Applications of PSMA-targeted and TSPO-targeted compounds for the assessment of peripheral nerve damage

JP2026519067APending Publication Date: 2026-06-11JOHNS HOPKINS UNIVERSITY
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Patent Information

Authority / Receiving Office
JP · JP
Patent Type
Applications
Current Assignee / Owner
JOHNS HOPKINS UNIVERSITY
Filing Date
2024-06-03
Publication Date
2026-06-11

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Abstract

The present invention discloses a method for diagnosing peripheral nervous system (PNS) neuropathy, comprising administering at least one of a translocator protein (TSPO)-targeted compound or a PSMA-targeted compound to a subject in need of treatment, and acquiring images.
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Claims

1. A method for diagnosing peripheral nervous system (PNS) neuropathy, comprising administering at least one translocator protein (TSPO)-targeted compound or PSMA-targeted compound to a subject in need of treatment, and acquiring imaging.

2. The method according to claim 1, wherein the peripheral nervous system (PNS) neuropathy comprises PNS invasion and / or neuropathy, recovery from PNS invasion and / or neuropathy, and denervation and / or renervation including denervation-induced muscle atrophy.

3. The method according to claim 1 or 2, wherein the PNS neuropathy is selected from peripheral nerve injury (PNI), brachial plexus injury (BPI), and spinal cord injury (SCI), and includes stretch-related PNI, laceration, compression PNI, and PNI associated with one or more conditions selected from radiation, electricity, injection, crush, cooling, and intraneuronal or extraneuronal lesions.

4. The TSPO-targeting compound comprises a compound of formula (I), 【Chemistry 1】 X １ It may or may not exist, and if it does exist, it is selected from the radioactive isotopes of fluorine, iodine, bromine, and astatine. However, X １ If X ２ is H or C １ -C ４ It is alkyl, X １ If X does not exist, ２ H is -L-I, where L is the linker and I is the contrast agent. R １ 、 R ２ 、 R ３ and R ４ are each independently selected from hydroxyl, C １ -C １０ alkyl, cycloalkyl, aryl, alkylamino, alkenyl, alkynyl, hydroxyalkyl, alkoxy, dialkylamino, thioalkyl, thioenyl, thioalkynyl, allyloxy, acyloxy, thioacyl, amide, sulfonamide, and each alkyl or aryl moiety may be unsubstituted or substituted with one or more substituents selected from the group consisting of halo, hydroxyl, carboxyl, phosphoryl, phosphonyl, phosphonoC １ -C ６ alkyl, carboxyC １ -C ６ alkyl, dicarboxyC １ -C ６ alkyl, dicarboxyhaloC １ -C ６ alkyl, sulfonyl, cyano, nitro, alkoxy, alkylthio, acyl, acyloxy, thioacyl, acylthio, allyloxy, amino, alkylamino, dialkylamino, trialkylamino, arylalkylamino, guanidino, aldehyde, ureido, aminocarbonyl, amino acid residue, substituted amino acid residue, and its pharmaceutically acceptable salt, The method according to claim 1.

5. The compound of formula (I) is the compound of formula (Ia), 【Chemistry 2】 R ５ is H or C １ -C ４ It is alkyl. The method according to claim 4.

6. X １ teeth, １８ F, １２３ I, １２４ I, １２５ I, １３１ I, ７５ Br, ７６ Br, ７７ Br, ８０ Br, ８０ｍ Br, ８２ Br, ８３ Br, ２１１ The method according to claim 4 or 5, selected from At.

7. The compound of formula (Ia) is 【Transformation 3】 The method according to claim 5.

8. (a) X １ teeth, １２３ I or １２５ I is, and the imaging is single-photon emission computed tomography (SPECT), or (b) X １ teeth, １８ F or １２４ The imaging method is positron emission tomography (PET). The method according to any one of claims 4 to 7.

9. The compound of formula (I) is the compound of formula (Ib) below, 【Chemistry 4】 The method according to claim 4.

10. The compound of formula (Ib) is 【Transformation 5】 The method according to claim 9, wherein the compound is [the compound].

