A USP16 inhibitor, its preparation method and its application in medicine

Abstract

The present invention relates to the field of biomedical technologies, and particularly relates to a USP16 inhibitor, a preparation method thereof, and an application in medicine. In the present invention, a novel benzoselenofuranone compound is obtained. The preparation process is simple and easy to implement, the raw material cost is low, and the functional group compatibility is good. The benzoselenofuranone compound has the property of highly inhibiting the activity of USP16, and can be used as a USP16 selective inhibitor, providing a safe and highly effective candidate drug molecule for targeted treatment of prostate cancer. The benzoselenofuranone compound can be used to prepare a drug for treating and / or preventing prostate cancer, so as to promote the treatment effect of prostate cancer.

Description

Technical Field

[0001] The present invention relates to the field of biomedical technologies, and particularly to a USP16 inhibitor, a preparation method thereof, and an application thereof in medicine. Background Art

[0002] Prostate cancer is a highly prevalent malignant tumor among men globally. In its castration-resistant phase (CRPC), the development of resistance to traditional therapies poses a severe challenge to clinical treatment. As a member of the deubiquitinating enzyme family, ubiquitin-specific protease 16 (USP16) plays a crucial regulatory role in the progression of prostate cancer. Research has shown that USP16 can prevent the degradation of c-Myc protein and maintain its stability by removing its ubiquitination modification, thereby activating downstream oncogenes (such as Cyclin D1 and CDK4), driving the proliferation and invasion of cancer cells. Analysis of clinical samples has shown that the expression level of USP16 in prostate cancer tissues is significantly higher than that in normal tissues, and is positively correlated with the degree of tumor malignancy (Gleason score), suggesting its potential as a therapeutic target.

[0003] However, existing broad-spectrum USP inhibitors (such as YM155) lack selectivity and can simultaneously inhibit multiple targets such as USP7 and USP28, leading to off-target effects (such as abnormal DNA damage response and immune imbalance), which limits their clinical translation value. For example, although YM155 shows anti-tumor activity in various tumor models, its low selectivity for USP16 may cause serious side effects.

[0004] USP16-selective inhibitors can not only be used alone or in combination with existing drugs (such as enzalutamide) to enhance the therapeutic effect, but may also be extended to other solid tumors with abnormal activation of USP16 (such as liver cancer and colon cancer), providing a new strategy for precision cancer treatment. Therefore, the development of highly selective inhibitors targeting USP16 has become a key need to break through the treatment bottleneck of CRPC and improve treatment safety. Summary of the Invention

[0005] In order to improve the therapeutic effect of prostate cancer, the present invention provides a USP16 inhibitor, a preparation method thereof, and an application thereof in medicine.

[0006] The first aspect of the present invention provides a benzoselenofuranone compound or a pharmaceutically acceptable salt thereof, and the above benzoselenofuranone compound has the structure shown in Formula 8:

[0007] ;

[0008] Wherein, R is selected from hydrogen, C1-C4 alkyl, C1-C4 alkoxy, halogen atom, and hydroxyl group.

[0009] The benzoselenofuranone compound shown in Formula 8 or a pharmaceutically acceptable salt thereof has the property of selectively inhibiting the activity of USP16 and is a USP16 selective inhibitor. The pharmaceutically acceptable salt of the benzoselenofuranone compound shown in Formula 8 can be easily prepared from the benzoselenofuranone compound shown in Formula 8 as a raw material. For example, reacting the benzoselenofuranone compound shown in Formula 8 with hydrochloric acid can obtain the hydrochloride salt of the benzoselenofuranone compound shown in Formula 8.

[0010] In some alternative embodiments, the above-mentioned R is selected from hydrogen, methyl, ethyl, fluorine atom, chlorine atom, bromine atom, iodine atom, and hydroxyl group.

[0011] In some alternative embodiments, the above-mentioned benzoselenofuranone compound has a structure shown in one of Formula 8a to Formula 8f:

[0012] , ,

[0013] , ,

[0014] , .

[0015] The second aspect of the present invention provides a method for preparing the benzoselenofuranone compound shown in Formula 8, which includes the following steps:

[0016] In the presence of persulfate, reacting the compound shown in Formula 6 with the benzeneselenide compound shown in Formula 7 to obtain the benzoselenofuranone compound shown in Formula 8;

[0017] , , ;

[0018] Wherein, R is selected from hydrogen, C1-C4 alkyl, C1-C4 alkoxy, halogen atom, and hydroxyl group.

