Novel chlorin E6 analogs

Abstract

The invention relates to a dihydroporphin e6 analogue and a pharmaceutically acceptable salt thereof, and a composition containing the dihydroporphin e6 analogue and the pharmaceutically acceptable salt thereof. The chlorin e6 analogs and pharmaceutically acceptable salts thereof are suitable for use in photodynamic therapy, cytoluminescence therapy and photodynamic diagnosis, for example for the treatment or detection of tumors or for antiviral therapy. The invention also relates to the use of dihydroporphin e6 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 dihydrochlorin e6 analogs and pharmaceutically acceptable salts thereof, as well as compositions comprising dihydrochlorin e6 analogs and pharmaceutically acceptable salts thereof. Dihydrochlorin e6 analogs and pharmaceutically acceptable salts thereof are suitable for use in photodynamic therapy, cell luminescence therapy and photodynamic diagnosis, for example, for treating or detecting tumors or for antiviral treatment. The present invention also relates to the use of dihydrochlorin e6 analogs and pharmaceutically acceptable salts thereof in the manufacture of phototherapeutic agents or photodiagnostic agents, and to methods for photodynamic therapy, cell luminescence therapy or photodynamic diagnosis, for example, for treating or detecting tumors or for antiviral treatment.

[0002] The structure of "dihydrochlorin e6" is shown below:

[0003] Background Art

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

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

[0006] Chlorin e4 has been shown to exhibit good photosensitizing activity. Chlorin e4 has been shown to have protective effects against indomethacin-induced gastric lesions in rats and acute liver injury induced by TAA or CCl4 in mice. Therefore, chlorin e4 has been suggested as a promising new drug candidate for gastric ulcer protection and liver damage protection. WO 2009 / 040411 proposes the use of chlorin e4 zinc complexes in photodynamic therapy, and WO 2014 / 091241 proposes the use of chlorin e4 disodium in photodynamic therapy.

[0007]

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

[0009] The 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 Selected from -CH2OR 2 、-CH2SR 2 、-CH2S(O)R 2 、-CH2S(O)2R 2 、-CH2N(R 2 )2. -R 2 、-C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )2. -C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R 3 )2;

[0013] -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 -X, -R α -[N(R 5 )3]Y、-R α -[P(R 5)3]Y、-R α -[R 8 ]Y、-R α -[N(R 5 )2(R 5’ )]、-R α -[P(R 5 )2(R 5’ )] or -R α -[R 8’ ];

[0014] -R 3 and -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 8 ]Y、-R α -[N(R 5 )2(R 5’ )]、-R α -[P(R 5 )2(R 5’ )] or -R α -[R 8’ ];

[0015] -R α - each independently selected from C1-C 42Alkylene, wherein the alkylene may be optionally substituted with one or more (such as one, two, three, four or five) C1-C4 alkyl, C1-C4 haloalkyl or halo, and wherein one or more (such as one, two, three, four, five, six, seven, eight, nine or ten) carbon atoms in the backbone of the alkylene may be optionally replaced with heteroatoms or groups independently selected from O, S, NH or NMe;

[0016] -R β each independently a saturated or unsaturated hydrocarbon group, wherein the hydrocarbon group may be linear or branched, or may be or include a cyclic group, wherein the hydrocarbon group may be optionally 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;

[0017] -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 be optionally replaced 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 substitution;

[0018] -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 replaced by -CO2 ￣ Substituted, wherein the phenyl or C5-C6 heteroaryl may be 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 substitution;

[0019] -R 6 Selected from -C(O)-OR 3、-C(O)-SR 3 、-C(O)-N(R 3 )2. -C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R 3 )2;

[0020] -R 7 Selected from -C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )2. -C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R 3 )2;

[0021] -R 8 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 -[NC5H5] substituted with -CH3 group;

[0022] -R 8’ is -[NC5H5], which is replaced 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), halo, -CO2H, -CO2Z, -CO2NH2, -O-(CH2CH2O) n -H or -O-(CH2CH2O) n -CH3 group substitution;

[0023] n is 1, 2, 3, 4, 5, or 6;

[0024] X is a halogen group;

[0025] Y is a counter anion;

[0026] Z is a counter cation; and

[0027] M 2+ It is a metal cation;

[0028] Provided that the compound or complex is not:

[0029] (1) (7S,8S)-7-(2-carboxyethyl)-5-(carboxymethyl)-18-ethyl-2,8,12,17-tetramethyl-13-vinyl-7H,8H-porphyrin-3-carboxylic acid [dihydrochlorin e6];

[0030] (2) (7S,8S)-18-ethyl-5-(2-methoxy-2-oxoethyl)-7-(3-methoxy-3-oxopropyl)-2,8,12,17-tetramethyl-13-vinyl-7H,8H-porphyrin-3-carboxylic acid;

[0031] (3) 2-((7S,8S)-18-ethyl-7-(3-methoxy-3-oxopropyl)-3-(methoxycarbonyl)-2,8,12,17-tetramethyl-13-vinyl-7H,8H-porphyrin-5-yl)acetic acid;

[0032] (4) 3-((7S,8S)-18-ethyl-5-(2-methoxy-2-oxoethyl)-3-(methoxycarbonyl)-2,8,12,17-tetramethyl-13-vinyl-7H,8H-porphyrin-7-yl)propanoic acid;

[0033] (5) (7S,8S)-5-(carboxymethyl)-18-ethyl-7-(3-methoxy-3-oxopropyl)-2,8,12,17-tetramethyl-13-vinyl-7H,8H-porphyrin-3-carboxylic acid;

[0034] (6) (7S,8S)-7-(2-carboxyethyl)-18-ethyl-5-(2-methoxy-2-oxoethyl)-2,8,12,17-tetramethyl-13-vinyl-7H,8H-porphyrin-3-carboxylic acid;

[0035] (7) 3-((7S,8S)-5-(carboxymethyl)-18-ethyl-3-(methoxycarbonyl)-2,8,12,17-tetramethyl-13-vinyl-7H,8H-porphyrin-7-yl)propanoic acid;

[0036] (8) (7S,8S)-18-ethyl-5-(2-methoxy-2-oxoethyl)-7-(3-methoxy-3-oxopropyl)-2,8,12,17-tetramethyl-13-vinyl-7H,8H-porphyrin-3-carboxylic acid methyl ester [dihydrochlorin e6 trimethyl ester];

[0037] (9) methyl 3-(3-carbamoyl-18-ethyl-5-(2-methoxy-2-oxoethyl)-2,8,12,17-tetramethyl-13-vinyl-7H,8H-porphyrin-7-yl)propanoate;

[0038] (10) methyl 3-(18-ethyl-5-(2-methoxy-2-oxoethyl)-2,8,12,17-tetramethyl-3-(methylcarbamoyl)-13-vinyl-7H,8H-porphyrin-7-yl)propanoate;

[0039] (11) methyl 3-(18-ethyl-3-(ethylcarbamoyl)-5-(2-methoxy-2-oxoethyl)-2,8,12,17-tetramethyl-13-vinyl-7H,8H-porphyrin-7-yl)propanoate;

[0040] (12) methyl 3-(3-(benzylcarbamoyl)-18-ethyl-5-(2-methoxy-2-oxoethyl)-2,8,12,17-tetramethyl-13-vinyl-7H,8H-porphyrin-7-yl)propanoate;

[0041] (13) methyl 3-(18-ethyl-5-(2-methoxy-2-oxoethyl)-2,8,12,17-tetramethyl-3-(piperidine-1-carbonyl)-13-vinyl-7H,8H-porphyrin-7-yl)propanoate;

[0042] (14) 5-(2-((3-((5-amino-1-carboxypentyl)carbamoyl)-17-(carboxymethyl)-14-(3-guanidinopropyl)-20-(hydroxymethyl)-1,9,12,15,18,21-hexaoxodocosahydro-7H-pyrrolo[2,1-g][1,2]dithia[5,8,11,14,17,20]hexaazacyclotricosan-8-yl)amino)-2-oxoethyl)-7-(2-carboxyethyl)-18-ethyl-2,8,12,17-tetramethyl-13-vinyl-7H,8H-porphyrin-3-carboxylic acid;

[0043] (15) (4-((2-(2-(3-carboxy-7-(2-carboxyethyl)-18-ethyl-2,8,12,17-tetramethyl-13-vinyl-7H,8H-porphyrin-5-yl)acetamido)ethyl)amino)-4-oxobutyl)triphenylphosphonium chloride;

[0044] (16)(1-(3-carboxy-5-(2,13-dioxo-16-(triphenylphosphino)-6,9-dioxa-3,12-diazahexadecyl)-18-ethyl-2,8,12,17-tetramethyl-13-vinyl-7H,8H-porphyrin-7-yl)-3,14-dioxo-7,10-dioxa-4,13-diazaheptadec-17-yl)triphenylphosphonium dichloride;

[0045] or a salt thereof.

[0046] 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, for use in medicine.

[0047] In the context of this specification, a "hydrocarbyl" substituent or a 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 can be saturated or unsaturated (including aromatics), and can be straight or branched, or can be or include a cyclic group, wherein 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 groups include alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, and aryl groups / moieties, and combinations of all of these groups / moieties. Typically, a hydrocarbyl group is C1-C 60 Hydrocarbyl, more typically C1-C 40 Hydrocarbyl, more typically C1-C 20 More typically, the hydrocarbyl group is C1-C 12 More typically, the hydrocarbyl group is C1-C 10 "Hydrocarbylene" is similarly defined as a divalent hydrocarbon radical.

[0048] An "alkyl" substituent or 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 indicated, the term "alkyl" does not include "cycloalkyl." Typically, an alkyl group is C1-C 12 Alkyl. More typically, an alkyl group is a C1-C6 alkyl group. "Alkylene" is defined in a similar manner as a divalent alkyl group. Typically, an alkylene group is a C1-C6 alkyl group. 42 More typically, an alkylene group is C1-C 32 Alkylene, or C1-C 22 Alkylene, or C1-C 12 Alkylene.

[0049] An "alkenyl" substituent or 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 ethenyl, propenyl, 1-butenyl, 2-butenyl, 1-pentenyl, 1-hexenyl, 1,3-butadienyl, 1,3-pentadienyl, 1,4-pentadienyl, and 1,4-hexadienyl groups / moieties. Unless otherwise indicated, the term "alkenyl" does not include "cycloalkenyl". Typically, alkenyl is a C2-C 12 Alkenyl. More typically, an alkenyl is a C2-C6 alkenyl. "Alkenylene" is similarly defined as a divalent alkenyl group.

[0050] An "alkynyl" substituent or alkynyl moiety of 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, an alkynyl group is C2-C 12 Alkynyl. More typically, the alkynyl group is a C2-C6 alkynyl group. "Alkynylene" is defined in a similar manner as a divalent alkynyl group.

[0051] The cyclic moiety in " cyclic " substituent or substituent refers to any hydrocarbyl ring, wherein the hydrocarbyl ring can be saturated or unsaturated (including aromatic), and can include one or more heteroatoms, such as N, O, S, P or Se in its carbon skeleton. The example of cyclic group includes cycloalkyl, cycloalkenyl, heterocycle, aryl and heteroaryl as discussed below. Cyclic group can be monocycle, dicycle (such as bridging, condensation or spirocycle) or polycycle. Usually, cyclic group is 3 to 12 yuan of cyclic groups, which means that it contains 3 to 12 ring atoms. More usually, cyclic group is 3 to 7 yuan of monocyclic groups, which means that it contains 3 to 7 ring atoms.

[0052] A "heterocyclic" substituent or 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, tetrahydrophenylthio, tetrahydropyranyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, oxetanyl, thietanyl, pyrazolidinyl, imidazolidinyl, dioxolanyl, oxathiolanyl, thianyl and dioxanyl.

[0053] A "cycloalkyl" substituent or cycloalkyl moiety in a substituent refers to a saturated hydrocarbon ring containing, for example, 3 to 7 carbon atoms, examples of which include cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. Unless otherwise specified, a cycloalkyl substituent or moiety may include a monocyclic, bicyclic, or polycyclic hydrocarbon ring.

[0054] A "cycloalkenyl" substituent or cycloalkenyl moiety of 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, examples of which include cyclopent-1-en-1-yl, cyclohex-1-en-1-yl, and cyclohexa-1,3-dien-1-yl. Unless otherwise specified, a cycloalkenyl substituent or moiety can include monocyclic, bicyclic, or polycyclic hydrocarbon rings.

[0055] The aryl moiety in an "aryl" substituent or substituent refers to an aromatic hydrocarbon ring. The term "aryl" includes monocyclic aromatic hydrocarbons and polycyclic condensed-ring aromatic hydrocarbons, wherein all condensed ring systems (excluding any ring system formed as a part of an optional substituent or by an optional substituent) are aromatic. Examples of aryl groups / parts include phenyl, naphthyl, anthracenyl and phenanthrenyl. Unless otherwise indicated, the term "aryl" does not include "heteroaryl".

[0056] A "heteroaryl" substituent or heteroaryl moiety of a substituent refers to an aromatic heterocyclic group or moiety. The term "heteroaryl" includes monocyclic aromatic heterocycles and polycyclic fused-ring aromatic heterocycles in which all fused ring systems (excluding any ring systems that are part of or formed by optional substituents) are aromatic. Examples of heteroaryl groups / moieties include the following:

[0057]

[0058] wherein G=O, S or NH.

[0059] For the purposes of this specification, when a combination of moieties is referred to as a group, for example arylalkyl, arylalkenyl, arylalkynyl, alkylaryl, alkenylaryl or alkynylaryl, the last-mentioned moiety contains the atoms through which the group is attached to the rest of the molecule. An example of an arylalkyl group is benzyl.

[0060] For the purposes of this specification, an optionally substituted group or moiety (such as -R β )middle:

[0061] (i) Each hydrogen atom may be optionally replaced by a monovalent substituent independently selected from the group consisting of: halo; -CN; -NO2; -N3; -R x ;-OH;-OR x ;-R y -halogen; -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

[0062] (ii) Any two hydrogen atoms attached to the same carbon atom may optionally be independently selected from oxo (=O), =S, =NH or =NR x substituted with a π-bonded substituent; and / or

[0063] (iii) Any two hydrogen atoms attached to the same or different atoms within the same optionally substituted group or moiety may optionally be independently selected from -O-, -S-, -NH-, -N(R x )-、-N + (R x )2-or-R y - is replaced by a bridging substituent;

[0064] Each of these -R y- is independently selected from alkylene, alkenylene or alkynylene, wherein the alkylene, alkenylene or alkynylene group contains 1 to 6 atoms in its main chain, wherein one or more carbon atoms in the main chain of the alkylene, alkenylene or alkynylene group may be optionally replaced by one or more heteroatoms N, O or S, and wherein the alkylene, alkenylene or alkynylene group may be optionally replaced by one or more halo and / or -R x group substitution; and

[0065] Each of these -R x independently selected from C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl or C2-C6 cyclic group, or any two or three -R x Together with the nitrogen atom to which they are attached, they can form a C2-C7 cyclic group, and any -R x It may be optionally substituted with one or more C1-C4 alkyl, C1-C4 haloalkyl, -O(C1-C4 alkyl), -O(C1-C4 haloalkyl), halo, -OH, -NH2, -CN or oxo (=O) groups.

[0066] Typically, a substituted group contains 1, 2, 3, or 4 substituents, more typically 1, 2, or 3 substituents, more typically 1 or 2 substituents, and more typically 1 substituent.

[0067] Unless otherwise indicated, any divalent bridging substituent (e.g., -O-, -S-, -NH-, -N(R)-) of an optionally substituted group or moiety is x )-、-N + (R x )2-or-R y -) must be attached only to the designated group or moiety and may not be attached to a second group or moiety, even if the second group or moiety may itself be optionally substituted.

[0068] The term "halo" includes fluorine, chlorine, bromine and iodine.

[0069] Unless otherwise stated, when a group is prefixed with the term "halo", such as haloalkyl or halomethyl, it should be understood that the group under discussion is replaced by one or more halo groups independently selected from fluorine, chlorine, bromine and iodine. Generally, the maximum number of halo substituents is only limited by the number of hydrogen atoms that can be used for replacement on the corresponding group without the halo prefix. For example, halomethyl can contain one, two or three halo substituents. Haloethyl or halophenyl can contain one, two, three, four or five halo substituents. Similarly, unless otherwise stated, when a group is prefixed with a specific halo, it should be understood that the group under discussion is replaced by one or more specific halo groups. For example, the term "fluoromethyl" refers to a methyl group substituted by one, two or three fluoro groups.

[0070] Unless otherwise indicated, when a group is referred to as "halo-substituted," it is understood that the group in question is substituted with one or more halo groups independently selected from fluorine, chlorine, bromine, and iodine. Typically, the maximum number of halo substituents is limited only by the number of hydrogen atoms available for substitution on the group referred to as halo-substituted. For example, a halo-substituted methyl group may contain one, two, or three halo substituents. A halo-substituted ethyl group or a halo-substituted phenyl group may contain one, two, three, four, or five halo substituents.

[0071] Unless otherwise stated, any reference to an element should be taken to include all isotopes of that element. Thus, for example, any reference to hydrogen should be taken to include all isotopes of hydrogen, including deuterium and tritium, unless otherwise stated.

[0072] Unless otherwise stated, any reference to a compound or group is to be considered as a reference to all tautomers of said compound or group.

[0073] When referring to a hydrocarbyl or other group containing one or more heteroatoms N, O, S, P or Se in its carbon skeleton, or when referring to a hydrocarbyl or other group having carbon atoms replaced by N, O, S, P or Se atoms, it is intended that:

[0074] Replacement;

[0075] -CH2- is replaced by -NH-, -PH-, -O-, -S- or -Se-;

[0076] -CH3 is replaced by -NH2, -PH2, -OH, -SH or -SeH;

[0077] -CH= is replaced by -N= or -P=;

[0078] CH2= is replaced by NH=, PH=, O=, S= or Se=; or

[0079] CH≡ is replaced by N≡ or P≡;

[0080] The proviso is that the resulting radical contains at least one carbon atom. For example, methoxy, dimethylamino and aminoethyl are considered to be hydrocarbon radicals containing one or more heteroatoms N, O, S, P or Se in their carbon skeleton.

[0081] In the context of this specification, unless otherwise stated, C x -C yA radical is defined as a radical containing from x to y carbon atoms. For example, a C1-C4 alkyl radical is defined as an alkyl radical containing from 1 to 4 carbon atoms. When calculating the total number of carbon atoms in a parent radical substituted with optional substituents and / or containing optional moieties, the optional substituents and moieties are not taken into account. For the avoidance of doubt, when calculating the total number of carbon atoms in a parent radical substituted with optional substituents and / or containing optional moieties, the optional substituents and moieties are not taken into account. x -C y When counting the number of carbon atoms in a group, replacing heteroatoms (such as N, O, S, P or Se) are not counted as carbon atoms. For example, morpholinyl is considered a C6 heterocyclic group rather than a C4 heterocyclic group.

[0082] The pi electrons of the chlorin ring are delocalized, and therefore 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:

[0083]

[0084] Typically, a complex comprises a central metal atom or ion, known as a coordination center, and a bound molecule or ion, known as a ligand. In this specification, the bond between the coordination center and the ligand is depicted as shown in the complex at the bottom left (where the attractive force 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 at the bottom right (where the attractive force between the ligand molecule and the central metal atom is represented by two covalent bonds and two dashed lines):

[0085]

[0086] As used herein, -[NC5H5]Y refers to:

[0087]

[0088] In one embodiment of the first or second aspect of the present invention, X is a halide selected from fluoro, chloro, bromo or iodo. In one embodiment, X is chloro or bromo.

[0089] In one embodiment of the first or second aspect of the present invention, there is provided a compound of formula (I).

[0090] In one embodiment of the first or second aspects of the invention, Y is a counter anion selected from the group consisting of: halide (e.g., fluoride, chloride, bromide, or iodide) or other inorganic anion (e.g., bisulfate, hexafluorophosphate (PF6), nitrate, perchlorate, phosphate, or sulfate) or an organic anion (e.g., acetate, ascorbate, aspartate, benzoate, besylate (benzenesulfonate), bicarbonate, bis(trifluoromethanesulfonyl)imide (TFSI), bitartrate, butyrate, camsylate (camphorsulfonate), carbonate, citrate, decanoate, edetate, ethanesulfonate (ethanesulfonate), fumarate, galactonate, glucoheptonate, gluconate, glutathione ... sulfonate, octanoate, oleate, ornithine, pamoate, pantothenate, polygalacturonate, propionate, salicylate, stearate, succinate, tartrate, teoclate, tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (BARF), tetrakis(pentafluorophenyl)borate (F5-TPB), tetraphenylborate (TPB), toluenesulfonate (p-toluenesulfonate), or trifluoromethanesulfonate (trifluoromethanesulfonate).

[0091] In another embodiment of the first or second aspects of the invention, Y is a counter anion selected from the group consisting of a halide (e.g., fluoride, chloride, bromide, or iodide) or other inorganic anion (e.g., bisulfate, nitrate, perchlorate, phosphate, or sulfate) or an organic anion (e.g., acetate, aspartate, benzoate, besylate (benzenesulfonate), butyrate, camsylate (camphorsulfonate), benzoate, ... In one embodiment, Y is fluoride, chloride, bromide, or iodide. In one embodiment, Y is chloride or bromide.

[0092] In one embodiment of the first or second aspect of the invention, Z is a counter cation selected from an inorganic cation such as a lithium, sodium, potassium, magnesium, calcium or ammonium cation or an organic cation such as an amine cation such as a choline or meglumine cation or an amino acid cation such as an arginine cation.

[0093] In one embodiment of the first or second aspect of the present invention, M 2+ is selected from Zn 2+ 、Cu 2+ 、Fe 2+ 、Pd 2+ or Pt 2+ In one embodiment, M 2+ It is Zn 2+ .

[0094] In one embodiment of the first or second aspect of the present invention, -R 1 Selected from -C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )2. -C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R 3 )2. In one embodiment, -R 1 Selected from -C(O)-OR 3 、-C(O)-SR 3、-C(O)-N(R 3 )2 or -C(S)-N(R 3 )2. In one embodiment, -R 1 Selected from -C(O)-OR 3 、-C(O)-SR 3 or -C(O)-N(R 3 )2.

[0095] In one embodiment of the first or second aspect of the present invention, -R 1 Selected from -C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )2. -C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R 3 )2, and each -R 3 is C1-C4 alkyl (preferably methyl). In one embodiment, -R 1 Selected from -C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )2 or -C(S)-N(R 3 )2, and each -R 3 is C1-C4 alkyl (preferably methyl). In one embodiment, -R 1 Selected from -C(O)-OR 3 、-C(O)-SR 3 or -C(O)-N(R 3 )2, and each -R 3 is C1-C4 alkyl (preferably methyl). In one embodiment, -R 1 is-C(O)-OR 3 , and -R 3 It is a C1-C4 alkyl group (preferably a methyl group).

[0096] In one embodiment of the first or second aspect of the present invention, -R 1 Selected from -C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )2. -C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R 3 )2, and each -R 3 Selected from -R α -OR β 、-Rα -SR β 、-R α -S(O)R β or -R α -S(O)2R β , and -R β In one embodiment, -R 1 Selected from -C(O)-OR 3 、-C(O)-SR 3 or -C(O)-N(R 3 )2, and each -R 3 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 In one embodiment, -R 1 Selected from -C(O)-OR 3 or -C(O)-SR 3 , and -R 3 Selected from -R α -OR β or -R α -SR β , and -R β Is a glycosyl group. Typically in these embodiments, -R α -It is C1-C 12 Alkylene (preferably C1-C8 alkylene, or C1-C6 alkylene), -(CH2CH2O) m - group or -(CH2CH2S) m - groups, all optionally substituted, wherein m is 1, 2, 3 or 4.

[0097] In one embodiment of the first or second aspect of the present invention, -R 1 Selected from -C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )(R 3’ ) or -C(S)-N(R 3 )(R 3’ ), where -R 3 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 sugar group, and -R 3’ Is H or C1-C4 alkyl (preferably methyl). In one embodiment, -R 1 Yes -C(O)-N(R 3 )(R 3’ ), where -R 3 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 sugar group, and -R 3’ Is H or C1-C4 alkyl (preferably methyl). In one embodiment, -R 1 Yes -C(O)-N(R 3 )(R 3’ ), where -R 3 Selected from -R α -OR β or -R α -SR β , and -R β is a sugar group, and -R 3’ Is H or C1-C4 alkyl (preferably methyl). In one embodiment, -R 1 Yes -C(O)-N(R 3 )(R 3’ ), where -R 3 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 sugar group, and -R 3’ is C1-C4 alkyl (preferably methyl). In one embodiment, -R 1 Yes -C(O)-N(R 3 )(R 3’ ), where -R 3 Selected from -R α -OR β or -R α -SRβ , and -R β is a sugar group, and -R 3’ Is C1-C4 alkyl (preferably methyl). Typically in these embodiments, -R α -It is C1-C 12 Alkylene (preferably C1-C8 alkylene, or C1-C6 alkylene), -(CH2CH2O) m - group or -(CH2CH2S) m - groups, all optionally substituted, wherein m is 1, 2, 3 or 4.

[0098] -R 3' A group is a group that is connected to another -R 3 Groups attached to the same atom -R 3 Group. -R 3 and -R 3’ Can be the same or different. Preferably, -R 3 and -R 3’ different.

[0099] In one embodiment of the first or second aspect of the present invention, -R 1 Selected from -C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )(R 3’ ) or -C(S)-N(R 3 )(R 3’ ), where -R 3 Selected from -R α -R β or -R β , and -R β is a sugar group, and -R 3’ Is H or C1-C4 alkyl (preferably methyl). In one embodiment, -R 1 Yes -C(O)-N(R 3 )(R 3’ ), where -R 3 Selected from -R α -R β or -R β , and -R β is a sugar group, and -R 3’ Is H or C1-C4 alkyl (preferably methyl). Typically in these embodiments, -R α -It is C1-C 12 Alkylene (preferably C1-C8 alkylene, or C1-C6 alkylene), -(CH2CH2O) m - group or -(CH2CH2S) m- groups, all optionally substituted, wherein m is 1, 2, 3 or 4.

[0100] In any of the embodiments of the four preceding paragraphs, the glycosyl group can be optionally substituted, for example, with a protecting group such as acetyl or a natural amino acid such as valine. The amino acid can be attached to the glycosyl group, for example, by forming an ester between the carboxylic acid group of the amino acid and the hydroxyl group of the glycosyl group.

[0101] In one embodiment of the first or second aspect of the present invention, -R 1 Selected from -C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )(R 3’ ) or -C(S)-N(R 3 )(R 3’ ), where -R 3 Selected from -R α -R β or -R β , and -R β is a C1-C8 alkyl group optionally substituted with one or more (such as one, two, three, four, five, six, seven or eight) hydroxy groups, and -R 3’ Is H or C1-C4 alkyl (preferably methyl). In one embodiment, -R 1 Yes -C(O)-N(R 3 )(R 3’ ), where -R 3 Selected from -R α -R β or -R β , and -R β is a C1-C8 alkyl group optionally substituted with one or more (such as one, two, three, four, five, six, seven or eight) hydroxy groups, and -R 3’ Is H or C1-C4 alkyl (preferably methyl). Typically in these embodiments, -R α - is an unsubstituted C1-C6 alkylene group, or an unsubstituted C1-C4 alkylene group, or an unsubstituted C1-C2 alkylene group.

[0102] In one embodiment of the first or second aspect of the present invention, -R 1 Selected from -C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )(R 3’ ) or -C(S)-N(R 3 )(R 3’ ); where -R 3Selected from -R α -H or -R α -OH; -R α -Selected from C1-C 12 Alkylene, wherein the alkylene may be optionally substituted with one or more C1-C4 alkyl, C1-C4 haloalkyl, or halo, and wherein one or more carbon atoms in the backbone of the alkylene may be optionally replaced with one or more heteroatoms O or S; and -R 3’ Is H or C1-C4 alkyl (preferably methyl). In one embodiment, -R 1 Yes -C(O)-N(R 3 )(R 3’ ); where -R 3 Selected from -R α -H or -R α -OH; -R α -Selected from C1-C 12 Alkylene, wherein one or more carbon atoms in the backbone of the alkylene may be optionally replaced by one or more heteroatoms O or S; and -R 3’ is H or C1-C4 alkyl (preferably methyl).