11. The method according to claim 4, 9, or 10, wherein L is an alkylene linker comprising 1 to 10 carbon atoms.

12. The method according to claim 4 or claims 9 to 11, wherein I is a contrast agent covalently bonded to linker L via an amide linkage.

13. The method according to claim 4 or 9 to 12, wherein the contrast agent comprises an optical dye.

14. The method according to claim 13, wherein the optical dye comprises a fluorescent dye.

15. The method according to claim 14, wherein the fluorescent dye is a fluorescent dye that emits light in the near-infrared spectral region.

16. The method according to claim 14, wherein the fluorescent dye is selected from polymethine dyes, coumarin dyes, xanthene dyes, and boron-dipyrromethene (BODIPY) dyes.

17. The method according to claim 16, wherein the polymethine dye is selected from carbocyanin dye, indocarbocyanin dye, oxacarbocyanin dye, thiacarbocyanin dye, and merocyanine dye.

18. The method according to claim 16, wherein the xanthene dye is selected from fluorescein dye and coumarin dye.

19. The aforementioned fluorescent dye is BODIPY FL、BODIPY R ６ G、BODIPY TR、BODIPY TMR、BODIPY 493 / 503、BODIPY 530 / 550、BODIPY 558 / 568、BODIPY 564 / 570、BODIPY 576 / 589、BODIPY 581 / 591、BODIPY 630 / 650、BODIPY 650 / 665、 VivoTag-645, VivoTag-680, VivoTag-S680, VivoTag-S750, VivoTag-800, Alexa Fluor 488, Alexa Fluor 532, Alexa Fluor 546, Alexa Fluor 555, Alexa Fluor 568, Alexa Fluor 594, Alexa Fluor 647, Alexa Fluor 660, Alexa Fluor 680, Alexa Fluor 700, Alexa Fluor 750, Alexa Fluor 790, Dy677, Dy676, Dy682, Dy752, Dy780, DyLight 350, DyLight 405, DyLight 488, DyLight 547, DyLight 550, DyLight 594, DyLight 633, DyLight 647, DyLight 650, DyLight 680, DyLight 755, DyLight 800, HiLyte Fluor 405, HiLyte Fluor 488, HiLyte Fluor 532, HiLyte Fluor 555, HiLyte(TM) Fluor 594, HiLyte Fluor 647, HiLyte Fluor 680, HiLyte Fluor 750, IR800 (dimethyl{4-[1,5,5-tris(4-dimethylaminophenyl)-2,4-pentadienylidene]-2,5-cyclohexadiene-1-ylidene}ammonium perchlorate), IRDye 650, IRDye 680RD, IRDye 680LT, IRDye 700, IRDye 700DX, IRDye 750, IRDye 800, IRDye 800CW, IRDye 800RS, and ADS1065A, ADS1075A, ADS775MI, ADS775MP, ADS775PI, ADS775PP, ADS780HO, ADS780WS, ADS785WS, ADS7 90WS, ADS795WS, ADS798SM, ADS800AT, ADS815EI, ADS830AT, ADS830WS, ADS832WS, ADS845MC, ADS920MC, The method according to claim 14, selected from among.

