CN112826812B - Pharmaceutical composition for treating colon cancer and application thereof - Google Patents
Pharmaceutical composition for treating colon cancer and application thereof Download PDFInfo
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K31/00—Medicinal preparations containing organic active ingredients
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Abstract
The invention discloses a pharmaceutical composition for treating colon cancer, which consists of an active ingredient and pharmaceutically acceptable auxiliary materials, wherein the active ingredient consists of R 1 A group, R group and R 2 The groups are sequentially connected to form the compound, and the molecular structural general formula of the compound is shown as formula 1. The invention also provides application of the pharmaceutical composition in preparing medicines for treating colon cancer. The inhibition rate of the organic compound provided by the invention to colon cancer cells reaches 0.1-1 mu m.
Description
Technical field:
the invention relates to the technical field of medicines for treating colon cancer, in particular to a medicine composition for treating colon cancer and application thereof.
The background technology is as follows:
colon cancer is one of the common cancers worldwide at present, early symptoms are not obvious, and later stage symptoms such as anemia, weight loss and the like are shown. The morbidity and mortality are high. By far, the most common clinical diagnosis is colonoscopy. However, the misdiagnosis rate of rectal cancer is 30% based on statistics of related data. The treatment of rectal cancer is surgery or radiation therapy. However, surgical radiation therapy is performed with recurrent, metastatic and severe pain. Therefore, the development of more effective diagnosis and minimally invasive treatments is not trivial.
Various combination therapies such as chemotherapy/photothermal therapy (CT/PTT), photothermal/photodynamic therapy (PTT/PDT), and photothermal/chemo-therapy (PTT/CDT) have been widely used in the research of cancer treatment, but still have drawbacks such as PTT not only killing tumor tissue but also injuring surrounding normal tissue cells, and sometimes accompanied by a series of inflammation problems after treatment; PDT is limited by oxygen deficiency of tumor cells; CT often presents problems with recurrence and metastasis after treatment.
The invention comprises the following steps:
the invention aims to provide a medicament for treating colon cancer.
The invention provides a pharmaceutical composition for treating cancers, which consists of an active ingredient and pharmaceutically acceptable auxiliary materials; the active ingredient is represented by R 1 A group, R group and R 2 The groups are sequentially connected to form, and the molecular structural general formula of the compound is shown as formula 1:
wherein, the liquid crystal display device comprises a liquid crystal display device,
R 1 the radicals being selected fromOne of R 5 Selected from hydroxy or alkoxy ether groups, R 6 One selected from halogeno, trifluoroalkoxy or trichloroalkoxy; r is R 7 One selected from alkyl, halo, trifluoroalkoxy or trichloroalkoxy; r is R 8 One selected from hydroxyl, alkoxy or alkoxy ether groups. The pharmaceutically acceptable auxiliary materials are selected from one or more of solvents, propellants, solubilizers, cosolvents, emulsifiers, colorants, binders, disintegrants, fillers, lubricants, wetting agents, osmotic pressure regulators, stabilizers, glidants, flavoring agents, preservatives, suspending agents, coating materials, fragrances, anti-adhesion agents, integration agents, permeation promoters, pH value regulators, buffering agents, plasticizers, surfactants, foaming agents, antifoaming agents, thickening agents, inclusion agents, humectants, absorbents, diluents, flocculating and deflocculating agents, filter aids and release retarders.
In one embodiment according to the invention, R 1 Selected from the group consisting of
Any one of them.
In one embodiment according to the invention, the R 2 Selected from the group consisting of
Any one of them.
In one embodiment according to the invention, the active ingredient is selected from (E) -1- (2-fluorophenyl) -3- (4-fluorophenyl) propyl-2-en-1-one;
(E) -3- (4-fluorophenyl) -1- (3-methoxyphenyl) propyl-2-en-1-one;
(E) -1- (p-tolyl) -3- (2, 4, 5-trimethoxyphenyl) propyl-2-en-1-one;
(E) -1- (3-methoxyphenyl) -3- (2, 4, 5-trimethoxyphenyl) propyl-2-en-1-one;
(E) -1-cyclopropyl-3- (3-hydroxyphenyl) propyl-2-en-1-one;
(E) -1-cyclopropyl-3- (3- (methoxymethoxy) phenyl) propyl-2-en-1-one;
(E) -1- (3, 5-dimethoxy-4- (methoxymethoxy) phenyl) -3- (3- (methoxymethoxy) phenyl) propyl-2-en-1-one;
(E) -1- (4-hydroxy-3, 5-dimethoxyphenyl) -3- (3-hydroxyphenyl) propyl-2-en-1-one;
(E) -1- (4-fluorophenyl) -3- (3-hydroxyphenyl) propyl-2-en-1-one;
(E) -1- (4-fluorophenyl) -3- (4- (trifluoromethoxy) phenyl) propyl-2-en-1-one;
(E) -1-cyclopropyl-3- (4- (trifluoromethoxy) phenyl) propyl-2-en-1-one;
(E) -1- (2-bromophenyl) -3- (4-fluorophenyl) propyl-2-en-1-one;
(E) -1- (4-bromophenyl) -3- (4-fluorophenyl) propyl-2-en-1-one;
(E) -1- (2-chlorophenyl) -3- (4-fluorophenyl) propyl-2-en-1-one;
(E) -1- (4-chlorophenyl) -3- (4-fluorophenyl) propyl-2-en-1-one;
(E) -3- (4-bromophenyl) -1- (4-fluorophenyl) propyl-2-en-1-one;
(E) -3- (4-chlorophenyl) -1- (4-fluorophenyl) propyl-2-en-1-one; or (b)
(E) -one or more of 1, 3-bis (4-fluorophenyl) propyl-2-en-1-one.
In one embodiment according to the invention, the organic compound is selected from (E) -1-cyclopropyl-3- (3-hydroxyphenyl) propyl-2-en-1-one;
(E) -1-cyclopropyl-3- (3- (methoxymethoxy) phenyl) propyl-2-en-1-one;
(E) -1- (3, 5-dimethoxy-4- (methoxymethoxy) phenyl) -3- (3- (methoxymethoxy) phenyl) propyl-2-en-1-one;
(E) -1- (4-hydroxy-3, 5-dimethoxyphenyl) -3- (3-hydroxyphenyl) propyl-2-en-1-one;
(E) -1- (4-fluorophenyl) -3- (3-hydroxyphenyl) propyl-2-en-1-one;
(E) -1- (4-fluorophenyl) -3- (4- (trifluoromethoxy) phenyl) propyl-2-en-1-one;
(E) -1-cyclopropyl-3- (4- (trifluoromethoxy) phenyl) propyl-2-en-1-one;
(E) -1- (4-bromophenyl) -3- (4-fluorophenyl) propyl-2-en-1-one;
(E) -1- (2-chlorophenyl) -3- (4-fluorophenyl) propyl-2-en-1-one;
(E) -1- (4-chlorophenyl) -3- (4-fluorophenyl) propyl-2-en-1-one;
(E) -3- (4-bromophenyl) -1- (4-fluorophenyl) propyl-2-en-1-one; or (b)
(E) -3- (4-chlorophenyl) -1- (4-fluorophenyl) propyl-2-en-1-one;
one or more of the following.
