CN113307758B - A Medical Radioisotope Labeled P2X7 Receptor Targeting Probe Precursor - Google Patents

Abstract

The invention relates to the field of organic synthesis, in particular to a medical radioisotope-labeled P2X7 receptor targeting probe precursor, wherein the structural formula of the targeting probe precursor is shown in formula (I):

Wherein, X is selected from the substituted or unsubstituted alkyl of C1-C4,

R ₀ is selected from hydrogen atom, halogen atom, C1-C5 substituted or unsubstituted saturated alkyl; R ₁ is selected from halogen atom; R ₂ is selected from C1-C5 substituted or unsubstituted saturated alkyl, C1-C4 substituted or unsubstituted unsaturated alkyl; _R is selected from halogen atom, C1-C5 substituted or unsubstituted saturated alkyl, substituted or unsubstituted 5-7-membered heterocycle, heterocyclic aryl; wherein The 5-7 membered heterocycle contains 1-3 N, P, O, S heteroatoms.

Description

A medical radioisotope-labeled P2X7 receptor targeting probe precursor

technical field

The invention relates to the field of organic synthesis, in particular to a medical radioisotope-labeled P2X7 receptor targeting probe precursor, a P2X7 receptor targeting molecular probe, and a kit for preparing a molecular probe for P2X7 receptor imaging .

Background technique

An important subtype of the P2X family of P2X7 receptors purinoceptors belong to adenosine triphosphate (ATP)-gated ion channels. It is widely distributed in the human body, especially in the immune system and central nervous system. Relevant studies have shown that it plays an important role in both normal humans and diseases.

P2X7 receptors are widely involved in processes related to cellular metabolism, and their expression is significantly up-regulated in immune system diseases, central nervous system diseases, inflammation, cancer and cardiovascular diseases related to metabolic disorders. Therefore, small molecule inhibitors of this target have become an important research direction for related therapeutic drugs, and many drugs have entered the clinical testing stage.

The transformation and development of P2X7 receptor small molecule inhibitor core drug backbone in positron emission tomography (PET) and single photon emission computed tomography (SPECT) will provide highly sensitive molecular imaging probes. Such molecular probes can provide accurate in vivo analysis tools for related disease analysis and drug development.

On the other hand, P2X7 receptors are highly expressed in microglia in the central nervous system. After brain stimulation or injury, extracellular ATP will significantly increase, which greatly stimulates the high expression of P2X7 receptors and activates the NRLP3 inflammatory signaling pathway associated with microglia. In addition, a significant increase in its expression was also confirmed in brain inflammation models such as mouse LPS. Therefore, P2X7 receptors are currently considered to be an important visualization tool for neuroinflammation.

SUMMARY OF THE INVENTION

On the basis of conforming to common knowledge in the art, the above preferred conditions can be combined arbitrarily without departing from the concept and protection scope of the present invention.

The first aspect of the present invention provides a medical radioisotope-labeled P2X7 receptor targeting probe precursor, characterized in that the structural formula of the targeting probe precursor is shown in formula (I):

Wherein, X is selected from C1-C4 substituted or unsubstituted alkyl,

R ₀ is selected from hydrogen atom, halogen atom, C1-C5 substituted or unsubstituted saturated alkyl;

R ₁ is selected from halogen atoms;

R ₂ is selected from C1-C5 substituted or unsubstituted saturated alkyl, C1-C4 substituted or unsubstituted unsaturated alkyl;

R ₃ is selected from halogen atom, C1-C5 substituted or unsubstituted saturated alkyl, substituted or unsubstituted 5-7-membered heterocycle, heterocyclic aryl; wherein the 5-7-membered heterocycle contains 1- 3 N, P, O, S heteroatoms.

时，R₁选自氟原子、溴原子。As a preferred technical solution, in the present invention, when X is selected from C1-C4 substituted or unsubstituted alkyl groups, R ₁ is selected from bromine atoms; or X is selected from

, R ₁ is selected from fluorine atom and bromine atom.