[0103] In one embodiment of the first or second aspect of the present invention, -R 1 Selected from -C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )(R 3’ ) or -C(S)-N(R 3 )(R 3’ ); where -R 3 Yes-R β ;-R β It is C1-C 12 Alkyl, which is optionally substituted by one or more (such as one, two, three, four or five) independently selected from halo, -CN, -NO2, -N3, -OH, -OR x 、-SH、-SR x 、-SOR x 、-SO2H、-SO2R x 、-SO2NH2、-SO2NHR x 、-SO2N(R x )2、-NH2、-NHR x 、-N(R x )2、-N + (R x )3, -CHO, -COR x 、-COOH、-COOR x 、-OCORx or -NH-CO-CR z -NH2 is substituted by a substituent; each -R x Independently selected from C1-C4 alkyl; -R z is the side chain of a natural amino acid; and -R 3' Is H or C1-C4 alkyl (preferably methyl). In one embodiment, -R 1 Yes -C(O)-N(R 3 )(R 3’ ); where -R 3 Yes-R β ;-R β is C1-C8 alkyl, which is optionally substituted by one or more (such as one, two or three) independently selected from halo, -CN, -NO2, -N3, -OH, -OR x 、-SH、-SR x 、-SOR x 、-SO2H、-SO2R x 、-SO2NH2、-SO2NHR x 、-SO2N(R x )2、-NH2、-NHR x 、-N(R x )2、-N + (R x )3, -CHO, -COR x 、-COOH、-COOR x 、-OCOR x or -NH-CO-CR z -NH2 is substituted by a substituent; each -R x Independently selected from C1-C4 alkyl; -R z is the side chain of a natural amino acid; and -R 3' is H or C1-C4 alkyl (preferably methyl).

[0104] In one embodiment of the first or second aspect of the present invention, -R 1 Selected from -C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )(R 3’ ) or -C(S)-N(R 3 )(R 3’ ); where -R 3 Yes-R α -[P(R 5 )3]Y; each -R 5independently selected from phenyl or C5-C6 heteroaryl, wherein the phenyl or C5-C6 heteroaryl may be optionally substituted with one or more C1-C4 alkyl, C1-C4 haloalkyl, -O(C1-C4 alkyl), -O(C1-C4 haloalkyl), halo, -O-(CH2CH2O) n -H or -O-(CH2CH2O) n -CH3 group substituted; n is 1, 2, 3 or 4; Y is fluoride, chloride, bromide or iodide; and -R 3' Is H or C1-C4 alkyl (preferably methyl). In one embodiment, -R 1 Yes -C(O)-N(R 3 )(R 3’ ); where -R 3 Yes-R α -[P(R 5 )3]Y; each -R 5 independently selected from phenyl or C5-C6 heteroaryl, wherein the phenyl or C5-C6 heteroaryl may be optionally substituted with one or more C1-C4 alkyl, C1-C4 haloalkyl, -O(C1-C4 alkyl), -O(C1-C4 haloalkyl), halo, -O-(CH2CH2O) n -H or -O-(CH2CH2O) n -CH3 group substituted; n is 1, 2, 3 or 4; Y is fluoride, chloride, bromide or iodide; and -R 3' Is H or C1-C4 alkyl (preferably methyl). Typically in these embodiments, -R α -It is C1-C 12 Alkylene (preferably C1-C8 alkylene, or C1-C6 alkylene), -(CH2CH2O) m - group or -(CH2CH2S) m - groups, all optionally substituted, wherein m is 1, 2, 3 or 4.

[0105] In one embodiment of the first or second aspect of the present invention, -R 1 YES-C(O)-OR 3 , where -R 3 is selected from C1-C4 alkyl (preferably methyl) or a cation such as lithium, sodium, potassium, magnesium, calcium, ammonium, an amine (such as choline or meglumine) or an amino acid (such as arginine) cation.

[0106] In one embodiment of the first or second aspect of the present invention, -R 1 Yes -C(O)-N(R 3 )2. In one embodiment, -R 1is -C(O)-N(C1-C4 alkyl)(R 3 ) or -C(O)-NHR 3 In one embodiment, -R 1 is -C(O)-N(CH3)(R 3 ) or -C(O)-NHR 3 In one embodiment, -R 1 is -C(O)-N(C1-C4 alkyl)(R 3 In one embodiment, -R 1 is -C(O)-N(CH3)(R 3 ).

[0107] In one embodiment of the first or second aspect of the present invention, -R 1 Selected from -CH2OR 2 、-CH2SR 2 、-CH2S(O)R 2 、-CH2S(O)2R 2 、-CH2N(R 2 )2 or -R 2 In one embodiment, -R 1 Selected from -CH2OR 2 、-CH2SR 2 、-CH2N(R 2 )2 or -R 2 In 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 2 , and -R 2 Yes-R α -X.

[0108] In one embodiment of the first or second aspect of the present invention, -R 2 Selected from -R α -H, -R β 、-R α -R β 、-R α -OH, -R α -OR β 、-Rα -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 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 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 In one embodiment, -R 2 Selected from -R α -OR β or -R α -SR β In one embodiment, -R 2 Selected from -R α -OR β or -R α -SR β , and -R β It's a sugar group.

[0109] In one embodiment of the first or second aspect of the present invention, -R 2 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 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 Selected from -C(O)R 4 、-C(O)-OR 4 、-C(O)-SR 4 or -C(O)-N(R 4 )2.

[0110] In one embodiment of the first or second aspect of the present invention, -R 2 Yes -C(O)-N(R 4 )(R 4’ ), where -R 4 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 sugar group, and -R 4’ Is H or C1-C4 alkyl (preferably methyl). In one embodiment, -R 2 Yes -C(O)-N(R 4 )(R 4’ ), where -R 4 Selected from -R α -OR β or -R α -SR β , and -R β is a sugar group, and -R 4’ Is H or C1-C4 alkyl (preferably methyl). In one embodiment, -R 2 Yes -C(O)-N(R 4 )(R 4’ ), where -R 4 Selected from -R α -OR β 、-R α -SRβ 、-R α -S(O)R β or -R α -S(O)2R β , and -R β is a sugar group, and -R 4’ is C1-C4 alkyl (preferably methyl). In one embodiment, -R 2 Yes -C(O)-N(R 4 )(R 4’ ), where -R 4 Selected from -R α -OR β or -R α -SR β , and -R β is a sugar group, and -R 4’ It is a C1-C4 alkyl group (preferably a methyl group).

[0111] -R 4' A group is a group that is connected to another -R 4 Groups attached to the same atom -R 4 Group. -R 4 and -R 4’ Can be the same or different. Preferably, -R 4 and -R 4’ different.

[0112] In one embodiment of the first or second aspect of the present invention, -R 2 Yes -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 ).

[0113] In one embodiment of the first or second aspect of the present invention, -R 6 Selected from -C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )2. -C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R 3 )2, and each -R 3 is a C1-C4 alkyl group, preferably each -R 3 In one embodiment, -R 6 Selected from -C(O)-OR3 、-C(O)-SR 3 or -C(O)-N(R 3 )2, and each -R 3 is a C1-C4 alkyl group, preferably each -R 3 In one embodiment, -R 6 is-C(O)-OR 3 , and -R 3 is C1-C4 alkyl, preferably -R 3 It's methyl.

[0114] In one embodiment of the first or second aspect of the present invention, -R 6 is-C(O)-OR 3 , where -R 3 is selected from hydrogen, C1-C4 alkyl (preferably methyl) or a cation such as lithium, sodium, potassium, magnesium, calcium, ammonium, an amine (such as choline or meglumine) or an amino acid (such as arginine) cation.

[0115] In one embodiment of the first or second aspect of the present invention, -R 6 Selected from -C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )2、-C(O)-N(R 3 )(R 3’ )、-C(S)-OR 3 、-C(S)-SR 3 、-C(S)-N(R 3 )2 or -C(S)-N(R 3 )(R 3’ ); where -R 3 Yes-R β ;-R β Selected from C1-C 20 alkyl, wherein the alkyl may be optionally substituted with one, two, three or four halo groups, and wherein one, two, three, four, five or six carbon atoms in the backbone of the alkyl may be optionally replaced with heteroatoms or groups independently selected from O, S, NH or NMe; and -R 3’ is H or C1-C4 alkyl (preferably methyl).

[0116] In one embodiment of the first or second aspect of the present invention, -R 6 Selected from -C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )2. -C(S)-OR 3、-C(S)-SR 3 or -C(S)-N(R 3 )2, and each -R 3 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 In one embodiment, -R 6 Selected from -C(O)-OR 3 、-C(O)-SR 3 or -C(O)-N(R 3 )2, and each -R 3 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 In one embodiment, -R 6 Selected from -C(O)-OR 3 or -C(O)-SR 3 , and -R 3 Selected from -R α -OR β or -R α -SR β , and -R β Is a glycosyl group. Typically in these embodiments, -R α -Selected from C1-C 12 Alkylene, wherein one, two, three or four carbon atoms in the backbone of the alkylene may be optionally replaced by heteroatoms or groups independently selected from O, S, NH or NMe. Alternatively, in these embodiments, -R α -It is C1-C 12 Alkylene (preferably C1-C8 alkylene, or C1-C6 alkylene), -(CH2CH2O) m -CH2CH2- group or -(CH2CH2S) m -CH2CH2- groups, all optionally substituted, wherein m is 1, 2, 3 or 4.

[0117] In one embodiment of the first or second aspect of the present invention, -R 6Selected from -C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )(R 3’ ) or -C(S)-N(R 3 )(R 3’ ), where -R 3 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 sugar group, and -R 3’ Is H or C1-C4 alkyl (preferably methyl). In one embodiment, -R 6 Selected from -C(O)-OR 3 、-C(O)-SR 3 or -C(O)-N(R 3 )(R 3’ ), where -R 3 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 sugar group, and -R 3’ Is H or C1-C4 alkyl (preferably methyl). In one embodiment, -R 6 Selected from -C(O)-OR 3 、-C(O)-SR 3 or -C(O)-N(R 3 )(R 3’ ), where -R 3 Selected from -R α -OR β or -R α -SR β , and -R β is a sugar group, and -R 3’ Is H or C1-C4 alkyl (preferably methyl). Typically in these embodiments, -R α -Selected from C1-C 12Alkylene, wherein one, two, three or four carbon atoms in the backbone of the alkylene may be optionally replaced by heteroatoms or groups independently selected from O, S, NH or NMe. Alternatively, in these embodiments, -R α -It is C1-C 12 Alkylene (preferably C1-C8 alkylene, or C1-C6 alkylene), -(CH2CH2O) m -CH2CH2- group or -(CH2CH2S) m -CH2CH2- groups, all optionally substituted, wherein m is 1, 2, 3 or 4.

[0118] -R 3' A group is a group that is connected to another -R 3 Groups attached to the same atom -R 3 Group. -R 3 and -R 3’ Can be the same or different. Preferably, -R 3 and -R 3’ different.

[0119] In one embodiment of the first or second aspect of the present invention, -R 6 Yes -C(O)-N(R 3 )2. In one embodiment, -R 6 is -C(O)-N(C1-C4 alkyl)(R 3 ) or -C(O)-NHR 3 In one embodiment, -R 6 is -C(O)-N(CH3)(R 3 ) or -C(O)-NHR 3 .

[0120] In one embodiment of the first or second aspect of the present invention, -R 7 Selected from -C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )2. -C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R 3 )2, and each -R 3 is a C1-C4 alkyl group, preferably each -R 3 In one embodiment, -R 7 Selected from -C(O)-OR 3 、-C(O)-SR 3 or -C(O)-N(R 3 )2, and each -R3 is a C1-C4 alkyl group, preferably each -R 3 In one embodiment, -R 7 YES-C(O)-OR 3 , and -R 3 is C1-C4 alkyl, preferably -R 3 It's methyl.

[0121] In one embodiment of the first or second aspect of the present invention, -R 7 YES-C(O)-OR 3 , where -R 3 is selected from hydrogen, C1-C4 alkyl (preferably methyl) or a cation such as lithium, sodium, potassium, magnesium, calcium, ammonium, an amine (such as choline or meglumine) or an amino acid (such as arginine) cation.

[0122] In one embodiment of the first or second aspect of the present invention, -R 7 Selected from -C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )2、-C(O)-N(R 3 )(R 3’ )、-C(S)-OR 3 、-C(S)-SR 3 、-C(S)-N(R 3 )2 or -C(S)-N(R 3 )(R 3’ ); where -R 3 Yes-R β ;-R β Selected from C1-C 20 alkyl, wherein the alkyl may be optionally substituted with one, two, three or four halo groups, and wherein one, two, three, four, five or six carbon atoms in the backbone of the alkyl may be optionally replaced with heteroatoms or groups independently selected from O, S, NH or NMe; and -R 3’ is H or C1-C4 alkyl (preferably methyl).

[0123] In one embodiment of the first or second aspect of the present invention, -R 7 Selected from -C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )2. -C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R 3 )2, and each -R 3Selected 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 In one embodiment, -R 7 Selected from -C(O)-OR 3 、-C(O)-SR 3 or -C(O)-N(R 3 )2, and each -R 3 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 In one embodiment, -R 7 Selected from -C(O)-OR 3 or -C(O)-SR 3 , and -R 3 Selected from -R α -OR β or -R α -SR β , and -R β Is a glycosyl group. Typically in these embodiments, -R α -Selected from C1-C 12 Alkylene, wherein one, two, three or four carbon atoms in the backbone of the alkylene may be optionally replaced by heteroatoms or groups independently selected from O, S, NH or NMe. Alternatively, in these embodiments, -R α -It is C1-C 12 Alkylene (preferably C1-C8 alkylene, or C1-C6 alkylene), -(CH2CH2O) m -CH2CH2- group or -(CH2CH2S) m -CH2CH2- groups, all optionally substituted, wherein m is 1, 2, 3 or 4.

[0124] In one embodiment of the first or second aspect of the present invention, -R 7 Selected from -C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3)(R 3’ ) or -C(S)-N(R 3 )(R 3’ ), where -R 3 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 sugar group, and -R 3’ Is H or C1-C4 alkyl (preferably methyl). In one embodiment, -R 7 Selected from -C(O)-OR 3 、-C(O)-SR 3 or -C(O)-N(R 3 )(R 3’ ), where -R 3 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 sugar group, and -R 3’ Is H or C1-C4 alkyl (preferably methyl). In one embodiment, -R 7 Selected from -C(O)-OR 3 、-C(O)-SR 3 or -C(O)-N(R 3 )(R 3’ ), where -R 3 Selected from -R α -OR β or -R α -SR β , and -R β is a sugar group, and -R 3’ Is H or C1-C4 alkyl (preferably methyl). Typically in these embodiments, -R α -Selected from C1-C 12 Alkylene, wherein one, two, three or four carbon atoms in the backbone of the alkylene may be optionally replaced by heteroatoms or groups independently selected from O, S, NH or NMe. Alternatively, in these embodiments, -R α -It is C1-C 12Alkylene (preferably C1-C8 alkylene, or C1-C6 alkylene), -(CH2CH2O) m -CH2CH2- group or -(CH2CH2S) m -CH2CH2- groups, all optionally substituted, wherein m is 1, 2, 3 or 4.

[0125] -R 3' A group is a group that is connected to another -R 3 Groups attached to the same atom -R 3 Group. -R 3 and -R 3’ Can be the same or different. Preferably, -R 3 and -R 3’ different.

[0126] In one embodiment of the first or second aspect of the present invention, -R 7 Yes -C(O)-N(R 3 )2. In one embodiment, -R 7 is -C(O)-N(C1-C4 alkyl)(R 3 ) or -C(O)-NHR 3 In one embodiment, -R 7 is -C(O)-N(CH3)(R 3 ) or -C(O)-NHR 3 .

[0127] In one embodiment of the first or second aspect of the invention, each -R α - independently C1-C 12 Alkylene, -(CH2CH2O) m - group or -(CH2CH2S) m - groups, all optionally substituted, wherein m is 1, 2, 3 or 4. In one embodiment, each -R α - independently C1-C 12 Alkylene or -(CH2CH2O) m - groups, both of which are optionally substituted, wherein m is 1, 2, 3 or 4. In one embodiment, each -R α - is independently optionally substituted -(CH2CH2O) m - group, wherein m is 1, 2, 3 or 4.

[0128] In one embodiment of the first or second aspect of the invention, each -R α - is independently C1-C8 alkylene, or C1-C6 alkylene, or C2-C4 alkylene, all optionally substituted.

[0129] In one embodiment of the first or second aspect of the invention, each -R α - is independently unsubstituted or substituted with one or more substituents independently selected from halo, C1-C4 alkyl or C1-C4 haloalkyl. In one embodiment, each -R α - is independently unsubstituted or substituted with one or two substituents independently selected from halo, C1-C4 alkyl or C1-C4 haloalkyl. In one embodiment, each -R α -Not superseded.

[0130] In one embodiment of the first or second aspect of the invention, each -R β is independently a saturated or unsaturated hydrocarbon group, wherein the hydrocarbon group may be linear or branched, or may be or include a cyclic group, wherein the hydrocarbon group may be optionally substituted, and wherein the hydrocarbon group may optionally include one or more heteroatoms N, O or S in its carbon skeleton.

[0131] In one embodiment of the first or second aspect of the present invention, at least one -R β is independently C1-C6 alkyl, or C1-C4 alkyl, or methyl, all optionally substituted. β are independently C1-C6 alkyl, or C1-C4 alkyl, or methyl, all optionally substituted.

[0132] In one embodiment of the first or second aspect of the present invention, at least one -R β In one embodiment, each -R β are independently glycosyl.

[0133] In one embodiment of the first or second aspect of the invention, each -R β is independently unsubstituted or substituted with one or more substituents independently selected from halo, C1-C4 alkyl or C1-C4 haloalkyl. β is independently unsubstituted or substituted with one or two substituents independently selected from halo, C1-C4 alkyl or C1-C4 haloalkyl. β Not replaced.

[0134] In one embodiment of the first or second aspect of the invention, each -R 3 Independently selected from -R α -H, -R β 、-R α -R β 、-R α -OH, -R α -ORβ 、-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 3 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 3 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 In one embodiment, each -R 3 Independently selected from -R α -OR β or -R α -SR β In one embodiment, each -R 3 Independently selected from -R α -OR β or -R α -SR β , and -R β It's a sugar group.

[0135] In one embodiment of the first or second aspect of the invention, each -R 4 Independently selected from -R α -H, -Rβ 、-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, each -R 4 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 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 In one embodiment, each -R 4 Independently selected from -R α -OR β or -R α -SR β In one embodiment, each -R 4 Independently selected from -R α -OR β or -R α -SR β , and -R β It's a sugar group.

[0136] In one embodiment of the first or second aspect of the present invention, -R 2 、-R 3 or -R 4 At least one of -R α -OR β 、-R α -SR β 、-R α -S(O)R β or -R α -S(O)2R β , and -R β In one embodiment, -R 2 、-R 3 or -R 4 At least one of -R α -OR β or -R α -SR β , and -R β It's a sugar group.

[0137] For the purposes of the present invention, a "glycosyl" is any group comprising at least one monosaccharide subunit, wherein each monosaccharide subunit may be optionally substituted and / or modified. Typically, a glycosyl group is composed of one or more monosaccharide subunits, wherein each monosaccharide subunit may be optionally substituted and / or modified.

[0138] Typically, a carbon atom of a single monosaccharide subunit of each glycosyl group is directly linked (most often via a single bond) to the rest of the compound.

[0139] For the purposes of this specification, when it is stated that a first atom or group is "directly attached" to a second atom or group, it is understood that the first atom or group is covalently bonded to the second atom or group without one or more intervening atoms 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 any methyl group.

[0140] Typically, each sugar group is derived from the corresponding sugar by replacing a hydroxyl group of the sugar with a group defined by the remainder of the compound.

[0141] The single bond between the anomeric carbon of a monosaccharide subunit and a substituent is called a glycosidic bond. The glycosidic group is connected to the anomeric carbon of the monosaccharide subunit via a glycosidic bond. The bond between the glycosyl and the rest of the compound can be a glycosidic bond or a non-glycosidic bond. Typically, the bond between the glycosyl and the rest of the compound is a glycosidic bond, such that the saccharidyl group is a glycosyl group. When the bond between the glycosyl and the rest of the compound is a glycosidic bond, the glycosidic bond can be in α or β configuration. Typically, this glycosidic bond is in β configuration.

[0142] For the purposes of the present invention, when a glycosyl group "contains x monosaccharide subunits," this means that the glycosyl group has only x monosaccharide subunits. In contrast, when a glycosyl group "comprises x monosaccharide subunits," this means that the glycosyl group has x or more monosaccharide subunits.

[0143] Each saccharide group can be independently selected from a monosaccharide group, a disaccharide group, an oligosaccharide group or a polysaccharide group. As will be understood, a monosaccharide group contains a single monosaccharide subunit. Similarly, a disaccharide group contains two monosaccharide subunits. As used herein, an "oligosaccharide group" contains 2 to 9 monosaccharide subunits. Examples of oligosaccharides include trisaccharides, tetrasaccharides, pentasaccharides, hexasaccharides, heptasaccharides, octasaccharides and nonasaccharides. As used herein, a "polysaccharide group" contains 10 or more monosaccharide subunits (such as 10-50, or 10-30, or 10-20, or 10-15 monosaccharide subunits).

[0144] Each monosaccharide subunit within a disaccharide, oligosaccharide, or polysaccharide group may be the same or different. Each monosaccharide subunit within a disaccharide, oligosaccharide, or polysaccharide group may be linked to another monosaccharide subunit within the group via a glycosidic bond or a non-glycosidic bond. Typically, each monosaccharide subunit within a disaccharide, oligosaccharide, or polysaccharide group is linked to another monosaccharide subunit within the group via a glycosidic bond, and the glycosidic bond may be in an α or β configuration.

[0145] Each oligosaccharide group or polysaccharide group may be a linear, branched or macrocyclic oligosaccharide group or polysaccharide group. Typically, each oligosaccharide group or polysaccharide group is a linear or branched oligosaccharide group or polysaccharide group.

[0146] In one embodiment, at least one -R β It is a monosaccharide or a disaccharide.

[0147] In another embodiment, at least one -R β Is a monosaccharide group. For example, at least one -R β It can be a saccharide group containing a single monosaccharide subunit, wherein the monosaccharide subunit can be optionally substituted and / or modified. Typically, at least one -R β is a glycosyl group containing a single monosaccharide subunit, wherein the monosaccharide subunit may be optionally substituted. More typically, at least one -R βA sugar moiety containing a single monosaccharide subunit, wherein the monosaccharide subunit is unsubstituted.

[0148] In one embodiment, at least one -R β is an aldose group, wherein the aldose group may be optionally substituted and / or modified. For example, at least one -R β It can be selected from a glycerosyl group, an aldotrosyl group (such as an erythrosyl group or a threosyl group), an aldopentosyl group (such as a ribosyl group, an arabinosyl group, a xylosyl group or a lyxosyl group) or an aldohexosyl group (such as an allosyl group, an altrosyl group, a glucosyl group, a mannosyl group, a gulosyl group, an idosyl group, a galactosyl group or a talosyl group), any of which can be optionally substituted and / or modified.

[0149] In another embodiment, at least one -R β is a ketose group, wherein the ketose group may be optionally substituted and / or modified. For example, at least one -R β It may be selected from erythrosyl, ketopentosyl (such as ribulosyl or xylulosyl) or hexokosyl (such as psicosyl, fructosyl, sorbosyl or tagatosyl), any of which may be optionally substituted and / or modified.

[0150] Each monosaccharide subunit can exist in a closed ring (cyclic) or open chain (acyclic) form. β Each monosaccharide subunit in the present invention exists in a closed ring (cyclic) form. For example, at least one -R β It may be a glycosyl group containing a single closed-ring monosaccharide subunit, wherein the monosaccharide subunit may be optionally substituted and / or modified. Typically in this case, at least one -R β is a pyranosyl or furanosyl group, such as pyranosyl, furanosyl, pyranonosyl or furanonosyl, any of which may be optionally substituted and / or modified. More typically, at least one -R β is a pyranosyl group, such as an aldopyranosyl group or a pyranonosyl group, either of which may be optionally substituted and / or modified.

[0151] In one embodiment, at least one -R β is selected from ribopyranosyl, arabinopyranosyl, xylopyranosyl, lyxopyranosyl, allopyranosyl, altropyranosyl, glucopyranosyl, mannopyranosyl, gulopyranosyl, idopyranosyl, galactopyranosyl or talopyranosyl, any of which may be optionally substituted and / or modified.

[0152] In another embodiment, at least one -R β is a glucosyl group, such as a glucopyranosyl group, wherein the glucosyl group or the glucopyranosyl group may be optionally substituted and / or modified. Typically, at least one -R βis a glucosyl group, wherein the glucosyl group is optionally substituted. More typically, at least one -R β It is an unsubstituted glucose group.

[0153] Each monosaccharide subunit can exist in the D- or L-configuration. Typically, each monosaccharide subunit exists in the configuration most commonly found in nature.

[0154] In one embodiment, at least one -R β Is a D-glucose group, such as a D-glucopyranosyl group, wherein the D-glucose group or the D-glucopyranosyl group may be optionally substituted and / or modified. Typically, at least one -R β is a D-glucose group, wherein the D-glucose group is optionally substituted. More typically, at least one -R β It is an unsubstituted D-glucose group.

[0155] For the purposes of the present invention, in a substituted monosaccharide group or monosaccharide subunit:

[0156] (a) one or more hydroxyl groups of a monosaccharide group or a monosaccharide subunit are each independently replaced by -H, -F, -Cl, -Br, -I, -CF3, -CCl3, -CBr3, -CI3, -SH, -NH2, -N3, -NH=NH2, -CN, -NO2, -COOH, -R b 、-OR b 、-SR b 、-R a -OR b 、-R a -SR 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 或 -R a -CO-N(R b ) 2替代;和 / 或

[0157] (b) one, two or three hydrogen atoms directly attached to a carbon atom of a monosaccharide group or a monosaccharide subunit are each independently replaced by -F, -Cl, -Br, -I, -CF3, -CCl3, -CBr3, -CI3, -OH, -SH, -NH2, -N3, -NH=NH2, -CN, -NO2, -COOH, -R b 、-OR b 、-SR b 、-R a -OR b 、-R a -SR 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 replace; and / or

[0158] (c) one or more hydroxyl groups of a monosaccharide group or monosaccharide subunit, together with the hydrogen atoms attached to the same carbon atoms as the hydroxyl groups, are each independently replaced by ═O, ═S, ═NR b or =N(R b )2 + Replacement; and / or

[0159] (d) Any two hydroxyl groups of a monosaccharide group or a monosaccharide subunit are combined with -OR c -、-SR c -、-SO-R c -、-SO2-R c -or-NR b -R c - Substitution;

[0160] in:

[0161] Each -R a - independently 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 to 10 carbon atoms;

[0162] Each -Rb is independently hydrogen, or a substituted or unsubstituted linear, branched 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 backbone and preferably contains 1-15 carbon atoms; and

[0163] Each -R c - is independently a chemical bond, or 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 to 10 carbon atoms;

[0164] Provided that the monosaccharide group or monosaccharide subunit contains at least one, preferably at least two or at least three -OH, -OR 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 )2OR-OR c -.

[0165] Typically, in a substituted monosaccharide group or monosaccharide subunit:

[0166] (a) one or more hydroxyl groups of a monosaccharide group or a monosaccharide subunit are each independently replaced by -H, -F, -CF3, -SH, -NH2, -N3, -CN, -NO2, -COOH, -R b 、-OR b 、-SR 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 replacement; and / or

[0167] (b) one or two hydrogen atoms directly attached to a carbon atom of a monosaccharide group or a monosaccharide subunit are each independently replaced by -F, -CF3, -OH, -SH, -NH2, -N3, -CN, -NO2, -COOH, -R b 、-OR b 、-SR 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 replacement; and / or

[0168] (c) one hydroxyl group of a monosaccharide group or a monosaccharide subunit, together with the hydrogen bonded to the same carbon atom as the hydroxyl group, is replaced by =0; and / or

[0169] (d) Any two hydroxyl groups of a monosaccharide group or a monosaccharide subunit are combined with -OR c -or-NR b -R c - Substitution;

[0170] in:

[0171] Each -R b is independently hydrogen, or a substituted or unsubstituted linear, branched 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 backbone and contains 1-8 carbon atoms; and

[0172] Each -R c - is independently 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;

[0173] Provided that the monosaccharide group or monosaccharide subunit contains at least two, preferably at least three -OH, -OR b 、-OPO(R b )2、-OSi(Rb )3. -O-CO-R b 、-O-CO-OR b 、-O-CO-N(R b )2OR-OR c -.

[0174] 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 Substitute, where each -R b are independently C1-C4 alkyl, preferably methyl. In one embodiment, -R β is a glycosyl group and all hydroxyl groups of the glycosyl group are independently substituted by -O-CO-R b Substitute, where each -R b are independently C1-C4 alkyl, preferably methyl.

[0175] In the modified monosaccharide group or monosaccharide subunit:

[0176] (a) the ring of the modified monosaccharide group or monosaccharide subunit or the ring in the closed ring form of the modified monosaccharide group or monosaccharide subunit is partially unsaturated; and / or

[0177] (b) the epoxy group of the modified monosaccharide group or monosaccharide subunit or the epoxy group in the closed ring form of the modified monosaccharide group or monosaccharide subunit is replaced by -S- or -NR d -Substitution, where -R d is independently hydrogen, or a substituted or unsubstituted linear, branched or cyclic alkyl, alkenyl, alkynyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, alkylaryl, alkenylaryl or alkynylaryl group, optionally including one or more heteroatoms each independently selected from O, N and S in its carbon skeleton and preferably containing 1 to 15 carbon atoms.

