CN114751891B - (2- (1H-indole-3-yl) -1H-imidazole-4-yl) phenyl ketone compound and application thereof - Google Patents

(2- (1H-indole-3-yl) -1H-imidazole-4-yl) phenyl ketone compound and application thereof Download PDF

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CN114751891B
CN114751891B CN202210455779.0A CN202210455779A CN114751891B CN 114751891 B CN114751891 B CN 114751891B CN 202210455779 A CN202210455779 A CN 202210455779A CN 114751891 B CN114751891 B CN 114751891B
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Abstract

The invention relates to a (2- (1H-indole-3-yl) -1H-imidazole-4-yl) phenyl ketone compound, the chemical structure of which is shown in the following formula (I); in the formula (I), one of X, Y and Z is a deuterium atom, or two of X, Y and Z are deuterium atoms, or all of X, Y and Z are deuterium atoms. The compound has obvious inhibition effect on human breast cancer cells MCF-7, human cervical cancer cells HeLa, human liver cancer cells HepG-2 and mouse melanoma cells B16-F10, and can be used for preparing antitumor drugs.

Description

(2- (1H-indole-3-yl) -1H-imidazole-4-yl) phenyl ketone compound and application thereof
Technical Field
The invention relates to (2- (1H-indole-3-yl) -1H-imidazole-4-yl) phenyl ketone compounds, which can inhibit the proliferation of tumor cells and can be used for treating tumors.
Background
Microtubules (microtubule) have a number of important functions, including cellular structure and support, movement of cells, transport of organelles, and segregation of chromosomes during cell division. Microtubules are long hollow tubular structures consisting of 13 tubulin fibrils (protofilament). Whereas tubulin fibrils are composed of tubulin (tubulin) subunits. Tubulin subunits are mainly dimers formed by the association of two structurally similar globular proteins (alpha-tubulin and beta-tubulin). The growth of cancer cells is highly dependent on the dynamic instability of tubulin (a dynamic balance of elongation and contraction), which, given the critical role microtubules play in cancer cell proliferation and division, becomes the target of many anticancer drugs (e.g. paclitaxel, vinblastine). Tubulin inhibitors interfere with the mitotic process of cancer cells by inhibiting tubulin polymerization (microtubule elongation) or depolymerization (microtubule shortening), disrupting mitosis and arresting the cell cycle in the G2/M phase, leading to apoptosis of cancer cells.
All currently marketed tubulin inhibitors bind to the paclitaxel or vinca alkaloid site. Although these inhibitors have a broad spectrum of anticancer activity, their clinical use faces a number of problems, including: it can not be taken orally, and has great toxic and side effects, drug resistance, etc. Whereas tubulin inhibitors targeted to the colchicine binding site substantially overcome the above-mentioned disadvantages, they have the following advantages over the tubulin inhibitors already on the market: (1) overcoming the drug resistance of paclitaxel and vinblastine: due to different binding sites and not being a substrate for multidrug resistance/MDR (e.g., P-gp); (2) the oral bioavailability is high: due to the relatively simple structure, good physicochemical property/water solubility and pharmacokinetic property; (3) the toxic and side effects are relatively small: high water solubility, no need of cosolvent and less side reaction.
Given the critical role tubulin plays in cancer cell proliferation and division, and currently there is no anticancer drug marketed against this target of the colchicine binding site. The novel microtubulin inhibitor which can overcome the drug resistance of the paclitaxel, can be orally taken and has good pharmacokinetic properties and targeted micro colchicine binding sites is designed and developed, and has important significance and wide application prospect as an anti-cancer drug.
Disclosure of Invention
The invention aims to solve the technical problem of providing a (2- (1H-indole-3-yl) -1H-imidazole-4-yl) phenyl ketone compound which has obvious inhibition effects on human cervical cancer cells HeLa, human breast cancer cells MCF-7, human liver cancer cells HepG-2 and mouse melanoma cells B16-F10.
