A radionuclide-labeled estrogen receptor molecular targeting compound and its application

A technology of estrogen receptors and radionuclides, which is applied in the field of estrogen receptor molecular targeting compounds, can solve the problems of non-specific uptake and unsatisfactory uptake of radiotracers, and achieve improved imaging contrast and good metabolic stability in the body Sexuality, the effect of increasing the ratio

Active Publication Date: 2022-02-18
XIAMEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the uptake of these novel radiotracers in target tissues is not ideal and they are rapidly metabolized in the liver, causing nonspecific uptake, which has become the biggest problem of this type of probes

Method used

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  • A radionuclide-labeled estrogen receptor molecular targeting compound and its application
  • A radionuclide-labeled estrogen receptor molecular targeting compound and its application
  • A radionuclide-labeled estrogen receptor molecular targeting compound and its application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0055] Synthesis of compound 4-1: when R in the above structural formula 1 to R 5 = H, R 6 = 131 I (radioactive iodine isotope), R 7 = 127 When I and n=0, it is compound 4-1. The radioactive iodine isotope is labeled by "click" chemical reaction, and its synthetic route and preparation method are as follows:

[0056]

[0057] Specifically include the following steps:

[0058] 1) Synthesis of 3-azidopropylamine:

[0059] 3-Bromopropylamine hydrochloride (5 g, 38 mmol) was dissolved in 20 mL of deionized water at room temperature. At 0°C, an aqueous solution of sodium azide (7.5 g, 115 mmol, 20 mL) was added dropwise to the above solution. After the dropwise addition, the temperature was raised to 80° C., and the reaction was carried out overnight. The reaction system was cooled to 0°C, and 50 mL of diethyl ether was added. Weigh 4g of potassium hydroxide particles and slowly add to the reaction flask, keeping the low temperature. Extracted with diethyl ether (50 m...

Embodiment 2

[0065] Synthesis of compound 4-2: when R in the above structural formula 1 = H, R 2 = F, R 3 , R 4 = H, R 5 =OCH 3 , R 6 = 131 I (radioactive iodine isotope), R 7 = 127 When I and n=0, it is compound 4-2. The radioactive iodine isotope is labeled by "click" chemical reaction, and its synthetic route and preparation method are as follows:

[0066]

[0067] 1) Synthesis of 4-fluoro-17α-alkynyl-11β-methoxyestradiol:

[0068] Under a nitrogen atmosphere, N-fluoropyridinium triflate (1.83 g, 7.4 mmol) was added to 17α-alkynyl-11β-methoxyl in 16 mL of 1,1,2-trichloroethane estradiol (1.2g, 3.7mmol). After the reaction was complete, the solvent was removed by rotary evaporation, and the residue was poured into water and extracted with dichloromethane. The crude product was purified by column chromatography (ethyl acetate / dichloromethane=1:9) to obtain 0.8 g of light yellow solid with a yield of 63%.

[0069] 2) Labeling of compound 4-2:

[0070] Add 4 mL of anhydrous...

Embodiment 3

[0072] Synthesis of compound 8-1: when R in the above structural formula 1 , R 2 , R 3 , R 4 , R 5 and R 6 = H, and R 7 = 125 I (radioactive iodine isotope), when n=3, it is compound 8-1. The radioactive iodine isotope is labeled with phenylboronic acid precursor, and then connected to the estrogen structure. The synthetic route and preparation method are as follows:

[0073]

[0074] Specifically include the following steps:

[0075] 1) Synthesis of (2-(2-(2-(2-(2-azidoethoxy) ethoxy) ethoxy) ethyl) tert-butyl carbamate:

[0076] 2-(2-(2-(2-(2-Azidoethoxy)ethoxy)ethoxy)ethylamine (1 g, 4.6 mmol) and triethylamine (0.7 g, 6.9 mmol) were mixed with Anhydrous 5mL tetrahydrofuran was dissolved and stirred at room temperature for 0.5h. Di-tert-butyl dicarbonate (1.1g, 5mmol) was added and reacted overnight at room temperature. The reaction solvent was spin-dried and extracted with ethyl acetate (40mL×3). The organic layer was collected and The solvent was removed, and...

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Abstract

The invention discloses a radionuclide-labeled estrogen receptor molecular targeting compound and its application. Its structural formula is that the present invention contains an estrogen structure and has good estrogen receptor targeting in vivo and in vitro; using radioactive iodine isotope ( 123 I. 124 I. 125 I or 131 I) and 18 F is used as a radioactive signaling group to perform SPECT or PET imaging on estrogen receptors in human or animal organs or tissues and to treat estrogen receptor positive tumors.

Description

technical field [0001] The invention belongs to the technical field of organic materials, and in particular relates to a radionuclide-labeled estrogen receptor molecular targeting compound and its application. Background technique [0002] Globally, the morbidity and mortality of breast cancer rank first among malignant tumors suffered by women. Early detection, early diagnosis and early treatment are the key to improving the survival rate of breast cancer patients. The 5-year relative survival rate of patients with early breast cancer is almost 100%, while the 5-year relative survival rate of patients with advanced breast cancer is only 26%. [0003] According to literature reports, 70-80% of breast cancers are estrogen receptor (ER) positive. Breast cancers expressing ER tend to have low malignancy, good differentiation, and patients have good prognosis. Whether or not ER is expressed and how much it is expressed has become an indispensable indicator for clinically guidi...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07J43/00A61P35/00A61K51/04A61K101/02
CPCC07J43/003A61K51/0493A61P35/00
Inventor 张现忠许多林晓茹文雪君曾馨莹李靖超郭志德
Owner XIAMEN UNIV
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