[0178] Alternatively, where the modified monosaccharide subunit forms part of a disaccharide, oligosaccharide or polysaccharide group, -R d There may be additional monosaccharide subunit(s) forming part of a di-, oligo- or polysaccharide group, wherein any such additional monosaccharide subunit(s) may optionally be substituted and / or modified.

[0179] Typically, in the modified monosaccharide group or monosaccharide subunit:

[0180] (a) the ring of the modified monosaccharide group or monosaccharide subunit, or the ring in the closed ring form of the modified monosaccharide group or monosaccharide subunit, contains a single C=C; and / or

[0181] (b) the epoxy group of the modified monosaccharide group or monosaccharide subunit or the epoxy group in the closed ring form of the modified monosaccharide group or monosaccharide subunit is replaced by -NRd -Substitution, where -R d is independently hydrogen, or a substituted or unsubstituted linear, branched or cyclic alkyl, alkenyl, alkynyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, alkylaryl, alkenylaryl or alkynylaryl group, optionally including one, two or three heteroatoms each independently selected from O and N in its carbon skeleton and containing 1-8 carbon atoms.

[0182] Representative examples of substituted and / or modified monosaccharide subunits include those corresponding to:

[0183] (i) deoxysugars, such as deoxyribose, fucose, fucose, and rhamnose, in which the hydroxyl group of a monosaccharide group or a monosaccharide subunit has been replaced by -H;

[0184] (ii) amino sugars, such as glucosamine and galactosamine, in which the hydroxyl group of a monosaccharide group or monosaccharide subunit has been replaced by -NH2, most commonly at the 2-position; and

[0185] (iii) Sugar acids containing a -COOH group, such as aldonic acid (eg gluconic acid), ketonic acid, uronic acid (eg glucuronic acid) and aldaric acid (eg gularic or galactaric acid).

[0186] In one embodiment of the first or second aspect of the present invention, at least one -R β It is a monosaccharide group selected from the following.

[0187]

[0188] Preferably, in the compound or complex according to the first or second aspect of the present invention, at least one -R β yes:

[0189]

[0190] In one embodiment of the first or second aspect of the present invention, -R 2 、-R 3 or -R 4 At least one of -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:

[0191]

[0192]

[0193] In one embodiment of the first or second aspect of the present invention, -R 2 、-R 3 or -R 4 At least one of -R α -[N(R 5 )3]Y、-R α -[P(R 5 )3]Y、-R α -[R 8 ]Y、-R α -[N(R 5 )2(R 5’ )]、-R α -[P(R 5 )2(R 5’ )] or -R α -[R 8’ In one embodiment, -R 2 、-R 3 or -R 4 At least one of -R α -[N(R 5 )3]Y、-R α -[P(R 5 )3]Y or -R α -[R 8 In one embodiment, -R 2 、-R 3 or -R 4 At least one of is independently selected from:

[0194]

[0195] In the first or second aspect of the present invention, each -R 5 Can be the same or different. In a preferred embodiment, each -R 5 same.

[0196] In one embodiment of the first or second aspect of the invention, each -R 5 In one embodiment, each -R 5 Not replaced.

[0197] In one embodiment of the first or second aspect of the present invention, -R 8is unsubstituted or substituted with one or two substituents. In one embodiment, -R 8 Not replaced.

[0198] In one embodiment, -R 8 The 4-position of the pyridine ring is not substituted by a halo group. 8 The 4-position of the pyridine ring is unsubstituted. In one embodiment, -R 8 Not replaced.

[0199] 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):

[0200]

[0201] or a pharmaceutically acceptable salt thereof, wherein:

[0202] -R 1 Selected from -C(O)-OR 3 、-C(O)-SR 3 or -C(O)-N(R 3 )(R 3’ ), -R 3 Selected from -R α -OR β or -R α -SR β , and -R β is a sugar group, and -R 3’ is H or C1-C4 alkyl;

[0203] -R 6 Selected from:

[0204] (a)-C(O)-OR 3 、-C(O)-SR 3 or -C(O)-N(R 3 )2, and -R 3 Each independently is a C1-C4 alkyl group, preferably -R 6 is-C(O)-OR 3 And -R 3 is C1-C4 alkyl; or

[0205] (b)-C(O)-OR 3 、-C(O)-SR 3 or -C(O)-N(R 3 )(R 3’ ), where -R 3 Selected from -R α -OR β or -Rα -SR β , and -R β is a sugar group, and -R 3’ is H or C1-C4 alkyl;

[0206] -R 7 Selected from:

[0207] (a)-C(O)-OR 3 、-C(O)-SR 3 or -C(O)-N(R 3 )2, and -R 3 Each independently is a C1-C4 alkyl group, preferably -R 7 is-C(O)-OR 3 And -R 3 is C1-C4 alkyl; or

[0208] (b)-C(O)-OR 3 、-C(O)-SR 3 or -C(O)-N(R 3 )(R 3’ ), where -R 3 Selected from -R α -OR β or -R α -SR β , and -R β is a sugar group, and -R 3’ is H or C1-C4 alkyl;

[0209] -R α -Selected from C1-C 12 Alkylene, wherein the alkylene may be optionally substituted with one or more C1-C4 alkyl, C1-C4 haloalkyl, or halo, and wherein one or more carbon atoms in the backbone of the alkylene may be optionally replaced with one or more heteroatoms O or S; and

[0210] M 2+ It is a metal cation.

[0211] 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):

[0212]

[0213] or a pharmaceutically acceptable salt thereof, wherein:

[0214] -R 1 Selected from:

[0215] (a)-C(O)-OR3 、-C(O)-SR 3 or -C(O)-N(R 3 )2, and -R 3 Each independently is -R β , and -R β is C1-C4 alkyl, more preferably, -R 1 is-C(O)-OR 3 And -R 3 Yes-R β , and -R β is C1-C4 alkyl; or

[0216] (b)-C(O)-OR 3 、-C(O)-SR 3 or -C(O)-N(R 3 )(R 3’ ), -R 3 Selected from -R α -OR β or -R α -SR β , and -R β is a sugar group, and -R 3’ is H or C1-C4 alkyl;

[0217] -R 6 Selected from -C(O)-OR 3 、-C(O)-SR 3 or -C(O)-N(R 3 )(R 3’ ), where -R 3 Selected from -R α -OR β or -R α -SR β , and -R β is a sugar group, and -R 3’ is H or C1-C4 alkyl;

[0218] -R 7 Selected from:

[0219] (a)-C(O)-OR 3 、-C(O)-SR 3 or -C(O)-N(R 3 )2, and -R 3 Each independently is a C1-C4 alkyl group, preferably -R 7 is-C(O)-OR 3 And -R 3 is C1-C4 alkyl; or

[0220] (b)-C(O)-OR 3 、-C(O)-SR 3 or -C(O)-N(R 3 )(R 3’ ), where -R 3 Selected from -R α -OR β or -R α -SR β , and -R β is a sugar group, and -R 3’ is H or C1-C4 alkyl;

[0221] -R α -Selected from C1-C 12 Alkylene, wherein the alkylene may be optionally substituted with one or more C1-C4 alkyl, C1-C4 haloalkyl, or halo, and wherein one or more carbon atoms in the backbone of the alkylene may be optionally replaced with one or more heteroatoms O or S; and

[0222] M 2+ It is a metal cation.

[0223] 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):

[0224]

[0225] or a pharmaceutically acceptable salt thereof, wherein:

[0226] -R 1 Selected from:

[0227] (a)-C(O)-OR 3 、-C(O)-SR 3 or -C(O)-N(R 3 )2, and -R 3 Each independently is -R β , and -R β is C1-C4 alkyl, more preferably, -R 1 is-C(O)-OR 3 And -R 3 Yes-R β , and -R β is C1-C4 alkyl; or

[0228] (b)-C(O)-OR 3 、-C(O)-SR 3 or -C(O)-N(R 3 )(R 3’ ), -R3 Selected from -R α -OR β or -R α -SR β , and -R β is a sugar group, and -R 3’ is H or C1-C4 alkyl;

[0229] -R 6 Selected from:

[0230] (a)-C(O)-OR 3 、-C(O)-SR 3 or -C(O)-N(R 3 )2, and -R 3 Each independently is a C1-C4 alkyl group, preferably -R 6 YES-C(O)-OR 3 And -R 3 is C1-C4 alkyl; or

[0231] (b)-C(O)-OR 3 、-C(O)-SR 3 or -C(O)-N(R 3 )(R 3’ ), where -R 3 Selected from -R α -OR β or -R α -SR β , and -R β is a sugar group, and -R 3’ is H or C1-C4 alkyl;

[0232] -R 7 Selected from -C(O)-OR 3 、-C(O)-SR 3 or -C(O)-N(R 3 )(R 3’ ), where -R 3 Selected from -R α -OR β or -R α -SR β , and -R β is a sugar group, and -R 3’ is H or C1-C4 alkyl;

[0233] -R α -Selected from C1-C 12Alkylene, wherein the alkylene may be optionally substituted with one or more C1-C4 alkyl, C1-C4 haloalkyl, or halo, and wherein one or more carbon atoms in the backbone of the alkylene may be optionally replaced with one or more heteroatoms O or S; and

[0234] M 2+ It is a metal cation.

[0235] 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):

[0236]

[0237] or a pharmaceutically acceptable salt thereof, wherein:

[0238] -R 1 Selected from -CH2OR 2 、-CH2SR 2 、-CH2S(O)R 2 、-CH2S(O)2R 2 、-CH2N(R 2 )(R 2’ ),-R 2 、-C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )(R 3’ )、-C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R 3 )(R 3’ ) [Preferably, -R 1 Selected from -C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )(R 3’ )、-C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R 3 )(R 3’ ); More preferably, -R 1 Yes -C(O)-N(R 3 )(R 3’ )];

[0239] -R 2 Selected from -H, -C(O)R 4 、-C(O)-OR 4 、-C(O)-SR 4, -C(O)-N(R 4 )(R 4’ ), -C(S)-OR 4 , -C(S)-SR 4 , -C(S)-N(R 4 )(R 4’ ), -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, -[(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 8 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 8 ’];

[0240] -R 3 and -R4 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, -[(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 8 ]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 8’ ];

[0241] Where -R 2 、-R 3 and -R 4 At least one selected from -[(CH2) p Q] r -(CH2) s -[N(R5 )3]Y、-[(CH2) p Q] r -(CH2) s -[P(R 5 )3]Y、-[(CH2) p Q] r -(CH2) s -[R 8 ]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 8’ ];

[0242] -R 2’ 、-R 3’ and -R 4’ Each independently selected from hydrogen or C1-C6 alkyl [preferably, -R 2’ 、-R 3’ and -R 4’ are each independently selected from hydrogen or C1-C3 alkyl; more preferably, -R 2’ 、-R 3’ and -R 4’ are each independently selected from hydrogen or methyl];

[0243] -R α - each independently selected from C1-C 42 Alkylene, wherein the alkylene may be optionally substituted with one or more (such as one, two, three, four or five) C1-C4 alkyl, C1-C4 haloalkyl or halo, and wherein one or more (such as one, two, three, four, five, six, seven, eight, nine or ten) carbon atoms in the backbone of the alkylene may be optionally replaced with heteroatoms or groups independently selected from O, S, NH or NMe;

[0244] -R βeach independently a saturated or unsaturated hydrocarbon group, wherein the hydrocarbon group may be linear or branched, or may be or include a cyclic group, wherein the hydrocarbon group may be optionally 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;

[0245] -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 be optionally replaced 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 substitution;

[0246] -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 replaced by -CO2 ￣ Substituted, wherein the phenyl or C5-C6 heteroaryl may be 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 substitution;

[0247] -R 6 Selected from -C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )(R 3’ )、-C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R 3 )(R 3’ ) [Preferably, -R 6 Yes -C(O)-N(R 3 )(R3’ )];

[0248] -R 7 Selected from -C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )(R 3’ )、-C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R 3 )(R 3’ ) [Preferably, -R 7 Yes -C(O)-N(R 3 )(R 3’ )];

[0249] -R 8 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 -[NC5H5] substituted with -CH3 group;

[0250] -R 8’ is -[NC5H5], which is replaced 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), halo, -CO2H, -CO2Z, -CO2NH2, -O-(CH2CH2O) n -H or -O-(CH2CH2O) n -CH3 group substitution;

[0251] Q is O, S, NH or NMe [preferably, Q is O];

[0252] X is a halogen group;

[0253] Y is a counter anion;

[0254] Z is a counter cation;

[0255] M 2+ It is a metal cation;

[0256] n is 1, 2, 3, 4, 5, or 6;

[0257] p is 0, 1, 2, 3, or 4;

[0258] r is 0, 1, 2, 3, 4, 5, or 6; and

[0259] s is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12.

[0260] 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):

[0261]

[0262] or a pharmaceutically acceptable salt thereof, wherein:

[0263] -R 1 Selected from -C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )(R 3’ )、-C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R 3 )(R 3’ ) [Preferably, -R 1 Yes -C(O)-N(R 3 )(R 3’ )];

[0264] -R 3 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, -[(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 8 ]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 8’ ]; at least one of them -R 3 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 8 ]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 8’ ];

[0265] -R 3’ Selected from hydrogen or C1-C3 alkyl [preferably, -R 3’ is hydrogen or methyl];

[0266] -R α - each independently selected from C1-C 42 Alkylene, wherein the alkylene may be optionally substituted with one or more (such as one, two, three, four or five) C1-C4 alkyl, C1-C4 haloalkyl or halo, and wherein one or more (such as one, two, three, four, five, six, seven, eight, nine or ten) carbon atoms in the backbone of the alkylene may be optionally replaced with heteroatoms or groups independently selected from O, S, NH or NMe;

[0267] -R β each independently a saturated or unsaturated hydrocarbon group, wherein the hydrocarbon group may be linear or branched, or may be or include a cyclic group, wherein the hydrocarbon group may be optionally 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;

[0268] -R 5 Each independently selected from C1-C3 alkyl or phenyl, wherein the phenyl group may be optionally independently selected from C1-C6 alkyl, -O(C1-C6 alkyl), -CO2H, -CO2Z, -CO2NH2, -O-(CH2CH2O) n -H or -O-(CH2CH2O) n -CH3 is substituted with one, two, three, four or five substituents;

[0269] -R 5’ Selected from -CO2 ￣ Substituted C1-C3 alkyl or -CO2 ￣ Substituted phenyl, wherein the phenyl group 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 is substituted with one, two, three or four substituents;

[0270] -R 6 Selected from -C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )(R 3’ )、-C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R 3 )(R 3’) [Preferably, -R 6 Yes -C(O)-N(R 3 )(R 3’ )];

[0271] -R 7 Selected from -C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )(R 3’ )、-C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R 3 )(R 3’ ) [Preferably, -R 7 Yes -C(O)-N(R 3 )(R 3’ )];

[0272] -R 8 is 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 of -CH3;

[0273] -R 8’ is -[NC5H5], which is replaced by -CO2 ￣ substituted and optionally further independently selected from C1-C6 alkyl, -O(C1-C6 alkyl), -CO2H, -CO2Z, -CO2NH2, -O-(CH2CH2O) n -H or -O-(CH2CH2O) n -CH3 is substituted with one, two, three or four substituents;

[0274] Q is O, S, NH or NMe [preferably, Q is O];

[0275] X is a halogen group;

[0276] Y is a counter anion;

[0277] Z is a counter cation;

[0278] M 2+ It is a metal cation;

[0279] n is 1, 2, 3, 4, 5, or 6;

[0280] p is 0, 1, 2, 3, or 4;

[0281] r is 0, 1, 2, 3, 4, 5, or 6; and

[0282] s is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12.

[0283] In the two preferred embodiments of the preceding paragraphs, each -R 5 Can be the same or different; preferably, each -R 5 same.

[0284] In another preferred embodiment of the first or second aspect of the invention, the compound is a compound of Formula (IA), (IB), (IC), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), (IL), (IM), (IN), (IO), (IP), (IQ), (IR), (IS), (IT), (IU) or (IV):

[0285]

[0286]

[0287]

[0288]

[0289] or a metal cation complex thereof or a pharmaceutically acceptable salt thereof, wherein:

[0290] -R 1 Selected from -C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )(R 3’ )、-C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R 3 )(R 3’ );

[0291] -R 3 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)Rβ 、-R α -S(O)2R β 、-R α -NH2、-R α -NH(R β ),-R α -N(R β )2 or -R α -X;

[0292] -R 3’ Selected from hydrogen or C1-C3 alkyl (preferably hydrogen or methyl);

[0293] -R 6 Selected from -C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )(R 3’ )、-C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R 3 )(R 3’ );

[0294] -R 7 Selected from -C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )(R 3’ )、-C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R 3 )(R 3’ );

[0295] -R α - each independently selected from C1-C 12 Alkylene, wherein the alkylene may be optionally substituted with one or more (such as one, two, three, four or five) C1-C4 alkyl, C1-C4 haloalkyl or halo, and wherein one or more (such as one, two, three, four, five or six) carbon atoms in the backbone of the alkylene may be optionally replaced with heteroatoms or groups independently selected from O, S, NH or NMe;

[0296] -R β each independently a saturated or unsaturated hydrocarbon group, wherein the hydrocarbon group may be linear or branched, or may be or include a cyclic group, wherein the hydrocarbon group may be optionally 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;

[0297] -R δ Selected from C1-C3 alkyl;

[0298] -R ε Selected from C1-C6 alkyl, -O(C1-C6 alkyl), -CO2H, -CO2Z, -CO2NH2, -O-(CH2CH2O) n -H or -O-(CH2CH2O) n -CH3;

[0299] X is a halogen group;

[0300] Y is a counter anion;

[0301] Z is a counter cation;

[0302] n is 1, 2, 3, or 4;

[0303] p is 0, 1, 2, 3, or 4;

[0304] r is 0, 1, 2, 3, 4, 5, or 6;

[0305] s is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12;

[0306] t is 0, 1, 2, 3, 4, or 5; and

[0307] u is 0, 1, 2, 3, and 4.

[0308] The compounds of formula (IA), (IB), (IC), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), (IL), (IM), (IN), (IO), (IP), (IQ), (IR), (IS), (IT), (IU), (IV) and their complexes and salts according to the first and second aspects of the present invention comprise the moiety -[(CH p O] r -(CH2) s -,in

[0309] p is 0, 1, 2, 3, or 4;

[0310] r is 0, 1, 2, 3, 4, 5, or 6; and

[0311] s is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12.

[0312] 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-.

[0313] 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-.

[0314] 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 -Yes-(CH2) 1-12 -.

[0315] Preferably, in the compound or complex according to the first or second aspect of the present invention, the compound or complex is:

[0316]

[0317] wherein Y is a counteranion, and q is 0, 1, 2, 3 or 4 (preferably q is 1);

[0318] or a metal cation complex thereof or a pharmaceutically acceptable salt thereof.

[0319] 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):

[0320]

[0321] or a pharmaceutically acceptable salt thereof, wherein:

[0322] -R 1 Selected from -CO2H or -CO2R 13 ;

[0323] -R 6 Selected from -CO2H or -CO2R 13 ;

[0324] -R 7 Selected from -C(O)-R 14 -R 15 ;

[0325] -R 13Selected from C1-C3 alkyl;

[0326] -R 14 - is selected from NMe, O or S;

[0327] -R 15 Selected from C1-C 20 alkyl, wherein one or more carbon atoms in the alkyl may be optionally replaced by heteroatoms or groups independently selected from O, S, NH or NMe, and wherein the alkyl may be optionally substituted with one or more (such as one, two, three, four, five, six, seven or eight) -OH or -NH groups; and

[0328] M 2+ It is a metal cation;

[0329] The condition is -R 7 Not a -CO2Me or -CO2Et group.

[0330] In one embodiment of this particularly preferred embodiment of the first or second aspect of the invention, the compound of formula (I) or the complex of formula (II) is not:

[0331] Compound CAS <![CDATA[R 1 ]]> <![CDATA[R 6 ]]> <![CDATA[R 7 ]]> <![CDATA[M 2+ ]]> a 1646330-79-1 <![CDATA[-CO2CH2CH2CH3]]> <![CDATA[-CO2H]]> <![CDATA[-CO2CH2CH2CH3]]> <![CDATA[Zn 2+ ]]> b 1810048-08-8 <![CDATA[-CO2Me]]> <![CDATA[-CO2Me]]> <![CDATA[-CO2CH2CH2CH(Me)2]]> -

[0332] or an enantiomer of any of them;

[0333] or a racemic mixture of any of them;

[0334] or a salt of any of them.

[0335] In other embodiments of this particularly preferred embodiment of the first or second aspect of the invention, M 2+ is as defined in any one of the embodiments described above for the first aspect of the invention.

[0336] In one embodiment of this particularly preferred embodiment, -R 1 It is -CO2H.

[0337] In another embodiment of this particularly preferred embodiment, -R 1 Yes-CO2R 13 In one embodiment, -R 13 is methyl, ethyl or propyl. Preferably, -R 13 is methyl or ethyl. Preferably, -R 13 It's methyl.

[0338] In one embodiment of this particularly preferred embodiment, -R 6 It is -CO2H.

[0339] In another embodiment of this particularly preferred embodiment, -R 6 Yes-CO2R 13 In one embodiment, -R 13 is methyl, ethyl or propyl. Preferably, -R 13 is methyl or ethyl. Preferably, -R 13 It's methyl.

[0340] In one embodiment of this particularly preferred embodiment, -R 7 Selected from -C(O)-R 14 -(CH2) x -H, -C(O)-R 14 -(CH2) x -OH, -C(O)-R 14 -(CH2CH2O) y -Me or -C(O)-R 14 -(CH2CH2O) y -H; wherein x is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12; and y is 0, 1, 2, 3, 4, 5 or 6. Preferably, -R 7 Selected from -C(O)-R 14 -(CH2) x -H or -C(O)-R 14 -(CH2CH2O) y -Me. In one embodiment, x is 1, 2, 3, 4, 5, or 6. Preferably, x is 3, 4, or 5. Preferably, x is 4. In one embodiment, y is 1, 2, 3, 4, 5, or 6. Preferably, y is 1, 2, 3, or 4. Preferably, y is 1.

[0341] In one embodiment, -R 14 - is NMe or O. Preferably, -R 14 -It's NMe.

[0342] In another particularly preferred embodiment, the first or second aspect of the present invention provides a compound of formula (I) or a complex of formula (II):

[0343]

[0344] or a pharmaceutically acceptable salt thereof, wherein:

[0345] -R 1 Selected from -CO2H or -CO2R 13 ;

[0346] -R 6 Selected from -CO2H or -CO2R13 ;

[0347] -R 7 Selected from -C(O)-R 14 -R 15 ;

[0348] -R 13 Selected from C1-C3 alkyl;

[0349] -R 14 - is selected from NH, NMe, O or S;

[0350] -R 15 Selected from C4-C 20 alkyl, wherein one or more carbon atoms in the alkyl may be optionally replaced by heteroatoms or groups independently selected from O, S, NH or NMe, and wherein the alkyl may be optionally substituted with one or more (such as one, two, three, four, five, six, seven or eight) -OH or -NH groups; and

[0351] M 2+ It is a metal cation;

[0352] The condition is -R 7 Not a -CO2Me or -CO2Et group.

[0353] In one embodiment of this particularly preferred embodiment of the first or second aspect of the invention, the compound of formula (I) or the complex of formula (II) is not:

[0354]

[0355]

[0356] or an enantiomer of any of them;

[0357] or a racemic mixture of any of them;

[0358] or a salt of any of them.

[0359] In other embodiments of this particularly preferred embodiment of the first or second aspect of the invention, M 2+ is as defined in any one of the embodiments described above for the first aspect of the invention.

[0360] In one embodiment of this particularly preferred embodiment, -R 1 It is -CO2H.

[0361] In another embodiment of this particularly preferred embodiment, -R 1 Yes-CO2R 13In one embodiment, -R 13 is methyl, ethyl or propyl. Preferably, -R 13 is methyl or ethyl. Preferably, -R 13 It's methyl.

[0362] In one embodiment of this particularly preferred embodiment, -R 6 It is -CO2H.

[0363] In another embodiment of this particularly preferred embodiment, -R 6 Yes-CO2R 13 In one embodiment, -R 13 is methyl, ethyl or propyl. Preferably, -R 13 is methyl or ethyl. Preferably, -R 13 It's methyl.

[0364] In one embodiment of this particularly preferred embodiment, -R 7 Selected from -C(O)-R 14 -(CH2) x -H, -C(O)-R 14 -(CH2) x -OH, -C(O)-R 14 -(CH2CH2O) y -Me or -C(O)-R 14 -(CH2CH2O) y’ -H; wherein x is 4, 5, 6, 7, 8, 9, 10, 11 or 12; y is 1, 2, 3, 4, 5 or 6; and y' is 2, 3, 4, 5 or 6. Preferably, -R 7 Selected from -C(O)-R 14 -(CH2) x -H or -C(O)-R 14 -(CH2CH2O) y -Me. In one embodiment, x is 4, 5 or 6. Preferably, x is 4 or 5. Preferably, x is 4. In one embodiment, y is 1, 2, 3, 4, 5 or 6. Preferably, y is 1, 2, 3 or 4. Preferably, y is 1. In one embodiment, y' is 2, 3, 4, 5 or 6. Preferably, y' is 2, 3 or 4.

[0365] In one embodiment, -R 14 - is NH, NMe or O. Preferably, -R 14 - is NH or NMe. Preferably, -R 14 -It's NMe.

[0366] In another particularly preferred embodiment, the first or second aspect of the present invention provides a compound of formula (I) or a complex of formula (II):

[0367]

[0368] or a pharmaceutically acceptable salt thereof, wherein:

[0369] -R 1 Selected from -CH2OR 2 、-CH2SR 2 、-CH2S(O)R 2 、-CH2S(O)2R 2 、-CH2N(R 2 )2. -R 2 、-C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )2. -C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R 3 )2;

[0370] -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 -X, -Rα -[N(R 5 )3]Y、-R α -[P(R 5 )3]Y、-R α -[R 8 ]Y、-R α -[N(R 5 )2(R 5’ )]、-R α -[P(R 5 )2(R 5’ )] or -R α -[R 8’ ];

[0371] -R 3 and -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 8 ]Y、-R α -[N(R 5 )2(R 5’ )]、-R α -[P(R 5 )2(R 5’ )] or -R α -[R 8’ ];

[0372] -R α - each independently selected from C1-C 42Alkylene, wherein the alkylene may be optionally substituted with one or more C1-C4 alkyl, C1-C4 haloalkyl, or halo, and wherein one or more carbon atoms in the backbone of the alkylene may be optionally replaced with heteroatoms or groups independently selected from O, S, NH, or NMe;

[0373] -R β each independently a saturated or unsaturated hydrocarbon group, wherein the hydrocarbon group may be linear or branched, or may be or include a cyclic group, wherein the hydrocarbon group may be optionally substituted, and wherein the hydrocarbon group may optionally include one or more heteroatoms N, O, S, P or Se in its carbon skeleton;

[0374] -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 be optionally replaced by one or more 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 substitution;

[0375] -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 replaced by -CO2 ￣ Substituted, wherein the phenyl or C5-C6 heteroaryl may be optionally further substituted by one or more 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 substitution;

[0376] -R 6 Selected from -C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )2. -C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R3 )2;

[0377] -R 7 Selected from -C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )2. -C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R 3 )2;

[0378] -R 8 is optionally substituted with one or more 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 -[NC5H5] substituted with -CH3 group;

[0379] -R 8’ is -[NC5H5], which is replaced by -CO2 ￣ and optionally further substituted with one or more 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 substitution;

[0380] n is 1, 2, 3, 4, 5, or 6;

[0381] X is a halogen group;

[0382] Y is a counter anion;

[0383] Z is a counter cation; and

[0384] M 2+ It is a metal cation;

[0385] The condition is -R 1 、-R 6 and -R 7 At least one of them contains -R α -[R 8 ]Y or -R α -[R 8’ ].

[0386] In other embodiments of this particularly preferred embodiment of the first or second aspect of the invention, -R1 、-R 2 、-R 3 、-R 4 、-R 5 、-R 5’ 、-R 6 、-R 7 、-R 8 、-R 8’ 、-R α -、-R β , n, X, Y, Z, and M 2+ is as defined in any one of the embodiments described above for the first aspect of the invention.

