Ligand compound of ubiquitin ligase and protac molecule comprising same

Abstract

The present invention relates to a ubiquitin ligase ligand compound and a proteolysis targeting chimera (PROTAC) molecule comprising same and, more specifically, to a compound acting as a ligand of E3 ubiquitin ligase or a prodrug thereof, and a PROTAC heterobifunctional molecule comprising same.

Description

Ligand compound of ubiquitin ligase and PROTAC molecule containing same

[0001] The present invention relates to a ligand compound of ubiquitin ligase and a PROTAC (proteolysis targeting chimera) molecule comprising the same, and more particularly, to a compound acting as a ligand of E3 ubiquitin ligase or a prodrug thereof, and a PROTAC heterobifunctional molecule comprising the same.

[0002] The N-end rule states that the lifetime of a protein depends on the characteristics of its N-terminal residue. The N-terminal residue that destabilizes the protein is called an N-degron, and is divided into type 1 and type 2. Type 1 N-degrons contain basic amino acid residues that can be positively charged, such as arginine (Arg), lysine (Lys), and histidine (His), while type 2 N-degrons contain hydrophobic amino acid residues, such as phenylalanine (Phe), tryptophan (Trp), tyrosine (Tyr), leucine (Leu), or isoleucine (Ile) (Varshavsky, A. et al. Protein Science 2011, 20, 1298-1345).

[0003] In mammals, seven isoforms of ubiquitin protein ligase E3 component N-recognin (UBR) proteins, which commonly contain the evolutionarily well-conserved UBR box, are known (see Fig. 1; Kim, JG et al. Int. J. Mol. Sci. 2021, 22, 8323). In addition to the UBR box, UBR proteins contain RING, HECT, F-box, or PHD domains that bind to the E2 enzyme of other E3 ligases. Among the UBR protein isoforms, UBR1, UBR2, UBR4, and UBR5 proteins bind to type 1 N-degrons (Tasaki, T. et al. J. Biol. Chem. 2009, 284, 1884-1895; Nillegoda, NB et al. Mol. Biol. Cell 2010, 21, 2102-2116).

[0004] The protein crystal structures of the UBR box of human UBR1, UBR2 and yeast UBR1 are known, and the UBR box contains three Zn cations, and Zn 2+There are two zinc finger motifs capable of coordinating ions and two binding pockets capable of recognizing the first and second amino acid residues of the N-degron (Choi, WS et al. Nat. Struct. Mol. Biol. 2010, 17, 1175-1181; Matta-Camacho, E. et al. Nat. Struct. Mol. Biol. 2010, 17, 1182-1187; Munoz-Escobar, J. Structure 2017, 25, 719-729). The first binding pocket is composed of aspartic acid (Asp), threonine (Thr), and phenylalanine (Phe) residues, which form a negatively charged protein surface and allow strong interactions with type 1 N-degrons, which have positively charged basic residues, through hydrogen bonding and charge-charge interactions. The second binding pocket also allows selective recognition of N-degrons through interactions with specific residues, such as serine (Ser), valine (Val), phenylalanine (Phe), and threonine (Thr).

[0005] The UBR box of the UBR protein recognizes N-degrons and plays a crucial role in cellular protein degradation. Ligand compounds that bind to the UBR box can participate in protein degradation pathways. Furthermore, UBR proteins are known to play essential regulatory roles in numerous signaling pathways, including G-protein signaling, apoptosis, and inflammation. Dysregulation in these signaling pathways can lead to disease states such as cancer and neurodegeneration.

[0006] In G-protein-coupled receptors (GPCRs), heterotrimeric G proteins are known to dissociate into downstream subunits by external ligands or signal mediators, and downstream signaling pathways are stimulated by activated GTP-bound proteins. Regulator of G-protein signaling (RGS) proteins, which play a key role in this signaling cascade, undergo arginylation of their N-terminal residues through metabolism and ubiquitination by UBR1 and UBR2, leading to protein degradation (Lee, MJ et al. Proc. Natl. Acad. Sci. USA 2005, 102, 15030-15035). Therefore, it has been reported that inhibition of the function of UBR1 and UBR2 stabilizes RGS proteins, promotes hydrolysis of GTP-binding subunits, inactivates G-protein signaling, and impairs neurodevelopment and cardiovascular development (Sjogren, B. et al. Mol. Pharmacol. 2010, 78, 550-557; Davydov, IV et al. J. Biol. Chem. 2000, 275, 22931-22941). Dysregulation of the apoptotic process, which maintains homeostasis by selectively eliminating damaged or abnormal cells, can lead to cancer and neurodegenerative diseases. Knockdown experiments using siRNA (small interfering RNA) have shown that depletion of UBR1, UBR2, UBR4, and UBR5 increases apoptosis in various cancer cells (Leboeuf, D. et al. Mol. Ther. 2020, 28, 1092-1104).Additionally, RIPK1 (receptor-interacting serine / threonine-protein kinase 1), known as a pro-apoptotic fragment, is known to be ubiquitinated by UBR protein and promote cell survival (Zhang, A. et al. Nat. Commun. 2019, 10, 4158).

[0007] Inflammation is a protective response induced by the well-conserved innate immune system to protect against pathogens, damaged cells, or harmful stimuli. Some inflammatory fragments contain unstable N-terminal residues, leading to their degradation via the N-degron pathway, such as UBR1, UBR2, UBR4, and UBR5. Indeed, knockdown of UBR1, UBR2, UBR4, and UBR5 via siRNA significantly increased IL-1β secretion (Leboeuf, D. Biomolecules 2020, 10, 903), suggesting that UBR E3 ligases are also involved in inflammatory responses.

[0008] Meanwhile, a proteolysis targeting chimera (PROTAC) is a heterobifunctional molecule consisting of a ligand for a target protein and a ligand that binds to an E3 ubiquitin ligase, linked via a linker. PROTACs simultaneously bind to both proteins, bringing the target protein into close proximity to the E3 ubiquitin ligase. This allows the E3 ubiquitin ligase to recognize the target protein as a substrate, triggering polyubiquitination and subsequent proteasomal degradation. This principle allows for the effective removal of specific proteins from cells. Therefore, PROTACs can be used as chemical probes for studying the function of target proteins and, furthermore, hold great potential as therapeutic agents for diseases. However, despite these advantages, the current use of PROTAC technology has limitations. One of these limitations is the limited number of cell types and tissues that can be targeted. Although there are over 600 E3 ubiquitin ligases in the human body, only a few, such as cereblon (CRBN) and Von Hippel-Lindau tumor suppressor (VHL), are currently used as E3 ubiquitin ligases in the PROTAC design.

[0009] Accordingly, the present invention has as a technical problem a compound or a prodrug thereof that can efficiently act as a ligand of an E3 ubiquitin ligase by binding to the UBR box of a UBR protein.

[0010] In addition, the present invention has as another technical object to provide a PROTAC (proteolysis targeting chimera) heterobifunctional molecule comprising a ligand compound of the E3 ubiquitin ligase or a prodrug thereof.

[0011] To solve the above technical problem, the present invention provides a compound of the following chemical formula 1 or a prodrug thereof:

[0012] [Chemical Formula 1]

[0013]

[0014]

[0015] In the above chemical formula 1, R1, R2, R3, R4, R5, R6, L, m and n are as defined herein.

[0016]

[0017] In addition, in order to solve the above other technical problems, the present invention provides a chimeric compound of the following chemical formula 2:

[0018] [Chemical Formula 2]

[0019]

[0020]

[0021] In the above chemical formula 2, A and B are as defined herein, and A and B are chemically linked by a linker.

[0022] The compound according to the present invention or a prodrug thereof can act as a ligand for an efficient E3 ubiquitin ligase, thereby efficiently degrading a target protein by the ubiquitin-proteasome system of a cell in a PROTAC (proteolysis targeting chimera) technology utilizing the compound.

[0023] Figure 1 shows the seven isoforms of ubiquitin protein ligase E3 component n-recognin (UBR) proteins.

[0024] Figure 2 shows the LC and Mass analysis data of PROTAC of Example 164.

[0025] Figure 3 is a graph showing the results of measuring the binding affinity of the compound of Example 31 and the PROTAC of Example 164 to the UBR1 protein in Experimental Example 2.

[0026] Figure 4 shows the results of evaluating the BRD4 protein decomposition ability of PROTAC of Example 164 in Experimental Example 3 (BRD4: bromodomain-containing protein 4, GAPDH: glyceraldehyde-3-phosphate dehydrogenase).

[0027] Figure 5 shows the results of evaluating the decomposition ability of BRD4 protein in Experimental Example 4 (JQ1: BET bromodomain inhibitor, MG132: proteasome inhibitor, BRD4: bromodomain-containing protein 4, GAPDH: glyceraldehyde-3-phosphate dehydrogenase).

[0028] Figure 6 shows the LC and Mass analysis data of the prodrug of Example 165.

[0029] Figure 7 shows the results of evaluating the decomposition ability of BRD4 protein of PROTAC of Example 164 and prodrug of Example 165 in Experimental Example 5 (BRD4: bromodomain-containing protein 4, GAPDH: glyceraldehyde-3-phosphate dehydrogenase).

[0030] The present invention is described in more detail below.

[0031]

[0032] According to one aspect of the present invention, a compound of the following chemical formula 1 or a prodrug thereof is provided:

[0033] [Chemical Formula 1]

[0034]

[0035]

[0036] In the above chemical formula 1,

[0037] R1 and R2 are each independently -H, -D, alkyl, deuterated alkyl or haloalkyl;

[0038] R3 is -DEG; wherein D is a direct bond or alkylene; E is alkylene, alkenylene, alkynylene, cycloalkylene, cycloalkenylene, heterocycloalkylene, heterocycloalkenylene, arylene, or heteroarylene; wherein the alkylene, alkenylene, alkynylene, cycloalkylene, cycloalkenylene, heterocycloalkylene, heterocycloalkenylene, arylene or heteroarylene is optionally -D, halo, hydroxy, thiol (-SH), amino, nitro, cyano, alkyl, haloalkyl, deuterated alkyl, hydroxyalkyl, alkoxy, haloalkoxy, alkoxyalkyl, alkylthio, alkylamino, dialkylamino, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, aminocarbonylalkyl, alkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, carboxy, carboxyalkyl, alkylcarbonyl, alkylcarbonylalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, alkenyl, alkynyl, cycloalkyl, may be substituted with one or more substituents selected from heterocycloalkyl, aryl and heteroaryl; G is amino, heteroaryl, , or and here R7, R8 and R9 is each independently -H, alkyl or haloalkyl; or R7 and R8 may be connected to each other to form a ring structure;

[0039] R4 is -H, -D, alkyl, deuterated alkyl or haloalkyl;

[0040] L is -C-, -CH-, or and here R 10 and R 11 are each independently -H, -D, halo, alkyl, deuterated alkyl or haloalkyl;

[0041] R5 is -JM; wherein J is a direct bond, alkylene, alkenylene, alkynylene, alkylene-O- or alkylene-NH-; M is -H, halo, hydroxy, amino, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl or heteroaryl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl or heteroaryl is optionally -D, hydroxy, thiol, amino, halo, nitro, cyano, alkyl, haloalkyl, deuterated alkyl, hydroxyalkyl, alkoxy, haloalkoxy, cycloalkyl-oxy, heterocycloalkyl-oxy, aryl-oxy, heteroaryl-oxy, alkoxyalkyl, alkylthio, aminoalkyl, alkylamino, dialkylamino, alkylaminoalkyl, dialkylaminoalkyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, aminocarbonylalkyl, alkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, carboxy, carboxyalkyl, alkylcarbonyl, alkylcarbonylalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, may be substituted with one or more substituents selected from alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl; or when L is -C- and m is 2, L may be connected to R5 to form cycloalkyl or heterocycloalkyl;

[0042] R6 is -H, , , , , , , , , , or and here R 12 Inland R 27are each independently -H, nitro, cyano, azido, halo, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, heteroaryl, cycloalkyl-alkyl, cycloalkenyl-alkyl, alkoxy-alkyl, alkylthio-alkyl, dialkylaminoalkyl, heterocycloalkyl-alkyl, heterocycloalkenyl-alkyl, aryl-alkyl, alkyl-aryl-alkyl, alkoxy-aryl-alkyl, heteroaryl-alkyl, partially unsaturated heterocyclyl-alkyl, alkyl-heterocycloalkyl, aryl-alkyl-heterocycloalkyl or partially unsaturated heterocyclyl-alkyl-heterocycloalkyl;The above alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, heteroaryl, cycloalkyl-alkyl, cycloalkenyl-alkyl, heterocycloalkyl-alkyl, heterocycloalkenyl-alkyl, aryl-alkyl, heteroaryl-alkyl is optionally -D, halo, hydroxy, thiol, amino, nitro, cyano, oxo, azido, carboxy, aminocarbonyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, cycloalkyl-oxy, heterocycloalkyl-oxy, aryl-oxy, heteroaryl-oxy, alkylthio, alkylamino, dialkylamino, cycloalkylamino, heterocycloalkylamino, arylamino, heteroarylamino, alkoxycarbonyl, cycloalkyl-oxycarbonyl, Heterocycloalkyl-oxycarbonyl, aryl-oxycarbonyl, heteroaryl-oxycarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, cycloalkylaminocarbonyl, heterocycloalkylaminocarbonyl, arylaminocarbonyl, heteroarylaminocarbonyl, alkylcarbonyl, cycloalkylcarbonyl, heterocycloalkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, sulfo(-SO3H), alkoxy-sulfonyl(SO2), aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, cycloalkylaminosulfonyl, heterocycloalkylaminosulfonyl, arylaminosulfonyl, heteroarylaminosulfonyl, carboxyalkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, alkoxyalkyl, alkoxycarbonylalkyl, alkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, which may be substituted with one or more substituents selected from alkylcarbonylalkyl, sulfoalkyl, alkoxysulfonylalkyl, aminosulfonylalkyl, alkylaminosulfonylalkyl, dialkylaminosulfonylalkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, heteroaryl, cycloalkyl-alkyl, cycloalkenyl-alkyl, heterocycloalkyl-alkyl, heterocycloalkenyl-alkyl, aryl-alkyl and heteroaryl-alkyl; p is 0, 1, 2, 3, 4, 5, 6 or 7;

[0043] n is 1, 2 or 3; when n is 2 and 3, the repeating units may be the same or different;

[0044] m is 1 or 2;

[0045] The above heterocycloalkylene, heterocycloalkenylene, heteroarylene, heterocycloalkyl, heterocycloalkenyl, partially unsaturated heterocyclyl and heteroaryl have one or more heteroatoms selected from N, O and S.

[0046]

[0047] Unless otherwise specified, the following terms used in the present invention have the meanings set forth below. Any undefined term has the meaning understood in the art.

[0048]

[0049] In the present invention, the term “-D” means deuterium.

[0050] In the present invention, the term “halo” or “halogen”, when used alone or in combination with other additional terms (e.g., haloalkyl), means fluorine (F), chlorine (Cl), bromine (Br), or iodine (I).

[0051] In the present invention, the term “hydroxy” group means -OH.

[0052] In the present invention, the term “nitro” group means -NO2.

[0053] In the present invention, the term “cyano” group means -CN.

[0054] In the present invention, the term “thiol” group means -SH.

[0055] In the present invention, the term “oxy” means -O-.

[0056] In the present invention, the term “carboxy” group means -C(=O)OH.

