JP3394566B2 - Pharmaceutical composition for photochemotherapy of cancer - Google Patents

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION This invention relates to pharmaceutical compositions useful in the photochemical treatment of many different types of cancer, especially carcinoma or melanoma.

[0002]

BACKGROUND OF THE INVENTION Photochemical therapy (PDT) for cancer is a rapidly developing therapy for treating malignant tumors in humans and animals. PDT is a method in which a photosensitizing agent is contained in tumor tissue and the tissue is exposed to light of an appropriate wavelength to generate singlet oxygen or oxygen radicals to destroy the tumor tissue. is there. So far, hematoporphyrin derivative (HPD) has been used as a photosensitizer.
(Thomas J. Dougherty et al.
U.S. Pat. Nos. 4,649,151, 4,866,168, 4,8
89,129, and 4,932,934), chlorin (US Pat. Nos. 4,656,186, 4,693,885, and 4,
861,876), expanded porphyrins, naphthalocyanines, phthalocyanines (US Pat. No. 5,166,197),
Platyline, Porphycene (US Pat. No. 4,649,151
And 4,913,907), purpurine, texaphyrin, verdine, merocyanine 540, xanthene (rhodamine 1236 G & B), cationic cyanine dye, chalcogenapyrylium dye (Japanese Patent Publication No. 2-16482).
No. 5), phenothiazinium derivatives, tetracycline, berbinsulfate, acridine orange, fluorescein and the like have been used.

A problem in using these photosensitizing reagents (dye) is a side effect caused by insufficient cancer cell selectivity of the reagent for normal cells. The most problematic is that after administration of the dye, If the patient is not left in the dark for 4 to 8 weeks, the skin will be exposed and blackened. In addition, various side effects can occur due to the dye destroying normal cells. So for now,
Photochemotherapy has the drawback of being limited to the treatment of extremely severe patients. On the other hand, the compound represented by the general formula (1) of the present invention is known as an antitumor agent having high selectivity for cancer cells (European Patent No. 527,
No. 494, Japanese Patent Application Laid-Open No. 5-117148, U.S. Patent Application No. 692,347), and its use as a photochemotherapy and a diagnostic agent is not known.

[0004]

OBJECTS OF THE INVENTION It is therefore an object of the present invention is to provide a photochemical therapy physicians <br/> drug composition having a high selectivity to cancer cells.

[0005]

It was found that the above object of the present invention can be achieved by a pharmaceutical composition containing a compound represented by the general formula (1) as an active ingredient. These compounds have hitherto been mainly used for the production of photographic light-sensitive materials, but they are also effective as a photochemotherapeutic drug for cancer or tumor, and particularly effective for carcinoma and melanoma. In one aspect, the present invention provides a pharmaceutical composition for photochemotherapy of cancer, which comprises at least one compound represented by the following general formula (1) as an active ingredient.

[0006]

[Chemical 3]

(In the formula, R represents an alkyl group which may have a substituent, an aryl group which may have a substituent or a heterocyclic group which may have a substituent, and A and B represents a 5- or 6-membered ring which may have a substituent containing at least one hetero atom or a condensed ring thereof, and Y
Represents S, O, Se or -NR- is, L _1, L _2, L
₃ , L ₄ and L ₅ each independently represent a methine group which may be substituted, and when L ₁ is a substituted methine group, L ₁
And the atoms constituting A may be bonded to form a 5- or 6-membered ring, and when L ₅ is a substituted methine group, the atoms constituting L ₅ and B are bonded to form a 5- or 6-membered ring. A ring may be formed, Q represents a counter anion, k represents a number required to make the charge of the entire molecule zero, and p and q each represent 0,
Represents 1, 2, or 3. ) In a preferred embodiment of the invention,
The compound represented by the general formula (1) is a compound selected from the group consisting of compounds represented by the following general formula (2).
Included are the compositions described above.

