Mesodiaryl tetra-acenaphthene porphyrin compound, mesodiaryl tetra-acenaphthene porphyrin complex, preparation method and application of mesodiaryl tetra-acenaphthene porphyrin complex, pharmaceutical composition and application of pharmaceutical composition

Abstract

The invention provides an intermediary diaryl tetra-acenaphthene porphyrin compound, an intermediary diaryl tetra-acenaphthene porphyrin complex, a preparation method and application of the intermediary diaryl tetra-acenaphthene porphyrin compound and the intermediary diaryl tetra-acenaphthene porphyrin complex, a pharmaceutical composition and application of the pharmaceutical According to the invention, a polar group is introduced as a hydrophilic group at the intermediate phenyl group of the intermediate diaryl tetra-acenaphthene porphyrin compound, so that the hydrophilicity of the compound is improved, the aggregation capability of the compound is inhibited, and the compound is stable in structure, good in water solubility and not easy to aggregate. The beta-position condensed acenaphthene ring of the porphyrin increases the conjugated system of the porphyrin, so that the absorption spectrum of the porphyrin has a certain degree of red shift, the infrared region absorption is strong, the singlet oxygen generation rate and the photodynamic biological activity of the porphyrin are greatly improved, the photodynamic activity is high, and the porphyrin derivative has good application prospects in the field of medicines. Particularly, the compound can be used for preparing photosensitive medicines for photodynamically diagnosing and treating diseases such as tumors, retina macular degeneration, actinic keratosis, nevus flammeus and condyloma acuminata, and has a good application prospect.

Description

Technical Field

[0001] The present invention relates to the field of medical technology, and in particular to an intermediate diaryl tetraacenaphthoporphyrin compound, an intermediate diaryl tetraacenaphthoporphyrin complex, a preparation method and application thereof, a pharmaceutical composition and application thereof. Background Art

[0002] Nowadays, cancer poses a serious threat to human health. Photodynamic therapy (PDT) is booming as a promising new method for tumor diagnosis and treatment. The principle is that after the photosensitizer is injected intravenously into the human body, a laser of a specific wavelength is used to directly irradiate the tumor site, eventually producing reactive oxygen (such as singlet oxygen) and killing tumor cells. Among them, photosensitizers, as the core element of photodynamic therapy, play a leading role in the entire PDT. The research and development of new photosensitizers has become a top priority in the development of photodynamic therapy.

[0003] Although photodynamic therapy has been developed for more than 100 years, there are only a few photosensitizing drugs on the market, and most of them are porphyrin compounds. In addition, these photosensitizing drugs also have different disadvantages, such as non-single components, weak absorption in the infrared region, strong skin phototoxicity, and high prices.

[0004] Mesodiaryl tetraacenaphthene porphyrins are a class of novel π-extended porphyrin compounds. Compared with traditional porphyrin compounds and mesodiaryl tetraacenaphthene porphyrin compounds, they have better photophysical and photochemical properties and have greater potential for development into photosensitizing drugs. Existing mesodiaryl tetraacenaphthene porphyrin derivatives are prone to self-aggregation or self-assembly, which causes a significant decrease in the solubility of the compound, making it difficult to dissolve in various solvents and difficult to prepare into preparations, which seriously affects its drugability and application in photodynamic therapy. Summary of the invention

[0005] In view of this, the object of the present invention is to provide an intermediate diaryl tetraacenaphthoporphyrin compound, an intermediate diaryl tetraacenaphthoporphyrin complex, and a preparation method and application thereof, a pharmaceutical composition and application thereof. The intermediate diaryl tetraacenaphthoporphyrin compound and the intermediate diaryl tetraacenaphthoporphyrin complex provided by the present invention have the advantages of stable properties, good water solubility, strong infrared absorption, high singlet oxygen yield, high photodynamic activity and other drug-forming properties.

[0006] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0007] The present invention provides a mesogenic diaryl tetraacenaphthoporphyrin compound having a structure shown in Formula I:

[0008]

[0009] wherein R1, R2 and R3 independently include polar groups or non-polar groups, and at least one of R1, R2 and R3 is a polar group;

[0010] The polar group contains one or more of carboxyl, hydroxyl and amino groups; the non-polar group does not contain carboxyl, hydroxyl or amino groups;

[0011] The non-polar group includes: hydrogen, halogen, alkyl, alkyl containing heteroatom, alkyl containing carbonyl or alkyl containing amide bond.

[0012] Preferably, the polar group comprises a carboxyl group, an alkyl carboxylic acid group, an alkyl carboxylic acid group containing a heteroatom, an alkyl carboxylic acid group containing a carbonyl group and / or an amide group, a hydroxyl group, an alkyl alcohol group, an alkyl alcohol group containing a heteroatom, an alkyl alcohol group containing a carbonyl group and / or an amide group, a phenol group, an alkyl phenol group, an alkyl phenol group containing a heteroatom, and a phenol group containing a carbonyl group and / or an amide group;

[0013] The heteroatom in the heteroatom-containing alkylcarboxylic acid group, the heteroatom-containing alkyl alcohol group and the heteroatom-containing alkylphenol group independently includes O or N.

[0014] Preferably, the alkyl carboxylic acid group comprises -(CH2) m COOH or -(CH2) m CH(CH3)COOH;

[0015] The heteroatom-containing alkyl carboxylic acid group includes -(CH2) m N[(CH2) n COOH]2 or -(CH2) m O(CH2) n COOH;

[0016] The alkyl carboxylic acid group containing a carbonyl group and / or an amide group includes -(CH2) m CO(CH2) n COOH or amino acid derivatives;

[0017] The alkyl alcohol group includes -(CH2) m OH or -(CH2) m CH(CH3)OH;

[0018] The heteroatom-containing alkyl alcohol group includes -(CH2) m N[(CH2) n OH]2, -(CH2) m O(CH2) n OH or -(CH2) m (OCH2CH2) p OH;

[0019] The alkyl alcohol group containing a carbonyl group and / or an amide group includes -(CH2) m CO(CH2) n OH or -(CH2) m CONH(CH2) n OH;

[0020] The alkylphenol group includes -(CH2) m C6H4OH;

[0021] Here, m is independently an integer of 0-7, n is independently an integer of 1-7, and p is an integer of 1-3.

[0022] Preferably, the amino acid derivative comprises -(CH2) c CONH(CH2) c COOH, -(CH2) c CONHCH(CH3)COOH, -(CH2) c CONH(CH2) c CO(CH2) c COOH, -(CH2) c CONHCH[CH(CH3)2]COOH, -(CH2) c CONHCH[CH2CH(CH3)2]COOH、-(CH2) c CONHCH[CH(CH3)CH2CH3]COOH, -(CH2) c CONHCH(CH2C6H5)COOH, -(CH2) c CON[(CH2) c COOH]2, -(CH2) c CONHCH(COOH)CH2COOH, wherein c is independently an integer of 0-7.

[0023] Preferably, the non-polar group includes -H, -F, -Cl, -Br, -I, -(CH2) a CH3, -(CH2) a CH(CH3)2, -(CH2) a C(CH3)3, -(CH2) a N[(CH2) b CH3]2, -(CH2) a O(CH2) b CH3, -(CH2) a O(CH2) b CH(CH3)2, -(CH2) a O(CH2) bC(CH3)3, -(CH2) a (OCH2CH2) q CH3, -(CH2) a CO(CH2) b CH3, -(CH2) a CO(CH2) b CH(CH3)2, -(CH2) a CO(CH2) b C(CH3)3, -(CH2) a CONH(CH2) b CH3, -(CH2) a CONH(CH2) b CH(CH3)2 or -(CH2) a CONH(CH2) b C(CH3)3, wherein a is independently an integer of 0 to 7, b is independently an integer of 1 to 7, and q is an integer of 1 to 3.

[0024] The present invention provides a method for preparing the mesogenic diaryl tetraacenaphthoporphyrin compound described in the above technical solution, comprising the following steps:

[0025] Compound VII is subjected to a cyclization-oxidation reaction with compound IX in the presence of a catalyst and an oxidant to obtain compound VIII;

[0026] The compound VIII is subjected to a deprotection reaction to obtain the intermediate diaryl tetraacenaphthene porphyrin compound;

[0027]

[0028] Among them, R4 is R1 containing an ester group or an acetyl protecting group, R5 is R2 containing an ester group or an acetyl protecting group, and R6 is R3 containing an ester group or an acetyl protecting group.

[0029] The present invention also provides a mesogenic diaryl tetraacenaphthenoporphyrin complex having a structure shown in Formula I';

[0030]

[0031] Wherein, M is hydrogen or metal;

[0032] R1, R2 and R3 are of the same type as R1, R2 and R3 in the intermediate diaryl tetraacenaphthoporphyrin compound described in the above technical solution.

[0033] The present invention provides a method for preparing the mesogenic diaryl tetraacenaphthoporphyrin complex described in the above technical solution, comprising the following steps:

[0034] The mesogenic diaryl tetraacenaphthene porphyrin compound described in the above technical solution is subjected to a coordination reaction with a metal source to obtain the mesogenic diaryl tetraacenaphthene porphyrin complex.

[0035] The present invention provides a pharmaceutical composition, comprising an active component and a pharmaceutically acceptable excipient; the active component comprises the mesogenic diaryl tetraacenaphthene porphyrin compound and / or the mesogenic diaryl tetraacenaphthene porphyrin complex described in the above technical solution.

[0036] The present invention provides the use of the mesogenic diaryl tetraacenaphthoporphyrin compound described in the above technical solution, the mesogenic diaryl tetraacenaphthoporphyrin complex described in the above technical solution or the pharmaceutical composition described in the above technical solution in the medical field.

