Iodine-containing compound with x-ray visualization function and application thereof

Abstract

The present application relates to a kind of iodine-containing compounds with X-ray imaging function and its application, belong to the field of tissue imaging.The present application provides a kind of iodine-containing compounds with X-ray imaging function, this iodine-containing compound is completely different from the existing iodine-containing contrast agent such as iodixanol in structure, and, this iodine-containing compound viscosity is lower than iodixanol, iodine content is higher than iodixanol, as the performance of iodine-containing contrast agent is superior.

Description

Cross-references to related applications

[0001] This application claims priority to Chinese Patent Application No. 202510243901.1, filed on February 28, 2025, entitled "An Iodine-Containing Compound with X-ray Imaging Function and Its Application", the entire contents of which are incorporated herein by reference. Technical Field

[0002] This invention relates to an iodine-containing compound with X-ray imaging function and its application, belonging to the field of tissue imaging technology. Background Technology

[0003] X-ray computed tomography (CT), as a mature tissue imaging technology, plays a vital role in the field of medical imaging due to its non-invasive, rapid, and high-resolution advantages, and is widely used in scientific research and clinical diagnosis. High-resolution CT can construct detailed three-dimensional images of various tissues and organs, including the gastrointestinal system, cardiovascular system, urinary system, liver, lungs, bones, cartilage, and tumor tissue. CT has become one of the most commonly used diagnostic tools in hospitals, and its usage continues to grow, with more than 45,000 CT scanners in clinical use worldwide. In the United States alone, more than 70 million patients undergo CT scans annually.

[0004] Enhanced CT scans typically require the use of contrast agents to increase the contrast of certain tissues or blood vessels in the images, thereby providing a clearer view of internal structures and lesions. Generally, contrast agents are administered intravenously and then circulate through the bloodstream to the lesion area. To achieve better X-ray attenuation and improve CT image contrast, elements with high atomic numbers need to be introduced into the contrast agent. Currently, various contrast agents are available, among which iodine-based contrast agents have become the most widely used type of contrast agent in CT imaging due to their excellent performance and safety.

[0005] Iodine-based contrast agents are mainly divided into two categories: ionic and non-ionic. Ionic iodine-based contrast agents originated in the 1930s when Moses Swick first invented a drug with a molecular structure of one benzene ring and one iodine atom, which could be used for intravenous pyelography—the earliest contrast agent. Non-ionic iodine-based contrast agents originated in the 1960s when Torsten Almen synthesized the first non-ionic iodine contrast agent, metrizamide, which was subsequently widely used in clinical diagnosis and treatment.

[0006] However, ionic contrast agents have drawbacks, including easy reaction with biological structures, potential nephrotoxicity and physiological problems due to high osmotic pressure, and difficulty in injection and prolonged renal retention time due to high viscosity. Therefore, they are rarely used clinically now. Compared to ionic iodine-based contrast agents, non-ionic iodine-based contrast agents have advantages such as low osmotic pressure and less impact on the heart, and have become the mainstream. Besides osmotic pressure, the viscosity of contrast agents is also an important consideration. High-viscosity contrast agents are difficult to inject, have a long renal retention time, and are prone to causing kidney damage. Therefore, although the contrast agent industry is mature, research on reducing osmotic pressure and viscosity remains a hot topic due to their potential nephrotoxicity and cardiotoxicity. Summary of the Invention

[0007] To address the above problems, the present invention provides an iodine-containing compound (iodophenyl-POX) with X-ray imaging function, wherein the iodine-containing compound has a structure as shown in formula (1) or formula (2):

[0008] Equation (1);

[0009] Equation (2); Where x represents a non-grafted repeating unit, and the value of x is a natural number greater than or equal to 0 and less than or equal to 80; y represents a grafted repeating unit, and the value of y is a natural number greater than or equal to 1 and less than or equal to 80; z represents the number of iodine atoms in each aryl group, and the value of z is a natural number greater than 0 and less than or equal to 3. i represents the capping terminal group of the non-grafted repeating unit, and i is selected from... , or ; e represents the capped terminal group of the grafted repeating unit, with the general structural formula -T1 or -T1-Q0; R1 represents a modifying group, selected from a straight bond or heteroatom (O, N, S, P), or selected from unsubstituted or substituted piperazine, hydroxypiperidine, etc. , , , , , , , , or ; In R1, a takes the value of a natural number greater than or equal to 2 and less than or equal to 20, w takes the value of a natural number greater than or equal to 2 and less than or equal to 20, b takes the value of a natural number greater than or equal to 2 and less than or equal to 20, c takes the value of a natural number greater than or equal to 2 and less than or equal to 20, d takes the value of a natural number greater than or equal to 2 and less than or equal to 20, s takes the value of a natural number greater than or equal to 2 and less than or equal to 20, j takes the value of a natural number greater than or equal to 1 and less than or equal to 18, p takes the value of a natural number greater than or equal to 2 and less than or equal to 20, and k takes the value of a natural number greater than or equal to 2 and less than or equal to 10. X is selected from carbon atoms (C) or heteroatoms (O, N, S); R3 represents a straight-chain or branched alkyl group from C1 to C20, or a straight-chain or branched alkyl group from C1 to C20 with one or more heteroatoms O, N, or S inserted. R4 represents a straight-chain or branched alkyl group from C1 to C20, or a straight-chain or branched alkyl group from C1 to C20 with one or more heteroatoms O, N, or S inserted.

[0010] In one embodiment of the present invention, -T1- is selected from -O-, -S-, -NH-, or The -T1 is selected from -NR5, -CH3, , , , , , , , , or ; In T1, R5 is selected from unsubstituted or substituted alkyl, alkenyl or aralkyl groups from C1 to C20.

[0011] In one embodiment of the present invention, Q0 is selected from hydrogen, unsubstituted or substituted alkyl, alkenyl, aralkyl, alkynyl, heterocyclic or aryl.

[0012] In one embodiment of the present invention, the iodine-containing compound has a structure as shown in formula (3):

[0013] Equation (3); Alternatively, the iodine-containing compound may have a structure as shown in formula (4):

[0014] Equation (4); Where n, m, and p all represent the number of carbon chains, and the values ​​of n, m, and p are natural numbers greater than or equal to 0 and less than or equal to 5.

[0015] In one embodiment of the present invention, the grafted repeating unit in the iodine-containing compound has a structure as shown in formula (5):

[0016] Equation (5); Alternatively, in the iodine-containing compound, the grafted repeating unit has a structure as shown in formula (6):

[0017] Equation (6).

[0018] In one embodiment of the present invention, the non-grafted repeating unit in the iodine-containing compound has a structure as shown in formula (7):

[0019] Equation (7); Alternatively, in the iodine-containing compound, the ungrafted repeating unit has a structure as shown in formula (8):

[0020] Equation (8).

[0021] In one embodiment of the present invention, the formula for calculating the degree of substitution of the iodine-containing compound is as follows: DS = Y / (X + Y); In the formula, DS represents the degree of substitution of the iodine-containing compound, X represents the number of non-grafted repeating units, Y represents the number of grafted repeating units, and X+Y represents the total number of repeating units, i.e., the sum of the number of grafted and non-grafted repeating units. Here, the degree of substitution refers to the proportion of units substituted by iodophenyl groups (i.e., grafted repeating units) to the total number of units (i.e., grafted repeating units + non-grafted repeating units) in the iodine-containing compound. Here, iodophenyl refers to an iodine-containing aromatic group.

[0022] In one embodiment of the invention, the iodine-containing compound has an iodine content of at least 50% by mass percentage.

[0023] In one embodiment of the present invention, when the iodine-containing compound is grafted with the same iodophenyl group, the iodine content of the iodine-containing compound is calculated using the following formula: ; In the formula, DS represents the degree of substitution of the iodine-containing compound; M_iodine represents the atomic weight of iodine atoms (when calculating the iodine content, M_iodine is rounded up, i.e., M_iodine = 127); z represents the number of iodine atoms in each benzyl group, and the value of z is a natural number greater than or equal to 0 and less than or equal to 4; M(non-grafted) represents the molar mass of the non-grafted repeating unit (when calculating the iodine content, M(non-grafted) is rounded up, i.e., M(non-grafted) = 127); M(grafted) represents the molar mass of the grafted repeating unit (when calculating the iodine content, M(grafted) is rounded up, for example, when the phenyl has one iodine as a substituent, M(grafted) = 375, when the phenyl has two iodine atoms as substituents, M(grafted) = 500, when the phenyl has three iodine atoms as substituents, M(grafted) = 626, and when the phenyl has four iodine atoms as substituents, M(grafted) = 752).