In one embodiment according to the invention, the IC of the active ingredient 50 0.1-1 μm.
The invention also provides application of the pharmaceutical composition in preparing medicines for treating colon cancer.
In one embodiment according to the invention, the active ingredient comprises (E) -1-cyclopropyl-3- (3-hydroxyphenyl) propyl-2-en-1-one;
(E) -1-cyclopropyl-3- (3- (methoxymethoxy) phenyl) propyl-2-en-1-one;
(E) -1- (3, 5-dimethoxy-4- (methoxymethoxy) phenyl) -3- (3- (methoxymethoxy) phenyl) propyl-2-en-1-one;
(E) -1- (4-hydroxy-3, 5-dimethoxyphenyl) -3- (3-hydroxyphenyl) propyl-2-en-1-one;
(E) -1- (4-fluorophenyl) -3- (3-hydroxyphenyl) propyl-2-en-1-one;
(E) -1- (4-fluorophenyl) -3- (4- (trifluoromethoxy) phenyl) propyl-2-en-1-one;
(E) -1-cyclopropyl-3- (4- (trifluoromethoxy) phenyl) propyl-2-en-1-one;
(E) -1- (4-bromophenyl) -3- (4-fluorophenyl) propyl-2-en-1-one;
(E) -1- (2-chlorophenyl) -3- (4-fluorophenyl) propyl-2-en-1-one;
(E) -1- (4-chlorophenyl) -3- (4-fluorophenyl) propyl-2-en-1-one;
(E) -3- (4-bromophenyl) -1- (4-fluorophenyl) propyl-2-en-1-one; or (b)
(E) -3- (4-chlorophenyl) -1- (4-fluorophenyl) propyl-2-en-1-one;
one or more of the following.
In one embodiment according to the invention, the IC of the organic compound 50 0.25-0.8 μm.
The beneficial effects of the invention are as follows:
the invention applies the organic compound to treat colon cancer for the first time, experiments prove that the organic compound has obvious effect on colon cancer, and part of organic compound has IC of colon cancer cells 50 Reaching 0.2-0.8 mu m.
The specific embodiment is as follows:
the following detailed description of the preferred embodiments of the invention will provide those skilled in the art with a better understanding of the invention with its advantages and features, and thus define the scope of the invention more clearly and clearly.
At room temperature, acetophenone compound is dissolved in absolute ethanol, 10% sodium hydroxide solution is added and stirred for 10 minutes, benzaldehyde compound is added and stirred overnight. After the reaction is finished, ethyl acetate is used for extraction for three times, saturated sodium chloride aqueous solution is used for washing, anhydrous sodium sulfate is used for drying, filtering and concentration are carried out, and silica gel chromatography is used for purification, thus obtaining a series of alpha, beta-unsaturated carbonyl compounds. Specific structures, names and synthetic routes thereof are shown in the following examples:
example 1 Synthesis of (E) -1- (2-fluorophenyl) -3- (4-fluorophenyl) propyl-2-en-1-one
(E) -1- (2-fluorophenyl) -3- (4-fluorophenyl) propyl-2-en-1-one
(E)-1-(2-fluorophenyl)-3-(4-fluorophenyl)prop-2-en-1-one
Product(s) 1 H NMR(500MHz,CDCl 3 )δ7.78(d,J＝15.7Hz,1H),7.66–7.62(m, 2H),7.59(d,J＝7.7Hz,1H),7.54(s,1H),7.44(d,J＝10.4Hz,1H),7.42–7.39(m, 1H),7.15–7.10(m,3H),3.89(s,3H). 13 C NMR(101MHz,DMSO)δ189.36, 165.28,162.80,161.93,159.43,143.89,134.78,134.69,131.75,131.66,131.42,131.39,130.98,130.95,127.41,127.27,125.93,125.34,125.31,117.22,117.00, 116.65,116.43.[M+H] + ＝245.0772.
The synthetic route is as follows:
to a solution of m-fluoro acetophenone (200 mg,1.45 mmol) in absolute ethanol (5 mL) was added 10% NaOH (3.6 mmol) at room temperature, and after stirring for 10 minutes, p-fluorobenzaldehyde (188.7 mg,1.52 mmol) was added and stirred at room temperature overnight. Ethyl acetate (3X 20 mL), the organic phases were combined and washed with saturated aqueous NaCl solution (2X 20 mL), filtered and dried over anhydrous Na 2 SO 4 And (5) drying. After concentrating the filtrate, it was separated and purified by column chromatography with EtOAc in petroleum ether=1:60 as eluent to give the compound as a white powder in 87% yield.
Example 2 Synthesis of (E) -3- (4-fluorophenyl) -1- (3-methoxyphenyl) propyl-2-en-1-one
(E) -3- (4-fluorophenyl) -1- (3-methoxyphenyl) propyl-2-en-1-one
(E)-3-(4-fluorophenyl)-1-(3-methoxyphenyl)prop-2-en-1-one
Product(s) 1 H NMR(500MHz,CDCl 3 )δ7.78(d,J＝15.7Hz,1H),7.65–7.63(m, 2H),7.59(d,J＝7.7Hz,1H),7.55–7.53(m,1H),7.44(d,J＝10.4Hz,1H),7.42– 7.39(m,1H),7.15–7.10(m,3H),3.89(s,3H). 13 C NMR(101MHz,DMSO)δ 196.15,162.13,161.16,145.17,130.97,130.83,130.44,130.32,130.26,121.38,120.13,115.48,115.32,114.86,114.01,55.84.[M+H] + ＝257.0980.
The synthetic route is as follows:
to a solution of m-methoxyacetophenone (200 mg,1.33 mmol) in absolute ethanol (5 mL) was added 10% NaOH (3.33 mmol) at room temperature, and after stirring for 10 min, p-fluorobenzaldehyde (173.5 mg,1.4 mmol) was added and stirred at room temperature overnight. Ethyl acetate (3×20 mL) and the organic phases were combined and washed with saturated aqueous NaCl (2×20 mL), filtered and dried over anhydrous Na 2 SO 4 And (5) drying. After concentrating the filtrate, it was separated and purified by column chromatography with EtOAc in the eluent of petroleum ether=1:60 to give the compound as a white powder in 83% yield.