As a preferred technical solution, X described in the present invention is selected from methyl, ethyl, n-propyl,

R ₀ is selected from hydrogen atom, chlorine atom, fluorine atom, bromine atom;

R ₁ is selected from fluorine atom, bromine atom;

R ₂ is selected from C1-C5 substituted or unsubstituted saturated alkyl;

R ₃ is selected from halogen atoms, C1-C5 substituted or unsubstituted saturated alkyl groups.

As a preferred technical solution, the P2X7 receptor targeting probe precursor described in the present invention, the formula (I) is selected from:

R in the compound ₁ is selected from C1-C3 unsubstituted saturated alkyl;

R ₂ in the compound 2 and compound 3 is independently selected from -(CH ₂ )n-; the n is 1-5.

The second aspect of the present invention provides a P2X7 receptor targeting molecular probe, the P2X7 receptor targeting molecular probe is prepared by radiolabeling the P2X7 receptor targeting probe precursor .

As a preferred technical solution, the radioisotope used in the radiolabeling process in the present invention is ¹⁸ F or ¹²⁵ I.

As a preferred technical solution, the structural formula of the P2X7 receptor targeting molecular probe described in the present invention is shown in formula (II):

wherein, the R ₅ is selected from ¹⁸ F or F;

The R ₆ is selected from H ¹²⁵ IC=CClR ₂ -, R ₃ HC=C ¹⁸ FR ₂ -.

As a preferred technical solution, the structural formula of the P2X7 receptor targeting molecular probe described in the present invention, such as formula (II), is selected from:

R in the compound 2-1 is selected from C1 _- C3 unsubstituted saturated alkyl;

R ₂ in the compound 2-2 is independently selected from -(CH ₂ )n-; the n is 1-5.

The third aspect of the present invention provides an application of a medical radioisotope-labeled P2X7 receptor targeting probe precursor for diagnosing central nervous degenerative diseases, inflammation and other diseases related to abnormal P2X7 receptor expression. Tumor imaging.

The fourth aspect of the present invention provides a kit for preparing a molecular probe for P2X7 receptor imaging, the kit contains the medical radioisotope-labeled P2X7 receptor targeting probe precursor.

Compared with the prior art, the present invention has the following significant advantages and effects: the use of such precursors only requires one-step labeling, and the radiation yield is generally high.

Description of drawings

FIG. 1 is the separation spectrum of the ¹⁸ F-labeled P2X7 receptor targeting molecular probe in Example 1. FIG.

FIG. 2 is the separation spectrum of the ¹²⁵ I-labeled P2X7 receptor-targeting molecular probe in Example 2. FIG.

FIG. 3 is the separation spectrum of the ¹⁸ F-labeled P2X7 receptor targeting molecular probe in Example 3. FIG.

Detailed ways

The technical solutions of the present invention will be described in detail below with reference to the accompanying drawings and embodiments, but the present invention is not limited to the scope of the described embodiments.

The first aspect of the present invention provides a medical radioisotope-labeled P2X7 receptor targeting probe precursor, the structural formula of the targeting probe precursor is shown in formula (I):

Wherein, X is selected from C1-C4 substituted or unsubstituted alkyl,

R ₀ is selected from hydrogen atom, halogen atom, C1-C5 substituted or unsubstituted saturated alkyl;

R ₁ is selected from halogen atoms;

R ₂ is selected from C1-C5 substituted or unsubstituted saturated alkyl, C1-C4 substituted or unsubstituted unsaturated alkyl;

R ₃ is selected from halogen atom, C1-C5 substituted or unsubstituted saturated alkyl, substituted or unsubstituted 5-7-membered heterocycle, heterocyclic aryl; wherein the 5-7-membered heterocycle contains 1- 3 N, P, O, S heteroatoms.

时，R1选自氟原子、溴原子。In some embodiments, when said X is selected from C1-C4 substituted or unsubstituted alkyl, R1 is selected from bromine atom; or said X is selected from

, R1 is selected from fluorine atom and bromine atom.