[0387] In another particularly preferred embodiment, the first or second aspect of the present invention provides a compound of formula (I) or a complex of formula (II):

[0388]

[0389] or a pharmaceutically acceptable salt thereof, wherein:

[0390] -R 1 Selected from -CH2OR 2 、-CH2SR 2 、-CH2S(O)R 2 、-CH2S(O)2R 2 、-CH2N(R 2 )2. -R 2 、-C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )2. -C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R 3 )2;

[0391] -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, -Rα -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 8 Y、-R α -[N(R 5 )₂(R 5’ )]、-R α -[P(R 5 )₂(R 5’ )] or -R α -[R 8’ ;

[0392] -R 3 和 -R 4 各自独立地选自 -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、-Rα -[R 8 ]Y、-R α -[N(R 5 )2(R 5’ )]、-R α -[P(R 5 )2(R 5’ )] or -R α -[R 8’ ];

[0393] -R α - each independently selected from C1-C 42 Alkylene, wherein the alkylene may be optionally substituted with one or more C1-C4 alkyl, C1-C4 haloalkyl, or halo, and wherein one or more carbon atoms in the backbone of the alkylene may be optionally replaced with heteroatoms or groups independently selected from O, S, NH, or NMe;

[0394] -R β each independently a saturated or unsaturated hydrocarbon group, wherein the hydrocarbon group may be linear or branched, or may be or include a cyclic group, wherein the hydrocarbon group may be optionally substituted, and wherein the hydrocarbon group may optionally include one or more heteroatoms N, O, S, P or Se in its carbon skeleton;

[0395] -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 be optionally replaced by one or more 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 substitution;

[0396] -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 replaced by -CO2 ￣Substituted, wherein the phenyl or C5-C6 heteroaryl may be optionally further substituted by one or more 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 substitution;

[0397] -R 6 Selected from -C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )2. -C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R 3 )2;

[0398] -R 7 Selected from -C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )2. -C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R 3 )2;

[0399] -R 8 is optionally substituted with one or more 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 -[NC5H5] substituted with -CH3 group;

[0400] -R 8’ is -[NC5H5], which is replaced by -CO2 ￣ and optionally further substituted with one or more 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 substitution;

[0401] n is 1, 2, 3, 4, 5, or 6;

[0402] X is a halogen group;

[0403] Y is a counter anion;

[0404] Z is a counter cation; and

[0405] M 2+ It is a metal cation;

[0406] The condition is -R 1 、-R 6 and -R 7 At least one of them contains -R 14 -[(CH2) p O)] r -(CH2) s -R 14 -R 16 ,in:

[0407] Each -R 14 - independently selected from NH, NMe, O or S;

[0408] -R 16 It is a sugar group;

[0409] p is 1, 2, 3, or 4;

[0410] r is 0, 1, 2, 3, 4, 5, or 6; and

[0411] s is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12.

[0412] In other embodiments of this particularly preferred embodiment of the first or second aspect of the invention, -R 1 、-R 2 、-R 3 、-R 4 、-R 5 、-R 5’ 、-R 6 、-R 7 、-R 8 、-R 8’ 、-R α -、-R β ,n,X,Y,Z,M 2+ and the glycosyl group is as defined in any of the embodiments described above for the first aspect of the invention.

[0413] In one embodiment of this particularly preferred embodiment, -R 1 、-R 6 and -R 7 At least one of them contains -R 14 -(CH2) s -R 14-R 16 wherein s is 1, 2, 3, 4, 5 or 6. Preferably, s is 2, 3, 4 or 5. Preferably, s is 3.

[0414] In another embodiment of this particularly preferred embodiment, -R 1 、-R 6 and -R 7 At least one of them contains -R 14 -(CH2)3-O-(CH2)3-R 14 -R 16 .

[0415] In another embodiment of this particularly preferred embodiment, -R 1 、-R 6 and -R 7 At least one of them contains -R 14 -(CH2CH2O)2-(CH2)2-R 14 -R 16 .

[0416] In another particularly preferred embodiment, the first or second aspect of the present invention provides a compound of formula (I) or a complex of formula (II):

[0417]

[0418] or a pharmaceutically acceptable salt thereof, wherein:

[0419] -R 1 Selected from -CH2OR 2 、-CH2SR 2 、-CH2S(O)R 2 、-CH2S(O)2R 2 、-CH2N(R 2 )2. -R 2 、-C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )2. -C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R 3 )2;

[0420] -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)-OR4 、 -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 -X、 -R α -[N(R 5 )3]Y、 -R α -[P(R 5 )3]Y、 -R α -[R 8 Y、 -R α -[N(R 5 )2(R 5’ )]、 -R α -[P(R 5 )2(R 5’ )] or -R α -[R 8’ ;

[0421] -R 3 和 -R 4 各自独立地选自 -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(Rβ ),-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 8 ]Y、-R α -[N(R 5 )2(R 5’ )]、-R α -[P(R 5 )2(R 5’ )] or -R α -[R 8’ ];

[0422] -R α - each independently selected from C1-C 42 Alkylene, wherein the alkylene may be optionally substituted with one or more C1-C4 alkyl, C1-C4 haloalkyl, or halo, and wherein one or more carbon atoms in the backbone of the alkylene may be optionally replaced with heteroatoms or groups independently selected from O, S, NH, or NMe;

[0423] -R β each independently a saturated or unsaturated hydrocarbon group, wherein the hydrocarbon group may be linear or branched, or may be or include a cyclic group, wherein the hydrocarbon group may be optionally substituted, and wherein the hydrocarbon group may optionally include one or more heteroatoms N, O, S, P or Se in its carbon skeleton;

[0424] -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 be optionally replaced by one or more 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 substitution;

[0425] -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 replaced by -CO2 ￣ Substituted, wherein the phenyl or C5-C6 heteroaryl may be optionally further substituted by one or more 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 substitution;

[0426] -R 6 Selected from -C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )2. -C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R 3 )2;

[0427] -R 7 Selected from -C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )2. -C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R 3 )2;

[0428] -R 8 is optionally substituted with one or more 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 -[NC5H5] substituted with -CH3 group;

[0429] -R 8’ is -[NC5H5], which is replaced by -CO2 ￣ and optionally further substituted with one or more 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 substitution;

[0430] n is 1, 2, 3, 4, 5, or 6;

[0431] X is a halogen group;

[0432] Y is a counter anion;

[0433] Z is a counter cation; and

[0434] M 2+ It is a metal cation;

[0435] The condition is -R 1 、-R 6 and -R 7 At least one of them contains -R 14 -[(CH2) p -R 14 ] r -(CH2) s -R 17 ,in:

[0436] Each -R 14 - independently selected from NH, NMe, O or S;

[0437] -R 17 Yes-[P(R 5 )3]Y or -[P(R 5 )2(R 5’ )];

[0438] p is 1, 2, 3, or 4;

[0439] r is 0, 1, 2, 3, 4, 5, or 6; and

[0440] s is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12.

[0441] In other embodiments of this particularly preferred embodiment of the first or second aspect of the invention, -R 1 、-R 2 、-R 3 、-R 4 、-R 5 、-R 5’ 、-R 6 、-R 7 、-R 8 、-R 8’ 、-R α -、-R β , n, X, Y, Z, and M 2+ is as defined in any one of the embodiments described above for the first aspect of the invention.

[0442] In one embodiment of this particularly preferred embodiment, -R1 、-R 6 and -R 7 At least one of them contains -R 14 -(CH2) s -R 17 wherein s is 1, 2, 3, 4, 5 or 6. Preferably, s is 2, 3, 4 or 5. Preferably, s is 3.

[0443] In another embodiment of this particularly preferred embodiment, -R 1 、-R 6 and -R 7 At least one of them contains -R 14 -(CH2)3-O-(CH2)3-R 17 .

[0444] In another embodiment of this particularly preferred embodiment, -R 1 、-R 6 and -R 7 At least one of them contains -R 14 -(CH2CH2O)2-(CH2)2-R 17 .

[0445] In one embodiment of this particularly preferred embodiment, -R 17 Yes -PPh3 + Cl - or -PPh3 + Br - .

[0446] In another particularly preferred embodiment, the first or second aspect of the present invention provides a compound of formula (I) or a complex of formula (II):

[0447]

[0448] or a pharmaceutically acceptable salt thereof, wherein:

[0449] -R 1 Selected from -CH2OR 2 、-CH2SR 2 、-CH2S(O)R 2 、-CH2S(O)2R 2 、-CH2N(R 2 )2. -R 2 、-C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )2. -C(S)-OR 3 、-C(S)-SR3 or -C(S)-N(R 3 )2;

[0450] -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 -X, -R α -[N(R 5 )3]Y、-R α -[P(R 5 )3]Y、-R α -[R 8 ]Y、-R α -[N(R 5 )2(R 5’ )]、-R α -[P(R 5 )2(R 5’ )] or -R α -[R 8’ ];

[0451] -R 3 and -R 4 Each independently selected from -H, -R α -H, -R β 、-R α -R β 、-R α -OH, -Rα -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 8 ]Y、-R α -[N(R 5 )2(R 5’ )]、-R α -[P(R 5 )2(R 5’ )] or -R α -[R 8’ ];

[0452] -R α - each independently selected from C1-C 42 Alkylene, wherein the alkylene may be optionally substituted with one or more C1-C4 alkyl, C1-C4 haloalkyl, or halo, and wherein one or more carbon atoms in the backbone of the alkylene may be optionally replaced with heteroatoms or groups independently selected from O, S, NH, or NMe;

[0453] -R β each independently a saturated or unsaturated hydrocarbon group, wherein the hydrocarbon group may be linear or branched, or may be or include a cyclic group, wherein the hydrocarbon group may be optionally substituted, and wherein the hydrocarbon group may optionally include one or more heteroatoms N, O, S, P or Se in its carbon skeleton;

[0454] -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 be optionally replaced by one or more 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 substitution;

[0455] -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 replaced by -CO2 ￣ Substituted, wherein the phenyl or C5-C6 heteroaryl may be optionally further substituted by one or more 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 substitution;

[0456] -R 6 Selected from -C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )2. -C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R 3 )2;

[0457] -R 7 Selected from -C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )2. -C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R 3 )2;

[0458] -R 8 is optionally substituted with one or more 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 -[NC5H5] substituted with -CH3 group;

[0459] -R 8’ is -[NC5H5], which is replaced by -CO2 ￣ and optionally further substituted with one or more 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 substitution;

[0460] n is 1, 2, 3, 4, 5, or 6;

[0461] X is a halogen group;

[0462] Y is a counter anion;

[0463] Z is a counter cation; and

[0464] M 2+ It is a metal cation;

[0465] The condition is -R 1 、-R 6 and -R 7 At least one of:

[0466] (i)-R 14 -[(CH2) p -R 14 ] r -(CH2) s -R 18 ,in:

[0467] Each -R 14 - independently selected from NH, NMe, O or S;

[0468] -R 18 Yes-[N(R 5 )3]Y or -[N(R 5 )2(R 5’ )];

[0469] p is 1, 2, 3, or 4;

[0470] r is 2, 3, 4, 5, or 6; and

[0471] s is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12; or

[0472] (ii)-R 14 -(CH2)s -R 18 ,in:

[0473] -R 14 is selected from NH, NMe, O or S;

[0474] -R 18 Yes-[N(R 5 )3]Y or -[N(R 5 )2(R 5’ )];and

[0475] s is 4, 5, 6, 7, 8, 9, 10, 11, or 12.

[0476] In other embodiments of this particularly preferred embodiment of the first or second aspect of the invention, -R 1 、-R 2 、-R 3 、-R 4 、-R 5 、-R 5’ 、-R 6 、-R 7 、-R 8 、-R 8’ 、-R α -、-R β , n, X, Y, Z, and M 2+ is as defined in any one of the embodiments described above for the first aspect of the invention.

[0477] In one embodiment of this particularly preferred embodiment of the first or second aspect of the invention, -R 1 、-R 6 and -R 7 At least one of them contains -R 14 -[(CH2) p -R 14 ] r -(CH2) s -R 18 ; wherein p is 2, 3 or 4; r is 2, 3, 4, 5 or 6; and s is 2, 3, 4, 5 or 6.

[0478] In another embodiment of this particularly preferred embodiment of the first or second aspect of the invention, -R 1 、-R 6 and -R 7 At least one of them contains -R 14 -(CH2) s -R 18 ; where s is 4, 5, or 6.

[0479] In one embodiment of this particularly preferred embodiment, -R 18 Yes-NMe3 + Cl - or-NMe3 + Br - .

[0480] In another particularly preferred embodiment, the first or second aspect of the present invention provides a compound of formula (I) or a complex of formula (II):

[0481]

[0482] or a pharmaceutically acceptable salt thereof, wherein:

[0483] -R 1 Selected from -CH2OR 2 、-CH2SR 2 、-CH2S(O)R 2 、-CH2S(O)2R 2 、-CH2N(R 2 )2. -R 2 、-C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )2. -C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R 3 )2;

[0484] -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)2Rβ 、 -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 8 Y、 -R α -[N(R 5 )₂(R 5’ )]、 -R α -[P(R 5 )₂(R 5’ )]或 -R α -[R 8’ ;

[0485] -R 3 和 -R 4 各自独立地选自 -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 8 Y、 -R α -[N(R 5 )₂(R 5’ )]、 -R α -[P(R 5 )₂(R 5’ )]或 -Rα -[R 8’ ];

[0486] -R α - each independently selected from C1-C 42 Alkylene, wherein the alkylene may be optionally substituted with one or more C1-C4 alkyl, C1-C4 haloalkyl, or halo, and wherein one or more carbon atoms in the backbone of the alkylene may be optionally replaced with heteroatoms or groups independently selected from O, S, NH, or NMe;

[0487] -R β each independently a saturated or unsaturated hydrocarbon group, wherein the hydrocarbon group may be linear or branched, or may be or include a cyclic group, wherein the hydrocarbon group may be optionally substituted, and wherein the hydrocarbon group may optionally include one or more heteroatoms N, O, S, P or Se in its carbon skeleton;

[0488] -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 be optionally replaced by one or more 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 substitution;

[0489] -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 replaced by -CO2 ￣ Substituted, wherein the phenyl or C5-C6 heteroaryl may be optionally further substituted by one or more 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 substitution;

[0490] -R 6 Selected from -C(O)-OR 3 、-C(O)-SR3 、-C(O)-N(R 3 )2. -C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R 3 )2;

[0491] -R 7 Selected from -C(O)-OR 19 ;

[0492] -R 8 is optionally substituted with one or more 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 -[NC5H5] substituted with -CH3 group;

[0493] -R 8’ is -[NC5H5], which is replaced by -CO2 ￣ and optionally further substituted with one or more 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 substitution;

[0494] -R 19 is a C3-C6 alkyl group;

[0495] n is 1, 2, 3, 4, 5, or 6;

[0496] X is a halogen group;

[0497] Y is a counter anion;

[0498] Z is a counter cation; and

[0499] M 2+ It is a metal cation.

[0500] In one embodiment of this particularly preferred embodiment of the first or second aspect of the invention, the compound of formula (I) or the complex of formula (II) is not:

[0501] Compound CAS <![CDATA[R 1 ]]> <![CDATA[R 6 ]]> <![CDATA[R 7 ]]> <![CDATA[M 2+ ]]> a <![CDATA[-CO2H]]> <![CDATA[-CO2CH2CH2CH3]]> <![CDATA[-CO2CH2CH2CH3]]> <![CDATA[Zn 2+ ]]> b 1810048-08-8 <![CDATA[-CO2Me]]> <![CDATA[-CO2Me]]> <![CDATA[-CO2CH2CH2CH(Me)2]]> - r 1646330-81-5 <![CDATA[-CO2CH2CH2CH2CH3]]> <![CDATA[-CO2H]]> <![CDATA[-CO2CH2CH2CH2CH3]]> <![CDATA[Zn 2+ ]]> s 1448805-26-2 <![CDATA[-CO2CH2CH2CH2CH3]]> <![CDATA[-CO2H]]> <![CDATA[-CO2CH2CH2CH2CH3]]> -

[0502] or an enantiomer of any of them;

[0503] or a racemic mixture of any of them;

[0504] or a salt of any of them.

[0505] In other embodiments of this particularly preferred embodiment of the first or second aspect of the invention, -R 1 、-R 2 、-R 3 、-R 4 、-R 5 、-R 5’ 、-R 6 、-R 8 、-R 8’ 、-R α -、-R β , n, X, Y, Z, and M 2+ is as defined in any one of the embodiments described above for the first aspect of the invention.

[0506] In one embodiment of this particularly preferred embodiment of the first or second aspect of the invention, -R 19 is propyl, butyl, pentyl or hexyl.

[0507] In another particularly preferred embodiment, the first or second aspect of the present invention provides a compound of formula (I) or a complex of formula (II):

[0508]

[0509] or a pharmaceutically acceptable salt thereof, wherein:

[0510] -R 1 Selected from -CH2OR 2 、-CH2SR 2 、-CH2S(O)R 2 、-CH2S(O)2R 2 、-CH2N(R 2 )2. -R 2 、-C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )2. -C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R 3 )2;

[0511] -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 -X, -R α -[N(R 5 )3]Y, -R α -[P(R 5 )3]Y, -R α -[R 8 Y, -R α -[N(R 5 )2(R 5’ )], -R α -[P(R 5 )2(R 5’ )] or -R α -[R 8’ ;

[0512] -R 3 and -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 , -Rα -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 8 ]Y、-R α -[N(R 5 )2(R 5’ )]、-R α -[P(R 5 )2(R 5’ )] or -R α -[R 8’ ];

[0513] -R α - each independently selected from C1-C 42 Alkylene, wherein the alkylene may be optionally substituted with one or more C1-C4 alkyl, C1-C4 haloalkyl, or halo, and wherein one or more carbon atoms in the backbone of the alkylene may be optionally replaced with heteroatoms or groups independently selected from O, S, NH, or NMe;

[0514] -R β each independently a saturated or unsaturated hydrocarbon group, wherein the hydrocarbon group may be linear or branched, or may be or include a cyclic group, wherein the hydrocarbon group may be optionally substituted, and wherein the hydrocarbon group may optionally include one or more heteroatoms N, O, S, P or Se in its carbon skeleton;

[0515] -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 be optionally replaced by one or more 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 substitution;

[0516] -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 replaced by -CO2 ￣ Substituted, wherein the phenyl or C5-C6 heteroaryl may be optionally further substituted by one or more 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 substitution;

[0517] -R 6 Selected from -C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )2. -C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R 3 )2;

[0518] -R 7 Selected from -C(O)-NR 20 R 21 ;

[0519] -R 8 is optionally substituted with one or more 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 -[NC5H5] substituted with -CH3 group;

[0520] -R 8’ is -[NC5H5], which is replaced by -CO2 ￣ and optionally further substituted with one or more 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 substitution;

[0521] -R 20 is a C1-C6 alkyl group, preferably a C1-C2 or C4-C6 alkyl group;

[0522] -R 21 is H or C1-C6 alkyl;

[0523] n is 1, 2, 3, 4, 5, or 6;

[0524] X is a halogen group;

[0525] Y is a counter anion;

[0526] Z is a counter cation; and

[0527] M 2+ It is a metal cation.

[0528] In one embodiment of this particularly preferred embodiment of the first or second aspect of the invention, the compound of formula (I) or the complex of formula (II) is not:

[0529] Compound CAS <![CDATA[R 1 ]]> <![CDATA[R 6 ]]> <![CDATA[R 7 ]]> <![CDATA[M 2+ ]]> c <![CDATA[-CO2H]]> <![CDATA[-CO2H]]> <![CDATA[-C(O)NH(CH2)3CH3]]> <![CDATA[Cu 2+ ]]> d 2459194-57-9 <![CDATA[-CO2H]]> <![CDATA[-CO2H]]> <![CDATA[-C(O)NH(CH2)3CH3]]> <![CDATA[Cu 2+ ]]> e 2459194-35-3 <![CDATA[-CO2H]]> <![CDATA[-CO2H]]> <![CDATA[-C(O)NH(CH2)3CH3]]> - t 1810047-98-3 <![CDATA[-CO2Me]]> <![CDATA[-CO2Me]]> <![CDATA[-C(O)NH(CH2)2CH3]]> - u 1810048-00-0 <![CDATA[-CO2Me]]> <![CDATA[-CO2Me]]> <![CDATA[-C(O)NHCH(CH3)2]]> - v 2627055-11-0 <![CDATA[-CO2Me]]> -C(O)NHMe <![CDATA[-C(O)NEt2]]> - w 2627055-07-4 <![CDATA[-CO2Me]]> -C(O)NHMe <![CDATA[-C(O)NH(CH2)3CH3]]> - x 2627055-12-1 <![CDATA[-CO2Me]]> <![CDATA[-C(O)N(Me)2]]> <![CDATA[-C(O)NEt2]]> - y 2627055-08-5 <![CDATA[-CO2Me]]> <![CDATA[-C(O)N(Me)2]]> <![CDATA[-C(O)NH(CH2)3CH3]]> - z 2459194-59-1 <![CDATA[-C(O)NH(CH2)3CH3]]> <![CDATA[-CO2H]]> <![CDATA[-C(O)NH(CH2)3CH3]]> <![CDATA[Cu 2+ ]]> aa 2459194-36-4 <![CDATA[-C(O)NH(CH2)3CH3]]> <![CDATA[-CO2H]]> <![CDATA[-C(O)NH(CH2)3CH3]]> - ab 2627055-14-3 <![CDATA[-CO2Me]]> -C(O)-morpholin-1-yl <![CDATA[-C(O)NEt2]]> - ac 2627055-10-9 <![CDATA[-CO2Me]]> -C(O)-morpholin-1-yl <![CDATA[-C(O)NH(CH2)3CH3]]> - ad 2627055-13-2 <![CDATA[-CO2Me]]> <![CDATA[-C(O)NH(CH2)3CH3]]> <![CDATA[-C(O)NEt2]]> - ae 2627055-09-6 <![CDATA[-CO2Me]]> <![CDATA[-C(O)NH(CH2)3CH3]]> <![CDATA[-C(O)NH(CH2)3CH3]]> - af 2627055-19-8 <![CDATA[-CO2Me]]> -C(O)NHMe <![CDATA[-C(O)N[(CH2)3CH3]2]]> - ag 2627055-24-5 <![CDATA[-CO2Me]]> -C(O)NHEt <![CDATA[-C(O)N[(CH2)3CH3]2]]> - ah 2627055-20-1 <![CDATA[-CO2Me]]> <![CDATA[-C(O)N(Me)2]]> <![CDATA[-C(O)N[(CH2)3CH3]2]]> - ai 2627055-21-2 <![CDATA[-CO2Me]]> -C(O)-morpholin-1-yl <![CDATA[-C(O)N[(CH2)3CH3]2]]> -

[0530] or an enantiomer of any of them;

[0531] or a racemic mixture of any of them;

[0532] or a salt of any of them.

[0533] In other embodiments of this particularly preferred embodiment of the first or second aspect of the invention, -R 1 、-R 2 、-R 3 、-R 4 、-R 5 、-R 5’ 、-R 6 、-R 8 、-R 8’ 、-R α -、-R β , n, X, Y, Z, and M 2+ is as defined in any one of the embodiments described above for the first aspect of the invention.

[0534] In one embodiment of this particularly preferred embodiment of the first or second aspect of the invention, -R 20 is methyl, ethyl, propyl, butyl, pentyl or hexyl. 20 is methyl, ethyl, butyl, pentyl or hexyl. 20 It's butyl.

[0535] In one embodiment of this particularly preferred embodiment of the first or second aspect of the invention, -R 21is hydrogen, methyl, ethyl, propyl, butyl, pentyl or hexyl. 21 is hydrogen or methyl.

[0536] Preferably, -R 20 is butyl, and -R 21 It's methyl.

[0537] In another particularly preferred embodiment, the first or second aspect of the present invention provides a pharmaceutically acceptable salt of a compound of formula (I) or a complex of formula (II):

[0538]

[0539] in:

[0540] -R 1 It is -CO2H;

[0541] -R 6 It is -CO2H;

[0542] -R 7 YES-C(O)-OR 22 or -C(O)-NR 20 R 21 ;

[0543] -R 20 is a C1-C6 alkyl group;

[0544] -R 21 is H or C1-C6 alkyl;

[0545] -R 22 is a C1-C6 alkyl group;

[0546] M 2+ is a metal cation; and

[0547] The pharmaceutically acceptable salt is a lithium salt, a sodium salt, a potassium salt, a magnesium salt, a calcium salt, an ammonium salt, an amine salt (such as choline or meglumine) or an amino acid salt (such as arginine), or a combination thereof.

[0548] In other embodiments of this particularly preferred embodiment of the first or second aspect of the invention, M 2+ is as defined in any one of the embodiments described above for the first aspect of the invention.

[0549] In one embodiment of this particularly preferred embodiment of the first or second aspect of the invention, -R 7 YES-C(O)-OR 22 In one embodiment, -R 22 is methyl, ethyl, propyl, butyl, pentyl or hexyl.22 is methyl, ethyl, propyl or butyl. 22 It is methyl or ethyl.

[0550] In one embodiment of this particularly preferred embodiment of the first or second aspect of the invention, -R 7 Yes -C(O)-NR 20 R 21 In one embodiment, -R 20 is methyl, ethyl, propyl, butyl, pentyl or hexyl. In one embodiment, -R 21 is hydrogen, methyl, ethyl, propyl, butyl, pentyl or hexyl. 20 is butyl, and -R 21 is hydrogen or methyl. Preferably, -R 20 is butyl, and -R 21 It's methyl.

[0551] In one embodiment, the pharmaceutically acceptable salt is a lithium salt, a sodium salt, a potassium salt, a magnesium salt, a calcium salt, an ammonium salt, a choline salt, a meglumine salt, or an amino acid salt, or a combination thereof. Preferably, the pharmaceutically acceptable salt is a lithium salt, a sodium salt, a potassium salt, or a meglumine salt, or a combination thereof. Preferably, the pharmaceutically acceptable salt is a sodium salt or a meglumine salt, or a combination thereof.

[0552] In one embodiment, the pharmaceutically acceptable salt is a monosodium salt. In another embodiment, the pharmaceutically acceptable salt is a disodium salt. In another embodiment, the pharmaceutically acceptable salt is a monomeglumine salt. In another embodiment, the pharmaceutically acceptable salt is a dimeglumine salt. In another embodiment, the pharmaceutically acceptable salt is a monosodium monomeglumine mixed salt.

[0553] Preferably, in the compound or complex according to the first or second aspect of the present invention, the compound or complex is:

[0554]

[0555]

[0556]

[0557]

[0558]

[0559]

[0560]

[0561]

[0562]

[0563]

[0564]

[0565]

[0566] or a metal cation complex thereof or a pharmaceutically acceptable salt thereof.

[0567] 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, a sodium salt, a potassium salt, a magnesium salt, a calcium salt or an 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., a choline or meglumine salt) or an amino acid salt (e.g., an arginine salt).

[0568] The compounds or complexes according to the first or second aspects of the invention have at least two chiral centers. The compounds or complexes of the first or second aspects of the invention are preferably substantially enantiomerically pure, which means that the compounds or complexes contain 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 as measured by XRPD or SFC.

[0569] Preferably, the compound or complex according to the first or second aspect of the invention has an HPLC purity of 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, percent HPLC purity is measured by the area normalization method.

[0570] The third aspect of the present invention provides a composition comprising the compound or complex according to the first or second aspect of the present invention and a pharmaceutically acceptable carrier or diluent.

[0571] In one embodiment, the composition according to the third aspect of the invention further comprises polyvinylpyrrolidone (PVP). In one embodiment, the composition comprises 0.01%-10% w / w PVP as a percentage of the total weight of the composition, preferably 0.1%-5% w / w PVP as a percentage of the total weight of the composition, preferably 0.5%-5% w / w PVP as a percentage of the total weight of the composition. In one embodiment, the PVP is K30.

[0572] In one embodiment, the composition according to the third aspect of the invention further comprises dimethyl sulfoxide (DMSO). In one embodiment, the composition comprises 0.01%-99% w / w DMSO as a percentage of the total weight of the composition, preferably 40%-99% w / w DMSO as a percentage of the total weight of the composition, preferably 65%-99% w / w DMSO as a percentage of the total weight of the composition.

[0573] 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, cemiplizumab, atezolizumab, avelumab, durvalumab or ipilimumab.

[0574] 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.

[0575] 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 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 (chicken) influenza virus, dengue virus, herpes simplex or herpes 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 by areas of neovascularization; benign or malignant tumors; early-stage cancers; cervical dysplasia; soft tissue sarcomas; germ cell tumors; retinoblastoma; age-related macular degeneration; lymphoma; Hodgkin lymphoma; head and neck cancer; oral cavity or mouth cancer; or cancer of the blood, prostate, cervix, uterus, vagina, or other female adnexa, breast, nasopharynx, trachea, larynx, bronchus, bronchioles, lung, hollow organ, esophagus, stomach, bile duct, intestinal cancer, colon, colorectal cancer, rectum, bladder, ureter, kidney, liver, gallbladder, spleen, brain, lymphatic system, bone, skin, or pancreas.

[0576] Preferably, the compounds or complexes according to the first or second aspect of the invention and the pharmaceutical compositions according to the third aspect of the invention are suitable for treating diseases characterized by excessive proliferation of benign or malignant cells or by areas of neovascularization.

[0577] Preferably, the compound or complex according to the first or second aspect of the invention and the pharmaceutical composition according to the third aspect of the invention are suitable for the treatment of benign or malignant tumors.