[0037] The present invention introduces a polar group as a hydrophilic group at the intermediate phenyl of the intermediate diaryl tetraacenaphthene porphyrin compound, thereby improving the hydrophilicity of the compound and inhibiting the aggregation ability of the compound. The compound has a stable structure, good water solubility, and is not easy to aggregate. The β-position fused acenaphthene ring of the porphyrin increases the conjugated system of the porphyrin, causing its absorption spectrum to undergo a certain degree of red shift, with strong absorption in the infrared region, and greatly improving its singlet oxygen generation rate and photodynamic biological activity. The photodynamic activity is high, and it has a good application prospect in the field of medicine, especially in the preparation of photosensitizers for photodynamic diagnosis and treatment of tumors, retinal macular degeneration, actinic keratosis, port wine stains, condyloma acuminatum and other diseases.

[0038] The preparation method of the mesodial tetraacenaphthoporphyrin compound provided by the invention has the advantages of simple preparation process, low production cost, low pollution and is suitable for industrial production.

[0039] The mesogenic diaryl tetraacenaphthene porphyrin complex provided by the present invention has the advantages of the mesogenic diaryl tetraacenaphthene porphyrin compound. At the same time, the introduction of the metal M can increase the probability of the photosensitizer to undergo intersystem crossing, which is beneficial to 1 O2 production, and the additional introduction of copper or iron can induce copper death and ferroptosis in tumor cells, while the introduction of manganese can be used for magnetic resonance imaging.

[0040] The preparation method of the mesogenic diaryl tetraacenaphthoporphyrin complex provided by the invention has the advantages of simple preparation process, low production cost, low pollution and is suitable for industrial production. BRIEF DESCRIPTION OF THE DRAWINGS

[0041] Figure 1 Compound I 11 and I 17 ~I 21 UV-Vis absorption spectrum at 10 μM. DETAILED DESCRIPTION

[0042] The present invention provides a mesogenic diaryl tetraacenaphthoporphyrin compound having a structure shown in Formula I:

[0043]

[0044] wherein R1, R2 and R3 independently include polar groups or non-polar groups, and at least one of R1, R2 and R3 is a polar group;

[0045] The polar group contains one or more of carboxyl, hydroxyl and amino groups; the non-polar group does not contain carboxyl, hydroxyl or amino groups;

[0046] The non-polar group includes: hydrogen, halogen, alkyl, alkyl containing heteroatom, alkyl containing carbonyl or alkyl containing amide bond.

[0047] In the present invention, the polar group preferably includes a carboxyl group, an alkyl carboxylic acid group, an alkyl carboxylic acid group containing a heteroatom, an alkyl carboxylic acid group containing a carbonyl group and / or an amide group, a hydroxyl group, an alkyl alcohol group, an alkyl alcohol group containing a heteroatom, an alkyl alcohol group containing a carbonyl group and / or an amide group, a phenol group, an alkyl phenol group, an alkyl phenol group containing a heteroatom, and a phenol group containing a carbonyl group and / or an amide group; the heteroatoms in the alkyl carboxylic acid group containing a heteroatom, the alkyl alcohol group containing a heteroatom and the alkyl phenol group containing a heteroatom preferably independently include O or N.

[0048] In the present invention, the alkyl carboxylic acid group preferably includes -(CH2) m COOH or -(CH2) m CH(CH3)COOH; the heteroatom-containing alkyl carboxylic acid group preferably includes -(CH2) m N[(CH2) n COOH]2 or -(CH2) m O(CH2) n COOH; the alkyl carboxylic acid group containing a carbonyl group and / or an amide group preferably includes -(CH2) m CO(CH2) n COOH or amino acid derivatives; the alkyl alcohol group preferably includes -(CH2) m OH or -(CH2) m CH(CH3)OH; the heteroatom-containing alkyl alcohol group preferably includes -(CH2) m N[(CH2) n OH]2, -(CH2) m O(CH2) n OH or -(CH2) m (OCH2CH2) p OH; the alkyl alcohol group containing a carbonyl group and / or an amide group preferably includes -(CH2) mCO(CH2) n OH; the alkylphenol group preferably includes -(CH2) m C6H4OH or -(CH2) m CONH(CH2) n OH; wherein m is independently preferably an integer of 0 to 7, more preferably 0, 1, 2, 3, 4, 5, 6 or 7; n is independently preferably an integer of 1 to 7, more preferably 1, 2, 3, 4, 5, 6 or 7; p is preferably an integer of 1 to 3, more preferably 1, 2 or 3. In the present invention, the polar group more preferably includes carboxymethyloxy, carboxyethoxy, carboxypropoxy, carboxybutoxy, carboxypentyloxy, carboxyhexyloxy, carboxyheptyloxy, carboxyoctyloxy, hydroxyethoxy, 2-(2-hydroxyethoxy)ethoxy, (2-oxo-2-carboxymethylamino)ethoxy, [2-oxo-2-(2-oxo-4-carboxy)butylamino]ethoxy or [2-oxo-2-(N,N-dicarboxymethyl)amino]ethoxy.

[0049] In the present invention, the amino acid derivative preferably includes -(CH2) c CONH(CH2) c COOH, -(CH2) c CONHCH(CH3)COOH, -(CH2) c CONH(CH2) c CO(CH2) c COOH, -(CH2) c CONHCH[CH(CH3)2]COOH, -(CH2) c CONHCH[CH2CH(CH3)2]COOH、-(CH2) c CONHCH[CH(CH3)CH2CH3]COOH, -(CH2) c CONHCH(CH2C6H5)COOH, -(CH2) c CON[(CH2) c COOH]2, -(CH2) c CONHCH(COOH)CH2COOH; wherein c is independently preferably an integer from 0 to 7, more preferably 0, 1, 2, 3, 4, 5, 6 or 7.

[0050] In the present invention, the non-polar groups preferably include -H, -F, -Cl, -Br, -I, -(CH2) a CH3, -(CH2) a CH(CH3)2, -(CH2) a C(CH3)3, -(CH2) a N[(CH2) bCH3]2, -(CH2) a O(CH2) b CH3, -(CH2) a O(CH2) b CH(CH3)2, -(CH2) a O(CH2) b C(CH3)3, -(CH2) a (OCH2CH2) q CH3, -(CH2) a CO(CH2) b CH3, -(CH2) a CO(CH2) b CH(CH3)2, -(CH2) a CO(CH2) b C(CH3)3, -(CH2) a CONH(CH2) b CH3, -(CH2) a CONH(CH2) b CH(CH3)2 or -(CH2) a CONH(CH2) b C(CH3)3; wherein a is independently preferably an integer from 0 to 7, more preferably 0, 1, 2, 3, 4, 5, 6 or 7; b is independently preferably an integer from 1 to 7, more preferably 1, 2, 3, 4, 5, 6 or 7; q is an integer from 1 to 3, more preferably 1, 2 or 3.

[0051] In the present invention, the mesodiaryl tetraacenaphthenoporphyrin compound preferably includes I1 to I 41 The compound represented by any one of the items: 5,15-bis[(3-carboxymethyloxy)phenyl]tetraacenaphthoporphyrin (I1), 5,15-bis[(3-carboxyethoxy)phenyl]tetraacenaphthoporphyrin (I2), 5,15-bis[(3-carboxypropyloxy)phenyl]tetraacenaphthoporphyrin (I3), 5,15-bis[(3-carboxybutyloxy)phenyl]tetraacenaphthoporphyrin (I4), 5,15-bis[(3-carboxypentyloxy)phenyl]tetraacenaphthoporphyrin (I5), Porphyrin (I5), 5,15-bis[(3-carboxyhexyloxy)phenyl]tetraacenaphthoporphyrin (I6), 5,15-bis[(3-carboxyheptyloxy)phenyl]tetraacenaphthoporphyrin (I7), 5,15-bis[(4-carboxymethyloxy)phenyl]tetraacenaphthoporphyrin (I8), 5,15-bis[(4-carboxyethoxy)phenyl]tetraacenaphthoporphyrin (I9), 5,15-bis[(4-carboxypropyloxy)phenyl]tetraacenaphthoporphyrin (I10), 10 )、5,15-bis[(4-carboxybutyloxy)phenyl]tetraacenaphthoporphyrin (I 11 )、5,15-bis[(4-carboxypentyloxy)phenyl]tetraacenaphthoporphyrin (I12 )、5,15-bis[(4-carboxyhexyloxy)phenyl]tetraacenaphthoporphyrin (I 13 )、5,15-bis[(4-carboxyheptyloxy)phenyl]tetraacenaphthoporphyrin (I 14 )、5,15-bis[3,5-bis(carboxymethyloxy)phenyl]tetraacenaphthoporphyrin (I 15 )、5,15-bis[3,5-bis(carboxyethoxy)phenyl]tetraacenaphthoporphyrin (I 16 )、5,15-bis[3,5-bis(carboxypropyloxy)phenyl]tetraacenaphthoporphyrin (I 17 )、5,15-bis[3,5-bis(carboxybutyloxy)phenyl]tetraacenaphthoporphyrin (I 18 )、5,15-bis[3,5-bis(carboxypentyloxy)phenyl]tetraacenaphthoporphyrin (I 19 )、5,15-bis[3,5-bis(carboxyhexyloxy)phenyl]tetraacenaphthoporphyrin (I 20 )、5,15-bis[3,5-bis(carboxyheptyloxy)phenyl]tetraacenaphthoporphyrin (I 21 )、5,15-bis[3,5-bis(2-hydroxyethoxy)phenyl]tetraacenaphthoporphyrin (I 22 )、5,15-bis[3,5-bis(2-(2-hydroxyethoxy)ethoxy)phenyl]tetraacenaphthoporphyrin (I 23 )、5,15-bis[(3,5-dimethoxy-4-carboxybutyloxy)phenyl]tetraacenaphthoporphyrin (I 24 )、5,15-bis[(3,5-dimethoxy-4-carboxypentyloxy)phenyl]tetraacenaphthoporphyrin (I 25 )、5,15-bis[(3,5-dimethoxy-4-carboxyhexyloxy)phenyl]tetraacenaphthoporphyrin (I 26 )、5,15-bis[(3,5-dimethoxy-4-carboxyheptyloxy)phenyl]tetraacenaphthoporphyrin (I 27 )、5,15-bis[(3,5-dimethoxy-4-(2-hydroxyethoxy))phenyl]tetraacenaphthoporphyrin (I 28 )、5,15-bis[(3,5-diethoxy-4-carboxybutyloxy)phenyl]tetraacenaphthoporphyrin (I 29 )、5,15-bis[(3,5-diethoxy-4-carboxypentyloxy)phenyl]tetraacenaphthoporphyrin (I 30 )、5,15-bis[(3,5-diethoxy-4-carboxyhexyloxy)phenyl]tetraacenaphthoporphyrin (I 31 )、5,15-bis[(3,5-diethoxy-4-carboxyheptyloxy)phenyl]tetraacenaphthoporphyrin (I 32 )、5,15-bis[(3,5-diethoxy-4-(2-hydroxyethoxy))phenyl]tetraacenaphthoporphyrin (I 33)、5,15-bis[[3,5-dimethoxy-4-(2-oxo-2-carboxymethylamino)ethoxy]phenyl]tetraacenaphthoporphyrin (I 34 )、5,15-bis[[3,5-dimethoxy-4-[2-oxo-2-(2-oxo-4-carboxyl)butylamino]ethoxy]phenyl]tetraacenaphthoporphyrin (I 35 )、5,15-bis[[3,5-dimethoxy-4-[2-oxo-2-(N,N-dicarboxymethyl)amino]ethoxy]phenyl]tetraacenaphthoporphyrin (I 36 )、5,15-bis[(3-carboxyoctyloxy)phenyl]tetraacenaphthoporphyrin (I 37 )、5,15-bis[(4-carboxyoctyloxy)phenyl]tetraacenaphthoporphyrin (I 38 )、5,15-bis[3,5-bis(carboxyoctyloxy)phenyl]tetraacenaphthoporphyrin (I 39 )、5,15-bis[(3,5-dimethoxy-4-carboxyoctyloxy)phenyl]tetraacenaphthoporphyrin (I 40 ) or 5,15-bis[(3,5-diethoxy-4-carboxyoctyloxy)phenyl]tetraacenaphthoporphyrin (I 41 ).

