CN109776529B - Synthesis method and application of 1, 2-diketone imidazole heterocyclic compound - Google Patents
Synthesis method and application of 1, 2-diketone imidazole heterocyclic compound Download PDFInfo
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Abstract
The invention belongs to the field of organic chemistry, and particularly relates to a synthesis method of a 1, 2-diketone imidazole heterocyclic compound, which is characterized by comprising the following steps: the compound has the following structure, and is prepared by taking dimethylbenzene as a solvent and imidazo [1,2-a ] in the absence of any catalyst or additive]Pyridine compounds and phenyl glyoxal hydrate react in a reaction bottle to obtain the product; the synthesis scheme realizes the direct construction of C-C bonds by a double C-H bond activation mode without adding any catalyst; the synthesis scheme does not use halogenated or activated substrates in advance, and has the advantages of environmental protection, mild reaction conditions, high reaction efficiency, good atom economy and the like. The evaluation result of the drug activity test shows that some heterocyclic compounds have better drug activity. The method provides help for the research of novel 1, 2-diketone imidazole heterocyclic compound molecular skeleton medicines in China.
Description
Technical Field
The invention relates to the field of organic chemistry, in particular to a novel synthesis method and application of a 1, 2-diketone imidazole heterocyclic compound.
Background
1, 2-diketone compounds are used as an important structural unit and widely used for synthesizing heterocyclic compounds (such as imidazole, quinoxaline, indolone-N-oxide and the like) in the field of organic synthesis; in the field of material science, 1, 2-dione derivatives have likewise proved to have great utility as photosensitizers and photoinitiators. In the field of medicine, diketones also exhibit very good pharmacological activity, for example, the existing drugs in the market, 4, 7-phenanthroline-5, 6-dione (also known as amphetamine, which is mainly used for chronic amebic dysentery and also for the treatment of amebic liver abscess), (rac) -5- [ [4- [ (1-methylcyclohexyl ] methoxy ] phenyl ] methyl ]2, 4-thiazolidinedione (also known as tyrlidazole, a hypoglycemic agent) etc. in recent years the imidazopyridine core backbone has become common in many commercially available drug molecules, including thalidomide, azolopyridine, pullulan, olpadone, alpiperidine and minodronic acid.
At present, two strategies are reported in the prior literature to construct 1, 2-diketone imidazole heterocyclic compounds, one is to construct 1, 2-diketone imidazole heterocyclic compounds by utilizing metal catalyst catalytic synthesis, for example, S.M.A. Shakoor et al (Tetrahedron 72.5 (2016): 645:. 652.) report that 1, 2-diketone imidazole heterocyclic compounds are constructed by a scheme of metal copper catalysis, in the method, under the condition of air, copper bromide is used as a catalyst, and 1, 2-diketone imidazole heterocyclic compounds are generated by the combined action of 2, 2-bipyridine as a ligand; similarly, Sadhanedu Samanta et al (The Journal of organic chemistry, 81(20), 10088-. And the other is to construct the 1, 2-diketone imidazole heterocyclic compound by the catalysis of nonmetal iodine simple substance, for example, Siddiq Pasha Shaik et al (Organic & biomolecular chemistry, 2017, 15(36): 7696-7704) in 2017 report a method for synthesizing the 1, 2-diketone imidazole heterocyclic compound by using nonmetal iodine simple substance as a catalyst, and the method synthesizes the 1, 2-diketone imidazole heterocyclic compound in DMSO solvent under the catalysis of simple substance iodine in the presence of oxygen.
Although these methods all obtain good yields and use inexpensive elemental metals of copper, iron and non-metallic iodine as catalysts, the reaction cost is reduced and the economy is better. However, the cost and atom economy of the reaction are still to be improved due to the influence of the catalyst or additive. Therefore, under the guidance of the environmental-friendly green chemistry development concept, it is important to develop a direct and effective synthesis strategy for constructing heteroaryl 1, 2-dione.