In some embodiments, the X is selected from methyl, ethyl, n-propyl,

R ₀ is selected from hydrogen atom, chlorine atom, fluorine atom, bromine atom;

R ₁ is selected from fluorine atom, bromine atom;

R ₂ is selected from C1-C5 substituted or unsubstituted saturated alkyl;

R ₃ is selected from halogen atoms, C1-C5 substituted or unsubstituted saturated alkyl groups.

In some preferred embodiments, the P2X7 receptor targeting probe precursor, formula (I) is selected from:

R in the compound ₁ is selected from C1-C3 unsubstituted saturated alkyl;

R ₂ in the compound 2 and compound 34 is independently selected from -(CH ₂ )n-; the n is 1-5.

In some more preferred embodiments, the P2X7 receptor targeting probe precursor, formula (I) is selected from:

A second aspect of the present invention provides a P2X7 receptor targeting molecular probe, the P2X7 receptor targeting molecular probe targeting the P2X7 receptor according to any one of claims 1-4 The probe precursor is prepared by radiolabeling.

In some preferred embodiments, the radioisotope used in the radiolabelling process ^{is18F or125I} .

In some preferred embodiments, the structural formula of the P2X7 receptor targeting molecular probe is shown in formula (II):

wherein, the R ₅ is selected from ¹⁸ F or F;

The R ₆ is selected from H ¹²⁵ IC=CClR ₂ -, R ₃ HC=C ¹⁸ FR ₂ -.

In some preferred embodiments, the structural formula of the P2X7 receptor targeting molecular probe such as formula (II) is selected from:

R4 in the compound 2-1 is selected from C1-C3 unsubstituted saturated alkyl;

R2 in the compound 2-2 is independently selected from -(CH2)n-; the n is 1-5.

In some preferred embodiments, R4 in the compound 2-1 is selected from methyl, ethyl, n-propyl, n-butyl, isopropyl;

R2 in the compound 2-2 and compound 2-3 is independently selected from -(CH2)n-; the n is an integer of 1, 2, and 3.

In some preferred embodiments, the structural formula of the P2X7 receptor targeting molecular probe such as formula (II) is selected from:

A third aspect of the present invention provides an application of a medical radioisotope-labeled P2X7 receptor targeting probe precursor for diagnosing central nervous degenerative diseases, inflammation and tumors associated with abnormal P2X7 receptor expression imaging.

The fourth aspect of the present invention provides a kit for preparing a molecular probe for P2X7 receptor imaging, the kit contains the medical radioisotope-labeled P2X7 receptor targeting probe precursor.

The experimental methods that do not specify specific conditions in the following examples are selected according to conventional methods and conditions, or according to the product description. The reagents and raw materials used in the present invention are all commercially available.

Example 1

A medical radioisotope-labeled P2X7 receptor targeting probe precursor, the structural formula of the targeting probe precursor is shown in compound 1-1:

The preparation method of the compound 1-1 is:

First, methyl dichloride was added to 2-chloro-3-methylbenzoic acid, and 50 mL of toluene was used as the reaction solvent to react at 100 °C for two hours. After the reaction was completed, it was monitored by gas chromatography-mass spectrometry. The crude acid chloride was obtained by evaporation; then the acid chloride solution prepared in the previous step was added dropwise to a suspension of potassium tert-butoxide in tetrahydrofuran at 0°C, and the resulting mixture was stirred at 0°C to room temperature for 12 hours, washed with water and methyl Extracted with tert-butyl ether, the combined organic layers were dried over Na ₂ SO ₄ , filtered and concentrated, and purified by silica gel column chromatography to give tert-butyl 2-chloro-3-methylbenzoate (yield: 72%). Then tert-butyl 2-chloro-3-methylbenzoate was dissolved in carbon tetrachloride (100 mL) at room temperature, and NBS and AIBN were added. The resulting mixture was heated to 80 °C under _N2 for 12 h. After cooling to room temperature, it was filtered and the filtrate was concentrated in vacuo to give the crude product tert-butyl 3-(bromomethyl) _-2 -chlorobenzoate as a white solid; a mixture _of this crude product and Na2SO3 in acetonitrile The mixture was heated at 80°C for 12 hours, and the crude product was purified by silica gel column chromatography to give tert-butyl 2-chloro-3-((trifluoromethyl)sulfonyl)methyl)benzoate (yield: 30%); A solution of the product from the previous section in 20 mL TFA was stirred at room temperature for 10 minutes. After the reaction was complete, the mixture was concentrated in vacuo to give pure product 2-chloro-3-(((trifluoromethyl)sulfonyl)methyl)benzoic acid as a white solid; LiAlH and THF _were added to a two-necked flask The mixture was vigorously stirred at 0°C for 5 minutes, a suspension of 2-chloro-3-((trifluoromethyl)sulfonyl)methyl)benzamide in THF was slowly added and stirred for 10 minutes, then heated to 60°C React for 2 hours. After completion of the reaction monitored by gas chromatography-mass spectrometry, the mixture was cooled to room temperature, quenched with 10 mmol of water, 10 mmol of 15% aqueous sodium hydroxide solution, anhydrous MgSO ₄ was added to the mixture, and the mixture was stirred at 0° C. for 30 minutes, Filtration and washing with ether gave pure product (2-chloro-3-((trifluoromethylsulfonyl)methyl)phenyl)methanamine (yield: 90%) as a pale yellow solid; then HATU, 1 -Methyl-5-oxopyrrolidine-2-carboxylic acid was stirred with acetonitrile as solvent at 25°C for 1 hour, and the residue was purified by silica gel column chromatography to give N-(2-chloro-3- (Trifluoromethylsulfonyl)methyl)benzyl)-1-methyl-5-oxopyrrolidine- ₂ -carboxamide (yield: 65%); mixture with NFSI and _K3PO4 After stirring in dry dimethylformamide at room temperature for 2 hours, the residue was purified by silica gel column chromatography to give the pure product N-(2-chloro-3-(difluoro((trifluoromethyl)) as a colorless oil Sulfonyl)methyl)benzyl)-1-methyl-5-oxopyrrolidine-2-carboxamide. (Yield: 74%); Finally, the product of the previous step, lithium bromide, and anhydrous acetonitrile were added to a 10-mL Schlenk tube. The reaction mixture was heated at 80°C for 12 hours, and the residue was further purified by silica gel column chromatography to give pure product N-(3-(bromodifluoromethyl)-2-chlorobenzyl)-1-methyl-5- Oxopyrrolidine-2-carboxamide (compound 1-1). (Yield: 78%)

The data of the P2X7 receptor targeting molecular probe (Compound 1-1) are shown below. ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.59-7.40 (m, 2H), 7.28 (t, J=7.8Hz, 1H), 7.10 (s, 1H), 4.55 (qd, J=15.0, 5.9Hz, 2H) ), 3.95 (dd, J=9.0, 3.9Hz, 1H), 2.71 (s, 3H), 2.47–2.13 (m, 2H), 2.04–1.90 (m, 1H). ¹⁹ F NMR (377MHz, CDCl ₃ ) δ-45.18(s,1H).8H), LC/MS (ESI): Calculated for C ₁₄ H ₁₄ BrClF ₂ N ₂ O ₂ (M+H ⁺ ) 394.9968, found 394.9972.

The P2X7 receptor targeting molecular probe is prepared by performing ¹⁸ F radiolabeling on the P2X7 receptor targeting probe precursor to obtain the P2X7 receptor targeting molecular probe.

The P2X7 receptor targeting molecular probe is subjected to ¹⁸ F radiolabeling of the P2X7 receptor targeting probe precursor as follows: in a vial, 2 mg of the labeled precursor (compound 1-1) is mixed with 10 mCi of anhydrous TBA ¹⁸ F was dissolved in 500 μL of acetonitrile solution, and then the mixture was reacted under blocking conditions at 110° C. for 20 min.