[0024] In one embodiment of the present invention, the iodine-containing compound has a structure as shown in formula (9):

[0025] Equation (9); Alternatively, the iodine-containing compound may have a structure as shown in formula (10):

[0026] Equation (10); Alternatively, the iodine-containing compound may have a structure as shown in formula (11):

[0027] Equation (11); Alternatively, the iodine-containing compound may have a structure as shown in formula (12):

[0028] Equation (12); Alternatively, the iodine-containing compound may have a structure as shown in formula (13):

[0029] Equation (13); Alternatively, the iodine-containing compound may have a structure as shown in formula (14):

[0030] Equation (14); Alternatively, the iodine-containing compound may have a structure as shown in formula (15):

[0031] Equation (15); Alternatively, the iodine-containing compound may have a structure as shown in formula (16):

[0032] Equation (16).

[0033] The present invention also provides a method for preparing the above-mentioned iodine-containing compound, the method comprising: polymerizing an intermediate and methyl trifluoromethanesulfonate to obtain compound A1; reacting compound A1 with potassium hydroxide to obtain compound B1; and reacting compound B1, triiodophenol, 4-dimethylaminopyridine and N,N'-dicyclohexylcarbodiimide to obtain the iodine-containing compound shown in formula (9) or formula (10); Alternatively, the method includes: polymerizing the intermediate and methyl trifluoromethanesulfonate to obtain compound A1; reacting compound A1 with potassium hydroxide to obtain compound B1; and reacting compound B1, aminoethanol, 4-dimethylaminopyridine and N,N'-dicyclohexylcarbodiimide to obtain the iodine-containing compound shown in formula (11). Alternatively, the method comprises: polymerizing 2-ethyl-4,5-dihydrooxazole, an intermediate and methyl trifluoromethanesulfonate to obtain compound A2; reacting compound A2 with potassium hydroxide to obtain compound B21; and reacting compound B21, triiodobenzoic acid, 4-dimethylaminopyridine and N,N'-dicyclohexylcarbodiimide to obtain the iodine-containing compound shown in formula (12); Alternatively, the method comprises: polymerizing 2-ethyl-4,5-dihydrooxazole and methyl trifluoromethanesulfonate to obtain compound A3; reacting compound A3 with an intermediate to obtain compound B3; reacting compound B3 with N-Boc-piperazine to obtain compound C3; reacting compound C3 with potassium hydroxide to obtain compound D3; reacting compound D3, ethylenediamine and N,N'-dicyclohexylcarbodiimide to obtain compound E3; reacting compound E3, triiodophenol and N,N'-dicyclohexylcarbodiimide to obtain compound F3; and after removing the protecting group from compound F3, reacting itaconic acid monomethyl ester and N,N'-dicyclohexylcarbodiimide to obtain the iodine-containing compound shown in formula (13); 2-Ethyl-4,5-dihydrooxazole, an intermediate, and methyl trifluoromethanesulfonate were polymerized to obtain compound A2; compound A2 was reacted with potassium hydroxide to obtain compound B21; compound B21, tert-butylpiperazine carboxylate, 4-dimethylaminopyridine, and N,N'-dicyclohexylcarbodiimide were reacted to obtain compound C21; after deprotecting compound C21, it was reacted with triiodobenzoic acid, 4-dimethylaminopyridine, and N,N'-dicyclohexylcarbodiimide to obtain the iodine-containing compound shown in formula (14); 2-Ethyl-4,5-dihydrooxazole, an intermediate, and methyl trifluoromethanesulfonate were polymerized to obtain compound A2; compound A2, 4-hydroxypiperidine, 4-dimethylaminopyridine, and N,N'-dicyclohexylcarbodiimide were reacted to obtain compound B22; compound B22, triiodobenzoic acid, 4-dimethylaminopyridine, and N,N'-dicyclohexylcarbodiimide were reacted to obtain the iodine-containing compound shown in formula (15); The intermediate and methyl trifluoromethanesulfonate were polymerized to obtain compound A4; compound A4 was reacted with N-Boc-piperazine to obtain compound B4; compound B4 was reacted with potassium hydroxide to obtain compound D4; compound D4, ethanolamine and N,N'-dicyclohexylcarbodiimide were reacted to obtain compound E4; compound E4, succinic anhydride and 4-dimethylaminopyridine were reacted to obtain compound F4; compound F4, N-hydroxysuccinimide and dicyclohexylcarbodiimide were reacted to obtain compound G4; compound G4, triiodobenzoic acid and N,N'-diisopropylcarbodiimide were reacted to obtain compound H4; after removing the protecting group from compound H4, itaconic acid monomethyl ester and N,N'-dicyclohexylcarbodiimide were reacted to obtain the iodine-containing compound shown in formula (16); The intermediate has a structure as shown in equation (17):

[0034] Equation (17); The 2-ethyl-4,5-dihydrooxazole has the structure shown in formula (18):

[0035] Equation (18); In formula (17), R2 represents a substituent group, and R2 is selected from... , or , where n is a natural number greater than or equal to 0 and less than or equal to 5, and g is a natural number greater than or equal to 0 and less than or equal to 5.

[0036] In one embodiment of the invention, the reaction is carried out in a solvent; the solvent comprises water or an organic solvent.

[0037] In one embodiment of the present invention, the organic solvent includes N,N-dimethylformamide, dimethyl sulfoxide, methanol and / or acetonitrile.

[0038] The present invention also provides the application of the above-mentioned iodine-containing compounds in the preparation of iodine-containing contrast agents.

[0039] In one embodiment of the present invention, the iodine-containing contrast agent further comprises a solvent; the solvent comprises dimethyl sulfoxide.

[0040] The present invention also provides an iodine-containing contrast agent, wherein the components of the iodine-containing contrast agent include the above-mentioned iodine-containing compound.

[0041] In one embodiment of the present invention, the iodine-containing contrast agent further comprises a solvent; the solvent comprises dimethyl sulfoxide.

[0042] The technical solution of this invention has the following advantages: This invention provides an iodine-containing compound. Because iodixanol is widely used clinically and has advantages such as low viscosity, high iodine content, and low toxicity, current research on iodine-containing contrast agents focuses on modifying the core structure of iodixanol, lacking entirely innovative products. Ideally, iodine-containing contrast agents should possess low toxicity, low viscosity, and high iodine content, and must also be completely soluble in the formulation medium. This invention provides an iodine-containing compound that is structurally completely different from existing iodixanol and other iodine-containing contrast agents. Furthermore, this iodine-containing compound has a lower viscosity and a higher iodine content than iodixanol, exhibiting superior performance as an iodine-containing contrast agent. Attached Figure Description

[0043] Figure 1 : The hydrogen spectrum of methyl 4-(2-chloroethylamine)-4-oxobutyrate.

[0044] Figure 2 : The hydrogen spectrum of methyl 3-(4,5-dihydrooxazol-2-yl)propionate.

[0045] Figure 3 : The hydrogen spectrum of iodine-containing compound I.

[0046] Figure 4 : The proton NMR spectrum of iodine-containing compound II.

[0047] Figure 5 : The proton NMR spectrum of iodine-containing compound III.

[0048] Figure 6 : The hydrogen spectrum of iodine-containing compound IV.

[0049] Figure 7 : The proton NMR spectrum of iodine-containing compound V.

[0050] Figure 8 : The proton NMR spectrum of iodine-containing compound VI.

[0051] Figure 9 : The proton NMR spectrum of iodine-containing compound VII.

[0052] Figure 10: The proton NMR spectrum of compound B4 in Example 16.

[0053] Figure 11 : The proton NMR spectrum of iodine-containing compound VIII.

[0054] Figure 12 The imaging effect of iodine-containing compound I in DSA (renal artery angiography).

[0055] Figure 13 The imaging effect of iodine-containing compound II in DSA (skull base microvascular network angiography).

[0056] Figure 14 The imaging effect of iodine-containing compound III in DSA (skull base microvascular network angiography). Detailed Implementation

[0057] As used herein, the term alkyl can be saturated or unsaturated (i.e., includes double bonds (olefinic bonds) and / or triple bonds (alkynyl groups)), and can also be cyclic, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc., or include cyclic portions (including polycyclic alkyl groups). Heteroatoms may be inserted into the hydrocarbon chain of the alkyl group, wherein one or more atoms such as oxygen, nitrogen, sulfur, or silicon are selected. Optionally, each alkane may be substituted with a free radical by available carbon atoms, said substituents including, for example, alkyl, halogen (F, Cl, Br, I), haloalkyl (e.g., CCl3 or CF3), alkoxy, aryloxy, alkylthio, hydroxy, methoxy, carboxyl, epoxy, alkoxycarbonyl, amino, carbamoyl, alkylurea, aryl, ether, ester, thioester, nitrile, nitro, amide, carbonyl, oxy, carboxylate, mercapto, alkyl sulfide, aryl sulfide, sulfone, sulfoxide, trialkylsilyl, dialkylarylsilyl, alkyldiaryl, and triarylsilyl. Simple examples include, but are not limited to, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, and nonyl.

