, 1H), 6.13 (dd, 1H), 4.51 (m, 2H), 3.96 (s, 3H), 3.84 (q, 2H), 3.64 (s, 3H), 3.53 (s, 3H), 3.49 - 3.42 (m, 2H), 3.38 (s, 3H), 2.35 - 2.25 (m, 1H), 2.08 - 1.95 (m, 1H), 1.94 - 1.85 (m, 1H), 1.80 - 1.72 (m, 6H), 1.71 - 1.60 (m, 1H), 1.04 - 1.01 (m, 3H), -2.10 (br, 1H), -2.23 (br, 1H).

[0310] Synthesis of Synthesis Example 4 – (2S,3R,4S,5S,6R)-2-((3-((3-((7S,8S)-18-Ethyl-2,5,8,12,17-pentamethyl-13-vinyl-7H,8H-porphyrin-7-yl)propyl)thio)propyl)thio)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol (Compound 4)

[0311]

[0312] (2R,3S,4S,5R,6S)-2-(hydroxymethyl)-6-((3-mercaptopropyl)thio)tetrahydro-2H-pyran-3,4,5-triol Synthesis

[0313]

[0314] Step 1: Add 1,3-propanedithiol (11.9 g, 110 mmol, 2 equiv) to a dry 3-necked 250 mL RBF equipped with a stir bar and a stopper. The flask is fitted with a reflux condenser having a gas inlet and a bubbler and then placed under nitrogen. Add chloroform (30 mL) and stir the solution under nitrogen at room temperature. Using a funnel, add 1,2,3,4,6-penta-O-acetyl-β-D-glucose (21.5 g, 55.0 mmol, 1 equiv) and wash with additional chloroform (10 mL). Finally, add indium(III) bromide (0.58 g, 1.64 mmol, 0.03 equiv), and place the mixture in a preheated oil bath (90 °C) and stir under nitrogen for 2.5 h. Cool the reaction mixture to room temperature and apply directly onto a silica gel column (250x50 mm) made in 100% DCM. Elute the column with 100% DCM, then with 30% EtOAc in hexane, with 60% EtOAc in hexane, and finally with 100% EtOAc, collecting 30x125 mL fractions. Combine and evaporate the strongest fractions (11 - 19) as elucidated by TLC to give a colorless viscous oil (10.33 g) which crystallizes on standing. 1 1H NMR shows this to be the desired product but containing EtOAc (4%) and acetic acid (5%). Therefore, dissolve the material in DCM (150 mL), wash with 1 M sodium bicarbonate solution (200 mL), back-extract the washings with DCM (50 mL), and wash the combined organic phases with water (150 mL), dry (Na2SO4) and evaporate to give a viscous colorless oil which crystallizes rapidly on standing. Triturate the material with 1:1 hexane / ether (ca. 30 mL) and crush the larger crystals with a glass rod. After stirring for one hour, filter the suspension and dry the solid in a vacuum oven at 25 °C overnight (7.50 g).

[0315] 11H NMR (400 MHz, CDCl3) δ 5.21 (dd, J = 9.8, 9.8 Hz, 1H), 5.08 (dd, J = 9.8, 9.8 Hz, 1H), 5.03 (dd, J = 9.8, 9.8 Hz, 1H), 4.49 (d, J = 9.8 Hz, 1H), 4.23 (dd, J = 12.3, 4.9 Hz, 1H), 4.14 (dd, J = 12.3, 2.4 Hz, 1H), 3.71 (ddd, J = 9.8, 4.9, 2.4 Hz, 1H), 2.85 (ddd, J = 12.7, 7.0, 7.0 Hz, 1H), 2.76 (ddd, J = 12.7, 7.0, 7.0 Hz, 1H), 2.63 (app. ddd, J = 8.1, 7.0, 7.0 Hz, 2H), 2.08 (s, 3H), 2.06 (s, 3H), 2.02 (s, 3H), 2.00 (s, 3H), 1.90 (app. p, J = 7.0 Hz, 2H), 1.37 (t, J = 8.1 Hz, 1H).

[0316] Step 2: Weigh (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-((3-sulfanylpropyl)thio)tetrahydro-2H-pyran-3,4,5-triyl triacetate (2.50 g, 5.7 mmol, 1 equiv) into a 100 mL dry single-necked RBF, and equip the flask with a stir bar and a three-way valve. Place the flask under nitrogen and add anhydrous MeOH (20 mL) via the three-way valve using a syringe while keeping the flask under nitrogen. Using a graduated pipette, add methanolamine (4.8 mL, ~57 mmol, 10 equiv), then close the flask and stir overnight at room temperature. After 21 h, remove the solvent to give (2R,3S,4S,5R,6S)-2-(hydroxymethyl)-6-((3-mercaptopropyl)thio)tetrahydro-2H-pyran-3,4,5-triol (1.74 g) as a light chestnut-colored transparent oil, which is used without further purification.

[0317] 1 1H NMR (400 MHz, d4-MeOH) δ 1.92 (quin, overlapping - acetamide), 2.04 (quin, 2H (major isomer)), 2.63 (t, 0.6H (minor isomer)), 2.73 - 2.94 (m, 4.4H), 3.19 (m, 1.3H), 3.25 - 3.38 (m, overlapping - NMR solvent), 3.62 - 3.69 (m, 1.3H), 3.83 - 3.89 (m, 1.3H), 4.34 - 4.39 (m, 1.3H).

[0318] (2S,3R,4S,5S,6R)-2-((3-((3-((7S,8S)-18-ethyl-2,5,8,12,17-pentamethyl-13-ethenyl-7H,8H-porphyrin-7-yl)propyl)thio)propyl)thio)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol (Compound 4) Synthesis (Compound 4) Synthesis

[0319]

[0320] Charge a single-neck 10 mL RBF with chlorophyll protein 3-chloropropyl (Compound 3) (100 mg, 0.195 mmol, 1 equiv), potassium carbonate (54 mg, 0.390 mmol, 2 equiv), sodium bromide (2 mg, 0.020 mmol, 0.1 equiv), and DMF (1 mL). Add (2R,3S,4S,5R,6S)-2-(hydroxymethyl)-6-((3-mercaptopropyl)thio)tetrahydro-2H-pyran-3,4,5-triol (58 mg, 0.215 mmol, 1.1 equiv), and stir the resulting solution under nitrogen at 30 °C. TLC after 3 h indicated the presence of only starting material, and then the flask was heated overnight at 70 °C. HPLC indicated consumption of approximately 50% of the starting material and formation of two products. The solvent was removed under reduced pressure. The residual blue solid was purified by column chromatography using 1.5%-10% MeOH / DCM to elute Compound 4 (9 mg, 6%).

