Dimethyl deuterated carnosol, preparation method thereof and application of dimethyl deuterated carnosol in preparation of medicine for treating cachexia

A technology of bismethyl deuterated carnosol and bismethyl deuterated sage, applied in the field of drug synthesis, can solve problems such as failure, no breakthrough progress of new drugs, shortened survival period, etc., so as to alleviate muscle atrophy , the effect of alleviating weight and food intake loss, alleviating lipolysis

Active Publication Date: 2021-08-13
EAST CHINA NORMAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

The most promising new drugs in the clinical research stage in the near future are Anamorelin (anamorelin, a ghrelin receptor agonist) and Enobosarm (a selective AR agonist), but the current phase III of these two drugs Clinical studies all ended in failure
[0007] In conclusion, since tumor cachexia is the main complication of various malignant tumor patients, it not only weakens the effect of chemotherapy and radiotherapy, shortens the survival period, but also seriously affects the quality of life of patients.
Although the importance and necessity of tumor cachexia treatment has gained a consensus, due to its complex pathogenesis, the current research is only the tip of the iceberg, and there is no breakthrough in the treatment of tumor cachexia and the development of new drugs. Currently, no drug has been approved as a specific drug for tumor cachexia, so the research and development of new drugs for tumor cachexia need to be deepened urgently

Method used

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  • Dimethyl deuterated carnosol, preparation method thereof and application of dimethyl deuterated carnosol in preparation of medicine for treating cachexia
  • Dimethyl deuterated carnosol, preparation method thereof and application of dimethyl deuterated carnosol in preparation of medicine for treating cachexia
  • Dimethyl deuterated carnosol, preparation method thereof and application of dimethyl deuterated carnosol in preparation of medicine for treating cachexia

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0163] Example 1 Synthesis of Dimethylcarnosol Add 300mg carnosol, 250mg potassium carbonate and 20mL anhydrous acetone into a 50mL reaction flask, add 1mL methyl iodide under nitrogen protection, and react in the dark for 48 hours at room temperature. The liquid turned from colorless to brown, and the solid was removed by suction filtration. The filtrate was concentrated to dryness and separated by column chromatography to obtain 70 mg of white solid, with a yield of 21.5%. LC-MS (ESI) m / z C 22 h 31 o 4 [M+H] + calcd for 359.2, found 359.4.

Embodiment 2

[0164] The synthesis of embodiment 2 bismethyl deuterated carnosol

[0165] Add 750mg of carnosol, 600mg of potassium carbonate and 50mL of anhydrous acetone to a 100mL reaction bottle, add 3mL of deuterated methyl iodide under nitrogen protection, and react in the dark for 48 hours at room temperature. The reaction solution turns from colorless to brown, and is filtered by suction The solid was removed, the filtrate was concentrated to dryness and separated by column chromatography to obtain 135 mg of white solid with a yield of 16.3%. LC-MS (ESI) m / z C 22 h 25 D. 6 o 4 [M+H]+ calcd for 364.3, found 365.5.

Embodiment 3

[0166] Example 3 Carnosol, dimethyl carnosol and dimethyl deuterated carnosol on mouse myoblast (C2C12) viability experiment

[0167] The survival rate of C2C12 cells was detected by MTT assay. The detection principle is that succinate dehydrogenase in the mitochondria of living cells can reduce exogenous MTT to water-insoluble blue-purple crystal formazan (Formazan) and deposit in the cells, while dead cells do not have this function. Triple solution (10% SDS + 5% isobutanol + 0.01% concentrated hydrochloric acid, aqueous solution) can dissolve formazan in cells, and measure its light absorption value at a wavelength of 570nm with an enzyme-linked immunosorbent assay, which can indirectly reflect the number of living cells . Within a certain cell number range, the amount of MTT crystal formation is proportional to the cell number.

[0168] The effect of the drug on the viability of mouse myoblasts (C2C12) can be evaluated by the above method. The specific method is as foll...

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Abstract

The invention innovatively provides application of a carnosol compound in preparing a medicine for treating cachexia for the first time. The carnosol compound comprises a carnosol compound shown as a formula X, dimethyl deuterated carnosol shown as a formula 1, dimethyl carnosol shown as a formula 2 and the like. The invention further provides a novel compound, namely the dimethyl deuterated carnosol shown in the formula 1 and a preparation method of the dimethyl deuterated carnosol. The invention also provides a pharmaceutical composition for treating cachexia diseases. The invention further provides application of the medicine in preparation of the medicine for treating the tumor cachexia, including muscle atrophy caused by tumor tissue, adipopenia caused by the tumor tissue, appetite reduction caused by the tumor tissue, inflammatory response caused by the tumor tissue and tumor cachexia caused by digestive tract related cancer, liver cancer, lung cancer and colon cancer. The invention also provides an application in preparation of drugs or inhibitors for treating or inhibiting amyotrophy, drugs or inhibitors for inhibiting or relieving fat cell lipolysis, and drugs or inhibitors for inhibiting or relieving weight loss or loss. A wide application prospect is achieved.

Description

technical field [0001] The present invention relates to the field of drug synthesis, in particular to a kind of formula (1) dimethyl deuterated carnosol and its preparation method and application. Background technique [0002] Cachexia is a progressive wasting syndrome accompanied by systemic failure such as weight loss, anemia, and mental decline. It is mostly caused by cancer and other serious chronic diseases (such as chronic pulmonary obstruction, chronic heart failure, AIDS, etc.) cachexia is called tumor cachexia. Cancer cachexia is the main complication of various malignant tumor patients and the main cause of death of many cancer patients. The prevention and treatment of tumor cachexia has become an important part of the multidisciplinary treatment of malignant tumors and is receiving more and more attention. Tumor cachexia is a wasting syndrome characterized by systemic metabolic disorders, progressive muscle and fat consumption, weight loss, and progressive failu...

Claims

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Application Information

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IPC IPC(8): C07D493/08A61K31/366A61P35/00A61P13/12A61P11/00A61P9/04A61P31/18
CPCC07D493/08A61K31/366A61P35/00A61P13/12A61P11/00A61P9/04A61P31/18C07B2200/05
Inventor 章雄文李奕伟潘俊芳刘璇
Owner EAST CHINA NORMAL UNIVERSITY
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