[0058] As used herein, the term aryl refers to a monocyclic or bicyclic aromatic hydrocarbon group comprising a 5- or 6-membered aryl monocyclic ring or an aromatic group containing 6 to 12 carbon atoms. Optionally, the aryl group may be substituted with available carbon atoms by substituents as defined above. The aromatic ring system may include 1 to 4 heteroatoms such as sulfur, oxygen, or nitrogen. Examples of the aforementioned aryl groups include, but are not limited to, phenyl, tolyl, hydroxyphenyl, benzyl, naphthyl, biphenyl, pyrrole, furan, thiophene, thiazole, isothiazole, imidazole, triazole, tetrazolium, pyrazole, oxazole, isoxazole, triazine, tetrazine, pyridine, pyrazine, pyridazine, and pyrimidine.

[0059] The following embodiments are provided to better understand the present invention and are not limited to the preferred embodiments described. They do not constitute a limitation on the content and scope of protection of the present invention. Any product that is the same as or similar to the present invention, derived by any person under the guidance of the present invention or by combining the features of the present invention with other prior art, falls within the protection scope of the present invention.

[0060] For any experimental steps or conditions not specified in the following examples, the procedures or conditions described in the literature in this field can be followed. Reagents or instruments whose manufacturers are not specified are all commercially available conventional reagent products.

[0061] Example 1: An iodine-containing compound with X-ray imaging function This embodiment provides an iodine-containing compound I with X-ray imaging function, wherein the iodine-containing compound I has the following structure:

[0062] Equation (9).

[0063] Example 2: A method for preparing an iodine-containing compound with X-ray imaging function This embodiment provides a method for preparing iodine-containing compound I as described in Example 1, and the specific steps are as follows: 1. Preparation of intermediates Step 1: Under ice bath conditions, 4-methoxy-4-oxobutyric acid (200 g, 1.52 mol, CAS: 3878-55-5) was added to a 2 L three-necked flask containing dichloromethane (1 L, Sinopharm) and N,N-dimethylformamide (10 mL, Sinopharm) to obtain a solution. When the temperature of the solution dropped to 0℃, oxaloyl chloride (326 mL, 3.8 mol, Sinopharm) was slowly added dropwise to the solution to obtain a reaction system. The reaction system was reacted at 0℃ for 0.5 hours, then restored to room temperature (25℃) and reacted for another 1.5 hours at room temperature (stirred at 160 rpm) to obtain the reaction product. The reaction product was concentrated under reduced pressure to obtain crude methyl 4-chloro-4-oxobutyrate (200 g). The crude product did not require purification and was used directly in the next step. The methyl 4-chloro-4-oxobutyrate has the following structure:

[0064] Equation (19).

[0065] Step 2: Under ice bath conditions, add methyl 4-chloro-4-oxobutyrate (200 g, 1.34 mol) and 2-chloroethylamine hydrochloride (172 g, 1.48 mol, CAS: 870-24-6) to a four-necked flask containing dichloromethane (2 L, Sinopharm) to obtain a solution; when the temperature of the solution drops to 0℃, slowly add triethylamine (410 mL, 2.95 mol, Sinopharm) to the solution to obtain a reaction system; react the reaction system at 0℃ for 0.5 hours, then restore to room temperature (25℃) and continue the reaction at room temperature for 0.5 hours (stirring at 160 rpm) to obtain the reaction product; filter the reaction product, collect the filtrate, and rinse the four-necked flask with dichloromethane (200 mL × 2) to obtain the rinsing solution; combine the filtrate and rinsing solution to obtain a mixture; add saturated saline solution (1 L, 2 L, Sinopharm) to the mixture. L) After washing and extraction, the organic phases were combined; the organic phases were concentrated under reduced pressure to obtain methyl 4-(2-chloroethylamine)-4-oxobutyrate (180 g). The methyl 4-(2-chloroethylamine)-4-oxobutyrate has the following structure:

[0066] Equation (20).

[0067] Step 3: At room temperature, methanol (250 mL, Sinopharm) and triethylamine (79.0 g, 0.78 mol, Sinopharm) were added to a 1 L single-necked flask containing methyl 4-(2-chloroethylamine)-4-oxobutyrate (50 g, 0.260 mol). The mixture was first purged with nitrogen three times, and then reacted at 90 °C for 16 hours (stirred at 160 rpm) to obtain the reaction product. The reaction product was first concentrated under reduced pressure, and then distilled under reduced pressure at 120 °C to obtain the intermediate methyl 3-(4,5-dihydrooxazol-2-yl)propionate (35 g). The methyl 3-(4,5-dihydrooxazol-2-yl)propionate has the following structure:

[0068] Equation (21).

[0069] The 1H NMR spectrum of methyl 4-(2-chloroethylamine)-4-oxobutyrate is shown in the figure. Figure 1 1H NMR data for methyl 4-(2-chloroethylamine)-4-oxobutyrate: 1H NMR (400 MHz, Chloroform-d) δ 6.27 (s, 1H), 3.70 (s, 3H), 3.63 – 3.59 (m, 4H), 2.69 (t, J = 6.7 Hz, 2H), 2.54 (d, J = 6.8 Hz, 2H). The 1H NMR spectrum of methyl 3-(4,5-dihydrooxazol-2-yl)propionate is shown in the figure. Figure 2 1H NMR data for methyl 3-(4,5-dihydrooxazol-2-yl)propionate: 1H NMR (400 MHz, Chloroform-d) δ 4.24 (t, J = 9.5 Hz, 2H), 3.85 – 3.79 (m, 2H), 3.70 (s, 3H), 2.70 – 2.64 (m, 2H), 2.62 – 2.56 (m, 2H). 2. Preparation of iodine-containing compounds Step 1: Under ice bath conditions, methyl 3-(4,5-dihydrooxazol-2-yl)propionate (5 g, 31.85 mmol) was added to a 100 mL three-necked flask containing acetonitrile (5 mL, Sinopharm). After purging with nitrogen three times, methyl trifluoromethanesulfonate (522.0 mg, 3.19 mmol, Sinopharm, CAS: 333-27-7) was slowly added dropwise to the reaction flask at 0°C. The reaction was then carried out at 0°C for 0.5 hours, and finally heated to 90°C and reacted at 90°C for 16 hours (stirred at 160 rpm) to obtain the reaction product. After the reaction product returned to room temperature, piperidine (2.7 g, 31.85 mmol) was added dropwise to the reaction product to obtain a mixture. The mixture was concentrated under reduced pressure to obtain a white solid compound A1 (4.2 g). The compound A1 has the following structure (n is a natural number greater than or equal to 30 and less than or equal to 50):

[0070] Equation (22).

[0071] Step 2: At room temperature, compound A1 (3.0 g) was added to 30 mL of a 5% (w / v, g / 100 mL) potassium hydroxide aqueous solution and reacted at room temperature for 6 hours (stirred at 160 rpm) to obtain the reaction product. The pH of the reaction product was adjusted to 7.0 by adding 1 M hydrochloric acid aqueous solution. The reaction product was then concentrated under reduced pressure to obtain crude compound B1 (2.6 g). The crude product did not require purification and was used directly in the next step. The compound B1 has the following structure (n is a natural number greater than or equal to 30 and less than or equal to 50):

[0072] Equation (23).

[0073] Step 3: At room temperature, triiodophenol (840 mg, CAS: 609-23-4), 4-dimethylaminopyridine (15.0 mg, CAS: 1122-58-3), and N,N'-dicyclohexylcarbodiimide (180 mg, CAS: 538-75-0) were added to a 50 mL single-necked flask containing compound B1 (100.0 mg) and dichloromethane (5 mL, Sinopharm). The mixture was first purged with nitrogen three times, and then reacted at room temperature for 6 hours (stirred at 160 rpm) to obtain the reaction product. Water (20 mL) was added to the reaction product, and then dichloromethane (20 mL) was used to purge the mixture. Extraction was performed using 3 mL of dichloromethane (dichloromethane was added to the aqueous phase three times sequentially for extraction), and the organic phases were combined. The organic phase was first dried with anhydrous sodium sulfate, then concentrated under reduced pressure, and then slurried with methyl tert-butyl ether to remove unreacted triiodophenol, 4-dimethylaminopyridine, N,N'-dicyclohexylcarbodiimide, and compound B1, to obtain iodine-containing compound I (210 mg) as described in Example 1. The iodine-containing compound I prepared here is a mixed system, wherein the value of y is a natural number greater than or equal to 30 and less than or equal to 50.

