Radiopharmaceutical composition targeting glypican 3 and its use

Abstract

Radiopharmaceuticals and conjugates targeting GPC3, as well as their compositions and uses, are provided herein. In one embodiment, a conjugate comprising a peptide having avidity to GPC3 and a metal chelating agent configured to bind to a radionuclide is provided herein. The conjugate described herein may further comprise a linker connecting the chelating agent and the peptide. The conjugate described herein may further comprise a radionuclide. In one embodiment, a radiopharmaceutical comprising a peptide and a metal chelating agent binding to a radionuclide is provided herein. The conjugate described herein may further comprise a linker connecting the chelating agent and the peptide. Methods for treating cancer by administering the radiopharmaceuticals, conjugates, and compositions thereof are further provided herein.

Description

[Technical Field]

[0001] Cross-reference with related applications This application claims the interests of U.S. Provisional Patent Application No. 63 / 506,721, filed on 7 June 2023, which is incorporated herein by reference in its entirety.

[0002] joint research agreement The subject matter disclosed herein was developed and the claimed invention was made by one or more parties to a Joint Research Agreement (JRA), which was effective on or before the effective filing date of the claimed invention, within the meaning of 35 U.S. SC §100(h) and 37 C.F. §1.9(e), or acting on their behalf. The aforementioned one or more parties to the JRA consist of PeptiDream, Inc. (Kanagawa, Japan) and RayzeBio, Inc. (San Diego, California, USA). The claimed invention was made as a result of activities carried out within the scope of the aforementioned Joint Research Agreement.

[0003] Sequence List This application includes a sequence listing submitted electronically as part of the specification in .xml format, the entirety of which is incorporated herein by reference. Created on 5 June 2024, the XML file is named 59541-732_601_SL.xml and has a size of 689,382 bytes.

[0004] In one embodiment, the disclosure relates to radiopharmaceutical conjugates comprising peptides bound to glypican 3 (GPC3), compositions comprising such radiopharmaceutical conjugates, and uses thereof. In one embodiment, the disclosure relates to the use of such radiopharmaceutical conjugates in the prevention, suppression, or treatment of diseases or disorders characterized by either overexpression or decreased expression of GPC3 in affected tissue (e.g., tumors, in the case of GPC3 overexpression). [Background technology]

[0005] Glypican 3 (GPC3) is a heparan sulfate (HS) glycoprotein belonging to the heparan sulfate proteoglycan family and is anchored to the cell membrane surface by a phosphatidylinositol (GPI) anchor. The GPC3 core protein contains 580 amino acids and has a molecular weight of approximately 70 kDa. It is cleaved by furin to produce a 40 kDa N-terminal subunit and a 30 kDa C-terminal subunit, which are linked to each other by disulfide bonds. The two HS side chains of GPC3 are linked near the C-terminus (Takahiro Nishida, Hiroaki Kataoka. Glypican 3-Targeted Therapy in Hepatocellular Carcinoma, Cancer 2019; 11 (9): 1339).

[0006] GPC3 may play an important role in the proliferation of germ layer tissues. Deletion of the GPC3 gene can cause hypergrowth syndrome, namely Simpson-Gorabi-Boehmell syndrome (SGBS). GPC3 may be clearly expressed throughout the fetal period, and from birth to adulthood, it is not clearly expressed in other normal tissues, except for weak expression in the placenta, breast, mesoderm, ovaries, lungs, and kidneys.

[0007] Abnormal GPC3 expression has been found in various tumor tissues in adults, such as hepatocellular carcinoma (HCC), squamous cell carcinoma of the lung, gastric cancer, and ovarian cancer. It is particularly highly expressed in HCC cells, where GPC3 enhances autocrine / paracrine classical Wnt signaling, promoting the proliferation and invasion of HCC cells (Capurro MI, Xiang YY, Lobe C, Filmus J. Glypican-3 promotes the growth of hepatocellular carcinoma by-stimulating canonical Wnt signaling; Cancer Res 2005, 65(14): 6245-54). Immunohistochemical staining has shown that approximately 70% of tumor tissues from HCC patients exhibit high GPC3 protein expression (Capurro M, Wanless IR, Sherman M, et al. Glypican-3: a novel serum and histochemical marker for hepatocellular carcinoma; Gastroenterology 2003, 125(1):89-97). Therefore, GPC3 is considered a candidate target for tumor therapy.

[0008] Codrituzumab (also known as GC33 antibody) is a recombinant humanized monoclonal antibody developed by Chugai Pharmaceutical Co., Ltd. in Japan and binds to the region near the membrane of GPC3 protein. The GC33 antibody targets GPC3-positive HCC cells and can induce antibody-dependent cell cytotoxicity (ADCC). In a phase I clinical trial, codrituzumab showed good immune tolerance. An antitumor effect may occur in HCC patients (Ikeda M, Ohkawa S, Okusaka T, et al. Japanese phase I study of GC33, a-antibody against glypican-3 for advanced hepatocellular carcinoma. Cancer Sci. 2014, 105, 455-462). However, in a phase II clinical trial involving 185 patients with advanced liver cancer, the therapeutic effect of codrituzumab was not significant compared to the control group.

[0009] Therefore, both the novel GPC3-binding peptide and the composition containing the GPC3-binding peptide are useful and are claimed. SUMMARY OF THE INVENTION

[0010] In one aspect, (a) Formula (I-1):

Chemical formula

[0011] In some embodiments, the radiopharmaceutical is selected from Table 3A or Table 3B.

[0012] In one embodiment, (a) Equation (I-1): [ka] [In the formula, R 1 is -NH2 or -OH; R2 C 1-3 It is alkyl; R 3 C 1-3 It is an alkylene and has one or more R 4 This may be substituted as appropriate; R 4 Each of them is independent of C 1-3 Alkyl or C 3-6 It is a cycloalkyl; kxR is 1, 2, 3, 4, 5, or 6; X R is -S-, -CH2-, or -O-; X1 is any amino acid; X2 is any amino acid; X3 is any amino acid; X4 is any amino acid; X5 is an amino acid containing an aromatic ring, or a cycloalkyl or heterocycloalkyl group, or X5 is a peptoid; X6 is a hydrophobic amino acid, a hydrophilic amino acid, or a polar amino acid, wherein the polar amino acid has a substituted side chain; X7 is a hydrophobic amino acid comprising a C1-C8 alkyl, cycloalkyl, or heterocycloalkyl group, where the alkyl, cycloalkyl, and heterocycloalkyl groups may be independently and appropriately substituted; X8 is A, I, L, V, Y, or F, or a variant thereof; X9 is an N-alkylated amino acid containing an aromatic ring; X10 is G or A, or their N-alkylated variants, or a D-amino acid; X11 is an amino acid that contains an aromatic ring. peptides of; and (b) A metal chelating agent configured to bind to a radionuclide, wherein the metal chelating agent is covalently bonded to the peptide. Conjugates containing or pharmaceutically acceptable salts thereof are disclosed herein.

[0013] In some embodiments, the conjugate is selected from Table 9.

[0014] In one aspect, this disclosure is, (a) A peptide having avidity to glypican 3 (GPC3), wherein SEQ ID NO: MeK-MeI-D-MeQ-F4COO-IIY-MeNal27N-G-3Py6Ph-MeC(Sequence ID 1) A peptide consisting of 10 to 12 amino acid residues or a pharmaceutically acceptable salt thereof, comprising an amino acid sequence containing one or more (e.g., 1 to 6) amino acid deletions, substitutions, and / or additions within the amino acid sequence; and (b)(i) a metal chelating agent configured to bind to a radionuclide, wherein the metal chelating agent binds to a peptide; or (ii) a radionuclide to which covalent bonding occurs. Regarding radiopharmaceutical conjugates, including [specific example].

[0015] In some embodiments, the radiopharmaceutical conjugate includes a metal chelating agent configured to bind to a radionuclide, and comprises a metal chelating agent that binds to a peptide. In some embodiments, the radiopharmaceutical conjugate includes a radionuclide that binds to the metal chelating agent. In some embodiments, the radiopharmaceutical conjugate includes a covalently bound radionuclide. In some embodiments, the peptide is a cyclic peptide. In some embodiments, the peptide is a monocyclic peptide.

[0016] In one aspect, this disclosure is, (a) A peptide having avidity to glypican 3 (GPC3), wherein formula (I): X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12 Equation (I) [In the formula, X1 is any amino acid; X2 is any amino acid; X3 is any amino acid; X4 is any amino acid; X5 is an amino acid containing an aromatic ring (e.g., W, F, Y, or variants thereof), a cycloalkyl group, or a heterocycloalkyl group, or X5 is a peptoid (e.g., Cha4cH, Cha4tH, A1mor, Atp, Cha4cOMe); X6 is a hydrophobic amino acid, a hydrophilic amino acid, or a polar amino acid, wherein the polar amino acid has a substituted side chain; X7 is a hydrophobic amino acid comprising a C1-C8 alkyl, cycloalkyl, or heterocycloalkyl group, where the alkyl, cycloalkyl, and heterocycloalkyl groups may be independently and appropriately substituted (for example, X7 is I, Eva, alI, TMe, SMe, Gcpr, Gcpe, Gthp, dMeS, TdMe, or Cbg); X8 is A, I, L, V, Y, or F, or a variant thereof; X9 is an N-alkylated amino acid containing an aromatic ring; X10 is a G, A, or D amino acid (e.g., da, ds, de, or dp); X11 is an amino acid containing an aromatic ring (e.g., F, Y, or their variants); X12 is an N-alkylated cysteine ​​(e.g., MeC). Peptides containing the amino acid sequence of the above, or pharmaceutically acceptable salts thereof; and (b)(i) a metal chelating agent configured to bind to a radionuclide, wherein the metal chelating agent binds to a peptide; or (ii) a radionuclide to which covalent bonding occurs. Regarding radiopharmaceutical conjugates, including [specific example].

[0017] In some embodiments, the radiopharmaceutical conjugate comprises a metal chelating agent configured to bind to a radionuclide, wherein the metal chelating agent binds to the peptide. In some embodiments, the radiopharmaceutical conjugate comprises a covalently bound radionuclide. In some embodiments, the peptide is a monocyclic peptide. In some embodiments, the peptide is of formula (I): X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12 Formula (I) [wherein X1 is I, R, Cit, F4G, 4Py, 3Py, KCOpipzaa, V, Eva, Q, E, MeI, Ahp, F4COO, KCOpip4COO, MeQdMe, MeA, MeSMe, MeG, MeV, MeHseMe, Aib, MeT, alI, TMe, MeKCOpipzaa, MeQ, Hpr, MeTMe, MeDapCOpipzaa, MeK, MeKAc, MeK(de), MeK(H), MeK(df), or MeK(datb); X2 is I, K, Cit, F4G, 4Py, 3Py, KCOpipzetOH, V, KCOpipzaa, Eva, Q, E, S, Ahp, F4COO, KCOpip4COO, MeQdMe, MeA, MeSMe, MeG, MeI, MeV, MeL, HseMe, MeY, Me3Py, MeHseMe, MeKAc, alI, TMe, MeKCOpipzaa, MeQ, Hpr, MeTMe, or MeDapCOpipzaaa; X3 is D, Har, KCOpipzetOH, Cit, KCOmeglumine, KCOpipzaa, A4paa, Q, A, E, MeD, S, N, Hgl, F4COO, KCOpip4COO, KAc, Hgn, MeY, or DapCOpipzaa; X4 is D, Har, KCOpipzetOH, KCOmeglumine, KCOpipzaa, A4paa, Q, A, E, MeD, S, N, Hgl, F4COO, KCOpip4COO, dd, MeQ, MeQdMe, MeA, MeSMe, MeG, EtG, MeeG, CmG, CmpG, CrmG, CeG, CrpG, MeK, MeKAc, MeHgl, Hgn, MeDapCOpipzaa, MeKCOpipzaa, Medd, Cit, MeCit, MeN, MeS, MeE, MeY, W5N, or MeA4paa; X5 is Y, F3G, 3Py6COO, 4Py2NH2, 3Py5COO, F3COO, 3Py6NHAc, F, F4C, F4OMe, F4COO, Nal2, F3aao, F4aa, F4aao, 3Py6NHaa, 5Pdo, F3CON, F4F, F4OEt, F4Me, F4CON, F4CONPEG4Me, F3OMe, F3CON, Yae, YaeCOpipzaa, F4aaopipzaa, 4Pdo, 3Py6CON, Atp, Cha4cH, Cha4tH, Cha4cOMe, A1mor, or F4amCOpipzaa; X6 is I, V, Eva, Chg, Tbg, A, L, Ahp, F4COO, Gcpr, Gcpe, alI, Cle, S3REt, TMe, Acpr, Cba, Gthp, NleCOO, NleOH, P, Atb, Nva, Nle, N, DapAc, Abu, Nmm, Ndm, Ncit, Cit, SMe, HseMe, HseEt, HseiPr, dMeS, TdMe, Cbg, NvaOMe, SiPr, Spr, NleOMe, Sbu, Scbm, Scpe, AhpOMe, HseBu, Spent, or Hsecpe; X7 is I, Eva, alI, TMe, SMe, Gcpr, Gcpe, Gthp, dMeS, TdMe, or Cbg; X8 is A, I, L, V, Y, F4OMe, F4COO, F4OEt, F4u, F4Me, F4CONdMe, F4CON, F4ms, F4CONPEG4Me, F34dOMe, F3OMe, F3C, F3CON, F3CONdMe, 3Py6CON, Yae, YaeCOpipzaa, 5Inda, F3aao, F3aa, F4aao, F4aa, 3Py6Nhae, 3Py6NHAc, 3Py6OMe, F4aaopipzaa, or F4amCOpipzaa; X9 is MeNal2, MeNal27N, MeF34diox, MeF34dOMe, MeF4T, MeY, MeW1Me, MeW7N, MeF3C4Me, or MeF3Me4C; X10 is a G, A, or D amino acid (e.g., da, ds, de, or dp); X11 is Bph, 3Py6Ph, F41Me4Pyz, F43Pyz, F44Pyz, F41Pyz, F41Me3Pyz, F41Et4Pyz, F41MeOe4Pyz, F41MeOp4Pyz, F44thp, F4Ac4pip, PhNva, PhNle, Yph, Ybn, F4tb, F4oPr, or F4CONdMe; X12 is a MeC. It has the amino acid sequence of the above, or a pharmaceutically acceptable salt thereof.

[0018] In one aspect, this disclosure is, (a) A peptide having avidity to glypican 3 (GPC3), wherein formula (I): X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12 Equation (I) [In the formula, X1 is any amino acid; X2 is any amino acid; X3 is any amino acid; X4 is any amino acid; The X5 is [ka] [In the formula, R n5 is hydrogen or C 1-3 It is alkyl; Ring A5 is aryl, heteroaryl, cycloalkyl, or heterocycloalkyl; R X5 Each of them is independent of C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, C 2-6 Alkenil, C 2-6 Alkynyl, halogen, -CN, -NO2, -OR a , -SR a -SF5, -NR c R d -S(=O)Ra -S(=O)2R a -S(=O)2NR c R d -S(=O)(=NR a )R a -N=S(=O)NR c R d , -NR a S(=O)2R a , amidinil, -NR a C(=NH)NR c R d , -NR a S(=O)2NR c R d -C(=O)R a , -C(=O)OR a -OC(=O)R a , -OC(=O)OR a -OC(=O)NR c R d , -NR a C(=O)R a , -NR a C(=O)OR a , -NR a C(=O)NR c R d -C(=O)NR c R d , -P(=O)(OR c )(OR d ), -P(=O)R c R d aryl, heteroaryl, cycloalkyl, heterocycloalkyl, -L X5 -heterocycloalkyl, -L X5 -Cycloalkyl, -L X5 -aryl, or -L X5 -A heteroaryl, where the alkyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl are one or more R X5a This may be substituted as appropriate; or, Two R's X5 Together, =O, =S, or =N(R a ) form; L X5 C1-6 Alkylene, C 1-6 Heteroalkylene, -O-, -S-, or -NR a -, where the alkylene and heteroalkylene may each be optionally substituted with one or more R X5a ; kx5 is 0, 1, 2, or 3; mx5 is 0, 1, 2, 3, 4, or 5; *X4 represents the point of attachment to X4; *X6 represents the point of attachment to X6] ; X6 is [In the formula, [wherein, R n6 is hydrogen or C 1-3 alkyl; R X6 is C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 aminoalkyl, C 1-6 heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, -L X6 -heterocycloalkyl, -L X6 -cycloalkyl, -L X6 -aryl, or -L X6 -heteroaryl, where the alkyl, heteroalkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl may each be optionally substituted with one or more R X6a ; Alternatively, R n6 and R x6 together with the intervening atoms form a 5- to 6-membered heterocycloalkyl, which may be optionally substituted with one or more R X6a ; L X6 is C 1-6Alkylene, C 1-6 Heteroalkylene, -O-, -S-, or -NR a -where the alkylene and heteroalkylene are one or more R X6a This may be substituted as appropriate; *X5 represents the connection point to X5; *X7 represents the connection point to X7. and; X7 is [ka] [In the formula, R n7 is hydrogen or C 1-3 It is alkyl; R X7 C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, C 2-6 Alkenil, C 2-6 Alkynyl, cycloalkyl, or heterocycloalkyl, where each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, and heterocycloalkyl is one or more R X7a This may be substituted as appropriate; *X6 represents the connection point to X6; *X8 represents the connection point to X8. and; The X8 is [ka] [In the formula, R n8 is hydrogen or C 1-3 It is alkyl; Ring A8 is either an aryl or heteroaryl ring; R X8 Each of them is independent of C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6Aminoalkyl, C 1-6 Heteroalkyl, C 2-6 Alkenil, C 2-6 Alkynyl, halogen, -CN, -NO2, -OR a , -SR a -SF5, -NR c R d -S(=O)R a -S(=O)2R a -S(=O)2R c R d -S(=O)(=NR a )R a -N=S(=O) R c R d , -NR a S(=O)2R a , amidinil, -NR a C(=NH)NR c R d , -NR a S(=O)2R c R d -C(=O)R a , -C(=O)OR a -OC(=O)R a , -OC(=O)OR a -OC(=O)NR c R d , -NR a C(=O)R a , -NR a C(=O)OR a , -NR a C(=O)NR c R d -C(=O)NR c R d , -P(=O)(OR c )(OR d ), -P(=O)R c R d aryl, heteroaryl, cycloalkyl, heterocycloalkyl, -L X8 -heterocycloalkyl, -L X8 -Cycloalkyl, -L X8 -aryl, or -L X8-A heteroaryl, where the alkyl, heteroalkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl each contain one or more R X8a This may be substituted as appropriate; or, Two R's X8 Together, =O, =S, or =N(R a ) form; L X8 C 1-6 Alkylene, C 1-6 Heteroalkylene, -O-, -S-, or -NR a -where the alkylene and heteroalkylene are one or more R X8a This may be substituted as appropriate; kx8 is 0, 1, 2, or 3; mx8 is 0, 1, 2, 3, 4, or 5; *X7 represents the connection point to X7; *X9 represents the connection point to X9. and; X9 is [ka] [In the formula, R n9 is hydrogen or C 1-3 It is alkyl; Ring A9 is either aryl or heteroaryl; R X9 Each of them is independent of C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, C 2-6 Alkenil, C 2-6 Alkynyl, halogen, -CN, -NO2, -OR a , -SR a -SF5, or -NR c R dHere, the alkyl, heteroalkyl, alkenyl, and alkynyl each have one or more R X9a This may be substituted as appropriate; or, Two R's X9 Together, =O, =S, or =N(R a ) form; kx9 is 0, 1, 2, or 3; mx9 is 0, 1, 2, 3, 4, or 5; *X8 represents the connection point to X8; *X10 represents the connection point to X10. and; X10 is glycine or a D-amino acid (e.g., da, ds, de, or dp); X11 is [ka] [In the formula, R n11 is hydrogen or C 1-3 It is alkyl; Ring A11 is either an aryl or heteroaryl ring; R X11 Each of them is independent of C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, halogen, -CN, -NO2, -OR a , -SR a -SF5, -NR c R d -S(=O)R a -S(=O)2R a -S(=O)2R c R d -S(=O)(=NR a )R a -N=S(=O)R c R d , -NR a S(=O)2R a , amidinil, -NR a C(=NH)NRc R d , -NR a S(=O)2R c R d -C(=O)R a , -C(=O)OR a -OC(=O)R a , -OC(=O)OR a -OC(=O)NR c R d , -NR a C(=O)R a , -NR a C(=O)OR a , -NR a C(=O)NR c R d -C(=O)NR c R d , -P(=O)(OR c )(OR d ), -P(=O)R c R d aryl, heteroaryl, cycloalkyl, heterocycloalkyl, -L X11 -heterocycloalkyl, -L X11 -Cycloalkyl, -L X11 -aryl, or -L X11 -A heteroaryl, where the alkyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl each contain one or more R X11a This may be substituted as appropriate; or, Two R's X11 Together, =O, =S, or =N(R a ) form; L X11 C 1-6 Alkylene, C 1-6 Heteroalkylene, -O-, -S-, or -NR a -where the alkylene and heteroalkylene are one or more R X11a This may be substituted as appropriate; kx11 is 0, 1, 2, 3, 4, or 5; mx11 is 0, 1, 2, 3, 4, or 5; *X10 represents the connection point to X10; *X12 represents the connection point to X12. and; X12 is an N-alkylated cysteine; R X5a , R X6a , R X7a , R X8a , R X9a , and R X11a These are, independently, halogen and C 1-6 Alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, -CN, -NO2, -OR a , -SR a , -NR c R d -S(=O)R a -S(=O)2R a -SF5, -S(=O)2NR c R d -S(=O)(=NR a )R a -N=S(=O)R c R d , -NR a S(=O)2R a , amidinil, -NR a C(=NH)(NR a )2, -NR a S(=O)2NR c R d -C(=O)R a , -C(=O)OR a -OC(=O)R a , -OC(=O)OR a -OC(=O)NR c R d , -NR a C(=O)R a , -NR a C(=O)OR a , -NR a C(=O)NR c R d -C(=O)NR c R d , -P(=O)(OR c )(ORd ), -P(=O)R c R d aryl, heteroaryl, cycloalkyl, heterocycloalkyl, =O, =S, or =N(R a ) where the alkyl, heteroalkyl, alkenyl, and alkynyl each have one or more R e This may be substituted as appropriate; R a Each of these is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(cycloalkyl), C1-C6 alkyl(heterocycloalkyl), C1-C6 alkyl(aryl), or C1-C6 alkyl(heteroaryl), where each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently one or more R e This may be substituted as appropriate; R e These are, independently, halogen, -CN, -OH, -O-C1-C6 alkyl, -SF5, -S(=O)C1-C6 alkyl, -S(=O)2C1-C6 alkyl, -S(=O)2NH2, -S(=O)2-halogen, -S(=O)2NHC1-C6 alkyl, -S(=O)2N(C1-C6 alkyl)2, -NH2, -NHC1-C6 alkyl, -N(C1-C6 alkyl)2, -NHC(=NH)NH2, -NHC(=O)OC1-C6alkyl, -C(=O)C1-C6alkyl, -C(=O)OH, C1-C6alkyl-C(=O)OH, -C(=O)OC1-C6alkyl, -C(=O)NH2, -C(=O)N(C1-C6alkyl)2, -C(=O)NHC1-C6alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, or C1-C6 heteroalkyl; or, Two R's e Together, they form =O; Rc and R d Each of these is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(cycloalkyl), C1-C6 alkyl(heterocycloalkyl), C1-C6 alkyl(aryl), or C1-C6 alkyl(heteroaryl), where each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently one or more R e This may be substituted as appropriate; or, R c and R d Along with the atoms to which they are bonded, one or more R e [This may form a heterocycloalkyl group which may be appropriately substituted.] Peptides having the amino acid sequence of the above, or pharmaceutically acceptable salts thereof; and (b)(i) a metal chelating agent configured to bind to a radionuclide, wherein the metal chelating agent binds to a peptide; or (ii) a radionuclide to which covalent bonding occurs. Regarding radiopharmaceutical conjugates, including [specific example].

[0019] In some embodiments, the radiopharmaceutical conjugate comprises a metal chelating agent configured to bind to a radionuclide, wherein the metal chelating agent binds to the peptide. In some embodiments, the radiopharmaceutical conjugate comprises a covalently bound radionuclide. In some embodiments, the peptide is a monocyclic peptide.

[0020] In some embodiments of the radiopharmaceutical conjugate, the peptide of formula (I) is: formula (I-1): [ka] [In the formula, R 1It is selected from the group consisting of -NH2 and -OH; R 2 C 1-3 It is alkyl; R 3 C 1-3 It is an alkylene and has one or more R 4 This may be substituted as appropriate; R 4 Each of them is independent of C 1-3 Alkyl or C 3-6 It is a cycloalkyl; kxR is 1, 2, 3, 4, 5, or 6; X R It is selected from the group consisting of -S-, -CH2-, or -O-; X1 to X11 have the definitions described in formula (I). It has the structure of [the object].

[0021] In some embodiments of the radiopharmaceutical conjugate, the peptide of formula (I) is: [ka] It has the structure of [the object].

[0022] In some embodiments, the radiopharmaceutical conjugate comprises a peptide having an amino acid sequence that is at least 90% identical to a sequence selected from SEQ ID NOs: 1 to 72, or a sequence having up to 1, 2, 3, 4, or 5 substitutions due to conserved variants compared to any one of the sequences selected from SEQ ID NOs: 1 to 72. In some embodiments, the radiopharmaceutical conjugate comprises a peptide having an amino acid that is at least 90% identical to a sequence selected from SEQ ID NOs: 1 to 72. In some embodiments, the peptide consists of an amino acid sequence selected from SEQ ID NOs: 1 to 72.

[0023] In some embodiments, the radiopharmaceutical conjugate comprises a metal chelating agent configured to bind to a radionuclide, the metal chelating agent binding to a peptide of formula (I) or SEQ ID NO: 1. In some embodiments, the radiopharmaceutical conjugate further comprises a linker that binds the peptide to the metal chelating agent. In some embodiments, the linker binds to the peptide via a non-terminal amino acid residue of the peptide. In some embodiments, the linker binds to the peptide via the N-terminus of the peptide. In some embodiments, the linker binds to the peptide via the C-terminus of the peptide. In some embodiments, the linker binds to the first amino acid residue (or X1), the second amino acid residue (or X2), the third amino acid residue (or X3), the fourth amino acid residue (or X4), the eighth amino acid residue (or X8), or the twelfth amino acid residue (or X12). In some embodiments, the linker contains 3 to 30 intervening non-hydrogen organic atoms between the metal chelating agent and the peptide. In some embodiments, the linker contains one or more amino acid residues. In some embodiments, the linker is a bond. In some embodiments, the metal chelating agent is DOTA, DOTA-GA, pBn-DOTA, pBn-SCN-DOTA, NH2-DOTA, NH2-DOTA-GA, p-NCS-Bn-DOTA-GA, p-NH2-Bn-oxo-DO3A, p-SCN-Bn-oxo-DO3A, NOTA, NODA-GA, NH2-NODA-GA, p-NCS-Bn-NODA-GA, p-NH2-Bn-NOTA, p-SCN-Bn-NOTA, NCS-MP- The present invention includes NODA, NH2-MPAA-NODA, PCTA, p-NH2-Bn-PCTA, p-SCN-Bn-PCTA, p-SCN-Bn-HEHA, H2-MACROPA-NCS, H1-MACROPA, H2-MACROPA-NH2, H4-OCTAPA, tetra-(S,S,S,S)-Me-DOTA, tetra-(S,S,S,S)-Et-DOTA, tetra-(S,S,S,S)-iBu-DOTA, or maleimide-nBu-DOTA. In some embodiments, the metal chelating agent is [ka] It has the following structure. In some embodiments, the radiopharmaceutical conjugate further comprises a radionuclide bound to a metal chelating agent. In some embodiments, the radionuclide is an alpha-emitting radionuclide. In some embodiments, the alpha-emitting radionuclide is Ac-225, Bi-213, Bi-209, Tb-149, Ra-223, Th-227, Fr-223, Gd-148, Th-229, Pb-212, or Po-213. In some embodiments, the alpha-emitting radionuclide is Ac-225. In some embodiments, the radionuclide is a beta-emitting radionuclide. In some embodiments, the beta-emitting radionuclide is Cu-67, Lu-177, Y-90, Rh-105, Yb-175, Tm-167, Pm-153, Sm-153, or In-111. In some embodiments, the beta-emitting radionuclide is lutetium-177. In some embodiments, the radionuclide is a positron-emitting radionuclide. In some embodiments, the positron-emitting radionuclides are Ga-68, Cu-62, Cu-64, Zr-89, and Tb-152.

[0024] In some embodiments, the radiopharmaceutical conjugate includes a covalently bonded radionuclide that binds to the peptide of formula (I) or SEQ ID NO: 1. In some embodiments, the radiopharmaceutical conjugate further includes a linker that binds the peptide to the covalently bonded radionuclide. In some embodiments, the radionuclide is covalently bonded to an amino acid containing an aromatic ring. In some embodiments, the radionuclide binds to the 5th amino acid or X5, the 8th amino acid or X8, the 9th amino acid or X9, or the 11th amino acid or X11. In some embodiments, the radionuclide is a residualizing agent that binds to the peptide, [ka] [In the formula, R* is a covalently bonded radionuclide.] It covalently bonds to a residual agent having the structure. In some embodiments, the radionuclide to be covalently bonded is 18 F, 74 As, 76 Br,123 I, 124 I, 125 I, 131 I, or 211 It is At.

[0025] In one embodiment, the disclosure relates to a pharmaceutical composition comprising a radiopharmaceutical conjugate or a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable excipient or carrier as described herein. In one embodiment, the disclosure relates to a pharmaceutical composition comprising a radiopharmaceutical or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient or carrier as described herein.

[0026] In one embodiment, the present disclosure relates to a method for treating a disease or disorder characterized by overexpression of glypican 3 (GPC3) in a subject requiring treatment, characterized by administering to the subject a therapeutically effective amount of a radiopharmaceutical or a pharmaceutically acceptable salt thereof described herein, or a pharmaceutical composition described herein. In one embodiment, the present disclosure relates to a method for treating a disease or disorder characterized by overexpression of GPC3 in a subject requiring treatment, characterized by administering to the subject a first radiopharmaceutical or a pharmaceutically acceptable salt thereof; and administering to the subject a therapeutically effective amount of a second radiopharmaceutical or a pharmaceutically acceptable salt thereof, wherein the first radiopharmaceutical or a pharmaceutically acceptable salt thereof is described herein, wherein the radionuclide is a diagnostic radionuclide; and the second radiopharmaceutical or a pharmaceutically acceptable salt thereof is described herein, wherein the radionuclide is a therapeutic radionuclide. In one embodiment, the disclosure relates to a method for diagnosing a disease or disorder characterized by overexpression of GPC3 in a subject requiring diagnosis, wherein the method comprises administering a radiopharmaceutical or a pharmaceutically acceptable salt thereof described herein to the subject, and imaging the subject to determine the expression level of GPC3 in the subject, wherein the radionuclide is suitable for use as an imaging isotope. In one embodiment, the disclosure relates to a method for treating a disease or disorder characterized by overexpression of GPC3 in a subject requiring treatment, wherein the method comprises administering a radiopharmaceutical conjugate or a pharmaceutically acceptable salt thereof described herein to the subject. In some embodiments, the disease or disorder is cancer. In some embodiments, the cancer is selected from hepatocellular carcinoma, squamous cell carcinoma of the lung, adenocarcinoma of the lung, germ cell tumor, hepatoblastoma, Wilms' tumor, malignant rhabdoid tumor, rhabdomyosarcoma, liposarcoma, thyroid cancer, pancreatic cancer, small intestine cancer, small cell neuroendocrine carcinoma (SCNC), hormone-treated castration-resistant adenocarcinoma of the prostate, ovarian cancer, gastric cancer, esophageal cancer, and malignant melanoma.

[0027] In one embodiment, this disclosure relates to a kit, tester, or composition for determining the expression level of GPC3 in a sample, comprising a radiopharmaceutical or conjugate described herein or a pharmaceutically acceptable salt thereof. In some embodiments, the kit, tester, or composition is suitable for use in a diagnostic method for a disease or disorder characterized by overexpression or decreased expression of GPC3. In some embodiments, the sample is derived from a subject suspected of having a disease or disorder characterized by overexpression or decreased expression of GPC3.

[0028] In one embodiment, the disclosure relates to the use of radiopharmaceuticals, conjugates, or pharmaceutically acceptable salts thereof described herein in the manufacture of agents for diagnosing and / or treating diseases or disorders characterized by overexpression or decreased expression of GPC3.

[0029] In one embodiment, the disclosure relates to the use of radiopharmaceuticals, conjugates, or pharmaceutically acceptable salts thereof described herein for use in diagnosing and / or treating diseases or disorders characterized by overexpression or decreased expression of GPC3.

[0030] Embedding by reference All publications, patents, and patent applications described herein are incorporated herein by reference for the specific purposes identified herein. [Brief explanation of the drawing]

[0031] All features of the embodiments described herein are not mutually exclusive and can be combined with each other. For example, elements of one embodiment can be used in other embodiments without further mention. Detailed descriptions of specific embodiments are provided below with reference to the accompanying drawings.

[0032] [Figure 1]Figure 1 shows a flowchart of HepG2 cells that have GPC3 on their cell surface and are stained with biotinylated peptides followed by a Streptavidin, R-Phycoerythrin conjugate. [Figure 2] Figure 2 shows a flowchart of Huh-7 cells that have GPC3 on their cell surface and are stained with biotinylated peptides followed by a Streptavidin, R-Phycoerythrin conjugate. [Figure 3] Figure 3 shows a flowchart of SK-Hep1 cells, a negative control cell line, stained with biotinylated peptide followed by Streptavidin, R-Phycoerythrin Conjugate. [Figure 4A] Figure 4A shows an exemplary metal chelating agent of the present disclosure, in which, [ka] This represents the binding site of the metal chelating agent to the remaining conjugate. [Figure 4B] Figure 4B shows the same metal chelating agent as in Figure 4A, except that the linker or peptide portion that forms a covalent bond with the metal chelating agent is indicated by the dashed circle. [ka] Excluding the points shown inside. [Figure 5A] Figure 5A shows an exemplary metal chelating agent of the present disclosure, in which, [ka] This represents the binding site of the metal chelating agent to the remaining conjugate. [Figure 5B] Figure 5B shows the same metal chelating agent as in Figure 5A, except that the linker or peptide portion that forms a covalent bond with the metal chelating agent is indicated by the dashed circle. [ka] Excluding the points shown inside. [Figure 6A]Figure 6A shows an exemplary metal chelating agent of the present disclosure, in which, [ka] This represents the binding site of the metal chelating agent to the remaining conjugate. [Figure 6B] Figure 6B shows the same metal chelating agent as in Figure 6A, except that the linker or peptide portion that forms a covalent bond with the metal chelating agent is indicated by the dashed circle. [ka] Excluding the points shown inside. [Figure 7A] Figure 7A shows an exemplary metal chelating agent of the present disclosure, in which, [ka] This represents the binding site of the metal chelating agent to the remaining conjugate. [Figure 7B] Figure 7B shows the same metal chelating agent as in Figure 7A, except that the linker or peptide portion that forms a covalent bond with the metal chelating agent is indicated by the dashed circle. [ka] Excluding the points shown inside. [Figure 8] Figure 8 shows the structure of a typical metal chelating agent. [Figure 9] Figure 9 shows the structure of a typical metal chelating agent. [Figure 10-1] Figure 10 shows the structure of a typical metal chelating agent. [Figure 10-2] Figure 10 shows the structure of a typical metal chelating agent. [Figure 11-1] Figure 11 shows the structure of a typical metal chelating agent. [Figure 11-2] Figure 11 shows the structure of a typical metal chelating agent. [Figure 12-1] Figure 12 shows the structure of a typical metal chelating agent. [Figure 12-2] Figure 12 shows the structure of a typical metal chelating agent. [Figure 13] Figure 13 shows the structure of a typical metal chelating agent. [Figure 14-1] Figure 14 shows the structure of a typical metal chelating agent. [Figure 14-2] Figure 14 shows the structure of a typical metal chelating agent. [Figure 15] Figure 15 shows the structure of a typical metal chelating agent. [Figure 16-1] Figure 16 shows the structure of a typical metal chelating agent. [Figure 16-2] Figure 16 shows the structure of a typical metal chelating agent. [Figure 17] Figure 17 shows the structure of a typical metal chelating agent. [Figure 18] Figure 18 shows the structure of a typical metal chelating agent. [Figure 19] Figure 19 shows the structure of a typical metal chelating agent. [Figure 20] Figure 20 shows the structure of a typical metal chelating agent. [Figure 21] Figure 21 shows the structure of a typical metal chelating agent. [Figure 22] Figure 22 shows the structure of a typical metal chelating agent. [Figure 23] Figure 23A shows a flowchart of SK-Hep1 cells, in which GPC3 is not expressed on the cell surface, and stained with the biotinylated GPC3-binding peptide (PLD-45) of the present invention or a negative control, followed by a Streptavidin, R-Phycoerythrin conjugate. Figure 23B shows a flowchart of Huh-7 cells, in which GPC3 is expressed on the cell surface, and stained with the biotinylated GPC3-binding peptide (PLD-45) of the present invention or a negative control, followed by a Streptavidin, R-Phycoerythrin conjugate. Figure 23C shows a flowchart of HepG2 cells, in which GPC3 is expressed on the cell surface, and stained with the biotinylated GPC3-binding peptide (PLD-45) of the present invention or a negative control, followed by a Streptavidin, R-Phycoerythrin conjugate. [Figure 24] Figure 24A shows a flowchart of SK-Hep1 cells, in which GPC3 is not expressed on the cell surface, and stained with the biotinylated GPC3-binding peptide (PLD-30) of the present invention or a negative control, followed by a Streptavidin, R-Phycoerythrin conjugate. Figure 24B shows a flowchart of Huh-7 cells, in which GPC3 is expressed on the cell surface, and stained with the biotinylated GPC3-binding peptide (PLD-30) of the present invention or a negative control, followed by a Streptavidin, R-Phycoerythrin conjugate. Figure 24C shows a flowchart of HepG2 cells, in which GPC3 is expressed on the cell surface, and stained with the biotinylated GPC3-binding peptide (PLD-30) of the present invention or a negative control, followed by a Streptavidin, R-Phycoerythrin conjugate. [Figure 25] Figure 25A shows a flowchart of SK-Hep1 cells, in which GPC3 is not expressed on the cell surface, and stained with the biotinylated GPC3-binding peptide (PLD-1) of the present invention or a negative control, followed by a Streptavidin, R-Phycoerythrin conjugate. Figure 25B shows a flowchart of Huh-7 cells, in which GPC3 is expressed on the cell surface, and stained with the biotinylated GPC3-binding peptide (PLD-1) of the present invention or a negative control, followed by a Streptavidin, R-Phycoerythrin conjugate. Figure 25C shows a flowchart of HepG2 cells, in which GPC3 is expressed on the cell surface, and stained with the biotinylated GPC3-binding peptide (PLD-1) of the present invention or a negative control, followed by a Streptavidin, R-Phycoerythrin conjugate. [Figure 26]Figure 26A shows a flowchart of SK-Hep1 cells, in which GPC3 is not expressed on the cell surface, and stained with the biotinylated GPC3-binding peptide (Mod-3) of the present invention or a negative control, followed by a Streptavidin, R-Phycoerythrin conjugate. Figure 26B shows a flowchart of Huh-7 cells, in which GPC3 is expressed on the cell surface, and stained with the biotinylated GPC3-binding peptide (Mod-3) of the present invention or a negative control, followed by a Streptavidin, R-Phycoerythrin conjugate. Figure 26C shows a flowchart of HepG2 cells, in which GPC3 is expressed on the cell surface, and stained with the biotinylated GPC3-binding peptide (Mod-3) of the present invention or a negative control, followed by a Streptavidin, R-Phycoerythrin conjugate. [Figure 27] Figure 27A shows a flowchart of SK-Hep1 cells, in which GPC3 is not expressed on the cell surface, and stained with the biotinylated GPC3-binding peptide (Mod-5) of the present invention or a negative control, followed by a Streptavidin, R-Phycoerythrin conjugate. Figure 27B shows a flowchart of Huh-7 cells, in which GPC3 is expressed on the cell surface, and stained with the biotinylated GPC3-binding peptide (Mod-5) of the present invention or a negative control, followed by a Streptavidin, R-Phycoerythrin conjugate. Figure 27C shows a flowchart of HepG2 cells, in which GPC3 is expressed on the cell surface, and stained with the biotinylated GPC3-binding peptide (Mod-5) of the present invention or a negative control, followed by a Streptavidin, R-Phycoerythrin conjugate. [Figure 28]Figure 28A shows a flowchart of SK-Hep1 cells, in which GPC3 is not expressed on the cell surface, and stained with the biotinylated GPC3-binding peptide (Mod-6) of the present invention or a negative control, followed by a Streptavidin, R-Phycoerythrin conjugate. Figure 28B shows a flowchart of Huh-7 cells, in which GPC3 is expressed on the cell surface, and stained with the biotinylated GPC3-binding peptide (Mod-6) of the present invention or a negative control, followed by a Streptavidin, R-Phycoerythrin conjugate. Figure 28C shows a flowchart of HepG2 cells, in which GPC3 is expressed on the cell surface, and stained with the biotinylated GPC3-binding peptide (Mod-6) of the present invention or a negative control, followed by a Streptavidin, R-Phycoerythrin conjugate. [Figure 29] Figure 29A shows a flowchart of SK-Hep1 cells, in which GPC3 is not expressed on the cell surface, and stained with the biotinylated GPC3-binding peptide (Mod-7) of the present invention or a negative control, followed by a Streptavidin, R-Phycoerythrin conjugate. Figure 29B shows a flowchart of Huh-7 cells, in which GPC3 is expressed on the cell surface, and stained with the biotinylated GPC3-binding peptide (Mod-7) of the present invention or a negative control, followed by a Streptavidin, R-Phycoerythrin conjugate. Figure 29C shows a flowchart of HepG2 cells, in which GPC3 is expressed on the cell surface, and stained with the biotinylated GPC3-binding peptide (Mod-7) of the present invention or a negative control, followed by a Streptavidin, R-Phycoerythrin conjugate. [Modes for carrying out the invention]

[0033] It should be understood that the following general and detailed descriptions are merely illustrative and descriptive and do not limit the technology of this application. Those skilled in the art will recognize that numerous variations and modifications of this disclosure exist and are included within its scope.

[0034] Various features of this disclosure can be described in the context of a single embodiment, but they can also be provided separately or in any preferred combination. Conversely, this disclosure can be described herein in the context of separate embodiments for clarity, but it can also be carried out in a single embodiment.

[0035] The headings used in this specification are for organizational purposes only and should not be construed as limiting the subjects described.

[0036] In this specification, the use of the singular form includes the plural form unless otherwise specified. In this specification, the use of "or" means "and / or" unless otherwise specified. Furthermore, terms such as "element" or "component" include both elements and components containing one unit, as well as elements and components containing two or more subunits, unless otherwise specified.

[0037] Numerical ranges indicated by endpoints in this specification are intended to include all numerical values ​​contained within that range (for example, the range 1 to 5 includes 1, 1.5, 2, 2.75, 3, 3.80, 4, 4.32, and 5).

[0038] All terms are intended to be understood as they are understood by those skilled in the art. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as they are generally understood by those skilled in the art to which this disclosure belongs.

[0039] The following definitions are supplementary to those skilled in the art, directed toward this application, and should not be attributed to any related or unrelated cases, such as any generally owned patent or patent application. Any methods and materials similar to or equivalent to those described herein may be used in the practice for testing of this disclosure, but preferred materials and methods are described herein. Accordingly, the terms used herein are for illustrative purposes only and are not intended to limit any particular embodiment.

[0040] I. Definition Where used herein and in the appended claims, the singular forms “a,” “an,” and “the” include multiple references unless otherwise explicitly stated herein. Thus, for example, a reference to “an agent” includes multiple such agents, and a reference to “the cell” includes a reference to one or more cells (or more cells) and their equivalents known to those skilled in the art. Where ranges relating to physical properties such as molecular weight or chemical properties such as chemical formulas are used herein, it is intended that all combinations and subcombinations of the range, as well as specific embodiments therein, are included.

[0041] The terms “about” or “approximately” mean within an acceptable margin of error for a particular value as determined by those skilled in the art, and depend in part on how that value is measured or determined, i.e., the limits of the measuring system. For example, “about” may mean within one or more standard deviations per practice in the art. Alternatively, “about” may mean within 20%, 15%, 10%, 5%, or 1% of a given value. Or, particularly with respect to biological systems or processes, the term may mean within one order of magnitude of a value, within five times, or within two times.

[0042] As used herein, the term “conjugate” is used interchangeably with “radiopharmaceutical conjugate.” Conjugates described herein may contain radionuclides. In some embodiments, conjugates described herein do not contain radionuclides.

[0043] As used herein, the term “radiopharmaceutical” refers to a conjugate containing a radionuclide. In some embodiments, the radionuclide is covalently bound to the conjugate. In some embodiments, the radionuclide is bound to the conjugate via a metal chelating agent.

[0044] The term “comprising” (and related terms such as “comprise,” “comprises,” “having,” or “including”) should be interpreted in an open, inclusive sense, i.e., “including, but not limited to.” The term “comprising” (and related terms such as “comprise,” “comprises,” “having,” or “including”) is not intended to exclude, in other particular embodiments, embodiments such as any composition, composition, method, or process of any substance described herein, from “consist of” or “consist essentially of” the described features.

[0045] "Amino" refers to the -NH2 radical.

[0046] "Cyano" refers to the -CN radical.

[0047] "Nitro" refers to the -NO2 radical.

[0048] "Oxo" refers to the =O radical.

[0049] "Imino" refers to the NH radical.

[0050] "Oxymo" refers to the =N-OH radical.

[0051] "Hydrazino" refers to the =N-NH2 radical.

[0052] "Hydroxy" or "hydroxyl" refers to the -OH radical.

[0053] "Hydroxyamino" refers to the -NH-OH radical.

[0054] "Acyl" refers to substituted or unsubstituted alkylcarbonyls, substituted or unsubstituted alkenylcarbonyls, substituted or unsubstituted alkynylcarbonyls, substituted or unsubstituted cycloalkylcarbonyls, substituted or unsubstituted heterocycloalkylcarbonyls, substituted or unsubstituted arylcarbonyls, substituted or unsubstituted heteroarylcarbonyls, amides, or esters, where the carbonyl atom of the carbonyl group is a bond site. Unless otherwise specifically described herein, alkylcarbonyl groups, alkenylcarbonyl groups, alkynylcarbonyl groups, cycloalkylcarbonyl groups, amide groups, or ester groups may be appropriately substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc.

[0055] "Alkyl" refers to a linear or branched saturated hydrocarbon monoradical, which may be substituted as appropriate. An alkyl group may have 1 to about 20 carbon atoms, 1 to about 10 carbon atoms, or 1 to 6 carbon atoms. Examples include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, 2-methyl-1-propyl, 2-methyl-2-propyl, 2-methyl-1-butyl, 3-methyl-1-butyl, 2-methyl-3-butyl, 2,2-dimethyl-1-propyl, 2-methyl-1-pentyl, 3-methyl-1-pentyl, 4-methyl-1-pentyl, 2-methyl-2-pentyl, 3-methyl-2-pentyl, 4-methyl-2-pentyl, 2,2-dimethyl-1-butyl, 3,3-dimethyl-1-butyl, 2-ethyl-1-butyl, n-butyl, isobutyl, sec-butyl, t-butyl, n-pentyl, isopentyl, neopentyl, tert-amyl, and hexyl, as well as longer alkyl groups such as heptyl and octyl. Numerical ranges such as "C1-C6 alkyl" mean, whenever they appear herein, that alkyl group consists of one, two, three, four, five, or six carbon atoms; however, this definition also includes appearances of the term "alkyl" without specifying a numerical range. In some embodiments, alkyl is C1-C 10 The alkyl group is an alkyl, C1-C9 alkyl, C1-C8 alkyl, C1-C7 alkyl, C1-C6 alkyl, C1-C5 alkyl, C1-C4 alkyl, C1-C3 alkyl, C1-C2 alkyl, or C1 alkyl. Unless otherwise specifically described herein, the alkyl group may be appropriately substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc. In some embodiments, the alkyl group may be appropriately substituted with oxo, halogen, -CN, -CF3, -OH, -OMe, -NH2, -NO2, or -C≡CH. In some embodiments, the alkyl group may be appropriately substituted with oxo, halogen, -CN, -CF3, -OH, or -OMe. In some embodiments, the alkyl group may be appropriately substituted with halogen.

