CN105646361B - A kind of 2,4,5 triarylimidazoles type compounds and its preparation method and purposes - Google Patents

A kind of 2,4,5 triarylimidazoles type compounds and its preparation method and purposes Download PDF

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CN105646361B
CN105646361B CN201610088955.6A CN201610088955A CN105646361B CN 105646361 B CN105646361 B CN 105646361B CN 201610088955 A CN201610088955 A CN 201610088955A CN 105646361 B CN105646361 B CN 105646361B
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triarylimidazoles
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CN105646361A (en
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王广成
彭知云
李涓
李欣
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Power Intellectual Property Tianjin Co ltd
Tianjin Institute of Advanced Equipment of Tsinghua University
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Jishou University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine

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Abstract

The invention discloses a kind of 2,4,5 triarylimidazoles type compounds and its preparation method and purposes.The compound has such as formula（I）Shown structure, preparation method is to obtain 2 chlorine N substituted-phenyl acetamides as raw material using substituted aniline and chloracetyl chloride, react to obtain 2 (4 aldehyde radical benzene oxygen) N substituted-phenyl acetamides with parahydroxyben-zaldehyde again, finally react to obtain target compound with various substitution benzils.The compound can be as the raw material of antineoplastic, and preparation method raw material is simple and easy to get, easy to operate.（I）.

Description

A kind of 2,4,5- triarylimidazoles type compound and its preparation method and purposes
Technical field
Suppress the present invention relates to a kind of 2,4,5- triarylimidazoles type compound and preparation method thereof and as tubulin Application of the agent in antineoplastic is prepared.
Background technology
At present, malignant tumour has turned into a kind of common disease and frequently-occurring disease for seriously endangering human health, and the whole world is new every year It was found that malignant tumor patient 7,600,000, is the second largest reason for causing human death, is only second to cardiovascular and cerebrovascular disease.And swell The trend risen year by year, the World Health Organization is presented in the incidence of disease of knurl（WHO）Prediction will have 1,200,000 people to die from cancer in 2030 Disease.In 27 kinds of tumor types, with dead most caused by lung cancer, stomach cancer, liver cancer, colon cancer and breast cancer.Due to constantly rising High tumor mortality rate is, it is necessary to find new, safe and efficient medicine to treat and prevent tumour.However, present many clinics On the antineoplastic that uses but have many shortcomings, for example higher toxicity, bioavilability be relatively low and drug resistance.Therefore, There is an urgent need to find the new medicine with the treatment tumour compared with high selectivity to solve the above problems.
Imidazole ring is a kind of 5-member heterocyclic ring containing nitrogen, is widely present in nature, thing in many natural products and organism Matter all contains glyoxaline structure.Glyoxaline compound has electronics, proton transfer performance, complex coordination performance and grips acid-base property altogether Can, enjoy " biocatalyst ", the good reputation of " bio-ligand ".Imidazole ring is the weight of histidine in organism, histamine or even nucleic acid Part is wanted, may make up a series of derivatives with physiologically active.And imidazole radicals is five yuan containing two nitrogen-atoms miscellaneous Cycle compound, it is easy to form the interaction of a variety of non-covalent bonds, such as with metallic ion coordination, hydrogen bond, with this special The imdazole derivatives that imidazole ring is constructed have antitumor activity, antibacterial activity, antihistamine, anti-hypertension, tranquilizing soporific etc. a variety of Physiologically active.Because imidazole derivative has such extensive physiologically active, therefore the synthesis of imdazole derivatives and study it Potential new application has become research field very active in the last few years, and developing it has certain theory significance and reality Value.
The content of the invention
Technical scheme is as follows：
One kind 2,4,5- triarylimidazoles type compounds, it is characterized in that they have such as formula（I）Shown general structure：
（I）
Wherein：R in formula I1、R2、R3Group is identical or differs, substituent R1、R2、R3Each independent is H, halogen Atom, C1 ~ C5 alkoxies, C1 ~ C5 alkyl, nitro, sulfonic group, alkyl amino or amino.