[0057] In the present invention, the term “carbonyl” group means -C(=O)-.

[0058] In the present invention, the term “sulfonyl” means -S(=O)2-.

[0059] The term “amino” in the present invention may refer to a primary, secondary, or tertiary amino group, alone or in combination, bonded via a nitrogen atom. In the present invention, the secondary amino group may refer to one having an alkyl substituent, and the tertiary amino group may refer to one having two similar or different alkyl substituents.

[0060] In the present invention, the term “azido” means -N3.

[0061] As used herein, the term “alkyl”, when used alone or in combination with other additional terms (e.g., haloalkyl), means a radical of a straight or branched saturated aliphatic hydrocarbon group having, for example, 1 to 7 carbon atoms or 1 to 5 carbon atoms. Typical examples of alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, tert-pentyl, 1-methylbutyl, 2-methylbutyl, 1-ethylpropyl, and 1,2-dimethylpropyl.

[0062] In the present invention, the term “deuterated alkyl” means an alkyl group having one or more deuterium atoms.

[0063] In the present invention, the term “alkenyl” means a radical of an aliphatic hydrocarbon group containing at least one carbon-carbon double bond, for example, having 2 to 7 carbon atoms or 2 to 5 carbon atoms.

[0064] In the present invention, the term “alkynyl” means a radical of an aliphatic hydrocarbon group containing at least one carbon-carbon triple bond, for example, having 2 to 7 carbon atoms or 2 to 5 carbon atoms.

[0065] In the present invention, the term “alkoxy” means an alkyloxy (-O-alkyl group), for example, an alkyloxy having 1 to 7 carbon atoms or 1 to 5 carbon atoms.

[0066] In the present invention, the term “alkylthio” means an -S-alkyl group, for example, an -S-alkyl group having 1 to 7 or 1 to 5 carbon atoms.

[0067] In the present invention, the term “alkylene” means a radical of a divalent straight-chain or branched-chain saturated aliphatic hydrocarbon group having, for example, 1 to 7 carbon atoms or 1 to 5 carbon atoms.

[0068] In the present invention, the term “alkynylene” means a radical of an aliphatic hydrocarbon group containing at least one carbon-carbon double bond of two valences, for example, having 2 to 7 carbon atoms or 2 to 5 carbon atoms.

[0069] In the present invention, the term “alkynylene” means a radical of an aliphatic hydrocarbon group containing at least one carbon-carbon triple bond of two valences, for example, having 2 to 7 carbon atoms or 2 to 5 carbon atoms.

[0070] In the present invention, the term “hydroxyalkyl” means an alkyl group substituted with hydroxy.

[0071] As used herein, the term “cycloalkyl” refers to a saturated aliphatic hydrocarbon radical having, for example, 3 to 10 carbon atoms or 3 to 8 carbon atoms in a ring shape. Typical examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and the like. The cycloalkyl may include a bridged structure, a fused structure, or a spiro structure.

[0072] The term “heterocycloalkyl” in the present invention means a radical of a saturated aliphatic hydrocarbon group containing one or more heteroatoms selected from N, O and S as a reducing group, for example, a 4 to 12 membered or a 4 to 10 membered group. The heterocycloalkyl may include a bridged structure, a fused structure or a spiro structure.

[0073] The term “partially unsaturated heterocyclyl” as used herein means a cyclic, for example, 4 to 12-membered or 4 to 10-membered, partially unsaturated hydrocarbon group containing one or more heteroatoms selected from N, O and S as a reducing group. The partially unsaturated heterocyclyl may include a bridged structure, a fused structure or a spiro structure.

[0074] In the present invention, the term “aryl” means an aromatic hydrocarbon having, for example, 6 to 12 or 6 to 10 carbon atoms, and specific examples include, but are not limited to, phenyl and naphthyl.

[0075] In the present invention, the term “heteroaryl” means, for example, a 5- to 12-membered or 5- to 10-membered aromatic hydrocarbon containing one or more heteroatoms selected from N, O and S as a reducing group and forming a single or fused ring that can be fused with benzo or cycloalkyl.

[0076]

[0077] In the present invention, the term “prodrug” includes a form in which the compound of the above chemical formula 1 is converted in vivo to exhibit the same effect, and can be prepared according to a method known in the art, and there are no particular limitations thereto. For example, the prodrug can be provided in the form of, but is not limited to, carbamates, esters, N-Mannich adducts, phosphates, phosphonooxymethylethers, phosphoramidates, acylsulfonamides, amides, sulfenamides, imines, azo conjugates, N-acyloxyalkylamines, etc.

[0078]

[0079] According to one specific example of the present invention, in the chemical formula 1

[0080] R1 and R2 are each independently -H, -D, C1-C7 alkyl, deuterated C1-C7 alkyl or halo-C1-C7 alkyl;

[0081] R3 is -DEG; where D is a direct bond or C1-C7 alkylene; E is C1-C7 alkylene, C2-C7 alkenylene, C2-C7 alkynylene, C3-C 10 Cycloalkylene, C3-C 10 Cycloalkenylene, C6-C 12Arylene, 4 to 12 membered heterocycloalkylene, 4 to 12 membered heterocycloalkenylene or 5 to 12 membered heteroarylene; wherein said alkylene, alkenylene, alkynylene, cycloalkylene. Cycloalkenylene, heterocycloalkylene, heterocycloalkenylene, arylene or heteroarylene is optionally -D, halo, hydroxy, thiol, amino, nitro, cyano, C1-C7 alkyl, halo-C1-C7 alkyl, deuterated C1-C7 alkyl, hydroxy-C1-C7 alkyl, C1-C7 alkoxy, halo-C1-C7 alkoxy, C1-C7 alkoxy-C1-C7 alkyl, C1-C7 alkylthio, C1-C7 alkylamino, di(C1-C7 alkyl)amino, amino-C1-C7 alkyl, C1-C7 alkylamino-C1-C7 alkyl, di(C1-C7 alkyl)amino-C1-C7 alkyl, aminocarbonyl, C1-C7 alkylaminocarbonyl, di(C1-C7 alkyl)aminocarbonyl, Aminocarbonyl-C1-C7 alkyl, C1-C7 alkylaminocarbonyl-C1-C7 alkyl, di(C1-C7 alkyl)aminocarbonyl-C1-C7 alkyl, carboxy, carboxy-C1-C7 alkyl, C1-C7 alkylcarbonyl, C1-C7 alkylcarbonyl-C1-C7 alkyl, C1-C7 alkoxycarbonyl, C1-C7 alkoxycarbonyl-C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C3-C 10 Cycloalkyl, 4 to 12 membered heterocycloalkyl, C6-C 12 may be substituted with 1 to 4 substituents selected from aryl or 5 to 12 membered heteroaryl; G is amino, 5 to 12 membered heteroaryl, , or and here R7, R8 and R9 is each independently -H, C1-C7 alkyl or halo-C1-C7 alkyl; or R7 and R8 may be connected to each other to form a ring structure;

[0082] R4 is -H, -D, C1-C7alkyl, deuterated C1-C7alkyl or halo-C1-C7alkyl;

[0083] L is -C-, -CH-, or and here R 10 and R 11 are each independently -H, -D, halo, C1-C7 alkyl, deuterated C1-C7 alkyl or halo-C1-C7 alkyl;

[0084] R5 is -JM; where J is a direct bond, C1-C7 alkylene, C2-C7 alkenylene, C2-C7 alkynylene, C1-C7 alkylene-O- or C1-C7 alkylene-NH-; M is -H, halo, hydroxy, amino, C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C3-C 10 Cycloalkyl, C3-C 10 Cycloalkenyl, 4 to 12 membered heterocycloalkyl, 4 to 12 membered heterocycloalkenyl, C6-C 12 Aryl or 5 to 12 membered heteroaryl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl or heteroaryl is optionally -D, hydroxy, thiol, amino, halo, nitro, cyano, C1-C7 alkyl, halo-C1-C7 alkyl, deuterated C1-C7 alkyl, hydroxy-C1-C7 alkyl, C1-C7 alkoxy, halo-C1-C7 alkoxy, C3-C 10 Cycloalkyl-oxy, 4 to 12 membered heterocycloalkyl-oxy, C6-C 12Aryl-oxy, 5 to 12 membered heteroaryl-oxy, C1-C7alkoxy-C1-C7alkyl, C1-C7alkylthio, amino-C1-C7alkyl, C1-C7alkylamino, di(C1-C7alkyl)amino, C1-C7alkylamino-C1-C7alkyl, di(C1-C7alkyl)amino-C1-C7alkyl, aminocarbonyl, C1-C7alkylaminocarbonyl, di(C1-C7alkyl)aminocarbonyl, aminocarbonyl-C1-C7alkyl, C1-C7alkylaminocarbonyl-C1-C7alkyl, di(C1-C7alkyl)aminocarbonyl-C1-C7alkyl, carboxy, carboxy-C1-C7alkyl, C1-C7alkylcarbonyl, C1-C7alkylcarbonyl-C1-C7alkyl, C1-C7 alkoxycarbonyl, C1-C7 alkoxycarbonyl-C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C3-C 10 Cycloalkyl, 4 to 12 membered heterocycloalkyl, C6-C 12 may be substituted with 1 to 4 substituents selected from aryl and 5 to 12 membered heteroaryl; or when L is -C- and m is 2, L is connected to R5 to form C3-C 10 can form a cycloalkyl or a 4 to 12 membered heterocycloalkyl;

[0085] R6 is -H, , , , , , , , , , or and here R 12 Inland R 27 are each independently -H, nitro, cyano, azido, halo, C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C3-C 10 Cycloalkyl, C3-C 10 Cycloalkenyl, 4 to 12 membered heterocycloalkyl, 4 to 12 membered heterocycloalkenyl, C6-C 12Aryl, 5 to 12 membered heteroaryl, C3-C 10 Cycloalkyl-C1-C7 alkyl, C3-C 10 Cycloalkenyl-C1-C7 alkyl, C1-C7 alkoxy-C1-C7 alkyl, C1-C7 alkylthio-C1-C7 alkyl, amino-C1-C7 alkyl, di(C1-C7 alkyl)amino-C1-C7 alkyl, 4 to 12 membered heterocycloalkyl-C1-C7 alkyl, 4 to 12 membered heterocycloalkenyl-C1-C7 alkyl, C6-C 12 Aryl-C1-C7 alkyl, C1-C7 alkyl-C6-C 12 Aryl-C1-C7 alkyl, C1-C7 alkoxy-C6-C 12 Aryl-C1-C7 alkyl, 5 to 12 membered heteroaryl-C1-C7 alkyl, partially unsaturated 4 to 12 membered heterocyclyl-C1-C7 alkyl, C1-C7 alkyl-4 to 12 membered heterocycloalkyl, C6-C 12 Aryl-C1-C7 alkyl-4 to 12 membered heterocycloalkyl or partially unsaturated 4 to 12 membered heterocyclyl-C1-C7 alkyl-4 to 12 membered heterocycloalkyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, heteroaryl, cycloalkyl-alkyl, cycloalkenyl-alkyl, heterocycloalkyl-alkyl, heterocycloalkenyl-alkyl, aryl-alkyl, heteroaryl-alkyl is optionally -D, halo, hydroxy, thiol, amino, nitro, cyano, oxo, azido, carboxy, aminocarbonyl, C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, halo-C1-C7 alkyl, C1-C7 alkoxy, C3-C 10 Cycloalkyl-oxy, 4 to 12 membered heterocycloalkyl-oxy, C6-C 12 Aryl-oxy, 5 to 12 membered heteroaryl-oxy, C1-C7 alkylthio, C1-C7 alkylamino, di(C1-C7 alkyl)amino, C3-C 10 Cycloalkylamino, 4 to 12 membered heterocycloalkylamino, C6-C 12Arylamino, 5-12 membered heteroarylamino, C1-C7 alkoxycarbonyl, C3-C 10 Cycloalkyl-oxycarbonyl, 4 to 12 membered heterocycloalkyl-oxycarbonyl, C6-C 12 Aryl-oxycarbonyl, 5 to 12 membered heteroaryl-oxycarbonyl, C1-C7 alkylaminocarbonyl, di(C1-C7 alkyl)aminocarbonyl, C3-C 10 Cycloalkylaminocarbonyl, 4 to 12 membered heterocycloalkylaminocarbonyl, C6-C 12 Arylaminocarbonyl, 5 to 12 membered heteroarylaminocarbonyl, C1-C7 alkylcarbonyl, C3-C 10 Cycloalkylcarbonyl, 4 to 12 membered heterocycloalkylcarbonyl, C6-C 12 Arylcarbonyl, 5-12 membered heteroarylcarbonyl, sulfo, C1-C7 alkoxy-sulfonyl, aminosulfonyl, C1-C7 alkylaminosulfonyl, di(C1-C7 alkyl)aminosulfonyl, C3-C 10 Cycloalkylaminosulfonyl, 4 to 12 membered heterocycloalkylaminosulfonyl, C6-C 12 Arylaminosulfonyl, 5 to 12 membered heteroarylaminosulfonyl, carboxy-C1-C7 alkyl, amino-C1-C7 alkyl, C1-C7 alkylamino-C1-C7 alkyl, di(C1-C7 alkyl)amino-C1-C7 alkyl, C1-C7 alkoxy-C1-C7 alkyl, C1-C7 alkoxycarbonyl-C1-C7 alkyl, C1-C7 alkylaminocarbonyl-C1-C7 alkyl, di(C1-C7 alkyl)aminocarbonyl-C1-C7 alkyl, C1-C7 alkylcarbonyl-C1-C7 alkyl, sulfo-C1-C7 alkyl, C1-C7 alkoxysulfonyl-C1-C7 alkyl, aminosulfonyl-C1-C7 alkyl, C1-C7 alkylaminosulfonyl-C1-C7 alkyl, Di(C1-C7 alkyl)aminosulfonyl-C1-C7 alkyl, C3-C 10 Cycloalkyl, C3-C 10 Cycloalkenyl, 4 to 12 membered heterocycloalkyl, 4 to 12 membered heterocycloalkenyl, C6-C 12 Aryl, 5 to 12 membered heteroaryl, C3-C 10Cycloalkyl-C1-C7 alkyl, C3-C 10 Cycloalkenyl-C1-C7 alkyl, 4 to 12 membered heterocycloalkyl-C1-C7 alkyl, 4 to 12 membered heterocycloalkenyl-C1-C7 alkyl, C6-C 12 which may be substituted with 1 to 4 substituents selected from aryl-C1-C7 alkyl and 5 to 12 membered heteroaryl-C1-C7 alkyl; p is 0, 1, 2, 3, 4, 5, 6 or 7;

[0086] n is 1, 2 or 3; when n is 2 and 3, the repeating units may be the same or different;

[0087] m is 1 or 2;

[0088] The above heterocycloalkylene, heterocycloalkenylene, heteroarylene, heterocycloalkyl, heterocycloalkenyl, partially unsaturated heterocyclyl and heteroaryl have 1 to 4 heteroatoms selected from N, O and S.

[0089]

[0090] According to one specific example of the present invention, in the above chemical formula 1, R1 and R2 are each independently -H or C1-C5 alkyl.

[0091] According to one specific example of the present invention, in the above chemical formula 1, R3 is -DEG; wherein D is C1-C5 alkylene; and E is C1-C5 alkylene, C6-C 10 Arylene or a 5 to 10 membered heterocycloalkylene having 1 to 3 N atoms; G is amino, 5 to 10 membered heteroaryl, , or and here R7, R8 and R9 is each independently -H, C1-C5 alkyl or halo-C1-C5 alkyl.