[0321] Synthesis Example 5–(2S,3R,4S,5S,6R)-2-((3-((3-((7S,8S)-18-Ethyl-2,5,8,12,17-pentamethyl-13-vinyl-7H,8H-porphyrin-7-yl)propyl)thio)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol (Compound 5)

[0322]

[0323] Charge a 5 mL RBF containing a stir bar with chlorophyll protein 3-chloropropyl (Compound 3) (71 mg, 0.1384 mmol, 1 equiv), then add a solution of sodium β-D-thioglucopyranoside (31 mg, 0.1421 mmol, 1.03 equiv) in methanol (1.4 mL) (partially dissolved). Stir the resulting mixture (420 rpm) for 3 h, but there was no obvious reaction, so potassium iodide (ca. 2 mg) was added. Further stirring at ambient temperature was unsuccessful, so the reaction mixture was heated overnight at 75 °C (externally), at which point the reaction was 50% complete as monitored by HPLC and TLC. Further heating had no effect, so the reaction mixture was dissolved in 1:1 MeOH / DCM and passed through a 5 cm silica pad (inside a glass pipette). The solvent was removed to give a black film. The crude product was purified by Biotage automated column chromatography to give Compound 5 as a black solid (10.4 mg, 11%).

[0324] 11H NMR (400 MHz, d6-DMSO) δ 9.76 (s, 1H), 9.74 (s, 1H), 9.12 (d, J = 2.5 Hz, 1H), 9.07 (d, J = 1.7 Hz, 1H), 8.34 (dd, J = 17.8, 11.6 Hz, 1H), 6.45 (dd, J = 17.8, 1.6 Hz, 1H), 6.17 (dd, J = 11.6, 1.5 Hz, 1H), 5.19 - 4.85 (m, 3H), 4.64 (q, J = 7.2 Hz, 1H), 4.58 - 4.44 (m, 2H), 4.25 (d, J = 9.6 Hz, 1H), 3.93 (d, J = 2.4 Hz, 3H), 3.82 (q, J = 7.6 Hz, 2H), 3.70 - 3.59 (m, 4H), 3.55 (s, 3H), 3.49 - 3.38 (m, 2H), 3.18 - 3.00 (m, 2H), 3.00 - 2.92 (m, 1H), 2.76 - 2.64 (m, 2H), 2.27 - 2.13 (m, 1H), 2.05 - 1.91 (m, 1H), 1.79 - 1.61 (m, 8H), -2.27 (s, 1H), -2.44 (d, J = 2.3 Hz, 1H).

[0325] Synthesis Example 6 - Synthesis of Chlorophyll Protein 3 - Azidoethyl (Compound 6)

[0326]

[0327] To a 100 mL RBF was added chlorophyll protein 3 - chloropropyl (Compound 3) (3.14 g, 6.12 mmol, 1 equiv) and DMF (30 mL). Then sodium azide (477 mg, 7.34 mmol, 1.2 equiv) was added and the resulting mixture was stirred overnight at 60 °C. Another portion of sodium azide (119 mg, 1.84 mmol, 0.3 equiv) was added and the reaction mixture was stirred at 60 °C for an additional 3 h, at which point the reaction was complete as monitored by HPLC. The solvent was removed by rotary evaporation to give the crude product as a dark residue. The crude product was purified by column chromatography using a step - column (40 / 57 mm), 35 cm of silica height, and a mobile phase of 0% - 5% MeOH in DCM. The fractions containing the product were combined to give Compound 6 as a blue / black solid (878 mg, 28%).

[0328] 11H NMR (400 MHz, CDCl3) δ 9.73 (d, J = 2.8 Hz, 2H), 8.87 (s, 1H), 8.84 (s, 1H), 8.16 (dd, J = 17.8, 11.5 Hz, 1H), 6.37 (dd, J = 17.8, 1.5 Hz, 1H), 6.14 (dd, J = 11.6, 1.5 Hz, 1H), 4.57 - 4.48 (m, 2H), 3.96 (s, 3H), 3.85 (q, J = 7.6 Hz, 2H), 3.65 (d, J = 1.0 Hz, 3H), 3.54 (s, 3H), 3.37 (s, 3H), 3.21 (t, J = 6.5 Hz, 2H), 2.27 - 2.16 (m, 1H), 1.90 - 1.81 (m, 1H), 1.79 (d, J = 7.3 Hz, 3H), 1.75 (t, J = 7.6 Hz, 3H), 1.52 (s, 2H), -2.11 (s, 1H), -2.22 (s, 1H).

[0329] Synthesis Example 7 - Synthesis of Chlorophyll Protein 3 - aminopropyl (Compound 7)

[0330]

[0331] Charge a 10 mL RBF with chlorophyll protein 3 - azidopropyl (Compound 6) (628 mg, 1.21 mmol, 1 equiv), THF (2 mL), and water (0.4 mL). Then add triphenylphosphine (380 mg, 1.45 mmol, 1.2 equiv) in one portion and stir the resulting mixture for 3 h, at which point the reaction is complete as monitored by TLC. Remove the solvent by rotary evaporation. Dissolve the residue in DCM (10 mL), dry over Na2SO4, filter, and concentrate to a dark residue, which is purified by column chromatography using a step - column (27 / 40 mm), 30 cm of silica height, and a gradient of 10% → 60% MeOH / DCM. Combine the major product fractions to give Compound 7 (393 mg, 66%) as a blue / black solid.

[0332] 11H NMR (400 MHz, d6-DMSO) δ 9.76 (d, J = 8.4 Hz, 2H), 9.12 (s, 1H), 9.09 (d, J = 1.8 Hz, 1H), 8.36 (dd, J = 17.9, 11.6 Hz, 1H), 7.10 (s, 2H), 6.46 (dd, J = 17.8, 1.6 Hz, 1H), 6.19 (dd, J = 11.6, 1.5 Hz, 1H), 4.59 (d, J = 7.6 Hz, 3H), 3.94 (s, 3H), 3.83 (q, J = 7.6 Hz, 2H), 3.64 (s, 3H), 3.56 (s, 3H), 2.75 (s, 1H), 2.70 - 2.58 (m, 1H), 2.19 - 2.06 (m, 1H), 1.87 - 1.64 (m, 9H), 1.23 (d, J = 9.5 Hz, 1H), -2.27 (s, 1H), -2.43 (d, J = 2.2 Hz, 1H).