The present invention also provides the method for the triarylimidazoles type compound of one kind 2,4,5- for preparing above-mentioned formula I, this method Comprise the following steps：
Step 1：Substituted aniline, triethylamine are placed in round-bottomed flask, add dichloromethane, then chloracetyl chloride is added dropwise, room 1 ~ 30 h is reacted under the conditions of temperature, stops reaction, obtains the chloro- N- substituted-phenyls acetamides of 2-；Described substituted aniline, triethylamine, chlorine The mol ratio of chloroacetic chloride is 1:（1~5）:（1~5）；
Step 2：The chloro- N- substituted-phenyls acetamides of 2-, parahydroxyben-zaldehyde, Anhydrous potassium carbonate are placed in reaction bulb, added Enter acetone solution, add KI, the h of back flow reaction 10 ~ 30, stop reaction, be cooled to room temperature, filter, passed through after filtrate revolving Silica gel column chromatography purifies to obtain 2- (4- aldehyde radical benzene oxygen)-N- substituted-phenyl acetamides；The chloro- N- substituted-phenyls acetamides of described 2-, Parahydroxyben-zaldehyde, potassium carbonate, the mol ratio of KI are 1:（1~5）:（1~5）:（0.1~2）；
Step 3：2- (4- aldehyde radical benzene oxygen)-N- substituted-phenyls acetamide, substitution benzil are placed in round-bottomed flask, added Glacial acetic acid dissolves, and adds ammonium acetate, the 80-120 DEG C of h of back flow reaction 5 ~ 20, is cooled to room temperature, adds water, filtering, filter cake warp Silica gel column chromatography purifies to obtain 2,4,5- triarylimidazoles type compounds（I）；Described 2- (4- aldehyde radical benzene oxygen)-N- substituted-phenyl second Acid amides, substitution benzil, the mol ratio of ammonium acetate are 1:（1~5）:（1~10）.
Of the present invention a kind of 2,4,5- triarylimidazoles type compounds have preferable inhibitory activity to tubulin, New selection is provided for the development and application of antineoplastic.
Brief description of the drawings
Fig. 1 is a kind of syntheti c route figure of 2,4,5- triarylimidazoles type compound.
Embodiment
Following embodiment is to describe the present invention in detail, is not intended to limit the present invention.
Embodiment one：2- (4- (4,5- diphenyl -1H- imidazoles -2- bases) phenoxy group)-N- phenyl acetamides（1）Preparation
Step 1：By aniline（1.86g 20mmol）, triethylamine（3.3mL, 24mmol）It is placed in round-bottomed flask, adds two Chloromethanes（20mL）, then chloracetyl chloride is added dropwise（2.71g 24mmol）, 20h is reacted under room temperature condition, stops reaction, solvent is revolved It is dry, then gained solid is washed with water 3 times, then with petroleum ether 3 times, obtain white solid, yield 90%.1H NMR (d6- DMSO, 400 MHz) δ: 4.23 (s, 2H), 7.16-7.21 (m, 1H), 7.30-7.37 (m, 2H), 7.45- 7.60 (m, 2H) , 8.24 (s, 1H); EIMS m/z = 170 [M+]。
Step 2：By the chloro- N- phenyl acetamides of 2-（1.69g 10mmol）, parahydroxyben-zaldehyde（1.34g 11mmol）, it is anhydrous Potassium carbonate（2.76g 20mmol）It is placed in three-necked bottle, adds the dissolving of 20 mL anhydrous propanones, add KI（166mg, 1mmol）, back flow reaction 24h, stop reaction, be cooled to room temperature, filter, yellow is purified to obtain through silica gel column chromatography after filtrate revolving Solid, yield 80%.1H NMR (d6-DMSO, 400 MHz) δ: 4.71 (s, 2H), 7.09-7.18 (m, 2H), 7.13-7.19 (m, 1H), 7.28-7.38 (m, 2H), 7.59 (d, 2H) , 7.86-7.96 (m, 2H), 8.17 (s, 1H), 9.94 (s, 1H); EIMS m/z = 254 [M+]。
Step 3：By 2- (4- aldehyde radical benzene oxygen)-N- phenyl acetamides（256mg, 1mmol）, benzil（210mg, 1mmol）Put In round-bottomed flask, appropriate glacial acetic acid dissolving is added, adds ammonium acetate（390mg, 5mmol）, 120 DEG C of back flow reaction 10h, instead After answering completely, room temperature is cooled to, adds water, it is pure through silica gel column chromatography in neutral, filtering, filter cake to solution to add natrium carbonicum calcinatum Change to obtain white solid, yield 63%.1H NMR (d6-DMSO, 400 MHz) δ: 4.77 (s, 2H), 7.05 (d, 2H), 7.21-7.40 (m, 3H), 7.45-7.63 (m, 10H), 7.67-7.78 (m, 2H), 7.82 (d, 2H), 10.14 (s, 1H) , 10.55 (s, 1H); EIMS m/z = 446 [M+]。
The preparation method of following examples is similar with embodiment one.
