Boron-containing compound for BNCT and preparation method and application thereof

A boron compound and the technology of the compound are applied in the fields of medicine and tumor-related drugs, which can solve the problems of false positive brain tumor imaging effect and the like, and achieve the effects of good application prospect, low cost and easy preparation.

Active Publication Date: 2017-01-04
NANJING PET TRACER
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Currently, clinically used 18 F-labeled tumor PET imaging agents mainly include 18 F-FDG, 18 F-FET, 18 F-FLT, 18 F-FMISO and 18 F-BPA, etc., these imaging agents can perform imaging on certain tumors a

Method used

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  • Boron-containing compound for BNCT and preparation method and application thereof
  • Boron-containing compound for BNCT and preparation method and application thereof
  • Boron-containing compound for BNCT and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0051] The preparation of embodiment 1 compound Ia

[0052] reaction route

[0053]

[0054] 1.1 Preparation of Intermediate 3a

[0055] Add 1 (13.00 mg, 0.1 mmol) and 2a (27.53 mg, 0.1 mmol) into a 50 mL reaction flask, add 20 mL of methanol solution and stir at room temperature for 24 hours, stop the reaction, and obtain 3a (34.87 mg, 90%) by suction filtration .

[0056] 1 H NMR (500MHz, CDCl 3 ): δppm 5.49 (1H, CH), 5.13 (1H, CH), 4.94 (1H, CH), 4.89 (1H, CH), 4.23 (2H, CH 2 ), 4.16 (2H, CH 2 ), 1.99 (9H, CH 3 ), 2.01 (1H, NH), 1.91 (3H, CH 3 ), 1.27 (3H, CH 3 ).

[0057] 1.2 Preparation of Intermediate 4a

[0058] Add 3a (38.74mg, 0.1mmol) and concentrated ammonia water (30.36mg, 0.5mmol) into a 50mL reaction flask, add 20mL of methanol solution, stir at room temperature for 1h, then raise the temperature to reflux for 6h, cool down and suction filter to obtain 4a (28.31 mg, 79%).

[0059] 1 H NMR (500MHz, CDCl 3 ): δppm 6.67 (1H, CH), 5.96 (2H, NH 2 ), ...

Embodiment 2

[0063] The preparation of embodiment 2 compound Ib

[0064] reaction route

[0065]

[0066] 2.1 Preparation of compound 3b

[0067] Add 1 (13.00mg, 0.1mmol) into a 50mL reaction flask, add 20mL of methanol solution and stir at room temperature, pass through ammonia gas, stop the reaction when the reaction is no longer monitored by TLC, and filter to obtain 3b (11.11mg, 86%).

[0068] 1 H NMR (500MHz, CDCl 3 ): δppm 6.97 (1H, CH), 4.18 (2H, CH 2 ), 2.01 (2H, NH 2 ), 1.91 (3H, CH 3 ), 1.27 (3H, CH 3 ).

[0069] 2.2 Preparation of compound 4b

[0070] Add 3b (12.92mg, 0.1mmol) and concentrated ammonia water (30.36mg, 0.5mmol) into a 50mL reaction flask, add 20mL of methanol solution, stir at room temperature for 1h, then raise the temperature to reflux for 6h, cool down and suction filter to obtain 4b (8.11 mg, 81%).

[0071] 1 H NMR (500MHz, CDCl 3 ): δppm 6.68 (1H, CH), 6.01 (2H, NH 2 ), 2.01 (2H, NH 2 ), 1.91 (3H, CH 3 ).

[0072] 2.3 Preparation of Compou...

Embodiment 3

[0075] The preparation of embodiment 3 compound IIa

[0076] reaction route

[0077]

[0078] 3.1 Preparation of intermediate 5a

[0079] Add Ia (38.61mg, 0.1mmol) and 10% NaOH solution (160mg, 0.4mmol) to a 50mL reaction flask, raise the temperature to 50°C and react for 6h, cool down to room temperature after the reaction, extract twice with ethyl acetate, concentrate , and recrystallized from methanol to give 5a (17.54mg, 68%).

[0080] 1H NMR (500MHz, CDCl 3 ): δppm 8.02 (1H, NH), 6.27 (1H, CH), 4.98 (1H, CH), 3.92 (1H, CH), 3.89 (1H, CH), 3.67 (2H, CH 2 ), 3.65 (1H, CH) 2.02 (4H, OH), 1.92 (3H, CH 3 ).

[0081] 3.2 Preparation of compound Ⅱa

[0082] with 15mg K 222 and 3 mg K 2 CO 3 Acetonitrile water rinse 18 f - For the enriched QMA column, after acetotropic water removal, use K 2 CO 3 , K 222 , [ 18 F]-F -The mixture of and the labeled precursor compound 5a are reacted in an acetonitrile solution under heating conditions, the reaction temperature is...

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Abstract

The invention discloses a boron-containing compound for BNCT and a preparation method and application thereof, and belongs to the field of medicines. The novel boron-containing compound is obtained through condensation, ammonolysis and cyclization reaction, and is easy to prepare, low in cost, and has good biological properties; the boron-containing compound is better than BPA on uptake, accumulation and reservation of tumour cells, free of any signs of toxicity, and has a good application prospect in BNCT. Moreover, the boron-containing compound is further expected to be a clinical potential positron emission tomography tumor imaging agent after being labeled through radioactive elements, and creates the advantage conditions for diagnosis of malignant tumor, identification of benign and malignant diseases, exploration of systematic metastatic lesions and the like.

Description

technical field [0001] The invention belongs to the field of medicine, in particular to the field of tumor-related medicines, and more specifically, to a boron-containing compound used for BNCT and its preparation method and application. Background technique [0002] Tumors, especially malignant tumors, have become one of the major diseases that have seriously threatened human health. Its mortality rate is second only to cardiovascular diseases and ranks second in the mortality rate of various diseases. In recent years, its incidence has shown an obvious upward trend. . Traditional treatment methods cannot completely kill tumor cells. Therefore, how to kill tumor cells to the greatest extent and improve the survival time and quality of life of patients is a major problem that we need to solve urgently. Since the 1970s, many scientists at home and abroad have devoted themselves to the research of tumor treatment, and found that boron neutron capture therapy (BNCT) has a very...

Claims

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Application Information

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IPC IPC(8): C07F5/02C07H23/00C07H1/00C07B59/00A61K31/69A61K31/706A61P35/00A61K51/02A61K101/02
CPCA61K51/02C07B59/005C07B2200/05C07F5/022C07H1/00C07H23/00
Inventor 王正罗志刚李世红徐建锋
Owner NANJING PET TRACER
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