[0333] Synthesis Example 8 - Synthesis of Chlorophyll Protein 3-aminopropyl-valine amide hydrochloride (Compound 8)

[0334]

[0335] Step 1: Charge Boc-L-valine (96.8 mg, 0.4456 mmol, 1.1 eq), PyBOP (252.98 mg, 0.4861 mmol, 1.2 eq), DCM (1 mL), and triethylamine (73 μL, 0.5266 mmol, 1.3 eq) into a 10 mL RBF. Stir the resulting mixture at ambient temperature (420 rpm) for 5 minutes, then add it to a 10 mL RBF containing a solution of chlorophyll protein 3-aminopropyl (Compound 7) (200 mg, 0.4051 mmol, 1 eq) in DCM (2 mL), and perform quantitative transfer using additional DCM (1 mL). Stir the mixture for 45 minutes, at which point the reaction is complete as monitored by TLC. Remove the solvent on a rotary evaporator to obtain a black residue, which is purified by Biotage automated column chromatography to give chlorophyll protein 3-aminopropyl(Boc)-valine amide as a dark purple solid (273 mg, 97%).

[0336] Step 2: Dissolve chlorophyll protein 3 - aminopropyl (Boc) - valine amide in DCM (1 mL) in a 10 mL RBF. Then add a solution of 4M HCl / dioxane (0.97 mL, 3.8964 mmol, 10 eq), and stir the resulting mixture for 1 hour, at which point the reaction is complete as monitored by HPLC. Remove the solvent by rotary evaporation to obtain a black residue, which is dissolved in the minimum amount of DMSO (2 mL) and purified by Biotage automated column chromatography using a C - 18 column (0.1M HCl / acetonitrile). Analyze the fractions by HPLC, and combine the fractions containing the product to give compound 8 as a black solid (25 mg, 9%) (HPLC purity: 91.9%).

[0337] 1 H NMR (400 MHz, d6 - DMSO) δ 10.18 (d, J = 6.3 Hz, 2H), 9.51 (s, 1H), 9.34 (s, 1H), 8.65 (t, J = 5.6 Hz, 1H), 8.47 (dd, J = 17.8, 11.7 Hz, 1H), 8.19 (d, J = 5.4 Hz, 3H), 6.51 (dd, J = 17.8, 1.4 Hz, 1H), 6.29 (d, J = 11.7 Hz, 1H), 4.76 (q, J = 7.2 Hz, 1H), 4.68 (dd, J = 9.6, 2.8 Hz, 1H), 4.04 (s, 3H), 3.98 (q, J = 7.6 Hz, 1H), 3.71 (s, 3H), 3.60 (s, 3H), 3.49 (dd, J = 7.6, 3.8 Hz, 1H), 3.44 (s, 3H), 3.24 (dq, J = 13.0, 6.5 Hz, 1H), 3.07 (dq, J = 12.7, 6.4 Hz, 1H), 2.25 - 2.13 (m, 1H), 2.00 (h, J = 6.8 Hz, 1H), 1.81 (d, J = 7.2 Hz, 4H), 1.72 - 1.63 (m, 1H), 1.60 (t, J = 7.5 Hz, 3H), 1.55 - 1.48 (m, 2H), 0.83 (dd, J = 6.9, 2.8 Hz, 6H), - 3.02 (s, 1H), - 3.24 (s, 1H).

[0338] Synthesis Example 9 - Synthesis of Chlorophyll Protein 3 - pyridinium iodopropane (Compound 9)

[0339]

[0340] Step 1:To a 50 mL RBF equipped with a reflux condenser and a stir bar and containing chlorophyll protein 3-chloropropyl (Compound 3) (300 mg, 0.585 mmol, 1 equiv) was added acetone (15 mL) and NaI (263 mg, 1.754 mmol, 3 equiv). The solution was heated at 65 °C under nitrogen and monitored by HPLC. After 4 h, another portion of NaI (263 mg, 1.754 mmol, 3 equiv) was added and heating was continued for a total of 30 h. The mixture was cooled and the acetone was removed by rotary evaporation. The residue was diluted with DCM (25 mL) and washed with water (25 mL), dried (Na2SO4) and concentrated by rotary evaporation to give the crude product as a dark green oil. The residue was purified by column chromatography (3 x 20 cm) using a gradient of 0%-0.5% MeOH / DCM. The fractions containing the major dark green spot (Rf = 0.50 in DCM) were combined to give chlorophyll protein 3-iodopropane as a dark green solid (270 mg, 76%) (HPLC purity: 93.3%), which was used directly in the next step. f = 0.50) of the fractions were combined to give Compound 9 as a dark green solid (90 mg, 66%).

[0341] Step 2: To a sealed tube (2.5 x 20 cm, with Teflon cap) containing chlorophyll protein 3-iodopropane (120 mg, 0.198 mmol, 1 equiv) and a stir bar was added MeCN (5 mL) and pyridine (157 mg, 1.985 mmol, 10 equiv). After flushing the tube with nitrogen and sealing the tube, the dark green mixture was stirred at 90 °C (300 rpm) for 20 h. The mixture was cooled, transferred to an RBF, and the solvent was removed by rotary evaporation to remove MeCN and most of the pyridine, giving the crude product as a dark green oil. The residue was purified by column chromatography (3 x 13 cm) using 8%-11% MeOH / DCM. The fractions containing the major dark green spot (Rf = 0.2 in 10% MeOH / DCM)

[0342] 11H NMR (400 MHz, CDCl3) δ 9.68 (s, 1H), 9.58 (s, 1H), 8.80 (m, 2H), 7.97 (dd, 1H), 7.41 (m, 2H), 7.12 (m, 1H), 6.47 (m, 2H), 6.24 (dd, 1H), 6.00 (dd, 1H), 4.39 (m, 1H), 4.27 (m, 1H), 3.80 (q, 2H), 3.74 (s, 3H), 3.61 (s, 3H), 3.44 (s, 3H), 3.30 (s, 3H), 3.25 (m, 1H), 2.73 (m, 1H), 1.71 (m, 4H), 1.63 - 1.55 (m, 7H), 1.52 - 1.35 (m, 2H), 1.00 (m, 1H), -2.47 (brs, 1H), -2.53 (brs, 1H).

[0343] Synthesis Example 10 - Synthesis of Chlorophyll Protein 3 - Triphenylphosphonium Iodopropane (Compound 10)

[0344]

[0345] To a sealed tube (2.5 x 20 cm, with Teflon nut) containing chlorophyll protein 3 - iodopropane (120 mg, 0.198 mmol, 1 equivalent) and a stir bar, MeCN (7 mL) and PPh3 (57 mg, 0.218 mmol, 1.1 equivalents) were added. After flushing the tube with nitrogen and sealing the tube, the dark - green mixture was stirred at 90 °C (300 rpm) for 20 h. The mixture was cooled, transferred to an RBF, and the solvent was removed by rotary evaporation to remove MeCN, giving a crude product as a dark - green oil. The residue was purified by column chromatography (3 x 13 cm) using 2% - 4% MeOH / DCM. The fractions containing the major dark - green spot (Rf = 0.15 in 5% MeOH / DCM) were combined to give Compound 10 as a dark - green solid (120 mg, 70%) (HPLC purity: 97.6%).