Embodiment two：N- (2- chlorphenyls) -2- (4- (4,5- diphenyl -1H- imidazoles -2- bases) phenoxy group) acetamide（2） Preparation
Yield 81%.1H NMR (d6-DMSO, 400 MHz) δ: 4.77 (s, 2H), 7.08 (d, 2H), 7.15- 7.35 (m, 2H), 7.40-7.54 (m, 4H), 7.55-7.65 (m, 2H), 7.67-7.76 (m, 4H), 7.78- 7.87 (m, 2H), 7.89 (d, 2H), 10.20 (s, 1H) , 10.52 (s, 1H); EIMS m/z = 480 [M+]。
Embodiment three：N- (2- fluorophenyls) -2- (4- (4,5- diphenyl -1H- imidazoles -2- bases) phenoxy group) acetamide（3） Preparation
Yield 72%.1H NMR (d6-DMSO, 400 MHz) δ: 4.74 (s, 2H), 6.90-7.02 (m, 1H), 7.05 (d, 2H), 7.19-7.25 (m, 2H), 7.32-7.42 (m, 4H), 7.45-7.56 (m, 2H), 7.60- 7.79 (m, 4H), 7.81-7.92 (m, 1H), 7.95 (d, 2H), 10.25 (s, 1H) , 10.54 (s, 1H); EIMS m/z = 464 [M+]。
Example IV：N- (2- bromophenyls) -2- (4- (4,5- diphenyl -1H- imidazoles -2- bases) phenoxy group) acetamide（4） Preparation
Yield 75%.1H NMR (d6-DMSO, 400 MHz) δ: 4.75 (s, 2H), 6.82-7.03 (m, 1H), 7.06 (d, 2H), 7.25-7.35 (m, 2H), 7.38-7.47 (m, 4H), 7.48-7.58 (m, 2H), 7.60- 7.72 (m, 4H), 7.80-7.91(m, 1H), 7.99 (d, 2H), 10.16 (s, 1H) , 10.61 (s, 1H); EIMS m/z = 525 [M+]。
Embodiment five：2- (4- (4,5- diphenyl -1H- imidazoles -2- bases) phenoxy group)-N- (2- aminomethyl phenyls) acetamide （5）Preparation
Yield 68%.1H NMR (d6-DMSO, 400 MHz) δ: 2.25 (s, 3H), 4.72 (s, 2H), 6.90- 7.06 (m, 1H), 7.09 (d, 2H), 7.21-7.30 (m, 2H), 7.32-7.41 (m, 4H), 7.43-7.54 (m, 2H), 7.56-7.69 (m, 4H), 7.81-7.92 (m, 1H), 7.95 (d, 2H), 10.19 (s, 1H) , 10.65 (s, 1H); EIMS m/z = 460 [M+]。
Embodiment six：2- (4- (4,5- diphenyl -1H- imidazoles -2- bases) phenoxy group)-N- (2- methoxyphenyls) acetamide （6）Preparation
Yield 61%.1H NMR (d6-DMSO, 400 MHz) δ: 3.85 (s, 3H), 4.76 (s, 2H), 6.93- 7.04 (m, 1H), 7.07 (d, 2H), 7.22-7.34 (m, 2H), 7.36-7.45 (m, 4H), 7.47-7.58 (m, 2H), 7.60-7.72 (m, 4H), 7.75-7.85 (m, 1H), 7.91 (d, 2H), 10.14 (s, 1H) , 10.60 (s, 1H); EIMS m/z = 476 [M+]。
Embodiment seven：2- (4- (4,5- diphenyl -1H- imidazoles -2- bases) phenoxy group)-N- (2- ethylphenyls) acetamide （7）Preparation
Yield 90%.1H NMR (d6-DMSO, 400 MHz) δ: 1.28 (t, 3H), 2.65 (q, 2H), 4.74 (s, 2H), 6.88-7.05 (m, 1H), 7.08 (d, 2H), 7.23-7.31 (m, 2H), 7.33-7.41 (m, 4H), 7.43-7.52 (m, 2H), 7.54-7.67 (m, 4H), 7.83-7.92 (m, 1H), 7.96 (d, 2H), 10.13 (s, 1H) , 10.60 (s, 1H); EIMS m/z = 474 [M+]。
Embodiment eight：2- (4- (4,5- diphenyl -1H- imidazoles -2- bases) phenoxy group)-N- (2- ethoxyl phenenyls) acetamide （8）Preparation
Yield 84%.1H NMR (d6-DMSO, 400 MHz) δ: 1.35 (t, 3H), 4.11 (q, 2H), 4.78 (s, 2H), 6.92-7.06 (m, 1H), 7.09 (d, 2H), 7.21-7.32 (m, 2H), 7.35-7.46 (m, 4H), 7.48-7.59 (m, 2H), 7.61-7.76 (m, 4H), 7.84-7.93 (m, 1H), 7.97 (d, 2H), 10.16 (s, 1H) , 10.63 (s, 1H); EIMS m/z = 490 [M+]。
Embodiment nine：2- (4- (4,5- diphenyl -1H- imidazoles -2- bases) phenoxy group)-N- (2- (trifluoromethyl) phenyl) second Acid amides（9）Preparation
Yield 79%.1H NMR (d6-DMSO, 400 MHz) δ: 4.71 (s, 2H), 6.85-7.00 (m, 1H), 7.04 (d, 2H), 7.15-7.22 (m, 2H), 7.30-7.41 (m, 4H), 7.46-7.58 (m, 2H), 7.60- 7.78 (m, 4H), 7.83-7.94 (m, 1H), 7.96 (d, 2H), 10.35 (s, 1H) , 10.64 (s, 1H); EIMS m/z = 514 [M+]。
