CN116041248A - Carbazole derivative with anticancer activity and preparation method and application thereof - Google Patents
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Abstract
The invention belongs to the technical field of pharmaceutical chemistry, and relates to a carbazole derivative with anticancer activity, a preparation method and application thereof, wherein the carbazole derivative with anticancer activity comprises a compound with a structure shown in a formula I or pharmaceutically acceptable salt or optical isomer of the compound with the structure shown in the formula I; the carbazole derivative has simple structure, is easy to synthesize and manufacture, and has anticancer bioactivity;
Description
Technical Field
The invention belongs to the technical field of pharmaceutical chemistry, and particularly relates to a carbazole derivative with anticancer activity, and a preparation method and application thereof.
Background
In 2012, the Jimmy Orjala team achieved the separation, identification of 12-epi-fischerindole W Nitrile and dechloro 12-epi-fischerindole W nitrile from fermentation broths of fischer sp. In 2014, li Ang, the combination of problems completed the synthesis and structural modification of dechloro 12-epi-fischerindole W nitrile by synthesis (angel. Chem. Int. Ed. 2014, 53, 13840).
Because of the separation and extraction of the Aflavazole, 12-epi-fischerindole W Nitrile and dechloro 12-epi-fischerindole W nitrile carbazole alkaloids, a sufficient amount of compounds are difficult to obtain, and the structural complexity of the compounds brings difficulty to subsequent patent drug research and commercialization.
Disclosure of Invention
The invention provides a carbazole derivative with anticancer activity, a preparation method and application thereof, aiming at the defects of the prior art. Can obtain the small molecular compound with anticancer biological activity, which has simple structure and is easy to synthesize and manufacture.
To this end, the first aspect of the present invention provides a carbazole derivative having anticancer activity, which includes a compound having a structure as shown in formula I or a pharmaceutically acceptable salt or optical isomer of a compound having a structure as shown in formula I,
In the formula I, R is selected from hydrogen, C containing substituent or not containing substituent 1 -C 10 Alkyl, C with or without substituents 1 -C 10 Alkoxy, C with or without substituents 6 -C 30 Any one of aryl and acyl;
R 1 to R 10 Identical or different, each independently selected from hydrogen, substituted or unsubstituted C 1 -C 10 Alkyl, C with or without substituents 1 -C 10 Alkoxy, amino, C with or without substituents 6 -C 30 Any one of aryl, acyl, cyano, hydroxyl and amido.
In some embodiments of the invention, in formula I, R is selected from hydrogen, substituted or unsubstituted C 2 -C 10 Alkyl, C with or without substituents 2 -C 10 Alkoxy, C with or without substituents 6 -C 20 Aryl, acyl.
In some embodiments of the invention, R is selected from hydrogen, C containing a heteroatom 2 -C 10 Alkyl, C with or without substituents 2 -C 10 Any one of alkoxy groups.
In some embodiments of the invention, in formula I, R is selected from substituent-containing or substituent-free C 2 -C 10 An alkoxy group.
According to the invention, in formula I, R is selected from methoxymethyl.
In some embodiments of the invention, in formula I, R 1 To R 10 Each independently selected from hydrogen, substituent-containing or substituent-free C 1 -C 10 Alkyl, C with or without substituents 2 -C 10 Alkoxy, amino, C with or without substituents 6 -C 20 Any one of aryl, acyl, cyano, hydroxyl and amido.
In some embodiments of the invention, in formula I, R 1 To R 10 Each independently selected from hydrogen, substituent-containing or substituent-free C 1 -C 8 Straight-chain alkyl, substituted or unsubstituted C 1 -C 8 Branched alkyl, substituted or unsubstituted C 3 -C 10 Cycloalkyl, C 1 -C 10 C with or without substituents on the alkyl linkage 3 -C 10 Cycloalkyl, C containing hetero atoms 2 -C 10 Alkyl, C with or without substituents 2 -C 10 Alkoxy, amino, phenyl with or without substituents, C 1 -C 10 Phenyl with or without substituent and C with or without substituent linked by alkyl 6 -C 15 Any one of heteroaryl, acyl, cyano, hydroxy, and amide.