[0008]

[Chemical 4]

(In the formula, R ₁ and R ₃ each represent an optionally substituted alkyl group, which may be the same or different, and R ₂ represents an alkyl group, an aryl group or a heterocyclic group, each of which is substituted. Alternatively, X ₁ and X ₂ are each O, S, Se, —CH═CH—, —CR ₄ R ₅ — (R ₄ and R ₅ each independently represent an alkyl group), or —NR ₆ — (R ₆
Represents an alkyl group, an aryl group or a heterocyclic group), which may be the same or different, and Y ₁ is O, S, S
e, or -NR ₇ - (R ₇ represents an alkyl group, an aryl group or a heterocyclic group) represents, Z ₁ and Z ₂ represents an atomic group necessary for forming a 5-membered or 6-membered ring, They may be the same or different, and L ₁ , L ₂ , L ₃ , L ₄ and L ₅ each independently represent a methine group which may be substituted, and when L ₁ is a substituted methine group, L ₁ and R ₁ may combine to form a 5- or 6-membered ring, and when L ₅ is a substituted methine group, L ₅ may combine with R ₃ to form a 5- or 6-membered ring. , L ₁ and L ₂ , and L _{3 to} L ₅ may be bonded to each other to form a 5- or 6-membered ring, R ₄
And R ₅ each represent an optionally substituted alkyl group, which may be the same or different, m and n each represent 0 or 1, and may be the same or different;
k, p and q are as defined above. ) In a specific embodiment of the present invention, the pharmaceutical composition of the present invention comprises a compound represented by the above general formula (1) or (2) as an active ingredient together with a suitable pharmaceutically acceptable carrier or diluent. A compound selected from the group consisting of:

The compounds represented by the above general formulas (1) and (2) will be described in more detail. R in general formula (1)
The alkyl group represented by is preferably one having 1 to 12 carbon atoms, more preferably one having 1 to 5 carbon atoms, which may be linear, branched or cyclic. Such an alkyl group may be substituted, and preferred examples of the substituents are those given as the substituents of A and B below. Specific alkyl groups include methyl, ethyl, hydroxyethyl,
Propyl and butyl groups are mentioned. R in general formula (1)
The aryl group represented by is preferably an aryl group having 6 to 15 carbon atoms, and more preferably 6 to 10 carbon atoms. Such an aryl group may be substituted, and as the substituent, those exemplified as the substituents of A and B below are preferable. Specific aryl groups include phenyl, tolyl, and p-chlorophenyl groups. The heterocyclic group represented by R in the general formula (1) is preferably a 5- to 8-membered, preferably 5- or 6-membered heterocyclic group. Examples of the hetero atom include a nitrogen atom, an oxygen atom, a sulfur atom, a selenium atom, a tellurium atom and a phosphorus atom, and a nitrogen atom, an oxygen atom, a sulfur atom and a selenium atom are preferable. Such a heterocyclic group may be substituted, and as the substituent, those exemplified as the substituents of A and B below are preferable. Specific heterocyclic groups include pyrrole, furan, piperidine, morpholine, pyridine and pyrrolidine.