[0074] The proton NMR spectrum of iodine-containing compound I is shown below. Figure 3 ¹H NMR spectroscopy revealed characteristic peaks for the benzene ring hydrogens and compound B1 in the target product. The chemical shifts and integrals matched the theoretical structure, confirming the successful preparation of the iodine-containing compound. (Since the prepared iodine-containing compound I was a mixed system with a y=30~50 distribution, ¹H NMR only provided the overall signal; therefore, spectral analysis primarily focused on confirming the characteristic peaks.) ¹H NMR data for iodine-containing compound I: 1 H NMR (400 MHz, DMSO-d6) δ7.94 (s, 2H,-Ar-), 3.51 (m, 2H,-C-CH2-CO), 2.50 (m, 2H,-C-CH2-CO), 1.15 (m,4H,-CH2-). Example 3: An iodine-containing compound with X-ray imaging function This embodiment provides an iodine-containing compound II with X-ray imaging function, wherein the iodine-containing compound II has the following structure:

[0075] Equation (10).

[0076] Example 4: A method for preparing an iodine-containing compound with X-ray imaging function This embodiment provides a method for preparing the iodine-containing compound II described in Example 3, and the specific steps are as follows: Compound B1 was prepared according to the method in Example 2. At room temperature, triiodophenol (420 mg, CAS: 609-23-4), 4-dimethylaminopyridine (15.0 mg, CAS: 1122-58-3), and N,N'-dicyclohexylcarbodiimide (180 mg, CAS: 538-75-0) were added to a 50 mL single-necked flask containing compound B1 (100.0 mg) and dichloromethane (5 mL, Sinopharm). The mixture was first purged with nitrogen three times, and then reacted at room temperature for 6 hours (stirred at 160 rpm) to obtain the reaction product. Water (20 mL) was added to the reaction product, and the mixture was extracted with dichloromethane (20 mL × 3) (dichloromethane was added to the aqueous phase three times for extraction), and the organic phases were combined. The organic phase was dried with anhydrous sodium sulfate and then concentrated under reduced pressure to obtain the iodine-containing compound II (210 mg) described in Example 3. (mg), the iodine-containing compound II prepared here is a mixed system, in which the value of x is a natural number greater than or equal to 30 and less than or equal to 50, and x:y = 1:1.

[0077] The proton NMR spectrum of iodine-containing compound II is shown in [reference needed]. Figure 4 ¹H NMR spectroscopy revealed characteristic peaks for the benzene ring hydrogens and compound B1 in the target product. The chemical shifts and integrals matched the theoretical structure, confirming the successful preparation of the iodine-containing compound. (Since the prepared iodine-containing compound II was a mixed system with a y=30~50 distribution, ¹H NMR only provided the overall signal; therefore, spectral analysis focused on confirming the characteristic peaks.) ¹H NMR data for iodine-containing compound II: 1 H NMR (400 MHz, DeuteriumOxide) δ 7.95 (d, J = 7.4 Hz, 1H), 6.82 (d, J = 7.3 Hz, 1H), 3.73 – 3.60 (m,4H), 3.53 (m, 4H), 3.46 (m, 2H), 2.56 (m, 4H), 2.38 (m, 4H). Example 5: An iodine-containing compound with X-ray imaging function This embodiment provides an iodine-containing compound III with X-ray imaging function, wherein the iodine-containing compound III has the following structure:

[0078] Equation (11).

[0079] Example 6: A method for preparing an iodine-containing compound with X-ray imaging function This embodiment provides a method for preparing the iodine-containing compound III described in Example 5, and the specific steps are as follows: Compound B1 was prepared according to the method in Example 2. At room temperature, aminoethanol (210 mg, CAS: 141-43-5), 4-dimethylaminopyridine (15.0 mg, CAS: 1122-58-3), and N,N'-dicyclohexylcarbodiimide (110 mg) were added to a 50 mL single-necked flask containing compound B1 (150.0 mg) and dichloromethane (5 mL, Sinopharm). The mixture was first purged with nitrogen three times, and then reacted at room temperature for 6 hours (stirred at 160 rpm) to obtain the reaction product. Water (20 mL) was added to the reaction product, and the mixture was extracted with dichloromethane (20 mL × 3) (dichloromethane was added to the aqueous phase in three separate additions), and the organic phases were combined. The organic phase was dried with anhydrous sodium sulfate and then concentrated under reduced pressure to obtain the iodine-containing compound III (210 mg) described in Example 5. The iodine-containing compound III obtained here is a mixed system, in which the value of y is a natural number greater than or equal to 30 and less than or equal to 50.

[0080] The proton NMR spectrum of iodine-containing compound III is shown below. Figure 5 ¹H NMR spectroscopy revealed characteristic peaks for the benzene ring hydrogen and compound B1 in the target product. The chemical shifts and integrals matched the theoretical structure, confirming the successful preparation of the iodine-containing compound. (Since the prepared iodine-containing compound III was a mixed system with a y=30~50 distribution, ¹H NMR only provided the overall signal; therefore, spectral analysis primarily focused on confirming the characteristic peaks.) ¹H NMR data for iodine-containing compound III: 1 NMR (400 MHz, DMSO-d6) δ8.18 (d, J = 2.0 Hz, 1H), 7.55 (d, J = 2.0 Hz, 1H), 5.60 (d, J = 8.0 Hz, 1H), 3.38 – 3.27 (m, 1H), 1.71 (m, 2H), 1.61 (m, 2H), 1.50 (m, 1H), 1.30 – 1.20 (m, 2H), 1.19 – 1.10 (m, 2H), 1.08 – 0.99 (m, 2H). Example 7: An iodine-containing compound with X-ray imaging function This embodiment provides an iodine-containing compound IV with X-ray imaging function, wherein the iodine-containing compound IV has the following structure:

[0081] Equation (12).

[0082] Example 8: A method for preparing an iodine-containing compound with X-ray imaging function This embodiment provides a method for preparing the iodine-containing compound IV described in Example 7, and the specific steps are as follows: Step 1: Under ice bath conditions, 2-ethyl-4,5-dihydrooxazole (5 g, 31.85 mmol / L, CAS: 10431-98-8) and methyl 3-(4,5-dihydrooxazole-2-yl)propionate (3.4 g, 21.24 mmol / L) were added to a 100 mL three-necked flask containing acetonitrile (5 mL, Sinopharm). The mixture was purged with nitrogen three times. Then, methyl trifluoromethanesulfonate (522.0 mg, 3.19 mmol / L, Sinopharm) was slowly added dropwise to the reaction flask at 0°C. The reaction was then carried out at 0°C for 0.5 hours, and finally heated to 90°C and reacted at 90°C for 16 hours (stirred at 160 rpm) to obtain the reaction product. After the reaction product returned to room temperature, piperidine (2.7 g, 31.85 mmol / L) was added dropwise to the reaction product to obtain a mixture. The mixture was concentrated under reduced pressure to obtain a white solid compound A2 (6 g). The 2-ethyl-4,5-dihydrooxazole has the following structure:

[0083] Equation (18); The compound A2 has the following structure (x is a natural number greater than or equal to 30 and less than or equal to 50, and x:y = 3:2):

[0084] Equation (24).

[0085] Step 2: At room temperature, compound A2 (5.0 g) was added to 30 mL of a 5% (w / v, g / 100 mL) potassium hydroxide aqueous solution and reacted at room temperature for 6 hours (stirred at 160 rpm) to obtain the reaction product. The pH of the reaction product was adjusted to 7.0 by adding 1 M hydrochloric acid aqueous solution. The reaction product was then concentrated under reduced pressure to obtain crude compound B21 (3.8 g). The crude product did not require purification and was used directly in the next step. The compound B21 has the following structure (x is a natural number greater than or equal to 30 and less than or equal to 50, and x:y = 3:2):

[0086] Equation (25).

[0087] Step 3: At room temperature, triiodobenzoic acid (560 mg), 4-dimethylaminopyridine (20.0 mg), and N,N'-dicyclohexylcarbodiimide (160 mg) were added to a 50 mL single-necked flask containing compound B21 (200.0 mg) and dichloromethane (5 mL, Sinopharm). The mixture was first purged with nitrogen three times, and then reacted at room temperature for 6 hours (stirred at 160 rpm) to obtain the reaction product. Water (20 mL) was added to the reaction product, and the mixture was extracted with dichloromethane (20 mL × 3) (dichloromethane was added to the aqueous phase three times for extraction), and the organic phases were combined. The organic phase was dried with anhydrous sodium sulfate and then concentrated under reduced pressure to obtain the iodine-containing compound IV (240 mg) described in Example 7. The iodine-containing compound IV obtained here is a mixed system, in which the value of x is a natural number greater than or equal to 30 and less than or equal to 50, and x:y = 3:2.