In some embodiments of the invention, in formula I, R 1 To R 10 Each independently selected from hydrogen, substitutedC being a radical or not containing substituents 1 -C 8 Straight-chain alkyl, substituted or unsubstituted C 1 -C 8 Branched alkyl, substituted or unsubstituted C 3 -C 10 Heterocyclyl, C 1 -C 10 C with or without substituents on the alkyl linkage 3 -C 10 Heterocyclyl, substituted or unsubstituted C 2 -C 10 Any one of alkoxy, acyl, cyano, hydroxy and amido.
According to the invention, in formula I, R 1 To R 10 Each independently selected from any one of hydrogen, methyl, ethoxy, acyl, cyano, hydroxy and amido.
In some embodiments of the invention, the substituents are selected from C 1 -C 10 Alkyl, C 1 -C 10 Alkoxy, C 6 -C 20 Any one of aryl, amino and hydroxyl.
In some embodiments of the invention, the substituents are selected from C 2 -C 10 Alkyl, C 2 -C 10 Alkoxy, phenyl, C 1 -C 10 Any one of phenyl, amino and hydroxyl substituted by alkyl.
In some embodiments of the invention, the substituent is selected from any one of methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, n-pentyl, isopentyl, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, t-butoxy, n-pentoxy, isopentoxy, phenyl, benzyl, phenethyl, amino, hydroxyl.
In some embodiments of the invention, the carbazole derivative is selected from 1, 1-diethoxy-5- (methoxymethyl) -3-methyl-2, 5-dihydro-1H-cyclobutane [ c ] carbazole, 5- (methoxymethyl) -3-methyl-2, 5-dihydro-1H-cyclobutane [ c ] carbazole-1-one, 5- (methoxymethyl) -3-methyl-2, 5-dihydro-1H-cyclobutane [ c ] carbazole-1-carbonitrile, 5- (methoxymethyl) -3-methyl-2, 5-dihydro-1H-cyclobutane [ c ] carbazole-1-ol or 5- (methoxymethyl) -3-methyl-2, 5-dihydro-1H-cyclobutane [ c ] carbazole-1-carboxamide.
In a second aspect, the present invention provides a method for producing a carbazole derivative having an anticancer activity, comprising: reacting the compound shown in the formula II with the compound shown in the formula III to generate a compound shown in the formula IV, reacting the compound shown in the formula IV with the compound shown in the formula I to generate a compound shown in the formula I, wherein the reaction formula is shown in the formula (1),
wherein R in formula II and formula IV are as defined for R in formula I, R in formula II 5 To R 10 And R in formula IV 5 To R 10 R in formula I 5 To R 10 R in formula III and formula IV a 、R b 、R 3 、R 4 R in formula I 1 To R 4 Is defined in (a).
In some embodiments of the invention, the reaction of formula (1) is carried out in a solvent; the solvent is at least one selected from ethers, alcohols and aprotic polar solvents.
According to the invention, the solvent is selected from at least one of tetrahydrofuran, methanol and dimethyl sulfoxide.
According to the invention, the preparation method is specifically shown in the following reaction formula,
according to the invention, the preparation method specifically comprises the following steps: alkylating the nitrogen atom of bromocarbazole 1-1, then carrying out Kumada coupling, then carrying out bromination, then carrying out a form [2+2] reaction, and hydrolyzing the [2+2] reaction product 2 under acidic conditions to obtain carbazolocyclobutanone 3; and the carbazol cyclobutanone 3 is reduced to obtain carbazol cyclobutanol 5; the carbazol cyclobutanone 3 reacts with p-toluenesulfonyl isonitrile under the action of alkali to generate carbazol cyclobutanenitrile 4; and (3) hydrolyzing the carbazolo-cyclobutanenitrile 4 under alkaline conditions to obtain the carbazolo-cyclobutanamide 6.