The scheme for solving the technical problems is as follows:
a (2- (1H-indole-3-yl) -1H-imidazole-4-yl) phenyl ketone compound has a chemical structure shown in the following formula (I),
Figure BDA0003618679260000021
in the formula (I), one of X, Y and Z is a deuterium atom, or two of X, Y and Z are deuterium atoms, or all of X, Y and Z are deuterium atoms.
The (2- (1H-indole-3-yl) -1H-imidazole-4-yl) phenyl ketone compound is one of the following compounds:
when X is deuterium atom and Y and Z are hydrogen atom, the chemical structure of the (2- (1H-indol-3-yl) -1H-imidazole-4-yl) phenyl ketone compound is as follows:
Figure BDA0003618679260000022
when Y is deuterium atom and X and Z are hydrogen atom, the chemical structure of the (2- (1H-indol-3-yl) -1H-imidazole-4-yl) phenyl ketone compound is as follows:
Figure BDA0003618679260000023
when X and Z are deuterium atoms and Y is a hydrogen atom, the chemical structure of the (2- (1H-indol-3-yl) -1H-imidazole-4-yl) phenyl ketone compound is as follows:
Figure BDA0003618679260000024
when X and Y are deuterium atoms and Z is a hydrogen atom, the chemical structure of the (2- (1H-indol-3-yl) -1H-imidazole-4-yl) phenyl ketone compound is as follows:
Figure BDA0003618679260000025
when X, Y and Z are deuterium atoms, the chemical structure of the (2- (1H-indol-3-yl) -1H-imidazole-4-yl) phenyl ketone compound is as follows:
Figure BDA0003618679260000031
the preparation method of the (2- (1H-indole-3-yl) -1H-imidazole-4-yl) phenyl ketone compound comprises the following steps:
(1) Dissolving the raw material indole 3-formaldehyde (1) in ethanol, adding 1.1 mol times of potassium hydroxide according to the mol weight of the raw material 1, and stirring the mixture until the mixture is completely dissolved. Ethanol was removed in vacuo and the concentrate was dissolved in acetone, then 1.1 molar fold benzenesulfonyl chloride was added and reacted at room temperature for half an hour. Filtering to remove precipitate, concentrating the filtrate and recrystallizing with methanol to obtain intermediate 2;
the chemical reaction formula of the step (1) is as follows:
Figure BDA0003618679260000032
(2) Dissolving the intermediate 2 obtained in the step (1) in ethanol, and adding 1.1 mol times of glyoxal aqueous solution and 10.0 mol times of ammonium hydroxide aqueous solution according to the molar weight of the intermediate 2 at 0 ℃. After stirring at room temperature for 2 days, the reaction was quenched with water and extracted with dichloromethane. Collecting an organic layer, concentrating, and performing column chromatography separation and purification to obtain an intermediate 3;
the chemical reaction formula of the step (2) is as follows:
Figure BDA0003618679260000033
(3) Dissolving the intermediate 3 obtained in the step (2) in super-dry tetrahydrofuran, adding 1.2 mol times of sodium hydride according to the mol amount of the intermediate 3, and stirring for 20 minutes. Then 1.2 molar times of benzenesulfonyl chloride was added and stirred overnight. Adding saturated NaHCO into reaction liquid 3 Extracting the aqueous solution with ethyl acetate, drying the organic layer with magnesium sulfate, concentrating, and separating and purifying by column chromatography to obtain an intermediate 4;
the chemical reaction formula of the step (3) is as follows:
Figure BDA0003618679260000041
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(4) And (3) dissolving the intermediate 4 obtained in the step (3) in an ultra-dry tetrahydrofuran solution, adding 1.2 mol times of a pentane solution of tert-butyl lithium at the temperature of 0 ℃ according to the molar weight of the intermediate 4, and stirring for 10 minutes. Then 1.2 times by mole of a THF solution of trimethoxybenzoyl chloride (5) was added and stirred overnight. Adding saturated NaHCO into reaction liquid 3 Extracting the aqueous solution with ethyl acetate, drying the organic layer with magnesium sulfate, concentrating, and performing column chromatography separation and purification to obtain an intermediate 6;
the chemical reaction formula of the step (4) is as follows:
Figure BDA0003618679260000042
(5) And (3) dissolving the intermediate 6 obtained in the step (4) in an ethanol/water (10/1) solution, adding 10.0 molar times of sodium hydroxide according to the molar amount of the intermediate 6, and refluxing and stirring under the condition of keeping out light overnight. The reaction solution was diluted with water and extracted with ethyl acetate. Drying and concentrating the organic layer by magnesium sulfate, and separating and purifying by column chromatography to obtain a compound Ia;
the chemical reaction formula of the step (5) is as follows:
Figure BDA0003618679260000043
the process route of the method for synthesizing the (2- (1H-indole-3-yl) -1H-imidazole-4-yl) phenyl ketone compound is as follows:
Figure BDA0003618679260000051
the (2- (1H-indole-3-yl) -1H-imidazole-4-yl) phenyl ketone compound has obvious inhibition effects on human breast cancer cells MCF-7, human cervical cancer cells HeLa, human liver cancer cells HepG-2 and mouse melanoma cells B16-F10, and can be used for preparing antitumor drugs.
