CN111393416B - Preparation method and application of pyrazole compound containing 1-methylpyridine-3- (4-chlorphenyl) pyrazole unit - Google Patents
Preparation method and application of pyrazole compound containing 1-methylpyridine-3- (4-chlorphenyl) pyrazole unit Download PDFInfo
- Publication number
- CN111393416B CN111393416B CN202010369362.3A CN202010369362A CN111393416B CN 111393416 B CN111393416 B CN 111393416B CN 202010369362 A CN202010369362 A CN 202010369362A CN 111393416 B CN111393416 B CN 111393416B
- Authority
- CN
- China
- Prior art keywords
- pyrazole
- methylpyridine
- chlorphenyl
- compound containing
- preparation
- 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.)
- Active
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Abstract
The invention relates to a preparation method and application of a pyrazole compound (I) containing a 1-methylpyridine-3- (4-chlorphenyl) pyrazole unit. Obtained by reacting 1-methylpyridine-3- (4-chlorphenyl) -4-chloropyrazole-5-methyl chloride with a pyrazole oxime compound. The pyrazole compound containing the 1-methylpyridine-3- (4-chlorphenyl) pyrazole unit has a good inhibition effect on tumor cells SGC-7901, and can be used for preparing anti-tumor cell medicines.
Description
Technical Field
The invention relates to the field of medicines, in particular to a preparation method and application of a pyrazole compound containing 1-methylpyridine-3- (4-chlorphenyl) pyrazole units.
Background
In recent years, malignant tumors seriously threaten human health, and the incidence rate of cancers is also on the rise. Therefore, the search and discovery of effective anticancer drugs and therapeutic methods are the hot areas of research in the medical community.
Substituted pyrazole groups are important heterocycles, substituted pyrazole derivatives have wide application in the field of pharmaceutical industry, and in recent years, some pyrazole derivatives are reported to show excellent inhibitory effect on tumor cells, such as analgesic antipyrine and the like.
Therefore, in order to further search for a drug which is found to have a good antitumor effect from the pyrazole compound, it is reasonable to link the 1-methylpyridine-3- (4-chlorophenyl) pyrazole unit to the pyrazole skeleton. The invention discloses a pyrazole compound containing 1-methylpyridine-3- (4-chlorphenyl) pyrazole unit with medicinal value.
Disclosure of Invention
The invention aims to provide a pyrazole compound containing 1-methylpyridine-3- (4-chlorphenyl) pyrazole units, which has good prevention and treatment effects on tumor cells.
Another object of the present invention is to provide a process for the preparation of the above compounds.
The invention also aims to provide the application of the compound in preparing anti-tumor cell medicines.
In order to solve the technical problems, the invention provides a pyrazole compound containing 1-methylpyridine-3- (4-chlorphenyl) pyrazole unit, which has a structure shown in a general formula I,
preferably, the pyrazole compound containing 1-methylpyridine-3- (4-chlorophenyl) pyrazole units has the following structure:
the present invention provides a process for producing the above-mentioned pyrazole compound containing a 1-methylpyridine-3- (4-chlorophenyl) pyrazole unit, which comprises the following reaction steps:
dissolving the intermediate II and the intermediate III in a certain amount of organic solvent, adding a proper amount of acid binding agent, reacting for a period of time, evaporating the solvent, separating the obtained crude product by silica gel column chromatography to obtain a target compound,
preferably, a process for the preparation of pyrazole compounds containing 1-methylpyridine-3- (4-chlorophenyl) pyrazole units, comprising the following reaction steps:
of these, intermediate II was synthesized by the method of the reference (j.agric.food chem.2008,56,10805), and intermediate III was synthesized by the method of the reference (chi.j.org.chem.2015, 35,2617).
The compound of the general formula I shows good inhibitory activity on human gastric cancer cells SGC-7901.
