Preparation and application of carboline derivative containing 1, 2, 3-thiadiazole structure
By synthesizing and connecting carbaline derivatives with 1,2,3-thiadiazole structure, the problem of lack of effective anti-tumor drugs in the prior art is solved, and a significant inhibitory effect on tumor cells is achieved.
Patent Information
- Application Number
- CN202510428264.5
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-04-08
- Publication Date
- 2025-07-11
- Estimated Expiration
- Not applicable · inactive patent
AI Technical Summary
In the prior art, there is a lack of effective application of carbaline derivatives containing 1,2,3-thiazole structure in anti-tumor cells, and it is difficult to meet the demand for inhibition of tumor cells.
Carboline derivatives containing the structure of 1,2,3-thiazole are synthesized and linked to carboline active units through specific methods to prepare compounds of medicinal value for the preparation of anti-tumor cell drugs.
The compounds showed good inhibitory activity on tumor cells SGC-7901 and A-549, with IC50 values of 9.57 μM and 0.22 μM, respectively, showing significant anti-tumor effects.
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Abstract
Description
Technical Field
[0001] The present invention relates to the field of medicine, and specifically relates to the preparation and use of carbazole derivatives containing a 1,2,3-thiadiazole structure. Background Art
[0002] In recent years, malignant tumors have always threatened human life and health. Therefore, searching for and discovering effective anti-cancer drugs and treatment methods is one of the important research topics in the medical field.
[0003] The 1,2,3-thiadiazole ring is an important nitrogen-containing heterocyclic unit, and 1,2,3-thiadiazole derivatives show good inhibitory effects on some tumor cells.
[0004] Carbazole derivatives are also an important class of nitrogen-containing heterocycles, and carbazole compounds also exhibit good inhibitory activity against tumor cells.
[0005] Therefore, in order to continue to search for and discover drugs with good anti-tumor activity from carbazole compounds, the 1,2,3-thiadiazole heterocyclic structure is reasonably connected to the carbazole active unit. The present invention discloses a class of carbazole derivatives containing a 1,2,3-thiadiazole structure with medicinal value. Summary of the Invention
[0006] The object of the present invention is to provide a class of carbazole derivatives containing a 1,2,3-thiadiazole structure that exhibit good inhibitory effects on tumor cells.
[0007] Another object of the present invention is to provide a preparation method for the above-mentioned compounds.
[0008] Another object of the present invention is to provide the use of the above-mentioned compounds in the preparation of anti-tumor cell drugs.
[0009] To solve the above technical problems, the present invention provides carbazole derivatives containing a 1,2,3-thiadiazole structure, which have the following structure:
[0010]
[0011]
[0012] The present invention provides a preparation method for the above-mentioned carbazole derivatives containing a 1,2,3-thiadiazole structure, which is characterized by including the following steps:
[0013]
[0014]
[0015] Among them, the intermediate carbazole compound and 4-methyl-1,2,3-thiadiazole-5-carbonyl chloride are both prepared by conventional methods.
[0016] The compounds of the present invention exhibit good anti-tumor effects against tumor cells SGC-7901 or A-549.
[0017] The carbazole derivatives containing 1,2,3-thiadiazole structure disclosed in the present invention have good inhibitory activity against tumor cells SGC-7901 or A-549, and thus can be used to prepare anti-tumor cell drugs. Detailed implementation manners
[0018] For better understanding of the present invention, the following examples provide more detailed descriptions thereof. These examples are for narrative purposes only and are not intended to limit the scope or implementation principles of the present invention.
[0019] Example 1:
[0020]
[0021] Dissolve 3 mmol of intermediate Ⅲa in 35 mL of acetonitrile. Under ice bath conditions, add 4 mmol of intermediate Ⅱ thereto. After adding, add 12 mmol of triethylamine, and continue stirring in the ice bath for 10 hours. After removing the solvent, the obtained crude product is purified by silica gel column chromatography to obtain the target product Ia; 1 H NMR (DMSO-d6, 400 MHz): δ 11.82 (s, 1H), 8.90~8.99 (m, 2H), 8.82 (s, 1H), 8.42 (d, J = 8.00 Hz, 1H), 8.08 (d, J = 8.00 Hz, 2H), 7.68~7.71 (m, 1H), 7.58~7.62 (m, 1H), 7.45 (d, J = 8.40 Hz, 2H), 7.30~7.33 (m, 1H), 3.61~3.64 (m, 2H), 3.52~3.54 (m, 2H), 2.73 (s, 3H), 2.47 (s, 3H).