Disclosure of Invention
The invention aims to provide a novel synthesis method of a 1, 2-diketone imidazole heterocyclic compound. The synthesis scheme is not applicable to any catalyst and additive, is green and environment-friendly, and has mild reaction conditions, high reaction yield and good atom economy. And some novel 1, 2-diketone imidazole heterocyclic compound molecular frameworks with better pharmaceutical activity are obtained through the evaluation of pharmaceutical activity tests.
The purpose of the invention is realized by the following technical scheme:
a novel synthesis method of 1, 2-diketone imidazole heterocyclic compounds is disclosed, and the compounds have the following structures:
wherein R is1Represents n-pentyl, cyclopropyl or phenyl etc., R2Represents methoxy, halogen or the like
The novel preparation method (synthetic reaction formula) of the 1, 2-diketone imidazole heterocyclic compound is as follows:
the method comprises the following steps: first, imidazo [1,2-a ] -pyridines are prepared: under the protection of oxygen, adding 2-aminopyridine, acetophenone compounds, cuprous iodide and boron trifluoride diethyl etherate into a DMF solvent, and reacting for 12 hours at 60 ℃; cooling to room temperature, extracting by ethyl acetate, drying by anhydrous sodium sulfate, concentrating, purifying by silica gel column chromatography (the volume ratio of petroleum ether to ethyl acetate is 3: 1) to obtain the imidazo [1,2-a ] -pyridine compound.
Step two (split reaction): adding the imidazo [1,2-a ] -pyridine compound synthesized in the step one, phenyl glyoxal hydrate and xylene into a reaction bottle to react; and cooling the reaction solution after the reaction at room temperature, extracting with ethyl acetate, drying with anhydrous sodium sulfate, and purifying by column chromatography to obtain the 1, 2-diketone imidazole heterocyclic compound.
The addition molar ratio of the imidazo [1,2-a ] -pyridine compound to the phenyl glyoxal hydrate is 1: 1-1: 1.2, preferably 1: 1.2. The reaction ratio of the imidazo [1,2-a ] -pyridine compound to the xylene is 0.1 mmol/mL-0.2 mmol/mL, preferably 0.1 mmol/mL.
The 2-phenylimidazo [1,2-a ] pyridine compound is 2- (2-amyl) imidazo [1,2-a ] pyridine, 2- (2- (cyclopropane) imidazo [1,2-a ] pyridine, imidazo [1,2-a ] -pyridine compound and the like.
The phenylglyoxal hydrate is phenylglyoxal hydrate, 3-methoxyphenyl glyoxal hydrate, 4-chlorophenyl glyoxal hydrate and the like.
And the splicing reaction (namely the step two) is stirred and reacts for 3 to 6 hours at the temperature of between 60 and 100 ℃.
Further, the split reaction is stirred and reacted for 6 hours at the temperature of 80 ℃.
In the second step, the eluent for the column chromatography purification of the reaction solution is a mixture of petroleum ether and ethyl acetate, and the volume ratio of the petroleum ether to the ethyl acetate is 4: 1.
The invention relates to a novel synthesis method of a 1, 2-diketone imidazole heterocyclic compound, and the specific optimization process is shown in the following table:
| serial number | Catalyst/additive | Temperature (. degree.C.) | Solvent(s) | Yield (%) |
| 1 | Ferric chloride | 80 | Toluene | 74 |
| 2 | Aluminium trichloride | 80 | Toluene | 68 |
| 3 | Zinc bromide | 80 | Toluene | 60 |
| 4 | Pyrrolidine as a therapeutic agent | 80 | Toluene | 71 |
| 5 | Aniline | 80 | Toluene | 76 |
| 6 | -- | 80 | Toluene | 78 |
| 7 | -- | 80 | N, N-dimethylformamide | 40 |
| 8 | -- | 80 | N, N-dimethyl acetamide | 45 |
| 9 | -- | 80 | Dimethyl sulfoxide | 33 |
| 10 | -- | 80 | Acetonitrile | 46 |
| 11 | -- | 80 | N-methyl pyrrolidone | 21 |
| 12 | -- | 80 | Xylene | 82 |
| 13 | -- | 80 | Dioxane (dioxane) | 61 |
| 14 | -- | 100 | Xylene | 75 |
| 15 | -- | 60 | Xylene | 66 |
| 16a | -- | 80 | Xylene | 74 |
| 17b | -- | 80 | Xylene | 70 |
| 18c | -- | 80 | Xylene | 65 |
a. Under the oxygen protection state, the solvent is 1mL, and the reaction time is 3h
The results show that: 1. experiments 1-6 show that the reaction has the best effect under the condition of not adding a catalyst, and the yield is 78%, 2. experiments 6-13 show that the reaction has the best effect when the solvent is dimethylbenzene, and the yield is 82%, and experiments 14-15 show that the experiment effect is influenced by overhigh and overlow temperature. The results of experiments 16-18 show that oxygen protection, increased concentration and decreased reaction time all affect the optimal results.