[0578] Preferably, the compounds or complexes according to the first or second aspect of the invention and the pharmaceutical compositions according to the third aspect of the invention are suitable for the treatment of early stage cancer; cervical dysplasia; soft tissue sarcoma; germ cell tumors; 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 adnexa cancer, breast cancer, nasopharyngeal cancer, tracheal cancer, laryngeal cancer, bronchial cancer, bronchiolar cancer, lung cancer, hollow organ cancer, esophageal cancer, stomach cancer, bile duct cancer, intestinal cancer, colon cancer, colorectal cancer, rectal cancer, bladder cancer, ureter cancer, kidney cancer, liver cancer, gallbladder cancer, spleen cancer, brain cancer, lymphatic system cancer, bone cancer, skin cancer or pancreatic cancer.

[0579] 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.

[0580] 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, chlamydia, bacterial, nanobacterial or parasitic infectious diseases; HIV; AIDS; SARS virus (preferably severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)), Asian (chicken) influenza virus, dengue virus, herpes simplex or herpes 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 by areas of neovascularization; benign or malignant tumors; early-stage cancers; cervical dysplasia; soft tissue sarcomas; germ cell tumors; retinoblastoma; age-related macular degeneration; lymphoma; Hodgkin lymphoma; head and neck cancer; oral cavity or mouth cancer; or cancer of the blood, prostate, cervix, uterus, vagina, or other female adnexa, breast, nasopharynx, trachea, larynx, bronchus, bronchioles, lung, hollow organ, esophagus, stomach, bile duct, intestinal cancer, colon, colorectal cancer, rectum, bladder, ureter, kidney, liver, gallbladder, spleen, brain, lymphatic system, bone, skin, or pancreas.

[0581] Preferably, the compounds or complexes according to the first or second aspect of the invention and the pharmaceutical compositions according to the third aspect of the invention are suitable for detecting areas affected by benign or malignant cell hyperproliferation or by neovascularization.

[0582] 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.

[0583] Preferably, the compounds or complexes according to the first or second aspect of the invention and the pharmaceutical compositions according to the third aspect of the invention are suitable for detecting early stage cancer; cervical dysplasia; soft tissue sarcoma; germ cell tumors; 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 adnexa cancer, breast cancer, nasopharyngeal cancer, tracheal cancer, laryngeal cancer, bronchial cancer, bronchiolar cancer, lung cancer, hollow organ cancer, esophageal cancer, stomach cancer, bile duct cancer, intestinal cancer, colon cancer, colorectal cancer, rectal cancer, bladder cancer, ureter cancer, kidney cancer, liver cancer, gallbladder cancer, spleen cancer, brain cancer, lymphatic system cancer, bone cancer, skin cancer or pancreatic cancer.

[0584] Preferably, the compound or complex according to the first or second aspect of the invention and the pharmaceutical composition according to the third aspect of the invention are suitable for fluorescent or phosphorescent detection of the diseases listed above, preferably for fluorescent or phosphorescent detection and quantification of said diseases.

[0585] Preferably, the compound or complex according to the first or second aspect of the invention and the pharmaceutical composition according to the third aspect of the invention are suitable for administration simultaneously with or before the administration of radiation or sound, preferably suitable for administration before the administration of radiation.

[0586] If the compounds or complexes according to the first or second aspect of the invention or the pharmaceutical compositions according to the third aspect of the invention are used in photodynamic therapy or cytoluminescence therapy, they are preferably suitable for administration 5 to 100 hours before irradiation, preferably 6 to 72 hours before irradiation, preferably 24 to 48 hours before irradiation.

[0587] If the compounds or complexes according to the first or second aspect of the invention or the pharmaceutical compositions according to the third aspect of the invention are used in photodynamic diagnosis, they are preferably suitable for administration 3 to 60 hours before irradiation, preferably 8 to 40 hours before irradiation.

[0588] Preferably, the irradiation used in photodynamic therapy, cell luminescence therapy or photodynamic diagnosis is electromagnetic radiation with a wavelength of 500nm to 1000nm, preferably 550nm to 750nm, preferably 600nm to 700nm, preferably 640nm to 670nm. Electromagnetic radiation can be applied for about 5-60 minutes, preferably for about 15-20 minutes, at about 0.1-5W, preferably with about 1W. In one embodiment of the invention, two electromagnetic radiation sources (such as lasers and LED lamps) are used, and both sources are suitable for providing irradiation with a wavelength of 550nm to 750nm, preferably 600nm to 700nm, preferably 640nm to 670nm. In another embodiment of the invention, irradiation can be provided by a prostate, anus, vagina, mouth and nose device for insertion into a body cavity. In another embodiment of the invention, irradiation can be provided by interstitial light activation, for example, a fiber laser is inserted into a lung, liver, lymph node or breast using a fine needle. In another embodiment of the invention, illumination can be provided by endoscopic photoactivation, for example, for delivery of light to the lungs, stomach, colon, bladder, or neck.

[0589] The pharmaceutical composition according to the third aspect of the present invention can be in a form suitable for oral, parenteral (including intravenous, subcutaneous, intramuscular, intradermal, intratracheal, intraperitoneal, intratumoral, intraarticular, intraperitoneal, intracranial and epidural), transdermal, airway (aerosol), rectal, vaginal or topical (including buccal, mucosal and sublingual) administration. The pharmaceutical composition can 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, preferably in a form suitable for oral administration.

[0590] 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, caplets, lozenges or lozenges, provides in powder or granular form, or provides in the form of an aqueous solution, a suspension or a dispersion. More preferably, the pharmaceutical composition is provided in the form of an aqueous solution, a suspension or a dispersion for oral administration, or alternatively provides in the form of a lyophilized powder, which can be mixed with water before use to provide an aqueous solution, a suspension or a dispersion for oral administration. Preferably, the pharmaceutical composition is in the form of a compound according to the first or second aspect of the present invention that is suitable for providing 0.01 to 10mg / kg / days, preferably 0.1 to 2mg / kg / days, preferably about 1mg / kg / days or a complex.

[0591] 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 provided 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 with a pH of 6 to 8.5. Preferably, the pharmaceutical composition is in the form of a compound or complex according to the first or second aspect of the present invention that is suitable for providing 0.01 to 10 mg / kg / day, preferably 0.1 to 2 mg / kg / day, preferably about 1 mg / kg / day.

[0592] 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 provided in the form of a lyophilized powder that 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 0.01 to 10 mg / kg / day, preferably 0.1 to 2 mg / kg / day, preferably about 1 mg / kg / day of the compound or complex according to the first or second aspect of the invention.

[0593] 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, chlamydia, bacterial, nanobacterial or parasitic infectious diseases; HIV; AIDS; SARS virus (preferably severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)), Asian (chicken) influenza virus, dengue virus, herpes simplex or herpes zoster infection; hepatitis; viral hepatitis; cardiovascular disease; coronary artery stenosis; carotid artery stenosis; intermittent claudication; skin disorders; acne; psoriasis any disease characterized by excessive proliferation of benign or malignant cells or by areas of neovascularization; any benign or malignant tumor; any early stage cancer; any cervical dysplasia; any soft tissue sarcoma; any germ cell tumor; any retinoblastoma; any age-related macular degeneration; any lymphoma; any Hodgkin lymphoma; any cancer of the head and neck; any cancer of the oral cavity or mouth; or any cancer of the blood, prostate, cervix, uterus, vagina, or other female appendages, breast, nasopharynx, trachea, larynx, bronchus, bronchioles, lung, or any hollow organ, esophagus, stomach, bile duct, intestinal tract, colon, colorectum, rectum, bladder, ureter, kidney, liver, gallbladder, spleen, brain, lymphatic system, bone, skin, or pancreas.

[0594] The fourth aspect of the present invention also provides the use of the 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 cell luminescence therapy. Preferably, the phototherapeutic agent is suitable for treating atherosclerosis; multiple sclerosis; diabetes; diabetic retinopathy; arthritis; rheumatoid arthritis; fungal, viral, chlamydia, bacterial, nanobacterial or parasitic infectious diseases; HIV; AIDS; sars virus (preferably severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)), Asian (chicken) influenza virus, dengue virus, herpes simplex or herpes zoster infection; hepatitis; viral hepatitis; cardiovascular disease; coronary artery stenosis; carotid artery stenosis; intermittent claudication; skin diseases; acne; psoriasis; diseases characterized by excessive proliferation of benign or malignant cells or by the formation of new blood vessels a disease characterized by a uterine septum; a benign or malignant tumor; early-stage cancer; cervical dysplasia; soft tissue sarcoma; germ cell tumor; retinoblastoma; age-related macular degeneration; lymphoma; Hodgkin lymphoma; head and neck cancer; oral cavity or mouth cancer; or cancer of the blood, prostate, cervix, uterus, vagina, or other female adnexa, breast, nasopharynx, trachea, larynx, bronchus, bronchioles, lung, hollow organ, esophagus, stomach, bile duct, intestinal cancer, colon, colorectal cancer, rectum, bladder, ureter, kidney, liver, gallbladder, spleen, brain, lymphatic system, bone, skin, or pancreas.

[0595] Preferably, the medicament or phototherapeutic agent of the fourth aspect of the invention is suitable for treating a disease characterized by excessive proliferation of benign or malignant cells or by areas of neovascularization.

[0596] Preferably, the medicament or phototherapeutic agent of the fourth aspect of the present invention is suitable for treating benign or malignant tumors.

[0597] Preferably, the medicament or phototherapy agent of the fourth aspect of the invention is suitable for treating early stage cancer; cervical dysplasia; soft tissue sarcoma; germ cell tumors; 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 adnexa cancer, breast cancer, nasopharyngeal cancer, tracheal cancer, laryngeal cancer, bronchial cancer, bronchiolar cancer, lung cancer, hollow organ cancer, esophageal cancer, stomach cancer, bile duct cancer, intestinal cancer, colon cancer, colorectal cancer, rectal cancer, bladder cancer, ureter cancer, kidney cancer, liver cancer, gallbladder cancer, spleen cancer, brain cancer, lymphatic system cancer, bone cancer, skin cancer or pancreatic cancer.

[0598] The fourth aspect of the present invention also provides use of the compound or complex according to the first or second aspect of the present invention in the manufacture of a photodiagnostic agent for photodynamic diagnosis.

[0599] Preferably, the optical 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, chlamydia, bacterial, nanobacterial or parasitic infectious diseases; HIV; AIDS; SARS virus (preferably severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)), Asian (chicken) influenza virus, dengue virus, herpes simplex or herpes zoster infection; hepatitis; viral hepatitis; cardiovascular disease; coronary artery stenosis; carotid artery stenosis; intermittent claudication; skin disorders; acne; psoriasis; diseases characterized by excessive proliferation or Diseases characterized by areas of neovascularization; benign or malignant tumors; early-stage cancers; cervical dysplasia; soft tissue sarcomas; germ cell tumors; retinoblastoma; age-related macular degeneration; lymphoma; Hodgkin lymphoma; head and neck cancer; oral or mouth cancer; or cancer of the blood, prostate, cervix, uterus, vagina, or other female adnexa, breast, nasopharynx, trachea, larynx, bronchus, bronchioles, lung, hollow organ, esophagus, stomach, bile duct, intestinal cancer, colon, colorectal cancer, rectum, bladder, ureter, kidney, liver, gallbladder, spleen, brain, lymphatic system, bone, skin, or pancreas.

[0600] Preferably, the photodiagnostic agent of the fourth aspect of the present invention is suitable for detecting areas affected by excessive proliferation of benign or malignant cells or by neovascularization.

[0601] Preferably, the photodiagnostic agent of the fourth aspect of the present invention is suitable for detecting benign or malignant tumors.

[0602] Preferably, the photodiagnostic agent of the fourth aspect of the invention is suitable for detecting early stage cancer; cervical dysplasia; soft tissue sarcoma; germ cell tumors; 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 adnexa cancer, breast cancer, nasopharyngeal cancer, tracheal cancer, laryngeal cancer, bronchial cancer, bronchiolar cancer, lung cancer, hollow organ cancer, esophageal cancer, stomach cancer, bile duct cancer, intestinal cancer, colon cancer, colorectal cancer, rectal cancer, bladder cancer, ureter cancer, kidney cancer, liver cancer, gallbladder cancer, spleen cancer, brain cancer, lymphatic system cancer, bone cancer, skin cancer or pancreatic cancer.

[0603] Preferably, the photodiagnostic 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.

[0604] Preferably, the pharmaceutical, phototherapeutic or photodiagnostic agent is adapted for administration simultaneously with or prior to the administration of the radiation or sound, preferably prior to the administration of the radiation.

[0605] If the pharmaceutical or phototherapeutic agent is used in photodynamic therapy or cytoluminescence therapy, it is preferably suitable for administration 5 to 100 hours before irradiation, preferably 6 to 72 hours before irradiation, preferably 24 to 48 hours before irradiation.

[0606] If the photodiagnostic agent is used in photodynamic diagnosis, it is preferably suitable for administration 3 to 60 hours before irradiation, preferably 8 to 40 hours before irradiation.

[0607] Preferably, the irradiation used in photodynamic therapy, cell luminescence therapy or photodynamic diagnosis is electromagnetic radiation with a wavelength of 500nm to 1000nm, preferably 550nm to 750nm, preferably 600nm to 700nm, preferably 640nm to 670nm. Electromagnetic radiation can be applied for about 5-60 minutes, preferably for about 15-20 minutes, at about 0.1-5W, preferably with about 1W. In one embodiment of the invention, two electromagnetic radiation sources (such as lasers and LED lamps) are used, and both sources are suitable for providing irradiation with a wavelength of 550nm to 750nm, preferably 600nm to 700nm, preferably 640nm to 670nm. In another embodiment of the invention, irradiation can be provided by a prostate, anus, vagina, mouth and nose device for insertion into a body cavity. In another embodiment of the invention, irradiation can be provided by interstitial light activation, for example, a fiber laser is inserted into a lung, liver, lymph node or breast using a fine needle. In another embodiment of the invention, illumination can be provided by endoscopic photoactivation, for example, for delivery of light to the lungs, stomach, colon, bladder, or neck.

[0608] A 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 (chicken) influenza virus, dengue virus, herpes simplex or herpes 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 by areas of neovascularization; benign or malignant tumors; early-stage cancer; A method of treating cervical dysplasia; soft tissue sarcoma; germ cell tumors; 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 adnexa cancer, breast cancer, nasopharyngeal cancer, tracheal cancer, laryngeal cancer, bronchial cancer, bronchiolar cancer, lung cancer, hollow organ cancer, esophageal cancer, stomach cancer, bile duct cancer, intestinal cancer, colon cancer, colorectal cancer, rectal cancer, bladder cancer, ureter 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.

[0609] The fifth aspect of the present invention also provides a method for photodynamic therapy or cell luminescence therapy of 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 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, chlamydia, bacterial, nanobacterial or parasitic infectious disease; HIV; AIDS; sars virus (preferably severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)), Asian (chicken) influenza virus, dengue virus, herpes simplex or herpes zoster infection; hepatitis; viral hepatitis; cardiovascular disease; coronary artery stenosis; carotid artery stenosis; intermittent claudication; skin disease; acne; psoriasis; benign or malignant cell hyperproliferation or neovascularization Disease characterized by a disease of the following areas: benign or malignant tumors; early-stage cancers; cervical dysplasia; soft tissue sarcoma; germ cell tumors; retinoblastoma; age-related macular degeneration; lymphoma; Hodgkin lymphoma; head and neck cancer; oral cavity or mouth cancer; or cancer of the blood, prostate, cervix, uterus, vagina, or other female adnexa, breast, nasopharynx, trachea, larynx, bronchus, bronchioles, lung, hollow organ, esophagus, stomach, bile duct, intestinal cancer, colon, colorectal cancer, rectum, bladder, ureter, kidney, liver, gallbladder, spleen, brain, lymphatic system, bone, skin, or pancreas.

[0610] Preferably, the method of the fifth aspect of the invention is a method of treating an area of benign or malignant cell hyperproliferation or neovascularization.

[0611] Preferably, the method of the fifth aspect of the present invention is a method for treating benign or malignant tumors.

[0612] Preferably, the method of the fifth aspect of the invention is a method of treating early stage cancer; cervical dysplasia; soft tissue sarcoma; germ cell tumors; 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 adnexa cancer, breast cancer, nasopharyngeal cancer, tracheal cancer, laryngeal cancer, bronchial cancer, bronchiolar cancer, lung cancer, hollow organ cancer, esophageal cancer, stomach cancer, bile duct cancer, intestinal cancer, colon cancer, colorectal cancer, rectal cancer, bladder cancer, ureter cancer, kidney cancer, liver cancer, gallbladder cancer, spleen cancer, brain cancer, lymphatic system cancer, bone cancer, skin cancer or pancreatic cancer.

[0613] The fifth aspect of the present invention also provides 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 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, chlamydia, bacterial, nanobacterial or parasitic infectious diseases; HIV; AIDS; sars virus (preferably severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)), Asian (chicken) influenza virus, dengue virus, herpes simplex or herpes zoster infection; hepatitis; viral hepatitis; cardiovascular disease; coronary artery stenosis; carotid artery stenosis; intermittent claudication; skin disorders; acne; psoriasis; benign or malignant cell hyperproliferation or neovascularization Preferably, the human or animal disease is characterized by an area of benign or malignant tumors; early stage cancers; cervical dysplasia; soft tissue sarcoma; germ cell tumors; 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 adnexa cancer, breast cancer, nasopharyngeal cancer, tracheal cancer, laryngeal cancer, bronchial cancer, bronchiolar cancer, lung cancer, cancer of the hollow organs, esophageal cancer, stomach cancer, bile duct cancer, intestinal cancer, colon cancer, colorectal cancer, rectal cancer, bladder cancer, ureter 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 an area of benign or malignant cell hyperproliferation or neovascularization. Preferably, the human or animal disease is a benign or malignant tumor. Preferably, the human or animal disease is an 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 adnexa cancer, breast cancer, nasopharyngeal cancer, tracheal cancer, laryngeal cancer, bronchial cancer, bronchiolar cancer, lung cancer, hollow organ cancer, esophageal cancer, stomach cancer, bile duct cancer, intestinal cancer, colon cancer, colorectal cancer, rectal cancer, bladder cancer, ureter 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 fluorescent or phosphorescent detection of the disease, preferably suitable for fluorescent or phosphorescent detection and quantification of the disease.

[0614] In any method of the fifth aspect of the invention, the human or animal is preferably further subjected to irradiation or sound while or after administering the compound or complex according to the first or second aspect of the invention. Preferably, the human or animal is irradiated after administering the compound or complex according to the first or second aspect of the invention.

[0615] If the method is a method of photodynamic therapy or cytoluminescence therapy, the human or animal is preferably irradiated 5 to 100 hours after administration of the compound or complex according to the first or second aspect of the invention, preferably 6 to 72 hours after administration, preferably 24 to 48 hours after administration.

[0616] If the method is a method of photodynamic diagnosis, the human or animal is preferably irradiated 3 to 60 hours after administration of the compound or complex according to the first or second aspect of the invention, preferably 8 to 40 hours after administration.

[0617] Preferably, the irradiation is electromagnetic radiation having a wavelength in the range of 500nm to 1000nm, preferably 550nm to 750nm, preferably 600nm to 700nm, preferably 640nm to 670nm. The electromagnetic radiation may be applied at about 0.1-5W, preferably at about 1W, for about 5-60 minutes, preferably for 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 550nm to 750nm, preferably 600nm to 700nm, preferably 640nm to 670nm. In another embodiment of the invention, the irradiation may be provided by a prostate, anus, vagina, mouth, and nose device for insertion into a body cavity. In another embodiment of the invention, the irradiation may be provided by interstitial photoactivation, for example, using a fine needle to insert a fiber laser into the lungs, liver, lymph nodes, or breast. In another embodiment of the invention, the irradiation may be provided by endoscopic photoactivation, for example, for delivering light to the lungs, stomach, colon, bladder, or neck.

[0618] In any of the methods of the fifth aspect of the invention, preferably the human or animal is a human.

[0619] A sixth aspect of the present invention provides a pharmaceutical combination or a kit comprising:

[0620] (a) a compound or complex according to the first or second aspect of the invention; and

[0621] (b) Immune checkpoint inhibitors.

[0622] 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.

[0623] Preferably, the combination or kit of the sixth aspect is for use in treating a disease, condition or illness, wherein the disease, condition or illness is responsive to inhibition of PD-1, PD-L1 or CTLA4. Preferably, the combination or kit of the sixth aspect is for use in treating cancer. In one embodiment, the cancer is melanoma, lung cancer (e.g., non-small cell lung cancer), renal cancer, bladder cancer, head and neck cancer or Hodgkin's lymphoma.

[0624] 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, condition or illness that 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 (e.g., non-small cell lung cancer), renal cancer, bladder cancer, head and neck cancer, or Hodgkin's lymphoma.

[0625] The sixth aspect of the present invention also provides a method for treating a disease, condition or illness that responds to PD-1, PD-L1 or CTLA4 inhibition, the method comprising administering a therapeutically effective amount of the combination or kit of the sixth aspect of the present invention to a person or animal in need. The sixth aspect of the present invention also provides a method for treating cancer, the method comprising administering a therapeutically effective amount of the combination or kit of the sixth aspect of the present invention to a person or animal in need. In one embodiment, the cancer is melanoma, lung cancer (e.g., non-small cell lung cancer), kidney cancer, bladder cancer, head and neck cancer, or Hodgkin's lymphoma.

[0626] For the combination or kit of the sixth aspect of the invention, the compound or complex according to the first or second aspect of the invention and the immune checkpoint inhibitor may be provided together in one pharmaceutical composition or separately in two pharmaceutical compositions. If provided in two pharmaceutical compositions, these may be administered simultaneously or at different times.

[0627] Preferably, the combination or kit of parts of the sixth aspect is suitable for administration simultaneously with or before the administration of irradiation or sound, preferably suitable for administration before the administration of irradiation. In one embodiment, the combination or kit of parts 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.

[0628] Preferably, the irradiation used in photodynamic therapy or cell luminescence therapy is electromagnetic radiation with a wavelength of 500nm to 1000nm, preferably 550nm to 750nm, preferably 600nm to 700nm, preferably 640nm to 670nm. Electromagnetic radiation can be applied for about 5-60 minutes, preferably for about 15-20 minutes, at about 0.1-5W, preferably with about 1W. In one embodiment of the invention, two electromagnetic radiation sources (such as lasers and LED lamps) are used, and both sources are suitable for providing irradiation with a wavelength of 550nm to 750nm, preferably 600nm to 700nm, preferably 640nm to 670nm. In another embodiment of the invention, irradiation can be provided by a prostate, anus, vagina, mouth and nose device for insertion into a body cavity. In another embodiment of the invention, irradiation can be provided by interstitial light activation, for example, a fiber laser is inserted into a lung, liver, lymph node or breast using a fine needle. In another embodiment of the invention, illumination can be provided by endoscopic photoactivation, for example, for delivery of light to the lungs, stomach, colon, bladder, or neck.

[0629] For the avoidance of doubt, any embodiment of a given aspect of the present invention may be combined with any other embodiment of the same aspect of the present invention within the practical scope. Additionally, it will be understood that any preferred or optional embodiment of any aspect of the present invention is also to be considered as a preferred or optional embodiment of any other aspect of the present invention within the practical scope.

[0630] Synthesis experiment details

[0631] Chlorin starting material:

[0632]

[0633]

[0634]

[0635] Glucose starting material:

[0636]

[0637] (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-((3-aminopropyl)thio)tetrahydro-2H-triacetate Synthesis of 3,4,5-pyran-triyl ester

[0638]

[0639] Step 1:A 2-neck 500 mL RBF equipped with a nitrogen inlet and a rubber septum was charged with a solution of 1,2,3,4,6-penta-O-acetyl-β-D-glucose (6.23 g, 15.95 mol, 1 equivalent) in anhydrous DCM (150 mL) and a stirring bar, and the mixture was placed under N2. To this solution was added (9H-fluoren-9-yl)methyl (3-mercaptopropyl)carbamate (ChemBioChem, 2010, 11 (6), 778-781) (6.00 g, 19.1 mmol, 1.2 equivalents), followed by dropwise addition of BF3.OEt2 (5.9 mL, 47.9 mmol, 3 equivalents) through a rubber septum over a period of 2-3 minutes. The mixture was stirred at room temperature under N2 at 315 rpm overnight. TLC analysis at this point indicated only trace amounts of starting material remaining. The reaction was quenched by adding 1M HCl (50 mL) and transferred to a separating funnel. The organic phase was collected and washed with saline (50 mL), then dried (MgSO 4 ) and concentrated by rotary evaporation to give a crude glycosylated product (18 g) in a light syrup. The residue was purified by column chromatography (50% EtOAc / hexane, as the solution load in the eluent, R f =0.5) to give N-Fmoc-(2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-((3-aminopropyl)thio)tetrahydro-2H-pyran-3,4,5-triyl triacetate (5.55 g, 54%) as a colorless syrup which solidified upon standing.

[0640] 1 H NMR (400MHz, CDCl3) δ7.76(d,J=7.4Hz,2H),7.60(d,J=7.4Hz,2H),7.39(dd,J=7.4,7.4Hz,2H),7.31(dd,J=7.4,7.4 Hz,2H),5.22(dd,J=9.4,9.4Hz,1H),5.05(dd,J=9.4,9.4Hz,1H),5.02(dd,J=9.4,9.4Hz,1H),4.93(br.s,1H),4.50 -4.42(m,3H),4.31-4.08(m,3H),3.69(ddd,J=10.1,4.8,2.7Hz,1H),3.36-3.19(m,2H),2.74(ddd,J=13.4,6.7,6.7 Hz,1H),2.64(ddd,J=13.4,6.7,6.7Hz,1H),2.05(s,3H),2.04(s,3H),2.03(s,3H),2.00(s,3H),1.87-1.70(m,2H).

[0641] Step 2:To a 50 mL flask containing N-Fmoc-(2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-((3-aminopropyl)thio)tetrahydro-2H-pyran-3,4,5-triyl triacetate (633 mg, 0.983 mmol, 2 eq) and a stir bar was added 20% piperidine / DMF (15 mL) and the resulting solution was stirred (420 rpm) under ambient atmosphere for 10 minutes. An aliquot was removed and concentrated for use. 1 H NMR analysis showed cleavage of the Fmoc group. The reaction mixture was concentrated and then reconstituted / concentrated five times from toluene (to remove all piperidine) to give (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-((3-aminopropyl)thio)tetrahydro-2H-pyran-3,4,5-triyl triacetate as a gummy beige solid, which was used without further purification.

[0642] (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-((3-thiopropyl)thio)tetrahydro-2H-triacetate Synthesis of 3,4,5-pyran-triyl ester

[0643]

[0644] 1,3-propanedithiol (11.9g, 110mmol, 2 equivalents) is added to a dry 3-neck 250mL RBF with a stirring bar and a stopper. The flask is equipped with a reflux condenser with a gas inlet and a bubbler and is then placed under N2. Chloroform (30mL) is added and the solution is stirred at room temperature under N2. Using a funnel, 1,2,3,4,6-five-O-acetyl-β-D-glucose (21.5g, 55.0mmol, 1 equivalent) is added and washed with additional chloroform (10mL). Finally, indium bromide (0.58g, 1.64mmol, 0.03 equivalent) is added, and the mixture is placed in a preheated oil bath (90 DEG C), and stirred under N2 for 2.5 hours. The reaction mixture is cooled to room temperature, and directly applied to a silica gel column (250x 50mm) made in 100% DCM. The column was eluted with 100% DCM, then with 30% EtOAc in hexane, then with 60% EtOAc in hexane, and finally with 100% EtOAc, collecting 30 x 125 mL fractions. The strongest fractions (11-19) as illustrated by TLC were combined and evaporated to give a colorless viscous oil (10.33 g) which crystallized upon standing. 1H NMR showed that this was the desired product, but contained EtOAc (4%) and acetic acid (5%). Therefore, the material was dissolved in DCM (150 mL), washed with 1M sodium bicarbonate solution (200 mL), the washings were stripped with DCM (50 mL), and the combined organic phases were washed with water (150 mL), dried (Na2SO4) and evaporated to give a viscous colorless oil that rapidly crystallized upon standing. The material was triturated with 1:1 hexane / diethyl ether (approximately 30 mL), and the larger crystals were crushed with a glass rod. After stirring for one hour, the suspension was filtered and the solid was dried in a vacuum oven at 25°C overnight (7.50 g).

[0645] 1 H NMR (400MHz, CDCl3) δ5.21(dd,J=9.8,9.8Hz,1H),5.08(dd,J=9.8,9.8Hz,1H),5.03(dd,J=9.8,9.8Hz,1H),4 .49(d,J=9.8Hz,1H),4.23(dd,J=12.3,4.9Hz,1H),4.14(dd,J=12.3,2.4Hz,1H),3.71(ddd,J=9.8,4.9,2.4Hz ,1H),2.85(ddd,J=12.7,7.0,7.0Hz,1H),2.76(ddd,J=12.7,7.0,7.0Hz,1H),2.63(app.ddd,J=8.1,7.0,7.0H z, 2H), 2.08 (s, 3H), 2.06 (s, 3H), 2.02 (s, 3H), 2.00 (s, 3H), 1.90 (app.p, J = 7.0Hz, 2H), 1.37 (t, J = 8.1Hz, 1H).