[0052] The mesogenic diaryl tetraacenaphthene porphyrin compound provided by the present invention has the advantages of single component, stable structure, strong absorption in the red light region, high singlet oxygen generation rate, high photodynamic activity, good water solubility, etc., and overcomes the defects of existing photosensitizing compounds and photosensitizing drugs, such as complex composition, unstable structure, difficult preparation, high cost, weak absorption in the infrared region, easy aggregation, poor water solubility, etc., and has good application prospects in the preparation of drugs for photodynamic diagnosis and treatment of diseases such as tumors, retinal macular degeneration, actinic keratosis, port wine stains, condyloma acuminatum, etc.

[0053] The present invention provides a method for preparing the mesogenic diaryl tetraacenaphthoporphyrin compound described in the above technical solution, comprising the following steps:

[0054] Compound VII is subjected to a cyclization-oxidation reaction with compound IX in the presence of a catalyst and an oxidant to obtain compound VIII;

[0055] The compound VIII is subjected to a deprotection reaction to obtain the intermediate diaryl tetraacenaphthene porphyrin compound;

[0056]

[0057] Among them, R4 is R1 containing an ester group or an acetyl protecting group, R5 is R2 containing an ester group or an acetyl protecting group, and R6 is R3 containing an ester group or an acetyl protecting group.

[0058] In the present invention, the preparation route of the mesogenic diaryl tetraacenaphthene porphyrin compound is as follows:

[0059]

[0060] Unless otherwise specified, the materials and equipment used in the present invention are all commercially available products in the art.

[0061] The present invention conducts a cyclization-oxidation reaction between compound VII and compound IX in the presence of a catalyst and an oxidant to obtain compound VIII. Specifically, compound VII, compound IX, a first organic solvent and a catalyst are mixed, subjected to a cyclization reaction, and then an oxidant (referred to as the first oxidant) is added to conduct an oxidation reaction to obtain compound VIII.

[0062] In the present invention, the catalyst preferably includes trifluoroacetic acid and / or boron trifluoride etherate solution; the molar ratio of the compound VII to the catalyst is preferably 1:0.1-1, more preferably 1:0.2-0.4. The present invention has no particular limitation on the concentration of the boron trifluoride etherate solution, and a commercially available boron trifluoride etherate solution well known to those skilled in the art can be used.

[0063] In the present invention, the first organic solvent preferably includes dichloromethane (DCM). In the present invention, the usage ratio of the compound VII to the first organic solvent is preferably 1 mol: 100-500L, more preferably 1 mol: 290-300L.

[0064] In the present invention, the mixing of compound VII, compound IX, a first organic solvent and trifluoroacetic acid is preferably performed by dissolving compound VII and compound IX in the first organic solvent and then dropping trifluoroacetic acid under a protective atmosphere.

[0065] In the present invention, the cyclization-oxidation reaction is preferably carried out under stirring conditions; the cyclization-oxidation reaction is preferably carried out under light-shielding conditions; the cyclization-oxidation reaction is preferably carried out under a protective atmosphere; the protective atmosphere preferably includes nitrogen, argon or helium.

[0066] In the present invention, the temperature of the cyclization reaction is preferably room temperature, and the time is preferably 2 to 24 hours, more preferably 5 to 12 hours.

[0067] In the present invention, the first oxidant preferably comprises dichlorodicyanobenzoquinone (DDQ) and / or tetrachlorobenzoquinone. In the present invention, the molar ratio of the compound VII to the first oxidant is preferably 1:0.5-5, more preferably 1:1.5.

[0068] In the present invention, the temperature of the oxidation reaction is preferably room temperature, and the time is preferably 4 to 24 hours, more preferably 8 to 12 hours.

[0069] After the cyclization-oxidation reaction is completed, the present invention preferably further comprises: removing the solvent from the obtained cyclization-oxidation reaction solution under reduced pressure and then separating and purifying by silica gel column chromatography to obtain compound VIII. In the present invention, the eluent used for separation and purification by silica gel column chromatography preferably comprises petroleum ether-dichloromethane, and the volume ratio of petroleum ether to dichloromethane in the petroleum ether-dichloromethane is preferably 1:1-10, more preferably 1:3-5.

[0070] After obtaining compound VIII, the present invention performs a deprotection reaction on the compound VIII (referred to as the first deprotection reaction) to obtain the intermediate diaryl tetraacenaphthene porphyrin. Specifically, compound VIII, alkali solution and a second organic solvent are mixed and subjected to a deprotection reaction to obtain the intermediate diaryl tetraacenaphthene porphyrin compound.

[0071] In the present invention, the alkali solution preferably includes an aqueous solution of an alkali metal hydroxide; the concentration of the alkali solution is preferably 0.1 to 10 mol / L, more preferably 1 to 2 mol / L; the alkali metal hydroxide preferably includes one or more of potassium hydroxide, sodium hydroxide and lithium hydroxide; the molar ratio of the compound VIII to the alkali metal hydroxide is preferably 1:10 to 200, more preferably 1:50 to 150, and further preferably 1:100 to 125.

[0072] In the present invention, the second organic solvent preferably comprises a mixed solvent of tetrahydrofuran (THF) and methanol (MeOH), and the volume ratio of tetrahydrofuran to methanol is preferably 1:0.1-10, more preferably 1:1-2.

[0073] In the present invention, the first deprotection reaction is preferably carried out under reflux conditions, the time of the first deprotection reaction is preferably 1 to 24 hours, more preferably 3 to 6 hours, and in a specific embodiment, thin layer chromatography (TLC) is preferably used to monitor the progress of the first deprotection reaction, and the reaction is stopped when compound VIII is not detected; the first deprotection reaction is preferably carried out under a protective atmosphere, and the protective atmosphere preferably includes nitrogen, argon or helium; the first deprotection reaction is preferably carried out under stirring conditions.

[0074] After completing the first deprotection reaction, the present invention preferably further comprises: removing the organic solvent from the obtained first deprotection reaction solution under reduced pressure, adding water, adjusting the pH to 5-6 with dilute hydrochloric acid, filtering, and drying the obtained solid component to constant weight to obtain the mesodiaryl tetraacenaphthene porphyrinization. In the present invention, the concentration of the dilute hydrochloric acid is preferably 0.1-10 mol / L, more preferably 1-2 mol / L.

[0075] In the present invention, the compound VII is preferably a commercially available product or self-made. In the present invention, the preparation route of the compound VII is as follows:

[0076]

[0077] In the present invention, the preparation method of compound VII preferably comprises the following steps:

[0078] Mixing compound II, a second oxidant and a third organic solvent, and performing a dehydrogenation reaction to obtain compound III;

[0079] The compound III, benzenesulfonyl chloride, a copper catalyst, triethylamine hydrochloride and a fourth organic solvent are mixed to carry out a sulfonylation reaction to obtain a compound IV;

[0080] The compound IV, ethyl isocyanoacetate, 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU) and a sixth organic solvent are mixed and subjected to a Barton-Zard reaction to obtain a compound V;

[0081] The compound V, dimethoxymethane, p-toluenesulfonic acid and acetic acid are mixed to carry out a condensation reaction to obtain a compound VI;

[0082] The compound VI, an alkaline reagent and a seventh organic solvent are mixed and subjected to a second deprotection reaction to obtain a compound VII.