Detailed Description
Example 1 (preparation Ia)
The structural formula of (2- (1H-indol-3-yl) -1H-imidazol-4-yl) (3, 4-dimethoxy-5- (trideuteromethoxy) phenyl) methanone (Ia) prepared in this example is:
Figure BDA0003618679260000052
the preparation method of the compound shown in the formula (Ia) comprises the following steps:
(1) The method comprises the following steps: preparation of Compound 2
The structural formula is prepared by the following method
Figure BDA0003618679260000053
The compound of (1):
Figure BDA0003618679260000061
indole-3-carbaldehyde (1) (14.5g, 100mmol) was dissolved in 500ml of ethanol, and potassium hydroxide (6.16g, 110mmol) was added thereto and the mixture was stirred at room temperature until it was completely dissolved. Ethanol was removed in vacuo and the concentrate was dissolved in 250ml acetone, then benzenesulfonyl chloride (19.5g, 110mmol) was added. After stirring the reaction solution at room temperature for half an hour, the precipitate was removed by filtration, and the filtrate was concentrated and recrystallized from methanol to give a white solid. Yield: 33 percent. 1 H NMR(400MHz,CDCl 3 )δ10.18(s,1H),8.24-8.38(m,2H),7.98-8.08(m,3H),7.68(t,J＝7.33Hz,1H),7.60(t,J＝7.5Hz,2H),7.38-7.53(m,2H).MS(ESI)C 15 H 11 NO 3 Calculated value of S is 285.1, and measured value is 286.0[ m ] +H] + 。
(2) Step two: preparation of Compound 3
The structural formula is prepared by the following method
Figure BDA0003618679260000062
The compound of (1):
Figure BDA0003618679260000063
1- (benzenesulfonyl) -1H-indole-3-carbaldehyde (2) (28.5g, 100mmol) was dissolved in 400ml of ethanol, and a 40% aqueous glyoxal solution (22mL, 110mmol) and a 29% aqueous ammonium hydroxide solution (136mL, 1000mmol) were added at 0 ℃. After stirring at room temperature for 2 days, the reaction mixture was quenched with water and extracted with dichloromethane. The collected organic layer was distilled under reduced pressure, and the concentrate was subjected to column chromatography using n-hexane/ethyl acetate (4. Yield: 12 percent. 1 H NMR(400MHz,DMSO-d 6 )δ8.34(d,J＝2.9Hz,2H),8.12(d,J＝7.8Hz,2H),7.99-8.05(m,1H),7.63-7.69(m,1H),7.56(d,J＝7.82Hz,2H),7.23-7.36(m,4H).MS(ESI)C 17 H 13 N 3 O 2 Calculated value of S is 323.1, found to be 324.0[ deg. ]M+H] + 。
(2) Step three: preparation of Compound 4
The structural formula is prepared by the following method
Figure BDA0003618679260000071
The compound of (1):
Figure BDA0003618679260000072
