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CN-121991164-A - Carbonic anhydrase IX protein targeted radiopharmaceuticals

CN121991164ACN 121991164 ACN121991164 ACN 121991164ACN-121991164-A

Abstract

The invention relates to a carbonic anhydrase IX protein targeted radiopharmaceuticals, in particular to a compound shown in a formula (I), which can effectively target carbonic anhydrase IX protein, has high in vivo metabolism speed, high specificity, less non-target organ uptake, small toxic and side effects on non-target organs, convenient imaging and high safety, and can be used for diagnosing or treating diseases with over-expressed carbonic anhydrase IX protein. (I)

Inventors

  • FANG PENG
  • YAN CHENGLONG
  • YU SHANYOU
  • WU WEISI
  • YANG SI

Assignees

  • 无锡诺宇医药科技有限公司

Dates

Publication Date
20260508
Application Date
20251107
Priority Date
20241108

Claims (20)

  1. 1. A compound of formula (I), or an isotopic variant, hydrate, ester or solvate, tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt thereof: (I) Wherein, the Ab is a ligand targeting carbonic anhydrase IX, e.g ; Ring A is selected from C 6-10 arylene and C 5-10 heteroarylene, optionally substituted with 1,2, 3, or 4R A ; R A is independently selected from H, D, halogen, CN, -OR a 、-SR a 、-NR b R c 、C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 3-10 membered heterocyclyl, C 6-10 aryl, and 5-10 membered heteroaryl; R 3 and R 4 are independently selected from H, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 3-7 cycloalkyl, and 3-7 membered heterocyclyl; Or R 4 and R A together form C 1-4 alkylene, C 2-4 alkenylene and C 2-4 alkynylene, one or more of which are optionally and independently substituted by-CR 2 -、-NR -、-NR C(O)-、-C(O)NR -、-NR S(O) 2 -、-S(O) 2 NR -O-, -C (O) -, -OC (O) -, -C (O) O-, -S (O) -or-S (O) 2 -substitutions; and the ring formed by connecting R 4 and R A is a parallel ring structure of the ring A; V 3 is selected from the group consisting of a bond, C 1-10 alkylene, C 2-10 alkenylene, C 2-10 alkynylene, and ; Ring B is a 3-7 membered heterocyclylene; W 3 is selected from the group consisting of a bond, -NR-, -O-, -S-, and-C (O) -; R Independently selected from H, D, halogen, C 1-6 alkyl, and C 1-6 haloalkyl; R is independently selected from H, C 1-6 alkyl and C 1-6 haloalkyl; R a 、R b and R c are independently selected from H, C 1-6 alkyl and C 1-6 haloalkyl, or R b 、R c and the atoms to which they are attached together form a 3-to 10-membered heterocyclyl; l 1 is a linker; L 2 is an amino acid chain of 2-8 amino acid residues, wherein each amino acid residue may optionally be further substituted with 1 or more amino acid residues, and the amino acid residues are optionally substituted with 1, 2, 3,4, 5 or 6R L ; R L is independently selected from halogen, NO 2 、-OR a 、-NR b R c 、C 1-6 alkyl, C 1-6 haloalkyl, ureido, C 1-6 acyl, -C (O) -C 1-6 alkylene-COOH, sulfonic acid, methanesulfonyl, phosphoric acid, and phosphorous acid; z is a chelating group derived from a chelating agent.
  2. 2. The compound of claim 1, having the structure: (II-1) (II-2) (II-3) (II-4) (III-1) (III-2) (III-3) (IV-1) (IV-2) (IV-3) Wherein, the A 1 、A 2 、A 3 is an amino acid residue; A 4 is H or an amino acid residue; V 1 is selected from the group consisting of C 1-10 alkylene, C 2-10 alkenylene, C 2-10 alkynylene, C 6-10 arylene, and C 5-10 heteroarylene, optionally substituted with 1, 2, 3,4, 5, or 6R 1s ; R 1s is independently selected from H, D, -OR a 、-SR a 、-NR b R c , halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 3-7 cycloalkyl, and 3-7 membered heterocyclyl; V 2 is a bond or- (CR 'R') 1-6 -; R 'and R' are independently selected from H, D, halogen, C 1-6 alkyl, C 1-6 haloalkyl, and-C 1-6 alkylene-Ar; Ar is selected from C 6-14 aryl and 5-14 membered heteroaryl; W 4 is selected from the group consisting of a bond, -C (O) -, -OC (O) -, -NRC (O) -, -NR-, -C (O) O-, -C (O) NR-, and-O-; n is 0,1, 2, 3, 4, 5 or 6; the remaining variables are as defined in claim 1.
  3. 3. The compound of claim 1 or 2, wherein, L 1 is-W 1 -V 1 -W 4 -V 2 -W 2 -; W 1 is selected from the group consisting of a bond, -NR-, -C (O) O-, and-C (O) NR-; W 2 is selected from the group consisting of-C (O) -, -OC (O) -, -NRC (O) -, -NR-, -C (O) NR-and-O-; V 1 is selected from the group consisting of C 1-10 alkylene, C 2-10 alkenylene, C 2-10 alkynylene, C 6-10 arylene, and C 5-10 heteroarylene, optionally substituted with 1,2, 3,4, 5, or 6R 1s , wherein one or more methylene units of the alkylene, alkenylene, and alkynylene are optionally and independently replaced by-NR-, -NRC (O) -, -C (O) NR-, -NRs (O) 2 -、-S(O) 2 NR-, -O-, -C (O) -, -OC (O) -, -C (O) O-, -S (O) -or-S (O) 2 -; R is independently selected from H, C 1-6 alkyl or C 1-6 haloalkyl; R 1s is independently selected from H, D, -OR a 、-SR a 、-NR b R c , halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 3-7 cycloalkyl, OR 3-7 membered heterocyclyl, preferably R 1s is independently in the (S) OR (R) configuration, OR in racemic form; V 2 is a bond or- (CR 'R') 1-6 -; R ' and R ' are independently selected from H, D, halogen, C 1-6 alkyl, C 1-6 haloalkyl and-C 1-6 alkylene-Ar, preferably R ' is independently in the (S) or (R) configuration, or in racemic form; Ar is independently selected from C 6-14 aryl and 5-14 membered heteroaryl; W 4 is selected from the group consisting of a bond, -C (O) -, -OC (O) -, -NRC (O) -, -NR-, -C (O) O-, -C (O) NR-, and-O-; R a 、R b and R c are independently selected from H, C 1-6 alkyl and C 1-6 haloalkyl, or R b 、R c and the atoms to which they are attached together form a 3-7 membered heterocyclyl; Preferably, the method comprises the steps of, L 1 is-W 1 -V 1 -W 4 -V 2 -W 2 -; W 1 is selected from the group consisting of-C (O) -, -C (O) O-and-C (O) NR-; preferably-C (O) -; W 2 is selected from the group consisting of-C (O) -, -OC (O) -and-NRC (O) -; preferably-C (O) -; V 1 is selected from the group consisting of C 1-8 alkylene, C 2-8 alkenylene, C 2-8 alkynylene, phenylene, and C 5-6 heteroarylene, preferably C 1-8 alkylene (e.g., - (CH 2 ) m -); optionally substituted with 1, 2,3, 4, 5, or 6R 1s ; wherein 1, 2, or 3 methylene units in the alkylene, alkenylene, and alkynylene are optionally and independently replaced by-NR-, -NRC (O) -, -C (O) NR-, -C (O) -, -OC (O) -or-C (O) O-; m is independently selected from 1,2, 3, 4, 5, 6, 7 or 8; R is independently selected from H, C 1-6 alkyl and C 1-6 haloalkyl; R 1s is independently selected from H, D, -OR a 、-NR b R c , halogen, C 1-6 alkyl and C 1-6 haloalkyl, preferably H, D, -OR a and-NR b R c ; V 2 is a bond or- (CR 'R') 1-4 -; r 'is independently selected from H, D or-C 1-4 alkylene-Ar, preferably R' is independently in the (S) or (R) configuration, or in racemic form, preferably in the (S) configuration, preferably in the (R) configuration; R "is independently selected from H, D, halogen, C 1-6 alkyl, and C 1-6 haloalkyl; Ar is independently selected from C 6-14 aryl and 5-14 membered heteroaryl, preferably C 6-14 aryl; W 4 is selected from the group consisting of a bond, -OC (O) -, -NRC (O) -, -C (O) O-, and-C (O) NR-; Preferably, the method comprises the steps of, L 1 is-C (O) -V 1 -W 4 -V 2 -C (O) -; Wherein V 1 is selected from C 1-6 alkylene (e.g., - (CH 2 ) m -), phenylene, and C 5-6 heteroarylene; preferably selected from C 1-6 alkylene (e.g., - (CH 2 ) m -), phenylene, pyrrolylene, furanylene or thiophenylene; preferably C 1-6 alkylene (e.g., - (CH 2 ) m -); preferably C 1-4 alkylene (e.g., - (CH 2 ) m -); which is optionally substituted by 1, 2, 3, 4, 5 or 6R 1s ; wherein 1, 2 or 3 methylene units in the alkylene are optionally and independently replaced by-NR-, -NRC (O) -, -C (O) NR-, -C (O) -, -OC (O) -or-C (O) O-; m is independently selected from 1,2, 3, 4, 5 or 6, preferably 1,2, 3 or 4; R is independently selected from H, C 1-6 alkyl and C 1-6 haloalkyl; R 1s is independently selected from H, D, -OR a 、C 1-6 alkyl and C 1-6 haloalkyl, preferably from H and-OR a ; V 2 is a bond or- (CR 'R ") 1-2 - (preferably-CHR' -); R 'is independently selected from H or-C 1-4 alkylene-Ar, preferably H or-CH 2 -Ar, preferably R' is independently in the (S) or (R) configuration, or in racemic form, preferably in the (S) configuration, preferably in the (R) configuration; R' is independently selected from H, D, C 1-6 alkyl and C 1-6 haloalkyl, preferably H or D; Ar is independently C 6-14 aryl, such as phenyl, naphthyl, anthryl or phenanthryl, preferably C 6-10 aryl, such as phenyl or naphthyl, preferably 2-naphthyl; W 4 is selected from the group consisting of a bond, -OC (O) -, -NRC (O) -, -C (O) O-, and-C (O) NR-, preferably a bond or-C (O) NR-; for example, the number of the cells to be processed, L 1 is selected from: 、 、 、 、 、 、 、 、 And (Preferably ); Wherein, the 1、 2 And 3 Is a chiral centre, independently selected from the (S) or (R) configuration, or in racemic form, preferably the (S) configuration, preferably the (R) configuration.
  4. 4. A compound according to any one of claim 1 to 3, wherein, L 2 is an amino acid chain of 2-5 amino acid residues, wherein each amino acid residue may be optionally further substituted with 1 or more (preferably 1, 2 or 3, preferably 1) amino acid residues, and the amino acid residues are optionally substituted with 1, 2, 3, 4, 5 or 6R L ; R L is independently selected from halogen, NO 2 、-OR a 、-NR b R c 、C 1-6 alkyl, C 1-6 haloalkyl, ureido, C 1-6 acyl, -C (O) -C 1-6 alkylene-COOH, sulfonic acid, methanesulfonyl, phosphoric acid, and phosphorous acid; Preferably, the method comprises the steps of, L 2 is ; A 1 、A 2 、A 3 and a 4 are amino acid residues, and the amino acid residues are optionally substituted with 1, 2, 3, 4, 5 or 6R L ; R L is independently selected from halogen, NO 2 、-OR a 、-NR b R c 、C 1-6 alkyl, C 1-6 haloalkyl, ureido, C 1-6 acyl, -C (O) -C 1-6 alkylene-COOH, sulfonic acid, methanesulfonyl, phosphoric acid, and phosphorous acid; Preferably, the method comprises the steps of, L 2 is ; A 1 、A 2 、A 3 and A 4 are selected from the group consisting of glycine residues, alanine residues, phenylalanine residues, lysine residues, tyrosine residues, aspartic acid residues, serine residues, glutamic acid residues, pyroglutamic acid residues, citrulline residues, or arginine residues, preferably selected from the group consisting of lysine residues, tyrosine residues, aspartic acid residues, serine residues, glutamic acid residues, pyroglutamic acid residues, citrulline residues, phenylalanine residues, or arginine residues, optionally substituted with 1, 2,3, or 4R L ; r L is independently selected from halogen, -OR a 、-NR b R c 、C 1-6 alkyl, C 1-6 haloalkyl, ureido, C 1-6 acyl, and-C (O) -C 1-6 alkylene-COOH, preferably halogen, C 1-6 alkyl, C 1-6 haloalkyl, ureido, C 1-6 acyl, and-C (O) -C 1-6 alkylene-COOH, preferably C 1-6 acyl; More preferably, the process is carried out, L 2 is ; A 1 is a lysine residue, preferably Preferably Preferably ; A 2 is selected from a tyrosine residue, an aspartic acid residue, a serine residue, a glutamic acid residue, a phenylalanine residue, or an arginine residue, optionally substituted with 1,2, 3, or 4R L ; R L is independently selected from halogen, -OR a 、-NR b R c 、C 1-6 alkyl, C 1-6 haloalkyl and ureido, preferably halogen, C 1-6 alkyl, C 1-6 haloalkyl and ureido; Preferably A 2 is selected from (Preferably Preferably )、 (Preferably )、 、 、 (Preferably )、 (Preferably )、 (Preferably ) And (Preferably ); A 3 is a lysine residue, preferably Preferably Preferably ; A 4 is selected from the group consisting of N-acetylglutamic acid residue, N- (4-carboxybutyryl) glutamic acid, glutamic acid residue, pyroglutamic acid residue, citrulline residue and aspartic acid residue, preferably (Preferably )、 (Preferably )、 (Preferably )、 (Preferably )、 And ; Wherein, the 4、 5、 6 And 7 Is a chiral center independently selected from the (S) or (R) configuration, or in racemic form, preferably the (S) configuration, preferably the (R) configuration; for example, the number of the cells to be processed, L 2 is selected from: (preferably Preferably, it is )、 、 、 (Preferably )、 、 、 (Preferably )、 (Preferably )、 (Preferably )、 (Preferably )、 (Preferably )、 (Preferably ) And (Preferably )。
  5. 5. The compound according to any one of claim 1 to 4, Z is a chelating group derived from a chelating agent selected from the group consisting of: 1,4,7, 10-tetraazacyclododecane-N, N ', N ", N' '' -tetraacetic acid (DOTA), N, N '-bis [ 2-hydroxy-5- (carboxyethyl) benzyl ] ethylenediamine-N, N' -diacetic acid (HBED-CC), 1,4, 7-Triazacyclononane-1, 4, 7-triacetic acid (NOTA), 2- (4, 7-Bis (carboxymethyl) -1,4, 7-trisazo-1-yl) glutaric acid (NODAGA), 2- (4, 7, 10-Tris (carboxymethyl) -1,4,7, 10-tetraazacyclododecane-1-yl) glutaric acid (DOTAGA), 1,4, 7-Triazacyclononane phosphinic acid (TRAP), 1,4, 7-Triazacyclononane-1- [ methyl (2-carboxyethyl) phosphinic acid ] -4, 7-bis [ methyl (2-hydroxymethyl) phosphinic acid ] (NOPO), 3,6,9,15-Tetraazabicyclo [9.3.1.] pentadec-1 (15), 11, 13-triene-3, 6, 9-triacetic acid (PCTA), N' - {5- [ acetyl (hydroxy) amino ] pentyl } -N- [5- ({ 4- [ (5-aminopentyl) (hydroxy) amino ] -4-oxobutanoyl } amino) pentyl ] -N-hydroxysuccinamide (DFO), Diethylenetriamine pentaacetic acid (DTPA), Trans-cyclohexyl-diethylenetriamine pentaacetic acid (CHX-DTPA), 1-Oxa-4, 7, 10-triazacyclododecane-4, 7, 10-triacetic acid (O-Do 3A), P-isocyanatobenzyl-DTPA (SCN-Bz-DTPA), 1- (P-isothiocyanatobenzyl) -3-methyl-DTPA (1B 3M), 2- (P-isothiocyanatobenzyl) -4-methyl-DTPA (1M 3B), 1- (2) -Methyl-4-isothiocyanatobenzyl-DTPA (MX-DTPA), (R) -2-amino-3- (4-isothiocyanatophenyl) propyl ] -trans- (S, S) -cyclohexane-1, 2-diamine pentaacetic acid (p-SCN-Bn-CHX-A "-DTPA), 6-Hydrazinopyridine-3-carboxylic acid (HYNIC), 2- (4-Isothiocyanophenyl) -1,4, 7-triazacyclononane-1, 4, 7-triacetic acid (p-SCN-Bn-NOTA) or 2- [ (4-Isothiocyanatophenyl) methyl ] -1,4,7, 10-tetraazacyclododecane-1, 4,7, 10-tetraacetic acid (p-SCN-Bn-DOTA); Preferably, the method comprises the steps of, Z is selected from DOTA、 NOTA、 NODAGA、 DOTAGA、 HBED-CC、 p-SCN-Bn-CHX-A"-DTPA、 P-SCN-Bn-NOTA and P-SCN-Bn-DOTA, preferably DOTA or NOTA, preferably DOTA。
  6. 6. The compound according to any one of claim 1 to 5, Ab is ; Ring A is selected from phenylene and C 5-6 heteroarylene, preferably from phenylene and 1,3, 4-thiadiazolylene, optionally substituted with 1,2,3 or 4R A ; R A is independently selected from H, D, halogen, CN, -OR a 、-SR a 、-NR b R c 、C 1-6 alkyl, C 1-6 haloalkyl, C 3-7 cycloalkyl and 3-7 membered heterocyclyl, preferably selected from H, D, halogen, C 1-6 alkyl and C 1-6 haloalkyl; R 3 and R 4 are independently selected from H, halogen, C 1-6 alkyl and C 1-6 haloalkyl; or R 4 together with R A form C 1-4 -alkylene, preferably C 1-2 -alkylene, in which 1,2 or 3 (preferably 1) methylene units are optionally and independently taken as-CR 2 -、-NR -, -O-, -C (O) -, -OC (O) -, -C (O) O-; -S-, -S (O) -or-S (O) 2 -substitution, preferably by-CR 2 -C (O) -, -OC (O) -or-C (O) O-, preferably by-C (O) -; and the ring formed by connecting R 4 and R A is a parallel ring structure of the ring A; V 3 is selected from the group consisting of a bond, C 1-6 alkylene, C 2-6 alkenylene, and C 2-6 alkynylene; w 3 is selected from the group consisting of-NR-and-O-; R Independently selected from H, D, halogen, C 1-6 alkyl, and C 1-6 haloalkyl; R is independently selected from H, C 1-6 alkyl and C 1-6 haloalkyl; R a 、R b and R c are independently selected from H, C 1-6 alkyl and C 1-6 haloalkyl, or R b 、R c and the atoms to which they are attached together form a 3-7 membered heterocyclyl; Preferably, the method comprises the steps of, Ab is selected from: 、 And ; R 3 and R 4 are independently selected from H, halogen, C 1-6 alkyl and C 1-6 haloalkyl; V 3 is selected from the group consisting of a bond, C 1-6 alkylene, C 2-6 alkenylene, and C 2-6 alkynylene; w 3 is selected from the group consisting of-NR-and-O-; R is independently selected from H, C 1-6 alkyl and C 1-6 haloalkyl; Preferably, the method comprises the steps of, Ab is selected from: 、 And ; V 3 is selected from the group consisting of a bond and C 1-6 alkylene (preferably C 1-4 alkylene, preferably C 1-2 alkylene); More preferably, the process is carried out, Ab is selected from: 、 And ; N is 0,1, 2, 3, 4, 5 or 6, preferably 0,1, 2, 3 or 4, preferably 0 or 2.
  7. 7. The compound according to any one of claim 1 to 6, wherein, Ab is ; Ring A is selected from phenylene and C 5-6 heteroarylene, preferably from phenylene and 1,3, 4-thiadiazolylene, optionally substituted with 1,2,3 or 4R A ; R A is independently selected from H, D, halogen, CN, -OR a 、-SR a 、-NR b R c 、C 1-6 alkyl, C 1-6 haloalkyl, C 3-7 cycloalkyl and 3-7 membered heterocyclyl, preferably selected from H, D, halogen, C 1-6 alkyl and C 1-6 haloalkyl; R 3 and R 4 are independently selected from H, halogen, C 1-6 alkyl and C 1-6 haloalkyl; or R 4 together with R A form C 1-4 -alkylene, preferably C 1-2 -alkylene, in which 1,2 or 3 (preferably 1) methylene units are optionally and independently taken as-CR 2 -、-NR -, -O-, -C (O) -, -OC (O) -, -C (O) O-; -S-, -S (O) -or-S (O) 2 -substitution, preferably by-CR 2 -C (O) -, -OC (O) -or-C (O) O-, preferably by-C (O) -; and the ring formed by connecting R 4 and R A is a parallel ring structure of the ring A; V 3 is selected from the group consisting of a bond, C 1-6 alkylene, C 2-6 alkenylene, and C 2-6 alkynylene; w 3 is selected from the group consisting of-NR-and-O-; R Independently selected from H, D, halogen, C 1-6 alkyl, and C 1-6 haloalkyl; L 1 is-W 1 -V 1 -W 4 -V 2 -W 2 -; W 1 is selected from the group consisting of a bond, -NR-, -C (O) O-, and-C (O) NR-; W 2 is selected from the group consisting of-C (O) -, -OC (O) -, -NRC (O) -, -NR-, -C (O) NR-and-O-; V 1 is selected from the group consisting of C 1-10 alkylene, C 2-10 alkenylene, C 2-10 alkynylene, C 6-10 arylene, and C 5-10 heteroarylene, optionally substituted with 1,2, 3,4, 5, or 6R 1s , wherein one or more methylene units of the alkylene, alkenylene, and alkynylene are optionally and independently replaced by-NR-, -NRC (O) -, -C (O) NR-, -NRs (O) 2 -、-S(O) 2 NR-, -O-, -C (O) -, -OC (O) -, -C (O) O-, -S (O) -or-S (O) 2 -; R 1s is independently selected from H, D, -OR a 、-SR a 、-NR b R c , halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 3-7 cycloalkyl, OR 3-7 membered heterocyclyl, preferably R 1s is independently in the (S) OR (R) configuration, OR in racemic form; V 2 is a bond or- (CR 'R') 1-6 -; R ' and R ' are independently selected from H, halogen, C 1-6 alkyl, C 1-6 haloalkyl, -C 1-6 alkylene-Ar, preferably R ' is independently in the (S) or (R) configuration, or in racemic form; Ar is independently selected from C 6-14 aryl and 5-14 membered heteroaryl; W 4 is selected from the group consisting of a bond, -C (O) -, -OC (O) -, -NRC (O) -, -NR-, -C (O) O-, -C (O) NR-, and-O-; R is independently selected from H, C 1-6 alkyl and C 1-6 haloalkyl; R a 、R b and R c are independently selected from H, C 1-6 alkyl and C 1-6 haloalkyl, or R b 、R c and the atoms to which they are attached together form a 3-7 membered heterocyclyl; L 2 is an amino acid chain of 2-5 amino acid residues, wherein each amino acid residue may be optionally further substituted with 1 or more (preferably 1, 2 or 3, preferably 1) amino acid residues, and the amino acid residues are optionally substituted with 1, 2, 3, 4, 5 or 6R L ; R L is independently selected from halogen, NO 2 、-OR a 、-NR b R c 、C 1-6 alkyl, C 1-6 haloalkyl, ureido, C 1-6 acyl, -C (O) -C 1-6 alkylene-COOH, sulfonic acid, methanesulfonyl, phosphoric acid, and phosphorous acid; z is a chelating group derived from a chelating agent.
  8. 8. The compound of any one of claim 1 to 7, wherein, Ab is selected from: 、 And ; R 3 and R 4 are independently selected from H, halogen, C 1-6 alkyl and C 1-6 haloalkyl; V 3 is selected from the group consisting of a bond, C 1-6 alkylene, C 2-6 alkenylene, and C 2-6 alkynylene; w 3 is selected from the group consisting of-NR-and-O-; L 1 is-W 1 -V 1 -W 4 -V 2 -W 2 -; W 1 is selected from the group consisting of-C (O) -, -C (O) O-and-C (O) NR-; preferably-C (O) -; W 2 is selected from the group consisting of-C (O) -, -OC (O) -and-NRC (O) -; preferably-C (O) -; V 1 is selected from the group consisting of C 1-8 alkylene, C 2-8 alkenylene, C 2-8 alkynylene, phenylene, and C 5-6 heteroarylene, preferably C 1-8 alkylene (e.g., - (CH 2 ) m -); optionally substituted with 1, 2,3, 4, 5, or 6R 1s ; wherein 1, 2, or 3 methylene units in the alkylene, alkenylene, and alkynylene are optionally and independently replaced by-NR-, -NRC (O) -, -C (O) NR-, -C (O) -, -OC (O) -or-C (O) O-; m is independently selected from 1,2, 3, 4, 5, 6, 7 or 8; R is independently selected from H, C 1-6 alkyl and C 1-6 haloalkyl; R 1s is independently selected from H, D, -OR a 、-NR b R c , halogen, C 1-6 alkyl and C 1-6 haloalkyl, preferably H, D, -OR a and-NR b R c ; V 2 is a bond or- (CR 'R') 1-4 -; r 'is independently selected from H, D or-C 1-4 alkylene-Ar, preferably R' is independently in the (S) or (R) configuration, or in racemic form, preferably in the (S) configuration, preferably in the (R) configuration; R "is independently selected from H, D, halogen, C 1-6 alkyl, and C 1-6 haloalkyl; Ar is independently selected from C 6-14 aryl and 5-14 membered heteroaryl, preferably C 6-14 aryl; W 4 is selected from the group consisting of a bond, -OC (O) -, -NRC (O) -, -C (O) O-, and-C (O) NR-; l 2 is ; A 1 、A 2 、A 3 and a 4 are amino acid residues, and the amino acid residues are optionally substituted with 1, 2, 3, 4, 5 or 6R L ; R L is independently selected from halogen, NO 2 、-OR a 、-NR b R c 、C 1-6 alkyl, C 1-6 haloalkyl, ureido, C 1-6 acyl, -C (O) -C 1-6 alkylene-COOH, sulfonic acid, methanesulfonyl, phosphoric acid, and phosphorous acid; z is a chelating group derived from a chelating agent.
  9. 9. The compound of any one of claim 1 to 8, wherein, Ab is selected from: 、 And ; N is 0,1, 2, 3, 4, 5 or 6, preferably 0,1, 2, 3 or 4, preferably 0 or 2; L 1 is-C (O) -V 1 -W 4 -V 2 -C (O) -; Wherein V 1 is selected from C 1-6 alkylene (e.g., - (CH 2 ) m -), phenylene, and C 5-6 heteroarylene; preferably selected from C 1-6 alkylene (e.g., - (CH 2 ) m -), phenylene, pyrrolylene, furanylene or thiophenylene; preferably C 1-6 alkylene (e.g., - (CH 2 ) m -); preferably C 1-4 alkylene (e.g., - (CH 2 ) m -); which is optionally substituted by 1, 2, 3, 4, 5 or 6R 1s ; wherein 1, 2 or 3 methylene units in the alkylene are optionally and independently replaced by-NR-, -NRC (O) -, -C (O) NR-, -C (O) -, -OC (O) -or-C (O) O-; m is independently selected from 1,2, 3, 4, 5 or 6, preferably 1,2, 3 or 4; R is independently selected from H, C 1-6 alkyl and C 1-6 haloalkyl; R 1s is independently selected from H, D, -OR a 、C 1-6 alkyl and C 1-6 haloalkyl, preferably from H and-OR a ; V 2 is a bond or- (CR 'R ") 1-2 - (preferably-CHR' -); R 'is independently selected from H or-C 1-4 alkylene-Ar, preferably H or-CH 2 -Ar, preferably R' is independently in the (S) or (R) configuration, or in racemic form, preferably in the (S) configuration, preferably in the (R) configuration; R' is independently selected from H, D, C 1-6 alkyl and C 1-6 haloalkyl, preferably H or D; Ar is independently C 6-14 aryl, such as phenyl, naphthyl, anthryl or phenanthryl, preferably C 6-10 aryl, such as phenyl or naphthyl, preferably 2-naphthyl; W 4 is selected from the group consisting of a bond, -OC (O) -, -NRC (O) -, -C (O) O-, and-C (O) NR-, preferably a bond or-C (O) NR-; l 2 is ; A 1 、A 2 、A 3 and A 4 are selected from the group consisting of glycine residues, alanine residues, phenylalanine residues, lysine residues, tyrosine residues, aspartic acid residues, serine residues, glutamic acid residues, pyroglutamic acid residues, citrulline residues, or arginine residues, preferably selected from the group consisting of lysine residues, tyrosine residues, aspartic acid residues, serine residues, glutamic acid residues, pyroglutamic acid residues, citrulline residues, phenylalanine residues, or arginine residues, optionally substituted with 1, 2,3, or 4R L ; r L is independently selected from halogen, -OR a 、-NR b R c 、C 1-6 alkyl, C 1-6 haloalkyl, ureido, C 1-6 acyl, and-C (O) -C 1-6 alkylene-COOH, preferably halogen, C 1-6 alkyl, C 1-6 haloalkyl, ureido, C 1-6 acyl, and-C (O) -C 1-6 alkylene-COOH, preferably C 1-6 acyl; z is a chelating group derived from a chelating agent selected from the group consisting of: 1,4,7, 10-tetraazacyclododecane-N, N ', N ", N' '' -tetraacetic acid (DOTA), N, N '-bis [ 2-hydroxy-5- (carboxyethyl) benzyl ] ethylenediamine-N, N' -diacetic acid (HBED-CC), 1,4, 7-Triazacyclononane-1, 4, 7-triacetic acid (NOTA), 2- (4, 7-Bis (carboxymethyl) -1,4, 7-trisazo-1-yl) glutaric acid (NODAGA), 2- (4, 7, 10-Tris (carboxymethyl) -1,4,7, 10-tetraazacyclododecane-1-yl) glutaric acid (DOTAGA), 1,4, 7-Triazacyclononane phosphinic acid (TRAP), 1,4, 7-Triazacyclononane-1- [ methyl (2-carboxyethyl) phosphinic acid ] -4, 7-bis [ methyl (2-hydroxymethyl) phosphinic acid ] (NOPO), 3,6,9,15-Tetraazabicyclo [9.3.1.] pentadec-1 (15), 11, 13-triene-3, 6, 9-triacetic acid (PCTA), N' - {5- [ acetyl (hydroxy) amino ] pentyl } -N- [5- ({ 4- [ (5-aminopentyl) (hydroxy) amino ] -4-oxobutanoyl } amino) pentyl ] -N-hydroxysuccinamide (DFO), Diethylenetriamine pentaacetic acid (DTPA), Trans-cyclohexyl-diethylenetriamine pentaacetic acid (CHX-DTPA), 1-Oxa-4, 7, 10-triazacyclododecane-4, 7, 10-triacetic acid (O-Do 3A), P-isocyanatobenzyl-DTPA (SCN-Bz-DTPA), 1- (P-isothiocyanatobenzyl) -3-methyl-DTPA (1B 3M), 2- (P-isothiocyanatobenzyl) -4-methyl-DTPA (1M 3B), 1- (2) -Methyl-4-isothiocyanatobenzyl-DTPA (MX-DTPA), (R) -2-amino-3- (4-isothiocyanatophenyl) propyl ] -trans- (S, S) -cyclohexane-1, 2-diamine pentaacetic acid (p-SCN-Bn-CHX-A "-DTPA), 6-Hydrazinopyridine-3-carboxylic acid (HYNIC), 2- (4-Isothiocyanophenyl) -1,4, 7-triazacyclononane-1, 4, 7-triacetic acid (p-SCN-Bn-NOTA) or 2- [ (4-Isothiocyanophenyl) methyl ] -1,4,7, 10-tetraazacyclododecane-1, 4,7, 10-tetraacetic acid (p-SCN-Bn-DOTA).
  10. 10. The compound of any one of claim 1 to 9, wherein, Ab is selected from: 、 And ; N is 0,1, 2, 3, 4, 5 or 6, preferably 0,1, 2, 3 or 4, preferably 0 or 2; L 1 is selected from: 、 、 、 、 、 、 、 、 And (Preferably ); Wherein, the 1、 2 And 3 Is a chiral center independently selected from the (S) or (R) configuration, or in racemic form, preferably the (S) configuration, preferably the (R) configuration; l 2 is ; A 1 is a lysine residue, preferably Preferably Preferably ; A 2 is selected from a tyrosine residue, an aspartic acid residue, a serine residue, a glutamic acid residue, a phenylalanine residue, or an arginine residue, optionally substituted with 1,2, 3, or 4R L ; R L is independently selected from halogen, -OR a 、-NR b R c 、C 1-6 alkyl, C 1-6 haloalkyl and ureido, preferably halogen, C 1-6 alkyl, C 1-6 haloalkyl and ureido; Preferably A 2 is selected from (Preferably Preferably )、 (Preferably )、 、 、 (Preferably )、 (Preferably )、 (Preferably ) And (Preferably ); A 3 is a lysine residue, preferably Preferably Preferably ; A 4 is selected from the group consisting of N-acetylglutamic acid residue, N- (4-carboxybutyryl) glutamic acid, glutamic acid residue, pyroglutamic acid residue, citrulline residue and aspartic acid residue, preferably (Preferably )、 (Preferably )、 (Preferably )、 (Preferably )、 And ; Wherein, the 4、 5、 6 And 7 Is a chiral center independently selected from the (S) or (R) configuration, or in racemic form, preferably the (S) configuration, preferably the (R) configuration; Z is selected from DOTA、 NOTA、 NODAGA、 DOTAGA、 HBED-CC、 p-SCN-Bn-CHX-A"-DTPA、 P-SCN-Bn-NOTA and P-SCN-Bn-DOTA, preferably DOTA or NOTA, preferably DOTA; Preferably, the method comprises the steps of, L 2 is selected from: (preferably Preferably, it is )、 、 、 (Preferably )、 、 、 (Preferably )、 (Preferably )、 (Preferably )、 (Preferably )、 (Preferably )、 (Preferably ) And (Preferably )。
  11. 11. The compound of any one of claims 1-10, wherein V 3 is selected from the group consisting of a bond, C 1-6 alkylene, C 2-6 alkenylene, and C 2-6 alkynylene and Preferred chemical bonds, C 1-6 alkylene (preferably C 1-4 alkylene, preferably C 1-2 alkylene) and Preferably chemical bond and ; Preferably, the method comprises the steps of, Ring B is a 3-7 membered heterocyclylene group, preferably a 4-6 membered heterocyclylene group, preferably a 5 membered heterocyclylene group, e.g ; Wherein, the 8 Is a chiral center independently selected from the (S) or (R) configuration, or in racemic form, preferably the (S) configuration, preferably the (R) configuration; The remaining variables are as defined in any one of claims 1 to 10.
  12. 12. A compound according to any one of claims 1 to 11 wherein W 3 is selected from-NR-, -O-and-C (O) -, preferably-NR-and-C (O) -, the remaining variables being as defined in any one of claims 1 to 11.
  13. 13. The compound of any one of claims 1-12, wherein Ab is selected from: 、 、 And Preferably 、 、 And Preferably 、 、 、 And , wherein, 8 Is a chiral center independently selected from the (S) or (R) configuration, or in racemic form, preferably the (S) configuration, preferably the (R) configuration; the remaining variables are as defined in any one of claims 1 to 12.
  14. 14. The compound of any one of claims 3-12, wherein L 1 is-W 1 -V 1 -W 4 -V 2 -W 2 -; W 1 is selected from the group consisting of-NR-, -C (O) -, -C (O) O-and-C (O) NR-; preferably-NR-or-C (O) -; Preferably, R 1s is independently selected from H, -OR a 、-NR b R c 、C 1-6 alkyl and C 1-6 haloalkyl, preferably H, -OR a and-NR b R c , preferably H and-NR b R c ; the remaining variables being as defined in any one of claims 1 to 13; Preferably, the method comprises the steps of, L 1 is selected from: 、 、 、 、 、 、 、 、 、 (preferably )、 (Preferably ) And (Preferably ); Wherein, the 1、 2、 3 Sum of 9 Is a chiral center independently selected from the (S) or (R) configuration, or in racemic form, preferably the (S) configuration, preferably the (R) configuration; The remaining variables being as defined in any one of claims 1 to 13.
  15. 15. The compound according to any one of claim 1 to 14, which has a structure represented by the formula (III-1) or the formula (IV-1), (III-1) or (IV-1) Wherein, the V 3 is selected from the group consisting of a bond, C 1-6 alkylene, C 2-6 alkenylene, and C 2-6 alkynylene; L 1 is-W 1 -V 1 -W 4 -V 2 -W 2 -; W 1 is selected from the group consisting of-C (O) -, -C (O) O-and-C (O) NR-; preferably-C (O) -; W 2 is selected from the group consisting of-C (O) -, -OC (O) -and-NRC (O) -; preferably-C (O) -; V 1 is selected from C 1-8 alkylene, C 2-6 alkenylene, and C 2-6 alkynylene, preferably C 1-8 alkylene (e.g., - (CH 2 ) m -), optionally substituted with 1, 2,3, 4, 5, or 6R 1s ; m is independently selected from 1,2, 3, 4, 5, 6, 7 or 8; R is independently selected from H, C 1-6 alkyl and C 1-6 haloalkyl; R 1s is independently selected from H, D, -OR a 、-NR b R c , halogen, C 1-6 alkyl and C 1-6 haloalkyl, preferably H, D, -OR a and-NR b R c , preferably R 1s is independently in the (S) OR (R) configuration, OR in racemic form; V 2 is a bond or- (CR 'R ") 1-6 -; preferably- (CR' R") 1-6 -; r 'is independently selected from H, D or-C 1-4 alkylene-Ar, preferably R' is independently in the (S) or (R) configuration, or in racemic form; R "is independently selected from H, D, halogen, C 1-6 alkyl, and C 1-6 haloalkyl; ar is independently selected from C 6-14 aryl and 5-14 membered heteroaryl, preferably C 6-14 aryl; W 4 is selected from the group consisting of a bond, -OC (O) -, -NRC (O) -, -C (O) O-, and-C (O) NR-; R a 、R b and R c are independently selected from H, C 1-6 alkyl and C 1-6 haloalkyl, or R b 、R c and the atoms to which they are attached together form a 3-7 membered heterocyclyl; A 1 、A 2 、A 3 and A 4 are selected from the group consisting of glycine residues, alanine residues, phenylalanine residues, lysine residues, tyrosine residues, aspartic acid residues, serine residues, glutamic acid residues, pyroglutamic acid residues, citrulline residues, or arginine residues, preferably selected from the group consisting of lysine residues, tyrosine residues, aspartic acid residues, serine residues, glutamic acid residues, pyroglutamic acid residues, citrulline residues, phenylalanine residues, or arginine residues, optionally substituted with 1, 2,3, or 4R L ; r L is independently selected from halogen, -OR a 、-NR b R c 、C 1-6 alkyl, C 1-6 haloalkyl, ureido, C 1-6 acyl, and-C (O) -C 1-6 alkylene-COOH, preferably halogen, C 1-6 alkyl, C 1-6 haloalkyl, ureido, C 1-6 acyl, and-C (O) -C 1-6 alkylene-COOH, preferably C 1-6 acyl; z is as defined in claim 1 or 5.
  16. 16. The compound of claim 15, wherein the compound is selected from the group consisting of, V 3 is selected from the group consisting of a bond and a C 1-6 alkylene (preferably a C 1-4 alkylene, preferably a C 1-2 alkylene); L 1 is-W 1 -V 1 -W 4 -V 2 -W 2 -; w 1 is-C (O) -; W 2 is-C (O) -; V 1 is selected from C 1-6 alkylene, C 2-6 alkenylene and C 2-6 alkynylene, preferably C 1-6 alkylene (e.g., - (CH 2 ) m -), preferably C 1-4 alkylene (e.g., - (CH 2 ) m -), optionally substituted with 1,2, 3,4, 5 or 6R 1s ; m is independently selected from 1,2, 3, 4, 5 or 6, preferably 1,2, 3 or 4; R 1s is independently selected from H, D, -OR a 、C 1-6 alkyl and C 1-6 haloalkyl, preferably from H and-OR a , preferably from H and D; V 2 is a bond or- (CR 'R') 1-4 -; preferably a chemical bond or- (CR 'R ") 1-2 - (preferably-CHR' -); preferably- (CR 'R") 1-2 - (preferably-CHR' -); R 'is independently selected from H or-C 1-4 alkylene-Ar, preferably H or-CH 2 -Ar, preferably R' is independently in the (S) or (R) configuration, or in racemic form, preferably in the (S) configuration; R' is independently selected from H, D, C 1-6 alkyl and C 1-6 haloalkyl, preferably H or D; Ar is independently C 6-14 aryl, such as phenyl, naphthyl, anthryl or phenanthryl, preferably C 6-10 aryl, such as phenyl or naphthyl, preferably 2-naphthyl; w 4 is selected from a bond or-C (O) NR-; R is independently selected from H, C 1-6 alkyl and C 1-6 haloalkyl; R a is independently selected from H, C 1-6 alkyl and C 1-6 haloalkyl; a 1 is a lysine residue; a 2 is a tyrosine residue; A 3 is a lysine residue; A 4 is a glutamic acid residue or an N-acetylglutamic acid residue, preferably a glutamic acid residue; Z is selected from DOTA、 NOTA、 NODAGA、 DOTAGA、 P-SCN-Bn-NOTA and P-SCN-Bn-DOTA, preferably DOTA or NOTA, preferably DOTA; Preferably, the method comprises the steps of, Is that Preferably ; Wherein, the 4、 5、 6 And 7 Is a chiral center independently selected from the (S) or (R) configuration, or in racemic form; Preferably, L 1 is Or (b) (Preferably ) Preferably, it is (Preferably ); Wherein, the 3 Is a chiral centre, independently selected from the (S) or (R) configuration, or in racemic form, preferably the (S) configuration.
  17. 17. The compound according to any one of claim 1 to 14, which has a structure represented by the formula (II-4), (II-4) Wherein, the V 3 is selected from the group consisting of a bond, C 1-6 alkylene, C 2-6 alkenylene and C 2-6 alkynylene and ; Ring B is a 3-7 membered heterocyclic group; W 3 is selected from the group consisting of-NR-and-C (O) -; preferably-C (O) -; L 1 is-W 1 -V 1 -W 4 -V 2 -W 2 -; W 1 is selected from the group consisting of-NR-, -C (O) -, -C (O) O-and-C (O) NR-; preferably-NR-or-C (O) -; W 2 is selected from the group consisting of-C (O) -, -OC (O) -and-NRC (O) -; preferably-C (O) -; V 1 is selected from C 1-8 alkylene, C 2-6 alkenylene, and C 2-6 alkynylene, preferably C 1-8 alkylene (e.g., - (CH 2 ) m -), optionally substituted with 1, 2,3, 4, 5, or 6R 1s ; m is independently selected from 1,2, 3, 4, 5, 6, 7 or 8; R is independently selected from H, C 1-6 alkyl and C 1-6 haloalkyl; R 1s is independently selected from H, D, -OR a 、-NR b R c , halogen, C 1-6 alkyl and C 1-6 haloalkyl, preferably H, D, -OR a and-NR b R c , preferably R 1s is independently in the (S) OR (R) configuration, OR in racemic form; V 2 is a bond or- (CR 'R ") 1-6 -; preferably- (CR' R") 1-6 -; r 'is independently selected from H, D or-C 1-4 alkylene-Ar, preferably R' is independently in the (S) or (R) configuration, or in racemic form; R "is independently selected from H, D, halogen, C 1-6 alkyl, and C 1-6 haloalkyl; ar is independently selected from C 6-14 aryl and 5-14 membered heteroaryl, preferably C 6-14 aryl; W 4 is selected from the group consisting of a bond, -OC (O) -, -NRC (O) -, -C (O) O-, and-C (O) NR-; R a 、R b and R c are independently selected from H, C 1-6 alkyl and C 1-6 haloalkyl, or R b 、R c and the atoms to which they are attached together form a 3-7 membered heterocyclyl; l 2 is ; A 1 、A 2 、A 3 and A 4 are selected from the group consisting of glycine residues, alanine residues, phenylalanine residues, lysine residues, tyrosine residues, aspartic acid residues, serine residues, glutamic acid residues, pyroglutamic acid residues, citrulline residues, or arginine residues, preferably selected from the group consisting of lysine residues, tyrosine residues, aspartic acid residues, serine residues, glutamic acid residues, pyroglutamic acid residues, citrulline residues, phenylalanine residues, or arginine residues, optionally substituted with 1, 2,3, or 4R L ; r L is independently selected from halogen, -OR a 、-NR b R c 、C 1-6 alkyl, C 1-6 haloalkyl, ureido, C 1-6 acyl, and-C (O) -C 1-6 alkylene-COOH, preferably halogen, C 1-6 alkyl, C 1-6 haloalkyl, ureido, C 1-6 acyl, and-C (O) -C 1-6 alkylene-COOH, preferably C 1-6 acyl; z is as defined in claim 1 or 5.
  18. 18. The compound of claim 17, wherein the compound is selected from the group consisting of, V 3 is selected from the group consisting of a bond, a C 1-6 alkylene (preferably a C 1-4 alkylene, preferably a C 1-2 alkylene) and Preferably chemical bond and ; Ring B is a 4-6 membered heterocyclic group, preferably a 5-membered heterocyclic group, for example ; W 3 is selected from the group consisting of-NR-and-C (O) -; preferably-C (O) -; L 1 is-W 1 -V 1 -W 4 -V 2 -W 2 -; w 1 is-NR-, preferably-NH-; W 2 is-C (O) -; V 1 is selected from C 1-6 alkylene, C 2-6 alkenylene and C 2-6 alkynylene, preferably C 1-6 alkylene (e.g., - (CH 2 ) m -), preferably C 1-4 alkylene (e.g., - (CH 2 ) m -), optionally substituted with 1,2, 3,4, 5 or 6R 1s ; m is independently selected from 1,2, 3, 4, 5 or 6, preferably 1,2, 3 or 4; R 1s is independently selected from H, D, -OR a 、-NR b R c 、C 1-6 alkyl and C 1-6 haloalkyl, preferably from H, -OR a and-NR b R c , preferably from H and-NR b R c ; V 2 is a bond or- (CR 'R') 1-4 -; preferably a chemical bond or- (CR 'R ") 1-2 - (preferably-CHR' -); preferably- (CR 'R") 1-2 - (preferably-CHR' -); R 'is independently selected from H or-C 1-4 alkylene-Ar, preferably H or-CH 2 -Ar, preferably R' is independently in the (S) or (R) configuration, or in racemic form, preferably in the (S) configuration; R' is independently selected from H, D, C 1-6 alkyl and C 1-6 haloalkyl, preferably H or D; Ar is independently C 6-14 aryl, such as phenyl, naphthyl, anthryl or phenanthryl, preferably C 6-10 aryl, such as phenyl or naphthyl, preferably 2-naphthyl; W 4 is selected from a bond or-C (O) NR-; R is independently selected from H, C 1-6 alkyl and C 1-6 haloalkyl; R a 、R b and R c are independently selected from H, C 1-6 alkyl and C 1-6 haloalkyl; l 2 is ; A 1 is a lysine residue; a 2 is a tyrosine residue; A 3 is a lysine residue; A 4 is a glutamic acid residue or an N-acetylglutamic acid residue, preferably a glutamic acid residue; Z is selected from DOTA、 NOTA、 NODAGA、 DOTAGA、 P-SCN-Bn-NOTA and P-SCN-Bn-DOTA, preferably DOTA or NOTA, preferably DOTA; Preferably, the method comprises the steps of, Is that Preferably ; Wherein, the 4、 5、 6、 7 And 8 Is a chiral center independently selected from the (S) or (R) configuration, or in racemic form; Preferably, L 1 is (Preferably ) Or (b) (Preferably ); Wherein, the 3 Sum of 9 Is a chiral centre independently selected from the (S) or (R) configuration, or in racemic form, preferably the (S) configuration.
  19. 19. The compound of any one of claims 1-14, wherein the compound is selected from the group consisting of: 。
  20. 20. A compound comprising a compound of formula (I), or an isotopic variant, hydrate, ester or solvate, tautomer, stereoisomer, or pharmaceutically acceptable salt thereof, and M complexed therewith, Wherein, the A compound of formula (I) as defined in any one of claims 1 to 19; m is selected from at least one of a radionuclide or a non-radioactive element (preferably a radionuclide); Preferably, the radionuclide is selected from 68 Ga、 18 F、 99 mTc、 89 Zr、 124 I、 76 Br、 43 Sc、 111 In、 45 Ti、 52 Mn、 59 Fe、 64 Cu、 94 mTc、 67 Ga、 71/72/74 As、 82m Rb or 86 Y, or from 177 Lu、 90 Y、 131 I、 153 Sm、 67 Cu、 89 Sr、 166 Ho、 177 Yb、 47 Sc、 186/188 Re、 212/213 Bi、 149 Pm、 212 Pb、 211 At、 223 Ra、 161 Tb、 225 Ac or 227 Th; Preferably, the radionuclide is selected from 68 Ga、 18 F、 64 Cu、 161 Tb or 177 Lu; Preferably, the radionuclide 18 F is formed by complexation of 18 FAl with a compound of formula (I); preferably, M is selected from 68 Ga、 18 F、 161 Tb or 177 Lu, preferably 68 Ga or 177 Lu.

Description

Carbonic anhydrase IX protein targeted radiopharmaceuticals The present application claims priority from chinese application CN202411595249.1 filed on day 11 and 08 of 2024, chinese application CN202510993967.2 filed on day 07 and 17 of 2025, and chinese application CN202511591437.1 filed on day 31 of 2025 and 10, which are incorporated herein by reference in their entireties. Technical Field The invention relates to the field of medicines, in particular to a Carbonic Anhydrase IX (CAIX) protein targeted radiopharmaceutical. Background A plurality of alpha-carbonic anhydrases (alpha-CAs) are distributed in most organ tissues of human body, and one CA is dominant in part organ tissues. The leading CA in the liver is CAVA/XIV, the leading one in most hypoxic solid tumors is CAIX/XII, and CAI/II in the blood is one of the major protein components of erythrocytes. Tumor-specific expressed CAIX/XII is a transmembrane protein type. CAIX is stably expressed in tumors such as RCC, is not expressed in normal kidney tissues, and is only partially weakly expressed in organ tissues other than kidney. CAIX is therefore a potentially superior target for ccRCC diagnosis and treatment. CAIX is also overexpressed in many other types of tumors, such as lung, colorectal, gastric, pancreatic, melanoma, breast, cervical, bladder, ovarian, brain, head and neck, astrocytoma, oral cancer, and the like. The CAIX over-expressed by the tumor catalyzes hydration reaction of carbon dioxide to generate bicarbonate ions and protons, and regulates the pH value of the cell environment. The acidic enhancement of the local microenvironment of the cells can activate VEGF signal channels, promote new angiogenesis and play an important role in tumorigenesis and development. Most CA targeted inhibitors bind to the metal active center of the CAIX extracellular enzyme catalytic domain to block its catalytic activity. The CAIX intracellular segment can be involved in the regulation of glucose metabolic pathways after phosphate. The structure of the CAIX specific inhibitor is mostly ionization, hypoxia activated structuring, glycosylation, nanoparticle inclusion and the like based on the sulfonamide structure. The marker of the nuclide for diagnosis and treatment is used for molecular image diagnosis and treatment of tumor. The current effective treatment for RCC is surgical excision, but limited RCC has a recurrence rate of 30% (or about 50%) 5 years after surgery, whereas advanced or metastatic RCC cannot be operated. The classical effective drug for transferred RCC is interleukin 2 at high doses, but only produces a sustained complete response in 7-10% of patients. Thus, developing more sensitive and accurate early diagnostic strategies, as well as effective systemic therapeutic agents for advanced and metastatic RCC, is a challenge that needs to continue to be addressed and addressed for patients at high risk of recurrence. The development of better CAIX targeting drugs and CAIX inhibitors for molecular image diagnosis and treatment has important scientific research value and wide application prospect. Disclosure of Invention The invention provides a carbonic anhydrase IX protein radiopharmaceutical which can be used for diagnosing and/or treating diseases which are over-expressed in carbonic anhydrase IX protein. The radiopharmaceuticals targeting carbonic anhydrase IX protein of the invention have the following advantages: (1) The metabolism speed in the body is high, and the toxic and side effects on non-target organs are small; (2) The specific targeted tumor has less uptake of in vivo non-target organs, is convenient for imaging and is beneficial to clinical diagnosis; (3) The tumor is specifically targeted, the retention time at the tumor is long, and the treatment effect on the tumor is good; (4) The non-target organ has less intake, less toxic side effect on normal tissues and good safety. In one aspect, the present invention relates to a compound of formula (I), or an isotopic variant, hydrate, ester or solvate, tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt thereof: (I) Wherein the variables are as defined herein. In another aspect, the present invention relates to a compound comprising a compound of formula (I), or an isotopic variant, hydrate, ester or solvate, tautomer, stereoisomer, or pharmaceutically acceptable salt thereof, and M complexed therewith, wherein, The compounds of formula (I) are as defined herein; m is selected from at least one of a radionuclide or a non-radioactive element. In another aspect, the invention relates to a compound of formula (V), or an isotopic variant, hydrate, ester or solvate, tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt thereof:(V) Wherein Ab, L 1 and L 2 are as defined herein; Z' is a coordinating group formed after complexing a chelating group Z derived from a chelating agent with M, Z being as defined herein; m is selected from at least one o