CN105646361A - 2,4,5-triarylimidazole compounds as well as preparation methods and application thereof - Google Patents

2,4,5-triarylimidazole compounds as well as preparation methods and application thereof Download PDF

Info

Publication number
CN105646361A
CN105646361A CN201610088955.6A CN201610088955A CN105646361A CN 105646361 A CN105646361 A CN 105646361A CN 201610088955 A CN201610088955 A CN 201610088955A CN 105646361 A CN105646361 A CN 105646361A
Authority
CN
China
Prior art keywords
substituted
acetamide
preparation
eimsm
hnmr
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN201610088955.6A
Other languages
Chinese (zh)
Other versions
CN105646361B (en
Inventor
王广成
彭知云
李涓
李欣
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Power Intellectual Property Tianjin Co ltd
Tianjin Institute of Advanced Equipment of Tsinghua University
Original Assignee
Jishou University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Jishou University filed Critical Jishou University
Priority to CN201610088955.6A priority Critical patent/CN105646361B/en
Publication of CN105646361A publication Critical patent/CN105646361A/en
Application granted granted Critical
Publication of CN105646361B publication Critical patent/CN105646361B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • 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

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Materials For Photolithography (AREA)

Abstract

The invention discloses 2,4,5-triarylimidazole compounds as well as preparation methods and an application thereof. The compounds have a structure shown as a formula (I). According to the preparation methods, substituted aniline and chloroacetyl chloride are taken as raw materials, 2-chloro-N-substituted phenylacetamide is obtained and reacts with p-hydroxybenzaldehyde, 2-(4-formylphenoxy)-N-substituted phenylacetamide is obtained and has reactions with various substituted benzil finally, and the target compounds are obtained. The compounds can be taken as raw materials of antitumor drugs, and the preparation methods have the advantages of simple and available raw materials and convenience in operation.