Embodiment ten：N- (3- chlorphenyls) -2- (4- (4,5- diphenyl -1H- imidazoles -2- bases) phenoxy group) acetamide（10） Preparation
Yield 77%.1H NMR (d6-DMSO, 400 MHz) δ: 4.77 (s, 2H), 7.08 (d, 2H), 7.22- 7.38 (m, 3H), 7.43-7.52 (m, 4H), 7.54-7.64 (m, 2H), 7.67-7.78 (m, 4H), 7.80- 7.89 (m, 1H), 7.91 (d, 2H), 10.25 (s, 1H) , 10.48 (s, 1H); EIMS m/z = 480 [M+]。
Embodiment 11：N- (3- fluorophenyls) -2- (4- (4,5- diphenyl -1H- imidazoles -2- bases) phenoxy group) acetamide （11）Preparation
Yield 69%.1H NMR (d6-DMSO, 400 MHz) δ: 4.72 (s, 2H), 6.92-7.12 (m, 1H), 7.15 (d, 2H), 7.30-7.45 (m, 2H), 7.47-7.58 (m, 4H), 7.59-7.68 (m, 2H), 7.70- 7.82 (m, 4H), 7.84-7.96 (m, 1H), 7.98 (d, 2H), 10.25 (s, 1H) , 10.48 (s, 1H); EIMS m/z = 464 [M+]。
Embodiment 12：N- (3- bromophenyls) -2- (4- (4,5- diphenyl -1H- imidazoles -2- bases) phenoxy group) acetamide （12）Preparation
Yield 65%.1H NMR (d6-DMSO, 400 MHz) δ: 4.73 (s, 2H), 7.08 (d, 2H), 7.20- 7.35 (m, 3H), 7.40-7.51 (m, 4H), 7.52-7.65 (m, 2H), 7.67-7.79 (m, 4H), 7.82- 7.93 (m, 1H), 7.95 (m, 2H), 10.29 (s, 1H) , 10.43 (s, 1H); EIMS m/z = 525 [M+]。
Embodiment 13：N- (4- bromophenyls) -2- (4- (4,5- diphenyl -1H- imidazoles -2- bases) phenoxy group) acetamide （13）Preparation
Yield 86%.1H NMR (d6-DMSO, 400 MHz) δ: 4.72 (s, 2H), 7.06 (d, 2H), 7.42- 7.52 (m, 4H), 7.56 (d, 2H), 7.58-7.67 (m, 2H), 7.70 (d, 2H), 7.73-7.86 (m, 4H), 7.93 (d, 2H), 10.26 (s, 1H) , 10.47 (s, 1H); EIMS m/z = 525 [M+]。
Embodiment 14：N- (4- chlorphenyls) -2- (4- (4,5- diphenyl -1H- imidazoles -2- bases) phenoxy group) acetamide （14）Preparation
Yield 79%.1H NMR (d6-DMSO, 400 MHz) δ: 4.78 (s, 2H), 7.05 (d, 2H), 7.39 (d, 2H), 7.45-7.56 (m, 4H), 7.59-7.68 (m, 2H), 7.72 (d, 2H), 7.76-7.88 (m, 4H), 7.97 (d, 2H), 10.29 (s, 1H) , 10.44 (s, 1H); EIMS m/z = 480 [M+]。
Embodiment 15：N- (4- fluorophenyls) -2- (4- (4,5- diphenyl -1H- imidazoles -2- bases) phenoxy group) acetamide （15）Preparation
Yield 73%.1H NMR (d6-DMSO, 400 MHz) δ: 4.73 (s, 2H), 7.04 (d, 2H), 7.22- 7.31 (m, 2H), 7.42-7.54 (m, 4H), 7.57-7.69 (m, 2H), 7.71 (d, 2H), 7.76-7.88 (m, 4H), 7.96 (d, 2H), 10.26 (s, 1H) , 10.47 (s, 1H); EIMS m/z = 464 [M+]。
Embodiment 16：：2- (4- (4,5- diphenyl -1H- imidazoles -2- bases) phenoxy group)-N- (4- (trifluoromethyl) benzene Base) acetamide（16）Preparation
Yield 78%.1H NMR (d6-DMSO, 400 MHz) δ: 4.72 (s, 2H), 7.07 (d, 2H), 7.42- 7.57 (m, 4H), 7.61-7.69 (m, 2H), 7.71-7.84 (m, 4H), 7.86 (d, 2H), 7.92 (d, 2H), 8.13 (d, 2H), 10.23 (s, 1H) , 10.54 (s, 1H); EIMS m/z = 514 [M+]。
Embodiment 17：2- (4- (4,5- diphenyl -1H- imidazoles -2- bases) phenoxy group)-N- (4- aminomethyl phenyls) acetamide （17）Preparation
Yield 74%.1H NMR (d6-DMSO, 400 MHz) δ: 2.25 (s, 3H), 4.75 (s, 2H), 7.09 (d, 2H), 7.23 (d, 2H), 7.40-7.55 (m, 4H), 7.59 (d, 2H), 7.61-7.70 (m, 2H), 7.72-7.87 (m, 4H), 7.94 (d, 2H), 10.28 (s, 1H) , 10.50 (s, 1H); EIMS m/z = 460 [M+]。
