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Naphthalimide derivative and preparing method and application thereof

A technology of naphthalimide and derivatives, applied in the field of naphthalimide derivatives and their preparation

Active Publication Date: 2016-06-01
HENAN UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, most of them were abandoned due to various side effects such as myelosuppression, dose limitation, etc.

Method used

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  • Naphthalimide derivative and preparing method and application thereof
  • Naphthalimide derivative and preparing method and application thereof
  • Naphthalimide derivative and preparing method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] 2-{3-[3-(3-Aminopropyl)-aminopropyl]-aminopropyl}-2-[(2-dimethylamino)-ethyl]1H-benzisoquinoline-1 Preparation of 3(2H)-diketoacetamide pentahydrochloride (17a):

[0022]

[0023] (1) Take 5mmol (1.04g) of compound 14, 7.5mmol (1.0g) of anhydrous potassium carbonate in 50ml of acetonitrile, slowly add 5ml of acetonitrile solution of chloroacetyl chloride (containing 6mmol of chloroacetyl chloride) with stirring at room temperature. , Stirring at room temperature overnight, the reaction is over, suction filtration under reduced pressure, collecting the solid, washing with acetonitrile, and drying to obtain compound 15a;

[0024] (2) 1mmol of compound 15a and 1.5mmol (0.2g) of anhydrous potassium carbonate in 15ml of dry acetonitrile, add 5ml of N,N-dimethylformamide to the mixed solution, stir at 45℃ for 15min, add 5a1mmol, 45℃ Stir under conditions and monitor by TLC. After the reaction, the solvent was evaporated under reduced pressure, extracted with chloroform, washed wi...

Embodiment 2

[0027] 2-{3-[4-(3-Aminopropyl)-aminobutyl]-aminopropyl}-2-[(2-dimethylamino)-ethyl]1H-benzisoquinoline-1 The preparation of 3(2H)-diketoacetamide pentahydrochloride (17b):

[0028]

[0029] Except that 5b is used instead of 5a in step (2), other synthesis and purification methods are the same as in Example 1. Yield: 78%, white solid: 1 HNMR(400MHz, D 2 O)δ: 8.21(d,J=7.2Hz,1H,Ar-H); 8.18(s,2H,Ar-H); 8.07(d,J=7.6Hz,1H,Ar-H); 7.65(t ,J=7.8Hz,1H,Ar-H); 4.38(t,J=6.2Hz,2H,1×CH 2 ); 4.20(s,2H,1×CH 2 ); 3.44(t,J=6.2Hz,2H,1×CH 2 ); 3.30(t,J=8.0Hz,2H,1×CH 2 ); 3.18(t,J=8.0Hz,2H,1×CH 2 ); 3.01~3.12(m,8H,4×CH 2 ); 2.96(s,6H,2×CH 3 ); 2.18~2.22(m,2H,1×CH 2 ); 2.01~2.05(m,2H,1×CH 2 ); 1.73~1.75(m,2H,1×CH 2 ).ESI-MIm / z:526.4[M+1-5HCl] + .Anal.calcd.forC 28 H 48 Cl 5 N 7 O 3 : C47.50%, H6.83%, N13.85%; found: C47.4%, H6.78%, N13.98%.

Embodiment 3

[0031] 2-{4-[4-(4-Aminobutyl)-aminobutyl]-aminobutyl}-2-[2-(dimethylamino)-ethyl]1H-benzisoquinoline-1 Preparation of 3(2H)-diketoacetamide pentahydrochloride (17c):

[0032]

[0033] Except that 5d is used instead of 5a in step (2), the other synthesis and purification methods are the same as in Example 1. Yield: 75%, white solid: 1 HNMR(400MHz, D 2 O)δ: 8.09(d,J=7.2Hz,1H,Ar-H); 8.0(d,J=2.0,2H,Ar-H); 7.97(d,J=2.0Hz,1H,Ar-H) ;7.94(d,J=8.0Hz,1H,Ar-H); 7.58(t,J=7.8,1H,Ar-H); 4.32(t,J=6.0Hz,2H,1×CH 2 ); 4.18(s,2H,1×CH 2 ); 3.43(t,J=6.4Hz,2H,1×CH 2 ); 3.26(t,J=7.6Hz,2H,1×CH 2 ); 3.03~3.13(m,8H,4×CH 2 ); 2.98(s,6H,3×CH 3 ); 1.79~1.93(m,4H,2×CH 2 ); 1.70~1.76(m,4H,2×CH 2 ).ESI-MIm / z:554.4[M+1-5HCl] + .Anal.calcd.forC 30 H 52 Cl 5 N 7 O 3 : C48.95%, H7.12%, N13.32%; found: C48.89%, H7.23%, N13.28%.

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Abstract

The invention relates to a naphthalimide derivative and an application thereof.The naphthalimide derivative is of the structure in the formula I or the formula II.The aphthalimide derivative shows obvious inhibitory activity for proliferation of multiple tumor cells such as HCT-116 cells, HepG2 cells, K562 cells and SMMC-7721 cells, and lung metastasis of tumors can be effectively inhibited in the body.

Description

Technical field [0001] The invention belongs to the field of medicinal chemistry, and specifically relates to a naphthimide derivative in which an aminonaphthylene ring is modified with a polyamine and alkane chain, and a preparation method and application thereof. Background technique [0002] Naphthimide is a kind of anti-cancer agent that has been proved to have broad application prospects. Many naphthalimide derivatives (such as DMP-840, Elinafide, Amonafide) have entered clinical phase I and phase II trials. But most of them were abandoned due to various side effects such as bone marrow suppression, dose limitation, etc. The representative drug Amonafide is a drug that combines cytarabine in patients with acute myelogenous leukemia and is undergoing clinical phase III trials. Its side effects include bone marrow suppression, vomiting, skin rash, and moderate phlebitis. The cause of this side effect may be that aminonafet is easily acetylated by the NAT2 enzyme in the body ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D221/14A61K31/473A61P35/00
CPCC07D221/14
Inventor 王玉霞田志勇谢松强苏雷棚王超杰
Owner HENAN UNIVERSITY
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