Description

A kind of 2,4,5-triarylimidazoles type compound and method for making thereof and purposes
Technical field
The present invention relates to a kind of 2,4,5-triarylimidazoles type compound and preparation method thereof and as Antitubulin application in preparing antitumor drug.
Background technology
At present, malignant tumor has become commonly encountered diseases and the frequently-occurring disease of a kind of serious harm human health, the whole world annual new discovery malignant tumor patient 7,600,000 example, is the second largest reason causing human death, is only second to cardiovascular and cerebrovascular disease. And the sickness rate of tumor presents the trend risen year by year, the World Health Organization's prediction will have 1,200,000 people to die from cancer in the year two thousand thirty. In 27 kinds of tumor types, maximum with the death that pulmonary carcinoma, gastric cancer, hepatocarcinoma, colon cancer and breast carcinoma cause. Due to the tumor mortality rate constantly raised, it is necessary to find that medicine novel, safe and efficient is to treat and prevent tumor. But, many antitumor drug used clinically but have many shortcomings now, and such as higher toxicity, bioavailability be relatively low and drug resistance. Therefore, in the urgent need to finding that the novel medicine with higher selective treatment tumor is to solve the problems referred to above.
Imidazole ring is a kind of 5-member heterocyclic ring containing nitrogen, is widely present in nature, and a lot of natural products and biological substance in vivo all contain glyoxaline structure. Glyoxaline compound has electronics, proton transfer performance, complex coordination performance and grips soda acid performance altogether, enjoys the good reputation of " biocatalyzer ", " bio-ligand ". Imidazole ring is the important component part of histidine in organism, histamine or even nucleic acid, may make up a series of derivant with physiologically active. And imidazole radicals is the five member ring heterocyclic compound containing two nitrogen-atoms, it is readily formed the interaction of multiple non-covalent bond, as with metallic ion coordination, hydrogen bond etc., with the imdazole derivatives that this special imidazole ring is constructed, there is the multiple physiologically actives such as anti-tumor activity, antibacterial activity, antihistamine, resisting hypertension, tranquilizing soporific. Owing to imidazole derivative has physiologically active so widely, the therefore synthesis of imdazole derivatives and study its potential new application and have become as research field very active in the last few years, develop it and there is certain theory significance and actual value.
Summary of the invention
Technical scheme is as follows:
A kind of 2,4,5-triarylimidazoles type compounds, is characterized in that they have general structure as shown in the formula (I):
(I)
Wherein: the R in formula I1��R2��R3Group is identical or differs, substituent R1��R2��R3Each independent is H, halogen atom, C1 ~ C5 alkoxyl, C1 ~ C5 alkyl, nitro, sulfonic group, alkyl amino or amino.
The present invention also provides for the method preparing one 2,4, the 5-triarylimidazoles type compound of above-mentioned formula I, and the method comprises the following steps:
Step 1: be placed in round-bottomed flask by substituted aniline, triethylamine, adds dichloromethane, then drips chloracetyl chloride, reacts 1 ~ 30h, stopped reaction, obtain the chloro-N-substituted-phenyl acetamide of 2-under room temperature condition; Described substituted aniline, triethylamine, chloracetyl chloride mol ratio be 1:(1 ~ 5): (1 ~ 5);
Step 2: chloro-for 2-N-substituted-phenyl acetamide, hydroxy benzaldehyde, Anhydrous potassium carbonate are placed in reaction bulb, add acetone solution, add potassium iodide, back flow reaction 10 ~ 30h, stopped reaction, being cooled to room temperature, filter, filtrate rotation obtains 2-(4-aldehyde radical benzene oxygen)-N-substituted-phenyl acetamide through purification by silica gel column chromatography after steaming; The chloro-N-substituted-phenyl acetamide of described 2-, hydroxy benzaldehyde, potassium carbonate, potassium iodide mol ratio be 1:(1 ~ 5): (1 ~ 5): (0.1 ~ 2);
Step 3: 2-(4-aldehyde radical benzene oxygen)-N-substituted-phenyl acetamide, replacement benzil are placed in round-bottomed flask, add glacial acetic acid to dissolve, add ammonium acetate, 80-120 DEG C of back flow reaction 5 ~ 20h, is cooled to room temperature, adds water, filter, filter cake obtains 2,4,5-triarylimidazoles type compound (I) through purification by silica gel column chromatography; Described 2-(4-aldehyde radical benzene oxygen)-N-substituted-phenyl acetamide, replace benzil, the mol ratio of ammonium acetate is 1:(1 ~ 5): (1 ~ 10).
