Pyropheophorbide analogs for therapy and diagnosis

Abstract

The present invention relates to pyropheophorbide a analogs and pharmaceutically acceptable salts thereof, and to compositions comprising pyropheophorbide a analogs and pharmaceutically acceptable salts thereof. Pyropheophorbide a analogs and pharmaceutically acceptable salts thereof are useful in photodynamic therapy, cytoluminescence therapy and photodynamic diagnostics, such as for the treatment or detection of tumors, or for antiviral therapy. The invention also relates to the use of pyropheophorbide a analogs and pharmaceutically acceptable salts thereof in the manufacture of phototherapeutic or photodiagnostic agents, as well as methods of photodynamic therapy, cytoluminescence therapy or photodynamic diagnosis, for example for the treatment or detection of tumors, or for antiviral therapy.

Description

Technical Field

[0001] This invention relates to pyrophyllin a analogues and pharmaceutically acceptable salts thereof, as well as compositions comprising pyrophyllin a analogues and pharmaceutically acceptable salts thereof. Pyrophyllin a analogues and pharmaceutically acceptable salts thereof are suitable for photodynamic therapy, chemiluminescence therapy, and photodynamic diagnostics, such as for treating or detecting tumors, or for antiviral therapy. This invention also relates to the use of pyrophyllin a analogues and pharmaceutically acceptable salts thereof in the manufacture of phototherapeutic or photodiagnostic agents, and methods for photodynamic therapy, chemiluminescence therapy, or photodynamic diagnostics, such as for treating or detecting tumors, or for antiviral therapy.

[0002] The structure of “pyrophyllite a” is shown below: Background Technology

[0003] Porphyrins and their analogues are known photosensitive chemical compounds that absorb visible photons and emit them at higher wavelengths. This unique property has many applications, and PDT (photodynamic therapy) is one of them.

[0004] Currently, there are two generations of photosensitizers for PDT. The first generation includes heme porphyrin (a blood derivative), and the second generation mainly consists of chlorophyll analogs. Later compounds are known as dihydroporphyrin and chlorophyll.

[0005] Dihydroporphyrin e4 has been shown to exhibit good photosensitizing activity. It has been indicated that dihydroporphyrin e4 has protective effects against indomethacin-induced gastric injury in rats and TAA or CCl4-induced acute liver injury in mice. Therefore, dihydroporphyrin e4 is proposed as a promising new drug candidate for the protection against gastric ulcers and liver injury. WO 2009 / 040411 proposes the use of dihydroporphyrin e4 zinc complex in photodynamic therapy, and WO 2014 / 091241 proposes the use of dihydroporphyrin e4 disodium in photodynamic therapy.

[0006] While it is known in the literature that conjugation of molecules with triphenylphosphonium cations enhances delivery to mitochondria, this is not always guaranteed, as demonstrated in a recent paper by Gilson et al. (Bioconjugate Chemistry, 2019, Vol. 30(5), pp. 1451-1458). Addition of one triphenylphosphonium cation to the known photodynamic agent dihydroporphyrin e6 resulted in the accumulation of the derivative in lysosomes, while the addition of two triphenylphosphonium cations resulted in distribution to both lysosomes and mitochondria. The authors concluded that "mitochondrial-localized PS did not improve cytotoxicity in this study," and that the unconjugated parent dihydroporphyrin e6 exhibited better photodynamic (cytotoxic) activity than the two triphenylphosphonium-conjugated derivatives.

[0007] There remains a need for better photosensitizers. Compounds with high singlet oxygen quantum yields in both organic and aqueous media and strong photosensitizing capabilities are preferred. Compounds with high fluorescence quantum yields are also required. Furthermore, compounds and / or compositions exhibiting high phototoxicity, low dark toxicity, good stability (such as increased resistance to ROS degradation), good solubility, and / or ease of manufacture and / or purification are desirable. Summary of the Invention

[0008] A first aspect of the present invention provides a compound of formula (I) or a complex of formula (II): Or its pharmaceutically acceptable salt, 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 is independently selected from -H, -C(O)R 4 -C(O)-OR 4 -C(O)-SR 4 -C(O)-N(R) 4 )2、-C(S)-OR 4 -C(S)-SR4 、 -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 7 Y, -R α -[N(R 5 )2(R 5’ )]、 -R α -[P(R 5 )2(R 5’ )]或 -R α -[R 7’ ; -R 3 和 -R 4 各自独立地选自 -H、 -R α -H、 -R β 、 -R α -R β ​​​​​​​​​​​​​​​​​​​​​​​​​​​​​β )2、-R α -X, -R α -[N(R 5 )3]Y、-R α -[P(R 5 )3]Y、-R α -[R 7 Y、-R α -[N(R 5 )2(R 5’ )]、-R α -[P(R 5 )2(R 5’ )] or -R α -[R 7’ ]; -R α - Each is independently selected from C1-C 42 Alkylene, wherein the alkylene can be optionally substituted with one or more C1-C4 alkyl, C1-C4 haloalkyl or halogroup, and wherein one or more carbon atoms in the main chain of the alkylene can be optionally substituted with heteroatoms or groups independently selected from O, S, NH or NMe; -R β Each is independently a saturated or unsaturated hydrocarbon group, wherein the hydrocarbon group can be straight-chain or branched, or can be or include cyclic groups, wherein the hydrocarbon group can optionally be substituted, and wherein the hydrocarbon group can optionally include one or more heteroatoms N, O, S, P or Se in its carbon skeleton. -R 5 Each is independently selected from C1-C4 alkyl, C1-C4 haloalkyl, and -(CH2CH2O). n -H, -(CH2CH2O) n -CH3, phenyl, or C5-C6 heteroaryl, wherein the phenyl or C5-C6 heteroaryl group can optionally be replaced by one or more C1-C6 alkyl, C1-C6 haloalkyl, -O(C1-C6 alkyl), -O(C1-C6 haloalkyl), halogroup, -CO2H, -CO2Z, -CO2NH2, or -O-(CH2CH2O). n -H or -O-(CH2CH2O) n -CH3 group substitution; -R 5’ Selected from C1-C4 alkyl, C1-C4 haloalkyl, and -(CH2CH2O) n -H, -(CH2CH2O) n -CH3, phenyl, or C5-C6 heteroaryl groups, each bonded by -CO2 -The phenyl or C5-C6 heteroaryl group may optionally be further replaced by one or more C1-C6 alkyl, C1-C6 haloalkyl, -O(C1-C6 alkyl), -O(C1-C6 haloalkyl), halogen, -CO2H, -CO2Z, -CO2NH2, -O-(CH2CH2O). n -H or -O-(CH2CH2O) n -CH3 group substitution; -R 6 Selected from -OR 2 -N(R) 2 )2、-SR 2 -S(O)R 2 -S(O)2R 2 Or -X; -R 7 It is -[NC5H5], which is optionally separated by one or more C1-C6 alkyl, C1-C6 haloalkyl, -O(C1-C6 alkyl), -O(C1-C6 haloalkyl), halogen, -CO2H, -CO2Z, -CO2NH2, -O-(CH2CH2O). n -H or -O-(CH2CH2O) n -CH3 group substitution; -R 7’ It is -[NC5H5], which is affected by -CO2 - It is substituted, and optionally further replaced by one or more C1-C6 alkyl, C1-C6 haloalkyl, -O(C1-C6 alkyl), -O(C1-C6 haloalkyl), halogen, -CO2H, -CO2Z, -CO2NH2, -O-(CH2CH2O). n -H or -O-(CH2CH2O) n -CH3 group substitution; n is 1, 2, 3, 4, 5, or 6; X is a halogroup; Y is a counteracting anion; Z is a counter cation; and M 2+ It is a metal cation; The condition is that the compound of formula (I) or the complex of formula (II) contains a component selected from -R α -[P(R 5 )3]Y、-R α -[R 7 Y、-R α -[P(R 5 )2(R 5’ )] or -R α -[R 7’ At least one group of ].

[0009] A second aspect of the invention provides a compound of formula (I) or a complex of formula (II) according to the first aspect of the invention, said compound or complex being used in medicine.

[0010] In the context of this specification, a "hydrocarbon" substituent or the hydrocarbon moiety in a substituent comprises 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 hydrocarbon group / mole can be saturated or unsaturated (including aromatics) and can be straight-chain or branched, or can be or include cyclic groups, wherein, unless otherwise stated, said cyclic groups do not include any heteroatoms such as N, O, S, P, or Se in their carbon skeleton. Examples of hydrocarbon groups include alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, and aryl / molecular groups, as well as combinations of all these groups / molecular groups. Typically, the hydrocarbon group is C1-C. 60 Hydrocarbon group, more commonly C1-C 40 Hydrocarbon group, more commonly C1-C 20 Hydrocarbon group. More typically, the hydrocarbon group is C1-C. 12 Hydrocarbon group. More typically, the hydrocarbon group is C1-C. 10 Hydrocarbon group. "Hydrocarbon group" is defined in a similar manner as a divalent hydrocarbon group.

[0011] The alkyl substituent or the alkyl moiety in a substituent can be linear (i.e., straight-chained) or branched. Examples of alkyl / molecular substituents include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, and n-pentyl / molecular substituents. Unless otherwise specified, the term "alkyl" does not include "cycloalkyl". Typically, alkyl groups are C1-C6. 12 Alkyl groups. More typically, alkyl groups are C1-C6 alkyl groups. "Alkylenes" are defined similarly as divalent alkyl groups. Typically, alkylenes are C1-C6 alkyl groups. 42 Alkylenes. More typically, alkylenes are C1-C60. 32 Alkylene, or C1-C 22 Alkylene, or C1-C 12 Alkylene.

[0012] The term "alkenyl" or the alkenyl moiety in a substituent refers to an unsaturated alkyl group or moiety having one or more carbon-carbon double bonds. Examples of alkenyl / molecular substituents include vinyl, propenyl, 1-butenyl, 2-butenyl, 1-pentenyl, 1-hexenyl, 1,3-butadienyl, 1,3-pentadienyl, 1,4-pentadienyl, and 1,4-hexadienyl / molecular substituents. Unless otherwise specified, the term "alkenyl" does not include "cycloalkenyl". Typically, alkenyl groups are C2-C... 12Alkenyl. More typically, alkenyl groups are C2-C6 alkenyl groups. "Alkenyl" is defined in a similar manner as a divalent alkenyl group.

[0013] The term "alkynyl" in a substituent or the alkynyl moiety within a substituent refers to an unsaturated alkyl group or moiety having one or more carbon-carbon triple bonds. Examples of alkynyl / molecular groups include ethynyl, propynyl, but-1-alkynyl, and but-2-alkynyl. Typically, the alkynyl group is C2-C. 12 Alkynyl group. More commonly, the alkynyl group is a C2-C6 alkynyl group. "Idemynyl" is defined in a similar manner as a divalent alkynyl group.

[0014] A “cyclic” substituent, or the cyclic portion of a substituent, refers to any hydrocarbon ring, which may be saturated or unsaturated (including aromatic rings) and may include one or more heteroatoms, such as N, O, S, P, or Se, in its carbon skeleton. Examples of cyclic groups include cycloalkyl, cycloalkenyl, heterocyclic, aryl, and heteroaryl groups, as discussed below. Cyclic groups can be monocyclic, bicyclic (e.g., bridged, fused, or spirocyclic), or polycyclic. Typically, cyclic groups are 3 to 12-membered cyclic groups, meaning they contain 3 to 12 ring atoms. More typically, cyclic groups are 3 to 7-membered monocyclic groups, meaning they contain 3 to 7 ring atoms.

[0015] A "heterocyclic" substituent or heterocyclic portion of a substituent refers to a cyclic group or portion 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 a ring structure. Examples of heterocyclic groups include heteroaryl and non-aromatic heterocyclic groups discussed below, such as azetinyl, tetrahydrofuranyl, pyrrolyl, tetrahydrophenylthio, tetrahydropyranyl, piperidinyl, piperazine, morpholinyl, thiomorpholinyl, oxoheterocyclic, thioheterocyclic, pyrazolyl, imidazoalkyl, dioxopentyl, oxothiocyclic, thiaalkyl, and dioxane.

[0016] "Cycloalkyl" substituents or the 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 stated, cycloalkyl substituents or moietyes may include monocyclic, bicyclic, or polycyclic hydrocarbon rings.

[0017] A “cycloalkenyl” substituent or the cycloalkenyl moiety in a substituent refers to a non-aromatic unsaturated hydrocarbon ring having one or more carbon-carbon double bonds and containing, for example, 3 to 7 carbon atoms, examples of which include cyclopent-1-en-1-yl, cyclohex-1-en-1-yl, and cyclohex-1,3-dien-1-yl. Unless otherwise stated, a cycloalkenyl substituent or moiety may include a monocyclic, bicyclic, or polycyclic hydrocarbon ring.

[0018] The term "aryl" refers to an aromatic hydrocarbon ring, or the aryl portion of a substituent. The term "aryl" includes both monocyclic and polycyclic aromatic hydrocarbons, wherein all fused-ring systems (excluding any ring system that is part of an optional substituent or formed by an optional substituent) are aromatic. Examples of aryl / partial compounds include phenyl, naphthyl, anthraceneyl, and phenanthrene. Unless otherwise stated, the term "aryl" does not include "heteroaryl".

[0019] The term "heteroaryl" refers to an aromatic heterocyclic group or part thereof. The term "heteroaryl" includes monocyclic and polycyclic fused-ring aromatic heterocycles, wherein all fused-ring systems (excluding any ring system that is part of an optional substituent or formed by an optional substituent) are aromatic. Examples of heteroaryl / parts include the following: Where G = O, S or NH.

[0020] For the purposes of this specification, when a combination of multiple parts is referred to as a single group, such as arylalkyl, arylalenyl, arylynyl, alkylaryl, alkenylaryl, or ynylaryl, the last part mentioned contains an atom through which the group is attached to the remainder of the molecule. An example of an arylalkyl group is benzyl.

[0021] For the purposes of this specification, optional substituted groups or portions (such as -R) β )middle: (i) Each hydrogen atom may optionally be substituted independently with a monovalent substituent selected from the following: halogroup; -CN; -NO2; -N3; ​​-R x -OH; -OR x ;-R y -halo group; -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 ;-R y -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 (ii) Any two hydrogen atoms bonded to the same carbon atom may optionally be independently selected from oxo (=O), =S, =NH, or =NR. x π-bonded substituents; and / or (iii) Any two hydrogen atoms, whether identical or different, attached to 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 -Bridging substituent substitution; Each of -R y - Independently selected from alkylene, alkenylene, or yntylide, wherein the alkylene, alkenylene, or yntylide contains 1 to 6 atoms in its main chain, wherein one or more carbon atoms in the main chain of the alkylene, alkenylene, or yntylide may optionally be replaced by one or more heteroatoms N, O, or S, and wherein the alkylene, alkenylene, or yntylide may optionally be replaced by one or more halogen groups and / or -R x Group substitution; and Each of -R x Independently selected from C1-C6 alkyl, C2-C6 alkenyl, C2-C6 ynyl or C2-C6 cyclic groups, or any two or three -R groups attached to the same nitrogen atom. x They can form C2-C7 cyclic groups together with the nitrogen atoms they are attached to, and any -R in them x It may optionally be substituted with one or more C1-C4 alkyl, C1-C4 haloalkyl, -O(C1-C4 alkyl), -O(C1-C4 haloalkyl), halogen, -OH, -NH2, -CN or oxo (=O) groups.

[0022] Typically, the substituted group contains 1, 2, 3 or 4 substituents, more usually 1, 2 or 3 substituents, more usually 1 or 2 substituents, and more usually 1 substituent.

[0023] Unless otherwise stated, any divalent bridging substituent (e.g., -O-, -S-, -NH-, -N(R)) of the optionally substituted group or part thereof x )-、-N + (R x )2- or -R y -) It must be attached only to the specified group or part and may not be attached to a second group or part, even if the second group or part itself may be optionally substituted.

[0024] The term "halogen" includes fluorine, chlorine, bromine, and iodine.

[0025] Unless otherwise stated, when a group is prefixed with the term "halogen," such as a haloalkyl or halomethyl group, it should be understood that the group in question is substituted by one or more halogen groups independently selected from fluorine, chlorine, bromine, and iodine. Generally, the maximum number of halogen substituents is limited only by the number of hydrogen atoms available for substitution on the corresponding group without the halogen prefix. For example, a halomethyl group may contain one, two, or three halogen substituents. A haloethyl or halophenyl group may contain one, two, three, four, or five halogen substituents. Similarly, unless otherwise stated, when a group is prefixed with a specific halogen group, it should be understood that the group in question is substituted by one or more of that specific halogen group. For example, the term "fluoromethyl" refers to a methyl group substituted with one, two, or three fluorine groups.

[0026] Unless otherwise stated, when a group is referred to as "halogenated," it should be understood that the group in question is substituted by one or more halogen groups independently selected from fluorine, chlorine, bromine, and iodine. Generally, the maximum number of halogenated substituents is limited only by the number of hydrogen atoms that can be substituted on the group referred to as halogenated. For example, a halogenated methyl group may contain one, two, or three halogenated substituents. A halogenated ethyl group or a halogenated phenyl group may contain one, two, three, four, or five halogenated substituents.

[0027] Unless otherwise stated, any reference to an element shall be regarded as a reference to all isotopes of that element. Thus, for example, unless otherwise stated, any reference to hydrogen shall be regarded as covering all isotopes of hydrogen, including deuterium and tritium.

[0028] Unless otherwise stated, any reference to a compound or group shall be regarded as a reference to all tautomers of the compound or group.

[0029] When referring to a hydrocarbon group or other group that contains one or more heteroatoms N, O, S, P, or Se in its carbon skeleton, or when referring to a hydrocarbon group or other group whose carbon atom is replaced by an N, O, S, P, or Se atom, the intention is: quilt or Substitute; -CH2- is replaced by -NH-, -PH-, -O-, -S- or -Se-; -CH3 is replaced by -NH2, -PH2, -OH, -SH or -SeH; -CH= is replaced by -N= or -P=; CH2= is replaced by NH=, PH=, O=, S= or Se=; or CH≡ is replaced by N≡ or P≡; The condition is that the resulting group contains at least one carbon atom. For example, methoxy, dimethylamino, and aminoethyl are considered hydrocarbon groups that contain one or more heteroatoms N, O, S, P, or Se in their carbon skeleton.

[0030] In the context of this specification, unless otherwise stated, C x -C y A group is defined as a group containing x to y carbon atoms. For example, C1-C4 alkyl is defined as an alkyl group containing 1 to 4 carbon atoms. Optional substituents and portions are not taken into account when calculating the total number of carbon atoms in a parent group that is optionally substituted and / or contains an optional moiety. To avoid ambiguity, when calculating C... x -C y When determining the number of carbon atoms in a group, substituted heteroatoms (such as N, O, S, P, or Se) are not counted as carbon atoms. For example, the morpholino group is considered a C6 heterocyclic group rather than a C4 heterocyclic group.

[0031] The π electrons of the dihydroporphyrin ring are delocalized, and therefore the dihydroporphyrin ring can be described by more than one resonance structure. Resonance structures are different ways of drawing the same compound. The two resonance structures of the dihydroporphyrin ring are described directly below: Typically, a complex comprises a central metal atom or ion called the coordination center and a bound molecule or ion called the ligand. In this specification, the bond between the coordination center and the ligand is depicted as shown in the complex in the lower left (where the 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 in the lower right (where the attractive force between the ligand molecule and the central metal atom is represented by two covalent bonds and two dashed lines): As used in this article, -[NC5H5]Y refers to: The compound of formula (I) or the complex of formula (II) contains a component selected from -R α -[P(R 5 )3]Y、-R α -[R 7 Y、-R α -[P(R 5 )2(R 5’ )] or -R α -[R 7’ At least one group of [], preferably the compound of formula (I) or the complex of formula (II) contains a group selected from -R α -[P(R 5 )3]Y or -R α -[P(R 5 )2(R 5’ At least one group of ]]. In a preferred embodiment, -R 6 Includes -R α -[P(R 5 )3]Y、-R α -[R 7 Y、-R α -[P(R 5 )2(R 5’ )] or -R α -[R 7’ ], Preferred -R 6 Includes -R α -[P(R 5 )3]Y or -R α -[P(R 5 )2(R 5’ )).

[0032] In one embodiment of the first or second aspect of the invention, X is a halogen group selected from fluorine, chlorine, bromine, or iodine. In one embodiment, X is chlorine or bromine.

[0033] In one embodiment of the first or second aspect of the present invention, a compound of formula (I) is provided.