3- (1H-imidazol-2-yl) -1- (phenylsulfonyl) -1H-indole (3) (6.46g, 20mmol) was dissolved in 300ml of ultra-dry tetrahydrofuran, and sodium hydride (60% dispersion in mineral oil) (0.96g, 24mmol) was added thereto at 0 ℃ and stirred for 20 minutes. Benzenesulfonyl chloride (4.25g, 24mmol) was then added and stirred overnight. 200ml of saturated NaHCO is added into the reaction solution 3 After dilution with water, the mixture was extracted with 600ml of ethyl acetate. The organic layer was dried over magnesium sulfate and concentrated, and subjected to column chromatography using n-hexane/ethyl acetate (5: 1) to give a white solid. Yield: 40 percent. 1 H NMR(CDCl 3 ,400MHz)δ8.01-8.09(m,4H),7.73(d,J＝1.5Hz,1H),7.37-7.63(m,8H),7.25(d,J＝1.5Hz,1H),7.12-7.18(m,3H).MS(ESI)C 23 H 17 N 3 O 4 S 2 Calcd for 463.1, found 486.0[ 2 ], [ M + ] Na] + 。
(2) Step four: preparation of Compound 6a
The structural formula is prepared by the following method
Figure BDA0003618679260000073
The compound of (1):
Figure BDA0003618679260000074
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1- (benzenesulfonyl) -3- (1- (benzenesulfonyl) -1H-imidazol-2-yl) -1H-indole (4) (2.32g, 5.0 mmol) was dissolved in 100ml of ultra-dry tetrahydrofuran, and a 1.7M solution of tert-butyllithium in pentane was added at-78 deg.C and stirred for 10 minutes. Followed by addition (1.38g, 6.0 mmol) of 3, 4-dimethoxy-5- (trideuteromethoxy) benzylA solution of the acid chloride (5 a) in tetrahydrofuran and stirred overnight. 100ml of saturated NaHCO is added into the reaction solution 3 The reaction was quenched with aqueous solution and extracted with 300ml of ethyl acetate. The organic layer was dried over magnesium sulfate and concentrated, and subjected to column chromatography using n-hexane/ethyl acetate (3: 1) to give a white solid. Yield: 30 percent. 1 H NMR(CDCl 3 400 MHz) δ 8.12 (d, J =10hz, 1h), 8.06 (d, J =10hz, 2h), 7.90 (s, 1H), 7.78 (d, J =5hz, 2h), 7.67 (t, J =10hz, 1h), 7.54-7.59 (m, 5H), 7.42 (s, 2H), 7.35-7.38 (m, 3H), 7.24 (t, J =10hz, 1h), 4.07 (s, 3H), 4.05 (s, 3H), MS (ESI) calculated as C 33 H 27 N 3 O 8 658.0, found 681.1[ M ] +Na] + 。
(2) Step five: preparation of Compound Ia
The structural formula is prepared by the following method
Figure BDA0003618679260000081
The compound of (1):
Figure BDA0003618679260000082
(0.66g, 1mmol) (1- (benzenesulfonyl) -2- (1- (benzenesulfonyl) -1H-indol-3-yl) -1H-imidazol-4-yl) (3, 4, 5-trimethoxyphenyl) methanone (6 a) was dissolved in 40ml ethanol and 4ml water, and sodium hydroxide (0.4 g, 10mmol) was added, and the mixture was stirred under reflux overnight with heating in the dark. The reaction solution was diluted with 50ml of water and extracted with 200ml of ethyl acetate. The organic layer was dried over magnesium sulfate and concentrated, and subjected to column chromatography using n-hexane/ethyl acetate (1: 1) to give a yellow solid. Yield: 60 percent.