[0083] The present invention mixes compound II, a second oxidant and a third organic solvent, and performs a dehydrogenation reaction to obtain compound III.

[0084] In the present invention, the second oxidant preferably includes 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) and / or tetrachlorobenzoquinone. In the present invention, the molar ratio of the compound II to the second oxidant is preferably 1:0.5-5, more preferably 1:1-2.

[0085] In the present invention, the third organic solvent preferably includes one or more of toluene, benzene and N,N-dimethylformamide. The present invention has no special limitation on the amount of the third organic solvent, as long as it can ensure the smooth progress of the dehydrogenation reaction.

[0086] In the present invention, the dehydrogenation reaction is preferably carried out under reflux conditions, and the dehydrogenation reaction time is preferably 2 to 24 hours, more preferably 6 to 10 hours. In a specific embodiment, TLC is preferably used to monitor the reaction progress, and the reaction is stopped when compound II is not detected.

[0087] After the dehydrogenation reaction is completed, the present invention preferably further comprises: cooling the obtained dehydrogenation reaction liquid to room temperature, adding dichloromethane to dilute, washing with saturated sodium sulfite solution and saturated brine 2 to 3 times respectively, drying with anhydrous sodium sulfate, filtering, and removing the solvent under reduced pressure, and subjecting the obtained residue to silica gel column chromatography separation and purification to obtain compound III. In the present invention, the eluent used for the silica gel column chromatography separation and purification is preferably petroleum ether.

[0088] After obtaining compound III, the present invention mixes compound III, benzenesulfonyl chloride, a copper catalyst, triethylamine hydrochloride and a fourth organic solvent to carry out a sulfonylation reaction to obtain compound IV.

[0089] In the present invention, the molar ratio of the compound III to benzenesulfonyl chloride is preferably 1:1-10, more preferably 1:1-2.

[0090] In the present invention, the copper catalyst preferably includes copper halide, more preferably includes one or more of copper chloride, copper bromide and copper iodide. In the present invention, the molar ratio of the compound III to the copper catalyst is preferably 1:0.001-0.1, more preferably 1:0.01-0.02.

[0091] In the present invention, the molar ratio of the compound III to triethylamine hydrochloride is preferably 1:0.001-1, more preferably 1:0.01-0.015.

[0092] In the present invention, the fourth organic solvent preferably includes acetonitrile and / or tetrahydrofuran. The present invention has no particular limitation on the amount of the fourth organic solvent, as long as the amount can ensure the smooth progress of the sulfonylation reaction.

[0093] In the present invention, the temperature of the sulfonylation reaction is preferably 50 to 100° C., more preferably 70 to 75° C.; the time of the sulfonylation reaction is preferably 2 to 24 h, more preferably 4 to 8 h.

[0094] After the sulfonylation reaction is completed, the present invention preferably further comprises: cooling the obtained sulfonylation reaction liquid to room temperature, adding benzene for dilution, dripping triethylamine and stirring for 1 to 12 hours (more preferably 1 to 3 hours), filtering, and removing the solvent from the obtained liquid component under reduced pressure, and separating and purifying the obtained residue by silica gel column chromatography to obtain compound IV. In the present invention, the molar ratio of the compound III to triethylamine is preferably 1:1 to 5, more preferably 1:1 to 1.5. In the present invention, the eluent used for separation and purification by silica gel column chromatography preferably includes petroleum ether.

[0095] After obtaining compound IV, the present invention mixes compound IV, ethyl isocyanoacetate, 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU) and a sixth organic solvent to perform a Barton-Zard reaction to obtain compound V.

[0096] In the present invention, the molar ratio of the compound IV to ethyl isocyanoacetate is preferably 1:1-5, more preferably 1:1.5-2.

[0097] In the present invention, the molar ratio of the compound IV to 1,8-diazabicyclo[5,4,0]undec-7-ene is preferably 1:1-5, more preferably 1:1.5-2.

[0098] In the present invention, the fifth organic solvent preferably includes tetrahydrofuran and / or acetonitrile; the fifth organic solvent is preferably a dry fifth organic solvent. The present invention has no particular limitation on the amount of the fifth organic solvent, as long as it can ensure the smooth progress of the Barton-Zard reaction.

[0099] In the present invention, the mixing of the compound IV, ethyl isocyanoacetate, DBU and a sixth organic solvent preferably comprises: dissolving the compound IV in the sixth organic solvent, and adding DBU dropwise under a protective atmosphere.

[0100] In the present invention, the temperature of the Barton-Zard reaction is preferably room temperature; the time of the Barton-Zard reaction is preferably 2 to 24 hours, more preferably 5 to 8 hours; in a specific embodiment, TLC is preferably used to monitor the reaction progress, and the reaction is stopped when compound IV is not detected; the Barton-Zard reaction is preferably carried out under a protective atmosphere, and the protective atmosphere preferably includes nitrogen, argon or helium.

[0101] After completing the Barton-Zard reaction, the present invention preferably further comprises: removing the solvent from the obtained Barton-Zard reaction solution by rotary evaporation, dissolving the residue with ethyl acetate, washing with water and saturated brine in sequence, drying over anhydrous sodium sulfate, filtering to remove sodium sulfate, distilling off the solvent under reduced pressure, and subjecting the obtained residue to silica gel column chromatography separation and purification to obtain compound V. In the present invention, the eluent used for the silica gel column chromatography separation and purification preferably comprises petroleum ether-dichloromethane, and the volume ratio of petroleum ether to dichloromethane in the petroleum ether-dichloromethane is preferably 1:1-10, more preferably 1:3-5.

[0102] After obtaining compound V, the present invention mixes compound V, dimethoxymethane, p-toluenesulfonic acid and acetic acid to carry out a condensation reaction to obtain compound VI.

[0103] In the present invention, the molar ratio of the compound V to dimethoxymethane is preferably 1:0.5-10, more preferably 1:0.5-1.

[0104] In the present invention, the molar ratio of the compound V to p-toluenesulfonic acid is preferably 1:0.001-1, and more preferably 1:0.03-0.05.

[0105] In the present invention, the usage ratio of the compound V to acetic acid is preferably 1 mol: 1 to 10 L, more preferably 1 mol: 3 to 5 L.

[0106] In the present invention, the temperature of the condensation reaction is preferably room temperature; the time of the condensation reaction is preferably 2 to 24 hours, more preferably 5 to 12 hours; in a specific embodiment, TLC is preferably used to monitor the reaction progress, and the reaction is stopped when compound V is not detected.

[0107] After the condensation reaction is completed, the present invention preferably further comprises: pouring ice water into the obtained condensation reaction solution to generate a white precipitate, filtering, washing the filter cake with ice water, and drying to constant weight to obtain compound VI.

[0108] After obtaining compound VI, the present invention mixes the compound VI, an alkaline reagent and a seventh organic solvent to perform a second deprotection reaction to obtain compound VII.

[0109] In the present invention, the alkaline agent preferably comprises an alkali metal hydroxide, more preferably comprises KOH and / or NaOH. In the present invention, the molar ratio of the compound VI to the alkaline agent is preferably 1:10-50, more preferably 1:15-25.

[0110] In the present invention, the seventh organic solvent preferably includes ethylene glycol and N-methylpyrrolidone; the present invention has no special limitation on the amount of the seventh organic solvent, as long as it can ensure the smooth progress of the second deprotection reaction.

[0111] In the present invention, the second deprotection reaction is preferably carried out under reflux conditions; the time of the second deprotection reaction is preferably 1 to 10 hours, more preferably 1 to 3 hours; the second deprotection reaction is preferably carried out under a protective atmosphere, and the protective atmosphere preferably includes nitrogen, argon or helium.

[0112] After completing the second deprotection reaction, the present invention preferably further comprises: rapidly cooling the obtained second deprotection reaction solution to 0°C, adding ice water, ethyl acetate (EA extraction), washing the obtained organic layer with saturated brine, drying over anhydrous sodium sulfate, filtering, and removing the solvent under reduced pressure, and subjecting the obtained residue to silica gel column chromatography separation and purification to obtain compound VII. In the present invention, the eluent used for the silica gel column chromatography separation and purification preferably comprises petroleum ether-dichloromethane, and the volume ratio of petroleum ether to dichloromethane in the petroleum ether-dichloromethane is preferably 1:1-10, more preferably 1:3-5.

[0113] The present invention also provides a mesogenic diaryl tetraacenaphthenoporphyrin complex having a structure shown in Formula I';

[0114]

[0115] Wherein, M is hydrogen or a metal, preferably Ni, Cu, Zn, Pd or Pt;

[0116] R1, R2 and R3 are of the same type as R1, R2 and R3 in the intermediate diaryl tetraacenaphthoporphyrin compound described in the above technical solution.

[0117] The present invention also provides a method for preparing the intermediate diaryl tetraacenaphthene porphyrin complex described in the above technical scheme, comprising the following steps: mixing the compound VIII, a metal source and an eighth organic solvent, performing a coordination reaction, and then performing a deprotection reaction (referred to as the third deprotection reaction) to obtain the intermediate diaryl tetraacenaphthene porphyrin complex.

[0118] In the present invention, the metal source preferably includes a nickel source, a copper source, a zinc source, a palladium source or a platinum source; the nickel source preferably includes nickel acetate; the copper source preferably includes copper acetate; the zinc source preferably includes zinc acetate; the palladium source preferably includes palladium acetate; and the platinum source preferably includes platinum acetate.

[0119] In the present invention, the molar ratio of the compound VIII to the metal source is preferably 1:1-10, more preferably 1:2-3.