In a third aspect, the invention provides an application of the carbazole derivative according to the first aspect or the carbazole derivative prepared by the preparation method according to the second aspect in preparation of anti-cancer drugs.
According to the invention, the cancers include breast cancer, lung cancer and glioma.
The invention has the beneficial effects that:
(1) The carbazole derivative provided by the invention has a simple structure, is easy to synthesize and manufacture, and is a small molecular compound with anticancer bioactivity.
(2) The preparation method provided by the invention is simple and convenient, and the carbazole derivative with anticancer activity provided by the invention is easy to synthesize and manufacture.
Detailed Description
In order that the invention may be more readily understood, the invention will be described in detail below with reference to the following examples, which are given by way of illustration only and are not limiting of the scope of application of the invention.
The invention provides a carbazole derivative with anticancer activity, a preparation method and application thereof, and a small molecular compound with anticancer biological activity, which has a simple structure and is easy to synthesize and manufacture.
Comparative example 1
The comparative example provides a preparation method of carbazole derivatives, the reaction formula is shown as the following formula,
the method comprises the following specific steps:
s1: naH (4.41g,60%wt in mineral oil,110 mmol) was weighed and added to a 1L round bottom bottle, THF (tetrahydrofuran, 500 mL) was added, cooled in an ice water bath, and compound 1-1 (24.67 g,100 mmol) was added to the round bottom bottle in 20 portions over 10min, and stirred in the ice water bath for 30 min; MOMCl (chloromethyl methyl ether, 8.0 mL,100 mmol) was then added to the round bottom flask over 5min and stirred for 2h under ice water bath conditions; subsequent addition of H 2 O (200 mL) to a round bottom bottle, the aqueous phase was extracted with EA (ethyl acetate, 200 mL. Times.3), the organic phases combined and dried over anhydrous sodium sulfate, filtered with suction, concentrated by rotary evaporation, and subjected toColumn chromatography (PE/ea=20/1), rotary evaporation concentration of the product followed by pumping to constant weight afforded 1-2 (28.01 g, yield=96%);
s2: weighing Pd (dppf) Cl 2 (1.83 g,2.5 mmol) was added to a 1L round bottom bottle, solid 1-2 (7.20 g, 25.0 mmol) was dissolved in THF (250 mL) was added to the round bottom bottle, cooled in an ice water bath, then MeMgBr (3M in THF,42.0mL,125.0mmol) was added dropwise to the round bottom bottle via a double-ended needle, heated to 60 ℃ for 12h, cooled to room temperature, then 500mL saturated aqueous ammonium chloride solution was added to the round bottom bottle to quench the reaction, the aqueous phase was extracted with EA (ethyl acetate, 100 mL x3 times), the organic phases were combined and dried over anhydrous sodium sulfate, suction filtered, rotary evaporation concentrated and column chromatography chromatographed (PE/ea=20/1), the product was rotary evaporated concentrated and dried to constant weight to give a white solid 1-3 (5.13 g, yield=91%);
s3: solid 1-3 (2.25 g,10.0 mmol) was dissolved in THF (50 mL) and added to a 250mL round bottom flask and placed in an ice water bath, then NBS (N-bromosuccinimide, 2.18g,12.0 mmol) was added to the round bottom flask, reacted for 10h under ice water bath conditions, quenched by adding 50mL saturated aqueous sodium bicarbonate to the round bottom flask, extracted with EA (ethyl acetate, 50mL x4 times), the organic phases combined and dried over anhydrous sodium sulfate, suction filtered, rotary evaporated concentrated and column chromatographed (PE/ea=20/1), the product was concentrated by rotary evaporation and then pumped to constant weight to give compound 1 as a white solid: 3-bromo-9- (methoxymethyl) -2-methyl-9H-carbazole (1.84 g, yield=60%).