Subsequently, 200 μL of mobile phase was injected into the reaction system to quench the reaction, and the mixture was separated and collected by HPLC (Dionex UltiMate 3000 Series). The mobile phase was MeCN and 0.1 mol/L ammonium formate buffer (35/65). The total radiochemical yield was greater than 50% (n=5), the radiochemical purity was greater than 98%, and the total duration of radiolabeling was about 40 minutes.

Example 2

A medical radioisotope-labeled P2X7 receptor targeting probe precursor, the structural formula of the targeting probe precursor is shown in compound 1-2:

The preparation method of the compound 1-2 is:

L-2-pyrrolidone-5-carboxylic acid (1.032 g, 8.0 mmol) and 2-chloro-3-(trifluoromethyl)benzylamine (1.672 g, 8.0 mmol) with 1-ethyl-3-(3- Dimethylaminopropyl)carbodiimide hydrochloride (1.917 g, 10.0 mmol) and 1-hydroxybenzotriazole (1.35 g, 10.0 mmol) were combined in dry dichloromethane (150 mL). The reaction mixture was stirred at room temperature overnight. The resulting mixture was then washed with 2N hydrochloric acid (50 mL x 3) and saturated aqueous sodium bicarbonate (40 mL). The organic layer was dried over anhydrous magnesium sulfate and concentrated. The residue was separated and purified by silica gel column chromatography to give the product as a white solid (1.5 g, 60%).

At 0°C, the product obtained in the previous step (960 mg, 3 mmol) was added to a glass reaction flask containing 15 mL of N,N-dimethylformamide, lithium bistrimethylsilylamide (4.5 mL) and 3-Bromopropyne (714 mg, 6 mmol), then the reaction mixture was stirred at room temperature overnight. After the reaction was completed, the mixture was extracted and separated with saturated sodium chloride solution and ethyl acetate solution, and the organic layer was collected, dried over anhydrous magnesium sulfate and concentrated. The residue was separated and purified by silica gel column chromatography to obtain compound 1-2 (210 mg, 20%) as a white solid. The data for the P2X7 receptor targeting molecular probes (compounds 1-2) are presented below. ¹ H NMR (400MHz, CDCl ₃ ) δ 7.58-7.72(m, 2H), 7.38(t, J=7.8Hz, 1H), 6.57(s, 1H), 4.72-4.55(m, 2H), 4.48( dd, J=17.7, 2.6Hz, 1H), 4.35–4.17 (m, 1H), 3.70 (dd, J=17.7, 2.5Hz, 1H), 2.59–2.46 (m, 1H), 2.45–2.31 (m, 2H), 2.18 (t, J=2.6Hz, 1H), 2.14–2.00 (m, 1H). LC/MS (ESI): Calculated for C ₁₆ H ₁₄ ClF ₃ N ₂ O ₂ (M+H ⁺ ) 359.0769 .found 359.0770.

The P2X7 receptor targeting molecular probe is prepared by performing ¹²⁵ I radiolabeling on the P2X7 receptor targeting probe precursor to obtain the P2X7 receptor targeting molecular probe.

The method that the P2X7 receptor targeting molecular probe carries out ¹²⁵ I radiolabeling to the P2X7 receptor targeting probe precursor is:

In a vial, dissolve 2 mg of labeled precursor (compound 1), 1 mg of m-chloroperoxybenzoic acid, 200 μCi aqueous Na ¹²⁵ I solution (Atom Kexing), 1 mg of lithium chloride in 300 μL of a mixed solution of dichloromethane and acetic acid (4 : 1), and then the mixture was reacted at 80 °C for 20 min under blocking conditions.

Subsequently, 200 μL of mobile phase was injected into the reaction system to quench the reaction, and the mixture was separated and collected by HPLC (Dionex UltiMate 3000 Series). The mobile phase was MeCN and 0.1 mol/L ammonium formate buffer (55/45). The total radiochemical yield was greater than 50% (n=5), the radiochemical purity was greater than 98%, and the total duration of radiolabeling was about 40 minutes.