[0092] According to one specific example of the present invention, in the above chemical formula 1, R4 is -H or C1-C5 alkyl.

[0093] According to one specific example of the present invention, in the above chemical formula 1, L is -C-, -CH- or -CH-CH2-; R5 is -JM; wherein J is a direct bond, C1-C5 alkylene or C2-C5 alkenylene; M is -H, hydroxy, C1-C5 alkyl, C3-C8 cycloalkyl, C6-C 10 Aryl, or 5 to 10 membered heteroaryl; wherein said cycloalkyl, aryl or heteroaryl is optionally selected from the group consisting of hydroxy, halo, cyano, C1-C5 alkyl, halo-C1-C5 alkyl, C1-C5 alkoxy and C6-C 10 may be substituted with 1 to 3 substituents selected from aryl; or when L is -C- and m is 2, L may be connected to R5 to form C3-C8 cycloalkyl or 4 to 10 membered heterocycloalkyl.

[0094] According to one specific example of the present invention, in the chemical formula 1, R6 is , or and here R 16 Inland R 19 are each independently -H, C1-C5 alkyl, C2-C5 alkenyl, C3-C8 cycloalkyl, 4 to 10 membered heterocycloalkyl, C1-C5 alkoxy-C1-C5 alkyl, C3-C8 cycloalkyl-C1-C5 alkyl, C3-C8 cycloalkenyl-C1-C5 alkyl, 4 to 10 membered heterocycloalkyl-C1-C5 alkyl, partially unsaturated 4 to 10 membered heterocyclyl-C1-C5 alkyl, amino-C1-C5 alkyl, di(C1-C5 alkyl)amino-C1-C5 alkyl, C1-C5 alkylthio-C1-C5 alkyl, C6-C 10 Aryl, 5-10 membered heteroaryl, C6-C 10 Aryl-C1-C5 alkyl, 5 to 10 membered heteroaryl-C1-C5 alkyl, C1-C5 alkyl-C6-C 10 Aryl-C1-C5 alkyl, C1-C5 alkoxy-C6-C 10 Aryl-C1-C5 alkyl, C1-C5 alkyl-4 to 10 membered heterocycloalkyl, C6-C10 Aryl-C1-C5 alkyl-4 to 10 membered heterocycloalkyl or partially unsaturated 4 to 10 membered heterocyclyl-C1-C5 alkyl-4 to 10 membered heterocycloalkyl; wherein said cycloalkyl and heterocycloalkyl may be optionally substituted with 1 to 3 substituents selected from halo, oxo, alkyl and haloalkyl; and wherein said aryl and heteroaryl may be substituted with 1 to 3 substituents selected from halo, hydroxy, alkyl, alkoxy, haloalkyl and aminosulfonyl.

[0095]

[0096] Representative compounds of the chemical formula 1 according to the present invention may include, but are not limited to, the following compounds:

[0097] (S)-2-amino-N-((S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)amino)-3,3-dimethyl-1-oxobutan-2-yl)-5-guanidinopentanamide;

[0098] (S)-2-amino-N-((S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)amino)-3-cyclopropyl-1-oxopropan-2-yl)-5-guanidinopentanamide;

[0099] (S)-2-amino-N-((S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)amino)-3-cyclopentyl-1-oxopropan-2-yl)-5-guanidinopentanamide;

[0100] (S)-2-amino-N-((S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-5-guanidinopentanamide;

[0101] (S)-2-amino-N-((S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)amino)-3-(naphthalen-1-yl)-1-oxopropan-2-yl)-5-guanidinopentanamide;

[0102] (S)-2-amino-N-((S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-3-(4-fluorophenyl)-1-oxopropan-2-yl)amino)-4-methyl-1-oxopentan-2-yl)-5-guanidinopentanamide;

[0103] (S)-2-amino-N-((S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-3-(naphthalen-1-yl)-1-oxopropan-2-yl)amino)-4-methyl-1-oxopentan-2-yl)-5-guanidinopentanamide;

[0104] (S)-2-amino-N-((S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)amino)-4-methyl-1-oxopentan-2-yl)-5-guanidinopentanamide;

[0105] (S)-2-amino-N-((S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-3-cyclopentyl-1-oxopropan-2-yl)amino)-4-methyl-1-oxopentan-2-yl)-5-guanidinopentanamide;

[0106] (S)-2-amino-N-((S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-3-cyclopropyl-1-oxopropan-2-yl)amino)-4-methyl-1-oxopentan-2-yl)-5-guanidinopentanamide;

[0107] (S)-2-amino-N-((S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-3,3-dimethyl-1-oxobutan-2-yl)amino)-4-methyl-1-oxopentan-2-yl)-5-guanidinopentanamide;

[0108] (S)-2-amino-N-((2S,3S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-3-(naphthalen-1-yl)-1-oxopropan-2-yl)amino)-3-methyl-1-oxopentan-2-yl)-5-guanidinopentanamide;

[0109] (S)-2-amino-N-((2S,3S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)amino)-3-methyl-1-oxopentan-2-yl)-5-guanidinopentanamide;

[0110] (S)-2-amino-N-((S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-3-(4-fluorophenyl)-1-oxopropan-2-yl)amino)-3-(4-hydroxyphenyl)-1-oxopropan-2-yl)-5-guanidinopentanamide;

[0111] (S)-2-amino-N-((S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-3-(4-chlorophenyl)-1-oxopropan-2-yl)amino)-3-(4-hydroxyphenyl)-1-oxopropan-2-yl)-5-guanidinopentanamide;

[0112] (S)-2-amino-N-((S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-3-(naphthalen-1-yl)-1-oxopropan-2-yl)amino)-3-(4-hydroxyphenyl)-1-oxopropan-2-yl)-5-guanidinopentanamide;

[0113] (S)-2-amino-N-((S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)amino)-3-(4-hydroxyphenyl)-1-oxopropan-2-yl)-5-guanidinopentanamide;

[0114] (S)-2-amino-N-((S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-3-(naphthalen-1-yl)-1-oxopropan-2-yl)amino)-3,3-dimethyl-1-oxobutan-2-yl)-5-guanidinopentanamide;

[0115] (S)-2-amino-N-((S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)amino)-3,3-dimethyl-1-oxobutan-2-yl)-5-guanidinopentanamide;

[0116] (S)-2-amino-N-((S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-3-cyclopropyl-1-oxopropan-2-yl)amino)-3,3-dimethyl-1-oxobutan-2-yl)-5-guanidinopentanamide;

[0117] (S)-2-amino-N-((S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-3-(naphthalen-1-yl)-1-oxopropan-2-yl)amino)-3-cyclopropyl-1-oxopropan-2-yl)-5-guanidinopentanamide;

[0118] (S)-2-amino-N-((S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-3,3-dimethyl-1-oxobutan-2-yl)amino)-3-cyclopropyl-1-oxopropan-2-yl)-5-guanidinopentanamide;

[0119] (S)-2-amino-N-((S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-3-(4-chlorophenyl)-1-oxopropan-2-yl)amino)-3-cyclopentyl-1-oxopropan-2-yl)-5-guanidinopentanamide;

[0120] (S)-2-amino-N-((S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-3-(4-fluorophenyl)-1-oxopropan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-5-guanidinopentanamide;

[0121] (S)-2-amino-N-((S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-3,3-dimethyl-1-oxobutan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-5-guanidinopentanamide;

[0122] (S)-2-amino-N-((S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)amino)-3-(4-fluorophenyl)-1-oxopropan-2-yl)-5-guanidinopentanamide;

[0123] (S)-2-amino-N-((S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-3-cyclopropyl-1-oxopropan-2-yl)amino)-3-(4-fluorophenyl)-1-oxopropan-2-yl)-5-guanidinopentanamide;

[0124] (S)-2-amino-N-((S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)amino)-3-(4-chlorophenyl)-1-oxopropan-2-yl)-5-guanidinopentanamide;

[0125] (S)-2-amino-N-((S)-1-(((S)-1-amino-1-oxo-3-phenylpropan-2-yl)amino)-4-methyl-1-oxopentan-2-yl)-5-guanidinopentanamide;

[0126] (S)-2-amino-N-((S)-1-(((S)-1-amino-1-oxo-3-phenylpropan-2-yl)amino)-3-(4-hydroxyphenyl)-1-oxopropan-2-yl)-5-guanidinopentanamide;

[0127] (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(naphthalen-1-yl)-1-oxopropan-2-yl)amino)-4-methyl-1-oxopentan-2-yl)-5-guanidinopentanamide;

[0128] (S)-2-amino-N-((S)-1-(((S)-1-amino-3-cyclohexyl-1-oxopropan-2-yl)amino)-4-methyl-1-oxopentan-2-yl)-5-guanidinopentanamide;

[0129] (S)-2-amino-N-((2S,3S)-1-(((S)-1-amino-3-(naphthalen-1-yl)-1-oxopropan-2-yl)amino)-3-methyl-1-oxopentan-2-yl)-5-guanidinopentanamide;

[0130] (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(4-fluorophenyl)-1-oxopropan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-5-guanidinopentanamide;

[0131] (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(naphthalen-1-yl)-1-oxopropan-2-yl)amino)-1-oxobutan-2-yl)-5-guanidinopentanamide;

[0132] (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(naphthalen-1-yl)-1-oxopropan-2-yl)amino)-1-oxopentan-2-yl)-5-guanidipentanamide;

[0133] (S)-N-((S)-1-amino-3-(naphthalen-1-yl)-1-oxopropan-2-yl)-2-((S)-2-amino-5-guanidinopentanamido)hexanamide;

[0134] (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(naphthalen-1-yl)-1-oxopropan-2-yl)amino)-3-cyclopropyl-1-oxopropan-2-yl)-5-guanidinopentanamide;

[0135] (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(naphthalen-1-yl)-1-oxopropan-2-yl)amino)-3-cyclopentyl-1-oxopropan-2-yl)-5-guanidinopentanamide;

[0136] (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(naphthalen-1-yl)-1-oxopropan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-5-guanidinopentanamide;

[0137] (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(naphthalen-1-yl)-1-oxopropan-2-yl)amino)-4-methyl-1-oxopentan-2-yl)-5-(3-methylguanidino)pentanamide;

[0138] (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(naphthalen-1-yl)-1-oxopropan-2-yl)amino)-4-methyl-1-oxopentan-2-yl)-5-(3,3-dimethylguanidino)pentanamide;

[0139] (S)-N-((S)-1-amino-3-(naphthalen-1-yl)-1-oxopropan-2-yl)-2-((S)-5-guanidino-2-(methylamino)pentanamido)-4-methylpentanamide;

[0140] (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(4-fluorophenyl)-1-oxopropan-2-yl)amino)-3-cyclopentyl-1-oxopropan-2-yl)-5-guanidinopentanamide;

[0141] (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(4-fluorophenyl)-1-oxopropan-2-yl)amino)-3-(naphthalen-1-yl)-1-oxopropan-2-yl)-5-guanidinopentanamide;

[0142] (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(4-fluorophenyl)-1-oxopropan-2-yl)amino)-3-(naphthalen-2-yl)-1-oxopropan-2-yl)-5-guanidinopentanamide;

[0143] (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(4-chlorophenyl)-1-oxopropan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-5-guanidinopentanamide;

[0144] (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(4-bromophenyl)-1-oxopropan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-5-guanidinopentanamide;

[0145] (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(4-iodophenyl)-1-oxopropan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-5-guanidinopentanamide;

[0146] (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(naphthalen-2-yl)-1-oxopropan-2-yl)amino)-4-methyl-1-oxopentan-2-yl)-5-guanidinopentanamide;

[0147] (S)-N-((S)-1-amino-3-(naphthalen-2-yl)-1-oxopropan-2-yl)-2-((S)-2-amino-5-guanidinopentanamido)hexanamide;

[0148] (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(naphthalen-2-yl)-1-oxopropan-2-yl)amino)-3-cyclopropyl-1-oxopropan-2-yl)-5-guanidinopentanamide;

[0149] (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(naphthalen-2-yl)-1-oxopropan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-5-guanidinopentanamide;

[0150] (S)-N-((S)-3-([1,1'-biphenyl]-4-yl)-1-amino-1-oxopropan-2-yl)-2-((S)-2-amino-5-ureidopentanamido)-4,4-dimethylpentanamide;

[0151] (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(3,4-difluorophenyl)-1-oxopropan-2-yl)amino)-1-oxo-3-(3-(trifluoromethyl)phenyl)propan-2-yl)-5-ureidopentanamide;

[0152] (S)-2-amino-N-((S)-1-(((S)-1-amino-1-oxo-3-(4-(trifluoromethyl)phenyl)propan-2-yl)amino)-3-(4-methoxyphenyl)-1-oxopropan-2-yl)-5-ureidopentanamide;

[0153] (S)-N-((S)-3-([1,1'-biphenyl]-4-yl)-1-(((S)-1-amino-1-oxo-3-(pyridin-3-yl)propan-2-yl)amino)-1-oxopropan-2-yl)-2-amino-5-ureidopentanamide;

[0154] (S)-2-amino-N-((S)-1-(((S)-1-amino-1-oxo-3-(3-(trifluoromethyl)phenyl)propan-2-yl)amino)-1-oxo-4-phenylbutan-2-yl)-4-guanidinobutanamide;

[0155] (S)-2-amino-N-((S)-1-(((S)-2-amino-2-oxo-1-phenylethyl)amino)-3-(5-bromo-1H-indole-3-yl)-1-oxopropan-2-yl)-4-guanidinobutanamide;

[0156] (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(4-methoxyphenyl)-1-oxopropan-2-yl)amino)-3-(3,4-difluorophenyl)-1-oxopropan-2-yl)-4-guanidinobutanamide;

[0157] (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(4-cyanophenyl)-1-oxopropan-2-yl)amino)-1-oxo-3-(thiophen-2-yl)propan-2-yl)-4-guanidinobutanamide;

[0158] N-((S)-1-amino-1-oxo-3-(thiophen-2-yl)propan-2-yl)-1-((S)-2-amino-3-(4-guanidinophenyl)propanamido)cyclopropanecarboxamide;

[0159] 1-((S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-3-(4-(trifluoromethyl)phenyl)propanamido)cyclopropanecarboxamide;

[0160] 4-((S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-3-(3,4-dichlorophenyl)propanamido)tetrahydro-2H-pyran-4-carboxamide;

[0161] (S)-2-((S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-3-(4-cyanophenyl)propanamido)-4,4-dimethylpentanamide;

[0162] N-((S)-1-amino-1-oxo-4-phenylbutan-2-yl)-4-((S)-2-amino-6-guanidinohexamido)tetrahydro-2H-pyran-4-carboxamide;

[0163] (S)-2-amino-N-((S)-2-(((S)-1-amino-3-(5-bromo-1H-indol-3-yl)-1-oxopropan-2-yl)amino)-2-oxo-1-phenylethyl)-6-guanidinohexanamide;

[0164] (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(3,4-dichlorophenyl)-1-oxopropan-2-yl)amino)-1-oxo-3-(pyridin-3-yl)propan-2-yl)-6-guanidinohexanamide;

[0165] 4-((S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-3-(3,4-difluorophenyl)propanamido)tetrahydro-2H-pyran-4-carboxamide;