[0056] "Alkylene" refers to a linear or branched divalent hydrocarbon chain. Unless otherwise specifically described herein, alkylene groups may be appropriately substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc. In some embodiments, alkylene may be appropriately substituted with oxo, halogen, -CN, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, alkylene may be appropriately substituted with oxo, halogen, -CN, -CF3, -OH, or -OMe. In some embodiments, alkylene may be appropriately substituted with halogen. In some embodiments, alkylene is -CH2-, -CH2CH2-, -CH2CH2CH2-, or -CH2CH(CH3)CH2-. In some embodiments, alkylene is -CH2-. In some embodiments, alkylene is -CH2CH2-. In some embodiments, the alkylene is -CH2CH2CH2-.

[0057] An "alkenyl" refers to a linear or branched hydrocarbon monoradical having one or more carbon-carbon double bonds, which may be optionally substituted. In some embodiments, the alkenyl group has 2 to about 10 carbon atoms, or 2 to about 6 carbon atoms. The group may be in either a cis or trans configuration with respect to the double bonds, and should be understood to include both isomers. Examples, but not limited to, include ethenyl (-CH=CH2), 1-propenyl (-CH2CH=CH2), isopropenyl [-C(CH3)=CH2], butenyl, and 1,3-butadienyl. Numerical ranges such as "C2-C6 alkenyl" mean that whenever they appear herein, the alkenyl group may have 2, 3, 4, 5, or 6 carbon atoms, but this definition also includes appearances of the term "alkenyl" without a specified numerical range. In some embodiments, the alkenyl is C2-C 10The alkenyl is an alkenyl, C2-C9 alkenyl, C2-C8 alkenyl, C2-C7 alkenyl, C2-C6 alkenyl, C2-C5 alkenyl, C2-C4 alkenyl, C2-C3 alkenyl, or C2 alkenyl. Unless otherwise specifically described herein, the alkenyl group may be appropriately substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc. In some embodiments, the alkenyl may be appropriately substituted with oxo, halogen, -CN, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, the alkenyl may be appropriately substituted with oxo, halogen, -CN, -CF3, -OH, or -OMe. In some embodiments, the alkenyl may be appropriately substituted with halogen.

[0058] The term "alkenylene" or "alkenylene chain" refers to a linear or branched divalent hydrocarbon chain, which may be substituted as appropriate, having at least one carbon-carbon double bond that links the rest of the molecule to a radical group. In some embodiments, the alkenylene is -CH=CH-, -CH2CH=CH-, or -CH=CHCH2-. In some embodiments, the alkenylene is -CH=CH-. In some embodiments, the alkenylene is -CH2CH=CH-. In some embodiments, the alkenylene is -CH=CHCH2-.

[0059] "Alkynyl" refers to a linear or branched hydrocarbon monoradical having one or more carbon-carbon triple bonds, which may be optionally substituted. In some embodiments, the alkynyl group has 2 to about 10 carbon atoms, more preferably 2 to about 6 carbon atoms. Examples, but not limited to, include ethynyl, 2-propynyl, 2-butynyl, and 1,3-butadiinyl. Numerical ranges such as "C2-C6 alkynyl" mean that whenever it appears herein, the alkynyl group may have 2, 3, 4, 5, or 6 carbon atoms, but this definition also includes instances of the term "alkynyl" without a specified numerical range. In some embodiments, the alkynyl is C2-C 10 The alkynyl group is an alkynyl, C2-C9 alkynyl, C2-C8 alkynyl, C2-C7 alkynyl, C2-C6 alkynyl, C2-C5 alkynyl, C2-C4 alkynyl, C2-C3 alkynyl, or C2 alkynyl. Unless otherwise specifically described herein, the alkynyl group may be appropriately substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc. In some embodiments, the alkynyl may be appropriately substituted with oxo, halogen, -CN, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, the alkynyl may be appropriately substituted with oxo, halogen, -CN, -CF3, -OH, or -OMe. In some embodiments, the alkynyl may be appropriately substituted with halogen. The term "alkynylene" refers to a linear or branched divalent hydrocarbon having one or more carbon-carbon triple bonds, which may be substituted as appropriate.

[0060] "Alkylamino" refers to the formula -N(R a )2(wherein, R a is either a defined alkyl radical or two R aThis refers to a radical (which may, together with a nitrogen atom, form a substituted or unsubstituted C2-C7 heterocycloalkyl ring). Unless otherwise specifically described herein, the alkylamino group may be appropriately substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc. In some embodiments, the alkylamino may be appropriately substituted with oxo, halogen, -CN, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, the alkylamino may be appropriately substituted with oxo, halogen, -CN, -CF3, -OH, or -OMe. In some embodiments, the alkylamino may be appropriately substituted with halogen.

[0061] "Alkoxy" refers to the formula -OR a (In the formula, R a α refers to a radical (which is a defined alkyl radical). Unless otherwise specifically described herein, the alkoxy group may be appropriately substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc. In some embodiments, the alkoxy may be appropriately substituted with oxo, halogen, -CN, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, the alkoxy may be appropriately substituted with oxo, halogen, -CN, -CF3, -OH, or -OMe. In some embodiments, the alkoxy may be appropriately substituted with halogen.

[0062] "Aminoalkyl" refers to the alkyl radical defined above, which is substituted with one or more amines. In some embodiments, the alkyl is substituted with one amine. In some embodiments, the alkyl is substituted with one, two, or three amines. Hydroxyalkyls include, for example, aminomethyl, aminoethyl, aminopropyl, aminobutyl, or aminopentyl. In some embodiments, the hydroxyalkyl is aminomethyl.

[0063] The term "aryl" refers to a radical containing at least one aromatic ring, where each atom forming the ring is a carbon atom. The aryl group may be substituted as appropriate. Examples of aryl groups include, but are not limited to, phenyl and naphthyl. In some embodiments, the aryl is phenyl. Depending on the structure, the aryl group may be a monoradical or a diradical (i.e., an arylene group). Unless otherwise specifically stated herein, the term "aryl" or the prefix "ar-" (as in "aralkyl") means that it includes aryl radicals, which may be substituted as appropriate. In some embodiments, the aryl group includes a partially reduced cycloalkyl group as defined herein (e.g., 1,2-dihydronaphthalene). In some embodiments, the aryl group includes a fully reduced cycloalkyl group as defined herein (e.g., 1,2,3,4-tetrahydronaphthalene). When the aryl includes a cycloalkyl group, the aryl is bonded to the rest of the molecule via the aromatic ring carbon atoms. The aryl radical may be a monocyclic or polycyclic (e.g., bicyclic, tricyclic, or tetracyclic) ring system, and may include condensed, spiro, or crosslinked ring systems. Unless otherwise specifically described herein, the aryl may be appropriately substituted with, for example, halogens, aminos, alkylaminos, aminoalkyls, nitriles, nitros, hydroxyls, alkyls, alkenyls, alkynyls, haloalkyls, heteroalkyls, alkoxys, aryls, cycloalkyls, heterocycloalkyls, heteroaryls, -S(O)2NH-C1-C6 alkyls, etc. In some embodiments, the aryl may be appropriately substituted with halogens, methyls, ethyls, -CN, -CF3, -OH, -OMe, -NH2, -NO2, -S(O)2NH2, -S(O)2NHCH3, -S(O)2NHCH2CH3, -S(O)2NHCH(CH3)2, -S(O)2N(CH3)2, or -S(O)2NHC(CH3)3. In some embodiments, the aryl group may be appropriately substituted with a halogen, methyl, ethyl, -CN, -CF3, -OH, or -OMe. In some embodiments, the aryl group may be appropriately substituted with a halogen.In some embodiments, the aryl is substituted with an alkyl, alkenyl, alkynyl, haloalkyl, or heteroalkyl group, where each alkyl, alkenyl, alkynyl, haloalkyl, or heteroalkyl group is independently unsubstituted or substituted with a halogen, methyl, ethyl, -CN, -CF3, -OH, -OMe, -NH2, or -NO2 group.

[0064] The term "cycloalkyl" refers to a monocyclic or polycyclic non-aromatic radical in which the ring-forming atoms (i.e., skeletal atoms) are each carbon atoms. In some embodiments, cycloalkyls are saturated or partially unsaturated. In some embodiments, cycloalkyls are spirocyclic compounds or crosslinked compounds. In some embodiments, cycloalkyls are condensed with an aromatic ring (in which case the cycloalkyl is bonded via non-aromatic ring carbon atoms). Cycloalkyl groups include groups having 3 to 10 ring atoms. Representative cycloalkyls, but not limited to, include cycloalkyls having 3 to 10 carbon atoms, 3 to 8 carbon atoms, 3 to 6 carbon atoms, or 3 to 5 carbon atoms. Examples of monocyclic cycloalkyl radicals include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. In some embodiments, the monocyclic cycloalkyl is cyclopentyl. In some embodiments, the monocyclic cycloalkyl is cyclopentenyl or cyclohexenyl. In some embodiments, the monocyclic cycloalkyl is cyclopentenyl. Examples of polycyclic radicals include adamantyl, 1,2-dihydronaphthalenyl, 1,4-dihydronaphthalenyl, tetrainyl, dekalinyl, 3,4-dihydronaphthalenyl-1(2H)-one, spiro[2.2]pentyl, norbornyl, and bicyclo[1.1.1]pentyl. Unless otherwise specifically described herein, cycloalkyl groups may be substituted as appropriate. Typical cycloalkyl groups include, but are not limited to, groups with 3 to 15 carbon atoms (e.g., C3-C 15 Totally saturated cycloalkyl or C3-C 15Cycloalkenyl), 3 to 10 carbon atoms (e.g., C3-C 10 Totally saturated cycloalkyl or C3-C 10Examples of cycloalkyls include cycloalkenyls, cycloalkyls having 3 to 8 carbon atoms (e.g., C3-C8 fully saturated cycloalkyl or C3-C8 cycloalkenyl), 3 to 6 carbon atoms (e.g., C3-C6 fully saturated cycloalkyl or C3-C6 cycloalkenyl), 3 to 5 carbon atoms (e.g., C3-C5 fully saturated cycloalkyl or C3-C5 cycloalkenyl), or cycloalkyls having 3 to 4 carbon atoms (e.g., C3-C4 fully saturated cycloalkyl or C3-C4 cycloalkenyl). In some embodiments, the cycloalkyl is a 3 to 6-membered cycloalkyl. In some embodiments, the cycloalkyl is a 5 to 6-membered cycloalkyl. Examples of monocyclic cycloalkyls include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Examples of polycyclic cycloalkyl or carbocyclic compounds include adamantyl, norbornyl, dekalinyl, bicyclo[3.3.0]octane, bicyclo[4.3.0]nonane, cis-decalin, trans-decalin, bicyclo[2.1.1]hexane, bicyclo[2.2.1]heptane, bicyclo[2.2.2]octane, bicyclo[3.2.2]nonane, and bicyclo[3.3.2]decane, and 7,7-dimethyl-bicyclo[2.2.1]heptanyl. Examples of partially saturated cycloalkyl compounds include cyclopentenyl, cyclohexenyl, cycloheptenyl, and cyclooctenyl. Unless otherwise specifically described herein, cycloalkyl compounds may be appropriately substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc. In some embodiments, the cycloalkyl group may be appropriately substituted with oxo, halogen, methyl, ethyl, -CN, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, the cycloalkyl group may be appropriately substituted with oxo, halogen, methyl, ethyl, -CN, -CF3, -OH, or -OMe. In some embodiments, the cycloalkyl group may be appropriately substituted with halogen.

[0065] "Halo" or "halogen" refers to bromo, chloro, fluoro, or iodine. In some embodiments, the halogen is fluoro or chloro. In some embodiments, the halogen is fluoro.

[0066] "Haloalkyl" refers to an alkyl radical as defined above, which is substituted with one or more halogens. In some embodiments, the alkyl is substituted with one, two, or three halogens. In some embodiments, the alkyl is substituted with one, two, three, four, five, or six halogens. Haloalkyls may include, for example, iodoalkyls, bromoalkyls, chloroalkyls, and fluoroalkyls. For example, "fluoroalkyl" refers to an alkyl radical as defined above, which is substituted with one or more fluoro radicals as defined above, such as trifluoromethyl, difluoromethyl, fluoromethyl, 2,2,2-trifluoroethyl, 1-fluoromethyl-2-fluoroethyl, etc. In some embodiments, the alkyl portion of the fluoroalkyl radical may be appropriately substituted as defined above for alkyl groups.

[0067] A "heteroalkyl" refers to an alkyl group in which one or more skeletal atoms of the alkyl group are atoms other than carbon, such as oxygen, nitrogen (e.g., -NH-, -N(alkyl)-), sulfur, or a combination thereof. In a heteroalkyl group, the carbon atoms of the heteroalkyl group are bonded to the rest of the molecule. In one embodiment, the heteroalkyl group is a C1-C6 heteroalkyl group in which the heteroalkyl group comprises 1 to 6 carbon atoms and one or more atoms other than carbon, such as oxygen, nitrogen (e.g., -NH-, -N(alkyl)-), sulfur, or a combination thereof, and the carbon atoms of the heteroalkyl group are bonded to the rest of the molecule. Examples of such heteroalkyl groups are, for example, -CH2-O-CH2-, -CH2-N(alkyl)-CH2-, -CH2-N(aryl)-CH2-, -OCH2CH2O-, -OCH2CH2OCH2CH2O-, or -OCH2CH2OCH2CH2OCH2CH2O-. Unless otherwise specifically described herein, heteroalkyls may be appropriately substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc. In some embodiments, heteroalkyls may be appropriately substituted with oxo, halogen, methyl, ethyl, -CN, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, heteroalkyls may be appropriately substituted with oxo, halogen, methyl, ethyl, -CN, -CF3, -OH, or -OMe. In some embodiments, heteroalkyls may be appropriately substituted with halogens.

[0068] As used herein, “heteroalkylene” refers to a divalent heteroalkyl group. Examples of such heteroalkylenes include, for example, -CH2-O-CH2-, -CH2-N(alkyl)-CH2-, -CH2-N(aryl)-CH2-, -OCH2CH2O-CH2CH2O-, or -OCH2CH2OCH2CH2OCH2CH2O-.

[0069] The term “heterocycloalkyl” refers to a cycloalkyl group comprising at least one heterocyclic atom, for example, a heteroatom selected from nitrogen, oxygen, and sulfur. Unless otherwise specifically described herein, heterocycloalkyl radicals may be monocyclic or bicyclic ring systems, including fused ring systems (when fused with an aryl or heteroaryl ring, the heterocycloalkyl is bonded via a non-aromatic ring atom) or bridging ring systems. The nitrogen, carbon, or sulfur atom in the heterocycloalkyl radical may be oxidized as appropriate. The nitrogen atom may be quaternized as appropriate. Heterocycloalkyl radicals are partially or completely saturated. Examples of heterocycloalkyl radicals, though not limited to them, include dioxolanil, thienyl[1,3]dithianil, tetrahydroquinolyl, tetrahydroisoquinolyl, decahydroquinolyl, decahydroisoquinolyl, imidazolinyl, imidazolidinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, piperidinyl, piperazinyl, 4-piperidonyl, pyrrolidinyl, pyrazolidinyl, quinuclidinyl, thiazolidinyl, tetrahydrofuryl, trithianil, tetrahydropyranil, thiomorpholinyl, thiamorpholinyl, 1-oxo-thiomorpholinyl, and 1,1-dioxo-thiomorpholinyl. Typical heterocycloalkyls are not limited to those with 2 to 15 carbon atoms (for example, C2-C2). 15 Totally saturated heterocycloalkyl or C2-C 15 Heterocycloalkenyl), 2 to 10 carbon atoms (e.g., C2-C 10 Totally saturated heterocycloalkyl or C2-C 10Examples of heterocycloalkyls include heterocycloalkenyls having 2 to 8 carbon atoms (e.g., C2-C8 fully saturated heterocycloalkyl or C2-C8 heterocycloalkenyl), 2 to 7 carbon atoms (e.g., C2-C7 fully saturated heterocycloalkyl or C2-C7 heterocycloalkenyl), 2 to 6 carbon atoms (e.g., C2-C6 fully saturated heterocycloalkyl or C2-C7 heterocycloalkenyl), 2 to 5 carbon atoms (e.g., C2-C5 fully saturated heterocycloalkyl or C2-C5 heterocycloalkenyl), or 2 to 4 carbon atoms (e.g., C2-C4 fully saturated heterocycloalkyl or C2-C4 heterocycloalkenyl). The term heterocycloalkyl also includes, but is not limited to, all cyclic carbohydrates, including monosaccharides, disaccharides, and oligosaccharides. Unless otherwise noted, heterocycloalkyls have 2 to 12 carbon atoms in the ring. In some embodiments, heterocycloalkyls have 2 to 10 carbon atoms in the ring. In some embodiments, the heterocycloalkyl has 2 to 10 carbon atoms and 1 or 2 nitrogen atoms in the ring. In some embodiments, the heterocycloalkyl has 2 to 10 carbon atoms and 3 or 4 nitrogen atoms in the ring. In some embodiments, the heterocycloalkyl has 2 to 12 carbon atoms, 0 to 2 nitrogen atoms, 0 to 2 oxygen atoms, 0 to 2 phosphorus atoms, and 0 to 1 sulfur atom in the ring. In some embodiments, the heterocycloalkyl has 2 to 12 carbon atoms, 1 to 3 nitrogen atoms, 0 to 1 oxygen atom, and 0 to 1 sulfur atom in the ring. When referring to the number of carbon atoms in a heterocycloalkyl, it should be understood that the number of carbon atoms in a heterocycloalkyl is not the same as the total number of atoms constituting the heterocycloalkyl (including heteroatoms) (i.e., the skeletal atoms of the heterocycloalkyl ring). Unless otherwise specifically described herein, heterocycloalkyls may be appropriately substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc.In some embodiments, the heterocycloalkyl group may be appropriately substituted with oxo, halogen, methyl, ethyl, -CN, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, the heterocycloalkyl group may be appropriately substituted with oxo, halogen, methyl, ethyl, -CN, -CF3, -OH, or -OMe. In some embodiments, the heterocycloalkyl group may be appropriately substituted with halogen.

[0070] A "heteroaryl" refers to a cyclic radical comprising a carbon atom and one or more cyclic heteroatoms selected from the group consisting of nitrogen, oxygen, phosphorus, and sulfur, as well as at least one aromatic ring. In some embodiments, heteroaryls are monocyclic, bicyclic, or polycyclic. Exemplary examples of monocyclic heteroaryls include pyridinyl, imidazolyl, pyrimidinyl, pyrazolyl, triazolyl, pyrazinyl, tetrazolyl, furyl, thienyl, isoxazolyl, thiazolyl, oxazolyl, isothiazolyl, pyrrolyl, pyridazinyl, triazinyl, oxadiazolyl, thiadiazolyl, flazanyl, indidine, indole, benzofuran, benzothiophene, indazole, benzimidazole, purine, quinolidine, quinoline, isoquinoline, cinnoline, phthalazine, quinazoline, quinoxaline, 1,8-naphthyridine, and pteridine. Exemplary examples of monocyclic heteroaryls include pyridinyl, imidazolyl, pyrimidinyl, pyrazolyl, triazolyl, pyrazinyl, tetrazolyl, furyl, thienyl, isoxazolyl, thiazolyl, oxazolyl, isothiazolyl, pyrrolyl, pyridazinyl, triazinyl, oxadiazolyl, thiadiazolyl, and flazanil. Exemplary examples of bicyclic heteroaryls include indidine, indole, benzofuran, benzothiophene, indazole, benzimidazole, purine, quinolidine, quinoline, isoquinoline, cinnoline, phthalazine, quinazoline, quinoxaline, 1,8-naphthyridine, and pteridine. In some embodiments, the heteroaryl is pyridinyl, pyrazinyl, pyrimidinyl, thiazolyl, thienyl, thiadiazolyl, or furyl. In some embodiments, the heteroaryl contains 0 to 6 nitrogen atoms in the ring. In some embodiments, the heteroaryl ring contains 1 to 4 N atoms. In some embodiments, the heteroaryl ring contains 4 to 6 N atoms. In some embodiments, the heteroaryl ring contains 0 to 4 N atoms, 0 to 1 O atom, 0 to 1 P atom, and 0 to 1 S atom. In some embodiments, the heteroaryl ring contains 1 to 4 N atoms, 0 to 1 O atom, and 0 to 1 S atom.In some embodiments, the heteroaryl is a C1-C9 heteroaryl. In some embodiments, the monocyclic heteroaryl is a C1-C5 heteroaryl. In some embodiments, the monocyclic heteroaryl is a 5-membered or 6-membered heteroaryl. In some embodiments, the bicyclic heteroaryl is a C6-C9 heteroaryl. In some embodiments, the heteroaryl group comprises a partially reduced cycloalkyl or heterocycloalkyl group as defined herein (e.g., 7,8-dihydroquinoline). In some embodiments, the heteroaryl group comprises a fully reduced cycloalkyl or heterocycloalkyl group as defined herein (e.g., 5,6,7,8-tetrahydroquinoline). When the heteroaryl comprises a cycloalkyl or heterocycloalkyl group, the heteroaryl is bonded to the rest of the molecule via a heteroaromatic ring carbon or heteroatom. The heteroaryl radical may be a monocyclic or polycyclic (e.g., bicyclic, tricyclic, or tetracyclic) ring system and may include condensed, spiro, or bridging ring systems. Unless otherwise specifically described herein, heteroaryls may be appropriately substituted with, for example, halogens, aminos, nitriles, nitros, hydroxyls, alkyls, alkenyls, alkynyls, haloalkyls, alkoxys, aryls, cycloalkyls, heterocycloalkyls, heteroaryls, etc. In some embodiments, heteroaryls may be appropriately substituted with halogens, methyls, ethyls, -CN, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, heteroaryls may be appropriately substituted with halogens, methyls, ethyls, -CN, -CF3, -OH, or -OMe. In some embodiments, heteroaryls may be appropriately substituted with halogens.

[0071] The term "part" refers to a specific segment or functional group of a molecule. A chemical part is a well-recognized chemical entity that is embedded in or attached to a molecule.

[0072] As used herein, the terms “treat,” “prevent,” “improve,” and “inhibit,” and words derived therefrom, do not necessarily imply 100% or complete treatment, prevention, improvement, or inhibition. Rather, there are varying degrees of treatment, prevention, improvement, and inhibition that a person skilled in the art would recognize as having a potential benefit or therapeutic effect. In this regard, the methods disclosed may provide any amount of treatment, prevention, improvement, or inhibition of any level of disorder in mammals. For example, a disorder, including its symptoms or condition, may be reduced by, for example, about 100%, about 90%, about 80%, about 70%, about 60%, about 50%, about 40%, about 30%, about 20%, or about 10%. Furthermore, the treatment, prevention, improvement, or inhibition provided by the methods disclosed herein may include the treatment, prevention, improvement, or inhibition of one or more conditions or symptoms of a disorder, such as cancer or an inflammatory disease.

[0073] In certain embodiments, “to treat” includes the concept of “to mitigate,” which means reducing the frequency or severity of the occurrence or recurrence of any symptoms or other pathological effects associated with a disorder and / or related side effects. In certain embodiments, the term “to treat” also includes the concept of “to manage,” which means reducing the severity of a particular disease or disorder in a patient or delaying its recurrence, for example, by lengthening the period of remission in a patient who has suffered from the disease.

[0074] In certain embodiments, the terms “prevent” or “prevent” in relation to a disease or disorder may refer to a compound that reduces the incidence of a disorder or condition in a treated sample compared to an untreated control sample, or delays the onset of one or more symptoms of a disorder or condition, or reduces their severity, compared to an untreated control sample.

[0075] As used herein, the term “therapeutic dose” refers to the amount effective in terms of the dosage and duration required to achieve the desired therapeutic outcome. The therapeutic dose of a composition may vary depending on factors such as the individual’s condition, age, sex, and weight, as well as the ability of the protein to elicit the desired response in the individual. The therapeutic dose may also exceed any toxic or adverse effects of the composition that have a beneficial therapeutic effect.

[0076] The terms "optional" or "optionally" mean that the events or situations described thereafter may or may not occur, and that the description includes examples of when such events or situations occur and examples of when they do not. For example, "optionally substituted alkyl" means either "alkyl" or "substituted alkyl" as defined above. Furthermore, the optionally substituted group may be unsubstituted (e.g., -CH2CH3), totally substituted (e.g., -CF2CF3), monosubstituted (e.g., -CH2CH2F), or substituted at any level between totally and monosubstituted (e.g., -CH2CHF2, -CH2CF3, -CF2CH3, -CFHCHF2, etc.).

[0077] As used herein, the term “substituent” means an atomic position variable of a core molecule that replaces one or more hydrogen atoms on a specified atom, provided that the substitution does not exceed the normal valence of the specified atom and the substitution results in a stable compound. A combination of substituents and / or variables is permitted only if such a combination results in a stable compound. Those skilled in the art should note that any carbon and heteroatoms having valences that are not considered to be satisfied as described or shown herein are assumed to have a sufficient number of hydrogen atoms to satisfy the described or shown valence. In certain specific examples, one or more substituents having double bonds as bonding sites (e.g., “oxo” or “=O”) may be described, shown or enumerated herein within substituents, and the structure may show only single bonds as bonding sites to the core structure. Those skilled in the art will understand that while only single bonds are shown, double bonds are intended for these substituents.

[0078] For the purposes of this disclosure, one event of an amino acid or amino acid sequence "substitution" is not considered to be two separate events: one deletion and one addition. Thus, to avoid doubt, for example, sequence changes of "up to two deletions, substitutions and / or additions" include one deletion and one substitution, one deletion and one addition (at different locations), one substitution and one addition, one deletion only, one substitution only, one addition only, two deletions, two substitutions, two additions, and so on. The location of the deletion, addition, or substitution may be at one or both ends of the peptide, or in the middle of the peptide.

[0079] The terms “may be substituted” or “substituted” mean that the referenced group may be substituted with one or more additional groups as appropriate. For example, “may be substituted” or “substituted” may mean that the referenced group may be substituted with one or more substituents individually and independently selected from D, halogen, -CN, -NH2, -NH(alkyl), -N(alkyl)2, -OH, -CO2H, -CO2alkyl, -C(=O)NH2, -C(=O)NH(alkyl), -C(=O)N(alkyl)2, -S(=O)2NH2, -S(=O)2NH(alkyl), -S(=O)2N(alkyl)2, alkyl, cycloalkyl, fluoroalkyl, heteroalkyl, alkoxy, fluoroalkoxy, heterocycloalkyl, aryl, heteroaryl, aryloxy, alkylthio, arylthio, alkylsulfoxide, arylsulfoxide, alkylsulfone, and arylsulfone. In some other embodiments, appropriate substituents are independently selected from D, halogen, -CN, -NH2, -NH(CH3), -N(CH3)2, -OH, -CO2H, -CO2(C1-C4 alkyl), -C(=O)NH2, -C(=O)NH(C1-C4 alkyl), -C(=O)N(C1-C4 alkyl)2, -S(=O)2NH2, -S(=O)2NH(C1-C4 alkyl), -S(=O)2N(C1-C4 alkyl)2, C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 fluoroalkyl, C1-C4 heteroalkyl, C1-C4 alkoxy, C1-C4 fluoroalkoxy, -SC1-C4 alkyl, -S(=O)C1-C4 alkyl, and -S(=O)2C1-C4 alkyl.In some embodiments, the group that "may be substituted as appropriate" is halogen, -CN, oxo, -OH, -SF5, -SH, -S(=O)C1-C3alkyl, -S(=O)2C1-C3alkyl, -S(=O)2NH2, -S(=O)2NHC1-C3alkyl, -S(=O)2N(C1-C3alkyl)2, -S(=O)(=NC1-C3alkyl)(C1-C3alkyl), -NH2, -NHC1-C3alkyl, -N(C1-C3alkyl)2, -N=S(=O)(C1-C3alkyl)2, -C(=O)C1-C3alkyl, -C They are independently substituted with 1 to 6 substituents selected from (=O)OH, -C(=O)OC1-C3alkyl, -C(=O)NH2, -C(=O)NHC1-C3alkyl, -C(=O)N(C1-C3alkyl)2, -P(=O)(C1-C3alkyl)2, C1-C6alkyl, C1-C6alkoxy, C1-C6haloalkyl, C1-C6haloalkoxy, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, aryl, heteroaryl, heterocycloalkyl, and cycloalkyl. In some embodiments, the group that "may be substituted as appropriate" is halogen, -CN, oxo, -OH, -SF5, -SH, -S(=O)C1-C3alkyl, -S(=O)2C1-C3alkyl, -S(=O)2NH2, -S(=O)2NHC1-C3alkyl, -S(=O)2N(C1-C3alkyl)2, -S(=O)(=NC1-C3alkyl)(C1-C3alkyl), -NH2, -NHC1-C3alkyl, -N(C1-C3alkyl)2, -N=S(=O)(C1-C3alkyl)2, -C(=O)C1-C3alkyl They are independently substituted with 1 to 6 substituents selected from -C(=O)OH, -C(=O)OC1-C3alkyl, -C(=O)NH2, -C(=O)NHC1-C3alkyl, -C(=O)N(C1-C3alkyl)2, -P(=O)(C1-C3alkyl)2, C1-C3alkyl, C1-C3alkoxy, C1-C3haloalkyl, C1-C3haloalkoxy, C1-C3hydroxyalkyl, C1-C3aminoalkyl, C1-C3heteroalkyl, 5-6 membered heterocycloalkyl, and C3-C6cycloalkyl.In some embodiments, the "may be substituted as appropriate" group is independently substituted with 1 to 6 substituents selected from halogen, oxo, -OH, -NH2, -NHC1-C3 alkyl, -N(C1-C3 alkyl)2, -C(=O)OH, -C(=O)NH2, C1-C3 alkyl, C1-C3 alkoxy, C1-C3 haloalkyl, C1-C3 haloalkoxy, C1-C3 hydroxyalkyl, C1-C3 aminoalkyl, C1-C3 heteroalkyl, and C3-C6 cycloalkyl. In some embodiments, the appropriate substituent is independently selected from D, halogen, -CN, -NH2, -OH, -NH(CH3), -N(CH3)2, -NH(cyclopropyl), -CH3, -CH2CH3, -CF3, -OCH3, and -OCF3. In some embodiments, the substituted group is substituted with one or two of the aforementioned groups. In some embodiments, appropriate substituents (acyclic or cyclic) on the aliphatic carbon atom include oxo (=O). When indicating the number of substituents, the term “one or more” means from one substituent to the maximum possible number of substituents, i.e., from the substitution of one hydrogen to the substitution of all hydrogens by substituents. In some embodiments, groups that “may be substituted as appropriate” are unsubstituted. In some embodiments, groups that “may be substituted as appropriate” are independently substituted with 1 to 6 substituents. In some embodiments, groups that “may be substituted as appropriate” are independently substituted with 1 to 3 substituents. In some embodiments, groups that “may be substituted as appropriate” are independently substituted with 1 to 2 substituents.

[0080] The term "unsubstituted" means that a particular group does not support a substituent.

[0081] Certain compounds described herein may exist in tautomeric forms, and all such tautomeric compounds are within the scope of this disclosure.

[0082] Unless otherwise stated, the structures described herein also mean the structures of all stereochemical forms, i.e., R and S configurations for each chiral center. Thus, single stereoisomers of the compound, as well as mixtures of enantiomers and diastereomers, are within the scope of this disclosure.

[0083] As used herein, the term "peptide" refers to a compound comprising two or more amino acids. Peptides described herein may contain one or more non-natural amino acids. The term "peptide" also encompasses peptidomimetics. In this disclosure, the term "amino acid" is used in its broadest sense, encompassing not only natural amino acids but also their derivatives and synthetic amino acids. For example, the term "amino acid" includes non-natural amino acids.

[0084] As used herein, the term "peptoid" refers to N-substituted glycine. Peptoids may be substituted as appropriate. Peptoids may also include further substitutions at the α-carbon as appropriate.

[0085] As used herein, the term “non-natural amino acids” refers to amino acids other than the 20 standard amino acids. The 20 standard amino acids are alanine (ala or A), arginine (arg or R), asparagine (asn or N), aspartic acid (asp or D), cysteine ​​(cys or C), glutamine (gln or Q), glutamic acid (glu or E), glycine (gly or G), histidine (his or H), isoleucine (ile or I), leucine (leu or L), lysine (lys or K), methionine (met or M), phenylalanine (phe or F), proline (pro or P), serine (ser or S), threonine (thr or T), tryptophan (trp or W), tyrosine (tyr or Y), and valine (val or V).

[0086] As used herein, the term "protein" refers to a polypeptide (i.e., a sequence of at least three amino acids linked together by peptide bonds). Proteins may also contain non-amino acid moieties (e.g., glycoproteins, proteoglycans, etc.) and / or may otherwise be processed or modified. Proteins may be complete polypeptides (with or without signal sequences) that are produced by and / or active in cells. In some embodiments, a protein is or contains a characteristic moiety, such as a polypeptide, that is produced by and / or active in cells. Proteins may contain two or more polypeptide chains. For example, polypeptide chains may be linked by one or more disulfide bonds or by other means.

[0087] The terms “peptidomimetic” or “mimetic” refer to bioactive compounds that mimic the bioactivity of peptides or proteins but are not peptides as a whole in terms of their chemical properties, for example, they may contain non-peptide bonds (bonds other than amide bonds between amino acids). As used herein, the term peptidomimetic is used in a broader sense and includes molecules that are not entirely peptides in nature, such as pseudopeptides, semipeptides, and peptoids. Whether completely non-peptide or partially non-peptide, the peptidomimetic described herein can provide a spatial arrangement of a reactive chemical moiety that is very similar to the three-dimensional arrangement of the active groups in the target amino acid sequence or target molecule on which the peptidomimetic is based. As a result of this similar arrangement of active sites, the peptidomimetic may have effects on biological systems similar to the bioactivity of the target entity.

[0088] In some embodiments, the peptimimeti is substantially similar to the target amino acid sequence or target molecule on which the peptimimeti is based, both in terms of three-dimensional shape and bioactivity. An example is described in the paper “Tritiated D-ala1-Peptide T Binding”, Smith CS et al., Drug Development Res., 15, pp. 371-379 (1988). A second method is to modify the cyclic structure for stability, such as N-to-C interchain imides and lactams (Ede et al. in Smith and Rivier (Eds.) “Peptides: Chemistry and Biology”, Escom, Leiden (1991), pp. 268-270). An example of this is provided in conformationally restricted thymopentin-like compounds, such as those disclosed in US4457489. A third method is to replace the peptide bond in the target entity with a pseudopeptide bond that confers resistance to proteolysis.

[0089] The term "organic atom" refers to atoms present in organic compounds, such as carbon, hydrogen, nitrogen, oxygen, sulfur, phosphorus, fluorine, chlorine, bromine, or iodine.

[0090] It is understood that the ranges provided herein are abbreviated representations of all values ​​within that range. For example, the range 1 to 50 is understood to include any number, combination of numbers, or subrange derived from the group consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50, as well as all decimal values ​​between the above integers, such as 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, and 1.9. With respect to subranges, "nested subranges" that extend from either endpoint of the range are specifically intended. For example, nested subranges of the exemplary range 1-50 may include 1-10, 1-20, 1-30, and 1-40 in one direction, or 50-40, 50-30, 50-20, and 50-10 in the other direction.

[0091] When used herein, C1-C x (or C 1-x ) are C1-C2, C1-C3...C1-C x This includes, for example, a group designated "C1-C4" indicates that the part contains 1 to 4 carbon atoms, i.e., a group containing 1 carbon atom, 2 carbon atoms, 3 carbon atoms, or 4 carbon atoms. Thus, for example, "C1-C4 alkyl" indicates that the alkyl group contains 1 to 4 carbon atoms, i.e., the alkyl group is selected from methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, and t-butyl. Also, for example, C0-C2 alkylenes include direct bonds, -CH2-, and -CH2CH2- bonds.

[0092] As used herein, the terms “cyclized” or “cyclization” mean that two amino acids separated from each other by at least one amino acid are directly or indirectly linked to each other within a peptide to form a cyclic structure within the molecule. In some cases, the two amino acids are linked via a linker or the like.

[0093] The terms “subject” or “patient” encompass mammals. Examples of mammals include, but are not limited to, any member of the mammalian class: non-human primates such as humans, chimpanzees, and other apes and monkey species; agricultural animals such as cattle, horses, sheep, goats, and pigs; domestic animals such as rabbits, dogs, and cats; and laboratory animals, including rodents such as rats, mice, and guinea pigs. In one embodiment, the mammal is a companion animal such as a dog or a cat. In another embodiment, the mammal is a human.

[0094] Sequence identity percentages can be calculated using computer programs or direct sequence comparisons. Preferred computer program methods for determining identity between two sequences include, but are not limited to, the GCG program package, FASTA, BLASTP, and TBLASTN (see, for example, DW Mount, 2001, Bioinformatics: Sequence and Genome Analysis, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY). BLASTP and TBLASTN programs are publicly available from NCBI and other sources. The Smith-Waterman algorithm can also be used to determine identity percentages. Exemplary parameters for amino acid sequence comparison include: 1) Needleman and Wunsch's algorithm (J. Mol. Biol., 48:443-453 (1970)); 2) Hentikoff and Hentikoff's BLOSSUM62 comparison matrix (Proc. Nat. Acad. Sci. USA., 89:10915-10919 (1992)); 3) a gap penalty of 12; and 4) a gap length penalty of 4. A useful program with these parameters may be publicly available as the “gap” program (Genetics Computer Group, Madison, Wis.). The above parameters are the default parameters for polypeptide comparison (there is no penalty for end gaps). Alternatively, polypeptide sequence identity can be calculated using the following formula: Identity % - (number of identical residues) / (length of alignment within amino acid residues) * 100. For this calculation, the alignment length includes internal gaps but excludes terminal gaps.

[0095] For clarity, it is understood that certain features of the Disclosure described in the context of separate embodiments may also be provided in combination in a single embodiment. Conversely, for brevity, various features of the Disclosure described in the context of a single embodiment may also be provided separately or in any preferred subcombination. For example, a conjugate of the Disclosure may include any peptide ligand described herein (e.g., formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5), or the peptide ligands of Table 1), any metal chelating agent described herein (e.g., metal chelating agents selected from Figures 4A, 5A, 6A, 7A, 4B, 5B, 6B, 7B, and 8-22), optionally a linker described herein (e.g., a linker of formula (II-1), (II-1a), or (II-1b)), and optionally a radionuclide described herein (e.g., the radionuclides of Table 7). As another example, the peptide of formula (I) (or any other formula such as (III-1) and (III-2)) may include the X1-X12 amino acids described herein, and any combination of the embodiments of the amino acids is encompassed by this disclosure (even if in some cases they are described in the context of separate embodiments).

[0096] Unless otherwise specified, the terms, procedures, and techniques used herein in relation to analytical chemistry, organic synthesis chemistry, and medicinal chemistry are well known and commonly used in the art. Standard techniques can be used for chemical synthesis and chemical analysis. Such techniques and procedures, if defined, are described, for example, in “KJ Jensen, PT Shelton, SL Pedersen, Peptide Synthesis and Applications, 2nd Edition, Springer, 2013,” and are incorporated herein by reference for all purposes. All patents, applications, published applications, and other publications and data referenced throughout this disclosure are incorporated herein by reference where permitted.

[0097] II. Radioactive Pharmaceutical Conjugates Radiopharmaceutical conjugates having avidity to glypican 3 (GPC3), or pharmaceutically acceptable salts thereof, and pharmaceutical compositions comprising such conjugates are provided herein. The conjugates and compositions may be useful in treating cancer. The conjugates and compositions may also be useful in imaging and disease diagnosis.

[0098] In one embodiment, a conjugate comprising a peptide having avidity to glypican 3 (GPC3) and a metal chelating agent configured to bind to a radionuclide is described herein. In some embodiments, GPC3 is human GPC3. The peptide may be cyclic or acyclic, and may be monocyclic, bicyclic, or polycyclic. In one embodiment, a conjugate comprising a cyclic peptide and a metal chelating agent configured to bind to a radionuclide is described herein. In some embodiments, the peptide (such as a cyclic peptide) is configured to bind to a target. The conjugate described herein may further include a linker that covalently bonds the peptide to the metal chelating agent. In some embodiments, the conjugate binds to the metal chelating agent. 225 Contains radioactive nuclides such as Ac.

[0099] In another embodiment, a conjugate comprising a peptide having avidity to glypican 3 (GPC3) and a covalently bound radionuclide is described herein. In some embodiments, GPC3 is human GPC3. The peptide may be cyclic or acyclic, and may be monocyclic, bicyclic, or polycyclic. In one embodiment, a conjugate comprising a cyclic peptide and a metal chelating agent configured to bind to a radionuclide is described herein. In some embodiments, the peptide (such as a cyclic peptide) is configured to bind to a target. The conjugate described herein may further comprise a linker that links a covalently bound radionuclide to the peptide. In some embodiments, the conjugate is bound to131 It contains covalent radionuclides such as 1.

[0100] In one embodiment, (a) A peptide having avidity to glypican 3 (GPC3), wherein SEQ ID NO: MeK-MeI-D-MeQ-F4COO-IIY-MeNal27N-G-3Py6Ph-MeC(Sequence ID 1) A peptide comprising 10 to 12 amino acid residues, or a pharmaceutically acceptable salt thereof, containing an amino acid sequence in which one or more (e.g., 1 to 6) amino acid deletions, substitutions, and / or additions are included; and (b)(i) a metal chelating agent configured to bind to a radionuclide, wherein the metal chelating agent binds to a peptide; or (ii) a radionuclide to which covalent bonding occurs. Radiopharmaceutical conjugates containing the above are described herein.

[0101] In some embodiments, the radiopharmaceutical conjugate includes a metal chelating agent configured to bind to a radionuclide. In some embodiments, the radiopharmaceutical conjugate includes a radionuclide that binds to the metal chelating agent.

[0102] In some embodiments, the radiopharmaceutical conjugate includes covalently bound radionuclides.

[0103] In some embodiments, the peptide is a cyclic peptide.

[0104] In some embodiments, the radiopharmaceutical conjugate includes a metal chelating agent configured to bind to a radionuclide, and comprises a metal chelating agent that binds to a peptide. In some embodiments, the radiopharmaceutical conjugate includes a metal chelating agent configured to bind to a radionuclide, and comprises a metal chelating agent that covalently binds to a peptide. In some embodiments, the radionuclide binds to the metal chelating agent. In some embodiments, the radiopharmaceutical conjugate includes a covalently bound radionuclide. In some embodiments, the peptide includes an amino acid sequence having two or fewer amino acid deletions in the amino acid sequence of SEQ ID NO: 1. In some embodiments, one amino acid is deleted from SEQ ID NO: 1. In some embodiments, the one amino acid deleted from SEQ ID NO: 1 is MeI at position 2. In some embodiments, the one amino acid deleted from SEQ ID NO: 1 is D at position 3. In some embodiments, one, two, three, or five amino acids are added to the peptide of SEQ ID NO: 1. In some embodiments, one, two, or three amino acids are added to the peptide of SEQ ID NO: 1. In some embodiments, one or two amino acids are added to the peptide of SEQ ID NO: 1. In some embodiments, one amino acid is added to the peptide of SEQ ID NO: 1. In some embodiments, two amino acids are added to the peptide of SEQ ID NO: 1.

[0105] In one embodiment, (a) A peptide having avidity to glypican 3 (GPC3), wherein formula (I): X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12 Equation (I) [In the formula, X1 is any amino acid; X2 is any amino acid; X3 is any amino acid; X4 is any amino acid; X5 is an amino acid containing an aromatic ring (e.g., W, F, Y, or variants thereof), a cycloalkyl group, or a heterocycloalkyl group, or X5 is a peptoid (e.g., Cha4cH, Cha4tH, A1mor, Atp, Cha4cOMe); X6 is a hydrophobic amino acid, a hydrophilic amino acid, or a polar amino acid, wherein the polar amino acid has a substituted side chain; X7 is a hydrophobic amino acid comprising a C1-C8 alkyl, cycloalkyl, or heterocycloalkyl group, where the alkyl, cycloalkyl, and heterocycloalkyl groups may be independently and appropriately substituted (for example, X7 is I, Eva, alI, TMe, SMe, Gcpr, Gcpe, Gthp, dMeS, TdMe, or Cbg); X8 is A, I, L, V, Y, or F, or a variant thereof; X9 is an N-alkylated amino acid containing an aromatic ring; X10 is a G, A, or D amino acid (e.g., da, ds, de, or dp); X11 is an amino acid containing an aromatic ring (e.g., F, Y, or their variants); X12 is an N-alkylated cysteine ​​(e.g., MeC). Peptides containing the amino acid sequence of the above or their pharmaceutically acceptable salts; and (b)(i) a metal chelating agent configured to bind to a radionuclide, wherein the metal chelating agent binds to a peptide; or (ii) a radionuclide to which covalent bonding occurs. Radiopharmaceutical conjugates containing the above are described herein.

[0106] In some embodiments, the radiopharmaceutical conjugate includes a metal chelating agent configured to bind to a radionuclide. In some embodiments, the radiopharmaceutical conjugate includes a radionuclide that binds to the metal chelating agent. In some embodiments, the radiopharmaceutical conjugate includes a covalently bound radionuclide.

[0107] In one embodiment, (a) A peptide having avidity to glypican 3 (GPC3), wherein formula (I): X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12 Equation (I) [In the formula, X1 is I, R, Cit, F4G, 4Py, 3Py, KCOpipzaa, V, Eva, Q, E, MeI, Ahp, F4COO, KCOpip4COO, MeQdMe, MeA, MeSMe, MeG, MeV, MeHseMe, A ib, MeT, alI, TMe, MeKCOpipzaa, MeQ, Hpr, MeTMe, MeDapCOpipzaa, MeK, MeKAc, MeK(de), MeK(H), MeK(df), or MeK(datb); X2 is I, K, Cit, F4G, 4Py, 3Py, KCOpipzetOH, V, KCOpipzaa, Eva, Q, E, S, Ahp, F4COO, KCOpip4COO, MeQdMe, MeA, MeSMe, MeG, MeI, MeV, MeL, HseMe, MeY, Me3Py, MeHseMe, MeKAc, alI, TMe MeKCOpipzaa, MeQ, Hpr, MeTMe, or MeDapCOpipzaaa; X3 is D, Har, KCOpipzetOH, Cit, KCOmeglumine, KCOpipzaa, A4paa, Q, A, E, MeD, S, N, Hgl, F4COO, KCOpip4COO, KAc, Hgn, MeY, or DapCOpipzaa; X4 is D, Har, KCOpipzetOH, KCOmeglumine, KCOpipzaa, A4paa, Q, A, E, MeD, S, N, Hgl, F4COO, KCOpip4COO, dd, MeQ, MeQdMe, MeA, MeSMe, MeG, EtG, Me eG, CmG, CmpG, CrmG, CeG, CrpG, MeK, MeKAc, MeHgl, Hgn, MeDapCOpipzaa, MeKCOpipzaa, Medd, Cit, MeCit, MeN, MeS, MeE, MeY, W5N, or MeA4paa; X5 is Y, F3G, 3Py6COO, 4Py2NH2, 3Py5COO, F3COO, 3Py6NHAc, F, F4C, F4OMe, F4COO, Nal2, F3aao, F4aa, F4aao, 3Py6NHaa, 5Pdo, F3CON, F4F, F4OEt, F4Me, F4CON, F4CONPEG4Me, F3OMe, F3CON, Yae, YaeCOpipzaa, F4aaopipzaa, 4Pdo, 3Py6CON, Atp, Cha4cH, Cha4tH, Cha4cOMe, A1mor, or F4amCOpipzaa; X6 is I, V, Eva, Chg, Tbg, A, L, Ahp, F4COO, Gcpr, Gcpe, alI, Cle, S3REt, TMe, Acpr, Cba, Gthp, NleCOO, NleOH, P, Atb, Nva, Nle, N, DapAc, Abu, Nmm, Ndm, Ncit, Cit, SMe, HseMe, HseEt, HseiPr, dMeS, TdMe, Cbg, NvaOMe, SiPr, Spr, NleOMe, Sbu, Scbm, Scpe, AhpOMe, HseBu, Spent, or Hsecpe; X7 is I, Eva, alI, TMe, SMe, Gcpr, Gcpe, Gthp, dMeS, TdMe, or Cbg; X8 is A, I, L, V, Y, F4OMe, F4COO, F4OEt, F4u, F4Me, F4CONdMe, F4CON, F4ms, F4CONPEG4Me, F34dOMe, F3OMe, F3C, F3CON, F3CONdMe, 3Py6CON, Yae, YaeCOpipzaa, 5Inda, F3aao, F3aa, F4aao, F4aa, 3Py6Nhae, 3Py6NHAc, 3Py6OMe, F4aaopipzaa, or F4amCOpipzaa; X9 is MeNal2, MeNal27N, MeF34diox, MeF34dOMe, MeF4T, MeY, MeW1Me, MeW7N, MeF3C4Me, or MeF3Me4C; X10 is a G, A, or D amino acid (e.g., da, ds, de, or dp); X11 is Bph, 3Py6Ph, F41Me4Pyz, F43Pyz, F44Pyz, F41Pyz, F41Me3Pyz, F41Et4Pyz, F41MeOe4Pyz, F41MeOp4Pyz, F44thp, F4Ac4pip, PhNva, PhNle, Yph, Ybn, F4tb, F4oPr, or F4CONdMe; X12 is a MeC. Peptides containing the amino acid sequence of the above or their pharmaceutically acceptable salts; and (b)(i) a metal chelating agent configured to bind to a radionuclide, wherein the metal chelating agent binds to a peptide; or (ii) a radionuclide to which covalent bonding occurs. Radiopharmaceutical conjugates containing the above are described herein.