The obtained yellow solid powder is subjected to nuclear magnetic resonance hydrogen spectrum and nuclear magnetic resonance carbon spectrum identification, and the identification result is as follows: 1 H NMR(CD 3 OD,400MHz)δ8.30(d,J＝6.5Hz,1H),8.00(s,1H),7.92(s,1H),7.50-7.53(m,3H),7.25-7.29(m,2H),4.02(s,3H),3.95(s,3H).MS(ESI)C 21 H 16 D 3 N 3 O 4 the calculated value is 380.16, and the measured value is 403.2[ deg. ] M + [ Na ]] + 。
Example 2 (preparation Ib)
The structural formula of (2- (1H-indol-3-yl) -1H-imidazol-4-yl) (3, 5-dimethoxy-4- (trideuteromethoxy) phenyl) methanone (Ib) prepared in this example is:
Figure BDA0003618679260000091
the compound represented by the formula (Ib) is prepared by using 1- (benzenesulfonyl) -3- (1- (benzenesulfonyl) -1H-imidazol-2-yl) -1H-indole (4), 3, 5-dimethoxy-4- (trideuteromethoxy) benzoyl chloride (5 b) as a raw material in the same manner as in example 1, wherein the chemical reaction formula is as follows:
Figure BDA0003618679260000092
the product obtained by the method is identified by nuclear magnetic resonance spectrum, and the result is as follows: 1 H NMR(CD 3 OD,500MHz)δ8.32(d,J＝6.5Hz,1H),8.00(s,1H),7.92(s,1H),7.48-7.53(m,3H),7.25-7.32(m,2H),4.00(s,6H).MS(ESI)C 21 H 16 D 3 N 3 O 4 the calculated value is 380.16, and the measured value is 403.1[ deg. ] M + [ Na ]] + 。
Example 3 (preparation Ic)
The structural formula of (2- (1H-indol-3-yl) -1H-imidazol-4-yl) (4-methoxy-3, 5-bis (trideuteromethoxy) phenyl) methanone (Ic) prepared in this example is:
Figure BDA0003618679260000093
the compound represented by the above formula (Ic) is prepared by the same specific preparation method as in example 1 using 1- (benzenesulfonyl) -3- (1- (benzenesulfonyl) -1H-imidazol-2-yl) -1H-indole (4), 4-methoxy-3, 5-bis (trideuteromethoxy) benzoyl chloride (5 c) as a starting material, and has the following chemical reaction formula:
Figure BDA0003618679260000094
obtained by the above methodThe product of (A) is identified by nuclear magnetic resonance spectrum, and the result is as follows: 1 H NMR(CD 3 OD,500MHz)δ8.33(d,J＝6.5Hz,1H),7.80(s,1H),7.92(s,1H),7.49-7.53(m,3H),7.25-7.30(m,2H),3.95(s,3H).MS(ESI)C 21 H 13 D 6 N 3 O 4 calculated value is 383.18, found value is 406.2[ deg. ] M + [ Na ]] + 。
Example 4 (preparation Id)
The formula of (2- (1H-indol-3-yl) -1H-imidazol-4-yl) (3-methoxy-4, 5-bis (trideuteromethoxy) phenyl) methanone (Id) prepared in this example is:
Figure BDA0003618679260000101
the compound represented by the above formula (Id) is prepared by the same specific preparation method as in example 1 using 1- (benzenesulfonyl) -3- (1- (benzenesulfonyl) -1H-imidazol-2-yl) -1H-indole (4), 3-methoxy-4, 5-bis (trideuteromethoxy) benzoyl chloride (5 d) as a starting material, and has the following chemical reaction formula:
Figure BDA0003618679260000102
the product obtained by the method is identified by nuclear magnetic resonance spectrum, and the result is as follows: 1 H NMR(CD 3 OD,500MHz)δ8.30(d,J＝6.5Hz,1H),7.98(s,1H),7.91(s,1H),7.47-7.51(m,3H),7.23-7.27(m,2H),4.03(s,3H).MS(ESI)C 21 H 13 D 6 N 3 O 4 calculated value is 383.18, found value is 406.3[ deg. ] M + [ Na ]] + 。
Example 5 (preparation Ie)
The formula of (2- (1H-indol-3-yl) -1H-imidazol-4-yl) (3, 4, 5-tris (trideuteromethoxy) phenyl) methanone (Ie) prepared in this example is:
Figure BDA0003618679260000103
the compound represented by the formula (Ie) is prepared by using 1- (benzenesulfonyl) -3- (1- (benzenesulfonyl) -1H-imidazol-2-yl) -1H-indole (4), 3,4, 5-tris (trideuteromethoxy) benzoyl chloride (5 e) as a raw material in the same manner as in example 1, wherein the chemical reaction formula is as follows:
Figure BDA0003618679260000104
the product obtained by the method is identified by nuclear magnetic resonance spectrum, and the result is as follows: 1 H NMR(CD 3 OD,500MHz)δ8.33(d,J＝6.5Hz,1H),8.02(s,1H),7.93(s,1H),7.51-7.54(m,3H),7.26-7.32(m,2H).MS(ESI)C 21 H 10 D 9 N 3 O 4 the calculated value is 386.19, and the measured value is 409.4[ deg. ] M + [ Na ]] + 。
Example 6 (anti-tumor Activity study)
The in vitro antitumor activity of the compounds of the present invention was demonstrated using the following assay. These effects indicate that the compounds of the present invention are useful for the treatment of cancer, in particular solid tumors such as human breast cancer, human cervical cancer, human liver cancer and mouse melanoma. The specific test method is as follows:
(1) Cells in logarithmic growth phase were arranged at 5X 10 4 one/mL, 100. Mu.L/well density was plated in 96-well plates. At 37 ℃,5% CO 2 And culturing in a saturated humidity incubator until the cells adhere to the wall.
(2) The original medium was aspirated, and different concentrations of compounds were added to each group, at 0.001. Mu.M, 0.003. Mu.M, 0.01. Mu.M, 0.03. Mu.M, 0.1. Mu.M, and 1. Mu.M, respectively. The control group was 0.1% DMSO and the cells were further incubated in a cell incubator for 48 hours.
(3) mu.L of MTT solution was added to each well and incubated for 4h in an incubator.
(4) The medium was discarded, 150. Mu.L of DMSO was added to each well, and formazan crystals were sufficiently dissolved by shaking for 10 min.
(5) The absorbance at 570nm was measured using an enzyme linked immunosorbent assay.
(6) The cell growth inhibition rate was calculated according to the following formula:
inhibition rate = [ (As-Ab)/(Ac-Ab) ]. Times.100%
As: absorbance of assay well (cell, MTT, compound)
Ac: absorbance of control wells (cell, MTT, no Compound)
Ab: absorbance of blank wells (cell and Compound free, MTT containing)
The results of the measured activities are shown in table 1:
TABLE 1 comparison of antitumor Activity (Mean. + -. SD)
Figure BDA0003618679260000111
The positive control 1 in the above table is compound 17ya disclosed in the patent publication No. CN 102883607B, and the structure of compound 17ya is as follows:
Figure BDA0003618679260000121
the in vitro experiment results show that the (2- (1H-indol-3-yl) -1H-imidazole-4-yl) phenyl methanone compound has stronger inhibition effects on human breast cancer cells MCF-7, human cervical cancer cells HeLa, human liver cancer cells HepG-2 and mouse melanoma cells B16-F10, wherein the inhibition effects of the compounds (Ia, ib, ic, id and Ie) on the cancer cells are obviously better than those of a positive control 1 (17 ya) and a positive control 2 (colchicine).

Claims (3)

1. A (2- (1H-indole-3-yl) -1H-imidazole-4-yl) phenyl ketone compound is characterized by being one of the following compounds:
Figure FDA0003917979950000011
2. the use of (2- (1H-indol-3-yl) -1H-imidazol-4-yl) phenyl methanones according to claim 1 for the preparation of anti-tumor medicaments.
3. The use according to claim 2, wherein the antitumor drug comprises (2- (1H-indol-3-yl) -1H-imidazol-4-yl) phenyl methanone compound according to claim 1 and pharmaceutically acceptable excipients.
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CN110551104B (en) * 2019-08-30 2022-04-05 佛山市晨康生物科技有限公司 Benzo five-membered nitrogen heterocyclic derivative and application thereof
CN110563732B (en) * 2019-09-04 2021-11-26 南方医科大学 7- (trimethoxyphenyl) -pyrrolo [2,3-d ] pyrimidine and application thereof

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