The hetero atom contained in the 5- or 6-membered ring represented by A and B in the general formula (1) is a nitrogen atom,
Examples thereof include an oxygen atom, a sulfur atom, a selenium atom, a tellurium atom, a phosphorus atom and a silicon atom, and it is preferable that at least one nitrogen atom is contained. A and B may form a condensed ring together with a saturated or unsaturated ring, and examples of the saturated or unsaturated ring are preferably cyclopentene ring, cyclohexene ring, benzene ring, naphthalene ring, anthracene ring and phenanthrene ring. , Thiophene ring, pyridine ring and the like. A and B may have a substituent, and preferable examples of the substituent include an alkyl group having 1 to 15 carbon atoms, an alkoxy group having 1 to 15 carbon atoms, and 6 carbon atoms.
~ 15 aryloxy group, halogen atom (chlorine, bromine, fluorine and iodine), aryl group having 6 to 15 carbon atoms, hydroxyl group, amino group, amino group substituted with alkyl group or aryl group, acylamino group, sulfonylamino Group, carbamoyl group, sulfamoyl group, carboxyl group, alkoxycarbonyl group having 2 to 15 carbon atoms, acyloxy group having 2 to 15 carbon atoms, 5- or 6-membered heterocycle (pyrrole ring, furan ring, piperidine ring, morpholine ring, Pyridine ring), a cyano group, a nitro group and the like, which may be further substituted with each other. Preferable examples of Y in the general formula (1) include S and O. When L ₁ , L ₂ , L ₃ , L ₄ and / or L _{5 in the} general formula (1) represents a substituted methine group, the substituent is preferably an alkyl group having 1 to 15 carbon atoms (for example, methyl or ethyl). , Propyl, butyl, etc.), aryl groups having 6 to 15 carbon atoms (eg, phenyl, tolyl groups, etc.), halogen atoms (eg, chlorine, bromine, fluorine and iodine), or C 1
To 15 alkoxy groups (eg, methoxy, ethoxy groups, etc.), and the ring formed by the bond of L ₁ and L ₂ and L _{3 to} L ₅ is preferably a 5-membered heterocycle (eg, pyrroline). Ring) and a 6-membered heterocycle (eg,
A tetrahydropyridine ring, an oxazine ring and the like). In the general formula (2) between _{L 1} and _R 1, _{L 5} and _{R 3}
The ring formed by bonding preferably has 5 members.
Carbocycle (eg cyclopentene ring), 6-membered carbocycle (eg
For example, cyclohexene ring, etc.), 5-membered heterocycle (thiazoline
Ring, oxazoline ring, imidazole ring, etc.) and 6-membered
Terror ring (thiazine ring, oxazine ring, piperazine ring, etc.)
Is mentioned.

The term "pharmaceutically acceptable anion" for Q, which is required for charge balance in the above compounds, is nontoxic when the compound is administered to a recipient and dissolves the compound in an aqueous system. It is intended to mean the ion that causes it. Suitable examples of pharmaceutically acceptable anions represented by Q include halogen ions such as chloride ion, bromide ion and iodide ion; for example, methanesulfonate ion, trifluoromethanesulfonate ion, p-toluenesulfonate ion. , Sulfonate ions such as aliphatic and aromatic sulfonate ions such as naphthalene sulfonate ion and 2-hydroxyethane sulfonate ion; Sulfamate ion such as cyclohexanesulfamate ion; Sulfate ion such as methylsulfate ion and ethylsulfate ion Hydrogen sulfate; borate ion; alkyl and dialkyl phosphate ions such as diethyl phosphate ion and methyl hydrogen phosphate ion; pyrophosphate ion such as trimethylpyrophosphate ion and diethyl hydrogen pyrophosphate ion; carbo Acid ion (carboxylate ions carboxy group and hydroxyl group is substituted with conveniently used) include and carbonate ions. Preferred examples of pharmaceutically acceptable anions include chloride ion, acetate ion, propionate ion, valerate ion,
Citrate ion, maleate ion, fumarate ion,
Examples include lactate ion, succinate ion, tartrate ion and benzoate ion.

Alkyl groups represented by R ₁ to R ₇ of the general formula (2), a hetero ring represented by R _2, R ₆ and aryl groups and R ₂ is represented by R _7, R ₆ and R ₇ Examples of the group include the same groups as those described for R in the general formula (1). Y in general formula (2)
Preferred are O of _1, S, Se, and -NR ₇ - it is.
Z ₁ and Z _{2 in} the general formula (2) each represent an atomic group necessary for forming a 5-membered or 6-membered ring (saturated or unsaturated 5-membered or 6-membered ring), and may be the same or different. Good. The ring formed by Z ₁ and Z ₂ may form a condensed ring together with a saturated or unsaturated ring, and examples of the saturated or unsaturated ring are preferably a cyclopentene ring, a cyclohexene ring and a benzene ring. , Naphthalene ring, anthracene ring, phenanthrene ring, thiophene ring, pyridine ring and the like.