Example 3 Synthesis of (E) -1- (p-tolyl) -3- (2, 4, 5-trimethoxyphenyl) propyl-2-en-1-one
(E) -1- (p-tolyl) -3- (2, 4, 5-trimethoxyphenyl) propyl-2-en-1-one
(E)-1-(p-tolyl)-3-(2,4,5-trimethoxyphenyl)prop-2-en-1-one)
Product(s) 1 H NMR(500MHz,CDCl 3 )δ8.33(d,J＝16.1Hz,1H),7.84–7.82(m, 1H),7.45–7.44(m,2H),7.28–7.26(m,1H),7.42(d,J＝16.1Hz,1H),6.71(s,1H), 6.42(s,1H),3.85(s,1H),3.84(s,1H),3.83(s,1H),2.34(s,3H). 13 C NMR(101MHz, DMSO)δ189.74,150.02,144.23,142.03,141.04,135.75,134.96,129.84,129.57,129.52,129.37,121.38,110.48,108.28,98.74,56.24,56.18,56.11,21.36. [M+H] + ＝313.1446.
The synthetic route is as follows:
to a solution of p-methylacetophenone (200 mg,1.49 mmol) in absolute ethanol (5 mL) was added 10% NaOH (3.7 mmol) at room temperature, and after stirring for 10 minutes, p-fluorobenzaldehyde (307 mg,1.56 mmol) was added and stirred at room temperature overnight. Ethyl acetate (3X 20 mL), the organic phases were combined and washed with saturated aqueous NaCl solution (2X 20 mL), filtered and dried over anhydrous Na 2 SO 4 And (5) drying. After concentrating the filtrate, separating and purifying by column chromatography, the eluent is EtOAc: petroleum ether=1:5, and the pure product is obtained as yellow solid with a yield of 85%.
EXAMPLE 4 Synthesis of (E) -1- (3-methoxyphenyl) -3- (2, 4, 5-trimethoxyphenyl) propyl-2-en-1-one
(E) -1- (3-methoxyphenyl) -3- (2, 4, 5-trimethoxyphenyl) propyl-2-en-1-one
(E)-1-(3-methoxyphenyl)-3-(2,4,5-trimethoxyphenyl)prop-2-en-1-one
Product(s) 1 H NMR(500MHz,CDCl 3 )δ8.33(d,J＝16.1Hz,1H),7.84–7.82(m, 1H),7.45–7.44(m,2H),7.28–7.26(m,1H),7.42(d,J＝16.1Hz,1H),6.71(s,1H), 6.42(s,1H),3.85(s,1H),3.84(s,1H),3.83(s,1H),3.82(s,1H). 13 C NMR(101MHz, DMSO)δ196.15,161.13,150.05,142.07,141.02,135.78,130.94,130.27,121.34,120.14,114.82,114.05,110.47,108.23,98.73,56.25,56.16,56.12,55.83. [M+H] + ＝329.1386.
The synthetic route is as follows:
to a solution of m-methoxyacetophenone (200 mg,1.33 mmol) in absolute ethanol (5 mL) was added 10% NaOH (3.33 mmol) at room temperature, and after stirring for 10 min, p-fluorobenzaldehyde (274 mg,1.4 mmol) was added and the mixture was stirred at room temperature overnight. Ethyl acetate (3X 20 mL), the organic phases were combined and washed with saturated aqueous NaCl solution (2X 20 mL), filtered and dried over anhydrous Na 2 SO 4 And (5) drying. After concentrating the filtrate, separating and purifying by column chromatography, the eluent was EtOAc: petroleum ether=1:5, and the pure product was obtained as yellow solid with a yield of 83%.
Example 5 Synthesis of (E) -1-cyclopropyl-3- (3-hydroxyphenyl) propyl-2-en-1-one
(E) -1-cyclopropyl-3- (3-hydroxyphenyl) propyl-2-en-1-one
(E)-1-cyclopropyl-3-(3-hydroxyphenyl)prop-2-en-1-one
Product(s) 1 H NMR(500MHz,CDCl 3 )δ7.58(d,J＝16.1Hz,1H),7.27–7.24(m, 1H),7.12–7.10(m,2H),6.93–6.89(m,1H),6.85(d,J＝16.1Hz,1H),2.30–2.23 (m,1H),1.21–1.16(m,2H),1.03–0.99(m,2H). 13 C NMR(101MHz,DMSO)δ 200.71,158.45,142.84,135.48,130.04,126.28,121.14,117.63,115.18,42.93,14.83,14.69.[M+H] + ＝189.0918.
The synthetic route is as follows:
m-hydroxybenzaldehyde (500 mg,4.09 mmol) was dissolved in 10mL of DMF, sodium hydride (196.3 mg,4.9 mmol) was added, and after stirring for 15 minutes chloromethyl methyl ether (410.6 mg,5.1 mmol) was added and the reaction stirred for 1 hour. Saturated NaHCO 3 The reaction was quenched with aqueous solution (20 mL), extracted with ethyl acetate (3X 20 mL), the combined organic phases were washed with saturated aqueous NaCl solution (2X 20 mL), filtered and taken up in anhydrous Na 2 SO 4 And (5) drying. After concentrating the filtrate, it was separated and purified by column chromatography with EtOAc as eluent, i.e. petroleum ether=1:10, to give the oily compound. To a solution of cyclopropylmethyl ketone (429 mg,2.58 mmol) in absolute ethanol (5 mL) was added 10% NaOH (6.15 mmol) at room temperature, and after stirring for 10 minutes, 3- (methoxymethoxy) benzaldehyde (207 mg,2.46 mmol) was added and the mixture was stirred at room temperature overnight. Ethyl acetate (3X 20 mL), the organic phases were combined and washed with saturated aqueous NaCl solution (2X 20 mL), filtered and dried over anhydrous Na 2 SO 4 And (5) drying. After concentrating the filtrate, separating and purifying by column chromatography, the eluent is EtOAc: petroleum ether=1:5, and the pure product is obtained as oily compound. The product (230 mg,0.99 mmol) was dissolved in 8mL of methanol and 3N HCl (2.97 mmol) was added dropwise with stirring and reacted for 3 hours. Saturated NaHCO 3 The reaction was quenched with aqueous solution (20 mL), extracted with ethyl acetate (3X 20 mL), the combined organic phases were washed with saturated aqueous NaCl solution (2X 20 mL), filtered and taken up in anhydrous Na 2 SO 4 And (5) drying. After concentrating the filtrate, it was separated and purified by column chromatography with EtOAc in the eluent of petroleum ether=1:5 to give the compound as a white solid. The yield thereof was found to be 73%.