[0646] (2R,3S,4S,5R,6S)-2-(Hydroxymethyl)-6-((3-mercaptopropyl)thio)tetrahydro-2H-pyran-3,4,5-triol Synthesis

[0647]

[0648] Into a 100 mL dry single-necked RBF was weighed (2R, 3R, 4S, 5R, 6S)-2-(acetoxymethyl)-6-((3-thiopropyl)thio)tetrahydro-2H-pyran-3,4,5-triyl triacetate (2.50 g, 5.7 mmol, 1 equivalent) and the flask was equipped with a stir bar and a 3-way valve. The flask was placed under N2 and anhydrous MeOH (20 mL) was added by syringe via a 3-way valve while the flask was maintained under N2. Using a graduated pipette, methanolic ammonia (4.8 mL, approximately 57 mmol, 10 equivalents) was added, and the flask was then closed and stirred at room temperature overnight. After 21 hours, the solvent was removed 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 maroon clear oil, which was used without further purification.

[0649] 1 H 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).

[0650] Synthesis Example 1 - Synthesis of Chlorin e6 Bis-β-D-1-Thioglucose Propylamide Conjugates 1 and 2 (Compounds 1 and 2)

[0651] Synthesis of glucose starting material

[0652]

[0653] To a 25 mL flask containing N-Boc-3'-amino-1-thioxo-2,3,4,6-tetra-O-acetyl-β-D-glucopyranose (699 mg, 1.34 mmol, 4 eq) and a stir bar was added DCM (6.0 mL) and TFA (1.5 mL), and the resulting solution was stirred (300 rpm) under N2 for 75 minutes. An aliquot was removed and concentrated for use. 1 H NMR analysis showed cleavage of the Boc group.The reaction mixture was concentrated and then reconstituted / concentrated twice from chloroform (15 mL) to give the crude amine as a colorless oil which was used without further purification.

[0654] Coupling and deprotection

[0655]

[0656] Step 1: Chlorin e6 (200mg, 0.3352mmol, 1 equivalent), PyBOP (610mg, 1.1732mmol, 3.5 equivalents), DCM (3.2mL) and triethylamine (418 μ L, 3.0167mmol, 9 equivalents) are loaded into the 25mL RBF containing stirring bar. The gained mixture is stirred (420rpm) 20 minutes, then the triacetic acid (2R, 3R, 4S, 5R, 6S)-2-(acetoxymethyl)-6-((3-aminopropyl) thio) tetrahydro-2H-pyrans-3,4,5-triyl ester prepared as described above is dissolved in DCM (3.2mL) and added to the mixture. Reaction process is monitored by HPLC, and the mixture containing product and activated intermediate ester is found, and there is no change in 1 to 2 hours. To the product of 4-chloro-2-thiazolinone (5-chloro-2-thiazolinone) esters, 1-chloro-2-thiazolinone (5-chloro-2-thiazolinone) esters were added. The mixture was stirred overnight at ambient temperature for 12 hours, and the reaction was completed as monitored by HPLC. The reaction mixture was diluted with DCM (8 mL), transferred to a separatory funnel and washed with 1 M HCl (2 x 15 mL), then washed with pH 7 buffer (15 mL). The organic phase was dried (Na2SO4) and concentrated by rotary evaporation to give 1.0998 g of a black film of crude amide. The residue was found to contain two main products, which were purified by column chromatography (3 x 30 cm) using 5% MeOH / DCM, then 8% MeOH / DCM, then 10% MeOH / DCM to two compounds eluted. The first chlorin e6 bis-conjugate peracetate (207.5 mg) as a dark green solid was obtained, while the second chlorin e6 tri-conjugate peracetate (265.1 mg) as a bluish-black solid was obtained. Deacetylation was performed without further purification.

[0657] Step 2: Chlorin e6 bis-β-D-1-thioglucosinolate propylamide conjugate 1 (Compound 1)

[0658] To a solution of the first chlorin e6 bis-β-1-thioglucosamide conjugate peracetate (207.5 mg, 0.146 mmol, 1 eq) in MeOH (7.5 mL) and DCM (5 mL) was added NaOMe (4.6 M in MeOH, 150 μL, 0.690 mmol, 5 eq) and the mixture was stirred under N2 (420 rpm) for 90 min. TLC analysis showed conversion to the deacetylated product (10% MeOH / DCM, R f (starting material) = 0.31, R f(Product) = 0). The reaction was quenched with AcOH (8 drops) and concentrated by rotary evaporation to give a black film. The residue was purified by column chromatography (3 x 34 cm, filled with 30% MeOH / DCM and using a gradient of 30% to 50% MeOH / DCM) to give chlorin e6 bis-β-D-1-thioglucosinolate propylamide conjugate 1 (Compound 1) (73.6 mg, 20% over 2 steps) as a dark blue-green solid.

[0659] 1 H NMR(400MHz,DMSO-d6)δ9.80(s,1H),9.67(s,1H),9.39-9.33(m,1H),9.14(s ,1H),8.37(dd,J=17.8,11.6Hz,1H),7.81(t,J=5.6Hz,1H),6.45(dd,J=17.8, 1.6Hz,1H),6.15(dd,J=11.7,1.5Hz,1H),5.90-5.84(m,1H),5.80-5.72(m,1 H),5.33-5.23(m,2H),5.14(d,J=5.6Hz,2H),5.03(d,J=4.7Hz,1H),4.92(d,J =4.5Hz,1H),4.61(t,J=5.8Hz,1H),4.57-4.51(m,1H),4.23(d,J=9.0Hz,1H) ,4.16(d,J=9.6Hz,1H),3.88-3.78(m,2H),3.65-3.57(m,2H),3.56(s,3H),3. 47(s,3H),3.20-3.00(m,6H),2.99-2.91(m,1H),2.79(s,1H),2.38(dd,J=13 .8,6.9Hz,1H),2.18(s,1H),1.82-1.52(m,13H),-2.08(s,1H),-2.72(s,1H).

[0660] LCMS: For C 52 H 71 N6O 14 S2(M+H + ):1067.4464; measured value:1067.4523.

[0661] Step 3: Chlorin e6 tri-β-D-1-thioglucosinolate propylamide conjugate 2 (Compound 2)

[0662] To a solution of the second chlorin e6 tris-β-1-thioglucosamide conjugate peracetate (265.1 mg, 0.187 mmol, 1 eq) in MeOH (7.5 mL) and DCM (5 mL) was added NaOMe (4.6 M in MeOH, 150 μL, 0.690 mmol, 5 eq) and the mixture was stirred under N2 (420 rpm) for 90 min. TLC analysis showed conversion to the deacetylated product (10% MeOH / DCM, R f (starting material) = 0.69, R f (Product) = 0). The reaction was quenched with AcOH (8 drops) and concentrated by rotary evaporation to give a black film. The residue was purified by column chromatography (3 x 34 cm, filled with 30% MeOH / DCM and using a gradient of 30% to 50% MeOH / DCM) to give chlorin e6 tris-β-D-1-thioglucosinolate propylamide conjugate 2 (Compound 2) (48.2 mg, 11% over 2 steps) as a dark blue-green solid.

[0663] 1 H NMR (400MHz, DMSO-d6) δ9.78(s,1H),9.77(s,1H),9.12(s,1H),9.00(s,1H),8.35(dd,J=17.8,11.7Hz,1H),7.97(s,1H),7.82 (t,J=5.6Hz,1H),6.47(dd,J=17.8,1.6Hz,1H),6.18(dd,J=11.6,1.5Hz,1H),5.21(d,J=5.7Hz,1H),5.17-4.88(m,10H),4.62 -4.47(m,4H),4.41-4.29(m,1H),4.21(dd,J=20.0,9.6Hz,2H),3.89-3.78(m,1H),3.76-3.58(m,2H),3.55(s,3H),3.51(s,3H ),3.12-3.02(m,2H),3.02-2.82(m,1H),2.71-2.55(m,3H),2.22-1.97(m,3H),1.79-1.56(m,7H),-1.88(s,1H),-2.23(s,1H).

[0664] LCMS: For C 61 H 88 N7O 18 S3(M+H + ):1302.5342; measured value:1302.5357.

[0665] Synthesis Example 2 - Synthesis of Chlorin e6 (2-methoxyethyl)methylamine (Compound 3)

[0666]

[0667] Step 1: Chlorin e6 (0.5 g, 1 eq), di-tert-butyl dicarbonate ((Boc)2O) (188 mg, 1.03 eq) and DCM (60 ml) were loaded into a 1-neck 250 mL RBF. DMAP (8 mg, 0.08 eq) was added and the resulting solution was stirred at 40 ° C under a nitrogen atmosphere for 2 hours. The resulting black solution was filtered using a cotton plug, and the filtrate was concentrated under reduced pressure. The resulting solid was washed with hexane (2 x 10 ml) and dried to give chlorin e6 anhydride (475 mg, 98%) as a black solid. It was used in the next step without further purification.

[0668] 1 H NMR(400MHz, CDCl3)δ9.52(m,2H),9.22(m,1H),8.45(m,1H),7.82(m,1H),6.34(m,1H),6.14(m,1H),5.40(m,2H),4.60-4.30(m,2H), 3.55(m,5H),3.32(s,3H),3.16(m,4H),2.75-2.50(m,2H),2.35(m,2H),1.95(m,1H),1.75-1.60(m,6H),1.15(t,2H),-0.5(brs,2H).

[0669] Step 2: Chlorin e6 anhydride (470mg, 1 equivalent), (2-methoxyethyl) methylamine (108mg, 1.5 equivalents) and DCM (30ml) were loaded into 1 neck 250mL RBF. The resulting solution was stirred overnight at 35°C under a nitrogen atmosphere. The gained black solution was concentrated under reduced pressure and precipitated with ether. The precipitate was filtered and washed with ether (2x 10ml). The remaining black solid was purified by column chromatography using 10%-50% MeOH / DCM, and the fractions containing the first dark band of elution were merged to obtain compound 3 (320mg, 59% yield, 95.33% according to HPLC purity) as a bluish-green solid.

[0670] 1H NMR(400MHz,DMSO-d6)δ9.80(s,1H),9.42(s,1H),9.10(s,1H),8.35(dd,1H),6.44(d,1H),6.14(d,1H),5.20(m,1H),4.50(m,1H),4.3 0-4.10(m,2H),3.85(m,3H),3.65-3.30(m,10H),3.20(m,2H),2.85(m,1H),2.15(m,1H),1.15(t,2H),-2.0(brs,1H),-2.68(brs,1H).

[0671] Synthesis Example 3 - Synthesis of Chlorin e6 (2-methoxyethyl) methylamine dimethyl ester (Compound 4)

[0672]

[0673] Compound 3 (310g, 1 equivalent), potassium carbonate (192mg, 3 equivalents), DMF (10mL) and stirring rod are added to 1 neck 250mL RBF.Flask is placed under nitrogen and stirred at 300rpm, is connected with air condenser.Then iodomethane (0.072mL, 3 equivalents) is added.Solution is stirred at 25 ℃ and goes through the weekend.Desolventizing under reduced pressure at 60 ℃, obtain dark green solid.Crude material is dissolved in DCM (30mL), washed with water (2x 10mL), dried (Na2SO4) and under reduced pressure, obtain the crude product (350mg) in dark blue / green solid.Now HPLC analysis shows that purity is about 96%.Residual blue / green solid is used 1%-5%MeOH / DCM purification by column chromatography, and merge the fraction containing the first dark band of wash-out, obtain compound 4 (310mg, 98% productive rate, according to HPLC purity, is 98.69%) in bluish green solid.

[0674] 1H NMR(400MHz, CDCl3)δ9.70(s,1H),9.55(m,1H),8.72(m,1H),8.10-8.00(m,2H),6.4 4(d,1H),6.14(d,1H),5.50-5.20(m,2H),4.50(m,2H),4.30-4.10(m,2H),3.90-3.6 5(m,5H),3.65(s,3H),3.60(m,6H),3.45(m,6H),3.30(s,3H),2.95(s,3H),2.85(s, 3H),2.60(m,1H),2.20(m,2H),1.75-1.55(m,7H),-1.30(brs,1H),-1.45(brs,1H).

[0675] Synthesis Example 4 - Synthesis of Chlorin e6 N-Methylbutylamine (Compound 5)

[0676]

[0677] Chlorin e6 anhydride (500mg, 1 equivalent), N-methylbutylamine (108mg, 1.5 equivalents) and DCM (30ml) were loaded into a 1-neck 250mL RBF. The resulting solution was stirred overnight at 35°C under a nitrogen atmosphere. The resulting black solution was concentrated under reduced pressure and precipitated with ether. The precipitate was filtered, washed with ether (2x 10ml) and dried over a rotary evaporator to give compound 5 (670mg, quantitative yield, 85.80% according to HPLC purity) as a bluish-green solid. The crude product was used in the next step without further purification.

[0678] 1 H NMR(400MHz,DMSO-d6)δ9.75(s,1H),9.70(s,1H),9.10(s,1H),8.35(dd,1H),6.44(d ,1H),6.14(d,1H),5.70(m,1H),5.30(m,1H),4.60(m,1H),4.40(m,1H),3.85(m,3H),3 .65-3.40(m,10H),2.85(m,1H),2.40-2.10(m,5H),1.70(t,3H),1.80-1.50(m,10H), 1.25(m,4H),1.00(t,2H),0.90(t,4H),0.80(t,1H),-1.90(brs,1H),-2.35(brs,1H).

[0679] Synthesis Example 5 - Synthesis of Chlorin e6 N-Methylbutylamine Dimethyl Ester (Compound 6)

[0680]

[0681] Compound 5 (650g, 1 equivalent), potassium carbonate (404mg, 3 equivalents), DMF (10mL) and stirring bar are added to 1 neck 250mL RBF. The flask is placed under nitrogen. Then iodomethane (0.150mL, 2.5 equivalents) is added. The solution is stirred overnight at 25°C. The solvent is removed under reduced pressure at 60°C to give a dark green solid. The crude material is dissolved in DCM (30mL), washed with water (2x 10mL), dried (Na2SO4) and concentrated under reduced pressure to give compound 6 (700mg, quantitative yield, 86.64% according to HPLC purity) as a dark blue / green solid. The crude product is used in the next step without further purification.

[0682] 1 H NMR(400MHz, CDCl3)δ9.70(s,1H),9.55(m,1H),8.72(m,1H),8.10-8.00(m,2H),6.44(d,1H) ,6.14(d,1H),5.50-5.20(m,2H),4.50(m,2H),4.20(m,3H),3.90-3.60(m,6H),3.65(s,3H), 3.55(m,4H),3.45(m,6H),3.30(s,3H),2.95(s,3H),2.85(s,3H),2.60(m,1H),2.20(m,2H), 1.75-1.55(m,9H),1.40(m,1H),1.10(t,1H),0.90(t,3H),-1.30(brs,1H),-1.45(brs,1H).

[0683] Synthesis Example 6 - Synthesis of Chlorin e6 N-(Methylaminopropyl)triphenylphosphonium Bromide (Compound 7)

[0684]

[0685] Into a 100 mL RBF was loaded chlorin e6 anhydride (500 mg, 1 equivalent), (3-(methylamino)propyl)triphenylphosphonium bromide hydrobromide (641 mg, 1.5 equivalents) and DCM (30 ml). The resulting solution was stirred at 35 ° C under a nitrogen atmosphere overnight. The resulting black solution was concentrated under reduced pressure and precipitated with diethyl ether. The precipitate was filtered, washed with diethyl ether (2 x 10 ml) and dried on a rotary evaporator to give compound 7 (1.20 gm, quantitative yield, 72.47% purity according to HPLC) as a blue / green solid. The crude product was used in the next step without further purification.

[0686] 1 H NMR(400MHz,DMSO-d6)δ9.75(m,1H),9.10(m,1H),9.10(s,1H),8.35(m,1H),8.00-7.75(m,11H),7.65(m,3H),6.44(d,1H),6.14(d,1H),4.6 0(m,1H),3.85(m,3H),3.65-3.40(m,10H),2.90(m,1H),2.20-2.15(m, 2H),1.80-1.50(m,6H),1.00(t,2H),-1.90(brm,1H),-2.40(brm,1H).

[0687] Synthesis Example 7 - Synthesis of Chlorin e6 N-(Methylaminopropyl)triphenylphosphonium dimethyl bromide (Compound 8)

[0688]

[0689] In 1 neck 250mL RBF, add compound 7 (1.0gm, 1 equivalent), potassium carbonate (415mg, 3 equivalents), DMF (10mL) and stirring bar.The flask is placed under nitrogen and stirred at 300rpm, is connected with air condenser.Then add iodomethane (0.150mL, 2.5 equivalents).The solution is stirred overnight at 30 ℃.Desolventizing under reduced pressure at 60 ℃ gives dark green solid.The crude material is dissolved in DCM (30mL), washed with water (2x 10mL), dried (Na2SO4) and concentrated under reduced pressure to give the crude product (700mg) as dark blue / green solid.Now HPLC analysis shows that purity is about 75%. The residual blue / green solid was purified by column chromatography using 2%-3% MeOH / DCM, and fractions containing the first dark band to elute were combined to give Compound 8 (440 mg, quantitative yield, 99.69% pure by HPLC) as a blue / green solid.

[0690] 1H NMR(400MHz, CDCl3)δ9.60(s,1H),9.50(s,1H),8.70(s,1H),8.10-8.00(dd,1H),7.65(m,6H) ,7.55(m,3H),7.40(m,6H),6.44(d,1H),6.14(d,1H),5.20(m,2H),4.30(m,2H),4.00-3.90(m, 5H),3.70(m,3H),3.65(s,3H),3.55(s,3H),3.40(s,3H),3.30(s,3H),3.20(s,3H),2.60(m,1H ),2.20(m,4H),1.70-1.55(m,6H),1.40(m,1H),1.20(m,1H),-1.40(brs,1H),-1.52(brs,1H).

[0691] Synthesis Example 8 - Synthesis of Chlorin e6β-D-1-thioglucose-N-methylpropylamide Conjugate Tetraacetate Diacid (Compound 9)

[0692]

[0693] Step 1: To a solution of (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-((3-((tert-butoxycarbonyl)(methyl)amino)propyl)thio)tetrahydro-2H-pyran-3,4,5-triyl triacetate (0.612 g, 1.14 mmol, 1.4 equiv) in DCM (5 mL) was added TFA (1 mL). The resulting solution was stirred (420 rpm) at ambient temperature for 1 hour and then concentrated on a rotary evaporator. The residue was resuspended and concentrated twice from chloroform (2 x 10 mL) to give (2R,3R,4S,5R,6R)-2-(acetoxymethyl)-6-(((3-methylamino)propyl)thio)tetrahydro-2H-pyran-3,4,5-triyl triacetate TFA salt as a viscous oil.

[0694] Step 2:Into a 1-neck 250 mL RBF was charged chlorin e6 anhydride (2.0 g, 1 eq), (2R, 3R, 4S, 5R, 6R)-2-(acetoxymethyl)-6-(((3-methylamino)propyl)thio)tetrahydro-2H-pyran-3,4,5-triyl triacetate TFA salt (2.84 g, 1.5 eq), sodium bicarbonate (435 mg, 1.5 eq) and DCM (30 ml). The resulting solution was stirred at 30 ° C under a nitrogen atmosphere overnight. The resulting black solution was concentrated under reduced pressure and precipitated with ether. The precipitate was filtered, washed with ether (2 x 10 ml) and dried over a rotary evaporator. The residual black solid was purified by column chromatography using 2%-10% MeOH / DCM, and the fractions containing the first dark band to elute were combined and concentrated to give compound 9 (1.2 g, 34% yield, 96.19% purity by HPLC) as a blue-green solid.

[0695] 1 H NMR(400MHz,DMSO-d6)δ9.75(s,1H),9.70(s,1H),9.10(s,1H),8.35(dd,1H),6 .44(d,1H),6.14(d,1H),5.70(m,1H),5.30(m,1H),5.00-4.70(m,2H),4.60(m,1 H),4.40(m,1H),4.10-3.85(m,5H),3.55(m,10H),2.75(m,2H),2.40-2.10(m,5H ),2.00-1.50(m,12H),1.70(t,3H),1.55(m,2H),-1.80(m,1H),-2.25(brs,1H).

[0696] Synthesis Example 9 - Synthesis of Chlorin e6β-D-1-thioglucose-N-methylpropylamide Conjugate Tetraacetate Dimethyl Ester (Compound 10)

[0697]

[0698] In 1 neck 250mL RBF, add compound 9 (1.0gm, 1 equivalent), potassium carbonate (490mg, 3 equivalents), DMF (10mL) and stirring bar.The flask is placed under nitrogen and stirred at 300rpm, is connected with air condenser.Then add iodomethane (0.218mL, 2.5 equivalents).The solution is stirred overnight at 30 ℃.Desolventizing under reduced pressure at 60 ℃, obtain dark green solid.The crude material is dissolved in DCM (30mL), washed with water (2x 10mL), dried (Na2SO4) and under reduced pressure, obtain the crude product (about 1.2g) in dark blue / green solid.Now HPLC analysis shows that purity is about 65%. The residual blue / green solid was purified by column chromatography using 2%-4% MeOH / DCM, and fractions containing the first dark band to elute were combined and concentrated to give compound 10 (700 mg, 69% yield, 85.89% pure by HPLC) as a blue / green solid.

[0699] 1 H NMR(400MHz, CDCl3)δ9.70(s,1H),9.55(s,1H),8.70(s,1H),8.10-8.00(dd,1H),6.44(d,1H),6.14(d,1H),5.30-5.00(m,3H),4. 50-4.00(m,8H),3.80-3.10(m,10H),3.55(s,3H),3.45(s,3H),3.30(s,3H),2.20-2.00(m,15H),1.80(m,5H),-1.20-1.52(m,2H).

[0700] Synthesis Example 10 - Synthesis of Chlorin e6 N-Methylbutylamine Bis(N-methyl-D-reduced Glucosamine) Salt (Compound 11)

[0701]

[0702] Chlorin e6 N-methylbutylamine (500 mg, 0.751 mmol, 1 equivalent) was weighed into a 25 mL RBF, followed by addition of distilled deionized water (5 mL) under a stirring bar. Meglumine (279 mg, 1.43 mmol, 1.9 equivalents) was added, and the mixture was stirred while heating at 70 ° C for 1 hour. The solution was cooled to ambient temperature and then filtered through a 3 porosity filter (7 cm diameter) into a 250 mL conical flask with a side arm. The reaction flask was rinsed with deionized water (approximately 10 mL) and then passed through a filter to complete the transfer. The filtrate was transferred to a 100 mL RBF using additional deionized water and freeze-dried overnight to give compound 11 (331 mg, 42% yield, 92.75% purity according to HPLC) as a light green fluffy solid.

[0703] 1 H NMR(400MHz, DMSO-d6)δ9.80(s,1H),9.66(s,1H),9.12(s,1H),8.36(ddd,J=18.0,11.8,2.4Hz,1H),6.45(dd,J=17.8,1.7Hz,1H), 6.23-6.00(m,2H),5.35(t,J=23.3Hz,1H),4.64-4.48(m,1H),4.30(d,J=10.6Hz,1H),3.93-3.77(m,4H),3.72(dd,J=5.1,1.5Hz,2H ),3.63(dd,J=10.8,3.3Hz,2H),3.57-3.38(m,12H),3.35(s,3H),2.93-2.77(m,5H),2.39(s,8H),1.74-1.66(m,2H),1.63(d,J=7. 0Hz, 2H), 1.51 (dt, J = 13.9, 7.5Hz, 1H), 1.34-1.22 (m, 2H), 0.86 (t, J = 7.3Hz, 2H), -1.98 (d, J = 14.1Hz, 1H), -2.56 (d, J = 14.2Hz, 1H).

[0704] Synthesis Example 11 - Synthesis of Chlorin e6 5-methyl ester monosodium mono(N-methyl-D-reduced glucosamine) salt (Compound 12)

[0705]

[0706] Chlorin e6 5-methyl ester (200 mg, 0.327 mmol, 1 eq) was weighed into a 100 mL RBF, followed by the addition of distilled deionized water (30 mL) under a stirring bar. Meglumine (64 mg, 0.327 mmol, 1 eq) and 0.1 M sodium hydroxide solution (3.27 mL, 0.327 mmol, 1 eq) were added, and the mixture was stirred at 25 ° C for 2 hours. The reaction mixture was then freeze-dried overnight (16 hours) to give compound 12 (253 mg, 93% yield, 85.98% purity according to HPLC) as a light green fluffy solid.

[0707] 1 H NMR(400MHz,DMSO-d6)δ9.74(s,1H),9.68(s,1H),9.11(s,1H),8.29(dd,J=1 7.8,11.7Hz,1H),6.44(dd,J=17.8,1.6Hz,1H),6.16(dd,J=11.6,1.4Hz,1H) ,5.29(d,J=18.2Hz,1H),5.01(d,J=18.1Hz,1H),4.56(q,J=7.2Hz,1H),4.48 (d,J=10.9Hz,1H),4.21(s,49H),3.88-3.75(m,4H),3.66(dd,J=5.1,1.5Hz, 2H),3.58(dd,J=10.8,3.2Hz,2H),3.54(s,14H),3.51(s,3H),3.47(dd,J=5. 5,3.2Hz,1H),3.44(d,J=1.4Hz,1H),3.44-3.36(m,2H),3.30(s,3H),2.86(d d,J=12.3,3.7Hz,2H),2.78(dd,J=12.3,7.7Hz,1H),2.41(s,5H),2.21(d,J= 17.0Hz, 2H), 1.83 (s, 4H), 1.68 (t, J = 7.5Hz, 7H), -1.71 (s, 1H), -1.99 (s, 1H).

[0708] Synthesis Example 12 - Synthesis of Chlorin e6 5-methyl ester disodium salt (Compound 13)

[0709]

[0710] Chlorin e6 5-methyl ester (200 mg, 0.327 mmol, 1 eq) was weighed into a 100 mL RBF, followed by addition of distilled deionized water (30 mL) under a stirring bar. 0.1 M sodium hydroxide solution (6.54 mL, 0.654 mmol, 2 eq) was added, and the mixture was stirred at 25 ° C for 2 hours. The reaction mixture was then freeze-dried overnight (16 hours) to give compound 13 (216 mg, quantitative yield, 87.74% purity according to HPLC) as a purple fluffy solid.

[0711] 1 H NMR(400MHz,DMSO-d6)δ9.73(s,1H),9.69(s,1H),9.10(s,1H),8.30(dd,J=17.8,11.7Hz,1H) ,6.44(dd,J=17.8,1.6Hz,1H),6.16(dd,J=11.6,1.5Hz,1H),5.38(d,J=17.9Hz,1H),4.98(d, J=17.9Hz,1H),4.60-4.44(m,2H),4.20(s,3H),3.85-3.77(m,4H),3.54(s,3H),3.51(s,3H), 3.31(s,3H),2.29-2.09(m,2H),1.73(s,4H),1.71-1.64(m,6H),-1.75(s,1H),-2.04(s,1H).

[0712] Synthesis Example 13 - Synthesis of Chlorin e6 5-methyl ester mono(N-methyl-D-reduced glucosamine) salt (Compound 14)

[0713]

[0714] Chlorin e6 5-methyl ester (200 mg, 0.327 mmol, 1 eq) was weighed into a 100 mL RBF, followed by the addition of distilled deionized water (50 mL) under a stirring bar. Meglumine (64 mg, 0.327 mmol, 1 eq) was added and the mixture was stirred at 70 ° C for 2 hours. The reaction mixture was then freeze-dried overnight (16 hours) to give compound 14 (262 mg, 99% yield, 78.36% purity according to HPLC) as a purple fluffy solid.

[0715] 1H NMR(400MHz, DMSO-d6)δ9.73(s,1H),9.64(s,1H),9.08(s,1H),8.26(dd,J=17.8,11.6Hz,1H),6.42(dd,J=17.8,1.6Hz,1H),6.23-6.11(m, 1H),5.25-5.06(m,4H),4.58(q,J=7.1Hz,1H),4.48-4.41(m,1H),4.21(s,3H),3.89-3.82(m,2H),3.82-3.73(m,2H),3.66(dd,J=5.1,1.6H z,2H),3.58(dd,J=10.8,3.2Hz,2H),3.53(s,3H),3.50-3.46(m,4H),3.45-3.36(m,3H),3.26(s,3H),2.94(dd,J=12.5,3.5Hz,1H),2.84(d d,J=12.4,8.4Hz,1H),2.65-2.52(m,1H),2.46(s,4H),2.34-2.06(m,2H),1.89(s,3H),1.66(t,J=7.3Hz,7H),-1.62(s,1H),-1.86(s,1H).