[0034] In one embodiment of the first or second aspect of the invention, Y is a counter anion selected from: halides (e.g., fluorides, chlorides, bromides, or iodides) or other inorganic anions (e.g., bisulfate, hexafluorophosphate (PF6), nitrate, perchlorate, phosphate, or sulfate) or organic anions (e.g., acetate, ascorbate, aspartate, benzoate, besylate, bicarbonate, bis(trifluoromethanesulfonyl)imide (TFSI), tartrate, butyrate, camphorsulfonate). Camphor sulfonate, carbonates, citrates, decanoates, edetates, ethanesulfonates, fumarates, galactobionates, gluconate, gluconate, glutamate, glycolates, hexanoates, β-hydroxybutyrate, 2-hydroxyethanesulfonate, hydroxymaleate, hydroxynaphthylcarboxylate, hydroxyethylsulfonate, lactates, lacturonates, malates, maleates, mandelates, methanesulfonate, methyl sulfates, mucilages, naphthalenesulfonate (naphthalene-2-sulfonate) The following salts are permitted: octanoate, oleate, ornithine, dihydroxynaphthyl salt, pantothenate, polygalacturonate, propanoate, propionate, salicylate, stearate, succinate, tartrate, teoclate, tetra[3,5-bis(trifluoromethyl)phenyl]borate (BARF), tetra(pentafluorophenyl)borate (F5-TPB), tetraphenylborate (TPB), toluenesulfonate (p-toluenesulfonate), or trifluoromethanesulfonate (trifluoromethanesulfonate). In one embodiment, Y is a fluoride, chloride, bromide, iodide, or hexafluorophosphate. In one embodiment, Y is a fluoride, chloride, bromide, or iodide. In one embodiment, Y is a chloride or bromide.

[0035] In one embodiment of the first or second aspect of the invention, Z is a counter cation selected from inorganic cations (e.g., lithium, sodium, potassium, magnesium, calcium, or ammonium cations) or organic cations (e.g., amine cations (e.g., choline or meglumine cations) or amino acid cations (e.g., arginine cations)).

[0036] In one embodiment of the first or second aspect of the present invention, M 2+ It is selected from Zn 2+ Cu 2+ Fe 2+ Pd 2+ or Pt2+ The metal cation. In one embodiment, M 2+ It is Zn 2+ .

[0037] 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 implementation scheme, -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 implementation scheme, -R 1 Selected from -C(O)-OR 3 -C(O)-SR 3 or -C(O)-N(R) 3 )2.

[0038] 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 It is a C1-C4 alkyl group (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 It is a C1-C4 alkyl group (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 3It is a C1-C4 alkyl group (preferably methyl). In one embodiment, -R 1 It is -C(O)-OR 3 And -R 3 It is a C1-C4 alkyl group (preferably methyl).

[0039] In one embodiment of the first or second aspect of the present invention, -R 1 Selected from -R 2 -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’ -R 3’ It is H or C1-C4 alkyl (preferably methyl); and -R 2 or -R 3 Selected from -R α -[N(R 5 )3]Y、-R α -[P(R 5 )3]Y、-R α -[R 7 Y、-R α -[N(R 5 )2(R 5’ )]、-R α -[P(R 5 )2(R 5’ )] or -R α -[R 7’ In one implementation, -R 1 Selected from -R 2 -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’ -R 3’It is H or C1-C4 alkyl (preferably methyl); and -R 2 or -R 3 Selected from -R α -[N(R 5 )3]Y、-R α -[P(R 5 )3]Y or -R α -[R 7 ]Y. In one implementation, -R 1 Selected from -R 2 -C(O)-OR 3 -C(O)-SR 3 -C(O)-N(R) 3 (R) 3’ ) or -C(S)-N(R 3 (R) 3’ -R 3’ It is H or C1-C4 alkyl (preferably methyl); -R 2 or -R 3 Selected from -R α -[N(R 5 )3]Y、-R α -[P(R 5 )3]Y or -R α -[R 7 ]Y; each -R 5 Independently selected from C1-C4 alkyl or phenyl, wherein the phenyl is optionally substituted with one, two, or three C1-C4 alkyl or C1-C4 alkoxy groups; -R 7 It is -[NC5H5], which is optionally substituted with one, two, or three C1-C4 alkyl or C1-C4 alkoxy groups; -R α -Selected from C1-C 12 Alkylene, wherein one, two, three or four carbon atoms in the main chain of the alkylene may optionally be replaced by heteroatoms or groups independently selected from O, S, NH or NMe; and Y is a counterion (preferably a halide or hexafluorophosphate).

[0040] In one embodiment of the first or second aspect of the present invention, -R 1 Selected from -R 2 -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 2 or -R 3 Yes -R α -[P(R 5 )3]Y; each -R 5 Independently selected from phenyl or C5-C6 heteroaryl groups, wherein the phenyl or C5-C6 heteroaryl group may optionally be converted by one or more C1-C4 alkyl, C1-C4 haloalkyl, -O(C1-C4 alkyl), -O(C1-C4 haloalkyl), halogen, or -O-(CH2CH2O). n -H or -O-(CH2CH2O) n -CH3 group substitution; n is 1, 2, 3 or 4; Y is a fluoride, chloride, bromide or iodide; and -R 3’ It is H or 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 (R) 3’ ) or -C(S)-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 groups, wherein the phenyl or C5-C6 heteroaryl group may optionally be converted by one or more C1-C4 alkyl, C1-C4 haloalkyl, -O(C1-C4 alkyl), -O(C1-C4 haloalkyl), halogen, or -O-(CH2CH2O). n -H or -O-(CH2CH2O) n -CH3 group substitution; n is 1, 2, 3 or 4; Y is a fluoride, chloride, bromide or iodide; and -R 3' It is H or C1-C4 alkyl (preferably methyl). In one embodiment, -R 1 It is -C(O)-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 groups, wherein the phenyl or C5-C6 heteroaryl group may optionally be converted by one or more C1-C4 alkyl, C1-C4 haloalkyl, -O(C1-C4 alkyl), -O(C1-C4 haloalkyl), halogen, or -O-(CH2CH2O). n -H or -O-(CH2CH2O) n -CH3 group substitution; n is 1, 2, 3 or 4; Y is a fluoride, chloride, bromide or iodide; and -R 3' It is H or C1-C4 alkyl (preferably methyl). Typically in these embodiments, -R α - is C1-C 12 Alkylene (preferably C1-C8 alkylene, or C1-C6 alkylene), -(CH2CH2O) m -CH2CH2- group or -(CH2CH2S) m -CH2CH2- groups, all of which are optionally substituted, wherein m is 1, 2, 3 or 4.

[0041] 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 -R α -SR β -R α -S(O)R β or -R α -S(O)2R β And -R β It is a glycosyl group. In one implementation, -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 βAnd -R β It is a glycosyl group. In one implementation, -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 It is a sugar group. Typically in these implementations, -R α - is C1-C 12 Alkylene (preferably C1-C8 alkylene, or C1-C6 alkylene), -(CH2CH2O) m -CH2CH2- group or -(CH2CH2S) m -CH2CH2- groups, all of which are optionally substituted, wherein m is 1, 2, 3 or 4.

[0042] In one embodiment of the first or second aspect of the present invention, -R 1 Selected from -R 2 -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 2 or -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 It is a glycosyl group, and -R 3’ It is H or 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 (R) 3’ ) or -C(S)-N(R3 (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 It is a glycosyl group, and -R 3’ It is H or C1-C4 alkyl (preferably methyl). In one embodiment, -R 1 It is -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 It is a glycosyl group, and -R 3’ It is H or C1-C4 alkyl (preferably methyl). In one embodiment, -R 1 It is -C(O)-N(R) 3 (R) 3’ ), where -R 3 Selected from -R α -OR β or -R α -SR β And -R β It is a glycosyl group, and -R 3’ It 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 main chain of the alkylene group may optionally be replaced by heteroatoms or groups independently selected from O, S, NH, or NMe. Alternatively, in these embodiments, -R α - is C1-C 12 Alkylene (preferably C1-C8 alkylene, or C1-C6 alkylene), -(CH2CH2O) m -CH2CH2- group or -(CH2CH2S) m -CH2CH2- groups, all of which are optionally substituted, wherein m is 1, 2, 3 or 4.

[0043] -R 3' A group refers to a group that interacts with another -R group. 3 Groups attached to the same atom -R 3 Group. -R 3 and -R 3’ They can be the same or different. Preferably, -R 3 and -R 3’ different.

[0044] In one embodiment of the first or second aspect of the present invention, -R 1 Selected from -R 2 -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 2 or -R 3 Selected from -R α -R β or -R β And -R β It is a glycosyl group, and -R 3’ It is H or 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 (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 It is a glycosyl group, and -R 3’ It is H or C1-C4 alkyl (preferably methyl). In one embodiment, -R 1 It is -C(O)-N(R) 3 (R) 3’ ), where -R 3 Selected from -R α -R β or -R β And -Rβ It is a glycosyl group, and -R 3’ It is H or C1-C4 alkyl (preferably methyl). Typically in these embodiments, -R α - is C1-C 12 Alkylene (preferably C1-C8 alkylene, or C1-C6 alkylene), -(CH2CH2O) m - group or -(CH2CH2S) m - Groups, all of which are optionally substituted, where m is 1, 2, 3 or 4.

[0045] In any of the embodiments described in the four preceding paragraphs, the glycosyl group may optionally be substituted, for example, by a protecting group such as an acetyl group or a natural amino acid such as valine. The amino acid may 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.

[0046] In one embodiment of the first or second aspect of the present invention, -R 1 Selected from -R 2 -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 2 or -R 3 Selected from -R α -R β or -R β And -R β It is a C1-C8 alkyl group optionally substituted with one or more (such as one, two, three, four, five, six, seven or eight) -OH or -OAc groups, and -R 3’ It is H or 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 (R) 3’ ) or -C(S)-N(R 3 (R) 3’ ), where -R 3 Selected from -R α -R βor -R β And -R β It is a C1-C8 alkyl group optionally substituted with one or more (such as one, two, three, four, five, six, seven or eight) hydroxyl groups, and -R 3’ It is H or C1-C4 alkyl (preferably methyl). In one embodiment, -R 1 It is -C(O)-N(R) 3 (R) 3’ ), where -R 3 Selected from -R α -R β or -R β And -R β It is a C1-C8 alkyl group optionally substituted with one or more (such as one, two, three, four, five, six, seven or eight) hydroxyl groups, and -R 3’ It is H or C1-C4 alkyl (preferably methyl). Typically in these embodiments, -R α - is an unsubstituted C1-C6 alkylene, or an unsubstituted C1-C4 alkylene, or an unsubstituted C1-C2 alkylene.

[0047] In one embodiment of the first or second aspect of the present invention, -R 1 Selected from -R 2 -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 2 or -R 3 Selected from -R α -H or -R α -OH;-R α -Selected from C1-C 12 Alkylene, wherein the alkylene may optionally be substituted with one or more C1-C4 alkyl, C1-C4 haloalkyl, or halogroups, and wherein one or more carbon atoms in the main chain of the alkylene may optionally be substituted with one or more heteroatoms O or S; and -R 3’ It is H or C1-C4 alkyl (preferably methyl). In one embodiment, -R 1 Selected from -C(O)-OR 3 -C(O)-SR3 -C(O)-N(R) 3 (R) 3’ ) or -C(S)-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 the alkylene may optionally be substituted with one or more C1-C4 alkyl, C1-C4 haloalkyl, or halogroups, and wherein one or more carbon atoms in the main chain of the alkylene may optionally be substituted with one or more heteroatoms O or S; and -R 3’ It is H or C1-C4 alkyl (preferably methyl). In one embodiment, -R 1 It is -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 main chain of the alkylene group may optionally be replaced by one or more heteroatoms O or S; and -R 3’ It is H or C1-C4 alkyl (preferably methyl).

[0048] In one embodiment of the first or second aspect of the present invention, -R 1 Selected from -R 2 -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 2 or -R 3 Yes -R β ;-R β It is C1-C 12 Alkyl or C2-C 12 Alkenyl groups, which may optionally be independently selected from one or more (such as one, two, three, four or five) halogen groups, -CN, -NO2, -N3, -OH, -ORx -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 substituents are substituted; each -R x Independently selected from C1-C4 alkyl groups; -R z It is the side chain of a natural amino acid; and -R 3’ It is H or 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 (R) 3’ ) or -C(S)-N(R 3 (R) 3’ ); where -R 3 Yes -R β ;-R β It is C1-C 12 Alkyl groups, optionally composed of one or more (such as one, two, three, four, or five) independently selected from halogen groups, -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 substituents are substituted; each -R xIndependently selected from C1-C4 alkyl groups; -R z It is the side chain of a natural amino acid; and -R 3' It is H or C1-C4 alkyl (preferably methyl). In one embodiment, -R 1 It is -C(O)-N(R) 3 (R) 3’ ); where -R 3 Yes -R β ;-R β It is a C1-C8 alkyl group, which is optionally composed of one or more (such as one, two or three) independently selected from halogen, -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 substituents are substituted; each -R x Independently selected from C1-C4 alkyl groups; -R z It is the side chain of a natural amino acid; and -R 3' It is H or C1-C4 alkyl (preferably methyl).

[0049] In one embodiment of the first or second aspect of the present invention, -R 1 Selected from -CO-(NR) zz -CHR z -CO) v -N(R zz )2 and -CO-(NR zz -CHR z -CO) v -OR zz ; where each -R z Side chains independently selected from natural amino acids; each -R zz It is independently selected from hydrogen and C1-C4 alkyl (preferably methyl); and v is 1, 2, 3, 4, 5, 6, 7 or 8.

[0050] In one embodiment of the first or second aspect of the present invention, -R 1Selected from -R 2 -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 2 or -R 3 Yes -R β ;-R β Selected from C1-C 20 Alkyl group, wherein the alkyl group may optionally be substituted with one, two, three, or four halogen groups, and wherein one, two, three, four, five, or six carbon atoms in the main chain of the alkyl group may optionally be substituted with heteroatoms or groups independently selected from O, S, NH, or NMe; and -R 3’ It is H or C1-C4 alkyl (preferably methyl).

[0051] In one embodiment of the first or second aspect of the present invention, -R 1 It is -C(O)-OR 3 , where -R 3 Selected from hydrogen, C1-C4 alkyl (preferably methyl), or cations (such as lithium, sodium, potassium, magnesium, calcium, ammonium, amines (such as choline or meglumine), or amino acid cations (such as arginine). In one embodiment, -R 1 It is -C(O)-OR 3 , where -R 3 Selected from C1-C4 alkyl (preferably methyl) or cations (such as lithium, sodium, potassium, magnesium, calcium, ammonium, amines (such as choline or meglumine) or amino acids (such as arginine) cations).

[0052] In one embodiment of the first or second aspect of the present invention, -R 1 It is -C(O)-N(R) 3 )2. In one implementation scheme, -R 1 It is -C(O)-N(C1-C4 alkyl)(R 3 ) or -C(O)-NHR 3 In one implementation, -R 1 It is -C(O)-N(CH3)(R 3 ) or -C(O)-NHR 3 In one implementation, -R1 It is -C(O)-N(C1-C4 alkyl)(R 3 In one implementation, -R 1 It is -C(O)-N(CH3)(R 3 ).

[0053] 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 implementation, -R 1 Selected from -CH2OR 2 -CH2SR 2 -CH2N(R) 2 )2 or -R 2 In one implementation, -R 1 Selected from -CH2OR 2 -CH2SR 2 or -CH2N(R) 2 )2. In one implementation scheme, -R 1 Selected from -CH2OR 2 or -CH2SR 2 In one implementation, -R 1 It is -CH2OR 2 In one implementation, -R 1 Yes -R 2 And -R 2 Yes -R α -X.

[0054] In one embodiment of the first or second aspect of the present invention, -R 2 Selected from -R α -[N(R 5 )3]Y、-R α -[P(R 5 )3]Y、-R α -[R 7 Y、-R α -[N(R 5 )2(R 5’ )]、-R α -[P(R 5 )2(R 5’ )] or -R α -[R 7’ In one implementation, -R2 Selected from -R α -[N(R 5 )3]Y、-R α -[P(R 5 )3]Y or -R α -[R 7 ]Y. In one implementation, -R 2 Selected from -R α -[N(R 5 )3]Y、-R α -[P(R 5 )3]Y or -R α -[R 7 ]Y; each -R 5 Independently selected from C1-C4 alkyl or phenyl, wherein the phenyl is optionally substituted with one, two, or three C1-C4 alkyl or C1-C4 alkoxy groups; -R 7 It is -[NC5H5], which is optionally substituted with one, two, or three C1-C4 alkyl or C1-C4 alkoxy groups; -R α -Selected from C1-C 12 Alkylene, wherein one, two, three or four carbon atoms in the main chain of the alkylene may optionally be replaced by heteroatoms or groups independently selected from O, S, NH or NMe; and Y is a counterion (preferably a halide or hexafluorophosphate).

[0055] In one embodiment of the first or second aspect of the present invention, -R 2 Yes -R α -[P(R 5 )3]Y; each -R 5 Independently selected from phenyl or C5-C6 heteroaryl groups, wherein the phenyl or C5-C6 heteroaryl group may optionally be converted by one or more C1-C4 alkyl, C1-C4 haloalkyl, -O(C1-C4 alkyl), -O(C1-C4 haloalkyl), halogen, or -O-(CH2CH2O). n -H or -O-(CH2CH2O) n -CH3 group substitution; n is 1, 2, 3 or 4; and Y is a fluoride, chloride, bromide or iodide. Typically in this embodiment, -R α - is C1-C 12 Alkylene (preferably C1-C8 or C1-C6 alkylene), -(CH2CH2O) m -CH2CH2- group or -(CH2CH2S) m -CH2CH2- groups, all of which are optionally substituted, wherein m is 1, 2, 3 or 4.

[0056] 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 -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 -[R 7 ]Y. In one implementation, -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 implementation, -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 It is a glycosyl group. In one implementation, -R 2 Selected from -R α -OR β or -R α -SR β In one implementation, -R 2 Selected from -R α -OR β or -R α-SR β And -R β It is a sugar group.

[0057] 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 implementation scheme, -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 implementation scheme, -R 2 Selected from -C(O)R 4 -C(O)-OR 4 -C(O)-SR 4 or -C(O)-N(R) 4 )2.

[0058] In one embodiment of the first or second aspect of the present invention, -R 2 It is -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 It is a glycosyl group, and -R 4’ It is H or C1-C4 alkyl (preferably methyl). In one embodiment, -R 2 It is -C(O)-N(R) 4 (R) 4’ ), where -R 4 Selected from -R α -OR β or -R α -SR β And -R β It is a glycosyl group, and -R4’ It is H or C1-C4 alkyl (preferably methyl).

[0059] -R 4' A group refers to a group that interacts with another -R group. 4 Groups attached to the same atom -R 4 Group. -R 4 and -R 4’ They can be the same or different. Preferably, -R 4 and -R 4’ different.

[0060] In one embodiment of the first or second aspect of the present invention, -R 2 It is -C(O)-N(R) 4 )2. In one implementation scheme, -R 2 It is -C(O)-N(C1-C4 alkyl)(R 4 In one implementation, -R 2 It is -C(O)-N(CH3)(R 4 ).

[0061] In one embodiment of the first or second aspect of the present invention, -R 6 Selected from OR 2 -N(R) 2 )2、-SR 2 -S(O)R 2 or -S(O)2R 2 In one implementation, -R 6 Selected from -OR 2 -SR 2 -S(O)R 2 or -S(O)2R 2 In one implementation, -R 6 Selected from -OR 2 or -SR 2 In one implementation, -R 6 Yes - OR 2 .

[0062] In one embodiment of the first or second aspect of the present invention, -R 6 Selected from -OR 2 -N(R) 2 )2、-SR 2 -S(O)R 2 or -S(O)2R 2 And -R 2 Selected from -H, -C(O)R 4 -R α -H, -R β -Rα -R β -R α -OH, -R α -OR β -R α -SH、-R α -SR β -R α -S(O)R β -R α -S(O)2R β -R α -NH2, -R α -NH(R β -R α -N(R β )2、-R α -X, -R α -[N(R 5 )3]Y、-R α -[P(R 5 )3]Y、-R α -[R 7 Y、-R α -[N(R 5 )2(R 5’ )]、-R α -[P(R 5 )2(R 5’ )] or -R α -[R 7’ In one implementation, -R 6 Selected from -OR 2 -SR 2 -S(O)R 2 or -S(O)2R 2 And -R 2 Selected from -H, -C(O)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 -Rα -N(R β )2、-R α -X, -R α -[N(R 5 )3]Y、-R α -[P(R 5 )3]Y、-R α -[R 7 Y、-R α -[N(R 5 )2(R 5’ )]、-R α -[P(R 5 )2(R 5’ )] or -R α -[R 7’ In one implementation, -R 6 Selected from -OR 2 or -SR 2 And -R 2 Selected from -H, -C(O)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, -R α -[N(R 5 )3]Y、-R α -[P(R 5 )3]Y、-R α -[R 7 Y、-R α -[N(R 5 )2(R 5’ )]、-R α -[P(R 5 )2(R 5’ )] or -R α -[R 7’ ].