[0108] In some embodiments, the radiopharmaceutical conjugate includes a metal chelating agent configured to bind to a radionuclide. In some embodiments, the radiopharmaceutical conjugate includes a radionuclide that binds to the metal chelating agent. In some embodiments, the radiopharmaceutical conjugate includes a covalently bound radionuclide.

[0109] In one embodiment, (a) A peptide having avidity to glypican 3 (GPC3), wherein formula (I): X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12 Equation (I) [In the formula, X1 is any amino acid; X2 is any amino acid; X3 is any amino acid; X4 is any amino acid; The X5 is [ka] [In the formula, R n5 is hydrogen or C 1-3 It is alkyl; Ring A5 is aryl, heteroaryl, cycloalkyl, or heterocycloalkyl; R X5 Each of them is independent of C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, C 2-6 Alkenil, C 2-6 Alkynyl, halogen, -CN, -NO2, -OR a , -SR a -SF5, -NR c R d -S(=O)R a -S(=O)2R a -S(=O)2NR c R d -S(=O)(=NR a )R a -N=S(=O)NR c R d , -NR a S(=O)2R a , amidinil, -NR a C(=NH)NR c R d , -NR a S(=O)2NR c R d -C(=O)R a , -C(=O)OR a -OC(=O)R a , -OC(=O)OR a -OC(=O)NR c R d , -NR a C(=O)R a , -NR a C(=O)OR a , -NR a C(=O)NR c R d -C(=O)NR c R d , -P(=O)(OR c )(OR d ), -P(=O)R c R daryl, heteroaryl, cycloalkyl, heterocycloalkyl, -L X5 -heterocycloalkyl, -L X5 -Cycloalkyl, -L X5 -aryl, or -L X5 -A heteroaryl, where the alkyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl are one or more R X5a This may be substituted as appropriate; or, Two R's X5 Together, =O, =S, or =N(R a ) form; L X5 C 1-6 Alkylene, C 1-6 Heteroalkylene, -O-, -S-, or -NR a -where the alkylene and heteroalkylene are one or more R X5a This may be substituted as appropriate; kx5 is 0, 1, 2, or 3; mx5 is 0, 1, 2, 3, 4, or 5; *X4 represents the connection point to X4; *X6 represents the connection point to X6. and; X6 is [ka] [In the formula, R n6 is hydrogen or C 1-3 It is alkyl; R X6 C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, C 2-6 Alkenil, C 2-6 Alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, -L X6 -heterocycloalkyl, -LX6 -Cycloalkyl, -L X6 -aryl, or -L X6 -A heteroaryl, where the alkyl, heteroalkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl each contain one or more R X6a This may be substituted as appropriate; or, R n6 and R x6 It forms a 5-6 member heterocycloalkyl group with the atoms in between, which consists of one or more R X6a This may be substituted as appropriate; L X6 C 1-6 Alkylene, C 1-6 Heteroalkylene, -O-, -S-, or -NR a -where the alkylene and heteroalkylene are one or more R X6a This may be substituted as appropriate; *X5 represents the connection point to X5; *X7 represents the connection point to X7. and; X7 is [ka] [In the formula, R n7 is hydrogen or C 1-3 It is alkyl; R X7 C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, C 2-6 Alkenil, C 2-6 Alkynyl, cycloalkyl, or heterocycloalkyl, where each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, and heterocycloalkyl is one or more R X7a This may be substituted as appropriate; *X6 represents the connection point to X6; *X8 represents the connection point to X8. and; The X8 is [ka] [In the formula, R n8 is hydrogen or C 1-3 It is alkyl; Ring A8 is either an aryl or heteroaryl ring; R X8 Each of them is independent of C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, C 2-6 Alkenil, C 2-6 Alkynyl, halogen, -CN, -NO2, -OR a , -SR a -SF5, -NR c R d -S(=O)R a -S(=O)2R a -S(=O)2R c R d -S(=O)(=NR a )R a -N=S(=O) R c R d , -NR a S(=O)2R a , amidinil, -NR a C(=NH)NR c R d , -NR a S(=O)2R c R d -C(=O)R a , -C(=O)OR a -OC(=O)R a , -OC(=O)OR a -OC(=O)NR c R d , -NR a C(=O)R a , -NR a C(=O)ORa , -NR a C(=O)NR c R d -C(=O)NR c R d , -P(=O)(OR c )(OR d ), -P(=O)R c R d aryl, heteroaryl, cycloalkyl, heterocycloalkyl, -L X8 -heterocycloalkyl, -L X8 -Cycloalkyl, -L X8 -aryl, or -L X8 -A heteroaryl, where the alkyl, heteroalkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl each contain one or more R X8a This may be substituted as appropriate; or, Two R's X8 Together, =O, =S, or =N(R a ) form; L X8 C 1-6 Alkylene, C 1-6 Heteroalkylene, -O-, -S-, or -NR a -where the alkylene and heteroalkylene are one or more R X8a This may be substituted as appropriate; kx8 is 0, 1, 2, or 3; mx8 is 0, 1, 2, 3, 4, or 5; *X7 represents the connection point to X7; *X9 represents the connection point to X9. and; X9 is [ka] [In the formula, R n9 is hydrogen or C 1-3 It is alkyl; Ring A9 is either aryl or heteroaryl; RX9 Each of them is independent of C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, C 2-6 Alkenil, C 2-6 Alkynyl, halogen, -CN, -NO2, -OR a , -SR a -SF5, or -NR c R d Here, the alkyl, heteroalkyl, alkenyl, and alkynyl each have one or more R X9a This may be substituted as appropriate; or, Two R's X9 Together, =O, =S, or =N(R a ) form; kx9 is 0, 1, 2, or 3; mx9 is 0, 1, 2, 3, 4, or 5; *X8 represents the connection point to X8; *X10 represents the connection point to X10. and; X10 is glycine or a D-amino acid (e.g., da, ds, de, or dp); X11 is [ka] [In the formula, R n11 is hydrogen or C 1-3 It is alkyl; Ring A11 is either an aryl or heteroaryl ring; R X11 Each of them is independent of C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, halogen, -CN, -NO2, -OR a , -SR a -SF5, -NRc R d -S(=O)R a -S(=O)2R a -S(=O)2R c R d -S(=O)(=NR a )R a -N=S(=O)R c R d , -NR a S(=O)2R a , amidinil, -NR a C(=NH)NR c R d , -NR a S(=O)2R c R d -C(=O)R a , -C(=O)OR a -OC(=O)R a , -OC(=O)OR a -OC(=O)NR c R d , -NR a C(=O)R a , -NR a C(=O)OR a , -NR a C(=O)NR c R d -C(=O)NR c R d , -P(=O)(OR c )(OR d ), -P(=O)R c R d aryl, heteroaryl, cycloalkyl, heterocycloalkyl, -L X11 -heterocycloalkyl, -L X11 -Cycloalkyl, -L X11 -aryl, or -L X11 -A heteroaryl, where the alkyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl each contain one or more R X11a This may be substituted as appropriate; or, Two R's X11 Together, =O, =S, or =N(R a ) form; L X11 C 1-6 Alkylene, C 1-6 Heteroalkylene, -O-, -S-, or -NR a -where the alkylene and heteroalkylene are one or more R X11a This may be substituted as appropriate; kx11 is 0, 1, 2, 3, 4, or 5; mx11 is 0, 1, 2, 3, 4, or 5; *X10 represents the connection point to X10; *X12 represents the connection point to X12. and; X12 is an N-alkylated cysteine; R X5a , R X6a , R X7a , R X8a , R X9a , and R X11a These are, independently, halogen and C 1-6 Alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, -CN, -NO2, -OR a , -SR a , -NR c R d -S(=O)R a -S(=O)2R a -SF5, -S(=O)2NR c R d -S(=O)(=NR a )R a -N=S(=O)R c R d , -NR a S(=O)2R a , amidinil, -NR a C(=NH)(NR a )2, -NR a S(=O)2NR c R d -C(=O)R a , -C(=O)OR a -OC(=O)R a, -OC(=O)OR a -OC(=O)NR c R d , -NR a C(=O)R a , -NR a C(=O)OR a , -NR a C(=O)NR c R d -C(=O)NR c R d , -P(=O)(OR c )(OR d ), -P(=O)R c R d aryl, heteroaryl, cycloalkyl, heterocycloalkyl, =O, =S, or =N(R a ) where the alkyl, heteroalkyl, alkenyl, and alkynyl each have one or more R e This may be substituted as appropriate; R a Each of these is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(cycloalkyl), C1-C6 alkyl(heterocycloalkyl), C1-C6 alkyl(aryl), or C1-C6 alkyl(heteroaryl), where each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently one or more R e This may be substituted as appropriate; R eThese are, independently, halogen, -CN, -OH, -O-C1-C6 alkyl, -SF5, -S(=O)C1-C6 alkyl, -S(=O)2C1-C6 alkyl, -S(=O)2NH2, -S(=O)2-halogen, -S(=O)2NHC1-C6 alkyl, -S(=O)2N(C1-C6 alkyl)2, -NH2, -NHC1-C6 alkyl, -N(C1-C6 alkyl)2, -NHC(=NH)NH2, -NHC(=O)OC1-C6alkyl, -C(=O)C1-C6alkyl, -C(=O)OH, C1-C6alkyl-C(=O)OH, -C(=O)OC1-C6alkyl, -C(=O)NH2, -C(=O)N(C1-C6alkyl)2, -C(=O)NHC1-C6alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, or C1-C6 heteroalkyl; or, Two R's e Together, they form =O; R c and R d Each of these is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(cycloalkyl), C1-C6 alkyl(heterocycloalkyl), C1-C6 alkyl(aryl), or C1-C6 alkyl(heteroaryl), where each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently one or more R e This may be substituted as appropriate; or, R c and R d Along with the atoms to which they are bonded, one or more R e [This may form a heterocycloalkyl group which may be appropriately substituted.] Peptides containing the amino acid sequence of the above or their pharmaceutically acceptable salts; and (b)(i) a metal chelating agent configured to bind to a radionuclide, wherein the metal chelating agent binds to a peptide; or (ii) a radionuclide to which covalent bonding occurs. Radiopharmaceutical conjugates containing the above are described herein.

[0110] In some embodiments, the radiopharmaceutical conjugate includes a metal chelating agent configured to bind to a radionuclide. In some embodiments, the radiopharmaceutical conjugate includes a radionuclide that binds to the metal chelating agent. In some embodiments, the radiopharmaceutical conjugate includes a covalently bound radionuclide.

[0111] In one embodiment, the following structure: [ka] [In the formula, [ka] [This represents the linker] A radiopharmaceutical conjugate having is described herein.

[0112] In some embodiments, the radiopharmaceutical conjugate includes a metal chelating agent configured to bind to a radionuclide, wherein the metal chelating agent binds to a peptide. In some embodiments, the metal chelating agent is covalently bonded to the peptide. In some embodiments, the conjugate further includes a linker that binds the peptide to the metal chelating agent. In some embodiments, the linker covalently bonds the peptide to the metal chelating agent. In some embodiments, the linker covalently bonds the metal chelating agent to the N-terminus of the peptide. In some embodiments, the linker covalently bonds the metal chelating agent to the C-terminus of the peptide. In some embodiments, the linker binds to the peptide via a non-terminal amino acid residue. In some embodiments, the linker binds to amino acid X1. In some embodiments, the linker binds to amino acid X2. In some embodiments, the linker binds to amino acid X3. In some embodiments, the linker binds to amino acid X4. In some embodiments, the linker binds to amino acid X5. In some embodiments, the linker binds to amino acid X6. In some embodiments, the linker binds to amino acid X7. In some embodiments, the linker binds to amino acid X8. In some embodiments, the linker binds to amino acid X9. In some embodiments, the linker binds to amino acid X10. In some embodiments, the linker binds to amino acid X11. In some embodiments, the linker binds to amino acid X12. In some embodiments, the linker binds to amino acids X1, X2, X3, X4, X8, or X12. In some embodiments, the linker binds to the lysine of the peptide. In some embodiments, the linker comprises one or more amino acid residues. In some embodiments, the linker comprises a lysine residue, an alanine residue, a glycine residue, a D-phenylalanine residue, a histidine residue, a dAtb residue, or a D-glutamate residue. In some embodiments, the linker comprises two amino acids selected from the group consisting of lysine, alanine, glycine, D-phenylalanine, histidine, dAtb, and D-glutamate. In some embodiments, the linker is C 1-6 It is a heteroalkylene. In some embodiments, the linker is a bond.

[0113] In one embodiment, the following structure: [ka] [In the formula, [ka] This represents the linker; R * [This represents covalently bonded radionuclides.] A radiopharmaceutical conjugate having the above is described herein.

[0114] In some embodiments, the radiopharmaceutical conjugate includes a covalently bonded radionuclide. In some embodiments, the conjugate further includes a linker that binds a peptide to the covalently bonded radionuclide. In some embodiments, the linker covalently bonds the peptide to the covalently bonded radionuclide. In some embodiments, the linker covalently bonds the covalently bonded radionuclide to the N-terminus of the peptide. In some embodiments, the linker covalently bonds the covalently bonded radionuclide to the C-terminus of the peptide. In some embodiments, the linker binds to the peptide via a non-terminal amino acid residue. In some embodiments, the linker binds to amino acid X1. In some embodiments, the linker binds to amino acid X2. In some embodiments, the linker binds to amino acid X3. In some embodiments, the linker binds to amino acid X4. In some embodiments, the linker binds to amino acid X5. In some embodiments, the linker binds to amino acid X6. In some embodiments, the linker binds to amino acid X7. In some embodiments, the linker binds to amino acid X8. In some embodiments, the linker binds to amino acid X9. In some embodiments, the linker binds to amino acid X10. In some embodiments, the linker binds to amino acid X11. In some embodiments, the linker binds to amino acid X12. In some embodiments, the covalently bonding radionuclide is directly covalently bonded to an amino acid containing an aromatic ring. In some embodiments, the covalently bonding radionuclide is directly covalently bonded to X5, X8, X9, X4, or X11. In some embodiments, the linker is a bond.

[0115] In some embodiments, a conjugate comprising (a) a monocyclic peptide having avidity to glypican 3 (GPC3), or a pharmaceutically acceptable salt thereof, and (b)(i) a metal chelating agent configured to bind to a radionuclide, wherein the metal chelating agent binds to the peptide, or (ii) a covalently bound radionuclide is described herein. In some embodiments, a conjugate comprising a monocyclic peptide configured to bind to GPC3 and a metal chelating agent configured to bind to a radionuclide is described herein. In some embodiments, a conjugate comprising a monocyclic peptide configured to bind to GPC3 and a covalently bound radionuclide is described herein. In some embodiments, the monocyclic peptide is cyclized by a non-disulfide bond. In some embodiments, the monocyclic peptide does not contain a disulfide bond. In some embodiments, the monocyclic peptide contains 5 to 20 amino acid residues. In some embodiments, the monocyclic peptide contains 7 to 14 amino acid residues. The conjugates described herein may further comprise a linker that covalently bonds a cyclic peptide to a metal chelating agent or a covalently bonded radionuclide. In some embodiments, the conjugate binds to the metal chelating agent. 225 Binding to Cl or cyclic peptides 131 Contains radioactive nuclides such as I.

[0116] In some embodiments, the conjugate described herein comprises two or more peptides (i.e., a first peptide, a second peptide, etc.). For example, the conjugate may comprise two different peptides configured so that both peptides bind to the same target (e.g., GPC3) at either the same or different binding sites. As another example, the conjugate may comprise two different peptides configured so that the two peptides bind to different targets (including GPC3). As yet another example, the conjugate may comprise two identical peptides.

[0117] In some embodiments, the conjugates described herein are in salt form. In some embodiments, the conjugates described herein are in free base form.

[0118] In some embodiments, the metal chelating agent is conjugated to the peptide directly or indirectly via a linker. In some embodiments, the metal chelating agent is conjugated to the peptide by covalent or non-covalent bonds.

[0119] In some embodiments, the conjugate of the Disclosure is selected from Tables 2, 3A–3B, and 9. In some embodiments, the conjugate of the Disclosure comprises a peptide from Table 1, a chelating agent selected from Figures 4–22, and a radionuclide from Table 7.

[0120] Radiopharmaceutical conjugates with GPC3 avidity Glypican 3 (GPC3) is a protein encoded by the GPC3 gene in humans. GPC3 is upregulated in several cancers and is often associated with disease progression, metastasis, and poor prognosis in solid tumors such as hepatocellular carcinoma, lung cancer, gastric cancer, and ovarian cancer.

[0121] GPC3 belongs to the heparan sulfate proteoglycan family and is anchored to the cell membrane surface by a phosphatidylinositol (GPI) anchor.

[0122] GPC3 may play an important role in the proliferation of germ layer tissues. Deletion of the GPC3 gene can cause hypergrowth syndrome, namely Simpson-Gorabi-Boehmell syndrome (SGBS). GPC3 may be expressed throughout the fetal period, and from birth to adulthood, it is not clearly expressed in other normal tissues, except for weak expression in the placenta, breast, mesoderm, ovaries, lungs, and kidneys.

[0123] In some embodiments, the radiopharmaceutical conjugate of the Disclosure binds to GPC3. In some embodiments, the radiopharmaceutical conjugate has GPC3 antagonist activity. In some embodiments, the radiopharmaceutical conjugate binds to human GPC3 (hGPC3) and has hGPC3 antagonist activity, for example, inhibiting GPC3's ability to promote or stabilize Wnt / Frizzled interactions and / or downstream signaling.

[0124] As used herein, the term “GPC3” refers to any form of GPC3 and its variants that retain at least some of the activity of GPC3. Unless otherwise specifically described as human GPC3 (hGPC3), GPC3 includes all natural sequences of GPC3 in mammals such as humans, dogs, cats, horses, and cattle. An example of GPC3 is human GPC3, which is the protein hGPC3 (gene ID: 2719) having the following amino acid sequence (SEQ ID NO: 398, isoform 1, P51654-1). MAGTVRTACLVVAMLLSLDFPGQAQPPPPPPDATCHQVRSFFQRLQPGLKWVPETPVPGSDLQVCLPKGPTCCSRKMEEKYQLTARLNMEQLLQSASMELKFLIIQNAAVFQEAFEIVVRHAKNYTNAMFKNNYPSLTPQAFEFV GEFFTDVSLYILGSDINVDDMVNELFDSLFPVIYTQLMNPGLPDSALDINECLRGARRDLKVFGNFPKLIMTQVSKSLQVTRIFLQALNLGIEVINTTDHLKFSKDCGRMLTRMWYCSYCQGLMMVKPCGGYCNVVMQGCMAGVV EIDKYWREYILSLEELVNGMYRIYDMENVLLGLFSTIHDSIQYVQKNAGKLTTTIGKLCAHSQQRQYRSAYYPEDLFIDKKVLKVAHVEHEETLSSRRRELIQKLKSFISFYSALPGYICSHSPVAENDTLCWNGQELVERYSQK AARNGMKNQFNLHELKMKGPEPVVSQIIDKLKHINQLLRTMSMPKGRVLDKNLDEEGFESGDCGDEDECIGSGDGMIKVKNQLRFLAELAYDLDVDDAPGNSQQATPKDNEISTFHNLGNVHSPLKLLTSMAISVVCFFFLVH

[0125] As used herein, the expressions “having avidity to GPC3” or “binding to GPC3” indicate that the peptide has activity to bind to GPC3. The binding site of the peptides of this disclosure on GPC3 is not limited, and the peptides can bind anywhere on the GPC3 protein. Binding to GPC3 can be measured by any known method for measuring intermolecular binding. This can be determined by, for example, surface plasmon resonance (SPR) assays, scattering analysis, and / or radioimmunoassays (RIA), enzyme immunoassays (EIA), and competitive assays such as sandwich and competitive assays, as well as by any known preferred method, including different variants of a given example known in the art.

[0126] In one embodiment, the binding affinity of the radiopharmaceutical conjugate of this disclosure is at most 100 nM, as determined by Kd in surface plasmon resonance (SPR) analysis. In some implementations, the Kd of the peptides of the radiopharmaceutical conjugates disclosed herein is ≤100 nM, ≤50 nM, ≤30 nM, ≤20 nM, ≤10 nM, ≤5 nM, ≤4 nM, ≤3 nM, ≤2 nM, ≤1 nM, ≤0.9 nM, ≤0.5 nM, ≤0.4 nM, ≤0.3 nM, ≤0.2 nM, ≤0.1 nM, ≤0.09 nM, ≤0.08 nM, ≤0.07 nM, ≤0.06 nM, ≤0.05 nM, ≤0.04 nM, ≤0.03 nM, ≤0.02 nM, and ≤0.01 nM.

[0127] In some embodiments, the radiopharmaceutical conjugates described herein have a binding affinity to human GPC3 of at most 1, 5, 10, 50, 100, 200, 500, 1000, 5000, or 10,000 nM, as determined by Kd in surface plasmon resonance (SPR) analysis. In some embodiments, the radiopharmaceutical conjugates described herein have a binding affinity to human GPC3 of at most 100 nM, as determined by Kd in surface plasmon resonance (SPR) analysis. In some embodiments, the radiopharmaceutical conjugates described herein have a binding affinity to human GPC3 of at most 1 nM, as determined by Kd in surface plasmon resonance (SPR) analysis. In some embodiments, the radiopharmaceutical conjugates described herein have a binding affinity to human GPC3 of at most 2 nM, as determined by Kd in surface plasmon resonance (SPR) analysis. In some embodiments, the radiopharmaceutical conjugates described herein have a binding affinity to human GPC3 of at most 5 nM, as determined by Kd in surface plasmon resonance (SPR) analysis. In some embodiments, the radiopharmaceutical conjugates described herein have a binding affinity to human GPC3 of at most 10 nM, as determined by Kd in surface plasmon resonance (SPR) analysis.

[0128] In one embodiment, the binding affinity of the peptide or radiopharmaceutical conjugate of the Disclosure is at most 100 nM, as determined by Kd in surface plasmon resonance (SPR) analysis. In some embodiments, the Kd of the peptide or radiopharmaceutical conjugate of the Disclosure is ≤100 nM, ≤50 nM, ≤30 nM, ≤20 nM, ≤10 nM, ≤5 nM, ≤4 nM, ≤3 nM, ≤2 nM, ≤1 nM, ≤0.9 nM, ≤0.5 nM, ≤0.4 nM, ≤0.3 nM, ≤0.2 nM, ≤0.1 nM, ≤0.09 nM, ≤0.08 nM, ≤0.07 nM, ≤0.06 nM, ≤0.05 nM, ≤0.04 nM, ≤0.03 nM, ≤0.02 nM, or ≤0.01 nM.

[0129] GPC3 peptide-binding ligand In one embodiment, the present disclosure relates to a radiopharmaceutical conjugate comprising a peptide (e.g., a binding peptide) having avidity to glypican 3 (GPC3). GPC3 may be mammalian GPC3. GPC3 may be human GPC3. GPC3 may be wild-type or mutant GPC3. In some embodiments, the conjugate of the present disclosure comprises two or more peptides, which may be the same or different. The peptides may be linear or cyclic. In some embodiments, the peptides are monocyclic. The peptides may contain any preferred number of amino acid residues. In some embodiments, the peptides may contain 5 to 50, 6 to 40, 7 to 30, 8 to 25, 12 to 25, or 9 to 20 amino acid residues. In some embodiments, the peptides may contain 5 to 14 amino acid residues. In some embodiments, the peptides may contain 7 to 12 amino acid residues. In some embodiments, the peptides may contain 8 to 12 amino acid residues. In some embodiments, the peptides may contain 8 to 10 amino acid residues. In some embodiments, the peptide contains 7 to 13 amino acid residues. In some embodiments, the peptide contains 12 to 15 amino acid residues. In some embodiments, the peptide contains 13 to 14 amino acid residues. In some embodiments, the peptide contains 6 amino acid residues. In some embodiments, the peptide contains 7 amino acid residues. In some embodiments, the peptide contains 8 amino acid residues. In some embodiments, the peptide contains 9 amino acid residues. In some embodiments, the peptide contains 10 amino acid residues. In some embodiments, the peptide contains 11 amino acid residues. In some embodiments, the peptide contains 12 amino acid residues. In some embodiments, the peptide contains 13 amino acid residues. In some embodiments, the peptide contains 14 amino acid residues. In some embodiments, the peptide contains 15 amino acid residues. In some embodiments, the peptide contains 16 amino acid residues. In some embodiments, the peptide consists of 6 amino acid residues. In some embodiments, the peptide consists of 7 amino acid residues. In some embodiments, the peptide consists of 8 amino acid residues. In some embodiments, the peptide consists of 9 amino acid residues.In some embodiments, the peptide consists of 10 amino acid residues. In some embodiments, the peptide consists of 11 amino acid residues. In some embodiments, the peptide consists of 12 amino acid residues. In some embodiments, the peptide consists of 13 amino acid residues. In some embodiments, the peptide consists of 14 amino acid residues. In some embodiments, the peptide consists of 15 amino acid residues. In some embodiments, the peptide consists of 16 amino acid residues. In some embodiments, the conjugate comprises a monocyclic peptide of 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues. The peptides described herein may also be binding peptides that bind to GPC3. In some embodiments, the binding peptide consists of 6 to 20 amino acid residues. In some embodiments, the binding peptide consists of 7 to 12 amino acid residues. In some embodiments, the binding peptide consists of 10 to 12 amino acid residues. In some embodiments, the binding peptide consists of 8 to 12 amino acid residues. In some embodiments, the binding peptide is monocyclic. In some embodiments, the peptides of this technology are isolated peptides. In some embodiments, the peptides in this technology are purified peptides.

[0130] In one embodiment, (a) A peptide having avidity to glypican 3 (GPC3), wherein SEQ ID NO: MeK-MeI-D-MeQ-F4COO-IIY-MeNal27N-G-3Py6Ph-MeC(Sequence ID 1) A peptide comprising 10 to 12 amino acid residues, or a pharmaceutically acceptable salt thereof, containing an amino acid sequence in which one or more (e.g., 1 to 6) amino acid deletions, substitutions, and / or additions are included; and (b)(i) a metal chelating agent configured to bind to a radionuclide, wherein the metal chelating agent binds to a peptide; or (ii) a radionuclide to which covalent bonding occurs. Radiopharmaceutical conjugates containing the above are described herein.

[0131] In some embodiments, the metal chelating agent is configured to bind to a radionuclide, where the metal chelating agent binds to a peptide. In some embodiments, the radionuclide binds to the metal chelating agent. In some embodiments, the radionuclide is a covalently bound radionuclide.

[0132] In some embodiments, the peptide includes an amino acid sequence containing at most six deletions, substitutions, and / or additions of one or more amino acids in the amino acid sequence of SEQ ID NO: 1. In some embodiments, the peptide includes an amino acid sequence containing at most five deletions, substitutions, and / or additions of one or more amino acids in the amino acid sequence of SEQ ID NO: 1. In some embodiments, the peptide includes an amino acid sequence containing at most four deletions, substitutions, and / or additions of one or more amino acids in the amino acid sequence of SEQ ID NO: 1. In some embodiments, the peptide includes an amino acid sequence containing at most three deletions, substitutions, and / or additions of one or more amino acids in the amino acid sequence of SEQ ID NO: 1. In some embodiments, the peptide includes an amino acid sequence containing at most two deletions, substitutions, and / or additions of one or more amino acids in the amino acid sequence of SEQ ID NO: 1. In some embodiments, the peptide includes an amino acid sequence containing at most one deletion, substitution, and / or addition of one or more amino acids in the amino acid sequence of SEQ ID NO: 1. In some embodiments, the amino acid substitutions are conservative amino acid substitutions. The location of deletions, additions, or substitutions may be terminal or in the middle of the peptide. In some embodiments, MeI at position 2 is deleted from SEQ ID NO: 1. In some embodiments, D at position 3 is deleted from SEQ ID NO: 1. In some embodiments, the peptide of SEQ ID NO: 1 is a cyclic peptide. In some embodiments, the peptide is a monocyclic peptide. In some embodiments, 1, 2, 3, 4, or 5 amino acids are added to the peptide of SEQ ID NO: 1. In some embodiments, 1, 2, or 3 amino acids are added to the peptide of SEQ ID NO: 1. In some embodiments, 1 or 2 amino acids are added to the peptide of SEQ ID NO: 1. In some embodiments, 5 amino acids are added to the peptide of SEQ ID NO: 1. In some embodiments, 4 amino acids are added to the peptide of SEQ ID NO: 1. In some embodiments, 3 amino acids are added to the peptide of SEQ ID NO: 1. In some embodiments, 2 amino acids are added to the peptide of SEQ ID NO: 1. In some embodiments, 1 amino acid is added to the peptide of SEQ ID NO: 1.The amino acid addition may be at the N-terminus, C-terminus, or middle of the peptide of SEQ ID NO: 1.

[0133] In one embodiment, a peptide having avidity to glypican 3 (GPC3) is provided, and formula (I): X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12 Equation (I) [In the formula, X1 is any amino acid; X2 is either nonexistent or any amino acid; X3 is either nonexistent or any amino acid; X4 is any amino acid; X5 is an amino acid containing an aromatic ring (e.g., W, F, Y, or variants thereof), a cycloalkyl group, or a heterocycloalkyl group, or X5 is a peptoid (e.g., Cha4cH, Cha4tH, A1mor, Atp, Cha4cOMe); X6 is a hydrophobic amino acid, a hydrophilic amino acid, or a polar amino acid, wherein the polar amino acid has a substituted side chain; X7 is a hydrophobic amino acid comprising a C1-C8 alkyl, cycloalkyl, or heterocycloalkyl group, where the alkyl, cycloalkyl, and heterocycloalkyl groups may be independently and appropriately substituted (for example, X7 is I, Eva, alI, TMe, SMe, Gcpr, Gcpe, Gthp, dMeS, TdMe, or Cbg); X8 is A, I, L, V, Y, or F, or a variant thereof; X9 is an N-alkylated amino acid containing an aromatic ring; X10 is a G, A, or D amino acid (e.g., da, ds, de, or dp); X11 is an amino acid containing an aromatic ring (e.g., F, Y, or their variants); X12 is an N-alkylated cysteine ​​(e.g., MeC). Peptides containing the amino acid sequence or pharmaceutically acceptable salts thereof are described herein.

[0134] In some embodiments, the peptide of formula (I) is a cyclic peptide. In some embodiments, the peptide is a monocyclic peptide.

[0135] In some embodiments, the peptide of formula (I) is a cyclic peptide. In some embodiments, the cyclic peptide of formula (I) is formula (I-1): [ka] [In the formula, R 1 It is selected from the group consisting of -NH2 and -OH; R 2 C 1-3 It is alkyl; R 3 C 1-3 It is an alkylene and has one or more R 4 This may be substituted as appropriate; R 4 Each of them is independent of C 1-3 Alkyl or C 3-6 It is a cycloalkyl; kxR is 1, 2, 3, 4, 5, or 6; X R It is selected from the group consisting of -S-, -CH2-, or -O-; X1 to X11 have the definitions described in formula (I). It has the structure of [the object].

[0136] In some embodiments, the peptide of formula (I-1) is replaced with the peptide of formula (I-2): [ka] [In the formula, X1 to X11 have the definitions described in formula (I)] It has the structure of [the object].

[0137] In some embodiments, the peptide of formula (I) is a cyclic peptide, and X2 is absent. In some embodiments, the cyclic peptide of formula (I) is formula (I-3): [ka] [In the formula, R 1 It is selected from the group consisting of -NH2 and -OH; R 2 C 1-3 It is alkyl; R 3 C 1-3 It is an alkylene and has one or more R 4 This may be substituted as appropriate; R 4 Each of them is independent of C 1-3 Alkyl or C 3-6 It is a cycloalkyl; kxR is 1, 2, 3, 4, 5, or 6; X R It is selected from the group consisting of -S-, -CH2-, or -O-; X1 to X11 have the definitions described in formula (I). It has the structure of [the object].

[0138] In some embodiments, the peptide of formula (I-3) is replaced with formula (I-4): [ka] [In the formula, X1 to X11 have the definitions described in formula (I)] It has the structure of [the object].

[0139] In some embodiments, the peptide of formula (I) is formula (I-5): [ka] [In the formula, X1 to X12 have the definitions described in formula (I), and Lcyc is a ring-closing group that covalently bonds X1 with X12.] It has the structure of or a pharmaceutically acceptable salt thereof. In some embodiments, Lcyc is a group selected from Table 4B. In some embodiments, Lcyc is formed by reacting the first and second functional groups in Table 4C.

[0140] In one embodiment, a peptide having avidity to glypican 3 (GPC3) is provided, and formula (I): X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12 Equation (I) [In the formula, X1 is any amino acid; X2 is any amino acid; X3 is any amino acid; X4 is any amino acid; The X5 is [ka] [In the formula, R n5 is hydrogen or C 1-3 It is alkyl; Ring A5 is aryl, heteroaryl, cycloalkyl, or heterocycloalkyl; R X5 Each of them is independent of C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, C 2-6 Alkenil, C 2-6 Alkynyl, halogen, -CN, -NO2, -OR a , -SR a -SF5, -NR c R d -S(=O)R a -S(=O)2R a -S(=O)2NR c R d -S(=O)(=NR a )R a -N=S(=O)NR cR d , -NR a S(=O)2R a , amidinil, -NR a C(=NH)NR c R d , -NR a S(=O)2NR c R d -C(=O)R a , -C(=O)OR a -OC(=O)R a , -OC(=O)OR a -OC(=O)NR c R d , -NR a C(=O)R a , -NR a C(=O)OR a , -NR a C(=O)NR c R d -C(=O)NR c R d , -P(=O)(OR c )(OR d ), -P(=O)R c R d aryl, heteroaryl, cycloalkyl, heterocycloalkyl, -L X5 -heterocycloalkyl, -L X5 -Cycloalkyl, -L X5 -aryl, or -L X5 -A heteroaryl, where the alkyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl are one or more R X5a This may be substituted as appropriate; or, Two R's X5 Together, =O, =S, or =N(R a ) form; L X5 C 1-6 Alkylene, C 1-6 Heteroalkylene, -O-, -S-, or -NR a -where the alkylene and heteroalkylene are one or more R X5a This may be substituted as appropriate; kx5 is 0, 1, 2, or 3; mx5 is 0, 1, 2, 3, 4, or 5; *X4 represents the connection point to X4; *X6 represents the connection point to X6. and; X6 is [ka] [In the formula, R n6 is hydrogen or C 1-3 It is alkyl; R X6 C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, C 2-6 Alkenil, C 2-6 Alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, -L X6 -heterocycloalkyl, -L X6 -Cycloalkyl, -L X6 -aryl, or -L X6 -A heteroaryl, where the alkyl, heteroalkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl each contain one or more R X6a This may be substituted as appropriate; or, R n6 and R x6 It forms a 5-6 member heterocycloalkyl group with the atoms in between, which consists of one or more R X6a This may be substituted as appropriate; L X6 C 1-6 Alkylene, C 1-6 Heteroalkylene, -O-, -S-, or -NR a -where the alkylene and heteroalkylene are one or more R X6a This may be substituted as appropriate; *X5 represents the connection point to X5; *X7 represents the connection point to X7. and; X7 is [ka] [In the formula, R n7 is hydrogen or C 1-3 It is alkyl; R X7 C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, C 2-6 Alkenil, C 2-6 Alkynyl, cycloalkyl, or heterocycloalkyl, where each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, and heterocycloalkyl is one or more R X7a This may be substituted as appropriate; *X6 represents the connection point to X6; *X8 represents the connection point to X8. and; The X8 is [ka] [In the formula, R n8 is hydrogen or C 1-3 It is alkyl; Ring A8 is either an aryl or heteroaryl ring; R X8 Each of them is independent of C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, C 2-6 Alkenil, C 2-6 Alkynyl, halogen, -CN, -NO2, -OR a , -SR a -SF5, -NRc R d -S(=O)R a -S(=O)2R a -S(=O)2R c R d -S(=O)(=NR a )R a -N=S(=O) R c R d , -NR a S(=O)2R a , amidinil, -NR a C(=NH)NR c R d , -NR a S(=O)2R c R d -C(=O)R a , -C(=O)OR a -OC(=O)R a , -OC(=O)OR a -OC(=O)NR c R d , -NR a C(=O)R a , -NR a C(=O)OR a , -NR a C(=O)NR c R d -C(=O)NR c R d , -P(=O)(OR c )(OR d ), -P(=O)R c R d aryl, heteroaryl, cycloalkyl, heterocycloalkyl, -L X8 -heterocycloalkyl, -L X8 -Cycloalkyl, -L X8 -aryl, or -L X8 -A heteroaryl, where the alkyl, heteroalkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl each contain one or more R X8a This may be substituted as appropriate; or, Two R's X8 Together, =O, =S, or =N(Ra ) form; L X8 C 1-6 Alkylene, C 1-6 Heteroalkylene, -O-, -S-, or -NR a -where the alkylene and heteroalkylene are one or more R X8a This may be substituted as appropriate; kx8 is 0, 1, 2, or 3; mx8 is 0, 1, 2, 3, 4, or 5; *X7 represents the connection point to X7; *X9 represents the connection point to X9. and; X9 is [ka] [In the formula, R n9 is hydrogen or C 1-3 It is alkyl; Ring A9 is either aryl or heteroaryl; R X9 Each of them is independent of C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, C 2-6 Alkenil, C 2-6 Alkynyl, halogen, -CN, -NO2, -OR a , -SR a -SF5, or -NR c R d Here, the alkyl, heteroalkyl, alkenyl, and alkynyl each have one or more R X9a This may be substituted as appropriate; or, Two R's X9 Together, =O, =S, or =N(R a ) form; kx9 is 0, 1, 2, or 3; mx9 is 0, 1, 2, 3, 4, or 5; *X8 represents the connection point to X8; *X10 represents the connection point to X10. and; X10 is glycine or a D-amino acid (e.g., da, ds, de, or dp); X11 is [ka] [In the formula, R n11 is hydrogen or C 1-3 It is alkyl; Ring A11 is either an aryl or heteroaryl ring; R X11 Each of them is independent of C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, halogen, -CN, -NO2, -OR a , -SR a -SF5, -NR c R d -S(=O)R a -S(=O)2R a -S(=O)2R c R d -S(=O)(=NR a )R a -N=S(=O)R c R d , -NR a S(=O)2R a , amidinil, -NR a C(=NH)NR c R d , -NR a S(=O)2R c R d -C(=O)R a , -C(=O)OR a -OC(=O)R a , -OC(=O)OR a -OC(=O)NR c R d , -NR a C(=O)Ra 、 -NR a C(=O)OR a 、 -NR a C(=O)NR c R d 、 -C(=O)NR c R d 、 -P(=O)(OR c )(OR d )、 -P(=O)R c R d 、 aryl, heteroaryl, cycloalkyl, heterocycloalkyl, -L X11 -heterocycloalkyl, -L X11 -cycloalkyl, -L X11 -aryl, or -L X11 -heteroaryl, wherein the alkyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl are each optionally substituted with one or more R X11a ; alternatively, two R X11 together form =O, =S, or =N(R a ); L X11 is C 1-6 alkylene, C 1-6 heteroalkylene, -O-, -S-, or -NR a -, wherein the alkylene and heteroalkylene are each optionally substituted with one or more R X11a ; kx11 is 0, 1, 2, 3, 4, or 5; mx11 is 0, 1, 2, 3, 4, or 5; *X10 represents the point of attachment to X10; *X12 represents the point of attachment to X12] ; X12 is N-alkylated cysteine; R X5a 、R X6a 、R X7a 、R X8a 、R X9a 、 and R X11a are each independently halogen, C 1-6Alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, -CN, -NO2, -OR a , -SR a , -NR c R d , -S(=O)R a , -S(=O)2R a , -SF5, -S(=O)2NR c R d , -S(=O)(=NR a )R a , -N=S(=O)R c R d , -NR a S(=O)2R a , amidinyl, -NR a C(=NH)(NR a )2, -NR a S(=O)2NR c R d , -C(=O)R a , -C(=O)OR a , -OC(=O)R a , -OC(=O)OR a , -OC(=O)NR c R d , -NR a C(=O)R a , -NR a C(=O)OR a , -NR a C(=O)NR c R d , -C(=O)NR c R d , -P(=O)(OR c )(OR d ), -P(=O)R c R d , aryl, heteroaryl, cycloalkyl, heterocycloalkyl, =O, =S, or =N(R a ), where the alkyl, heteroalkyl, alkenyl, and alkynyl may each be optionally substituted with one or more R e ; R aEach of these is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(cycloalkyl), C1-C6 alkyl(heterocycloalkyl), C1-C6 alkyl(aryl), or C1-C6 alkyl(heteroaryl), where each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently one or more R e This may be substituted as appropriate; R e These are, independently, halogen, -CN, -OH, -O-C1-C6 alkyl, -SF5, -S(=O)C1-C6 alkyl, -S(=O)2C1-C6 alkyl, -S(=O)2NH2, -S(=O)2-halogen, -S(=O)2NHC1-C6 alkyl, -S(=O)2N(C1-C6 alkyl)2, -NH2, -NHC1-C6 alkyl, -N(C1-C6 alkyl)2, -NHC(=NH)NH2, -NHC(=O)OC1-C6alkyl, -C(=O)C1-C6alkyl, -C(=O)OH, C1-C6alkyl-C(=O)OH, -C(=O)OC1-C6alkyl, -C(=O)NH2, -C(=O)N(C1-C6alkyl)2, -C(=O)NHC1-C6alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, or C1-C6 heteroalkyl; or, Two R's e Together, they form =O; R c and R dEach of these is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(cycloalkyl), C1-C6 alkyl(heterocycloalkyl), C1-C6 alkyl(aryl), or C1-C6 alkyl(heteroaryl), where each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently one or more R e It may be replaced as appropriate; or, R c and R d Along with the atoms to which they are bonded, one or more R e [This may form a heterocycloalkyl group which may be appropriately substituted.] Radiopharmaceutical conjugates comprising a peptide containing the amino acid sequence or a pharmaceutically acceptable salt thereof are described herein.

[0141] In some embodiments of formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X1 is an N-methylated amino acid. In some embodiments, X1 is an N-methylated amino acid containing a polar side chain (e.g., MeK, MeQ, or a variant thereof).

[0142] In some embodiments of formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X1 is I, R, Cit, F4G, 4Py, 3Py, KCOpipzaa, V, Eva, Q, E, MeI, Ahp, F4COO, KCOpip4COO, MeQdMe, MeA, MeSMe, MeG, MeV, MeHseMe, Aib, MeT, alI, TMe, MeKCOpipzaa, MeQ, Hpr, MeTMe, MeDapCOpipzaa, MeK, MeKAc, MeK(de), MeK(H), MeK(df), or MeK(datb). In some embodiments of formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X1 is I, R, Cit, F4G, 4Py, 3Py, KCOpipzaa, V, Eva, Q, E, MeI, Ahp, F4COO, KCOpip4COO, MeQdMe, MeA, MeSMe, MeG, MeV, MeHseMe, Aib, MeT, alI, TMe, MeKCOpipzaa, MeQ, Hpr, MeTMe, MeDapCOpipzaa, MeK, MeKAc, MeK(de), MeK(H), MeK(df), or MeK(datb), each of which may be substituted as appropriate. In some embodiments, X1 is I, which may be substituted as appropriate. In some embodiments, X1 may be R, which may be substituted as appropriate. In some embodiments, X1 may be Cit, which may be substituted as appropriate. In some embodiments, X1 may be F4G, which may be substituted as appropriate. In some embodiments, X1 may be 4Py, which may be substituted as appropriate. In some embodiments, X1 may be 3Py, which may be substituted as appropriate. In some embodiments, X1 may be KCOpipzaa, which may be substituted as appropriate. In some embodiments, X1 may be V, which may be substituted as appropriate. In some embodiments, X1 may be Eva, which may be substituted as appropriate. In some embodiments, X1 may be Q, which may be substituted as appropriate. In some embodiments, X1 may be E, which may be substituted as appropriate. In some embodiments, X1 may be MeI, which may be substituted as appropriate. In some embodiments, X1 may be Ahp, which may be substituted as appropriate.In some embodiments, X1 is F4COO, which may be substituted as appropriate. In some embodiments, X1 is KCOpip4COO, which may be substituted as appropriate. In some embodiments, X1 is MeQdMe, which may be substituted as appropriate. In some embodiments, X1 is MeA, which may be substituted as appropriate. In some embodiments, X1 is MeSMe, which may be substituted as appropriate. In some embodiments, X1 is MeG, which may be substituted as appropriate. In some embodiments, X1 is MeV, which may be substituted as appropriate. In some embodiments, X1 is MeHseMe, which may be substituted as appropriate. In some embodiments, X1 is Aib, which may be substituted as appropriate. In some embodiments, X1 is MeT, which may be substituted as appropriate. In some embodiments, X1 is alI, which may be substituted as appropriate. In some embodiments, X1 is TMe, which may be substituted as appropriate. In some embodiments, X1 is MeKCOpipzaa, which may be substituted as appropriate. In some embodiments, X1 is MeQ, which may be substituted as appropriate. In some embodiments, X1 is Hpr, which may be substituted as appropriate. In some embodiments, X1 is MeTMe, which may be substituted as appropriate. In some embodiments, X1 is MeDapCOpipzaa, which may be substituted as appropriate. In some embodiments, X1 is MeK, which may be substituted as appropriate. In some embodiments, X1 is MeKAc, which may be substituted as appropriate. In some embodiments, X1 is MeK(de), which may be substituted as appropriate. In some embodiments, X1 is MeK(H), which may be substituted as appropriate. In some embodiments, X1 is MeK(df), which may be substituted as appropriate. In some embodiments, X1 is MeK(datb), which may be substituted as appropriate. In some embodiments, X1 is MeQ or a derivative thereof. In some embodiments, X1 is MeK or a derivative thereof.

[0143] In some embodiments of peptides of formula (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X1 is any amino acid. In some embodiments, X1 is a D-amino acid. In some embodiments, X1 is an L-amino acid. In some embodiments, X1 is an N-alkylated amino acid. In some embodiments, X1 is an N-methylated amino acid. In some embodiments, X1 does not contain a ring group. In some embodiments, X1 contains a ring group. In some embodiments, X1 contains a 5-6 member heterocycloalkyl group. In some embodiments, X1 contains a 5-6 member heteroaryl group. In some embodiments, X1 contains a phenyl group. In some embodiments, X1 is a peptoid.

[0144] In some embodiments of the peptides of formula (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X1 has the following structure: [ka] [In the formula, R n1 is hydrogen or C 1-3 It is alkyl; R X1 is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, C 2-6 Alkenil, C 2-6 Alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, -L X1 -heterocycloalkyl, -L X1 -Cycloalkyl, -L X1 -aryl, or -L X1-heteroaryl, wherein the alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl are each optionally substituted with one or more R X1a ; R X1’ is hydrogen or C 1-6 alkyl, wherein the alkyl is optionally substituted with one or more R X1a ; or R n1 and R X1’ together with the intervening atoms form a 5- or 6-membered heterocycloalkyl, which is optionally substituted with one or more R X1a ; L X1 is C 1-6 alkylene, C 1-6 heteroalkylene, -O-, -S-, or -NR a -, wherein the alkylene and heteroalkylene are optionally substituted with one or more R X1a ; [[ID=3)4]]R X1a are each independently halogen, C 1-6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, -CN, -NO2, -OR a , -SR a , -NR c R d , -S(=O)R a , -S(=O)2R a , -SF5, -S(=O)2NR c R d , -S(=O)(=NR a )R a , -N=S(=O)R c R d , -NR a S(=O)2R a , amidinyl, -NR a C(=NH)(NR a )2, -NR a S(=O)2NR c Rd -C(=O)R a , -C(=O)OR a -OC(=O)R a , -OC(=O)OR a -OC(=O)NR c R d , -NR a C(=O)R a , -NR a C(=O)OR a , -NR a C(=O)NR c R d -C(=O)NR c R d , -P(=O)(OR c )(OR d ), -P(=O)R c R d aryl, heteroaryl, cycloalkyl, heterocycloalkyl, =O, =S, or =N(R a ) where the aryl, heteroaryl, cycloalkyl, heterocycloalkyl, alkyl, heteroalkyl, alkenyl, and alkynyl each consist of one or more R e This may be substituted as appropriate; *X12 represents the bond point to X12, or *X12 is C(O)(CH2) kxR Represents the connection point to (for example, in equations (I-1) and (I-2)); *X2 represents the connection point to X2; Other groups (R a , R c , R d , and R e (etc.) have the meaning defined by formula (I). It has the following structure: In some embodiments, X1 has the following structure: [ka] It has the following structure: In some embodiments, X1 has the following structure: [ka] It has.

[0145] In some embodiments of the peptides of formula (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X1 has the following structure: [ka] [In the formula, R n1 is hydrogen or methyl; R X1 is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, -L X1 -5-6 member heterocycloalkyl, -L X1 -C 4-6 Cycloalkyl, -L X1 -C 6-10 Aryl, or -L X1 -5 to 10 member heteroaryls, where each alkyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl is a heteroaryl compound with one or more R X1a This may be substituted as appropriate; R X1’ is hydrogen or methyl; or, R n1 and R X1’ It forms a 5-6 member heterocycloalkyl group with the atoms in between, which consists of one or more R X1a This may be substituted as appropriate; L X1 C 1-6 Alkylene or C 1-6 It is a heteroalkylene, where the alkylene and heteroalkylene are one or more R X1a This may be substituted as appropriate; R X1a These are, independently, halogen and C 1-6Alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, -CN, -NO2, -OR a , -SR a , -NR c R d -S(=O)R a -S(=O)2R a -SF5, -S(=O)2NR c R d -S(=O)(=NR a )R a -N=S(=O)R c R d , -NR a S(=O)2R a , amidinil, -NR a C(=NH)(NR a )2, -NR a S(=O)2NR c R d -C(=O)R a , -C(=O)OR a -OC(=O)R a , -OC(=O)OR a -OC(=O)NR c R d , -NR a C(=O)R a , -NR a C(=O)OR a , -NR a C(=O)NR c R d -C(=O)NR c R d , -P(=O)(OR c )(OR d ), -P(=O)R c R d aryl, heteroaryl, cycloalkyl, heterocycloalkyl, =O, =S, or =N(R a ) where the aryl, heteroaryl, cycloalkyl, heterocycloalkyl, alkyl, heteroalkyl, alkenyl, and alkynyl each consist of one or more R e This may be substituted as appropriate; *X12 represents the bond point to X12, or *X12 is C(O)(CH2) kxR Represents the connection point to (for example, in equations (I-1) and (I-2)); *X2 represents the connection point to X2; Other groups (R a , R c , R d , and R e (etc.) have the meaning defined by formula (I). It holds.

[0146] In some embodiments, R n1 is hydrogen. In some embodiments, R n1 C 1-3 It is alkyl. In some embodiments, R n1 It is methyl.

[0147] In some embodiments, R X1 is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, C 2-6 Alkenil, C 2-6 Alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, -L X1 -heterocycloalkyl, -L X1 -Cycloalkyl, -L X1 -aryl, or -L X1 -A heteroaryl, where the alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl each contain one or more R X1a This may be substituted as appropriate.

[0148] In some embodiments, R X1 is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C1-6 Heteroalkyl, -L X1 -5-6 member heterocycloalkyl, -L X1 -C 4-6 Cycloalkyl, -L X1 -C 6-10 Aryl, or -L X1 -5 to 10 member heteroaryls, where each alkyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl is a heteroaryl compound with one or more R X1a This may be replaced as appropriate. In some embodiments, R X1 is hydrogen, C 1-6 Alkyl, C 1-6 Heteroalkyl, -L X1 -Piperidinil, -L X1 -piperazinyl, -L X1 -phenyl, or -L X1 -Pyridinyl, where the alkyl, heteroalkyl, phenyl, pyridinyl, piperidinyl, and piperazinyl each consist of one or more R X1a This may be substituted as appropriate.

[0149] In some embodiments, R X1 is hydrogen. In some embodiments, R X1 C may be substituted as appropriate. 1-6 It is alkyl. In some embodiments, R X1 is one or more R X1a C may be replaced as appropriate. 1-6 It is alkyl. In some embodiments, R X1 C may be substituted as appropriate. 1-6 It is heteroalkyl. In some embodiments, R X1 is one or more R X1a C may be replaced as appropriate. 1-6 It is heteroalkyl. In some embodiments, R X1 C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, or C 1-6 They are heteroalkyl groups, and each of them has one or more RX1a This may be replaced as appropriate. In some embodiments, R X1 C 1-6 It is an aminoalkyl compound. In some embodiments, R X1 is, -(CH) 1-6 It is NH2. In some embodiments, R X1 is -(CH)4NH2. In some embodiments, R X1 C 2-6 Alkenyl or C 2-6 These are alkynyls, and each of them is one or more R X1a This may be replaced as appropriate. In some embodiments, R X1 These are aryl, heteroaryl, cycloalkyl, or heterocycloalkyl, and each of these is one or more R X1a This may be replaced as appropriate. In some embodiments, R X1 These are aryl or heteroaryl compounds, each consisting of one or more R X1a This may be replaced as appropriate. In some embodiments, R X1 These are cycloalkyl or heterocycloalkyl, and each of them has one or more R X1a This may be replaced as appropriate. In some embodiments, R X1 is, -L X1 -heterocycloalkyl, -L X1 -Cycloalkyl, -L X1 -aryl, or -L X1 - These are heteroaryls, each of which has one or more R X1a This may be replaced as appropriate. In some embodiments, R X1 is, -L X1 - It is a heterocycloalkyl, which is one or more R X1a This may be replaced as appropriate. In some embodiments, R X1 is, -L X1 - It is a cycloalkyl, which is one or more R X1a This may be replaced as appropriate. In some embodiments, R X1 is, -L X1 -It is an aryl, which is one or more R X1a This may be replaced as appropriate. In some embodiments, RX1 is, -L X1 -It is a heteroaryl compound, which is one or more R X1a This may be substituted as appropriate.

[0150] In some embodiments, R X1’ is hydrogen. In some embodiments, R X1’ C 1-6 It is an alkyl group, where the alkyl group is one or more R X1a This may be replaced as appropriate. In some embodiments, R X1’ C 1-6 It is alkyl. In some embodiments, R X1’ It is methyl.

[0151] In some embodiments, R n1 and R X1’ It forms a 5-6 member heterocycloalkyl group with the atoms in between, which consists of one or more R X1a This may be substituted as appropriate.

[0152] In some embodiments, L X1 C 1-6 It is an alkylene, where the alkylene is one or more R X1a This may be replaced as appropriate. In some embodiments, L X1 C 1-6 It is alkylene. X1 C 1-6 It is a heteroalkylene, where the heteroalkylene is one or more R X1a This may be replaced as appropriate. In some embodiments, L X1 C 1-6 It is a heteroalkylene. In some embodiments, L X1 is -O-. In some embodiments, L X1 is -S-. In some embodiments, L X1 -NR a - is. In some embodiments, L X1 It is -NH-.

[0153] In some embodiments, RX1a These are, independently, halogen and C 1-6 Alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, -CN, -NO2, -OR a , -SR a , -NR c R d -S(=O)R a -S(=O)2R a -S(=O)2NR c R d , -NR a S(=O)2R a , -NR a C(=NH)(NR a )2, -C(=O)R a , -C(=O)OR a -OC(=O)R a , -OC(=O)OR a -OC(=O)NR c R d , -NR a C(=O)R a , -NR a C(=O)OR a , -NR a C(=O)NR c R d -C(=O)NR c R d , or = O, where the alkyl and heteroalkyl are each one or more R e This may be substituted as appropriate.

[0154] In some embodiments, R X1a These are, independently, halogen and C 1-6 Alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, -CN, -NO2, -OR a , -SR a , -NR c R d -S(=O)R a -S(=O)2R a -S(=O)2NR c Rd , -NR a S(=O)2R a , -NR a C(=NH)(NR a )2, -C(=O)R a , -C(=O)OR a -OC(=O)R a , -OC(=O)OR a -OC(=O)NR c R d , -NR a C(=O)R a , -NR a C(=O)OR a , -NR a C(=O)NR c R d -C(=O)NR c R d , or = O, where the alkyl and heteroalkyl are each one or more R e This may be substituted as appropriate.

[0155] In some embodiments, R X1a Each of them is independent of C 1-6 Alkyl, C 1-6 Alkoxyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, OH, -CN, -NO2, NH2, -C(=O)R a , -C(=O)OR a , -NR a C(=O)NR c R d , or oxo.

[0156] In some embodiments, R n1 It is methyl, and R X1’ is hydrogen, and R X1 C 1-6 It is an aminoalkyl compound. In some embodiments, R n1 It is methyl, and R X1’ is hydrogen, and R X1 C 3-6 It is an aminoalkyl compound. In some embodiments, R n1 It is methyl, and R X1’is hydrogen, and R X1 C 3-6 It is an alkyl group, and the alkyl group is substituted with an amino group.

[0157] In some embodiments of formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X2 is either absent or an L-amino acid. In some embodiments, X2 is absent. In some embodiments, X2 is an L-amino acid. In some embodiments, X2 is an N-methylated amino acid.

[0158] In some embodiments of formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X2 is I, K, Cit, F4G, 4Py, 3Py, KCOpipzetOH, V, KCOpipzaa, Eva, Q, E, S, Ahp, F4COO, KCOpip4COO, MeQdMe, MeA, MeSMe, MeG, MeI, MeV, MeL, HseMe, MeY, Me3Py, MeHseMe, MeKAc, alI, TMe, MeKCOpipzaa, MeQ, Hpr, MeTMe, or MeDapCOpipzaaa. In some embodiments of formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X2 is I, K, Cit, F4G, 4Py, 3Py, KCOpipzetOH, V, KCOpipzaa, Eva, Q, E, Ahp, F4COO, KCOpip4COO, MeQdMe, MeA, MeSMe, MeG, MeI, MeV, MeHseMe, MeKAc, alI, TMe, MeKCOpipzaa, MeQ, Hpr, MeTMe, or MeDapCOpipzaaa. In some embodiments of formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X2 is I, K, Cit, F4G, 4Py, 3Py, KCOpipzetOH, V, KCOpipzaa, Eva, Q, E, S, Ahp, F4COO, KCOpip4COO, MeQdMe, MeA, MeSMe, MeG, MeI, MeV, MeL, HseMe, MeY, Me3Py, MeHseMe, MeKAc, alI, TMe, MeKCOpipzaa, MeQ, Hpr, MeTMe, or MeDapCOpipzaaa, each of which may be substituted as appropriate. In some embodiments, X2 is I, which may be substituted as appropriate. In some embodiments, X2 is K, which may be substituted as appropriate. In some embodiments, X2 may be replaced with Cit as appropriate. In some embodiments, X2 may be replaced with F4G as appropriate. In some embodiments, X2 may be replaced with 4Py as appropriate.In some embodiments, X2 may be 3Py, which may be substituted as appropriate. In some embodiments, X2 may be KCOpipzetOH, which may be substituted as appropriate. In some embodiments, X2 may be V, which may be substituted as appropriate. In some embodiments, X2 may be KCOpipzaa, which may be substituted as appropriate. In some embodiments, X2 may be Eva, which may be substituted as appropriate. In some embodiments, X2 may be Q, which may be substituted as appropriate. In some embodiments, X2 may be E, which may be substituted as appropriate. In some embodiments, X2 may be S, which may be substituted as appropriate. In some embodiments, X2 may be MeL, which may be substituted as appropriate. In some embodiments, X2 may be HseMe, which may be substituted as appropriate. In some embodiments, X2 may be MeY, which may be substituted as appropriate. In some embodiments, X2 may be Me3Py, which may be substituted as appropriate. In some embodiments, X2 may be Ahp, which may be substituted as appropriate. In some embodiments, X2 may be F4COO, which may be substituted as appropriate. In some embodiments, X2 may be KCOpip4COO, which may be substituted as appropriate. In some embodiments, X2 may be MeQdMe, which may be substituted as appropriate. In some embodiments, X2 is MeA, which may be substituted as appropriate. In some embodiments, X2 is MeSMe, which may be substituted as appropriate. In some embodiments, X2 is MeG, which may be substituted as appropriate. In some embodiments, X2 is MeI, which may be substituted as appropriate. In some embodiments, X2 is MeV, which may be substituted as appropriate. In some embodiments, X2 is MeHseMe, which may be substituted as appropriate. In some embodiments, X2 is MeKAc, which may be substituted as appropriate. In some embodiments, X2 is alI, which may be substituted as appropriate. In some embodiments, X2 is TMe, which may be substituted as appropriate. In some embodiments, X2 is MeKCOpipzaa, which may be substituted as appropriate. In some embodiments, X2 is MeQ, which may be substituted as appropriate. In some embodiments, X2 is Hpr, which may be substituted as appropriate. In some embodiments, X2 is MeTMe, which may be substituted as appropriate. In some embodiments, X2 is substituted as appropriate.In some embodiments, X2 is MeDapCOpipzaaa, which may be substituted as appropriate.

[0159] In some embodiments of peptides of formula (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X2 is any amino acid. In some embodiments, X2 is a D-amino acid. In some embodiments, X2 is an L-amino acid. In some embodiments, X2 is an N-alkylated amino acid. In some embodiments, X2 is an N-methylated amino acid. In some embodiments, X2 does not contain a ring group. In some embodiments, X2 contains a ring group. In some embodiments, X2 contains a 5-6 member heterocycloalkyl group. In some embodiments, X2 contains a 5-6 member heteroaryl group. In some embodiments, X2 contains a phenyl group. In some embodiments, X2 is a peptoid.

[0160] In some embodiments of the peptides of formula (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X2 has the following structure: [ka] [In the formula, R n2 is hydrogen or C 1-3 It is an alkyl group, where the alkyl group is one or more R X2a This may be substituted as appropriate; R X2 is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, C 2-6 Alkenil, C 2-6 Alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, -L X2 -heterocycloalkyl, -L X2-Cycloalkyl, -L X2 -aryl, or -L X2 -A heteroaryl, where the alkyl, heteroalkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl each contain one or more R X2a This may be substituted as appropriate; R X2’ is hydrogen or C 1-6 It is an alkyl group, where the alkyl group is one or more R X2a This may be substituted as appropriate; or, R n2 and R X2’ It forms a 5-6 member heterocycloalkyl group with the atoms in between, which consists of one or more R X2a This may be substituted as appropriate; L X2 C 1-6 Alkylene, C 1-6 Heteroalkylene, -O-, -S-, or -NR a -where the alkylene and heteroalkylene are one or more R X2a This may be substituted as appropriate; R X2a These are, independently, halogen and C 1-6 Alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, -CN, -NO2, -OR a , -SR a , -NR c R d -S(=O)R a -S(=O)2R a -SF5, -S(=O)2NR c R d -S(=O)(=NR a )R a -N=S(=O)R c R d , -NR a S(=O)2R a , amidinil, -NR a C(=NH)(NR a)2, -NR a S(=O)2NR c R d -C(=O)R a , -C(=O)OR a -OC(=O)R a , -OC(=O)OR a -OC(=O)NR c R d , -NR a C(=O)R a , -NR a C(=O)OR a , -NR a C(=O)NR c R d -C(=O)NR c R d , -P(=O)(OR c )(OR d ), -P(=O)R c R d aryl, heteroaryl, cycloalkyl, heterocycloalkyl, =O, =S, or =N(R a ) where the aryl, heteroaryl, cycloalkyl, heterocycloalkyl, alkyl, heteroalkyl, alkenyl, and alkynyl each consist of one or more R e This may be substituted as appropriate; *X1 represents a connection point to X1; *X3 represents the connection point to X3; Other groups (R a , R c , R d , and R e (etc.) have the meaning defined by formula (I). It holds.

[0161] In some embodiments of the peptides of formula (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X2 has the following structure: [ka] [In the formula, R n2is hydrogen or methyl; R X2 is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, -L X2 -5-6 member heterocycloalkyl, -L X2 -C 4-6 Cycloalkyl, -L X2 -C 6-10 Aryl, or -L X2 -5 to 10 member heteroaryls, where each alkyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl is a heteroaryl compound with one or more R X2a This may be substituted as appropriate; R X2’ is hydrogen or methyl; or, R n2 and R X2’ It forms a 5-6 member heterocycloalkyl group with the atoms in between, which consists of one or more R X2a This may be substituted as appropriate; L X2 C 1-6 Alkylene or C 1-6 It is a heteroalkylene, where the alkylene and heteroalkylene are one or more R X2a This may be substituted as appropriate; R X2a These are, independently, halogen and C 1-6 Alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, -CN, -NO2, -OR a , -SR a , -NR c R d -S(=O)R a -S(=O)2R a -SF5, -S(=O)2NR c R d -S(=O)(=NRa )R a -N=S(=O)R c R d , -NR a S(=O)2R a , amidinil, -NR a C(=NH)(NR a )2, -NR a S(=O)2NR c R d -C(=O)R a , -C(=O)OR a -OC(=O)R a , -OC(=O)OR a -OC(=O)NR c R d , -NR a C(=O)R a , -NR a C(=O)OR a , -NR a C(=O)NR c R d -C(=O)NR c R d , -P(=O)(OR c )(OR d ), -P(=O)R c R d aryl, heteroaryl, cycloalkyl, heterocycloalkyl, =O, =S, or =N(R a ) where the alkyl, heteroalkyl, alkenyl, and alkynyl each have one or more R e This may be substituted as appropriate; *X1 represents a connection point to X1; *X3 represents the connection point to X3; Other groups (R a , R c , R d , and R e (etc.) have the meaning defined by formula (I). It holds.

[0162] In some embodiments, R n2 is hydrogen. In some embodiments, R n2 C 1-3It is alkyl. In some embodiments, R n2 It is methyl.

[0163] In some embodiments, R X2 is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, C 2-6 Alkenil, C 2-6 Alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, -L X2 -heterocycloalkyl, -L X2 -Cycloalkyl, -L X2 -aryl, or -L X2 -A heteroaryl, where the alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl each contain one or more R X2a This may be substituted as appropriate.

[0164] In some embodiments, R X2 is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, -L X2 -5-6 member heterocycloalkyl, -L X2 -C 4-6 Cycloalkyl, -L X2 -C 6-10 Aryl, or -L X2 -5 to 10 member heteroaryls, where each alkyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl is a heteroaryl compound with one or more R X2a This may be replaced as appropriate. In some embodiments, R X2 is hydrogen, C 1-6 Alkyl, C 1-6 Heteroalkyl, -L X2 -Piperidinil, LX2 -piperazinyl, -L X2 -phenyl, or -L X2 -Pyridinyl, where the alkyl, heteroalkyl, phenyl, pyridinyl, piperidinyl, and piperazinyl each consist of one or more R X2a This may be substituted as appropriate.

[0165] In some embodiments, R X2 is hydrogen. In some embodiments, R X2 C may be substituted as appropriate. 1-6 It is alkyl. In some embodiments, R X2 is one or more R X2a C may be replaced as appropriate. 1-6 It is alkyl. In some embodiments, R X2 C may be substituted as appropriate. 1-6 It is heteroalkyl. In some embodiments, R X2 is one or more R X2a C may be replaced as appropriate. 1-6 It is heteroalkyl. In some embodiments, R X2 C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, or C 1-6 They are heteroalkyl groups, and each of them has one or more R X2a This may be replaced as appropriate. In some embodiments, R X2 C 2-6 Alkenyl or C 2-6 These are alkynyls, and each of them is one or more R X2a This may be replaced as appropriate. In some embodiments, R X2 These are aryl, heteroaryl, cycloalkyl, or heterocycloalkyl, and each of these is one or more R X2a This may be replaced as appropriate. In some embodiments, R X2 These are aryl or heteroaryl compounds, each consisting of one or more R X2a This may be replaced as appropriate. In some embodiments, R X2These are cycloalkyl or heterocycloalkyl, and each of them has one or more R X2a This may be replaced as appropriate. In some embodiments, R X2 is, -L X2 -heterocycloalkyl, -L X2 -Cycloalkyl, -L X2 -aryl, or -L X2 - These are heteroaryls, each of which has one or more R X2a This may be replaced as appropriate. In some embodiments, R X2 is, -L X2 - It is a heterocycloalkyl, which is one or more R X2a This may be replaced as appropriate. In some embodiments, R X2 is, -L X2 - It is a cycloalkyl, which is one or more R X2a This may be replaced as appropriate. In some embodiments, R X2 is, -L X2 -It is an aryl, which is one or more R X2a This may be replaced as appropriate. In some embodiments, R X2 is, -L X2 -It is a heteroaryl compound, which is one or more R X2a This may be substituted as appropriate.

[0166] In some embodiments, R X2’ is hydrogen. In some embodiments, R X2’ C 1-6 It is an alkyl group, where the alkyl group is one or more R X2a This may be replaced as appropriate. In some embodiments, R X2’ C 1-6 It is alkyl. In some embodiments, R X2’ It is methyl.

[0167] In some embodiments, R n2 and R X2’ It forms a 5-6 member heterocycloalkyl group with the atoms in between, which consists of one or more R X2a This may be substituted as appropriate.

[0168] In some embodiments, L X2 C 1-6 It is an alkylene, where the alkylene is one or more R X2a This may be replaced as appropriate. In some embodiments, L X2 C 1-6 It is alkylene. X2 C 1-6 It is a heteroalkylene, where the heteroalkylene is one or more R X2a This may be replaced as appropriate. In some embodiments, L X2 C 1-6 It is a heteroalkylene. In some embodiments, L X2 is -O-. In some embodiments, L X2 is -S-. In some embodiments, L X2 -NR a - is. In some embodiments, L X2 It is -NH-.

[0169] In some embodiments, R X2a These are, independently, halogen and C 1-6 Alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, -CN, -NO2, -OR a , -SR a , -NR c R d -S(=O)R a -S(=O)2R a -S(=O)2NR c R d , -NR a S(=O)2R a , -NR a C(=NH)(NR a )2, -C(=O)R a , -C(=O)OR a -OC(=O)R a , -OC(=O)OR a -OC(=O)NR c R d , -NR a C(=O)Ra , -NR a C(=O)OR a , -NR a C(=O)NR c R d -C(=O)NR c R d , or = O, where the alkyl and heteroalkyl are each one or more R e This may be substituted as appropriate.

[0170] In some embodiments, R X2a These are, independently, halogen and C 1-6 Alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, -CN, -NO2, -OR a , -SR a , -NR c R d -S(=O)R a -S(=O)2R a -S(=O)2NR c R d , -NR a S(=O)2R a , -NR a C(=NH)(NR a )2, -C(=O)R a , -C(=O)OR a -OC(=O)R a , -OC(=O)OR a -OC(=O)NR c R d , -NR a C(=O)R a , -NR a C(=O)OR a , -NR a C(=O)NR c R d -C(=O)NR c R d , or = O, where the alkyl and heteroalkyl are each one or more R e This may be substituted as appropriate.

[0171] In some embodiments, R X2aEach of them is independent of C 1-6 Alkyl, C 1-6 Alkoxyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, OH, -CN, -NO2, NH2, -C(=O)R a , -C(=O)OR a , -NR a C(=O)NR c R d , or oxo.

[0172] In some embodiments, R n2 It is methyl, and R X2’ is hydrogen, and R X2 C 1-6 It is alkyl. In some embodiments, R n2 It is methyl, and R X2’ is hydrogen, and R X2 is branch C 1-6 It is alkyl. In some embodiments, R n2 It is methyl, and R X2’ is hydrogen, and R X2 is branch C 3-6 It is alkyl. In some embodiments, R X2 This is -CH(CH3)CH2CH3.

[0173] In some embodiments of formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X3 is a polar and / or L-amino acid. In some embodiments, X3 is an amino acid containing a hydrophilic side chain (e.g., D, K, Q, or variants thereof) or an N-methylated variant thereof. In some embodiments, X3 is absent.

[0174] In some embodiments of formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X3 is D, Har, KCOpipzetOH, Cit, KCOmeglumine, KCOpipzaa, A4paa, Q, A, E, MeD, S, N, Hgl, F4COO, KCOpip4COO, KAc, Hgn, MeY, or DapCOpipzaa. In some embodiments of formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X3 is D, Har, KCOpipzetOH, Cit, KCOmeglumine, KCOpipzaa, A4paa, Q, A, E, MeD, S, N, Hgl, F4COO, KCOpip4COO, KAc, Hgn, MeY, or DapCOpipzaa, each of which may be substituted as appropriate. In some embodiments, X3 is D, which may be substituted as appropriate. In some embodiments, X3 is Har, which may be substituted as appropriate. In some embodiments, X3 is KCOpipzetOH, which may be substituted as appropriate. In some embodiments, X3 is Cit, which may be substituted as appropriate. In some embodiments, X3 is KCOmeglumine, which may be substituted as appropriate. In some embodiments, X3 is KCOpipzaa, which may be substituted as appropriate. In some embodiments, X3 may be A4paa as appropriate. In some embodiments, X3 may be Q as appropriate. In some embodiments, X3 may be A as appropriate. In some embodiments, X3 may be E as appropriate. In some embodiments, X3 may be MeD as appropriate. In some embodiments, X3 may be S as appropriate. In some embodiments, X3 may be N as appropriate. In some embodiments, X3 may be Hgl as appropriate. In some embodiments, X3 may be F4COO as appropriate. In some embodiments, X3 may be KCOpip4COO as appropriate. In some embodiments, X3 may be KAc as appropriate. In some embodiments, X3 may be Hgn as appropriate.In some embodiments, X3 is MeY, which may be substituted as appropriate. In some embodiments, X3 is DapCOpipzaa, which may be substituted as appropriate.

[0175] In some embodiments of peptides of formula (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X3 is any amino acid. In some embodiments, X3 is a D-amino acid. In some embodiments, X3 is an L-amino acid. In some embodiments, X3 is an N-alkylated amino acid. In some embodiments, X3 is an N-methylated amino acid. In some embodiments, X3 does not contain a ring group. In some embodiments, X3 contains a ring group. In some embodiments, X3 contains a 5-6 member heterocycloalkyl group. In some embodiments, X3 contains a 5-6 member heteroaryl group. In some embodiments, X3 contains a phenyl group. In some embodiments, X3 is a peptoid. In some embodiments, X3 is a polar amino acid.

[0176] In some embodiments of the peptides of formula (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X3 has the following structure: [ka] [In the formula, R n3 is hydrogen or C 1-3 It is an alkyl group, where the alkyl group is one or more R X3a This may be substituted as appropriate; R X3 is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, C 2-6 Alkenil, C 2-6Alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, -L X3 -heterocycloalkyl, -L X3 -Cycloalkyl, -L X3 -aryl, or -L X3 -A heteroaryl, where the alkyl, heteroalkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl each contain one or more R X3a This may be substituted as appropriate; R X3’ is hydrogen or C 1-6 It is an alkyl group, where the alkyl group is one or more R X3a This may be substituted as appropriate; or, R n3 and R X3’ It forms a 5-6 member heterocycloalkyl group with the atoms in between, which consists of one or more R X3a This may be substituted as appropriate; L X3 C 1-6 Alkylene, C 1-6 Heteroalkylene, -O-, -S-, or -NR a -where the alkylene and heteroalkylene are one or more R X3a This may be substituted as appropriate; R X3a These are, independently, halogen and C 1-6 Alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, -CN, -NO2, -OR a , -SR a , -NR c R d -S(=O)R a -S(=O)2R a -SF5, -S(=O)2NR c R d -S(=O)(=NR a )R a -N=S(=O)R c R d, -NR a S(=O)2R a , amidinil, -NR a C(=NH)(NR a )2, -NR a S(=O)2NR c R d -C(=O)R a , -C(=O)OR a -OC(=O)R a , -OC(=O)OR a -OC(=O)NR c R d , -NR a C(=O)R a , -NR a C(=O)OR a , -NR a C(=O)NR c R d -C(=O)NR c R d , -P(=O)(OR c )(OR d ), -P(=O)R c R d aryl, heteroaryl, cycloalkyl, heterocycloalkyl, =O, =S, or =N(R a ) where the aryl, heteroaryl, cycloalkyl, heterocycloalkyl, alkyl, heteroalkyl, alkenyl, and alkynyl each consist of one or more R e This may be substituted as appropriate; *X2 represents the connection point to X2; *X4 represents the connection point to X4; Other groups (R a , R c , R d , and R e (etc.) have the meaning defined by formula (I). It holds.

[0177] In some embodiments of the peptides of formula (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X3 has the following structure: [ka] [In the formula, R n3 is hydrogen or methyl; R X3 C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, -L X3 -5-6 member heterocycloalkyl, -L X3 -C 3-6 Cycloalkyl, -L X3 -C 6-10 Aryl, or -L X3 -5 to 10 member heteroaryls, where each alkyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl is a heteroaryl compound with one or more R X3a This may be substituted as appropriate; L X3 C 1-6 Alkylene or C 1-6 It is a heteroalkylene, where the alkylene and heteroalkylene are one or more R X3a This may be substituted as appropriate; R X3a These are, independently, halogen and C 1-6 Alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, -CN, -NO2, -OR a , -SR a , -NR c R d -S(=O)R a -S(=O)2R a -SF5, -S(=O)2NR c R d -S(=O)(=NR a )R a -N=S(=O)R c R d , -NR a S(=O)2R a, amidinil, -NR a C(=NH)(NR a )2, -NR a S(=O)2NR c R d -C(=O)R a , -C(=O)OR a -OC(=O)R a , -OC(=O)OR a -OC(=O)NR c R d , -NR a C(=O)R a , -NR a C(=O)OR a , -NR a C(=O)NR c R d -C(=O)NR c R d , -P(=O)(OR c )(OR d ), -P(=O)R c R d aryl, heteroaryl, cycloalkyl, heterocycloalkyl, =O, =S, or =N(R a ) where the aryl, heteroaryl, cycloalkyl, heterocycloalkyl, alkyl, heteroalkyl, alkenyl, and alkynyl each consist of one or more R e This may be substituted as appropriate; *X2 represents the connection point to X2; *X4 represents the connection point to X4; Other groups (R a , R c , R d , and R e (etc.) have the meaning defined by formula (I). It holds.

[0178] In some embodiments, R n3 is hydrogen. In some embodiments, R n3 C 1-3 It is alkyl. In some embodiments, R n3 It is methyl.

[0179] In some embodiments, R X3 is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, C 2-6 Alkenil, C 2-6 Alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, -L X3 -heterocycloalkyl, -L X3 -Cycloalkyl, -L X3 -aryl, or -L X3 -A heteroaryl, where the alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl each contain one or more R X3a This may be replaced as appropriate. In some embodiments, R X3 C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, -L X3 -5-6 member heterocycloalkyl, -L X3 -C 3-6 Cycloalkyl, -L X3 -C 6-10 Aryl, or -L X3 -5 to 10 member heteroaryls, where each alkyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl is a heteroaryl compound with one or more R X3a This may be substituted as appropriate.

[0180] In some embodiments, R X3 is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, -L X3 -5-6 member heterocycloalkyl, -L X3-C 4-6 Cycloalkyl, -L X3 -C 6-10 Aryl, or -L X3 -5 to 10 member heteroaryls, where each alkyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl is a heteroaryl compound with one or more R X3a This may be replaced as appropriate. In some embodiments, R X3 is hydrogen, C 1-6 Alkyl, C 1-6 Heteroalkyl, -L X3 -Piperidinil, L X3 -piperazinyl, -L X3 -phenyl, or -L X3 -Pyridinyl, where the alkyl, heteroalkyl, phenyl, pyridinyl, piperidinyl, and piperazinyl each consist of one or more R X3a This may be substituted as appropriate.

[0181] In some embodiments, R X3 is hydrogen. In some embodiments, R X3 C may be substituted as appropriate. 1-6 It is alkyl. In some embodiments, R X3 is one or more R X3a C may be replaced as appropriate. 1-6 It is alkyl. In some embodiments, R X3 C may be substituted as appropriate. 1-6 It is heteroalkyl. In some embodiments, R X3 is one or more R X3a C may be replaced as appropriate. 1-6 It is heteroalkyl. In some embodiments, R X3 C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, or C 1-6 They are heteroalkyl groups, and each of them has one or more R X3a This may be replaced as appropriate. In some embodiments, R X3 C 2-6Alkenyl or C 2-6 These are alkynyls, and each of them is one or more R X3a This may be replaced as appropriate. In some embodiments, R X3 These are aryl, heteroaryl, cycloalkyl, or heterocycloalkyl, and each of these is one or more R X3a This may be replaced as appropriate. In some embodiments, R X3 These are aryl or heteroaryl compounds, each consisting of one or more R X3a This may be replaced as appropriate. In some embodiments, R X3 These are cycloalkyl or heterocycloalkyl, and each of them has one or more R X3a This may be replaced as appropriate. In some embodiments, R X3 is, -L X3 -heterocycloalkyl, -L X3 -Cycloalkyl, -L X3 -aryl, or -L X3 - These are heteroaryls, each of which has one or more R X3a This may be replaced as appropriate. In some embodiments, R X3 is, -L X3 - It is a heterocycloalkyl, which is one or more R X3a This may be replaced as appropriate. In some embodiments, R X3 is, -L X3 - It is a cycloalkyl, which is one or more R X3a This may be replaced as appropriate. In some embodiments, R X3 is, -L X3 -It is an aryl, which is one or more R X3a This may be replaced as appropriate. In some embodiments, R X3 is, -L X3 -It is a heteroaryl compound, which is one or more R X3a This may be substituted as appropriate.

[0182] In some embodiments, R X3’ is hydrogen. In some embodiments, R X3’ C 1-6 It is an alkyl group, where the alkyl group is one or more RX3a This may be replaced as appropriate. In some embodiments, R X3’ C 1-6 It is alkyl. In some embodiments, R X3’ It is methyl.

[0183] In some embodiments, R n3 and R X3’ It forms a 5-6 member heterocycloalkyl group with the atoms in between, which consists of one or more R X3a This may be substituted as appropriate.

[0184] In some embodiments, L X3 C 1-6 It is an alkylene, where the alkylene is one or more R X3a This may be replaced as appropriate. In some embodiments, L X3 C 1-6 It is alkylene. X3 C 1-6 It is a heteroalkylene, where the heteroalkylene is one or more R X3a This may be replaced as appropriate. In some embodiments, L X3 C 1-6 It is a heteroalkylene. In some embodiments, L X3 is -O-. In some embodiments, L X3 is -S-. In some embodiments, L X3 -NR a - is. In some embodiments, L X3 It is -NH-.

[0185] In some embodiments, R X3a These are, independently, halogen and C 1-6 Alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, -CN, -NO2, -OR a , -SR a , -NR c R d -S(=O)R a-S(=O)2R a -S(=O)2NR c R d , -NR a S(=O)2R a , -NR a C(=NH)(NR a )2, -C(=O)R a , -C(=O)OR a -OC(=O)R a , -OC(=O)OR a -OC(=O)NR c R d , -NR a C(=O)R a , -NR a C(=O)OR a , -NR a C(=O)NR c R d -C(=O)NR c R d , or = O, where the alkyl and heteroalkyl are each one or more R e This may be substituted as appropriate.

[0186] In some embodiments, R X3a These are, independently, halogen and C 1-6 Alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, -CN, -NO2, -OR a , -SR a , -NR c R d -S(=O)R a -S(=O)2R a -S(=O)2NR c R d , -NR a S(=O)2R a , -NR a C(=NH)(NR a )2, -C(=O)R a , -C(=O)OR a -OC(=O)R a , -OC(=O)OR a -OC(=O)NR c R d , -NRa C(=O)R a , -NR a C(=O)OR a , -NR a C(=O)NR c R d -C(=O)NR c R d , or = O, where the alkyl and heteroalkyl are each one or more R e This may be substituted as appropriate.

[0187] In some embodiments, R X3a Each of them is independent of C 1-6 Alkyl, C 1-6 Alkoxyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, OH, -CN, -NO2, NH2, -C(=O)R a , -C(=O)OR a , -NR a C(=O)NR c R d , or oxo.

[0188] In some embodiments, R n3 is hydrogen, R X3’ is hydrogen, and R X3 is one or more R X3a C may be replaced as appropriate. 1-6 It is alkyl. In some embodiments, R n3 is hydrogen, R X3’ is hydrogen, and R X3 is one or more R X3a C may be replaced as appropriate. 1-3 It is alkyl. In some embodiments, R n3 is hydrogen, R X3’ is hydrogen, and R X3 C is substituted with -COOH. 1-3 It is alkyl.

[0189] In some embodiments of formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X4 is a polar and / or L-amino acid. In some embodiments, X4 is an N-methylated amino acid, a polar amino acid (e.g., D, K, Q, S, or variants thereof), or a peptoid (e.g., EtG, MeeG, CmG, CmpG, CrmG, CeG, or CrpG).

[0190] In some embodiments of formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X4 is D, Har, KCOpipzetOH, KCOmeglumine, KCOpipzaa, A4paa, Q, A, E, MeD, S, N, Hgl, F4COO, KCOpip4COO, dd, MeQ, MeQdMe, MeA, MeSMe, MeG, EtG, MeeG, CmG, CmpG, CrmG, CeG, CrpG, MeK, MeKAc, MeHgl, Hgn, MeDapCOpipzaa, MeKCOpipzaa, Medid, Cit, MeCit, MeN, MeS, MeE, MeY, W5N, or MeA4paa. In some embodiments of formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X4 is D, Har, KCOpipzetOH, KCOmeglumine, KCOpipzaa, A4paa, Q, A, E, MeD, S, N, Hgl, F4COO, KCOpip4COO, dd, MeQ, MeQdMe, MeA, MeSMe, MeG, EtG, MeeG, CmG, CmpG, CrmG, CeG, CrpG, MeK, MeKAc, MeHgl, Hgn, MeDapCOpipzaa, MeKCOpipzaa, Medid, Cit, MeCit, MeN, MeS, MeE, MeY, W5N, or MeA4paa, each of which may be substituted as appropriate. In some embodiments, X4 may be replaced with D as appropriate. In some embodiments, X4 may be replaced with Har as appropriate. In some embodiments, X4 may be replaced with KCOpipzetOH as appropriate. In some embodiments, X4 may be replaced with KCOmeglumine as appropriate. In some embodiments, X4 may be replaced with KCOpipzaa as appropriate. In some embodiments, X4 may be replaced with A4paa as appropriate. In some embodiments, X4 may be replaced with Q as appropriate. In some embodiments, X4 may be replaced with A as appropriate. In some embodiments, X4 may be replaced with E as appropriate. In some embodiments, X4 may be replaced with MeD as appropriate.In some embodiments, X4 may be replaced with S as appropriate. In some embodiments, X4 may be replaced with N as appropriate. In some embodiments, X4 may be replaced with Hgl as appropriate. In some embodiments, X4 may be replaced with F4COO as appropriate. In some embodiments, X4 may be replaced with KCOpip4COO as appropriate. In some embodiments, X4 may be replaced with dd as appropriate. In some embodiments, X4 may be replaced with MeQ as appropriate. In some embodiments, X4 may be replaced with MeQdMe as appropriate. In some embodiments, X4 may be replaced with MeA as appropriate. In some embodiments, X4 may be replaced with MeSMe as appropriate. In some embodiments, X4 may be replaced with MeG as appropriate. In some embodiments, X4 may be replaced with EtG as appropriate. In some embodiments, X4 may be replaced with MeeG as appropriate. In some embodiments, X4 may be replaced with CmG as appropriate. In some embodiments, X4 may be replaced with CmpG as appropriate. In some embodiments, X4 may be replaced with CrmG as appropriate. In some embodiments, X4 is CeG, which may be substituted as appropriate. In some embodiments, X4 is CrpG, which may be substituted as appropriate. In some embodiments, X4 is MeK, which may be substituted as appropriate. In some embodiments, X4 is MeKAc, which may be substituted as appropriate. In some embodiments, X4 is MeHgl, which may be substituted as appropriate. In some embodiments, X4 is Hgn, which may be substituted as appropriate. In some embodiments, X4 is MeDapCOpipzaa, which may be substituted as appropriate. In some embodiments, X4 is MeKCOpipzaa, which may be substituted as appropriate. In some embodiments, X4 is Medd, which may be substituted as appropriate. In some embodiments, X4 is Cit, which may be substituted as appropriate. In some embodiments, X4 is MeCit, which may be substituted as appropriate. In some embodiments, X4 is MeN, which may be substituted as appropriate. In some embodiments, X4 is MeS, which may be substituted as appropriate. In some embodiments, X4 is MeE, which may be substituted as appropriate. In some embodiments, X4 is MeY, which may be substituted as appropriate.In some embodiments, X4 is W5N, which may be substituted as appropriate. In some embodiments, X4 is MeA4paa, which may be substituted as appropriate.

[0191] In some embodiments of peptides of formula (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X4 is any amino acid. In some embodiments, X4 is a D-amino acid. In some embodiments, X4 is an L-amino acid. In some embodiments, X4 is an N-alkylated amino acid. In some embodiments, X4 is an N-methylated amino acid. In some embodiments, X4 does not contain a ring group. In some embodiments, X4 contains a ring group. In some embodiments, X4 contains a 5-6 member heterocycloalkyl group. In some embodiments, X4 contains a 5-6 member heteroaryl group. In some embodiments, X4 contains a phenyl group. In some embodiments, X4 is a peptoid. In some embodiments, X4 is a polar amino acid.

[0192] In some embodiments of the peptides of formula (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X4 has the following structure: [ka] [In the formula, R n4 is hydrogen or C 1-3 It is an alkyl group, where the alkyl group is one or more R X4a This may be substituted as appropriate; R X4 is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, C 2-6 Alkenil, C 2-6 Alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, -LX4 -heterocycloalkyl, -L X4 -Cycloalkyl, -L X4 -aryl, or -L X4 -A heteroaryl, where the alkyl, heteroalkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl each contain one or more R X4a This may be substituted as appropriate; R X4’ is hydrogen or C 1-6 It is an alkyl group, where the alkyl group is one or more R X4a This may be substituted as appropriate; or, R n4 and R X4’ It forms a 5-6 member heterocycloalkyl group with the atoms in between, which consists of one or more R X4a This may be substituted as appropriate; L X4 C 1-6 Alkylene or C 1-6 Heteroalkylene, -O-, -S-, or -NR a -where the alkylene and heteroalkylene are one or more R X4a This may be substituted as appropriate; R X4a These are, independently, halogen and C 1-6 Alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, -CN, -NO2, -OR a , -SR a , -NR c R d -S(=O)R a -S(=O)2R a -SF5, -S(=O)2NR c R d -S(=O)(=NR a )R a -N=S(=O)R c R d , -NR a S(=O)2R a, amidinil, -NR a C(=NH)(NR a )2, -NR a S(=O)2NR c R d -C(=O)R a , -C(=O)OR a -OC(=O)R a , -OC(=O)OR a -OC(=O)NR c R d , -NR a C(=O)R a , -NR a C(=O)OR a , -NR a C(=O)NR c R d -C(=O)NR c R d , -P(=O)(OR c )(OR d ), -P(=O)R c R d aryl, heteroaryl, cycloalkyl, heterocycloalkyl, =O, =S, or =N(R a ) where the aryl, heteroaryl, cycloalkyl, heterocycloalkyl, alkyl, heteroalkyl, alkenyl, and alkynyl each consist of one or more R e This may be substituted as appropriate; *X3 represents the connection point to X3; *X5 represents the connection point to X5; Other groups (R a , R c , R d , and R e (etc.) have the meaning defined by formula (I). It holds.

[0193] In some embodiments of the peptides of formula (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X4 has the following structure: [ka] [In the formula, R n4 is hydrogen or C 1-3 It is an alkyl group, where the alkyl group is one or more R X4a This may be substituted as appropriate; R X4 is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, -L X4 -5-6 member heterocycloalkyl, -L X4 -C 3-6 Cycloalkyl, -L X4 -C 6-10 Aryl, or -L X4 -5 to 10 member heteroaryls, where each alkyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl is a heteroaryl compound with one or more R X4a This may be substituted as appropriate; L X4 C 1-6 Alkylene or C 1-6 It is a heteroalkylene, where the alkylene and heteroalkylene are one or more R X4a This may be substituted as appropriate; R X4a These are, independently, halogen and C 1-6 Alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, -CN, -NO2, -OR a , -SR a , -NR c R d -S(=O)R a -S(=O)2R a -SF5, -S(=O)2NR c R d -S(=O)(=NR a )R a -N=S(=O)R c R d , -NRa S(=O)2R a , amidinil, -NR a C(=NH)(NR a )2, -NR a S(=O)2NR c R d -C(=O)R a , -C(=O)OR a -OC(=O)R a , -OC(=O)OR a -OC(=O)NR c R d , -NR a C(=O)R a , -NR a C(=O)OR a , -NR a C(=O)NR c R d -C(=O)NR c R d , -P(=O)(OR c )(OR d ), -P(=O)R c R d aryl, heteroaryl, cycloalkyl, heterocycloalkyl, =O, =S, or =N(R a ) where the aryl, heteroaryl, cycloalkyl, heterocycloalkyl, alkyl, heteroalkyl, alkenyl, and alkynyl each consist of one or more R e This may be substituted as appropriate; *X3 represents the connection point to X3; *X5 represents the connection point to X5; Other groups (R a , R c , R d , and R e (etc.) have the meaning defined by formula (I). It holds.

[0194] In some embodiments, R n4 is hydrogen. In some embodiments, R n4 C 1-3 It is alkyl. In some embodiments, R n4 It is methyl.

[0195] In some embodiments, R X4 is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, C 2-6 Alkenil, C 2-6 Alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, -L X4 -heterocycloalkyl, -L X4 -Cycloalkyl, -L X4 -aryl, or -L X4 -A heteroaryl, where the alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl each contain one or more R X4a This may be replaced as appropriate. In some embodiments, R X4 C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, -L X4 -5-6 member heterocycloalkyl, -L X4 -C 3-6 Cycloalkyl, -L X4 -C 6-10 Aryl, or -L X4 -5 to 10 member heteroaryls, where each alkyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl is a heteroaryl compound with one or more R X4a This may be substituted as appropriate.

[0196] In some embodiments, R X4 is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, -L X4-5-6 member heterocycloalkyl, -L X4 -C 4-6 Cycloalkyl, -L X4 -C 6-10 Aryl, or -L X4 -5 to 10 member heteroaryls, where each alkyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl is a heteroaryl compound with one or more R X4a This may be replaced as appropriate. In some embodiments, R X4 is hydrogen, C 1-6 Alkyl, C 1-6 Heteroalkyl, -L X4 -Piperidinil, L X4 -piperazinyl, -L X4 -phenyl, or -L X4 -Pyridinyl, where the alkyl, heteroalkyl, phenyl, pyridinyl, piperidinyl, and piperazinyl each consist of one or more R X4a This may be substituted as appropriate.

[0197] In some embodiments, R X4 is hydrogen. In some embodiments, R X4 C may be substituted as appropriate. 1-6 It is alkyl. In some embodiments, R X4 is one or more R X4a C may be replaced as appropriate. 1-6 It is alkyl. In some embodiments, R X4 C may be substituted as appropriate. 1-6 It is heteroalkyl. In some embodiments, R X4 is one or more R X4a C may be replaced as appropriate. 1-6 It is heteroalkyl. In some embodiments, R X4 C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, or C 1-6 They are heteroalkyl groups, and each of them has one or more R X4aThis may be replaced as appropriate. In some embodiments, R X4 C 2-6 Alkenyl or C 2-6 These are alkynyls, and each of them is one or more R X4a This may be replaced as appropriate. In some embodiments, R X4 These are aryl, heteroaryl, cycloalkyl, or heterocycloalkyl, and each of these is one or more R X4a This may be replaced as appropriate. In some embodiments, R X4 These are aryl or heteroaryl compounds, each consisting of one or more R X4a This may be replaced as appropriate. In some embodiments, R X4 These are cycloalkyl or heterocycloalkyl, and each of them has one or more R X4a This may be replaced as appropriate. In some embodiments, R X4 is, -L X4 -heterocycloalkyl, -L X4 -Cycloalkyl, -L X4 -aryl, or -L X4 - These are heteroaryls, each of which has one or more R X4a This may be replaced as appropriate. In some embodiments, R X4 is, -L X4 - It is a heterocycloalkyl, which is one or more R X4a This may be replaced as appropriate. In some embodiments, R X4 is, -L X4 - It is a cycloalkyl, which is one or more R X4a This may be replaced as appropriate. In some embodiments, R X4 is, -L X4 -It is an aryl, which is one or more R X4a This may be replaced as appropriate. In some embodiments, R X4 is, -L X4 -It is a heteroaryl compound, which is one or more R X4a This may be substituted as appropriate.

[0198] In some embodiments, R X4’ is hydrogen. In some embodiments, RX4’ C 1-6 It is an alkyl group, where the alkyl group is one or more R X4a This may be replaced as appropriate. In some embodiments, R X4’ C 1-6 It is alkyl. In some embodiments, R X4’ It is methyl.

[0199] In some embodiments, R n4 and R X4’ It forms a 5-6 member heterocycloalkyl group with the atoms in between, which consists of one or more R X4a This may be substituted as appropriate.

[0200] In some embodiments, L X4 C 1-6 It is an alkylene, where the alkylene is one or more R X4a This may be replaced as appropriate. In some embodiments, L X4 C 1-6 It is alkylene. X4 C 1-6 It is a heteroalkylene, where the heteroalkylene is one or more R X4a This may be replaced as appropriate. In some embodiments, L X4 C 1-6 It is a heteroalkylene. In some embodiments, L X4 is -O-. In some embodiments, L X4 is -S-. In some embodiments, L X4 -NR a - is. In some embodiments, L X4 It is -NH-.

[0201] In some embodiments, R X4a These are, independently, halogen and C 1-6 Alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, -CN, -NO2, -OR a , -SR a , -NRc R d -S(=O)R a -S(=O)2R a -S(=O)2NR c R d , -NR a S(=O)2R a , -NR a C(=NH)(NR a )2, -C(=O)R a , -C(=O)OR a -OC(=O)R a , -OC(=O)OR a -OC(=O)NR c R d , -NR a C(=O)R a , -NR a C(=O)OR a , -NR a C(=O)NR c R d -C(=O)NR c R d , or = O, where the alkyl and heteroalkyl are each one or more R e This may be substituted as appropriate.

[0202] In some embodiments, R X4a These are, independently, halogen and C 1-6 Alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, -CN, -NO2, -OR a , -SR a , -NR c R d -S(=O)R a -S(=O)2R a -S(=O)2NR c R d , -NR a S(=O)2R a , -NR a C(=NH)(NR a )2, -C(=O)R a , -C(=O)OR a -OC(=O)R a , -OC(=O)ORa -OC(=O)NR c R d , -NR a C(=O)R a , -NR a C(=O)OR a , -NR a C(=O)NR c R d -C(=O)NR c R d , or = O, where the alkyl and heteroalkyl are each one or more R e This may be substituted as appropriate.

[0203] In some embodiments, R X4a Each of them is independent of C 1-6 Alkyl, C 1-6 Alkoxyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, OH, -CN, -NO2, NH2, -C(=O)R a , -C(=O)OR a , -NR a C(=O)NR c R d , or oxo. In some embodiments, R X4a These are, independently, halogen and C 1-6 Alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, -OR a -CN, -NO2, NH2, -C(=O)R a , -C(=O)OR a , -NR a C(=O)NR c R d , or oxo.

[0204] In some embodiments, R n4 It is methyl, and R X4’ is hydrogen, and R X4 is one or more R X4a C may be replaced as appropriate. 1-6 It is alkyl. In some embodiments, R n4 It is methyl, and R X4’ is hydrogen, and RX4 is one or more R X4a C may be replaced as appropriate. 1-3 It is alkyl. In some embodiments, R n4 It is methyl, and R X4’ is hydrogen, and R X4 C may be appropriately substituted with one or more -C(=O)NH2. 1-6 It is alkyl. In some embodiments, R n4 It is methyl, and R X4’ is hydrogen, and R X4 C is substituted with -C(=O)NH2. 1-3 It is alkyl.

[0205] In some embodiments of formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X5 has an aromatic side chain, such as F, Y, or variants thereof. In some embodiments, X5 is F, or a variant thereof including phenyl, pyridinyl, or naphthalyl, where phenyl, pyridinyl, or naphthalyl is a halogen, -C 1-3 Alkyl, -OH, -NH2, -CN, -C(=O)OH, -C(=O)NH2, -NHC(=O)CH3, -C 1-3 Alkylene -C(=O)OH, -C 1-3 Alkylene -C(=O)NH2, -OC 1-3 Alkylene -C(=O)OH, -OC 1-3 Alkylene -C(=O)NH2, -C 1-3 Alkylene-C(=O)-5~6 member heterocycloalkylene-C 1-3 Alkylene -C(=O)OH, -OC 1-3 Alkylene-C(=O)-5~6 member heterocycloalkylene-C 1-3 Alkylene -C(=O)OH, -C 1-3 Alkylene-NHC(=O)-5~6 member heterocycloalkylene-C 1-3 Alkylene -C(=O)OH, -OC 1-3 Alkylene-NHC(=O)-5~6 member heterocycloalkylene-C 1-3Alkylene-C(=O)OH and -NH-C 1-3 The alkylene-C(=O)OH may be appropriately substituted with one or more substituents independently selected from each. In some embodiments, X5 is Y, or a variant thereof containing hydroxyphenyl, where the hydrogen atom in the hydroxyphenyl of Y or the variant is -C 1-3 Alkyl, , and -C 1-3 It may be appropriately substituted with one or more substituents selected from alkylene-C(=O)OH.

[0206] In some embodiments of formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X5 is Y, F3G, 3Py6COO, 4Py2NH2, 3Py5COO, F3COO, 3Py6NHAc, F, F4C, F4OMe, F4COO, Nal2, F3aao, F4aa ,F4aao,3Py6NHaa,5Pdo,F3CON,F4F,F4OEt,F4Me,F4CON,F4CONPEG4Me,F3OMe,F3CON,YaeCOpipzaa,F4aaopipzaa,4Pdo,3Py6CON,Atp,Cha4cH,Cha4tH,Cha4cOMe,A1mor, or F4amCOpipzaa. In some embodiments of formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X5 is Y, F3G, 3Py6COO, 4Py2NH2, 3Py5COO, F3COO, 3Py6NHAc, F, F4C, F4OMe, F4COO, Nal2, F3aao, F4aa, F4aao, 3Py6N Haa, 5Pdo, F3CON, F4F, F4OEt, F4Me, F4CON, F4CONPEG4Me, F3OMe, F3CON, Yae, YaeCOpipzaa, F4aaopipzaa, 4Pdo, 3Py6CON, Atp, Cha4cH, Cha4tH, Cha4cOMe, A1mor, or F4amCOpipzaa, each of which may be substituted as appropriate. In some embodiments, X5 is Y, which may be substituted as appropriate. In some embodiments, X5 is F3G, which may be substituted as appropriate. In some embodiments, X5 is 3Py6COO, which may be substituted as appropriate. In some embodiments, X5 is 4Py2NH2, which may be substituted as appropriate. In some embodiments, X5 is 3Py5COO, which may be substituted as appropriate. In some embodiments, X5 is F3COO, which may be substituted as appropriate. In some embodiments, X5 is 3Py6NHAc, which may be substituted as appropriate. In some embodiments, X5 is F, which may be substituted as appropriate. In some embodiments, X5 is F4C, which may be substituted as appropriate. In some embodiments, X5 is F4OMe, which may be substituted as appropriate.In some embodiments, X5 may be replaced with F4COO as appropriate. In some embodiments, X5 may be replaced with Nal2 as appropriate. In some embodiments, X5 may be replaced with F3aao as appropriate. In some embodiments, X5 may be replaced with F4aa as appropriate. In some embodiments, X5 may be replaced with F4aao as appropriate. In some embodiments, X5 may be replaced with 3Py6NHaa as appropriate. In some embodiments, X5 may be replaced with 5Pdo as appropriate. In some embodiments, X5 may be replaced with F3CON as appropriate. In some embodiments, X5 may be replaced with F4F as appropriate. In some embodiments, X5 may be replaced with F4OEt as appropriate. In some embodiments, X5 may be replaced with F4Me as appropriate. In some embodiments, X5 may be replaced with F4CON as appropriate. In some embodiments, X5 may be replaced with F4CONPEG4Me as appropriate. In some embodiments, X5 may be replaced with F3OMe as appropriate. In some embodiments, X5 may be replaced with F3CON as appropriate. In some embodiments, X5 may be Yae, which may be substituted as appropriate. In some embodiments, X5 may be YaeCOpipzaa, which may be substituted as appropriate. In some embodiments, X5 may be F4aaopipzaa, which may be substituted as appropriate. In some embodiments, X5 may be 4Pdo, which may be substituted as appropriate. In some embodiments, X5 may be 3Py6CON, which may be substituted as appropriate. In some embodiments, X5 may be Atp, which may be substituted as appropriate. In some embodiments, X5 may be Cha4cH, which may be substituted as appropriate. In some embodiments, X5 may be Cha4tH, which may be substituted as appropriate. In some embodiments, X5 may be Cha4cOMe, which may be substituted as appropriate. In some embodiments, X5 may be A1mor, which may be substituted as appropriate. In some embodiments, X5 may be F4amCOpipzaa, which may be substituted as appropriate.

[0207] In some embodiments of peptides of formula (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X5 is any amino acid. In some embodiments, X5 is a D-amino acid. In some embodiments, X5 is an L-amino acid. In some embodiments, X5 is an N-alkylated amino acid. In some embodiments, X5 is an N-methylated amino acid. In some embodiments, X5 does not contain a ring group. In some embodiments, X5 contains a ring group. In some embodiments, X5 contains a 5-6 member heterocycloalkyl group. In some embodiments, X5 contains a 5-6 member heteroaryl group. In some embodiments, X5 contains a phenyl group. In some embodiments, X5 is a peptoid.

[0208] In some embodiments of the peptides of formula (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X5 has the following structure: [ka] [In the formula, R n5 is hydrogen or C 1-3 It is alkyl; Ring A5 is aryl, heteroaryl, cycloalkyl, or heterocycloalkyl; R X5 Each of them is independent of C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, C 2-6 Alkenil, C 2-6 Alkinyl, halogen, -CN, -NO2, -OR a , -SR a -SF5, -NR c R d -S(=O)R a -S(=O)2R a -S(=O)2NRc R d -S(=O)(=NR a )R a -N=S(=O)NR c R d , -NR a S(=O)2R a , amidinil, -NR a C(=NH)NR c R d , -NR a S(=O)2NR c R d -C(=O)R a , -C(=O)OR a -OC(=O)R a , -OC(=O)OR a -OC(=O)NR c R d , -NR a C(=O)R a , -NR a C(=O)OR a , -NR a C(=O)NR c R d -C(=O)NR c R d , -P(=O)(OR c )(OR d ), -P(=O)R c R d aryl, heteroaryl, cycloalkyl, heterocycloalkyl, -L X5 -heterocycloalkyl, -L X5 -Cycloalkyl, -L X5 -aryl, or -L X5 -A heteroaryl, where the alkyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl are one or more R X5a This may be substituted as appropriate; or, Two R's X5 Together, =O, =S, or =N(R a ) form; L X5 C 1-6 Alkylene, C 1-6Heteroalkylene, -O-, -S-, or -NR a -where the alkylene and heteroalkylene are one or more R X5a This may be substituted as appropriate; kx5 is 0, 1, 2, or 3; mx5 is 0, 1, 2, 3, 4, or 5; *X4 represents the connection point to X4; *X6 represents the connection point to X6; Other groups (R a , R c , R d , and R e (etc.) have the meaning defined by formula (I). It holds.

[0209] In some embodiments of the peptides of formula (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), R n5 is hydrogen or methyl; Ring A5 is C 6-10 Aryl, 5-10 member heteroaryl, C 6-10 They are cycloalkyl or 5-10 member heterocycloalkyl; R X5 Each of them is independent of C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, C 2-6 Alkenil, C 2-6 Alkinyl, halogen, -CN, -NO2, -OR a , -SR a -SF5, -NR c R d -S(=O)R a -S(=O)2R a -S(=O)2NR c R d -S(=O)(=NR a )R a -N=S(=O)NRc R d , -NR a S(=O)2R a , amidinil, -NR a C(=NH)NR c R d , -NR a S(=O)2NR c R d -C(=O)R a , -C(=O)OR a -OC(=O)R a , -OC(=O)OR a -OC(=O)NR c R d , -NR a C(=O)R a , -NR a C(=O)OR a , -NR a C(=O)NR c R d -C(=O)NR c R d , -P(=O)(OR c )(OR d ), -P(=O)R c R d , C 6-10 Aryl, 5-10 member heteroaryl, C 3-6 Cycloalkyl, 5-6 member heterocycloalkyl, -L X5 -5-6 member heterocycloalkyl, -L X5 -C 3-6 Cycloalkyl, -L X5 -C 6-10 Aryl, or -L X5 -5 to 10 member heteroaryls, where the alkyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl are one or more R X5a This may be substituted as appropriate; or, Two R's X5 Together, they form =O; L X5 C 1-6 Alkylene or C 1-6 It is a heteroalkylene, where the alkylene and heteroalkylene are one or more RX5a This may be substituted as appropriate.

[0210] In some embodiments of the peptides of formula (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), Ring A5 is phenyl, naphthyl, pyridinyl, cyclohexyl, piperidinyl, piperazinyl, morpholinyl, or tetrahydropyranyl; R X5 These are, independently, halogen and C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, -CN, -NO2, -OR a , -SR a , -NR c R d -S(=O)R a -S(=O)2R a -S(=O)2NR c R d , -NR a S(=O)2R a , -NR a C(=NH)NR c R d , -NR a S(=O)2NR c R d -C(=O)R a , -C(=O)OR a -OC(=O)R a , -OC(=O)OR a -OC(=O)NR c R d , -NR a C(=O)R a , -NR a C(=O)OR a , -NR a C(=O)NR c R d -C(=O)NR c R d , -L X5 -Piperidinil, or L X5-Piperadinyl, where the alkyl, heteroalkyl, piperidinyl, and piperadinyl each consist of one or more R X5a This may be substituted as appropriate; or, Two R's X5 Together, they form =O; kx5 is either 1 or 2; mx5 is 0, 1, or 2.

[0211] In some embodiments, R n5 is hydrogen. In some embodiments, R n5 C 1-3 It is alkyl. In some embodiments, R n5 It is methyl.

[0212] In some embodiments, ring A5 is C 6-10 Aryl, 5-10 member heteroaryl, C 3-10 It is a cycloalkyl or a 3- to 10-membered heterocycloalkyl. In some embodiments, ring A5 is C 6-10 Aryl, 5-10 member heteroaryl, C 6-10 It is a cycloalkyl or a 5-10 member heterocycloalkyl. In some embodiments, ring A5 is phenyl, naphthyl, pyridinyl, cyclohexyl, piperidinyl, piperazinyl, morpholinyl, or tetrahydropyranil. In some embodiments, ring A5 is C 6-10 It is an aryl group. In some embodiments, ring A5 is phenyl. In some embodiments, ring A5 is naphthyl. In some embodiments, ring A5 is a 5-10 membered heteroaryl group. In some embodiments, ring A5 is a 6-10 membered heteroaryl group. In some embodiments, ring A5 is a 5-6 membered heteroaryl group. In some embodiments, ring A5 is pyridine. In some embodiments, ring A5 is pyridine. In some embodiments, ring A5 is C 3-10 It is a cycloalkyl. In some embodiments, ring A5 is C 5-10 It is a cycloalkyl. In some embodiments, ring A5 is C 5-6It is a cycloalkyl. In some embodiments, ring A5 is C 3-6 It is a cycloalkyl group. In some embodiments, ring A5 is cyclohexane. In some embodiments, ring A5 is a 3- to 10-membered heterocycloalkyl group. In some embodiments, ring A5 is a 5- to 6-membered heterocycloalkyl group. In some embodiments, ring A5 is tetrahydropyran. In some embodiments, ring A5 is morpholine.

[0213] In some embodiments, R X5 Each of them is independent of C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, C 2-6 Alkenil, C 2-6 Alkinyl, halogen, -CN, -NO2, -OR a , -SR a -SF5, -NR c R d -S(=O)R a -S(=O)2R a -S(=O)2NR c R d -S(=O)(=NR a )R a -N=S(=O)NR c R d , -NR a S(=O)2R a , amidinil, -NR a C(=NH)NR c R d , -NR a S(=O)2NR c R d -C(=O)R a , -C(=O)OR a -OC(=O)R a , -OC(=O)OR a -OC(=O)NR c R d , -NR a C(=O)R a , -NR a C(=O)OR a, -NR a C(=O)NR c R d -C(=O)NR c R d , -P(=O)(OR c )(OR d ), -P(=O)R c R d , C 6-10 Aryl, 5-10 member heteroaryl, C 3-6 Cycloalkyl, 5-6 member heterocycloalkyl, -L X5 -5-6 member heterocycloalkyl, -L X5 -C 3-6 Cycloalkyl, -L X5 -C 6-10 Aryl, or -L X5 -5 to 10 member heteroaryls, where the alkyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl are one or more R X5a This may be replaced as appropriate. In some embodiments, R X5 Each of them is independent of C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, C 2-6 Alkenil, C 2-6 Alkinyl, halogen, -CN, -NO2, -OR a , -SR a , -NR c R d , -NR a C(=NH)NR c R d , -NR a S(=O)2NR c R d -C(=O)R a , -C(=O)OR a -OC(=O)R a , -NR a C(=O)R a , -NR a C(=O)OR a -C(=O)NR c R d , C6-10 Aryl, 5-10 member heteroaryl, C 3-6 Cycloalkyl, 5-6 member heterocycloalkyl, -L X5 -5-6 member heterocycloalkyl, -L X5 -C 3-6 Cycloalkyl, -L X5 -C 6-10 Aryl, or -L X5 -5 to 10 member heteroaryls, where the alkyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl are one or more R X5a This may be replaced as appropriate. In some embodiments, R X5 These are, independently, halogen and C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, -CN, -NO2, -OR a , -SR a , -NR c R d -S(=O)R a -S(=O)2R a -S(=O)2NR c R d , -NR a S(=O)2R a , -NR a C(=NH)NR c R d , -NR a S(=O)2NR c R d -C(=O)R a , -C(=O)OR a -OC(=O)R a , -OC(=O)OR a -OC(=O)NR c R d , -NR a C(=O)R a , -NR a C(=O)OR a , -NR a C(=O)NR c R d -C(=O)NRc R d , -L X5 -Piperidinil, or L X5 -Piperadinyl, where the alkyl, heteroalkyl, piperidinyl, and piperadinyl each consist of one or more R X5a This may be substituted as appropriate.

[0214] In some embodiments, R X5a These are, independently, halogen and C 1-6 Alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, -CN, -NO2, -OR a , -SR a , -NR c R d -S(=O)R a -S(=O)2R a -S(=O)2NR c R d , -NR a S(=O)2R a , -NR a C(=NH)(NR a )2, -C(=O)R a , -C(=O)OR a -OC(=O)R a , -OC(=O)OR a -OC(=O)NR c R d , -NR a C(=O)R a , -NR a C(=O)OR a , -NR a C(=O)NR c R d -C(=O)NR c R d , or = O, where the alkyl and heteroalkyl are each one or more R e This may be substituted as appropriate.

[0215] In some embodiments, two R X5 Together, they form =O.

[0216] In some embodiments, kx5 is 0. In some embodiments, kx5 is 1. In some embodiments, kx5 is 2. In some embodiments, kx5 is 3.

[0217] In some embodiments, mx5 is 0. In some embodiments, mx5 is 1. In some embodiments, mx5 is 2. In some embodiments, mx5 is 3. In some embodiments, mx5 is 4. In some embodiments, mx5 is 5.

[0218] In some embodiments, Rn5 is hydrogen, kx5 is 1 or 2, mx5 is 0, 1 or 2, ring A5 is phenyl, and R X5 These are, independently, halogen and C 1-6 Alkyl, C 1-6 Haloalkyl, or -C(=O)OR a In some embodiments, Rn5 is hydrogen, kx5 is 1, mx5 is 1, ring A5 is phenyl, and R X5 This is -C(=O)OH.

[0219] In some embodiments of formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X6 is an aliphatic amino acid (e.g., V, L, I, A, G, or variants thereof), a hydrophilic amino acid (e.g., D, E, or variants thereof), threonine (T), serine (S), O-methylthreonine (TMe), or methionine (M).

[0220] In some embodiments of formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X6 is I, V, Eva, Chg, Tbg, A, L, Ahp, F4COO, Gcpr, Gcpe, alI, Cle, S3REt, TMe, Acpr, Cba, Gthp, NleCOO, NleOH, P, Atb, Nva, Nle, N, DapAc, Abu, Nmm, Ndm, Ncit, Cit, SMe, HseMe, HseEt, HseiPr, dMeS, TdMe, Cbg, NvaOMe, SiPr, Spr, NleOMe, Sbu, Scbm, Scpe, AhpOMe, HseBu, Spent, or Hsecpe. In some embodiments of formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X6 is I, V, Eva, Chg, Tbg, A, L, Ahp, F4COO, Gcpr, Gcpe, alI, Cle, S3REt, TMe, Acpr, Cba, Gthp, NleCOO, NleOH, P, Atb, Nva, Nle, N, DapAc, Abu, Nmm, Ndm, Ncit, Cit, SMe, HseMe, HseEt, HseiPr, dMeS, TdMe, Cbg, NvaOMe, SiPr, Spr, NleOMe, Sbu, Scbm, Scpe, AhpOMe, HseBu, Spent, or Hsecpe, each of which may be substituted as appropriate. In some embodiments, X6 may be I, which may be substituted as appropriate. In some embodiments, X6 may be V, which may be substituted as appropriate. In some embodiments, X6 may be Eva, which may be substituted as appropriate. In some embodiments, X6 may be Chg, which may be substituted as appropriate. In some embodiments, X6 may be Tbg, which may be substituted as appropriate. In some embodiments, X6 may be A, which may be substituted as appropriate. In some embodiments, X6 may be L, which may be substituted as appropriate. In some embodiments, X6 may be Ahp, which may be substituted as appropriate. In some embodiments, X6 may be F4COO, which may be substituted as appropriate. In some embodiments, X6 may be replaced with Gcpr as appropriate. In some embodiments, X6 may be replaced with Gcpe as appropriate.In some embodiments, X6 may be replaced with alI as appropriate. In some embodiments, X6 may be replaced with Cle as appropriate. In some embodiments, X6 may be replaced with S3REt as appropriate. In some embodiments, X6 may be replaced with TMe as appropriate. In some embodiments, X6 may be replaced with Acpr as appropriate. In some embodiments, X6 may be replaced with Cba as appropriate. In some embodiments, X6 may be replaced with Gthp as appropriate. In some embodiments, X6 may be replaced with NleCOO as appropriate. In some embodiments, X6 may be replaced with NleOH as appropriate. In some embodiments, X6 may be replaced with P as appropriate. In some embodiments, X6 may be replaced with Atb as appropriate. In some embodiments, X6 may be replaced with Nva as appropriate. In some embodiments, X6 may be replaced with Nle as appropriate. In some embodiments, X6 may be replaced with N as appropriate. In some embodiments, X6 may be replaced with N as appropriate. In some embodiments, X6 may be replaced with DapAc as appropriate. In some embodiments, X6 may be replaced with Abu as appropriate. In some embodiments, X6 may be replaced with Nmm as appropriate. In some embodiments, X6 may be replaced with Ndm as appropriate. In some embodiments, X6 may be replaced with Ncit as appropriate. In some embodiments, X6 may be replaced with Cit as appropriate. In some embodiments, X6 may be replaced with SMe as appropriate. In some embodiments, X6 may be replaced with HseMe as appropriate. In some embodiments, X6 may be replaced with HseEt as appropriate. In some embodiments, X6 may be replaced with HseiPr as appropriate. In some embodiments, X6 may be replaced with dMeS as appropriate. In some embodiments, X6 may be replaced with TdMe as appropriate. In some embodiments, X6 may be replaced with Cbg as appropriate. In some embodiments, X6 may be replaced with NvaOMe as appropriate. In some embodiments, X6 may be replaced with SiPr as appropriate. In some embodiments, X6 may be replaced with Spr as appropriate. In some embodiments, X6 may be replaced with NleOMe as appropriate.In some embodiments, X6 may be replaced with Sbu as appropriate. In some embodiments, X6 may be replaced with Scbm as appropriate. In some embodiments, X6 may be replaced with Scpe as appropriate. In some embodiments, X6 may be replaced with AhpOMe as appropriate. In some embodiments, X6 may be replaced with HseBu as appropriate. In some embodiments, X6 may be replaced with Spent as appropriate. In some embodiments, X6 may be replaced with Hsecpe as appropriate.

[0221] In some embodiments of peptides of formula (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X6 is any amino acid. In some embodiments, X6 is a D-amino acid. In some embodiments, X6 is an L-amino acid. In some embodiments, X6 is an N-alkylated amino acid. In some embodiments, X6 is an N-methylated amino acid. In some embodiments, X6 does not contain a ring group. In some embodiments, X6 contains a ring group. In some embodiments, X6 contains a 5-6 member heterocycloalkyl group. In some embodiments, X6 contains a 5-6 member heteroaryl group. In some embodiments, X6 contains a phenyl group. In some embodiments, X6 is a peptoid.

[0222] In some embodiments of the peptides of formula (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X6 has the following structure: [ka] [In the formula, R n6 is hydrogen or C 1-3 It is alkyl; R X6 Independently, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6Aminoalkyl, C 1-6 Heteroalkyl, C 2-6 Alkenil, C 2-6 Alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, -L X6 -heterocycloalkyl, -L X6 -Cycloalkyl, -L X6 -aryl, or -L X6 -A heteroaryl, where the alkyl, heteroalkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl each contain one or more R X6a This may be substituted as appropriate; or, R n6 and R x6 It forms a 5-6 member heterocycloalkyl group with the atoms in between, which consists of one or more R X6a This may be substituted as appropriate; L X6 C 1-6 Alkylene, C 1-6 Heteroalkylene, O, S, or NR a Here, the alkylene and heteroalkylene are one or more R X6a This may be substituted as appropriate; *X5 represents the connection point to X5; *X7 represents the connection point to X7; Other groups (R a , R c , R d , and R e (etc.) have the meaning defined by formula (I). It holds.

[0223] In some embodiments of the peptides of formula (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), R n6 is hydrogen or methyl; R X6 C 1-6 Alkyl, C 1-6 Haloalkyl, C1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 6-10 Aryl, 5-10 member heteroaryl, C 3-6 Cycloalkyl, 5-6 member heterocycloalkyl, -L X6 -5-6 member heterocycloalkyl, -L X6 -C 3-6 Cycloalkyl, -L X6 -C 6-10 Aryl, or -L X6 -5 to 10 member heteroaryls, where each alkyl, heteroalkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl is a single R X6a This may be substituted as appropriate; L X6 C 1-6 Alkylene or C 1-6 It is a heteroalkylene, where the alkylene and heteroalkylene are one or more R X6a This may be substituted as appropriate.

[0224] In some embodiments, R n6 is hydrogen. In some embodiments, R n6 C 1-3 It is alkyl. In some embodiments, R n6 It is methyl.

[0225] In some embodiments, R X6 C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, C 3-6 Cycloalkyl, 5-6 member heterocycloalkyl, -L X6 -5-6 member heterocycloalkyl, -L X6 -C 3-6 Cycloalkyl, -L X6-phenyl, or -L X6 - A 6-membered heteroaryl, where the alkyl, heteroalkyl, phenyl, heteroaryl, cycloalkyl, and heterocycloalkyl each contain one or more R X6a This may be substituted as appropriate.

[0226] In some embodiments, R X6 C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, -L X6 -5-6 member heterocycloalkyl, -L X6 -C 3-6 Cycloalkyl, -L X6 -C 6-10 Aryl, or -L X6 -5 to 10 member heteroaryls, where each alkyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl is a heteroaryl compound with one or more R X6a This may be substituted as appropriate.

[0227] In some embodiments, R X6 C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, -L X6 -5-6 member heterocycloalkyl, -L X6 -C 4-6 Cycloalkyl, -L X6 -C 6-10 Aryl, or -L X6 -5 to 10 member heteroaryls, where each alkyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl is a heteroaryl compound with one or more R X6a This may be replaced as appropriate. In some embodiments, R X6 C 1-6 Alkyl, C 1-6Heteroalkyl, 6-L X6 -phenyl, or -L X6 -Pyridinyl, where the alkyl, heteroalkyl, phenyl, and pyridinyl are each one or more R X6a This may be substituted as appropriate.

[0228] In some embodiments, R X6 C may be substituted as appropriate. 1-6 It is alkyl. In some embodiments, R X6 is one or more R X6a C may be replaced as appropriate. 1-6 It is alkyl. In some embodiments, R X6 C may be substituted as appropriate. 1-6 It is heteroalkyl. In some embodiments, R X6 is one or more R X6a C may be replaced as appropriate. 1-6 It is heteroalkyl. In some embodiments, R X6 C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, or C 1-6 They are heteroalkyl groups, and each of them has one or more R X6a This may be replaced as appropriate. In some embodiments, R X6 C 2-6 Alkenyl or C 2-6 These are alkynyls, and each of them is one or more R X6a This may be replaced as appropriate. In some embodiments, R X6 These are aryl, heteroaryl, cycloalkyl, or heterocycloalkyl, and each of these is one or more R X6a This may be replaced as appropriate. In some embodiments, R X6 These are aryl or heteroaryl compounds, each consisting of one or more R X6a This may be replaced as appropriate. In some embodiments, R X6 These are cycloalkyl or heterocycloalkyl, and each of them has one or more R X6aThis may be replaced as appropriate. In some embodiments, R X6 C 3-6 It is a cycloalkyl group, which is one or more R X6a This may be replaced as appropriate. In some embodiments, R X6 is, -L X6 -heterocycloalkyl, -L X6 -Cycloalkyl, -L X6 -aryl, or -L X6 - These are heteroaryls, each of which has one or more R X6a This may be replaced as appropriate. In some embodiments, R X6 is, -L X6 - It is a heterocycloalkyl, which is one or more R X6a This may be replaced as appropriate. In some embodiments, R X6 is, -L X6 - It is a cycloalkyl, which is one or more R X6a This may be replaced as appropriate. In some embodiments, R X6 is, -L X6 -It is an aryl, which is one or more R X6a This may be replaced as appropriate. In some embodiments, R X6 is, -L X6 -It is a heteroaryl compound, which is one or more R X6a This may be substituted as appropriate.

[0229] In some embodiments, R n6 and R x6 It forms a 5-6 member heterocycloalkyl group with the atoms in between, which consists of one or more R X6a This may be substituted as appropriate.

[0230] In some embodiments, R X6a These are, independently, halogen and C 1-6 Alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, -CN, -NO2, -OR a , -SR a , -NR c R d -S(=O)Ra -S(=O)2R a -S(=O)2NR c R d , -NR a S(=O)2R a , -NR a C(=NH)(NR a )2, -C(=O)R a , -C(=O)OR a -OC(=O)R a , -OC(=O)OR a -OC(=O)NR c R d , -NR a C(=O)R a , -NR a C(=O)OR a , -NR a C(=O)NR c R d -C(=O)NR c R d , or = O, where the alkyl and heteroalkyl are each one or more R e This may be substituted as appropriate.

[0231] In some embodiments, R n6 is hydrogen, and R X6 C 1-6 It is alkyl, and this is one or more R X6a This may be replaced as appropriate. In some embodiments, R X6a These are, independently, halogen and C 1-6 Alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, or -OR a In some embodiments, R X6a These are, independently, halogen or -OC. 1-6 It is alkyl. In some embodiments, R X6a is -O-CH3. In some embodiments, R X6 It is -CH(CH3)OCH3.

[0232] In some embodiments of formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X7 is a branched alkyl side chain, C 3-5 The amino acid is an amino acid containing a cycloalkyl side chain or a 3- to 5-membered heterocycloalkyl side chain, or an N-methylated variant thereof. In some embodiments, the branched alkyl side chain contains 3 to 5 carbon atoms. In some embodiments, the alkyl, cycloalkyl, or heterocycloalkyl side chain may be appropriately substituted with -O-C1-C6 alkyl.

[0233] In some embodiments of formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X7 is I, Eva, alI, TMe, SMe, Gcpr, Gcpe, Gthp, dMeS, TdMe, or Cbg. In some embodiments of formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X7 is I, Eva, alI, TMe, SMe, Gcpr, Gcpe, Gthp, dMeS, TdMe, or Cbg, each of which may be substituted as appropriate. In some embodiments, X7 is I, which may be substituted as appropriate. In some embodiments, X7 may be replaced with Eva as appropriate. In some embodiments, X7 may be replaced with alI as appropriate. In some embodiments, X7 may be replaced with TMe as appropriate. In some embodiments, X7 may be replaced with SMe as appropriate. In some embodiments, X7 may be replaced with Gcpr as appropriate. In some embodiments, X7 may be replaced with Gcpe as appropriate. In some embodiments, X7 may be replaced with Gthp as appropriate. In some embodiments, X7 may be replaced with dMeS as appropriate. In some embodiments, X7 may be replaced with TdMe as appropriate. In some embodiments, X7 may be replaced with Cbg as appropriate.

[0234] In some embodiments of peptides of formula (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X7 is any amino acid. In some embodiments, X7 is a D-amino acid. In some embodiments, X7 is an L-amino acid. In some embodiments, X7 is an N-alkylated amino acid. In some embodiments, X7 is an N-methylated amino acid. In some embodiments, X7 does not contain a ring group. In some embodiments, X7 contains a ring group. In some embodiments, X7 contains a 5-6 member heterocycloalkyl group. In some embodiments, X7 contains a 5-6 member heteroaryl group. In some embodiments, X7 contains a phenyl group. In some embodiments, X7 is a peptoid.

[0235] In some embodiments of the peptides of formula (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X7 has the following structure: [ka] [In the formula, R n7 is hydrogen or C 1-3 It is alkyl; R X7 C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, C 2-6 Alkenil, C 2-6 Alkynyl, cycloalkyl, or heterocycloalkyl, where each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, and heterocycloalkyl is one or more R X7a This may be substituted as appropriate; *X6 represents the connection point to X6; *X8 represents the connection point to X8; Other groups (R a , Rc , R d , and R e (etc.) have the meaning defined by formula (I). It holds.

[0236] In some embodiments, R n7 R is hydrogen or methyl; X7 C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-6 A cycloalkyl or a 5-6 member heterocycloalkyl, where each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, and heterocycloalkyl is one or more R X7a This may be substituted as appropriate.

[0237] In some embodiments, R n7 is hydrogen. In some embodiments, R n7 C 1-3 It is alkyl. In some embodiments, R n7 It is methyl.

[0238] In some embodiments, R X7 C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-6 A cycloalkyl or a 5-6 member heterocycloalkyl, where each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, and heterocycloalkyl is one or more R X7a This may be replaced as appropriate. In some embodiments, R X7 C 1-6Alkyl, C 1-6 Heteroalkyl, C 3-6 A cycloalkyl or a 5-6 member heterocycloalkyl, where each alkyl, heteroalkyl, cycloalkyl, and heterocycloalkyl is one or more R X7a This may be replaced as appropriate. In some embodiments, R X7 C 1-6 It is alkyl, and this is one or more R X7a This may be replaced as appropriate. In some embodiments, R X7 C 1-6 It is alkyl. In some embodiments, R X7 is branch C 1-6 It is alkyl. In some embodiments, R X7 C 1-6 It is a heteroalkyl group, which is one or more R X7a This may be replaced as appropriate. In some embodiments, R X7 C 1-6 It is heteroalkyl. In some embodiments, R X7 C 3-6 It is a cycloalkyl group, which is one or more R X7a This may be replaced as appropriate. In some embodiments, R X7 C 3-6 It is cycloalkyl. In some embodiments, R X7 It is a 5-6 member heterocycloalkyl, which has one or more R X7a This may be replaced as appropriate. In some embodiments, R X7 It is a 5-6 member heterocycloalkyl group.

[0239] In some embodiments, R X7a These are, independently, halogen, -CN, and -OR. a , -SR a , -NR c R d -C(=O)R a , -C(=O)OR a -OC(=O)R a , -OC(=O)OR a -OC(=O)NR c R d, -NR a C(=O)R a , -NR a C(=O)OR a , -NR a C(=O)NR c R d -C(=O)NR c R d , or = O.

[0240] In some embodiments, R n7 is hydrogen, and R X7 C 1-6 It is alkyl, and this is one or more R X7a This may be replaced as appropriate. In some embodiments, R n7 is hydrogen, and R X7 C 1-6 It is alkyl. In some embodiments, R n7 is hydrogen, and R X7 C 3-6 It is alkyl. In some embodiments, R n7 is hydrogen, and R X7 is branch C 1-6 It is alkyl.

[0241] In some embodiments of formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X8 is Y, or a variant thereof comprising a hydroxyphenyl ring, where Y or the hydroxyphenyl ring of the variant is a halogen, -C 1-3 Alkyl, -OH, -C(=O)OH, -O-CH3, -C 1-3 Alkylene -C(=O)OH, -C 1-3 Alkylene-C(=O)-5~6 member heterocycloalkylene-C 1-3 Alkylene-C(=O)OH and -C 1-3 Alkylene-NHC(=O)-5~6 member heterocycloalkylene-C 1-3The alkylene-C(=O)OH may be appropriately substituted with one or more substituents selected from alkylene-C(=O)OH. In some embodiments of formula (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X8 is F, or a variant thereof comprising phenyl, pyridinyl, or indazolyl, where phenyl F of F or phenyl, pyridinyl, or indazolyl of the variant is a halogen, -C 1-3 alkyl, -OH, -C(=O)OH, -C(=O)NH2, -NHC(=O)NH2, -C 1-3 Alkylene-C(NH2)-COOH, -NH-CO-CH3, -NH-C 1-3 Alkylene -NH2, -C(=O)-N(CH2)2, -S(=O)2-CH3, -C 1-3 Alkylene-NH-C(=O)-5~6 member heterocycloalkylene-C 1-3 Alkylene -C(=O)OH and -OC 1- 3-alkylene-NH-C(=O)-5~6 member heterocycloalkylene-C 1-3 The alkylene-C(=O)OH group may be appropriately substituted with one or more substituents independently selected from each of them.

[0242] In some embodiments of formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X8 is Y, F4OMe, F4COO, F4OEt, F4u, F4Me, F4CONdMe, F4CON, F4ms, F4CONPEG4Me, F34dOMe, F3OMe, F3C, F3CON, F3CONdMe, 3Py6CON, Yae, YaeCOpipzaa, 5Inda, F3aao, F3aa, F4aao, F4aa, 3Py6Nhae, 3Py6NHAc, 3Py6OMe, F4aaopipzaa, or F4amCOpipzaa. In some embodiments of formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X8 is Y, F4OMe, F4COO, F4OEt, F4u, F4Me, F4CONdMe, F4CON, F4ms, F4CONPEG4Me, F34dOMe, F3OMe, F3C, F3CON, F3CONdMe, 3Py6CON, Yae, YaeCOpipzaa, 5Inda, F3aao, F3aa, F4aao, F4aa, 3Py6Nhae, 3Py6NHAc, 3Py6OMe, F4aaopipzaa, or F4amCOpipzaa, each of which may be substituted as appropriate. In some embodiments, X8 is Y, which may be substituted as appropriate. In some embodiments, X8 may be replaced with F4OMe as appropriate. In some embodiments, X8 may be replaced with F4COO as appropriate. In some embodiments, X8 may be replaced with F4OEt as appropriate. In some embodiments, X8 may be replaced with F4u as appropriate. In some embodiments, X8 may be replaced with F4Me as appropriate. In some embodiments, X8 may be replaced with F4CONdMe as appropriate. In some embodiments, X8 may be replaced with F4CON as appropriate. In some embodiments, X8 may be replaced with F4ms as appropriate. In some embodiments, X8 may be replaced with F4CONPEG4Me as appropriate. In some embodiments, X8 may be replaced with F34dOMe as appropriate. In some embodiments, X8 may be replaced with F3OMe as appropriate.In some embodiments, X8 may be replaced with F3C as appropriate. In some embodiments, X8 may be replaced with F3CON as appropriate. In some embodiments, X8 may be replaced with F3CONdMe as appropriate. In some embodiments, X8 may be replaced with 3Py6CON as appropriate. In some embodiments, X8 may be replaced with Yae as appropriate. In some embodiments, X8 may be replaced with YaeCOpipzaa as appropriate. In some embodiments, X8 may be replaced with 5Inda as appropriate. In some embodiments, X8 may be replaced with F3aao as appropriate. In some embodiments, X8 may be replaced with F3aa as appropriate. In some embodiments, X8 may be replaced with F4aao as appropriate. In some embodiments, X8 may be replaced with F4aa as appropriate. In some embodiments, X8 may be replaced with 3Py6Nhae as appropriate. In some embodiments, X8 may be replaced with 3Py6NHAc as appropriate. In some embodiments, X8 may be replaced with 3Py6OMe as appropriate. In some embodiments, X8 is F4aaopipzaa, which may be substituted as appropriate. In some embodiments, X8 is F4amCOpipzaa, which may be substituted as appropriate.

[0243] In some embodiments of formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X8 is A, I, L, or V. In some embodiments, X8 is A. In some embodiments, X8 is A or a derivative thereof. In some embodiments, X8 is I or a derivative thereof. In some embodiments, X8 is L or a derivative thereof. In some embodiments, X8 is V or a derivative thereof.

[0244] In some embodiments of peptides of formula (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X8 is any amino acid. In some embodiments, X8 is a D-amino acid. In some embodiments, X8 is an L-amino acid. In some embodiments, X8 is an aliphatic amino acid. In some embodiments, X8 is an N-alkylated amino acid. In some embodiments, X8 is an N-methylated amino acid. In some embodiments, X8 does not contain a ring group. In some embodiments, X8 contains a ring group. In some embodiments, X8 contains a 5-6 member heterocycloalkyl group. In some embodiments, X8 contains a 5-6 member heteroaryl group. In some embodiments, X8 contains a phenyl group. In some embodiments, X8 is a peptoid.

[0245] In some embodiments of the peptides of formula (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X8 has the following structure: [ka] [In the formula, R n8 is hydrogen or C 1-3 It is alkyl; Ring A8 is either an aryl or heteroaryl ring; R X8 These are, independently, halogen and C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, C 2-6 Alkenil, C 2-6 Alkinyl, -CN, -NO2, -OR a , -SR a -SF5, -NR c R d -S(=O)R a -S(=O)2R a -S(=O)2Rc R d -S(=O)(=NR a )R a -N=S(=O)R c R d , -NR a S(=O)2R a , amidinil, -NR a C(=NH)NR c R d , -NR a S(=O)2R c R d -C(=O)R a , -C(=O)OR a -OC(=O)R a , -OC(=O)OR a -OC(=O)NR c R d , -NR a C(=O)R a , -NR a C(=O)OR a , -NR a C(=O)NR c R d -C(=O)NR c R d , -P(=O)(OR c )(OR d ), -P(=O)R c R d aryl, heteroaryl, cycloalkyl, heterocycloalkyl, -L X8 -heterocycloalkyl, -L X8 -Cycloalkyl, -L X8 -aryl, or -L X8 -A heteroaryl, where the alkyl, heteroalkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl each contain one or more R X8a This may be substituted as appropriate; or, Two R's X8 Together, =O, =S, or =N(R a ) form; L X8 C 1-6 Alkylene, C 1-6Heteroalkylene, -O-, -S-, or -NR a -where the alkylene and heteroalkylene are one or more R X8a This may be substituted as appropriate; kx8 is 0, 1, 2, or 3; mx8 is 0, 1, 2, 3, 4, or 5; *X7 represents the connection point to X7; *X9 represents the connection point to X9; Other groups (R a , R c , R d , and R e (etc.) have the meaning defined by formula (I). It holds.

[0246] In some embodiments of the peptides of formula (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), Ring A8 is C 6-10 It is an aryl or a 5- to 10-membered heteroaryl; R X8 Each of them is independent of C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, C 2-6 Alkenil, C 2-6 Alkinyl, halogen, -CN, -NO2, -OR a , -SR a -SF5, -NR c R d -S(=O)R a -S(=O)2R a -S(=O)2R c R d -S(=O)(=NR a )R a -N=S(=O) R c R d , -NR a S(=O)2R a , amidinil, -NRa C(=NH)NR c R d , -NR a S(=O)2R c R d -C(=O)R a , -C(=O)OR a -OC(=O)R a , -OC(=O)OR a -OC(=O)NR c R d , -NR a C(=O)R a , -NR a C(=O)OR a , -NR a C(=O)NR c R d -C(=O)NR c R d , -P(=O)(OR c )(OR d ), -P(=O)R c R d , C 6-10 Aryl, 5-10 member heteroaryl, C 3-6 Cycloalkyl, 5-6 member heterocycloalkyl, -L X8 -5-6 member heterocycloalkyl, -L X8 -C 3-6 Cycloalkyl, -L X8 -C 6-10 Aryl, or -L X8 -5 to 10 member heteroaryls, where each alkyl, heteroalkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl is a single R X8a This may be substituted as appropriate; or, Two R's X8 Together, they form =O; L X8 C 1-6 Alkylene or C 1-6 It is a heteroalkylene, where the alkylene and heteroalkylene are one or more R X8a This may be substituted as appropriate.

[0247] In some embodiments of the peptides of formula (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), Ring A8 is phenyl, pyridinyl, indolyl, azaindolyl, indazolyl, or benzimidazolyl; R X8 These are, independently, halogen and C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, -CN, -NO2, -OR a , -SR a , -NR c R d -S(=O)R a -S(=O)2R a -S(=O)2NR c R d , -NR a S(=O)2R a , -NR a C(=NH)NR c R d , -NR a S(=O)2NR c R d -C(=O)R a , -C(=O)OR a -OC(=O)R a , -OC(=O)OR a -OC(=O)NR c R d , -NR a C(=O)R a , -NR a C(=O)OR a , -NR a C(=O)NR c R d -C(=O)NR c R d , -L X5 -Piperidinil, or L X5 -Piperadinyl, where the alkyl, heteroalkyl, piperidinyl, and piperadinyl each consist of one or more R X8aThis may be substituted as appropriate; or, Two R's X5 Together, they form =O; kx8 is either 1 or 2; mx8 is 0, 1, or 2.

[0248] In some embodiments, R n8 is hydrogen. In some embodiments, R n8 C 1-3 It is alkyl. In some embodiments, R n8 It is methyl.

[0249] In some embodiments, ring A8 is C 6-10 It is an aryl group. In some embodiments, ring A8 is phenyl. In some embodiments, ring A8 is naphthyl.

[0250] In some embodiments, ring A8 is a 5- to 10-membered heteroaryl. In some embodiments, ring A8 is a 5- to 6-membered heteroaryl. In some embodiments, ring A8 is a monocyclic heteroaryl. In some embodiments, ring A8 is a bicyclic heteroaryl. In some embodiments, ring A8 is a bicyclic condensed heteroaryl. In some embodiments, ring A8 is a bicyclic 5-6 or 6-5 condensed heteroaryl. In some embodiments, ring A8 is phenyl, pyridinyl, indolyl, azaindolyl, indazolyl, or benzimidazolyl.

[0251] In some embodiments, R X8 Each of them is independent of C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, C 2-6 Alkenil, C 2-6 Alkinyl, halogen, -CN, -NO2, -OR a , -SR a -SF5, -NR c R d-S(=O)R a -S(=O)2R a -S(=O)2R c R d -S(=O)(=NR a )R a -N=S(=O)R c R d , -NR a S(=O)2R a , amidinil, -NR a C(=NH)NR c R d , -NR a S(=O)2R c R d -C(=O)R a , -C(=O)OR a -OC(=O)R a , -OC(=O)OR a -OC(=O)NR c R d , -NR a C(=O)R a , -NR a C(=O)OR a , -NR a C(=O)NR c R d -C(=O)NR c R d , -P(=O)(OR c )(OR d ), -P(=O)R c R d , C 6-10 Aryl, 5-10 member heteroaryl, C 3-6 Cycloalkyl, 5-6 member heterocycloalkyl, -L X8 -5-6 member heterocycloalkyl, -L X8 -C 3-6 Cycloalkyl, -L X8 -C 6-10 Aryl, or -L X8 -5 to 10 member heteroaryls, where each alkyl, heteroalkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl is a single R X8a This may be substituted as appropriate.

