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Low-toxicity 1,8-naphthalimide derivative and synthetic method and application thereof

A synthesis method and reaction technology, applied in the field of medicine, can solve the problems of retention, side effects, adverse reactions, etc., and achieve the effects of small side effects, significant inhibitory activity, and significant biological activity

Inactive Publication Date: 2018-06-12
GUANGXI NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Existing studies have shown that the study of naphfemate on breast cancer has entered phase II clinical trials, but as a chemotherapy drug, it has certain adverse reactions to human bone marrow; it is easily acetylated by N-acetyltransferase II (NAT2) in vivo. N-acetylaminonaphtamide is produced by chemical synthesis, and the metabolism of the acetylated product in the body due to individual differences will produce uncertain toxic and side effects, making it currently in phase III clinical research

Method used

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  • Low-toxicity 1,8-naphthalimide derivative and synthetic method and application thereof
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  • Low-toxicity 1,8-naphthalimide derivative and synthetic method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Get 1mmol of naphthalene, add it to 4mL of acetonitrile and stir to dissolve, dissolve 1.5mmol of 2-fluorobenzoyl chloride in 2mL of acetonitrile, put it in a constant pressure dropping funnel, and use nitrogen protection for the reaction system, and pour into the naphthalene-acetonitrile solution Slowly add 2-fluorobenzoyl chloride-acetonitrile solution dropwise, and react for 2.5h after the dropwise addition is completed. After the reaction, remove the solvent and purify using silica gel column chromatography (dichloromethane:methanol=20:1, v / v) , to obtain a pale yellow solid (about 90% yield).

[0032] The obtained light yellow solid is identified:

[0033] (1) The H NMR and C NMR data are shown below, respectively.

[0034] 1 H NMR (500MHz, DMSO) δ11.06(s, 1H), 8.92(s, 1H), 8.83(d, J=1.9Hz, 1H), 8.48(d, J=8.3Hz, 1H), 8.44(d ,J=7.3Hz,1H),7.90–7.87(m,1H),7.78(d,J=7.4Hz,1H),7.67–7.63(m,1H),7.45–7.37(m,2H),4.41( t, J=5.7Hz, 2H), 3.48(d, J=5.1Hz, 2H), 2.93(d, J=4.1H...

Embodiment 2

[0040] Repeat Example 1, the difference is:

[0041] The reaction time was changed to 1 h, and the rest of the reaction conditions remained unchanged (the yield was about 75%).

[0042] The product obtained in this example was analyzed by proton nuclear magnetic resonance spectrum and carbon nuclear magnetic resonance spectrum, and it was determined to be the target product.

Embodiment 3

[0044] Repeat Example 1, the difference is:

[0045] The reaction time was changed to 3 h, and the rest of the reaction conditions remained unchanged (the yield was about 87%).

[0046] The product obtained in this example was analyzed by proton nuclear magnetic resonance spectrum and carbon nuclear magnetic resonance spectrum, and it was determined to be the target product.

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Abstract

The invention discloses a low-toxicity 1,8-naphthalimide derivative and a synthetic method and application thereof. The synthetic method of the 1,8-naphthalimide derivative mainly comprises the following steps: dissolving amonafide and 2-fluorobenzoyl chloride in an organic solvent and reacting; and after reaction is finished, removing a solvent to obtain a coarse product as a target object. Testsshow that the derivative has remarkable bioactivity, and particularly has remarkable inhibition activity to non-small cell lung cancer cell strains HCC-827 and other tumor cell strains, moreover, toxic and side effects of human normal cells are small, and thus, the 1,8-naphthalimide derivative is expected to be developed into a targeted therapy drug. The structure of the 1,8-naphthalimide derivative is as shown in a formula (I) as shown in the specification.

Description

technical field [0001] The invention relates to a 1,8-naphthalimide derivative with low toxicity and its synthesis method and application, belonging to the technical field of medicine. Background technique [0002] Naphthalimide derivatives have a unique planar rigid structure, which enables them to have a strong ability to embed DNA. More and more studies have shown that naphthalimide and its derivatives have good anti-tumor activity. It has a high affinity for DNA molecules, can bind to DNA through intercalation, and exhibits a micromolar level of IC in the experiment of inhibiting tumor cell growth in vitro 50 , but they are also more toxic to normal cells. [0003] At present, naphthalimide derivatives that have entered clinical research include mitonafide, amonafide, elinafide and bisnafide. Wherein the structure of nafate is as shown in the following formula (II): [0004] [0005] Existing studies have shown that the study of naphfemate on breast cancer has ente...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D221/14A61P35/00
CPCC07D221/14
Inventor 曾淑兰李亮萍张国海彭艳石镇豪
Owner GUANGXI NORMAL UNIV
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