[0063] In one embodiment of the first or second aspect of the present invention, -R 6 Selected from -OR 2 -N(R) 2 )2、-N(R 2 (R) 2’ ), -SR 2 -S(O)R 2 or -S(O)2R 2 ;-R 2’ Selected from hydrogen, C1-C4 alkyl, or -CO2 (C1-C4 alkyl); -R 2 Selected from -C(O)R 4 -C(O)-OR 4 -C(O)-N(R) 4 (R) 4’ -R α -[N(R 5 )3]Y、-R α -[P(R 5 )3]Y、-R α -[R 7 Y、-R α -[N(R 5 )2(R 5’ )]、-R α -[P(R 5 )2(R 5’ )] or -R α -[R 7’ ]; -R 4’ Selected from hydrogen or C1-C4 alkyl; and -R 4 Selected from -R α -[N(R 5 )3]Y、-R α -[P(R 5 )3]Y、-R α -[R 7 Y、-R α -[N(R 5 )2(R 5’ )]、-R α -[P(R 5 )2(R 5’ )] or -R α -[R 7’ In one implementation, -R 6 Selected from -OR 2 -N(R) 2 (R) 2’ ), -SR 2 -S(O)R 2 or -S(O)2R2 ;-R 2’ Selected from hydrogen, C1-C4 alkyl, or -CO2 (C1-C4 alkyl); -R 2 Selected from -C(O)R 4 -C(O)-OR 4 -C(O)-N(R) 4 (R) 4’ -R α -[N(R 5 )3]Y、-R α -[P(R 5 )3]Y、-R α -[R 7 Y、-R α -[N(R 5 )2(R 5’ )]、-R α -[P(R 5 )2(R 5’ )] or -R α -[R 7’ ]; -R 4’ Selected from hydrogen or C1-C4 alkyl; -R 4 Selected from -R α -[N(R 5 )3]Y、-R α -[P(R 5 )3]Y、-R α -[R 7 Y、-R α -[N(R 5 )2(R 5’ )]、-R α -[P(R 5 )2(R 5’ )] or -R α -[R 7’ ]; Each -R 5 Independently selected from C1-C4 alkyl or phenyl, wherein the phenyl is optionally substituted with one, two, or three C1-C4 alkyl or C1-C4 alkoxy groups; each -R 5’ Selected from C1-C4 alkyl or phenyl groups, each coated with -CO2 - Substitution, wherein the phenyl group is optionally further substituted with one, two, or three C1-C4 alkyl or C1-C4 alkoxy groups; -R 7 It is -[NC5H5], which is optionally substituted with one, two, or three C1-C4 alkyl or C1-C4 alkoxy groups; -R 7’ It is -[NC5H5], which is affected by -CO2 - Substitution, and optionally further substituted with one, two, or three C1-C4 alkyl or C1-C4 alkoxy groups; -Rα -Selected from C1-C 12 An alkylene group, wherein one, two, three, or four carbon atoms in the main chain of the alkylene group may optionally be replaced by heteroatoms or groups independently selected from O, S, NH, or NMe; and Y is a counterion (preferably a halide or hexafluorophosphate). In one embodiment, -R 6 Selected from -OR 2 or -N(R) 2 (R) 2’ -R 2’ Selected from hydrogen, C1-C4 alkyl, or -CO2 (C1-C4 alkyl); -R 2 Selected from -C(O)R 4 -C(O)-OR 4 -C(O)-N(R) 4 (R) 4’ -R α -[N(R 5 )3]Y、-R α -[P(R 5 )3]Y、-R α -[R 7 Y、-R α -[N(R 5 )2(R 5’ )]、-R α -[P(R 5 )2(R 5’ )] or -R α -[R 7’ ]; -R 4’ Selected from hydrogen or C1-C4 alkyl; -R 4 Selected from -R α -[N(R 5 )3]Y、-R α -[P(R 5 )3]Y、-R α -[R 7 Y、-R α -[N(R 5 )2(R 5’ )]、-R α -[P(R 5 )2(R 5’ )] or -R α -[R 7’ ]; Each -R 5 Independently selected from C1-C4 alkyl or phenyl, wherein the phenyl is optionally substituted with one, two, or three C1-C4 alkyl or C1-C4 alkoxy groups; each -R 5’ Selected from C1-C4 alkyl or phenyl groups, each coated with -CO2 -Substitution, wherein the phenyl group is optionally further substituted with one, two, or three C1-C4 alkyl or C1-C4 alkoxy groups; -R 7 It is -[NC5H5], which is optionally substituted with one, two, or three C1-C4 alkyl or C1-C4 alkoxy groups; -R 7’ It is -[NC5H5], which is affected by -CO2 - Substitution, and optionally further substituted with one, two, or three C1-C4 alkyl or C1-C4 alkoxy groups; -R α -Selected from C1-C 12 Alkylene, wherein one, two, three or four carbon atoms in the main chain of the alkylene may optionally be replaced by heteroatoms or groups independently selected from O, S, NH or NMe; and Y is a counterion (preferably a halide or hexafluorophosphate).

[0064] In one embodiment of the first or second aspect of the present invention, -R 6 Selected from -OC(O)R 14 -N(R) 12 )-C(O)R 14 -OC(O)-OR 14 -N(R) 12 )-C(O)-OR 14 -OC(O)-N(R) 12 (R) 14 ) or -N(R 12 )-C(O)-N(R 12 (R) 14 -R 12 Selected from hydrogen or C1-C3 alkyl (preferably hydrogen or methyl); -R 14 Selected from -R α -[P(R 5 )3]Y、-R α -[R 7 Y、-R α -[P(R 5 )2(R 5’ )] or -R α -[R 7’ ]; Each -R 5 Independently selected from C1-C4 alkyl or phenyl, wherein the phenyl is optionally substituted with one, two, or three C1-C4 alkyl or C1-C4 alkoxy groups; each -R 5’ Selected from C1-C4 alkyl or phenyl groups, each coated with -CO2 - Substitution, wherein the phenyl group is optionally further substituted with one, two, or three C1-C4 alkyl or C1-C4 alkoxy groups; -R 7It is -[NC5H5], which is optionally substituted with one, two, or three C1-C4 alkyl or C1-C4 alkoxy groups; -R 7’ It is -[NC5H5], which is affected by -CO2 - Substitution, and optionally further substituted with one, two, or three C1-C4 alkyl or C1-C4 alkoxy groups; -R α -Selected from C1-C 12 Alkylene, wherein one, two, three or four carbon atoms in the main chain of the alkylene may optionally be replaced by heteroatoms or groups independently selected from O, S, NH or NMe; and Y is a counterion (preferably a halide or hexafluorophosphate).

[0065] In one embodiment of the first or second aspect of the present invention, -R 6 Selected from -OR 2 -N(R) 2 )2、-N(R 2 (R) 2’ ), -SR 2 -S(O)R 2 or -S(O)2R 2 ;-R 2’ Selected from hydrogen or C1-C4 alkyl (preferably hydrogen or methyl); -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 optionally, -R β It is a glycosyl group. In one implementation, -R 6 Selected from -OR 2 -SR 2 -S(O)R 2 or -S(O)2R 2 And -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 optionally, -R β It is a glycosyl group. In one implementation, -R 6 Selected from -OR 2 -SR 2 -S(O)R2 or -S(O)2R 2 And -R 2 Selected from -R α -OR β or -R α -SR β And optionally, -R β It is a glycosyl group. In one implementation, -R 6 Selected from -OR 2 or -SR 2 And -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 optionally, -R β It is a glycosyl group. In one implementation, -R 6 Selected from -OR 2 or -SR 2 And -R 2 Selected from -R α -OR β or -R α -SR β And optionally, -R β It is a sugar group.

[0066] In one embodiment of the first or second aspect of the present invention, -R 6 Selected from -OR 2 -N(R) 2 )2、-N(R 2 (R) 2’ ), -SR 2 -S(O)R 2 or -S(O)2R 2 ;-R 2’ Selected from hydrogen or C1-C4 alkyl (preferably hydrogen or methyl); and -R 2 It is -C(O)R 4 In one implementation, -R 6 Selected from -OR 2 -N(R) 2 )2、-N(R 2 (R) 2’ ), -SR 2 -S(O)R 2 or -S(O)2R 2 ;-R 2’Selected from hydrogen or C1-C4 alkyl (preferably hydrogen or methyl); -R 2 It is -C(O)R 4 ;-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 It is a glycosyl group. In one implementation, -R 6 Selected from -OR 2 -N(R) 2 )2、-N(R 2 (R) 2’ ), -SR 2 -S(O)R 2 or -S(O)2R 2 ;-R 2’ Selected from hydrogen or C1-C4 alkyl (preferably hydrogen or methyl); -R 2 It is -C(O)R 4 ;-R 4 Selected from -R α -OR β or -R α -SR β And -R β It is a sugar group.

[0067] In one embodiment of the first or second aspect of the present invention, -R 6 Selected from -OR 2 -SR 2 -S(O)R 2 or -S(O)2R 2 And -R 2 It is -C(O)R 4 In one implementation, -R 6 Selected from -OR 2 -SR 2 -S(O)R 2 or -S(O)2R 2 And -R 2 It is -C(O)R 4 And -R 4 Selected from -R α -OR β -R α -SR β -R α -S(O)R β or -Rα -S(O)2R β And -R β It is a glycosyl group. In one implementation, -R 6 Selected from -OR 2 -SR 2 -S(O)R 2 or -S(O)2R 2 And -R 2 It is -C(O)R 4 And -R 4 Selected from -R α -OR β or -R α -SR β And -R β It is a sugar group.

[0068] In one embodiment of the first or second aspect of the present invention, -R 6 Selected from -OR 2 or -SR 2 And -R 2 It is -C(O)R 4 In one implementation, -R 6 Selected from -OR 2 or -SR 2 And -R 2 It is -C(O)R 4 And -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 It is a glycosyl group. In one implementation, -R 6 Selected from -OR 2 or -SR 2 And -R 2 It is -C(O)R 4 And -R 4 Selected from -R α -OR β or -R α -SR β And -R β It is a sugar group.

[0069] In one embodiment of the first or second aspect of the present invention, -R 6 Selected from -OR 2 -N(R)2 )2、-N(R 2 (R) 2’ ), -SR 2 -S(O)R 2 or -S(O)2R 2 ;-R 2’ Selected from hydrogen or C1-C4 alkyl (preferably hydrogen or methyl); -R 2 Selected from -R β -R α -OR β -R α -SR β -R α -S(O)R β or -R α -S(O)2R β ;-R β It is a glycosyl group; and -R α -Selected from C1-C 12 Alkylene, wherein one, two, three, or four carbon atoms in the main chain of the alkylene group may optionally be replaced by heteroatoms or groups independently selected from O, S, NH, or NMe. In one embodiment, -R 6 Selected from -OR 2 -N(R) 2 (R) 2’ ) or -SR 2 ;-R 2’ Selected from hydrogen or C1-C4 alkyl (preferably hydrogen or methyl); -R 2 Selected from -R β -R α -OR β or -R α -SR β ;-R β It is a glycosyl group; and -R α -Selected from C1-C 12 Alkylene, wherein one, two, three, or four carbon atoms in the main chain of the alkylene may optionally be replaced by heteroatoms or groups independently selected from O, S, NH, or NMe.

[0070] In any of the embodiments described in the five preceding paragraphs, the glycosyl group may optionally be substituted, for example, by a protecting group such as an acetyl group or a natural amino acid such as valine. The amino acid may 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.

[0071] In one embodiment of the first or second aspect of the present invention, -R 6 Selected from -OR 2 -N(R) 2 )2、-SR 2-S(O)R 2 or -S(O)2R 2 And -R 2 Selected from hydrogen, C1-C4 alkyl, -CO (C1-C4 alkyl), or -CO2 (C1-C4 alkyl). In one embodiment, -R 6 Selected from -OR 2 or -N(R) 2 )2; and -R 2 It is selected from hydrogen, C1-C4 alkyl, -CO (C1-C4 alkyl) or -CO2 (C1-C4 alkyl).

[0072] In one embodiment of the first or second aspect of the present invention, -R 6 Selected from -OR 2 Halogen-N(R) 2 )2-Halogen-N(R) 2 (R) 2’ )halogen-SR 2 Halogen-S(O)R 2 or -S(O)2R 2 ;-R 2’ Selected from hydrogen or C1-C4 alkyl; -R 2 Selected from -R 4 Halogen-C(O)R 4 Halogenated -C(O)-OR 4 or -C(O)-N(R) 4 (R) 4’ -R 4’ Selected from hydrogen or C1-C4 alkyl; and -R 4 Selected from C1-C 12 Alkyl group, wherein the alkyl group may optionally be substituted with one, two, three, or four halogen groups, and wherein one, two, three, or four carbon atoms in the main chain of the alkyl group may optionally be substituted with heteroatoms or groups independently selected from O, S, NH, or NMe. In one embodiment, -R 6 Selected from -OR 2 or -N(R) 2 (R) 2’ -R 2’ Selected from hydrogen or C1-C4 alkyl; -R 2 Selected from -R 4 Halogen-C(O)R 4 Halogenated -C(O)-OR 4 or -C(O)-N(R) 4 (R) 4’ -R 4’ Selected from hydrogen or C1-C4 alkyl; and -R 4 Selected from C1-C 12Alkyl group, wherein the alkyl group may optionally be substituted with one, two, three or four halogen groups, and wherein one, two, three or four carbon atoms in the main chain of the alkyl group may optionally be substituted with heteroatoms or groups independently selected from O, S, NH or NMe.

[0073] In one embodiment of the first or second aspect of the present invention, each -R α - Independently for C1-C 12 Alkylene, -(CH2CH2O) m -group, -(CH2CH2S) m -group, -(CH2CH2O) m -CH2CH2- group or -(CH2CH2S) m The -CH2CH2- groups are all optionally substituted, where m is 1, 2, 3, or 4. In one embodiment, each -R α - Independently for 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 for C1-C 12 Alkylene or -(CH2CH2O) m -Groups, both optionally substituted, wherein m is 1, 2, 3, or 4. In one embodiment, each -R α - Independently, the optionally substituted -(CH2CH2O) m - group, where m is 1, 2, 3 or 4.

[0074] In one embodiment of the first or second aspect of the present invention, each -R α - Independently, it is a C1-C8 alkylene, or a C1-C6 alkylene, or a C2-C4 alkylene, all of which are optionally substituted.

[0075] In one embodiment of the first or second aspect of the present invention, each -R α - Independently unsubstituted or substituted by one or more substituents selected independently of a halogen, C1-C4 alkyl, or C1-C4 haloalkyl. In one embodiment, each -R α - Independently unsubstituted or substituted by one or two independent substituents selected from halogen groups, C1-C4 alkyl groups, or C1-C4 haloalkyl groups. In one embodiment, each -R α - Not replaced.

[0076] In one embodiment of the first or second aspect of the present invention, each -Rβ The hydrocarbon group is independently saturated or unsaturated, wherein the hydrocarbon group may be straight-chain or branched, or may be or include cyclic groups, wherein the hydrocarbon group may optionally be substituted, and wherein the hydrocarbon group may optionally include one or more heteroatoms N, O or S in its carbon skeleton.

[0077] In one embodiment of the first or second aspect of the present invention, at least one -R β Independently, it is a C1-C6 alkyl, or C1-C4 alkyl, or methyl, all optionally substituted. In one embodiment, each -R β It is independently a C1-C6 alkyl, or C1-C4 alkyl, or methyl, all of which may optionally be substituted.

[0078] In one embodiment of the first or second aspect of the present invention, at least one -R β Independent of the glycosyl group. In one implementation, each -R β It is a sugar group on its own.

[0079] In one embodiment of the first or second aspect of the present invention, each -R β Independently unsubstituted or substituted by one or more substituents selected from halogen groups, C1-C4 alkyl groups, or C1-C4 haloalkyl groups. In one embodiment, each -R β Independently unsubstituted or substituted by one or two independent substituents selected from halogen groups, C1-C4 alkyl groups, or C1-C4 haloalkyl groups. In one embodiment, each -R β It has not been replaced.

[0080] In one embodiment of the first or second aspect of the present invention, each -R 3 Independently selected from -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 7 Y、-R α -[N(R 5 )2(R 5’ )]、-R α -[P(R 5 )2(R 5’ )] or -R α -[R 7’ In one implementation, at least one -R 3 Independently selected from -R α -[N(R 5 )3]Y、-R α -[P(R 5 )3]Y、-R α -[R 7 Y、-R α -[N(R 5 )2(R 5’ )]、-R α -[P(R 5 )2(R 5’ )] or -R α -[R 7’ In one implementation, at least one -R 3 Independently selected from -R α -[N(R 5 )3]Y、-R α -[P(R 5 )3]Y、-R α -[R 7 Y、-R α -[N(R 5 )2(R 5’ )]、-R α -[P(R 5 )2(R 5’ )] or -R α -[R 7’ ]; Each -R 5 Independently selected from C1-C4 alkyl or phenyl, wherein the phenyl group is optionally substituted with one, two, or three C1-C4 alkyl or C1-C4 alkoxy groups; each -R 5’ Selected from C1-C4 alkyl or phenyl groups, each coated with -CO2 - Substitution, wherein the phenyl group is optionally further substituted with one, two, or three C1-C4 alkyl or C1-C4 alkoxy groups; -R 7It is -[NC5H5], which may optionally be substituted with one, two, or three C1-C4 alkyl or C1-C4 alkoxy groups; -R 7’ It is -[NC5H5], which is affected by -CO2 - Substitution, and optionally further substituted with one, two, or three C1-C4 alkyl or C1-C4 alkoxy groups; -R α -Selected from C1-C 12 Alkylene, wherein one, two, three or four carbon atoms in the main chain of the alkylene may optionally be replaced by heteroatoms or groups independently selected from O, S, NH or NMe; and Y is a counterion (preferably a halide or hexafluorophosphate).

[0081] In one embodiment of the first or second aspect of the present invention, 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 implementation, 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 It is a glycosyl group. In one implementation, each -R 3 Independently selected from -R α -OR β or -R α -SR β In one implementation, each -R 3 Independently selected from -R α -OR β or -R α -SR β And -R β It is a sugar group.

[0082] In one embodiment of the first or second aspect of the present invention, each -R 4 Independently selected from -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 7 Y、-R α -[N(R 5 )2(R 5’ )]、-R α -[P(R 5 )2(R 5’ )] or -R α -[R 7’ In one implementation, at least one -R 4 Independently selected from -R α -[N(R 5 )3]Y、-R α -[P(R 5 )3]Y、-R α -[R 7 Y、-R α -[N(R 5 )2(R 5’ )]、-R α -[P(R 5 )2(R 5’ )] or -R α -[R 7’ In one implementation, at least one -R 4 Independently selected from -R α -[N(R 5 )3]Y、-R α -[P(R 5 )3]Y、-R α -[R 7 Y、-R α -[N(R 5 )2(R 5’ )]、-R α-[P(R 5 )2(R 5’ )] or -R α -[R 7’ ]; Each -R 5 Independently selected from C1-C4 alkyl or phenyl, wherein the phenyl group is optionally substituted with one, two, or three C1-C4 alkyl or C1-C4 alkoxy groups; each -R 5’ Selected from C1-C4 alkyl or phenyl groups, each coated with -CO2 - Substitution, wherein the phenyl group is optionally further substituted with one, two, or three C1-C4 alkyl or C1-C4 alkoxy groups; -R 7 It is -[NC5H5], which may optionally be substituted with one, two, or three C1-C4 alkyl or C1-C4 alkoxy groups; -R 7’ It is -[NC5H5], which is affected by -CO2 - Substitution, and optionally further substituted with one, two, or three C1-C4 alkyl or C1-C4 alkoxy groups; -R α -Selected from C1-C 12 Alkylene, wherein one, two, three or four carbon atoms in the main chain of the alkylene may optionally be replaced by heteroatoms or groups independently selected from O, S, NH or NMe; and Y is a counterion (preferably a halide or hexafluorophosphate).