Specific examples of the 5- or 6-membered hetero ring formed by Z ₁ and Z ₂ include a thiazole ring (eg, thiazole, 4-methylthiazole, 4-
Phenylthiazole, 4,5-diphenylthiazole,
4,5-dimethylthiazole, etc.), benzothiazole ring (eg, benzothiazole, 5-chlorobenzothiazole, 5-methylbenzothiazole, 5-phenylbenzothiazole, 5-methoxybenzothiazole, 4
-Fluorobenzothiazole, 5,6-dioxymethylenebenzothiazole, 5-nitrobenzothiazole, 5
-Trifluoromethylbenzothiazole, 5-methoxycarbonylbenzothiazole, 5-hydroxybenzothiazole, 6-hydroxybenzothiazole, 5-cyanobenzothiazole, 5-iodobenzothiazole, etc., naphthothiazole ring (for example, α- Naphthothiazole, β-naphthothiazole, γ-naphthothiazole, 5-methoxy-β-naphthothiazole, 8-methoxy-α-naphthothiazole, 6-methoxy-8-acetyloxy-β-naphthothiazole, 8,9-dihydro -
β-naphthothiazole, etc.), oxazole ring (eg, 4-methyloxazole, 4,5-diphenyloxazole, 4-phenoxyoxazole, etc.), benzoxazole ring (eg, benzoxazole, 5-
Chlorobenzoxazole, 5,6-dimethylbenzoxazole, 6-hydroxybenzoxazole, 5-
Phenylbenzoxazole etc.),

A ring of naphthoxazole system (for example, α-
Naphthoxazole, β-naphthoxazole, γ-naphthoxazole, etc.), selenazole ring (for example,
4-methylselenazole, 4-phenylselenazole, etc.), a benzoselenazole-based ring (eg, benzoselenazole, 5-chlorobenzoselenazole, 5-methoxybenzoselenazole, 5-hydroxybenzoselenazole, etc.), Thiazoline-based rings (eg, thiazoline,
4,4-dimethylthiazoline, etc.), a 2-pyridine ring (eg, 2-pyridine, 5-methyl-2-pyridine,
5-methoxy-2-pyridine, 4-chloro-2-pyridine, 5-carbamoyl-2-pyridine, 5-methoxycarbonyl-2-pyridine, 4-acetylamino-2-pyridine, 6-methylthio-2-pyridine, 6-methyl-
2-pyridine, etc.), 4-pyridine ring (eg, 4-pyridine
Pyridine, 3-methoxy-4-pyridine, 3,5-dimethyl-4-pyridine, 3-chloro-4-pyridine, 3-
Methyl-4-pyridine, etc., 2-quinoline-based ring (for example, 2-quinoline, 6-methyl-2-quinoline, 6-chloro-2-quinoline, 6-ethoxy-2-quinoline, 6
-Hydroxy-2-quinoline, 6-nitro-2-quinoline, 6-acetylamino-2-quinoline, 6-dimethylaminocarbonyl-2-quinoline, 8-fluoro-2-
Quinoline, etc.),

4-quinoline-based rings (eg 4-quinoline, 6-methoxy-4-quinoline, 6-acetylamino-4-quinoline, 8-chloro-4-quinoline, 6-trifluoromethyl-4-quinoline) Etc.) 1-isoquinoline-based ring (eg, 1-isoquinoline, 6-methoxy-1
-Isoquinoline, 6-chloro-1-isoquinoline, etc.),
3,3-dialkylindolenine-based rings (eg, 3,
3-dimethylindolenine, 3,3,7-trimethylindolenine, 5-chloro-3,3-dimethylindolenine, 5-ethoxycarbonyl-3,3-dimethylindolenine, 5-nitro-3,3-dimethyl Indolenine,
3,3-dimethyl-4,5-phenyleneindolenine,
3,3-dimethyl-6,7-phenylene indolenine,
5-acetylamino-3,3-dimethylindolenine,
5-diethylamino-3,3-dimethylindolenine,
5-methanesulfonylamino-3,3-dimethylindolenine, 5-benzoylamino-3,3-dimethylindolenine, etc., imidazole ring (eg, imidazole, 1-alkyl-4-phenylimidazole, 1-
Alkyl-4,5-dimethylimidazole, etc.),

