CN108863860B - N-substituted phenyl-3-sulfonyl aminobenzamide compound, preparation thereof and application thereof in resisting breast cancer activity - Google Patents
N-substituted phenyl-3-sulfonyl aminobenzamide compound, preparation thereof and application thereof in resisting breast cancer activity Download PDFInfo
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Abstract
The invention discloses an N-substituted phenyl-3-sulfonyl amino benzamide compound and preparation and application thereof in breast cancer resistance activity.3-sulfonamide benzoic acid is taken as a raw material, corresponding acyl chloride is prepared by refluxing with thionyl chloride, and then the prepared acyl chloride reacts with a corresponding substituted aromatic amine derivative under the ice bath condition to synthesize a Ciyan series target product; the N-substituted phenyl-3-sulfonyl aminobenzamide compound shows certain antitumor activity. According to the result of the anti-tumor activity test, the compound Ciyan 13 with the best activity shows excellent biological activity, and the biological activity is the IC of breast cancer cells MDA-MB-23150The value was 0.70. mu.M, and in addition, it had better water solubility and low cytotoxicity compared to Niclosamide, and was easier to synthesize.
Description
Technical Field
The invention relates to the technical field of medical chemistry, in particular to an N-substituted phenyl-3-sulfonyl aminobenzamide compound, a preparation method thereof and an anti-breast cancer application thereof.
Background
The Signal Transduction and Activators of Transcription (STAT) family is a class of cytoplasmic proteins capable of signal transduction and transcriptional activation that can transmit extracellular signals into the nucleus of the cell, which in turn lead to transcription of the corresponding target genes. STAT3 is one of the 7 known members of the STAT protein family, with a variety of important functions. Studies show that STAT3 is closely related to the occurrence and development of various malignant tumors, and STAT3 is abnormally activated in about 70 percent of human solid tumors and hematological tumors (such as malignant tumors including breast cancer, prostate cancer, non-small cell lung cancer, ovarian cancer, lymphoma, leukemia and the like). Studies have shown that continuously activated STAT3 promotes anti-apoptotic signals and proliferation of cancer cells, promotes tumor development, and also destroys immune system function.
In addition, studies show that when activation of STAT3 is inhibited, apoptosis of tumor cells can be promoted, and for example, overexpression of STAT3 in colon cancer cells can be inhibited and apoptosis of colon cancer cells can be promoted by using an RNA interference technology. Since activation of STAT3 can exert immunosuppressive effects, inhibition of overexpression thereof not only can block abnormal proliferation of cancer cells to exert an effect against cancer progression, but also can enhance the immunocompetence against cancer, which is more suitable as a subject for tumor therapy than other members of the STAT family. Thus, STAT3 is widely recognized as a key target in cancer therapy, and in recent years, research on antitumor drugs aiming at inhibiting STAT 3-related signaling pathways has been receiving attention.
Niclosamide (formula I) is an approved anthelmintic for FDA, has been applied for more than 50 years, and has the characteristics of high drug effect and low toxicity. Through screening of a dual fluorescein reporter gene experiment carried out on 1500 marketed drugs based on STAT 3-dependent cells, the dual fluorescein reporter gene can selectively inhibit phosphorylation of STAT3, intervene STAT3 signal pathways, inhibit proliferation of tumor cells, induce apoptosis and the like; it has no obvious inhibition effect on the activation of STAT1, STAT5 and upstream kinases JAK and Src. However, the possibility of Niclosamide becoming an antitumor drug is limited due to the disadvantages of poor water solubility, low oral availability, unsatisfactory pharmacokinetics and the like. Also, Niclosamide makes demethylation synthesis difficult due to the presence of the hydroxyl group at the 2-position.
Disclosure of Invention
The invention provides an N-substituted phenyl-3-sulfonyl aminobenzamide compound, a preparation method thereof and an application of the compound in resisting breast cancer activity.
The invention adopts the following technical scheme:
the chemical structure of the N-substituted sulfamide phenyl benzamide STAT3 small molecule inhibitor is as follows:
wherein, the structures of X and R1 are shown in the table 1-1:
tables 1 to 1: structure of Ciyan (CY) series compound
In Table 1-1, diOCH3Is dimethyl.