The invention has the advantages that the invention provides a new method for synthesizing 1, 2-diketone imidazole heterocyclic compound, which is obtained by taking dimethylbenzene as a solvent and reacting imidazo [1,2-a ] pyridine compound and phenyl glyoxal hydrate in a reaction bottle without adding any catalyst and additive; the synthesis scheme realizes the direct construction of C-C bonds by a double C-H bond activation mode without adding any catalyst; the raw materials used in the synthesis method are common chemical commodities, and are cheap and easy to obtain; the novel synthesis scheme provided by the invention is environment-friendly, mild in reaction condition, high in reaction efficiency and good in atom economy. In addition, some compounds were evaluated for their in vitro cell growth inhibitory activity against two cancer cell lines, PC-9 (human lung carcinoma), H2170 (human lung carcinoma) by MTT assay.
Detailed Description
The invention is further described below with reference to the following examples:
the structural formula of the 1, 2-diketone imidazole heterocyclic compound is as follows:
wherein R is1Represents n-pentyl, cyclopropyl or phenyl etc., R2Represents methoxy, halogen, or the like.
The preparation method comprises the following steps: adding 2-phenylimidazo [1,2-a ] pyridine, phenylglyoxal hydrate and xylene into a reaction bottle for reaction, wherein the addition molar ratio of the 2-phenylimidazo [1,2-a ] pyridine to the phenylglyoxal hydrate is 1:1.2, 2-phenylimidazo [1,2-a ] pyridine is reacted with the xylene in a ratio of 0.1 mmol/mL, and the reaction is stirred at a temperature of 80 ℃ for 6 h. And cooling, extracting with ethyl acetate, drying with anhydrous sodium sulfate, and purifying by column chromatography to obtain the 1, 2-diketone imidazole heterocyclic compound. Wherein the eluent for the column chromatography purification in the reaction is a mixture of petroleum ether and ethyl acetate, and the volume ratio of the petroleum ether to the ethyl acetate is 4: 1.
In addition, some compounds were evaluated for their in vitro cell growth inhibitory activity against two cancer cell lines, PC-9 (human lung carcinoma), H2170 (human lung carcinoma) by MTT assay.
Example 1
The method comprises the following steps: adding 2-aminopyridine (0.5 mmol), methyl pentanone (10.0 mmol), cuprous iodide (0.25 mmol) and boron trifluoride diethyl etherate (0.14 mL) into 2 mL of DMF solvent under the protection of oxygen, and reacting at 60 ℃ for 12 hours; after the reaction is finished, cooling to room temperature, extracting by ethyl acetate (30 mL), drying by anhydrous sodium sulfate, concentrating, and purifying by silica gel column chromatography (the volume ratio of petroleum ether to ethyl acetate is 3: 1) to obtain the 2- (2-pentyl) imidazo [1,2-a ] pyridine.
