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Novel bimodal micromolecular contrast agent and preparation method and application thereof

A dual-modality, contrast agent technology, used in X-ray contrast agent preparation, general/multifunctional contrast agents, pharmaceutical formulations, etc., can solve problems such as inability to identify liver tumors and weak penetration

Inactive Publication Date: 2019-07-09
NANJING DRUM TOWER HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The technical problem to be solved by the present invention is to overcome the weak penetrating power of existing near-infrared imaging reagents such as indocyanine green, the imaging depth is only 5-10mm, and the tumor tissue on the surface of the liver can only be detected, and the tumor inside the liver cannot be identified etc., and provide a novel dual-mode small molecule contrast agent and its preparation method

Method used

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  • Novel bimodal micromolecular contrast agent and preparation method and application thereof
  • Novel bimodal micromolecular contrast agent and preparation method and application thereof
  • Novel bimodal micromolecular contrast agent and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0089] Preparation of compound CNCI-1, the structural formula is as follows:

[0090]

[0091]Step 1: Put 4g 4-hydrazinobenzoic acid, 3.96mL 3-methyl-2-butanone, 4.32g sodium acetate, and 60mL acetic acid into a 250mL three-neck flask, under nitrogen protection; stir at 25°C for 3h, and then react at 120°C 7h; after the reaction, the mixture was transferred to dichloromethane (DCM) for extraction with water, and the organic phases were combined and concentrated; separated by column chromatography (DCM:methanol=50:1), and concentrated to obtain yellow solid compound 2 with a yield of 61%.

[0092] 1 H NMR (300MHz, CDCl 3 )δ(ppm): 8.17(d, J=8.19Hz, 1H), 8.08(s, 1H), 7.67(d, J=8.19Hz, 1H), 2.41(s, 3H, ), 1.40(s, 6H ).

[0093] Step 2: Put 4g of compound 2, 11.93mL of 1,4-butanesultone, 50mL of o-dichlorobenzene into a 250mL three-neck flask in sequence, under nitrogen protection, and refluxed at 180°C for 9h; After washing with acetone three times, a pink solid compound 3 ...

Embodiment 2

[0110] Preparation of compound CNCI-2, the structural formula is as follows:

[0111]

[0112] The preparation method is the same as that of Example 1, except that 1,3-propanediamine is used instead of ethylenediamine for the reaction in step 4, and the rest of the synthesis steps remain unchanged to obtain the final product compound CNCI-2 with a yield of 39%.

[0113] 1 H NMR (300MHz, DMSO) δ (ppm): 9.95 (m, 4H), 8.63-8.46 (m, 4H), 8.03 (s, 2H), 8.03-7.88 (m, 5H), 7.48 (d, J= 8.13Hz, 2H), 6.66-6.48(m, 4H), 4.11(br, 4H), 3.40(m, 8H), 2.53(m, 4H), 2.01(s, 12H), 1.85(m, 4H), 1.74(m, 8H), 1.66(s, 12H).

Embodiment 3

[0115] Preparation of compound CNCI-3, the structural formula is as follows:

[0116]

[0117] The preparation method is the same as that of Example 1, except that 1,4-butanediamine is used instead of ethylenediamine for the reaction in step 4, and the rest of the synthesis steps remain unchanged to obtain the final product compound CNCI-3 with a yield of 30%.

[0118] 1 H NMR (300MHz, DMSO) δ (ppm): 9.95 (m, 4H), 8.63-8.46 (m, 4H), 8.02-7.87 (m, 7H), 7.47 (d, J=7.65Hz, 2H), 6.62 -6.49(m,4H),4.11(br,4H),3.42(m,8H),2.54(m,4H),2.01(s,12H),1.92-1.73(m,16H),1.66(s,12H) ).

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Abstract

The invention discloses a novel bimodal micromolecular contrast agent and a preparation method and application thereof. According to the contrast agent, by utilizing the characteristic that ICG can beselectively enriched in a liver cancer area and form strong contrast with surrounding tissue, a key structure of ICG is selected as a carrier to be connected with diatrizoic acid, iohexol and other functional groups of CT contrast agents rich in iodine group in order to obtain a liver cancer targeting property and enhance the penetration capacity at the same time, and correspondingly the micromolecular near-infrared / CT bimodal contrast agent is designed and synthesized. The micromolecular contrast agent has high water solubility and low toxicity, and two contrast modes are mutually verified;diagnosis information is enriched, the diagnosis precision is improved, and the feasible novel contrast agent is provided for clinical early diagnosis of liver cancer.

Description

technical field [0001] The invention belongs to the field of contrast agents, and in particular relates to a novel dual-modality small molecule contrast agent and a preparation method and application thereof. Background technique [0002] Liver cancer is one of the malignant tumors with the highest mortality rate. About 383,000 people die of liver cancer every year in my country, accounting for 51% of the global liver cancer deaths. The severe situation has brought a heavy burden to society and medical care. The early onset of liver cancer is quite insidious, with no obvious symptoms and signs. When patients are diagnosed with liver cancer, they are often staged at a later stage, with poor prognosis and a low 5-year survival rate. Therefore, the development of an effective and reliable diagnostic method can enable early detection of liver cancer and early treatment to improve the survival rate of patients, which has high clinical application value. [0003] Computed tomogr...

Claims

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Application Information

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IPC IPC(8): A61K49/00A61K49/04C07D209/08
CPCA61K49/0002A61K49/0034A61K49/0052A61K49/0438C07D209/08
Inventor 徐庆祥周益舟帅天白王乐天王景霖任陇飞王锦涛赵丽李玉艳
Owner NANJING DRUM TOWER HOSPITAL
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