CN117185993A - Preparation and application of amide compound containing substituted benzene mercapto pyridine structural unit - Google Patents
Preparation and application of amide compound containing substituted benzene mercapto pyridine structural unit Download PDFInfo
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- CN117185993A CN117185993A CN202311097278.0A CN202311097278A CN117185993A CN 117185993 A CN117185993 A CN 117185993A CN 202311097278 A CN202311097278 A CN 202311097278A CN 117185993 A CN117185993 A CN 117185993A
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- China
- Prior art keywords
- substituted benzene
- structural unit
- amide compound
- compound containing
- mercapto pyridine
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- -1 amide compound Chemical class 0.000 title claims abstract description 31
- 238000002360 preparation method Methods 0.000 title abstract description 7
- 210000004881 tumor cell Anatomy 0.000 claims abstract description 7
- 150000001875 compounds Chemical class 0.000 claims description 12
- 230000002401 inhibitory effect Effects 0.000 claims description 3
- 238000000034 method Methods 0.000 claims description 3
- 239000002246 antineoplastic agent Substances 0.000 claims description 2
- 229940041181 antineoplastic drug Drugs 0.000 claims description 2
- 210000004027 cell Anatomy 0.000 abstract description 13
- 230000000259 anti-tumor effect Effects 0.000 abstract description 6
- 239000003814 drug Substances 0.000 abstract description 6
- 229940079593 drug Drugs 0.000 abstract description 5
- 230000000694 effects Effects 0.000 abstract description 3
- 230000005764 inhibitory process Effects 0.000 abstract description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 abstract 2
- 239000005711 Benzoic acid Substances 0.000 abstract 1
- 150000004982 aromatic amines Chemical class 0.000 abstract 1
- 235000010233 benzoic acid Nutrition 0.000 abstract 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 150000001408 amides Chemical class 0.000 description 5
- 206010009944 Colon cancer Diseases 0.000 description 4
- 208000005718 Stomach Neoplasms Diseases 0.000 description 4
- 208000029742 colonic neoplasm Diseases 0.000 description 4
- 206010017758 gastric cancer Diseases 0.000 description 4
- 201000011549 stomach cancer Diseases 0.000 description 4
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 229960002949 fluorouracil Drugs 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- DWBYVHWWZMMIOT-UHFFFAOYSA-N 2-phenylsulfanylpyridine Chemical group C=1C=CC=NC=1SC1=CC=CC=C1 DWBYVHWWZMMIOT-UHFFFAOYSA-N 0.000 description 1
- GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 description 1
- GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 description 1
- ZBNZXTGUTAYRHI-UHFFFAOYSA-N Dasatinib Chemical compound C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1Cl ZBNZXTGUTAYRHI-UHFFFAOYSA-N 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 239000002067 L01XE06 - Dasatinib Substances 0.000 description 1
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 1
- 235000005811 Viola adunca Nutrition 0.000 description 1
- 240000009038 Viola odorata Species 0.000 description 1
- 235000013487 Viola odorata Nutrition 0.000 description 1
- 235000002254 Viola papilionacea Nutrition 0.000 description 1
- 230000003698 anagen phase Effects 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 229960004117 capecitabine Drugs 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 238000004737 colorimetric analysis Methods 0.000 description 1
- 229960002448 dasatinib Drugs 0.000 description 1
- 230000005918 in vitro anti-tumor Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to preparation and application of an amide compound containing a substituted benzene mercapto pyridine structural unit. Is formed by the reaction of aromatic amine and benzoic acid containing substituted benzene mercapto pyridine methyl thiourea unit. The amide compound containing the substituted benzene mercapto pyridine structural unit has a good inhibition effect on tumor cells, and can be used for preparing antitumor cell medicines.
Description
Technical Field
The invention relates to the field of medicines, in particular to preparation and application of an amide compound containing a substituted benzene mercapto pyridine structural unit.
Background
In recent years, malignant tumors have been threatening to human life and health, and the incidence of cancer has been increasing. Therefore, research and development personnel are required to find and develop efficient antitumor drugs.
Amide medicines are very important compounds, and because of their excellent biological and pharmacological activities, some medicines containing amide skeleton units, such as dasatinib, capecitabine and the like, have been used for treating tumor diseases. Meanwhile, the substituted pyridyl is also an important pharmacophore, and the substituted pyridine derivative has good antiproliferation effect on tumor cells, and has wide application in medical care and other aspects.
In order to further develop a novel compound having an excellent antitumor effect from the amide derivative, a substituted phenylmercaptopyridine structure is linked to the amide active fragment. The invention discloses an amide compound containing a substituted benzene mercapto pyridine structural unit with medicinal value.
Disclosure of Invention
The invention aims to provide an amide compound containing a substituted benzene mercapto pyridine structural unit, which has an inhibiting effect on tumor cells HCT116 and HGC-27.
It is another object of the present invention to provide a process for the preparation of the above compounds.
It is a further object of the present invention to provide the use of the above compounds for the preparation of a medicament for treating tumor cells.
In order to solve the technical problems, the invention provides an amide compound containing a substituted benzene mercapto pyridine structural unit, which has the following structure:
the invention provides a preparation method of the amide compound containing the substituted benzene mercapto pyridine structural unit, which is characterized by comprising the following reaction steps:
the amide compound containing the substituted benzene mercapto pyridine structural unit disclosed by the invention has an inhibiting effect on tumor cells HCT116 and HGC-27, so that the amide compound can be used for preparing antitumor cell medicines.
Detailed Description
The examples provided below are presented in more detail to facilitate a further understanding of the present invention. These examples are provided only for illustration and are not intended to limit the scope or practice of the invention.