[0088] The proton NMR spectrum of iodine-containing compound IV is shown below. Figure 6 ¹H NMR spectroscopy revealed characteristic peaks for the benzene ring hydrogens and B21 in the target product. The chemical shifts and integrals matched the theoretical structure, confirming the successful preparation of the iodine-containing compound. (Since the prepared iodine-containing compound IV was a mixed system with a y=30~50 distribution, ¹H NMR only provided the overall signal; therefore, spectral analysis primarily focused on confirming the characteristic peaks.) ¹H NMR data for iodine-containing compound IV: 1 H NMR (400 MHz, Chloroform-d)δ 7.52 (s, 1H), 7.00 (s, 1H), 1.33 (m, 2H), 1.28 (m, 1H), 1.26 (m, 4H),1.24(m, 2H)0.88 (m, 2H), 0.85 (m, 2H), 0.84 (m, 2H), 0.07 (m, 2H). Example 9: An iodine-containing compound with X-ray imaging function This embodiment provides an iodine-containing compound V with X-ray imaging function, wherein the iodine-containing compound V has the following structure:

[0089] Equation (13).

[0090] Example 10: A method for preparing an iodine-containing compound with X-ray imaging function This embodiment provides a method for preparing the iodine-containing compound V described in Example 9, and the specific steps are as follows: Step 1: Under ice bath conditions, 2-ethyl-4,5-dihydrooxazole (9.5 g, 95.55 mmol) was added to a 100 mL three-necked flask containing acetonitrile (5 mL, Sinopharm). The mixture was first purged three times with nitrogen. Then, methyl trifluoromethanesulfonate (1.58 g, 9.60 mmol, Sinopharm) was slowly added dropwise to the reaction flask at 0°C. The reaction was then carried out at 0°C for 0.5 hours, and finally heated to 90°C and reacted at 90°C for 12 hours (stirred at 160 rpm) to obtain a reaction product containing compound A3. After the reaction product containing compound A3 returned to room temperature, methyl 3-(4,5-dihydrooxazole-2-yl)propionate (10 g, 63.7 mmol) was added to the reaction product. The reaction system B was obtained by heating reaction system B to 100°C and reacting at 100°C for 12 hours (stirred at 160 rpm) to obtain a reaction product containing compound B3. After the reaction product containing compound B3 returned to room temperature, acetonitrile (20 mL) containing N-Boc-piperazine (5.93 g, 31.85 mmol) was added dropwise to the reaction product to obtain reaction system C. The reaction system C was reacted at room temperature for 2 hours (stirred at 160 rpm) to obtain a reaction product containing compound C3. The reaction product containing compound C3 was concentrated under reduced pressure to obtain a white solid compound C3 (11 g). The compound C3 has the following structure (x is a natural number greater than or equal to 30 and less than or equal to 50, and x:y = 3:2):

[0091] Equation (26).

[0092] Step 2: At room temperature, compound C3 (1.0 g) was added to 10 mL of a 5% (w / v, g / 100 mL) potassium hydroxide aqueous solution to obtain a reaction system; the reaction system was reacted at room temperature for 6 hours (stirred at 160 rpm) to obtain the reaction product; the pH of the reaction product was adjusted to 7.0 by adding 1 M hydrochloric acid aqueous solution, and then the reaction product was concentrated under reduced pressure to obtain crude compound D3 (800 mg). The crude product did not need to be purified and was used directly in the next step. The compound D3 has the following structure (x is a natural number greater than or equal to 30 and less than or equal to 50, and x:y = 3:2):

[0093] Equation (27).

[0094] Step 3: At room temperature, ethylenediamine (120 mg) and N,N'-dicyclohexylcarbodiimide (730 mg) were added to a 50 mL single-necked flask containing compound D3 (600.0 mg) and dichloromethane (5 mL, Sinopharm). The mixture was first purged with nitrogen three times, and then reacted at room temperature for 6 hours (stirred at 160 rpm) to obtain the reaction product. Water (20 mL) was added to the reaction product, and the mixture was extracted with dichloromethane (20 mL × 3) (dichloromethane was added to the aqueous phase three times for extraction). The organic phases were then combined. The organic phase was dried with anhydrous sodium sulfate and then concentrated under reduced pressure to obtain crude compound E3 (210 mg). The crude product did not require purification and was used directly in the next step. The compound E3 has the following structure (x is a natural number greater than or equal to 30 and less than or equal to 50, and x:y = 3:2):

[0095] Equation (28).

[0096] Step 4: At room temperature, triiodophenol (210 mg) and N,N'-dicyclohexylcarbodiimide (730 mg) were added to a 50 mL single-necked flask containing compound E3 (100.0 mg) and dichloromethane (5 mL, Sinopharm). The mixture was first purged with nitrogen three times, and then reacted at room temperature for 6 hours (stirred at 160 rpm) to obtain the reaction product. Water (20 mL) was added to the reaction product, and the mixture was extracted with dichloromethane (20 mL × 3) (dichloromethane was added to the aqueous phase three times for extraction). The organic phases were then combined. The organic phase was dried with anhydrous sodium sulfate and then concentrated under reduced pressure to obtain crude compound F3 (260 mg). The crude product did not require purification and was used directly in the next step. The compound F3 has the following structure (x is a natural number greater than or equal to 30 and less than or equal to 50, and x:y = 3:2):

[0097] Equation (29).

[0098] Step 5: At room temperature, trifluoroacetic acid (1 mL) was added to a 50 mL single-necked flask containing compound F3 (200 mg) and dichloromethane (5 mL, Sinopharm), and the mixture was reacted at room temperature for 1 hour (stirred at 160 rpm) to obtain the reaction product; the reaction product was concentrated under reduced pressure to obtain crude compound G3 (180 mg). The crude product did not require purification and was used directly in the next step. The compound G3 has the following structure (x is a natural number greater than or equal to 30 and less than or equal to 50, and x:y = 3:2):

[0099] Equation (30).

[0100] Step Six: At room temperature, itaconic acid monomethyl ester (30 mg, CAS: 7338-27-4) and N,N'-dicyclohexylcarbodiimide (730 mg) were added to a 50 mL single-necked flask containing compound G3 (180 mg) and dichloromethane (5 mL, Sinopharm). The mixture was first purged with nitrogen three times, and then reacted at room temperature for 6 hours (stirred at 160 rpm) to obtain the reaction product. Water (20 mL) was added to the reaction product, and the mixture was extracted with dichloromethane (20 mL × 3) (dichloromethane was added to the aqueous phase three times for extraction), and the organic phases were combined. The organic phase was dried with anhydrous sodium sulfate and then concentrated under reduced pressure to obtain the iodine-containing compound V (150 mg) described in Example 9. The iodine-containing compound V obtained here is a mixed system, where x is a natural number greater than or equal to 30 and less than or equal to 50, and x:y = 3:2.

[0101] The 1H NMR spectrum of iodine-containing compound V is shown in [reference needed]. Figure 7 ¹H NMR spectroscopy revealed characteristic peaks for the benzene ring hydrogen, amide hydrogen, and G3 in the target product. The chemical shifts and integrals matched the theoretical structure, confirming the successful preparation of the iodine-containing compound. (Since the prepared iodine-containing compound V is a mixed system with a y=30~50 distribution, ¹H NMR only provides the overall signal; therefore, spectral analysis primarily focuses on confirming characteristic peaks.) ¹H NMR data for iodine-containing compound V: 1 H NMR (500 MHz, Chloroform-d) δ 8.16 (s, J = 2.0 Hz, 1H), 7.88 (s, J = 2.0 Hz, 1H), 6.75 (s,1H), 6.17 (s, 1H), 5.48 (dt, J = 13.7, 0.9 Hz, 1H), 3.98 (t, J = 7.4 Hz, 2H), 3.79 – 3.71 (m, 5H), 3.58 (t, J = 7.4 Hz, 2H), 3.49 – 3.40 (m, 8H), 2.91 (d,J = 9.4 Hz, 5H), 2.78 (t, J = 7.2 Hz, 2H), 2.46 (s, 4H), 2.21 (t, J = 5.1 Hz, 4H), 2.16 (tt, J = 7.6, 5.2 Hz, 2H), 1.93 (q, J = 8.0 Hz, 2H), 0.95 (t, J =8.0 Hz, 3H). Example 11: An iodine-containing compound with X-ray imaging function This embodiment provides an iodine-containing compound VI with X-ray imaging function, wherein the iodine-containing compound VI has the following structure:

[0102] Equation (14).

[0103] Example 12: A method for preparing an iodine-containing compound with X-ray imaging function This embodiment provides a method for preparing the iodine-containing compound VI described in Example 11, and the specific steps are as follows: Step 1: Prepare compound B21 according to the method in Example 8.

[0104] Step 2: At room temperature, tert-butylpiperazine carboxylate (655 mg), 4-dimethylaminopyridine (33.0 mg), and N,N'-dicyclohexylcarbodiimide (210 mg) were added to a 50 mL single-necked flask containing compound B21 (200.0 mg) and dichloromethane (5 mL, Sinopharm). The mixture was first purged with nitrogen three times, and then reacted at room temperature for 6 hours (stirred at 160 rpm) to obtain the reaction product. Water (20 mL) was added to the reaction product, and the mixture was extracted with dichloromethane (20 mL × 3) (dichloromethane was added to the aqueous phase three times for extraction), and the organic phases were combined. The organic phase was dried with anhydrous sodium sulfate and then concentrated under reduced pressure to obtain compound C21 (240 mg). The compound C21 has the following structure (x is a natural number greater than or equal to 30 and less than or equal to 50, and x:y = 3:2):

[0105] Equation (31).

[0106] Step 3: At room temperature, trifluoroacetic acid (1 mL) was added to a 50 mL single-necked flask containing compound C21 (240 mg) and dichloromethane (5 mL, Sinopharm), and the mixture was reacted at room temperature for 1 hour (stirred at 160 rpm) to obtain the reaction product; the reaction product was concentrated under reduced pressure to obtain crude compound D21 (210 mg). The crude product did not require purification and was used directly in the next step. The compound D21 has the following structure (x is a natural number greater than or equal to 30 and less than or equal to 50, and x:y = 3:2):

[0107] Equation (32).

[0108] Step 4: At room temperature, triiodobenzoic acid (690 mg), 4-dimethylaminopyridine (30.0 mg), and N,N'-dicyclohexylcarbodiimide (174 mg) were added to a 50 mL single-necked flask containing compound D21 (200.0 mg) and dichloromethane (5 mL, Sinopharm). The mixture was first purged with nitrogen three times, and then reacted at room temperature for 6 hours to obtain the reaction product. Water (20 mL) was added to the reaction product, and the mixture was extracted with dichloromethane (20 mL × 3) (dichloromethane was added to the aqueous phase three times for extraction), and the organic phases were combined. The organic phase was first dried with anhydrous sodium sulfate, and then concentrated under reduced pressure to obtain the iodine-containing compound VI (240 mg) described in Example 11. The iodine-containing compound VI obtained here is a mixed system, in which the value of x is a natural number greater than or equal to 30 and less than or equal to 50, and x:y = 3:2.

[0109] The proton NMR spectrum of iodine-containing compound VI is shown in [reference needed]. Figure 8 ¹H NMR spectroscopy revealed characteristic peaks for the benzene ring hydrogens and D21 in the target product. The chemical shifts and integrals matched the theoretical structure, confirming the successful preparation of the iodine-containing compound. (Since the prepared iodine-containing compound VI is a mixed system with a y=30~50 distribution, ¹H NMR only provides the overall signal; therefore, spectral analysis primarily focuses on confirming characteristic peaks.) ¹H NMR data for iodine-containing compound VI: 1 H NMR (400 MHz, Chloroform-d)δ 8.22 (d, J = 1.9 Hz, 1H), 7.43 (d, J = 1.9 Hz, 1H), 4.19 (m 8H), 3.85 (m,9H), 1.80 (m, 2H), 1.50 (m, 2H), 1.41 (m, 2H), 1.14 (m, 6H). Example 13: An iodine-containing compound with X-ray imaging function This embodiment provides an iodine-containing compound VII with X-ray imaging function, wherein the iodine-containing compound VII has the following structure:

[0110] Equation (15).

[0111] Example 14: A method for preparing an iodine-containing compound with X-ray imaging function This embodiment provides a method for preparing the iodine-containing compound VII described in Example 7, and the specific steps are as follows: Step 1: Prepare compound A2 according to the method in Example 8; Step 2: Add 4-hydroxypiperidine (170 mg), 4-dimethylaminopyridine (35.0 mg), and N,N'-dicyclohexylcarbodiimide (205 mg) to a 50 mL single-necked flask containing compound A2 (200.0 mg) and dichloromethane (5 mL, Sinopharm). First, purge with nitrogen three times, then react at room temperature for 6 hours to obtain the reaction product. Add water (20 mL) to the reaction product, then extract with dichloromethane (20 mL × 3) (dichloromethane was added to the aqueous phase three times for extraction), and combine the organic phases. Dry the organic phase with anhydrous sodium sulfate, then concentrate under reduced pressure to obtain compound B22 (240 mg). The compound B22 has the following structure (x is a natural number greater than or equal to 30 and less than or equal to 50, and x:y = 3:2):

[0112] Equation (33).

[0113] Step 3: At room temperature, triiodobenzoic acid (660 mg), 4-dimethylaminopyridine (30.0 mg), and N,N'-dicyclohexylcarbodiimide (170 mg) were added to a 50 mL single-necked flask containing compound B22 (240.0 mg) and dichloromethane (5 mL, Sinopharm). The mixture was first purged with nitrogen three times, and then reacted at room temperature for 6 hours (stirred at 160 rpm) to obtain the reaction product. Water (20 mL) was added to the reaction product, and the mixture was extracted with dichloromethane (20 mL × 3) (dichloromethane was added to the aqueous phase three times for extraction), and the organic phases were combined. The organic phase was dried with anhydrous sodium sulfate and then concentrated under reduced pressure to obtain the iodine-containing compound VII (300 mg) described in Example 13. The iodine-containing compound IV obtained here is a mixed system, in which the value of x is a natural number greater than or equal to 30 and less than or equal to 50, and x:y = 3:2.

[0114] The proton NMR spectrum of iodine-containing compound VII is shown in [reference needed]. Figure 9 ¹H NMR spectroscopy revealed characteristic peaks for the benzene ring hydrogens and B22 in the target product. The chemical shifts and integrals matched the theoretical structure, confirming the successful preparation of the iodine-containing compound. (Since the prepared iodine-containing compound VII is a mixed system with a y=30~50 distribution, ¹H NMR only provides the overall signal; therefore, spectral analysis primarily focuses on confirming characteristic peaks.) ¹H NMR data for iodine-containing compound VII: 1H NMR (400 MHz, Chloroform-d) δ 8.22 (d, J = 1.9 Hz, 1H), 7.43 (d, J = 1.9 Hz, 1H), 4.25 –4.17 (m, 6H), 3.91 – 3.79 (m, 8H), 1.81 (s, 2H), 1.49 (s, 3H), 1.42 (s, 2H), 1.15 (s, 6H). Example 15: An iodine-containing compound with X-ray imaging function This embodiment provides an iodine-containing compound VIII with X-ray imaging function, wherein the iodine-containing compound VIII has the following structure:

[0115] Equation (16).

[0116] Example 16: A method for preparing an iodine-containing compound with X-ray imaging function This embodiment provides a method for preparing the iodine-containing compound VIII described in Example 15, and the specific steps are as follows: Step 1: Under ice bath conditions, methyl 3-(4,5-dihydrooxazol-2-yl)propionate (5 g, 31.85 mmol) was added to a 100 mL three-necked flask containing acetonitrile (5 mL, Sinopharm). The mixture was first purged three times with nitrogen. Then, methyl trifluoromethanesulfonate (522.0 mg, 3.19 mmol, Sinopharm, CAS: 333-27-7) was slowly added dropwise to the reaction flask at 0°C. The reaction was then carried out at 0°C for 0.5 hours, and finally heated to 90°C and reacted at 90°C for 16 hours (stirred at 160 rpm) to obtain the reaction product containing compound A4. After the reaction product containing compound A4 returned to room temperature, N-Boc-piperazine (5.9 g, 31.85 mmol) was added to the reaction product to obtain reaction system B. Reaction system B was then reacted at room temperature for 2 hours (stirred at 160 rpm) to obtain reaction system B. The reaction was stirred at rpm to obtain a reaction product containing compound B4; the reaction product containing compound B4 was concentrated under reduced pressure to obtain a white solid compound B4 (4.6 g). The compound B4 has the following structure (n is a natural number greater than or equal to 30 and less than or equal to 50):

[0117] Equation (34).

[0118] The proton NMR spectrum of compound B4 is shown below. Figure 10The characteristic peak of N-Boc piperazine in the target product was detected by ¹H NMR spectroscopy, and the chemical shift and integral were consistent with the theoretical structure, proving that compound B4 was successfully prepared. ¹H NMR data for compound B4: 1 H NMR (400 MHz, Deuterium Oxide) δ 3.82 (t, J = 6.0 Hz, 2H), 3.71 (t, J = 5.8Hz, 2H), 3.68 – 3.54 (m, 7H), 3.54 – 3.39 (m, 4H), 3.15 – 3.09 (m, 1H), 2.82 – 2.50 (m, 11H). Step 2: At room temperature, compound B4 (2.0 g) was added to 20 mL of a 5% (w / v, g / 100 mL) potassium hydroxide aqueous solution and reacted at room temperature for 6 hours (stirred at 160 rpm) to obtain the reaction product. The pH of the reaction product was adjusted to 7.0 by adding 1 M hydrochloric acid aqueous solution. The reaction product was then concentrated under reduced pressure to obtain crude compound C4 (1.8 g). The crude product did not require purification and was used directly in the next step. The compound C4 has the structure shown below (n is a natural number greater than or equal to 30 and less than or equal to 50):

[0119] Equation (35).

[0120] Step 3: At room temperature, ethanolamine (120 mg) and N,N'-dicyclohexylcarbodiimide (730 mg) were added to a 50 mL single-necked flask containing compound C4 (600.0 mg) and dichloromethane (5 mL, Sinopharm). The mixture was first purged with nitrogen three times, and then reacted at room temperature for 6 hours (stirred at 160 rpm) to obtain the reaction product. Water (20 mL) was added to the reaction product, and the mixture was extracted with dichloromethane (20 mL × 3) (dichloromethane was added to the aqueous phase three times for extraction). The organic phases were then combined. The organic phase was dried with anhydrous sodium sulfate and then concentrated under reduced pressure to obtain crude compound D4 (650 mg). The crude product did not require purification and was used directly in the next step. The compound D4 has the following structure (n is a natural number greater than or equal to 30 and less than or equal to 50):

[0121] Equation (36).

[0122] Step 4: At room temperature, succinic anhydride (120 mg, CAS: 108-30-5) and 4-dimethylaminopyridine (56.5 mg) were added to a 50 mL single-necked flask containing compound D4 (200.0 mg) and tetrahydrofuran (5 mL, Sinopharm). The mixture was first purged with nitrogen three times, and then reacted at 50 °C for 6 hours (stirred at 180 rpm) to obtain the reaction product. Water (20 mL) was added to the reaction product, and the mixture was extracted with dichloromethane (20 mL × 3) (dichloromethane was added to the aqueous phase three times for extraction), and the organic phases were combined. The organic phase was dried with anhydrous sodium sulfate and then concentrated under reduced pressure to obtain crude compound E4 (210 mg). The crude product did not require purification and was used directly in the next step. The compound E4 has the following structure (x is a natural number greater than or equal to 30 and less than or equal to 50, and x:y = 3:2):

[0123] Equation (37).

[0124] Step 5: At room temperature, N-hydroxysuccinimide (46.7 mg, CAS: 6066-82-6) and dicyclohexylcarbonimide (80.0 mg) were added to a 50 mL single-necked flask containing compound E4 (200.0 mg) and dichloromethane (5 mL, Sinopharm). The mixture was first purged with nitrogen three times, and then reacted at room temperature for 12 hours (stirred at 180 rpm) to obtain the reaction product. Water (20 mL) was added to the reaction product, and the mixture was extracted with dichloromethane (20 mL × 3) (dichloromethane was added to the aqueous phase three times for extraction), and the organic phases were combined. The organic phase was dried with anhydrous sodium sulfate and then concentrated under reduced pressure to obtain crude compound F4 (220 mg). The crude product did not require purification and was used directly in the next step. The compound F4 has the following structure (x is a natural number greater than or equal to 30 and less than or equal to 50, and x:y = 3:2):

[0125] Equation (38).

[0126] Step Six: At room temperature, triiodobenzoic acid (160 mg, CAS: 88-82-4) and N,N'-diisopropylcarbodiimide (40.0 mg) were added to a 50 mL single-necked flask containing compound F4 (200.0 mg) and dichloromethane (5 mL, Sinopharm). The mixture was first purged with nitrogen three times, and then reacted at room temperature for 12 hours (stirred at 180 rpm) to obtain the reaction product. Water (20 mL) was added to the reaction product, and the mixture was extracted with dichloromethane (20 mL × 3) (dichloromethane was added to the aqueous phase three times for extraction), and the organic phases were combined. The organic phase was dried with anhydrous sodium sulfate and then concentrated under reduced pressure to obtain crude compound G4 (220 mg). The crude product did not require purification and was used directly in the next step. The compound G4 has the following structure (x is a natural number greater than or equal to 30 and less than or equal to 50, and x:y = 3:2):

[0127] Equation (39).

[0128] Step 7: At room temperature, trifluoroacetic acid (1 mL) was added to a 50 mL single-necked flask containing compound G4 (200.0 mg) and dichloromethane (5 mL, Sinopharm), and the mixture was reacted at room temperature for 2 hours (stirred at 180 rpm) to obtain the reaction product; the reaction product was concentrated under reduced pressure to obtain crude compound H4 (180 mg). The crude product did not require purification and was used directly in the next step. The compound H4 has the following structure (x is a natural number greater than or equal to 30 and less than or equal to 50, and x:y = 3:2):

[0129] Equation (40).

[0130] Step 8: At room temperature, itaconic acid monomethyl ester (15.0 mg, CAS:7338-27-4) and N,N'-dicyclohexylcarbodiimide (360 mg) were added to a 50 mL single-necked flask containing compound H4 (90.0 mg) and dichloromethane (5 mL, Sinopharm). The mixture was first purged with nitrogen three times, and then reacted at room temperature for 6 hours (stirred at 180 rpm) to obtain the reaction product. Water (20 mL) was added to the reaction product, and the mixture was extracted with dichloromethane (20 mL × 3) (dichloromethane was added to the aqueous phase three times for extraction), and the organic phases were combined. The organic phase was dried with anhydrous sodium sulfate and then concentrated under reduced pressure to obtain the iodine-containing compound VI (120 mg) described in Example 11. The iodine-containing compound VIII obtained here is a mixed system, in which the value of x is a natural number greater than or equal to 30 and less than or equal to 50, and x:y = 3:2.

[0131] The proton NMR spectrum of iodine-containing compound VIII is shown below. Figure 11 ¹H NMR spectroscopy revealed characteristic peaks for the benzene ring hydrogen, amide, and H4 in the target product. The chemical shifts and integrals matched the theoretical structure, confirming the successful preparation of the iodine-containing compound. (Since the prepared iodine-containing compound VIII is a mixed system with a y=30~50 distribution, ¹H NMR only provides the overall signal; therefore, spectral analysis primarily focuses on confirming characteristic peaks.) ¹H NMR data for iodine-containing compound VIII: 1 H NMR (400 MHz, DMSO-d6) δ 8.38 (s, 1H), 8.23 ​​(s, 1H), 7.78 (s, 1H), 7.47 (s, 1H), 6.26 (m,2H), 4.56 – 4.06 (m, 1H), 3.82 – 3.33 (m, 6H), 3.33 (s, 10H), 3.19 – 2.64 (m,2H), 2.65 – 2.49 (m, 7H), 2.45 – 2.12 (m, 2H), 2.14 – 1.68 (m, 2H), 1.68 –1.55 (m, 2H),1.40 – 1.19 (m, 2H) 1.43 – 1.20 (m, 3H), 1.19 – 1.12 (m, 2H), 1.10 – 0.98 (m, 2H), 0.98 – 0.81 (m, 3H), 0.87 – 0.66 (m, 1H). Experiment Example 1: Performance Verification Experiment of Iodine-Containing Compounds This experiment provides a performance verification experiment for iodine-containing compounds, and the specific procedure is as follows: Experiment 1: Using iodixanol as a control, the iodine content of iodine-containing compounds I to VIII in Examples 1, 3, 5, 7, 9 and 15 was calculated. The calculation results are shown in Table 1.

[0132] Experiment 2: Using iodixanol as a control, the viscosity of iodine-containing compounds I to VIII in Examples 1, 3, 5, 7, 9 and 15 was measured using a cone rotational viscometer. The results are shown in Table 1.

[0133] Experiment 3: One healthy common white pig was selected as the experimental animal. Test samples were injected into the right skull base microvascular network and renal artery of the experimental animal, and DSA angiography was performed immediately to evaluate the imaging performance of the iodine-containing compounds. All surgical procedures were performed under aseptic conditions, and the experimental animal was under general anesthesia during the operation. The specific procedures included: on the day of surgery, the experimental animal was given an intramuscular injection of Supra-Syne® 50 for sedation and induction anesthesia; after successful induction anesthesia, the anesthetized, intubated experimental animal was placed on the operating table in a lateral or supine position and restrained with straps; the surgical area was prepared, disinfected, and draped; a vascular access was established by inserting a vascular sheath through a puncture of one femoral artery; the guiding catheter and guide wire were inserted into the body through the vascular sheath and reached the imaging site under the guidance of a digital subtraction angiography (DSA) X-ray fluoroscopy system; after the guiding catheter entered the opening, quantitative angiography was performed, and the imaging performance was evaluated immediately during the operation. The angiography results of iodine-containing compounds I-III are shown below. Figures 12-14 .

[0134] Table 1 shows that the viscosities of iodine-containing compounds I through VIII are all lower than those of iodixanol, while the iodine content of iodine-containing compounds I through III is higher than that of iodixanol. Figures 12-14 It is evident that iodine-containing compounds I-III show clear imaging under X-rays, resulting in a highly effective contrast agent. In conclusion, iodine-containing compounds I-VIII exhibit superior performance as iodine-containing contrast agents.

[0135] Table 1. Viscosity and iodine content of iodine-containing compounds I-VI

[0136] Obviously, the above embodiments are merely illustrative examples for clear explanation and are not intended to limit the implementation. Those skilled in the art will recognize that other variations or modifications can be made based on the above description. It is neither necessary nor possible to exhaustively list all possible implementations here. However, obvious variations or modifications derived therefrom are still within the scope of protection of this invention.

Claims

1. An iodine-containing compound with X-ray imaging function, characterized in that, The iodine-containing compound has a structure as shown in formula (1) or formula (2): Equation (1); Equation (2); Where x represents a non-grafted repeating unit, and the value of x is a natural number greater than or equal to 0 and less than or equal to 80; y represents a grafted repeating unit, and the value of y is a natural number greater than or equal to 1 and less than or equal to 80; z represents the number of iodine atoms in each aryl group, and the value of z is a natural number greater than 0 and less than or equal to 3. i represents the capping terminal group of the non-grafted repeating unit, and i is selected from... , or ; e represents the capped terminal group of the grafted repeating unit, with the general structural formula -T1 or -T1-Q0; R1 represents a modifying group, selected from a straight bond or heteroatom, or from unsubstituted or substituted piperazine, hydroxypiperidine, etc. , , , , , , , , or ; In R1, a takes the value of a natural number greater than or equal to 2 and less than or equal to 20, w takes the value of a natural number greater than or equal to 2 and less than or equal to 20, b takes the value of a natural number greater than or equal to 2 and less than or equal to 20, c takes the value of a natural number greater than or equal to 2 and less than or equal to 20, d takes the value of a natural number greater than or equal to 2 and less than or equal to 20, s takes the value of a natural number greater than or equal to 2 and less than or equal to 20, j takes the value of a natural number greater than or equal to 1 and less than or equal to 18, p takes the value of a natural number greater than or equal to 2 and less than or equal to 20, and k takes the value of a natural number greater than or equal to 2 and less than or equal to 10. X is selected from carbon atoms or heteroatoms; R3 represents a straight-chain or branched alkyl group from C1 to C20, or a straight-chain or branched alkyl group from C1 to C20 with one or more heteroatoms O, N, or S inserted. R4 represents a straight-chain or branched alkyl group from C1 to C20, or a straight-chain or branched alkyl group from C1 to C20 with one or more heteroatoms O, N, or S inserted.

2. The iodine-containing compound according to claim 1, characterized in that, The -T1- is selected from -O-, -S-, -NH-, or The -T1 is selected from -NR5, -CH3, , , , , , , , , or ; In T1, R5 is selected from unsubstituted or substituted alkyl, alkenyl or aralkyl groups from C1 to C20.

3. The iodine-containing compound as described in claim 1 or 2, characterized in that, The Q0 is selected from hydrogen, unsubstituted or substituted alkyl, alkenyl, aralkyl, alkynyl, heterocyclic or aryl.

4. The iodine-containing compound according to any one of claims 1 to 3, characterized in that, The iodine-containing compound has the structure shown in formula (3): Equation (3); Alternatively, the iodine-containing compound may have a structure as shown in formula (4): Equation (4); Where n, m, and p all represent the number of carbon chains, and the values ​​of n, m, and p are natural numbers greater than or equal to 0 and less than or equal to 5.

5. The iodine-containing compound according to any one of claims 1 to 4, characterized in that, In the iodine-containing compound, the grafted repeating unit has the structure shown in formula (5): Equation (5); Alternatively, in the iodine-containing compound, the grafted repeating unit has a structure as shown in formula (6): Equation (6).

6. The iodine-containing compound according to any one of claims 1 to 5, characterized in that, In the iodine-containing compound, the non-grafted repeating unit has the structure shown in formula (7): Equation (7); Alternatively, in the iodine-containing compound, the ungrafted repeating unit has a structure as shown in formula (8): Equation (8).

7. The iodine-containing compound according to any one of claims 1 to 6, characterized in that, The iodine-containing compound has the structure shown in formula (9): Equation (9); Alternatively, the iodine-containing compound may have a structure as shown in formula (10): Equation (10); Alternatively, the iodine-containing compound may have a structure as shown in formula (11): Equation (11); Alternatively, the iodine-containing compound may have a structure as shown in formula (12): Equation (12); Alternatively, the iodine-containing compound may have a structure as shown in formula (13): Equation (13); Alternatively, the iodine-containing compound may have a structure as shown in formula (14): Equation (14); Alternatively, the iodine-containing compound may have a structure as shown in formula (15): Equation (15); Alternatively, the iodine-containing compound may have a structure as shown in formula (16): Equation (16).

8. A method for preparing the iodine-containing compound of claim 7, characterized in that, The method includes: polymerizing an intermediate and methyl trifluoromethanesulfonate to obtain compound A1; reacting compound A1 with potassium hydroxide to obtain compound B1; and reacting compound B1, triiodophenol, 4-dimethylaminopyridine and N,N'-dicyclohexylcarbodiimide to obtain an iodine-containing compound as shown in formula (9) or formula (10). Alternatively, the method includes: polymerizing the intermediate and methyl trifluoromethanesulfonate to obtain compound A1; reacting compound A1 with potassium hydroxide to obtain compound B1; and reacting compound B1, aminoethanol, 4-dimethylaminopyridine and N,N'-dicyclohexylcarbodiimide to obtain the iodine-containing compound shown in formula (11). Alternatively, the method comprises: polymerizing 2-ethyl-4,5-dihydrooxazole, an intermediate and methyl trifluoromethanesulfonate to obtain compound A2; reacting compound A2 with potassium hydroxide to obtain compound B21; and reacting compound B21, triiodobenzoic acid, 4-dimethylaminopyridine and N,N'-dicyclohexylcarbodiimide to obtain the iodine-containing compound shown in formula (12); Alternatively, the method comprises: polymerizing 2-ethyl-4,5-dihydrooxazole and methyl trifluoromethanesulfonate to obtain compound A3; reacting compound A3 with an intermediate to obtain compound B3; reacting compound B3 with N-Boc-piperazine to obtain compound C3; reacting compound C3 with potassium hydroxide to obtain compound D3; reacting compound D3, ethylenediamine and N,N'-dicyclohexylcarbodiimide to obtain compound E3; reacting compound E3, triiodophenol and N,N'-dicyclohexylcarbodiimide to obtain compound F3; and after removing the protecting group from compound F3, reacting itaconic acid monomethyl ester and N,N'-dicyclohexylcarbodiimide to obtain the iodine-containing compound shown in formula (13); 2-Ethyl-4,5-dihydrooxazole, an intermediate, and methyl trifluoromethanesulfonate were polymerized to obtain compound A2; compound A2 was reacted with potassium hydroxide to obtain compound B21; compound B21, tert-butylpiperazine carboxylate, 4-dimethylaminopyridine, and N,N'-dicyclohexylcarbodiimide were reacted to obtain compound C21; after deprotecting compound C21, it was reacted with triiodobenzoic acid, 4-dimethylaminopyridine, and N,N'-dicyclohexylcarbodiimide to obtain the iodine-containing compound shown in formula (14); 2-Ethyl-4,5-dihydrooxazole, an intermediate, and methyl trifluoromethanesulfonate were polymerized to obtain compound A2; compound A2, 4-hydroxypiperidine, 4-dimethylaminopyridine, and N,N'-dicyclohexylcarbodiimide were reacted to obtain compound B22; compound B22, triiodobenzoic acid, 4-dimethylaminopyridine, and N,N'-dicyclohexylcarbodiimide were reacted to obtain the iodine-containing compound shown in formula (15); The intermediate and methyl trifluoromethanesulfonate were polymerized to obtain compound A4; compound A4 was reacted with N-Boc-piperazine to obtain compound B4; compound B4 was reacted with potassium hydroxide to obtain compound C4; compound C4, ethanolamine and N,N'-dicyclohexylcarbodiimide were reacted to obtain compound D4; compound D4, succinic anhydride and 4-dimethylaminopyridine were reacted to obtain compound E4; compound E4, N-hydroxysuccinimide and dicyclohexylcarbodiimide were reacted to obtain compound F4; compound F4, triiodobenzoic acid and N,N'-diisopropylcarbodiimide were reacted to obtain compound G4; after removing the protecting group from compound G4, itaconic acid monomethyl ester and N,N'-dicyclohexylcarbodiimide were reacted to obtain the iodine-containing compound shown in formula (16); The intermediate has a structure as shown in equation (17): Equation (17); The 2-ethyl-4,5-dihydrooxazole has the structure shown in formula (18): Equation (18); In formula (17), R2 represents a substituent group, and R2 is selected from... , or Where n is a natural number greater than or equal to 0 and less than or equal to 5, and g is a natural number greater than or equal to 0 and less than or equal to 5.

9. The use of the iodine-containing compound according to any one of claims 1 to 7 in the preparation of iodine-containing contrast agents.

10. An iodine-containing contrast agent, characterized in that, The iodine-containing contrast agent comprises the iodine-containing compound as described in any one of claims 1 to 7.

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