[0019] In some alternative embodiments, the above-mentioned persulfate is potassium persulfate or sodium persulfate.

[0020] In some alternative embodiments, the above-mentioned reaction is carried out in an organic solvent.

[0021] In some alternative embodiments, the above-mentioned reaction is carried out in dimethyl sulfoxide solvent.

[0022] In some alternative embodiments, the above-mentioned reaction is carried out under the condition of 75°C - 90°C.

[0023] The third aspect of the present invention provides the use of the benzoselenofuranone compound represented by Formula 8 or a pharmaceutically acceptable salt thereof in the preparation of a drug for treating and / or preventing prostate cancer.

[0024] The fourth aspect of the present invention provides a drug for treating and / or preventing prostate cancer, which comprises the benzoselenofuranone compound represented by Formula 8 or a pharmaceutically acceptable salt thereof. The benzoselenofuranone compound represented by Formula 8 or a pharmaceutically acceptable salt thereof is the main active ingredient (main drug) in the above-mentioned drug for treating and / or preventing prostate cancer.

[0025] In some alternative embodiments, the above-mentioned drug for treating and / or preventing prostate cancer further comprises an excipient. The dosage form of the above-mentioned drug for treating and / or preventing prostate cancer is any pharmaceutically acceptable dosage form. The above-mentioned excipient is stable in nature, has no incompatibility with the main drug, does not produce side effects, does not affect the curative effect, is not easily deformed, cracked, or mildewed at room temperature, and is harmless to the human body.

[0026] In some alternative embodiments, the above-mentioned excipient is at least one of gum arabic, syrup, lanolin, and starch.

[0027] The technical solutions of the embodiments of the present invention have the following beneficial effects:

[0028] A new benzoselenofuranone compound is prepared. The preparation process is simple and easy to implement, the raw material cost is low, and the functional group compatibility is good; this benzoselenofuranone compound has the property of efficiently inhibiting the activity of USP16 and can be used as a USP16 selective inhibitor, providing a safe and efficient candidate drug molecule for targeted treatment of prostate cancer; this benzoselenofuranone compound can be used to prepare a drug for treating and / or preventing prostate cancer to promote the treatment effect of prostate cancer. Specific Embodiments

[0029] The technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all of the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the protection scope of the present invention.

[0030] In the following embodiments, the benzoselenofuranone compound represented by Formula 8 is synthesized according to the following route:

[0031] The compound represented by Formula 6 reacts with the phenyl selenide represented by Formula 7 through a radical reaction to obtain a product, that is, the benzoselenofuranone compound represented by Formula 8;

[0032]

[0033] Among them, R is any one of hydrogen, methyl, methoxy, bromine, chlorine, and hydroxyl. The compound shown in Formula 6 can be synthesized according to the following route:

[0034] Using dimethyl sulfide shown in Formula 1 and 4-bromobut-1-yne shown in Formula 2 as starting materials, the compound shown in Formula 3 is prepared by a nucleophilic substitution reaction in an acetonitrile solvent; then, under the action of sodium ethoxide, the compound shown in Formula 3 reacts with 5-methylcyclohexane-1,3-dione shown in Formula 4 in an ethanol solvent to generate an intermediate compound shown in Formula 5; then, under acidic conditions (conditions involving p-toluenesulfonic acid), the exocyclic double bond of the intermediate compound shown in Formula 5 migrates to the ring interior in a toluene solvent to obtain the compound shown in Formula 6;

[0035]