[0346] 11H NMR (400 MHz, CDCl3) δ 9.73 (m, 2H), 8.82 (s, 1H), 8.69 (s, 1H), 8.18 (dd, 1H), 7.02 (m, 3H), 6.60 (m, 6H), 6.40 (m, 7H), 6.19 (d, 1H), 4.72 (m, 1H), 4.50 (m, 1H), 3.94 (s, 3H), 3.88 (q, 2H), 3.68 (s, 3H), 3.48 (s, 3H), 3.39 (s, 3H), 3.20 (m, 1H), 2.72 (m, 1H), 2.61 (m, 1H), 2.08 (m, 1H), 1.80 - 1.71 (m, 6H), 1.25 - 1.10 (m, 1H), 0.40 - 0.30 (m, 1H), -2.25 (brs, 1H), -2.35 (brs, 1H).

[0347] Details of biological experiments

[0348] Example 1 - Determination of the solubility of chlorophyll - protein analogues

[0349] The maximum absorbance was used as a surrogate measure of solubility. The relevant chlorophyll - protein analogues were diluted to 50 μM in PBS (phosphate - buffered saline) solutions containing decreasing amounts of DMSO from 100% to 0%.

[0350] When required, polyvinylpyrrolidone (K30) was added to a final concentration of 1% w / v. Absorbance was measured using a Cytation 3 multimode plate reader (Biotek) in spectral scan mode, capturing spectra at 2 nm increments between 500 - 800 nm. An equivalent blank solution was also measured and subtracted accordingly. Each spectrum was normalized to have a minimum signal of 0 and a maximum signal of 100% in a pure DMSO solution (the most soluble state).

[0351] Example 2 - Cytotoxicity, phototoxicity and therapeutic index

[0352] Preparation of photosensitizer stock solution

[0353] Photosensitizers (such as chlorophyll - protein analogues, meso - tetra (4 - sulfonatophenyl) porphine disodium (supplied by Advanced Molecular Technologies, Scoresby) or talaporfin sodium (purchased from Focus Bioscience catalogue number HY - 16477 - 5MG)) were resuspended in 100% dimethyl sulfoxide (DMSO) at a concentration of 5.5 mM. The samples were stored in the dark at 4 °C.

[0354] Preparation of photosensitizer for in vitro studies

[0355] For in vitro experiments, the photosensitizer (stock solution 5.5 mM in 100% DMSO) was diluted 1:100 in the concentrated excipient solution (final 55 μM photosensitizer in 10% w / v Kollidon-12, 42.4% w / v polysorbate 80, 0.6% w / v anhydrous citric acid, 40% w / v ethanol, 1.0% DMSO). Serial dilutions were prepared at a constant 1:55 dilution in cell culture medium (Dulbecco's Modified Eagle's Medium / Nutrient Mixture F-12 (DMEM / F-12)) supplemented with 10% v / v fetal bovine serum, 100 U / mL penicillin, 100 μg / mL streptomycin, and the same excipient solution.

[0356] Cell culture

[0357] The human ovarian cancer cell line SKOV3 (ATCC# HTB-77) was maintained in Dulbecco's Modified Eagle's Medium / Nutrient Mixture F-12 (DMEM / F-12) supplemented with 10% v / v fetal bovine serum, 100 U / mL penicillin, and 100 μg / mL streptomycin. Monolayer cultures were grown in a humidified incubator at 37 °C with 5% CO2. Once the cells reached approximately 80% confluence, the used medium was replaced with medium containing the desired concentration of the photosensitizer, and the cells were incubated for the required period of time to allow photosensitizer uptake.

[0358] Statistical analysis

[0359] All data were analyzed using GraphPad PRISM v8.3.1 (549) (GraphPad Software, CA). Spectral absorbance and viability measurements were normalized in the range of 0% - 100%, with a minimum of 0 and a maximum determined by the data set. Dose responses were determined using a sigmoidal four-parameter non-linear regression with variable slope, and the IC10 or IC90 for each compound was calculated. All data are shown as mean ± SD (where appropriate).

[0360] Cytotoxicity

[0361] SKOV3 cells were seeded at a cell density of 5000 cells per well in 100 μl of medium in a 96-well black-walled plate (Greiner# 655090). At approximately 60% confluence, the medium was aspirated and replaced with fresh medium containing the relevant chlorophyll protein analog in DMSO at 0 - 100 μM. The cells were incubated for an additional 24 hours to allow uptake of the chlorophyll protein analog.

[0362] To test the intrinsic cytotoxicity (i.e., "dark toxicity") of chlorophyll protein analogs, the medium was replaced with fresh medium containing 10% (v / v) AlamarBlue cell viability reagent (ThermoFisher) after 24 h, and the cells were incubated at 37 °C for 6 h. Untreated cells were used as controls. Fluorescence (Ex 555 nm / Em 596 nm) was measured using a Cytation 3 cell imaging multimode reader (Biotek), and cytotoxicity was evaluated based on the percentage of remaining live cells. All measurements were performed in quadruplicate.

[0363] Phototoxicity

[0364] SKOV3 cells were seeded in a 96-well black-walled plate (Greiner #655090) at a cell density of 5000 cells in 100 μl of medium per well. At approximately 60% confluence, the medium was aspirated and replaced with fresh medium containing the relevant chlorophyll protein analog at 0 - 100 μM in DMSO. The cells were incubated for an additional 24 h to allow uptake of the chlorophyll protein analog.

[0365] To test for phototoxicity, cells incubated with chlorophyll protein analogs (0 - 10 μM in DMSO) had their medium changed after 24 h (as described above), and then were exposed to a 652 nm laser (Invion) at a laser density of 50 mW / cm 2 for 5 min (total of 15 J / cm 2 ). After activation, the cells were cultured for an additional 24 h. Then the medium was replaced with fresh medium containing AlamarBlue, and the percentage of remaining live cells was evaluated as described above. Controls included cells treated with chlorophyll protein analogs but not laser-activated; cells not treated with chlorophyll protein analogs but laser-treated; and untreated controls. All measurements were performed in quadruplicate.

[0366] Toxicity profiles of chlorophyll protein analogs

[0367] The phototoxicity and intrinsic cytotoxicity (i.e., "dark toxicity") of several chlorophyll protein analogs were evaluated using SKOV3 ovarian cancer cells as described previously. For comparison purposes, the chlorophyll protein analogs were compared to chlorin e4 disodium and talaporfin sodium, a clinically approved photosensitizer for the photodynamic therapy of lung cancer. Phototoxicity IC90 values and dark toxicity IC10 values were calculated using a log[ inhibitor]-versus-normalized response dose curve with variable slope, using the formula Y = 100 / (1 + (IC90 / X)^Hill slope (phototoxicity IC90)) or Y = 100 / (1 + (IC10 / X)^Hill slope (dark toxicity IC10)).