20. The optical dye is 【Transformation 6】 The method according to claim 13, selected from among.

21. The PSMA-targeted compound is a compound of formula (II), 【Transformation 7】 Z is tetrazole or CO ２ Q is, Each Q is independently selected from hydrogen or a protecting group. (A) m is 0, 1, 2, 3, 4, 5, or 6, R is, 【Transformation 8】 A pyridine ring selected from, X is fluorine, iodine, radioactive isotopes of fluorine, radioactive isotopes of iodine, chlorine, bromine, radioactive isotopes of bromine, radioactive isotopes of astatine, NO ２ NH ２ , N ＋ (R ２ ) ３ , Sn(R ２ ) ３ , Si(R ２ ) ３ , Hg(R ２ ), B (OH) ２ , -NHNH ２ , -NHN=CHR ３ ,-NHNH-CH ２ R ３ Selected from, n is 1, 2, 3, or 4. Y is O, S, N(R'), C(O), NR'C(O), C(O)N(R'), OC(O), C(O)O, NR'C(O)NR', ​​NR'C(S)NR', ​​NR'S(O) ２ , S (CH ２ ) ｐ , NR' (CH ２ ) ｐ , O(CH ２ ) ｐ OC(O)CHR ８ NHC(O), NHC(O)CHR ８ NHC(O), or covalent bond, p is 1, 2, or 3, R' is H or C １ -C ６ Alkyl, R ８ is hydrogen, alkyl, aryl, or heteroaryl, and each may be substituted. R ２ is C １ -C ６ It is alkyl, R ３ These are fluorine, iodine, radioactive isotopes of fluorine, radioactive isotopes of iodine, chlorine, bromine, radioactive isotopes of bromine, radioactive isotopes of astatine, and NO. ２ NH ２ , N ＋ (R ２ ) ３ , Sn(R ２ ) ３ , Si(R ２ ) ３ , Hg(R ２ ), or B(OH) ２ Substituted with alkyl, alkenyl, alkynyl, aryl or heteroaryl, or (B) m is 0, 1, 2, 3, 4, 5 or Y is O, S, N(R'), C(O), NR'C(O), C(O)N(R'), OC(O), C(O)O, NR'C(O)NR', NR'C(S)NR', NR'S(O) ２ , S(CH ２ ) ｐ , NR'(CH ２ ) ｐ , O(CH ２ ) ｐ , OC(O)CHR ８ NH C(O), NH C(O)CHR ８ NH C(O), or a covalent bond, p is 1, 2, or 3, R' is H or C １ -C ６ Alkyl, R ８ is hydrogen, alkyl, aryl, or heteroaryl, and each may be substituted. R is, 【Chemistry 9】 And, X' is NHNH ２ , -NHN=CHR ３ ,-NHNH-CH ２ R ３ Selected from, R ３ These are fluorine, iodine, radioactive isotopes of fluorine, radioactive isotopes of iodine, bromine, radioactive isotopes of bromine, radioactive isotopes of astatine, and NO. ２ NH ２ , N ＋ (R ２ ) ３ , Sn(R ２ ) ３ , Si(R ２ ) ３ , Hg(R ２ ), or B(OH) ２ A alkyl, alkenyl, alkynyl, aryl, or heteroaryl molecule substituted from the group consisting of the following: R ２ is C １ -C ６ It is alkyl, n is 1, 2, 3, 4, or 5. (C)m is 4, Y is NR', R is, 【Chemistry 10】 And, G is O, NR', or a covalent bond. R is H or C １ -C ６ It is an alkyl group, and p is 1, 2, 3, or 4. R ７ NH ２ N=CHR ３ NH-CH ２ R ３ Selected from, R ３ These are fluorine, iodine, radioactive isotopes of fluorine, radioactive isotopes of iodine, chlorine, bromine, radioactive isotopes of bromine, radioactive isotopes of astatine, and NO. ２ NH ２ , N ＋ (R ２ ) ３ , Sn(R ２ ) ３ , Si(R ２ ) ３ , Hg(R ２ ), B (OH) ２ A alkyl, alkenyl, alkynyl, aryl, or heteroaryl substituted from the group consisting of R ２ is C １ -C ６ It is alkyl. The method according to claim 1.

