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Glycosyl modified naphthalimide-polyamine conjugate as well as preparation method and application thereof

A technology of naphthalimide and sugar modification, applied in the preparation of sugar derivatives, sugar derivatives, sugar derivatives, etc., to achieve the effects of improving water solubility and fat solubility, reducing toxic side effects, and improving maximum tolerance

Active Publication Date: 2021-06-11
HENAN UNIVERSITY
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Studies in recent years have shown that glycosyl-modified products have a better effect in anti-tumor metastasis, but how to design glycosyl-modified naphthalimide conjugates to target liver cancer and liver cancer metastasis has not been reported.

Method used

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  • Glycosyl modified naphthalimide-polyamine conjugate as well as preparation method and application thereof
  • Glycosyl modified naphthalimide-polyamine conjugate as well as preparation method and application thereof
  • Glycosyl modified naphthalimide-polyamine conjugate as well as preparation method and application thereof

Examples

Experimental program
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Effect test

preparation example Construction

[0055] Preparation of Compound 8a, 8b:

[0056] Compound 1 (glucose) reacts fully in the presence of acetic anhydride and sodium acetate to obtain compound 2 (fully acetylated glucose), and compound 2 reacts with a mixed solvent of THF / water under conditions of ammonia gas to obtain 1 The deprotected compound 3, after the compound 3 passed through the trichloroacetonitrile donor at the 1 position, and then reacted with 5a(5b) through glycosylation coupling reaction, the compound 6a(6b) was obtained, and the compound 6a(6b) was obtained under hydrogen atmosphere Compound 7a (7b) was obtained by debenzylation at 1-position. Compound 7a (7b) was catalyzed by DMF under the action of oxalyl chloride and reacted at room temperature to obtain compound 8a (8b).

[0057] The specific preparation process of compound 8a (8b) and compound 11 is not the invention point of the present invention, so it will not be described again.

[0058] Specific synthetic methods and process parameters o...

Embodiment 1

[0060] Example 1: 12a

[0061]

[0062] 1 H NMR (300MHz, Chloroform-d) δ9.06(s,1H),8.54(s,1H),8.36(d,J=12.3Hz,1H),7.96(s,1H),7.58(s,1H) ,5.32–4.96(m,4H),4.20(d,J=28.8Hz,3H),3.80(s,2H),3.36(s,2H),2.83(s,6H),2.00(s,12H). 13 C NMR(75MHz,Chloroform-d)δ170.58,170.20,170.01,169.41,167.22,164.09,163.62,136.32,133.98,130.00,127.35,124.06,121.80,100.66,72.15,72.02,71.54,68.39,68.12,61.61,55.25 ,43.64,35.42,20.95,20.68,20.56.ESI-MS(positive ion mode):m / z[M+H] + :calcd:672.2405; obsd:672.2407.Calcdfor C 32 h 37 N 3 o 13 : C 57.22%, H 5.55%, N 6.26%. Found: C 57.20%, H 5.50%, N 6.24%.

[0063] Its preparation method is as follows:

[0064] Compound 11 (1 mmol) and compound 8a (1.5 mmol) were ice-bathed in anhydrous acetone (5 mL) for half an hour, then reacted overnight at room temperature to obtain the target compound 12a.

[0065] Concrete synthetic route is as follows:

[0066]

Embodiment 2

[0067] Example 2: 12b

[0068]

[0069] 1 H NMR (300MHz, Chloroform-d) δ8.89(s, 1H), 8.33(d, J=7.0Hz, 1H), 8.15(s, 1H), 7.96(d, J=8.1Hz, 1H), 7.64 (s,1H),5.19(t,J=9.3Hz,1H),5.11–4.92(m,2H),4.54(t,J=6.5Hz,1H),4.31(d,J=5.8Hz,2H) ,4.21(s,2H),3.66(d,J=27.8Hz,2H),3.32(s,2H),2.87–2.73(m,2H),2.47(d,J=27.1Hz,6H),2.03( dt,J=13.0,8.2Hz,12H),1.23(s,2H). 13C NMR(75MHz,Chloroform-d)δ171.84,170.87,170.20,169.62,169.39,164.26,163.69,133.72,132.33,129.53,127.30,123.72,122.85,122.07,121.48,100.92,72.72,71.90,71.42,69.33,68.41 ,61.80,57.29,45.62,37.70,33.66,25.41,20.80,20.74,20.58.ESI-MS(positive ion mode):m / z[M+H] + :calcd:700.2718; obsd:700.2715.Calcdfor C 34 h 41 N 3 o 13 : C 58.36%, H 5.91%, N 6.01%. Found: C 58.26%, H 5.87%, N 5.98%.

[0070] Its preparation method is as follows:

[0071] The difference between the preparation method of compound 8b in Example 2 and Example 1 is that compound 6a is replaced by 5a for the reaction to finally obtain compound 8b.

[0072] Compoun...

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Abstract

The invention belongs to the technical field of medicinal chemistry, and particularly relates to a glycosyl modified naphthalimide-polyamine conjugate as well as a preparation method and application thereof. According to the invention, a naphthalimide mother nucleus is modified by glycosyl groups such as peracetyl or deprotected glucose, galactose, mannose, rhamnose, maltose, lactose, cane sugar and the like, so that the glycosyl transporter (GLUTs) with high expression of targeted tumor cells is realized, and better targeting on liver cancer and advanced liver cancer is realized. The novel naphthalimide-polyamine conjugate targeting liver cancer and advanced liver cancer is found for the first time, the naphthalimide complex capable of regulating subcellular organelles is found for the first time, and a new thought and a research direction are provided for treatment of the advanced liver cancer.

Description

technical field [0001] The invention belongs to the technical field of medicinal chemistry, and in particular relates to a glycosyl-modified naphthalimide-polyamine conjugate, a preparation method and application thereof. Background technique [0002] Hepatocellular carcinoma (HCC) is a malignant tumor that is discovered late and has a high fatality rate, ranking sixth among malignant tumors. About 90% of HCC patients do not survive for more than 5 years even after surgery, and despite advances in rational and combined drug-based cancer treatment techniques, current anticancer drugs cannot cure recurrence and metastasis after HCC resection. Therefore, it is imminent to develop new drugs targeting HCC and HCC metastasis. [0003] In recent years, in addition to photophysical properties, the activity of naphthalimide as a multifunctional antitumor active compound has also been continuously improved. Naphthimide and its derivatives, represented by naphthalene, are DNA interca...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07H15/26C07H1/00A61P35/00A61P37/02
CPCC07H15/26C07H1/00A61P35/00A61P37/02
Inventor 马静王佳佳方东孙华谢松强
Owner HENAN UNIVERSITY
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