[0716] Synthesis Example 14 - Synthesis of Chlorin e6 15-Methyl Ester (Compound 15)

[0717]

[0718] Chlorin e6 anhydride (3.00g, 0.005mol, 1 equivalent), ethanol (4.77g, 0.103mol, 2 equivalents), NaHCO3 (13.06g, 0.155mol, 10 equivalents) and DCM (150mL) are loaded into 1 neck 500mL RBF. The gained solution is stirred (400rpm) and spends the night at 35 DEG C under a nitrogen atmosphere. Then the reaction mixture is filtered on a sintered glass funnel and concentrated by rotary evaporation to obtain the crude product (about 3.0g) as a dark purple-brown solid. The crude product is purified by column chromatography (silica gel, 4x 20cm). The crude product is loaded onto post as the solution in 10% MeOH / DCM. The eluent gradient of 5%, 10%, 15% and 50% MeOH in DCM is used to elute the product band from post. The product is analyzed by TLC in 10% MeOH / DCM. f Fractions containing a blue-green spot at 5% RI = 0.5 were combined and concentrated by rotary evaporation to give compound 15 (510 mg, 16% yield, 97.95% purity by HPLC) as a dark blue solid.

[0719] 1 H NMR (400MHz, DMSO-d6) δ9.75(s,1H),9.69(s,1H),9.11(s,1H),8.32(dd,J=17.8,11.6Hz,1H),6.43(dd,J=17.8,1.6Hz ,1H),6.14(dd,J=11.6,1.5Hz,1H),5.80(d,J=19.6Hz,1H),5.45(d,J=18.8Hz,1H),4.60(q,J=7.1Hz,1H),4.37(d,J=9. 9Hz,1H),4.11(q,J=7.1Hz,2H),3.79(q,J=7.6Hz,2H),3.51(d,J=6.6Hz,5H),3.31(s,3H),2.61(q,J=7.8,7.4Hz,0H), 2.32-2.19(m,1H),2.12(q,J=14.5,10.1Hz,1H),1.73-1.49(m,5H),1.19(t,J=7.0Hz,3H),-1.89(s,1H),-2.36(s,1H).

[0720] Synthesis Example 15 - Synthesis of Chlorin e6 15-Methyl Ester Bis(N-Methyl-D-Reduced Glucosamine) Salt (Compound 16)

[0721]

[0722] Chlorin e6 15-ethyl ester (compound 15) (200mg, 0.320mmol, 1 equivalent) is weighed into 25mL RBF, and then distilled deionized water (5mL) is added under stirring bar.Meglumine (119mg, 0.608mmol, 1.9 equivalents) is added, and then the mixture is stirred, and heated at 40 DEG C for 1 hour simultaneously.The solution is cooled to ambient temperature, diluted with water (20mL), and then filtered into the 250mL RBF with side arm adapter through 3 porosity filters (3cm diameter).The reaction flask is rinsed with deionized water (about 10mL), and then passed through a filter to complete the transfer.Then the filtrate is freeze-dried overnight to obtain compound 16 (321mg, 99% yield, 96.95% according to HPLC purity) as a dark brown solid.

[0723] 1H NMR (400MHz, DMSO-d6) δ9.80(s,1H),9.68(s,1H),9.13(s,1H),8.36(dd,J=17.8,11.6Hz,1H),6.45(d,J=17.9Hz,1H),6.15(d,J= 11.6Hz,1H),5.98(d,J=18.8Hz,1H),5.54(d,J=19.0Hz,1H),4.57(q,J=7.4Hz,1H),4.37(d,J=10.2Hz,1H),4.17-4.03(m,2H),3.9 0-3.78(m,4H),3.72(d,J=5.0Hz,2H),3.62(dd,J=10.8,3.1Hz,3H),3.56-3.41(m,19H),3.34(s,3H),2.89-2.74(m,5H),2.42(s, 8H), 2.12 (t, J = 12.0Hz, 2H), 1.70 (t, J = 7.5Hz, 3H), 1.62 (d, J = 7.0Hz, 3H), 1.16 (q, J = 9.5, 8.3Hz, 3H), -2.00 (s, 1H), -2.56 (s, 1H).

[0724] Synthesis Example 16 - Synthesis of Chlorin e6 15-ethyl Ester Disodium Salt (Compound 17)

[0725]

[0726] Chlorin e6 15-ethyl ester (Compound 15) (100 mg, 0.160 mmol, 1 eq) was weighed into a 100 mL RBF, followed by addition of distilled deionized water (5 mL) under a stirring bar. 0.1 M sodium hydroxide solution (3.04 mL, 0.304 mmol, 1.9 eq) was added, and the mixture was stirred at 25 ° C for 2 hours. The reaction mixture was then freeze-dried overnight (16 hours) to give Compound 17 (110 mg, quantitative yield, 72.67% purity according to HPLC) as a purple fluffy solid.

[0727] 1H NMR (400MHz, DMSO-d6) δ9.79(s,1H),9.63(s,1H),9.11(s,1H),8.36(dd,J=17.8,11.6Hz,1H),6.44(dd,J=17.8,1.7 Hz,1H),6.23-6.05(m,2H),5.39(d,J=18.6Hz,1H),4.56(q,J=7.2Hz,1H),4.27(d,J=10.1Hz,1H),4.10(q,J=6.9Hz,2 H),3.83(q,J=7.5Hz,2H),3.55(s,3H),3.45(s,2H),3.34(s,2H),2.33-2.24(m,1H),2.09(q,J=7.1Hz,1H),2.05-1. 93(m,1H),1.70(t,J=7.5Hz,3H),1.65(s,1H),1.54-1.42(m,1H),1.17(t,J=7.1Hz,5H),-2.00(s,1H),-2.63(s,1H).

[0728] Synthesis Example 17 - Synthesis of Chlorin e6 15-Ethyl Ester Mono(N-Methyl-D-Reduced Glucosamine) Salt (Compound 18)

[0729]

[0730] Chlorin e6 15-ethyl ester (Compound 15) (100 mg, 0.160 mmol, 1 eq) was weighed into a 25 mL RBF, followed by the addition of distilled deionized water (5 mL) under a stirring bar. Meglumine (31 mg, 0.160 mol, 1 eq) was added and the mixture was stirred at 40° C. for 2 hours. The reaction mixture was then freeze-dried overnight (16 hours) to afford Compound 18 (132 mg, quantitative yield, 93.03% purity by HPLC) as a dark brown, fluffy solid.

[0731] 1H NMR (400MHz, DMSO-d6) δ9.79(s,1H),9.67(s,1H),9.12(s,1H),8.36(dd,J=17.8,11.7Hz,1H),6.44(d,J=17.8Hz,1H),6.15(d,J=11 .6Hz,1H),5.97(d,J=18.7Hz,1H),5.50(d,J=19.0Hz,1H),4.66-4.50(m,1H),4.35(d,J=10.1Hz,1H),4.09(q,J=7.0Hz,2H),3.91-3 .76(m,3H),3.72(d,J=4.9Hz,1H),3.61(dd,J=10.8,2.9Hz,2H),3.55-3.52(m,4H),3.47(s,3H),3.34(s,3H),2.91-2.76(m,3H),2. 44(s,5H),2.14(d,J=10.8Hz,2H),1.69(t,J=7.5Hz,3H),1.61(d,J=7.0Hz,2H),1.16(t,J=7.1Hz,3H),-2.01(s,1H),-2.58(s,1H).

[0732] Synthesis Example 18 - Synthesis of Chlorin e6 15-(3-((Triphenylphosphonium)chloride)propyl)ester (Compound 19)

[0733]

[0734] Chlorin e6 anhydride (1.00g, 1.73mmol, 1 equivalent), (3-hydroxypropyl) triphenylphosphonium chloride (6.16g, 17.3mmol, 10 equivalents), NaHCO (2.91g, 34.6mmol, 20 equivalents) and DCM (70mL) were loaded into 1 neck 250mL RBF. The resulting solution was stirred (400rpm) for 24 hours at 35°C under a nitrogen atmosphere. The reaction process was monitored by HPLC. The reaction mixture was filtered on a sintered glass funnel and concentrated by rotary evaporation to obtain a crude product in the form of a dark purple-brown solid. The crude product was purified by column chromatography. The crude product was loaded onto a post as a solution in 10% MeOH / DCM. The product band (final main band) was eluted from the post using an eluent gradient of 10%, 20%, 35% and 50% MeOH in DCM. The product was analyzed by TLC in 10% MeOH / DCM. f Fractions containing a blue-green spot at ΔH = 0.6 were combined and concentrated by rotary evaporation to give compound 19 as a dark blue solid.

[0735] 1H NMR (400MHz, DMSO-d6) δ9.81 (s, 1H), 9.62 (s, 1H), 9.11 (s, 1H), 8.36 (dd, J = 17.8, 11.6Hz, 1H), 7.89-7.73 (m, 6H), 7.6 9-7.59(m,3H),7.46(td,J=7.8,3.2Hz,6H),6.43(dd,J=17.8,1.6Hz,1H),6.14(dd,J=11.6,1.5Hz,1H),4.60(q,J=7.2 Hz,1H),4.43(s,1H),4.19(d,J=24.5Hz,3H),3.95(d,J=13.2Hz,0H),3.83(d,J=7.6Hz,1H),3.52(s,2H),3.37-3.35(m ,6H),2.65-2.54(m,1H),2.26-2.07(m,2H),1.69(t,J=7.5Hz,3H),1.59(d,J=7.1Hz,3H),-1.98(s,1H),-2.56(s,1H).

[0736] Synthesis Example 19 - Synthesis of Chlorin e6 5-Methyl Ester Bis(N-Methyl-D-Reduced Glucosamine) Salt (Compound 20)

[0737]

[0738] To the 50mL RBF containing chlorin e6 5- methyl ester (300mg, 0.491mmol, 1 equivalent), distilled deionized water (10mL) and stirring bar (about 20mm) are added. The mixture is heated at 70°C in the dark under stirring (200rpm) for 30 minutes. Add meglumine (192mg, 0.982mmol, 2 equivalents), then the mixture is stirred at 70°C under nitrogen in the dark for 3 hours. Under stirring (30 minutes), the solution is cooled to ambient temperature and then filtered into a 500mL conical flask with a side arm through a 3-porosity filter. The reaction flask is rinsed with distilled deionized water (2x5mL) to transfer the remaining residue. The filtrate is transferred to a 250mL RBF, and the solution is freeze-dried overnight to obtain compound 20 (0.44g, 89%) as a powdery brown / black solid.

[0739] 1H NMR(400MHz,d6-DMSO)δ9.72(s,1H),9.67(s,1H),9.09(s,1H),8.38(dd,1H),6.43(dd,1H),6 .16(dd,1H),5.16(d,1H),5.01(d,1H),4.58-4.46(m),4.19(s),3.83-3.77(m,7H),3.66-3.63 (m),3.61-3.56(m),3.55-3.45(m),3.45-3.36(m),3.29(s,3H),2.86-2.79(m,3H),2.78-2.7 2(m,3H),2.39(s,8H),2.20-2.12(m,2H),1.70-1.66(m,7H),-1.69(brs,1H),-1.97(brs,1H).

[0740] Synthesis Example 20 - Synthesis of Chlorin e6 15-Butyl Ester (Compound 21)

[0741]

[0742] Chlorin e6 anhydride (1.00g, 1.73mmol, 1 equivalent), n-butanol (2.56g, 34.6mmol, 20 equivalents), NaHCO (4.36g, 51.8mmol, 30 equivalents) and DCM (50mL) are loaded into 1 neck 250mL RBF. The resulting solution is stirred overnight at 35°C under a nitrogen atmosphere. The reaction mixture is then filtered on a sintered glass funnel and concentrated by rotary evaporation to obtain a crude product (1.9g) as a dark purple-brown solid. The crude product is purified by column chromatography. The crude product is loaded onto a post as a solution in 5% MeOH / DCM. The product band is eluted from the post using the eluent gradient of 5%-10% MeOH in DCM. The product is analyzed by TLC in 10% MeOH / DCM. f Fractions containing a blue-green spot at δ = 0.3 were combined and concentrated by rotary evaporation to give compound 21 (520 mg) as a dark blue-green solid.

[0743] 1H NMR (400MHz, DMSO-d6) δ9.75(s,1H),9.69(s,1H),9.11(s,1H),8.32(dd,J=17.8,11.6Hz,1H),6.43(dd,J=17.8,1.6Hz,1H),6 .14(dd,J=11.6,1.5Hz,1H),5.80(d,J=19.6Hz,1H),5.45(d,J=18.8Hz,1H),4.60(q,J=7.1Hz,1H),4.37(d,J=9.9Hz,1H),4.1 1(q,J=7.1Hz,2H),3.79(q,J=7.6Hz,2H),3.51(d,J=6.6Hz,5H),3.31(s,3H),2.61(q,J=7.8,7.4Hz,0H),2.32-2.19(m,1H),2 .12(q,J=14.5,10.1Hz,1H),1.73-1.49(m,6H),1.50(m,2H),1.20(m,2H),1.19(t,J=7.0Hz,3H),-1.60(s,1H),-1.90(s,1H).

[0744] Synthesis Example 21 - Synthesis of Chlorin e6 15-Hexyl Ester (Compound 22)

[0745]

[0746] Chlorin e6 anhydride (1.00g, 1.73mmol, 1 equivalent), hexanol (3.53g, 34.6mmol, 20 equivalents), NaHCO (4.36g, 51.8mmol, 30 equivalents) and DCM (50mL) are loaded into 1 neck 250mL RBF. Gained solution is stirred overnight at 35 DEG C under a nitrogen atmosphere. Then the reaction mixture is filtered on a sintered glass funnel and concentrated by rotary evaporation to obtain a crude product (1.8g) as a dark purple-brown solid. The crude product is purified by column chromatography. The crude product is loaded onto a post as a solution in 5%MeOH / DCM. The eluent gradient of 5%-10%MeOH in DCM is used to elute the product band from the post. Fractions containing a blue-green spot at Rf = 0.3 by TLC analysis in 10% MeOH / DCM were combined and concentrated by rotary evaporation to give compound 22 (310 mg) as a dark blue-green solid.

[0747] 1H NMR(400MHz,DMSO-d6)δ9.74(s,1H),9.63(s,1H),9.08(s,1H),8.23(dd,1H),6.40(dd,1H),6.12(d d,1H),5.51-5.39(m,2H),4.60(q,1H),4.44(d,1H),4.04(m,2H),3.75(q,2H),3.57(s,3H),3.47(s ,3H),3.24(s,3H),2.68-2.55(m,1H),2.28-2.18(m,1H),2.17-2.09(m,1H),1.69-1.62(m,6H),1.6 1-1.55(m,1H),1.52-1.45(m,2H),1.10-0.97(m,6H),0.61(t,3H),-1.63(brs,1H),-1.89(brs,1H).

[0748] Biological experiment details

[0749] Example 1 - Determination of the Solubility of Chlorin e6 Analogs

[0750] The absorbance maximum was used as a surrogate measure of solubility.The relevant chlorin e6 analogs were diluted to 50 μM in PBS (phosphate buffered saline) solutions containing decreasing amounts of DMSO from 100% to 0%.

[0751] Where necessary, polyvinyl pyrrolidone (K30) was added to a final concentration of 1% w / v. Absorbance was measured using a Cytation 3 multi-mode plate reader (Biotek) in spectral scanning mode, capturing spectra at 2 nm increments between 500 and 800 nm. An equivalent blank solution was also measured and subtracted accordingly. Each spectrum was normalized to a minimum signal of 0 and a maximum signal of 100% in pure DMSO solution (the most soluble state).

[0752] Example 2 - Cytotoxicity, Phototoxicity and Therapeutic Index

[0753] Preparation of photosensitizer stock solution

[0754] Photosensitizers such as chlorin e6 analogs, chlorin e4 disodium (supplied by Advanced Molecular Technologies, Scoresby) or talaporfin sodium (purchased from Focus Bioscience, catalog number HY-16477-5MG) were resuspended in 100% dimethyl sulfoxide (DMSO) at a concentration of 5.5 mM. Samples were stored at 4°C in the dark.

[0755] Preparation of photosensitizers for in vitro studies

[0756] For in vitro experiments, the photosensitizer (stock solution 5.5 mM in 100% DMSO) was diluted 1:100 in a concentrated vehicle 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 vehicle solution.

[0757] Cell culture

[0758] 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 spent medium was replaced with medium containing the desired concentration of photosensitizer, and the cells were incubated for the desired period of time to allow for photosensitizer uptake.

[0759] Statistical analysis

[0760] All data were analyzed using GraphPad PRISM v8.3.1 (549) (GraphPad Software, CA). Spectral absorbance and activity measurements were normalized within 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-point nonlinear regression with a variable slope, and the IC10 or IC90 for each compound was calculated. All data are shown as mean ± SD (where appropriate).

[0761] Cytotoxicity

[0762] SKOV3 cells were seeded in 96-well black-walled plates (Greiner #655090) at a cell density of 5,000 cells per well in 100 μl of culture medium. Upon reaching approximately 60% confluence, the culture medium was aspirated and replaced with fresh culture medium containing 0-100 μM of the relevant chlorin e6 analog in DMSO. The cells were incubated for an additional 24 hours to allow for uptake of the chlorin e6 analog.

[0763] To test the intrinsic cytotoxicity (i.e., "dark toxicity") of the chlorin e6 analog, the culture medium was replaced after 24 hours with fresh culture medium containing 10% (v / v) AlamarBlue cell viability reagent (ThermoFisher), and the cells were incubated at 37°C for 6 hours. Untreated cells served as a control. Fluorescence (Ex 555 nm / Em 596 nm) was measured using a Cytation 3 Cell Imaging Multimode Reader (Biotek), and cytotoxicity was assessed based on the percentage of remaining viable cells. All measurements were performed in quadruplicate.

[0764] Phototoxicity

[0765] SKOV3 cells were seeded in 96-well black-walled plates (Greiner #655090) at a cell density of 5,000 cells per well in 100 μl of culture medium. Upon reaching approximately 60% confluence, the culture medium was aspirated and replaced with fresh culture medium containing 0-100 μM of the relevant chlorin e6 analog in DMSO. The cells were incubated for an additional 24 hours to allow for uptake of the chlorin e6 analog.

[0766] To test phototoxicity, cells incubated with chlorin e6 analogs (0–10 μM in DMSO) were exposed to a laser at a density of 50 mW / cm2 for 24 h after medium replacement (as described above). 2 652 nm laser (Invion) for 5 min (total 15 J / cm 2 After activation, cells were cultured for an additional 24 hours. The medium was then replaced with fresh medium containing AlamarBlue, and the remaining viable cell percentage was assessed as described above. Controls included cells treated with the chlorin e6 analog but not activated by laser; cells not treated with the chlorin e6 analog but treated with laser; and an untreated control. All measurements were performed in quadruplicate.

[0767] Toxicity characteristics of chlorin e6 analogs

[0768] The phototoxicity and intrinsic cytotoxicity (i.e., "dark toxicity") of the chlorin e6 analogs were evaluated using SKOV3 ovarian cancer cells as previously described. For comparative purposes, the chlorin e6 analogs were compared with chlorin e4 disodium and talaporfin sodium, a clinically approved photosensitizer for photodynamic therapy of lung cancer. Phototoxicity IC90 and dark toxicity IC10 values were calculated using a log[inhibitor]-normalized response dose curve with a 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)).

[0769] The in vitro phototoxicity of dihydrochlorin e4 disodium and talaporfin sodium was significantly lower than that of compounds 1, 2 and 8.

[0770] Therapeutic index of chlorin e6 analogs

[0771] To evaluate the therapeutic potential of chlorin e6 analogs, the therapeutic index (TI) was calculated. By comparing the drug concentration required for a desired effect with the concentration that causes undesirable off-target toxicity, the TI provides a quantitative measure describing relative drug safety. The TI was calculated using the phototoxicity IC90 versus the dark toxicity IC10.

[0772] 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 is lower, its potential therapeutic window of use is smaller. The chlorin e6 analog of the present invention has a relatively significantly improved TI and significantly greater phototoxicity (Table 1).

[0773] Therefore, the chlorin e6 analogs of the present invention have a better ideal therapeutic index than clinically used photosensitizers. Furthermore, the greater phototoxicity of the chlorin e6 analogs suggests their potential for use at significantly reduced doses in vivo. Therefore, the chlorin e6 analogs have an acceptable therapeutic profile for clinical use.

[0774] Table 1. Toxicity profile and therapeutic index of chlorin e6 analogs:

[0775]

[0776] Example 3 - Study on the Stability of Chlorin e6 Analog Salts in Aqueous Solutions

[0777] program

[0778] The reaction solution was prepared by dissolving 2-3 mg of the corresponding chlorin e6 analog salt in 5 mL of distilled deionized water in a 50 mL test tube with a lid. The solution was stirred in the test tube at 30°C. Air (oxygen) and ambient light were not excluded. Sample HPLC analysis was performed at 0.5, 4, or 66 hours (unless otherwise stated). The goal was to look for degradation over time.

[0779] The test results are summarized in Table 2 below.

[0780]

[0781]

[0782] Table 2: HPLC of chlorin e6 analog salts in aqueous solution after 0.5, 4 and 66 hours

[0783] Purity (unless otherwise stated).

[0784] *The starting material was approximately 77.7% pure by HPLC.

[0785] The structure of Photolon and Photodithiazine is as follows:

[0786]

[0787] HPLC method

[0788] Column and instrument details

[0789] Instrument: Waters Alliance HPLC equipped with a Waters e2695 separation module and a Waters 2998 PDA detector

[0790] Column: YMC-Pack Pro C18 / S-3μm / 12nm. 150 x 4.6mm. DS / N: 112YB00270

[0791] Guard cartridge: Phenomenex Security Guard Cartridge C18 4 x 3.0 mm ID PRD-281272

[0792] HPLC method

[0793] time Flow rate (ml / min) ％A ％B 1 0.01 1.00 85.0 15.0 2 25.00 1.00 2.0 98.0 3 29.00 1.00 2.0 98.0 4 30.00 1.00 85.0 15.0 5 31.00 1.50 85.0 15.0 6 35.00 1.50 85.0 15.0 7 36.00 0 85.0 15.0

[0794] Mobile phase: A = 0.05% w / v phosphoric acid in distilled water; B = acetonitrile

[0795] Injection volume: 5 μL

[0796] HPLC run time: 35 minutes

[0797] Detection wavelength: 406nm

[0798] Column temperature: 40°C

[0799] in conclusion

[0800] From the experimental results, it can be seen that in -R 7 There is an ester or amide group (such as -C(O)-R 14 -R 15 、-C(O)-NR 20 R 21 OR-C(O)-OR 22 The compound containing the α-amino group is more stable in aqueous solution than the compound without the α-amino group.

[0801] It should be understood that the present invention has been described above by way of example only. The embodiments are not intended to limit the scope of the present invention. Various modifications and embodiments may be made without departing from the scope and spirit of the present invention, which is limited 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. -R 2 、-C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )2. -C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R 3 )2; -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 -X, -R α -[N(R 5 )3]Y, -R α -[P(R 5 )3]Y, -R α -[R 8 Y, -R α -[N(R 5 )2(R 5’ )], -R α -[P(R 5 )2(R 5’ )] or -R α -[R 8’ ; -R 3 and -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 8 ]Y、-R α -[N(R 5 )2(R 5’ )]、-R α -[P(R 5 )2(R 5’ )] or -R α -[R 8’ ]; -R α - each independently selected from C1-C 42 Alkylene, wherein the alkylene may be optionally substituted with one or more C1-C4 alkyl, C1-C4 haloalkyl, or halo, and wherein one or more carbon atoms in the backbone of the alkylene may be optionally replaced with heteroatoms or groups independently selected from O, S, NH, or NMe; -R β each independently a saturated or unsaturated hydrocarbon group, wherein the hydrocarbon group may be linear or branched, or may be or include a cyclic group, wherein the hydrocarbon group may be optionally substituted, and wherein the hydrocarbon group may optionally include 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 be optionally replaced by one or more 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 substitution; -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 replaced by -CO2 ￣ Substituted, wherein the phenyl or C5-C6 heteroaryl may be optionally further substituted by one or more 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 substitution; -R 6 selected from -C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )2、-C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R 3 )2; -R 7 selected from -C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )2、-C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R 3 )2; -R 8 is optionally substituted with one or more 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 -[NC5H5] substituted with -CH3 group; -R 8’ is -[NC5H5], which is replaced by -CO2 ￣ and optionally further substituted with one or more 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 substitution; n is 1, 2, 3, 4, 5, or 6; X is a halogen group; Y is a counter anion; Z is a counter cation; and M 2+ It is a metal cation; Provided that the compound or complex is not: (1) (7S,8S)-7-(2-carboxyethyl)-5-(carboxymethyl)-18-ethyl-2,8,12,17-tetramethyl-13-vinyl-7H,8H-porphyrin-3-carboxylic acid [dihydrochlorin e6]; (2) (7S,8S)-18-ethyl-5-(2-methoxy-2-oxoethyl)-7-(3-methoxy-3-oxopropyl)-2,8,12,17-tetramethyl-13-vinyl-7H,8H-porphyrin-3-carboxylic acid; (3) 2-((7S,8S)-18-ethyl-7-(3-methoxy-3-oxopropyl)-3-(methoxycarbonyl)-2,8,12,17-tetramethyl-13-vinyl-7H,8H-porphyrin-5-yl)acetic acid; (4) 3-((7S,8S)-18-ethyl-5-(2-methoxy-2-oxoethyl)-3-(methoxycarbonyl)-2,8,12,17-tetramethyl-13-vinyl-7H,8H-porphyrin-7-yl)propanoic acid; (5) (7S,8S)-5-(carboxymethyl)-18-ethyl-7-(3-methoxy-3-oxopropyl)-2,8,12,17-tetramethyl-13-vinyl-7H,8H-porphyrin-3-carboxylic acid; (6) (7S,8S)-7-(2-carboxyethyl)-18-ethyl-5-(2-methoxy-2-oxoethyl)-2,8,12,17-tetramethyl-13-vinyl-7H,8H-porphyrin-3-carboxylic acid; (7) 3-((7S,8S)-5-(carboxymethyl)-18-ethyl-3-(methoxycarbonyl)-2,8,12,17-tetramethyl-13-vinyl-7H,8H-porphyrin-7-yl)propanoic acid; (8) (7S,8S)-18-ethyl-5-(2-methoxy-2-oxoethyl)-7-(3-methoxy-3-oxopropyl)-2,8,12,17-tetramethyl-13-vinyl-7H,8H-porphyrin-3-carboxylic acid methyl ester [dihydrochlorin e6 trimethyl ester]; (9) methyl 3-(3-carbamoyl-18-ethyl-5-(2-methoxy-2-oxoethyl)-2,8,12,17-tetramethyl-13-vinyl-7H,8H-porphyrin-7-yl)propanoate; (10) methyl 3-(18-ethyl-5-(2-methoxy-2-oxoethyl)-2,8,12,17-tetramethyl-3-(methylcarbamoyl)-13-vinyl-7H,8H-porphyrin-7-yl)propanoate; (11) methyl 3-(18-ethyl-3-(ethylcarbamoyl)-5-(2-methoxy-2-oxoethyl)-2,8,12,17-tetramethyl-13-vinyl-7H,8H-porphyrin-7-yl)propanoate; (12) methyl 3-(3-(benzylcarbamoyl)-18-ethyl-5-(2-methoxy-2-oxoethyl)-2,8,12,17-tetramethyl-13-vinyl-7H,8H-porphyrin-7-yl)propanoate; (13) methyl 3-(18-ethyl-5-(2-methoxy-2-oxoethyl)-2,8,12,17-tetramethyl-3-(piperidine-1-carbonyl)-13-vinyl-7H,8H-porphyrin-7-yl)propanoate; (14) 5-(2-((3-((5-amino-1-carboxypentyl)carbamoyl)-17-(carboxymethyl)-14-(3-guanidinopropyl)-20-(hydroxymethyl)-1,9,12,15,18,21-hexaoxodocosahydro-7H-pyrrolo[2,1-g][1,2]dithia[5,8,11,14,17,20]hexaazacyclotricosan-8-yl)amino)-2-oxoethyl)-7-(2-carboxyethyl)-18-ethyl-2,8,12,17-tetramethyl-13-vinyl-7H,8H-porphyrin-3-carboxylic acid; (15) (4-((2-(2-(3-carboxy-7-(2-carboxyethyl)-18-ethyl-2,8,12,17-tetramethyl-13-vinyl-7H,8H-porphyrin-5-yl)acetamido)ethyl)amino)-4-oxobutyl)triphenylphosphonium chloride; (16)(1-(3-carboxy-5-(2,13-dioxo-16-(triphenylphosphino)-6,9-dioxa-3,12-diazahexadecyl)-18-ethyl-2,8,12,17-tetramethyl-13-vinyl-7H,8H-porphyrin-7-yl)-3,14-dioxo-7,10-dioxa-4,13-diazaheptadec-17-yl)triphenylphosphonium dichloride; or a salt thereof.

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

3. A compound or complex according to any preceding claim, wherein -R 2 、-R 3 and -R 4 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 It's a sugar group.