[0022] Example 2:
[0023]
[0024] Dissolve 6 mmol of intermediate Ⅲb in 55 mL of dichloromethane. Under ice bath stirring, add 8 mmol of intermediate Ⅱ thereto. After adding, add 15 mmol of triethylamine, and continue stirring in the ice bath for 13 hours. After removing the solvent, the obtained crude product is purified by silica gel column chromatography to obtain the target product Ib; 11H NMR (DMSO-d6, 400 MHz): δ 11.82 (s, 1H), 8.84 - 8.88 (m, 2H), 8.81 (s, 1H), 8.41 (d, J = 8.00 Hz, 1H), 8.08 (d, J = 8.00 Hz, 2H), 7.69 (d, J = 8.00 Hz, 1H), 7.57 - 7.61 (m, 1H), 7.45 (d, J = 8.00 Hz, 2H), 7.29 - 7.33 (m, 1H), 3.45 - 3.49 (m, 2H), 3.36 - 3.39 (m, 2H), 2.79 (s, 3H), 2.46 (s, 3H), 1.81 - 1.86 (m, 2H).
[0025] Example 3:
[0026]
[0027] Dissolve 6 mmol of intermediate Ⅲc in 30 mL of chloroform. Add 5 mmol of intermediate Ⅱ under ice bath conditions. After adding, add 30 mmol of 4-dimethylaminopyridine (DMAP), and continue to stir under ice bath for 16 hours. After removing the solvent, the obtained crude product is purified by silica gel column chromatography to obtain the target product Ic; 1 1H NMR (DMSO-d6, 400 MHz): δ 11.84 (s, 1H), 8.99 - 9.02 (m, 1H), 8.93 - 8.96 (m, 1H), 8.81 (s, 1H), 8.42 (d, J = 8.00 Hz, 1H), 8.16 (d, J = 8.80 Hz, 2H), 7.71 (d, J = 8.00 Hz, 1H), 7.58 - 7.62 (m, 1H), 7.30 - 7.33 (m, 1H), 7.18 (d, J = 8.80 Hz, 2H), 3.91 (s, 3H), 3.62 - 3.64 (m, 2H), 3.51 - 3.56 (m, 2H), 2.74 (s, 3H).
[0028] Example 4:
[0029] Activity test of the sample on tumor cells
[0030] The in vitro anti-tumor activity of the sample was tested by the tetramethyl thiazolyl blue colorimetric method (MTT). The test cells were human gastric cancer cells SGC-7901 and human lung cancer cells A549. Take cancer cells in the exponential growth phase to prepare 4×10 3A cell suspension of [[number]] cells / mL was inoculated into a 96-well plate and cultured in a CO₂ incubator for 36 hours. The test solution (10 μL) of the sample to be tested was added to the test wells, with parallel wells set for each concentration, and an equal amount of DMSO was used as a blank control. After culturing in a CO₂ incubator for 24 hours, the supernatant was discarded. 10 μL of 5% MTT was added to each well and cultured for 4 hours. Then, the supernatant was aspirated and discarded. 100 μL of DMSO was added to each well and shaken on a shaker for 20 minutes. The OD value was measured at a wavelength of 570 nm using an enzyme-linked immunosorbent assay (ELISA) reader, and the cell inhibition rate was calculated. The cell inhibition rate = (OD value of the negative control group - OD value of the test substance group) / OD value of the negative control group × 100%. The IC 50 value of the sample was calculated by the probit weighted regression method.
[0031] Table 1. Antitumor activity data of Ia - Ic (IC 50 , μM)
[0032] Compound SGC-7901 A549 Ia 9.57 - Ib 0.22 - Ic - 2.52
[0033] “-”: indicates not determined
[0034] As can be seen from the data in Table 1, compounds Ia and Ib showed good antitumor activity against human gastric cancer cell line SGC - 7901, with IC 50 values of 9.57 and 0.22 μM, respectively; compound Ic had a good inhibitory effect on human lung cancer cell line A549, with an IC 50 value of 2.52 μM.
[0035] The above shows and describes the basic principles, main features, and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited by the above examples. The above examples and the descriptions in the specification only illustrate the principles of the present invention. Without departing from the spirit and scope of the present invention, various changes and improvements will occur to the present invention, and these changes and improvements fall within the scope of the present invention claimed. The scope of protection claimed by the present invention is defined by the appended claims and their equivalents.
Claims
1. A carboline derivative (I) containing a 1,2,3-thiadiazole structure, characterized in that There is the following structure:
2. The preparation method of the carbazole derivative (I) containing 1,2,3-thiadiazole structure according to claim 1, characterized in that The method is as follows:
3. Use of the carbazole derivative (I) containing 1,2,3-thiadiazole structure as described in claim 1 in anti-tumor cells, characterized in that: The carbazole derivative (I) containing 1,2,3-thiadiazole structure as described in claim 1 shows good inhibitory effects on tumor cells SGC-7901 or A549.