[0083] In one embodiment of the first or second aspect of the present invention, 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 implementation, 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 It is a glycosyl group. In one implementation, each -R 4 Independently selected from -R α -OR β or -R α -SR β In one implementation, each -R 4Independently selected from -R α -OR β or -R α -SR β And -R β It is a sugar group.

[0084] In one embodiment of the first or second aspect of the present invention, -R 2 -R 3 or -R 4 At least one of them is independently selected from -R α -OR β -R α -SR β -R α -S(O)R β or -R α -S(O)2R β And -R β It is a glycosyl group. In one implementation, -R 2 -R 3 or -R 4 At least one of them is independently selected from -R α -OR β or -R α -SR β And -R β It is a sugar group.

[0085] For the purposes of this invention, "glycosyl" is any group comprising at least one monosaccharide subunit, wherein each monosaccharide subunit may optionally be substituted and / or modified. Typically, a glycosyl group consists of one or more monosaccharide subunits, wherein each monosaccharide subunit may optionally be substituted and / or modified.

[0086] Typically, the carbon atom of each monosaccharide subunit of a sugar is directly (most usually via a single bond) attached to the rest of the compound.

[0087] For the purposes of this specification, when a statement is made that a first atom or group is "directly attached" to a second atom or group, it should be understood that the first atom or group is covalently bonded to the second atom or group, and there are no one or more intermediary atoms or groups. For example, for the group -(C=O)N(CH3)2, the carbon atom of each methyl group is directly attached to a nitrogen atom and the carbonyl group is directly attached to a nitrogen atom, but the carbonyl group carbon atom is not directly attached to any of the methyl group carbon atoms.

[0088] Typically, each sugar moiety is derived from the corresponding sugar by replacing the hydroxyl group of the sugar with a group defined by the rest of the compound.

[0089] The single bond between the anomeric carbon of a monosaccharide subunit and a substituent is called a glycosidic bond. The glycosidic group is attached to the anomeric carbon of the monosaccharide subunit via a glycosidic bond. The bond between the glycosyl group and the rest of the compound can be a glycosidic bond or a non-glycosidic bond. Typically, the bond between the glycosyl group and the rest of the compound is a glycosidic bond, making the saccharidyl group a glycosyl group. When the bond between the glycosyl group and the rest of the compound is a glycosidic bond, the glycosidic bond can be α or β configured. Typically, this glycosidic bond is β configured.

[0090] For the purposes of this invention, when a glycosyl group "contains x monosaccharide subunits", it means that the glycosyl group has only x monosaccharide subunits. In contrast, when a glycosyl group "contains x monosaccharide subunits", it means that the glycosyl group has x or more monosaccharide subunits.

[0091] Each sugar syl group may be independently selected from monosaccharides, disaccharides, oligosaccharides, or polysaccharides. As will be understood, a monosaccharide contains a single monosaccharide subunit. Similarly, a disaccharide contains two monosaccharide subunits. As used herein, an "oligosaccharide" contains 2 to 9 monosaccharide subunits. Examples of oligosaccharides include trisaccharides, tetrasaccharides, pentasaccharides, hexasaccharides, heptasaccharides, octasaccharides, and nonasaccharides. As used herein, a "polysaccharide" contains 10 or more monosaccharide subunits (such as 10-50, 10-30, 10-20, or 10-15 monosaccharide subunits).

[0092] Each monosaccharide subunit within a disaccharide, oligosaccharide, or polysaccharide group may be identical 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, which may be α or β configured.

[0093] Each oligosaccharide or polysaccharide group can be a linear, branched, or macrocyclic oligosaccharide or polysaccharide group. Typically, each oligosaccharide or polysaccharide group is a linear or branched oligosaccharide or polysaccharide group.

[0094] In one implementation, at least one -R β It is a monosaccharide or a disaccharide.

[0095] In another embodiment, at least one -R β It is a monosaccharide. For example, at least one -R β It can be a glycosyl group containing a single monosaccharide subunit, wherein the monosaccharide subunit may optionally be substituted and / or modified. Typically, at least one -R β It is a glycosyl group containing a single monosaccharide subunit, wherein the monosaccharide subunit may optionally be substituted. More typically, at least one -R βIt is a sugar syl group containing a single monosaccharide subunit, in which the monosaccharide subunit is not replaced.

[0096] In one implementation, at least one -R β It is an aldose group, wherein the aldose group may optionally be substituted and / or modified. For example, at least one -R β The aldose can be selected from glycerolose, butyrosose (such as erythrosose or threosose), pentoose (such as ribosose, arabinose, xylose or lysoose), or hexanoose (such as alloose, azoose, glucosose, mannose, gulosose, idooose, galactosose or tarosose), any of which may optionally be substituted and / or modified.

[0097] In another implementation, at least one -R β It is a ketose group, wherein the ketose group may optionally be substituted and / or modified. For example, at least one -R β It may be selected from erythrosyl, pentyl (such as ribulosyl or xylulosyl) or hexyl (such as allulosyl, fructose, sorbitol or tagatose), any of which may optionally be substituted and / or modified.

[0098] Each monosaccharide subunit can exist in a closed-ring (cyclic) or open-chain (acyclic) form. Typically, at least one -R β Each monosaccharide subunit exists in a closed-ring (cyclic) form. For example, at least one -R β It can be a glycosyl group containing a single closed-ring monosaccharide subunit, wherein the monosaccharide subunit may optionally be substituted and / or modified. Typically, in this case, at least one -R β It is a pyranose or furanose group, such as pyranolose, furanolose, pyranolisose, or furanolisose, any of which may optionally be substituted and / or modified. More generally, at least one -R β It is a pyranose group, such as a pyranolose group or a pyranolose group, any of which may optionally be substituted and / or modified.

[0099] In one implementation, at least one -R β It is selected from ribopyranosyl, arabinopyranosyl, xylopyranosyl, lysopyranosyl, allopyranosyl, arazosyl, glucopyranosyl, mannosyl, gulosyl, idoosyl, galactosyl, or tarosyl, any of which may optionally be substituted and / or modified.

[0100] In another embodiment, at least one -R β It is a glucosyl group, such as pyranosel, wherein the glucosyl or pyranosel group may optionally be substituted and / or modified. Typically, at least one -R βIt is a glucosyl group, wherein the glucosyl group is optionally substituted. More typically, at least one -R β It is an unsubstituted glucose unit.

[0101] Each monosaccharide subunit can exist in either the D- or L-configuration. Typically, each monosaccharide subunit exists in its most common configuration found in nature.

[0102] In one implementation, at least one -R β It is a D-glucose group, such as D-glucopyranosyl, wherein the D-glucose group or D-glucopyranosyl may optionally be substituted and / or modified. Typically, at least one -R β It is D-glucose, wherein the D-glucose group is optionally substituted. More generally, at least one -R β It is unsubstituted D-glucose.

[0103] For the purposes of this invention, in the substituted monosaccharide group or monosaccharide subunit: (a) One or more hydroxyl groups of a monosaccharide syl group or a monosaccharide subunit are each independently marked with -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(R b)2, -O-SO2-N(R b )2, -NR b -SO-N(R b )2, -NR b -SO2-N(R b )2, -R a -SO-N(R b )2, -R a -SO2-N(R b )2, -N(R b )2, -N(R b )3 + , -R a -N(R b )2, -R a -N(R b )3 + , -P(R b )2, -PO(R b )2, -OP(R b )2, -OPO(R b )2, -R a -P(R b )2, -R a -PO(R b )2, -OSi(R b )3, -R a -Si(R b )3, -CO-R b , -CO-OR b , -CO-N(R b )2, -O-CO-R b , -O-CO-OR b , -O-CO-N(R b )2, -NR b -CO-R b , -NR b -CO-OR b , -NR b -CO-N(R b )2, -R a -CO-R b , -R a -CO-OR b or -R a -CO-N(R b )2 substituted; and / or (b) One, two, or three hydrogen atoms of the carbon atom directly attached to the monosaccharide syl group or monosaccharide subunit are each independently bound 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 substitution; and / or (c) One or more hydroxyl groups of a monosaccharide syl group or monosaccharide subunit, together with hydrogen atoms attached to the same carbon atom as the hydroxyl group, are each independently marked with =O, =S, or =NR. b or = N(R) b )2 + Substitute; and / or (d) Any two hydroxyl groups of a monosaccharide or monosaccharide subunit are combined with -OR c -、-SR c -、-SO-R c -、-SO2-R c -or-NR b -R c -Alternative; in: Each -R a - Independently substituted or unsubstituted alkylene, alkenyl or ynylene groups, which optionally include one or more heteroatoms, each independently selected from O, N and S, in their carbon skeleton and preferably contain 1 to 10 carbon atoms; Each -R bIndependently hydrogen, or substituted or unsubstituted straight-chain, branched, or cyclic alkyl, alkenyl, alkynyl, arylalkyl, arylalkenyl, arylalkynyl, alkylaryl, alkenylaryl, or alkynylaryl, optionally comprising one or more heteroatoms each independently selected from O, N, and S in its carbon skeleton and preferably containing 1-15 carbon atoms; and Each -R c - Independently chemically bonded, or substituted or unsubstituted alkylene, alkenyl or ynylene groups, which optionally include one or more heteroatoms, each independently selected from O, N and S, in their carbon skeleton and preferably contain 1 to 10 carbon atoms; The condition is that the monosaccharide syl 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 )2 or -OR c -

[0104] Typically, in substituted monosaccharide groups or monosaccharide subunits: (a) One or more hydroxyl groups of a monosaccharide syl group or a monosaccharide subunit are each independently marked with -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 substitution; and / or (b) One or two hydrogen atoms of the carbon atom directly attached to the monosaccharide group or monosaccharide subunit are each independently bound 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 substitution; and / or (c) One hydroxyl group of the monosaccharide syl or monosaccharide subunit, along with the hydrogen atom attached to the same carbon atom as the hydroxyl group, is replaced by =O; and / or (d) Any two hydroxyl groups of a monosaccharide or monosaccharide subunit are combined with -OR c -or-NR b -R c -Alternative; in: Each -R b Independently hydrogen, or substituted or unsubstituted straight-chain, branched or cyclic alkyl, alkenyl, ynyl, arylalkyl, arylalkenyl, arylynyl, alkylaryl, alkenylaryl or ynylaryl, optionally comprising one, two or three heteroatoms each independently selected from O and N in its carbon skeleton and containing 1-8 carbon atoms; and Each -R c - Independently substituted or unsubstituted alkylene, alkenyl or ynylene groups, which optionally include one, two or three heteroatoms each independently selected from O and N and contain 1 to 8 carbon atoms in their carbon skeleton; The condition is that the monosaccharide syl or monosaccharide subunit contains at least two, preferably at least three -OH, -OR. b -OPO(R) b )2、-OSi(R b )3、-O-CO-R b -O-CO-OR b -O-CO-N(R) b )2 or -OR c -

[0105] In one implementation, -R β It is a glycosyl group, and one or more hydroxyl groups of the glycosyl group are each independently marked with -O-CO-R b Replacement, where each -R b Independently, it is a C1-C4 alkyl group, preferably methyl. In one embodiment, -R β It is a glycosyl group and all the hydroxyl groups of the glycosyl group are independently converted to -O-CO-R b Replacement, where each -R b It is independently a C1-C4 alkyl group, preferably methyl.

[0106] In modified monosaccharide units or monosaccharide subunits: (a) The ring of the modified monosaccharide or monosaccharide subunit, or the ring in the closed-loop form of the modified monosaccharide or monosaccharide subunit, is partially unsaturated; and / or (b) The epoxide in the modified monosaccharide or monosaccharide subunit, or in the cyclic form of the modified monosaccharide or monosaccharide subunit, is -S- or -NR-. d - Replacement, where -R d Independently hydrogen, or substituted or unsubstituted straight-chain, branched or cyclic alkyl, alkenyl, alkynyl, aryl, arylalkyl, arylalenyl, arylalkynyl, alkylaryl, alkenylaryl or alkynylaryl, optionally including one or more heteroatoms, each independently selected from O, N and S, and preferably containing 1 to 15 carbon atoms in its carbon skeleton.

[0107] Alternatively, in cases where the modified monosaccharide subunit forms part of a disaccharide, oligosaccharide, or polysaccharide, -R d It may be one or more additional monosaccharide subunits that form part of a disaccharide, oligosaccharide, or polysaccharide, wherein any such additional one or more monosaccharide subunits may optionally be substituted and / or modified.

[0108] Typically, in modified monosaccharide units or monosaccharide subunits: (a) The ring of the modified monosaccharide or monosaccharide subunit, or the ring in the closed ring form of the modified monosaccharide or monosaccharide subunit, contains a single C=C; and / or (b) The epoxide in the modified monosaccharide or monosaccharide subunit, or in the cyclic form of the modified monosaccharide or monosaccharide subunit, is coated with -NR. d - Replacement, where -R d It is independently hydrogen, or a substituted or unsubstituted straight-chain, branched or cyclic alkyl, alkenyl, alkynyl, aryl, arylalkyl, arylalenyl, arylalkynyl, alkylaryl, alkenylaryl or alkynylaryl, which optionally includes one, two or three heteroatoms each independently selected from O and N in its carbon skeleton and contains 1 to 8 carbon atoms.

[0109] Typical examples of substituted and / or modified monosaccharide subunits include those corresponding to the following: (i) Deoxy sugars, such as deoxyribose, fucose, fucoidose and rhamnose, wherein the hydroxyl group of the monosaccharide syl or monosaccharide subunit has been replaced by -H; (ii) Amino sugars, such as glucosamine and galactosamine, wherein the hydroxyl group of the monosaccharide or monosaccharide subunit has been replaced by -NH2, most commonly at the 2-position; and (iii) Sugar acids containing a -COOH group, such as aldonic acids (e.g., gluconic acid), ketonic acids, uronic acids (e.g., glucuronic acid), and aldonic diacids (e.g., gularic or galactosic acid).

[0110] In one embodiment of the first or second aspect of the present invention, at least one -R β It is selected from the following monosaccharides: In one embodiment of the first or second aspect of the present invention, at least one -R β yes: .

[0111] In one embodiment of the first or second aspect of the present invention, -R 2 -R 3 or -R 4 At least one of them is independently selected from -R α -OR β -R α -SR β -R α -S(O)R β or -R α -S(O)2R β (preferably selected from -R) α -OR β or -R α -SR β ), and -R β Selected from: In one embodiment of the first or second aspect of the present invention, -R 2 -R 3 or -R 4 At least one of them is independently selected from -R α -[N(R5 )3]Y、-R α -[P(R 5 )3]Y、-R α -[R 7 Y、-R α -[N(R 5 )2(R 5’ )]、-R α -[P(R 5 )2(R 5’ )] or -R α -[R 7’ Preferably, -R 2 -R 3 or -R 4 At least one of them is independently selected from -R α -[P(R 5 )3]Y or -R α -[P(R 5 )2(R 5’ In one implementation, -R 2 -R 3 or -R 4 At least one of them is independently selected from -R α -[N(R 5 )3]Y、-R α -[P(R 5 )3]Y or -R α -[R 7 Y, preferably, -R 2 -R 3 or -R 4 At least one of them is -R α -[P(R 5 )3]Y. In one implementation, -R 2 -R 3 or -R 4 At least one of them is independently selected from: , Preferably, -R 2 -R 3 or -R 4 At least one of them is -R α -[PPh3]Y.

[0112] In the first or second aspect of the invention, each -R 5 They can be the same or different. In a preferred embodiment, each -R 5 same.

[0113] In one embodiment of the first or second aspect of the present invention, each -R 5Independently unsubstituted or substituted with one or two substituents. In one embodiment, each -R 5 It has not been replaced.

[0114] In one embodiment of the first or second aspect of the present invention, -R 7 It is either unsubstituted or substituted with one or two substituents. In one embodiment, -R 7 It has not been replaced.

[0115] In one embodiment of the first or second aspect of the present invention, -R 7 The 4-position of the pyridine ring is not substituted with a halogen group. In one embodiment, -R 7 The 4-position of the pyridine ring is not substituted. In one embodiment, -R 7 It has not been replaced.

[0116] In one embodiment of the first or second aspect of the present invention, -R 1 and -R 6 Each of them independently contains 1 to 100 atoms other than hydrogen, preferably 1 to 80 atoms other than hydrogen, preferably 1 to 60 atoms other than hydrogen, preferably 1 to 50 atoms other than hydrogen, and preferably 1 to 45 atoms other than hydrogen.

[0117] In a particularly preferred embodiment, the first or second aspect of the invention provides a compound of formula (I) or a complex of formula (II): Or its pharmaceutically acceptable salt, wherein: -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 It is -C(O)-N(R) 3 (R) 3’ )]; -R 2 Each is independently 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 7 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 7’ ]; -R 3 and -R 4 Each is 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 7 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 7’ ]; -R 2’ -R 3’ and -R 4’ Each is independently selected from hydrogen or C1-C6 alkyl [preferably, -R] 2’ -R 3’ and -R 4’ Each is independently selected from hydrogen or C1-C3 alkyl; more preferably, -R 2’ -R 3’ and -R 4’ Each is independently selected from hydrogen or methyl; -R α - Each is independently selected from C1-C 42 Alkylene, wherein the alkylene may optionally be substituted with one or more (such as one, two, three, four or five) C1-C4 alkyl, C1-C4 haloalkyl or halogroup, and wherein one or more (such as one, two, three, four, five, six, seven, eight, nine or ten) carbon atoms in the main chain of the alkylene may optionally be substituted with heteroatoms or groups independently selected from O, S, NH or NMe. -R β Each is independently a saturated or unsaturated hydrocarbon group, wherein the hydrocarbon group may be straight-chain or branched, or may be or include cyclic groups, wherein the hydrocarbon group may optionally be substituted, and wherein the hydrocarbon group may optionally include one or more (such as one, two, three, four or five) heteroatoms N, O, S, P or Se in its carbon skeleton. -R 5 Each is independently selected from C1-C4 alkyl, C1-C4 haloalkyl, and -(CH2CH2O). n -H, -(CH2CH2O) n -CH3, phenyl, or C5-C6 heteroaryl, wherein the phenyl or C5-C6 heteroaryl group may optionally be 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), halogroup, -CO2H, -CO2Z, -CO2NH2, -O-(CH2CH2O). n -H or -O-(CH2CH2O) n -CH3 group substitution; -R5’ Selected from C1-C4 alkyl, C1-C4 haloalkyl, and -(CH2CH2O) n -H, -(CH2CH2O) n -CH3, phenyl, or C5-C6 heteroaryl groups, each bonded by -CO2 - The phenyl or C5-C6 heteroaryl group may optionally be further replaced 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), halogroup, -CO2H, -CO2Z, -CO2NH2, -O-(CH2CH2O). n -H or -O-(CH2CH2O) n -CH3 group substitution; -R 6 Selected from -OR 2 -N(R) 2 )2、-SR 2 -S(O)R 2 -S(O)2R 2 Or -X [preferably, -R] 6 Selected from -OR 2 -SR 2 -S(O)R 2 -S(O)2R 2 or -X]; -R 7 It is -[NC5H5], which is optionally separated by one or more (such as one, two, three, four or five) C1-C6 alkyl, C1-C6 haloalkyl, -O(C1-C6 alkyl), -O(C1-C6 haloalkyl), halogen, -CO2H, -CO2Z, -CO2NH2, -O-(CH2CH2O). n -H or -O-(CH2CH2O) n -CH3 group substitution; -R 7’ It is -[NC5H5], which is affected by -CO2 - Substituted, and optionally further replaced by one or more (such as one, two, three or four) C1-C6 alkyl, C1-C6 haloalkyl, -O(C1-C6 alkyl), -O(C1-C6 haloalkyl), halogen, -CO2H, -CO2Z, -CO2NH2, -O-(CH2CH2O). n -H or -O-(CH2CH2O) n -CH3 group substitution; Q is O, S, NH or NMe [preferably, Q is O]; X is a halogroup; Y is a counter anion [preferably Y is a counter anion selected from halides or hexafluorophosphates]; Z is a counter cation [preferably Z is selected from Li] + Na + K + Mg 2+ Ca 2+ or NH4 + [Counter cations]; M 2+ It is a metal cation [preferably M] 2+ It is selected from Zn 2+ Cu 2+ Fe 2+ Pd 2+ or Pt 2+ [Metal cations]; n is 1, 2, 3, 4, 5, or 6; p is 0, 1, 2, 3 or 4; r is 0, 1, 2, 3, 4, 5, or 6; and s is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12; The condition is -R 2 -R 3 and -R 4 At least one of them is selected from -[(CH2)] p Q] r -(CH2) s -[P(R 5 )3]Y、-[(CH2) p Q] r -(CH2) s -[R 7 Y、-[(CH2) p Q] r -(CH2) s -[P(R 5 )2(R 5’ )] or -[(CH2) p Q] r -(CH2) s -[R 7’ [Preferably, the condition is -R] 2 -R 3 and -R 4 At least one of them is selected from -[(CH2)] p Q] r -(CH2) s -[P(R 5 )3]Y or -[(CH2) p Q] r-(CH2) s -[P(R 5 )2(R 5’ )]).