[0166] 4-((S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-3-(4-(trifluoromethyl)phenyl)propanamido)tetrahydro-2H-pyran-4-carboxamide;

[0167] (S)-2-amino-N-((S)-1-(((S)-2-amino-2-oxo-1-phenylethyl)amino)-3-(3,4-dichlorophenyl)-1-oxopropan-2-yl)-3-(4-guanidinophenyl)propanamide;

[0168] (S)-2-((S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-3-(3,4-dichlorophenyl)propanamido)-4,4-dimethylpentanamide;

[0169] 4-((S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-3-(4-cyanophenyl)propanamido)tetrahydro-2H-pyran-4-carboxamide;

[0170] (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(4-fluorophenyl)-1-oxopropan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-3-(4-guanidinophenyl)propanamide;

[0171] (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-N-((S)-1-amino-3-(naphthalen-1-yl)-1-oxopropan-2-yl)-4-methylpentanamide;

[0172] (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(naphthalen-1-yl)-1-oxopropan-2-yl)amino)-4-methyl-1-oxopentan-2-yl)-5-ureidopentanamide;

[0173] (S)-N-((S)-1-amino-3-(naphthalen-1-yl)-1-oxopropan-2-yl)-2-((S)-2-amino-4-guanidinobutanamido)-4-methylpentanamide;

[0174] (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(naphthalen-1-yl)-1-oxopropan-2-yl)amino)-4-methyl-1-oxopentan-2-yl)-6-guanidinohexanamide;

[0175] (S)-N-((S)-1-amino-3-(naphthalen-1-yl)-1-oxopropan-2-yl)-2-((S)-2-amino-5-guanidinopentanamido)-4,4-dimethylpentanamide;

[0176] (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(naphthalen-1-yl)-1-oxopropan-2-yl)amino)-3-cyclopentyl-1-oxopropan-2-yl)-3-(4-guanidinophenyl)propanamide;

[0177] (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(4-fluorophenyl)-1-oxopropan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-3-(4-guanidinophenyl)propanamide;

[0178] (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(4-fluorophenyl)-1-oxopropan-2-yl)amino)-3-(4-methoxyphenyl)-1-oxopropan-2-yl)-3-(4-guanidinophenyl)propanamide;

[0179] (S)-N-((S)-1-amino-3-(4-fluorophenyl)-1-oxopropan-2-yl)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-phenylbutanamide;

[0180] (S)-3-([1,1'-biphenyl]-4-yl)-N-((S)-1-amino-3-(4-fluorophenyl)-1-oxopropan-2-yl)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)propanamide;

[0181] (S)-N-((S)-1-amino-3-(4-fluorophenyl)-1-oxopropan-2-yl)-3-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-5-cyclohexylpentanamide;

[0182] (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(4-fluorophenyl)-1-oxopropan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-3-(3-guanidinophenyl)propanamide;

[0183] (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(4-fluorophenyl)-1-oxopropan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-3-(2-guanidinophenyl)propanamide;

[0184] (R)-2-amino-N-((S)-1-(((S)-1-amino-3-(4-fluorophenyl)-1-oxopropan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-3-(4-guanidinophenyl)propanamide;

[0185] 2-amino-N-((S)-1-(((S)-1-amino-3-(4-fluorophenyl)-1-oxopropan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-3-(4-guanidinophenyl)propanamide;

[0186] (S)-2-amino-N-((R)-1-(((S)-1-amino-3-(4-fluorophenyl)-1-oxopropan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-3-(4-guanidinophenyl)propanamide;

[0187] (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(4-fluorophenyl)-1-oxopropan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-3-(4-guanidinophenyl)-N-methylpropanamide;

[0188] (2S)-2-amino-N-(1-(((S)-1-amino-3-(4-fluorophenyl)-1-oxopropan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-3-(4-guanidinophenyl)propanamide;

[0189] (S)-2-amino-N-((S)-1-(((R)-1-amino-3-(4-fluorophenyl)-1-oxopropan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-3-(4-guanidinophenyl)propanamide;

[0190] (S)-N-((S)-1-amino-3-(4-fluorophenyl)-1-oxopropan-2-yl)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-3-cyclohexyl-N-methylpropanamide;

[0191] (2S)-2-amino-N-((2S)-1-((1-amino-3-(4-fluorophenyl)-1-oxopropan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-3-(4-guanidinophenyl)propanamide;

[0192] (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(4-fluorophenyl)-1-oxopropan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-3-(1-carbamimidoylpiperidin-4-yl)propanamide;

[0193] (S)-N-((S)-1-amino-3-(4-fluorophenyl)-1-oxopropan-2-yl)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexylbutanamide;

[0194] (S)-N-((R)-1-amino-3-(4-fluorophenyl)-1-oxopropan-2-yl)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexylbutanamide;

[0195] (2S)-N-(1-amino-3-(4-fluorophenyl)-1-oxopropan-2-yl)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexylbutanamide;

[0196] (S)-2-amino-N-((S)-1-amino-3-cyclohexyl-1-oxopropan-2-yl)-3-(4-guanidinophenyl)propanamide;

[0197] (S)-2-amino-N-((S)-1-amino-3-(3,4-dichlorophenyl)-1-oxopropan-2-yl)-5-guanidinopentanamide;

[0198] (S)-N-((S)-3-([1,1'-biphenyl]-4-yl)-1-amino-1-oxopropan-2-yl)-2-amino-5-guanidinopentanamide;

[0199] (S)-2-amino-N-((S)-1-amino-3-(3,4-dichlorophenyl)-1-oxopropan-2-yl)-3-(4-guanidinophenyl)propanamide;

[0200] (S)-3-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-5-cyclohexylpentanamide;

[0201] (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-phenylbutanamide;

[0202] (S)-N-((S)-3-([1,1'-biphenyl]-4-yl)-1-amino-1-oxopropan-2-yl)-2-amino-3-(4-guanidinophenyl)propanamide;

[0203] (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexylbutanamide;

[0204] (S)-2-amino-N-((S)-2-amino-2-oxo-1-phenylethyl)-3-(4-guanidinophenyl)propanamide;

[0205] (R)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexylbutanamide;

[0206] 2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexylbutanamide;

[0207] (S)-2-((S)-2-amino-3-(1-carbamimidoylpiperidin-4-yl)propanamido)-4-cyclohexylbutanamide;

[0208] (S)-2-amino-N-((S)-2-amino-1-cyclohexyl-2-oxoethyl)-3-(4-guanidinophenyl)propanamide;

[0209] (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclopentylbutanamide;

[0210] (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cycloheptylbutanamide;

[0211] (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-(4,4-difluorocyclohexyl)butanamide;

[0212] (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-5-cyclohexylpentanamide;

[0213] (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-5-phenylpentanamide;

[0214] (S,E)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-5-phenylpent-4-enamide;

[0215] (S)-2-((S)-2-amino-3-(1-carbamimidoylpiperidin-4-yl)propanamido)-4-phenylbutanamide;

[0216] (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-isopropylbutanamide;

[0217] (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-(cyclohexylmethyl)butanamide;

[0218] (S)-N-allyl-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexylbutanamide;

[0219] (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-(2-morpholinoethyl)butanamide;

[0220] (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-isopentylbutanamide;

[0221] (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-N-(2-(cyclohex-1-en-1-yl)ethyl)-4-cyclohexylbutanamide;

[0222] (2S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-((tetrahydrofuran-3-yl)methyl)butanamide;

[0223] (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-cyclopentylbutanamide;

[0224] (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-N,4-dicyclohexylbutanamide;

[0225] (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-(2-(methylthio)ethyl)butanamide;

[0226] (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-phenethylbutanamide;

[0227] (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-(4-methoxybenzyl)butanamide;

[0228] (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-neopentylbutanamide;

[0229] (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-N-(4-(tert-butyl)benzyl)-4-cyclohexylbutanamide;

[0230] (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-N-(benzo[d][1,3]dioxol-5-ylmethyl)-4-cyclohexylbutanamide;

[0231] (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-(4-(trifluoromethyl)benzyl)butanamide;

[0232] (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-(naphthalen-2-ylmethyl)butanamide;

[0233] (2S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-((tetrahydrofuran-2-yl)methyl)butanamide;

[0234] (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-ethylbutanamide;

[0235] (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-(4-isopropylphenyl)butanamide;

[0236] (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-hexylbutanamide;

[0237] (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-(3-methylbenzyl)butanamide;

[0238] (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-(4-fluorophenethyl)butanamide;

[0239] (2S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-(1-phenylethyl)butanamide;

[0240] (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-(4-hydroxyphenethyl)butanamide;

[0241] (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-methylbutanamide;

[0242] (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-isobutylbutanamide;

[0243] (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-N-benzyl-4-cyclohexylbutanamide;

[0244] (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-(2-methoxyethyl)butanamide;

[0245] (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-N-cyclobutyl-4-cyclohexylbutanamide;

[0246] (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-propylbutanamide;

[0247] (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-(3-(2-oxopyrrolidin-1-yl)propyl)butanamide;

[0248] (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-N-(4-chlorobenzyl)-4-cyclohexylbutanamide;

[0249] (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-(3-(dimethylamino)propyl)butanamide;

[0250] (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-(4-sulfamoylphenethyl)butanamide;

[0251] (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-(3,4-dimethoxybenzyl)butanamide;

[0252] (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-(furan-2-ylmethyl)butanamide;

[0253] (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-(4-hydroxybenzyl)butanamide;

[0254] (S)-2-amino-N-((S)-4-cyclohexyl-1-(4-(2-ethylbutyl)piperazin-1-yl)-1-oxobutan-2-yl)-3-(4-guanidinophenyl)propanamide;

[0255] (S)-2-amino-N-((S)-4-cyclohexyl-1-oxo-1-(4-pentylpiperazin-1-yl)butan-2-yl)-3-(4-guanidinophenyl)propanamide;

[0256] (S)-2-amino-N-((S)-4-cyclohexyl-1-(4-(4-methoxybenzyl)piperazin-1-yl)-1-oxobutan-2-yl)-3-(4-guanidinophenyl)propanamide;

[0257] (S)-2-amino-N-((S)-1-(4-(benzo[d][1,3]dioxol-4-ylmethyl)piperazin-1-yl)-4-cyclohexyl-1-oxobutan-2-yl)-3-(4-guanidinophenyl)propanamide;

[0258] (S)-2,6-diamino-N-((S)-1-amino-4-cyclohexyl-1-oxobutan-2-yl)hexanamide; and

[0259] (S)-2-((S)-2-amino-3-(1H-imidazol-4-yl)propanamido)-4-cyclohexylbutanamide.

[0260]

[0261] The names of the above compounds are described according to the nomenclature provided by PerkinElmer's ChemDraw Professional software (version 21.0.0.28).

[0262]

[0263] According to another aspect of the present invention, a chimeric compound of the following chemical formula 2 is provided:

[0264] [Chemical Formula 2]

[0265]

[0266]

[0267] In the above chemical formula 2,

[0268] A is a ubiquitin ligase binding moiety (ULM) and is a compound of the above chemical formula 1 or a prodrug thereof;

[0269] B is a protein target moiety (PTM);

[0270] A and B are chemically linked by a linker.

[0271]

[0272] In the above chemical formula 2, any linker used in the production of PROTAC in the relevant field can be used, and there are no special limitations thereto. For example, the linker can be a compound having the structure of the following chemical formula 3,

[0273] [Chemical Formula 3]

[0274]

[0275]

[0276] In the above chemical formula 3,

[0277] Y1 does not exist, or , , , , , , , , , , , , , , , , cycloalkylene, cycloalkenylene, heterocycloalkylene, heterocycloalkenylene, arylene, heteroarylene, bridged cyclclylene, fused cyclylene, spiro-cyclylene, poly-cyclylene, bridged heterocyclclylene, fused heterocyclylene, spiro-heterocyclylene and poly-heterocyclylene; wherein R'" and R"" are each independently -H, -D, halo, hydroxy, amino, cyano, alkyl, haloalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, alkylthio, alkylamino, dialkylamino, alkylaminoalkyl, dialkylaminoalkyl, alkyl-oxo, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, carboxy, carboxyalkyl, or alkoxycarbonyl; n is an integer from 1 to 20;

[0278] Y2 is - does not exist, or , , , , , , , , , , , , , , , , cycloalkylene, cycloalkenylene, heterocycloalkylene, heterocycloalkenylene, arylene, heteroarylene, bridged cyclclylene, fused cyclylene, spiro-cyclylene, poly-cyclylene, bridged heterocyclclylene, fused heterocyclylene, spiro-heterocyclylene and poly-heterocyclylene; wherein R'" and R"" are each independently -H, -D, halo, hydroxy, amino, cyano, alkyl, haloalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, alkylthio, alkylamino, dialkylamino, alkylaminoalkyl, dialkylaminoalkyl, alkyl-oxo, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, carboxy, carboxyalkyl, or alkoxycarbonyl; n is an integer from 1 to 20;

[0279] Y3 does not exist, or , , , , , , , , , , , , , , , , cycloalkylene, cycloalkenylene, heterocycloalkylene, heterocycloalkenylene, arylene, heteroarylene, bridged cyclclylene, fused cyclylene, spiro-cyclylene, poly-cyclylene, bridged heterocyclclylene, fused heterocyclylene, spiro-heterocyclylene and poly-heterocyclylene; wherein R'" and R"" are each independently -H, -D, halo, hydroxy, amino, cyano, alkyl, haloalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, alkylthio, alkylamino, dialkylamino, alkylaminoalkyl, dialkylaminoalkyl, alkyl-oxo, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, carboxy, carboxyalkyl, or alkoxycarbonyl; n is an integer from 1 to 20.

[0280] For example, a linker having the structure shown below may be used, and as another specific example, the linker is as described and defined in International Publication Nos. WO 2016 / 149668 A1, WO 2020 / 051564 A1 and WO 2023 / 076161 A1, which are incorporated herein by reference, but are not limited thereto.

[0281] , ,

[0282] , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,

[0283]

[0284] In the above chemical formula 2, B, which is a protein target moiety (PTM), can be any target protein ligand used in the production of PROTAC in the art, and there are no special limitations thereon.

[0285] For example, compounds targeting BET bromodomain-containing proteins such as those shown in Table 1 below may be used, but are not limited thereto.

[0286] [Table 1]

[0287]

[0288]

[0289] For example, kinase and phosphatase inhibitor compounds such as those shown in Table 2 below may be used, but are not limited thereto.

[0290] [Table 2]

[0291]

[0292]

[0293]

[0294] For example, compounds targeting JAK (Janus kinase) family proteins, such as those shown in Table 3 below, may be used, but are not limited thereto.

[0295] [Table 3]

[0296]

[0297]

[0298] For example, compounds targeting PARP-1 (poly [ADP-ribose] polymerase 1) such as those shown in Table 4 below may be used, but are not limited thereto.

[0299] [Table 4]

[0300]

[0301]

[0302] For example, compounds targeting the focal adhesion kinase (FAK) protein, such as those shown in Table 5 below, may be used, but are not limited thereto.

[0303] [Table 5]

[0304]

[0305]

[0306] For example, but not limited to, compounds targeting the RAF (rapidly accelerated fibrosarcoma) receptor (kinase) as shown in Table 6 below may be used.

[0307] [Table 6]

[0308]

[0309]

[0310] For example, compounds targeting the androgen receptor (AR) such as those shown in Table 7 below may be used, but are not limited thereto.

[0311] [Table 7]

[0312]

[0313]

[0314] For example, compounds targeting the estrogen receptor (ER) such as those shown in Table 8 below may be used, but are not limited thereto.

[0315] [Table 8]

[0316]

[0317]

[0318] For example, compounds targeting BTK (Bruton tyrosine kinase) inhibitors such as those shown in Table 9 below may be used, but are not limited thereto.

[0319] [Table 9]

[0320]

[0321]

[0322] For example, compounds targeting heat shock protein 90 (HSP90) inhibitors such as those shown in Table 10 below may be used, but are not limited thereto.

[0323] [Table 10]

[0324]

[0325]

[0326] For example, compounds targeting HDM2 / MDM2 (human double minute 2 / mouse double minute 2) inhibitors such as those shown in Table 11 below may be used, but are not limited thereto.

[0327] [Table 11]

[0328]

[0329]

[0330] For example, immunosuppressive compounds such as those shown in Table 12 below may be used, but are not limited thereto.

[0331] [Table 12]

[0332]

[0333]

[0334] Example

[0335] Hereinafter, the present invention will be described in more detail by the following examples, which are provided for illustrative purposes only and the present invention is not limited thereto.

[0336]

[0337] The definitions of abbreviations used in the examples below are as follows.

[0338]

[0339]

[0340] Examples 1 to 163: Synthesis of ligands for E3 ubiquitin ligases

[0341] The UBR1 ligand was prepared through the following solid phase synthesis.

[0342]

[0343]

[0344]

[0345]

[0346]

[0347]

[0348] Rink amide MBHA resin (50 mg, 0.52 mmol / g loading, 0.026 mmol, 1.0 equiv.) was placed in a 5.0 mL fritted syringe and incubated with DMF for 2 h at room temperature. After removing the Fmoc protecting group with 20% piperidine (v / v) in DMF (0.50 mL) for 20 min, the resin was treated with HATU (0.078 mmol, 3 equiv.), HOAt (0.078 mmol, 3 equiv.), DIPEA (0.156 mmol, 6 equiv.), and the Fmoc-protected amino acid (0.078 mmol, 3 equiv.). After the amide coupling reaction at room temperature for 2 h, the reaction mixture was discarded, and the resin was washed with DMF (3×), MeOH (3×), CH2Cl2 (3×), and DMF (3×). This process was repeated to obtain the desired compound (Method AB). After removing the Fmoc protecting group, the compound on the resin was cleaved by treating with 1.0 mL of a cleavage cocktail (95% TFA, 2.5% TIPS, and 2.5% DDW) at room temperature for 3 h, and the compound was purified using reverse-phase column chromatography (C18 Silica Kelp, YL9100 GPC system) (solvent A: DDW with 0.1% TFA added, solvent B: ACN with 0.1% TFA added; gradient). The compound was analyzed by LC (Agilent 1220 LC system Ontario, CA, USA) and MALDI-TOF MS (Autoflex Speed ​​LRF, Bruker, Billerica, MA, USA). The purified compound was lyophilized to obtain a white solid, and Examples 1 to 95, Examples 97 to 110, and Examples 112 to 118 were synthesized using the above synthetic method.

[0349] Compound (Ⅰ) or (Ⅱ) on the resin synthesized by Method B was treated with 20% piperidine (v / v) in DMF (0.50 mL) for 20 min to remove the Fmoc protecting group, and then the coupling reaction was performed by treating with HATU (0.078 mmol, 3 equiv.), HOAt (0.078 mmol, 3 equiv.), DIPEA (0.156 mmol, 6 equiv.), and Boc-protected amino acid (0.078 mmol, 3 equiv.) (Method CD). Next, the Fmoc protecting group on the piperidine ring was removed by treatment with 20% piperidine (v / v) in DMF (0.50 mL), and then the guanidination reaction was carried out by treating with 1-aminopyrazole hydrochloride (0.26 mmol, 10 equiv.), DMAP (0.52 mmol, 20 equiv.), and DMF (0.50 mL) at room temperature for 24 hours. The purification and analysis methods of the compounds were the same as in the above examples, and the purified compounds were freeze-dried to obtain a white solid, and Examples 96, 111, and 119 were synthesized.

[0350] PAL resin (50 mg, 0.92 mmol / g loading, 0.046 mmol, 1.0 equiv.) was placed in a 4.0 mL vial using Method E and THF was added and left for 2 h. After all THF was removed, the resin was treated with the primary amine (0.23 mmol, 5.0 equiv.) together with 1.0 mL of THF at room temperature for 2 h. The solution was then treated with NaBH(OAc)3 (0.32 mmol, 7.0 equiv.) and AcOH (0.46 mmol, 10 equiv.) at room temperature for 12 h. The reaction mixture was transferred to a 5.0 mL fritted syringe, and the resin was washed with THF (3×), MeOH (3×), CH2Cl2 (3×), and DMF (3×). The Fmoc-protected amino acid (0.23 mmol, 5.0 equiv.) was then treated on the resin. After the amide coupling reaction at room temperature for 2 h, the reaction mixture was discarded, and the resin was washed with DMF (3x), MeOH (3x), CH2Cl2 (3x), and DMF (3x). This process was repeated to obtain the desired compound. After removing the Fmoc protecting group, the compound on the resin was cleaved by treating with 1.0 mL of a cleavage cocktail (95% TFA, 2.5% TIPS, and 2.5% DDW) for 3 h at room temperature, and the compound was purified using reverse-phase column chromatography (C18 Silica Kelp, YL9100 GPC system) (solvent A: DDW with 0.1% TFA, solvent B: ACN with 0.1% TFA; gradient). The compound was analyzed by LC (Agilent 1220 LC system Ontario, CA, USA) and MALDI-TOF MS (Autoflex Speed ​​LRF, Bruker, Billerica, MA, USA). The purified compound was freeze-dried to obtain a white solid, and Examples 120 to 163 were synthesized using the above synthetic method.

[0351] The above synthesis results are summarized and shown in Table 13.

[0352] [Table 13]

[0353] [Correction pursuant to Rule 91, June 17, 2025]

[0354] [Correction pursuant to Rule 91, June 17, 2025]

[0355] [Correction pursuant to Rule 91, June 17, 2025]

[0356] [Correction pursuant to Rule 91, June 17, 2025]

[0357] [Correction pursuant to Rule 91, June 17, 2025]

[0358] [Correction pursuant to Rule 91, June 17, 2025]

[0359] [Correction pursuant to Rule 91, June 17, 2025]

[0360] [Correction pursuant to Rule 91, June 17, 2025]

[0361] [Correction pursuant to Rule 91, June 17, 2025]

[0362] [Correction pursuant to Rule 91, June 17, 2025]

[0363] [Correction pursuant to Rule 91, June 17, 2025]

[0364] [Correction pursuant to Rule 91, June 17, 2025]

[0365] [Correction pursuant to Rule 91, June 17, 2025]

[0366] [Correction pursuant to Rule 91, June 17, 2025]

[0367] [Correction pursuant to Rule 91, June 17, 2025]

[0368] [Correction pursuant to Rule 91, June 17, 2025]

[0369] [Correction pursuant to Rule 91, June 17, 2025]

[0370] [Correction pursuant to Rule 91, June 17, 2025]

[0371] [Correction pursuant to Rule 91, June 17, 2025]

[0372] [Correction pursuant to Rule 91, June 17, 2025]

[0373] [Correction pursuant to Rule 91, June 17, 2025]

[0374] [Correction pursuant to Rule 91, June 17, 2025]

[0375] [Correction pursuant to Rule 91, June 17, 2025]

[0376] [Correction pursuant to Rule 91, June 17, 2025]

[0377] [Correction pursuant to Rule 91, June 17, 2025]

[0378] [Correction pursuant to Rule 91, June 17, 2025]

[0379] [Correction pursuant to Rule 91, June 17, 2025]

[0380] [Correction pursuant to Rule 91, June 17, 2025]

[0381] [Correction pursuant to Rule 91, June 17, 2025]

[0382] [Correction pursuant to Rule 91, June 17, 2025]

[0383] [Correction pursuant to Rule 91, June 17, 2025]

[0384] [Correction pursuant to Rule 91, June 17, 2025]

[0385]

[0386] Experimental Example 1: Competitive Fluorescence Polarization Assay

[0387] Competitive fluorescence polarization analysis was performed to evaluate the binding affinity of the example compounds. Fluorescently labeled Example 7 (K d = 125 nM) was incubated with the UBR Box domain of UBR1 (300 nM) in binding buffer (20 mM Tris·HCl pH 7.6, 150 mM NaCl, 1 mM TCEP·HCl, 0.01% Tween 20), and then treated with various concentrations of compounds. After incubation for an additional 1 hour, the polarization of fluorescence was measured using a Tecan F200 Microplate reader (Excitation: 485 nm; Emission: 535 nm). IC was calculated using nonlinear regression. 50 Determine the value and use the following equation Y = Bottom+(Top-Bottom) / (1+(X / IC 50 )) was fitted using GraphPad Prism 7 software. The results of measuring the binding affinity of the example compounds to the UBR1 protein are shown in Table 14.

[0388] [Table 14]

[0389]

[0390]

[0391]

[0392] Example 164: Synthesis of PROTAC in which the compound of Example 31 and a bromodomain-containing protein 4 (BRD4) ligand are linked via a linker

[0393] [Correction pursuant to Rule 91, June 17, 2025]

[0394]

[0395] CTC resin (100 mg, 1.35 mmol / g loading, 0.135 mmol, 1.0 equiv.) was placed in a 6.0 mL fritted syringe and treated with 1,6-diaminohexane (2.7 mmol, 20 equiv.) in DCM overnight at room temperature. The reaction mixture was then discarded, and the resin was washed with DCM (3×), MeOH (3×), and DMF (3×). The beads were treated with HBTU (0.675 mmol, 5 equiv.), HOBt (0.675 mmol, 5 equiv.), DIPEA (1.35 mmol, 10 equiv.), Fmoc-1-Nal-OH (0.675 mmol, 5 equiv.) at room temperature for 2 h to initiate the amide coupling reaction, and then the resin was washed with DMF (3x), MeOH (3x), DCM (3x), and DMF (3x). Next, the Fmoc protecting group was removed by treating with a 20% piperidine in DMF (1 mL) solution. After washing the resin with DMF (3x), MeOH (3x), DCM (3x), and DMF (3x), the amino acids Leu and Arg were coupled via the amide coupling reaction in the same manner as described above. After this, 2 mL of cleavage cocktail (95% TFA, 2.5% TIPS, 2.5% DDW) was treated to cleave the resinous compound and purified by reverse phase HPLC. The purified compound was lyophilized to obtain a light brown solid. The obtained compound was treated with a solution of HATU (0.27 mmol, 2.0 equiv.), HOAt (0.27 mmol, 2.0 equiv.), DIPEA (0.54 mmol, 4.0 equiv.), JQ1 carboxylic acid (0.135 mmol, 1.0 equiv.) in DMF at room temperature for 2 hours, and then piperidine was added to obtain a final 20% piperidine in DMF solution.After reacting at room temperature for 30 minutes, purification was performed using reverse-phase HPLC. The purification and analysis methods of the synthesized compound were the same as in the above examples, and the purified compound, (S)-2-amino-N-((S)-1-(((S)-1-((6-(2-((S)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetamido)hexyl)amino)-3-(naphthalen-1-yl)-1-oxopropan-2-yl)amino)-4-methyl-1-oxopentan-2-yl)-5-guanidinopentanamide, was freeze-dried to obtain an off-white solid (Fig. 2).

[0396]

[0397] Experimental Example 2: Competitive FP Assay of the Compound of Example 31 and the PROTAC of Example 164 against the UBR1 protein

[0398] To evaluate the binding affinity of the compound of Example 31 and the PROTAC of Example 164 for the UBR1 protein, a competitive fluorescence polarization assay was performed. The analysis was performed in the same manner as in Experimental Example 1 above. The PROTAC of Example 164 had a K of 104 nM for the UBR Box domain of the UBR1 protein. i It was bound by value and was confirmed to have a similar binding affinity to the compound of Example 31, which is a UBR1 ligand (K i = 98 nM). This indicates that the PROTAC of Example 164 can form a ternary complex with the UBR1 protein and the BRD4 protein without a decrease in binding affinity compared to existing ligands. The results of measuring the binding affinity of the compound of Example 31 and the PROTAC of Example 164 to the UBR1 protein are shown in Figure 3.

[0399]

[0400] Experimental Example 3: Confirmation of BRD4 protein degradation by PROTAC of Example 164

[0401] MDA-MB-231 cells were cultured in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% fetal bovine serum (FBS) and penicillin-streptomycin at 37°C with 5% CO2.

[0402] To evaluate the BRD4 protein degradation ability of PROTAC of Example 164, human triple-negative breast cancer (TNBC) MDA-MB-231 cells were treated with DMSO or various concentrations of PROTAC. MDA-MB-231 cells were seeded in 6-well plates and cultured at 37°C for 24 hours, and then treated with DMSO or PROTAC in Opti-MEM medium for 18 hours. Before cell lysis, cells were washed twice with cold Dulbecco's phosphate-buffered saline (DPBS). Next, cells were treated with lysis buffer (50 mM Tris-HCl pH 7.4, 150 mM NaCl, 1% Triton X, 0.1% SDS, 0.5% Sodium deoxycholate, 1x protease inhibitor cocktail) to lyse the cells and then placed on ice. Afterwards, the cell lysate was centrifuged at 13,000 rpm for 15 min at 4°C. The supernatant was collected and the protein concentration was determined using Pierce TMThe 660 nm Assay Reagent was used. 6x SDS loading buffer was added to the cell lysate and heated at 95°C for 5 minutes. Equal amounts of protein were loaded onto SDS-PAGE and transferred to PVDF membranes. The PVDF membranes were blocked with 5% skim milk in TBST (Tris-buffered saline containing 0.01% Tween-20) and treated with primary antibodies at 4°C for 15 hours. After incubation with HRP-conjugated secondary antibodies for 1 hour at room temperature, Western blot images were obtained with ECL solution. The PROTAC of Example 164 reduced the intracellular BRD4 protein expression level by more than 50% at a concentration of about 0.5 μM, and exhibited stronger BRD4 protein degradation activity as the concentration increased (Fig. 4).

[0403]

[0404] Experimental Example 4: Confirmation of target protein degradation through the proteasome-mediated pathway of PROTAC of Example 164 and formation of a ternary complex with BRD4 and UBR1 proteins.