As a further preference, the compound is 3-sulfonylamino-N- (4-tert-butylphenyl) benzamide (Ciyan 13) having the following chemical structure:
the invention also provides a specific method for preparing the compound 3-sulfamide-N- (4-tert-butyl butylphenyl) benzamide (Ciyan 13) as follows:
(1) weighing the raw material 3-sulfamide benzoic acid (3mmol) and freshly distilled SOCl2(30mL), refluxing for 3h, cooling and standing, and concentrating and drying thionyl chloride under reduced pressure to obtain 3-sulfonamidobenzoyl chloride;
(2) 4-tert-butylalaniline (0.5mmol) was weighed and dissolved in dichloromethane (10mL), 65. mu.L of acid-binding agent DIPEA (0.5mmol) was added, and stirred in ice bath for 15min, followed by the addition of the aforementioned obtained 3-sulfonylaminobenzoyl chloride (0.75mmol) dissolved in DMA (1mL), and stirred in ice bath for 12h, and the progress of the reaction was monitored by TLC. After the reaction is ended, concentrating and drying dichloromethane under reduced pressure, adding a sodium carbonate solution with the pH value of 10, stirring for 2 hours, then carrying out suction filtration, drying the obtained product or extracting the product with ethyl acetate for three times, washing an organic layer with a saturated sodium bicarbonate solution and a saturated sodium chloride solution for three times respectively, adding anhydrous sodium sulfate to dry the organic layer, carrying out spin drying on the organic layer to prepare sand, carrying out separation and purification by column chromatography, and carrying out identification results on UPLC-MS, 1H-NMR and 13C-NMR to obtain a target compound with the melting point of 282.3-284.2 ℃ and the yield of 84.3%; (ii) a
The N-substituted phenyl-3-sulfonyl aminobenzamide compound can effectively inhibit the proliferation of STAT3 high-expression breast cancer cell MDA-MB-231.
The invention also provides an application of the N-substituted phenyl-3-sulfonyl aminobenzamide compound, wherein the N-substituted phenyl-3-sulfonyl aminobenzamide compound is used for preparing an antitumor drug;
the anti-tumor medicine is used for treating tumors.
Preferably, the antitumor drug is used for inhibiting breast cancer cells.
Compared with the prior art, the N-substituted phenyl-3-sulfonyl aminobenzamide compound shows better antitumor activity. According to the result of an anti-tumor activity test, the compound Ciyan 13 has better biological activity; its IC for breast cancer cell MDA-MB-23150The value was 0.70. mu.M, and in addition, it had better water solubility and was easier to synthesize than Niclosamide.
Detailed Description
The following examples are further detailed descriptions of the present invention.
Synthesis of the Compound of example 1
1.1A specific synthetic route for the compounds is shown below:
the formula I, compound synthesis general formula: i: SOCl2,105℃,3h；ii:DIPEA,DCM,DMA,0℃,12h；
1.2 synthetic procedure
a. Weighing corresponding raw material 3-sulfamide benzoic acid (3mmol) and freshly distilled SOCl2(30mL), refluxing for 3h, cooling and standing, and concentrating and drying thionyl chloride under reduced pressure to obtain 3-sulfonamidobenzoyl chloride;