[0118] In a particularly preferred embodiment, the first or second aspect of the invention provides a compound of formula (I) or a complex of formula (II): Or its pharmaceutically acceptable salt, wherein: -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 It is -C(O)-N(R) 3 (R) 3’ )]; -R 2 Each is independently 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、-Rα -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 7 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 7’ ]; -R 3 and -R 4 Each is 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 7 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 7’ ]; -R 3’ and -R 4’ Each is independently selected from hydrogen or C1-C3 alkyl [preferably, -R] 3’ and -R 4’ Each is independently selected from hydrogen or methyl; -R α - Each is independently selected from C1-C 42 Alkylene, wherein the alkylene may optionally be substituted with one or more (such as one, two, three, four or five) C1-C4 alkyl, C1-C4 haloalkyl or halogroup, and wherein one or more (such as one, two, three, four, five, six, seven, eight, nine or ten) carbon atoms in the main chain of the alkylene may optionally be substituted with heteroatoms or groups independently selected from O, S, NH or NMe. -R β Each is independently a saturated or unsaturated hydrocarbon group, wherein the hydrocarbon group may be straight-chain or branched, or may be or include cyclic groups, wherein the hydrocarbon group may optionally be substituted, and wherein the hydrocarbon group may optionally include one or more (such as one, two, three, four or five) heteroatoms N, O, S, P or Se in its carbon skeleton. -R 5 Each phenyl group is independently selected from C1-C3 alkyl or phenyl groups, wherein the phenyl group may optionally be independently selected from C1-C6 alkyl, -O(C1-C6 alkyl), -CO2H, -CO2Z, -CO2NH2, -O-(CH2CH2O). n -H or -O-(CH2CH2O) n-CH3 can be substituted with one, two, three, four or five substituents; -R 5’ Selected from -CO2 - Substituted C1-C3 alkyl groups or those with -CO2 - The substituted phenyl group, wherein the phenyl group may optionally be further selected independently from C1-C6 alkyl, -O(C1-C6 alkyl), -CO2H, -CO2Z, -CO2NH2, -O-(CH2CH2O). n -H or -O-(CH2CH2O) n -CH3 may be substituted with one, two, three or four substituents; -R 6 Selected from -OR 2 -N(R) 2 )2、-SR 2 -S(O)R 2 -S(O)2R 2 Or -X [preferably, -R] 6 Selected from -OR 2 -SR 2 -S(O)R 2 -S(O)2R 2 or -X]; -R 7 It is -[NC5H5], which is optionally selected independently by one, two, three, four or five C1-C6 alkyl, -O(C1-C6 alkyl), -CO2H, -CO2Z, -CO2NH2, -O-(CH2CH2O). n -H or -O-(CH2CH2O) n -CH3 substituents; -R 7’ It is -[NC5H5], which is affected by -CO2 - The substituted substance may optionally be further replaced by one, two, three, or four independently selected from C1-C6 alkyl, -O(C1-C6 alkyl), -CO2H, -CO2Z, -CO2NH2, -O-(CH2CH2O). n -H or -O-(CH2CH2O) n -CH3 substituents; Q is O, S, NH or NMe [preferably, Q is O]; X is a halogroup; Y is a counter anion [preferably Y is a counter anion selected from halides or hexafluorophosphates]; Z is a counter cation [preferably Z is selected from Li] + Na + K + Mg2+ Ca 2+ or NH4 + [Counter cations]; M 2+ It is a metal cation [preferably M] 2+ It is selected from Zn 2+ Cu 2+ Fe 2+ Pd 2+ or Pt 2+ [Metal cations]; n is 1, 2, 3, 4, 5, or 6; p is 0, 1, 2, 3 or 4; r is 0, 1, 2, 3, 4, 5, or 6; and s is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12; The condition is -R 2 -R 3 and -R 4 At least one of them is selected from -[(CH2)] p Q] r -(CH2) s -[P(R 5 )3]Y、-[(CH2) p Q] r -(CH2) s -[R 7 Y、-[(CH2) p Q] r -(CH2) s -[P(R 5 )2(R 5’ )] or -[(CH2) p Q] r -(CH2) s -[R 7’ [Preferably, the condition is -R] 2 -R 3 and -R 4 At least one of them is selected from -[(CH2)] p Q] r -(CH2) s -[P(R 5 )3]Y or -[(CH2) p Q] r -(CH2) s -[P(R 5 )2(R 5’ )]).

[0119] In the two preferred embodiments described in the preceding paragraphs, each -R 5They may be the same or different; preferably, each -R 5 same.

[0120] 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), or (IH) [preferably, the compound is a compound of formula (IF)]: Or its metal cation complex or its pharmaceutically acceptable salt, wherein: -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 Selected from -C(O)-OR 3’ or -C(O)-N(R) 3 (R) 3’ )]; -R 2 Each is independently 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, -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 or -R α -X; -R 3 and -R 4 Each is 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 or -R α -X; -R 3’ and -R 4’ Each is independently selected from hydrogen or C1-C3 alkyl [preferably, -R] 3’ and -R 4’ Each is independently selected from hydrogen or methyl; -R 6 Selected from -OR 2 -N(R) 2 )2、-SR 2 -S(O)R 2 -S(O)2R 2 Or -X [preferably, -R] 6 Selected from -OR 2 -SR 2 -S(O)R 2 -S(O)2R 2 or -X]; -R 30 -Selected from -O-, -O(CO)-, -O(CO)NH-, -O(CO)NMe-, -NH-, -NH(CO)-, -NMe-, -NMe(CO)-, -N(CO2Me)- or -N(CO2Et)-; -R α - Each is independently selected from C1-C 12 Alkylene, wherein the alkylene may optionally be substituted with one or more (such as one, two, three, four or five) C1-C4 alkyl, C1-C4 haloalkyl or halogroup, and wherein one or more (such as one, two, three, four, five or six) carbon atoms in the main chain of the alkylene may optionally be substituted with heteroatoms or groups independently selected from O, S, NH or NMe. -R β Each is independently a saturated or unsaturated hydrocarbon group, wherein the hydrocarbon group may be straight-chain or branched, or may be or include cyclic groups, wherein the hydrocarbon group may optionally be substituted, and wherein the hydrocarbon group may optionally include one or more (such as one, two, three, four or five) heteroatoms N, O, S, P or Se in its carbon skeleton. -R ε Selected from C1-C6 alkyl, -O(C1-C6 alkyl), -CO2H, -CO2Z, -CO2NH2, -O-(CH2CH2O). n -H or -O-(CH2CH2O) n -CH3; X is a halogroup; Y is a counter anion [preferably Y is a counter anion selected from halides or hexafluorophosphates]; Z is a counter cation [preferably Z is selected from Li] + Na + K + Mg 2+ Ca 2+ or NH4 + [Counter cations]; n is 1, 2, 3 or 4; p is 0, 1, 2, 3 or 4; r is 0, 1, 2, 3, 4, 5, or 6; s is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12; t is 0, 1, 2, 3, 4, or 5; and u is 0, 1, 2, 3, and 4.

[0121] In another preferred embodiment of the first or second aspect of the invention, the compound is a compound of formula (IA), (IB), (IC), (ID), (IJ), (IK), (IL), or (IM): Or its metal cation complex or its pharmaceutically acceptable salt, wherein: -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 Selected from -C(O)-OR 3’ or -C(O)-N(R) 3 (R) 3’ )]; -R 2 Each is independently 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 -Rα -S(O)R β -R α -S(O)2R β -R α -NH2, -R α -NH(R β -R α -N(R β )2 or -R α -X; -R 3 and -R 4 Each is 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 or -R α -X; -R 3’ and -R 4’ Each is independently selected from hydrogen or C1-C3 alkyl [preferably, -R] 3’ and -R 4’ Each is independently selected from hydrogen or methyl; -R 6 Selected from -OR 2 -N(R) 2 )2、-SR 2 -S(O)R 2 -S(O)2R 2 Or -X [preferably, -R] 6 Selected from -OR 2 -SR 2 -S(O)R 2 -S(O)2R 2 or -X]; -R α - Each is independently selected from C1-C 12Alkylene, wherein the alkylene may optionally be substituted with one or more (such as one, two, three, four or five) C1-C4 alkyl, C1-C4 haloalkyl or halogroup, and wherein one or more (such as one, two, three, four, five or six) carbon atoms in the main chain of the alkylene may optionally be substituted with heteroatoms or groups independently selected from O, S, NH or NMe. -R β Each is independently a saturated or unsaturated hydrocarbon group, wherein the hydrocarbon group may be straight-chain or branched, or may be or include cyclic groups, wherein the hydrocarbon group may optionally be substituted, and wherein the hydrocarbon group may optionally include one or more (such as one, two, three, four or five) heteroatoms N, O, S, P or Se in its carbon skeleton. -R ε Selected from C1-C6 alkyl, -O(C1-C6 alkyl), -CO2H, -CO2Z, -CO2NH2, -O-(CH2CH2O). n -H or -O-(CH2CH2O) n -CH3; X is a halogroup; Y is a counter anion [preferably Y is a counter anion selected from halides or hexafluorophosphates]; Z is a counter cation [preferably Z is selected from Li] + Na + K + Mg 2+ Ca 2+ or NH4 + [Counter cations]; n is 1, 2, 3 or 4; p is 0, 1, 2, 3 or 4; r is 0, 1, 2, 3, 4, 5, or 6; s is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12; t is 0, 1, 2, 3, 4, or 5; and u is 0, 1, 2, 3, and 4.

[0122] Compounds of formulas (IA), (IB), (IC), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), (IL), (IM) according to the first and second aspects of the present invention, their complexes and salts comprising the moiety -[(CH2)]. p O] r -(CH2) s -,in: p is 0, 1, 2, 3 or 4; r is 0, 1, 2, 3, 4, 5, or 6; and s is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12.

[0123] 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-.

[0124] 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-.

[0125] In another implementation, r is 0; and s is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12; such that -[(CH2)] p O] r -(CH2) s -is-(CH2) 1-12 -

[0126] In another preferred embodiment, the first or second aspect of the invention provides a compound of formula (I''') or a complex of formula (II'''): Or its pharmaceutically acceptable salt, wherein: -U- is -O-, -N(R u - or -S-; -V- is a key, -O-, -N(R) v )- or -S-; -W-is-R α -[P(R 5 )3]Y、-R α -[R 7 Y、-R α -[P(R 5 )2(R 5’ )] or -R α -[R 7’ [Preferred-W-is-R] α -[P(R 5 )3]Y or -R α -[P(R5 )2(R 5’ )]]; -R 10 Selected from -OH or -O- (C1-C4 alkyl); -R α -Selected from C1-C 12 Alkylene, wherein the alkylene may optionally be substituted with one or more (such as one, two, three or four) C1-C4 alkyl, C1-C4 haloalkyl or halogroup; and wherein one or more (such as one, two, three or four) carbon atoms in the main chain of the alkylene may optionally be substituted with heteroatoms or groups independently selected from O, S, NH or NMe; -R 5 Each is independently selected from C1-C4 alkyl, C1-C4 haloalkyl, and -(CH2CH2O). n -H, -(CH2CH2O) n -CH3, phenyl, or C5-C6 heteroaryl, wherein the phenyl or C5-C6 heteroaryl group may optionally be replaced by one or more C1-C6 alkyl, C1-C6 haloalkyl, -O(C1-C6 alkyl), -O(C1-C6 haloalkyl), halogroup, -CO2H, -CO2Z, -CO2NH2, or -O-(CH2CH2O). n -H or -O-(CH2CH2O) n -CH3 group substitution; -R 5’ Selected from C1-C4 alkyl, C1-C4 haloalkyl, and -(CH2CH2O) n -H, -(CH2CH2O) n -CH3, phenyl, or C5-C6 heteroaryl groups, each bonded by -CO2 - The phenyl or C5-C6 heteroaryl group may optionally be further replaced by one or more C1-C6 alkyl, C1-C6 haloalkyl, -O(C1-C6 alkyl), -O(C1-C6 haloalkyl), halogen, -CO2H, -CO2Z, -CO2NH2, -O-(CH2CH2O). n -H or -O-(CH2CH2O) n -CH3 group substitution; -R 7 It is -[NC5H5], which is optionally separated by one or more C1-C6 alkyl, C1-C6 haloalkyl, -O(C1-C6 alkyl), -O(C1-C6 haloalkyl), halogen, -CO2H, -CO2Z, -CO2NH2, -O-(CH2CH2O). n -H or -O-(CH2CH2O) n -CH3 group substitution; -R 7’ It is -[NC5H5], which is affected by -CO2 - It is substituted, and optionally further replaced by one or more C1-C6 alkyl, C1-C6 haloalkyl, -O(C1-C6 alkyl), -O(C1-C6 haloalkyl), halogen, -CO2H, -CO2Z, -CO2NH2, -O-(CH2CH2O). n -H or -O-(CH2CH2O) n -CH3 group substitution; -R u It is hydrogen, C1-C4 alkyl, or CO2 (C1-C4 alkyl); -R v It is hydrogen, C1-C4 alkyl, or CO2 (C1-C4 alkyl); c is 0 or 1; n is 1, 2, 3, 4, 5, or 6; Y is a counter anion [preferably Y is a counter anion selected from halides or hexafluorophosphates]; Z is a counter cation [preferably Z is selected from Li] + Na + K + Mg 2+ Ca 2+ or NH4 + [Counter cations]; and M 2+ It is a metal cation [preferably M] 2+ It is selected from Zn 2+ Cu 2+ Fe 2+ Pd 2+ or Pt 2+ (metal cations).

[0127] In another preferred embodiment, the first or second aspect of the invention provides a compound of formula (I') or a complex of formula (II'): Or its pharmaceutically acceptable salt, wherein: -U- is -O-, -N(R u )- or -S-; -V- represents -CH2-, -O-, -N(R) v )- or -S-; -W-is-R α -[P(R 5 )3]Y、-R α -[R 7 Y、-R α -[P(R5 )2(R 5’ )] or -R α -[R 7’ [Preferred-W-is-R] α -[P(R 5 )3]Y or -R α -[P(R 5 )2(R 5’ )]]; -R 10 Selected from -OH or -O- (C1-C4 alkyl); -R α -Selected from C1-C 12 Alkylene, wherein the alkylene may optionally be substituted with one or more (such as one, two, three or four) C1-C4 alkyl, C1-C4 haloalkyl or halogroup; and wherein one or more (such as one, two, three or four) carbon atoms in the main chain of the alkylene may optionally be substituted with heteroatoms or groups independently selected from O, S, NH or NMe; -R 5 Each is independently selected from C1-C4 alkyl, C1-C4 haloalkyl, and -(CH2CH2O). n -H, -(CH2CH2O) n -CH3, phenyl, or C5-C6 heteroaryl, wherein the phenyl or C5-C6 heteroaryl group may optionally be replaced by one or more C1-C6 alkyl, C1-C6 haloalkyl, -O(C1-C6 alkyl), -O(C1-C6 haloalkyl), halogroup, -CO2H, -CO2Z, -CO2NH2, or -O-(CH2CH2O). n -H or -O-(CH2CH2O) n -CH3 group substitution; -R 5’ Selected from C1-C4 alkyl, C1-C4 haloalkyl, and -(CH2CH2O) n -H, -(CH2CH2O) n -CH3, phenyl, or C5-C6 heteroaryl groups, each bonded by -CO2 - The phenyl or C5-C6 heteroaryl group may optionally be further replaced by one or more C1-C6 alkyl, C1-C6 haloalkyl, -O(C1-C6 alkyl), -O(C1-C6 haloalkyl), halogen, -CO2H, -CO2Z, -CO2NH2, -O-(CH2CH2O). n -H or -O-(CH2CH2O) n -CH3 group substitution; -R 7It is -[NC5H5], which is optionally separated by one or more C1-C6 alkyl, C1-C6 haloalkyl, -O(C1-C6 alkyl), -O(C1-C6 haloalkyl), halogen, -CO2H, -CO2Z, -CO2NH2, -O-(CH2CH2O). n -H or -O-(CH2CH2O) n -CH3 group substitution; -R 7’ It is -[NC5H5], which is affected by -CO2 - It is substituted, and optionally further replaced by one or more C1-C6 alkyl, C1-C6 haloalkyl, -O(C1-C6 alkyl), -O(C1-C6 haloalkyl), halogen, -CO2H, -CO2Z, -CO2NH2, -O-(CH2CH2O). n -H or -O-(CH2CH2O) n -CH3 group substitution; -R u It is hydrogen or C1-C4 alkyl; -R v It is hydrogen or C1-C4 alkyl; n is 1, 2, 3, 4, 5, or 6; Y is a counter anion [preferably Y is a counter anion selected from halides or hexafluorophosphates]; Z is a counter cation [preferably Z is selected from Li] + Na + K + Mg 2+ Ca 2+ or NH4 + [Counter cations]; and M 2+ It is a metal cation [preferably M] 2+ It is selected from Zn 2+ Cu 2+ Fe 2+ Pd 2+ or Pt 2+ (metal cations).

[0128] In another preferred embodiment, the first or second aspect of the invention provides a compound of formula (I') or a complex of formula (II'): Or its pharmaceutically acceptable salt, wherein: -U- is -O-, -N(R u )- or -S-; -V- represents -CH2-, -O-, -N(R) v )- or -S-; -W-is-R α -[P(R 5 )3]Y or -R α -[R 7 Y [Preferred-W-Is-R] α -[P(R 5 )3]Y]; -R 10 Selected from -OH or -O- (C1-C4 alkyl); -R α -Selected from C1-C 12 Alkylene (preferably C1-C9 alkylene, preferably C2-C6 alkylene), wherein one or more (such as one, two, three or four, preferably one or two) carbon atoms in the main chain of the alkylene may optionally be replaced by heteroatoms or groups independently selected from O, S, NH or NMe (preferably O, NH or NMe, preferably O); -R 5 Each is independently selected from C1-C4 alkyl, C1-C4 haloalkyl, and -(CH2CH2O). n -H, -(CH2CH2O) n -CH3, phenyl or C5-C6 heteroaryl, wherein the phenyl or C5-C6 heteroaryl may optionally be substituted with one or more C1-C4 alkyl, C1-C4 haloalkyl, -O(C1-C4 alkyl) or -O(C1-C4 haloalkyl); -R 7 It is -[NC5H5], which may optionally be substituted with one or more C1-C4 alkyl, C1-C4 haloalkyl, -O(C1-C4 alkyl) or -O(C1-C4 haloalkyl); -R u It is hydrogen or C1-C4 alkyl; -R v It is hydrogen or C1-C4 alkyl; n is 1, 2, 3, 4, 5, or 6; Y is a counter anion [preferably Y is a counter anion selected from halides or hexafluorophosphates]; and M 2+ It is a metal cation [preferably M] 2+ It is selected from Zn 2+ Cu 2+ Fe 2+ Pd 2+ or Pt 2+ (metal cations).

[0129] In another preferred embodiment, the first or second aspect of the invention provides a compound of formula (I'') or a complex of formula (II''): Or its pharmaceutically acceptable salt, wherein: -R 19 Selected from -R α -[P(R 5 )3]Y or -R α -[R 7 ]Y; -R α -Selected from C1-C 12 Alkylene (preferably C1-C9 alkylene, preferably C2-C6 alkylene), wherein one or more (such as one, two, three or four, preferably one or two) carbon atoms in the main chain of the alkylene may optionally be replaced by heteroatoms or groups independently selected from O, S, NH or NMe (preferably O, NH or NMe, preferably O); -R 5 Each is independently selected from C1-C3 alkyl or phenyl groups; -R 7 Yes - [NC5H5]; Y is a counter anion [preferably Y is a counter anion selected from halides or hexafluorophosphates]; and M 2+ It is a metal cation [preferably M] 2+ It is selected from Zn 2+ Cu 2+ Fe 2+ Pd 2+ or Pt 2+ (metal cations).

[0130] Preferably, in the compound or complex according to the first or second aspect of the invention, the compound or complex is: ; Wherein Y is a counter anion [preferably Y is a counter anion selected from halides or hexafluorophosphates], and q is 0, 1, 2, 3 or 4 (preferably q is 1); Or its metal cation complex or its pharmaceutically acceptable salt.