[0120] In the present invention, the eighth organic solvent preferably includes N,N-dimethylformamide, methanol, tetrahydrofuran. In the present invention, the usage ratio of the compound VII to the eighth organic solvent is preferably 1 mol: 10-50L, more preferably 1 mol: 25-30L.

[0121] In the present invention, the temperature of the coordination reaction is preferably room temperature, and the time is preferably 2 to 24 hours, more preferably 5 to 8 hours.

[0122] In the present invention, the conditions and post-treatment of the third deprotection reaction are the same as those of the first deprotection reaction, and will not be described in detail here.

[0123] The present invention also provides a pharmaceutical composition, comprising an active component and a pharmaceutically acceptable excipient; the active component comprises the mesogenic diaryl tetraacenaphthoporphyrin compound and / or the mesogenic diaryl tetraacenaphthoporphyrin complex described in the above technical solution. The present invention has no special limitation on the pharmaceutically acceptable excipient, and any pharmaceutically acceptable excipient well known to those skilled in the art can be used.

[0124] The present invention also provides the use of the mesogenic diaryl tetraacenaphthenoporphyrin compound described in the above technical solution, the mesogenic diaryl tetraacenaphthenoporphyrin complex described in the above technical solution or the pharmaceutical composition described in the above technical solution in the preparation of photosensitizing drugs.

[0125] In the present invention, the photosensitizing drug preferably includes photodynamic diagnostic and therapeutic drugs, and more preferably includes photodynamic diagnostic and therapeutic drugs for one or more diseases selected from the group consisting of tumors, macular degeneration, actinic keratosis, port-wine stains and condyloma acuminatum.

[0126] The mesogenic diaryl tetraacenaphthene porphyrin compound and the mesogenic diaryl tetraacenaphthene porphyrin complex provided by the present invention have stable chemical properties, good water solubility, are not easy to aggregate, have strong absorption in the infrared region, have an obvious red shift in the ultraviolet-visible absorption spectrum, significantly increase the singlet oxygen generation rate and have significant photodynamic activity. They have good application prospects as drugs for photodynamic diagnosis and treatment of diseases such as tumors, retinal macular degeneration, actinic keratosis, port-wine stains, and condyloma acuminatum.

[0127] To further illustrate the present invention, the following detailed description of the mesogenic diaryl tetraacenaphthoporphyrin compound, the mesogenic diaryl tetraacenaphthoporphyrin complex, the preparation method and application thereof, the pharmaceutical composition and application thereof provided by the present invention are given in conjunction with the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0128] Example 1

[0129] Preparation of Compound VII

[0130] 65.7 mmol of compound II and 65.7 mmol of 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) were dissolved in 250 mL of toluene, and the mixture was heated under reflux for 6 h. The reaction was stopped by monitoring the disappearance of the raw material of compound II by thin layer chromatography (TLC), and the mixture was cooled to room temperature, diluted with dichloromethane, washed with saturated sodium sulfite solution and saturated brine for 3 times, dried over anhydrous sodium sulfate, filtered, and the solvent was evaporated under reduced pressure. The residue was separated and purified by silica gel column chromatography (eluent: petroleum ether) to obtain compound III (light yellow powder, 8.5 g, yield: 85%, purity: 98%). Compound III: 1 H NMR (400MHz, CDCl3): δppm 7.79 (d, J = 8.2 Hz, 2H), 7.67 (d, J = 6.8 Hz, 2H), 7.53 (dd, J = 8.1, 6.9 Hz, 2H), 7.07 (s, 2H).

[0131] Dissolve 100 mmol of compound III in 10 mL of acetonitrile, add 100 mmol of benzenesulfonyl chloride (sulfonylation), 1 mmol of CuCl2 and 1 mmol of triethylamine hydrochloride in sequence, stir the reaction mixture at 75°C for 4 hours and then cool to room temperature, add benzene to the reaction solution for dilution, then dropwise add 100 mmol of triethylamine, and continue stirring for 1 hour. Filter and remove the solvent under reduced pressure, and purify the residue by silica gel column chromatography (eluent: dichloromethane) to obtain compound IV (bright yellow powder, 17.833 g, yield: 61%, purity: 98%). Compound IV: 1 H NMR (600MHz, CDCl3): δppm 8.13(d,J=7.3Hz,3H),8.02(d,J=8.1Hz,1H),7.95(dd,J=17.0,7.6Hz,2H),7 .90(s,1H),7.68-7.64(m,2H),7.58(t,J=4.9Hz,1H),7.53(d,J=7.0Hz,2H).

[0132] 30mmol of compound IV and 45mmol of ethyl isocyanoacetate were added to 200mL of dry tetrahydrofuran in sequence, and 45mmol of DBU was slowly added dropwise to the above reaction solution under nitrogen protection, and stirred at room temperature for 8h. TLC was monitored until the reaction was complete, and THF in the reaction solution was removed by rotary evaporation. The residue was dissolved in ethyl acetate, washed with water and saturated brine in sequence, dried over anhydrous sodium sulfate, and the solvent was removed by evaporation under reduced pressure. The mixture was separated and purified by silica gel column chromatography (eluent was petroleum ether and dichloromethane, volume ratio was 1:3), and compound V (white solid, 6.951g, yield was 88%, purity was 98%) was obtained. Compound V: 1HNMR (400MHz, CDCl3): δppm 9.01(s,1H),8.11(d,J=6.9Hz,1H),7.76(d,J=8.2Hz,1H),7.70(d,J=8.2Hz,1H),7.65-7.57( m, 2H), 7.54-7.50 (m, 1H), 7.19 (d, J = 2.7Hz, 1H), 4.51 (q, J = 7.1Hz, 2H), 1.54 (t, J = 7.1Hz, 3H).

[0133] 9 mmol of compound V, 4.5 mmol of dimethoxymethane and 0.45 mmol of p-toluenesulfonic acid were added to 45 mL of acetic acid in sequence, and the reaction solution was stirred at room temperature for 12 h. TLC was monitored until the reaction was complete. Ice water was poured into the reaction solution, and a white precipitate was generated. The filter cake was filtered and washed with ice water and vacuum dried to constant weight to obtain compound VI (white solid, 2.205 g, yield 91%, purity 98%). Compound VI: 1 H NMR (400MHz, DMSO-d6): δppm 12.07(s,2H),8.03(d,J=6.9Hz,2H),7.73(d,J=8.2Hz,2H),7.59(dd,J=7.7,3.3Hz,4H),7.33- 7.29 (m, 2H), 7.10 (d, J = 6.9Hz, 2H), 4.58 (s, 2H), 4.46 (d, J = 7.1Hz, 4H), 1.48 (d, J = 7.1Hz, 6H).

[0134] 10 mmol of compound VI and 200 mmol of KOH were added to 50 mL of ethylene glycol in sequence, and heated under argon protection for 1 h. The reaction solution was then quickly cooled to 0°C and poured into ice water, extracted with EA, the organic layers were combined, washed with saturated NaCl solution, dried over anhydrous sodium sulfate, filtered, and the solvent was evaporated under reduced pressure. The residue was separated and purified by silica gel column chromatography (eluent: petroleum ether and dichloromethane, volume ratio: 1:3) to obtain compound VII (yellow-brown solid, 2.091 g, yield: 53%, purity: 98%). Compound VII: 1 H NMR (400MHz, CDCl3): δppm 8.03(s,2H),7.62(d,J=8.4Hz,3H),7.58-7.55(m,3H),7.51-7.47(m,2H),7.4 2(t,J=7.5Hz,2H), 7.34(d,J=6.9Hz,2H), 6.87(d,J=2.3Hz,2H), 4.51(s,2H).

[0135] Example 2

[0136] Preparation of 5,15-bis[(3-carboxybutyloxy)phenyl]tetraacenaphthoporphyrin (I4)

[0137]

[0138] 1.7mmol of compound IX (compound 1) and 1.7mmol of compound VII were dissolved in 500mL of DCM, and 0.34mmol of trifluoroacetic acid was added dropwise under argon protection, and the mixture was stirred at room temperature for 12h. 2.55mmol of dichlorodicyanobenzoquinone (DDQ) was added, and the mixture was stirred for 12h. The solvent was evaporated under reduced pressure, and the residue was separated and purified by silica gel column chromatography (eluent was petroleum ether and dichloromethane, volume ratio was 1:3), and compound VIII4 (5,15-bis[(3-ethoxycarbonylbutyloxy)phenyl]tetraacenaphthoporphyrin, dark green powder, 276mg, yield was 26.0%, purity was 95%). Compound VIII4: 1 H NMR (400MHz, CDCl3): δppm11.25(s,2H),9.04(d,J=7.0Hz,4H),8.40-8.30(m, 4H),8.18(d,J=8.1Hz,4H),8.04(t,J=3.8Hz,8H),7.80(dd,J=8.5,2.4Hz,4H) ,7.49(d,J=7.7Hz,4H),6.20(d,J=7.2Hz,4H),4.18(d,J=7.1Hz,4H),4.15(d, J=5.3Hz,4H),2.33(td,J=7.1,2.2Hz,4H),1.77(d,J=5.3Hz,8H),1.28(s,6H).