Embodiment 18：2- (4- (4,5- diphenyl -1H- imidazoles -2- bases) phenoxy group)-N- (4- ethylphenyls) acetamide （18）Preparation
Yield 66%.1H NMR (d6-DMSO, 400 MHz) δ: 1.32 (t, 3H), 2.62 (q, 2H), 4.79 (s, 2H), 7.11 (d, 2H), 7.28 (d, 2H), 7.42-7.57 (m, 4H), 7.60 (d, 2H), 7.63- 7.70 (m, 2H), 7.74-7.88 (m, 4H), 7.99 (d, 2H), 10.22 (s, 1H) , 10.48 (s, 1H); EIMS m/z = 474 [M+]。
Embodiment 19：2- (4- (4,5- diphenyl -1H- imidazoles -2- bases) phenoxy group)-N- (4- methoxyphenyls) acetyl Amine（19）Preparation
Yield 61%.1H NMR (d6-DMSO, 400 MHz) δ: 3.85 (s, 3H), 4.68 (s, 2H), 7.01 (d, 2H), 7.11 (d, 2H), 7.36-7.52 (m, 4H), 7.55 (d, 2H), 7.57-7.65 (m, 2H), 7.69-7.80 (m, 4H), 7.86 (d, 2H), 10.38 (s, 1H) , 10.44 (s, 1H); EIMS m/z = 476 [M+]。
Embodiment 20：2- (4- (4,5- diphenyl -1H- imidazoles -2- bases) phenoxy group)-N- (4- ethoxyl phenenyls) acetyl Amine（20）Preparation
Yield 82%.1H NMR (d6-DMSO, 400 MHz) δ: 1.39 (t, 3H), 4.18 (q, 2H), 4.65 (s, 2H), 6.99 (d, 2H), 7.16 (d, 2H), 7.33-7.48 (m, 4H), 7.53 (d, 2H), 7.54- 7.64 (m, 2H), 7.66-7.83 (m, 4H), 7.85 (d, 2H), 10.35 (s, 1H) , 10.48 (s, 1H); EIMS m/z = 490 [M+]。
Embodiment 21：N- (3,4- Dimethoxyphenyls) -2- (4- (4,5- diphenyl -1H- imidazoles -2- bases) benzene oxygen Base) acetamide（21）Preparation
Yield 62%.1H NMR (d6-DMSO, 400 MHz) δ: 3.72 (s, 6H), 4.82 (s, 2H), 6.91 (d, 1H), 7.01 (d, 2H), 7.15 (d, 1H), 7.34-7.46 (m, 5H), 7.55-7.67 (m, 2H), 7.69-7.82 (m, 4H), 7.88 (d, 2H), 10.22 (s, 1H) , 10.40 (s, 1H); EIMS m/z = 506 [M+]。
Embodiment 22：N- (3,4- diethoxies phenyl) -2- (4- (4,5- diphenyl -1H- imidazoles -2- bases) benzene oxygen Base) acetamide（22）Preparation
Yield 84%.1H NMR (d6-DMSO, 400 MHz) δ: 1.33 (t, 6H), 2.65 (q, 4H), 4.83 (s, 2H), 6.90 (d, 1H), 7.03 (d, 2H), 7.17 (d, 1H), 7.35-7.48 (m, 5H), 7.52- 7.63 (m, 2H), 7.65-7.77 (m, 4H), 7.82 (d, 2H), 10.25 (s, 1H) , 10.42 (s, 1H); EIMS m/z = 534 [M+]。
Embodiment 23：N- (2,4 dichloro benzene base) -2- (4- (4,5- diphenyl -1H- imidazoles -2- bases) phenoxy group) second Acid amides（23）Preparation
Yield 85%.1H NMR (d6-DMSO, 400 MHz) δ: 4.94 (s, 2H), 7.11 (d, 2H), 7.17- 7.28 (m, 1H), 7.42-7.53 (m, 5H), 7.59-7.68 (m, 2H), 7.76-7.87 (m, 4H), 7.89 (d, 1H), 7.97 (d, 2H), 10.29 (s, 1H) , 10.44 (s, 1H); EIMS m/z = 515 [M+]。
Embodiment 24：N- (2,4- dibromo phenyls) -2- (4- (4,5- diphenyl -1H- imidazoles -2- bases) phenoxy group) second Acid amides（24）Preparation
Yield 88%.1H NMR (d6-DMSO, 400 MHz) δ: 4.90 (s, 2H), 7.13 (d, 2H), 7.40- 7.52 (m, 5H), 7.56-7.68 (m, 3H), 7.72-7.80 (m, 5H), 7.95 (d, 2H), 10.20 (s, 1H) , 10.43 (s, 1H); EIMS m/z = 604 [M+]。
Embodiment 25：N- (2,4 difluorobenzene base) -2- (4- (4,5- diphenyl -1H- imidazoles -2- bases) phenoxy group) second Acid amides（25）Preparation
Yield 86%.1H NMR (d6-DMSO, 400 MHz) δ: 4.85 (s, 2H), 6.70-6.95 (m,2H), 7.15 (d, 2H), 7.36-7.47 (m, 4H), 7.50-7.62 (m, 2H), 7.69-7.79 (m, 5H), 7.88 (d, 2H), 10.27 (s, 1H) , 10.53 (s, 1H); EIMS m/z = 482 [M+]。
Embodiment 26：N- (3,5- dichlorophenyls) -2- (4- (4,5- diphenyl -1H- imidazoles -2- bases) phenoxy group) second Acid amides（26）Preparation