Step two: adding the 2- (2-pentyl) imidazo [1,2-a ] pyridine (0.20 mmol), phenylglyoxal hydrate (0.24 mmol) and xylene (2 mL) synthesized in the step one into a reaction bottle for reaction; stirring for 6 hours at 80 ℃ in the presence of air; after the reaction was completed, the reaction system was cooled to room temperature. Extracting with ethyl acetate, drying with anhydrous sodium sulfate, concentrating, purifying with silica gel column chromatography (the volume ratio of petroleum ether to ethyl acetate is 4: 1) to obtain 1- (2-pentylimidazo [1,2-a ] pyridin-3-yl) -2-phenylethane-1, 2-dione. The reaction yield was 52%, and its structural formula was as follows:
spectral data for 1- (2-pentylimidazo [1,2-a ] pyridin-3-yl) -2-phenylethane-1, 2-dione are as follows:
eluent for column chromatography (petroleum ether: ethyl acetate = 4: 1) yellow solid melting point 76-78 deg.C
1H NMR (500 MHz, CDCl3) δ 9.80 (d, J = 7.0 Hz, 1H), 8.04 (d, J = 7.5 Hz, 2H), 7.75 (d, J = 9.0 Hz, 1H), 7.68 (t, J = 7.5 Hz, 1H), 7.60 (t, J = 8.0 Hz, 1H), 7.54 (t, J = 8.0 Hz, 2H), 7.17 (t, J = 6.5 Hz, 1H), 2.66 (t, J = 8.0 Hz, 2H), 1.61 – 1.56 (m, 2H), 1.14 – 1.12 (m, 4H), 0.76 (t, J = 7.0 Hz, 3H)
13C NMR (125 MHz, CDCl3) δ 192.8, 183.7, 161.2, 148.8, 135.0, 133.1, 130.9, 130.2, 129.6, 129.2, 118.9, 117.1, 115.5, 31.8, 30.2, 29.5, 22.3, 14.0
IR (KBr) 2923, 2854, 1671, 1603, 1491, 1409, 1262, 1179, 716 cm-1
HRMS for C20H21N2O2+(M++ H) calculated 321.15975, found 321.15985
Example 2
The method comprises the following steps: adding 2-aminopyridine (0.5 mmol), cyclopropylmethyl ketone (10.0 mmol), cuprous iodide (0.25 mmol) and boron trifluoride diethyl etherate (0.14 mL) into 2 mL of DMF solvent under the protection of oxygen, and reacting at 60 ℃ for 12 hours; after the reaction is finished, cooling to room temperature, extracting by ethyl acetate (30 mL), drying by anhydrous sodium sulfate, concentrating, and purifying by silica gel column chromatography (the volume ratio of petroleum ether to ethyl acetate is 4: 1) to obtain the 2- (2- (cyclopropane) imidazo [1,2-a ] pyridine.
Step two: adding the 2- (2- (cyclopropane) imidazo [1,2-a ] pyridine (0.20 mmol), phenylglyoxal hydrate (0.24 mmol) and xylene (2 mL) synthesized in the step one into a reaction bottle for reaction, stirring at 80 ℃ for 6 hours in the presence of air, cooling a reaction system to room temperature after the reaction is finished, extracting by ethyl acetate, drying by anhydrous sodium sulfate, concentrating and purifying by silica gel column chromatography (the volume ratio of petroleum ether to ethyl acetate is 4: 1) to obtain a product 1- (2-cyclopropyl imidazo [1,2-a ] pyridin-3-yl) -2-phenylethane-1, 2-dione, wherein the reaction yield is 56%, and the structural formula is as follows:
spectral data for 1- (2-cyclopropylimidazo [1,2-a ] pyridin-3-yl) -2-phenylethane-1, 2-dione are as follows:
column chromatography eluent (petroleum ether: ethyl acetate = 4: 1) yellow solid melting point 142-143 deg.C
1H NMR (500 MHz, CDCl3) δ 9.77 (d, J = 7.0 Hz, 1H), 8.04 (d, J = 7.5 Hz, 2H), 7.68 – 7.66 (m, 2H), 7.59 – 7.52 (m, 3H), 7.13 (t, J = 6.5 Hz, 1H), 1.88 – 1.83 (m, 1H), 1.13 – 1.12 (m, 2H), 0.84 – 0.83 (m, 2H)
13C NMR (125 MHz, CDCl3) δ 193.3, 183.5, 162.2, 148.9, 134.9, 133.3, 131.0, 130.2, 129.4, 129.2, 119.7, 116.9, 115.2, 10.7, 10.4
IR (KBr) 2920, 2851, 1672, 1574, 1442, 1239, 1081, 724 cm-1
HRMS for C18H15N2O2 + (M++ H) calculated value 291.11280 found value 291.11292
Example 3
The method comprises the following steps: adding 2-aminopyridine (0.5 mmol), acetophenone (10.0 mmol), cuprous iodide (0.25 mmol) and boron trifluoride diethyl etherate (0.14 mL) into 2 mL of DMF solvent under the protection of oxygen, and reacting at 60 ℃ for 12 hours; after the reaction is finished, cooling to room temperature, extracting by ethyl acetate (30 mL), drying by anhydrous sodium sulfate, concentrating by silica gel column chromatography (the volume ratio of petroleum ether to ethyl acetate is 3: 1), and purifying to obtain the imidazo [1,2-a ] -pyridine compound.