[0368] The in vitro phototoxicity of chlorophyll protein analogs was significantly lower than that of all the chlorophyll protein analogs tested, with IC90 values in the μM range (compared to the nM range of chlorophyll protein analogs). Compounds 4, 5, 7, and 8 had greater phototoxicity than all other substances tested, with apparent IC90 < 100 nM in each case. Thus, compared to the clinically approved photosensitizer talaporfin sodium, the chlorophyll protein analogs achieved an approximately 450-fold increase in phototoxicity.

[0369] Therapeutic index of chlorophyll protein analogs

[0370] To evaluate the therapeutic potential of the chlorophyll protein analogs, the therapeutic index (TI) was calculated. TI provides a quantitative measure for describing relative drug safety by comparing the drug concentration required for the desired effect with the concentration that causes adverse off-target toxicity. TI was calculated using the phototoxicity IC90 versus the dark toxicity IC10.

[0371] The TI values are provided in Table 1. Talaporfin sodium had the lowest therapeutic index (TI = 0.49), and chlorin e4 disodium was only slightly better (TI = 1.89), indicating that although its relative cytotoxicity was low, its potential therapeutic window for use was small. The chlorophyll protein analogs of the present invention had a relatively significantly improved TI and significantly greater phototoxicity (Table 1).

[0372] Therefore, the chlorophyll protein analogs of the present invention have a better ideal therapeutic index than the photosensitizers used in clinical applications. In addition, the greater phototoxicity of the chlorophyll protein analogs indicates their potential for use at greatly reduced doses in vivo. Thus, the chlorophyll protein analogs have an acceptable spectrum of therapeutic characteristics for clinical applications.

[0373] Table 1. Toxicity characteristics and therapeutic index of chlorophyll protein analogs:

[0374]

[0375]

[0376] It should be understood that the present invention has been described above only by way of example. The embodiments are not intended to limit the scope of the present invention. Various modifications and implementation schemes can be made without departing from the scope and spirit of the present invention, and the scope and spirit of the present invention are defined only by the appended claims.

Claims

1. A compound of formula (I) or a complex of formula (II): or a pharmaceutically acceptable salt thereof, wherein: -R 1 selected from -CH2OR 2 , -CH2SR 2 , -CH2S(O)R 2 , -CH2S(O)2R 2 , -CH2N(R 2 )2 or -R 2x ; -R 2 each independently selected from -H, -C(O)R 4 , -C(O)-OR 4 , -C(O)-SR 4 , -C(O)-N(R 4 )2, -C(S)-OR 4 , -C(S)-SR 4 , -C(S)-N(R 4 )2, -R α -H, -R β , -R α -R β , -R α -OH, -R α -OR β , -R α -SH, -R α -SR β , -R α -S(O)R β , -R α -S(O)2R β , -R α -NH2, -R α -NH(R β ), -R α -N(R β )2, -R α -N3, -R α -X, -R α -[N(R 5 )3]Y, -R α -[P(R 5 )3]Y, -R α -[R 6 Y, -R α -[N(R 5 )2(R 5’ )], -R α -[P(R 5 )2(R 5’ )] or -R α -[R 6’ ; -R 2x Selected from -H, -R α -H, -R α -R β , -R α -OH, -R α -OR β , -R α -SH, -R α -SR β , -R α -S(O)R β , -R α -S(O)2R β , -R α -NH2, -R α -NH(R β ), -R α -N(R β )2, -R α -N3, -R α -X, -R α -[N(R 5 )3]Y, -R α -[P(R 5 )3]Y, -R α -[R 6 Y, -R α -[N(R 5 )2(R 5’ )], -R α -[P(R 5 )2(R 5’ )] or -R α -[R 6’ ; -R 4 Each independently selected from -H, -R α -H, -R β , -R α -R β , -R α -OH, -R α -OR β , -R α -SH, -R α -SR β , -R α -S(O)R β , -R α -S(O)2R β , -R α -NH2, -R α -NH(R β ), -R α -N(R β )2, -R α -X, -R α -[N(R 5 )3]Y, -R α -[P(R 5 )3]Y, -R α -[R 6 Y, -R α -[N(R 5 )2(R 5’ )], -R α -[P(R 5 )2(R 5’ )] or -R α -[R 6’ ; -R α - Each independently selected from C1-C 42 alkylene, wherein the alkylene may optionally be substituted by one or more C1-C4 alkyl groups, C1-C4 haloalkyl groups or halogen atoms, and wherein one or more carbon atoms in the main chain of the alkylene may optionally be replaced independently by a heteroatom or group selected from O, S, NH or NMe; -R β Each independently is a saturated or unsaturated hydrocarbon group, wherein the hydrocarbon group may be straight-chain or branched, or may be or include a cyclic group, wherein the hydrocarbon group is optionally substituted, and wherein the hydrocarbon group optionally includes one or more heteroatoms N, O, S, P or Se in its carbon skeleton; -R 5 each independently selected from C1-C4 alkyl, C1-C4 haloalkyl, -(CH2CH2O) n -H, -(CH2CH2O) n -CH3, phenyl or C5-C6 heteroaryl, wherein the phenyl or C5-C6 heteroaryl may optionally be substituted by one or more C1-C6 alkyl, C1-C6 haloalkyl, -O(C1-C6 alkyl), -O(C1-C6 haloalkyl), halogen, -CO2H, -CO2Z, -CO2NH2, -O-(CH2CH2O) n -H or -O-(CH2CH2O) n -CH3 group; -R 5’ selected from C1-C4 alkyl, C1-C4 haloalkyl, -(CH2CH2O) n -H, -(CH2CH2O) n -CH3, phenyl or C5-C6 heteroaryl, each of which is substituted by -CO2 - and wherein the phenyl or C5-C6 heteroaryl may optionally be further substituted by one or more C1-C6 alkyl, C1-C6 haloalkyl, -O(C1-C6 alkyl), -O(C1-C6 haloalkyl), halogen, -CO2H, -CO2Z, -CO2NH2, -O-(CH2CH2O) n -H or -O-(CH2CH2O) n -CH3 groups; -R 6 is optionally substituted by one or more C1-C6 alkyl, C1-C6 haloalkyl, -O(C1-C6 alkyl), -O(C1-C6 haloalkyl), halogen, -CO2H, -CO2Z, -CO2NH2, -O-(CH2CH2O) n -H or -O-(CH2CH2O) n -CH3 group-substituted -[NC5H5]; -R 6’ is -[NC5H5], which is substituted by -CO2 - and optionally further substituted by one or more C1-C6 alkyl, C1-C6 haloalkyl, -O(C1-C6 alkyl), -O(C1-C6 haloalkyl), halogen, -CO2H, -CO2Z, -CO2NH2, -O-(CH2CH2O) n -H or -O-(CH2CH2O) n -CH3 groups; n is 1, 2, 3, 4, 5 or 6; X is a halogen group; Y is a counteranion; Z is a countercation; and M 2+ is a metal cation.

