Synthesis and application of naphthalimide derivative containing 1,2,3-triazole on amide side chain

A technology of naphthalimide and derivatives, applied in the field of synthesis of naphthalimide derivatives

Inactive Publication Date: 2014-09-24
DALIAN UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, they have been shown to cause side effects such as myelosuppression, vomiting, and skin rashes in clin

Method used

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  • Synthesis and application of naphthalimide derivative containing 1,2,3-triazole on amide side chain
  • Synthesis and application of naphthalimide derivative containing 1,2,3-triazole on amide side chain
  • Synthesis and application of naphthalimide derivative containing 1,2,3-triazole on amide side chain

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] Synthesis of N-[3'-(4-morpholinomethyl-[1,2,3]-triazole)-propyl]-1,8-naphthalimide (E1)

[0021] ①In a 50mL two-necked bottle, add 1.98g naphthalene anhydride and 30mL ethanol, stir evenly, add 0.92mL n-propanolamine, reflux for 2 hours, pour into cold water after standing still, suction filter, wash with water, and dry to obtain the compound b White solid 2.23g, yield 87%.

[0022]

[0023] ②In a 25mL two-necked bottle, add 0.51g of compound b and 5mL of ethyl acetate, stir well at room temperature, and dissolve 380μL of PBr 3 It was slowly dropped into the reaction system, refluxed for 3 hours, and evaporated to obtain a solid. The solid was washed with water and dried to obtain 0.50 g of compound c as a light yellow solid with a yield of 79%.

[0024]

[0025] ③In a 25mL two-necked bottle, add 0.50g of compound c, 8mL of DMF and 0.31g of NaN3, heat to 50°C for 2h, pour into cold water after standing, filter with suction, wash with water, and dry to obtain comp...

Embodiment 2

[0032] Synthesis of N-[3'-(4-thiomorpholinemethyl-[1,2,3]-triazole)-propyl]-1,8-naphthalimide (E2)

[0033] Except that 3-thiomorpholinopropyne was used instead of 3-morpholinopropyne, other synthesis and purification methods were the same as in Example 1 to obtain the target compound E2 as an off-white solid with a yield of 72%.

[0034]

[0035] 1 H NMR (400MHz, CDCl 3 )δ8.61(d, J=6.7Hz, 2H), 8.25(d, J=8.0Hz, 2H), 7.84(s, 1H), 7.79(t, J=7.1Hz, 2H), 4.50(t, J=6.4Hz, 2H), 4.26(t, J=6.7Hz, 2H), 3.83(s, 2H), 3.02–2.85(m, 4H), 2.85–2.68(m, 4H), 2.48–2.34(m ,2H).

[0036] TOF MS(m / z):C 22 h 24 N 5 o 2 S+, Calculated: 422.1651, Found: 422.1644.

Embodiment 3

[0038] Synthesis of N-[3'-(4-piperidinylmethyl-[1,2,3]-triazole)-propyl]-1,8-naphthalimide (E3)

[0039] Except that 3-morpholinopropyne was replaced by 3-piperidylpropyne, other synthesis and purification methods were the same as in Example 1 to obtain the target compound E3 as a gray solid with a yield of 80%.

[0040]

[0041] 1 H NMR (400MHz, CDCl 3 )δ8.57(d, J=7.2Hz, 2H), 8.21(d, J=8.3Hz, 2H), 7.81–7.73(m, 2H), 7.73(s, 1H), 4.45(t, J=7.2 Hz, 2H), 4.25(t, J=6.7Hz, 2H), 3.68(s, 2H), 2.64–2.43(m, 4H), 2.43–2.30(m, 2H), 1.72–1.51(m, 4H) ,1.49–1.34(m,2H).

[0042] TOF MS(m / z):C 23 h 26 N 5 o 2 +, calculated value: 404.2087, measured value: 404.2083.

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Abstract

The invention relates to synthesis and an application of a naphthalimide derivative containing 1,2,3-triazole on an amide side chain, belonging to the field of organic synthesis. The derivative is a compound which has the structure shown in a general formula A. A preparation method of the derivative comprises the following steps: by taking anhydride naphthalene as a raw material, amidating the anhydride naphthalene with propyl alcohol amine, subsequently substituting hydroxyl by using phosphorus tribromide, then performing azidation of bromine and finally reacting with amino allylene connected with ring amine to prepare the naphthalimide derivative. The derivative is applied to a drug for inhibiting cancer cells.

Description

technical field [0001] The invention relates to the synthesis and application of a class of naphthalimide derivatives containing 1,2,3-triazole in the amide side chain, and belongs to the field of organic synthesis. Background technique [0002] The DNA intercalator is a research hotspot in the cross-discipline of chemistry, medicine and molecular biology. The intercalator intercalates into the base pairs of DNA, changes its conformation, causes the DNA chain to unwind and lengthen, thereby restricting its replication and exhibiting anti-tumor activity. Naphthalimide derivatives have made great progress in the research of antitumor drugs, such as the famous naphthalimide lead drugs Amonafide and Mitonafide, which have entered clinical trials. However, they have been shown to cause side effects such as bone marrow suppression, vomiting, and skin rashes in clinical trials. Therefore, the design and synthesis of new and effective DNA-targeted drugs has important application va...

Claims

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Application Information

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IPC IPC(8): C07D401/06C07D401/14A61K31/473A61K31/5377A61K31/541A61K31/496A61P35/00
CPCC07D401/06C07D401/14
Inventor 李晓莲于汀汀张英利马黎明孟扬陈思宇
Owner DALIAN UNIV OF TECH
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