Yield 79%.1H NMR (d6-DMSO, 400 MHz) δ: 4.86 (s, 2H), 7.01 (d, 2H), 7.42 (s, 1H), 7.41-7.53 (m, 4H), 7.56-7.67 (m, 2H), 7.74 (d, 2H), 7.78-7.89 (m, 4H), 7.93 (d, 2H), 10.22 (s, 1H) , 10.51 (s, 1H); EIMS m/z = 515 [M+]。
Embodiment 27：N- (3,5- dibromo phenyls) -2- (4- (4,5- diphenyl -1H- imidazoles -2- bases) phenoxy group) second Acid amides（27）Preparation
Yield 70%.1H NMR (d6-DMSO, 400 MHz) δ: 4.83 (s, 2H), 7.04 (d, 2H), 7.40- 7.51 (m, 4H), 7.54-7.66 (m, 2H), 7.70-7.88 (m, 7H), 7.90 (d, 2H), 10.18 (s, 1H) , 10.50 (s, 1H); EIMS m/z = 604 [M+]。
Embodiment 28：N- (the bromo- 2- chlorphenyls of 4-) -2- (4- (4,5- diphenyl -1H- imidazoles -2- bases) phenoxy group) Acetamide（28）Preparation
Yield 88%.1H NMR (d6-DMSO, 400 MHz) δ: 4.86 (s, 2H), 7.10 (d, 2H), 7.36- 7.50 (m, 5H), 7.53-7.69 (m, 3H), 7.71-7.85 (m, 5H), 7.93 (d, 2H), 10.21 (s, 1H) , 10.45 (s, 1H); EIMS m/z = 559 [M+]。
Embodiment 29：N- (3,4- difluorophenyls) -2- (4- (4,5- diphenyl -1H- imidazoles -2- bases) phenoxy group) second Acid amides（29）Preparation
Yield 73%.1H NMR (d6-DMSO, 400 MHz) δ: 4.82 (s, 2H), 7.00 (d, 2H), 7.39 (d, 1H), 7.43-7.55 (m, 4H), 7.57-7.69 (m, 3H), 7.73 (d, 1H), 7.75-7.86 (m, 4H), 7.92 (d, 2H), 10.23 (s, 1H) , 10.49 (s, 1H); EIMS m/z = 482 [M+]。
Embodiment 30：2- (4- (4,5- bis- (4- chlorphenyls) -1H- imidazoles -2- bases) phenoxy group)-N- (2- chlorphenyls) second Acid amides（30）Preparation
Yield 83%.1H NMR (d6-DMSO, 400 MHz) δ: 4.72 (s, 2H), 7.05 (d, 2H), 7.16- 7.25 (m, 2H), 7.50-7.65 (m, 4H), 7.73 (d, 2H), 7.75-7.86 (m, 2H), 7.88-7.98 (m, 4H), 10.22 (s, 1H) , 10.53 (s, 1H); EIMS m/z = 549 [M+]。
Embodiment 31：2- (4- (4,5- bis- (4- bromophenyls) -1H- imidazoles -2- bases) phenoxy group)-N- (2- bromophenyls) Acetamide（31）Preparation
Yield 80%.1H NMR (d6-DMSO, 400 MHz) δ: 4.81 (s, 2H), 7.09 (d, 2H), 7.18- 7.29 (m, 2H), 7.50-7.69 (m, 4H), 7.72 (d, 2H), 7.75-7.86 (m, 6H), 10.28 (s, 1H) , 10.56 (s, 1H); EIMS m/z = 683 [M+]。
Embodiment 32：2- (4- (4,5- bis- (4- fluorophenyls) -1H- imidazoles -2- bases) phenoxy group)-N- (2- fluorophenyls) Acetamide（32）Preparation
Yield 89%.1H NMR (d6-DMSO, 400 MHz) δ: 4.83 (s, 2H), 7.11 (d, 2H), 7.13- 7.24 (m, 2H), 7.30-7.42 (m, 4H), 7.63 (d, 2H), 7.70-7.82 (m, 2H), 7.84-7.98 (m, 4H), 10.27 (s, 1H) , 10.47 (s, 1H); EIMS m/z = 500 [M+]。
Embodiment 33：2- (4- (4,5- bis- (4- chlorphenyls) -1H- imidazoles -2- bases) phenoxy group)-N- (2- methylbenzenes Base) acetamide（33）Preparation
Yield 68%.1H NMR (d6-DMSO, 400 MHz) δ: 2.26 (s, 3H), 4.82 (s, 2H), 6.91- 7.07 (m, 1H), 7.12 (d, 2H), 7.23-7.34 (m, 2H), 7.52-7.69 (m, 4H), 7.81-7.91 (m, 5H), 7.93 (d, 2H), 10.18 (s, 1H) , 10.60 (s, 1H); EIMS m/z = 529 [M+]。
Embodiment 34：2- (4- (4,5- bis- (4- bromophenyls) -1H- imidazoles -2- bases) phenoxy group)-N- (2- methylbenzenes Base) acetamide（34）Preparation
Yield 62%.1H NMR (d6-DMSO, 400 MHz) δ: 2.28 (s, 3H), 4.89 (s, 2H), 6.92- 7.05 (m, 1H), 7.13 (d, 2H), 7.23-7.35 (m, 3H), 7.52-7.69 (m, 4H), 7.75-7.88 (m, 4H), 7.90 (d, 2H), 10.25 (s, 1H) , 10.64 (s, 1H); EIMS m/z = 618 [M+]。