22. The compound of formula (III) is 【Chemistry 11】 Having a structure m is 0, 1, 2, 3, 4, 5, or 6. R is, 【Chemistry 12】 A pyridine ring selected from the group consisting of, X is fluorine, iodine, radioactive isotopes of fluorine, radioactive isotopes of iodine, chlorine, bromine, radioactive isotopes of bromine, radioactive isotopes of astatine, NO ２ NH ２ , N ＋ (R ２ ) ３ , Sn(R ２ ) ３ , Si(R ２ ) ３ , Hg(R ２ ), B (OH) ２ , -NHNH ２ , -NHN=CHR ３ ,-NHNH-CH ２ R ３ Selected from, Each Q is independently selected from hydrogen or a protecting group. Y is O, S, N(R'), C(O), NR'C(O), C(O)N(R'), OC(O), C(O)O, NR'C(O)NR', ​​NR'C(S)NR', ​​NR'S(O) ２ , S (CH ２ ) ｐ , NR' (CH ２ ) ｐ , O(CH ２ ) ｐ OC(O)CHR ８ NHC(O), NHC(O)CHR ８ NHC(O), or covalent bond, p is 1, 2, or 3, R' is H or C １ -C ６ Alkyl, R ８ is hydrogen, alkyl, aryl, or heteroaryl, and each may be substituted. Z is tetrazole or CO ２ Q is, R ２ is C １ -C ６ It is alkyl, R ３ These are fluorine, iodine, radioactive isotopes of fluorine, radioactive isotopes of iodine, chlorine, bromine, radioactive isotopes of bromine, radioactive isotopes of astatine, and NO. ２ NH ２ , N ＋ (R ２ ) ３ , Sn(R ２ ) ３ , Si(R ２ ) ３ , Hg(R ２ ), B (OH) ２ Alkyl, alkenyl, alkynyl, aryl, or heteroaryl substituted with The method according to claim 21.

23. The compound of formula (II) is 【Chemistry 13】 It has a structure, The method according to claim 22, wherein M is not 0.

24. The compound of formula (II) has the following structure: 【Chemistry 14】 It has a structure, The method according to claim 22, wherein M is not 0.

25. Regarding the compound of formula (II), m is 0, 1, 2, 3, 4, 5, or 6. Y is O, S, N(R'), C(O), NR'C(O), C(O)N(R'), OC(O), C(O)O, NR'C(O)NR', ​​NR'C(S)NR', ​​NR'S(O) ２ , S (CH ２ ) ｐ , NR' (CH ２ ) ｐ , O(CH ２ ) ｐ OC(O)CHR ８ NHC(O), NHC(O)CHR ８ NHC(O), or covalent bond, p is 1, 2, or 3, and R' is H or C １ -C ６ Alkyl, R ８ is hydrogen, alkyl, aryl, or heteroaryl, and each may be substituted. R is, 【Chemistry 15】 And, X' is NHNH ２ , -NHN=CHR ３ ,-NHNH-CH ２ R ３ Selected from the group consisting of R ３ These are fluorine, iodine, radioactive isotopes of fluorine, radioactive isotopes of iodine, bromine, radioactive isotopes of bromine, radioactive isotopes of astatine, and NO. ２ NH ２ , N ＋ (R ２ ) ３ , Sn(R ２ ) ３ , Si(R ２ ) ３ , Hg(R ２ ), B (OH) ２ Alkyl, alkenyl, alkynyl, aryl, or heteroaryl substituted with R ２ is C １ -C ６ It is alkyl, n is 1, 2, 3, 4, or 5. The method according to claim 21.

26. The method according to claim 21, wherein, for the compound of formula (II), X or X' is selected from fluorine, iodine, a radioactive isotope of fluorine or iodine, bromine, a radioactive isotope of bromine, and a radioactive isotope of astatine.

27. For the compound of formula (II), X or X' is １８ F, １２３ I, １２４ I, １２５ I, １３１ I, ７５ Br, ７６ Br, ７７ Br, ８０ Br, ８０ｍ Br, ８２ Br, ８３ Br, ２１１ The method according to claim 26, selected from At.