EXAMPLE 6 Synthesis of (E) -1-cyclopropyl-3- (3- (methoxymethoxy) phenyl) propyl-2-en-1-one
(E) -1-cyclopropyl-3- (3- (methoxymethoxy) phenyl) propyl-2-en-1-one
(E)-1-cyclopropyl-3-(3-(methoxymethoxy)phenyl)prop-2-en-1-one
Product(s) 1 H NMR(400MHz,CDCl 3 )δ7.50(d,J＝16.1Hz,1H),7.23(d,J＝7.9 Hz,1H),7.20–7.12(m,2H),7.02–6.96(m,1H),6.78(d,J＝16.1Hz,1H),5.13(s, 2H),3.42(s,3H),2.26–2.11(m,1H),1.12–1.04(m,2H),0.93–0.88(m,2H). 13 C NMR(101MHz,DMSO)δ200.71,160.53,142.84,135.08,129.64,126.28,120.84,113.51,113.26,94.93,55.62,42.93,14.83,14.69.[M+H] + ＝233.1176.
The synthetic route is as follows:
m-hydroxybenzaldehyde (500 mg,4.09 mmol) was dissolved in 10mL of DMF, sodium hydride (196.3 mg,4.9 mmol) was added, and after stirring for 15 minutes chloromethyl methyl ether (410.6 mg,5.1 mmol) was added and the reaction stirred for 1 hour. Saturated NaHCO 3 The reaction was quenched with aqueous solution (20 mL), extracted with ethyl acetate (3X 20 mL), the combined organic phases were washed with saturated aqueous NaCl solution (2X 20 mL), filtered and taken up in anhydrous Na 2 SO 4 And (5) drying. After concentrating the filtrate, it was separated and purified by column chromatography with EtOAc as eluent, i.e. petroleum ether=1:10, to give the oily compound. To a solution of cyclopropylmethyl ketone (429 mg,2.58 mmol) in absolute ethanol (5 mL) was added 10% NaOH (6.15 mmol) at room temperature, and after stirring for 10 minutes, 3- (methoxymethoxy) benzaldehyde (207 mg,2.46 mmol) was added and the mixture was stirred at room temperature overnight. Ethyl acetate (3X 20 mL), the organic phases were combined and washed with saturated aqueous NaCl solution (2X 20 mL), filtered and dried over anhydrous Na 2 SO 4 And (5) drying. After concentrating the filtrate, separating and purifying by column chromatography, the eluent is EtOAc: petroleum ether=1:5, and the pure product is obtained as oily compound with a yield of 81%.
EXAMPLE 7 Synthesis of (E) -1- (3, 5-dimethoxy-4- (methoxymethoxy) phenyl) -3- (3- (methoxymethoxy) phenyl) propyl-2-en-1-one
(E) -1- (3, 5-dimethoxy-4- (methoxymethoxy) phenyl) -3- (3- (methoxymethoxy) phenyl) propyl-2-en-1-one
(E)-1-(3,5-dimethoxy-4-(methoxymethoxy)phenyl)-3-(3-(methoxymethoxy)phenyl)pr op-2-en-1-one
Product(s) 1 H NMR(500MHz,CDCl 3 )δ7.76(d,J＝15.6Hz,1H),7.47(d,J＝15.6 Hz,1H),7.30–7.25(m,1H),7.22–7.15(m,2H),6.92(dd,J＝8.0,1.6Hz,1H), 6.38(s,1H),6.08(s,1H),5.21(s,4H),3.93(s,6H),3.60(s,3H),3.49(s,3H). 13 C NMR(101MHz,DMSO)δ189.73,160.54,153.68,153.47,145.14,140.03,135.06,129.63,128.54,121.38,120.84,113.58,113.27,99.48,99.27,98.24,94.92,56.18, 56.01,55.63,55.39.[M+H] + ＝389.1602.
The synthetic route is as follows:
m-hydroxybenzaldehyde (200 mg,1.64 mmol) was dissolved in 5mL of DMF, sodium hydride (78.6 mg,1.96 mmol) was added, and after stirring for 15 minutes chloromethyl methyl ether (161 mg,2 mmol) was added and the reaction stirred for 1 hour. Saturated NaHCO 3 The reaction was quenched with aqueous solution (20 mL), extracted with ethyl acetate (3X 20 mL), the combined organic phases were washed with saturated aqueous NaCl solution (2X 20 mL), filtered and taken up in anhydrous Na 2 SO 4 And (5) drying. After concentrating the filtrate, it was separated and purified by column chromatography with EtOAc as eluent, petroleum ether=1:10, to give compound a as an oil. Acetosyringone (200 mg,1 mmol) was dissolved in 10mL DMF, sodium hydride (48 mg,1.2 mmol) was added, chloromethyl methyl ether (100.6 mg,1.25 mmol) was added after stirring for 15 min, and the reaction was stirred for 1 hour. Saturated NaHCO 3 The reaction was quenched with aqueous solution (20 mL), extracted with ethyl acetate (3X 20 mL), the combined organic phases were washed with saturated aqueous NaCl solution (2X 20 mL), filtered and taken up in anhydrous Na 2 SO 4 And (5) drying. After concentrating the filtrate, it was separated and purified by column chromatography with EtOAc as eluent, i.e. petroleum ether=1:10, to give compound B as an oil. To a solution of Compound B (287 mg,1.19 mmol) in absolute ethanol (8 mL) was added 10% NaOH (2.98 mmol) at room temperature, and after stirring for 10 minutes, compound A (2)08mg, 1.25 mmol) and stirred at room temperature overnight. Ethyl acetate (3X 20 mL), the organic phases were combined and washed with saturated aqueous NaCl solution (2X 20 mL), filtered and dried over anhydrous Na 2 SO 4 And (5) drying. After concentrating the filtrate, separating and purifying by column chromatography, the eluent is EtOAc: petroleum ether=1:6, and the pure product is obtained as yellow oily compound with a yield of 74%.
EXAMPLE 8 Synthesis of (E) -1- (4-hydroxy-3, 5-dimethoxyphenyl) -3- (3-hydroxyphenyl) propyl-2-en-1-one
(E) -1- (4-hydroxy-3, 5-dimethoxyphenyl) -3- (3-hydroxyphenyl) propyl-2-en-1-one
(E)-1-(4-hydroxy-3,5-dimethoxyphenyl)-3-(3-hydroxyphenyl)prop-2-en-1-one
Product(s) 1 H NMR(500MHz,CDCl 3 )δ7.76(d,J＝15.6Hz,1H),7.47(d,J＝15.6 Hz,1H),7.30–7.25(m,1H),7.22–7.15(m,2H),6.92(dd,J＝8.0,1.6Hz,1H), 6.38(s,1H),6.08(s,1H),3.96(s,6H). 13 C NMR(101MHz,DMSO)δ189.72, 158.44,148.69,148.49,145.17,143.24,135.47,130.01,128.83,121.38,121.17, 117.63,115.18,99.84,99.69,56.17,56.03.[M+H] + ＝301.1075.