[0036] Specifically, under an argon atmosphere, dimethyl sulfide (7.5 mL, 100 mmol, 1.25 eq.) and 4-bromobut-1-yne (7.35 mL, 80 mmol, 1.0 eq.) are dissolved in 6 mL of dry acetonitrile, and the reaction is carried out at room temperature in the dark for 16 h. The white solid is obtained by filtration, which is the compound shown in Formula 3. Then, 5-methylcyclohexane-1,3-dione (5 g, 44.5 mmol, 1.0 eq.) and sodium ethoxide (17.5 mL, 44.5 mmol, 1.0 eq.) are dissolved in 32.5 mL of dry ethanol. Subsequently, the compound shown in Formula 3 (8.0 g, 44.5 mmol, 1.0 eq.) is added, and the system is reacted in the dark in an oil bath at 80 °C for 1 h. Saturated ammonium chloride is added to the system to quench the reaction, and the reaction mixture is extracted with ethyl acetate. The organic phase is dried and concentrated to obtain the intermediate compound shown in Formula 5. Then, the intermediate compound shown in Formula 5 (7.3 g, 44.5 mmol, 1.0 eq.) and p-toluenesulfonic acid (8.5 g, 44.5 mmol, 1.0 eq.) are dissolved in 50 mL of toluene. Under argon protection, the reaction is carried out at room temperature for 1 h, and the system becomes a brown solution. After monitoring the completion of the reaction, saturated sodium bicarbonate solution is added to quench the reaction, and the reaction mixture is extracted with ethyl acetate. After drying and rotary evaporation of the organic phase, the compound shown in Formula 6 (2.5 g of yellow solid, yield 38%) is obtained by column chromatography.

[0037] The characterization results of the compound shown in Formula 6 are as follows: 11H NMR (400 MHz, CDCl3) δ 7.05 (s, 1H), 2.89 (dd, J = 16.4, 4.5 Hz, 1H), 2.54 – 2.43 (m, 2H), 2.44 – 2.34 (m, 1H), 2.26 – 2.19 (m, 1H), 2.17 (s, 3H), 1.80 (s, 1H), 1.14 (d, J = 6.3 Hz, 3H). 13 13C NMR (100 MHz, CDCl3) δ 195.4, 167.2, 139.2, 120.2, 119.1, 46.9, 31.9, 31.0, 21.2, 9.1.

[0038] Example 1: Synthesis of the benzoselenofuranone compound shown in Formula 8a

[0039]

[0040] Under an argon atmosphere, compound 6 (100.0 mg, 0.6 mmol, 1.0 eq), diphenyldiselenide (93.6 mg, 0.3 mmol, 0.5 eq), and potassium persulfate (81.1 mg, 0.3 mmol, 0.5 eq.) were dissolved in 3 mL of dimethyl sulfoxide and reacted at 80 °C for 3 hours; after monitoring the completion of the reaction, saturated ammonium chloride was added to quench the reaction, and the mixture was extracted with ethyl acetate. After drying and concentrating the organic phase, the benzoselenofuranone compound shown in Formula 8a (82.6 mg, 86%) was obtained by silica gel column chromatography.

[0041] The characterization results of the benzoselenofuranone compound shown in Formula 8a are as follows: 1 1H NMR (400 MHz, CDCl3) δ 7.33– 7.18 (m, 5H), 2.95 (ddd, J = 17.1, 4.8, 1.1 Hz, 1H), 2.58 – 2.48 (m, 2H), 2.46 – 2.38 (m, 1H), 2.33 (s, 3H), 2.27 – 2.17 (m, 1H), 1.16 (d, J = 6.5 Hz, 3H). 13 13C NMR (100 MHz, CDCl3) δ 194.5, 170.0, 137.6, 131.2, 130.1, 129.4, 128.9, 127.0, 121.2, 46.7, 31.9, 30.7, 21.1, 11.1.

[0042] Example 2: Synthesis of the benzoselenofuranone compound shown in Formula 8b

[0043]

[0044] The synthesis route and the post-treatment process were the same as those in Example 1, except that the raw material diphenyl diselenide (93.6 mg, 0.3 mmol, 0.5 eq) was replaced with 1,2-bis(4-methylphenyl) diselenide (102.0 mg, 0.3 mmol, 0.5 eq), and the benzoselenofuranone compound shown in Formula 8b (75.2 mg, 75%) was obtained.

[0045] The characterization results of the benzoselenofuranone compound shown in Formula 8b are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.23(d, J = 7.8 Hz, 2H), 7.05 (d, J = 7.8 Hz, 2H), 2.94 (dd, J = 16.9, 4.7 Hz,1H), 2.57 – 2.52 (m, 1H), 2.50 (dd, J = 6.8, 3.2 Hz, 1H), 2.47 – 2.36 (m,1H), 2.32 (s, 3H), 2.30 (s, 3H), 2.23 (dd, J = 16.1, 11.3 Hz, 1H), 1.15 (d, J= 6.4 Hz, 3H). 13 C NMR (100 MHz, CDCl3) δ 194.5, 169.8, 138.1, 137.2, 130.8,130.2, 128.3, 127.2, 121.1, 46.7, 31.9, 30.7, 21.1, 21.0, 11.1.