The pyrazole compound containing the 1-methylpyridine-3- (4-chlorphenyl) pyrazole unit disclosed by the invention has good inhibitory activity on human gastric cancer cells SGC-7901, and therefore, can be used for preparing anti-tumor cell medicines.
Detailed Description
To facilitate a further understanding of the invention, the following examples are provided to illustrate it in more detail. These examples are provided for illustrative purposes only and are not intended to limit the scope or the principles of the invention.
Example 1:
5mmol of intermediate IIa, 8mmol of intermediate III and 35mL of acetonitrile were added to a reaction flask at room temperature, 20mmol of pyridine was added thereto, and the reaction mixture was heated under reflux for 20 hours. Stopping the reaction, concentrating the reaction solution to dryness, and purifying the obtained crude product by silica gel column chromatography to obtain a compound Ia; 1 H NMR(400MHz,CDCl 3 ):δ8.26(d,J＝2.0Hz,1H,Py-H),7.83(d,J＝8.8Hz,2H,Ar-H),7.62(s,1H,CH＝N),7.38～7.45(m,3H,Py-H and Ar-H),7.19(d,J＝7.6Hz,1H,Py-H),6.82(s,4H,Ar-H),5.34(s,2H,CH 2 ),5.01(s,2H,CH 2 ),3.75(s,3H,OCH 3 ),3.59(s,3H,N-CH 3 ),2.32(s,3H,CH 3 ).
example 2:
in a reaction flask, 8mmol of intermediate IIb, 7mmol of intermediate III and 30mL of acetone were added at room temperature, 20mmol of potassium carbonate was then added thereto, and the reaction solution was further stirred at room temperature for 16 hours. Stopping the reaction, concentrating the reaction solution to dryness, and purifying the obtained crude product by silica gel column chromatography to obtain a compound Ib; 1 H NMR(400MHz,CDCl 3 ):δ8.25(d,J＝2.0Hz,1H,Py-H),7.84(d,J＝8.4Hz,2H,Ar-H),7.61(s,1H,CH＝N),7.39～7.47(m,5H,Py-H and Ar-H),7.21(d,J＝8.4Hz,1H,Py-H),6.77(d,J＝8.8Hz,2H,Ar-H),5.33(s,2H,CH 2 ),5.00(s,2H,CH 2 ),3.58(s,3H,N-CH 3 ),2.32(s,3H,CH 3 ).
example 3:
10mmol of intermediate IIc, 15mmol of intermediate III and 30mL of DMF were added to a reaction flask at room temperature, 15mmol of cesium carbonate was added thereto, and the reaction solution was heated to 85 ℃ for reaction for 13 hours. Stopping the reaction, concentrating the reaction solution to dryness, and purifying the obtained crude product by silica gel column chromatography to obtain a compound Ic; 1 H NMR(400MHz,CDCl 3 ):δ8.25(d,J＝2.4Hz,1H,Py-H),7.84(d,J＝8.8Hz,2H,Ar-H),7.62(s,1H,CH＝N),7.39～7.48(m,3H,Py-H and Ar-H),7.22(d,J＝8.0Hz,1H,Py-H),6.90～6.95(m,1H,Ar-H),6.74～6.77(m,2H,Ar-H),5.36(s,2H,CH 2 ),4.99(s,2H,CH 2 ),3.64(s,3H,N-CH 3 ),2.30(s,3H,CH 3 ).
example 4:
screening of samples for Activity against tumor cells
The in vitro anti-tumor activity of the compound on human gastric cancer cells SGC-7901 is tested by adopting a tetramethylazole blue colorimetric Method (MTT). Preparing 1 × 10 from human gastric cancer cell SGC-7901 in exponential growth phase 4 Cell suspension of individual cells/mL, seeded in 96-well plates at 37 ℃ with 5% CO 2 The culture was carried out in an incubator for 24 hours. Compound test solution (10. mu.L) was added to the test wells in 5 parallel wells per concentration and equal amount of DMSO was used as a blank in 5% CO 2 After culturing for 72 hours in an incubator, removing supernatant, adding 20 μ L of MTT (2mg/mL in PBS) to each well, after culturing for 4 hours, removing the culture medium by aspiration, adding 150 μ L of dimethyl sulfoxide to each well, dissolving the formed bluish purple precipitate by shaking for 10 minutes in a vibrator, measuring OD value by using an enzyme-labeling instrument at 490nm wavelength, and calculating the cell inhibition rate. The cell inhibition rate (negative control OD value-test substance OD value)/negative control OD value × 100%.