[0252] In some embodiments, R X8 These are, independently, halogen and C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, -CN, -NO2, -OR a , -SR a , -NR c R d -S(=O)R a -S(=O)2R a -S(=O)2NR c R d , -NR a S(=O)2R a , -NR a C(=NH)NR c R d , -NR a S(=O)2NR c R d -C(=O)R a , -C(=O)OR a -OC(=O)R a , -OC(=O)OR a -OC(=O)NR c R d , -NR a C(=O)R a , -NR a C(=O)OR a , -NR a C(=O)NR c R d -C(=O)NR c R d , or -L X8 -5-6 member heterocycloalkyl (e.g., -L X8 -Piperidinil or L X8 -piperazinyl), where the alkyl, heteroalkyl, heterocycloalkyl (e.g., piperidinyl, and piperazinyl) is one or more R X8a This may be substituted as appropriate.

[0253] In some embodiments, R X8 Together, they form an oxoplasm.

[0254] In some embodiments, L X8 C 1-6 It is an alkylene, which is one or more R X8a This may be replaced as appropriate. In some embodiments, L X8 C 1-6 It is a heteroalkylene, which is one or more R X8a This may be replaced as appropriate. In some embodiments, L X8 is -O-. In some embodiments, L X8 is -S-. In some embodiments, L X8 -NR a - is

[0255] In some embodiments, kx8 is 0. In some embodiments, kx8 is 1. In some embodiments, kx8 is 2. In some embodiments, kx8 is 0 or 3.

[0256] In some embodiments, mx8 is 0. In some embodiments, mx8 is 1. In some embodiments, mx8 is 2. In some embodiments, mx8 is 3. In some embodiments, mx8 is 4. In some embodiments, mx8 is 5.

[0257] In some embodiments, R n8 is hydrogen, kx8 is 0, 1, or 2, mx8 is 0, 1, or 2, ring A8 is phenyl, R X8 These are, independently, halogen and C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, or -OR a Here, the alkyl or heteroalkyl is each one or more R X8a This may be replaced as appropriate. In some embodiments, R n8is hydrogen, kx8 is 1, mx8 is 1, ring A8 is phenyl, R X8 These are, independently, halogen and C 1-6 Alkyl, or -OR a Here, the alkyl or heteroalkyl is each one or more R X8a This may be replaced as appropriate. In some embodiments, R n8 is hydrogen, kx8 is 1, mx8 is 1, ring A8 is phenyl, R X8 These are, independently, halogen and C 1-6 It is alkyl or -OCH2C(=O)OH. In some embodiments, R n8 is hydrogen, kx8 is 1, mx8 is 1, ring A8 is phenyl, R X8 This is -OCH2C(=O)OH.

[0258] In some embodiments of formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X9 is an N-methyl aromatic amino acid, optionally a bicyclic aromatic amino acid. In some embodiments, X9 is an N-methyl amino acid containing phenyl or a monocyclic heteroaryl, which may be substituted as appropriate. In some embodiments, X9 is an N-methyl amino acid containing naphthalyl or a bicyclic heteroaryl, which may be substituted as appropriate. In some embodiments, the bicyclic heteroaryl is a 5-6, 6-6, or 6-5 condensed heteroaryl. In some embodiments, the heteroaryl contains 1 to 3 ring nitrogen atoms. In some embodiments, the heteroaryl contains 1 to 2 ring nitrogen atoms. In some embodiments, the heteroaryl contains 1 ring nitrogen atom. In some embodiments, the N-methyl aromatic amino acid is a halogen, -C 1-3 An N-methyl monocyclic aromatic amino acid comprising phenyl or pyridinyl, which may be appropriately substituted with one or more substituents independently selected from alkyl and trifluoromethyl groups. In some embodiments, the N-methyl aromatic amino acid is H or C1-3 These are N-methyl bicyclic aromatic amino acids comprising naphthalyl, quinolyl, or indazolyl, which may be optionally substituted with one or more substituents independently selected from the alkyl group.

[0259] In some embodiments of formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X9 is MeNal2, MeNal27N, MeF34diox, MeF34dOMe, MeF4T, MeY, MeW1Me, MeW7N, MeF3C4Me, or MeF3Me4C. In some embodiments of formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X9 is MeNal2, MeNal27N, MeF34diox, MeF34dOMe, MeF4T, MeY, MeW1Me, MeW7N, MeF3C4Me, or MeF3Me4C, each of which may be substituted as appropriate. In some embodiments, X9 is MeNal2, which may be substituted as appropriate. In some embodiments, X9 is MeNal27N, which may be substituted as appropriate. In some embodiments, X9 is MeF34diox, which may be substituted as appropriate. In some embodiments, X9 is MeF34dOMe, which may be substituted as appropriate. In some embodiments, X9 is MeF4T, which may be substituted as appropriate. In some embodiments, X9 is MeY, which may be substituted as appropriate. In some embodiments, X9 is MeW1Me, which may be substituted as appropriate. In some embodiments, X9 is MeW7N, which may be substituted as appropriate. In some embodiments, X9 is MeF3C4Me, which may be substituted as appropriate. In some embodiments, X9 is MeF3Me4C, which may be substituted as appropriate.

[0260] In some embodiments of peptides of formula (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X9 is a D-amino acid. In some embodiments of peptides of formula (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X9 is an L-amino acid. In some embodiments, X9 is an N-alkylated amino acid. In some embodiments, X9 is an N-methylated amino acid. In some embodiments, X9 contains a ring group. In some embodiments, X9 contains a 5-6 member heterocycloalkyl group. In some embodiments, X9 contains a 5-6 member heteroaryl group. In some embodiments, X9 contains a bicyclic heteroaryl group. In some embodiments, X9 contains a phenyl group. In some embodiments, X9 is a peptoid.

[0261] In some embodiments of the peptides of formula (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X9 has the following structure: [ka] [In the formula, R n9 is hydrogen or C 1-3 It is alkyl; Ring A9 is either aryl or heteroaryl; R X9 Each of them is independent of C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, C 2-6 Alkenil, C 2-6 Alkinyl, halogen, -CN, -NO2, -OR a , -SR a -SF5, or -NR c R dHere, the alkyl, heteroalkyl, alkenyl, and alkynyl each have one or more R X9a This may be substituted as appropriate; or, Two R's X9 Together, =O, =S, or =N(R a ) form; kx9 is 0, 1, 2, or 3; mx9 is 0, 1, 2, 3, 4, or 5; *X8 represents the connection point to X8; *X10 represents the connection point to X10; Other groups (R a , R c , R d , and R e (etc.) have the meaning defined by formula (I). It holds.

[0262] In some embodiments of the peptides of formula (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), R n9 is hydrogen or methyl; Ring A9 is C 6-10 It is an aryl or a 5- to 10-membered heteroaryl; R X9 These are, independently, halogen and C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, C 2-6 Alkenil, C 2-6 Alkinyl, -CN, -NO2, -OR a , -SR a -SF5, or -NR c R d Here, the alkyl, heteroalkyl, alkenyl, and alkynyl each have one or more R X9a This may be substituted as appropriate; or, Two R's X9 Together, they form =O.

[0263] In some embodiments of the peptides of formula (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), Ring A9 is phenyl, naphthyl, pyridinyl, indolyl, azaindolyl, indazolyl, benzimidazolyl, or isoquinolinyl; R X9 These are, independently, halogen and C 1-6 Alkyl, C 1-6 Haloalkyl, -CN, -OR a , -SR a , or -NR c R d Here, the alkyl and heteroalkyl are each one or more R X9a This may be substituted as appropriate; kx9 is either 1 or 2; mx9 is 0, 1, or 2.

[0264] In some embodiments, R n9 is hydrogen. In some embodiments, R n9 C 1-3 It is alkyl. In some embodiments, R n9 It is methyl.

[0265] In some embodiments, ring A9 is C 6-10 It is an aryl compound. In some embodiments, ring A9 is a 5- to 10-membered heteroaryl compound. In some embodiments, ring A9 is a monocyclic heteroaryl compound. In some embodiments, ring A9 is a bicyclic heteroaryl compound. In some embodiments, ring A9 is a bicyclic 6-6 condensed heteroaryl compound. In some embodiments, ring A9 is a bicyclic 6-5 or 5-6 condensed heteroaryl compound. In some embodiments, ring A9 is phenyl, naphthyl, pyridinyl, indolyl, azaindolyl, indazolyl, benzimidazolyl, or isoquinolinyl.

[0266] In some embodiments, R X9a These are, independently, halogen and C 1-6 Alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, -CN, -NO2, -OR a , -SR a , -NR c R d -S(=O)R a -S(=O)2R a -S(=O)2NR c R d , -NR a S(=O)2R a , -NR a C(=NH)(NR a )2, -C(=O)R a , -C(=O)OR a -OC(=O)R a , -OC(=O)OR a -OC(=O)NR c R d , -NR a C(=O)R a , -NR a C(=O)OR a , -NR a C(=O)NR c R d -C(=O)NR c R d , or = O, where the alkyl and heteroalkyl are each one or more R e This may be replaced as appropriate. In some embodiments, R X9 These are, independently, halogen and C 1-6 Alkyl, C 1-6 Haloalkyl, -CN, -OR a , -SR a , or -NR c R d Here, the alkyl and heteroalkyl are each one or more R X9a This may be substituted as appropriate.

[0267] In some embodiments, kx9 is 0. In some embodiments, kx9 is 1. In some embodiments, kx9 is 2. In some embodiments, kx9 is 3.

[0268] In some embodiments, mx9 is 0. In some embodiments, mx9 is 1. In some embodiments, mx9 is 2. In some embodiments, mx9 is 3. In some embodiments, mx9 is 4. In some embodiments, mx9 is 5.

[0269] In some embodiments, R n9 is methyl, kx9 is 1, and ring A9 is a bicyclic 6-6 condensed heteroaryl. In some embodiments, ring A9 is isoquinolinyl.

[0270] In some embodiments of formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X10 is G. In some embodiments, X10 is a D-amino acid (e.g., da, ds, de, or dp). In some embodiments, X10 is a D-amino acid selected from da, ds, de, and dp. In some embodiments, X10 is da.

[0271] In some embodiments of formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X11 is F or a variant thereof, or -C 1-6 It is an amino acid containing alkylene-phenyl. In some embodiments, F or its variant is F, or a variant thereof containing phenyl or heteroaryl (e.g., monocyclic or bicyclic), which may be substituted as appropriate. In some embodiments, F or its variant is F, or phenyl, -O-phenyl, -OC 1-3 Alkylene-phenyl, pyridinyl, imidazolyl, pyrazolyl, NC 1-3 Alkilen pyrazolyl, NC1-3 Alkylene (-OC) 1-3 Alkyl) pyrazolyl, pyranil, tetrahydropyranil, piperidinil, NC 1-3 This is a variant containing phenyl or pyridinyl, which may be appropriately substituted with one or more substituents independently selected from alkylene-C(=O)-piperidinyl.

[0272] In some embodiments of formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X11 is Bph, 3Py6Ph, F41Me4Pyz, F43Pyz, F44Pyz, F41Pyz, F41Me3Pyz, F41Et4Pyz, F41MeOe4Pyz, F41MeOp4Pyz, F44thp, F4Ac4pip, PhNva, PhNle, Yph, Ybn, F4tb, F4oPr, or F4CONdMe. In some embodiments of formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X11 is Bph, 3Py6Ph, F41Me4Pyz, F43Pyz, F44Pyz, F41Pyz, F41Me3Pyz, F41Et4Pyz, F41MeOe4Pyz, F41MeOp4Pyz, F44thp, F4Ac4pip, PhNva, PhNle, Yph, Ybn, F4tb, F4oPr, or F4CONdMe, each of which may be substituted as appropriate. In some embodiments, X11 is Bph, which may be substituted as appropriate. In some embodiments, X11 is 3Py6Ph, which may be substituted as appropriate. In some embodiments, X11 may be replaced with F41Me4Pyz as appropriate. In some embodiments, X11 may be replaced with F43Pyz as appropriate. In some embodiments, X11 may be replaced with F44Pyz as appropriate. In some embodiments, X11 may be replaced with F41Pyz as appropriate. In some embodiments, X11 may be replaced with F41Me3Pyz as appropriate. In some embodiments, X11 may be replaced with F41Et4Pyz as appropriate. In some embodiments, X11 may be replaced with F41MeOe4Pyz as appropriate. In some embodiments, X11 may be replaced with F41MeOp4Pyz as appropriate. In some embodiments, X11 may be replaced with F44thp as appropriate. In some embodiments, X11 may be replaced with F4Ac4pip as appropriate. In some embodiments, X11 may be replaced with PhNva as appropriate. In some embodiments, X11 may be replaced with PhNle as appropriate.In some embodiments, X11 may be Yph, which may be substituted as appropriate. In some embodiments, X11 may be Ybn, which may be substituted as appropriate. In some embodiments, X11 may be F4tb, which may be substituted as appropriate. In some embodiments, X11 may be F4oPr, which may be substituted as appropriate. In some embodiments, X11 may be F4CONdMe, which may be substituted as appropriate.

[0273] In some embodiments of peptides of formula (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X11 is any amino acid. In some embodiments, X11 is a D-amino acid. In some embodiments, X11 is an L-amino acid. In some embodiments, X11 is an N-alkylated amino acid. In some embodiments, X11 is an N-methylated amino acid. In some embodiments, X11 contains a ring group. In some embodiments, X11 contains a 5-6 member heterocycloalkyl group. In some embodiments, X11 contains a 5-6 member heteroaryl group. In some embodiments, X11 contains a bicyclic heteroaryl group. In some embodiments, X11 contains a phenyl group. In some embodiments, X11 is a peptoid.

[0274] In some embodiments of the peptides of formula (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X11 has the following structure: [ka] [In the formula, R n11 is hydrogen or C 1-3 It is alkyl; Ring A11 is either an aryl or heteroaryl ring; R X11 Each of them is independent of C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6Aminoalkyl, C 1-6 Heteroalkyl, halogen, -CN, -NO2, -OR a , -SR a -SF5, -NR c R d -S(=O)R a -S(=O)2R a -S(=O)2R c R d -S(=O)(=NR a )R a -N=S(=O)R c R d , -NR a S(=O)2R a , amidinil, -NR a C(=NH)NR c R d , -NR a S(=O)2R c R d -C(=O)R a , -C(=O)OR a -OC(=O)R a , -OC(=O)OR a -OC(=O)NR c R d , -NR a C(=O)R a , -NR a C(=O)OR a , -NR a C(=O)NR c R d -C(=O)NR c R d , -P(=O)(OR c )(OR d ), -P(=O)R c R d aryl, heteroaryl, cycloalkyl, heterocycloalkyl, -L X11 -heterocycloalkyl, -L X11 -Cycloalkyl, -L X11 -aryl, or -L X11 -A heteroaryl, where the alkyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl each contain one or more R X11a This may be substituted as appropriate; or, Two R's X11 Together, =O, =S, or =N(R a ) form; L X11 C 1-6 Alkylene, C 1-6 Heteroalkylene, -O-, -S-, or -NR a -where the alkylene and heteroalkylene are one or more R X11a This may be substituted as appropriate; kx11 is 0, 1, 2, 3, 4, or 5; mx11 is 0, 1, 2, 3, 4, or 5; *X10 represents the connection point to X10; *X12 represents a connection point to X12, or *X12 is N(R 2 This represents the connection point to (for example, in equations (I-1) and (I-2)); Other groups (R a , R c , R d , and R e (etc.) have the meaning defined by formula (I). It holds.

[0275] In some embodiments of the peptides of formula (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), Ring A11 is C 6-10 It is an aryl or a 5- to 10-membered heteroaryl; R X11 Each of them is independent of C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, halogen, -CN, -NO2, -OR a , -SR a -SF5, -NR c R d -S(=O)R a -S(=O)2Ra -S(=O)2R c R d -S(=O)(=NR a )R a -N=S(=O)R c R d , -NR a S(=O)2R a , amidinil, -NR a C(=NH)NR c R d , -NR a S(=O)2R c R d -C(=O)R a , -C(=O)OR a -OC(=O)R a , -OC(=O)OR a -OC(=O)NR c R d , -NR a C(=O)R a , -NR a C(=O)OR a , -NR a C(=O)NR c R d -C(=O)NR c R d , -P(=O)(OR c )(OR d ), -P(=O)R c R d , C 6-10 Aryl, 5-10 member heteroaryl, C 3-6 Cycloalkyl, 5-6 member heterocycloalkyl, -L X11 -5-6 member heterocycloalkyl, -L X11 -C 3-6 Cycloalkyl, -L X11 -C 6-10 Aryl, or -L X11 -5 to 10 member heteroaryls, where each alkyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl is a heteroaryl compound with one or more R X11a This may be substituted as appropriate; or, Two R's X11 Together, they form =O; L X11 C 1-6 Alkylene, C 1-6 A heteroalkylene, or -O-, where the alkylene and heteroalkylene are one or more R X11a This may be substituted as appropriate.

[0276] In some embodiments of the peptides of formula (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), Ring A11 is phenyl or pyridinyl; R X11 Each of them is independent of C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, halogen, -CN, -NO2, -OR a , -SR a , -NR c R d -S(=O)R a -S(=O)2R a -S(=O)2R c R d , -NR a S(=O)2R a , -NR a C(=NH)NR c R d , -NR a S(=O)2R c R d -C(=O)R a , -C(=O)OR a -OC(=O)R a , -OC(=O)OR a -OC(=O)NR c R d , -NR a C(=O)R a , -NR a C(=O)OR a , -NR a C(=O)NR c R d -C(=O)NR c Rd , C 6-10 Aryl, 5-10 member heteroaryl, C 3-6 Cycloalkyl, 5-6 member heterocycloalkyl, -L X11 -5-6 member heterocycloalkyl, -L X11 -C 3-6 Cycloalkyl, -L X11 -C 6-10 Aryl, or -L X11 -5 to 10 member heteroaryls, where each alkyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl is a heteroaryl compound with one or more R X11a This may be substituted as appropriate; or, Two R's X11 Together, they form =O; kx11 is 1, 2, 3, or 4; mx11 is 0, 1, or 2.

[0277] In some embodiments, R n11 is hydrogen. In some embodiments, R n11 C 1-3 It is alkyl. In some embodiments, R n11 It is methyl.

[0278] In some embodiments, A11 is C 6-10 It is an aryl compound. In some embodiments, A11 is phenyl. In some embodiments, A11 is a 5- to 10-membered heteroaryl compound. In some embodiments, A11 is a 5- to 6-membered heteroaryl compound. In some embodiments, A11 is a monocyclic heteroaryl compound. In some embodiments, A11 is a bicyclic heteroaryl compound.

[0279] In some embodiments, R X11 Each of them is independent of C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6Heteroalkyl, halogen, -CN, -NO2, -OR a , -SR a -SF5, -NR c R d -S(=O)R a -S(=O)2R a -S(=O)2R c R d -S(=O)(=NR a )R a -N=S(=O)R c R d , -NR a S(=O)2R a , amidinil, -NR a C(=NH)NR c R d , -NR a S(=O)2R c R d -C(=O)R a , -C(=O)OR a -OC(=O)R a , -OC(=O)OR a -OC(=O)NR c R d , -NR a C(=O)R a , -NR a C(=O)OR a , -NR a C(=O)NR c R d -C(=O)NR c R d , -P(=O)(OR c )(OR d ), -P(=O)R c R d , C 6-10 Aryl, 5-10 member heteroaryl, C 3-6 Cycloalkyl, 5-6 member heterocycloalkyl, -L X11 -5-6 member heterocycloalkyl, -L X11 -C 3-6 Cycloalkyl, -L X11 -C 6-10 Aryl, or -L X11-5 to 10 member heteroaryls, where each alkyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl is a heteroaryl compound with one or more R X11a This may be substituted as appropriate.

[0280] In some embodiments, R X11 Each of them is independent of C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, halogen, -CN, -NO2, -OR a , -SR a , -NR c R d -S(=O)R a -S(=O)2R a -S(=O)2R c R d , -NR a S(=O)2R a , -NR a C(=NH)NR c R d , -NR a S(=O)2R c R d -C(=O)R a , -C(=O)OR a -OC(=O)R a , -OC(=O)OR a -OC(=O)NR c R d , -NR a C(=O)R a , -NR a C(=O)OR a , -NR a C(=O)NR c R d -C(=O)NR c R d , C 6-10 Aryl, 5-10 member heteroaryl, C 3-6 Cycloalkyl, 5-6 member heterocycloalkyl, -L X11 -5-6 member heterocycloalkyl, -L X11 -C 3-6Cycloalkyl, -L X11 -C 6-10 Aryl, or -L X11 -5 to 10 member heteroaryls, where each alkyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl is a heteroaryl compound with one or more R X11a This may be substituted as appropriate.

[0281] In some embodiments, R X11 Each of them is independent of C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Aminoalkyl, C 1-6 Heteroalkyl, halogen, -CN, -NO2, -OR a , -SR a , -NR c R d -C(=O)R a , -C(=O)OR a -OC(=O)R a , -NR a C(=O)R a -C(=O)NR c R d , C 6-10 Aryl, 5-10 member heteroaryl, C 3-6 Cycloalkyl, 5-6 member heterocycloalkyl, -L X11 -5-6 member heterocycloalkyl, -L X11 -C 3-6 Cycloalkyl, -L X11 -C 6-10 Aryl, or -L X11 -5 to 10 member heteroaryls, where each alkyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl is a heteroaryl compound with one or more R X11a This may be substituted as appropriate.

[0282] In some embodiments, R X11These are, independently, phenyl, pyridinyl, pyrrolyl, pyrazolyl, imidazolyl, cyclohexyl, piperidinyl, piperazinyl, morpholinyl, tetrahydropyranyl, -L X11 -5-6 member heterocycloalkyl, -L X11 -phenyl, or -L X11 -Pyridinyl, where phenyl, pyridinyl, pyrrolyl, pyrazolyl, imidazolyl, cyclohexyl, piperidinyl, piperazinyl, morpholinyl, tetrahydropyranyl, and heterocycloalkyl each contain one or more R X11a This may be substituted as appropriate.

[0283] In some embodiments, two R X11 Together, they form an oxoplasm.

[0284] In some embodiments, L X11 C 1-6 It is an alkylene, which is one or more R X11a This may be replaced as appropriate. In some embodiments, L X11 C 1-6 It is a heteroalkylene, which is one or more R X11a This may be replaced as appropriate. In some embodiments, L X11 is -O-. In some embodiments, L X11 is -S-. In some embodiments, L X11 -NR a - is

[0285] In some embodiments, R X11a These are, independently, halogen and C 1-6 Alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, -CN, -NO2, -OR a , -SR a , -NR c R d -S(=O)R a -S(=O)2R a -S(=O)2NR c R d , -NRa S(=O)2R a , -NR a C(=NH)(NR a )2, -C(=O)R a , -C(=O)OR a -OC(=O)R a , -OC(=O)OR a -OC(=O)NR c R d , -NR a C(=O)R a , -NR a C(=O)OR a , -NR a C(=O)NR c R d -C(=O)NR c R d , or = O, where the alkyl and heteroalkyl are each one or more R e This may be substituted as appropriate.

[0286] In some embodiments, kx11 is 0. In some embodiments, kx11 is 1. In some embodiments, kx11 is 2. In some embodiments, kx11 is 3. In some embodiments, kx11 is 4. In some embodiments, kx11 is 5.

[0287] In some embodiments, mx11 is 0. In some embodiments, mx11 is 1. In some embodiments, mx11 is 2. In some embodiments, mx11 is 3. In some embodiments, mx11 is 4. In some embodiments, mx11 is 5.

[0288] In some embodiments, R n11 is hydrogen, kx11 is 0, 1, or 2, mx11 is 1, ring A11 is a monocyclic heteroaryl, and R X11 is phenyl. In some embodiments, R n11 is hydrogen, kx11 is 1, mx11 is 1, ring A11 is pyridinyl, R X11 It is phenyl.

[0289] In some embodiments of formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X12 is an N-methylated cysteine ​​or a derivative thereof. In some embodiments, X12 is an N-methylated cysteine. In some embodiments, X12 is an N-methylated cysteine ​​which may be substituted as appropriate.

[0290] In some embodiments of formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X1 is I, R, Cit, F4G, 4Py, 3Py, KCOpipzaa, V, Eva, Q, E, MeI, Ahp, F4COO, KCOpip4COO, MeQdMe, MeA, MeSMe, MeG, MeV, MeHseMe, A ib, MeT, alI, TMe, MeKCOpipzaa, MeQ, Hpr, MeTMe, MeDapCOpipzaa; MeK, MeKAc, MeK(de), MeK(H), MeK(df), or MeK(datb); The MeKCOpipzaa, MeQ, Hpr, MeTMe, or MeDapCOpipzaaa; X3 is D, Har, KCOpipzetOH, Cit, KCOmeglumine, KCOpipzaa, A4paa, Q, A, E, MeD, S, N, Hgl, F4COO, KCOpip4COO, KAc, Hgn, MeY, or DapCOpipzaa; X4は、D、Har、KCOpipzetOH、KCOmeglumine、KCOpipzaa、A4paa、Q、A、E、MeD S, N, Hgl, F4COO, KCOpip4COO, dd, MeQ, MeQdMe, MeA, MeSMe, MeG, EtG, Me eG, CmG, CmpG, CrmG, CeG, CrpG, MeK, MeKAc, MeHgl, Hgn, MeDapCOpipzaa. MeKCOpipzaa, Medd, Cit, MeCit, MeN, MeS, MeE, MeY, W5N, MeA4paa; X5はY、F3G、3Py6COO,4Py2NH2、3Py5COO、F3COO、3Py6NHAc、F、F4C、F4OMe. F4COO, Nal2, F3aao, F4aa, F4aao, 3Py6NHaa, 5Pdo, F3CON, F4F, F4OEt, F4Me F4CON, F4CONPEG4Me, F3OMe, F3CON, Yae, YaeCOpipzaa, F4aaopipzaa, 4Pd o, 3Py6CON, Atp, Cha4cH, Cha4tH, Cha4cOMe, A1mor, F4amCOpipzaa; X6, I, V, Eva, Chg, Tbg, A, L, Ahp, F4COO, Gcpr, Gcpe, alI, Cle, S3REt, T Me, Acpr, Cba, Gthp, NleCOO, NleOH, P, Atb, Nva, Nle, N, DapAc, Abu, Nmm. Ndm, Ncit, Cit, SMe, HseMe, HseEt, HseiPr, dMeS, TdMe, Cbg, NvaOMe, Si Pr, Spr, NleOMe, Sbu, Scbm, Scpe, AhpOMe, HseBu, Spent, and Hsecpe; X7, I, Eva, alI, TMe, SMe, Gcpr, Gcpe, Gthp, dMeS, TdMe, Cbg; X8 is A, I, L, V, Y, F4OMe, F4COO, F4OEt, F4u, F4Me, F4CONdMe, F4CON, F4ms, F4CONPEG4Me, F34dOMe, F3OMe, F3C, F3CON, F3CONdMe, 3Py6CON, Yae, YaeCOpipzaa, 5Inda, F3aao, F3aa, F4aao, F4aa, 3Py6Nhae, 3Py6NHAc, 3Py6OMe, F4aaopipzaa, or F4amCOpipzaa; X9 is MeNal2, MeNal27N, MeF34diox, MeF34dOMe, MeF4T, MeY, MeW1Me, MeW7N, MeF3C4Me, or MeF3Me4C; X10 is a G or D amino acid (e.g., da, ds, de, or dp); X11 is Bph, 3Py6Ph, F41Me4Pyz, F43Pyz, F44Pyz, F41Pyz, F41Me3Pyz, F41Et4Pyz, F41MeOe4Pyz, F41MeOp4Pyz, F44thp, F4Ac4pip, PhNva, PhNle, Yph, Ybn, F4tb, F4oPr, or F4CONdMe; X12 is a MeC.

[0291] In some embodiments of formulas (I), (I-5), (III-2), or (IV-2), X1 is MeA, MeK, MeK(datb), MeK(de), MeK(df), MeK(H), MeKAc, MeKCOpipzaa, MeDapCOpipzaa, or MeQ; X2 is MeA, HseMe, MeHseMe, MeI, MeL, MeQ, MeY, S, TMe, MeKCOpipzaa, or Me3Py; X3 is D, Hgn, KAc, MeY, or Q; X4 is MeA4paa, MeD, MeK, Q, MeQ, MeY, W5N, MeDapCOpipzaa, or MeKCOpipzaa; X5 is 3Py6NHaa, F4aao, F4COO, Y, or Yae; X6 is alI, Cle, I, S3REt, or TMe; X7 is I; X8 is F4aa, F4aao, F4aaopipzaa, F4amCOpipzaa, F4COO, F4u, Y, Yae, or YaeCOpipzaa; X9 is MeNal2, MeNal27N, or MeY; X10 is G; X11 is either 3Py6Ph or F41Me4Pyz; X12 is a MeC.

[0292] In some embodiments of formulas (I), (I-1), (I-2), (I-3), (I-4), (I-5), (III-1), (III-2), (IV-1), or (IV-2), X1 is MeA, MeK, MeK(datb), MeK(de), MeK(df), MeK(H), MeKAc, MeKCOpipzaa, MeDapCOpipzaa, or MeQ; X2 is MeA, HseMe, MeHseMe, MeI, MeL, MeQ, MeY, S, TMe, MeKCOpipzaa, or Me3Py; X3 is D, Hgn, KAc, MeY, or Q; X4 is MeA4paa, MeD, MeK, Q, MeQ, MeY, W5N, MeDapCOpipzaa, or MeKCOpipzaa; X5 is 3Py6NHaa, F4aao, F4COO, Y, or Yae; X6 is alI, Cle, I, S3REt, or TMe; X7 is I; X8 is F4aa, F4aao, F4aaopipzaa, F4amCOpipzaa, F4COO, F4u, Y, Yae, or YaeCOpipzaa; X9 is MeNal2, MeNal27N, or MeY; X10 is G; X11 is either 3Py6Ph or F41Me4Pyz.

[0293] In some embodiments, the radiopharmaceutical conjugate of this disclosure, comprising a cyclic peptide of formula (I), is of formula (III-1): [ka] [In the formula, -Linker- represents a linker; R 1 It is selected from the group consisting of -NH2 and -OH; R 2 C 1-3 It is alkyl; R 3 C 1-3 It is an alkylene and has one or more R 4 This may be substituted as appropriate; R 4 Each of them is independent of C 1-3 Alkyl or C 3-6 It is a cycloalkyl; kxR is 1, 2, 3, 4, 5, or 6; X R It is selected from the group consisting of -S-, -CH2-, or -O-; X1 to X11 have the definitions described in formula (I). It has the structure of [the object].

[0294] In some embodiments, the linker is the first amino acid residue (or X1), the second amino acid residue (or X2), the third amino acid residue (or X3), the fourth amino acid residue (or X4), the eighth amino acid residue (or X8), or R 1It binds to the 12th amino acid residue. In some embodiments, the linker binds to the 1st amino acid residue (or X1). In some embodiments, the linker binds to the 2nd amino acid residue (or X2). In some embodiments, the linker binds to the 3rd amino acid residue (or X3). In some embodiments, the linker binds to the 3rd amino acid residue (or X3). In some embodiments, the linker binds to the 4th amino acid residue (or X4). In some embodiments, the linker binds to the 8th amino acid residue (or X8). In some embodiments, the linker binds to R 1 It binds to the 12th amino acid residue. In some embodiments, the linker is a bond. In some embodiments, the metal chelating agent is [ka] In some embodiments, the radiopharmaceutical conjugate further comprises a radionuclide that binds to the metal chelating agent.

[0295] In some embodiments, the radiopharmaceutical conjugate of this disclosure, comprising a cyclic peptide of formula (I), is of formula (III-2): [ka] [In the formula, X1 to X12 have the definitions described in formula (I), and Lcyc is a ring-closing group that covalently bonds X1 with X12; -Linker- represents the linker. It has the structure of [the object].

[0296] In some embodiments, the linker binds to the first amino acid residue (or X1), the second amino acid residue (or X2), the third amino acid residue (or X3), the fourth amino acid residue (or X4), the eighth amino acid residue (or X8), or the twelfth amino acid residue (or X12). In some embodiments, the linker binds to the first amino acid residue (or X1). In some embodiments, the linker binds to the second amino acid residue (or X2). In some embodiments, the linker binds to the third amino acid residue (or X3). In some embodiments, the linker binds to the third amino acid residue (or X3). In some embodiments, the linker binds to the fourth amino acid residue (or X4). In some embodiments, the linker binds to the eighth amino acid residue (or X8). In some embodiments, the linker binds to the twelfth amino acid residue (or X12). In some embodiments, the linker is a bond. In some embodiments, the metal chelating agent is [ka] In some embodiments, the radiopharmaceutical conjugate further comprises a radionuclide that binds to the metal chelating agent.

[0297] In some embodiments, the radiopharmaceutical conjugate of this disclosure, comprising a cyclic peptide of formula (I), is of formula (IV-1): [ka] [In the formula, -Linker- represents a linker; R* is a covalently bonded radionuclide; R 1 It is selected from the group consisting of -NH2 and -OH; R 2 C 1-3 It is alkyl; R 3 C 1-3 It is an alkylene and has one or more R 4 This may be substituted as appropriate; R4 Each of them is independent of C 1-3 Alkyl or C 3-6 It is a cycloalkyl; kxR is 1, 2, 3, 4, 5, or 6; X R It is selected from the group consisting of -S-, -CH2-, or -O-; X1 to X11 have the definitions described in formula (I). It has the structure of [the object].

[0298] In some embodiments, the linker binds to the 5th amino acid residue (or X5), the 8th amino acid residue (or X8), the 9th amino acid residue (or X9), or the 11th amino acid residue (or X11). In some embodiments, the linker binds to the 5th amino acid residue (or X5). In some embodiments, the linker binds to the 8th amino acid residue (or X8). In some embodiments, the linker binds to the 9th amino acid residue (or X9). In some embodiments, the linker binds to the 11th amino acid residue (or X11). In some embodiments, the linker is a bond.

[0299] In some embodiments, the radiopharmaceutical conjugate of this disclosure, comprising a cyclic peptide of formula (I), is derived from formula (IV-2): [ka] [In the formula, X1 to X12 have the definitions described in formula (I), and Lcyc is a ring-closing group that covalently bonds X1 with X12; -Linker- represents the linker. It has the structure of [the object].

[0300] In some embodiments, the linker binds to the 5th amino acid residue (or X5), the 8th amino acid residue (or X8), the 9th amino acid residue (or X9), or the 11th amino acid residue (or X11). In some embodiments, the linker binds to the 5th amino acid residue (or X5). In some embodiments, the linker binds to the 8th amino acid residue (or X8). In some embodiments, the linker binds to the 9th amino acid residue (or X9). In some embodiments, the linker binds to the 11th amino acid residue (or X11). In some embodiments, the linker is a bond.

[0301] In some embodiments, Lcyc is a group selected from Table 4B. In some embodiments, Lcyc is formed by reacting the first and second functional groups in Table 4C. In some embodiments, Lcyc is -C(=O)-CH2-. In some embodiments, Lcyc is -C(=O)-CH2- formed by reacting a chloroacetylated (or bromoacetylated) amino acid with cysteine. In some embodiments, Lcyc is -C(=O)-CH2-S- formed by reacting a chloroacetylated (or bromoacetylated) amino acid with an amino acid containing an SH group.

[0302] In some embodiments, the radiopharmaceutical conjugates or pharmaceutically acceptable salts disclosed herein have a cyclic structure in which an amino acid (e.g., a chloroacetylated amino acid) and a cysteine ​​residue or a variant thereof at the first residue X1 are bonded together. In some embodiments, the radiopharmaceutical conjugates or pharmaceutically acceptable salts disclosed herein have a cyclic structure in which an amino acid (e.g., a chloroacetylated amino acid) and a cysteine ​​residue or a variant thereof at the first residue X1 are bonded together. In some embodiments, the radiopharmaceutical conjugates or pharmaceutically acceptable salts disclosed herein have a cyclic structure in which a bromoacetylated amino acid and a cysteine ​​residue or a variant thereof at the first residue X1 are bonded together.

[0303] In some embodiments, the radiopharmaceutical conjugate consists of an amino acid sequence selected from SEQ ID NOs: 1 to 72, and the peptide has a cyclic structure having a cysteine ​​residue or a variant thereof at the 12th residue (X12). In some embodiments, the peptide consists of an amino acid sequence selected from SEQ ID NOs: 1 to 72, and the peptide has a cysteine ​​residue or a variant thereof at the 12th residue (X12), and the chloroacetylated amino acid and the cysteine ​​residue or a variant thereof at the 12th residue form a covalent bond. In some embodiments, the chloroacetyl group may be replaced with a bromoacetyl group.

[0304] In some embodiments, the peptide consists of an amino acid sequence selected from any one of SEQ ID NOs. 66 to 71 that lacks an X3 amino acid residue, and the peptide has a cyclic structure with a cysteine ​​residue or a variant thereof at the "12th residue" (X12). In some embodiments, the peptide consists of an amino acid sequence selected from SEQ ID NOs. 1 to 72, and the peptide has a cyclic structure with a cysteine ​​residue or a variant thereof at the 12th residue (X12), and the amino acid of X1 (e.g., a chloroacetylated amino acid) and the cysteine ​​residue or a variant at the 12th residue form a covalent bond. In some embodiments, the chloroacetyl group may be replaced with a bromoacetyl group.

[0305] In some embodiments, the radiopharmaceutical conjugates or pharmaceutically acceptable salts thereof disclosed herein have a cyclic structure in which the first amino acid is covalently bonded to the last amino acid.

[0306] In some embodiments, the radiopharmaceutical conjugate or a pharmaceutically acceptable salt thereof has a cyclic structure in which a chloroacetylated amino acid and cysteine ​​or a cysteine ​​variant residue in X1 are bound to the chloroacetylated amino acid and cysteine ​​or a substituted cysteine ​​in X1. In some embodiments, the peptide consists of an amino acid sequence selected from SEQ ID NOs: 1 to 72. In some embodiments, the peptide consists of an amino acid sequence selected from SEQ ID NOs: 1 to 72, and the peptide has a cyclic structure. In some embodiments, the peptide consists of an amino acid sequence selected from SEQ ID NOs: 1 to 72, and the peptide has a cyclic structure in which a chloroacetylated amino acid and a C-terminal cysteine ​​or a cysteine ​​variant residue are bound to the chloroacetylated amino acid and a C-terminal cysteine ​​or a cysteine ​​variant. In some embodiments, the peptide has a chloroacetylated amino acid and a cyclic structure comprising: (i) a total of 12 or more amino acids, with cysteine ​​or a cysteine ​​variant residue at the 12th residue, to which the chloroacetylated amino acid and the cysteine ​​or cysteine ​​variant at the 12th residue are bound; or (ii) a total of 11 or fewer amino acids, particularly those without an X3 residue, with cysteine ​​or a cysteine ​​variant residue at the 12th residue, to which the chloroacetylated amino acid and the cysteine ​​or substituted cysteine ​​at the 12th residue are bound. In some embodiments, the chloroacetyl group may be replaced with a bromoacetyl group.

[0307] In some embodiments, the radiopharmaceutical conjugate or a pharmaceutically acceptable salt thereof comprises a peptide containing an amino acid sequence that is at least 95% identical to a sequence selected from X1 to X12 of SEQ ID NOs: 1 to 72. In some embodiments, the peptide or a salt thereof comprises an amino acid sequence that is at least 80%, 85%, 90%, 95%, or 98% identical to a sequence selected from X1 to X12 of SEQ ID NOs: 1 to 72. In some embodiments, the peptide or a salt thereof comprises an amino acid sequence that has at most 1, 2, 3, 4, or 5 amino acid residues that are different from the sequence selected from X1 to X12 of SEQ ID NOs: 1 to 72. In some embodiments, the peptide or a salt thereof comprises an amino acid sequence that has at most 1, 2, 3, 4, or 5 additions, deletions, and / or substitutions (including synonymous substitutions) to the sequence selected from X1 to X12 of SEQ ID NOs: 1 to 72. In some embodiments, the peptide or a salt thereof comprises an amino acid sequence having at most one addition, deletion, or substitution (including synonymous substitution) to a sequence selected from X1 to X12 of SEQ ID NOs: 1 to 72.

[0308] In some embodiments, the peptide or a salt thereof contains an amino acid sequence that lacks one X3 amino acid residue from any of SEQ ID NOs: 1 to 72 and is at least 70%, 80%, or 90% identical to the remaining residue of any one of SEQ ID NOs: 1 to 72. In some embodiments, the peptide or a salt thereof contains an amino acid sequence that is at least 70%, 80%, or 90% identical to a sequence selected from SEQ ID NOs: 66 to 71.

[0309] Exemplary peptides of this disclosure include the peptides listed in Table 1. In some embodiments, the peptides of Table 1 have a -C(=O)-halogen group bound to the N-terminus. In some embodiments, the peptides of Table 1 have a -C(=O)-CH2-halogen group bound to the N-terminus. In some embodiments, the peptides of Table 1 have a -C(=O)-halogen group bound to the residue at position 1. In some embodiments, the peptides of Table 1 have a -C(=O)-CH2-halogen group bound to the residue at position 1. In some embodiments, the peptides of Table 1 have a -C(=O)-Cl group bound to the N-terminus. In some embodiments, the peptides of Table 1 have a -C(=O)-CH2-Cl group bound to the N-terminus. In some embodiments, the peptides of Table 1 have a -C(=O)-Cl group bound to the residue at position 1. In some embodiments, the peptides of Table 1 have a -C(=O)-CH2-Cl group bound to the residue at position 1. In some embodiments, the peptides of Table 1 have a -C(=O)-Br group bound to the residue at position 1. In some embodiments, the peptides in Table 1 have a -C(=O)-CH2-Br group bound to the residue at position 1.

[0310] In some embodiments, the radiopharmaceutical conjugate of this disclosure has a -C(=O)-halogen group bound to the N-terminus. In some embodiments, the radiopharmaceutical conjugate of this disclosure has a -C(=O)-CH2-halogen group bound to the N-terminus. In some embodiments, the radiopharmaceutical conjugate of this disclosure has a -C(=O)-halogen group bound to the residue at position 1. In some embodiments, the radiopharmaceutical conjugate of this disclosure has a -C(=O)-CH2-halogen group bound to the residue at position 1. In some embodiments, the radiopharmaceutical conjugate of this disclosure has a -C(=O)-Cl group bound to the N-terminus. In some embodiments, the radiopharmaceutical conjugate of this disclosure has a -C(=O)-CH2-Cl group bound to the N-terminus. In some embodiments, the radiopharmaceutical conjugate of this disclosure has a -C(=O)-Cl group bound to the residue at position 1. In some embodiments, the radiopharmaceutical conjugate of this disclosure has a -C(=O)-CH2-Cl group bound to the residue at position 1. In some embodiments, the radiopharmaceutical conjugate of the present disclosure has a -C(=O)-Br group bound to the residue at position 1. In some embodiments, the radiopharmaceutical conjugate of the present disclosure has a -C(=O)-CH2-Br group bound to the residue at position 1. In some embodiments, the peptide in the radiopharmaceutical conjugate is monocyclic.

[0311] In some embodiments, the peptide of the radiopharmaceutical conjugate described herein is a monocyclic peptide in which the -C(=O)-Cl residue at position 1 forms a bond with the cysteine ​​residue at position 12. In some embodiments, the peptide of the radiopharmaceutical conjugate described herein is a monocyclic peptide in which the -C(=O)-CH2-Cl residue at position 1 forms a bond with the cysteine ​​residue at position 12. In some embodiments, the peptide in the radiopharmaceutical conjugate described herein is a monocyclic peptide having 12 amino acid residues that form a ring.

[0312] In some embodiments, the conjugates described herein are selected from the conjugates listed in Table 2, Table 3A, or Table 3B.

[0313] In some embodiments, the following structure: [ka] Conjugates having the same, or pharmaceutically acceptable salts thereof, are described herein. In some embodiments, the following structure: [ka] Conjugates having the same, or pharmaceutically acceptable salts thereof, are described herein. In some embodiments, the following structure: [ka] Conjugates having or pharmaceutically acceptable salts thereof are described herein. In some embodiments, Cu-C-30NOTA is 64 It is Cu-C-30NOTA. In some embodiments, the structure is as follows: [ka] A conjugate having the same, or a pharmaceutically acceptable salt thereof (SEQ ID NO: 376), is described herein. In some embodiments, the following structure: [ka] [where, X M [ is a radioactive nuclide] A radiopharmaceutical having the following structure, or a pharmaceutically acceptable salt thereof (SEQ ID NO: 376), is described herein. In some embodiments, the following structure: [ka] [where, X M [ is a radioactive nuclide] A radiopharmaceutical having the following structure, or a pharmaceutically acceptable salt thereof (SEQ ID NO: 376), is described herein. In some embodiments, the following structure: [ka] [where, X M [ is a radioactive nuclide] A radiopharmaceutical having X, or a pharmaceutically acceptable salt thereof (SEQ ID NO: 376), is described herein. In some embodiments, X M is a radionuclide selected from Table 7. In some embodiments, X M This is Ac-225. In some embodiments, X M This is Lu-177. In some embodiments, X M This is the Ga-68.

[0314] In some embodiments, conjugates having the same peptide sequence and linker as the conjugates described in Table 2, Table 3A, or Table 3B are provided herein, except that the ring-closing bond between the amino acid residue at position 1 and the cysteine ​​(for example, at position 12) is a covalent bond formed by a different group. For example, the amino acid residue at position 1 may include a group selected from maleimides, halides, disulfides, electron-deficient alkynes, thioesters, and alkenes that forms a covalent bond with the cysteine.

[0315] In some embodiments, the peptides in the conjugates of Table 1 are monocyclic peptides in which the -C(=O)-Cl residue at position 1 forms a bond with the cysteine ​​residue at position 12. In some embodiments, the peptides in the conjugates of Table 1 are monocyclic peptides in which the -C(=O)-CH2-Cl residue at position 1 forms a bond with the cysteine ​​residue at position 12. In some embodiments, the peptides in the conjugates of Table 1 are monocyclic peptides having 12 amino acid residues that form a ring.

[0316] In one embodiment, a peptide having avidity to GPC3, wherein SEQ ID NO: MeK-MeI-D-MeQ-F4COO-IIY-MeNal27N-G-3Py6Ph-MeC(Sequence ID 1) Peptides having amino acid sequences containing one or more amino acid deletions, substitutions, and / or additions in the amino acids, and peptides that compete for binding to human GPC3, or pharmaceutically acceptable salts thereof, are described herein.

[0317] In one embodiment, peptides having avidity to GPC3 and having the structure of formula (I) described herein (e.g., formulas (I-1), (I-2), (I-3), (I-4), and (I-5)) are described herein, and peptides that compete for binding to human GPC3, or pharmaceutically acceptable salts thereof, are described herein.

[0318] In some embodiments, the radiopharmaceutical conjugate is used in surface plasmon resonance (SPR) analysis. d When determined by this method, it has a binding affinity to human GPC3 of at most 100 nM. In some embodiments, the radiopharmaceutical conjugate is K in surface plasmon resonance (SPR) analysis. d If determined by this method, it has a binding affinity to human GPC3 of at most 1 nM.

[0319] The structure of an example non-natural amino acid in Table 1 is shown in Table 5G.

[0320] As shown in Table 1 or other tables, the abbreviations have the following meanings:

[0321] The lowercase letter 'd' stands for D-amino acid; for example, dF refers to d-phenylalanine.

[0322] Me refers to a methyl group; for example, MeG represents N-methylglycine.

[0323] Ala or A refers to alanine.

[0324] Arg or R refers to arginine.

[0325] Asn or N refers to asparagine.

[0326] Asp or D refers to aspartic acid.

[0327] Cys or C refers to cysteine.

[0328] Gln or Q refers to glutamine.

[0329] Gly or G refers to glycine.

[0330] His or H refers to histidine.

[0331] Ile or I refers to isoleucine.

[0332] Leu or L refers to leucine.

[0333] Lys or K refers to ricin.

[0334] Met or M refers to methionine.