The nuclear magnetic resonance hydrogen spectrum of the compound 1 is 1 H NMR(400 MHz, CDCl 3 ) δ 8.22 (s, 1H), 7.99 (d, J=7.8Hz, 1H), 7.52 (d, J=8.1Hz, 1H), 7.49–7.44 (m, 1H), 7.42 (s, 1H), 7.27 (s, 1H), 5.64 (s, 2H), 3.29 (s, 3H), 2.59 (s, 4H)。
Example 1
The embodiment provides a preparation method of carbazole derivatives with anticancer activity, the reaction formula is shown in the following formula,
the method comprises the following specific steps: weighing NaNH in a glove box 2 (sodium amide, 23.5mg,0.60 mmol) and compound 1 (91.2 mg, 0.30 mmol) were added to a reaction tube, THF (0.5 mL) and 1, 1-diethoxyethylene (0.10 mL, 0.75 mmol) were then added to the reaction tube, the mixture was cooled to room temperature after stirring at 60 ℃ for 12h, saturated aqueous ammonium chloride solution was added to the reaction tube to quench the reaction, EA (5 mL x3 times) was extracted, the organic phases were combined and dried over anhydrous sodium sulfate, suction filtration, rotary evaporation concentration and column chromatography (PE/ea=30/1), the product was concentrated by rotary evaporation and then pumped to constant weight to give compound 2 as a white solid: 1, 1-diethoxy-5- (methoxymethyl) -3-methyl-2, 5-dihydro-1H-cyclobutane [ c ]]Carbazole (55.0 mg, yield=54%).
1 H NMR(400 MHz, CDCl 3 ) δ 8.09 (d, J=7.8 Hz, 1H), 7.55–7.49 (m, 1H), 7.49–7.40 (m, 1H), 7.33 (s, 1H), 7.23 (s, 1H), 5.67 (s, 2H), 4.09–3.95 (m, 2H), 3.93–3.81 (m, 2H), 3.45 (s, 2H), 3.27 (s, 3H), 2.41 (s, 3H), 1.33–1.23 (m, 6H)。
Example 2
The embodiment provides a preparation method of carbazole derivatives with anticancer activity, the reaction formula is shown in the following formula,
the method comprises the following specific steps: compound 2 (55.0 mg) and THF (6 mL) were added to a 25mL round bottom bottle, cooled in an ice water bath, aqueous HCl (1M strength aqueous solution, 3 mL) was added, stirred for 1h under ice water bath conditions, the aqueous phase was extracted with EA (ethyl acetate, 5mL x3 times), the organic phases were combined and dried over anhydrous sodium sulfate, filtered off with suction, concentrated by rotary evaporation and chromatographed on column (PE/ea=30/1), and the product was concentrated by rotary evaporation and pumped to constant weight to give compound 3 as a white solid: 5- (methoxymethyl) -3-methyl-2, 5-dihydro-1H-cyclobuta [ c ] carbazol-1-one (34.7 mg, yield=80%).
The nuclear magnetic resonance hydrogen spectrum of the compound 3 is 1 H NMR(400 MHz, CDCl 3 ) δ 8.22 (d, J=7.8Hz, 1H), 7.56–7.46 (m, 3H), 7.30 (t, J=7.3Hz, 1H), 5.69 (s, 2H), 4.04 (s, 2H), 3.29 (s, 3H), 2.54 (s, 3H)。
Example 3
The embodiment provides a preparation method of carbazole derivatives with anticancer activity, the reaction formula is shown in the following formula,
the method comprises the following specific steps: tBuOK (potassium tert-butoxide, 39.7.0 mg,0.35mmol) was added to the reaction tube, followed by THF (1.50 mL) and MeOH (methanol, 0.05 mL), the reaction tube was cooled in an ice water bath for 10min, p-toluenesulfonyl isonitrile (31.0 mg,0.15 mmol) was added to the reaction tube and stirred for 30min, then compound 3 (13.6 mg,0.05 mmol) was dissolved in THF (3.00 mL) and MeOH (0.08 mL) and added dropwise to the reaction tube via syringe for 8min, stirred for 25min under ice water bath conditions and warmed to 30 ℃ for 12h, the reaction solution was back-quenched into 6% aqueous hydrochloric acid (10 mL) and stirred at room temperature for 30min, the aqueous phase was extracted with EA (10 mL x4 times), the combined organic phases were dried over anhydrous sodium sulfate, suction filtered, concentrated by rotary evaporation and column chromatography (PE/ea=10/1), the product was concentrated by rotary evaporation and pumped to constant weight to give compound 4 as a yellow powder: 5- (methoxymethyl) -3-methyl-2, 5-dihydro-1H-cyclobutane [ c ] carbazole-1-carbonitrile (8.2 mg, yield=60%).
The nuclear magnetic resonance hydrogen spectrum of the compound 4 is 1 H NMR(400 MHz, CDCl 3 ) δ 8.02 (d, J=7.8Hz, 1H), 7.54 (t, J=7.0Hz, 1H), 7.48 (s, 1H), 7.34 (s, 1H), 7.29 (s, 1H), 5.67 (s, 2H), 4.54 (s, 1H), 3.79 (d, J=5.3Hz, 1H), 3.70 (d, J=2.5Hz, 1H), 3.28 (s, 3H), 2.39 (s, 3H)。
Example 4
The embodiment provides a preparation method of carbazole derivatives with anticancer activity, the reaction formula is shown in the following formula,
the method comprises the following specific steps: compound 3 (13.6 mg,0.05 mmol) was dissolved in MeOH (1.0 mL) and added to the reaction tube, which was cooled in an ice-water bath for 10min; subsequently NaBH is applied 4 (sodium borohydride, 3.8mg,0.10 mmol) was added to the reaction tube and ice-water bathReacting for 30min under cooling condition; the reaction was quenched by adding 3mL saturated aqueous ammonium chloride to the reaction tube, extracting the aqueous phase with EA (5 ml x3 times), combining the organic phases and drying over anhydrous sodium sulfate, suction filtration, rotary evaporation concentration and column chromatography (PE/ea=5/1), the product was concentrated by rotary evaporation and dried by suction to constant weight to give a yellow-white powder solid compound 5:5- (methoxymethyl) -3-methyl-2, 5-dihydro-1H-cyclobutane [ c ]]Carbazole-1-ol (12.4 mg, yield=92%).
The nuclear magnetic resonance hydrogen spectrum of the compound 5 is 1 H NMR(400 MHz, CDCl 3 ) δ 8.06 (d, J=7.8Hz, 1H), 7.57 (t, J=7.1Hz, 1H), 7.46 (m, 1H), 7.32 (s, 1H), 7.31 (m, 1H), 5.67 (s, 2H), 4.82 (s, 1H),4.54–4.39 (m, 1H), 4.08–3.82 (m, 1H), 3.71–3.60 (m, 1H), 3.31 (s, 3H), 2.36 (s, 3H)。
Example 5
The embodiment provides a preparation method of carbazole derivatives with anticancer activity, the reaction formula is shown in the following formula,
the method comprises the following specific steps: compound 4 (13.6 mg,0.05 mmol) was dissolved in DMSO (dimethylsulfoxide, 1.0 mL) and added to the reaction tube, which was cooled in an ice-water bath for 10min; liOH (lithium hydroxide, 4.1mg,0.10 mmol) and 30% hydrogen peroxide solution (0.02 mL) were then added to the reaction tube and allowed to react for 30min with ice-water bath cooling; EA (10 mL) was added for extraction, the combined organic phases were washed with water (5 mL x3 times) and dried over anhydrous sodium sulfate, filtered off with suction, concentrated by rotary evaporation and chromatographed on column (PE/ea=5/1), the product was concentrated by rotary evaporation and pumped down to constant weight to give the white powdery solid compound 6:5- (methoxymethyl) -3-methyl-2, 5-dihydro-1H-cyclobutane [ c ] carbazole-1-carboxamide (12.4 mg, yield=92%).
