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Isocorydine derivative, preparation method and applications thereof

一种异紫堇碱、衍生物的技术，应用在异紫堇碱的化学结构衍生物及其制备领域，能够解决药物毒副作用、耐药性影响患者生活质量和治疗效果等问题，达到好抗癌活性、改善体内药代动力学行为、增强体内药理活性的效果

Active Publication Date: 2017-12-19
LANZHOU INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although sonafenib can effectively prolong the overall survival time of HCC patients (2 months), the side effects and drug resistance after taking it will seriously affect the quality of life and treatment effect of patients. In addition, it is expensive The cost is also beyond the reach of most patients

Method used

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  • Isocorydine derivative, preparation method and applications thereof
  • Isocorydine derivative, preparation method and applications thereof
  • Isocorydine derivative, preparation method and applications thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0051] Example 1: Synthesis of 8-(N-(3'-trifluoromethyl-4'-chloro-phenyl))-ureido-isocordyrine (FICD).

[0052] The NICD compound (0.7915 g, 2.23 mmol) was dissolved in 50 mL of dichloromethane, and the solution was cooled to below 0 °C in ice-brine. Another 4-chloro-3-trifluoromethylphenyl isocyanate (0.5822 g, 2.63 mmol) was added to 50 mL of dichloromethane to dissolve the compound, cooled to below 0°C, and added dropwise to the above NICD solution under mechanical stirring During the process, the mixture was mechanically stirred for 90 min, and the end of the reaction was detected by TLC, and the reaction was stopped. Use ammonia water to adjust the pH value of the above reaction solution, add 100×3mL dichloromethane respectively, extract three times, combine the organic phases, recover the organic solvent, separate by silica gel column chromatography, petroleum ether: ethyl acetate: methanol = 6:2:1, 0.9278 g of the target compound FICD was obtained with a yield of 72.3%...

Embodiment 2

[0055] Example 2: Synthesis of 8-(N-(3',4'-dichloro-phenyl))-ureido-isocordyline.

[0056] The NICD compound (0.0906 g, 0.25 mmol) was dissolved in 50 mL of dichloromethane, and the solution was cooled to below 0 °C in ice-brine. Another 3,4-dichlorophenyl isocyanate (0.0480 g, 0.25 mmol) was added to 50 mL of dichloromethane to dissolve the compound, cooled to below 0°C, added dropwise to the above NICD solution under mechanical stirring, and mechanically stirred After 90 min, TLC detected the reaction end point, and stopped the reaction. Use ammonia water to adjust the pH value of the above reaction solution, add 100×3 mL dichloromethane respectively, extract three times, combine the organic phases, recover the organic solvent, and separate by silica gel column chromatography, petroleum ether: ethyl acetate: methanol = 6:2:1 , to obtain 0.0825 g of the target compound 8-(N-(3',4'-dichloro-phenyl))-ureido-isocordyrine with a yield of 46.9%. Compounds were detected as target...

Embodiment 3

[0059] Example 3: Synthesis of 8-(N-p-methylphenyl)-ureido-11-O-p-toluyl-isocordyline.

[0060] The NICD compound (0.3032 g, 0.85 mmol) was dissolved in 50 mL of dichloromethane, and the solution was cooled to below 0 °C in ice-brine. Another 4-tolyl isocyanate (0.1137 g, 0.85 mmol) was added to 50 mL of dichloromethane to dissolve the compound, cooled to below 0°C, added dropwise to the above NICD solution under mechanical stirring, mechanically stirred for 90 min, and TLC Detect the end point of the reaction and stop the reaction. Use ammonia water to adjust the pH value of the above reaction solution, add 100×3 mL dichloromethane respectively, extract three times, combine the organic phases, recover the organic solvent, and separate by silica gel column chromatography, petroleum ether: ethyl acetate: methanol = 6:2:1 , 0.1628 g of the target compound 8-(N-p-methylphenyl)-ureido-11-O-p-toluyl-isocordyrine was obtained, with a yield of 30.7%. Compounds were detected as targ...

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Abstract

The present invention discloses a chemical structure derivative of isocorydine (represented by a formula I), wherein the amino of NICD and the carbonyl of aryl isocyanate, carboxylic acid and acyl chloride are subjected to an amidation condensation reaction or NICD and aromatic amino are subjected to a symmetric amidation condensation reaction through solid phosgene to obtain the chemical structure derivative, wherein the compound has a certain in vitro and in vivo anticancer activity, and can be used as cancer prevention and treatment drug. The formula I is defined in the specification.

Description

technical field [0001] The present invention relates to the chemical structure derivation of natural product compounds, and belongs to the field of organic synthetic chemistry. Specifically, the present invention relates to a chemical structure derivative of isochoryline and its preparation method and application. Background technique [0002] Aporphine alkaloids are distributed in more than 100 kinds of plants in more than 20 families, and are important plant secondary metabolites. Most of these compounds have significant pharmacological activities, such as anti-oxidation, anti-platelet aggregation, anti-convulsion, Spasm, anti-malarial, anti-protozoal, anti-poliomyelitis virus, cytotoxicity, anti-Parkinson's disease, etc. Isocorydine (also known as isocorydine, English translation name: isocorydine, English name: isocorydine) is a typical aporphylloid alkaloid, widely distributed in bald acne flowers (see ZL201310107231.8) , Zijinlong, Dirong, Yanhusuo, Nandina, white lin...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D221/18C07D401/12A61P35/00
CPCC07D221/18C07D401/12A61K31/40C07D211/18Y02P20/582A61P35/00
Inventor 柳军玺邸多隆闫倩李如霞
Owner LANZHOU INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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