[0139] 0.16 mmol of compound VIII4 was dissolved in 50 mL of THF / MeOH (V THF / V MeOH =1 / 1), then add 10 mL of KOH aqueous solution (2 mol / L), heat under reflux and stir for 6 h under nitrogen atmosphere, monitor the reaction completion by TLC, remove the organic solvent under reduced pressure, add 5 mL of water, adjust the pH to 5-6 with 2 mol / L dilute hydrochloric acid, filter, and vacuum dry the filter cake to constant weight to obtain compound I4 (purple-red solid, 175 mg, yield 91.6%, purity 91.6%). Compound I4: 1HNMR (400MHz, DMSO-d6): δppm11.50(s,2H),9.49(d,J=6.7Hz,4H),8.12-8.30(m,4H),8.05(d,J=7.8Hz,4H),8.01(t,J=3.8Hz,8H),7.7 7(m,4H),7.51(t,J=2.5Hz,4H),6.18(d,J=7.2Hz,4H),4.17(d,J=7.1Hz,4H),4.15(t,J=4.5Hz,4H),2.83(m,4H),2.31(d,J=5.5Hz,4H). 13 C NMR (101MHz, DMSO-d6): δppm 174.53,163.22,159.35,158.87,158.42,158.20,136.54,135.23,130.18,129.21,128. 89,127.27,117.12,114.36,68.83,57.24,31.98,25.85.HRMS(MALDI-TOF):calculated for C 82 H 56 N4O6[M+H] + ,1190.40;found 1191.4030.

[0140] Example 3

[0141] 5,15-Bis[(4-carboxybutyloxy)phenyl]tetraacenaphthoporphyrin (I 11 )

[0142]

[0143] The only difference from Example 2 is that the structural formula of compound IX is

[0144] Compound I 11 : 1 H NMR (400MHz, DMSO-d6): δppm 10.93(s,2H),9.16(d,J=6.8Hz,4H),8.07(d,J=7.9Hz,4H),8.00(d,J=8.1Hz,4H),7.92-7.88(m,8H),7.46(s ,4H),5.88(d,J=7.2Hz,4H),4.37(t,J=5.5Hz,4H),4.33(d,J=7.1Hz,4H),2.70(s,4H),2.16(d,J=3.5Hz,4H). 13C NMR (101MHz, DMSO-d6): δppm 175.32,165.43,159.59,158.78,158.54,158.20,138.91,136.52,130.92,129.33,128. 88,127.42,117.32,115.34,69.75,56.81,32.87,26.99.HRMS(MALDI-TOF):calculated for C 82 H 56 N4O6[M+H] + ,1190.42;found 1191.4098.

[0145] Example 4

[0146] 5,15-Bis[3,5-di(carboxypropyloxy)phenyl]tetraacenaphthoporphyrin (I 17 )

[0147]

[0148] The only difference from Example 2 is that the structural formula of compound IX is

[0149] Compound I 17 :. 1 H NMR (400MHz, DMSO-d6): δppm 11.49(s,2H),9.51(s,4H),8.27(d,J=7.8Hz,4H),8.13(q,J=8.4,7.4Hz,8H),8.01-7.85(m,4H),7.63(t,J=7.7 Hz, 4H), 7.55 (t, J = 2.2Hz, 2H), 6.28 (s, 4H), 4.28 (t, J = 6.5Hz, 8H), 2.36 (t, J = 7.2Hz, 8H), 1.98 (p, J = 6.9Hz, 8H). 13 C NMR (101MHz, DMSO-d6): δppm 174.45,162.32,159.29,158.92,158.54,158.17,137.41,135.31,130.29,129.26,1 28.90,127.25,117.22,114.34,68.16,30.43,24.44.HRMS(MALDI-TOF):calculated for C 88 H 64 N4O 12 [M+H] + ,1368.45;found 1369.4512.

[0150] Example 5

[0151] 5,15-Bis[3,5-di(carboxybutyloxy)phenyl]tetraacenaphthoporphyrin (I 18 )

[0152]

[0153] The only difference from Example 2 is that the structural formula of compound IX is

[0154]

[0155] Compound I 18 : 1 H NMR (600MHz, Pyridine-d5): δppm 11.57(s,2H),9.55(t,J=6.6Hz,4H),8.07(d,J=7.9Hz,4H),8.03-7.99(m,8H),7.98-7.94(m,4H),7.86(d,J=2.4Hz,2 H),7.77(t,J=7.3Hz,4H),6.64(d,J=6.9Hz,4H),4.35(t,J=5.9Hz,8H),2.53(t,J=6.9Hz,8H),1.98(h,J=7.8Hz,16H). 13 C NMR (151MHz, Pyridine-d5): δppm 175.57,163.04,148.72,145.22,145.11,143.51,138.31,135.64,134.82,133.07,130.61,128.73,128.39,127.15, 124.32,122.94,120.34,114.95,112.79,104.00,103.17,68.72,34.21,28.84,21.98.HRMS(MALDI-TOF):calculated for C 92 H 72 N4O 12 [M+H] + ,1424.51;found 1425.5105.

[0156] Example 6

[0157] 5,15-Bis[3,5-di(carboxypentyloxy)phenyl]tetraacenaphthoporphyrin (I 19 )

[0158]

[0159] The only difference from Example 2 is that the structural formula of compound IX is

[0160]

[0161] Compound I9: 1 H NMR (400MHz, DMSO-d6): δppm 11.68(s,2H),9.61(d,J=7.0Hz,4H),8.31(d,J=8.0Hz,4H),8.17(dd,J=15.2,7.7Hz,8H),8.07(s,4H),7.62(t,J=7.7Hz, 2H),7.48(s,4H),6.38(d,J=7.1Hz,4H),4.30-4.18(m,8H),2.14(t,J=7.2Hz,8H),1.71-1.64(m,8H),1.41-1.33(m,16H). 13 C NMR (101MHz, DMSO-d6): δppm 174.81,162.32,159.40,159.02,158.64,158.26,140.16,137.54,135.27,131.75,130.72,130.29,128.95,127 .37,119.88,117.01,116.71,114.14,111.27,68.77,34.05,28.57,25.44,24.57.HRMS(MALDI-TOF):calculated for C 96 H 80 N4O 12 [M+H] + ,1480.58;found 1481.5821.

[0162] Example 7

[0163] 5,15-Bis[3,5-bis(carboxyhexyloxy)phenyl]tetraacenaphthoporphyrin (I 20 )

[0164]

[0165] The only difference from Example 2 is that the structural formula of compound IX is

[0166]

[0167] Compound I 20 : 1H NMR (400MHz, DMSO-d6): δppm 11.67(s,2H),9.62(d,J=7.0Hz,4H),8.32(d,J=8.1Hz,4H),8.22-8.13(m,8H),8.06(s,4H),7.63(t,J=7.7Hz,4H),7.48(s,2H),6.36(d,J=7. 2Hz, 4H), 4.23 (t, J = 6.5Hz, 8H), 2.15 (t, J = 7.4Hz, 8H), 1.65 (t, J = 7.3Hz, 8H), 1.42 (t, J = 7.6Hz, 8H), 1.31 (t, J = 7.7Hz, 8H), 1.16-1.11 (m, 8H). 13 C NMR (101MHz, DMSO-d6): δppm 174.93,162.31,159.38,159.00,158.62,158.24,137.39,135.27,130.31,129.45,119.92,117 .05,114.17,111.30,68.74,34.08,28.67,28.63,25.57,24.88.HRMS(MALDI-TOF):calculated for C 100 H 88 N4O 12 [M+H] + ,1536.64;found1537.6410.

[0168] Example 8

[0169] 5,15-Bis[3,5-di(carboxyheptyloxy)phenyl]tetraacenaphthoporphyrin (I 21 )

[0170]

[0171] The only difference from Example 2 is that the structural formula of compound IX is

[0172]

[0173] Compound I 21 : 1H NMR (400MHz, DMSO-d6): δppm 11.64(s,2H),9.63(d,J=7.0Hz,4H),8.34(d,J=8.1Hz,4H),8.24-8.15(m,8H),8.02(s,4H),7.64(t,J=7.7Hz,4H),7.50(s,2H),6.35(d,J= 7.2Hz, 4H), 4.23 (t, J = 6.5Hz, 8H), 2.18 (t, J = 7.3Hz, 8H), 1.66 (q, J = 7.3Hz, 8H), 1.43 (t, J = 7.4Hz, 8H), 1.30 (t, J = 7.4Hz, 8H), 1.16 (s, 16H). 13 C NMR (101MHz, DMSO-d6): δppm 174.97,162.41,159.38,159.00,158.62,158.25,119.90,117.03,114.16,111.29,34.13,28.97,28.78,25.72,24.90.HRMS(MALDI-TOF): calculated for C 104 H 96 N4O 12 [M+H] + ,1592.70;found1593.6989.

[0174] Example 9

[0175] 5,15-Bis[3,5-bis(2-hydroxyethoxy)phenyl]tetraacenaphthoporphyrin (I 22 )

[0176]

[0177] The only difference from Example 2 is that the structural formula of compound IX is

[0178] Compound I 22 : 1 H NMR (400MHz, DMSO-d6): δppm 11.60(s,2H),9.78(d,J=7.7Hz,4H),8.40(d,J=7.6Hz,4H),8.21(m,8H),8.06(d,J=6.9Hz,4H),7.52(t, J=6.8Hz,4H),7.37(d,J=5.2Hz,2H),6.25(d,J=6.3Hz,4H),4.32(t,J=5.4Hz,8H),3.91(t,J=5.5Hz,8H). 13C NMR (101MHz, DMSO-d6): δppm 174.89,162.35,159.27,158.99,158.58,158.20,137.52,135.26,130.31,129.2 5,128.89,127.30,117.15,114.23,68.16,65.34.HRMS(MALDI-TOF):calculated for C 80 H 56 N4O8[M+H] + ,1200.41;found 1201.4111.

