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

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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
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