[0335] Phe or F refers to phenylalanine.

[0336] Pro or P refers to proline.

[0337] Ser or S refers to serine.

[0338] Thr or T refers to threonine.

[0339] Trp or W refers to tryptophan.

[0340] Tyr or Y refers to tyrosine.

[0341] Val or V refers to valine.

[0342] Unless otherwise specified herein, the following abbreviations for non-natural amino acids are used in accordance with the following meanings. F4G 2-amino-3-(4-guanidinophenyl)propanoic acid, e.g., (S)-2-amino-3-(4-guanidinophenyl)propanoic acid (CAS 59574-11-7), etc. 4Py 2-amino-3-(pyridine-4-yl)propanoic acid, e.g., (S)-2-amino-3-(pyridine-4-yl)propanoic acid (CAS 37535-49-2), etc. 3Py 2-amino-3-(pyridine-3-yl)propanoic acid, e.g., (S)-2-amino-3-(pyridine-3-yl)propanoic acid (CAS 64090-98-8), etc. Cit 2-amino-5-ureidopentanoic acid, e.g., (S)-2-amino-5-ureidopentanoic acid (CAS 372-75-8), etc. KCOpipzaa 2-amino-6-{[4-(carboxymethyl)piperazine-1-carbonyl]amino}hexanoic acid, for example, (2S)-2-amino-6-{[4-(carboxymethyl)piperazine-1-carbonyl]amino}hexanoic acid [ka] etc; Eva 2-amino-3-ethylpentanoic acid, e.g., (S)-2-amino-3-ethylpentanoic acid (CAS 14328-49-5), etc. Ahp 2-aminoheptanoic acid, for example, (S)-2-aminoheptanoic acid (CAS number 44902-02-5), etc. F4COO 4-(2-amino-2-carboxyethyl)benzoic acid, e.g., (S)-4-(2-amino-2-carboxyethyl)benzoic acid (CAS 126109-42-0), etc. KCOpip4COO 1-((5-amino-5-carboxypentyl)carbamoyl)piperidine-4-carboxylic acid, e.g., (S)-1-((5-amino-5-carboxypentyl)carbamoyl)piperidine-4-carboxylic acid [ka] etc; Aib 2-amino-2-methylpropanoic acid (CAS 62-57-7); Hpr piperidine-2-carboxylic acid, e.g., (S)-piperidine-2-carboxylic acid (CAS 3105-95-1), etc. Sbu 2-amino-3-butoxypropanoic acid, e.g., (2S)-2-amino-3-butoxypropanoic acid (CAS 138320-46-4), etc. MeDapCOpipzaa 3-(4-(carboxymethyl)piperazine-1-carboxamide)-2-(methylamino)propanoic acid, e.g., (S)-3-(4-(carboxymethyl)piperazine-1-carboxamide)-2-(methylamino)propanoic acid [ka] etc; Scbm 2-amino-3-(cyclobutylmethoxy)propanoic acid, e.g., (2S)-2-amino-3-(cyclobutylmethoxy)propanoic acid [ka] etc; Sbu 2-amino-3-butoxypropanoic acid, e.g., (2S)-2-amino-3-butoxypropanoic acid (CAS 138320-46-4), etc. SciPe 2-amino-3-(cyclopentyloxy)propanoic acid, e.g., (2S)-2-amino-3-(cyclopentyloxy)propanoic acid (CAS 1509921-28-1), etc. HseBu 2-amino-4-butoxybutanoic acid, e.g., (2S)-2-amino-4-butoxybutanoic acid (CAS 17673-71-1), etc. A4paa 2-amino-3-(1-(carboxymethyl)piperidine-4-yl)propanoic acid, e.g., (S)-2-amino-3-(1-(carboxymethyl)piperidine-4-yl)propanoic acid [ka] etc; Spent 2-amino-3-(pentyloxy)propanoic acid, e.g., (2S)-2-amino-3-(pentyloxy)propanoic acid (CAS 1502644-74-7), etc. Hgl 2-aminohexanedioxide, e.g., (S)-2-aminohexanedioxide (CAS 1118-90-7), etc. Hsecpe 2-amino-4-(cyclopentyloxy)butanoic acid, e.g., (2S)-2-amino-4-(cyclopentyloxy)butanoic acid (CAS 1501949-22-9), etc. Hgn 2,6-diamino-6-oxohexanoic acid, e.g., (S)-2,6-diamino-6-oxohexanoic acid (CAS 7433-32-1), etc. DapCOpipzaa 2-amino-3-(4-(carboxymethyl)piperazine-1-carboxamide)propanoic acid, e.g., (S)-2-amino-3-(4-(carboxymethyl)piperazine-1-carboxamide)propanoic acid, etc. [ka] ; MeD 2-(methylamino)butanediic acid, e.g., (2S)-2-(methylamino)butanediic acid (CAS 4226-18-0); CmG 2-[(2-carbamoylethyl)amino]acetic acid (CAS 34299-32-6); Medd 2-(methylamino)butanediol, e.g., (2R)-2-(methylamino)butanediol (CAS 6384-92-5), etc. HseEt 2-amino-4-ethoxybutanoic acid, e.g., (2S)-2-amino-4-ethoxybutanoic acid (CAS 17268-93-8), etc. HseiPr 2-amino-4-(propan-2-yloxy)butanoic acid, e.g., (2S)-2-amino-4-(propan-2-yloxy)butanoic acid (CAS 685842-10-8), etc. CrmG 2,2'-Azandiyldiacetic acid (CAS 142-73-4); CeG 3-((carboxymethyl)amino)propanoic acid (CAS 505-72-6); CrpG 4-((carboxymethyl)amino)butanoic acid (CAS 4386-04-3); MeHgl 2-(methylamino)hexanedioxide, e.g., (S)-2-(methylamino)hexanedioxide (CAS 261943-13-9), etc. MeCit 2-(methylamino)-5-ureidopentanoic acid, e.g., (S)-2-(methylamino)-5-ureidopentanoic acid (CAS 2226129-88-8), etc. F3G 2-amino-3-(3-guanidinophenyl)propanoic acid, e.g., (S)-2-amino-3-(3-guanidinophenyl)propanoic acid (CAS 1019057-42-1), etc. 3Py6COO 5-(2-amino-2-carboxyethyl) picolinic acid, e.g., (S)-5-(2-amino-2-carboxyethyl) picolinic acid (CAS 1269945-31-4), etc. 4Py2NH2 2-amino-3-(2-aminopyridine-4-yl)propanoic acid, e.g., (S)-2-amino-3-(2-aminopyridine-4-yl)propanoic acid (CAS 1269969-46-1), etc. 3Py5COO 5-(2-amino-2-carboxyethyl)nicotinic acid, e.g., (S)-5-(2-amino-2-carboxyethyl)nicotinic acid (CAS 1270138-35-6), etc. F3COO 3-(2-amino-2-carboxyethyl)benzoic acid, e.g., (S)-3-(2-amino-2-carboxyethyl)benzoic acid (CAS 13861-02-4), etc. 3Py6NHAc 3-(6-acetamidopyridine-3-yl)-2-aminopropanoic acid, e.g., (S)-3-(6-acetamidopyridine-3-yl)-2-aminopropanoic acid (CAS 1270189-35-9), etc. F4C 2-amino-3-(4-chlorophenyl)propanoic acid, e.g., (S)-2-amino-3-(4-chlorophenyl)propanoic acid (CAS 14173-39-8), etc. F4OMe 2-amino-3-(4-methoxyphenyl)propanoic acid, e.g., (S)-2-amino-3-(4-methoxyphenyl)propanoic acid (CAS 6230-11-1), etc. NaL2 2-amino-3-(naphthalene-2-yl)propanoic acid, e.g., (S)-2-amino-3-(naphthalene-2-yl)propanoic acid (CAS 58438-03-2), etc. F3aao 2-amino-3-(3-(carboxymethoxy)phenyl)propanoic acid, e.g., (S)-2-amino-3-(3-(carboxymethoxy)phenyl)propanoic acid [ka] etc; F4aa 2-amino-3-(4-(carboxymethyl)phenyl)propanoic acid, e.g., (S)-2-amino-3-(4-(carboxymethyl)phenyl)propanoic acid (CAS 140233-60-9), etc. F4aao 2-amino-3-(4-(carboxymethoxy)phenyl)propanoic acid, e.g., (S)-2-amino-3-(4-(carboxymethoxy)phenyl)propanoic acid (CAS 24558-63-2), etc. 3Py6NHaa 2-amino-3-(6-((carboxymethyl)amino)pyridine-3-yl)propanoic acid, e.g., (S)-2-amino-3-(6-((carboxymethyl)amino)pyridine-3-yl)propanoic acid [ka] etc; 5Pdo 2-amino-3-(6-oxo-1,6-dihydropyridine-3-yl)propanoic acid, e.g., (S)-2-amino-3-(6-oxo-1,6-dihydropyridine-3-yl)propanoic acid (CAS 140681-92-1), etc. F3CON 2-amino-3-(3-carbamoylphenyl)propanoic acid, e.g., (S)-2-amino-3-(3-carbamoylphenyl)propanoic acid (CAS 1217651-22-3), etc. F4F 2-amino-3-(4-fluorophenyl)propanoic acid, e.g., (S)-2-amino-3-(4-fluorophenyl)propanoic acid (CAS 1132-68-9), etc. F4OEt 2-amino-3-(4-ethoxyphenyl)propanoic acid, e.g., (S)-2-amino-3-(4-ethoxyphenyl)propanoic acid (CAS 32795-52-1), etc. F4Me 2-amino-3-(p-tolyl)propanoic acid, e.g., (S)-2-amino-3-(p-tolyl)propanoic acid (CAS 1991-87-3), etc. F4CON 2-amino-3-(4-carbamoylphenyl)propanoic acid, e.g., (S)-2-amino-3-(4-carbamoylphenyl)propanoic acid (CAS 223593-04-2), etc. F4CONPEG4Me 3-(4-((2,5,8,11-tetraoxatridecane-13-yl)carbamoyl)phenyl)-2-aminopropanoic acid, e.g., (S)-3-(4-((2,5,8,11-tetraoxatridecane-13-yl)carbamoyl)phenyl)-2-aminopropanoic acid [ka] etc; F3OMe 2-amino-3-(3-methoxyphenyl)propanoic acid, e.g., (S)-2-amino-3-(3-methoxyphenyl)propanoic acid (CAS 33879-32-2), etc. YaeCOpipzaa 2-amino-3-(4-(2-(4-(carboxymethyl)piperazine-1-carboxamide)ethoxy)phenyl)propanoic acid, e.g., (S)-2-amino-3-(4-(2-(4-(carboxymethyl)piperazine-1-carboxamide)ethoxy)phenyl)propanoic acid [ka] etc; F4aaopipzaa 2-amino-3-(4-(2-(4-(carboxymethyl)piperazine-1-yl)-2-oxoethoxy)phenyl)propanoic acid, e.g., (S)-2-amino-3-(4-(2-(4-(carboxymethyl)piperazine-1-yl)-2-oxoethoxy)phenyl)propanoic acid [ka] etc; 4Pdo 2-amino-3-(2-oxo-1,2-dihydropyridine-4-yl)propanoic acid, e.g., (S)-2-amino-3-(2-oxo-1,2-dihydropyridine-4-yl)propanoic acid (CAS 1270061-10-3), etc. 3Py6CON 2-amino-3-(6-carbamoylpyridine-3-yl)propanoic acid, e.g., (S)-2-amino-3-(6-carbamoylpyridine-3-yl)propanoic acid [ka] etc; Atp 2-amino-3-(tetrahydro-2H-pyran-4-yl)propanoic acid, e.g., (S)-2-amino-3-(tetrahydro-2H-pyran-4-yl)propanoic acid (CAS 1344910-91-3), etc. Cha4cH 2-amino-3-((1s,4R)-4-hydroxycyclohexyl)propanoic acid, e.g., (S)-2-amino-3-((1s,4R)-4-hydroxycyclohexyl)propanoic acid [ka] etc; Cha4tH 2-amino-3-((1r,4S)-4-hydroxycyclohexyl)propanoic acid, e.g., (S)-2-amino-3-((1r,4S)-4-hydroxycyclohexyl)propanoic acid (CAS 221243-22-7), etc. Cha4cOMe 2-amino-3-((1s,4R)-4-methoxycyclohexyl)propanoic acid, e.g., (S)-2-amino-3-((1s,4R)-4-methoxycyclohexyl)propanoic acid [ka] etc; A1mor 2-amino-3-morpholinopropanoic acid, e.g., (S)-2-amino-3-morpholinopropanoic acid (CAS 1931924-34-3), etc. F4amCOpipzaa 2-amino-3-(4-((4-(carboxymethyl)piperazine-1-carboxamide)methyl)phenyl)propanoic acid, e.g., (S)-2-amino-3-(4-((4-(carboxymethyl)piperazine-1-carboxamide)methyl)phenyl)propanoic acid [ka] etc; Chg 2-amino-2-cyclohexylacetic acid, e.g., (S)-2-amino-2-cyclohexylacetic acid (CAS 14328-51-9), etc. Cle 1-aminocyclopentane-1-carboxylic acid (CAS 52-52-8); Tbg 2-amino-3,3-dimethylbutanoic acid, e.g., (S)-2-amino-3,3-dimethylbutanoic acid (CAS 20859-02-3), etc. Gcpr 2-amino-2-cyclopropylacetic acid, e.g., (S)-2-amino-2-cyclopropylacetic acid (CAS 49606-99-7), etc. Gcpe 2-amino-2-cyclopentylacetic acid, e.g., (S)-2-amino-2-cyclopentylacetic acid (CAS 2521-84-8), etc. Acpr 2-amino-3-cyclopropylpropanoic acid, e.g., (S)-2-amino-3-cyclopropylpropanoic acid (CAS 102735-53-5), etc. Cba 2-amino-3-cyc...

Claims

1. (a) Equation (I-1): 【Chemistry 1】 [In the formula, R １ is, -NH ２ or -OH; R ２ C １－３ It is alkyl; R ３ C １－３ It is an alkylene and has one or more R ４ It may be replaced as appropriate; R ４ is, independently of each other, C １－３ alkyl or C ３－６ cycloalkyl; kxR is 1, 2, 3, 4, 5, or 6; X Ｒ is -S-, -CH ２ -, or -O-; X1 is any amino acid; X2 is any amino acid; X3 is any amino acid; X4 is any amino acid; X5 is an amino acid containing an aromatic ring, or a cycloalkyl or heterocycloalkyl group, or X5 is a peptoid; X6 is a hydrophobic amino acid, a hydrophilic amino acid, or a polar amino acid, wherein the polar amino acid has a substituted side chain; X7 is C １ -C ８ A hydrophobic amino acid comprising an alkyl, cycloalkyl, or heterocycloalkyl group, wherein the alkyl, cycloalkyl, and heterocycloalkyl groups may be independently and appropriately substituted; X8 is A, I, L, V, Y, or F, or a variant thereof; X9 is an N-alkylated amino acid containing an aromatic ring; X10 is G or A, or their N-alkylated variants, or a D-amino acid; X11 is an amino acid containing an aromatic ring. peptides of; and (b) A metal chelating agent that binds to a radionuclide, the metal chelating agent that covalently binds to the peptide. Radiopharmaceuticals or their pharmaceutically acceptable salts, including [specific substances].

2. The radiopharmaceutical according to claim 1, wherein the radiopharmaceutical conjugate is selected from Table 3A or Table 3B, or a pharmaceutically acceptable salt thereof.

3. The following structure: 【Chemistry 2】 [In the formula, X Ｍ [It is a radioactive nuclide.] A radiopharmaceutical or a pharmaceutically acceptable salt thereof.

4. (a) Equation (I-1): 【Transformation 3】 [In the formula, R １ is, -NH ２ or -OH; R ２ C １－３ It is alkyl; R ３ C １－３ It is an alkylene and has one or more R ４ It may be replaced as appropriate; R ４ Each of them is independent of C １－３ Alkyl or C ３－６ It is cycloalkyl; kxR is 1, 2, 3, 4, 5, or 6; X Ｒ is -S-, -CH ２ -, or -O-; X1 is any amino acid; X2 is any amino acid; X3 is any amino acid; X4 is any amino acid; X5 is an amino acid containing an aromatic ring, or a cycloalkyl or heterocycloalkyl group, or X5 is a peptoid; X6 is a hydrophobic amino acid, a hydrophilic amino acid, or a polar amino acid, wherein the polar amino acid has a substituted side chain; X7 is C １ -C ８ A hydrophobic amino acid comprising an alkyl, cycloalkyl, or heterocycloalkyl group, wherein the alkyl, cycloalkyl, and heterocycloalkyl groups may be independently and appropriately substituted; X8 is A, I, L, V, Y, or F, or a variant thereof; X9 is an N-alkylated amino acid containing an aromatic ring; X10 is G or A, or their N-alkylated variants, or a D-amino acid; X11 is an amino acid containing an aromatic ring. peptides of; and (b) A metal chelating agent configured to bind to a radionuclide, wherein the metal chelating agent is covalently bonded to the peptide. Conjugates or pharmaceutically acceptable salts thereof, including [the specified substance].

5. The metal chelating agent is DOTA, DOTA-GA, pBn-DOTA, pBn-SCN-DOTA, NH2-DOTA, NH2-DOTA-GA, p-NCS-Bn-DOTA-GA, p-NH2-Bn-oxo-DO3A, p-SCN-Bn-oxo-D O3A, NOTA, NODA-GA, NH2-NODA-GA, p-NCS-Bn-NODA-GA, p-NH2-Bn-NOT A, p-SCN-Bn-NOTA, NCS-MP-NODA, NH2-MPAA-NODA, PCTA, p-NH2-Bn-PCT A radiopharmaceutical according to claim 1 or a pharmaceutically acceptable salt thereof, comprising A, p-SCN-Bn-PCTA, p-SCN-Bn-HEHA, H2-MACROPA-NCS, H1-MACROPA, H2-MACROPA-NH2, H4-OCTAPA, tetra-(S,S,S,S)-Me-DOTA, tetra-(S,S,S,S)-Et-DOTA, tetra-(S,S,S,S)-iBu-DOTA, or maleimide-nBu-DOTA, or a conjugate according to claim 4 or a pharmaceutically acceptable salt thereof.

6. The aforementioned metal chelating agent 【Chemistry 4】 A radiopharmaceutical according to claim 1 or a pharmaceutically acceptable salt thereof, having the structure of the radiopharmaceutical according to claim 1, or a conjugate according to claim 4 or a pharmaceutically acceptable salt thereof.

7. The aforementioned metal chelating agent 【Transformation 5】 A radiopharmaceutical according to claim 6, or a pharmaceutically acceptable salt thereof, or a conjugate thereof, having the structure of the radiopharmaceutical according to claim 6.

8. The radiopharmaceutical or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 3 and 5 to 7, wherein the radionuclide is an alpha-particle emitting radionuclide, or the conjugate or a pharmaceutically acceptable salt thereof according to any one of claims 4 to 7.

9. The radiopharmaceutical or a pharmaceutically acceptable salt thereof, or a conjugate or a pharmaceutically acceptable salt thereof, according to claim 8, wherein the alpha particle-emitting radionuclide is Ac-225, Bi-213, Bi-209, Tb-149, Ra-223, Th-227, Fr-223, Gd-148, Th-229, Pb-212, or Po-213.

10. The radiopharmaceutical or a pharmaceutically acceptable salt thereof, or a conjugate or a pharmaceutically acceptable salt thereof, according to claim 9, wherein the alpha particle-emitting radionuclide is Ac-225.

11. The radiopharmaceutical or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 3 and 5 to 7, wherein the radionuclide is a β-particle emitting radionuclide, or the conjugate or a pharmaceutically acceptable salt thereof according to any one of claims 4 to 7.

12. The radiopharmaceutical or a pharmaceutically acceptable salt thereof, or a conjugate or a pharmaceutically acceptable salt thereof, according to claim 11, wherein the β-particle emitting radionuclide is Cu-67, Lu-177, Y-90, Rh-105, Yb-175, Tm-167, Pm-153, Sm-153, or In-111.

13. The radiopharmaceutical or a pharmaceutically acceptable salt thereof, or a conjugate or a pharmaceutically acceptable salt thereof, according to claim 12, wherein the β-particle emitting radionuclide is Lu-177.

14. A radiopharmaceutical or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 3 and 5 to 7, wherein the radionuclide is a positron-emitting radionuclide, or a conjugate or a pharmaceutically acceptable salt thereof according to any one of claims 4 to 7.

15. The radiopharmaceutical or a pharmaceutically acceptable salt thereof, or a conjugate or a pharmaceutically acceptable salt thereof, according to claim 14, wherein the positron-emitting radionuclide is Ga-68, Cu-62, Cu-64, Zr-89, or Tb-152.

16. The radiopharmaceutical or a pharmaceutically acceptable salt thereof, or a conjugate or a pharmaceutically acceptable salt thereof, according to claim 15, wherein the positron-emitting radionuclide is Ga-68.

17. A radiopharmaceutical or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 3 and 5 to 7, wherein the radionuclide is Ac-225, Lu-177, or Ga-68, or a conjugate or a pharmaceutically acceptable salt thereof according to any one of claims 4 to 7.

18. A radiopharmaceutical or a pharmaceutically acceptable salt thereof according to any one of claims 1 and 5 to 17, further comprising a linker that covalently bonds the peptide with the metal chelating agent, or a conjugate or a pharmaceutically acceptable salt thereof according to any one of claims 4 to 17.

19. A radiopharmaceutical or a pharmaceutically acceptable salt thereof according to any one of claims 1 and 5 to 18, wherein the linker is bound to the lysine of the peptide, or a conjugate or a pharmaceutically acceptable salt thereof according to any one of claims 4 to 18.

20. A radiopharmaceutical or a pharmaceutically acceptable salt thereof according to any one of claims 1 and 5 to 19, wherein the linker is bonded to X1, X2, X3, X4, X8, or X12, or a conjugate or a pharmaceutically acceptable salt thereof according to any one of claims 4 to 19.

21. The linker is bonded to X1 by a radiopharmaceutical or a pharmaceutically acceptable salt thereof according to any one of claims 1 and 5 to 20, or by a conjugate or a pharmaceutically acceptable salt thereof according to any one of claims 4 to 20.

22. The linker is a bond, wherein the radiopharmaceutical or a pharmaceutically acceptable salt thereof according to any one of claims 1 and 5 to 21, or the conjugate or a pharmaceutically acceptable salt thereof according to any one of claims 4 to 21.

23. A radiopharmaceutical or a pharmaceutically acceptable salt thereof according to any one of claims 1 and 5 to 21, wherein the linker contains 3 to 30 interposing non-hydrogen organic atoms between the metal chelating agent and the peptide, or a conjugate or a pharmaceutically acceptable salt thereof according to any one of claims 4 to 21.

24. The peptide is given by formula (I-2): 【Transformation 6】 A radiopharmaceutical or a pharmaceutically acceptable salt thereof according to any one of claims 1 and 5 to 23, having the structure of, or a conjugate or a pharmaceutically acceptable salt thereof according to any one of claims 4 to 23.

25. X1 is I, R, Cit, F4G, 4Py, 3Py, KCOpipzaa, V, Eva, Q, E, MeI, Ahp, F4COO, KCOpip4COO, MeQdMe, MeA, MeSMe, MeG, MeV, MeHseMe, Aib , MeT, alI, TMe, MeKCOpipzaa, MeQ, Hpr, MeTMe, MeDapCOpipzaa, MeE, MeK, MeKAc, MeK(de), MeK(H), MeK(df), or MeK(datb); 82,41,41,305,000,000 COpipzetOH、6、KOpipzaa、･va The 9、ｭeQdMe、ｭe2、ｭe3ee、7111、719 、e6、、、、、、、 、 、、、 、、、、、、、、、、、、、、、、、 eｨseee、ｭee｡c、alｩ、4Me、ｭee4e . eTｭe、またはｭe､apOOipzaaaaであり! X3が、､、HarraKCOpipzetｯｨ、^itt、!Cｯm 、KCOpipzaa、A4paa、#、 A、da、Me｡、|bu、ap、diiｭeDap、1、7511、6、5、75、 3、4、8、22、、04439、500 ip4439ｯ、ｫ、K｡c、2gn、7eｹ、またはDapCOpipzaaであり{ X4が、､、ｨarr、KCOpipzetｯｨ、!!Oeglu mine、KCOpipzaaaa｡4paaa 、″、༮、、、、、4439、439、、、、、 * eｱMMeddeeaｭe2、ｭe3ee、e11、t11、71 e1、311、351、31211、3111、3101、751、 MeK｡c、ｭeeglagnn MeKCOiipzaaaaedd、Citt、eeCit、ee The The 99,0339, 300,68822, 00,043, 049,000,000 44,440, 85,22, 03,500, 40,450,000 o、301468225、5018、03398、040、044554、 04718、04439800514715147151531 ON、aae、aaeCpipzaaaaoｾaaaopipzaaaaa The atcｯｭe、2cmor、または.44am!ｯpipzaaであり゛ X6 is I, V, Eva, Chg, Tbg, A, L, Ahp, F4COO, Gcpr, Gcpe, alI, Cle, S3Ret, TMe, alTMe, Acpr, Cba, Gthp, NleCOO, NleOH, P, Atb, Nva, Nle, N, DapAc, Abu, Nmm, Ndm, Ncit, Cit, SMe, HseMe, HseEt, HseiPr, dMeS, TdMe, Cbg, NvaOMe, SiPr, Spr, NleOMe, Sbu, Scbm, Scpe, AhpOMe, HseBu, Spent, or Hsecp; X7 is I, A, L, V, Eva, alI, TMe, SMe, Gcpr, Gcpe, Gthp, dMeS, TdMe, or Cbg; X8 is A, I, L, V, Y, Cha, Aph, F4OMe, F4COO, F4OEt, F4u, F4Me, F4F, F4CONdMe, F4CON, F4ms, F4CONPEG4Me, F34dOMe, F3OMe, F3C, F3CON, F3CONdMe, 3Py6CON, Yae, YaeCOpipzaa, 5Inda, F3OH, F3aaO, F3aa, F4aaO, F4aa, 3Py6Nhae, 3Py6NHAc, 3Py6OMe, F4aaOpipzaa, or F4amCOpipzaa; X9 is MeNal2, MeNal27N, MeF34diox, MeF34dOMe, MeF4T, MeY, MeW1Me, MeiW, Me(7Me)6inda, Me(7Me)6indol, Me6inda, MeW7N, MeF3C4Me, or MeF3Me4C; X10 is G, MeG, A, or a D - amino acid; X11 is Bph, 3Py6Ph, F41Me4Pyz, F43Pyz, F44Pyz, F41Pyz, F41Me3Pyz, F41Et4Pyz, F41MeOe4Pyz, F41M eOp4Pyz, F44thp, F4Ac4pip, PhNva, PhNle, Yph, Ybn, F4tb, F4oPr, F4CONdMe, 3Py(6-(2-Py)), 3Py(6- (3-Py)), 3Py(6-(4-Py)), 3Py6(Pip1), 3Py6Imidaz1, 3Py6Me, 3Py6Oxaz5, 3Py6Pipza, 3Py6Pyrazol1, 3Py6Pyrazol3, 3Py6Pyrrol1, Phe(4-(2-Py)), Phe(4-(3-Py)), Phe(4-(4-Py)), or Phe35N4Ph, A radiopharmaceutical according to any one of claims 1 and 5 to 24, or a pharmaceutically acceptable salt thereof according to any one of claims 4 to 24.

26. X1 is any amino acid; X2 is any amino acid; X3 is any amino acid; X4 is any amino acid; X5, 【Transformation 7】 [In the formula, R ｎ５ is hydrogen or C １－３ It is alkyl; Ring A5 is aryl, heteroaryl, cycloalkyl, or heterocycloalkyl; R Ｘ５ Each of them is independent of C １－６ Alkyl, C １－６ Haloalkyl, C １－６ Hydroxyalkyl, C １－６ Aminoalkyl, C １－６ Heteroalkyl, C ２－６ Alkenil, C ２－６ Alkynyl, halogen, -CN, -NO ２ , -OR ａ , -SR ａ , -SF ５ , -NR ｃ R ｄ , -S(=O)R ａ , -S (=O) ２ R ａ , -S (=O) ２ NR ｃ R ｄ , -S(=O)(=NR ａ ) R ａ , -N=S(=O)NR ｃ R ｄ , -NR ａ S (=O) ２ R ａ Amidinil, -NR ａ C(=NH)NR ｃ R ｄ , -NR ａ S (=O) ２ NR ｃ R ｄ , -C(=O)R ａ , -C (=O) OR ａ -OC(=O)R ａ , -OC(=O)OR ａ , -OC(=O)NR ｃ R ｄ , -NR ａ C(=O)R ａ , -NR ａ C (=O) OR ａ , -NR ａ C(=O)NR ｃ R ｄ , -C(=O)NR ｃ R ｄ , -P(=O)(OR ｃ ) ( OR ｄ ), -P(=O)R ｃ R ｄ aryl, heteroaryl, cycloalkyl, heterocycloalkyl, -L Ｘ５ - Heterocycloalkyl, - L Ｘ５ -Cycloalkyl, -L Ｘ５ -aryl, or -L Ｘ５ -A heteroaryl, where the alkyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl are one or more R Ｘ５ａ It may be replaced as appropriate; or, Two Rs Ｘ５ together form =O, =S, or =N(R ａ ) and; L Ｘ５ C １－６ Alkylene, C １－６ Heteroalkylene, -O-, -S-, or -NR ａ - and here, the alkylene and heteroalkylene are one or more R Ｘ５ａ It may be replaced as appropriate; kx5 is 0, 1, 2, or 3; mx5 is 0, 1, 2, 3, 4, or 5; *X4 represents the connection point to X4; *X6 represents the connection point to X6. And, X6 【Transformation 8】 [In the formula, R ｎ６ is hydrogen or C １－３ alkyl; R Ｘ６ C １－６ Alkyl, C １－６ Haloalkyl, C １－６ Hydroxyalkyl, C １－６ Aminoalkyl, C １－６ Heteroalkyl, C ２－６ Alkenil, C ２－６ Alkinyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, -L Ｘ６ - Heterocycloalkyl, - L Ｘ６ -Cycloalkyl, -L Ｘ６ -aryl, or -L Ｘ６ -A heteroaryl, where each alkyl, heteroalkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl is one or more R Ｘ６ａ It may be replaced as appropriate; or, R ｎ６ and R ｘ６ It forms a 5-6 member heterocycloalkyl group with the atoms in between, which consists of one or more R Ｘ６ａ It may be replaced as appropriate; L Ｘ６ C １－６ Alkylene, C １－６ Heteroalkylene, -O-, -S-, or -NR ａ - and here, the alkylene and heteroalkylene are one or more R Ｘ６ａ It may be replaced as appropriate; *X5 represents the connection point to X5; *X7 represents the connection point to X7. And; X7, 【Chemistry 9】 [In the formula, R ｎ７ is hydrogen or C １－３ It is alkyl; R Ｘ７ C １－６ Alkyl, C １－６ Haloalkyl, C １－６ Hydroxyalkyl, C １－６ Aminoalkyl, C １－６ Heteroalkyl, C ２－６ Alkenil, C ２－６ Alkynyl, cycloalkyl, or heterocycloalkyl, where each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, and heterocycloalkyl is one or more R Ｘ７ａ It may be replaced as appropriate; R Ｘ７’ is hydrogen or C １－３ It is alkyl; *X6 represents the connection point to X6; *X8 represents the connection point to X8. And; X8, 【Chemistry 10】 [In the formula, R ｎ８ is hydrogen or C １－３ It is alkyl; Ring A8 is aryl or heteroaryl; R Ｘ８ Each of them is independent of C １－６ Alkyl, C １－６ Haloalkyl, C １－６ Hydroxyalkyl, C １－６ Aminoalkyl, C １－６ Heteroalkyl, C ２－６ Alkenil, C ２－６ Alkynyl, halogen, -CN, -NO ２ , -OR ａ , -SR ａ , -SF ５ , -NR ｃ R ｄ , -S(=O)R ａ , -S (=O) ２ R ａ , -S (=O) ２ R ｃ R ｄ , -S(=O)(=NR ａ ) R ａ , -N=S(=O) R ｃ R ｄ , -NR ａ S (=O) ２ R ａ Amidinil, -NR ａ C(=NH)NR ｃ R ｄ , -NR ａ S (=O) ２ R ｃ R ｄ , -C(=O)R ａ , -C (=O) OR ａ -OC(=O)R ａ , -OC(=O)OR ａ , -OC(=O)NR ｃ R ｄ , -NR ａ C(=O)R ａ , -NR ａ C (=O) OR ａ , -NR ａ C(=O)NR ｃ R ｄ , -C(=O)NR ｃ R ｄ , -P(=O)(OR ｃ ) ( OR ｄ ), -P(=O)R ｃ R ｄ aryl, heteroaryl, cycloalkyl, heterocycloalkyl, -L Ｘ８ - Heterocycloalkyl, - L Ｘ８ -Cycloalkyl, -L Ｘ８ -aryl, or -L Ｘ８ -A heteroaryl, where each alkyl, heteroalkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl is one or more R Ｘ８ａ It may be replaced as appropriate; or, Two R's Ｘ８ Together, =O, =S, or =N(R) ａ ) form; L Ｘ８ C １－６ Alkylene, C １－６ Heteroalkylene, -O-, -S-, or -NR ａ - and here, the alkylene and heteroalkylene are one or more R Ｘ８ａ It may be replaced as appropriate; kx8 is 0, 1, 2, or 3; mx8 is 0, 1, 2, 3, 4, or 5; *X7 represents the connection point to X7; *X9 represents the connection point to X9. And; X9 is 【Chemistry 11】 [In the formula, R ｎ９ is hydrogen or C １－３ It is alkyl; Ring A9 is aryl or heteroaryl; R Ｘ９ Each of them is independent of C １－６ Alkyl, C １－６ Haloalkyl, C １－６ Hydroxyalkyl, C １－６ Aminoalkyl, C １－６ Heteroalkyl, C ２－６ Alkenil, C ２－６ Alkynyl, halogen, -CN, -NO ２ , -OR ａ , -SR ａ , -SF ５ , or -NR ｃ R ｄ Here, the alkyl, heteroalkyl, alkenyl, and alkynyl each have one or more R Ｘ９ａ It may be replaced as appropriate; or, Two R's Ｘ９ Together, =O, =S, or =N(R) ａ ) form; kx9 is 0, 1, 2, or 3; mx9 is 0, 1, 2, 3, 4, or 5; *X8 represents the connection point to X8; *X10 represents the connection point to X10. And; X10 is glycine, methylglycine, or a D-amino acid; X11 is 【Chemistry 12】 [In the formula, R ｎ１１ is hydrogen or C １－３ It is alkyl; Ring A11 is aryl or heteroaryl; R Ｘ１１ Each of them is independent of C １－６ Alkyl, C １－６ Haloalkyl, C １－６ Hydroxyalkyl, C １－６ Aminoalkyl, C １－６ Heteroalkyl, halogen, -CN, -NO ２ , -OR ａ , -SR ａ , -SF ５ , -NR ｃ R ｄ , -S(=O)R ａ , -S (=O) ２ R ａ , -S (=O) ２ R ｃ R ｄ , -S(=O)(=NR ａ ) R ａ , -N=S(=O)R ｃ R ｄ , -NR ａ S (=O) ２ R ａ Amidinil, -NR ａ C(=NH)NR ｃ R ｄ , -NR ａ S (=O) ２ R ｃ R ｄ , -C(=O)R ａ , -C (=O) OR ａ -OC(=O)R ａ , -OC(=O)OR ａ , -OC(=O)NR ｃ R ｄ , -NR ａ C(=O)R ａ , -NR ａ C (=O) OR ａ , -NR ａ C(=O)NR ｃ R ｄ , -C(=O)NR ｃ R ｄ , -P(=O)(OR ｃ ) ( OR ｄ ), -P(=O)R ｃ R ｄ aryl, heteroaryl, cycloalkyl, heterocycloalkyl, -L Ｘ１１ - Heterocycloalkyl, - L Ｘ１１ -Cycloalkyl, -L Ｘ１１ -aryl, or -L Ｘ１１ -A heteroaryl, where each alkyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl is one or more R Ｘ１１ａ It may be replaced as appropriate; or, Two R's Ｘ１１ Together, =O, =S, or =N(R) ａ ) form; L Ｘ１１ C １－６ Alkylene, C １－６ Heteroalkylene, -O-, -S-, or -NR ａ - and here, the alkylene and heteroalkylene are one or more R Ｘ１１ａ It may be replaced as appropriate; kx11 is 0, 1, 2, 3, 4, or 5; mx11 is 0, 1, 2, 3, 4, or 5; *X10 represents the connection point to X10; *X12 is N(R ２ [Represents a connection point to )] And; R Ｘ５ａ , R Ｘ６ａ , R Ｘ７ａ , R Ｘ８ａ , R Ｘ９ａ , and R Ｘ１１ａ These are, independently, halogen and C １－６ Alkyl, C １ -C ６ Haloalkyl, C １ -C ６ Hydroxyalkyl, C １ -C ６ Aminoalkyl, C １ -C ６ Heteroalkyl, C ２ -C ６ Alkenil, C ２ -C ６ Alkinyl, -CN, -NO ２ , -OR ａ , -SR ａ , -NR ｃ R ｄ , -S(=O)R ａ , -S (=O) ２ R ａ , -SF ５ , -S (=O) ２ NR ｃ R ｄ , -S(=O)(=NR ａ ) R ａ , -N=S(=O)R ｃ R ｄ , -NR ａ S (=O) ２ R ａ Amidinil, -NR ａ C (=NH) (NR ａ ) ２ , -NR ａ S (=O) ２ NR ｃ R ｄ , -C(=O)R ａ , -C (=O) OR ａ -OC(=O)R ａ , -OC(=O)OR ａ , -OC(=O)NR ｃ R ｄ , -NR ａ C(=O)R ａ , -NR ａ C (=O) OR ａ , -NR ａ C(=O)NR ｃ R ｄ , -C(=O)NR ｃ R ｄ , -P(=O)(OR ｃ ) ( OR ｄ ), -P(=O)R ｃ R ｄ aryl, heteroaryl, cycloalkyl, heterocycloalkyl, =O, =S, or =N(R) ａ ) where the alkyl, heteroalkyl, alkenyl, and alkynyl each have one or more R ｅ It may be replaced as appropriate; R ａ These are, independently, hydrogen and C １ -C ６ Alkyl, C １ -C ６ Haloalkyl, C １ -C ６ Hydroxyalkyl, C １ -C ６ Aminoalkyl, C １ -C ６ Heteroalkyl, C ２ -C ６ Alkenil, C ２ -C ６ Alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C １ -C ６ Alkyl (cycloalkyl), C １ -C ６ Alkyl (heterocycloalkyl), C １ -C ６ Alkyl (aryl), or C １ -C ６ Alkyl (heteroaryl), where each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl independently comprises one or more R ｅ It may be replaced as appropriate; R ｅ These are, independently, halogen, -CN, -OH, and -O-C. １ -C ６ Alkyl, -SF ５ , -S(=O)C １ -C ６ Alkyl, -S (=O) ２ C １ -C ６ Alkyl, -S (=O) ２ NH ２ , -S (=O) ２ -Halogen, -S (=O) ２ NHC １ -C ６ Alkyl, -S (=O) ２ N(C) １ -C ６ Alkyl) ２ , -NH ２ , - NHC １ -C ６ Alkyl, -N(C) １ -C ６ Alkyl) ２ , -NHC(=NH)NH ２ , -NHC(=O)OC １ -C ６ Alkyl, -C(=O)C １ -C ６ Alkyl, -C(=O)OH, C １ -C ６ Alkyl-C(=O)OH, -C(=O)OC １ -C ６ Alkyl, -C(=O)NH ２ , -C(=O)N(C １ -C ６ Alkyl) ２ , -C(=O)NHC １ -C ６ Alkyl, C １ -C ６ Haloalkyl, C １ -C ６ Hydroxyalkyl, C １ -C ６ Aminoalkyl, or C １ -C ６ It is heteroalkyl; or, Two R's ｅ Together, they form = O; R ｃ and R ｄ These are, independently, hydrogen and C １ -C ６ Alkyl, C １ -C ６ Haloalkyl, C １ -C ６ Hydroxyalkyl, C １ -C ６ Aminoalkyl, C １ -C ６ Heteroalkyl, C ２ -C ６ Alkenil, C ２ -C ６ Alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C １ -C ６ Alkyl (cycloalkyl), C １ -C ６ Alkyl (heterocycloalkyl), C １ -C ６ Alkyl (aryl), or C １ -C ６ Alkyl (heteroaryl), where each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl independently comprises one or more R ｅ It may be replaced as appropriate; or, R ｃ and R ｄ Along with the atoms to which they are bonded, one or more R ｅ This forms a heterocycloalkyl which may be appropriately substituted. A radiopharmaceutical according to any one of claims 1 and 5 to 24, or a pharmaceutically acceptable salt thereof according to any one of claims 4 to 24.

27. The radiopharmaceutical or a pharmaceutically acceptable salt thereof according to claim 26, or a conjugate or a pharmaceutically acceptable salt thereof, wherein X1 is an N-alkylated amino acid.

28. X1, 【Chemistry 13】 [In the formula, R ｎ１ is hydrogen or C １－３ It is alkyl; R Ｘ１ is hydrogen, C １－６ Alkyl, C １－６ Haloalkyl, C １－６ Hydroxyalkyl, C １－６ Aminoalkyl, C １－６ Heteroalkyl, C ２－６ Alkenil, C ２－６ Alkinyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, -L Ｘ１ - Heterocycloalkyl, - L Ｘ１ -Cycloalkyl, -L Ｘ１ -aryl, or -L Ｘ１ - A heteroaryl, where the alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl each contain one or more R Ｘ１ａ It may be replaced as appropriate; R Ｘ１’ is hydrogen or C １－６ It is an alkyl group, where the alkyl group is one or more R Ｘ１ａ It may be replaced as appropriate; or, R ｎ１ and R Ｘ１’ It forms a 5-6 member heterocycloalkyl group with the atoms in between, which consists of one or more R Ｘ１ａ It may be replaced as appropriate; L Ｘ１ C １－６ Alkylene, C １－６ Heteroalkylene, -O-, -S-, or -NR ａ - and here, the alkylene and heteroalkylene are one or more R Ｘ１ａ It may be replaced as appropriate; R Ｘ１ａ These are, independently, halogen and C １－６ Alkyl, C １ -C ６ Haloalkyl, C １ -C ６ Hydroxyalkyl, C １ -C ６ Aminoalkyl, C １ -C ６ Heteroalkyl, C ２ -C ６ Alkenil, C ２ -C ６ Alkinyl, -CN, -NO ２ , -OR ａ , -SR ａ , -NR ｃ R ｄ , -S(=O)R ａ , -S (=O) ２ R ａ , -SF ５ , -S (=O) ２ NR ｃ R ｄ , -S(=O)(=NR ａ ) R ａ , -N=S(=O)R ｃ R ｄ , -NR ａ S (=O) ２ R ａ Amidinil, -NR ａ C (=NH) (NR ａ ) ２ , -NR ａ S (=O) ２ NR ｃ R ｄ , -C(=O)R ａ , -C (=O) OR ａ -OC(=O)R ａ , -OC(=O)OR ａ , -OC(=O)NR ｃ R ｄ , -NR ａ C(=O)R ａ , -NR ａ C (=O) OR ａ , -NR ａ C(=O)NR ｃ R ｄ , -C(=O)NR ｃ R ｄ , -P(=O)(OR ｃ ) ( OR ｄ ), -P(=O)R ｃ R ｄ aryl, heteroaryl, cycloalkyl, heterocycloalkyl, =O, =S, or =N(R) ａ ) where the aryl, heteroaryl, cycloalkyl, heterocycloalkyl, alkyl, heteroalkyl, alkenyl, and alkynyl each have one or more R ｅ It may be replaced as appropriate; *X12 is C(O)(CH ２ ) ｋｘＲ Represents the connection point to; *X2 represents the connection point to X2. The radiopharmaceutical or a pharmaceutically acceptable salt thereof according to claim 26, or a conjugate or a pharmaceutically acceptable salt thereof.

29. X1, 【Chemistry 14】 [In the formula, R ｎ１ is hydrogen or methyl; R Ｘ１ is hydrogen, C １－６ Alkyl, C １－６ Haloalkyl, C １－６ Hydroxyalkyl, C １－６ Aminoalkyl, C １－６ Heteroalkyl, -L Ｘ１ -5-6 member heterocycloalkyl, -L Ｘ１ -C ４－６ Cycloalkyl, -L Ｘ１ -C ６－１０ Aryl, or -L Ｘ１ -5 to 10 member heteroaryls, where each alkyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl is one or more R Ｘ１ａ It may be replaced as appropriate; R Ｘ１’ is hydrogen or methyl; or, R ｎ１ and R Ｘ１’ It forms a 5-6 member heterocycloalkyl group with the atoms in between, which consists of one or more R Ｘ１ａ It may be replaced as appropriate; L Ｘ１ C １－６ Alkylene or C １－６ It is a heteroalkylene, where the alkylene and heteroalkylene are one or more R Ｘ１ａ It may be replaced as appropriate; R Ｘ１ａ These are, independently, halogen and C １－６ Alkyl, C １ -C ６ Haloalkyl, C １ -C ６ Hydroxyalkyl, C １ -C ６ Aminoalkyl, C １ -C ６ Heteroalkyl, C ２ -C ６ Alkenil, C ２ -C ６ Alkinyl, -CN, -NO ２ , -OR ａ , -SR ａ , -NR ｃ R ｄ , -S(=O)R ａ , -S (=O) ２ R ａ , -SF ５ , -S (=O) ２ NR ｃ R ｄ , -S(=O)(=NR ａ ) R ａ , -N=S(=O)R ｃ R ｄ , -NR ａ S (=O) ２ R ａ Amidinil, -NR ａ C (=NH) (NR ａ ) ２ , -NR ａ S (=O) ２ NR ｃ R ｄ , -C(=O)R ａ , -C (=O) OR ａ -OC(=O)R ａ , -OC(=O)OR ａ , -OC(=O)NR ｃ R ｄ , -NR ａ C(=O)R ａ , -NR ａ C (=O) OR ａ , -NR ａ C(=O)NR ｃ R ｄ , -C(=O)NR ｃ R ｄ , -P(=O)(OR ｃ ) ( OR ｄ ), -P(=O)R ｃ R ｄ aryl, heteroaryl, cycloalkyl, heterocycloalkyl, =O, =S, or =N(R) ａ ) where the aryl, heteroaryl, cycloalkyl, heterocycloalkyl, alkyl, heteroalkyl, alkenyl, and alkynyl each have one or more R ｅ It may be replaced as appropriate; *X12 is C(O)(CH ２ ) ｋｘＲ Represents the connection point to; *X2 represents the connection point to X2. The radiopharmaceutical or a pharmaceutically acceptable salt thereof according to claim 28, or a conjugate or a pharmaceutically acceptable salt thereof.

30. R Ｘ１ However, hydrogen, C １－６ Alkyl, C １－６ Heteroalkyl, -L Ｘ１ -Piperidinil, -L Ｘ１ -Piperazinil, -L Ｘ１ -phenyl, or -L Ｘ１ -Pyridinyl, where the alkyl, heteroalkyl, phenyl, pyridinyl, piperidinyl, and piperazinyl each have one or more R Ｘ１ａ A radiopharmaceutical or a pharmaceutically acceptable salt thereof according to claim 28 or 29, or a conjugate or a pharmaceutically acceptable salt thereof, which may be appropriately substituted with.

31. R Ｘ１ａ However, each is independent of halogen and C １－６ Alkyl, C １ -C ６ Haloalkyl, C １ -C ６ Hydroxyalkyl, C １ -C ６ Aminoalkyl, C １ -C ６ Heteroalkyl, -CN, -NO ２ , -OR ａ , -SR ａ , -NR ｃ R ｄ , -S(=O)R ａ , -S (=O) ２ R ａ , -S (=O) ２ NR ｃ R ｄ , -NR ａ S (=O) ２ R ａ , -NR ａ C (=NH) (NR ａ ) ２ , -C(=O)R ａ , -C (=O) OR ａ -OC(=O)R ａ , -OC(=O)OR ａ , -OC(=O)NR ｃ R ｄ , -NR ａ C(=O)R ａ , -NR ａ C (=O) OR ａ , -NR ａ C(=O)NR ｃ R ｄ , -C(=O)NR ｃ R ｄ , or = O, where the alkyl and heteroalkyl groups each have one or more R ｅ A radiopharmaceutical or a pharmaceutically acceptable salt thereof according to any one of claims 28 to 30, or a conjugate or a pharmaceutically acceptable salt thereof, which may be appropriately substituted with.