[0179] Example 10

[0180] 5,15-Bis[(3,5-dimethoxy-4-carboxybutyloxy)phenyl]tetraacenaphthoporphyrin (I 24 )

[0181]

[0182] The only difference from Example 2 is that the structural formula of compound IX is

[0183] Compound I 24 : 1 H NMR (400MHz, DMSO-d6): δppm 11.58(s,2H),9.60(d,J=7.2Hz,4H),8.23(d,J=7.0Hz,4H),8.14(m,J=6.8Hz,8H),8.03(m,4H),7.57(t,J=7.5Hz,4H),6. 28(d,J=7.0Hz,4H),4.64(t,J=5.6Hz,4H),4.24(t,J=6.7Hz,4H),3.95(s,12H),3.58(t,J=7.2Hz,4H),2.58-2.47(m,4H). 13 C NMR (101MHz, DMSO-d6): δppm 174.93,163.52,159.41,159.13,158.77,158.29,119.96,117.19,114.21,111.30,68.23,61.96,34.85,28.98,25.17.HRMS(MALDI-TOF): calculated for C 86 H 62 N4O 10 [M+H] + ,1310.45;found 1311.4523.

[0184] Embodiment 11

[0185] 5,15-Bis[(3,5-dimethoxy-4-(2-hydroxyethoxy))phenyl]tetraacenaphthoporphyrin (I 28 );

[0186]

[0187] The only difference from Example 2 is that the structural formula of compound IX is

[0188] Compound I 28 : 1 H NMR (400MHz, DMSO-d6): δppm 11.64(s,2H),9.57(d,J=7.0Hz,4H),8.28(d,J=7.0Hz,4H),8.11(m,J=7.2Hz,8H),8.03(m,4H),7.6 3(t,J=7.1Hz,4H),6.32(d,J=5.5Hz,4H),4.66(t,J=5.6Hz,4H),4.25(t,J=6.8Hz,4H),3.91(s,12H. 13 C NMR (101MHz, DMSO-d6): δppm 174.89,163.76,159.43,159.21,158.73,158.32,120.01,117.18,114.32,111.20,67.94,35.89,30.38.HRMS(MALDI-TOF):calculated forC 80 H 54 N4O8[M+H] + ,1198.39;found 1199.3922.

[0189] Example 12

[0190] 5,15-Bis[[3,5-dimethoxy-4-[2-oxo-2-(2-oxo-4-carboxyl)butylamino]ethoxy]phenyl]tetraacenaphthoporphyrin (I 35 )

[0191]

[0192] The only difference from Example 2 is that the structural formula of compound IX is

[0193] Compound I 35 : 1H NMR (400MHz, DMSO-d6): δppm 11.63(s,2H),9.58(d,J=6.0Hz,4H),8.20(d,J=5.8Hz,4H),8.05(m,J=6.0Hz,8H),7.97(m,J=5.5Hz,4H),7.56(t,J=6.8Hz,4H), 6.31(d,J=7.0Hz,4H),4.55(t,J=6.2Hz,4H),4.21(d,J=5.0Hz,4H),3.95(s,12H),2.70(t,J=5.9Hz,4H),2.52(t,J=6.0Hz,4H). 13 C NMR (101MHz, DMSO-d6): δppm 175.33,164.49,158.21,159.10,158.89,158.32,119.86,117.25,114.71,111.28,68.27,60.95,34.51,31.68,25.23.HRMS(MALDI-TOF): calculated for C 90 H 64 N6O 14 [M+H] + ,1452.45;found1453.4515.

[0194] Test Example 1

[0195] Determination of UV-Visible Absorption Spectra of Photosensitizers

[0196] A 10 μM DMSO solution of the compound prepared in Examples 2 to 12 was accurately prepared, and then its UV-visible absorption spectrum at 300 to 800 nm was measured using a Shimadzu UV-2600 ultraviolet spectrophotometer. The results are shown in Figure 1 The experimental results show that compound I 11 and I 17 ~I 21 The UV-visible absorption spectrum of porphyrin compounds shows a strong absorption peak of the B band at around 515 nm, and weak absorption peaks of the Q band at around 536 nm, 648 nm, and 718 nm. The addition of acenaphthene rings to the β-position of porphyrin compounds can red-shift the UV absorption spectrum of porphyrin compounds to a certain extent, compared with the intermediate diphenylporphyrin DPP (λ max=630nm), the longest absorption wavelength of the mesodiaryl tetraacenaphthene porphyrin red-shifted by 88nm and the absorption intensity increased, which indicates that the prepared mesodiaryl tetraacenaphthene porphyrin derivatives can treat deeper or larger tumors and can better exert the photodynamic therapy effect. In addition, the mesodiaryl tetraacenaphthene porphyrin has multiple absorption peaks with different absorption intensities at 500-750nm. According to the location and size of lesions such as tumors, a light source with a suitable wavelength can be selected for photodynamic, photothermal or photodynamic-cooperative photothermal therapy, thereby realizing personalized treatment of diseases.

[0197]

[0198] Test Example 2

[0199] Determination of Singlet Oxygen in Photosensitizer

[0200] Light source: MW-GX-660 laser; VLP-2000 laser power meter.

[0201] Drugs to be tested: 5,15-bis[(3-carboxybutyloxy)phenyl]tetraacenaphthoporphyrin (I4); 5,15-bis[(4-carboxybutyloxy)phenyl]tetraacenaphthoporphyrin (I 11 ); 5,15-bis[3,5-bis(carboxypropyloxy)phenyl]tetraacenaphthoporphyrin (I 17 ); 5,15-bis[3,5-bis(carboxybutyloxy)phenyl]tetraacenaphthoporphyrin (I 18 ); 5,15-bis[3,5-bis(carboxypentyloxy)phenyl]tetraacenaphthoporphyrin (I 19 ); 5,15-bis[3,5-bis(carboxyhexyloxy)phenyl]tetraacenaphthoporphyrin (I 20 ); 5,15-bis[3,5-bis(carboxyheptyloxy)phenyl]tetraacenaphthoporphyrin (I 21 ); 5,15-bis[3,5-bis(2-hydroxyethoxy)phenyl]tetraacenaphthoporphyrin (I 22 ); 5,15-bis[(3,5-dimethoxy-4-carboxybutyloxy)phenyl]tetraacenaphthoporphyrin (I 24 ); 5,15-bis[(3,5-dimethoxy-4-(2-hydroxyethoxy))phenyl]tetraacenaphthoporphyrin (I 28 ); 5,15-bis[[3,5-dimethoxy-4-[2-oxo-2-(2-oxo-4-carboxyl)butylamino]ethoxy]phenyl]tetraacenaphthoporphyrin (I 35 ); control drug dihydrochlorin e6 (Ce6).

[0202] Accurately prepare a DMF solution of 2 μM of the drug to be tested and 60 μM 1,3-diphenylisobenzofuran (DPBF). Take 2 μM of the drug to be tested solution (1.0 mL) and 60 μM of DPBF (1.0 mL), mix them thoroughly and place them in a quartz cuvette. Irradiate the sample with a laser (wavelength of 660 nm, power of 10 mW / cm 2 , each exposure for 2 seconds), and then the UV-visible absorption spectrum at 300-800nm ​​was measured using a Shimadzu UV-2600 ultraviolet spectrophotometer. Each sample was exposed to light six times. The singlet oxygen generation rate k of the drug to be tested is calculated according to the formula k = -ln(DPBF t / DPBF0) calculation, where DPBF t and DPBF0 represent the absorbance values ​​of the mixed solution at 414 nm after t seconds of illumination and before illumination, respectively, as shown in Table 1.

[0203] Table 1 Singlet oxygen generation rate k of each compound

[0204] Compound <![CDATA[k[s -1 ]]]> Compound <![CDATA[k[s -1 ]]]> Compound <![CDATA[k[s -1 ]]]> Compound <![CDATA[k[s -1 ]]]> <![CDATA[I4]]> 0.082 <![CDATA[I 18 ]]> 0.102 <![CDATA[I 21 ]]> 0.075 <![CDATA[I 28 ]]> 0.097 <![CDATA[I 11 ]]> 0.084 <![CDATA[I 19 ]]> 0.098 <![CDATA[I 22 ]]> 0.086 <![CDATA[I 35 ]]> 0.089 <![CDATA[I 17 ]]> 0.117 <![CDATA[I 20 ]]> 0.090 <![CDATA[I 24 ]]> 0.092 Ce6 0.021

[0205] The results show that the singlet oxygen generation rate of the mesogenic diaryl tetraacenaphthene porphyrin compound provided by the present invention is significantly better than that of DPP. This is because the conjugated system of the mesogenic diaryl tetraacenaphthene porphyrin compound obtained by fusing the acenaphthene ring at the β-position of porphyrin is enlarged, making it easy for the photosensitizer to transition from the singlet excited state to the triplet excited state, which is beneficial to the generation of singlet oxygen.

[0206] Test Example 3

[0207] Photodynamic antiproliferation experiment of photosensitizer on B16-F10 and A-375 melanoma cells

[0208] Test cells: Mouse melanoma cells B16-F10 and human melanoma cells A-375 were purchased from Shanghai Yunchuan Biotechnology Co., Ltd.

[0209] Light source: MW-GX-660 laser; VLP-2000 laser power meter.

[0210] Test drugs: 5,15-bis[(3-carboxybutyloxy)phenyl]tetraacenaphthoporphyrin (I4); 5,15-bis[(4-carboxybutyloxy)phenyl]tetraacenaphthoporphyrin (I 11 ); 5,15-bis[3,5-bis(carboxypropyloxy)phenyl]tetraacenaphthoporphyrin (I 17 ); 5,15-bis[3,5-bis(carboxybutyloxy)phenyl]tetraacenaphthoporphyrin (I 18 ); 5,15-bis[3,5-bis(carboxypentyloxy)phenyl]tetraacenaphthoporphyrin (I 19); 5,15-bis[3,5-bis(carboxyhexyloxy)phenyl]tetraacenaphthoporphyrin (I 20 ); 5,15-bis[3,5-bis(carboxyheptyloxy)phenyl]tetraacenaphthoporphyrin (I 21 ); 5,15-bis[3,5-bis(2-hydroxyethoxy)phenyl]tetraacenaphthoporphyrin (I 22 ); 5,15-bis[(3,5-dimethoxy-4-carboxybutyloxy)phenyl]tetraacenaphthoporphyrin (I 24 ); 5,15-bis[(3,5-dimethoxy-4-(2-hydroxyethoxy))phenyl]tetraacenaphthoporphyrin (I 28 ); 5,15-bis[[3,5-dimethoxy-4-[2-oxo-2-(2-oxo-4-carboxyl)butylamino]ethoxy]phenyl]tetraacenaphthoporphyrin (I 35 ); control compound 1; control compound 2; control drug chlorin e6 (Ce6).