Step two: adding the imidazo [1,2-a ] -pyridine (0.20 mmol) synthesized in the step one, 3-methoxyphenyl glyoxal hydrate (0.24 mmol) and xylene (2 mL) into a reaction bottle for reaction; stirring for 6 hours at 80 ℃ in the presence of air; after the reaction was completed, the reaction system was cooled to room temperature. Extracting with ethyl acetate, drying with anhydrous sodium sulfate, concentrating, purifying with silica gel column chromatography (the volume ratio of petroleum ether to ethyl acetate is 4: 1) to obtain 1- (3-methoxyphenyl) -2- (2-phenylimidazo [1,2-a ] pyridin-3-yl) ethane-1, 2-diketone. The reaction yield was 67%, and its structural formula was as follows:
spectral data for 1- (3-methoxyphenyl) -2- (2-phenylimidazo [1,2-a ] pyridin-3-yl) ethane-1, 2-dione are as follows:
column chromatography eluent (petroleum ether: ethyl acetate = 4: 1) yellow solid melting point 102-104 DEG C
1H NMR (500 MHz, CDCl3) δ 9.83 (d, J = 7.0 Hz, 1H), 7.85 (d, J = 9.0 Hz, 1H), 7.66 (t, J = 8.0 Hz, 1H), 7.36 – 7.28 (m, 5H), 7.24 (t, J = 7.0 Hz, 1H), 7.15 – 7.11 (m, 4H), 3.78 (s, 3H)
13C NMR (125 MHz, CDCl3) δ 191.4, 184.5, 159.8, 158.8, 148.4, 134.8, 133.0, 131.1, 130.2, 130.0, 129.5, 129.4, 128.1, 123.0, 121.4, 119.0, 117.8, 116.0, 112.6, 55.5
IR (KBr) 2922, 2853, 1667, 1593, 1403, 1268, 1142, 725 cm-1
HRMS for C22H17N2O3 +(M++ H) calculated 357.12337, found 357.12338
Example 4
The method comprises the following steps: adding 2-aminopyridine (0.5 mmol), acetophenone (10.0 mmol), cuprous iodide (0.25 mmol) and boron trifluoride diethyl etherate (0.14 mL) into 2 mL of DMF solvent under the protection of oxygen, and reacting at 60 ℃ for 12 hours; after the reaction is finished, cooling to room temperature, extracting by ethyl acetate (30 mL), drying by anhydrous sodium sulfate, concentrating by silica gel column chromatography (the volume ratio of petroleum ether to ethyl acetate is 3: 1), and purifying to obtain the imidazo [1,2-a ] -pyridine compound.