The synthetic route is as follows:
m-hydroxybenzaldehyde (200 mg,1.64 mmol) was dissolved in 5mL of DMF, sodium hydride (78.6 mg,1.96 mmol) was added, and after stirring for 15 minutes chloromethyl methyl ether (161 mg,2 mmol) was added and the reaction stirred for 1 hour. Saturated NaHCO 3 The reaction was quenched with aqueous solution (20 mL), extracted with ethyl acetate (3X 20 mL), the combined organic phases were washed with saturated aqueous NaCl solution (2X 20 mL), filtered and taken up in anhydrous Na 2 SO 4 And (5) drying. After concentrating the filtrate, it was separated and purified by column chromatography with EtOAc as eluent, petroleum ether=1:10, to give compound a as an oil. Acetosyringone (2) was taken at 0 ℃00mg,1 mmol) was dissolved in 10mL of DMF, sodium hydride (48 mg,1.2 mmol) was added, chloromethyl methyl ether (100.6 mg,1.25 mmol) was added after stirring for 15 min, and the reaction was stirred for 1 hour. Saturated NaHCO 3 The reaction was quenched with aqueous solution (20 mL), extracted with ethyl acetate (3X 20 mL), the combined organic phases were washed with saturated aqueous NaCl solution (2X 20 mL), filtered and taken up in anhydrous Na 2 SO 4 And (5) drying. After concentrating the filtrate, it was separated and purified by column chromatography with EtOAc as eluent, i.e. petroleum ether=1:10, to give compound B as an oil. To a solution of compound B (287 mg,1.19 mmol) in absolute ethanol (8 mL) was added 10% naoh (2.98 mmol) at room temperature, and after stirring for 10 minutes, compound a (208 mg,1.25 mmol) was added and stirred at room temperature overnight. Ethyl acetate (3X 20 mL), the organic phases were combined and washed with saturated aqueous NaCl solution (2X 20 mL), filtered and dried over anhydrous Na 2 SO 4 And (5) drying. After concentrating the filtrate, separating and purifying by column chromatography, the eluent is EtOAc: petroleum ether=1:6, to obtain pure product as yellow oily compound. The product (170 mg,0.44 mmol) was dissolved in 6mL of methanol and 3N HCl (2.6 mmol) was added dropwise with stirring and reacted for 3 hours. Saturated NaHCO 3 The reaction was quenched with aqueous solution (20 mL), extracted with ethyl acetate (3X 20 mL), the combined organic phases were washed with saturated aqueous NaCl solution (2X 20 mL), filtered and taken up in anhydrous Na 2 SO 4 And (5) drying. After concentrating the filtrate, it was separated and purified by column chromatography with EtOAc in the eluent of petroleum ether=1:5 to give an oily liquid compound in 73% yield.
EXAMPLE 9 Synthesis of (E) -1- (4-fluorophenyl) -3- (3-hydroxyphenyl) propyl-2-en-1-one
(E) -1- (4-fluorophenyl) -3- (3-hydroxyphenyl) propyl-2-en-1-one
(E)-1-(4-fluorophenyl)-3-(3-hydroxyphenyl)prop-2-en-1-one
Product(s) 1 H NMR(500MHz,CDCl 3 )δ7.78(d,J＝15.7Hz,1H),7.65–7.63(m, 2H),7.59(d,J＝7.7Hz,1H),7.55–7.53(m,1H),7.44(d,J＝15.7Hz,1H),7.42– 7.39(m,1H),7.15–7.10(m,3H). 13 C NMR(101MHz,DMSO)δ189.76,168.73, 158.54,145.16,135.48,133.52,131.59,131.48,130.03,121.14,121.03,117.69, 116.02,115.93,115.12.[M+H] + ＝243.0820.
The synthetic route is as follows:
m-hydroxybenzaldehyde (200 mg,1.64 mmol) was dissolved in 4mL of DMF, sodium hydride (78.6 mg,1.92 mmol) was added, and after stirring for 15 minutes chloromethyl methyl ether (161 mg,2 mmol) was added and the reaction stirred for 1 hour. Saturated NaHCO 3 The reaction was quenched with aqueous solution (20 mL), extracted with ethyl acetate (3X 20 mL), the combined organic phases were washed with saturated aqueous NaCl solution (2X 20 mL), filtered and taken up in anhydrous Na 2 SO 4 And (5) drying. After concentrating the filtrate, it was separated and purified by column chromatography with EtOAc as eluent, i.e. petroleum ether=1:10, to give the oily compound. To a solution of 4-fluoroacetophenone (214 mg,1.3 mmol) in absolute ethanol (5 mL) was added 10% NaOH (3 mmol) at room temperature, and after stirring for 10 min, 3- (methoxymethoxy) benzaldehyde (169 mg,1.2 mmol) was added and stirred at room temperature overnight. Ethyl acetate (3X 20 mL), the organic phases were combined and washed with saturated aqueous NaCl solution (2X 20 mL), filtered and dried over anhydrous Na 2 SO 4 And (5) drying. The filtrate was concentrated and purified by column chromatography with EtOAc as eluent, i.e. petroleum ether=1:15, to give the pure product as an oily compound. The product (284 mg,1 mmol) was dissolved in methanol and 3N HCl (3 mmol) was added dropwise with stirring and reacted for 3 hours. Saturated NaHCO 3 The reaction was quenched with aqueous solution (20 mL), extracted with ethyl acetate (3X 20 mL), the combined organic phases were washed with saturated aqueous NaCl solution (2X 20 mL), filtered and taken up in anhydrous Na 2 SO 4 And (5) drying. After concentration of the filtrate, it was purified by column chromatography with EtOAc as eluent, i.e. petroleum ether=1:10, to give the compound as a white solid. The yield thereof was found to be 73%.
EXAMPLE 10 Synthesis of (E) -1- (4-fluorophenyl) -3- (4- (trifluoromethoxy) phenyl) propyl-2-en-1-one
(E) -1- (4-fluorophenyl) -3- (4- (trifluoromethoxy) phenyl) propyl-2-en-1-one
(E)-1-(4-fluorophenyl)-3-(4-(trifluoromethoxy)phenyl)prop-2-en-1-one
Product(s) 1 H NMR(500MHz,CDCl 3 )δ7.84(d,J＝16.0Hz,1H),7.87(d,J＝7.5 Hz,2H),7.62(d,J＝7.5Hz,2H),7.43(d,J＝8.0Hz,2H),6.94(d,J＝8.2Hz,2H), 6.57(d,J＝16.0Hz,1H). 13 C NMR(101MHz,DMSO)δ189.75,168.72,149.85, 145.14,133.52,131.59,131.47,130.27,130.03,129.73,127.57,121.38,116.05, 115.89,114.23,114.05.[M+H] + ＝311.0693.