[0211] The structural formulas of reference compound 1 and reference compound 2 are as follows:

[0212]

[0213] Photodynamic anti-tumor cell proliferation experiment: The cells in the logarithmic growth phase were digested with trypsin and resuspended in complete medium to form a cell suspension, which was then inoculated into a 96-well plate, 100 μL per well, and placed in a 37°C, 5% CO2 incubator for 24 h; then the photosensitizer was added and incubated for another 24 h; then the light treatment (power 300 mW / cm 2 , wavelength 660nm, light dose 18J / cm 2 ) and add culture medium to continue culturing overnight; finally, add CCK-8, and use a microplate reader to measure the OD value at 450nm to determine the cell survival rate. The experiment was repeated three times, and the experimental results are shown in Table 2.

[0214] Table 2 Inhibitory effect of compounds on proliferation of B16-F10 mouse melanoma cells

[0215]

[0216]

[0217] Compared with control compounds 1-2, Δ P<0.05, ΔΔ P<0.01, ΔΔΔ P<0.001; compared with the control compound, the cell inhibition rate of the compound provided by the present invention is better than that of the control compound, which is statistically significant.

[0218] Compared with the control drug Ce6, the compounds provided by the present invention had *P<0.05, **P<0.01, ***P<0.001.

[0219] Results: Compounds I4, I 11 ,I 17 ~I 22 ,I 24 ,I 28 and I 35 It has anti-proliferative effects on both mouse and human melanoma cells, and its photodynamic activity is significantly better than that of the control drug Ce6.

[0220] Test Example 4

[0221] The LogP value was determined using the (n-octanol-water) shake flask test method, with n-octanol as the oil phase and water as the aqueous phase. The n-octanol and water were pre-saturated for 24 hours. The above compound (10 mg) was dissolved in the pre-saturated n-octanol (1 mL), mixed with the aqueous phase (9 mL), and continued to shake for 72 hours. The content of the compound in n-octanol and water was determined using an ultraviolet spectrophotometer. The test data was calculated using the formula P ow =C n-o / C w Calculate (C n-o : Concentration of compound in n-octanol (mg / L), C w : Concentration of compound in water phase (mg / L).

[0222] As shown in Table 3, the oil-water partition coefficients (LogP) of the mesogenic diaryl tetraacenaphthoporphyrin compounds provided by the present invention are all between -1.0 and 3.0, indicating that these compounds have good water solubility and are significantly improved relative to the solubility of the control compound 1.

[0223] Table 3 LogP values ​​of each compound

[0224] Compound LogP Compound LogP <![CDATA[I4]]> 1.56±0.11 <![CDATA[I 22 ]]> 1.42±0.23 <![CDATA[I 11 ]]> 1.85±0.25 <![CDATA[I 24 ]]> 0.36±0.17 <![CDATA[I 17 ]]> 2.69±0.13 <![CDATA[I 28 ]]> -0.90±0.12 <![CDATA[I 18 ]]> 2.50±0.10 <![CDATA[I 35 ]]> 0.23±0.21 <![CDATA[I 19 ]]> 2.37±0.21 Ce6 2.66±0.10 <![CDATA[I 20 ]]> 2.18±0.11 Control compound 1 >3 <![CDATA[I 21 ]]> 1.89±0.18

[0225] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A mesodiaryl tetraacenaphthoporphyrin compound having a structure shown in Formula I: in, R1, R2 and R3 independently include polar groups or non-polar groups, and at least one of R1, R2 and R3 is a polar group; The polar group contains one or more of carboxyl, hydroxyl and amino groups; the non-polar group does not contain carboxyl, hydroxyl or amino groups; The non-polar group includes hydrogen, halogen, alkyl, alkyl containing heteroatom, alkyl containing carbonyl or alkyl containing amide bond.

2. The mesodiaryl tetraacenaphthoporphyrin compound according to claim 1, characterized in that: The polar groups include carboxyl, alkyl carboxylic acid, alkyl carboxylic acid containing heteroatoms, alkyl carboxylic acid containing carbonyl and / or amide groups, hydroxyl, alkyl alcohol, alkyl alcohol containing heteroatoms, alkyl alcohol containing carbonyl and / or amide groups, phenol, alkyl phenol, alkyl phenol containing heteroatoms, phenol containing carbonyl and / or amide groups; The heteroatom in the heteroatom-containing alkylcarboxylic acid group, the heteroatom-containing alkyl alcohol group and the heteroatom-containing alkylphenol group independently includes O or N.

3. The mesodiaryl tetraacenaphthoporphyrin compound according to claim 2, characterized in that: The alkyl carboxylic acid group includes -(CH2) m COOH or -(CH2) m CH(CH3)COOH; The heteroatom-containing alkyl carboxylic acid group includes -(CH2) m N[(CH2) n COOH]2 or -(CH2) m O(CH2) n COOH; The alkyl carboxylic acid group containing a carbonyl group and / or an amide group includes -(CH2) m CO(CH2) n COOH or amino acid derivatives; The alkyl alcohol group includes -(CH2) m OH or -(CH2) m CH(CH3)OH; The heteroatom-containing alkyl alcohol group includes -(CH2) m N[(CH2) n OH]2, -(CH2) m O(CH2) n OH or -(CH2) m (OCH2CH2) p OH; The alkyl alcohol group containing a carbonyl group and / or an amide group includes -(CH2) m CO(CH2) n OH or -(CH2) m CONH(CH2) n OH; The alkylphenol group includes -(CH2) m C6H4OH; Here, m is independently an integer of 0-7, n is independently an integer of 1-7, and p is an integer of 1-3.

4. The mesodiaryl tetraacenaphthoporphyrin compound according to claim 3, characterized in that: The amino acid derivatives include -(CH2) c CONH(CH2) c COOH, -(CH2) c CONHCH(CH3)COOH, -(CH2) c CONH(CH2) c CO(CH2) c COOH, -(CH2) c CONHCH[CH(CH3)2]COOH, -(CH2) c CONHCH[CH2CH(CH3)2]COOH、-(CH2) c CONHCH[CH(CH3)CH2CH3]COOH, -(CH2) c CONHCH(CH2C6H5)COOH, -(CH2) c CON[(CH2) c COOH]2, -(CH2) c CONHCH(COOH)CH2COOH, wherein c is independently an integer of 0-7.

5. The mesodiaryl tetraacenaphthoporphyrin compound according to claim 1, characterized in that: The non-polar groups include -H, -F, -Cl, -Br, -I, -(CH2) a CH3, -(CH2) a CH(CH3)2, -(CH2) a C(CH3)3, -(CH2) a N[(CH2) b CH3]2, -(CH2) a O(CH2) b CH3, -(CH2) a O(CH2) b CH(CH3)2, -(CH2) a O(CH2) b C(CH3)3, -(CH2) a (OCH2CH2) q CH3, -(CH2) a CO(CH2) b CH3, -(CH2) a CO(CH2) b CH(CH3)2, -(CH2) a CO(CH2) b C(CH3)3, -(CH2) a CONH(CH2) b CH3, -(CH2) a CONH(CH2) b CH(CH3)2 or -(CH2) a CONH(CH2) b C(CH3)3, wherein a is independently an integer of 0 to 7, b is independently an integer of 1 to 7, and q is an integer of 1 to 3.

6. A method for preparing the mesodiaryl tetraacenaphthoporphyrin compound according to any one of claims 1 to 5, comprising the following steps: Compound VII is subjected to a cyclization-oxidation reaction with compound IX in the presence of a catalyst and an oxidant to obtain compound VIII; The compound VIII is subjected to a deprotection reaction to obtain the intermediate diaryl tetraacenaphthene porphyrin compound; Among them, R4 is R1 containing an ester group or an acetyl protecting group, R5 is R2 containing an ester group or an acetyl protecting group, and R6 is R3 containing an ester group or an acetyl protecting group.

7. A mesogenic diaryl tetraacenaphthoporphyrin complex having a structure shown in formula I'; in, M is hydrogen or a metal; R1, R2 and R3 are the same as R1, R2 and R3 in the mesodiaryltetraacenaphthoporphyrin compound according to any one of claims 1 to 5.

8. The method for preparing the mesodiaryl tetraacenaphthoporphyrin complex according to claim 7, comprising the following steps: The mesodialotetraacenaphthenoporphyrin compound according to any one of claims 1 to 5 is subjected to a coordination reaction with a metal source to obtain the mesodialotetraacenaphthenoporphyrin complex.

9. A pharmaceutical composition comprising an active ingredient and a pharmaceutically acceptable excipient; the active ingredient comprises the mesogenic diaryl tetraacenaphthene porphyrin compound according to any one of claims 1 to 5 and / or the mesogenic diaryl tetraacenaphthene porphyrin complex according to claim 7.

10. Use of the mesodithriacenaphthoporphyrin compound according to any one of claims 1 to 5, the mesodithriacenaphthoporphyrin complex according to claim 7 or the pharmaceutical composition according to claim 9 in the medical field.

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