Step two: adding the imidazo [1,2-a ] -pyridine (0.20 mmol), 4-chlorophenyl glyoxal hydrate (0.24 mmol) and xylene (2 mL) synthesized in the step one into a reaction bottle for reaction; stirring for 6 hours at 80 ℃ in the presence of air; after the reaction was completed, the reaction system was cooled to room temperature. Extracting with ethyl acetate, drying with anhydrous sodium sulfate, concentrating, purifying with silica gel column chromatography (the volume ratio of petroleum ether to ethyl acetate is 4: 1) to obtain 1- (4-chlorophenyl) -2- (2-phenylimidazo [1,2-a ] pyridin-3-yl) ethane-1, 2-diketone. The reaction yield was 76%, and its structural formula was as follows:
spectral data for 1- (4-chlorophenyl) -2- (2-phenylimidazo [1,2-a ] pyridin-3-yl) ethane-1, 2-dione are as follows:
column chromatography eluent (petroleum ether: ethyl acetate = 4: 1) yellow solid melting point 124-126 DEG C
1H NMR (500 MHz, CDCl3) δ 9.81 (d, J = 7.0 Hz, 1H), 7.87 (d, J = 9.0 Hz, 1H), 7.69 – 7.66 (m, 3H), 7.37 (d, J = 8.0 Hz, 2H), 7.30 – 7.23 (m, 4H), 7.14 (t, J = 7.5 Hz, 2H)
13C NMR (125 MHz, CDCl3) δ 190.2, 184.0, 158.9, 148.6, 140.8, 133.0, 131.9, 131.3, 131.0, 130.1, 129.7, 129.4, 129.1, 128.1, 119.0, 117.8, 116.1
IR (KBr) 2923, 2853, 1682, 1588, 1397, 1247, 1091, 752 cm-1
HRMS for C21H14ClN2O2 +(M++ H) calculated value 36107383 found 361.07379
Example 5
The method comprises the following steps: adding 2-aminopyridine (0.5 mmol), acetophenone (10.0 mmol), cuprous iodide (0.25 mmol) and boron trifluoride diethyl etherate (0.14 mL) into 2 mL of DMF solvent under the protection of oxygen, and reacting at 60 ℃ for 12 hours; after the reaction is finished, cooling to room temperature, extracting by ethyl acetate (30 mL), drying by anhydrous sodium sulfate, concentrating by silica gel column chromatography (the volume ratio of petroleum ether to ethyl acetate is 3: 1), and purifying to obtain the imidazo [1,2-a ] -pyridine compound.
Step two: adding the imidazo [1,2-a ] -pyridine (0.20 mmol) synthesized in the step one, 4-bromophenyl glyoxal hydrate (0.24 mmol) and xylene (2 mL) into a reaction bottle for reaction; stirring for 6 hours at 80 ℃ in the presence of air; after the reaction was completed, the reaction system was cooled to room temperature. Extracting with ethyl acetate, drying with anhydrous sodium sulfate, concentrating, purifying with silica gel column chromatography (the volume ratio of petroleum ether to ethyl acetate is 4: 1) to obtain 1- (4-bromophenyl) -2- (2-phenylimidazo [1,2-a ] pyridin-3-yl) ethane-1, 2-diketone. The reaction yield was 78%, which has the following structural formula:
spectral data for 1- (4-bromophenyl) -2- (2-phenylimidazo [1,2-a ] pyridin-3-yl) ethane-1, 2-dione are as follows:
column chromatography eluent (petroleum ether: ethyl acetate = 4: 1) yellow solid melting point 138-140 deg.C
1H NMR (500 MHz, CDCl3) δ 9.80 (d, J = 6.5 Hz, 1H), 7.87 (d, J = 9.0 Hz, 1H), 7.68 (t, J = 7.5 Hz, 1H), 7.60 – 7.53 (m, 4H), 7.30 – 7.28 (m, 3H), 7.25 (t, J = 7.0 Hz, 1H), 7.14 (t, J = 7.5 Hz, 2H)
13C NMR (125 MHz, CDCl3) δ 190.4, 183.9, 158.9, 148.5, 132.9, 132.3, 132.1, 131.3, 131.0, 130.1, 129.7, 129.7, 129.4, 128.1, 118.9, 117.8, 116.1
IR (KBr) 2922, 2852, 1682, 1588, 1406, 1248, 1147, 750 cm-1
HRMS for C21H14BrN2O2 +(M++ H) calculated value 405.02332 found value 405.02319
Test example:
selecting the obtained compound for activity determination
Experimental materials:
1. human cancer cell line: all purchased from the Shanghai cell bank of Chinese academy of sciences.
2. The tested drugs are: after dissolving in DMSO, the mixture was prepared to an initial concentration of 10000 mg/mL and was ready for use.
