7 site-connected bis(beta-carboline alkaloid) compound and its preparation method, pharmaceutical composition and use

A compound, carboline base technology, applied in the preparation of anti-tumor drugs, the field of 7-position double β-carboline base compounds, can solve the problem of not disclosing the anti-tumor effect

Inactive Publication Date: 2015-07-01
XINJIANG HUASHIDAN PHARMA RES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] According to the synthesis method of Winckler et al., Zheng et al. (2011) synthesized the 9-position methylene bridge link and 11 C-labeled bis-3,4-dihydro-β-carbolines and bis-β-carbolines were foun

Method used

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  • 7 site-connected bis(beta-carboline alkaloid) compound and its preparation method, pharmaceutical composition and use
  • 7 site-connected bis(beta-carboline alkaloid) compound and its preparation method, pharmaceutical composition and use
  • 7 site-connected bis(beta-carboline alkaloid) compound and its preparation method, pharmaceutical composition and use

Examples

Experimental program
Comparison scheme
Effect test

preparation example 1

[0178]

[0179] 1,9-Dimethyl-β-carboline-7-ol:

[0180] Synthesis of 1,9-Dimethyl-β-carboline-7-ol:

[0181] (a) Synthesis of 7‐methoxy‐1,9‐dimethyl‐β‐carboline:

[0182] Add dehydrohaeline (2.12g, 10mmol) and DMF (50ml) into a 100ml eggplant-shaped bottle, stir well, add NaH (0.8g, 20mmol) and stir for 10min, then add iodomethane (1.73ml, 15mmol) and stir at room temperature , TLC tracking detection. After the reaction was completed, the reaction solution was poured into 200 ml of ice water, and extracted three times with ethyl acetate. The organic phases were combined, washed with water and saturated brine. Add saturated hydrogen chloride-ethanol solution to the organic phase to pH = 2-3, distill under reduced pressure, recrystallize from acetone, and filter to obtain a yellow solid. The above solid was dissolved in 100ml of water, with NaHCO 3 Adjust pH=8‐9, extract with ethyl acetate three times, combine organic phases, wash with water and saturated brine. The org...

preparation example 2

[0186]

[0187] Synthesis of 9‐ethyl‐1‐methyl‐β‐carboline‐7‐ol:

[0188] (a) Synthesis of 9‐ethyl‐7‐methoxy‐1‐methyl‐β‐carboline:

[0189] Add dehydrohaeline (2.12g, 10mmol) and DMF (50ml) into a 100ml eggplant-shaped bottle, stir well, add NaH (0.8g, 20mmol) and stir for 10min, then add iodoethane (1.6ml, 15mmol) at room temperature Stirring, TLC follow-up detection. After the reaction was completed, the reaction solution was poured into 200 ml of ice water, and extracted three times with ethyl acetate. The organic phases were combined, washed with water and saturated brine. Add saturated hydrogen chloride-ethanol solution to the organic phase to pH = 2-3, distill under reduced pressure, crystallize acetone, and filter to obtain a yellow solid. The above solid was dissolved in 100ml of water, with NaHCO 3 Adjust the pH to 8‐9, extract 3 times with ethyl acetate, combine the organic phases, wash with water, and wash with saturated brine. The organic phase was dehydrate...

preparation example 3

[0193]

[0194] Synthesis of 9-n-butyl-1-methyl-β-carboline-7-ol:

[0195] (a) Synthesis of 9-n-butyl-7-methoxy-1-methyl-β-carboline:

[0196] Add dehydrobamaline (2.12g, 10mmol) and DMF (50ml) into a 100ml eggplant-shaped bottle, stir well, add NaH (0.8g, 20mmol) and stir for 10min, then add iodo-n-butane (1.38ml, 15mmol ) Stirring at room temperature, followed by TLC detection. After the reaction was completed, the reaction solution was poured into 200 ml of ice water, and extracted three times with ethyl acetate. The organic phases were combined, washed with water and saturated brine. Add saturated hydrogen chloride-ethanol solution to the organic phase to pH = 2-3, distill under reduced pressure, crystallize acetone, and filter to obtain a yellow solid. The above solid was dissolved in 100ml of water, with NaHCO 3 Adjust the pH to 8‐9, extract 3 times with ethyl acetate, combine the organic phases, wash with water, and wash with saturated brine. The organic phase w...

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Abstract

The invention discloses a 7 site-connected bis(beta-carboline alkaloid) compound and its preparation method, pharmaceutical composition and use. The bis(beta-carboline alkaloid) compound and its medicinal salt are shown in the general formula I. The bis(beta-carboline alkaloid) compound is prepared by condensation of a beta-carboline intermediate and dihalogenated alkane. The invention discloses a pharmaceutical composition. The pharmaceutical composition comprises an effective dose of the bis(beta-carboline alkaloid) compound shown in the formula I and pharmaceutically acceptable carriers. The invention relates to a use of the bis(beta-carboline alkaloid) compound in preparation of drugs for resisting cancers such as melanoma, stomach cancer, lung cancer, breast cancer, kidney cancer, liver cancer, human oral epidermoid carcinoma, cervical carcinoma, ovarian cancer, pancreas cancer, prostate cancer and colorectal carcinoma.

Description

technical field [0001] The invention relates to a class of 7-position-connected bis-carboline base compounds and pharmaceutically acceptable salts thereof, a preparation method thereof, a pharmaceutical composition of such compounds, and an application thereof in the preparation of antitumor drugs; belonging to medicine technology field. Background technique [0002] Jiang et al. (2002) reported the design and synthesis of bis-3,4-dihydro-β-carbolines and bis-β-carbolines linked by a methylene bridge at the 1-position, and found that such bis-β-carbolines Alkali is cytotoxic to the L1210 cell line. [0003] Cook et al. (2005, 2010) reported the synthesis of bis-β-carbolines linked by a 6-alkyne bridge, and subsequently confirmed that the bis-β-carboline bases are sensitive to benzodiazepine receptors (Bz) and γ-aminobutyric acid Acid (GABA) receptors have good affinity. [0004] Winckler et al. (2010) designed bis-3,4-dihydro-β-carboline and bis-β-carboline compounds conn...

Claims

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Application Information

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IPC IPC(8): C07D519/00C07D471/04A61K31/437A61P35/00
Inventor 马芹王子厚郭亮范文玺武嘉林陈雪梅周凡
Owner XINJIANG HUASHIDAN PHARMA RES
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