Camptothecin derivative and preparation method and application thereof

A technology of camptothecin and derivatives, applied in the field of medicinal chemistry and therapeutics, which can solve the problems of urinary system and digestive system side effects

Inactive Publication Date: 2012-08-29
NORTHEAST FORESTRY UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

What's more serious is that the sodium salt in the open-loop form has great toxic and s...

Method used

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  • Camptothecin derivative and preparation method and application thereof
  • Camptothecin derivative and preparation method and application thereof
  • Camptothecin derivative and preparation method and application thereof

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preparation example Construction

[0058] The preparation method of described 20 (S)-camptothecin derivatives, described organic solvent is dimethyl sulfoxide and N, N-dimethylformamide; Described coupling agent is DCC, CDI and EDC.HCl; The catalyst is pyridine and DMAP.

[0059] A pharmaceutical composition, containing the camptothecin derivative and a pharmacodynamically acceptable carrier.

[0060] The pharmaceutical composition can be tablets, capsules, pills, injections, sustained-release preparations, controlled-release preparations or various particle delivery systems.

[0061] The application of the compound in the preparation of antitumor drugs.

Embodiment 1

[0062] The preparation of embodiment 1 intermediate II

[0063] Dissolve 2.1 g of N-tert-butoxycarbonylglycine at room temperature in 40 ml of N, N-dimethylformamide, add 1 g of camptothecin, 2 g of DCC and 0.25 g of DMAP under stirring, and react for 12 After 1 hour, the precipitate was removed by filtration, and the filtrate was diluted with 100 milliliters of distilled water to separate out a white precipitate. The precipitate was filtered, washed with water, dried and recrystallized to obtain 860 mg of milky white powder crystal intermediate II (86% yield).

Embodiment 2

[0064] The preparation of embodiment 2 intermediate III

[0065] Dissolve 0.5 g of intermediate II in 20 ml of a mixed solution of dichloromethane and trifluoroacetic acid 1:1 (V:V), stir at room temperature for 1 hour, remove dichloromethane by rotary evaporation, and pour the remaining liquid into 50 mL of distilled water precipitated out. The precipitate was filtered, washed with water and dried. 390 mg of intermediate III was obtained as a milky white solid (yield 78%).

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Abstract

The invention provides a camptothecin derivative shown as a formula (I). In the formula, R is selected from alkyl with 1-6 carbon atoms, halogenated alkyl with 1-6 carbon atoms, aryl-substituted alkyl with 1-6 carbon atoms, phosphate-substituted radical with 1-6 carbon atoms, amino-substituted alkyl with 1-6 carbon atoms, carboxyl-substituted alkyl with 1-6 carbon atoms, hydroxyl-substituted alkyl with 1-6 carbon atoms and amido-substituted alkyl with 1-6 carbon atoms. The invention further provides a preparation method of the derivative and an application of the derivative to preparation of an antitumor medicament.

Description

technical field [0001] The invention relates to the fields of medicinal chemistry and therapeutics, in particular to novel camptothecin derivatives, their preparation methods and uses. Background technique [0002] Camptothecin (CPT) is an alkaloid extracted from the unique plant Camptothecus in my country. In the early in vitro activity screening, camptothecin showed strong anti-tumor activity and had obvious inhibitory effect on a variety of solid tumors and leukemia. However, camptothecin has poor water solubility and strong toxicity, which limits its use in tumor therapy. on the application. In 1985, Hsiang Y.H. found that camptothecin exerted cytotoxic activity by inhibiting topoisomerase I, which aroused people's attention again. Many researchers have begun to invest in the modification and improvement of the chemical structure of camptothecin, and are committed to improving its absorption in the human body and enhancing its therapeutic effect. So far, the U.S. Food...

Claims

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Application Information

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IPC IPC(8): C07K5/072A61K38/05A61P35/00
Inventor 王洋阎秀峰井立佳丁为民于涛国静庞秋颖
Owner NORTHEAST FORESTRY UNIVERSITY
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