b. the corresponding substituted aromatic amine (0.5mmol) was weighed and dissolved in dichloromethane (10mL), acid-binding agent DIPEA (0.5mmol) was added, stirring was carried out in ice bath for 15min, then the previously obtained 3-sulfonylaminobenzoyl chloride or 4-chloro-3-sulfonylaminobenzoyl chloride (0.75mmol) dissolved in 1mL DMA was added, stirring was carried out in ice bath for 12h, and the progress of the reaction was monitored by TLC. Inverse directionConcentrating and drying dichloromethane under reduced pressure after termination, adding sodium carbonate solution with pH of 10, stirring for 2h, then performing suction filtration, drying the obtained product or extracting with ethyl acetate for three times, washing the organic layer with saturated sodium bicarbonate and saturated sodium chloride solution for three times respectively, adding anhydrous sodium sulfate to dry the organic layer, performing spin drying on the organic layer to prepare sand, performing separation and purification by column chromatography to obtain Ciyan series compounds, drying and weighing, measuring melting point, calculating yield, performing UPLC-MS,1H-NMR，13C-NMR identification results;
1.3 results of the experiment
All the target compound structures synthesized are shown in the table 1-1 above; UPLC-MS of a portion of the target compound synthesized including the active compound,1H-NMR and13the physicochemical data such as C-NMR are as follows:
N-(3-methoxyphenyl)-3-sulfamoylbenzamide(CY 02)
Chemical Formula:C14H14N2O4S；Yield/％:85.7％；MP:182.8～185.0℃；Purity:96.8％；ESI-MS:307.05[M+H]+；1H-NMR(600MHz,DMSO-d6)δ(ppm):10.482(s,1H,CONH),8.377(s,1H,2-PhH),8.169(d,1H,J＝7.8Hz,6-PhH),8.020(d,1H,J＝7.8Hz,4-PhH),7.746(t,1H,J＝7.8Hz,5-PhH),7.510(s,2H,SO2NH2),7.455(t,1H,J＝1.8Hz,2’-PhH),7.380(d,1H,J＝8.4Hz,4’-PhH),7.275(t,1H,J＝8.4Hz,5’-PhH),6.715(dd,1H,J1＝8.4Hz,J2＝1.8Hz,6’-PhH),3.759(s,3H,3’-OCH3)；13C-NMR(151MHz,DMSO-d6):165.028,160.045,145.062,140.640,136.221,131.286,130.095,129.846,129.070,125.704,113.307,110.050,106.831,55.645；
3-sulfamoyl-N-(3,4,5-trimethoxyphenyl)benzamide(CY 06)
Chemical Formula:C16H18N2O6S；Yield/％:84.6％；MP:243.3～246.1℃；Purity:89.9％；ESI-MS:367.09[M+H]+；1H-NMR(600MHz,DMSO-d6)δ(ppm):10.415(s,1H,CONH),8.386(s,1H,2-PhH),8.167(d,1H,J＝7.8Hz,6-PhH),8.022(d,1H,J＝7.8Hz,4-PhH),7.749(t,1H,J＝7.8Hz,5-PhH),7.510(s,2H,SO2NH2),7.222(s,2H,2’,6’-PhH),3.775(s,6H,3’,5’-OCH3),3.644(s,3H,4’-OCH3)；13C-NMR(151MHz,DMSO-d6):164.754,153.238,145.091,136.183,135.571,134.541,131.191,129.849,129.060,125.584,98.829,60.735,56.366；
4,5-dimethoxy-2-(3-sulfamoylbenzamido)benzoic acid(CY 12)
Chemical Formula:C16H16N2O7S；Yield/％:49.6％；MP:273.3～275.2℃；Purity:98.4％；ESI-MS:381.11[M+H]+；1H-NMR(600MHz,DMSO-d6)δ(ppm):13.671(br-s,1H,COOH),12.424(s,1H,CONH),8.462(s,1H,2-PhH),8.434(s,1H,3’-PhH),8.140(d,1H,J＝7.8Hz,4-PhH),8.073(d,1H,J＝7.8Hz,6-PhH),7.813(t,1H,J＝7.8Hz,5-PhH),7.537(s,2H,SO2NH2),7.498(s,1H,6’-PhH),3.875(s,3H,4’-OCH3),3.793(s,3H,5’-OCH3)；13C-NMR(151MHz,DMSO-d6):170.521,163.774,153.875,145.589,144.618,137.134,135.754,130.598,130.482,129.635,124.971,113.444,108.723,103.989,56.244；
4,5-dimethoxy-2-(3-sulfamoylbenzamido)benzoic acid(CY 13)
Chemical Formula:C18H20N2O5S；Yield/％:84.3％；MP:282.3～284.2℃；Purity:95.6％；ESI-MS:377.24[M+H]+；1H-NMR(500MHz,DMSO-d6)δ(ppm):10.787(s,1H,CONH),8.413(s,1H,2-PhH),8.205(d,1H,J＝7.5Hz,6-PhH),8.053(d,1H,J＝7.5Hz,4-PhH),7.930(m,4H,2’,3’,5’,6’-PhH),7.766(t,1H,J＝7.5Hz,5-PhH),7.504(s,2H,SO2NH2),1.557(s,9H,C(CH3)3)；13C-NMR(125MHz,DMSO-d6):164.754,164.568,144.532,142.950,135.265,130.797,129.908,129.222,128.678,126.432,125.182,119.657,80.356,27.839；
