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Flazin analog and preparation method and application thereof

A technology of analogs and drugs, applied in the field of drug synthesis, can solve the problem of no anti-tumor activity of Flazin analogs

Inactive Publication Date: 2007-09-19
KUNMING INST OF BOTANY - CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] So far, there is no report in the prior art that the Flazin analogs containing the compound of formula I have anti-tumor activity, and there is no report containing the compound of formula I as an active ingredient in the treatment of tumor diseases

Method used

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  • Flazin analog and preparation method and application thereof
  • Flazin analog and preparation method and application thereof
  • Flazin analog and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048] Example 1: Preparation of 1-(2'-quinoline)-6-methoxy-β-carboline-3-carboxylic acid (compound 1)

[0049] Step A: Synthesis of L-5-methoxy-tryptophan methyl ester

[0050] Add 100mL of dry methanol to 10mmol of L-5-methoxy-tryptophan, under magnetic stirring, cool to below -10°C, slowly add 10mL of thionyl chloride, then let it rise to room temperature naturally, and then heat to reflux for 3h . Spin off excess methanol and thionyl chloride under reduced pressure, then add an appropriate amount of water to dissolve, adjust the pH value to 9-10, extract with ethyl acetate, combine the organic phases, dry over anhydrous sodium sulfate, evaporate the solvent under reduced pressure, and obtain a white Solid 2.38g, Yield: 96%, mp 89-92°C, C 13 h 16 N 2 o 3 .FAB + -MS m / z: 249(M+1).

[0051] Step B: Synthesis of methyl 1-(2'-quinoline)-6-methoxy-β-carboline-3-carboxylate

[0052] Add 10 mL of dry dichloromethane to 1 mmol of L-5-methoxy-tryptophan methyl ester, 1 mmol ...

Embodiment 2

[0055] Example 2 Preparation of 1-(4'-trifluoromethylphenyl)-6-methoxy-β-carboline-3-carboxylic acid (compound 2)

[0056] Step A: Synthesis of 1-(4'-trifluoromethylphenyl)-6-methoxy-β-carboline-3-carboxylic acid methyl ester with L-5-methoxy-tryptophan methyl ester and 4'-trifluoromethylbenzaldehyde was used as raw material, and the operation was similar to step B of Example 1 to obtain 340.0 mg of light yellow solid, Yield: 85%, mp 165-168 °C, C 21 h 15 N 2 o 3 f 3 .FAB + -MS m / z: 401(M+1). 1 H NMR (400MHz, CDCl 3 ) δ (ppm) 8.89 (1H, s), 8.15 (2H, d, J = 8.0Hz), 7.84 (2H, d, J = 8.0Hz), 7.68 (1H, d, J = 2.4Hz), 7.55 ( 1H, d, J=8.8Hz), 7.27(1H, dd, J=2.4Hz, J=8.4Hz), 4.09(3H, s), 4.00(3H, s).

[0057] Step B: Synthesis of -(4'-trifluoromethylphenyl)-6-methoxy-β-carboline-3-carboxylic acid as 1-(4'-trifluoromethylphenyl)-6-methanol Oxy-β-carboline-3-carboxylic acid methyl ester was used as raw material, and the operation was similar to Example 1 step C to obtain 191.0...

Embodiment 3

[0058] Example 3 Preparation of 1-(2'-methylphenyl)-6-fluoro-β-carboline-3-carboxylic acid (compound 3)

[0059] Step A: Synthesis of L-5-fluoro-tryptophan methyl ester

[0060] Using L-5-fluoro-tryptophan as raw material, the operation is similar to step A of Example 1 to obtain 2.24 g of white solid L-5-fluoro-tryptophan methyl ester, Yield: 95%, mp 87-89 ° C, C 12 h 13 FN 2 o 2 .FAB + -MS m / z: 237(M+1).

[0061] Step B: Methyl 1-(2'-phenyl)-6-fluoro-β-carboline-3-carboxylate

[0062] Using L-5-fluoro-tryptophan methyl ester and 2-methylbenzaldehyde as raw materials, the operation is similar to step B of Example 1 to obtain 273.8 mg of yellow solid, Yield: 82%, 158-160 ° C, C 20 h 15 N 2 o 2 F FAB + -MS m / z: 335(M+1). 1 HNMR (500MHz, CDCl 3 )δ (ppm) 10.54 (1H, s), 8.72 (1H, s), 7.71 (1H, d, J=6.7Hz), 7.42 (2H, m), 7.25 (3H, m), 7.16 (1H, m ), 3.89(3H,s), 2.13(3H,s).

[0063] Step C: 1-(2'-phenyl)-6-fluoro-β-carboline-3-carboxylic acid

[0064] Using methyl 1-(...

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Abstract

The invention provides Flazin analog (abstract formula I compound) and the preparing method thereof, belonging to medicine synthesis field, meanwhile provides a medicine combination for preventing and treating tumor which has the formula I compound or pharmacological acceptable salt as active components and the applications in the preparation treatment and anti-tumor medicine areas of said compound and its medicine combination.

Description

Technical field: [0001] The invention belongs to the field of drug synthesis, and specifically relates to a Flazin analogue, a preparation method thereof, and an application thereof in medicines for treating and preventing tumors. Background technique: [0002] In 1936, Japanese scholar Higashi first isolated a strong fluorescent compound from Japanese rice wine and named it Flazin, but did not determine its chemical structure (Sci.Pap.Phys.Chem.Res.Inst.1936, 15, 1060); until 1986, Japanese scholar Nakatsuka used the Flazin isolated from Japanese soybean paste (Japanesesoy sauce) as raw material, and through chemical reactions such as esterification and hydrogenation, just deduced its chemical structure (Tetrahedron Letters.1986, 27 , 3399-3402); in 2002, American scholar Sun also isolated Flazin from a common Chinese herbal medicine Brucea javanica, and reported its spectral data for the first time, and relied on 2D-NMR ( 1 H- 1 H COZY, HMQC, HMBC) spectroscopic techniqu...

Claims

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Application Information

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IPC IPC(8): C07D471/04A61K31/437A61P35/00
Inventor 刘吉开卿晨汤建国李春雷董泽军张雁丽
Owner KUNMING INST OF BOTANY - CHINESE ACAD OF SCI
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