Benzimidazole-based rings (eg, benzimidazole, 1-alkylbenzimidazoles, 1
-Alkyl-5-trifluorobenzimidazoles, 1
-Alkyl-5-chlorobenzimidazole, 1-alkyl-5-sulfamoylbenzimidazole, 1-aryl-5-methoxycarbonylbenzimidazole,
1-alkyl-5-acetylaminobenzimidazole, 1-alkyl-5-nitrobenzimidazole, 1
-Alkyl-5-diethylaminobenzimidazole,
Nucleus-containing ring containing 1-alkyl-5-pentyloxybenzimidazole), naphthimidazole-based ring (eg 1-alkyl-α-naphthimidazole, 1-alkyl-5-methoxy-β-naphthimidazole, etc.) And 5- and 6-membered heterocycles such as

The ring formed by Z ₁ and Z ₂ may be substituted with one or more substituents and may be fused with another saturated or unsaturated ring. Preferable examples of the substituent that may be present on the ring formed by Z ₁ and Z ₂ include 1 or 2 or more alkyl groups having 1 to 15 carbon atoms,
Alkoxy group having 1 to 15 carbon atoms, aryloxy group having 6 to 15 carbon atoms, halogen atom (chlorine, bromine, fluorine and iodine), aryl group having 6 to 15 carbon atoms, hydroxyl group, amino group, alkyl group or aryl group An amino group substituted with, an acylamino group, a sulfonylamino group, a carbamoyl group, a sulfamoyl group, a carboxyl group, a carbon number of 2 to
15 alkoxycarbonyl group, C2-C15 acyloxy group, 5- or 6-membered heterocycle (pyrrole ring, furan ring, piperidine ring, morpholine ring, pyridine ring, etc.),
A cyano group, a nitro group and the like, and preferable examples of a saturated or unsaturated ring condensed therewith are a cyclopentene ring, a cyclohexene ring, a benzene ring, a naphthalene ring, an anthracene ring, a phenanthrene ring, a thiophene ring, a pyridine ring and the like. Can be mentioned.

The compounds of the present invention are described in European Patent No. 52
7,494, JP-A-5-117148, U.S. Patent Application No. 692,347, British Patents 489,335 and 487,
051; U.S. Pat. No. 2,388,963, 2,454,629
And 2,504,468; EB Knott et al., J.
Chem. Soc., 4762 (1952) and Knot et al., J.
Chem. Soc., 949 (1955). It can be easily prepared from known starting materials according to the method disclosed in, and the disclosure content is included in the present specification. Typical examples of the compounds of the general formulas (1) and (2) that can be used in the present invention include compounds 1 to 348 (in order from A to EP 527,494, pages 15 to 129). −
1 to A-348) and JP-A-5-117148.
No., page 12 to page 139, compound 1 to compound 382 (referred to as B-1 to B-382 in order), and the following compound groups. However, the invention should not be construed as limited to these compounds.

[0020]

[Chemical 5]

[0021]

[Chemical 6]

[0022]

[Chemical 7]

Of these exemplified compounds, more preferred are compounds A-28, A-254, A-283 and B-
185 and C-4. The pharmaceutical composition of the present invention containing one or more compounds of the above general formulas (1) and (2) is
Melanoma, liver cancer, glioma, neuroblastoma, sarcoma and lung,
Colon, breast, bladder, ovary, testis, prostate, neck, pancreas,
It can be effectively used for photochemical treatment of various types of cancer including cancer of stomach, small intestine and other organs. The pharmaceutical composition of the present invention may contain one or more compounds of the above general formulas (1) and (2), and if desired, a conventionally used known antitumor agent. It may be used in combination with other therapeutic agents including. Preferable examples of such conventionally used antitumor agents include adriamycin, cisplatin, colchicine, CCNU (Lomastine)
, BCNU (Carmustine), actinomycin D, 5-
Fluorouracil, thiotepa, cytosine arabinoside, cyclophosphamide, mitomycin C and the like can be mentioned.

