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Tetrahydro-beta-carboline derivative, preparation method thereof and use thereof

A technology of tetrahydrocarboline and compound, applied in the field of tetrahydro-β-carboline derivatives, can solve the problems of limited application, poor bioavailability, poor solubility and the like

Active Publication Date: 2012-03-28
CAPITAL UNIVERSITY OF MEDICAL SCIENCES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Tetrahydro-β-carboline-3-carboxylic acid is an indole alkaloid with definite biological activity from vegetables in southern my country, so it has reliable safety, low toxicity and side effects, and has potential clinical application value, but its solubility is very poor , almost insoluble in any solvent, resulting in extremely poor bioavailability
This shortcoming severely limits its application in food and medicine

Method used

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  • Tetrahydro-beta-carboline derivative, preparation method thereof and use thereof
  • Tetrahydro-beta-carboline derivative, preparation method thereof and use thereof
  • Tetrahydro-beta-carboline derivative, preparation method thereof and use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] Example 1 Preparation of N-tert-butoxycarbonyl-tetrahydrocarboline-2-amino-tetraacetyl-D-glucose 4

[0030]

[0031] Under ice bath, N-Boc-tetrahydrocarboline-3-carboxylic acid 3 (3.48g, 11.0mmol) was dissolved in anhydrous THF (150ml), and HOBt (1.62g, 12.0mmol), DCC (2.47g, 12.0mmol) was activated to obtain liquid A. 2-Amino-tetraacetyl-D-glucose (4.45 g, 10.0 mmol) was dissolved in anhydrous THF, and NMM was added to adjust the pH value to 7 to obtain liquid B. Add B to A, adjust the pH to 8, and stir at room temperature for 18 hours. TLC showed disappearance of starting material spots. The reaction mixture was filtered, the filtrate was concentrated to dryness under reduced pressure, and the residue was dissolved in ethyl acetate. The resulting solution was sequentially washed with saturated NaHCO 3 Aqueous solution and 5% KHSO 4 Washing with aqueous solution and saturated NaCl aqueous solution. Separate the ethyl acetate layer, anhydrous Na 2 SO 4 After ...

Embodiment 2 4

[0032] Example 2 Preparation of Tetrahydrocarboxyloyl-2-amino-tetraacetyl-D-glucose 5

[0033]

[0034] N-Boc-tetrahydrocarbolinoyl-2-amino-tetraacetyl-D-glucose 4 (645 mg, 1.00 mmol) was dissolved in 5 ml of 4N hydrogen chloride-ethyl acetate solution. The reaction mixture was stirred at 0°C for 1 h, the reaction mixture was concentrated to dryness under reduced pressure, the residue was dissolved in 10 ml of ethyl acetate, and the resulting solution was concentrated to dryness under reduced pressure. This operation was repeated three times to remove free hydrogen chloride. The obtained solid was used in the next reaction immediately without purification.

Embodiment 3

[0035] Example 3 Preparation of N-(Boc-alanyl)-tetrahydrocarbolinoyl-2-amino-tetraacetyl-D-glucose 7a

[0036]

[0037] According to the operation of Example 1, THC-2-amino-tetraacetyl-D-glucose 5 (582mg, 1.00mmol) and Boc-L-Ala-OH 6a (207mg, 1.10mmol), HOBT ( Condensation of 162mg, 1.20mmol) and DCC (247mg, 0.980mmol) in anhydrous THF (10ml) afforded 7a (259mg, 0.362mmol (36%) of the title compound. [α] 25 D -5.8 (c 0.1, CHCl 3 ); IR (cm -1 , KBr, neat): 3381, 1747, 1658; 1 HNMR (300MHz, CDCl 3 ): δ9.41(1H, s, N-H), 8.67(1H, s, N-H), 7.53-7.07(4H, m, Ar-H), 6.21(1H, d, J 2，NH 8.7Hz, N-H), 5.93 (1H, d, J NH，α 5.4Hz, N-H), 5.63 (1H, d, J 1’，2’ 8.7Hz, H-1'), 5.60(1H, m, H-3'), 5.30-5.03(2H, m, H-α, H-2'), 4.96(1H, m, H-3), 4.87-4.74 (2H, m, H-1a, H-1b), 4.36-4.12 (2H, m, H-5', H-6a'), 4.04 (1H, t, J 3’，4’ =J 4’，5’ =12.0Hz, H-4'), 3.74(1H, m, H-6b'), 3.46(1H, m, H-4a), 3.16(1H, m, H-4b), 2.03(3H, s, CH 3 ), 1.99 (3H, s, CH 3 ), 1.95 (3H, s, CH 3 ), 1.58 (3H, d, ...

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PUM

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Abstract

The invention relates to a tetrahydro-beta-carboline derivative, a preparation method thereof and a use thereof. The invention discloses the tetrahydro-beta-carboline derivative described as a general formula (I), wherein R1 is H, benzyl, benzoyl or C1-6 acyl, R2 is H, C1-6 alkyl, C1-6 alkoxyl, COOH, COOR3, AA or AA-R4, R3 is C1-6 alkyl, R4 is COOH or COOR3 and AA is amino acid group. The invention further discloses the preparation method of a compound described as the general formula (I), a pharmaceutical composition containing the compound described as the general formula (I) and the use ofthe compound in the preparation of anti-inflammatory medicaments.

Description

technical field [0001] The present invention relates to tetrahydro-β-carboline derivatives with anti-inflammatory activity, their preparation method, pharmaceutical composition containing the compound and the use of the compound for preparing anti-inflammatory drugs. Background technique [0002] There are two types of anti-inflammatory drugs: one is steroidal anti-inflammatory drugs, that is, the glucocorticoid hydrocortisone secreted by the adrenal cortex and its synthetic derivatives. The other is non-steroidal anti-inflammatory drugs such as aspirin and phenylbutazone. [0003] The chemical essence of steroidal anti-inflammatory drugs is natural or synthetic glucocorticoids. In 1949, Hench et al first used cortisone to treat arthritis, rheumatism, etc. Although it was found that it had a strong anti-inflammatory effect, its side effects were serious, especially when it was applied in large doses, it may not only cause dependence, but also cause adrenal cortex function. ...

Claims

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Application Information

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IPC IPC(8): C07H13/06C07H5/04C07H1/00A61K31/706A61P29/00
Inventor 张建伟彭师奇赵明曾莉
Owner CAPITAL UNIVERSITY OF MEDICAL SCIENCES
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