[0131] Preferably, in the compound or complex according to the first or second aspect of the invention, the compound or complex is: Or its metal cation complex or its pharmaceutically acceptable salt.

[0132] In one embodiment, the compound or complex according to the first or second aspect of the invention is in the form of a pharmaceutically acceptable salt. In one embodiment, the compound or complex is in the form of an inorganic salt, such as a lithium salt, sodium salt, potassium salt, magnesium salt, calcium salt, or ammonium salt. In one embodiment, the compound or complex is in the form of a sodium or potassium salt. In one embodiment, the compound is in the form of a sodium salt. In another embodiment, the compound or complex is in the form of an organic salt, such as an amine salt (e.g., choline or meglumine salt) or an amino acid salt (e.g., arginine salt).

[0133] The compound or complex according to the first or second aspect of the invention has at least two chiral centers. The compound or complex according to the first or second aspect of the invention is preferably substantially enantiomerically pure, which means that, as measured by XRPD or SFC, the compound or complex contains less than 10%, preferably less than 5%, preferably less than 3%, preferably less than 2%, preferably less than 1%, preferably less than 0.5% (all by weight) of other stereoisomers.

[0134] 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, percentage HPLC purity is measured by an area normalization method.

[0135] A third aspect of the invention provides a composition comprising a compound or complex according to a first or second aspect of the invention and a pharmaceutically acceptable carrier or diluent.

[0136] In one embodiment, the composition according to a third aspect of the invention further comprises polyvinylpyrrolidone (PVP). In one embodiment, the composition comprises 0.01-10% w / w PVP based on the total weight of the composition, preferably 0.1-5% w / w PVP based on the total weight of the composition, and more preferably 0.5-5% w / w PVP based on the total weight of the composition. In one embodiment, the PVP is K30.

[0137] 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 by weight of the total composition, preferably 40-99% w / w DMSO by weight of the total composition, and more preferably 65-99% w / w DMSO by weight of the total composition.

[0138] In one embodiment, the composition according to a third aspect of the 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, cimipril, atezolizumab, avelumab, durvalumab, or ipilimumab.

[0139] 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 use in photodynamic therapy or chemiluminescence therapy.

[0140] 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 atherosclerosis; multiple sclerosis; diabetes; diabetic retinopathy; arthritis; rheumatoid arthritis; fungal, viral, chlamydial, bacterial, nanobacterial, or parasitic infections; 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 areas of neovascularization; benign or malignant tumors; early-stage cancer; cervical dysplasia; soft tissue sarcoma; germ cell tumors; retinoblastoma; age-related diseases. Age-related macular degeneration; lymphoma; Hodgkin's lymphoma; head and neck cancer; oral or pharyngeal cancer; or blood cancer, prostate cancer, cervical cancer, uterine cancer, vaginal cancer or other female adnexal 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, ureteral cancer, kidney cancer, liver cancer, gallbladder cancer, spleen cancer, brain cancer, lymphatic system cancer, bone cancer, skin cancer, or pancreatic cancer.

[0141] 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.

[0142] 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 benign or malignant tumors.

[0143] 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 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 stomach cancer; or leukemia, prostate cancer, cervical cancer, uterine cancer, vaginal cancer or other female adnexal cancers, breast cancer, nasopharyngeal cancer, tracheal cancer, laryngeal cancer, bronchial cancer, bronchiolar cancer, lung cancer, hollow organ cancer, esophageal cancer, gastric cancer, bile duct cancer, intestinal cancer, colon cancer, colorectal cancer, rectal cancer, bladder cancer, ureteral cancer, kidney cancer, liver cancer, gallbladder cancer, spleen cancer, brain cancer, lymphatic system cancer, bone cancer, skin cancer, or pancreatic cancer.

[0144] 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 use in photodynamic diagnostics.

[0145] 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 atherosclerosis; multiple sclerosis; diabetes; diabetic retinopathy; arthritis; rheumatoid arthritis; fungal, viral, chlamydial, bacterial, nanobacterial, or parasitic infections; 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 areas of neovascularization; benign or malignant tumors; early-stage cancer; cervical dysplasia; soft tissue sarcoma; germ cell tumors; retinoblastoma; age-related diseases. Age-related macular degeneration; lymphoma; Hodgkin's lymphoma; head and neck cancer; oral or pharyngeal cancer; or blood cancer, prostate cancer, cervical cancer, uterine cancer, vaginal cancer or other female adnexal 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, ureteral cancer, kidney cancer, liver cancer, gallbladder cancer, spleen cancer, brain cancer, lymphatic system cancer, bone cancer, skin cancer, or pancreatic cancer.

[0146] 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 excessive proliferation of benign or malignant cells or by neovascularization.

[0147] 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 benign or malignant tumors.

[0148] 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 cancers; cervical dysplasia; soft tissue sarcoma; germ cell tumors; retinoblastoma; age-related macular degeneration; lymphoma; Hodgkin's lymphoma; head and neck cancer; oral or stomatous cancer; or leukemia, prostate cancer, cervical cancer, uterine cancer, vaginal cancer or other female adnexal cancers, breast cancer, nasopharyngeal cancer, tracheal cancer, laryngeal cancer, bronchial cancer, bronchiolar cancer, lung cancer, hollow organ cancer, esophageal cancer, gastric cancer, bile duct cancer, intestinal cancer, colon cancer, colorectal cancer, rectal cancer, bladder cancer, ureteral cancer, kidney cancer, liver cancer, gallbladder cancer, spleen cancer, brain cancer, lymphatic system cancer, bone cancer, skin cancer, or pancreatic cancer.

[0149] 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 fluorescence or phosphorescence detection of the diseases listed above, and are preferably used for fluorescence or phosphorescence detection and quantification of the diseases.

[0150] 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 administration at the same time as or before the application of irradiation or sound, preferably suitable for administration before the application of irradiation.

[0151] 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 chemiluminescence therapy, they are preferably suitable for administration 5 to 100 hours before irradiation, preferably 6 to 72 hours before irradiation, and preferably 24 to 48 hours before irradiation.

[0152] 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 diagnostics, they are preferably suitable for administration 3 to 60 hours, more preferably 8 to 40 hours, before irradiation.

[0153] Preferably, the irradiation used in photodynamic therapy, chemiluminescence therapy, or photodynamic diagnostics is electromagnetic radiation with wavelengths in the range of 500 nm to 1000 nm, preferably 550 nm to 750 nm, preferably 600 nm to 700 nm, and preferably 640 nm to 670 nm. The electromagnetic radiation can be applied at about 0.1-5 W, preferably about 1 W, for about 5-60 minutes, and more 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 adapted to provide irradiation with wavelengths in the range of 550 nm to 750 nm, preferably 600 nm to 700 nm, and preferably 640 nm to 670 nm. In another embodiment of the invention, the irradiation can be provided by a device for insertion into a body cavity, such as the prostate, anus, vagina, mouth, or nose. In another embodiment of the invention, irradiation can be provided by interstitial photoactivation, for example, by inserting a fiber laser into the lung, liver, lymph nodes, or breast using a fine needle. In another embodiment of the invention, irradiation can be provided by endoscopic light activation, for example, to deliver light to the lungs, stomach, colon, bladder, or neck.

[0154] The pharmaceutical composition according to a third aspect of the invention may be in a form suitable for oral, parenteral (including intravenous, subcutaneous, intramuscular, intradermal, intratracheal, intraperitoneal, intratumoral, intra-articular, intra-abdominal, intracranial, and epidural), transdermal, airway (aerosol), rectal, vaginal, or local (including buccal, mucosal, and sublingual) administration. The pharmaceutical composition may also be in a form suitable for administration by enema or by injection into the tumor. Preferably, the pharmaceutical composition is in a form suitable for oral, parenteral (such as intravenous, intraperitoneal, and intratumoral), or airway administration; preferably, it is in a form suitable for oral or parenteral administration; and preferably, it is in a form suitable for oral administration.

[0155] 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, sachets, sugar tablets, or lozenges, in powder or granule form, or in the form of an aqueous solution, suspension, or dispersion. More preferably, the pharmaceutical composition is provided in the form of an aqueous solution, suspension, or dispersion for oral administration, or alternatively, in the form of a lyophilized powder that can be mixed with water prior to administration to provide an aqueous solution, suspension, or dispersion for oral administration. Preferably, the pharmaceutical composition is in the form of a compound or complex according to the first or second aspect of the invention, suitable for providing 0.01 to 10 mg / kg / day, preferably 0.1 to 2 mg / kg / day, preferably about 1 mg / kg / day.

[0156] 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 as an aqueous solution for parenteral administration, or alternatively as a lyophilized powder that can be mixed with water prior to administration to provide an aqueous solution for parenteral administration. Preferably, the pharmaceutical composition is an aqueous solution or suspension having a pH of 6 to 8.5. Preferably, the pharmaceutical composition is in a form suitable for providing 0.01 to 10 mg / kg / day, preferably 0.1 to 2 mg / kg / day, preferably about 1 mg / kg / day, of a compound or complex according to the first or second aspect of the invention.

[0157] In another preferred embodiment, the pharmaceutical composition is in a form suitable for airway administration. Preferably, the pharmaceutical composition is provided as an aqueous solution, suspension, or dispersion for airway administration, or alternatively as a lyophilized powder that can be mixed with water prior to 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 a compound or complex according to the first or second aspect of the invention.

[0158] A fourth aspect of the invention provides the use of compounds or complexes according to the first or second aspect of the invention in the manufacture of pharmaceutical agents for treating the following diseases: atherosclerosis; multiple sclerosis; diabetes; diabetic retinopathy; arthritis; rheumatoid arthritis; fungal, viral, chlamydial, bacterial, nanobacterial, or parasitic infections; 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 areas of neovascularization; benign or malignant tumors; early-stage cancer; cervical dysplasia; soft tissue sarcoma; germ cell tumors; retinoblastoma; age-related diseases. Age-related macular degeneration; lymphoma; Hodgkin's lymphoma; head and neck cancer; oral or pharyngeal cancer; or blood cancer, prostate cancer, cervical cancer, uterine cancer, vaginal cancer or other female adnexal 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, ureteral cancer, kidney cancer, liver cancer, gallbladder cancer, spleen cancer, brain cancer, lymphatic system cancer, bone cancer, skin cancer, or pancreatic cancer.

[0159] A fourth aspect of the invention also provides the use of compounds or complexes according to the first or second aspect of the invention in the manufacture of phototherapy agents for photodynamic therapy or chemiluminescence therapy. Preferably, the phototherapy agents are suitable for treating atherosclerosis; multiple sclerosis; diabetes; diabetic retinopathy; arthritis; rheumatoid arthritis; fungal, viral, chlamydial, bacterial, nanobacterial, or parasitic infections; 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 areas of neovascularization; benign or malignant tumors; early-stage cancers; cervical dysplasia; soft tissue sarcoma; germ cell tumors; retinoblastoma; age-related diseases. Age-related macular degeneration; lymphoma; Hodgkin's lymphoma; head and neck cancer; oral or pharyngeal cancer; or blood cancer, prostate cancer, cervical cancer, uterine cancer, vaginal cancer or other female adnexal 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, ureteral cancer, kidney cancer, liver cancer, gallbladder cancer, spleen cancer, brain cancer, lymphatic system cancer, bone cancer, skin cancer, or pancreatic cancer.

[0160] Preferably, the pharmaceutical or phototherapy agent of the fourth aspect of the present invention is suitable for treating diseases characterized by excessive proliferation of benign or malignant cells or by areas of neovascularization.

[0161] Preferably, the pharmaceutical or phototherapy agent of the fourth aspect of the present invention is suitable for treating benign or malignant tumors.

[0162] Preferably, the pharmaceutical or phototherapy agent of the fourth aspect of the present invention is suitable for treating 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 stomach cancer; or leukemia, prostate cancer, cervical cancer, uterine cancer, vaginal cancer or other female adnexal cancers, breast cancer, nasopharyngeal cancer, tracheal cancer, laryngeal cancer, bronchial cancer, bronchiolar cancer, lung cancer, hollow organ cancer, esophageal cancer, gastric cancer, bile duct cancer, intestinal cancer, colon cancer, colorectal cancer, rectal cancer, bladder cancer, ureteral cancer, kidney cancer, liver cancer, gallbladder cancer, spleen cancer, brain cancer, lymphatic system cancer, bone cancer, skin cancer, or pancreatic cancer.

[0163] A fourth aspect of the invention also provides the use of compounds or complexes according to the first or second aspect of the invention in the manufacture of photodiagnostic agents for photodynamic diagnostics.

[0164] Preferably, the photodiagnostic agent of the fourth aspect of the present invention is suitable for detecting atherosclerosis; multiple sclerosis; diabetes; diabetic retinopathy; arthritis; rheumatoid arthritis; fungal, viral, chlamydial, bacterial, nanobacterial, or parasitic infectious diseases; HIV; AIDS; SARS virus (preferably Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)), Asian (chicken) influenza virus, dengue virus, herpes simplex or herpes zoster infection; hepatitis; viral hepatitis; cardiovascular diseases; coronary artery stenosis; carotid artery stenosis; intermittent claudication; skin diseases; acne; psoriasis; diseases characterized by excessive proliferation of benign or malignant cells or areas of neovascularization; benign or malignant tumors; early cancers; cervical dysplasia; soft tissue sarcoma; germ cell tumors; retinoblastoma; age-related diseases. Age-related macular degeneration; lymphoma; Hodgkin's lymphoma; head and neck cancer; oral or pharyngeal cancer; or blood cancer, prostate cancer, cervical cancer, uterine cancer, vaginal cancer or other female adnexal 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, ureteral cancer, kidney cancer, liver cancer, gallbladder cancer, spleen cancer, brain cancer, lymphatic system cancer, bone cancer, skin cancer, or pancreatic cancer.

[0165] 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 angiogenesis.

[0166] Preferably, the photodiagnostic agent of the fourth aspect of the present invention is suitable for detecting benign or malignant tumors.

[0167] Preferably, the photodiagnostic agent of the fourth aspect of the present invention is suitable for detecting 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 stomach cancer; or leukemia, prostate cancer, cervical cancer, uterine cancer, vaginal cancer or other female adnexal cancers, breast cancer, nasopharyngeal carcinoma, tracheal cancer, laryngeal cancer, bronchial cancer, bronchiolar cancer, lung cancer, hollow organ cancer, esophageal cancer, gastric cancer, bile duct cancer, intestinal cancer, colon cancer, colorectal cancer, rectal cancer, bladder cancer, ureteral cancer, kidney cancer, liver cancer, gallbladder cancer, spleen cancer, brain cancer, lymphatic system cancer, bone cancer, skin cancer, or pancreatic cancer.

[0168] Preferably, the photodiagnostic agent of the fourth aspect of the present invention is suitable for detecting the disease by fluorescence or phosphorescence, and more preferably for detecting and quantifying the disease by fluorescence or phosphorescence.

[0169] Preferably, the pharmaceutical, phototherapy, or photodiagnostic agent is suitable for application simultaneously with or before the application of irradiation or sound, and preferably suitable for application before the application of irradiation.

[0170] If the agent or phototherapy agent is used in photodynamic therapy or chemiluminescence therapy, it is preferably suitable to be applied 5 to 100 hours before irradiation, preferably 6 to 72 hours before irradiation, or preferably 24 to 48 hours before irradiation.

[0171] If the photodiagnostic agent is used in photodynamic diagnosis, it is preferably suitable to be applied 3 to 60 hours before irradiation, more preferably 8 to 40 hours before irradiation.

[0172] Preferably, the irradiation used in photodynamic therapy, chemiluminescence therapy, or photodynamic diagnostics is electromagnetic radiation with wavelengths in the range of 500 nm to 1000 nm, preferably 550 nm to 750 nm, preferably 600 nm to 700 nm, and preferably 640 nm to 670 nm. The electromagnetic radiation can be applied at about 0.1-5 W, preferably about 1 W, for about 5-60 minutes, and more 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 adapted to provide irradiation with wavelengths in the range of 550 nm to 750 nm, preferably 600 nm to 700 nm, and preferably 640 nm to 670 nm. In another embodiment of the invention, the irradiation can be provided by a device for insertion into a body cavity, such as the prostate, anus, vagina, mouth, or nose. In another embodiment of the invention, irradiation can be provided by interstitial photoactivation, for example, by inserting a fiber laser into the lung, liver, lymph nodes, or breast using a fine needle. In another embodiment of the invention, irradiation can be provided by endoscopic light activation, for example, to deliver light to the lungs, stomach, colon, bladder, or neck.

[0173] The fifth aspect of the invention provides a treatment for: atherosclerosis; multiple sclerosis; diabetes; diabetic retinopathy; arthritis; rheumatoid arthritis; fungal, viral, chlamydial, bacterial, nanobacterial, or parasitic infections; 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 areas of neovascularization; benign or malignant tumors; 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... Methods for treating oral cancer; or leukemia, prostate cancer, cervical cancer, uterine cancer, vaginal cancer or other female adnexal cancer, breast cancer, nasopharyngeal cancer, tracheal cancer, laryngeal cancer, bronchial cancer, bronchiolar cancer, lung cancer, hollow organ cancer, esophageal cancer, gastric cancer, bile duct cancer, intestinal cancer, colon cancer, colorectal cancer, rectal cancer, bladder cancer, ureteral cancer, kidney cancer, liver cancer, gallbladder cancer, spleen cancer, brain cancer, lymphatic system cancer, bone cancer, skin cancer or pancreatic cancer; said methods comprising administering a therapeutically effective amount of a compound or complex according to the first or second aspect of the invention to a person or animal in need.

[0174] A fifth aspect of the invention also provides a method for photodynamic therapy or chemiluminescence therapy for human or animal diseases, the method comprising administering a therapeutically effective amount of a compound or complex according to the first or second aspect of the invention to a person or animal in need. Preferably, the human or animal diseases are atherosclerosis; multiple sclerosis; diabetes; diabetic retinopathy; arthritis; rheumatoid arthritis; fungal, viral, chlamydial, bacterial, nanobacterial, or parasitic infections; 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 diseases; coronary artery stenosis; carotid artery stenosis; intermittent claudication; skin diseases; acne; psoriasis; diseases characterized by excessive proliferation of benign or malignant cells or areas of neovascularization; benign or malignant tumors; early-stage cancers; cervical dysplasia; soft tissue sarcoma; germ cell tumors; retinoblastoma; age-related diseases. Age-related macular degeneration; lymphoma; Hodgkin's lymphoma; head and neck cancer; oral or pharyngeal cancer; or blood cancer, prostate cancer, cervical cancer, uterine cancer, vaginal cancer or other female adnexal 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, ureteral cancer, kidney cancer, liver cancer, gallbladder cancer, spleen cancer, brain cancer, lymphatic system cancer, bone cancer, skin cancer, or pancreatic cancer.

[0175] Preferably, the fifth aspect of the present invention is a method for treating areas of excessive proliferation of benign or malignant cells or areas of neovascularization.

[0176] Preferably, the method of the fifth aspect of the present invention is a method for treating benign or malignant tumors.

[0177] Preferably, the method of the fifth aspect of the present invention is a method 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 stomach cancer; or leukemia, prostate cancer, cervical cancer, uterine cancer, vaginal cancer or other female adnexal cancer, breast cancer, nasopharyngeal cancer, tracheal cancer, laryngeal cancer, bronchial cancer, bronchiolar cancer, lung cancer, hollow organ cancer, esophageal cancer, gastric cancer, bile duct cancer, intestinal cancer, colon cancer, colorectal cancer, rectal cancer, bladder cancer, ureteral cancer, kidney cancer, liver cancer, gallbladder cancer, spleen cancer, brain cancer, lymphatic system cancer, bone cancer, skin cancer or pancreatic cancer.