28. For the compound of formula (II), X or X' is １８ The method according to claim 27, wherein F.

29. The compound of formula (II) is 【Chemistry 16】 The method according to claim 21, selected from among.

30. The compound of formula (II) is 【Chemistry 17】 The method according to claim 21.

31. The PSMA-targeted compound comprises a compound of formula (III), [Chemistry 18] q and s are each independently either 0 or 1. p is 0, 1, 2, or 3. a is 1, 2, 3, or 4. m is 1, 2, 3, 4, 5, or 6. n is 1, 2, 3, 4, 5, or 6. Z is tetrazole or CO ２ Q is, Each Q is independently selected from hydrogen or a protecting group. V may or may not exist, and if it exists, it is selected from -C(O)-, -NRC(O)-, and -NRC(S)-. W is selected from -NRC(O)-, -NRC(O)NR-, NRC(S)NR-, -NRC(O)O-, -OC(O)NR-, -OC(O)-, -C(O)NR-, or -C(O)O-. Y is selected from -C(O)-, -NRC(O)-, -NRC(S)-, -OC(O), Each R is independently H or C １ -C ４ It is alkyl, Each R １ H and C are independent of each other. １ -C ６ Alkyl, C ２ -C １２ Ariel, C ４ -C １６ It is an alkylaryl, and when p is 2 or 3, each R １ They may be the same or they may be different. R ２ and R ３ H and CO are independent of each other. ２ H, or CO ２ R ４ And R ４ is C １ -C ６ Alkyl, C ２ -C １２ Ariel, C ４ -C １６ It is an alkylaryl, R ２ or R ３ One of them is CO ２ H or CO ２ R ４ When that is the case, the other is H. G is a metal chelate moiety containing a chelate metal as needed, or a fluorescent dye moiety that emits light in the visible or near-infrared spectrum, and G may contain any additional atoms or linkers necessary to attach the metal chelate moiety or fluorescent dye moiety to the rest of the compound. The method according to claim 1.

32. The compound of formula (III) is 【Chemistry 19】 It has a structure, Z is tetrazole or CO ２ Q is, Each Q is independently selected from hydrogen or a protecting group. a is 1, 2, 3, or 4. m is 1, 2, 3, 4, 5, or 6. n is 1, 2, 3, 4, 5, or 6. p is 0, 1, 2, or 3. Each R is independently H or C １ -C ４ It is alkyl, V is selected from -C(O)-, -NRC(O)-, and -NRC(S)-. W is selected from -NRC(O)-, -NRC(O)NR-, NRC(S)NR-, -NRC(O)O-, -OC(O)NR-, -OC(O)-, -C(O)NR-, -C(O)O-, Y is selected from -C(O)-, -NRC(O)-, -NRC(S)-, -OC(O)-, R １ H, C １ -C ６ Alkyl, C ２ -C １２ Ariel, C ４ -C １６ It is an alkylaryl, and when p is 2 or 3, each R １ They may be the same or they may be different. R ２ and R ３ H and CO are independent of each other. ２ H, or CO ２ R ４ And R ４ is C １ -C ６ Alkyl, C2-C １２ Ariel, C ４ -C １６ It is an alkylaryl, R ２ or R ３ One of them is CO ２ H or CO ２ R ４ If that is the case, then the other is H. G is a metal chelate portion or fluorescent dye portion that emits light in the visible or near-infrared spectrum. The method according to claim 31.

33. The compound of formula (III) is 【Chemistry 20】 The method according to claim 31, having the structure described above.

34. The compound of formula (III) is 【Chemistry 21】 The method according to claim 31, having the structure described above.

35. The compound of formula (III) is 【Chemistry 22】 The method according to claim 31, having the structure described above.

36. For the compound of formula (III) above, R １ The method according to claim 31, wherein is phenyl.

37. Regarding the compound of formula (III) above, (a) R ２ H is R ３ H is, (b) R ３ CO ２ H is R ２ H is, (c) R ２ CO ２ H is R ３ H is, (d) R ２ CO ２ R ４ And R ３ is H, or, (e) R ３ CO ２ R ４ And R ２ H is The method according to claim 31.

38. For the compound of formula (III) above, R ４ The method according to claim 31, wherein is benzyl.

39. The method according to claim 31, wherein G is an optical dye selected from any one of the dyes of claims 14 to 20.

40. G is an optical dye, and the compound of formula (III) is 【Chemistry 23-1】 【Chemistry 23-2】 The method according to claim 31, selected from among.

41. The compound of formula (III) is 【Chemistry 24】 The method according to claim 31, wherein the compound is [the compound].

42. For the compound of formula (III), the metal chelate portion is DOTAGA (1,4,7,10-tetraazacyclododecane-1-(glutaric acid)-4,7,10-triacetic acid), DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), DOTASA (1,4,7,10-tetraazacyclododecane-1-(2-succinic acid)-4,7,10-triacetic acid), CB-DO2A (10-bis(carboxymethyl)-1,4,7,10-tetraazabicyclo[5.5.2]tetradecane), DEPA (7-[2-(bis-carboxymethylamino)-ethyl]-4,10-bis-carboxymethyl Lu-1,4,7,10-tetraazacyclododecane-1-ylacetic acid), 3p-C-DEPA (2-[(carboxymethyl)][5-(4-nitrophenyl-1-[4,7,10-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecane-1-yl]pentan-2-yl)amino]acetic acid), TCMC (2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraaza-1,4,7,10-tetra-(2-carbamonylmethyl)-cyclododecane), oxo-DO3A (1-oxa-4,7,10-triazacyclododecane-5-S-(4-isothiocyanatobenzyl)-4,7,10-triacetic acid), p-NH ２ -Bn-Oxo-DO3A(1-oxa-4,7,10-tetraazacyclododecane-5-S-(4-aminobenzyl)-4,7,10-triacetic acid),TE2A((1,8-N,N'-bis-(carboxymethyl)-1,4,8,11-tetraazacyclotetradecane),MM-TE2A,DM-TE2A,CB-TE2A(4,11-bis(carboxymethyl)-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane),CB-TE1A1P(4,8,11-tetraazacyclotetradecane Can-1-(methanephosphonic acid)-8-(methanecarboxylic acid)), CB-TE2P(1,4,8,11-tetraazacyclotetradecane-1,8-bis(methanephosphonic acid), TETA(1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid), NOTA(1,4,7-triazacyclononane-N,N',N''-triacetic acid), NODA(1,4,7-triazacyclononane-1,4-diacetate), NODAGA(1,4,7-triazacyclononane,1-g Rutaric acid-4,7-acetic acid), (NOTAGA) 1,4,7-triazonan-1,4-diyl) diacetic acid, DFO (deferoxamine), NETA ([4-[2-(bis-carboxymethylamino)-ethyl]-7-carboxymethyl-[1,4,7]triazonan-1-yl}acetic acid), TACN-TM (N,N',N'', Tris(2-mercaptoethyl)-1,4,7-triazacyclononane), Diamsar (1,8-diamino-3,6,10,13,16,19-hexaazabicyclo( The method according to claim 31, wherein a 6,6,6) eicosane, 3,6,10,13,16,19-hexaazabicyclo[6.6.6]eicosane-1,8-diamine), Sarar (1-N-(4-aminobenzyl)-3,6,10,13,16,19-hexaazabicyclo[6.6.6]eicosane-1,8-diamine), AmBaSar (4-((8-amino-3,6,10,13,16,19-hexaazabicyclo[6.6.6]icosane-1-ylamino)methyl)benzoic acid), and BaBaSar are selected.

43. With respect to the compound of formula (III), the chelating agent is 【Chemistry 25-1】 【Chemistry 25-2】 【Chemistry 25-3】 The method according to claim 31, selected from among.

44. The compound of formula (III) is 【Chemistry 26-1】 【Chemistry 26-2】 【Chemistry 26-3】 The method according to claim 31, selected from among.

45. For the compound of formula (III), the chelate metal is ６０ Cd, ６２ Cd, ６４ Cd, ６７ Cd, ５５ Co, ５７ Co, ２０３ Pb, ２１２ Pb, ２２５ Ac, １７７ Lu, ９９ mTc, ６７ Ga, ６８ Ga, １４９ Tb, ８６ Y, ９０ Y, １１１ In, １８６ Re, １８８ Re, １５３ Sm, ８９ Zr, ２１３ Bi, ２１２ Bi, ２１２ Pb, ６７ Ga, ４７ Sc, １６６ Dy, Al １８ F, １６６ Ho, and １７７ The method according to claim 31, selected from Lu.

