Beta-carboline compound containing pyridine biaryloxy unit as well as preparation method and application of beta-carboline compound
By synthesizing β-carboline compounds containing pyridine biaryloxy units, the problem of effectively inhibiting tumor cells in existing technologies has been solved, and significant anti-tumor effects against human gastric cancer cells have been achieved.
Patent Information
- Application Number
- CN202511487532.7
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-10-17
- Publication Date
- 2025-12-19
AI Technical Summary
In the existing technology, there is a lack of highly efficient antitumor drugs that organically combine substituted pyridine units with β-carboline structures, making it difficult to effectively inhibit tumor cells.
A β-carboline compound containing a pyridine biaryloxy unit was designed and synthesized. The compound with good inhibitory activity against tumor cells was prepared by reacting aryloxypyridine acyl chloride with a substituted β-carboline intermediate.
The synthesized compounds showed significant antitumor effects against human gastric cancer cells SGC-7901 and HGC-27, with IC50 values of 3.35 μM and 1.07 μM, respectively, demonstrating good inhibitory activity.
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Abstract
Description
Technical Field
[0001] This invention relates to the pharmaceutical field, specifically to a β-carboline compound containing a pyridine biaryloxy unit, its preparation method, and its application. Background Technology
[0002] In recent years, malignant tumors have been a persistent threat to human health. Therefore, medicinal chemists are required to continuously develop highly effective anti-tumor drugs.
[0003] As an important nitrogen-containing heterocycle, β-carboline compounds play a vital role in the field of healthcare.
[0004] Meanwhile, the pyridine ring is also an important nitrogen heterocyclic unit, and many pyridine compounds exhibit excellent inhibitory effects on tumor cells.
[0005] Therefore, in order to continue searching for drugs with good antitumor effects from β-carboline compounds, a substituted pyridine unit is organically linked to the β-carboline structure. This invention discloses a β-carboline compound containing a pyridine biaryloxy unit with pharmaceutical value. Summary of the Invention
[0006] The purpose of this invention is to provide a pyridine-biaryloxy unit containing a pyridine-biaryloxy group that exhibits good inhibitory activity against tumor cells. β -Carboline compounds.
[0007] Another object of the present invention is to provide a method for preparing the above-mentioned compound.
[0008] Another object of the present invention is to provide the use of the above-mentioned compounds in the preparation of antitumor cell drugs.
[0009] To solve the above-mentioned technical problems, the present invention provides a pyridine biaryloxy unit. β -Carboline compounds, which have the following structures: or .
[0010] This invention provides a pyridine-biaryloxy unit containing the above-mentioned... β A method for preparing α-carboline compounds, characterized by comprising the following reaction steps: or .
[0011] Among them, aryloxypyridine chloride, substituted β -The carboline intermediate compound was prepared by conventional methods.
[0012] The compounds of this invention exhibit good anti-tumor effects against tumor cells.
[0013] This invention discloses a pyridine-biaryloxy unit. β -Carboline compounds have good inhibitory activity against tumor cells SGC-7901 or HGC-27, and therefore can be used to prepare anti-tumor cell drugs. Detailed Implementation
[0014] To facilitate a further understanding of the present invention, the following embodiments are provided for more detailed description. These embodiments are for illustrative purposes only and are not intended to limit the scope or implementation principles of the present invention.
[0015] Example 1: ,
[0016] 3 mmol of intermediate III, 2 mL of triethylamine, and 30 mL of dichloromethane were added to a reaction flask. Under ice bath conditions, 4 mmol of intermediate IIa was added dropwise, and the mixture was stirred in an ice bath for 13 hours. The reaction was then stopped, the solvent was removed under reduced pressure, and the residue was separated by silica gel column chromatography to obtain the target compound Ia. 1 H NMR (400 MHz, DMSO- d 6): d 11.93 (s, 1H),8.67 (s, 1H), 8.58~8.63 (m, 3H), 8.35 (d, J = 8.0 Hz, 1H), 8.24~8.26 (m, 1H), 7.65 (d, J = 8.0 Hz, 1H), 7.58 (t, J = 8.0 Hz, 1H), 7.49 (d, J = 9.2 Hz, 2H), 7.28 (t, J = 8.0 Hz, 1H), 7.22 (d, J = 8.8 Hz, 2H), 7.14 (d, J = 8.8 Hz, 1H), 3.37~3.42 (m, 2H), 3.29~3.34 (m, 2H), 2.84 (s, 3H), 1.60~1.62 (m, 4H).