[0046] Example 3: Synthesis of the benzoselenofuranone compound shown in Formula 8c

[0047]

[0048] The synthesis route and the post-treatment process were the same as those in Example 1, except that the raw material diphenyl diselenide (93.6 mg, 0.3 mmol, 0.5 eq) was replaced with 1,2-bis(4-methoxyphenyl) diselenide (111.9 mg, 0.3 mmol, 0.5 eq), and the benzoselenofuranone compound shown in Formula 8c (88.2 mg, 84%) was obtained.

[0049] The characterization results of the benzoselenofuranone compound shown in Formula 8c are as follows: 11H NMR (400 MHz, CDCl3) δ 7.40– 7.31 (m, 2H), 6.84 – 6.75 (m, 2H), 3.77 (s, 3H), 2.98 – 2.86 (m, 1H), 2.55– 2.51 (m, 1H), 2.51 – 2.46 (m, 1H), 2.44 – 2.35 (m, 1H), 2.33 (s, 3H), 2.22(dd, J = 16.1, 11.3 Hz, 1H), 1.15 (d, J = 6.5 Hz, 3H). 13 13C NMR (100 MHz,CDCl3) δ 194.5, 169.6, 159.4, 138.8, 133.3, 127.6, 121.1, 120.8, 115.1, 55.3,46.7, 31.9, 30.7, 21.1, 11.1.

[0050] Example 4: Synthesis of the benzoselenofuranone compound shown in Formula 8d

[0051]

[0052] The synthesis route and the post-treatment process were the same as those in Example 1, except that the raw material diphenyl diselenide (93.6 mg, 0.3 mmol, 0.5 eq) was replaced with bis(4-bromophenyl) diselenide (141.0 mg, 0.3 mmol, 0.5 eq), and the benzoselenofuranone compound shown in Formula 8d (101.5 mg, 85%) was obtained.

[0053] The characterization results of the benzoselenofuranone compound shown in Formula 8d are as follows: 1 1H NMR (400 MHz, CDCl3) δ 7.40– 7.30 (m, 2H), 7.19 – 7.11 (m, 2H), 2.95 (dd, J = 17.0, 4.7 Hz, 1H), 2.59 –2.54 (m, 1H), 2.54 – 2.50 (m, 1H), 2.48 – 2.37 (m, 1H), 2.31 (s, 3H), 2.25(dd, J = 16.1, 11.3 Hz, 1H), 1.17 (d, J = 6.5 Hz, 3H). 1313C NMR (100 MHz, CDCl3) δ 194.4, 170.1, 137.1, 132.4, 131.8, 130.1, 129.2, 121.2, 121.2, 46.7, 31.8, 30.6, 21.1, 11.1.

[0054] Example 5: Synthesis of the benzoselenofuranone compound shown in Formula 8e

[0055]

[0056] The synthesis route and post-treatment process were the same as those in Example 1, except that the raw material diphenyl diselenide (93.6 mg, 0.3 mmol, 0.5 eq) was replaced with bis(4-chlorophenyl) diselenide (114.3 mg, 0.3 mmol, 0.5 eq), and the benzoselenofuranone compound shown in Formula 8e (85.0 mg, 80%) was obtained.

[0057] The characterization results of the benzoselenofuranone compound shown in Formula 8e are as follows: 1 1H NMR (400 MHz, CDCl3) δ 7.29–7.15 (m, 4H), 3.00 – 2.91 (m, 1H), 2.59 – 2.54 (m, 1H), 2.54 – 2.50 (m, 1H), 2.48 – 2.38 (m, 1H), 2.32 (s, 3H), 2.25 (dd, J = 16.1, 11.3 Hz, 1H), 1.17 (d, J = 6.5 Hz, 3H). 13 13C NMR (100 MHz, CDCl3) δ 194.4, 170.1, 137.2, 133.3, 131.6, 129.5, 129.3, 129.1, 121.2, 46.7, 31.8, 30.6, 21.1, 11.1.