Suitable examples of pharmaceutical carriers or diluents which can be used in the pharmaceutical composition of the present invention in combination with the compounds of the general formulas (1) and (2) are glucose; saccharose; lactose; ethyl alcohol; glycerin. Mannitol; sorbitol; pentaerythritol; diethylene glycol, triethylene glycol,
Ethylene glycol, propylene glycol, dipropylene glycol, polyethylene glycol 400, other polyethylene glycols; glyceryl trilaurate,
Mono-, di- and triglycerides of saturated fatty acids such as glyceryl monostearate, glyceryl tristearate and glyceryl distearate; pectin; starch; alginic acid; xylose; talc; Ishimatsu; olive oil, peanut oil, castor oil, corn oil, wheat Malt oil,
Oils and fats such as sesame oil, cottonseed oil, sunflower oil and cod liver oil; gelatin; lecithin; silica; cellulose;
Cellulose derivatives such as methyl hydroxypropyl cellulose, methyl cellulose, hydroxyethyl cellulose; calcium stearate, calcium laurate,
1 such as magnesium oleate, calcium palmitate, calcium behenate and magnesium stearate
Magnesium or calcium salts of fatty acids having 2 to 22 carbon atoms; cyclodextrins; eg α-
Cyclodextrin, β-cyclodextrin, γ-cyclodextrin, hydroxyethyl-β-cyclodextrin, hydroxypropyl-β-cyclodextrin, dihydroxypropyl-β-cyclodextrin,
Carboxymethylethyl-β-cyclodextrin and dimethyl-β-cyclodextrin; emulsifiers;
Saturated and unsaturated fatty acids having 2 to 22, especially 10 to 18 carbon atoms and monohydric aliphatic alcohols such as glycols, glycerin, diethylene glycol, pentaerythritol, ethyl alcohol, butyl alcohol, octadecyl alcohol (for example, alkanol With 1 to 20 carbon atoms) or esters with polyhydric alcohols; or silicones such as dimethyl polysiloxane. Also, the additional carriers conventionally used in pharmaceutical compositions are suitable for the present invention. Examples of the light source used for photochemotherapy using the pharmaceutical composition of the present invention include tungsten light, fluorescent light, laser light and the like.

The pharmaceutically effective amount of the compound of the present invention and the administration method or administration means are as follows: nature of cancer, treatment course, severity of disease, degree of malignancy, degree of metastasis, amount of tumor, general health condition. , Weight, age, sex, and the (genetic) racial background of the patient. However, in general, the dosage of the compound of the invention will be from 10 to 500 mg, more usually 1
The dosage is from 00 to 200 mg / day / 70 kg of body weight. Suitable administration methods include, for example, the compounds of the general formulas (1) and (2) dissolved in, for example, a 5% aqueous glucose solution, or other methods as described above. Intravenous, intraperitoneal, intramuscular or intravesical injection, followed by light irradiation in the form of a suitable carrier or diluent. In order to clarify the effectiveness of the compounds of the general formulas (1) and (2) and the pharmaceutical composition thereof of the present invention, the following examples are shown and the above-mentioned general formula (1) used in the composition of the present invention is shown. ), (2) revealed the efficacy value of many compounds. The results obtained are shown in the table.

[0026]