the properties and solubility of the target compound synthesized by the present invention are as follows:
the yield of the target compound is generally higher; the color is mainly white, light yellow, yellow brown and red brown; all compounds are insoluble in petroleum ether, n-hexane and the like, can be dissolved in DCM, EA, DMSO, DMA, MeOH and EtOH, and have generally good water solubility (the hydrophobicity parameters of the lead compound Niclosamide and related active compounds are shown in the following table 2-1);
the target compound synthesized by the invention can be seen as [ M + H ] as a result of mass spectrum]+Molecular ion peak, a small part of product is visible [ M + Na]+A peak;1H-NMR spectrum results show that all compound hydrogen numbers, corresponding chemical shifts, coupling constants and the like can be consistent with theoretical values of corresponding compounds;13C-NMR spectrum results show that all compound carbon peak shifts and numbers accord with theoretical data;
EXAMPLE 2 cellular Activity of Compounds
2.1 screening of cellular Activity of Compounds by the MTT method
The experiment adopts an MTT method to detect the cell survival rate of the breast cancer cell MDA-MB-231h and the human normal mammary epithelial cell MCF-10A. Tumor cells in logarithmic growth phase (MDA-MB-231) were individually cultured in 96-well plates at a plating concentration of 6X 10 cells per well for each tumor cell line3Single cell, 5% CO thermostatted at 37 ℃2Culturing for 24h under the condition; then, 1 mu L of target compound solution with final concentration of 10 mu M or different concentration gradients (0.1-20 mu M) dissolved by DMSO is given; after 48h of administration, 20. mu.L of MTT solution dissolved in 5mg/mL PBS was added to each well and the culture was continued for 4h to form purple formazan precipitate visible to the naked eye; discard the solution from each well, add 150 μ L of DMSO to each well to dissolve formazan crystals and shake on a shaker for 10 min; finally, detecting the light absorption value of each hole with ultraviolet absorption wavelength of 490nm by a microplate reader, and calculating the corresponding cell survival rate, inhibition rate or IC50Values, etc. The experiment needs to be repeated at least three times, so that the experiment error is reduced.
2.2 results of the experiment
All the active compounds screened out were IC-tested by MTT method on STAT 3-highly activated breast cancer MDA-MB-23150The values are determined, and the corresponding experimental results are shown in the table 2-1;
table 2-1: partially active Compounds IC50(μM)
a clogP of Niclosamide under the same condition was 4.05, indicating that it was less hydrophilic.
The results show that: IC of compound Ciyan 13 on breast cancer cells MDA-MB-23150IC value of 0.70. mu.M for colon cancer cells HCT-116 and SW-48050The values are respectively 9.82 mu M and 17.12 mu M, which are 14-25 times of the result of MDA-MB-231, and the selectivity for breast cancer is better;
although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that changes, modifications, substitutions and alterations can be made in these embodiments without departing from the principles and spirit of the invention, the scope of which is defined in the appended claims and their equivalents.