[0058] Example 6: Synthesis of the benzoselenofuranone compound shown in Formula 8f

[0059]

[0060] The synthesis route and post-treatment process were the same as those in Example 1, except that the raw material diphenyl diselenide (93.6 mg, 0.3 mmol, 0.5 eq) was replaced with 4,4'-diselenyl diphenol (103.2 mg, 0.3 mmol, 0.5 eq), and the benzoselenofuranone compound shown in Formula 8f (83.7 mg, 83%) was obtained.

[0061] The characterization results of the benzoselenofuranone compound shown in Formula 8f are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.32– 7.27 (m, 2H), 6.80 – 6.73 (m, 2H), 6.55 – 6.43 (m, 1H), 2.98 – 2.89 (m,1H), 2.56 – 2.51 (m, 1H), 2.51 – 2.47 (m, 1H), 2.46 – 2.35 (m, 1H), 2.23 (dd,J = 16.1, 11.3 Hz, 1H), 1.14 (d, J = 6.5 Hz, 3H). 13 C NMR (100 MHz, CDCl3) δ195.6, 170.1, 156.1, 139.2, 133.7, 127.4, 121.0, 120.2, 116.6, 46.5, 31.8,30.7, 21.0, 11.1.

[0062] Example 7: USP kinase inhibition rate test

[0063] The benzoselenofuranone compounds shown in Formulas 8a - 8f prepared by the methods of Examples 1 - 6 were respectively subjected to the USP kinase inhibition rate test according to the following fluorescence assay method:

[0064] First, the benzoselenofuranone compound was diluted to 10 μM, and then the optimal concentration of deubiquitinating enzyme (DUB) was added. After brief mixing, it was placed in a reaction system with a volume of 200 μL and incubated at room temperature for 1 hour; after adding 200 nM ubiquitin rhodamine 110 (Ub - Rho110, catalog number # M3022, UBPBio), the final fluorescence signal was obtained using a TECAN SPARK multimode microplate reader (excitation wavelength: 485 nm, emission wavelength: 535 nm), and based on this, the inhibition rate of the benzoselenofuranone compound on enzyme activity was calculated.

[0065] Among them, the reaction system used contained 50 mM HEPES (pH 8.0), 150 mM NaCl, 0.5 mM EDTA, 1 mM DTT, and 0.1 mg / mL bovine serum albumin (BSA).

[0066] The test results are shown in Table 1. The benzoselenofuranone compounds shown in Formulas 8a - 8f can all selectively inhibit the kinase activity of USP16 at the protein level, and the inhibition rate is greater than 80%.

[0067] Table 1 Determination results of the inhibition of USP activity by benzoselenofuranone compounds

[0068]

[0069] In Table 1, +++ represents an inhibition rate greater than 80%, ++ represents an inhibition rate between 50% and 80%, and + represents an inhibition rate less than 50%.

[0070] Example 8: Determination of cell anti - proliferative activity

[0071] The in vitro anti - proliferative activities of the benzoselenofuranone compounds shown in Formula 8a - Formula 8f prepared by the methods of Examples 1 - 6 against the prostate cancer cell lines PC - 3 and DU145 were evaluated by the CCK - 8 assay. The procedure is as follows:

[0072] The highest concentration was set at 10 μM and serially diluted by a factor of 3, with the lowest concentration at 0 μM, resulting in a total of 10 concentration gradients. These were co - incubated with PC - 3 and DU145 cells for 72 h, and the cell viability was detected by CCK - 8. Data processing was performed using GraphPad Prism 9 to calculate the IC 50 value. Meanwhile, UBD1031 was used as a control to determine its in vitro anti - proliferative activity against the prostate cancer cell lines PC - 3 and DU145.

[0073] The results are shown in Table 2. The benzoselenofuranone compounds shown in Formula 8a - Formula 8f all have excellent in vitro anti - proliferative activities.

[0074] Table 2 Results of the determination of the anti - proliferative activity of benzoselenofuranone compounds against prostate cancer cells

[0075]

[0076] In Table 2, + represents greater than 1000 nM; ++ represents 1000 - 100 nM; +++ represents less than 100 nM.