[0405] To determine whether the PROTAC of Example 164 induces BRD4 protein degradation through the proteasome-mediated pathway, the PROTAC of Example 164 (1 μM) was treated alone or together with the proteasome inhibitor MG-132 (5 μM). MDA-MB-231 cells were seeded in 6-well plates and cultured at 37°C for 24 h, and then treated with the compound in Opti-MEM medium. Afterwards, the cells were washed twice with cold DPBS to lyse the cells, and the lysis buffer was applied to the cells and placed on ice. The cell lysate was centrifuged at 13,000 rpm for 15 min at 4°C, and the supernatant was collected and the protein concentration was determined using Pierce TMThe 660 nm Assay Reagent was used. Afterwards, 6x SDS loading buffer was added to the cell lysate and heated at 95°C for 5 minutes. The same amount of protein was loaded onto SDS-PAGE and transferred to a PVDF membrane, and then blocked with 5% skim milk in TBST. After incubating with primary and secondary antibodies in the same manner as described above, Western blot images were obtained with ECL solution. When the PROTAC of Example 164 was treated with the proteasome inhibitor MG-132, no BRD4 degradation effect was observed, thereby proving that the degradation of BRD4 by the PROTAC of Example 164 was via the proteasome-mediated pathway. In addition, to confirm whether the PROTAC of Example 164 induces BRD4 protein degradation by forming a ternary complex with the BRD4 protein and UBR1 protein, MDA-MB-231 cells were treated with the PROTAC of Example 164 (1 μM) and JQ1 (10 μM) or the compound of Example 31 (10 μM), and then the amount of intracellular BRD4 was measured by Western blot. When the PROTAC of Example 164 was treated with JQ1 (10 μM) or the compound of Example 31 (10 μM), no BRD4 degradation effect was observed, thereby proving that the degradation of BRD4 by the PROTAC of Example 164 was due to the formation of a ternary complex with the BRD4 protein and UBR1 protein (Fig. 5).

[0406]

[0407] Example 165: Prodrug synthesis of PROTAC in which the compound of Example 31 and a bromodomain-containing protein 4 (BRD4) ligand are linked via a linker

[0408] [Correction pursuant to Rule 91, June 17, 2025]

[0409]

[0410] CTC resin (100 mg, 1.35 mmol / g loading, 0.14 mmol, 1.0 equiv.) was placed in a 6.0 mL fritted syringe and treated with 1,6-diaminohexane (2.7 mmol, 20 equiv.) in DCM overnight at room temperature. The reaction mixture was then discarded, and the resin was washed with DCM (3×), MeOH (3×), and DMF (3×). The beads were treated with HBTU (0.68 mmol, 5.0 equiv.), HOBt (0.68 mmol, 5.0 equiv.), DIPEA (1.4 mmol, 10 equiv.), Fmoc-1-Nal-OH (0.68 mmol, 5.0 equiv.) at room temperature for 2 h to initiate the amide coupling reaction, and then the resin was washed with DMF (3x), MeOH (3x), DCM (3x), and DMF (3x). Next, the Fmoc protecting group was removed by treating with a 20% piperidine in DMF (1.0 mL) solution. After washing the resin with DMF (3x), MeOH (3x), DCM (3x), and DMF (3x), leucine (Leu) and arginine (Arg) amino acids were coupled via the amide coupling reaction in the same manner as described above. After this, 2.0 mL of cleavage cocktail (95% TFA, 2.5% TIPS, 2.5% DDW) was treated to cleave the resinous compound and purified by reverse phase HPLC. The purified compound was lyophilized to obtain a light brown solid. The obtained compound was treated with a solution of HATU (0.27 mmol, 2.0 equiv.), HOAt (0.27 mmol, 2.0 equiv.), DIPEA (0.54 mmol, 4.0 equiv.), and JQ1 carboxylic acid (0.14 mmol, 1.0 equiv.) in DMF at room temperature for 2 hours, and then piperidine was added to obtain a final 20% piperidine in DMF solution.After reacting at room temperature for 30 minutes, purification was performed using reverse-phase HPLC. The purified compound was freeze-dried to obtain an off-white solid. Thereafter, the obtained compound (10 mg, 0.01 mmol, 1.0 equiv.) was treated with a solution of 1-((2,5-dioxopyrrolidin-1-yloxy)carbonyloxy)ethyl isobutyrate (0.01 mmol, 1.0 equiv.) and DIPEA (0.04 mmol, 4.0 equiv.) in dry DMF, reacted at room temperature for 2 hours, and then purified using reverse-phase HPLC. The purification and analysis methods of the synthesized compound were the same as in the above examples, and the purified compound (6S,9S,12S)-23-((S)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)-6-(4-guanidinobutyl)-9-isobutyl-12-(naphthalen-1-ylmethyl)-4,7,10,13,22-pentaoxo-3-oxa-5,8,11,14,21-pentaazatricosan-2-ylisobutyrate was freeze-dried to obtain an off-white solid (Fig. 6).

[0411]

[0412] Experimental Example 5: Confirmation of BRD4 protein degradation by prodrug of Example 165

[0413] To evaluate the BRD4 protein degradation ability of the synthesized Example 165 prodrug, human prostate cancer PC-3 cells were treated with DMSO or various concentrations of protac compounds. PC-3 cells were seeded in 6-well plates and cultured at 37°C for 24 hours, and then treated with DMSO or protac compounds in Opti-MEM medium for 48 hours. Before cell lysis, cells were washed twice with cold Dulbecco's phosphate-buffered saline (DPBS). Next, cells were treated with lysis buffer (50 mM Tris·HCl pH 7.4, 150 mM NaCl, 1% Triton X, 0.1% SDS, 0.5% Sodium deoxycholate, 1x protease inhibitor cocktail) to lyse the cells and then placed on ice. The cell lysate was then centrifuged at 13,000 rpm for 15 minutes at 4°C. Collect the supernatant and measure the protein concentration using Pierce TM The 660 nm assay reagent was used. 6x SDS loading buffer was added to the cell lysate and heated at 95°C for 5 minutes. Equal amounts of protein were loaded onto SDS-PAGE and transferred to PVDF membranes. The PVDF membranes were blocked with 5% skim milk in TBST (Tris-buffered saline containing 0.01% Tween-20) and treated with primary antibodies for 15 hours at 4°C. After incubation with HRP-conjugated secondary antibodies for 1 hour at room temperature, Western blot images were obtained with ECL solution (Fig. 7).

Claims

1. A compound of the following chemical formula 1 or a prodrug thereof: [Chemical Formula 1] In the above chemical formula 1, R1 and R2 are each independently -H, -D, alkyl, deuterated alkyl or haloalkyl; R3 is -DEG; wherein D is a direct bond or alkylene; E is alkylene, alkenylene, alkynylene, cycloalkylene, cycloalkenylene, arylene, heterocycloalkylene, heterocycloalkenylene or heteroarylene; wherein said alkylene, alkenylene, alkynylene, cycloalkylene. Cycloalkenylene, arylene, heterocycloalkylene, heterocycloalkenylene or heteroarylene may be optionally substituted with one or more substituents selected from -D, halo, hydroxy, thiol (-SH), amino, nitro, cyano, alkyl, haloalkyl, deuterated alkyl, hydroxyalkyl, alkoxy, haloalkoxy, alkoxyalkyl, alkylthio, alkylamino, dialkylamino, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, aminocarbonylalkyl, alkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, carboxy, alkoxycarbonyl, carboxyalkyl, alkylcarbonyl, alkylcarbonylalkyl, alkoxycarbonylalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; G is amino, heteroaryl, , or and here R7, R8 and R9 is each independently -H, alkyl or haloalkyl; or R7 and R8 may be connected to each other to form a ring structure; R4 is -H, -D, alkyl, deuterated alkyl or haloalkyl; L is -C-, -CH-, or and here R 10 and R 11 are each independently -H, -D, halo, alkyl, deuterated alkyl or haloalkyl; R5 is -JM; wherein J is a direct bond, alkylene, alkenylene, alkynylene, alkylene-O- or alkylene-NH-; M is -H, halo, hydroxy, amino, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl or heteroaryl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl or heteroaryl is optionally -D, hydroxy, thiol, amino, halo, nitro, cyano, alkyl, haloalkyl, deuterated alkyl, hydroxyalkyl, alkoxy, haloalkoxy, cycloalkyl-oxy, heterocycloalkyl-oxy, aryl-oxy, heteroaryl-oxy, alkoxyalkyl, alkylthio, aminoalkyl, alkylamino, dialkylamino, alkylaminoalkyl, dialkylaminoalkyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, aminocarbonylalkyl, alkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, carboxy, carboxyalkyl, alkylcarbonyl, alkylcarbonylalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, may be substituted with one or more substituents selected from alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl; or when L is -C- and m is 2, L may be connected to R5 to form cycloalkyl or heterocycloalkyl; R6 is -H, , , , , , , , , , or and here R 12 Inland R 27 are each independently -H, nitro, cyano, azido, halo, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, heteroaryl, cycloalkyl-alkyl, cycloalkenyl-alkyl, alkoxy-alkyl, alkylthio-alkyl, aminoalkyl, dialkylaminoalkyl, heterocycloalkyl-alkyl, heterocycloalkenyl-alkyl, aryl-alkyl, alkyl-aryl-alkyl, alkoxy-aryl-alkyl, heteroaryl-alkyl, partially unsaturated heterocyclyl-alkyl, alkyl-heterocycloalkyl, aryl-alkyl-heterocycloalkyl or partially unsaturated heterocyclyl-alkyl-heterocycloalkyl;wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, heteroaryl, cycloalkyl-alkyl, cycloalkenyl-alkyl, heterocycloalkyl-alkyl, heterocycloalkenyl-alkyl, aryl-alkyl, heteroaryl-alkyl is optionally -D, halo, hydroxy, thiol, amino, nitro, cyano, oxo, azido, carboxy, aminocarbonyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, cycloalkyl-oxy, heterocycloalkyl-oxy, aryl-oxy, heteroaryl-oxy, alkylthio, alkylamino, dialkylamino, cycloalkylamino, heterocycloalkylamino, arylamino, heteroarylamino, alkoxycarbonyl, cycloalkyl-oxycarbonyl, Heterocycloalkyl-oxycarbonyl, aryl-oxycarbonyl, heteroaryl-oxycarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, cycloalkylaminocarbonyl, heterocycloalkylaminocarbonyl, arylaminocarbonyl, heteroarylaminocarbonyl, alkylcarbonyl, cycloalkylcarbonyl, heterocycloalkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, sulfo(-SO3H), alkoxy-sulfonyl(SO2), aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, cycloalkylaminosulfonyl, heterocycloalkylaminosulfonyl, arylaminosulfonyl, heteroarylaminosulfonyl, carboxyalkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, alkoxyalkyl, alkoxycarbonylalkyl, alkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, which may be substituted with one or more substituents selected from alkylcarbonylalkyl, sulfoalkyl, alkoxysulfonylalkyl, aminosulfonylalkyl, alkylaminosulfonylalkyl, dialkylaminosulfonylalkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, heteroaryl, cycloalkyl-alkyl, cycloalkenyl-alkyl, heterocycloalkyl-alkyl, heterocycloalkenyl-alkyl, aryl-alkyl and heteroaryl-alkyl; p is 0, 1, 2, 3, 4, 5, 6 or 7; n is 1, 2 or 3; when n is 2 and 3, the repeating units may be the same or different; m is 1 or 2; The above heterocycloalkylene, heterocycloalkenylene, heteroarylene, heterocycloalkyl, heterocycloalkenyl, partially unsaturated heterocyclyl and heteroaryl have one or more heteroatoms selected from N, O and S.