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

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

6. The compound or complex according to claim 3, wherein -R β is a saccharide selected from the group consisting of: Where -R 9 Selected from C1-C4 alkyl.

7. The compound or complex according to claim 6, wherein -R 9 It's methyl.

8. A compound or complex according to any preceding claim, wherein -R 1 YES-C(O)-OR 3 , R 3 Yes-R β , and -R β It is a C1-C4 alkyl group.

9. The compound or complex according to any one of claims 1 to 7, wherein -R 1 Selected from -C(O)-OR 3 、-C(O)-SR 3 or -C(O)-N(R 3 )(R 3’ ), where -R 3 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 sugar group, and -R 3’ is H or C1-C4 alkyl.

10. A compound or complex according to any preceding claim, wherein -R 6 YES-C(O)-OR 3 , and -R 3 It is a C1-C4 alkyl group.

11. The compound or complex according to any one of claims 1 to 9, wherein -R 6 Selected from -C(O)-OR 3 、-C(O)-SR 3 or -C(O)-N(R 3 )(R 3’ ), where -R 3 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 sugar group, and -R 3’ is H or C1-C4 alkyl.

12. A compound or complex according to any preceding claim, wherein -R 7 YES-C(O)-OR 3 , and -R 3 It is a C1-C4 alkyl group.

13. The compound or complex according to any one of claims 1 to 11, wherein -R 7 Selected from -C(O)-OR 3 、-C(O)-SR 3 or -C(O)-N(R 3 )(R 3’ ), where -R 3 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 sugar group, and -R 3’ is H or C1-C4 alkyl.

14. A compound of formula (I) or a complex of formula (II): or a pharmaceutically acceptable salt thereof, wherein: -R 1 Selected from -CO2H or -CO2R 13 ; -R 6 Selected from -CO2H or -CO2R 13 ; -R 7 Selected from -C(O)-R 14 -R 15 ; -R 13 Selected from C1-C3 alkyl; -R 14 - is selected from NMe, O or S; -R 15 Selected from C1-C 20 alkyl, wherein one or more carbon atoms in the alkyl may be optionally replaced by heteroatoms or groups independently selected from O, S, NH or NMe, and wherein the alkyl may be optionally substituted with one or more -OH or -NH groups; and M 2+ It is a metal cation; The condition is -R 7 is not a -CO2Me or -CO2Et group; and Provided that the compound of formula (I) or the complex of formula (II) is not: or an enantiomer of any of them; or a racemic mixture of any of them; or a salt of any of them.

15. A compound of formula (I) or a complex of formula (II): or a pharmaceutically acceptable salt thereof, wherein: -R 1 Selected from -CO2H or -CO2R 13 ; -R 6 Selected from -CO2H or -CO2R 13 ; -R 7 Selected from -C(O)-R 14 -R 15 ; -R 13 Selected from C1-C3 alkyl; -R 14 - is selected from NH, NMe, O or S; -R 15 Selected from C4-C 20 alkyl, wherein one or more carbon atoms in the alkyl may be optionally replaced by heteroatoms or groups independently selected from O, S, NH or NMe, and wherein the alkyl may be optionally substituted with one or more -OH or -NH groups; and M 2+ It is a metal cation; The condition is -R 7 is not a -CO2Me or -CO2Et group; and provided that the compound of formula (I) or the complex of formula (II) is not: or an enantiomer of any of them; or a racemic mixture of any of them; or a salt of any of them.

16. 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. -R 2 、-C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )2. -C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R 3 )2; -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 -X, -R α -[N(R 5 ),3]Y, -R α -[P(R 5 ),3]Y, -R α -[R 8 Y, -R α -[N(R 5 ),2(R 5’ ), -R α -[P(R 5 ),2(R 5’ ),] or -R α -[R 8’ ; -R 3 and -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 8 ]Y、-R α -[N(R 5 )2(R 5’ )]、-R α -[P(R 5 )2(R 5’ )] or -R α -[R 8’ ]; -R α - each independently selected from C1-C 42 Alkylene, wherein the alkylene may be optionally substituted with one or more C1-C4 alkyl, C1-C4 haloalkyl, or halo, and wherein one or more carbon atoms in the backbone of the alkylene may be optionally replaced with heteroatoms or groups independently selected from O, S, NH, or NMe; -R β each independently a saturated or unsaturated hydrocarbon group, wherein the hydrocarbon group may be linear or branched, or may be or include a cyclic group, wherein the hydrocarbon group may be optionally substituted, and wherein the hydrocarbon group may optionally include 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 be optionally replaced by one or more 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 substitution; -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 replaced by -CO2 ￣ Substituted, wherein the phenyl or C5-C6 heteroaryl may be optionally further substituted by one or more 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 substitution; -R 6 selected from -C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )2、-C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R 3 )2; -R 7 selected from -C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )2、-C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R 3 )2; -R 8 is optionally substituted with one or more 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 -[NC5H5] substituted with -CH3 group; -R 8’ is -[NC5H5], which is replaced by -CO2 ￣ and optionally further substituted with one or more 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 substitution; n is 1, 2, 3, 4, 5, or 6; X is a halogen group; Y is a counter anion; Z is a counter cation; and M 2+ It is a metal cation; The condition is -R 1 、-R 6 and -R 7 At least one of them contains -R α -[R 8 ]Y or -R α -[R 8’ ].

17. 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. -R 2 、-C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )2. -C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R 3 )2; -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 -X, -R α -[N(R 5 )3]Y, -R α -[P(R 5 )3]Y, -R<000​​​​​​​​​​​​​​​​​​​ -R 3 and -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 8 ]Y、-R α -[N(R 5 )2(R 5’ )]、-R α -[P(R 5 )2(R 5’ )] or -R α -[R 8’ ]; -R α - each independently selected from C1-C 42 Alkylene, wherein the alkylene may be optionally substituted with one or more C1-C4 alkyl, C1-C4 haloalkyl, or halo, and wherein one or more carbon atoms in the backbone of the alkylene may be optionally replaced with heteroatoms or groups independently selected from O, S, NH, or NMe; -R β each independently a saturated or unsaturated hydrocarbon group, wherein the hydrocarbon group may be linear or branched, or may be or include a cyclic group, wherein the hydrocarbon group may be optionally substituted, and wherein the hydrocarbon group may optionally include 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 be optionally replaced by one or more 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 substitution; -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 replaced by -CO2 ￣ Substituted, wherein the phenyl or C5-C6 heteroaryl may be optionally further substituted by one or more 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 substitution; -R 6 selected from -C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )2、-C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R 3 )2; -R 7 selected from -C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )2、-C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R 3 )2; -R 8 is optionally substituted with one or more 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 -[NC5H5] substituted with -CH3 group; -R 8’ is -[NC5H5], which is -CO2 ￣ and optionally further substituted with one or more 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 substitution; n is 1, 2, 3, 4, 5, or 6; X is a halogen group; Y is a counter anion; Z is a counter cation; and M 2+ It is a metal cation; The condition is -R 1 、-R 6 and -R 7 At least one of them contains -R 14 -[(CH2) p O)] r -(CH2) s -R 14 -R 16 ,in: Each -R 14 - independently selected from NH, NMe, O or S; -R 16 It is a sugar group; p is 1, 2, 3, or 4; r is 0, 1, 2, 3, 4, 5, or 6; and s is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12.

18. 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. -R 2 、-C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )2. -C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R 3 )2; -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 -X, -R α -[N(R 5 )3]Y, -R α -[P(R 5 )3]Y, -R α -[R 8 Y, -R α -[N(R 5 )2(R 5’ )], -R α -[P(R 5 )2(R 5’ )] or -R α -[R 8’ ; -R 3 and -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 8 ]Y、-R α -[N(R 5 )2(R 5’ )]、-R α -[P(R 5 )2(R 5’ )] or -R α -[R 8’ ]; -R α - each independently selected from C1-C 42 Alkylene, wherein the alkylene may be optionally substituted with one or more C1-C4 alkyl, C1-C4 haloalkyl, or halo, and wherein one or more carbon atoms in the backbone of the alkylene may be optionally replaced with heteroatoms or groups independently selected from O, S, NH, or NMe; -R β each independently a saturated or unsaturated hydrocarbon group, wherein the hydrocarbon group may be linear or branched, or may be or include a cyclic group, wherein the hydrocarbon group may be optionally substituted, and wherein the hydrocarbon group may optionally include 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 be optionally replaced by one or more 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 substitution; -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 replaced by -CO2 ￣ Substituted, wherein the phenyl or C5-C6 heteroaryl may be optionally further substituted by one or more 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 substitution; -R 6 selected from -C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )2、-C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R 3 )2; -R 7 selected from -C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )2、-C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R 3 )2; -R 8 is optionally substituted with one or more 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 -[NC5H5] substituted with -CH3 group; -R 8’ is -[NC5H5], which is replaced by -CO2 ￣ and optionally further substituted with one or more 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 substitution; n is 1, 2, 3, 4, 5, or 6; X is a halogen group; Y is a counter anion; Z is a counter cation; and M 2+ It is a metal cation; The condition is -R 1 、-R 6 and -R 7 At least one of them contains -R 14 -[(CH2) p -R 14 ] r -(CH2) s -R 17 ,in: Each -R 14 - independently selected from NH, NMe, O or S; -R 17 Yes-[P(R 5 )3]Y or -[P(R 5 )2(R 5’ )]; p is 1, 2, 3, or 4; r is 0, 1, 2, 3, 4, 5, or 6; and s is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12.

19. 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. -R 2 、-C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )2. -C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R 3 )2; -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 -X, -R α -[N(R 5 )3]Y, -R α -[P(R 5 )3]Y, -R α -[R 8 Y, -R α -[N(R 5 )2(R 5’ )], -R α -[P(R 5 )2(R 5’ )] or -R α -[R 8’ ; -R 3 and -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 8 ]Y、-R α -[N(R 5 )2(R 5’ )]、-R α -[P(R 5 )2(R 5’ )] or -R α -[R 8’ ]; -R α - each independently selected from C1-C 42 Alkylene, wherein the alkylene may be optionally substituted with one or more C1-C4 alkyl, C1-C4 haloalkyl, or halo, and wherein one or more carbon atoms in the backbone of the alkylene may be optionally replaced with heteroatoms or groups independently selected from O, S, NH, or NMe; -R β each independently a saturated or unsaturated hydrocarbon group, wherein the hydrocarbon group may be linear or branched, or may be or include a cyclic group, wherein the hydrocarbon group may be optionally substituted, and wherein the hydrocarbon group may optionally include 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 be optionally replaced by one or more 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 substitution; -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 replaced by -CO2 ￣ Substituted, wherein the phenyl or C5-C6 heteroaryl may be optionally further substituted by one or more 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 substitution; -R 6 selected from -C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )2、-C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R 3 )2; -R 7 selected from -C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )2、-C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R 3 )2; -R 8 is optionally substituted with one or more 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 -[NC5H5] substituted with -CH3 group; -R 8’ is -[NC5H5], which is replaced by -CO2 ￣ and optionally further substituted with one or more 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 substitution; n is 1, 2, 3, 4, 5, or 6; X is a halogen group; Y is a counter anion; Z is a counter cation; and M 2+ It is a metal cation; The condition is -R 1 、-R 6 and -R 7 At least one of: (i)-R 14 -[(CH2) p -R 14 ] r -(CH2) s -R 18 ,in: Each -R 14 - independently selected from NH, NMe, O or S; -R 18 Yes-[N(R 5 )3]Y or -[N(R 5 )2(R 5’ )]; p is 1, 2, 3, or 4; r is 2, 3, 4, 5, or 6; and s is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12; or (ii)-R 14 -(CH2) s -R 18 ,in: -R 14 - is selected from NH, NMe, O or S; -R 18 Yes-[N(R 5 )3]Y or -[N(R 5 )2(R 5’ )];and s is 4, 5, 6, 7, 8, 9, 10, 11, or 12.

20. 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. -R 2 、-C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )2. -C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R 3 )2; -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 -X, -R α -[N(R 5 )3]Y, -R α -[P(R 5 )3]Y, -R α -[R 8 Y, -R α -[N(R 5 )2(R 5’ )], -R α -[P(R 5 )2(R 5’ )] or -R α -[R 8’ ; -R 3 and -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 8 ]Y、-R α -[N(R 5 )2(R 5’ )]、-R α -[P(R 5 )2(R 5’ )] or -R α -[R 8’ ]; -R α - each independently selected from C1-C 42 Alkylene, wherein the alkylene may be optionally substituted with one or more C1-C4 alkyl, C1-C4 haloalkyl, or halo, and wherein one or more carbon atoms in the backbone of the alkylene may be optionally replaced with heteroatoms or groups independently selected from O, S, NH, or NMe; -R β each independently a saturated or unsaturated hydrocarbon group, wherein the hydrocarbon group may be linear or branched, or may be or include a cyclic group, wherein the hydrocarbon group may be optionally substituted, and wherein the hydrocarbon group may optionally include 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 be optionally replaced by one or more 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 substitution; -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 replaced by -CO2 ￣ Substituted, wherein the phenyl or C5-C6 heteroaryl may be optionally further substituted by one or more 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 substitution; -R 6 selected from -C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )2、-C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R 3 )2; -R 7 selected from -C(O)-OR 19 ; -R 8 is optionally substituted with one or more 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 -[NC5H5] substituted with -CH3 group; -R 8’ is -[NC5H5], which is replaced by -CO2 ￣ and optionally further substituted with one or more 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 substitution; -R 19 is a C3-C6 alkyl group; n is 1, 2, 3, 4, 5, or 6; X is a halogen group; Y is a counter anion; Z is a counter cation; and M 2+ It is a metal cation; Provided that the compound of formula (I) or the complex of formula (II) is not: or an enantiomer of any of them; or a racemic mixture of any of them; or a salt of any of them.

21. 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. -R 2 、-C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )2. -C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R 3 )2; -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 -X, -R α -[N(R 5 )3]Y, -R α -[P(R 5 )3]Y, -R α -[R 8 Y, -R α -[N(R 5 )2(R 5’ )], -R α -[P(R 5 )2(R 5’ )] or -R α -[R 8’ ; -R 3 and -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 8 ]Y、-R α -[N(R 5 )2(R 5’ )]、-R α -[P(R 5 )2(R 5’ )] or -R α -[R 8’ ]; -R α - each independently selected from C1-C 42 Alkylene, wherein the alkylene may be optionally substituted with one or more C1-C4 alkyl, C1-C4 haloalkyl, or halo, and wherein one or more carbon atoms in the backbone of the alkylene may be optionally replaced with heteroatoms or groups independently selected from O, S, NH, or NMe; -R β each independently a saturated or unsaturated hydrocarbon group, wherein the hydrocarbon group may be linear or branched, or may be or include a cyclic group, wherein the hydrocarbon group may be optionally substituted, and wherein the hydrocarbon group may optionally include 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 be optionally replaced by one or more 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 substitution; -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 replaced by -CO2 ￣ Substituted, wherein the phenyl or C5-C6 heteroaryl may be optionally further substituted by one or more 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 substitution; -R 6 selected from -C(O)-OR 3 、-C(O)-SR 3 、-C(O)-N(R 3 )2、-C(S)-OR 3 、-C(S)-SR 3 or -C(S)-N(R 3 )2; -R 7 Selected from -C(O)-NR 20 R 21 ; -R 8 is optionally substituted with one or more 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 -[NC5H5] substituted with -CH3 group; -R 8’ is -[NC5H5], which is replaced by -CO2 ￣ and optionally further substituted with one or more 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 substitution; -R 20 is a C1-C6 alkyl group, preferably a C1-C2 or C4-C6 alkyl group; -R 21 is H or C1-C6 alkyl; n is 1, 2, 3, 4, 5, or 6; X is a halogen group; Y is a counter anion; Z is a counter cation; and M 2+ It is a metal cation; Provided that the compound of formula (I) or the complex of formula (II) is not: or an enantiomer of any of them; or a racemic mixture of any of them; or a salt of any of them.

22. A pharmaceutically acceptable salt of a compound of formula (I) or a complex of formula (II): in: -R 1 It is -CO2H; -R 6 It is -CO2H; -R 7 is-C(O)-OR 22 or -C(O)-NR 20 R 21 ; -R 20 is a C1-C6 alkyl group; -R 21 is H or C1-C6 alkyl; -R 22 is a C1-C6 alkyl group; M 2+ is a metal cation; and The pharmaceutically acceptable salt is a lithium salt, a sodium salt, a potassium salt, a magnesium salt, a calcium salt, an ammonium salt, an amine salt (such as choline or meglumine) or an amino acid salt (such as arginine), or a combination thereof.

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

24. A compound or complex according to any preceding claim for use in medicine.

25. A compound or complex according to any preceding claim for use in photodynamic therapy or cytoluminescent therapy.

26. A compound or complex according to any preceding claim for use in 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 (chicken) influenza virus, dengue virus, herpes simplex or herpes zoster infection; hepatitis; viral hepatitis; cardiovascular disease; coronary artery stenosis; carotid artery stenosis; intermittent claudication; skin disorders; acne; psoriasis; benign or malignant Diseases characterized by excessive cell proliferation or areas of new blood vessel formation; benign or malignant tumors; early-stage cancers; cervical dysplasia; soft tissue sarcomas; germ cell tumors; retinoblastoma; age-related macular degeneration; lymphoma; Hodgkin lymphoma; head and neck cancer; oral or mouth cancer; or cancer of the blood, prostate, cervix, uterus, vagina, or other female appendages, breast, nasopharynx, trachea, larynx, bronchus, bronchioles, lung, hollow organ, esophagus, stomach, bile duct, intestinal cancer, colon, colorectal cancer, rectum, bladder, ureter, kidney, liver, gallbladder, spleen, brain, lymphatic system, bone, skin, or pancreas.

27. A compound or complex according to any preceding claim for use in the treatment of a disease characterised by excessive proliferation of benign or malignant cells or by areas of neovascularisation.

28. A compound or complex according to any preceding claim for use in the treatment of benign or malignant tumours.

29. A compound or complex according to any preceding claim for use in the treatment of early stage cancer; cervical dysplasia; soft tissue sarcoma; germ cell tumors; retinoblastoma; age-related macular degeneration; lymphoma; Hodgkin lymphoma; head and neck cancer; oral or buccal cancer; or cancer of the blood, prostate, cervix, uterus, vagina or other female adnexa, breast, nasopharynx, trachea, larynx, bronchus, bronchioles, lung, hollow organ cancer, esophagus, stomach, bile duct, intestinal cancer, colon cancer, colorectal cancer, rectum cancer, bladder cancer, ureter cancer, kidney cancer, liver cancer, gallbladder cancer, spleen cancer, brain cancer, lymphatic system cancer, bone cancer, skin cancer or pancreas cancer.

30. A compound or complex according to any preceding claim for use in photodynamic diagnosis.

31. A compound or complex according to any preceding claim, wherein the compound is suitable for administration prior to administration of radiation.

32. The compound or complex of claim 31 , wherein the radiation is electromagnetic radiation having a wavelength in the range of 500 nm to 1000 nm.

33. A pharmaceutical composition comprising a compound or complex according to any preceding claim and a pharmaceutically acceptable carrier or diluent.

34. The pharmaceutical composition of claim 33, further comprising polyvinylpyrrolidone.

35. The pharmaceutical composition according to claim 33 or 34, further comprising an immune checkpoint inhibitor.

36. The pharmaceutical composition of claim 35, wherein the immune checkpoint inhibitor is selected from pembrolizumab, nivolumab, cemiplizumab, atezolizumab, avelumab, durvalumab, or ipilimumab.

37. The pharmaceutical composition according to any one of claims 33 to 36, which is used in photodynamic therapy or cell luminescence therapy.

38. The pharmaceutical composition according to any one of claims 33 to 37, wherein the pharmaceutical composition is used to treat 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 (chicken) influenza virus, dengue virus, herpes simplex or herpes zoster infection; hepatitis; viral hepatitis; cardiovascular disease; coronary artery stenosis; carotid artery stenosis; intermittent claudication; skin disorders; acne; psoriasis; benign or malignant Diseases characterized by excessive sex cell proliferation or areas of neovascularization; benign or malignant tumors; early-stage cancers; cervical dysplasia; soft tissue sarcomas; germ cell tumors; retinoblastoma; age-related macular degeneration; lymphoma; Hodgkin lymphoma; head and neck cancer; oral or mouth cancer; or cancer of the blood, prostate, cervix, uterus, vagina, or other female appendages, breast, nasopharynx, trachea, larynx, bronchus, bronchioles, lung, hollow organ, esophagus, stomach, bile duct, intestinal cancer, colon, colorectal cancer, rectum, bladder, ureter, kidney, liver, gallbladder, spleen, brain, lymphatic system, bone, skin, or pancreas.

39. The pharmaceutical composition according to any one of claims 33 to 38, for use in treating a disease characterized by excessive proliferation of benign or malignant cells or by areas of neovascularization.

40. The pharmaceutical composition according to any one of claims 33 to 39, which is used to treat benign or malignant tumors.

41. A pharmaceutical composition according to any one of claims 33-40, wherein the pharmaceutical composition is used to treat early-stage cancer; cervical dysplasia; soft tissue sarcoma; germ cell tumors; 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 adnexa cancer, breast cancer, nasopharyngeal cancer, tracheal cancer, laryngeal cancer, bronchial cancer, bronchiolar cancer, lung cancer, hollow organ cancer, esophageal cancer, stomach cancer, bile duct cancer, intestinal cancer, colon cancer, colorectal cancer, rectal cancer, bladder cancer, ureter cancer, kidney cancer, liver cancer, gallbladder cancer, spleen cancer, brain cancer, lymphatic system cancer, bone cancer, skin cancer or pancreatic cancer.

42. The pharmaceutical composition according to claim 33 or 34, which is used in photodynamic diagnosis.

43. The pharmaceutical composition of any one of claims 33-42, wherein the pharmaceutical composition is suitable for administration prior to administration of radiation.

44. The pharmaceutical composition of claim 43, wherein the radiation is electromagnetic radiation having a wavelength in the range of 500 nm to 1000 nm.

45. The pharmaceutical composition of any one of claims 33-44, wherein the pharmaceutical composition is in a form suitable for oral, parenteral (including intravenous, subcutaneous, intramuscular, intradermal, intratracheal, intraperitoneal, intratumoral, intraarticular, intraabdominal, intracranial, and epidural), transdermal, airway (aerosol), rectal, vaginal, or topical (including buccal, mucosal, and sublingual) administration.

46. The pharmaceutical composition of claim 45, wherein the pharmaceutical composition is in a form suitable for oral or parenteral administration.

47. Use of a compound or complex according to any one of claims 1 to 32 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 (chicken) influenza virus, dengue virus, herpes simplex or herpes 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 by areas of neovascularization; benign or malignant tumors; early-stage cancers; cervical dysplasia; soft tissue sarcomas; germ cell tumors; retinoblastoma; age-related macular degeneration; lymphoma; Hodgkin lymphoma; head and neck cancer; oral or mouth cancer; or cancer of the blood, prostate, cervix, uterus, vagina, or other female adnexa, breast, nasopharynx, trachea, larynx, bronchus, bronchioles, lung, hollow organ, esophagus, stomach, bile duct, intestinal cancer, colon, colorectal cancer, rectum, bladder, ureter, kidney, liver, gallbladder, spleen, brain, lymphatic system, bone, skin, or pancreas.

48. Use of the compound or complex according to any one of claims 1 to 32 in the manufacture of a phototherapeutic agent for photodynamic therapy or cell luminescence therapy.

49. The use according to claim 48, wherein the phototherapeutic agent is used to treat 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 (chicken) influenza virus, dengue virus, herpes simplex or herpes zoster infection; hepatitis; viral hepatitis; cardiovascular disease; coronary artery stenosis; carotid artery stenosis; intermittent claudication; skin disorders; acne; psoriasis; diseases characterized by excessive growth of benign or malignant cells Diseases characterized by proliferation or areas of neovascularization; benign or malignant tumors; early-stage cancers; cervical dysplasia; soft tissue sarcomas; germ cell tumors; retinoblastoma; age-related macular degeneration; lymphoma; Hodgkin lymphoma; head and neck cancer; oral or mouth cancer; or cancer of the blood, prostate, cervix, uterus, vagina, or other female adnexa, breast, nasopharynx, trachea, larynx, bronchus, bronchioles, lung, hollow organ, esophagus, stomach, bile duct, intestinal cancer, colon, colorectal cancer, rectum, bladder, ureter, kidney, liver, gallbladder, spleen, brain, lymphatic system, bone, skin, or pancreas.

50. The use according to any one of claims 47 to 49, wherein the medicament or the phototherapeutic agent is used to treat a disease characterized by excessive proliferation of benign or malignant cells or by areas of neovascularization.

51. The use according to any one of claims 47-50, wherein the medicament or the phototherapeutic agent is used to treat a benign or malignant tumor.

52. The use of any one of claims 47-51, wherein the medicament or the phototherapeutic agent is used to treat early-stage cancer; cervical dysplasia; soft tissue sarcoma; germ cell tumors; 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 adnexa cancer, breast cancer, nasopharyngeal cancer, tracheal cancer, laryngeal cancer, bronchial cancer, bronchiolar cancer, lung cancer, hollow organ cancer, esophageal cancer, stomach cancer, bile duct cancer, intestinal cancer, colon cancer, colorectal cancer, rectal cancer, bladder cancer, ureter cancer, kidney cancer, liver cancer, gallbladder cancer, spleen cancer, brain cancer, lymphatic system cancer, bone cancer, skin cancer or pancreatic cancer.

53. Use of the compound or complex according to any one of claims 1 to 32 in the manufacture of a photodiagnostic agent for photodynamic diagnosis.

54. The use of any one of claims 47-53, wherein the pharmaceutical agent, the phototherapeutic agent or the photodiagnostic agent is adapted for administration prior to administration of radiation.

55. Use according to claim 54, wherein the radiation is electromagnetic radiation having a wavelength in the range of 500nm to 1000nm.

56. 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 (chicken) influenza virus, dengue virus, herpes simplex or herpes 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 by areas of neovascularization; benign or malignant tumors; early cancer; cervical dysplasia a method of treating a person or animal in need thereof; wherein the method comprises 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 to 32.

57. A method for photodynamic therapy or cell luminescence therapy of 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 1-32.

58. The method of claim 57, 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 (chicken) influenza virus, dengue virus, herpes simplex or herpes zoster infection; hepatitis; viral hepatitis; cardiovascular disease; coronary artery stenosis; carotid artery stenosis; intermittent claudication; skin disorders; acne; psoriasis; excessive growth of benign or malignant cells; Diseases characterized by proliferation or areas of neovascularization; benign or malignant tumors; early-stage cancers; cervical dysplasia; soft tissue sarcomas; germ cell tumors; retinoblastoma; age-related macular degeneration; lymphoma; Hodgkin lymphoma; head and neck cancer; oral or mouth cancer; or cancer of the blood, prostate, cervix, uterus, vagina, or other female adnexa, breast, nasopharynx, trachea, larynx, bronchus, bronchioles, lung, hollow organ, esophagus, stomach, bile duct, intestinal cancer, colon, colorectal cancer, rectum, bladder, ureter, kidney, liver, gallbladder, spleen, brain, lymphatic system, bone, skin, or pancreas.

59. The method of any one of claims 56-58, wherein the human or animal disease is characterized by excessive proliferation of benign or malignant cells or by areas of neovascularization.

60. The method according to any one of claims 56-59, wherein the human or animal disease is a benign or malignant tumor.

61. The method of any one of claims 56-60, 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 lymphoma; head and neck cancer; oral or mouth cancer; or blood cancer, prostate cancer, cervical cancer, uterine cancer, vaginal cancer or other female adnexa cancer, breast cancer, nasopharyngeal cancer, tracheal cancer, laryngeal cancer, bronchial cancer, bronchiolar cancer, lung cancer, hollow organ cancer, esophageal cancer, stomach cancer, bile duct cancer, intestinal cancer, colon cancer, colorectal cancer, rectal cancer, bladder cancer, ureter cancer, kidney cancer, liver cancer, gallbladder cancer, spleen cancer, brain cancer, lymphatic system cancer, bone cancer, skin cancer or pancreatic cancer.

62. A method for photodynamic diagnosis of a disease in a human or animal, the method comprising administering to the human or animal a diagnostically effective amount of a compound or complex according to any one of claims 1 to 32.

63. The method according to any one of claims 56-62, wherein the human or animal is irradiated after administration of the compound or complex according to any one of claims 1-32.

64. The method of claim 63, wherein the radiation is electromagnetic radiation having a wavelength in the range of 500 nm to 1000 nm.

65. A pharmaceutical combination or kit comprising: (a) a compound or complex according to any one of claims 1 to 32; and (b) As a combination agent with immune checkpoint inhibitors.

66. The pharmaceutical combination or kit of claim 65, wherein the immune checkpoint inhibitor is selected from pembrolizumab, nivolumab, cemiplimab, atezolizumab, avelumab, durvalumab, or ipilimumab.

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