Embodiment 35：2- (4- (4,5- bis- (4- fluorophenyls) -1H- imidazoles -2- bases) phenoxy group)-N- (2- methylbenzenes Base) acetamide（35）Preparation
Yield 61%.1H NMR (d6-DMSO, 400 MHz) δ: 2.18 (s, 3H), 4.84 (s, 2H), 6.95- 7.09 (m, 1H), 7.15 (d, 2H), 7.22-7.39 (m, 7H), 7.80-7.93 (m, 4H), 7.95 (d, 2H), 10.27 (s, 1H) , 10.60 (s, 1H); EIMS m/z = 496 [M+]。
Embodiment 36：2- (4- (4,5- bis- (4- aminomethyl phenyls) -1H- imidazoles -2- bases) phenoxy group)-N- (2- methyl Phenyl) acetamide（36）Preparation
Yield 69%.1H NMR (d6-DMSO, 400 MHz) δ: 2.15 (s, 3H), 2.35 (s, 6H), 4.84 (s, 2H), 6.91-7.09 (m, 1H), 7.15 (d, 2H), 7.23-7.39 (m, 7H), 7.62-7.78 (m, 4H), 7.86 (d, 2H), 10.23 (s, 1H) , 10.55 (s, 1H); EIMS m/z = 488 [M+]。
Embodiment 37：2- (4- (4,5- bis- (4- methoxyphenyls) -1H- imidazoles -2- bases) phenoxy group)-N- (2- first Base phenyl) acetamide（37）Preparation
Yield 67%.1H NMR (d6-DMSO, 400 MHz) δ: 2.15 (s, 3H), 2.85 (s, 6H), 4.74 (s, 2H), 6.93-7.14 (m, 5H), 7.18 (d, 2H), 7.22-7.39 (m, 3H), 7.52-7.68 (m, 4H), 7.77 (d, 2H), 10.28 (s, 1H) , 10.57 (s, 1H); EIMS m/z = 520 [M+]。
Embodiment 38：2- (4- (4,5- bis- (4- methoxyphenyls) -1H- imidazoles -2- bases) phenoxy group)-N- (2- first Phenyl) acetamide（38）Preparation
Yield 72%.1H NMR (d6-DMSO, 400 MHz) δ: 3.88 (s, 9H), 4.72 (s, 2H), 6.91- 7.13 (m, 7H), 7.16 (d, 2H), 7.45-7.58 (m, 4H), 7.75-7.88 (m, 1H), 7.95 (d, 2H), 10.17 (s, 1H) , 10.43 (s, 1H); EIMS m/z = 536 [M+]。
Embodiment 39：2- (4- (4,5- bis- (4- ethoxyl phenenyls) -1H- imidazoles -2- bases) phenoxy group)-N- (2- second Phenyl) acetamide（39）Preparation
Yield 76%.1H NMR (d6-DMSO, 400 MHz) δ: 1.38 (t, 9H), 4.12 (q, 6H), 4.84 (s, 2H), 6.89-7.05 (m, 7H), 7.17 (d, 2H), 7.48-7.59 (m, 4H), 7.77-7.89 (m, 1H), 7.90 (d, 2H), 10.19 (s, 1H) , 10.40 (s, 1H); EIMS m/z = 578 [M+]。
Example IV ten：2- (4- ((4- chloros the phenyl) -1H- imidazoles -2- of 4,5- bis- bases) phenoxy group)-N- (2- methoxyl groups Phenyl) acetamide（38）Preparation
Yield 72%.1H NMR (d6-DMSO, 400 MHz) δ: 3.85 (s, 3H), 4.81 (s, 2H), 6.90- 7.10 (m, 3H), 7.13 (d, 2H), 7.42-7.57 (m, 4H), 7.80-7.96 (m, 5H), 7.96 (d, 2H), 10.15 (s, 1H) , 10.48 (s, 1H); EIMS m/z = 545 [M+]。
Example IV 11：The antiproliferative activity test for the compound on tumor cell that embodiment is prepared：
This assay activity measure is carried out using 96 orifice plates, by tumor cell inoculation in 96 orifice plates, is cultivated 24 h, is sucked training Base is supported, adds candidate compound, blank control group adds isometric solvent, cultivates 24 h ~ 48h, sucks culture medium, per hole The mg/mL MTT solution of 200 μ L 0.5 is added, cultivates 4h, sucks supernatant, adds 150 μ L DMSO, concussion mixes, with enzyme mark Instrument（Wavelength is 570nm）Detect absorbance, processing data.Each experiment is repeated 3 times, and it is swollen in difference to measure each compound LC50 μM in oncocyte（IC50）.