The synthetic route is as follows:
to a solution of p-fluoro acetophenone (200 mg,1.45 mmol) in absolute ethanol (5 mL) was added 10% NaOH (3.6 mmol) at room temperature, and after stirring for 10 minutes, p-trifluoromethoxybenzaldehyde (289 mg,1.52 mmol) was added and stirred at room temperature for 6 hours. EtOAc (3X 20 mL) was extracted, the organic phases combined and washed with saturated aqueous NaCl solution (2X 20 mL), filtered and dried over anhydrous Na 2 SO 4 And (5) drying. After concentrating the filtrate, separating and purifying by column chromatography, the eluent is EtOAc: petroleum ether=1:80, obtaining pure white solid with 86% yield.
EXAMPLE 11 Synthesis of (E) -1-cyclopropyl-3- (4- (trifluoromethoxy) phenyl) propyl-2-en-1-one
(E) -1-cyclopropyl-3- (4- (trifluoromethoxy) phenyl) propyl-2-en-1-one
(E)-1-cyclopropyl-3-(4-(trifluoromethoxy)phenyl)prop-2-en-1-one
Product(s) 1 H NMR(500MHz,CDCl 3 )δ7.60(d,J＝16.1Hz,1H),7.27–7.24(m, 1H),7.12–7.10(m,2H),6.95–6.93(m,1H),6.91(d,J＝16.1Hz,1H),2.30–2.23 (m,1H),1.21–1.16(m,2H),1.03–0.99(m,2H). 13 C NMR(101MHz,DMSO)δ 200.74,149.83,142.83,130.48,130.28,130.19,129.74,126.28,114.24,114.15,42.98,14.86,14.68.[M+H] + ＝257.0788.
The synthetic route is as follows:
to a solution of cyclopropylmethyl ketone (200 mg,2.4 mmol) in absolute ethanol (5 mL) was added 10% NaOH (5.9 mmol) at room temperature, and after stirring for 10 minutes, p-trifluoromethoxybenzaldehyde (470 mg,2.5 mmol) was added and the mixture was stirred at room temperature for 6 hours. EtOAc (3X 20 mL) was extracted, the organic phases combined and washed with saturated aqueous NaCl solution (2X 20 mL), filtered and dried over anhydrous Na 2 SO 4 And (5) drying. The filtrate was concentrated and purified by column chromatography with EtOAc as eluent (1:60 to 1:40) to give pure white solid in 88% yield.
EXAMPLE 12 Synthesis of (E) -1- (2-bromophenyl) -3- (4-fluorophenyl) propyl-2-en-1-one
(E) -1- (2-bromophenyl) -3- (4-fluorophenyl) propyl-2-en-1-one
(E)-1-(2-bromophenyl)-3-(4-fluorophenyl)prop-2-en-1-one
Product(s) 1 H NMR(400MHz,CDCl 3 )δ7.64(d,J＝7.8Hz,1H),7.58–7.52(m, 2H),7.44–7.37(m,3H),7.36–7.31(m,1H),7.12–7.06(m,2H),7.02(d,J＝16.1 Hz,1H). 13 C NMR(101MHz,CDCl 3 )δ194.50,165.54,163.03,145.19,141.09, 133.48,131.46,130.61,130.52,129.19,127.41,125.90,125.87,119.50,116.35,116.13.[M+H] + ＝304.9982.
The synthetic route is as follows:
to a solution of o-bromoacetophenone (200 mg,1 mmol) in absolute ethanol (5 mL) was added 10% NaOH (2.5 mmol) at room temperature, and after stirring for 10 minutes, p-fluorobenzaldehyde (131 mg,1.06 mmol) was added and stirred at room temperature overnight. EtOAc (3X 20 mL) was extracted, and the organic phases were combined and washed with saturated aqueous NaCl (2X 20 mL), filtered, and then with anhydrous Na 2 SO 4 And (5) drying. After concentrating the filtrate, separating and purifying by column chromatography, the eluent is EtOAc: petroleum ether=1:30, and the pure product is obtained as a transparent oily liquid with a yield of 82%.
EXAMPLE 13 Synthesis of (E) -1- (4-bromophenyl) -3- (4-fluorophenyl) propyl-2-en-1-one
(E) -1- (4-bromophenyl) -3- (4-fluorophenyl) propyl-2-en-1-one
(E)-1-(4-bromophenyl)-3-(4-fluorophenyl)prop-2-en-1-one
Product(s) 1 H NMR(400MHz,CDCl 3 )δ7.91–7.86(m,2H),7.78(d,J＝15.7Hz, 1H),7.68–7.61(m,4H),7.40(d,J＝15.7Hz,1H),7.17–7.08(m,2H). 13 C NMR (101MHz,CDCl 3 )δ189.17,165.46,162.95,144.10,136.85,131.98,130.98,130.51, 130.02,128.00,121.15,116.34,116.12.[M+H] + ＝304.9980.
The synthetic route is as follows:
to a solution of p-bromoacetophenone (200 mg,1 mmol) in absolute ethanol (5 mL) was added 10% NaOH (2.5 mmol) at room temperature, and after stirring for 10 minutes, p-fluorobenzaldehyde (131 mg,1.06 mmol) was added and stirred at room temperature overnight. EtOAc (3X 20 mL) was extracted, and the organic phases were combined and washed with saturated aqueous NaCl (2X 20 mL), filtered, and then with anhydrous Na 2 SO 4 And (5) drying. The filtrate was concentrated and purified by column chromatography with EtOAc in the eluent petroleum ether=1:30 to give pure white productThe solid was found to be 82% in yield.
EXAMPLE 14 Synthesis of (E) -1- (2-chlorophenyl) -3- (4-fluorophenyl) propyl-2-en-1-one
(E) -1- (2-chlorophenyl) -3- (4-fluorophenyl) propyl-2-en-1-one
(E)-1-(2-chlorophenyl)-3-(4-fluorophenyl)prop-2-en-1-one
Product(s) 1 H NMR(400MHz,CDCl 3 )δ7.59–7.54(m,2H),7.50–7.44(m,3H), 7.44–7.40(m,1H),7.39–7.34(m,1H),7.13–7.03(m,3H). 13 C NMR(101MHz, CDCl 3 )δ189.17,165.46,162.95,144.10,136.85,131.98,130.98,130.51,130.02, 128.00,121.15,116.34,116.12.[M+H] + ＝261.0488.