Example 1 Human maxillary epithelial cancer cell line KB-cell was selected as a representative of cancer cells. KB-cell (4000 cells / well) was inoculated into a 96-well microplate for cell culture. The compound of the present invention was dissolved in dimethyl sulfoxide to a concentration of 10 μg / mL, and this solution was serially diluted with 5% glucose solution to 300 to 0.01 μg / mL, and 20 μL was added to each well. In addition, it was left to stand for 1 hour. The microplate was irradiated with light under the following conditions. [Conditions] Light source 250W CABIN AF-2500 Slide projector filter L-42 (A-283, D-50, A-
28, for A-254) Y-50 (for B-185) light intensity 119 to 139 J · m ⁻² · S ⁻¹ (L-4
2) 20.5 to 21.4 J · m ⁻² · S ⁻¹ (when using Y-50) Temperature 28 to 30 ° C Irradiation time 10 After irradiation of 10 spectra, KB-cell is incubated for 3 days. did. The cells were fixed with 10% formalin, stained with 0.1% crystal violet, and washed with water. After drying, the crystal violet was eluted with 100 μL of dimethyl sulfoxide, and the absorbance was measured with an ELISA analyzer. The ratio of the absorbance to the control was determined, and the compound concentration at which the ratio was 50% was taken as the IC ₅₀ value. The table below shows the IC ₅₀ values with and without light irradiation.

[0027]

[Table 1] ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ Compound No. IC ₅₀ value [μg / mL] Activity Specific light irradiation Irradiated IC ₅₀ (irradiated) / IC ₅₀ (irradiated) A-283 0.0512 0.495 9.67 A-28 0.00358 0.164 45.8 A-254 <0.001 0.0849> 84.9 B-185 0.0133 0.24 18.0 ━━━━━ ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━

As is clear from this table, the compound of the present invention having a high cancer cell selectivity has a markedly increased cancer cell toxicity upon irradiation with light, and is thus suitable for photochemotherapy of cancer.

[0029]

[0030]

[0031]

Continuation of the front page (56) References JP-A-5-117148 (JP, A) JP-A-4-139186 (JP, A) European Patent Application Publication 527494 (EP, A1) (58) Fields investigated (Int .Cl. ⁷ , DB name) C07D 417/12 CA (STN) REGISTRY (STN)

Claims (2)

(57) [Claims] 1. A pharmaceutical composition for photochemotherapy of cancer, which comprises, as an active ingredient, at least one compound represented by the following general formula (1). [Chemical 1] (In the formula, R represents an alkyl group, an aryl group or a heterocyclic group, A and B represent a 5- or 6-membered ring containing at least one hetero atom or a condensed ring thereof, and Y represents S, O, Se, Or -NR-, L ₁ , L ₂ , L ₃ , L ₄ and L ₅ each independently represent a methine group, and when L ₁ is a substituted methine group, the atoms constituting L ₁ and A are May combine with each other to form a 5- or 6-membered ring, and when L ₅ is a substituted methine group, L ₅ and B
The atoms constituting the above may be bonded to form a 5- or 6-membered ring, Q represents a counter anion, k represents the number necessary for reducing the charge of the entire molecule to zero,
p and q represent 0, 1, 2, or 3, respectively. ) 2. The composition according to claim 1, wherein the compound represented by the general formula (1) is a compound selected from the group consisting of compounds represented by the following general formula (2). [Chemical 2] (In the formula, R ₁ and R ₃ each represent an alkyl group, which may be the same or different, R ₂ represents an alkyl group, an aryl group or a heterocyclic group, and X ₁ and X ₂ each represent O, S, Se, -CH = CH-, -CR ₄ R _5- (R ₄ and R ₅ each independently represent an alkyl group), or -NR _6- (R ₆ represents an alkyl group, an aryl group or a heterocyclic group. ), Which may be the same or different, Y ₁ is O, S, Se,
Or —NR ₇ — (R ₇ represents an alkyl group, an aryl group or a heterocyclic group), Z ₁ and Z ₂ represent an atomic group necessary for forming a 5-membered or 6-membered ring, and are the same. L ₁ , L ₂ , L ₃ , L ₄ and L ₅ each independently represent a methine group, and when L ₁ is a substituted methine group, L ₁ and R ₁ are combined to form 5 or It may form a 6-membered ring, and when L ₅ is a substituted methine group, L ₅ and R ₃ may combine to form a 5- or 6-membered ring, and R ₄ and R ₅ are respectively It represents an alkyl group, which may be the same or different, m and n each represent 0 or 1, and may be the same or different, and Q, k, p and q are as defined above. )