[0178] A fifth aspect of the invention also provides a method for photodynamic diagnosis of diseases in humans or animals, 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 invention. Preferably, the human or animal diseases are: atherosclerosis; multiple sclerosis; diabetes; diabetic retinopathy; arthritis; rheumatoid arthritis; fungal, viral, chlamydial, bacterial, nanobacterial, or parasitic infections; 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 diseases; coronary artery stenosis; carotid artery stenosis; intermittent claudication; skin diseases; acne; psoriasis; diseases characterized by excessive proliferation of benign or malignant cells or areas of neovascularization; benign or malignant tumors; early-stage cancers; cervical dysplasia; soft tissue sarcoma; germ cell tumors; retinoblastoma; age-related diseases. Age-related macular degeneration; lymphoma; Hodgkin's lymphoma; head and neck cancer; oral or stomach cancer; or leukemia, prostate cancer, cervical cancer, uterine cancer, vaginal cancer or other female adnexal cancer, breast cancer, nasopharyngeal carcinoma, tracheal cancer, laryngeal cancer, bronchial cancer, bronchiolar cancer, lung cancer, hollow organ cancer, esophageal cancer, gastric cancer, bile duct cancer, intestinal cancer, colon cancer, colorectal cancer, rectal cancer, bladder cancer, ureteral cancer, kidney cancer, liver cancer, gallbladder cancer, spleen cancer, brain cancer, lymphatic system cancer, bone cancer, skin cancer, or pancreatic cancer. Preferably, the human or animal disease is characterized by excessive proliferation of benign or malignant cells or by areas of neovascularization. Preferably, the human or animal disease is a benign or malignant tumor. Preferably, the human or animal disease is early-stage cancer; cervical dysplasia; soft tissue sarcoma; germ cell tumor; retinoblastoma; age-related macular degeneration; lymphoma; Hodgkin's lymphoma; head and neck cancer; oral or stomach cancer; or leukemia, prostate cancer, cervical cancer, uterine cancer, vaginal cancer or other female adnexal cancer, breast cancer, nasopharyngeal carcinoma, tracheal cancer, laryngeal cancer, bronchial cancer, bronchiolar cancer, lung cancer, hollow organ cancer, esophageal cancer, gastric cancer, bile duct cancer, intestinal cancer, colon cancer, colorectal cancer, rectal cancer, bladder cancer, ureteral cancer, kidney cancer, liver cancer, gallbladder cancer, spleen cancer, brain cancer, lymphatic system cancer, bone cancer, skin cancer, or pancreatic cancer. Preferably, the photodynamic diagnostic method is suitable for fluorescence or phosphorescence detection of the said disease, and more preferably suitable for fluorescence or phosphorescence detection and quantification of the said disease.

[0179] In any method according to the fifth aspect of the invention, a person or animal is preferably subjected to further irradiation or sound during or after application of the compound or complex according to the first or second aspect of the invention. Preferably, the person or animal is irradiated after application of the compound or complex according to the first or second aspect of the invention.

[0180] If the method is photodynamic therapy or chemiluminescence therapy, then humans or animals are preferably irradiated 5 to 100 hours, more preferably 6 to 72 hours, or more preferably 24 to 48 hours after application of the compound or complex according to the first or second aspect of the invention.

[0181] If the method is a photodynamic diagnostic method, then it is preferable to irradiate a person or animal 3 to 60 hours, more preferably 8 to 40 hours, after application of the compound or complex according to the first or second aspect of the invention.

[0182] Preferably, the irradiation is electromagnetic radiation with wavelengths in the range of 500 nm to 1000 nm, preferably 550 nm to 750 nm, preferably 600 nm to 700 nm, and preferably 640 nm to 670 nm. The electromagnetic radiation can be applied at about 0.1-5 W, preferably about 1 W, for about 5-60 minutes, and more preferably for about 15-20 minutes. In one embodiment of the invention, two electromagnetic radiation sources (e.g., a laser and an LED light) are used, both adapted to provide irradiation with wavelengths in the range of 550 nm to 750 nm, preferably 600 nm to 700 nm, and preferably 640 nm to 670 nm. In another embodiment of the invention, the irradiation can be provided by a device for insertion into a body cavity, such as the prostate, anus, vagina, mouth, or nose. In another embodiment of the invention, the irradiation can be provided by interstitial photoactivation, for example, by inserting a fiber laser into the lungs, liver, lymph nodes, or breast using a fine needle. In another embodiment of the invention, the irradiation can be provided by endoscopic photoactivation, for example, for delivering light to the lungs, stomach, colon, bladder, or neck.

[0183] In any method of the fifth aspect of the invention, preferably the person or animal is a human being.

[0184] A sixth aspect of the present invention provides a drug combination or pillbox, the drug combination or pillbox comprising: (a) A compound or complex according to the first or second aspect of the invention; and (b) Immune checkpoint inhibitors.

[0185] 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, cimipril, atezolizumab, avelumab, durvalumab, or ipilimumab.

[0186] Preferably, the combination or kit of the sixth aspect is used to treat a disease, condition, or ailment that responds to PD-1, PD-L1, or CTLA4 inhibition. Preferably, the combination or kit of the sixth aspect is used to treat cancer. 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.

[0187] The sixth aspect also provides the use of the combination or kit of the sixth aspect of the invention in the manufacture of a medicament for treating a disease, condition, or ailment that responds to inhibition of PD-1, PD-L1, or CTLA4. The sixth aspect also provides the use of the combination or kit of the sixth aspect of the 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), kidney cancer, bladder cancer, head and neck cancer, or Hodgkin's lymphoma.

[0188] A sixth aspect of the invention also provides a method for treating a disease, condition, or disorder 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 invention to a person or animal in need. A sixth aspect of the 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 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.

[0189] For the combination or kit of the sixth aspect of the invention, the compound or complex of 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.

[0190] Preferably, the combination or kit of the sixth aspect is suitable for application simultaneously with or before the application of irradiation or sound, and more preferably for application before the application of irradiation. In one embodiment, the combination or kit of the sixth aspect is suitable for application 5 to 100 hours before irradiation, preferably 6 to 72 hours before irradiation, and more preferably 24 to 48 hours before irradiation.

[0191] Preferably, the irradiation used in photodynamic therapy or chemiluminescence therapy is electromagnetic radiation with wavelengths in the range of 500 nm to 1000 nm, preferably 550 nm to 750 nm, preferably 600 nm to 700 nm, and preferably 640 nm to 670 nm. The electromagnetic radiation can be applied at about 0.1-5 W, preferably about 1 W, for about 5-60 minutes, and more preferably 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 adapted to provide irradiation with wavelengths in the range of 550 nm to 750 nm, preferably 600 nm to 700 nm, and preferably 640 nm to 670 nm. In another embodiment of the invention, irradiation can be provided by a device for insertion into a body cavity, such as the prostate, anus, vagina, mouth, or nose. In another embodiment of the invention, irradiation can be provided by interstitial photoactivation, for example, by inserting a fiber laser into the lung, liver, lymph nodes, or breast using a fine needle. In another embodiment of the invention, irradiation can be provided by endoscopic light activation, for example, to deliver light to the lungs, stomach, colon, bladder, or neck.

[0192] For the avoidance of doubt, within the scope of practice, any embodiment of a given aspect of the invention may be combined with any other embodiment of the same aspect of the invention. Furthermore, within the scope of practice, it should be understood that any preferred or optional embodiment of any aspect of the invention should also be considered a preferred or optional embodiment of any other aspect of the invention.

[0193] Synthesis Experiment Details Synthesis Comparative Example 1 – Synthesis of pyrophoric acid α-9-hydroxymethyl methyl ester (Comparative Compound 1) Step 1:Add pyrophyllin a (500 mg, 0.935 mmol, 1 equivalent), potassium carbonate (323 mg, 2.34 mmol, 2.5 equivalent), DMF (20 mL), and a stir bar (12 mm) to 100 mL of RBF. Rinse the flask with nitrogen and stir at 300 rpm. Then add iodomethane (87 μL, 199 mg, 1.40 mmol, 1.5 equivalent) and stir the mixture at room temperature for 20 hours. Monitor the reaction progress by HPLC. Remove the solvent under reduced pressure to give a dark blue solid. Dissolve the crude material in DCM (30 mL) and wash with water (30 mL). The aqueous layer was extracted with DCM (30 mL), and the combined organic layers were dried (Na2SO4) and concentrated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography (silica, 4 x 20 cm) using 1-2.5% MeOH in DCM as a solvent to obtain a dark blue solid of methyl pyrophyllin a (334 mg, 65%) (purity determined by HPLC to be 93.92%).

[0194] 1 H NMR (400 MHz, chloroform-) d ) δ 9.45 (s, 1H), 9.34 (s, 1H), 8.55 (s, 1H), 7.98 (dd, J = 17.8, 11.5 Hz, 1H), 6.27 (dd, J = 17.8, 1.5 Hz, 1H), 6.16 (dd, J =11.6, 1.5 Hz, 1H), 5.32-5.19 (m, 1H), 5.11 (d, J = 19.8 Hz, 1H), 4.48 (qd, J =7.3, 2.2 Hz, 1H), 4.29 (dt, J = 9.0, 2.9 Hz, 1H), 3.65 (d, J = 4.4 Hz, 5H), 3.62(s, 3H), 3.40 (s, 3H), 3.20 (s, 3H), 2.75-2.64 (m, 1H), 2.62-2.50 (m, 1H), 2.36-2.23 (m, 2H), 1.82 (d, J = 7.3 Hz, 3H), 1.68 (t, J = 7.6 Hz, 3H), -1.73 (s, 1H).

[0195] Step 2: Methyl pyrophyllin a (240 mg, 0.437 mmol, 1 equivalent), THF (65 mL), and osmium tetroxide (2.2 mg, 0.00874 mmol, 0.02 equivalent) were added to 250 mL of RBF. A solution of sodium periodate (560 mg, 2.62 mmol, 6 equivalent) in water (25 mL) was then added dropwise to the reaction mixture over 15 minutes at 0 °C. The reaction mixture was then stirred at room temperature for 20 hours, and the reaction progress was monitored by HPLC. The reaction mixture was quenched with saturated sodium thiosulfate solution (50 mL), the organic layer was separated, and the aqueous layer was extracted with DCM (30 mL). The combined organic layers were washed with water (50 mL) and brine (50 mL), dried over Na₂SO₄, and concentrated by rotary evaporation to give a deep blue solid. The crude product was purified by silica gel column chromatography (4 x 20 cm) using a 1–2% MeOH eluent gradient in DCM. The first major band was concentrated by rotary evaporation to obtain pyromethoxyphylla α-9-formylmethyl ester (217 mg, 90%), a dark blue solid (purity determined by HPLC to be 92.57%).

[0196] 1 H NMR (400 MHz, chloroform-) d ) δ 11.52 (s, 1H), 10.24 (s, 1H), 9.55 (s, 1H), 8.82 (s, 1H), 5.39-5.28 (m, 1H), 5.18 (d, J = 19.9 Hz, 1H), 4.57 (qd, J = 7.3,2.1 Hz, 1H), 4.42-4.27 (m, 1H), 3.76 (s, 3H), 3.69 (s, 5H), 3.62 (s, 5H),3.27 (s, 3H), 2.80-2.68 (m, 1H), 2.66-2.54 (m, 1H), 2.37-2.24 (m, 2H), 1.85(d, J = 7.3 Hz, 3H), 1.69 (t, J = 7.6 Hz, 3H), -2.12 (s, 1H).

[0197] Step 3:Add pyrophyllophosphophylate α-9-formylmethyl ester (120 mg, 0.218 mmol, 1 equivalent) and DCM (20 mL) to 50 mL of RBF, and cool the mixture to 5 °C using an ice-water bath. Then add borane tert-butylamine complex (19 mg, 0.218 mmol, 1 equivalent), and stir the reaction mixture for 10 min. Remove the ice-water bath, and stir the resulting mixture again at ambient temperature (600 rpm) under nitrogen for 110 min. Then quench the reaction mixture with 1 M HCl (20 mL) and stir for 10 min. Separate the organic layer and wash with 1 M HCl (20 mL), water (20 mL), saturated NaHCO3 solution (20 mL), and brine (20 mL), dry (Na2SO4), filter on a sintered glass funnel, and concentrate by rotary evaporation to give a dark blue solid residue (106 mg). The residue was purified by column chromatography (4 x 20 cm) using 2% MeOH / DCM as the solution in DCM. The samples were loaded with the product (mainly dark green spots, R in 5% MeOH / DCM). f The fraction was divided into fractions of 0.60 to obtain comparative compound 1 (95 mg, 79%) as a dark blue solid (purity determined by HPLC to be 98.09%).

[0198] 1 H NMR (400 MHz, chloroform-) d ) δ 9.38 (s, 1H), 9.35 (s, 1H), 8.51 (s, 1H), 5.84 (s, 2H), 5.14 (d, J = 19.8 Hz, 1H), 5.01 (d, J = 19.8 Hz, 1H), 4.42 (qd, J =7.3, 2.2 Hz, 1H), 4.19 (dt, J = 9.1, 2.7 Hz, 1H), 3.69-3.60 (m, 5H), 3.56 (s,3H), 3.39 (s, 3H), 3.22 (s, 3H), 2.66-2.45 (m, 2H), 2.32-2.17 (m, 2H), 1.76(d, J = 7.3 Hz, 3H), 1.66 (t, J = 7.6 Hz, 3H), -1.91 (s, 1H).

[0199] Synthesis Example 1 – Synthesis of pyromethoxyphylla α-methyl ester 9-(N-(3-triphenylphosphonium propyl)bromide)carbamate (Compound 1) Add pyrophyllophosphochlorophyllin α-9-hydroxymethyl methyl ester (Comparative Compound 1) (41 mg, 0.0741 mmol, 1 equivalent), carbonyl diimidazole (24 mg, 0.0148 mmol, 2 equivalents), DCM (5 mL), and 4-dimethylaminopyridine (DMAP) (2 mg) to 10 mL of RBF. Stir the resulting mixture under nitrogen (600 rpm) for 3 h and monitor by TLC. Then add 3-aminopropyltriphenylphosphonium bromide (89 mg, 0.222 mmol, 3 equivalents) to the reaction mixture and continue stirring for 18 h. Then add another portion of 3-aminopropyltriphenylphosphonium bromide (30 mg, 0.074 mmol, 1 equivalent) and continue stirring for 7 h. Dilute the reaction mixture with DCM (20 mL), transfer to a separatory funnel, wash with water (2 x 20 mL), dry (Na₂SO₄), and concentrate by rotary evaporation to give a deep blue-green residue. The sample was loaded with 5-15% MeOH / DCM as a solution, and the residue was purified by column chromatography (3 x 18 cm). The sample containing a dark green band (R in 5% MeOH / DCM) was then purified. f The fraction with a concentration of 0.2 was concentrated by rotary evaporation to give compound 1 (11 mg, 15%) as a dark blue solid (purity determined by HPLC to be 98.51%).

[0200] 1 H NMR (400 MHz, chloroform-) d ) δ 9.54 (s, 1H), 9.45 (s, 1H), 8.55 (s, 1H),7.79-7.60 (m, 2H), 7.51 (ddd, J = 12.7, 8.2, 1.5 Hz, 6H), 7.39-7.27 (m, 9H), 7.07-6.91 (m, 1H), 6.80 (d, J = 18.2 Hz, 1H), 6.31 (s, 2H), 5.26 (d, J = 19.8 Hz, 1H), 5.11 (d, J = 19.8 Hz, 1H), 4.53-4.42 (m, 1H), 4.33-4.24 (m, 1H), 3.64 (d, J = 5.9 Hz, 4H), 3.60 (s, 4H), 3.52 (t, J= 5.8 Hz, 2H), 3.44 (s, 3H), 3.23 (s, 3H), 2.76-2.63 (m, 1H), 2.56 (p, J = 9.1 Hz, 1H), 2.33-2.18 (m, 3H), 1.95 (s,7H), 1.79 (d, J = 7.2 Hz, 5H), 1.64 (t, J = 7.6 Hz, 3H), -1.79 (s, 1H).

[0201] Synthesis Example 2 – Synthesis of methyl pyromethoxyphylla α-ester 9-(oxopentyl)triphenylphosphonium bromide (Compound 2) Add pyrophyllophosphinate α-9-hydroxymethyl methyl ester (comparative compound 1) (40 mg, 0.0723 mmol, 1 equivalent), 4-(carboxybutyl)triphenylphosphonium bromide (64 mg, 0.145 mmol, 2 equivalents), EDC.HCl (24 mg, 0.145 mmol, 2 equivalents), 4-dimethylaminopyridine (DMAP) (18 mg, 0.145 mmol, 2 equivalents), and DCM (5 mL) to 25 mL of RBF. Stir the resulting mixture at 25 °C (600 rpm) under nitrogen and monitor the reaction by TLC. After 2 hours, remove the solvent by rotary evaporation, leaving a purple oil. Using a gradient of 5–10% MeOH / DCM, as a solution in 5% MeOH / DCM, purify the residue by column chromatography (3 x 16 cm). Collect a 25 mL fraction when the main color begins to elute. The combined product contains (mainly dark green spots, R in 5% MeOH / DCM) f The fraction was divided into fractions of 0.25 to give compound 2 (60 mg, 85%) as a dark blue solid (purity determined by HPLC to be 97.92%).

[0202] 1 H NMR (400 MHz, chloroform-) d ) δ 9.51 (s, 1H), 9.39 (s, 1H), 8.60 (s, 1H), 7.58-7.47 (m, 6H), 7.46-7.38 (m, 3H), 7.36-7.29 (m, 6H), 6.31 (s, 2H), 5.28(d, J = 13.7 Hz, 3H), 5.13 (d, J= 19.9 Hz, 1H), 4.55-4.45 (m, 1H), 4.36-4.27 (m,1H), 3.80-3.65 (m, 6H), 3.61 (s, 3H), 3.41 (s, 3H), 3.23 (s, 3H), 2.77-2.65(m, 1H), 2.63-2.51 (m, 3H), 2.35-2.23 (m, 2H), 2.09 (p, J = 7.1 Hz, 2H), 1.82(d, J = 7.3 Hz, 3H), 1.68 (q, J = 5.7, 3.9 Hz, 8H), 1.61-1.48 (m, 2H), -1.89 (s, 1H).

[0203] Synthesis Example 3 – Synthesis of pyromethoxyphylla α-9-N-(methyl-5-triphenylphosphonopentanamide) methyl ester (Compound 3) Step 1: Add pyrophyllophosphinate α-9-formylmethyl ester (0.22 g, 1 equivalent), DCM (2 mL), methanol (8 mL), TEA (202 mg, 5 equivalent), and methylamine hydrochloride (134 mg, 5 equivalent) to 250 mL RBF. Stir the resulting mixture in the dark under nitrogen for 1 hour, then add TEA (202 mg, 5 equivalent) and a 4 Å sieve (100 mg), and continue stirring for 3 hours. Add NaCNBH4 (251 mg, 10 equivalent), and continue stirring overnight. Acidify the reaction mixture with 2 M HCl (1 mL) and stir for 10 minutes. Add phosphate buffer (pH=7, 15 mL) and extract the mixture with DCM. Dry the combined organic matter (Na2SO4) and concentrate by rotary evaporation to give a dark green residue. Purify the residue by column chromatography using a solution of 1–8% MeOH / DCM as the eluent. The main dark green band (R in 10% MeOH / DCM) was observed. f =0.30) was concentrated to obtain pyromethoxyphylla α-9-N-methylaminomethyl ester (90 mg, purity of 86.90% as determined by HPLC), which is a dark green solid.

[0204] 1H NMR (400 MHz, CDCl3) δ 9.20 (s, 1H), 9.10 (s, 1H), 8.90 (s, 1H), 8.30 (s, 1H), 4.72 (br m, 2H), 4.00 (m, 2H), 3.42 (s, 3H), 3.10 (m, 4H), 3.00(s, 3H), 2.59-2.38 (m, 6H), 2.20 (m, 2H), 1.96-1.86 (m, 2H), 1.50-1.40 (m,9H), 0.60 (m, 4H), -2.32 (brs, 1H), -2.55 (brs, 1H).

[0205] Step 2: Add pyrophyllophosphinate α-9-N-methylaminomethyl ester (70 mg, 0.123 mmol, 1 equivalent), 4-(carboxybutyl)triphenylphosphonium bromide (109 mg, 0.247 mmol, 2 equivalents), triethylamine (37 mg, 0.371 mmol, 3 equivalents), DCM (5 mL), and DMTMM (72 mg, 0.247 mmol, 2 equivalents) to 50 mL of RBF. Stir the resulting mixture in the dark at 25 °C (400 rpm) for 2 hours under nitrogen. Transfer the reaction mixture to a separatory funnel, dilute with DCM (50 mL), and wash with 0.5 M HCl (20 mL). Re-extract the aqueous layer with DCM, and wash the combined organic phase with pH 7 phosphate buffer (20 mL), followed by washing with 1 M NaHCO3 (10 mL). Dry the organic phase (Na2SO4) and concentrate by rotary evaporation to give a blue-black membrane (approximately 100 mg). The residue was subjected to column chromatography. The crude product was dissolved in 4% MeOH / DCM and eluted using a gradient of 4-7% MeOH / DCM. The samples containing the product (mainly dark green spots, in 7% MeOH / DCM) were combined. R f The fraction was divided into fractions of 0.3 to obtain compound 3 (45 mg, purity 68.02% as determined by HPLC), which was a dark green solid.