[0017] Example 2: , 3 mmol of intermediate III, 6 mmol of sodium acetate, and 30 mL of chloroform were added to a reaction flask. Under ice bath conditions, 3 mmol of intermediate IIb was added dropwise, and the mixture was stirred at room temperature for 16 hours. The reaction was stopped, the solvent was removed under reduced pressure, and the residue was separated by silica gel column chromatography to obtain the target compound Ib. 1 H NMR (400 MHz, DMSO- d 6): d 11.92 (s, 1H),8.66 (s, 1H), 8.55~8.62 (m, 3H), 8.33 (d, J = 8.0 Hz, 1H), 8.24~8.26 (m, 1H), 7.64 (d, J = 8.0 Hz, 1H), 7.56~7.59 (m, 1H), 7.19~7.30 (m, 5H), 7.09 (d, J =8.8 Hz, 1H), 3.37~3.41 (m, 2H), 3.30~3.32 (m, 2H), 2.84 (s, 3H), 1.60~1.61(m, 4H).
[0018] Example 3: Activity screening of compounds on tumor cells The in vitro antitumor activity of the compound was tested using the MTT assay. The test subjects were human gastric cancer cells SGC-7901 and HGC-27. First, cancer cells in the exponential growth phase were used to prepare 4 × 10⁻⁶ cells. 3 Cell suspensions of 10 cells / mL were seeded into 96-well plates and incubated in a CO2 incubator for 36 h. Then, 10 μL of the test compound solution was added to each well, with parallel wells for each concentration. An equal volume of DMSO was used as a blank control. The plates were incubated in a CO2 incubator for 24 h. After discarding the supernatant, 10 μL of 5% MTT was added to each well, and the plates were incubated for 4 h. The supernatant was then discarded, and 100 μL of DMSO was added to each well. The plates were shaken for 20 min, and the OD value was measured at 570 nm using a microplate reader. The cell inhibition rate was calculated as follows: Cell inhibition rate = (OD value of negative control group - OD value of test compound group) / OD value of negative control group × 100%. The IC50 of the compound was calculated using a probability-weighted regression method. 50 value.
[0019] Table 1. Antitumor activity data of compounds Ia-Ib (IC50, 100 mg / L) 50 (μM)
[0020] As can be seen from the data in Table 1, the synthesized compound Ia exhibits a good inhibitory effect on human gastric cancer cells SGC-7901, with an IC50 value of [missing information]. 50 The concentration was 3.35 μM; compound Ib exhibited good inhibitory activity against human gastric cancer cells HGC-27, with an IC50 value of 3.35 μM. 50 The value is 1.07 μM.
[0021] The foregoing has shown and described 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 to the above examples; the examples and descriptions in the specification are merely illustrative of the principles of the invention. Various changes and modifications can be made to the invention without departing from its spirit and scope, and all such changes and modifications fall within the scope of the present invention as claimed. The scope of protection of this invention is defined by the appended claims and their equivalents.
Claims
1. A β-carboline compound (I) containing a pyridine biaryloxy unit, characterized in that... The structure is as follows: or .
2. The method for preparing a β-carboline compound (I) containing a pyridine biaryloxy unit as described in claim 1, characterized in that... The method is as follows: or .
3. The pyridine-biaryloxy unit as described in claim 1 β The use of carboline compound (I) in the preparation of antitumor cell drugs, characterized by: The pyridine-biaryloxy unit as described in claim 1 β -Carboline compound (I) showed good inhibitory effects on tumor cells SGC-7901 or HGC-27.