The synthetic route is as follows:
to a solution of o-chloroacetophenone (200 mg,1.3 mmol) in absolute ethanol (5 mL) was added 10% NaOH (3.23 mmol) at room temperature, and after stirring for 10 minutes, p-fluorobenzaldehyde (168.6 mg,1.4 mmol) was added and the mixture was stirred at room temperature overnight. EtOAc (3X 20 mL) was extracted, and the organic phases were combined and washed with saturated aqueous NaCl (2X 20 mL), filtered, and then with anhydrous Na 2 SO 4 And (5) drying. After concentrating the filtrate, it was separated and purified by column chromatography with EtOAc in petroleum ether=1:30 as eluent to give pure white solid in 83% yield.
EXAMPLE 15 Synthesis of (E) -1- (4-chlorophenyl) -3- (4-fluorophenyl) propyl-2-en-1-one
(E) Synthesis of (E) -1- (4-chlorophenyl) -3- (4-fluorophenyl) propyl-2-en-1-one
(E)-1-(4-chlorophenyl)-3-(4-fluorophenyl)prop-2-en-1-one
Product(s) 1 H NMR(400MHz,CDCl 3 )δ7.99–7.93(m,2H),7.79(d,J＝15.7Hz, 1H),7.68–7.61(m,2H),7.52–7.46(m,2H),7.41(d,J＝15.7Hz,1H),7.16–7.09 (m,2H). 13 C NMR(101MHz,CDCl 3 )δ188.55,166.97,164.44,143.55,136.59, 134.39,134.36,133.26,131.17,131.08,129.63,129.31,121.97,115.95,115.73. [M+H] + ＝261.0482.
The synthetic route is as follows:
to a solution of p-chloroacetophenone (200 mg,1.3 mmol) in absolute ethanol (5 mL) was added 10% NaOH (3.23 mmol) at room temperature, and after stirring for 10 minutes, p-fluorobenzaldehyde (168.6 mg,1.4 mmol) was added and the mixture was stirred at room temperature overnight. EtOAc (3X 20 mL) was extracted, and the organic phases were combined and washed with saturated aqueous NaCl (2X 20 mL), filtered, and then with anhydrous Na 2 SO 4 And (5) drying. After concentrating the filtrate, it was separated and purified by column chromatography with EtOAc in petroleum ether=1:30 as eluent to give pure white solid in 83% yield.
EXAMPLE 16 Synthesis of (E) -3- (4-bromophenyl) -1- (4-fluorophenyl) propyl-2-en-1-one
(E) -3- (4-bromophenyl) -1- (4-fluorophenyl) propyl-2-en-1-one
(E)-3-(4-bromophenyl)-1-(4-fluorophenyl)prop-2-en-1-one
Product(s) 1 H NMR(400MHz,CDCl 3 )δ8.09–8.01(m,2H),7.75(d,J＝15.7Hz, 1H),7.58–7.54(m,2H),7.53–7.47(m,3H),7.22–7.15(m,2H). 13 C NMR(101 MHz,CDCl 3 )δ188.53,166.98,164.44,143.61,134.37,134.34,133.69,132.27, 131.17,131.08,129.83,124.96,122.06,115.95,115.74.[M+H] + ＝304.9979.
The synthetic route is as follows:
to a solution of p-fluoro acetophenone (200 mg,1.45 mmol) in absolute ethanol (5 mL) was added 10% NaOH (3.62 mmol) at room temperature, and after stirring for 10 minutes, p-bromobenzaldehyde (281mg, 1.52 mmol) was added and stirred at room temperature overnight. EtOAc (3X 20 mL) was extracted, and the organic phases were combined and washed with saturated aqueous NaCl (2X 20 mL), filtered, and then with anhydrous Na 2 SO 4 And (5) drying. After concentrating the filtrate, separating and purifying by column chromatography, the eluent is EtOAc: petroleum ether=1:30, obtaining pure white solid with 85% yield.
EXAMPLE 17 Synthesis of (E) -3- (4-chlorophenyl) -1- (4-fluorophenyl) propyl-2-en-1-one
(E) -3- (4-chlorophenyl) -1- (4-fluorophenyl) propyl-2-en-1-one
(E)-3-(4-chlorophenyl)-1-(4-fluorophenyl)prop-2-en-1-one
Product(s) 1 H NMR(400MHz,CDCl 3 )δ8.08–8.03(m,2H),7.76(d,J＝15.7Hz, 1H),7.60–7.56(m,2H),7.48(d,J＝15.7Hz,1H),7.42–7.38(m,2H),7.22–7.15 (m,2H). 13 C NMR(101MHz,CDCl 3 )δ188.55,166.97,164.44,143.55,136.59, 134.39,134.36,133.26,131.17,131.08,129.63,129.31,121.97,115.95,115.73. [M+H] + ＝261.0482.
The synthetic route is as follows:
to a solution of p-fluoro acetophenone (200 mg,1.45 mmol) in absolute ethanol (5 mL) was added 10% NaOH (3.62 mmol) at room temperature, and after stirring for 10 minutes, p-chlorobenzaldehyde (281mg, 1.52 mmol) was added and stirred at room temperature overnight. EtOAc (3X 20 mL) was extracted, and the organic phases were combined and washed with saturated aqueous NaCl (2X 20 mL), filtered, and then with anhydrous Na 2 SO 4 And (5) drying. FilteringAfter concentration, the solution was purified by column chromatography with EtOAc in petroleum ether=1:30 as eluent to give pure white solid in 85% yield.
EXAMPLE 18 Synthesis of (E) -1, 3-bis (4-fluorophenyl) propyl-2-en-1-one
(E) -1, 3-bis (4-fluorophenyl) propyl-2-en-1-one
(E)-1,3-bis(4-fluorophenyl)prop-2-en-1-one
Product(s) 1 H NMR(400MHz,CDCl 3 )δ8.08–8.02(m,2H),7.78(d,J＝15.7Hz, 1H),7.67–7.61(m,2H),7.43(d,J＝15.6Hz,1H),7.21–7.15(m,2H),7.15–7.08 (m,2H). 13 C NMR(101MHz,CDCl 3 )δ188.60,166.92,165.39,164.39,162.88, 143.73,134.47,134.44,131.14,131.04,130.45,130.36,121.27,121.25,116.30,116.08,115.90,115.69.[M+H] + ＝245.0780.
The synthetic route is as follows:
to a solution of p-fluoro acetophenone (200 mg,1.45 mmol) in absolute ethanol (5 mL) was added 10% NaOH (3.62 mmol) at room temperature, and after stirring for 10 minutes, p-fluorobenzaldehyde (189 mg,1.52 mmol) was added and stirred at room temperature overnight. EtOAc (3X 20 mL) was extracted, and the organic phases were combined and washed with saturated aqueous NaCl (2X 20 mL), filtered, and then with anhydrous Na 2 SO 4 And (5) drying. After concentrating the filtrate, separating and purifying by column chromatography, the eluent is EtOAc: petroleum ether=1:30, obtaining pure white solid with 82% yield.
Example 19 experiment of proliferation of colon cancer cells
Colon cancer HCT-116 cells (5×10 per well) 3 ) Inoculated into 96-well plates. The culture was carried out in a medium containing the organic compounds prepared according to examples 1 to 18, respectively, for 72 hours. The medium was then removed and the wells were washed with Phosphate Buffered Saline (PBS). Will 1mu.L of 3- (4, 5-dimethylthiazole-2) -2, 5-diphenyltetrazolium bromide (MTT) was added to each well at a working concentration of 5 mg/mL. After 4 hours incubation, the medium was removed and 150 μldmso was added to each well to dissolve formazan crystals. Absorbance was measured at 490nm on a microplate reader. The median inhibitory concentration (IC 50) of the compound on tumor cells was calculated by absorbance. The positive control is tripterine, and IC is measured 50 1.86 μm.
TABLE 1 inhibition of colon cancer by Compounds described in examples 1-18
| Numbering of compounds | IC 50 (μm) | Numbering of compounds | IC 50 (μm) | Numbering of compounds | IC 50 (μm) |
| 1 | 1.83 | 7 | 0.47 | 13 | 0.23 |
| 2 | 6.32 | 8 | 0.37 | 14 | 0.14 |
| 3 | 5.48 | 9 | 0.27 | 15 | 1.54 |
| 4 | 2.1 | 10 | 1.03 | 16 | 0.83 |
| 5 | 0.72 | 11 | 0.37 | 17 | 0.12 |
| 6 | 0.49 | 12 | 1.83 | 18 | 2.43 |
The inhibitory activities of the organic compounds prepared according to examples 1 to 18 on colon cancer are shown in Table 1, and it can be seen that the organic compounds according to the present invention have a significant therapeutic effect on colon cancer in large part, and especially the organic compounds prepared according to examples 5, 6, 7, 8, 9, 10, 11, 13, 14, 15, 16 and 17 have a significantly stronger therapeutic effect than that of tripterine, and have a broad application prospect in clinical treatment of colon cancer
The above summary and the detailed description are intended to demonstrate practical applications of the technical solutions provided by the present invention, and should not be construed as limiting the scope of the present invention. Various modifications, equivalent alterations, or improvements will occur to those skilled in the art, and are within the spirit and principles of the invention. The scope of the invention is defined by the appended claims.
Claims (2)
1. A pharmaceutical composition for treating colon cancer, which is characterized by comprising an active ingredient and pharmaceutically acceptable auxiliary materials; the active ingredient is selected from (E) -1- (2-fluorophenyl) -3- (4-fluorophenyl) propyl-2-en-1-one;
(E) -3- (4-fluorophenyl) -1- (3-methoxyphenyl) propyl-2-en-1-one;
(E) -1-cyclopropyl-3- (3-hydroxyphenyl) propyl-2-en-1-one;
(E) -1-cyclopropyl-3- (3- (methoxymethoxy) phenyl) propyl-2-en-1-one;
(E) -1- (3, 5-dimethoxy-4- (methoxymethoxy) phenyl) -3- (3- (methoxymethoxy) phenyl) propyl-2-en-1-one;
(E) -1- (4-hydroxy-3, 5-dimethoxyphenyl) -3- (3-hydroxyphenyl) propyl-2-en-1-one;
(E) -one or more of 1-cyclopropyl-3- (4- (trifluoromethoxy) phenyl) propyl-2-en-1-one.
2. The application of a pharmaceutical composition in preparing medicines for treating colon cancer is characterized in that the pharmaceutical composition consists of an active ingredient and pharmaceutically acceptable auxiliary materials; the active ingredient is selected from (E) -1- (2-fluorophenyl) -3- (4-fluorophenyl) propyl-2-en-1-one;
(E) -3- (4-fluorophenyl) -1- (3-methoxyphenyl) propyl-2-en-1-one;
(E) -1- (p-tolyl) -3- (2, 4, 5-trimethoxyphenyl) propyl-2-en-1-one;
(E) -1- (3-methoxyphenyl) -3- (2, 4, 5-trimethoxyphenyl) propyl-2-en-1-one;
(E) -1-cyclopropyl-3- (3-hydroxyphenyl) propyl-2-en-1-one;
(E) -1-cyclopropyl-3- (3- (methoxymethoxy) phenyl) propyl-2-en-1-one;
(E) -1- (3, 5-dimethoxy-4- (methoxymethoxy) phenyl) -3- (3- (methoxymethoxy) phenyl) propyl-2-en-1-one;
(E) -1- (4-hydroxy-3, 5-dimethoxyphenyl) -3- (3-hydroxyphenyl) propyl-2-en-1-one;
(E) -1- (4-fluorophenyl) -3- (3-hydroxyphenyl) propyl-2-en-1-one;
(E) -1- (4-fluorophenyl) -3- (4- (trifluoromethoxy) phenyl) propyl-2-en-1-one;
(E) -1-cyclopropyl-3- (4- (trifluoromethoxy) phenyl) propyl-2-en-1-one;
(E) -1- (2-bromophenyl) -3- (4-fluorophenyl) propyl-2-en-1-one;
(E) -1- (4-bromophenyl) -3- (4-fluorophenyl) propyl-2-en-1-one;
(E) -1- (2-chlorophenyl) -3- (4-fluorophenyl) propyl-2-en-1-one;
(E) -1- (4-chlorophenyl) -3- (4-fluorophenyl) propyl-2-en-1-one;
(E) -3- (4-bromophenyl) -1- (4-fluorophenyl) propyl-2-en-1-one;
(E) -3- (4-chlorophenyl) -1- (4-fluorophenyl) propyl-2-en-1-one; or (b)
(E) -one or more of 1, 3-bis (4-fluorophenyl) propyl-2-en-1-one.
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| WO2011151789A2 (en) * | 2010-05-31 | 2011-12-08 | University Of The Free State | Aminoalkyl substituted chalcones and analogues and derivatives thereof |
| CN109467549A (en) * | 2018-12-07 | 2019-03-15 | 中国药科大学 | Quinoline replaces chalcone compounds, preparation method and the usage |
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