TABLE 1 tumor cell inhibition (%), Compounds Ia-Ic
The antitumor activity data (table 1) show that the compounds Ia-Ic have better inhibition effect on human gastric cancer cell SGC-7901, and the inhibition rates of the compounds Ia-Ic on human gastric cancer cell SGC-7901 at the tested concentration of 40 mu mol/L are 82.6%, 83.8% and 86.9% respectively. The experimental data show that the target formed by combining the 1-methylpyridine-3- (4-chlorphenyl) pyrazole unit and the pyrazole skeleton has a good inhibition effect on human gastric cancer cells SGC-7901.
The foregoing shows and describes the general principles, essential features, and advantages of the invention. It will be understood by those skilled in the art that the present invention is not limited by the foregoing examples, which are provided to illustrate the principles of the invention, and that various changes and modifications may be made without departing from the spirit and scope of the invention, which is also intended to be covered by the appended claims. The scope of the invention is defined by the appended claims and equivalents thereof.
Claims (3)
1. A pyrazole compound containing a 1-methylpyridine-3- (4-chlorophenyl) pyrazole unit, characterized by having the following structure:
2. a process for the preparation of a pyrazole compound containing 1-methylpyridine-3- (4-chlorophenyl) pyrazole units according to claim 1, characterized by the following steps:
3. use of a pyrazole compound containing a 1-methylpyridine-3- (4-chlorophenyl) pyrazole unit according to claim 1 for the preparation of a medicament for combating tumor cells, wherein: the pyrazole compound containing 1-methylpyridine-3- (4-chlorophenyl) pyrazole units according to claim 1, having inhibitory effect on tumor cells SGC-7901.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010369362.3A CN111393416B (en) | 2020-05-05 | 2020-05-05 | Preparation method and application of pyrazole compound containing 1-methylpyridine-3- (4-chlorphenyl) pyrazole unit |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010369362.3A CN111393416B (en) | 2020-05-05 | 2020-05-05 | Preparation method and application of pyrazole compound containing 1-methylpyridine-3- (4-chlorphenyl) pyrazole unit |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN111393416A CN111393416A (en) | 2020-07-10 |
| CN111393416B true CN111393416B (en) | 2022-08-12 |
Family
ID=71425607
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010369362.3A Active CN111393416B (en) | 2020-05-05 | 2020-05-05 | Preparation method and application of pyrazole compound containing 1-methylpyridine-3- (4-chlorphenyl) pyrazole unit |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111393416B (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105712932A (en) * | 2016-03-08 | 2016-06-29 | 南通大学 | Preparation and application of pyrazole oxime ether compound with 1-methyl-3-aryl-4-chloropyrazole structure |
| CN110105334A (en) * | 2019-04-30 | 2019-08-09 | 南通大学 | The preparation and application of pyrazol oxime ether derivatives containing 1- (3- chloropyridine -2- base) -3- trifluoromethyl pyrazol structure |
| CN110804040A (en) * | 2019-11-25 | 2020-02-18 | 南通大学 | Preparation method and application of pyrazole oxime compound containing difluoromethyl pyrazole bipyridyl |
-
2020
- 2020-05-05 CN CN202010369362.3A patent/CN111393416B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105712932A (en) * | 2016-03-08 | 2016-06-29 | 南通大学 | Preparation and application of pyrazole oxime ether compound with 1-methyl-3-aryl-4-chloropyrazole structure |