[0206] 1 H NMR (400 MHz, chloroform-) d) δ 9.60 (s, 1H), 9.32 (s, 1H), 8.60-8.40 (m, 2H), 7.88-7.79 (m, 2H), 7.76-7.58 (m, 15H), 7.40-7.30 (m, 2H), 5.60 (s, 2H),4.59-4.54 (m, 1H), 4.51 (q, 1H), 3.89 (s, 3H), 3.90-3.75 (m, 4H), 3.64 (s,3H), 3.57 (s, 4H), 3.46 (s, 3H), 3.10 (s, 4H), 2.90 (s, 3H), 2.78 (t, 2H),2.63-2.44 (m, 2H), 2.23-1.99 (m, 3H), 1.90-1.80 (m, 1H), 1.78 (d, 3H), 1.74-1.64 (m, 8H), -2.22 (s, 1H), -2.32 (s, 1H).

[0207] Synthesis Example 4 – Synthesis of pyromethoxyphylla α-9-(N-3-triphenylphosphonium propyl bromide)aminomethyl methyl ester (Compound 4) Add pyrophyllophosphinate α-9-formylmethyl ester (220 mg, 0.399 mmol, 1 equivalent), DCM (2 mL), MeOH (8 mL), (3-aminopropyl)triphenylphosphonium bromide (479 mg, 3 equivalent), sodium cyanoborohydride (150 mg, 2.397 mmol, 6 equivalent), and 200 mg of 4 Å sieve to 50 mL of RBF. Stir the resulting mixture at 22 °C under nitrogen. Add water (10 mL), stir the mixture for 10 min, and then extract with DCM. Wash the combined organic extracts with saturated NaHCO3, dry to (Na2SO4), and concentrate by rotary evaporation to give a dark green residue. Perform column chromatography on the residue. Dissolve the crude product in 3% MeOH / DCM and elute using a gradient of 3–5% MeOH / DCM. Combine the extracts containing the product (mainly dark green spots, in 5% MeOH / DCM). R f The fraction was divided into fractions of 0.20 and 0.20 to obtain compound 4 (66 mg, purity 90.63% as determined by HPLC), which was a dark green solid.

[0208] 1H NMR (400 MHz, CDCl3) δ 9.40 (s, 1H), 9.30 (s, 1H), 8.60 (s, 1H), 7.31-7.26 (m, 3H), 7.13-7.06 (m, 12H), 5.12 (br m, 2H), 4.59-4.47 (m, 2H), 4.00 (m, 4H), 3.67 (m, 8H), 3.20 (m, 4H), 3.12 (s, 3H), 3.00 (m, 5H), 2.66-2.48 (m, 3H), 2.24-2.17 (m, 1H), 2.15-1.95 (m, 3H), 1.80-1.60 (m, 6H), 1.50(t, 4H), -1.98(br m, 1H).

[0209] Synthesis Example 5 – Synthesis of pyromethoxyphylla α-9-(N-3-triphenylphosphonium propyl bromide ethyl carbamate) aminomethyl methyl ester (Compound 5) Add pyrophyllophosphochlorophyllin a-9-(N-3-triphenylphosphonium propyl bromide)aminomethyl methyl ester (compound 4) (50 mg, 0.0496 mmol, 1 equivalent), DCM (3 mL), and diethyl dicarbonate (40 mg, 0.248 mmol, 5 equivalent) to 25 mL of RBF. The resulting mixture was stirred under nitrogen at ambient temperature. After 30 minutes, the reaction mixture was concentrated under reduced pressure to give a blue-black oil (approximately 80 mg). The residue was subjected to column chromatography. The crude product was dissolved in 3% MeOH / DCM and eluted using a gradient of 3–4% MeOH / DCM. The mixtures containing the product (in 5% MeOH / DCM) were combined. R f The fraction was divided into fractions of 0.15 to obtain compound 5 (35 mg, purity 90.41% as determined by HPLC), which was a dark green solid.

[0210] 1H NMR(400 MHz, CDCl3) δ 9.55 (s, 2H), 9.40 (s, 1H), 8.60 (s, 1H), 6.70-6.42 (m, 15H), 5.71 (s, 2H), 5.30 (m, 4H), 4.65-4.52 (m, 3H), 4.50 (m,2H), 4.20 (m, 6H), 3.81 (m, 2H), 3.68-3.63 (m, 9H), 3.46 (s, 3H), 3.22-3.13(m, 3H), 2.75-2.65 (m, 2H), 2.60-2.50 (m, 2H), 2.40-2.30 (m, 3H), 2.00-1.91 (m, 3H), 1.83-1.79 (m, 3H), 1.75-1.55 (m, 9H), -2.41 (br m, 2H).

[0211] Biological Experiment Details Example 1 – Cytotoxicity, Phototoxicity, and Therapeutic Index Preparation of photosensitizer stock solution The photosensitizer (e.g., pyrophyllin a analog, disodium dihydroporphyrin E4 (provided by Advanced Molecular Technologies, Scoresby), or tarapofen sodium (purchased from Focus Bioscience, catalog number HY-16477-5MG)) was resuspended at 5.5 mM in 100% dimethyl sulfoxide (DMSO). The sample was stored at 4°C protected from light.

[0212] Preparation of photosensitizers for in vitro studies For in vitro experiments, the photosensitizer (5.5 mM stock solution in 100% DMSO) was diluted 1:100 in the concentrated excipient solution (final 55 µM photosensitizer in 10% w / v Kollidon-12, 42.4% w / v polysorbate 80, 0.6% w / v anhydrous citric acid, 40% w / v ethanol, and 1.0% DMSO). Continuous dilutions were prepared at a constant 1:55 dilution in cell culture medium (Dürbeco modified Eagle's medium / nutrient mixture F-12 (DMEM / F-12)) supplemented with 10% v / v fetal bovine serum, 100 U / mL penicillin, 100 μg / mL streptomycin, and the same excipient solution.

[0213] Cell culture Human ovarian cancer cell line SKOV3 (ATCC #HTB-77) was kept in Durbecox 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 and 5% CO2. Once cells reached approximately 80% confluence, the used medium was replaced with medium containing the desired concentration of photosensitizer, and the cells were incubated for the required period to allow for photosensitizer uptake.

[0214] Statistical analysis All data were analyzed using GraphPad PRISM v8.3.1 (549) (GraphPad Software, CA). Spectroscopic absorbance and activity measurements were normalized to 0%–100%, with a minimum of 0 and maximum values ​​determined by the dataset. Dose-response was determined using a sigmoid four-point nonlinear regression with a variable slope, and IC10 or IC90 was calculated for each compound. All data are presented as mean ± SD (where appropriate).

[0215] Cytotoxicity SKOV3 cells were seeded at a density of 5000 cells per well in 100 μl of medium in 96-well black-walled plates (Greiner #655090). When approximately 60% confluence was reached, the medium was aspirated and replaced with fresh medium containing 0–100 µM of the associated pyrophyllin a analogue in DMSO. The cells were then incubated for another 24 hours to allow them to absorb the pyrophyllin a analogue.

[0216] To test the inherent cytotoxicity (i.e., “dark toxicity”) of pyrophyllin a analogues, the medium was replaced with fresh medium containing 10% (v / v) AlamarBlue cell viability reagent (ThermoFisher) after 24 hours, and the cells were incubated at 37°C for 6 hours. Untreated cells served as controls. Fluorescence (Ex 555nm / Em 596nm) was measured using a Cytation 3 Cell Imaging Multimode Reader (Biotek) or a CLARIOstar Plus Microplate Reader (BMG Labtech), and cytotoxicity was assessed based on the percentage of viable cells remaining. All measurements were performed in quadruplicate.

[0217] Phototoxicity SKOV3 cells were seeded at a density of 5000 cells per well in 100 μl of medium in 96-well black-walled plates (Greiner #655090). When approximately 60% confluence was reached, the medium was aspirated and replaced with fresh medium containing 0–100 µM of the associated pyrophyllin a analogue in DMSO. The cells were then incubated for another 24 hours to allow them to absorb the pyrophyllin a analogue.

[0218] To test phototoxicity, cells incubated with a pyrophyllin a analogue (0-20 μM in DMSO) were replaced with a different medium (as described above) after 24 hours and then exposed to a light power density of 50 mW / cm². 2 A 660nm laser (Invion) ​​or light-emitting diode (LED) panel (Invion) ​​for 5 minutes (total 15J / cm²) 2 Laser and LED exposure induced equivalent responses to phototoxicity. After activation, cells were cultured for another 24 hours. The medium was then replaced with fresh medium containing AlamarBlue, and the percentage of viable cells remaining was assessed as described above. Controls included cells treated with pyrophyllin a analogue but not laser-activated; cells treated with laser but not with pyrophyllin a analogue; and untreated controls. All measurements were performed in quadruplicate.

[0219] Toxicity characteristics of pyrophyllite a analogues As previously described, the phototoxicity and inherent cytotoxicity (i.e., “dark toxicity”) of pyromethoxyphylla analogues were evaluated using SKOV3 ovarian cancer cells. For comparative purposes, pyromethoxyphylla analogues were compared with disodium dihydroporphyrin E4 and tarapophene sodium (a clinically approved photosensitizer for photodynamic therapy of lung cancer). The phototoxicity IC90 and dark toxicity IC10 values ​​were calculated using log[inhibitor]-contrast normalized response-dose curves with variable slopes, using the formulas Y = 100 / (1 + (IC90 / X)^Hill slope (phototoxicity IC90)) or Y = 100 / (1 + (IC10 / X)^Hill slope (dark toxicity IC10)).

[0220] Table 1 provides phototoxicity and dark toxicity values. The IC90 of pyrophyllite a analogues was significantly superior to that of disodium dihydroporphyrin E4 (IC90 21.32 µM) or tarapofen sodium (IC90 22.83 µM). Therefore, compared with the clinically approved photosensitizer tarapofen sodium, pyrophyllite a analogues achieved a phototoxicity increase of up to approximately 11,000-fold.

[0221] Significant differences in dark toxicity were observed in the pyromethoxyphylla a analogs of the present invention (Table 1). However, it is anticipated that the greater phototoxicity provided by the pyromethoxyphylla a analogs of the present invention will offset any dark toxicity issues by reducing the dosage requirements in use.

[0222] The therapeutic index of pyrophylloxera a analogues To assess the therapeutic potential of pyrophyllin a analogues, the Therapeutic Index (TI) was calculated. TI provides a quantitative measure of relative drug safety by comparing the drug concentration required for optimal efficacy with the concentration that leads to adverse off-target toxicity. TI was calculated using the phototoxicity IC90 versus the dark toxicity IC10.

[0223] The therapeutic index (TI) values ​​are provided in Table 1. Tarapofen sodium has a low therapeutic index (TI = 0.49), and dihydroporphyrin e4 disodium is only slightly better (TI = 1.89), indicating that although it has relatively low cytotoxicity, its potential therapeutic window is small. The pyrophyllite a analogue of the present invention has a relatively significantly improved TI and significantly greater phototoxicity (Table 1).

[0224] Therefore, the pyrophyllin a analogues of the present invention have a better desired therapeutic index than photosensitizers used clinically. Furthermore, the greater phototoxicity of the pyrophyllin a analogues indicates their potential for use in vivo at significantly reduced doses. Therefore, the pyrophyllin a analogues possess acceptable therapeutic characteristics for clinical application.

[0225] Table 1. Toxicity characteristics and therapeutic index of pyrophyllate a analogues: It should be understood that the invention has been described above by way of example only. The embodiments described are not intended to limit the scope of the invention. Various modifications and implementations can be made without departing from the scope and spirit of the invention, which is defined only by the appended claims.

Claims

1. A compound of formula (I) or a complex of formula (II): Or its pharmaceutically acceptable salt, 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 [[ID= for]], -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 ​​​​​​​​​​​​​​​​​​​​​​​​ -R 3 and -R 4 Each is 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 7 Y、-R α -[N(R 5 )2(R 5’ )]、-R α -[P(R 5 )2(R 5’ )] or -R α -[R 7’ ]; -R α - Each is independently selected from C1-C 42 Alkylene, wherein the alkylene can be optionally substituted with one or more C1-C4 alkyl, C1-C4 haloalkyl or halogroup, and wherein one or more carbon atoms in the main chain of the alkylene can be optionally substituted with heteroatoms or groups independently selected from O, S, NH or NMe; -R β Each is independently a saturated or unsaturated hydrocarbon group, wherein the hydrocarbon group can be straight-chain or branched, or can be or include cyclic groups, wherein the hydrocarbon group can optionally be substituted, and wherein the hydrocarbon group can optionally include one or more heteroatoms N, O, S, P or Se in its carbon skeleton. -R 5 Each is independently selected from C1-C4 alkyl, C1-C4 haloalkyl, and -(CH2CH2O). n -H, -(CH2CH2O) n -CH3, phenyl, or C5-C6 heteroaryl, wherein the phenyl or C5-C6 heteroaryl group can optionally be replaced by one or more C1-C6 alkyl, C1-C6 haloalkyl, -O(C1-C6 alkyl), -O(C1-C6 haloalkyl), halogroup, -CO2H, -CO2Z, -CO2NH2, or -O-(CH2CH2O). n -H or -O-(CH2CH2O) n -CH3 group substitution; -R 5’ Selected from C1-C4 alkyl, C1-C4 haloalkyl, and -(CH2CH2O) n -H, -(CH2CH2O) n -CH3, phenyl, or C5-C6 heteroaryl groups, each bonded by -CO2 - The phenyl or C5-C6 heteroaryl group may optionally be further replaced by one or more C1-C6 alkyl, C1-C6 haloalkyl, -O(C1-C6 alkyl), -O(C1-C6 haloalkyl), halogen, -CO2H, -CO2Z, -CO2NH2, -O-(CH2CH2O). n -H or -O-(CH2CH2O) n -CH3 group substitution; -R 6 Selected from -OR 2 -N(R) 2 )2、-SR 2 -S(O)R 2 -S(O)2R 2 Or -X; -R 7 It is -[NC5H5], which is optionally separated by one or more C1-C6 alkyl, C1-C6 haloalkyl, -O(C1-C6 alkyl), -O(C1-C6 haloalkyl), halogen, -CO2H, -CO2Z, -CO2NH2, -O-(CH2CH2O). n -H or -O-(CH2CH2O) n -CH3 group substitution; -R 7’ It is -[NC5H5], which is affected by -CO2 - It is substituted, and optionally further replaced by one or more C1-C6 alkyl, C1-C6 haloalkyl, -O(C1-C6 alkyl), -O(C1-C6 haloalkyl), halogen, -CO2H, -CO2Z, -CO2NH2, -O-(CH2CH2O). n -H or -O-(CH2CH2O) n -CH3 group substitution; n is 1, 2, 3, 4, 5, or 6; X is a halogroup; Y is a counteracting anion; Z is a counter cation; and M 2+ It is a metal cation; The condition is that the compound of formula (I) or the complex of formula (II) contains a component selected from -R α -[P(R 5 )3]Y、-R α -[R 7 Y、-R α -[P(R 5 )2(R 5’ )] or -R α -[R 7’ At least one group of ].

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

3. The compound or complex according to any of the preceding claims, wherein -R 6 Selected from -OC(O)R 14 -N(R) 12 )-C(O)R 14 -OC(O)-OR 14 -N(R) 12 )-C(O)-OR 14 -OC(O)-N(R) 12 (R) 14 ) or -N(R 12 )-C(O)-N(R 12 (R) 14 -R 12 Selected from hydrogen or C1-C3 alkyl; -R 14 Selected from -R α -[P(R 5 )3]Y、-R α -[R 7 Y、-R α -[P(R 5 )2(R 5’ )] or -R α -[R 7’ ]; Each -R 5 Independently selected from C1-C4 alkyl or phenyl, wherein the phenyl is optionally substituted with one, two, or three C1-C4 alkyl or C1-C4 alkoxy groups; each -R 5’ Selected from C1-C4 alkyl or phenyl groups, each coated with -CO2 - Substitution, wherein the phenyl group is optionally further substituted with one, two, or three C1-C4 alkyl or C1-C4 alkoxy groups; -R 7 It is -[NC5H5], which is optionally substituted with one, two, or three C1-C4 alkyl or C1-C4 alkoxy groups; -R 7’ It is -[NC5H5], which is affected by -CO2 - Substitution, and optionally further substituted with one, two, or three C1-C4 alkyl or C1-C4 alkoxy groups; -R α -Selected from C1-C 12 Alkylene, wherein one, two, three, or four carbon atoms in the main chain of the alkylene can optionally be replaced by heteroatoms or groups independently selected from O, S, NH, or NMe; and Y is a counterion.

4. The compound or complex according to any of the preceding claims, wherein -R 1 It is -C(O)-OR 3 -R 3 Yes -R β And -R β It is a C1-C4 alkyl group.

5. The compound or complex according to claim 1, wherein the compound or complex is: Or its metal cation complex or its pharmaceutically acceptable salt.

6. The compound or complex according to any of the preceding claims, wherein the compound or complex is used in medicine.

7. The compound or complex according to any of the preceding claims, wherein the compound or complex is used in photodynamic therapy or chemiluminescence therapy.

8. The compound or complex according to any of the preceding claims, wherein the compound or complex is used to treat atherosclerosis; multiple sclerosis; diabetes; diabetic retinopathy; arthritis; rheumatoid arthritis; fungal, viral, chlamydial, bacterial, nanobacterial, or parasitic infections; 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 areas of neovascularization; benign or malignant tumors; early-stage cancers; cervical dysplasia; soft tissue sarcoma; germ cell tumors; retinoblastoma; age-related Age-related macular degeneration; lymphoma; Hodgkin's lymphoma; head and neck cancer; oral or pharyngeal cancer; or blood cancer, prostate cancer, cervical cancer, uterine cancer, vaginal cancer or other female adnexal 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, ureteral cancer, kidney cancer, liver cancer, gallbladder cancer, spleen cancer, brain cancer, lymphatic system cancer, bone cancer, skin cancer, or pancreatic cancer.

9. The compound or complex according to any of the preceding claims, said compound or complex for treating diseases characterized by excessive proliferation of benign or malignant cells or by areas of neovascularization.

10. The compound or complex according to any of the preceding claims, wherein the compound or complex is used to treat benign or malignant tumors.

11. The compound or complex according to any of the preceding claims, wherein the compound or complex is used to treat 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 stomach cancer; or leukemia, prostate cancer, cervical cancer, uterine cancer, vaginal cancer or other female adnexal cancer, breast cancer, nasopharyngeal carcinoma, tracheal cancer, laryngeal cancer, bronchial cancer, bronchiolar cancer, lung cancer, hollow organ cancer, esophageal cancer, gastric cancer, bile duct cancer, intestinal cancer, colon cancer, colorectal cancer, rectal cancer, bladder cancer, ureteral cancer, kidney cancer, liver cancer, gallbladder cancer, spleen cancer, brain cancer, lymphatic system cancer, bone cancer, skin cancer, or pancreatic cancer.

12. The compound or complex according to any of the preceding claims, wherein the compound or complex is used in photodynamic diagnostics.

13. The compound or complex according to any of the preceding claims, wherein the compound is suitable for application prior to irradiation.

14. The compound or complex according to claim 13, wherein the irradiation is electromagnetic radiation with a wavelength in the range of 500 nm to 1000 nm.

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

16. The pharmaceutical composition of claim 15, wherein the pharmaceutical composition further comprises polyvinylpyrrolidone.

17. The pharmaceutical composition according to claim 15 or 16, wherein the pharmaceutical composition further comprises an immune checkpoint inhibitor.

18. The pharmaceutical composition of claim 17, wherein the immune checkpoint inhibitor is selected from pembrolizumab, nivolumab, cimiprilumab, atezolizumab, avelumab, durvalumab, or ipilimumab.

19. The pharmaceutical composition according to any one of claims 15 to 18, wherein the pharmaceutical composition is in a form suitable for oral, parenteral (including intravenous, subcutaneous, intramuscular, intradermal, intratracheal, intraperitoneal, intratumoral, intra-articular, intra-abdominal, intracranial, and epidural), transdermal, airway (aerosol), rectal, vaginal, or local (including buccal, mucosal, and sublingual) administration.

20. The pharmaceutical composition of claim 19, wherein the pharmaceutical composition is in a form suitable for oral or parenteral administration.

21. A drug combination or pillbox, said drug combination or pillbox comprising: (a) The compound or complex according to any one of claims 1 to 14; and (b) As a combination of immune checkpoint inhibitors.

22. The drug combination or kit according to claim 21, wherein the immune checkpoint inhibitor is selected from pembrolizumab, nivolumab, cimipril, atezolizumab, avelumab, durvalumab, or ipilimumab.

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