The computational methods of inhibiting rate：
Inhibiting rate（%）=（Control group OD values-test group OD values）/ control group OD value × 100%
Sample is to the height of the antiproliferative activity activity of tumour cell with IC50To represent, IC50It is smaller, the work of this compound Property is higher, the results are shown in Table 1.
A kind of antiproliferative activity test result of the 2,4,5- triarylimidazoles type compound of table 1. to 5 kinds of tumour cells （IC50）
Most of 2,4,5- triarylimidazoles type compound all has to the kinds of tumor cells of test as can be seen from Table 1 The activity of preferable Inhibit proliferaton, the wherein activity of compound 1,7,10,18,20,24,26,31,39 are preferably.
Above-mentioned simply presently preferred embodiments of the present invention, not makees any formal limitation to the present invention.It is any to be familiar with sheet The technical staff in field, in the case where not departing from technical solution of the present invention scope, all using the technology contents of the disclosure above Many possible changes and modifications are made to technical solution of the present invention, or are revised as the equivalent embodiment of equivalent variations.Therefore, it is all It is the content without departing from technical solution of the present invention, any is simply repaiied to made for any of the above embodiments according to the technology of the present invention essence Change, equivalent variations and modification, all should fall in the range of technical solution of the present invention protection.

Claims (3)

1. one kind 2,4,5- triarylimidazoles type compounds, it is characterised in that：The compound has such as formula（I）Shown structure：
（I）
Wherein：R in formula I1、R2、R3Group is identical or differs, substituent R1、R2、R3Each independent is H, halogen original Son, C1 ~ C5 alkoxies, C1 ~ C5 alkyl, nitro, sulfonic group or amino.
2. the preparation method of 2,4,5- triarylimidazoles type compounds described in a kind of claim 1, it is characterised in that including following Several steps：
Step 1：Substituted aniline, triethylamine are placed in round-bottomed flask, add dichloromethane, then chloracetyl chloride is added dropwise, room temperature bar 1 ~ 30 h is reacted under part, stops reaction, obtains the chloro- N- substituted-phenyls acetamides of 2-；Described substituted aniline, triethylamine, chloracetyl The mol ratio of chlorine is 1：1~5：1~5；
Step 2：The chloro- N- substituted-phenyls acetamides of 2-, parahydroxyben-zaldehyde, Anhydrous potassium carbonate are placed in reaction bulb, add third Ketone dissolves, and adds KI, the h of back flow reaction 10 ~ 30, stops reaction, be cooled to room temperature, filters, through silica gel after filtrate revolving Column chromatography purifies to obtain 2- (4- aldehyde radical benzene oxygen)-N- substituted-phenyl acetamides；The chloro- N- substituted-phenyls acetamides of described 2-, to hydroxyl Benzaldehyde, potassium carbonate, the mol ratio of KI are 1：1~5：1~5：0.1~2；
Step 3：2- (4- aldehyde radical benzene oxygen)-N- substituted-phenyls acetamide, substitution benzil are placed in round-bottomed flask, add ice second Acid dissolving, ammonium acetate is added, the 80-120 DEG C of h of back flow reaction 5 ~ 20, is cooled to room temperature, add water, filtering, filter cake is through silica gel Column chromatography purifies to obtain 2,4,5- triarylimidazoles type compounds（I）；Described 2- (4- aldehyde radical benzene oxygen)-N- substituted-phenyl acetyl Amine, substitution benzil, the mol ratio of ammonium acetate are 1：1~5：1~10.
3. application of the 2,4,5- triarylimidazoles type compounds in antineoplastic is prepared described in claim 1.
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