| CN110105334A (en) * | 2019-04-30 | 2019-08-09 | 南通大学 | The preparation and application of pyrazol oxime ether derivatives containing 1- (3- chloropyridine -2- base) -3- trifluoromethyl pyrazol structure |
| CN110804040A (en) * | 2019-11-25 | 2020-02-18 | 南通大学 | Preparation method and application of pyrazole oxime compound containing difluoromethyl pyrazole bipyridyl |
Non-Patent Citations (1)
| Title |
|---|
| Design, Synthesis, and Biological Evaluation of Novel Thiazolyl Substituted Bis-pyrazole Oxime Derivatives with Potent Antitumor Activities by Selectively Inducing Apoptosis and ROS in Cancer Cells;Biao Xiong等;《Medicinal Chemistry》;20191231;第15卷(第7期);第743-754页，尤其是第746页table1，第745页Scheme 1 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN111393416A (en) | 2020-07-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| TWI585088B (en) | Imidazo[1,2-b]pyridazine analogues as kinase inhibitors | |
| JPH01168689A (en) | K-252 derivative | |
| JP7420403B2 (en) | Compounds used as kinase inhibitors and their applications | |
| CN110105356B (en) | Azaindole compound and preparation method and application thereof | |
| CN111393416B (en) | Preparation method and application of pyrazole compound containing 1-methylpyridine-3- (4-chlorphenyl) pyrazole unit | |
| CN109516926B (en) | Preparation and application of piperlonguminine derivative | |
| CN111961048B (en) | Trifluoromethyl pyrazole amide containing substituted beta-carboline structure and preparation method and application thereof | |
| CN116096372A (en) | EGFR inhibitor, preparation method and pharmaceutical application thereof | |
| CN111440163B (en) | Pyrazole compound containing methoxy-substituted 1,3, 4-thiadiazole unit, and preparation and application thereof | |
| CN108358858B (en) | Deuterium labeled 1-substituted phenyl-4-substituted aniline methyl-1, 2, 3-triazole derivative and preparation method and application thereof | |
| CN111518084B (en) | Pyrazole derivative containing pyrimidine heterocyclic unit and preparation method and application thereof | |
| CN111875605B (en) | Preparation and application of bisamide compound containing substituted pyrazole and beta-carboline units | |
| CN111393413B (en) | Pyrazole compound containing chloropyridine biphenyl unit, and preparation method and application thereof | |
| CN112004809A (en) | 5-chloro-2, 4-pyrimidine derivatives as antitumor agents | |
| CN111423413B (en) | Preparation and application of pyrazole derivative containing (3-methoxy-4-substituted pyridylmethoxy) phenyl unit | |
| CN111333578B (en) | Preparation and application of cyanoacrylate containing 1-methyl-3- (4-fluorophenyl) -4-chloropyrazole unit | |
| CN111892596B (en) | Preparation and application of beta-carboline compound containing polyfluoropyrazole structure | |
| CN111499568B (en) | Preparation and application of cyanoacrylate derivative containing pyridine bi-4-mercaptoaryl unit | |
| CN111892595B (en) | Preparation method and application of carboline derivative containing 1-methyl-3-difluoromethyl pyrazole unit | |
| CN111961049B (en) | Beta-carboline derivative containing 1, 3-dimethyl-5-aryloxy pyrazole and preparation method and application thereof | |
| CN111333579A (en) | Preparation and application of cyanoacrylate derivative containing 4-chloro-1-methyl-3-substituent pyrazole | |
| CN111440153B (en) | Preparation and application of pyrazole compound containing (3-methoxy-4-pyrimidinyloxy) phenyl unit | |
| CN115057850B (en) | Aloe-emodin derivative and preparation method and application thereof | |
| CN115010642B (en) | Beta-elemene imide derivative and application thereof | |
| CN114621161B (en) | Rhein-piperazine-dithiocarbamic acid ester hybrid and preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |