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Furazan NO donor type evodiamine derivatives with anti-tumor activity

A kind of technology of evodiamine and derivatives, applied in the field of natural medicine and medicinal chemistry

Inactive Publication Date: 2016-06-01
SHENYANG PHARMA UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Compared with the reports on extraction, separation, and mechanism of action, there are fewer reports on medicinal chemistry such as evodiamine structural modification and transformation, derivative synthesis, etc.

Method used

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  • Furazan NO donor type evodiamine derivatives with anti-tumor activity
  • Furazan NO donor type evodiamine derivatives with anti-tumor activity
  • Furazan NO donor type evodiamine derivatives with anti-tumor activity

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] 13-N-ethyl-2-(4-benzenesulfonyl-5-oxo-furazan-3-oxyl)-8,13,13b,14-tetrahydro-14-methylindole[2′, 3′;3,4]pyrido[2,1-b]quinazolin-5-(7H)-one (8a)

[0028] Mix 60gNaOH with 480mLH 2 The solution prepared by O was poured into a reaction flask, thiophenol (75mL, 0.63mol) was taken, and then chloroacetic acid (78g, 0.825mol) was added, and a large amount of white precipitates were precipitated in the reaction solution. 6N HCl was added to obtain phenylthioacetic acid (5) as a white solid. Dissolve 5 (20g, 0.12mol) in 90mL glacial acetic acid, add 24.3mL30% H 2 o 2 , stirring at room temperature. After the reaction is complete, add HNO 3 48mL. Heating reaction, after 4 hours, white needle-like crystals precipitated, filtered and dried to obtain 3,4-diphenylsulfonylfurazan nitrogen oxide (7). 7 (219.6 mg, 0.6 mmol) was dissolved in 5 mL CH 2 Cl 2 In, take evodiamine (1) (104mg, 0.3mmol), add DBU (0.4mmol) to CH 2 Cl 2 In, stir for 3h. The reaction was monitored by T...

Embodiment 2

[0030] 13-N-propyl-3-(4-benzenesulfonyl-5-oxo-furazan-3-oxyl)-8,13,13b,14-tetrahydro-14-methylindole[2′, 3'; 3,4]pyrido[2,1-b]quinpyridine-5(7H)-one (8b)

[0031] Referring to the synthetic method of Example 1. Yellow oil, 80% yield, ESI-MSm / z586.2[M+H] + . 1 H-NMR (400MHz, CDCl 3 )δ7.16~8.14(13H,m,H-1~4,9~12,-Ph),5.98(1H,br.s,H-3),4.40~4.51(1H,m,H-7b) ,3.20(1H,m,H-7a),3.03(1H,m,H-8b),2.92(1H,m,H-8a),2.40(3H,s,-NCH 3 ).

Embodiment 3

[0033] 13-N-Propyl-3-(3-(4-Benzenesulfonyl-5-oxo-furazan-3-oxyl)-propoxy)-8,13,13b,14-tetrahydro-14- Methylindole[2′,3′;3,4]pyrido[2,1-b]quinpyridine-5(7H)-one (8c)

[0034] Referring to the synthetic method of Example 1. Yellow oil, yield 81%, ESI-MSm / z644.3[M+H] + . 1 H-NMR (400MHz, CDCl 3 )δ7.16~8.12(13H,m,H-1~4,9~12,-Ph),6.00(1H,br.s,H-3),4.39(1H,m,H-7b),3.19 (1H,m,H-7a),3.02(1H,m,H-8b),2.92(1H,m,H-8a),2.40(3H,s,-NCH 3 ).

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Abstract

The invention relates to the field of natural medicines and medicinal chemistry and particularly relates to derivatives with modified 13-N of evodiamine. The invention discloses a preparation method of the 13-N furazan NO donor substituted evodiamine derivatives and evaluation of the anti-tumor activity. The structure of the compounds is shown in the specification, wherein R1 and R2 are (CH2)n or (CH2)n1O(CH2)n2, and n, n1 and n2 are integers between 1 and 8.

Description

technical field [0001] The invention relates to the fields of natural medicine and medicinal chemistry, in particular to derivatives modified at the 13-N position of evodiamine. The invention discloses the preparation method and antitumor activity evaluation of these evodiamine derivatives substituted by the 13-N furoxan NO donors. Background technique [0002] Evodiamine is an indolequinazolone alkaloid compound isolated from Rutaceae Evodia plants. Evodiamine is a light yellow needle-like crystal, insoluble in water, easily soluble in dichloromethane, chloroform, soluble in methanol, ethyl acetate and other organic solvents. It has a good inhibitory effect on a variety of tumor cells. Evodiamine has anti-tumor cell proliferation, inhibits the formation and invasion of tumor cell microtubules, induces tumor cell apoptosis and necrosis, and enhances cell autophagy. It is a good topoisomerase inhibitor. Studies have shown that evodiamine has certain inhibitory effects on c...

Claims

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Application Information

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IPC IPC(8): C07D471/14A61K31/519A61P35/00
CPCC07D471/14
Inventor 李达翃华会明李占林赵楠田康涛韩通胡旭方春艳
Owner SHENYANG PHARMA UNIVERSITY