2. The compound or complex according to claim 1, wherein each -R α - is independently selected from C1-C6 alkylene.

3. A compound or complex according to any one of the preceding claims, wherein -R 2 , -R 2x or -R 4 is at least one selected from -R α -OR β , -R α -SR β , -R α -S(O)R β or -R α -S(O)2R β , and -R β is a glycosyl group.

4. The compound or complex according to claim 3, wherein -R β is a glycosyl group selected from the following:

5. The compound or complex according to claim 4, wherein the glycosyl group is:

6. The compound or complex according to claim 3, wherein -Rβ is a glycosyl group selected from the following: wherein -R 7 is selected from C1-C4 alkyl groups.

7. The compound or complex according to claim 6, wherein -R 7 is methyl.

8. A compound or complex according to any one of the preceding claims, wherein -R 1 is selected from -CH2OR 2 or -CH2SR 2 , wherein -R 2 is selected from -H, -C(O)R 4 , -R α -H, -R β , -R α -R β , -R α -OR β or -R α -SR β , and -R β is a glycosyl group, and -R 4 is a C1-C4 alkyl group.

9. The compound or complex according to claim 1, wherein the compound or complex is: or a metal cation complex thereof or a pharmaceutically acceptable salt thereof.

10. The compound or complex according to any one of the preceding claims, wherein the compound or complex is for use in medicine.

11. The compound or complex according to any one of the preceding claims, wherein the compound or complex is for use in photodynamic therapy or cytoluminescence therapy.

12. The compound or complex according to any one of the preceding claims, wherein the compound or complex is for the treatment of atherosclerosis; multiple sclerosis; diabetes; diabetic retinopathy; arthritis; rheumatoid arthritis; fungal, viral, chlamydial, bacterial, nanobacterial or parasitic infectious diseases; HIV; AIDS; sars virus (preferably severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)), Asian (avian) influenza virus, dengue virus, herpes simplex or varicella-zoster infection; hepatitis; viral hepatitis; cardiovascular diseases; coronary artery stenosis; carotid artery stenosis; intermittent claudication; skin disorders; acne; psoriasis; diseases characterized by excessive proliferation of benign or malignant cells or areas of neovascularization; benign or malignant tumors; early cancer; cervical dysplasia; soft tissue sarcoma; germ cell tumor; retinoblastoma; age-related macular degeneration; lymphoma; Hodgkin lymphoma; head and neck cancer; oral or mouth cancer; or blood cancer, prostate cancer, cervical cancer, uterine cancer, vaginal cancer or other female accessory cancers, breast cancer, nasopharyngeal cancer, tracheal cancer, laryngeal cancer, bronchial cancer, bronchioloalveolar carcinoma, lung cancer, cancer of the hollow organs, esophageal cancer, gastric cancer, cholangiocarcinoma, intestinal cancer, colon cancer, colorectal cancer, rectal cancer, bladder cancer, ureteral cancer, kidney cancer, liver cancer, gallbladder cancer, spleen cancer, brain cancer, lymphatic system cancer, bone cancer, skin cancer or pancreatic cancer.

13. The compound or complex according to any one of the preceding claims, wherein the compound or complex is for the treatment of a disease characterized by excessive proliferation of benign or malignant cells or areas of neovascularization.

14. The compound or complex according to any one of the preceding claims, wherein the compound or complex is for the treatment of benign or malignant tumors.

15. A compound or complex according to any one of the preceding claims, wherein the compound or complex is for the treatment of early cancer; cervical dysplasia; soft tissue sarcoma; germ cell tumor; retinoblastoma; age-related macular degeneration; lymphoma; Hodgkin lymphoma; head and neck cancer; oral or mouth cancer; or blood cancer, prostate cancer, cervical cancer, uterine cancer, vaginal cancer or other female accessory cancers, breast cancer, nasopharyngeal cancer, tracheal cancer, laryngeal cancer, bronchial cancer, bronchioloalveolar carcinoma, lung cancer, hollow organ cancer, esophageal cancer, gastric cancer, cholangiocarcinoma, intestinal cancer, colon cancer, colorectal cancer, rectal cancer, bladder cancer, ureteral cancer, kidney cancer, liver cancer, gallbladder cancer, spleen cancer, brain cancer, lymphatic system cancer, bone cancer, skin cancer or pancreatic cancer.

16. A compound or complex according to any one of the preceding claims, wherein the compound or complex is for use in photodynamic diagnosis.

17. A compound or complex according to any one of the preceding claims, wherein the compound is suitable for administration before irradiation is applied.

18. A compound or complex according to claim 17, wherein the irradiation is electromagnetic radiation having a wavelength in the range of 500 nm to 1000 nm.

19. A pharmaceutical composition comprising a compound or complex according to any one of the preceding claims and a pharmaceutically acceptable carrier or diluent.

20. The pharmaceutical composition according to claim 19, wherein the pharmaceutical composition further comprises polyvinylpyrrolidone.

21. The pharmaceutical composition according to claim 19 or 20, wherein the pharmaceutical composition further comprises an immune checkpoint inhibitor.

22. The pharmaceutical composition according to claim 21, wherein the immune checkpoint inhibitor is selected from pembrolizumab, nivolumab, cemiplimab, atezolizumab, avelumab, durvalumab or ipilimumab.

23. The pharmaceutical composition according to any one of claims 19 - 22, wherein the pharmaceutical composition is for use in photodynamic therapy or cytoluminescence therapy.

24. The pharmaceutical composition according to any one of claims 19 - 23, wherein the pharmaceutical composition is for the treatment of atherosclerosis; multiple sclerosis; diabetes; diabetic retinopathy; arthritis; rheumatoid arthritis; fungal, viral, chlamydial, bacterial, nanobacterial or parasitic infectious diseases; HIV; AIDS; sars virus (preferably severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)), Asian (avian) influenza virus, dengue virus, herpes simplex or varicella-zoster infection; hepatitis; viral hepatitis; cardiovascular diseases; coronary artery stenosis; carotid artery stenosis; intermittent claudication; skin disorders; acne; psoriasis; diseases characterized by excessive proliferation of benign or malignant cells or areas of new blood vessel formation; benign or malignant tumors; early cancer; cervical dysplasia; soft tissue sarcoma; germ cell tumor; retinoblastoma; age-related macular degeneration; lymphoma; Hodgkin's lymphoma; head and neck cancer; oral or mouth cancer; or blood cancer, prostate cancer, cervical cancer, uterine cancer, vaginal cancer or other female accessory cancers, breast cancer, nasopharyngeal cancer, tracheal cancer, laryngeal cancer, bronchial cancer, bronchioloalveolar carcinoma, lung cancer, cancer of the hollow organs, esophageal cancer, gastric cancer, cholangiocarcinoma, intestinal cancer, colon cancer, colorectal cancer, rectal cancer, bladder cancer, ureteral cancer, kidney cancer, liver cancer, gallbladder cancer, spleen cancer, brain cancer, lymphatic system cancer, bone cancer, skin cancer or pancreatic cancer.