32. A radiopharmaceutical or a pharmaceutically acceptable salt thereof according to any one of claims 26 to 31, wherein X2 is an N-alkylated amino acid.

33. X2, 【Chemistry 15】 [In the formula, R ｎ２ is hydrogen or C １－３ It is an alkyl group, where the alkyl group is one or more R Ｘ２ａ It may be replaced as appropriate; R Ｘ２ is hydrogen, C １－６ Alkyl, C １－６ Haloalkyl, C １－６ Hydroxyalkyl, C １－６ Aminoalkyl, C １－６ Heteroalkyl, C ２－６ Alkenil, C ２－６ Alkinyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, -L Ｘ２ - Heterocycloalkyl, - L Ｘ２ -Cycloalkyl, -L Ｘ２ -aryl, or -L Ｘ２ -A heteroaryl, where each alkyl, heteroalkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl is one or more R Ｘ２ａ It may be replaced as appropriate; R Ｘ２’ is hydrogen or C １－６ It is an alkyl group, where the alkyl group is one or more R Ｘ２ａ It may be replaced as appropriate; or, R ｎ２ and R Ｘ２’ It forms a 5-6 member heterocycloalkyl group with the atoms in between, which consists of one or more R Ｘ２ａ It may be replaced as appropriate; L Ｘ２ C １－６ Alkylene, C １－６ Heteroalkylene, -O-, -S-, or -NR ａ - and here, the alkylene and heteroalkylene are one or more R Ｘ２ａ It may be replaced as appropriate; R Ｘ２ａ These are, independently, halogen and C １－６ Alkyl, C １ -C ６ Haloalkyl, C １ -C ６ Hydroxyalkyl, C １ -C ６ Aminoalkyl, C １ -C ６ Heteroalkyl, C ２ -C ６ Alkenil, C ２ -C ６ Alkinyl, -CN, -NO ２ , -OR ａ , -SR ａ , -NR ｃ R ｄ , -S(=O)R ａ , -S (=O) ２ R ａ , -SF ５ , -S (=O) ２ NR ｃ R ｄ , -S(=O)(=NR ａ ) R ａ , -N=S(=O)R ｃ R ｄ , -NR ａ S (=O) ２ R ａ Amidinil, -NR ａ C (=NH) (NR ａ ) ２ , -NR ａ S (=O) ２ NR ｃ R ｄ , -C(=O)R ａ , -C (=O) OR ａ -OC(=O)R ａ , -OC(=O)OR ａ , -OC(=O)NR ｃ R ｄ , -NR ａ C(=O)R ａ , -NR ａ C (=O) OR ａ , -NR ａ C(=O)NR ｃ R ｄ , -C(=O)NR ｃ R ｄ , -P(=O)(OR ｃ ) ( OR ｄ ), -P(=O)R ｃ R ｄ aryl, heteroaryl, cycloalkyl, heterocycloalkyl, =O, =S, =N(R ａ ), aryl, heteroaryl, cycloalkyl, or heterocycloalkyl, where each of the aryl, heteroaryl, cycloalkyl, heterocycloalkyl, alkyl, heteroalkyl, alkenyl, and alkynyl is one or more R ｅ It may be replaced as appropriate; *X1 represents the connection point to X1; *X3 represents the connection point to X3. A radiopharmaceutical or a pharmaceutically acceptable salt thereof according to any one of claims 26 to 31, or a conjugate or a pharmaceutically acceptable salt thereof.

34. X2, 【Chemistry 16】 [In the formula, R ｎ２ is hydrogen or methyl; R Ｘ２ is hydrogen, C １－６ Alkyl, C １－６ Haloalkyl, C １－６ Hydroxyalkyl, C １－６ Aminoalkyl, C １－６ Heteroalkyl, -L Ｘ２ -5-6 member heterocycloalkyl, -L Ｘ２ -C ４－６ Cycloalkyl, -L Ｘ２ -C ６－１０ Aryl, or -L Ｘ２ -5 to 10 member heteroaryls, where each alkyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl is one or more R Ｘ２ａ It may be replaced as appropriate; R Ｘ２’ is hydrogen or methyl; or, R ｎ２ and R Ｘ２’ It forms a 5-6 member heterocycloalkyl group with the atoms in between, which consists of one or more R Ｘ２ａ It may be replaced as appropriate; L Ｘ２ C １－６ Alkylene or C １－６ It is a heteroalkylene, where the alkylene and heteroalkylene are one or more R Ｘ２ａ It may be replaced as appropriate; R Ｘ２ａ These are, independently, halogen and C １－６ Alkyl, C １ -C ６ Haloalkyl, C １ -C ６ Hydroxyalkyl, C １ -C ６ Aminoalkyl, C １ -C ６ Heteroalkyl, C ２ -C ６ Alkenil, C ２ -C ６ Alkinyl, -CN, -NO ２ , -OR ａ , -SR ａ , -NR ｃ R ｄ , -S(=O)R ａ , -S (=O) ２ R ａ , -SF ５ , -S (=O) ２ NR ｃ R ｄ , -S(=O)(=NR ａ ) R ａ , -N=S(=O)R ｃ R ｄ , -NR ａ S (=O) ２ R ａ Amidinil, -NR ａ C (=NH) (NR ａ ) ２ , -NR ａ S (=O) ２ NR ｃ R ｄ , -C(=O)R ａ , -C (=O) OR ａ -OC(=O)R ａ , -OC(=O)OR ａ , -OC(=O)NR ｃ R ｄ , -NR ａ C(=O)R ａ , -NR ａ C (=O) OR ａ , -NR ａ C(=O)NR ｃ R ｄ , -C(=O)NR ｃ R ｄ , -P(=O)(OR ｃ ) ( OR ｄ ), -P(=O)R ｃ R ｄ aryl, heteroaryl, cycloalkyl, heterocycloalkyl, =O, =S, or =N(R) ａ ) where the alkyl, heteroalkyl, alkenyl, and alkynyl each have one or more R ｅ It may be replaced as appropriate; *X1 represents the connection point to X1; *X3 represents the connection point to X3. The radiopharmaceutical or a pharmaceutically acceptable salt thereof according to claim 33, or a conjugate or a pharmaceutically acceptable salt thereof.

35. R Ｘ２ However, hydrogen, C １－６ Alkyl, C １－６ Heteroalkyl, -L Ｘ２ -Piperidinil, L Ｘ２ -Piperazinil, -L Ｘ２ -phenyl, or -L Ｘ２ -Pyridinyl, where the alkyl, heteroalkyl, phenyl, pyridinyl, piperidinyl, and piperazinyl each have one or more R Ｘ２ａ A radiopharmaceutical or a pharmaceutically acceptable salt thereof according to claim 33 or 34, or a conjugate or a pharmaceutically acceptable salt thereof, which may be appropriately substituted with.

36. R Ｘ２ａ These are, independently, halogen and C １－６ Alkyl, C １ -C ６ Haloalkyl, C １ -C ６ Hydroxyalkyl, C １ -C ６ Aminoalkyl, C １ -C ６ Heteroalkyl, -CN, -NO ２ , -OR ａ , -SR ａ , -NR ｃ R ｄ , -S(=O)R ａ , -S (=O) ２ R ａ , -S (=O) ２ NR ｃ R ｄ , -NR ａ S (=O) ２ R ａ , -NR ａ C (=NH) (NR ａ ) ２ , -C(=O)R ａ , -C (=O) OR ａ -OC(=O)R ａ , -OC(=O)OR ａ , -OC(=O)NR ｃ R ｄ , -NR ａ C(=O)R ａ , -NR ａ C (=O) OR ａ , -NR ａ C(=O)NR ｃ R ｄ , -C(=O)NR ｃ R ｄ , or = O, where the alkyl and heteroalkyl groups each have one or more R ｅ A radiopharmaceutical or a pharmaceutically acceptable salt thereof according to any one of claims 33 to 35, or a conjugate or a pharmaceutically acceptable salt thereof, which may be appropriately substituted with.

37. X3 is 【Chemistry 17】 [In the formula, R ｎ３ is hydrogen or C １－３ alkyl, where said alkyl may be optionally substituted with one or more R Ｘ３ａ ; R Ｘ３ is hydrogen, C １－６ alkyl, C １－６ haloalkyl, C １－６ hydroxyalkyl, C １－６ aminoalkyl, C １－６ heteroalkyl, C ２－６ alkenyl, C ２－６ alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, -L Ｘ３ -heterocycloalkyl, -L Ｘ３ -cycloalkyl, -L Ｘ３ -aryl, or -L Ｘ３ -heteroaryl, where the alkyl, heteroalkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl may each be optionally substituted with one or more R Ｘ３ａ ; and may be R Ｘ３’ is hydrogen or C １－６ It is an alkyl group, where the alkyl group is one or more R Ｘ３ａ It may be replaced as appropriate; or, R ｎ３ and R Ｘ３’ It forms a 5-6 member heterocycloalkyl group with the atoms in between, which consists of one or more R Ｘ３ａ It may be replaced as appropriate; L Ｘ３ C １－６ Alkylene, C １－６ Heteroalkylene, -O-, -S-, or -NR ａ - and here, the alkylene and heteroalkylene are one or more R Ｘ３ａ It may be replaced as appropriate; R Ｘ３ａ is, independently of one another, halogen, C １－６ alkyl, C １ -C ６ haloalkyl, C １ -C ６ hydroxyalkyl, C １ -C ６ aminoalkyl, C １ -C ６ heteroalkyl, C ２ -C ６ alkenyl, C ２ -C ６ alkynyl, -CN, -NO ２ , -OR ａ , -SR ａ , -NR ｃ R ｄ , -S(=O)R ａ , -S(=O)[[ID=​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​ ｄ , -P(=O)(OR ｃ ) ( OR ｄ ), -P(=O)R ｃ R ｄ aryl, heteroaryl, cycloalkyl, heterocycloalkyl, =O, =S, or =N(R) ａ ) where the aryl, heteroaryl, cycloalkyl, heterocycloalkyl, alkyl, heteroalkyl, alkenyl, and alkynyl each have one or more R ｅ It may be replaced as appropriate; *X2 represents the connection point to X2; *X4 represents the connection point to X4. A radiopharmaceutical or a pharmaceutically acceptable salt thereof according to any one of claims 26 to 36, or a conjugate or a pharmaceutically acceptable salt thereof.

38. X3 is [Chemistry 18] [In the formula, R ｎ３ is hydrogen or methyl; R Ｘ３ C １－６ Alkyl, C １－６ Haloalkyl, C １－６ Hydroxyalkyl, C １－６ Aminoalkyl, C １－６ Heteroalkyl, -L Ｘ３ -5-6 member heterocycloalkyl, -L Ｘ３ -C ３－６ Cycloalkyl, -L Ｘ３ -C ６－１０ Aryl, or -L Ｘ３ -5 to 10 member heteroaryls, where each alkyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl is one or more R Ｘ３ａ It may be replaced as appropriate; L Ｘ３ C １－６ Alkylene or C １－６ It is a heteroalkylene, where the alkylene and heteroalkylene are one or more R Ｘ３ａ It may be replaced as appropriate; R Ｘ３ａ These are, independently, halogen and C １－６ Alkyl, C １ -C ６ Haloalkyl, C １ -C ６ Hydroxyalkyl, C １ -C ６ Aminoalkyl, C １ -C ６ Heteroalkyl, C ２ -C ６ Alkenil, C ２ -C ６ Alkinyl, -CN, -NO ２ , -OR ａ , -SR ａ , -NR ｃ R ｄ , -S(=O)R ａ , -S (=O) ２ R ａ , -SF ５ , -S (=O) ２ NR ｃ R ｄ , -S(=O)(=NR ａ ) R ａ , -N=S(=O)R ｃ R ｄ , -NR ａ S (=O) ２ R ａ Amidinil, -NR ａ C (=NH) (NR ａ ) ２ , -NR ａ S (=O) ２ NR ｃ R ｄ , -C(=O)R ａ , -C (=O) OR ａ -OC(=O)R ａ , -OC(=O)OR ａ , -OC(=O)NR ｃ R ｄ , -NR ａ C(=O)R ａ , -NR ａ C (=O) OR ａ , -NR ａ C(=O)NR ｃ R ｄ , -C(=O)NR ｃ R ｄ , -P(=O)(OR ｃ ) ( OR ｄ ), -P(=O)R ｃ R ｄ aryl, heteroaryl, cycloalkyl, heterocycloalkyl, =O, =S, or =N(R) ａ ) where the aryl, heteroaryl, cycloalkyl, heterocycloalkyl, alkyl, heteroalkyl, alkenyl, and alkynyl each have one or more R ｅ It may be replaced as appropriate; *X2 represents the connection point to X2; *X4 represents the connection point to X4. The radiopharmaceutical or a pharmaceutically acceptable salt thereof according to claim 37, or a conjugate or a pharmaceutically acceptable salt thereof.

39. R Ｘ３ However, C １－６ Alkyl, C １－６ Heteroalkyl, -L Ｘ３ -Piperidinil, L Ｘ３ -Piperazinil, -L Ｘ３ -phenyl, or -L Ｘ３ -Pyridinyl, where the alkyl, heteroalkyl, phenyl, pyridinyl, piperidinyl, and piperazinyl each have one or more R Ｘ２ａ A radiopharmaceutical or a pharmaceutically acceptable salt thereof according to claim 37 or 38, or a conjugate or a pharmaceutically acceptable salt thereof, which may be appropriately substituted with.

40. R Ｘ３ａ However, each is independent of halogen and C １－６ Alkyl, C １ -C ６ Haloalkyl, C １ -C ６ Hydroxyalkyl, C １ -C ６ Aminoalkyl, C １ -C ６ Heteroalkyl, -CN, -NO ２ , -OR ａ , -SR ａ , -NR ｃ R ｄ , -S(=O)R ａ , -S (=O) ２ R ａ , -S (=O) ２ NR ｃ R ｄ , -NR ａ S (=O) ２ R ａ , -NR ａ C (=NH) (NR ａ ) ２ , -C(=O)R ａ , -C (=O) OR ａ -OC(=O)R ａ , -OC(=O)OR ａ , -OC(=O)NR ｃ R ｄ , -NR ａ C(=O)R ａ , -NR ａ C (=O) OR ａ , -NR ａ C(=O)NR ｃ R ｄ , -C(=O)NR ｃ R ｄ , or = O, where the alkyl and heteroalkyl groups each have one or more R ｅ A radiopharmaceutical or a pharmaceutically acceptable salt thereof according to any one of claims 37 to 39, or a conjugate or a pharmaceutically acceptable salt thereof, which may be appropriately substituted with.

41. X4, 【Chemistry 19】 [In the formula, R ｎ４ is hydrogen or C １－３ It is an alkyl group, where the alkyl group is one or more R Ｘ４ａ It may be replaced as appropriate; R Ｘ４ is hydrogen, C １－６ Alkyl, C １－６ Haloalkyl, C １－６ Hydroxyalkyl, C １－６ Aminoalkyl, C １－６ Heteroalkyl, C ２－６ Alkenil, C ２－６ Alkinyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, -L Ｘ４ - Heterocycloalkyl, - L Ｘ４ -Cycloalkyl, -L Ｘ４ -aryl, or -L Ｘ４ -A heteroaryl, where each alkyl, heteroalkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl is one or more R Ｘ４ａ It may be replaced as appropriate; R Ｘ４’ is hydrogen or C １－６ It is an alkyl group, where the alkyl group is one or more R Ｘ４ａ It may be replaced as appropriate; or, R ｎ４ and R Ｘ４’ It forms a 5-6 member heterocycloalkyl group with the atoms in between, which consists of one or more R Ｘ４ａ It may be replaced as appropriate; L Ｘ４ C １－６ Alkylene or C １－６ Heteroalkylene, -O-, -S-, or -NR ａ - and here, the alkylene and heteroalkylene are one or more R Ｘ４ａ It may be replaced as appropriate; R Ｘ４ａ These are, independently, halogen and C １－６ Alkyl, C １ -C ６ Haloalkyl, C １ -C ６ Hydroxyalkyl, C １ -C ６ Aminoalkyl, C １ -C ６ Heteroalkyl, C ２ -C ６ Alkenil, C ２ -C ６ Alkinyl, -CN, -NO ２ , -OR ａ , -SR ａ , -NR ｃ R ｄ , -S(=O)R ａ , -S (=O) ２ R ａ , -SF ５ , -S (=O) ２ NR ｃ R ｄ , -S(=O)(=NR ａ ) R ａ , -N=S(=O)R ｃ R ｄ , -NR ａ S (=O) ２ R ａ Amidinil, -NR ａ C (=NH) (NR ａ ) ２ , -NR ａ S (=O) ２ NR ｃ R ｄ , -C(=O)R ａ , -C (=O) OR ａ -OC(=O)R ａ , -OC(=O)OR ａ , -OC(=O)NR ｃ R ｄ , -NR ａ C(=O)R ａ , -NR ａ C (=O) OR ａ , -NR ａ C(=O)NR ｃ R ｄ , -C(=O)NR ｃ R ｄ , -P(=O)(OR ｃ ) ( OR ｄ ), -P(=O)R ｃ R ｄ aryl, heteroaryl, cycloalkyl, heterocycloalkyl, =O, =S, or =N(R) ａ ) where the aryl, heteroaryl, cycloalkyl, heterocycloalkyl, alkyl, heteroalkyl, alkenyl, and alkynyl each have one or more R ｅ It may be replaced as appropriate; *X3 represents the connection point to X3; *X5 represents the connection point to X5. A radiopharmaceutical or a pharmaceutically acceptable salt thereof according to any one of claims 26 to 40, or a conjugate or a pharmaceutically acceptable salt thereof.

42. X4, 【Chemistry 20】 [In the formula, R ｎ４ is hydrogen or C １－３ It is an alkyl group, where the alkyl group is one or more R Ｘ４ａ It may be replaced as appropriate; R Ｘ４ is hydrogen, C １－６ Alkyl, C １－６ Haloalkyl, C １－６ Hydroxyalkyl, C １－６ Aminoalkyl, C １－６ Heteroalkyl, -L Ｘ４ -5-6 member heterocycloalkyl, -L Ｘ４ -C ３－６ Cycloalkyl, -L Ｘ４ -C ６－１０ Aryl, or -L Ｘ４ -5 to 10 member heteroaryls, where each alkyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl is one or more R Ｘ４ａ It may be replaced as appropriate; L Ｘ４ C １－６ Alkylene or C １－６ It is a heteroalkylene, where the alkylene and heteroalkylene are one or more R Ｘ４ａ It may be replaced as appropriate; R Ｘ４ａ These are, independently, halogen and C １－６ Alkyl, C １ -C ６ Haloalkyl, C １ -C ６ Hydroxyalkyl, C １ -C ６ Aminoalkyl, C １ -C ６ Heteroalkyl, C ２ -C ６ Alkenil, C ２ -C ６ Alkinyl, -CN, -NO ２ , -OR ａ , -SR ａ , -NR ｃ R ｄ , -S(=O)R ａ , -S (=O) ２ R ａ , -SF ５ , -S (=O) ２ NR ｃ R ｄ , -S(=O)(=NR ａ ) R ａ , -N=S(=O)R ｃ R ｄ , -NR ａ S (=O) ２ R ａ Amidinil, -NR ａ C (=NH) (NR ａ ) ２ , -NR ａ S (=O) ２ NR ｃ R ｄ , -C(=O)R ａ , -C (=O) OR ａ -OC(=O)R ａ , -OC(=O)OR ａ , -OC(=O)NR ｃ R ｄ , -NR ａ C(=O)R ａ , -NR ａ C (=O) OR ａ , -NR ａ C(=O)NR ｃ R ｄ , -C(=O)NR ｃ R ｄ , -P(=O)(OR ｃ ) ( OR ｄ ), -P(=O)R ｃ R ｄ aryl, heteroaryl, cycloalkyl, heterocycloalkyl, =O, =S, or =N(R) ａ ) where the aryl, heteroaryl, cycloalkyl, heterocycloalkyl, alkyl, heteroalkyl, alkenyl, and alkynyl each have one or more R ｅ It may be replaced as appropriate; *X3 represents the connection point to X3; *X5 represents the connection point to X5. The radiopharmaceutical or a pharmaceutically acceptable salt thereof according to claim 41, or a conjugate or a pharmaceutically acceptable salt thereof.

43. R Ｘ４ However, C １－６ Alkyl, C １－６ Heteroalkyl, -L Ｘ４ -Piperidinil, L Ｘ４ -Piperazinil, -L Ｘ４ -phenyl, or -L Ｘ４ -Pyridinyl, where the alkyl, heteroalkyl, phenyl, pyridinyl, piperidinyl, and piperazinyl each have one or more R Ｘ４ａ A radiopharmaceutical or a pharmaceutically acceptable salt thereof according to claim 41 or 42, or a conjugate or a pharmaceutically acceptable salt thereof, which may be appropriately substituted with.

44. R Ｘ４ａ However, each is independent of halogen and C １－６ Alkyl, C １ -C ６ Haloalkyl, C １ -C ６ Hydroxyalkyl, C １ -C ６ Aminoalkyl, C １ -C ６ Heteroalkyl, -CN, -NO ２ , -OR ａ , -SR ａ , -NR ｃ R ｄ , -S(=O)R ａ , -S (=O) ２ R ａ , -S (=O) ２ NR ｃ R ｄ , -NR ａ S (=O) ２ R ａ , -NR ａ C (=NH) (NR ａ ) ２ , -C(=O)R ａ , -C (=O) OR ａ -OC(=O)R ａ , -OC(=O)OR ａ , -OC(=O)NR ｃ R ｄ , -NR ａ C(=O)R ａ , -NR ａ C (=O) OR ａ , -NR ａ C(=O)NR ｃ R ｄ , -C(=O)NR ｃ R ｄ , or = O, where the alkyl and heteroalkyl groups each have one or more R ｅ A radiopharmaceutical or a pharmaceutically acceptable salt thereof according to any one of claims 41 to 43, or a conjugate or a pharmaceutically acceptable salt thereof, which may be appropriately substituted with.

45. A radiopharmaceutical or a pharmaceutically acceptable salt thereof according to any one of claims 26 to 44, wherein X4 is an N-alkylated amino acid.

46. X4 is a peptoid, the radiopharmaceutical or a pharmaceutically acceptable salt thereof according to any one of claims 26 to 44, or a conjugate or a pharmaceutically acceptable salt thereof.

47. R ｎ５ However, it is hydrogen or methyl; Ring A5 is C ６－１０ Aryl, 5-10 member heteroaryl, C ６－１０ They are cycloalkyl or 5-10 member heterocycloalkyl; R Ｘ５ However, each is independent of C １－６ Alkyl, C １－６ Haloalkyl, C １－６ Hydroxyalkyl, C １－６ Aminoalkyl, C １－６ Heteroalkyl, C ２－６ Alkenil, C ２－６ Alkynyl, halogen, -CN, -NO ２ , -OR ａ , -SR ａ , -SF ５ , -NR ｃ R ｄ , -S(=O)R ａ , -S (=O) ２ R ａ , -S (=O) ２ NR ｃ R ｄ , -S(=O)(=NR ａ ) R ａ , -N=S(=O)NR ｃ R ｄ , -NR ａ S (=O) ２ R ａ Amidinil, -NR ａ C(=NH)NR ｃ R ｄ , -NR ａ S (=O) ２ NR ｃ R ｄ , -C(=O)R ａ , -C (=O) OR ａ -OC(=O)R ａ , -OC(=O)OR ａ , -OC(=O)NR ｃ R ｄ , -NR ａ C(=O)R ａ , -NR ａ C (=O) OR ａ , -NR ａ C(=O)NR ｃ R ｄ , -C(=O)NR ｃ R ｄ , -P(=O)(OR ｃ ) ( OR ｄ ), -P(=O)R ｃ R ｄ , C ６－１０ Aryl, 5-10 member heteroaryl, C ３－６ Cycloalkyl, 5-6 member heterocycloalkyl, -L Ｘ５ -5-6 member heterocycloalkyl, -L Ｘ５ -C ３－６ Cycloalkyl, -L Ｘ５ -C ６－１０ Aryl, or -L Ｘ５ -5 to 10 member heteroaryl, where the alkyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl are one or more R Ｘ５ａ It may be replaced as appropriate; or, Two R's Ｘ５ Together, they form = O; L Ｘ５ C １－６ Alkylene or C １－６ It is a heteroalkylene, where the alkylene and heteroalkylene are one or more R Ｘ５ａ This may be substituted as appropriate. A radiopharmaceutical or a pharmaceutically acceptable salt thereof according to any one of claims 26 to 46, or a conjugate or a pharmaceutically acceptable salt thereof.

48. Ring A5 is phenyl, naphthyl, pyridinyl, cyclohexyl, piperidinyl, piperazinyl, morpholinyl, or tetrahydropyranyl; R Ｘ５ However, each is independent of halogen and C １－６ Alkyl, C １－６ Haloalkyl, C １－６ Hydroxyalkyl, C １－６ Aminoalkyl, C １－６ Heteroalkyl, -CN, -NO ２ , -OR ａ , -SR ａ , -NR ｃ R ｄ , -S(=O)R ａ , -S (=O) ２ R ａ , -S (=O) ２ NR ｃ R ｄ , -NR ａ S (=O) ２ R ａ , -NR ａ C(=NH)NR ｃ R ｄ , -NR ａ S (=O) ２ NR ｃ R ｄ , -C(=O)R ａ , -C (=O) OR ａ -OC(=O)R ａ , -OC(=O)OR ａ , -OC(=O)NR ｃ R ｄ , -NR ａ C(=O)R ａ , -NR ａ C (=O) OR ａ , -NR ａ C(=O)NR ｃ R ｄ , -C(=O)NR ｃ R ｄ , -L Ｘ５ -Piperidinil, or L Ｘ５ -Piperadinyl, where the alkyl, heteroalkyl, piperadinyl, and piperadinyl each consist of one or more R Ｘ５ａ It may be replaced as appropriate; or, Two R's Ｘ５ Together, they form = O; kx5 is 1 or 2; mx5 is 0, 1, or 2. A radiopharmaceutical or a pharmaceutically acceptable salt thereof according to any one of claims 26 to 47, or a conjugate or a pharmaceutically acceptable salt thereof.

49. R Ｘ５ａ However, each is independent of halogen and C １－６ Alkyl, C １ -C ６ Haloalkyl, C １ -C ６ Hydroxyalkyl, C １ -C ６ Aminoalkyl, C １ -C ６ Heteroalkyl, -CN, -NO ２ , -OR ａ , -SR ａ , -NR ｃ R ｄ , -S(=O)R ａ , -S (=O) ２ R ａ , -S (=O) ２ NR ｃ R ｄ , -NR ａ S (=O) ２ R ａ , -NR ａ C (=NH) (NR ａ ) ２ , -C(=O)R ａ , -C (=O) OR ａ -OC(=O)R ａ , -OC(=O)OR ａ , -OC(=O)NR ｃ R ｄ , -NR ａ C(=O)R ａ , -NR ａ C (=O) OR ａ , -NR ａ C(=O)NR ｃ R ｄ , -C(=O)NR ｃ R ｄ , or = O, where the alkyl and heteroalkyl groups each have one or more R ｅ A radiopharmaceutical or a pharmaceutically acceptable salt thereof according to any one of claims 26 to 48, or a conjugate or a pharmaceutically acceptable salt thereof, which may be appropriately substituted with.

50. R ｎ６ However, it is hydrogen or methyl; R Ｘ６ However, C １－６ Alkyl, C １－６ Haloalkyl, C １－６ Hydroxyalkyl, C １－６ Aminoalkyl, C １－６ Heteroalkyl, C ２－６ Alkenil, C ２－６ Alkinyl, C ６－１０ Aryl, 5-10 member heteroaryl, C ３－６ Cycloalkyl, 5-6 member heterocycloalkyl, -L Ｘ６ -5-6 member heterocycloalkyl, -L Ｘ６ -C ３－６ Cycloalkyl, -L Ｘ６ -C ６－１０ Aryl, or -L Ｘ６ -5 to 10 member heteroaryls, where each alkyl, heteroalkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl is one or more R Ｘ６ａ It may be replaced as appropriate; L Ｘ６ However, C １－６ Alkylene or C １－６ It is a heteroalkylene, where the alkylene and heteroalkylene are one or more R Ｘ６ａ This may be substituted as appropriate. A radiopharmaceutical or a pharmaceutically acceptable salt thereof according to any one of claims 26 to 49, or a conjugate or a pharmaceutically acceptable salt thereof.

51. R Ｘ６ However, C １－６ Alkyl, C １－６ Haloalkyl, C １－６ Hydroxyalkyl, C １－６ Aminoalkyl, C １－６ Heteroalkyl, C ３－６ Cycloalkyl, 5-6 member heterocycloalkyl, -L Ｘ６ -5-6 member heterocycloalkyl, -L Ｘ６ -C ３－６ Cycloalkyl, -L Ｘ６ -phenyl, or -L Ｘ６ - A 6-membered heteroaryl, where the alkyl, heteroalkyl, phenyl, heteroaryl, cycloalkyl, and heterocycloalkyl each have one or more R Ｘ６ａ A radiopharmaceutical or a pharmaceutically acceptable salt thereof according to any one of claims 26 to 50, or a conjugate or a pharmaceutically acceptable salt thereof, which may be appropriately substituted with.

52. R Ｘ６ａ However, each is independent of halogen and C １－６ Alkyl, C １ -C ６ Haloalkyl, C １ -C ６ Hydroxyalkyl, C １ -C ６ Aminoalkyl, C １ -C ６ Heteroalkyl, -CN, -NO ２ , -OR ａ , -SR ａ , -NR ｃ R ｄ , -S(=O)R ａ , -S (=O) ２ R ａ , -S (=O) ２ NR ｃ R ｄ , -NR ａ S (=O) ２ R ａ , -NR ａ C (=NH) (NR ａ ) ２ , -C(=O)R ａ , -C (=O) OR ａ -OC(=O)R ａ , -OC(=O)OR ａ , -OC(=O)NR ｃ R ｄ , -NR ａ C(=O)R ａ , -NR ａ C (=O) OR ａ , -NR ａ C(=O)NR ｃ R ｄ , -C(=O)NR ｃ R ｄ , or = O, where the alkyl and heteroalkyl groups each have one or more R ｅ A radiopharmaceutical or a pharmaceutically acceptable salt thereof according to any one of claims 26 to 51, or a conjugate or a pharmaceutically acceptable salt thereof, which may be appropriately substituted with.

53. R ｎ７ However, it is hydrogen or methyl; R Ｘ７ However, C １－６ Alkyl, C １－６ Haloalkyl, C １－６ Hydroxyalkyl, C １－６ Aminoalkyl, C １－６ Heteroalkyl, C ２－６ Alkenil, C ２－６ Alkinyl, C ３－６ A cycloalkyl or a 5-6 member heterocycloalkyl, where each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, and heterocycloalkyl is one or more R Ｘ７ａ This may be substituted as appropriate. A radiopharmaceutical or a pharmaceutically acceptable salt thereof according to any one of claims 26 to 52, or a conjugate or a pharmaceutically acceptable salt thereof.

54. R Ｘ７ However, C １－６ Alkyl, C １－６ Heteroalkyl, C ３－６ A cycloalkyl or a 5-6 member heterocycloalkyl, where each alkyl, heteroalkyl, cycloalkyl, and heterocycloalkyl is one or more R Ｘ７ａ A radiopharmaceutical or a pharmaceutically acceptable salt thereof according to any one of claims 26 to 53, or a conjugate or a pharmaceutically acceptable salt thereof, which may be appropriately substituted with.

55. R Ｘ７ａ However, each is independent of halogen, -CN, and -OR ａ , -SR ａ , -NR ｃ R ｄ , -C(=O)R ａ , -C (=O) OR ａ -OC(=O)R ａ , -OC(=O)OR ａ , -OC(=O)NR ｃ R ｄ , -NR ａ C(=O)R ａ , -NR ａ C (=O) OR ａ , -NR ａ C(=O)NR ｃ R ｄ , -C(=O)NR ｃ R ｄ A radiopharmaceutical or a pharmaceutically acceptable salt thereof according to any one of claims 26 to 54, or a conjugate or a pharmaceutically acceptable salt thereof, wherein the latter is equal to O.

56. Ring A8 is C ６－１０ They are aryl or 5- to 10-membered heteroaryl; R Ｘ８ However, each is independent of C １－６ Alkyl, C １－６ Haloalkyl, C １－６ Hydroxyalkyl, C １－６ Aminoalkyl, C １－６ Heteroalkyl, C ２－６ Alkenil, C ２－６ Alkynyl, halogen, -CN, -NO ２ , -OR ａ , -SR ａ , -SF ５ , -NR ｃ R ｄ , -S(=O)R ａ , -S (=O) ２ R ａ , -S (=O) ２ R ｃ R ｄ , -S(=O)(=NR ａ ) R ａ , -N=S(=O) R ｃ R ｄ , -NR ａ S (=O) ２ R ａ Amidinil, -NR ａ C(=NH)NR ｃ R ｄ , -NR ａ S (=O) ２ R ｃ R ｄ , -C(=O)R ａ , -C (=O) OR ａ -OC(=O)R ａ , -OC(=O)OR ａ , -OC(=O)NR ｃ R ｄ , -NR ａ C(=O)R ａ , -NR ａ C (=O) OR ａ , -NR ａ C(=O)NR ｃ R ｄ , -C(=O)NR ｃ R ｄ , -P(=O)(OR ｃ ) ( OR ｄ ), -P(=O)R ｃ R ｄ , C ６－１０ Aryl, 5-10 member heteroaryl, C ３－６ Cycloalkyl, 5-6 member heterocycloalkyl, -L Ｘ８ -5-6 member heterocycloalkyl, -L Ｘ８ -C ３－６ Cycloalkyl, -L Ｘ８ -C ６－１０ Aryl, or -L Ｘ８ -5 to 10 member heteroaryls, where each alkyl, heteroalkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl is one or more R Ｘ８ａ It may be replaced as appropriate; or, Two R's Ｘ８ Together, they form = O; L Ｘ８ However, C １－６ Alkylene or C １－６ It is a heteroalkylene, where the alkylene and heteroalkylene are one or more R Ｘ８ａ This may be substituted as appropriate. A radiopharmaceutical or a pharmaceutically acceptable salt thereof according to any one of claims 26 to 55, or a conjugate or a pharmaceutically acceptable salt thereof.

57. Ring A8 is phenyl, pyridinyl, indolyl, azaindolyl, indazolyl, or benzimidazolyl; R Ｘ８ However, each is independent of halogen and C １－６ Alkyl, C １－６ Haloalkyl, C １－６ Hydroxyalkyl, C １－６ Aminoalkyl, C １－６ Heteroalkyl, -CN, -NO ２ , -OR ａ , -SR ａ , -NR ｃ R ｄ , -S(=O)R ａ , -S (=O) ２ R ａ , -S (=O) ２ NR ｃ R ｄ , -NR ａ S (=O) ２ R ａ , -NR ａ C(=NH)NR ｃ R ｄ , -NR ａ S (=O) ２ NR ｃ R ｄ , -C(=O)R ａ , -C (=O) OR ａ -OC(=O)R ａ , -OC(=O)OR ａ , -OC(=O)NR ｃ R ｄ , -NR ａ C(=O)R ａ , -NR ａ C (=O) OR ａ , -NR ａ C(=O)NR ｃ R ｄ , -C(=O)NR ｃ R ｄ , -L Ｘ８ -Piperidinil, or L Ｘ８ -Piperadinyl, where the alkyl, heteroalkyl, piperadinyl, and piperadinyl each consist of one or more R Ｘ８ａ It may be replaced as appropriate; or, Two R's Ｘ５ Together, they form = O; kx8 is 1 or 2; mx8 is 0, 1, or 2. A radiopharmaceutical or a pharmaceutically acceptable salt thereof according to any one of claims 26 to 56, or a conjugate or a pharmaceutically acceptable salt thereof.

58. R Ｘ８ａ However, each is independent of halogen and C １－６ Alkyl, C １ -C ６ Haloalkyl, C １ -C ６ Hydroxyalkyl, C １ -C ６ Aminoalkyl, C １ -C ６ Heteroalkyl, -CN, -NO ２ , -OR ａ , -SR ａ , -NR ｃ R ｄ , -S(=O)R ａ , -S (=O) ２ R ａ , -S (=O) ２ NR ｃ R ｄ , -NR ａ S (=O) ２ R ａ , -NR ａ C (=NH) (NR ａ ) ２ , -C(=O)R ａ , -C (=O) OR ａ -OC(=O)R ａ , -OC(=O)OR ａ , -OC(=O)NR ｃ R ｄ , -NR ａ C(=O)R ａ , -NR ａ C (=O) OR ａ , -NR ａ C(=O)NR ｃ R ｄ , -C(=O)NR ｃ R ｄ , or = O, where the alkyl and heteroalkyl groups each have one or more R ｅ A radiopharmaceutical or a pharmaceutically acceptable salt thereof according to any one of claims 26 to 57, or a conjugate or a pharmaceutically acceptable salt thereof, which may be appropriately substituted with.

59. R ｎ９ However, it is hydrogen or methyl; Ring A9 is C ６－１０ They are aryl or 5- to 10-membered heteroaryl; R Ｘ９ However, each is independent of halogen and C １－６ Alkyl, C １－６ Haloalkyl, C １－６ Hydroxyalkyl, C １－６ Aminoalkyl, C １－６ Heteroalkyl, C ２－６ Alkenil, C ２－６ Alkinyl, -CN, -NO ２ , -OR ａ , -SR ａ , -SF ５ , or -NR ｃ R ｄ Here, the alkyl, heteroalkyl, alkenyl, and alkynyl each have one or more R Ｘ９ａ It may be replaced as appropriate; or, Two R's Ｘ９ Together, they form = O. A radiopharmaceutical or a pharmaceutically acceptable salt thereof according to any one of claims 26 to 58, or a conjugate or a pharmaceutically acceptable salt thereof.

60. Ring A9 is phenyl, naphthyl, pyridinyl, indolyl, azaindolyl, indazolyl, benzimidazolyl, or isoquinolinyl; R Ｘ９ However, each is independent of halogen and C １－６ Alkyl, C １－６ Haloalkyl, -CN, -OR ａ , -SR ａ , or -NR ｃ R ｄ Here, the alkyl and heteroalkyl each have one or more R Ｘ９ａ It may be replaced as appropriate; kx9 is 1 or 2; mx9 is 0, 1, or 2. A radiopharmaceutical or a pharmaceutically acceptable salt thereof according to any one of claims 26 to 59, or a conjugate or a pharmaceutically acceptable salt thereof.

61. R Ｘ９ａ However, each is independent of halogen and C １－６ Alkyl, C １ -C ６ Haloalkyl, C １ -C ６ Hydroxyalkyl, C １ -C ６ Aminoalkyl, C １ -C ６ Heteroalkyl, -CN, -NO ２ , -OR ａ , -SR ａ , -NR ｃ R ｄ , -S(=O)R ａ , -S (=O) ２ R ａ , -S (=O) ２ NR ｃ R ｄ , -NR ａ S (=O) ２ R ａ , -NR ａ C (=NH) (NR ａ ) ２ , -C(=O)R ａ , -C (=O) OR ａ -OC(=O)R ａ , -OC(=O)OR ａ , -OC(=O)NR ｃ R ｄ , -NR ａ C(=O)R ａ , -NR ａ C (=O) OR ａ , -NR ａ C(=O)NR ｃ R ｄ , -C(=O)NR ｃ R ｄ , or = O, where the alkyl and heteroalkyl groups each have one or more R ｅ A radiopharmaceutical or a pharmaceutically acceptable salt thereof according to any one of claims 26 to 60, or a conjugate or a pharmaceutically acceptable salt thereof, which may be appropriately substituted with.

62. Ring A11 is C ６－１０ They are aryl or 5- to 10-membered heteroaryl; R Ｘ１１ However, each is independent of C １－６ Alkyl, C １－６ Haloalkyl, C １－６ Hydroxyalkyl, C １－６ Aminoalkyl, C １－６ Heteroalkyl, halogen, -CN, -NO ２ , -OR ａ , -SR ａ , -SF ５ , -NR ｃ R ｄ , -S(=O)R ａ , -S (=O) ２ R ａ , -S (=O) ２ R ｃ R ｄ , -S(=O)(=NR ａ ) R ａ , -N=S(=O)R ｃ R ｄ , -NR ａ S (=O) ２ R ａ Amidinil, -NR ａ C(=NH)NR ｃ R ｄ , -NR ａ S (=O) ２ R ｃ R ｄ , -C(=O)R ａ , -C (=O) OR ａ -OC(=O)R ａ , -OC(=O)OR ａ , -OC(=O)NR ｃ R ｄ , -NR ａ C(=O)R ａ , -NR ａ C (=O) OR ａ , -NR ａ C(=O)NR ｃ R ｄ , -C(=O)NR ｃ R ｄ , -P(=O)(OR ｃ ) ( OR ｄ ), -P(=O)R ｃ R ｄ , C ６－１０ Aryl, 5-10 member heteroaryl, C ３－６ Cycloalkyl, 5-6 member heterocycloalkyl, -L Ｘ１１ -5-6 member heterocycloalkyl, -L Ｘ１１ -C ３－６ Cycloalkyl, -L Ｘ１１ -C ６－１０ Aryl, or -L Ｘ１１ -5 to 10 member heteroaryls, where each alkyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl is one or more R Ｘ１１ａ It may be replaced as appropriate; or, Two R's Ｘ１１ Together, they form = O; L Ｘ１１ However, C １－６ Alkylene, C １－６ A heteroalkylene or -O-, where the alkylene and heteroalkylene are one or more R Ｘ１１ａ This may be substituted as appropriate. A radiopharmaceutical or a pharmaceutically acceptable salt thereof according to any one of claims 26 to 61, or a conjugate or a pharmaceutically acceptable salt thereof.

63. Ring A11 is phenyl or pyridinyl; R Ｘ１１ However, each is independent of C １－６ Alkyl, C １－６ Haloalkyl, C １－６ Hydroxyalkyl, C １－６ Aminoalkyl, C １－６ Heteroalkyl, halogen, -CN, -NO ２ , -OR ａ , -SR ａ , -NR ｃ R ｄ , -S(=O)R ａ , -S (=O) ２ R ａ , -S (=O) ２ R ｃ R ｄ , -NR ａ S (=O) ２ R ａ , -NR ａ C(=NH)NR ｃ R ｄ , -NR ａ S (=O) ２ R ｃ R ｄ , -C(=O)R ａ , -C (=O) OR ａ -OC(=O)R ａ , -OC(=O)OR ａ , -OC(=O)NR ｃ R ｄ , -NR ａ C(=O)R ａ , -NR ａ C (=O) OR ａ , -NR ａ C(=O)NR ｃ R ｄ , -C(=O)NR ｃ R ｄ , C ６－１０ Aryl, 5-10 member heteroaryl, C ３－６ Cycloalkyl, 5-6 member heterocycloalkyl, -L Ｘ１１ -5-6 member heterocycloalkyl, -L Ｘ１１ -C ３－６ Cycloalkyl, -L Ｘ１１ -C ６－１０ Aryl, or -L Ｘ１１ -5 to 10 member heteroaryls, where each alkyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl is one or more R Ｘ１１ａ It may be replaced as appropriate; or, Two R's Ｘ１１ Together, they form = O; kx11 is 1, 2, 3, or 4; mx11 is 0, 1, or 2. A radiopharmaceutical or a pharmaceutically acceptable salt thereof according to any one of claims 26 to 62, or a conjugate or a pharmaceutically acceptable salt thereof.

64. R Ｘ１１ However, each is independent of phenyl, pyridinyl, pyrrolyl, pyrazolyl, imidazolyl, cyclohexyl, piperidinyl, piperazinyl, morpholinyl, tetrahydropyranil, -L Ｘ１１ -5-6 member heterocycloalkyl, -L Ｘ１１ -phenyl, or -L Ｘ１１ -Pyridinyl, where phenyl, pyridinyl, pyrrolyl, pyrazolyl, imidazolyl, cyclohexyl, piperidinyl, piperazinyl, morpholinyl, tetrahydropyranyl, and heterocycloalkyl each have one or more R Ｘ１１ａ A radiopharmaceutical or a pharmaceutically acceptable salt thereof according to any one of claims 26 to 63, or a conjugate or a pharmaceutically acceptable salt thereof, which may be appropriately substituted with.

65. R Ｘ１１ａ However, each is independent of halogen and C １－６ Alkyl, C １ -C ６ Haloalkyl, C １ -C ６ Hydroxyalkyl, C １ -C ６ Aminoalkyl, C １ -C ６ Heteroalkyl, -CN, -NO ２ , -OR ａ , -SR ａ , -NR ｃ R ｄ , -S(=O)R ａ , -S (=O) ２ R ａ , -S (=O) ２ NR ｃ R ｄ , -NR ａ S (=O) ２ R ａ , -NR ａ C (=NH) (NR ａ ) ２ , -C(=O)R ａ , -C (=O) OR ａ -OC(=O)R ａ , -OC(=O)OR ａ , -OC(=O)NR ｃ R ｄ , -NR ａ C(=O)R ａ , -NR ａ C (=O) OR ａ , -NR ａ C(=O)NR ｃ R ｄ , -C(=O)NR ｃ R ｄ , or = O, where the alkyl and heteroalkyl groups each have one or more R ｅ A radiopharmaceutical or a pharmaceutically acceptable salt thereof according to any one of claims 26 to 64, or a conjugate or a pharmaceutically acceptable salt thereof, which may be appropriately substituted with.

66. A conjugate according to claim 5 or a pharmaceutically acceptable salt thereof, selected from Table 9.

67. The following structure: 【Chemistry 21】 A conjugate having or a pharmaceutically acceptable salt thereof.

68. A pharmaceutical composition comprising a radiopharmaceutical according to any one of claims 1 to 3 and 5 to 65 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient or carrier.

69. A method for treating a disease or disorder characterized by overexpression of glypican 3 (GPC3) in a subject requiring treatment, characterized by administering to the subject a therapeutically effective amount of a radiopharmaceutical or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 3 and 5 to 65, or a pharmaceutical composition according to claim 68.

70. A method for treating a disease or disorder characterized by overexpression of GPC3 in a subject requiring treatment, wherein the method is Administering the subject a first radiopharmaceutical or a pharmaceutically acceptable salt thereof; and The method is characterized by administering a therapeutically effective dose of a second radiopharmaceutical or a pharmaceutically acceptable salt thereof to the subject. The first radiopharmaceutical or a pharmaceutically acceptable salt thereof is one of the claims 1 to 3 and 5 to 65, wherein the radionuclide is a diagnostic radionuclide. A method wherein the second radiopharmaceutical or a pharmaceutically acceptable salt thereof is one of the claims 1 to 3 and 5 to 65, wherein the radionuclide is a therapeutic radionuclide.

71. A method for diagnosing a disease or disorder characterized by overexpression of GPC3 in a subject requiring diagnosis, the method comprising administering to the subject a radiopharmaceutical according to any one of claims 1 to 3 and 5 to 65 or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to claim 68, and imaging the subject to determine the expression level of GPC3 in the subject, wherein the radionuclide is suitable for use as an imaging isotope.

72. The method according to any one of claims 69 to 71, wherein the disease or disorder is cancer.

73. The method according to claim 72, wherein the cancer is hepatocellular carcinoma, squamous cell carcinoma of the lung, adenocarcinoma of the lung, germ cell tumor, hepatoblastoma, Wilms' tumor, malignant rhabdoid tumor, rhabdomyosarcoma, liposarcoma, thyroid cancer, pancreatic cancer, small intestine cancer, small cell neuroendocrine carcinoma (SCNC), castration-resistant prostate adenocarcinoma treated with hormone therapy, ovarian cancer, gastric cancer, esophageal cancer, or malignant melanoma.

74. A kit, tester, or composition for determining the expression level of GPC3 in a sample, comprising a radiopharmaceutical, conjugate, or pharmaceutically acceptable salt thereof according to any one of claims 1 to 67, or the pharmaceutical composition according to claim 68.

75. A kit, tester, or composition according to claim 74, suitable for use in a diagnostic method for a disease or disorder characterized by overexpression or decreased expression of GPC3.

76. The kit, tester, or composition according to claim 74 or 75, wherein the sample is derived from a subject suspected of having a disease or disorder characterized by overexpression or decreased expression of GPC3.

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