46. The aforementioned PSMA-targeted compound is a compound of the following formula (IV): 【Chemistry 27】 Each Q is independently selected from hydrogen, metal ions, negative charge, or protecting groups. a, h, m, and n are integers selected from the group consisting of 1, 2, 3, 4, 5, and 6, respectively. s is either 0 or 1, r is 0 or 1, q is either 0 or 1, p is an integer selected from the group consisting of 0, 1, 2, and 3, and if p is 2 or 3, each R and R １ They may be the same or they may be different. Each R, R', R １ Hydrogen and C are independent of each other. １ -C ６ Substituted or unsubstituted alkyl, C ６ -C １２ Substitutive or non-substitutive aryl, C ６ -C １２ Substituted or unsubstituted heteroaryl, or C ６ -C １６ It is an alkylaryl, R ２ , R ３ , R ３ 'Each is independently hydrogen, C １ -C ４ Substituted or unsubstituted alkyl groups, -CO ２ H, -CO ２ Q, -CO ２ R ４ And R ４ is C １ -C ６ Substituted or unsubstituted alkyl, C ６ -C １２ Substitutive or non-substitutive aryl, C ６ -C １２ Substituted or unsubstituted heteroaryl, or C ６ -C １６ It is an alkylaryl, R ２ or R ３ One of them is -CO ２ H or -CO ２ R ４ If that is the case, the other is H, Tz is, 【Chemistry 28】 A triazole-containing portion selected from the group consisting of the following: L １ teeth, 【Chemistry 29】 And, L ２ teeth, 【Transformation 30】 And, X １ is selected from -NRC(O)-, -NRC(O)NR-, -NRC(S)NR, or -NRC(O)O-, X ２ is selected from -C(O)NR-, -NRC(O)NR-, -NRC(S)NR-, or -OC(O)NR-, R ５ H, -CO ２ H, or -CO ２ R ６ And R ６ is C １ -C ６ Alkyl, C ６ -C １２ Aryl, or C ６ -C １６ It is an alkylaryl compound, where b is 1, 2, 3, or 4, and d is 1, 2, 3, or 4. Y is -C(O)-, -NRC(O)-, -NRC(S)-, -OC(O)-, W is a bond, -(CH ２ -O) ｔ -, -NRC(O)-, -NRC(O)NR-, -NRC(S)NR-, -NRC(O)O-, -OC(O)NR-, -OC(O)-, -C(O)NR-, or -C(O)O-, where t is an integer selected from the group consisting of 1, 2, 3, 4, 5, 6, 7, and 8. G is, 【Chemistry 31】 And, FG is the fluorescent dye portion that emits light in the near-infrared spectrum, V is -C(O)-, -NRC(O)-, -NRC(S)-, or -OC(O)-, and g is an integer selected from the group consisting of 1, 2, 3, 4, 5, and 6. When r is 0, under the condition that q and s are both 0 or both are 1, or a pharmaceutically acceptable salt thereof, However, if R' is hydrogen, the fluorescent dye portion is 【Chemistry 32】 That's impossible. The method according to claim 1.

47. Regarding the compound of formula (IV) above, the fluorescent dye portion is 【Transformation 33】 And, i, j, and k are integers selected from the group consisting of 1, 2, 3, 4, 5, and 6, respectively. X ３ It is either a single bond, -O-, or -S-. R ７ , R ８ , R ９ Each of them is independently hydrogen, C １ -C ４ Unsubstituted or substituted alkyl, or -CO ２ Q is, Each Q is independently selected from hydrogen, metal ions, negative charge, or protecting groups. The method according to claim 46.

48. The compound of formula (IV) is 【Transformation 34】 The method according to claim 46.

49. The compound of formula (IV) is 【Chemistry 35】 The method according to claim 46.

50. The compound of formula (IV) is 【Chemistry 36-1】 【Chemistry 36-2】 【Chemistry 36-3】 The method according to claim 46, selected from the following.

51. The PSMA-targeted compound is 【Chemistry 37】 The method according to claim 1.