25. The pharmaceutical composition according to any one of claims 19 - 24, wherein the pharmaceutical composition is for the treatment of diseases characterized by excessive proliferation of benign or malignant cells or areas of new blood vessel formation.

26. The pharmaceutical composition according to any one of claims 19 - 25, wherein the pharmaceutical composition is for the treatment of benign or malignant tumors.

27. The pharmaceutical composition according to any one of claims 19 - 26, wherein the pharmaceutical composition is for the treatment of early cancer; cervical dysplasia; soft tissue sarcoma; germ cell tumor; retinoblastoma; age-related macular degeneration; lymphoma; Hodgkin's lymphoma; head and neck cancer; oral or mouth cancer; or blood cancer, prostate cancer, cervical cancer, uterine cancer, vaginal cancer or other female accessory cancers, breast cancer, nasopharyngeal cancer, tracheal cancer, laryngeal cancer, bronchial cancer, bronchioloalveolar carcinoma, lung cancer, cancer of the hollow organs, esophageal cancer, gastric cancer, cholangiocarcinoma, intestinal cancer, colon cancer, colorectal cancer, rectal cancer, bladder cancer, ureteral cancer, kidney cancer, liver cancer, gallbladder cancer, spleen cancer, brain cancer, lymphatic system cancer, bone cancer, skin cancer or pancreatic cancer.

28. The pharmaceutical composition according to claim 19 or 20, wherein the pharmaceutical composition is for use in photodynamic diagnosis.

29. The pharmaceutical composition according to any one of claims 19 - 28, wherein the pharmaceutical composition is suitable for administration before the administration of irradiation.

30. The pharmaceutical composition according to claim 29, wherein the irradiation is electromagnetic radiation having a wavelength in the range of 500 nm to 1000 nm.

31. The pharmaceutical composition according to any one of claims 19 - 30, wherein the pharmaceutical composition is in a form suitable for oral, parenteral (including intravenous, subcutaneous, intramuscular, intradermal, intratracheal, intraperitoneal, intratumoral, intra-articular, intra-abdominal, intracranial, and epidural), transdermal, airway (aerosol), rectal, vaginal, or topical (including buccal, mucosal, and sublingual) administration.

32. The pharmaceutical composition according to claim 31, wherein the pharmaceutical composition is in a form suitable for oral or parenteral administration.

33. Use of the compound or complex according to any one of claims 1 - 18 in the manufacture of a medicament for the treatment of the following diseases: atherosclerosis; multiple sclerosis; diabetes; diabetic retinopathy; arthritis; rheumatoid arthritis; fungal, viral, chlamydial, bacterial, nanobacterial, or parasitic infectious diseases; HIV; AIDS; sars virus (preferably severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)), Asian (avian) influenza virus, dengue virus, herpes simplex or varicella-zoster infection; hepatitis; viral hepatitis; cardiovascular diseases; coronary artery stenosis; carotid artery stenosis; intermittent claudication; skin disorders; acne; psoriasis; diseases characterized by excessive proliferation of benign or malignant cells or areas of new blood vessel formation; benign or malignant tumors; early cancer; cervical dysplasia; soft tissue sarcoma; germ cell tumor; retinoblastoma; age-related macular degeneration; lymphoma; Hodgkin lymphoma; head and neck cancer; oral or mouth cancer; or blood cancer, prostate cancer, cervical cancer, uterine cancer, vaginal cancer, or other female accessory cancers, breast cancer, nasopharyngeal cancer, tracheal cancer, laryngeal cancer, bronchial cancer, bronchioloalveolar carcinoma, lung cancer, cancer of the hollow organs, esophageal cancer, gastric cancer, cholangiocarcinoma, intestinal cancer, colon cancer, colorectal cancer, rectal cancer, bladder cancer, ureteral cancer, kidney cancer, liver cancer, gallbladder cancer, spleen cancer, brain cancer, lymphatic system cancer, bone cancer, skin cancer, or pancreatic cancer.

34. Use of the compound or complex according to any one of claims 1 - 18 in the manufacture of a phototherapeutic agent for photodynamic therapy or cytoluminescence therapy.

35. The use according to claim 34, wherein the photo-therapeutic agent is used for treating atherosclerosis; multiple sclerosis; diabetes; diabetic retinopathy; arthritis; rheumatoid arthritis; fungal, viral, chlamydial, bacterial, nanobacterial or parasitic infectious diseases; HIV; AIDS; sars virus (preferably severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)), Asian (avian) influenza virus, dengue virus, herpes simplex or varicella-zoster infection; hepatitis; viral hepatitis; cardiovascular diseases; coronary artery stenosis; carotid artery stenosis; intermittent claudication; skin disorders; acne; psoriasis; diseases characterized by excessive proliferation of benign or malignant cells or areas of neovascularization; benign or malignant tumors; early cancer; cervical dysplasia; soft tissue sarcoma; germ cell tumor; retinoblastoma; age-related macular degeneration; lymphoma; Hodgkin lymphoma; head and neck cancer; oral or mouth cancer; or blood cancer, prostate cancer, cervical cancer, uterine cancer, vaginal cancer or other female accessory cancers, breast cancer, nasopharyngeal cancer, tracheal cancer, laryngeal cancer, bronchial cancer, bronchioloalveolar carcinoma, lung cancer, cancer of hollow organs, esophageal cancer, gastric cancer, cholangiocarcinoma, intestinal cancer, colon cancer, colorectal cancer, rectal cancer, bladder cancer, ureteral cancer, kidney cancer, liver cancer, gallbladder cancer, spleen cancer, brain cancer, lymphatic system cancer, bone cancer, skin cancer or pancreatic cancer.

36. The use according to any one of claims 33-35, wherein the agent or the photo-therapeutic agent is used for treating diseases characterized by excessive proliferation of benign or malignant cells or areas of neovascularization.

37. The use according to any one of claims 33-36, wherein the agent or the photo-therapeutic agent is used for treating benign or malignant tumors.