Example 3

A medical radioisotope-labeled P2X7 receptor targeting probe precursor, the structural formula of the targeting probe precursor is shown in compound 1-3:

The preparation method of the compound 1-3 is:

Ethyl 5-oxo-1-(prop-2-yn-1-yl)pyrrolidine-2-carboxylate:

To a stirred suspension of powdered potassium hydroxide (924 mg, 16.5 mmol) and tetra-n-butylammonium bromide (966 mg, 3 mmol) in 100 mL of dry tetrahydrofuran was added 3-bromopropyne (1.78 g, 15 mmol) and D-pyroglutamate ethyl ester (2.35 g, 15 mmol) in 100 mL of dry tetrahydrofuran, then the reaction was stirred at room temperature for one hour, the precipitate was filtered off, and the filtrate was evaporated to give an oily residue. Ethyl acetate was added and the precipitated material was filtered off. The filtrate was washed with water and brine, and the organic layer was dried over anhydrous magnesium sulfate and evaporated. Isolation and purification by column chromatography gave the product as a light brown oil. (2.1 g, 72%).

1-(3-Bromoprop-2-yn-1-yl)-5-oxopyrrolidine-2-carboxylate ethyl ester:

In the dark, acetone (20 mL) was added to the reaction glass vial, the product obtained in the previous step (1.95 g, 10 mmol), and then NBS (2.136 g, 12 mmol) and silver nitrate (170 mg, 1 mmol) were added. The resulting mixture was stirred at room temperature for 3 h. After the reaction was complete it was filtered through celite and the filtrate was evaporated. Then 20 mL of n-hexane was added, filtered again, and the filtrate was evaporated in vacuo to give an oily liquid (1.5 g, 56%).

1-(3-Bromoprop-2-yn-1-yl)-5-oxopyrrolidine-2-carboxylic acid:

The product of the previous step (1.5 g, 5 mmol), sodium hydroxide (400 mg, 10 mmol) and 50 mL of a solution of water and ethanol (5 mL of water, 45 mL of ethanol) were added to a dry reaction glass bottle, and the reaction mixture was then stirred at room temperature for the reaction 15min. After the reaction, the mixture was concentrated, washed with dichloromethane, and the aqueous layer was collected, adjusted to pH=1 with 1M hydrochloric acid, and extracted with dichloromethane. The combined organic phases were dried over anhydrous magnesium sulfate, then the solvent was removed under reduced pressure to give a white solid (720 mg, 59%).

1-(3-Bromoprop-2-yn-1-yl)-N-(2-chloro-3-(trifluoromethyl)benzyl)-5-oxopyrrolidine-2-carboxamide:

1-(3-Bromoprop-2-yn-1-yl)-5-oxopyrrolidine-2-carboxylic acid (492 mg, 2 mmol), 2-chloro-3-(trifluoromethyl)benzylamine (420 mg) , 2 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (480 mg, 2.5 mmol) and 1-hydroxybenzotriazole (312 mg, 2.5 mmol) in Mix in dry dichloromethane (100 mL). The reaction mixture was stirred at room temperature overnight. Then, the resulting mixture was washed with 2N hydrochloric acid (50 mL*3) and saturated aqueous sodium bicarbonate solution (40 mL). The organic layer was dried over anhydrous magnesium sulfate. The residue was purified by silica gel column chromatography to give compound 1-3 as a white solid (393 mg, 45%)

The data for the P2X7 receptor targeting molecular probes (compounds 1-3) are presented below. ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.58-7.72 (m, 2H), 7.39 (t, J=7.7 Hz, 1H), 6.48 (s, 1H), 4.64 (qd, J=15.0, 6.1 Hz, 2H) ),4.56(d,J=8.2,1H),4.25(dd,J=8.2,4.1Hz,1H),3.71(d,J=17.6Hz,1H),2.62–2.45(m,1H),2.45– 2.30 (m, 2H), 2.15–1.95 (m, 1H). LC/MS (ESI): Calculated for C ₁₆ H ₁₃ BrClF ₃ N ₂ O ₂ (M+H ⁺ ) 436.9873, found436.9875.