3.0.9% physiological saline: the specification is 250 mL; 2.25 g, Zheng Zhou Yong and pharmaceuticals, Inc.
The test method comprises the following steps:
cells were routinely seeded in complete medium at 37 ℃ with 5% CO2Culturing and amplifying at saturated humidity. Cells were digested with 0.25% trypsin and diluted to 1X 10 with culture medium5one/mL cancer cell suspension (placenta blue staining, number of living cells > 95%) was used for the experiment. A96-well sterile culture plate is provided with a negative control well, a positive control well and test sample wells with different concentrations, the concentrations are set to be 64, 32, 16, 8, 4, 2, 1 and 0.5 micrograms per milliliter, and each concentration is provided with 3 multiple wells. The prepared cell suspension was inoculated into a 96-well sterile culture plate, and compounds of different concentrations were added after 24 hours of culture. And adding an equal amount of culture solution into the negative control hole, and culturing in an incubator. And taking out after 72 hours respectively, adding 20 microliters of MTT into each hole, continuously culturing for 4 hours, taking out, centrifuging, sucking and removing supernatant. DMSO was added in an amount of 150. mu.l per well, and after shaking, the violet formazan crystals were completely dissolved. OD value of each well was measured by a microplate reader, and IC thereof was calculated from SPSS50.
Test results
The data for the evaluation of the anticancer activity of the above compounds on two human cancer cells are as follows (IC)50）：
The results show that the method has the advantages of high yield,
the synthesized novel compounds 3a, 3b and 3e have obvious inhibition effect on the proliferation of human lung squamous cell carcinoma (H2170);
the synthesized new compounds 3c and 3d have obvious inhibition effect on the proliferation of human adenocarcinoma cells (PC-9).
Claims (3)
1. A synthetic method of 1, 2-diketone imidazole heterocyclic compounds is characterized in that: the compound has the following structure:
wherein R is1Represents n-pentyl, cyclopropyl or phenyl, R2Represents methoxy or halogen, is synthesized by the following method: imidazo [1, 2-a)]Adding a pyridine compound, a phenyl glyoxal hydrate and xylene into a reaction bottle to react at 80 ℃ for 6 hours; cooling the reaction solution after the reaction at room temperature, extracting with ethyl acetate, drying with anhydrous sodium sulfate, and purifying by column chromatography to obtain the 1, 2-diketone imidazole heterocyclic compound;
the imidazo [1,2-a ] pyridine compounds are 2- (2-amyl) imidazo [1,2-a ] pyridine, 2- (2-cyclopropane) imidazo [1,2-a ] pyridine and imidazo [1,2-a ] -pyridine compounds;
the addition molar ratio of the imidazo [1,2-a ] pyridine compound to the phenyl glyoxal hydrate is 1: 1-1: 1.2; the phenylglyoxal hydrate is 3-methoxyphenyl glyoxal hydrate and 4-chlorophenyl glyoxal hydrate;
the reaction ratio of the imidazo [1,2-a ] pyridine compound to the xylene is 0.1-0.2 mmol/mL.
2. The synthesis method according to claim 1, characterized in that the molar ratio of the imidazo [1,2-a ] pyridine compound to the phenyl glyoxal hydrate added is 1: 1.2; the reaction ratio of imidazo [1,2-a ] pyridine to xylene was 0.1 mmol/mL.
3. The synthesis method of claim 1, wherein the eluent for column chromatography purification is a mixture of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate is 4: 1.
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| CN107163044A (en) * | 2017-06-19 | 2017-09-15 | 广东药科大学 | Naphthylethylenedione compound with protease modification activity and derivative thereof |
| CN108003156A (en) * | 2018-01-29 | 2018-05-08 | 辽宁科技大学 | A kind of synthetic method of imidazopyridyl 1,2- second derovatives |
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| CN107163044A (en) * | 2017-06-19 | 2017-09-15 | 广东药科大学 | Naphthylethylenedione compound with protease modification activity and derivative thereof |
| CN108003156A (en) * | 2018-01-29 | 2018-05-08 | 辽宁科技大学 | A kind of synthetic method of imidazopyridyl 1,2- second derovatives |
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