38. The use according to any one of claims 33-37, wherein the agent or the photo-therapeutic agent is used for treating early cancer; cervical dysplasia; soft tissue sarcoma; germ cell tumor; retinoblastoma; age-related macular degeneration; lymphoma; Hodgkin lymphoma; head and neck cancer; oral or mouth cancer; or blood cancer, prostate cancer, cervical cancer, uterine cancer, vaginal cancer or other female accessory cancers, breast cancer, nasopharyngeal cancer, tracheal cancer, laryngeal cancer, bronchial cancer, bronchioloalveolar carcinoma, lung cancer, cancer of hollow organs, esophageal cancer, gastric cancer, cholangiocarcinoma, intestinal cancer, colon cancer, colorectal cancer, rectal cancer, bladder cancer, ureteral cancer, kidney cancer, liver cancer, gallbladder cancer, spleen cancer, brain cancer, lymphatic system cancer, bone cancer, skin cancer or pancreatic cancer.

39. The use of the compound or complex according to any one of claims 1-18 in the manufacture of a photo-diagnostic agent for photodynamic diagnosis.

40. The use according to any one of claims 33-39, wherein the agent, the photo-therapeutic agent or the photo-diagnostic agent is suitable for administration before irradiation.

41. The use according to claim 40, wherein the irradiation is electromagnetic radiation with a wavelength in the range of 500 nm to 1000 nm.

42. A method for treating atherosclerosis; multiple sclerosis; diabetes; diabetic retinopathy; arthritis; rheumatoid arthritis; fungal, viral, chlamydial, bacterial, nanobacterial or parasitic infectious diseases; HIV; AIDS; sars virus (preferably severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)), Asian (avian) influenza virus, dengue virus, herpes simplex or varicella-zoster infection; hepatitis; viral hepatitis; cardiovascular diseases; coronary artery stenosis; carotid artery stenosis; intermittent claudication; skin disorders; acne; psoriasis; diseases characterized by excessive proliferation of benign or malignant cells or areas of new blood vessel formation; benign or malignant tumors; early cancer; cervical dysplasia; soft tissue sarcoma; germ cell tumor; retinoblastoma; age-related macular degeneration; lymphoma; Hodgkin lymphoma; head and neck cancer; oral or mouth cancer; or blood cancer, prostate cancer, cervical cancer, uterine cancer, vaginal cancer or other female accessory cancers, breast cancer, nasopharyngeal cancer, tracheal cancer, laryngeal cancer, bronchial cancer, bronchioloalveolar carcinoma, lung cancer, cancer of hollow organs, esophageal cancer, gastric cancer, cholangiocarcinoma, intestinal cancer, colon cancer, colorectal cancer, rectal cancer, bladder cancer, ureteral cancer, kidney cancer, liver cancer, gallbladder cancer, spleen cancer, brain cancer, lymphatic system cancer, bone cancer, skin cancer or pancreatic cancer; the method comprising administering to a human or animal in need thereof a therapeutically effective amount of a compound or complex according to any one of claims 1-18.

43. A method of photodynamic therapy or cytoluminescence therapy for a human or animal disease, the method comprising administering to a human or animal in need thereof a therapeutically effective amount of a compound or complex according to any one of claims 1-18.

44. The method according to claim 43, wherein the human or animal disease is atherosclerosis; multiple sclerosis; diabetes; diabetic retinopathy; arthritis; rheumatoid arthritis; fungal, viral, chlamydial, bacterial, nanobacterial or parasitic infectious diseases; HIV; AIDS; sars virus (preferably severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)), Asian (avian) influenza virus, dengue virus, herpes simplex or varicella-zoster infection; hepatitis; viral hepatitis; cardiovascular diseases; coronary artery stenosis; carotid artery stenosis; intermittent claudication; skin disorders; acne; psoriasis; diseases characterized by excessive proliferation of benign or malignant cells or areas of new blood vessel formation; benign or malignant tumors; early cancer; cervical dysplasia; soft tissue sarcoma; germ cell tumor; retinoblastoma; age-related macular degeneration; lymphoma; Hodgkin lymphoma; head and neck cancer; oral or mouth cancer; or blood cancer, prostate cancer, cervical cancer, uterine cancer, vaginal cancer or other female accessory cancers, breast cancer, nasopharyngeal cancer, tracheal cancer, laryngeal cancer, bronchial cancer, bronchioloalveolar carcinoma, lung cancer, cancer of hollow organs, esophageal cancer, gastric cancer, cholangiocarcinoma, intestinal cancer, colon cancer, colorectal cancer, rectal cancer, bladder cancer, ureteral cancer, kidney cancer, liver cancer, gallbladder cancer, spleen cancer, brain cancer, lymphatic system cancer, bone cancer, skin cancer or pancreatic cancer.

45. A method according to any one of claims 42 - 44, wherein the human or animal disease is characterized by excessive proliferation of benign or malignant cells or by regions of neovascularization.

46. A method according to any one of claims 42 - 45, wherein the human or animal disease is a benign or malignant tumor.

47. A method according to any one of claims 42 - 46, wherein the human or animal disease is early - stage cancer; cervical dysplasia; soft - tissue sarcoma; germ - cell tumor; retinoblastoma; age - related macular degeneration; lymphoma; Hodgkin's lymphoma; head and neck cancer; oral or mouth cancer; or blood cancer, prostate cancer, cervical cancer, uterine cancer, vaginal cancer or other female adnexal cancers, breast cancer, nasopharyngeal cancer, tracheal cancer, laryngeal cancer, bronchial cancer, bronchioloalveolar carcinoma, lung cancer, cancer of hollow organs, esophageal cancer, gastric cancer, cholangiocarcinoma, intestinal cancer, colon cancer, colorectal cancer, rectal cancer, bladder cancer, ureteral cancer, kidney cancer, liver cancer, gallbladder cancer, spleen cancer, brain cancer, lymphatic system cancer, bone cancer, skin cancer or pancreatic cancer.

48. A method for photodynamic diagnosis of a human or animal disease, the method comprising administering to a human or animal a diagnostically effective amount of a compound or complex according to any one of claims 1 - 18.

49. A method according to any one of claims 42 - 48, wherein the human or animal is irradiated after administering a compound or complex according to any one of claims 1 - 18.

50. The method according to claim 49, wherein the irradiation is electromagnetic radiation having a wavelength in the range of 500 nm to 1000 nm.

51. A pharmaceutical combination or kit, the pharmaceutical combination or kit comprising: (a) A compound or complex according to any one of claims 1 - 18; and (b) An immune checkpoint inhibitor.

52. The pharmaceutical combination or kit according to claim 51, wherein the immune checkpoint inhibitor is selected from pembrolizumab, nivolumab, cemiplimab, atezolizumab, avelumab, durvalumab or ipilimumab.

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