Beta-carboline derivative as well as preparation method and application thereof

A technology of derivatives and carbolines, which is applied in the field of β-carboline derivatives and its preparation, can solve the problems of reduced curative effect due to drug resistance, decreased therapeutic effect, and restrictions on long-term use, and achieves obvious anti-tumor effects, significant phototoxicity, and The effect of the novel mechanism of action

Active Publication Date: 2022-02-18
GUANGDONG ZHANJIANG PROVINCIAL LAB OF SOUTHERN MARINE SCI & ENG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, since the tumor's resistance to platinum drugs reduces its efficacy, resulting in a decline in therapeutic effect, and its toxicity restricts its long-term clinical use, so other transition metal complexes are being searched for in related technologies as potential candidates. anticancer reagents

Method used

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  • Beta-carboline derivative as well as preparation method and application thereof
  • Beta-carboline derivative as well as preparation method and application thereof
  • Beta-carboline derivative as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0265] The present embodiment is a preparation method of β-carboline derivatives, comprising the following steps:

[0266] S1. Preparation of compound 2:

[0267]

[0268] Tryptophan (compound 1, 0.82g, 4mmol) was dissolved in 20mL of methanol, and thionyl chloride (0.29mL, 4mmol) was added dropwise under ice-cooling, condensed and refluxed at 100°C for 7h, and the obtained solution was distilled off under reduced pressure to remove the solvent. After rinsing with ethyl acetate, suction filtration and drying, 0.98 g of white powder (compound 2) was obtained with a yield of 96.4%.

[0269] S2, preparation of compound 3:

[0270]

[0271] Add compound 2 (1.019g, 4mmol) to the reaction tube, then add benzaldehyde (408μL, 4mmol), dissolve in 15mL of isopropanol, heat and reflux at 90°C for 10h under the protection of argon, and distill off the solvent from the obtained liquid under reduced pressure , add benzene to stir, filter with suction, and dry to obtain 1.12 g of lig...

Embodiment 2

[0287] This embodiment is a preparation method of an iridium complex, comprising the following steps:

[0288] S1. Preparation of Compound 8:

[0289]

[0290] IrCl 3 ·nH 2 O (1.192g, 2mmol) and ppy (0.62g, 4mmol) were added to a mixed solution of ethylene glycol-ether and water (3:1, v / v) at a molar ratio of 1:2, heated to reflux for 24h, filtered, The crude product was passed through a silica gel column to obtain 0.90g Ir 2 (ppy) 4 Cl 2 (Compound 8), yield 84.0%.

[0291] S2. Preparation of compound 9:

[0292]

[0293] Ir 2 (ppy) 4 Cl 2 (Compound 8, 2.054g, 2mmol) and PPβC (Compound 7, 1.86g, 4mmol) were dissolved in the mixed solution of dichloromethane / methanol (2:1, v / v), refluxed for 4h under the protection of argon, and the reaction After the solution was cooled to room temperature, CH was removed by rotary evaporation. 2 Cl 2 After transferring to a beaker, 20 mL of KPF was added to the solution 6 saturated aqueous solution. After cooling overnight...

Embodiment 3

[0299] This embodiment is a preparation method of an iridium complex, comprising the following steps:

[0300] S1. Preparation of compound 10:

[0301]

[0302] IrCl 3 ·nH 2 O (1.192g, 2mmol) and dfppy (0.76g, 4mmol) were added to a mixed solution of ethylene glycol-ether and water (3:1, v / v) at a molar ratio of 1:2, heated to reflux for 24h, and filtered 0.91g Ir 2 (dfppy) 4 Cl 2 (Compound 10), yield 75.0%.

[0303] S2. Preparation of compound 11:

[0304]

[0305] Ir 2 (dfppy) 4 Cl 2 (2.432g, 2mmol) and compound 7 (1.86g, 4mmol) were dissolved in a mixed solution of dichloromethane / methanol (2:1, v / v), refluxed for 4h under the protection of argon, and the solution was cooled after the reaction to room temperature, rotary evaporation to remove CH 2 Cl 2 After transferring to a beaker, 20 mL of KPF was added to the solution 6 saturated aqueous solution. After cooling overnight at 4°C in the refrigerator, it was collected by filtration, dried in vacuo, and ...

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Abstract

The invention discloses a beta-carboline derivative as well as a preparation method and application thereof. The beta-carboline derivative is used for preparing an iridium complex. A novel iridium complex is prepared by utilizing the beta-carboline derivative, is rapidly absorbed by cells and has an obvious targeting effect on tumor cell mitochondria, so that mitochondrial morphological change is caused, mitochondrial dysfunction is induced; e.g. mitochondrial membrane potential is influenced, active oxygen is increased and the like. Meanwhile, the compound shows phototoxicity to cancer cells, and compared with the dark, the toxicity of the compound to tumor cells after illumination is improved. Finally, the anti-tumor effect is achieved by inducing cell apoptosis.

Description

technical field [0001] The invention relates to the technical field of compound synthesis, in particular to a β-carboline derivative and its preparation method and application. Background technique [0002] In recent years, the mortality and morbidity of malignant tumors have continued to rise. Under the action of carcinogenic factors, the proto-oncogenes of the cells in the local tissue are activated, and the tumor suppressor genes are inactivated, thus losing the regulation of normal cell growth and apoptosis at the gene level, and finally forming a primary tumor. At present, the main methods for treating malignant tumors include surgery, chemotherapy, and radiation therapy. Most patients are already in the middle and advanced stages when they are discovered, and chemotherapy becomes the main treatment method for treatment. Based on the above status quo, the research and development of chemotherapy drugs has also received more and more attention. Metal complexes have be...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D519/00C07F15/00A61K31/555A61P35/00C09K11/06A61K41/00
CPCC07D519/00C07F15/0033C09K11/06A61P35/00A61K41/0057C09K2211/185
Inventor 陈锦灿陈兰美郭欣华陈伟钢黄鹤鸣罗辉
Owner GUANGDONG ZHANJIANG PROVINCIAL LAB OF SOUTHERN MARINE SCI & ENG
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