2. In paragraph 1, R1 and R2 are each independently -H, -D, C1-C7 alkyl, deuterated C1-C7 alkyl or halo-C1-C7 alkyl; R3 is -DEG; where D is a direct bond or C1-C7 alkylene; E is C1-C7 alkylene, C2-C7 alkenylene, C2-C7 alkynylene, C3-C 10 Cycloalkylene, C3-C 10 Cycloalkenylene, C6-C 12 Arylene, 4 to 12 membered heterocycloalkylene, 4 to 12 membered heterocycloalkenylene or 5 to 12 membered heteroarylene; wherein said alkylene, alkenylene, alkynylene, cycloalkylene, cycloalkenylene, heterocycloalkylene, heterocycloalkenylene, arylene or heteroarylene is optionally -D, halo, hydroxy, thiol, amino, nitro, cyano, C1-C7 alkyl, halo-C1-C7 alkyl, deuterated C1-C7 alkyl, hydroxy-C1-C7 alkyl, C1-C7 alkoxy, halo-C1-C7 alkoxy, C1-C7 alkoxy-C1-C7 alkyl, C1-C7 alkylthio, C1-C7 alkylamino, di(C1-C7 alkyl)amino, amino-C1-C7 alkyl, C1-C7 alkylamino-C1-C7 alkyl, di(C1-C7 alkyl)amino-C1-C7 alkyl, aminocarbonyl, C1-C7 alkylaminocarbonyl, di(C1-C7 alkyl)aminocarbonyl, aminocarbonyl-C1-C7 alkyl, C1-C7 alkylaminocarbonyl-C1-C7 alkyl, di(C1-C7 alkyl)aminocarbonyl-C1-C7 alkyl, carboxy, carboxy-C1-C7 alkyl, C1-C7 alkylcarbonyl, C1-C7 alkylcarbonyl-C1-C7 alkyl, C1-C7 alkoxycarbonyl, C1-C7 alkoxycarbonyl-C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C3-C 10 Cycloalkyl, 4 to 12 membered heterocycloalkyl, C6-C 12 may be substituted with 1 to 4 substituents selected from aryl or 5 to 12 membered heteroaryl; G is amino, 5 to 12 membered heteroaryl, , or and here R7, R8 and R9 is each independently -H, C1-C7 alkyl or halo-C1-C7 alkyl; or R7 and R8 may be connected to each other to form a ring structure; R4 is -H, -D, C1-C7alkyl, deuterated C1-C7alkyl or halo-C1-C7alkyl; L is -C-, -CH-, or and here R 10 and R 11 are each independently -H, -D, halo, C1-C7 alkyl, deuterated C1-C7 alkyl or halo-C1-C7 alkyl; R5 is -JM; where J is a direct bond, C1-C7 alkylene, C2-C7 alkenylene, C2-C7 alkynylene, C1-C7 alkylene-O- or C1-C7 alkylene-NH-; M is -H, halo, hydroxy, amino, C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C3-C 10 Cycloalkyl, C3-C 10 Cycloalkenyl, 4 to 12 membered heterocycloalkyl, 4 to 12 membered heterocycloalkenyl, C6-C 12 Aryl or 5 to 12 membered heteroaryl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl or heteroaryl is optionally -D, hydroxy, thiol, amino, halo, nitro, cyano, C1-C7 alkyl, halo-C1-C7 alkyl, deuterated C1-C7 alkyl, hydroxy-C1-C7 alkyl, C1-C7 alkoxy, halo-C1-C7 alkoxy, C3-C 10 Cycloalkyl-oxy, 4 to 12 membered heterocycloalkyl-oxy, C6-C 12 Aryl-oxy, 5 to 12 membered heteroaryl-oxy, C1-C7alkoxy-C1-C7alkyl, C1-C7alkylthio, amino-C1-C7alkyl, C1-C7alkylamino, di(C1-C7alkyl)amino, C1-C7alkylamino-C1-C7alkyl, di(C1-C7alkyl)amino-C1-C7alkyl, aminocarbonyl, C1-C7alkylaminocarbonyl, di(C1-C7alkyl)aminocarbonyl, aminocarbonyl-C1-C7alkyl, C1-C7alkylaminocarbonyl-C1-C7alkyl, di(C1-C7alkyl)aminocarbonyl-C1-C7alkyl, carboxy, carboxy-C1-C7alkyl, C1-C7alkylcarbonyl, C1-C7alkylcarbonyl-C1-C7alkyl, C1-C7 alkoxycarbonyl, C1-C7 alkoxycarbonyl-C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C3-C 10 Cycloalkyl, 4 to 12 membered heterocycloalkyl, C6-C 12 may be substituted with 1 to 4 substituents selected from aryl and 5 to 12 membered heteroaryl; or when L is -C- and m is 2, L is connected to R5 to form C3-C 10 can form a cycloalkyl or a 4 to 12 membered heterocycloalkyl; R6 is -H, , , , , , , , , , or and here R 12 Inland R 27 are each independently -H, nitro, cyano, azido, halo, C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C3-C 10 Cycloalkyl, C3-C 10 Cycloalkenyl, 4 to 12 membered heterocycloalkyl, 4 to 12 membered heterocycloalkenyl, C6-C 12 Aryl, 5 to 12 membered heteroaryl, C3-C 10 Cycloalkyl-C1-C7 alkyl, C3-C 10 Cycloalkenyl-C1-C7 alkyl, C1-C7 alkoxy-C1-C7 alkyl, C1-C7 alkylthio-C1-C7 alkyl, amino-C1-C7 alkyl, di(C1-C7 alkyl)amino-C1-C7 alkyl, 4 to 12 membered heterocycloalkyl-C1-C7 alkyl, 4 to 12 membered heterocycloalkenyl-C1-C7 alkyl, C6-C 12 Aryl-C1-C7 alkyl, C1-C7 alkyl-C6-C 12 Aryl-C1-C7 alkyl, C1-C7 alkoxy-C6-C 12 Aryl-C1-C7 alkyl, 5 to 12 membered heteroaryl-C1-C7 alkyl, partially unsaturated 4 to 12 membered heterocyclyl-C1-C7 alkyl, C1-C7 alkyl-4 to 12 membered heterocycloalkyl, C6-C 12 Aryl-C1-C7 alkyl-4 to 12 membered heterocycloalkyl or partially unsaturated 4 to 12 membered heterocyclyl-C1-C7 alkyl-4 to 12 membered heterocycloalkyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, heteroaryl, cycloalkyl-alkyl, cycloalkenyl-alkyl, heterocycloalkyl-alkyl, heterocycloalkenyl-alkyl, aryl-alkyl, heteroaryl-alkyl is optionally -D, halo, hydroxy, thiol, amino, nitro, cyano, oxo, azido, carboxy, aminocarbonyl, C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkynyl, halo-C1-C7 alkyl, C1-C7 alkoxy, C3-C 10 Cycloalkyl-oxy, 4 to 12 membered heterocycloalkyl-oxy, C6-C 12 Aryl-oxy, 5 to 12 membered heteroaryl-oxy, C1-C7 alkylthio, C1-C7 alkylamino, di(C1-C7 alkyl)amino, C3-C 10 Cycloalkylamino, 4 to 12 membered heterocycloalkylamino, C6-C 12 Arylamino, 5-12 membered heteroarylamino, C1-C7 alkoxycarbonyl, C3-C 10 Cycloalkyl-oxycarbonyl, 4 to 12 membered heterocycloalkyl-oxycarbonyl, C6-C 12 Aryl-oxycarbonyl, 5 to 12 membered heteroaryl-oxycarbonyl, C1-C7 alkylaminocarbonyl, di(C1-C7 alkyl)aminocarbonyl, C3-C 10 Cycloalkylaminocarbonyl, 4 to 12 membered heterocycloalkylaminocarbonyl, C6-C 12 Arylaminocarbonyl, 5 to 12 membered heteroarylaminocarbonyl, C1-C7 alkylcarbonyl, C3-C 10 Cycloalkylcarbonyl, 4 to 12 membered heterocycloalkylcarbonyl, C6-C 12 Arylcarbonyl, 5-12 membered heteroarylcarbonyl, sulfo, C1-C7 alkoxy-sulfonyl, aminosulfonyl, C1-C7 alkylaminosulfonyl, di(C1-C7 alkyl)aminosulfonyl, C3-C 10 Cycloalkylaminosulfonyl, 4 to 12 membered heterocycloalkylaminosulfonyl, C6-C 12 Arylaminosulfonyl, 5 to 12 membered heteroarylaminosulfonyl, carboxy-C1-C7 alkyl, amino-C1-C7 alkyl, C1-C7 alkylamino-C1-C7 alkyl, di(C1-C7 alkyl)amino-C1-C7 alkyl, C1-C7 alkoxy-C1-C7 alkyl, C1-C7 alkoxycarbonyl-C1-C7 alkyl, C1-C7 alkylaminocarbonyl-C1-C7 alkyl, di(C1-C7 alkyl)aminocarbonyl-C1-C7 alkyl, C1-C7 alkylcarbonyl-C1-C7 alkyl, sulfo-C1-C7 alkyl, C1-C7 alkoxysulfonyl-C1-C7 alkyl, aminosulfonyl-C1-C7 alkyl, C1-C7 alkylaminosulfonyl-C1-C7 alkyl, Di(C1-C7 alkyl)aminosulfonyl-C1-C7 alkyl, C3-C 10 Cycloalkyl, C3-C 10 Cycloalkenyl, 4 to 12 membered heterocycloalkyl, 4 to 12 membered heterocycloalkenyl, C6-C 12 Aryl, 5 to 12 membered heteroaryl, C3-C 10 Cycloalkyl-C1-C7 alkyl, C3-C 10 Cycloalkenyl-C1-C7 alkyl, 4 to 12 membered heterocycloalkyl-C1-C7 alkyl, 4 to 12 membered heterocycloalkenyl-C1-C7 alkyl, C6-C 12 which may be substituted with 1 to 4 substituents selected from aryl-C1-C7 alkyl and 5 to 12 membered heteroaryl-C1-C7 alkyl; p is 0, 1, 2, 3, 4, 5, 6 or 7; n is 1, 2 or 3; when n is 2 and 3, the repeating units may be the same or different; m is 1 or 2; A compound or a prodrug thereof, wherein the heterocycloalkylene, heterocycloalkenylene, heteroarylene, heterocycloalkyl, heterocycloalkenyl, partially unsaturated heterocyclyl and heteroaryl have 1 to 4 heteroatoms selected from N, O and S.

3. In paragraph 1, A compound or a prodrug thereof, wherein R1 and R2 are each independently -H or C1-C5 alkyl.

4. In paragraph 1, R3 is -DEG; where D is C1-C5 alkylene; E is C1-C5 alkylene, C6-C 10 Arylene or a 5 to 10 membered heterocycloalkylene having 1 to 3 N atoms; G is amino, 5 to 10 membered heteroaryl, , or and here R7, R8 and A compound or a prodrug thereof, wherein each R9 is independently -H, C1-C5 alkyl or halo-C1-C5 alkyl.

5. In paragraph 1, A compound or a prodrug thereof, wherein R4 is -H or C1-C5 alkyl.

6. In paragraph 1, L is -C-, -CH- or -CH-CH2-; R5 is -JM; where J is a direct bond, C1-C5 alkylene or C2-C5 alkenylene; M is -H, hydroxy, C1-C5 alkyl, C3-C8 cycloalkyl, C6-C 10 Aryl, or 5 to 10 membered heteroaryl; wherein said cycloalkyl, aryl or heteroaryl is optionally selected from the group consisting of hydroxy, halo, cyano, C1-C5 alkyl, halo-C1-C5 alkyl, C1-C5 alkoxy and C6-C 10 A compound or a prodrug thereof, characterized in that it may be substituted with 1 to 3 substituents selected from aryl; or when L is -C- and m is 2, L may be connected to R5 to form a C3-C8 cycloalkyl or a 4 to 10 membered heterocycloalkyl.

7. In paragraph 1, R6 , or and here R 16 Inland R 19 are each independently -H, C1-C5 alkyl, C2-C5 alkenyl, C3-C8 cycloalkyl, 4 to 10 membered heterocycloalkyl, C1-C5 alkoxy-C1-C5 alkyl, C3-C8 cycloalkyl-C1-C5 alkyl, C3-C8 cycloalkenyl-C1-C5 alkyl, 4 to 10 membered heterocycloalkyl-C1-C5 alkyl, partially unsaturated 4 to 10 membered heterocyclyl-C1-C5 alkyl, amino-C1-C5 alkyl, di(C1-C5 alkyl)amino-C1-C5 alkyl, C1-C5 alkylthio-C1-C5 alkyl, C6-C 10 Aryl, 5-10 membered heteroaryl, C6-C 10 Aryl-C1-C5 alkyl, 5 to 10 membered heteroaryl-C1-C5 alkyl, C1-C5 alkyl-C6-C 10 Aryl-C1-C5 alkyl, C1-C5 alkoxy-C6-C 10 Aryl-C1-C5 alkyl, C1-C5 alkyl-4 to 10 membered heterocycloalkyl, C6-C 10 A compound or a prodrug thereof, characterized in that the aryl-C1-C5 alkyl-4 to 10 membered heterocycloalkyl or partially unsaturated 4 to 10 membered heterocyclyl-C1-C5 alkyl-4 to 10 membered heterocycloalkyl; wherein the cycloalkyl and heterocycloalkyl may be optionally substituted with 1 to 3 substituents selected from halo, oxo, alkyl and haloalkyl; and wherein the aryl and heteroaryl may be substituted with 1 to 3 substituents selected from halo, hydroxy, alkyl, alkoxy, haloalkyl and aminosulfonyl.