Example 1:
2mmol of intermediate II a, 2mmol of benzotriazole-N, N, N ', N' -tetramethyluronium Hexafluorophosphate (HBTU) were dissolved in 20mL of DMSO, 8mmol of N, N-Diisopropylethylamine (DIPEA) and 2mmol of intermediate IIIa were added thereto in this order with stirring at room temperature, and after the addition, the reaction was carried out at room temperature for 18 hours. Removing the solvent, and purifying the obtained crude product by silica gel column chromatography to obtain a target object Ia; 1 H NMR(400MHz，DMSO-d 6 )：δ9.93(s，1H，NH)，9.60(s，1H，NH)，8.40～8.42(m，2H，NH and Py-H)，7.67～7.95(m，3H，Ar-H and Py-H)，7.48～7.59(m，7H，Ar-H and Py-H)，7.15(d，J＝7.2Hz，1H，Ar-H)，6.95～6.99(m，2H，Ar-H)，6.57～6.79(m，2H，Ar-H)，4.91(s，2H，NH 2 )，4.71(d，J＝5.6Hz，2H，CH 2 ).
example 2:
3mmol of intermediate IIb, 4mmol of benzotriazole-N, N, N ', N' -tetramethyluronium Hexafluorophosphate (HBTU) were dissolved in 25mL of DMF, 12mmol of triethylamine and 4mmol of intermediate IIIa were added thereto in this order under stirring at room temperature, and after the addition, the reaction was carried out at room temperature for 22 hours. Removing the solvent, and purifying the obtained crude product by silica gel column chromatography to obtain a target object Ib; 1 H NMR(400MHz，DMSO-d 6 )：δ9.94(s，1H，NH)，9.59(s，1H，NH)，8.41～8.43(m，2H，NH and Py-H)，7.67～7.95(m，3H，Ar-H and Py-H)，7.53～7.59(m，6H，Ar-H and Py-H)，6.95～7.16(m，3H，Ar-H)，6.58～6.79(m，2H，Ar-H)，4.89(s，2H，NH 2 )，4.70(d，J＝5.2Hz，2H，CH 2 ).
example 3:
determination of Activity of Compounds on tumor cells
The compounds were tested for in vitro antitumor activity by the tetramethylazoblue colorimetric Method (MTT). Human gastric cancer cell HGC-27 and human colon cancer cell HCT116 were selected as subjects. 5-fluorouracil (5-FU) is a positive control. Preparing 4×10 human gastric cancer cell HGC-27 and human colon cancer cell HCT116 in exponential growth phase 3 Cell suspensions of individual cells/mL were seeded in 96-well plates at 37℃in 5% CO 2 Is cultured in an incubator for 24 hours. Test solutions (10. Mu.L) of test compounds were added to the test wells, 5 parallel wells were set for each concentration, and an equivalent amount of DMSO was used as a blank, followed by a treatment with 5% CO 2 After culturing for 72 hours, the supernatant was discarded, 20. Mu.L of MTT (2 mg/mL in PBS) was added to each well, and after culturing for 4 hours, 150. Mu.L of DMSO was added to each well, and the resulting blue-violet precipitate was dissolved by shaking with a shaker for 10 minutes, and the OD value was measured at 490nm by using an ELISA reader, to thereby calculate the cell inhibition ratio. Cell inhibition ratio= (OD value of negative control group-OD value of test substance group)/OD value of negative control group multiplied by 100%, and IC of the compound is calculated by probability unit weighted regression method 50 Values.
Data on antitumor Activity of Ia-Ib (IC 50 ，μM)
| Compounds of formula (I) | HCT116 | HGC-27 |
| Ia | 3.57 | 2.21 |
| Ib | 1.02 | 0.69 |
| 5-FU | 19.60 | 34.10 |
As can be seen from the data in Table 1, the prepared compounds Ia-Ib have good anti-tumor activity on human colon cancer cells HCT116 and human gastric cancer cells HGC-27. The experimental result shows that the compound prepared by reasonably connecting the substituted benzene mercapto pyridine unit with the amide active fragment has better anti-tumor effect on human colon cancer cells HCT116 and human gastric cancer cells HGC-27.
The foregoing has shown and described the basic principles, principal 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 by way of illustration of the principles of the present invention, and that various changes and modifications may be made therein without departing from the spirit and scope of the invention as defined in the appended claims. The scope of the invention is defined by the appended claims and equivalents thereof.
Claims (3)
1. An amide compound I containing a substituted benzene mercapto pyridine structural unit is characterized by comprising the following structure:
2. the method for preparing the amide compound I containing the substituted benzene mercapto pyridine structural unit as claimed in claim 1, which is characterized by comprising the following steps:
3. the use of an amide compound I containing a substituted benzene mercapto pyridine structural unit in preparing an antitumor drug according to claim 1, wherein: compound I according to claim 1 shows an inhibitory effect on tumor cells HCT116 and HGC-27.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311097278.0A CN117185993A (en) | 2023-08-28 | 2023-08-28 | Preparation and application of amide compound containing substituted benzene mercapto pyridine structural unit |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311097278.0A CN117185993A (en) | 2023-08-28 | 2023-08-28 | Preparation and application of amide compound containing substituted benzene mercapto pyridine structural unit |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN117185993A true CN117185993A (en) | 2023-12-08 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202311097278.0A Pending CN117185993A (en) | 2023-08-28 | 2023-08-28 | Preparation and application of amide compound containing substituted benzene mercapto pyridine structural unit |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN117185993A (en) |
-
2023
- 2023-08-28 CN CN202311097278.0A patent/CN117185993A/en active Pending
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