Tubulin is had good inhibitory activity by a kind of 2,4,5-triarylimidazoles type compounds of the present invention, and the development and application for antitumor drug provides new selection.
Accompanying drawing explanation
Fig. 1 is the syntheti c route figure of a kind of 2,4,5-triarylimidazoles type compound.
Detailed description of the invention
Below example is in that to describe the present invention, and the unrestricted present invention in detail.
The preparation of embodiment one: 2-(4-(4,5-diphenyl-1H-imidazoles-2-base) phenoxy group)-N-phenyl acetamide (1)
Step 1: aniline (1.86g, 20mmol), triethylamine (3.3mL, 24mmol) are placed in round-bottomed flask, add dichloromethane (20mL), drip chloracetyl chloride (2.71g, 24mmol) again, under room temperature condition, react 20h, stopped reaction, solvent is spin-dried for, then by gained solids washed with water 3 times, then by petroleum ether 3 times, obtain white solid, productivity 90%.1HNMR(d6-DMSO,400MHz)��: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);EIMSm/z=170[M+]��
Step 2: by chloro-for 2-N-phenyl acetamide (1.69g, 10mmol), hydroxy benzaldehyde (1.34g, 11mmol), Anhydrous potassium carbonate (2.76g, 20mmol) it is placed in three-necked bottle, add 20mL anhydrous propanone to dissolve, add potassium iodide (166mg, 1mmol), back flow reaction 24h, stopped reaction, is cooled to room temperature, filters, filtrate rotation obtains yellow solid, productivity 80% through purification by silica gel column chromatography after steaming.1HNMR(d6-DMSO,400MHz)��: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);EIMSm/z=254[M+]��
Step 3: 2-(4-aldehyde radical benzene oxygen)-N-phenyl acetamide (256mg, 1mmol), benzil (210mg, 1mmol) are placed in round-bottomed flask, add appropriate glacial acetic acid to dissolve, add ammonium acetate (390mg, 5mmol), 120 DEG C of back flow reaction 10h, after reacting completely, it is cooled to room temperature, adds water, add natrium carbonicum calcinatum to solution in neutrality, filtering, filter cake obtains white solid, productivity 63% through purification by silica gel column chromatography.1HNMR(d6-DMSO,400MHz)��: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);EIMSm/z=446[M+]��
The preparation method of following example is similar with embodiment one.
The preparation of embodiment two: N-(2-chlorphenyl)-2-(4-(4,5-diphenyl-1H-imidazoles-2-base) phenoxy group) acetamide (2)
Productivity 81%.1HNMR(d6-DMSO,400MHz)��: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);EIMSm/z=480[M+]��
The preparation of embodiment three: N-(2-fluorophenyl)-2-(4-(4,5-diphenyl-1H-imidazoles-2-base) phenoxy group) acetamide (3)
Productivity 72%.1HNMR(d6-DMSO,400MHz)��: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);EIMSm/z=464[M+]��
The preparation of embodiment four: N-(2-bromophenyl)-2-(4-(4,5-diphenyl-1H-imidazoles-2-base) phenoxy group) acetamide (4)
Productivity 75%.1HNMR(d6-DMSO,400MHz)��: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);EIMSm/z=525[M+]��
The preparation of embodiment five: 2-(4-(4,5-diphenyl-1H-imidazoles-2-base) phenoxy group)-N-(2-aminomethyl phenyl) acetamide (5)
Productivity 68%.1HNMR(d6-DMSO,400MHz)��: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);EIMSm/z=460[M+]��
The preparation of embodiment six: 2-(4-(4,5-diphenyl-1H-imidazoles-2-base) phenoxy group)-N-(2-methoxyphenyl) acetamide (6)
Productivity 61%.1HNMR(d6-DMSO,400MHz)��: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);EIMSm/z=476[M+]��
The preparation of embodiment seven: 2-(4-(4,5-diphenyl-1H-imidazoles-2-base) phenoxy group)-N-(2-ethylphenyl) acetamide (7)
Productivity 90%.1HNMR(d6-DMSO,400MHz)��: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);EIMSm/z=474[M+]��
The preparation of embodiment eight: 2-(4-(4,5-diphenyl-1H-imidazoles-2-base) phenoxy group)-N-(2-ethoxyl phenenyl) acetamide (8)
Productivity 84%.1HNMR(d6-DMSO,400MHz)��: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);EIMSm/z=490[M+]��
The preparation of embodiment nine: 2-(4-(4,5-diphenyl-1H-imidazoles-2-base) phenoxy group)-N-(2-(trifluoromethyl) phenyl) acetamide (9)
Productivity 79%.1HNMR(d6-DMSO,400MHz)��: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);EIMSm/z=514[M+]��
The preparation of embodiment ten: N-(3-chlorphenyl)-2-(4-(4,5-diphenyl-1H-imidazoles-2-base) phenoxy group) acetamide (10)
Productivity 77%.1HNMR(d6-DMSO,400MHz)��: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);EIMSm/z=480[M+]��
The preparation of embodiment 11: N-(3-fluorophenyl)-2-(4-(4,5-diphenyl-1H-imidazoles-2-base) phenoxy group) acetamide (11)
Productivity 69%.1HNMR(d6-DMSO,400MHz)��: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);EIMSm/z=464[M+]��
The preparation of embodiment 12: N-(3-bromophenyl)-2-(4-(4,5-diphenyl-1H-imidazoles-2-base) phenoxy group) acetamide (12)
Productivity 65%.1HNMR(d6-DMSO,400MHz)��: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);EIMSm/z=525[M+]��
The preparation of embodiment 13: N-(4-bromophenyl)-2-(4-(4,5-diphenyl-1H-imidazoles-2-base) phenoxy group) acetamide (13)
Productivity 86%.1HNMR(d6-DMSO,400MHz)��: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);EIMSm/z=525[M+]��
The preparation of embodiment 14: N-(4-chlorphenyl)-2-(4-(4,5-diphenyl-1H-imidazoles-2-base) phenoxy group) acetamide (14)
Productivity 79%.1HNMR(d6-DMSO,400MHz)��: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);EIMSm/z=480[M+]��
The preparation of embodiment 15: N-(4-fluorophenyl)-2-(4-(4,5-diphenyl-1H-imidazoles-2-base) phenoxy group) acetamide (15)
Productivity 73%.1HNMR(d6-DMSO,400MHz)��: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);EIMSm/z=464[M+]��
Embodiment 16:: the preparation of 2-(4-(4,5-diphenyl-1H-imidazoles-2-base) phenoxy group)-N-(4-(trifluoromethyl) phenyl) acetamide (16)
Productivity 78%.1HNMR(d6-DMSO,400MHz)��: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);EIMSm/z=514[M+]��
The preparation of embodiment 17: 2-(4-(4,5-diphenyl-1H-imidazoles-2-base) phenoxy group)-N-(4-aminomethyl phenyl) acetamide (17)
Productivity 74%.1HNMR(d6-DMSO,400MHz)��: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);EIMSm/z=460[M+]��
The preparation of embodiment 18: 2-(4-(4,5-diphenyl-1H-imidazoles-2-base) phenoxy group)-N-(4-ethylphenyl) acetamide (18)
Productivity 66%.1HNMR(d6-DMSO,400MHz)��: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);EIMSm/z=474[M+]��
The preparation of embodiment 19: 2-(4-(4,5-diphenyl-1H-imidazoles-2-base) phenoxy group)-N-(4-methoxyphenyl) acetamide (19)
Productivity 61%.1HNMR(d6-DMSO,400MHz)��: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);EIMSm/z=476[M+]��
The preparation of embodiment 20: 2-(4-(4,5-diphenyl-1H-imidazoles-2-base) phenoxy group)-N-(4-ethoxyl phenenyl) acetamide (20)
Productivity 82%.1HNMR(d6-DMSO,400MHz)��: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);EIMSm/z=490[M+]��
The preparation of embodiment 21: N-(3,4-Dimethoxyphenyl)-2-(4-(4,5-diphenyl-1H-imidazoles-2-base) phenoxy group) acetamide (21)
Productivity 62%.1HNMR(d6-DMSO,400MHz)��: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);EIMSm/z=506[M+]��
The preparation of embodiment 22: N-(3,4-diethoxy phenyl)-2-(4-(4,5-diphenyl-1H-imidazoles-2-base) phenoxy group) acetamide (22)
Productivity 84%.1HNMR(d6-DMSO,400MHz)��: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);EIMSm/z=534[M+]��
The preparation of embodiment 23: N-(2,4 dichloro benzene base)-2-(4-(4,5-diphenyl-1H-imidazoles-2-base) phenoxy group) acetamide (23)
Productivity 85%.1HNMR(d6-DMSO,400MHz)��: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);EIMSm/z=515[M+]��
The preparation of embodiment 24: N-(2,4-dibromo phenyl)-2-(4-(4,5-diphenyl-1H-imidazoles-2-base) phenoxy group) acetamide (24)
Productivity 88%.1HNMR(d6-DMSO,400MHz)��: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);EIMSm/z=604[M+]��
The preparation of embodiment 25: N-(2,4 difluorobenzene base)-2-(4-(4,5-diphenyl-1H-imidazoles-2-base) phenoxy group) acetamide (25)
Productivity 86%.1HNMR(d6-DMSO,400MHz)��: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);EIMSm/z=482[M+]��
The preparation of embodiment 26: N-(3,5-Dichlorobenzene base)-2-(4-(4,5-diphenyl-1H-imidazoles-2-base) phenoxy group) acetamide (26)
Productivity 79%.1HNMR(d6-DMSO,400MHz)��: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);EIMSm/z=515[M+]��
The preparation of embodiment 27: N-(3,5-dibromo phenyl)-2-(4-(4,5-diphenyl-1H-imidazoles-2-base) phenoxy group) acetamide (27)
Productivity 70%.1HNMR(d6-DMSO,400MHz)��: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);EIMSm/z=604[M+]��
The preparation of embodiment 28: N-(the bromo-2-chlorphenyl of 4-)-2-(4-(4,5-diphenyl-1H-imidazoles-2-base) phenoxy group) acetamide (28)
Productivity 88%.1HNMR(d6-DMSO,400MHz)��: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);EIMSm/z=559[M+]��
The preparation of embodiment 29: N-(3,4-difluorophenyl)-2-(4-(4,5-diphenyl-1H-imidazoles-2-base) phenoxy group) acetamide (29)
Productivity 73%.1HNMR(d6-DMSO,400MHz)��: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);EIMSm/z=482[M+]��
The preparation of embodiment 30: 2-(4-(4,5-bis-(4-chlorphenyl)-1H-imidazoles-2-base) phenoxy group)-N-(2-chlorphenyl) acetamide (30)
Productivity 83%.1HNMR(d6-DMSO,400MHz)��: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);EIMSm/z=549[M+]��
The preparation of embodiment 31: 2-(4-(4,5-bis-(4-bromophenyl)-1H-imidazoles-2-base) phenoxy group)-N-(2-bromophenyl) acetamide (31)
Productivity 80%.1HNMR(d6-DMSO,400MHz)��: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);EIMSm/z=683[M+]��
The preparation of embodiment 32: 2-(4-(4,5-bis-(4-fluorophenyl)-1H-imidazoles-2-base) phenoxy group)-N-(2-fluorophenyl) acetamide (32)
Productivity 89%.1HNMR(d6-DMSO,400MHz)��: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);EIMSm/z=500[M+]��
The preparation of embodiment 33: 2-(4-(4,5-bis-(4-chlorphenyl)-1H-imidazoles-2-base) phenoxy group)-N-(2-aminomethyl phenyl) acetamide (33)
Productivity 68%.1HNMR(d6-DMSO,400MHz)��: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);EIMSm/z=529[M+]��
The preparation of embodiment 34: 2-(4-(4,5-bis-(4-bromophenyl)-1H-imidazoles-2-base) phenoxy group)-N-(2-aminomethyl phenyl) acetamide (34)
Productivity 62%.1HNMR(d6-DMSO,400MHz)��: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);EIMSm/z=618[M+]��
The preparation of embodiment 35: 2-(4-(4,5-bis-(4-fluorophenyl)-1H-imidazoles-2-base) phenoxy group)-N-(2-aminomethyl phenyl) acetamide (35)
Productivity 61%.1HNMR(d6-DMSO,400MHz)��: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);EIMSm/z=496[M+]��
The preparation of embodiment 36: 2-(4-(4,5-bis-(4-aminomethyl phenyl)-1H-imidazoles-2-base) phenoxy group)-N-(2-aminomethyl phenyl) acetamide (36)
Productivity 69%.1HNMR(d6-DMSO,400MHz)��: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);EIMSm/z=488[M+]��
The preparation of embodiment 37: 2-(4-(4,5-bis-(4-methoxyphenyl)-1H-imidazoles-2-base) phenoxy group)-N-(2-aminomethyl phenyl) acetamide (37)
Productivity 67%.1HNMR(d6-DMSO,400MHz)��: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);EIMSm/z=520[M+]��
The preparation of embodiment 38: 2-(4-(4,5-bis-(4-methoxyphenyl)-1H-imidazoles-2-base) phenoxy group)-N-(2-methoxyphenyl) acetamide (38)
Productivity 72%.1HNMR(d6-DMSO,400MHz)��: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);EIMSm/z=536[M+]��
The preparation of embodiment 39: 2-(4-(4,5-bis-(4-ethoxyl phenenyl)-1H-imidazoles-2-base) phenoxy group)-N-(2-ethoxyl phenenyl) acetamide (39)
Productivity 76%.1HNMR(d6-DMSO,400MHz)��: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);EIMSm/z=578[M+]��
The preparation of embodiment 40: 2-(4-(4,5-bis-(4-chloro phenyl)-1H-imidazoles-2-base) phenoxy group)-N-(2-methoxyphenyl) acetamide (38)
Productivity 72%.1HNMR(d6-DMSO,400MHz)��: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);EIMSm/z=545[M+]��
Embodiment 41: the antiproliferative activity test of the compound on tumor cell that embodiment prepares:
This assay activity measures and adopts 96 orifice plates to carry out, and by tumor cell inoculation in 96 orifice plates, cultivates 24h, sucking culture medium, add candidate compound, blank group adds isopyknic solvent, cultivating 24h ~ 48h, suck culture medium, every hole adds 200 �� L0.5mg/mLMTT solution, cultivate 4h, suck supernatant, add 150 �� LDMSO, concussion mixing, detect absorbance by microplate reader (wavelength is 570nm), process data. Each experiment all repeats 3 times, measures each compound median lethal concentration ��M (IC in different tumor cells50).
The computational methods of suppression ratio:
Suppression ratio (%)=(matched group OD value-test group OD value)/matched group OD value �� 100%
Sample to the height of the antiproliferative activity of tumor cell activity with IC50Represent, IC50More little, the activity of this compound is more high, and result is in Table 1.
The 1. 1 kinds of 2,4,5-triarylimidazoles type compounds of the table antiproliferative activity test result (IC to 5 kinds of tumor cells50)
The kinds of tumor cells of test is all had the activity of good Inhibit proliferaton by major part 2,4,5-triarylimidazoles type compounds as can be seen from Table 1, and wherein compound 1,7,10,18,20,24,26,31,39 activity is better.
Above-mentioned simply presently preferred embodiments of the present invention, not does any pro forma restriction to the present invention. Any those of ordinary skill in the art, when without departing from technical solution of the present invention scope, may utilize the technology contents of the disclosure above and technical solution of the present invention are made many possible variations and modification, or be revised as the Equivalent embodiments of equivalent variations. Therefore, every content without departing from technical solution of the present invention, according to the technology of the present invention essence to any simple modification made for any of the above embodiments, equivalent variations and modification, all should drop in the scope of technical solution of the present invention protection.

Claims (3)

1. a triarylimidazoles type compound, it is characterised in that: this compound has structure as shown in the formula (I):
(I)
Wherein: the R in formula I1��R2��R3Group is identical or differs, substituent R1��R2��R3Each independent is H, halogen atom, C1 ~ C5 alkoxyl, C1 ~ C5 alkyl, nitro, sulfonic group, alkyl amino or amino.
2. the preparation method of a triarylimidazoles type compound, it is characterised in that include following step:
Step 1: be placed in round-bottomed flask by substituted aniline, triethylamine, adds dichloromethane, then drips chloracetyl chloride, reacts 1 ~ 30h, stopped reaction, obtain the chloro-N-substituted-phenyl acetamide of 2-under room temperature condition; Described substituted aniline, triethylamine, chloracetyl chloride mol ratio be 1:(1 ~ 5): (1 ~ 5);
Step 2: chloro-for 2-N-substituted-phenyl acetamide, hydroxy benzaldehyde, Anhydrous potassium carbonate are placed in reaction bulb, add acetone solution, add potassium iodide, back flow reaction 10 ~ 30h, stopped reaction, being cooled to room temperature, filter, filtrate rotation obtains 2-(4-aldehyde radical benzene oxygen)-N-substituted-phenyl acetamide through purification by silica gel column chromatography after steaming; The chloro-N-substituted-phenyl acetamide of described 2-, hydroxy benzaldehyde, potassium carbonate, potassium iodide mol ratio be 1:(1 ~ 5): (1 ~ 5): (0.1 ~ 2);
Step 3: 2-(4-aldehyde radical benzene oxygen)-N-substituted-phenyl acetamide, replacement benzil are placed in round-bottomed flask, add glacial acetic acid to dissolve, add ammonium acetate, 80-120 DEG C of back flow reaction 5 ~ 20h, is cooled to room temperature, adds water, filter, filter cake obtains 2,4,5-triarylimidazoles type compound (I) through purification by silica gel column chromatography; Described 2-(4-aldehyde radical benzene oxygen)-N-substituted-phenyl acetamide, replace benzil, the mol ratio of ammonium acetate is 1:(1 ~ 5): (1 ~ 10).
3. the application in preparing antitumor drug of the class 2,4,5-triarylimidazoles type compound described in claim 1.
CN201610088955.6A 2016-02-17 2016-02-17 A kind of 2,4,5 triarylimidazoles type compounds and its preparation method and purposes Active CN105646361B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201610088955.6A CN105646361B (en) 2016-02-17 2016-02-17 A kind of 2,4,5 triarylimidazoles type compounds and its preparation method and purposes

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201610088955.6A CN105646361B (en) 2016-02-17 2016-02-17 A kind of 2,4,5 triarylimidazoles type compounds and its preparation method and purposes

Publications (2)

Publication Number Publication Date
CN105646361A true CN105646361A (en) 2016-06-08
CN105646361B CN105646361B (en) 2017-12-01

Family

ID=56489530

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201610088955.6A Active CN105646361B (en) 2016-02-17 2016-02-17 A kind of 2,4,5 triarylimidazoles type compounds and its preparation method and purposes

Country Status (1)

Country Link
CN (1) CN105646361B (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111892510A (en) * 2020-06-17 2020-11-06 青岛农业大学 N- (2-bromo-4-fluorophenyl) -2- (2-chloro-4-fluorophenoxy) acetamide and application thereof

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101939005A (en) * 2007-12-14 2011-01-05 诺瓦提斯公司 Kinesin inhibitors as cancer therapeutics
CN102260260A (en) * 2010-05-24 2011-11-30 中国科学院上海药物研究所 8-phenyl xanthine compound, preparation method, medicine composition including the compound and purpose thereof
CN103467385A (en) * 2006-05-08 2013-12-25 阿里亚德医药股份有限公司 Monocyclic heteroaryl compounds
WO2015096982A1 (en) * 2013-12-23 2015-07-02 Bayer Pharma Aktiengesellschaft Antibody drug conjugates (adcs) with kinesin spindel protein (ksp)

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103467385A (en) * 2006-05-08 2013-12-25 阿里亚德医药股份有限公司 Monocyclic heteroaryl compounds
CN101939005A (en) * 2007-12-14 2011-01-05 诺瓦提斯公司 Kinesin inhibitors as cancer therapeutics
CN102260260A (en) * 2010-05-24 2011-11-30 中国科学院上海药物研究所 8-phenyl xanthine compound, preparation method, medicine composition including the compound and purpose thereof
WO2015096982A1 (en) * 2013-12-23 2015-07-02 Bayer Pharma Aktiengesellschaft Antibody drug conjugates (adcs) with kinesin spindel protein (ksp)

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
于晨.: "咪唑类衍生物设计合成及生物活性研究", 《中国优秀硕士学位论文全文数据库·医药卫生科技辑》 *
蔡佳利,等.: "咪唑类抗癌药物研究进展", 《中国新药杂志》 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111892510A (en) * 2020-06-17 2020-11-06 青岛农业大学 N- (2-bromo-4-fluorophenyl) -2- (2-chloro-4-fluorophenoxy) acetamide and application thereof
CN111892510B (en) * 2020-06-17 2023-06-16 青岛农业大学 N- (2-bromo-4-fluorophenyl) -2- (2-chloro-4-fluorophenoxy) acetamide and use thereof

Also Published As

Publication number Publication date
CN105646361B (en) 2017-12-01

Similar Documents

Publication Publication Date Title
CN101906076B (en) Naphthaline amide derivative serving as protein kinase inhibitor and histone deacetylase inhibitor and preparation method and application thereof
CN106831730B (en) A kind of substituted diaminopyrimidines and its preparing the purposes in anti-malignant tumor medicine
CN104292170B (en) There is quinazoline-Arylurea derivatives and the application thereof of antitumor action
EP2915806B1 (en) Quinoline compound and use thereof
CN102417479A (en) STAT3 small molecular selective inhibitor and preparation method and application thereof
CN104610166A (en) Pyrimidine benzyl hydroxamic acid histone deacetylase inhibitor, and preparation method and application thereof
CN104829608A (en) Coumarin-thiazole-indolone compounds, and preparation method and application thereof
CN109734674B (en) Aniline WDR5 protein-protein interaction inhibitor and preparation method and application thereof
CN101503402A (en) 2-aniline pyrimidine derivative, as well as preparation and uses thereof
CN105646361A (en) 2,4,5-triarylimidazole compounds as well as preparation methods and application thereof
CN102775381A (en) Substituted hydrazide compound, and its preparation method, medicinal compositions and application
CN102942529A (en) 4-(4-substituted piperazine)-5,6,7-trialkoxy quinazoline type compound as well as preparation method and application of 4-(4-substituted piperazine)-5,6,7-trialkoxy quinazoline type compound
CN105384697A (en) 2-subsituted quinazoline preparation method
CN108341831A (en) 7H- [1,2,4] triazole [3,4-b] [1,3,4] thiadiazine-phenylhydrazone type compound
CN105481778A (en) Pyrimidine derivative, preparation method and applications thereof
CN115105503A (en) TRPV1 antagonistic/COX inhibition double-target-point drug or pharmaceutically acceptable salt thereof, pharmaceutical preparation and application
CN103121991A (en) Aryl carboxylic acid imatinib derivative as well as preparation and application thereof
CN105399686A (en) Pyrimidine derivative, preparation method and applications thereof
CN106008458A (en) Azobenzene compound and preparation method thereof
CN107311933A (en) One class benzimidizole derivatives, and its production and use
CN110105286B (en) Substituted heterocyclic compound containing urea skeleton and preparation method and application thereof
CN108440440B (en) Naphthalene ring-containing 1,2, 4-oxadiazole-cinnamoyl piperazine compound and preparation method and application thereof
CN108395428B (en) Benzothiazole-triazole-isatin type compound and synthesis and application thereof
CN103450091A (en) Imidazole derivatives, preparation method and applications thereof
CN105732476B (en) A kind of carbazole isatin type compound and its preparation method and purposes

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant
TR01 Transfer of patent right
TR01 Transfer of patent right

Effective date of registration: 20191114

Address after: Room 302, No. 8319, Yanshan Road, Bengbu City, Anhui Province

Patentee after: Bengbu Lichao Information Technology Co.,Ltd.

Address before: 416000 Hunan, Xiangxi Tujia and Miao Autonomous Prefecture, Jishou City People's road, No. 120

Patentee before: Jishou University

TR01 Transfer of patent right
TR01 Transfer of patent right

Effective date of registration: 20220111

Address after: 300304 building 4, Huiguyuan, Dongli District, Tianjin

Patentee after: TIANJIN INSTITUTE OF ADVANCED EQUIPMENT, TSINGHUA University

Address before: 300300 No. 2002, building 4, block B, No. 6, Huafeng Road, Huaming high tech Industrial Zone, Dongli District, Tianjin

Patentee before: Power intellectual property (Tianjin) Co.,Ltd.

Effective date of registration: 20220111

Address after: 300300 No. 2002, building 4, block B, No. 6, Huafeng Road, Huaming high tech Industrial Zone, Dongli District, Tianjin

Patentee after: Power intellectual property (Tianjin) Co.,Ltd.

Address before: 8319 Yanshan Road, Bengbu City, Anhui Province

Patentee before: Bengbu Lichao Information Technology Co.,Ltd.