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Banisterine derivant and uses thereof

A drug, compound technology

Active Publication Date: 2013-10-23
XINJIANG HUASHIDAN PHARMA RES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

For example, CN1552711A and WO / 2004 / 106335 disclosed that the chemical structure of dehydrocamelides has been systematically modified, and found that the anti-tumor activity in vivo is significantly improved and the neurotoxicity is significantly reduced. However, these modified compounds The tumor-inhibitory rate of the experimental model of tumor-bearing mice is only 46.9%.
[0005] In summary, most of the existing dehydrohalamine derivatives have no clinical application prospects due to their low antitumor activity or high neurotoxicity. Therefore, an improved dehydrohalamine derivative is urgently needed to meet the clinical need

Method used

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  • Banisterine derivant and uses thereof
  • Banisterine derivant and uses thereof
  • Banisterine derivant and uses thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0324] Example 1 7-hydroxy-9-ethyl-1-methyl-β-carboline (1)

[0325] Step A: 7-Methoxy-9-ethyl-1-methyl-β-carboline

[0326] Harmaine (2.12g, 10mmol), DMF (50ml), 60% NaH (0.6g, 15mmol) were mixed, stirred at room temperature for 10 minutes, added with ethyl iodide (15mmol), stirred at room temperature for reaction, followed by TLC detection. After the reaction is completed, the reaction mixture solution is poured into 100 ml of ice water, stirred at room temperature for 2 hours, filtered, and washed with a large amount of water to obtain a pale yellow solid. The above solid was dissolved in anhydrous ethanol, adjusted to pH 2 with concentrated hydrochloric acid, and then concentrated to dryness under reduced pressure. The anhydrous ethanol was taken with water 3 times to obtain a yellow oil, which was recrystallized from acetone and filtered to obtain white crystals. Hydrochloride. It can be used directly in the next step without further purification.

[0327] Step B: 7-Hydroxy-9...

Embodiment 2

[0331] Example 2 7-hydroxy-9-n-butyl-1-methyl-β-carboline (2)

[0332] The operation is the same as in Example 1. In step A, iodo n-butane is used as the alkylating agent.

[0333] Obtained 2.2g of white crystals, yield 87%, mp 205-206°C;

[0334] FAB-MS m / e(M+1)255;

[0335] IR (KBr) 3500-1750, 1618, 1566, 1492, 1451, 1413, 1325, 1238, 1187, 1137, 1112, 980;

[0336] 1 H-NMR(500MHz, DMSO-d 6 )δ9.72 (1H, s, OH); 8.12-8.13 (1H, d, J=5.0Hz, H-3); 7.95-7.97 (1H, d, J=8.5Hz, H-4); 7.78- 7.79 (1H, d, J = 5.0 Hz, H-5); 6.90-6.91 (1H, m, H-6); 6.72-6.75 (1H, m, H-8); 4.41-4.44 (2H, m, NCH 2 CH 2 CH 2 CH 3 ); 2.91(3H, s, CH 3 ); 1.67-1.74 (2H, m, NCH 2 CH 2 CH 2 CH 3 ); 1.36-1.40 (2H, m, NCH 2 CH 2 CH 2 CH 3 ); 0.92-0.94(2H, m, NCH 2 CH 2 CH 2 CH 3 ).

Embodiment 3

[0337] Example 3 7-hydroxy-9-isobutyl-1-methyl-β-carboline (3)

[0338] The operation is the same as in Example 1. In step A, 1-iodo-2-methylpropane is used as the alkylating agent. Obtained 2.0 g of white crystals, yield 79%, mp 246-248°C;

[0339] FAB-MS m / e(M+1)255;

[0340] IR (KBr) 3500-1750, 1626, 1568, 1447, 1392, 1203, 1136, 977, 820;

[0341] 1 H-NMR(500MHz, DMSO-d 6 )δ9.70 (1H, s, OH); 8.13-8.14 (1H, d, H-3); 7.95-7.97 (1H, d, H-4); 7.79-7.80 (1H, d, H-5) ; 6.93 (1H, s, H-6); 6.72-6.74 (1H, d, H-8), 4.26-4.27 (2H, d, NCH 2 CH[CH 3 ] 2 ); 2.90(3H, s, CH 3 ); 2.11-2.17(1H, m, NCH 2 CH[CH 3 ] 2 ); 0.85-0.87(6H, s, NCH 2 CH[CH 3 ] 2 ).

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Abstract

The invention relates to a yageine derivative and salts of compounds. The invention synthesizes the novel yageine derivative compounds which can strengthen the antineoplastic activity and reduce the toxicity of a nervous system through the structural modification to locus 1, 2, 3, 7 and 9 of beta-carboline parent nuclei of yageine. The compounds can be used for preparing drugs used to treat various tumor diseases through the screening study of in vivo and in vitro anti-tumor experimental models.

Description

Technical field [0001] The present invention belongs to the field of pharmaceutical compounds, and relates to β-carboline alkaloid compounds and their applications, and more specifically, to harmine derivatives and their applications in anti-tumor drugs. Background technique [0002] Harmaine and its analogs have a wide range of pharmacological effects, mainly in two aspects: nerve activity and anti-tumor activity. The neural activity of harmine and its derivatives is mainly manifested in its excitatory effect on the cerebral cortex, motor center, spinal cord, etc. It can cause hallucinations, tremors, paroxysmal convulsions, excitement of the pons, and cause certain specific movements and limbs. Rigid; in the study of the anti-tumor effect of the total alkaloids of harmine extracted from the seeds of harmine, it was found that the two mixed alkaloids of harmine and harmine have significant effects on 6 kinds of human tumor cell lines cultured in vitro The cytotoxic effect of cy...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D471/04A61K31/437A61P35/00
Inventor 曹日晖武嘉林于富生王子厚彭文烈
Owner XINJIANG HUASHIDAN PHARMA RES