8. In the first paragraph, a compound or a prodrug thereof, characterized in that the compound of the chemical formula 1 is selected from the following group: (S)-2-amino-N-((S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)amino)-3,3-dimethyl-1-oxobutan-2-yl)-5-guanidinopentanamide; (S)-2-amino-N-((S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)amino)-3-cyclopropyl-1-oxopropan-2-yl)-5-guanidinopentanamide; (S)-2-amino-N-((S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)amino)-3-cyclopentyl-1-oxopropan-2-yl)-5-guanidinopentanamide; (S)-2-amino-N-((S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-5-guanidinopentanamide; (S)-2-amino-N-((S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)amino)-3-(naphthalen-1-yl)-1-oxopropan-2-yl)-5-guanidinopentanamide; (S)-2-amino-N-((S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-3-(4-fluorophenyl)-1-oxopropan-2-yl)amino)-4-methyl-1-oxopentan-2-yl)-5-guanidinopentanamide; (S)-2-amino-N-((S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-3-(naphthalen-1-yl)-1-oxopropan-2-yl)amino)-4-methyl-1-oxopentan-2-yl)-5-guanidinopentanamide; (S)-2-amino-N-((S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)amino)-4-methyl-1-oxopentan-2-yl)-5-guanidinopentanamide; (S)-2-amino-N-((S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-3-cyclopentyl-1-oxopropan-2-yl)amino)-4-methyl-1-oxopentan-2-yl)-5-guanidinopentanamide; (S)-2-amino-N-((S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-3-cyclopropyl-1-oxopropan-2-yl)amino)-4-methyl-1-oxopentan-2-yl)-5-guanidinopentanamide; (S)-2-amino-N-((S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-3,3-dimethyl-1-oxobutan-2-yl)amino)-4-methyl-1-oxopentan-2-yl)-5-guanidinopentanamide; (S)-2-amino-N-((2S,3S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-3-(naphthalen-1-yl)-1-oxopropan-2-yl)amino)-3-methyl-1-oxopentan-2-yl)-5-guanidinopentanamide; (S)-2-amino-N-((2S,3S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)amino)-3-methyl-1-oxopentan-2-yl)-5-guanidinopentanamide; (S)-2-amino-N-((S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-3-(4-fluorophenyl)-1-oxopropan-2-yl)amino)-3-(4-hydroxyphenyl)-1-oxopropan-2-yl)-5-guanidinopentanamide; (S)-2-amino-N-((S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-3-(4-chlorophenyl)-1-oxopropan-2-yl)amino)-3-(4-hydroxyphenyl)-1-oxopropan-2-yl)-5-guanidinopentanamide; (S)-2-amino-N-((S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-3-(naphthalen-1-yl)-1-oxopropan-2-yl)amino)-3-(4-hydroxyphenyl)-1-oxopropan-2-yl)-5-guanidinopentanamide; (S)-2-amino-N-((S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)amino)-3-(4-hydroxyphenyl)-1-oxopropan-2-yl)-5-guanidinopentanamide; (S)-2-amino-N-((S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-3-(naphthalen-1-yl)-1-oxopropan-2-yl)amino)-3,3-dimethyl-1-oxobutan-2-yl)-5-guanidinopentanamide; (S)-2-amino-N-((S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)amino)-3,3-dimethyl-1-oxobutan-2-yl)-5-guanidinopentanamide; (S)-2-amino-N-((S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-3-cyclopropyl-1-oxopropan-2-yl)amino)-3,3-dimethyl-1-oxobutan-2-yl)-5-guanidinopentanamide; (S)-2-amino-N-((S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-3-(naphthalen-1-yl)-1-oxopropan-2-yl)amino)-3-cyclopropyl-1-oxopropan-2-yl)-5-guanidinopentanamide; (S)-2-amino-N-((S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-3,3-dimethyl-1-oxobutan-2-yl)amino)-3-cyclopropyl-1-oxopropan-2-yl)-5-guanidinopentanamide; (S)-2-amino-N-((S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-3-(4-chlorophenyl)-1-oxopropan-2-yl)amino)-3-cyclopentyl-1-oxopropan-2-yl)-5-guanidinopentanamide; (S)-2-amino-N-((S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-3-(4-fluorophenyl)-1-oxopropan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-5-guanidinopentanamide; (S)-2-amino-N-((S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-3,3-dimethyl-1-oxobutan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-5-guanidinopentanamide; (S)-2-amino-N-((S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)amino)-3-(4-fluorophenyl)-1-oxopropan-2-yl)-5-guanidinopentanamide; (S)-2-amino-N-((S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-3-cyclopropyl-1-oxopropan-2-yl)amino)-3-(4-fluorophenyl)-1-oxopropan-2-yl)-5-guanidinopentanamide; (S)-2-amino-N-((S)-1-(((S)-1-(((S)-1-amino-3-hydroxy-1-oxopropan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)amino)-3-(4-chlorophenyl)-1-oxopropan-2-yl)-5-guanidinopentanamide; (S)-2-amino-N-((S)-1-(((S)-1-amino-1-oxo-3-phenylpropan-2-yl)amino)-4-methyl-1-oxopentan-2-yl)-5-guanidinopentanamide; (S)-2-amino-N-((S)-1-(((S)-1-amino-1-oxo-3-phenylpropan-2-yl)amino)-3-(4-hydroxyphenyl)-1-oxopropan-2-yl)-5-guanidinopentanamide; (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(naphthalen-1-yl)-1-oxopropan-2-yl)amino)-4-methyl-1-oxopentan-2-yl)-5-guanidinopentanamide; (S)-2-amino-N-((S)-1-(((S)-1-amino-3-cyclohexyl-1-oxopropan-2-yl)amino)-4-methyl-1-oxopentan-2-yl)-5-guanidinopentanamide; (S)-2-amino-N-((2S,3S)-1-(((S)-1-amino-3-(naphthalen-1-yl)-1-oxopropan-2-yl)amino)-3-methyl-1-oxopentan-2-yl)-5-guanidinopentanamide; (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(4-fluorophenyl)-1-oxopropan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-5-guanidinopentanamide; (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(naphthalen-1-yl)-1-oxopropan-2-yl)amino)-1-oxobutan-2-yl)-5-guanidinopentanamide; (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(naphthalen-1-yl)-1-oxopropan-2-yl)amino)-1-oxopentan-2-yl)-5-guanidipentanamide; (S)-N-((S)-1-amino-3-(naphthalen-1-yl)-1-oxopropan-2-yl)-2-((S)-2-amino-5-guanidinopentanamido)hexanamide; (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(naphthalen-1-yl)-1-oxopropan-2-yl)amino)-3-cyclopropyl-1-oxopropan-2-yl)-5-guanidinopentanamide; (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(naphthalen-1-yl)-1-oxopropan-2-yl)amino)-3-cyclopentyl-1-oxopropan-2-yl)-5-guanidinopentanamide; (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(naphthalen-1-yl)-1-oxopropan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-5-guanidinopentanamide; (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(naphthalen-1-yl)-1-oxopropan-2-yl)amino)-4-methyl-1-oxopentan-2-yl)-5-(3-methylguanidino)pentanamide; (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(naphthalen-1-yl)-1-oxopropan-2-yl)amino)-4-methyl-1-oxopentan-2-yl)-5-(3,3-dimethylguanidino)pentanamide; (S)-N-((S)-1-amino-3-(naphthalen-1-yl)-1-oxopropan-2-yl)-2-((S)-5-guanidino-2-(methylamino)pentanamido)-4-methylpentanamide; (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(4-fluorophenyl)-1-oxopropan-2-yl)amino)-3-cyclopentyl-1-oxopropan-2-yl)-5-guanidinopentanamide; (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(4-fluorophenyl)-1-oxopropan-2-yl)amino)-3-(naphthalen-1-yl)-1-oxopropan-2-yl)-5-guanidinopentanamide; (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(4-fluorophenyl)-1-oxopropan-2-yl)amino)-3-(naphthalen-2-yl)-1-oxopropan-2-yl)-5-guanidinopentanamide; (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(4-chlorophenyl)-1-oxopropan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-5-guanidinopentanamide; (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(4-bromophenyl)-1-oxopropan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-5-guanidinopentanamide; (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(4-iodophenyl)-1-oxopropan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-5-guanidinopentanamide; (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(naphthalen-2-yl)-1-oxopropan-2-yl)amino)-4-methyl-1-oxopentan-2-yl)-5-guanidinopentanamide; (S)-N-((S)-1-amino-3-(naphthalen-2-yl)-1-oxopropan-2-yl)-2-((S)-2-amino-5-guanidinopentanamido)hexanamide; (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(naphthalen-2-yl)-1-oxopropan-2-yl)amino)-3-cyclopropyl-1-oxopropan-2-yl)-5-guanidinopentanamide; (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(naphthalen-2-yl)-1-oxopropan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-5-guanidinopentanamide; (S)-N-((S)-3-([1,1'-biphenyl]-4-yl)-1-amino-1-oxopropan-2-yl)-2-((S)-2-amino-5-ureidopentanamido)-4,4-dimethylpentanamide; (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(3,4-difluorophenyl)-1-oxopropan-2-yl)amino)-1-oxo-3-(3-(trifluoromethyl)phenyl)propan-2-yl)-5-ureidopentanamide; (S)-2-amino-N-((S)-1-(((S)-1-amino-1-oxo-3-(4-(trifluoromethyl)phenyl)propan-2-yl)amino)-3-(4-methoxyphenyl)-1-oxopropan-2-yl)-5-ureidopentanamide; (S)-N-((S)-3-([1,1'-biphenyl]-4-yl)-1-(((S)-1-amino-1-oxo-3-(pyridin-3-yl)propan-2-yl)amino)-1-oxopropan-2-yl)-2-amino-5-ureidopentanamide; (S)-2-amino-N-((S)-1-(((S)-1-amino-1-oxo-3-(3-(trifluoromethyl)phenyl)propan-2-yl)amino)-1-oxo-4-phenylbutan-2-yl)-4-guanidinobutanamide; (S)-2-amino-N-((S)-1-(((S)-2-amino-2-oxo-1-phenylethyl)amino)-3-(5-bromo-1H-indole-3-yl)-1-oxopropan-2-yl)-4-guanidinobutanamide; (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(4-methoxyphenyl)-1-oxopropan-2-yl)amino)-3-(3,4-difluorophenyl)-1-oxopropan-2-yl)-4-guanidinobutanamide; (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(4-cyanophenyl)-1-oxopropan-2-yl)amino)-1-oxo-3-(thiophen-2-yl)propan-2-yl)-4-guanidinobutanamide; N-((S)-1-amino-1-oxo-3-(thiophen-2-yl)propan-2-yl)-1-((S)-2-amino-3-(4-guanidinophenyl)propanamido)cyclopropanecarboxamide; 1-((S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-3-(4-(trifluoromethyl)phenyl)propanamido)cyclopropanecarboxamide; 4-((S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-3-(3,4-dichlorophenyl)propanamido)tetrahydro-2H-pyran-4-carboxamide; (S)-2-((S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-3-(4-cyanophenyl)propanamido)-4,4-dimethylpentanamide; N-((S)-1-amino-1-oxo-4-phenylbutan-2-yl)-4-((S)-2-amino-6-guanidinohexamido)tetrahydro-2H-pyran-4-carboxamide; (S)-2-amino-N-((S)-2-(((S)-1-amino-3-(5-bromo-1H-indol-3-yl)-1-oxopropan-2-yl)amino)-2-oxo-1-phenylethyl)-6-guanidinohexanamide; (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(3,4-dichlorophenyl)-1-oxopropan-2-yl)amino)-1-oxo-3-(pyridin-3-yl)propan-2-yl)-6-guanidinohexanamide; 4-((S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-3-(3,4-difluorophenyl)propanamido)tetrahydro-2H-pyran-4-carboxamide; 4-((S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-3-(4-(trifluoromethyl)phenyl)propanamido)tetrahydro-2H-pyran-4-carboxamide; (S)-2-amino-N-((S)-1-(((S)-2-amino-2-oxo-1-phenylethyl)amino)-3-(3,4-dichlorophenyl)-1-oxopropan-2-yl)-3-(4-guanidinophenyl)propanamide; (S)-2-((S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-3-(3,4-dichlorophenyl)propanamido)-4,4-dimethylpentanamide; 4-((S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-3-(4-cyanophenyl)propanamido)tetrahydro-2H-pyran-4-carboxamide; (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(4-fluorophenyl)-1-oxopropan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-3-(4-guanidinophenyl)propanamide; (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-N-((S)-1-amino-3-(naphthalen-1-yl)-1-oxopropan-2-yl)-4-methylpentanamide; (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(naphthalen-1-yl)-1-oxopropan-2-yl)amino)-4-methyl-1-oxopentan-2-yl)-5-ureidopentanamide; (S)-N-((S)-1-amino-3-(naphthalen-1-yl)-1-oxopropan-2-yl)-2-((S)-2-amino-4-guanidinobutanamido)-4-methylpentanamide; (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(naphthalen-1-yl)-1-oxopropan-2-yl)amino)-4-methyl-1-oxopentan-2-yl)-6-guanidinohexanamide; (S)-N-((S)-1-amino-3-(naphthalen-1-yl)-1-oxopropan-2-yl)-2-((S)-2-amino-5-guanidinopentanamido)-4,4-dimethylpentanamide; (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(naphthalen-1-yl)-1-oxopropan-2-yl)amino)-3-cyclopentyl-1-oxopropan-2-yl)-3-(4-guanidinophenyl)propanamide; (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(4-fluorophenyl)-1-oxopropan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-3-(4-guanidinophenyl)propanamide; (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(4-fluorophenyl)-1-oxopropan-2-yl)amino)-3-(4-methoxyphenyl)-1-oxopropan-2-yl)-3-(4-guanidinophenyl)propanamide; (S)-N-((S)-1-amino-3-(4-fluorophenyl)-1-oxopropan-2-yl)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-phenylbutanamide; (S)-3-([1,1'-biphenyl]-4-yl)-N-((S)-1-amino-3-(4-fluorophenyl)-1-oxopropan-2-yl)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)propanamide; (S)-N-((S)-1-amino-3-(4-fluorophenyl)-1-oxopropan-2-yl)-3-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-5-cyclohexylpentanamide; (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(4-fluorophenyl)-1-oxopropan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-3-(3-guanidinophenyl)propanamide; (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(4-fluorophenyl)-1-oxopropan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-3-(2-guanidinophenyl)propanamide; (R)-2-amino-N-((S)-1-(((S)-1-amino-3-(4-fluorophenyl)-1-oxopropan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-3-(4-guanidinophenyl)propanamide; 2-amino-N-((S)-1-(((S)-1-amino-3-(4-fluorophenyl)-1-oxopropan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-3-(4-guanidinophenyl)propanamide; (S)-2-amino-N-((R)-1-(((S)-1-amino-3-(4-fluorophenyl)-1-oxopropan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-3-(4-guanidinophenyl)propanamide; (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(4-fluorophenyl)-1-oxopropan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-3-(4-guanidinophenyl)-N-methylpropanamide; (2S)-2-amino-N-(1-(((S)-1-amino-3-(4-fluorophenyl)-1-oxopropan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-3-(4-guanidinophenyl)propanamide; (S)-2-amino-N-((S)-1-(((R)-1-amino-3-(4-fluorophenyl)-1-oxopropan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-3-(4-guanidinophenyl)propanamide; (S)-N-((S)-1-amino-3-(4-fluorophenyl)-1-oxopropan-2-yl)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-3-cyclohexyl-N-methylpropanamide; (2S)-2-amino-N-((2S)-1-((1-amino-3-(4-fluorophenyl)-1-oxopropan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-3-(4-guanidinophenyl)propanamide; (S)-2-amino-N-((S)-1-(((S)-1-amino-3-(4-fluorophenyl)-1-oxopropan-2-yl)amino)-3-cyclohexyl-1-oxopropan-2-yl)-3-(1-carbamimidoylpiperidin-4-yl)propanamide; (S)-N-((S)-1-amino-3-(4-fluorophenyl)-1-oxopropan-2-yl)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexylbutanamide; (S)-N-((R)-1-amino-3-(4-fluorophenyl)-1-oxopropan-2-yl)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexylbutanamide; (2S)-N-(1-amino-3-(4-fluorophenyl)-1-oxopropan-2-yl)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexylbutanamide; (S)-2-amino-N-((S)-1-amino-3-cyclohexyl-1-oxopropan-2-yl)-3-(4-guanidinophenyl)propanamide; (S)-2-amino-N-((S)-1-amino-3-(3,4-dichlorophenyl)-1-oxopropan-2-yl)-5-guanidinopentanamide; (S)-N-((S)-3-([1,1'-biphenyl]-4-yl)-1-amino-1-oxopropan-2-yl)-2-amino-5-guanidinopentanamide; (S)-2-amino-N-((S)-1-amino-3-(3,4-dichlorophenyl)-1-oxopropan-2-yl)-3-(4-guanidinophenyl)propanamide; (S)-3-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-5-cyclohexylpentanamide; (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-phenylbutanamide; (S)-N-((S)-3-([1,1'-biphenyl]-4-yl)-1-amino-1-oxopropan-2-yl)-2-amino-3-(4-guanidinophenyl)propanamide; (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexylbutanamide; (S)-2-amino-N-((S)-2-amino-2-oxo-1-phenylethyl)-3-(4-guanidinophenyl)propanamide; (R)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexylbutanamide; 2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexylbutanamide; (S)-2-((S)-2-amino-3-(1-carbamimidoylpiperidin-4-yl)propanamido)-4-cyclohexylbutanamide; (S)-2-amino-N-((S)-2-amino-1-cyclohexyl-2-oxoethyl)-3-(4-guanidinophenyl)propanamide; (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclopentylbutanamide; (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cycloheptylbutanamide; (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-(4,4-difluorocyclohexyl)butanamide; (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-5-cyclohexylpentanamide; (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-5-phenylpentanamide; (S,E)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-5-phenylpent-4-enamide; (S)-2-((S)-2-amino-3-(1-carbamimidoylpiperidin-4-yl)propanamido)-4-phenylbutanamide; (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-isopropylbutanamide; (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-(cyclohexylmethyl)butanamide; (S)-N-allyl-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexylbutanamide; (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-(2-morpholinoethyl)butanamide; (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-isopentylbutanamide; (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-N-(2-(cyclohex-1-en-1-yl)ethyl)-4-cyclohexylbutanamide; (2S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-((tetrahydrofuran-3-yl)methyl)butanamide; (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-cyclopentylbutanamide; (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-N,4-dicyclohexylbutanamide; (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-(2-(methylthio)ethyl)butanamide; (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-phenethylbutanamide; (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-(4-methoxybenzyl)butanamide; (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-neopentylbutanamide; (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-N-(4-(tert-butyl)benzyl)-4-cyclohexylbutanamide; (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-N-(benzo[d][1,3]dioxol-5-ylmethyl)-4-cyclohexylbutanamide; (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-(4-(trifluoromethyl)benzyl)butanamide; (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-(naphthalen-2-ylmethyl)butanamide; (2S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-((tetrahydrofuran-2-yl)methyl)butanamide; (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-ethylbutanamide; (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-(4-isopropylphenyl)butanamide; (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-hexylbutanamide; (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-(3-methylbenzyl)butanamide; (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-(4-fluorophenethyl)butanamide; (2S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-(1-phenylethyl)butanamide; (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-(4-hydroxyphenethyl)butanamide; (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-methylbutanamide; (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-isobutylbutanamide; (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-N-benzyl-4-cyclohexylbutanamide; (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-(2-methoxyethyl)butanamide; (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-N-cyclobutyl-4-cyclohexylbutanamide; (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-propylbutanamide; (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-(3-(2-oxopyrrolidin-1-yl)propyl)butanamide; (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-N-(4-chlorobenzyl)-4-cyclohexylbutanamide; (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-(3-(dimethylamino)propyl)butanamide; (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-(4-sulfamoylphenethyl)butanamide; (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-(3,4-dimethoxybenzyl)butanamide; (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-(furan-2-ylmethyl)butanamide; (S)-2-((S)-2-amino-3-(4-guanidinophenyl)propanamido)-4-cyclohexyl-N-(4-hydroxybenzyl)butanamide; (S)-2-amino-N-((S)-4-cyclohexyl-1-(4-(2-ethylbutyl)piperazin-1-yl)-1-oxobutan-2-yl)-3-(4-guanidinophenyl)propanamide; (S)-2-amino-N-((S)-4-cyclohexyl-1-oxo-1-(4-pentylpiperazin-1-yl)butan-2-yl)-3-(4-guanidinophenyl)propanamide; (S)-2-amino-N-((S)-4-cyclohexyl-1-(4-(4-methoxybenzyl)piperazin-1-yl)-1-oxobutan-2-yl)-3-(4-guanidinophenyl)propanamide; (S)-2-amino-N-((S)-1-(4-(benzo[d][1,3]dioxol-4-ylmethyl)piperazin-1-yl)-4-cyclohexyl-1-oxobutan-2-yl)-3-(4-guanidinophenyl)propanamide; (S)-2,6-diamino-N-((S)-1-amino-4-cyclohexyl-1-oxobutan-2-yl)hexanamide; and (S)-2-((S)-2-amino-3-(1H-imidazol-4-yl)propanamido)-4-cyclohexylbutanamide.

9. Chimeric compound of the following chemical formula 2: [Chemical Formula 2] In the above chemical formula 2, A is a ubiquitin ligase binding moiety (ULM), which is a compound according to any one of claims 1 to 8 or a prodrug thereof; B is a protein target moiety (PTM); A and B are chemically linked by a linker.

Images