[0077] Example 9: Animal tumor inhibition experiment

[0078] An animal experiment was conducted on a xenograft tumor model of two prostate cancer cells (PC - 3 and DU145) in BALB / c mice to evaluate the anti - tumor ability of the benzoselenofuranone compounds in vivo. A subcutaneous tumor - bearing mouse model was constructed, and the anti - tumor effects of the benzoselenofuranone compounds shown in Formula 8a - Formula 8f prepared by the methods of Examples 1 - 6 on BALB / c mice were evaluated respectively. The procedure is as follows:

[0079] PC-3 and DU145 were cultured in an incubator at 37 °C with 5% carbon dioxide; all mice were raised under standard specific pathogen-free (SPF) conditions. PC-3 and DU145 cells were subcutaneously injected into 6- to 8-week-old female BALB / c mice. The mice were examined for tumor formation daily to determine the development of the tumors. When the tumors grew to a certain size, the mice were randomly divided into a control group and a drug administration group, with 5 mice in each group. The drug administration group was given intraperitoneal injection of the drug at a dose of 50 mpk. The tumor diameter was measured daily using vernier calipers, and the body weight of the mice was recorded. After 21 days, the tumor tissues were excised, and the antitumor effect of the benzoselenophene ketone compound was evaluated based on the change in tumor volume.

[0080] As shown in Table 3, the benzoselenophene ketone compounds represented by Formula 8a to Formula 8f all have excellent in vivo anti-proliferative activity.

[0081] Table 3 Results of animal experiments

[0082]

[0083] In Table 3, + represents that the tumor inhibition rate is less than 50%, ++ represents that the tumor inhibition rate is between 50% and 80%; +++ represents that the tumor inhibition rate is greater than 80%.

[0084] The above are only the preferred embodiments of the present invention, and do not impose any formal or substantial limitations on the present invention. It should be noted that for those of ordinary skill in the art of this technology, without departing from the method of the present invention, several improvements and supplements can still be made, and these improvements and supplements should also be regarded as the protection scope of the present invention. Any equivalent changes, such as slight modifications, evolutions, and variations made by those skilled in the art who are familiar with this specialty without departing from the spirit and scope of the present invention, using the technical content disclosed above, are equivalent embodiments of the present invention; at the same time, any equivalent changes, modifications, and evolutions made to the above embodiments based on the essential technology of the present invention still fall within the scope of the technical solutions of the present invention.

Claims

1. A benzoselenofuranone compound or a pharmaceutically acceptable salt thereof, characterized in that, The benzoselenofuranone compound has the structure shown in Formula 8: ； Wherein, R is selected from hydrogen, C1-C4 alkyl, C1-C4 alkoxy, halogen atom, and hydroxyl group.

2. The benzoselenofuranone compound according to claim 1 or a pharmaceutically acceptable salt thereof, characterized in that, Said R is selected from hydrogen, methyl, ethyl, fluorine atom, chlorine atom, bromine atom, iodine atom, and hydroxyl group.

3. The benzoselenofuranone compound according to claim 1 or a pharmaceutically acceptable salt thereof, characterized in that, The benzoselenofuranone compound has the structure shown in one of Formula 8a to Formula 8f: 、 、 、 、 、 。 4. A method for preparing a benzoselenofuranone compound, characterized in that, Comprising the following steps: In the presence of persulfate, reacting the compound shown in Formula 6 with the benzoselenide compound shown in Formula 7 to obtain the benzoselenofuranone compound shown in Formula 8; 、 、 ； Wherein, R is selected from hydrogen, C1-C4 alkyl, C1-C4 alkoxy, halogen atom, and hydroxyl group.

5. The method according to claim 4, characterized in that, The persulfate is potassium persulfate or sodium persulfate.

6. The method according to claim 4, wherein The reaction is carried out in an organic solvent.

7. The method according to claim 6, wherein The reaction is carried out in dimethyl sulfoxide solvent.

8. The method according to claim 4, wherein The reaction is carried out under the condition of 75°C - 90°C.

9. Use of the benzoselenofuranone compound according to claim 1 or a pharmaceutically acceptable salt thereof in the preparation of a drug for treating and / or preventing prostate cancer.

10. A drug for treating and / or preventing prostate cancer, characterized in that, Comprising the benzoselenofuranone compound according to claim 1 or a pharmaceutically acceptable salt thereof.

Images