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Triptolide derivatives, and preparation methods, medicinal composition and uses thereof

A technology for triptolide and derivatives, which is applied in the fields of triptolide derivatives, preparation method thereof, and pharmaceutical compositions and uses thereof, and can solve the problems of few reports on the activity of derivatives and the like

Active Publication Date: 2012-11-21
INST OF MATERIA MEDICA AN INST OF THE CHINESE ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

According to existing literature reports, there are few derivatives that introduce an aromatic ring at the 14-position of triptolide through esterification, and there are few reports on the activity of such derivatives.

Method used

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  • Triptolide derivatives, and preparation methods, medicinal composition and uses thereof
  • Triptolide derivatives, and preparation methods, medicinal composition and uses thereof
  • Triptolide derivatives, and preparation methods, medicinal composition and uses thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] The synthesis of embodiment 1 compound 1

[0021]

[0022] Dissolve 36mg (0.1mmol) triptolide and 140mg (1mmol) benzoyl chloride in 20ml of anhydrous dichloromethane, add dropwise 1ml of anhydrous pyridine, stir and react at room temperature for 24h, TLC detects that the reaction is complete, stop stirring, and use 1M Dilute hydrochloric acid aqueous solution to wash off pyridine, adjust saturated aqueous sodium bicarbonate solution to neutral, dry over anhydrous sodium sulfate, evaporate to dryness under reduced pressure, and go through silica gel column chromatography, using cyclohexane-acetone (10:1-7:1) gradient After elution, 37 mg of a white solid was obtained, namely compound 1, with a yield of about 87%.

[0023] Compound 1C 27 h 28 o 7 ,ESI-MS m / z:465[M+H] + . 1 H-NMR (500MHz, CDCl 3 )δ: 1.256(1H,m,H-1a),1.591(1H,m,H-1b),1.898~2.172(5H,m,H-2a,2b,6a,6b,15),2.729(1H, m,H-5),3.537(1H,d,J=5.5Hz,H-7),3.886(1H,d,J=1.5Hz,H-11),3.583(1H,br.s,H-12 ),5.294(1H,...

Embodiment 2

[0024] The synthesis of embodiment 2 compound 2

[0025]

[0026] Dissolve 36mg (0.1mmol) triptolide and 0.15ml (1mmol) p-chlorobenzoyl chloride in 10ml anhydrous dichloromethane, add dropwise 1ml anhydrous pyridine, stir and react at room temperature for 24h, TLC detects that the reaction is complete, stop stirring , wash off pyridine with 1M dilute hydrochloric acid aqueous solution, adjust to neutral with saturated aqueous sodium bicarbonate solution, dry over anhydrous sodium sulfate, evaporate to dryness under reduced pressure, go through silica gel column chromatography, use cyclohexane-acetone (10:1-7: 1) Gradient elution to obtain 20 mg of white solid, namely compound 2, with a yield of about 40%.

[0027] Compound 2C 27 h 27 ClO 7 ,ESI-MS m / z:499[M+H] + . 1 H-NMR (400MHz, CDCl 3 )δ: 1.247(1H,m,H-1a),1.584(1H,m,H-1b),1.890~2.316(5H,m,H-2a,2b,6a,6b,15),2.711(1H, m,H-5),3.529(1H,d,J=5.6Hz,H-7),3.883(1H,d,J=2.4Hz,H-11),3.576(1H,d,J=2.4Hz, H-12),5.260(1H,s,H-14)...

Embodiment 3

[0028] The synthesis of embodiment 3 compound 3

[0029]

[0030] Dissolve 50mg (0.13mmol) triptolide and 0.5ml p-toluoyl chloride in 10ml anhydrous dichloromethane, add dropwise 0.5ml anhydrous pyridine, stir and react at room temperature for 48h, TLC detects that the reaction is complete, stop stirring, Wash off pyridine with 1M dilute hydrochloric acid aqueous solution, adjust to neutral with saturated aqueous sodium bicarbonate solution, dry over anhydrous sodium sulfate, evaporate to dryness under reduced pressure, go through silica gel column chromatography, and use cyclohexane-acetone (10:1-7:1 ) gradient elution to obtain 37 mg of white solid, namely compound 3, with a yield of about 77.8%.

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PUM

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Abstract

The invention discloses fifteen new triptolide derivatives, a medicinal composition containing one or more of the derivatives, and uses of the derivatives in the inhibition of the generation of NO by macrophages, especially anti-inflammation and immunological suppression, as medicines. The above compounds treat triptolide as a raw material, the fourteenth hydroxy group of triptolide and aromatic groups comprising benzoic acid, cinnamic acid and benzene sulfonic acid analogs are acylated to form ester derivatives. Active evaluation shows that the compounds have substantial inhibition activities on the generation of the inflammation factor NO by the macrophages.

Description

technical field [0001] The present invention relates to research on 15 new triptolide derivatives, their preparation method and their anti-inflammatory and immunosuppressive activity. Background technique [0002] Triptolide is one of the main active ingredients of the traditional Chinese herbal medicine Tripterygium wilfordii Hook f. An abietane-type diterpene compound with a unique configuration has obvious biological activities such as anti-inflammation, immunosuppression, anti-tumor and anti-male fertility. [0003] [0004] AIA: anti-inflammatory activity; ISA: immunosuppressive activity; TI: therapeutic index; CSF: safety factor; LESD: lowest effective dose; AFA: antifertility activity [0005] With the in-depth research on triptolide, people's understanding of its pharmacology, toxicology, pharmacokinetics and clinical application has become more and more in-depth and extensive. In addition to its high biological activity, it also has high toxicity and adverse re...

Claims

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Application Information

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IPC IPC(8): C07J73/00A61K31/585A61P29/00A61P37/02
Inventor 张东明侯琦魏佰兴王超袁绍鹏李创军白金叶
Owner INST OF MATERIA MEDICA AN INST OF THE CHINESE ACAD OF MEDICAL SCI
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