Claims (5)
1. An N-substituted phenyl-3-sulfonyl aminobenzamide compound is characterized in that the compound is CY02, CY06, CY12 or CY13, and the structure of the compound is shown as the formula (I) in CY02, CY06, CY12 or CY 13;
wherein R is1And the structures of X are shown in Table 1-1:
TABLE 1-1
2. An N-substituted phenyl-3-sulfonylaminobenzamide compound according to claim 1, which is the compound 3-sulfonylamino-N- (4-tert-butylphenyl) benzamide (Ciyan 13) having the following chemical structure:
3. a process for the preparation of N-substituted phenyl-3-sulfonylaminobenzamides according to claim 2, characterized by the following specific steps:
(1) weighing raw material 3-sulfamide benzoic acid and newly distilled SOCl2Refluxing for 3h, cooling and standing, concentrating and drying thionyl chloride under reduced pressure to obtain 3-sulfonamidobenzoyl chloride;
(2) weighing 4-tert-butyl ester aniline, dissolving the 4-tert-butyl ester aniline in dichloromethane, adding 65 mu L of acid-binding agent DIPEA, stirring in ice bath for 15min, then adding the 3-sulfonamide benzoyl chloride dissolved by DMA, stirring for 12h under the ice bath condition, and monitoring the reaction process by a TLC method; after the reaction is finished, concentrating and drying dichloromethane under reduced pressure, adding a sodium carbonate solution with the pH value of 10, stirring for 2 hours, then carrying out suction filtration, drying the obtained product or extracting the obtained product three times by using ethyl acetate, respectively washing an organic layer three times by using a saturated sodium bicarbonate solution and a saturated sodium chloride solution, adding anhydrous sodium sulfate to dry the organic layer, carrying out spin drying on the organic layer to prepare sand, and carrying out separation and purification by column chromatography to obtain the target compound.
4. The application of the N-substituted phenyl-3-sulfonyl aminobenzamide compound as claimed in any one of claims 1 to 2, wherein the N-substituted phenyl-3-sulfonyl aminobenzamide compound is used for preparing an antitumor drug;
the anti-tumor medicine is used for treating tumors.
5. The use of N-substituted phenyl-3-sulfonylaminobenzamides according to claim 4, characterized in that the antitumor agent is used for inhibiting breast cancer cells.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103130696A (en) * | 2013-03-21 | 2013-06-05 | 山东大学 | Anthranilamide compound as well as preparation method and application thereof |
| CN103889953A (en) * | 2011-07-01 | 2014-06-25 | 肝炎与病毒研究所 | Sulfamoylbenzamide derivatives as antiviral agents against hbv infection |
| WO2015138377A1 (en) * | 2014-03-10 | 2015-09-17 | The University Of Chicago | Methods of treating cancer using rad51small molecule stimulators |
Family Cites Families (1)
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103889953A (en) * | 2011-07-01 | 2014-06-25 | 肝炎与病毒研究所 | Sulfamoylbenzamide derivatives as antiviral agents against hbv infection |
| CN106166157A (en) * | 2011-07-01 | 2016-11-30 | 巴鲁·S·布隆伯格研究所 | Sulfonamides heterocyclic carbamate derivatives as anti-hepatitis b virus infected antiviral agent |
| CN103130696A (en) * | 2013-03-21 | 2013-06-05 | 山东大学 | Anthranilamide compound as well as preparation method and application thereof |
| WO2015138377A1 (en) * | 2014-03-10 | 2015-09-17 | The University Of Chicago | Methods of treating cancer using rad51small molecule stimulators |
Non-Patent Citations (5)
| Title |
|---|
| "A pharmacophore-based virtual screening approach for the discovery of Trypanosoma cruzi GAPDH inhibitors";Fernando V Maluf等;《Future Med. Chem.》;20131231;第5卷;Table 2 化合物18，Figure 7 * |
| "Benzam idobenzoic acids as potent PqsD inhibitors for the treatment of Pseudomonas aeruginosa infections";Stefan Hinsberger等;《European Journal of Medicinal Chemistry》;20140211;第76卷;Supporting Information TableS1 化合物78 * |
| "STN检索记录";STN;《Registry》;20100915;第1-33页 * |
| "Structure Optimization of 2-Benzamidobenzoic Acids as PqsD Inhibitors for Pseudomonas aeruginosa Infections and Elucidation of Binding Mode by SPR, STD NMR, and Molecular Docking";Elisabeth Weidel等;《J. Med. Chem.》;20130708;第56卷;Table 1,化合物57 * |
| "Targeting the Binding Function 3 (BF3) Site of the Human Androgen Receptor through Virtual Screening.";Nathan A. Lack等;《J. Med. Chem.》;20111102;第54卷;第8563-8573页 * |
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