The P2X7 receptor targeting molecular probe is prepared by performing ¹⁸ F radiolabeling on the P2X7 receptor targeting probe precursor to obtain the P2X7 receptor targeting molecular probe.

The method for carrying out ¹⁸ F radiolabeling to the P2X7 receptor targeting probe precursor by the P2X7 receptor targeting molecular probe is as follows:

In a vial, 2 mg of labeled precursor (compound 1), 10 mCiAg ¹⁸ F and 1 mg of silver acetate were dissolved in 500 μL of acetonitrile solution, and the mixture was reacted under blocking conditions at 110° C. for 20 min.

Subsequently, 200 μL of mobile phase was injected into the reaction system to quench the reaction, and the mixture was separated and collected by HPLC (Dionex UltiMate 3000 Series). The mobile phase was MeCN and 0.1 mol/L ammonium formate buffer (55/45). The total radiochemical yield was greater than 50% (n=5), the radiochemical purity was greater than 98%, and the total duration of radiolabeling was about 45 minutes.

The above-mentioned embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited by the above-mentioned embodiments, and any other changes, modifications, substitutions, combinations, The simplification should be equivalent replacement manners, which are all included in the protection scope of the present invention.

Claims (6)

1. A medical radioisotope-labeled P2X7 receptor targeting probe precursor is characterized in that the structural formula of the targeting probe precursor is shown as a formula (I):

wherein X is selected from the group consisting of C1-C4 substituted or unsubstituted alkyl,

R ₀ Selected from hydrogen atoms, halogen atomsA C1-C5 substituted or unsubstituted saturated alkyl group;

R ₁ selected from halogen atoms;

R ₂ selected from the group consisting of C1-C5 substituted or unsubstituted saturated alkyl groups, C1-C4 substituted or unsubstituted unsaturated alkyl groups;

R ₃ selected from halogen atoms;

when X is selected from C1-C4 substituted or unsubstituted alkyl, R ₁ Selected from bromine atoms; x is selected from

When R is ₁ Selected from fluorine atom and bromine atom.

2. The P2X7 receptor targeting probe precursor of claim 1, wherein X is selected from the group consisting of methyl, ethyl, n-propyl, and,

R ₀ Selected from hydrogen atom, chlorine atom, fluorine atom, bromine atom;

R ₁ selected from fluorine atom, bromine atom;

R ₂ selected from C1-C5 substituted or unsubstituted saturated alkyl;

R ₃ selected from halogen atoms.

3. The P2X7 receptor targeting probe precursor of claim 1 wherein formula (i) is selected from the group consisting of:

r in the Compound 1 ₄ Selected from the group consisting of C1-C3 unsubstituted saturated alkyl;

r2 in the compound 3 is selected from- (CH 2) n-; and n is 1 to 5.

4. A P2X7 receptor-targeting molecular probe prepared by radiolabeling the P2X7 receptor-targeting probe precursor of any one of claims 1 to 3, wherein the P2X7 receptor-targeting molecular probe has the structural formula shown in compound 2-1 or compound 2-3:

r in the Compound 2-1 ₄ Selected from the group consisting of C1-C3 unsubstituted saturated alkyl groups.

5. Use of a radioisotope labeled P2X7 receptor targeted probe precursor for medical use as claimed in any one of claims 1 to 3 for the preparation of an imaging agent for detecting central nervous degeneration type progressive disease, inflammation and tumor associated with abnormal expression of P2X7 receptor.

6. A kit for preparing a molecular probe for P2X7 receptor imaging, comprising a precursor of a P2X7 receptor targeting probe labeled with a medical radioisotope according to any one of claims 1 to 3 in the kit.

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