The nuclear magnetic resonance hydrogen spectrum of the compound 6 is 1 H NMR(400 MHz, CDCl 3 ) δ 10.02 (s, 2H), 7.99 (t, J=8.4Hz, 1H), 7.59–7.52 (m, 1H), 7.45 (dt, J=19.2, 7.6 Hz, 1H), 7.35 (s, 1H), 7.24 (dt, J=14.9, 7.8Hz, 2H), 5.67 (s, 2H), 4.62–4.43 (m, 1H), 4.15–3.78 (m, 1H), 3.69–3.60 (m, 1H), 3.30 (d, J=3.2 Hz, 3H), 2.47 (s, 3H)。
Experimental example 1
Culturing HC-29 (colon cancer cell), MCF-7 (human breast cancer cell), NCI-H460 (human large cell lung cancer cell), A549 (human non-small cell lung cancer cell), SF268 (human glioma cell), hela (cervical cancer cell), HCT116 (colon cancer cell) according to ATCC standard method, incubating in 24 deg.C incubator for 24 hr, adding compound (DMSO solution) with serial concentration prepared in comparative example 1 and examples 1-5, incubating in incubator for 24 hr, measuring absorbance (a) at 450nm wavelength by cck8 method, calculating compound concentration when inhibiting cell growth by 50%, and using IC 50 (semi-inhibitory concentration) representation; the results are shown in Table 1.
Inhibition of cell growth by the compounds of Table 1 (IC 50 )
As shown in Table 1, the carbazole derivatives with anticancer activity, namely compounds 2-6, with the structure shown in formula I provided by the invention have excellent inhibition effect on proliferation activity of MCF-7, NCI-H460, A549 and SF268 cells.
It should be noted that the above-described embodiments are only for explaining the present invention and do not constitute any limitation of the present invention. The invention has been described with reference to exemplary embodiments, but it is understood that the words which have been used are words of description and illustration, rather than words of limitation. Modifications may be made to the invention as defined in the appended claims, and the invention may be modified without departing from the scope and spirit of the invention. Although the invention is described herein with reference to particular means, materials and embodiments, the invention is not intended to be limited to the particulars disclosed herein, as the invention extends to all other means and applications which perform the same function.
Claims (10)
1. A carbazole derivative with anticancer activity is characterized by comprising a compound with a structure shown in a formula I or a pharmaceutically acceptable salt or optical isomer of the compound with the structure shown in the formula I,
In the formula I, R is selected from hydrogen, C containing substituent or not containing substituent 1 -C 10 Alkyl, C with or without substituents 1 -C 10 Alkoxy, C with or without substituents 6 -C 30 Any one of aryl and acyl;
R 1 to R 10 Identical or different, each independently selected from hydrogen, substituted or unsubstituted C 1 -C 10 Alkyl, C with or without substituents 1 -C 10 Alkoxy, amino, C with or without substituents 6 -C 30 Any one of aryl, acyl, cyano, hydroxyl and amido.
2. Carbazole derivative according to claim 1, characterized in that in formula I R is selected from hydrogen, substituted or unsubstituted C 2 -C 10 Alkyl, C with or without substituents 2 -C 10 Alkoxy, C with or without substituents 6 -C 20 Any one of aryl and acyl;
and/or R 1 To R 10 Each independently selected from hydrogen, substituent-containing or substituent-free C 1 -C 10 Alkyl, C with or without substituents 2 -C 10 Alkoxy, amino, C with or without substituents 6 -C 20 Any one of aryl, acyl, cyano, hydroxyl and amido.
3. Carbazole derivative according to claim 2, characterized in that in formula I R is selected from hydrogen, heteroatom-containing C 2 -C 10 Alkyl, C with or without substituents 2 -C 10 Any one of alkoxy groups;
and/or R 1 To R 10 Each independently selected from hydrogen, substituent-containing or substituent-free C 1 -C 8 Straight-chain alkyl, substituted or unsubstituted C 1 -C 8 Branched alkyl, substituted or unsubstituted C 3 -C 10 Cycloalkyl, C 1 -C 10 C with or without substituents on the alkyl linkage 3 -C 10 Cycloalkyl, C containing hetero atoms 2 -C 10 Alkyl, C with or without substituents 2 -C 10 Alkoxy, amino, phenyl with or without substituents, C 1 -C 10 Phenyl with or without substituent and C with or without substituent linked by alkyl 6 -C 15 Any one of heteroaryl, acyl, cyano, hydroxy, and amide.
4. A carbazole derivative according to claim 3, wherein in formula I R is selected from the group consisting of substituted or unsubstituted C 2 -C 10 An alkoxy group;
and/or R 1 To R 10 Each independently selected from hydrogen, substituent-containing or substituent-free C 1 -C 8 Straight-chain alkyl, substituted or unsubstituted C 1 -C 8 Branched alkyl, substituted or unsubstituted C 3 -C 10 Heterocyclyl, C 1 -C 10 C with or without substituents on the alkyl linkage 3 -C 10 Heterocyclyl, substituted or unsubstituted C 2 -C 10 Any one of alkoxy, acyl, cyano, hydroxy and amido.
5. Carbazole derivative according to any one of claims 1 to 4, characterized in that the substituents are selected from C 1 -C 10 Alkyl, C 1 -C 10 Alkoxy, C 6 -C 20 Any one of aryl, amino and hydroxyl.
6. Carbazole derivative according to claim 5, characterized in that the substituents are chosen from C 2 -C 10 Alkyl, C 2 -C 10 Alkoxy, phenyl, C 1 -C 10 Any one of phenyl, amino and hydroxyl substituted by alkyl.
7. The carbazole derivative according to any one of claims 1 to 4, characterized in that the carbazole derivative is selected from 1, 1-diethoxy-5- (methoxymethyl) -3-methyl-2, 5-dihydro-1H-cyclobutane [ c ] carbazole, 5- (methoxymethyl) -3-methyl-2, 5-dihydro-1H-cyclobutane [ c ] carbazole-1-one, 5- (methoxymethyl) -3-methyl-2, 5-dihydro-1H-cyclobutane [ c ] carbazole-1-carbonitrile, 5- (methoxymethyl) -3-methyl-2, 5-dihydro-1H-cyclobutane [ c ] carbazole-1-ol or 5- (methoxymethyl) -3-methyl-2, 5-dihydro-1H-cyclobutane [ c ] carbazole-1-carboxamide.
8. A method for producing a carbazole derivative having an anticancer activity according to any one of claims 1 to 7, characterized by comprising: reacting the compound shown in the formula II with the compound shown in the formula III to generate a compound shown in the formula IV, reacting the compound shown in the formula IV with the compound shown in the formula I to generate a compound shown in the formula I, wherein the reaction formula is shown in the formula (1),
wherein R in formula II and formula IV are as defined for R in formula I, R in formula II 5 To R 10 And R in formula IV 5 To R 10 R in formula I 5 To R 10 R in formula III and formula IV a 、R b 、R 3 、R 4 R in formula I 1 To R 4 Is defined in (a).
9. The process according to claim 8, wherein the reaction of formula (1) is carried out in a solvent; the solvent is at least one selected from ethers, alcohols and aprotic polar solvents.
10. Use of a carbazole derivative as claimed in any one of claims 1 to 7 or a carbazole derivative produced by the production method as claimed in claim 8 or 9 in the production of an anti-cancer drug.
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