Compounds and methods for treating protein aggregation disorders

Abstract

This specification describes, in particular, compounds and methods for treating protein aggregation disorders.

Description

[Technical Field]

[0001] (Cross-reference of related applications) This application claims the benefit of U.S. Provisional Application No. 63 / 459,198, filed April 13, 2023, and U.S. Provisional Application No. 63 / 612,107, filed December 19, 2023, which are incorporated herein by reference in their entirety for all purposes. [Background technology]

[0002] Toxic protein aggregates stimulate neuronal degeneration and are a prominent pathological feature of several neurodegenerative diseases, including Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, and frontotemporal dementia. These toxic aggregates can be present both inside and outside cells. Across each of these diseases, there are many protein species capable of generating toxic aggregates, including β-amyloid, alpha-synuclein, tau, and TDP-43. The majority of patients have two or more of these toxic protein aggregate species in their brains at the time of post-mortem examination. Patients are usually appropriately diagnosed after a large accumulation of these toxic aggregates in the brain. Current FDA-approved therapies for protein aggregates, such as recently approved anti-β-amyloid antibody therapies, fail to completely treat these protein aggregate diseases in some ways, as they have poor cell permeability and do not physically destroy existing protein aggregates. Solutions to these and other problems in the art, among others, are disclosed herein. [Overview of the project]

[0003] In one embodiment, the formula is:

[0004] [ka] A compound having, or a pharmaceutically acceptable salt thereof, is provided.

[0005] R 1 and R2 is independently hydrogen, -CCl3, -CBr3, -CF3, -CI3, -CHCl2, -CHBr2, -CHF2, -CHI2, -CH2Cl, -CH2Br, -CH2F, -CH2I, -CN, -OH, -NH2, -COOH, -CONH2, -OCCl3, -OCF3, -OCBr3, -OCI3, -OCHCl2, -OCHBr2, -OCHI2, -OCHF2, -OCH2Cl, -OCH2Br, -OCH2I, -OCH2F, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, and R bonded to the same nitrogen atom 1 and R 2 The substituents may optionally be linked to form a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heteroaryl.

[0006] R 3 is independently oxo, halogen, -CCl3, -CBr3, -CF3, -CI3, -CH2Cl, -CHBr2, -CH2F, -CH2I, -CHCl2, -CHBr2, -CHF2, -CHI2, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NH2, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl3, -OCBr3, -OCF3, -OCI3, -OCH2Cl, -OCH2Br, -OCH2F, -OCH2I, -OCHCl2, -OCHBr2, -OCHF2, -OCHI2, -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0007] R 4 is independently halogen, -CX 4 3, -CHX 4 2, -CH2X 4 , -OCX4 3. -OCH2X 4 ,-OCHX 4 2, -CN, -SO n4 R 4D , -SO v4 NR 4A R 4B , -NR 4C NR 4A R 4B ,-ONR 4A R 4B , -NR 4C C(O)NR 4A R 4B , -N(O) m4 , -NR 4A R 4B , -C(O)R 4C , -C(O)OR 4C ,-OC(O)R 4C -OC(O)OR 4C -C(O)NR 4A R 4B -OC(O)NR 4A R 4B , -OR 4D , -SR 4D , -NR 4A SO2R 4D , -NR 4A C(O)R 4C , -NR 4A C(O)OR 4C , -NR 4A Ure 4C -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, with two R 4 The substituents may optionally be linked to form substituted or unsubstituted cycloalkyl groups, substituted or unsubstituted heterocycloalkyl groups, substituted or unsubstituted aryl groups, or substituted or unsubstituted heteroaryl groups.

[0008] R 5 These are, independently, halogen, -CX 5 3, -CHX 5 2, -CH2X 5 ,-OCX 53. -OCH2X 5 ,-OCHX 5 2, -CN, -SO n5 R 5D , -SO v5 NR 5A R 5B , -NR 5C NR 5A R 5B ,-ONR 5A R 5B , -NR 5C C(O)NR 5A R 5B , -N(O) m5 , -NR 5A R 5B , -C(O)R 5C , -C(O)OR 5C ,-OC(O)R 5C -OC(O)OR 5C -C(O)NR 5A R 5B -OC(O)NR 5A R 5B , -OR 5D , -SR 5D , -NR 5A SO2R 5D , -NR 5A C(O)R 5C , -NR 5A C(O)OR 5C , -NR 5A Ure 5C These are -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0009] R 6is hydrogen, halogen, -CCl3, -CBr3, -CF3, -CI3, -CH2Cl, -CH2Br, -CH2F, -CH2I, -CHCl2, -CHBr2, -CHF2, -CHI2, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NH2, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl3, -OCBr3, -OCF3, -OCI3, -OCH2Cl, -OCH2Br, -OCH2F, -OCH2I, -OCHCl2, -OCHBr2, -OCHF2, -OCHI2, -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0010] <~ R 4A , R 4B , R 4C , R 4D , R 5A , R 5B , R 5C , and R 5D are independently hydrogen, -CCl3, -CBr3, -CF3, -CI3, -CHCl2, -CHBr2, -CHF2, -CHI2, -CH2Cl, -CH2Br, -CH2F, -CH2I, -CN, -OH, -NH2, -COOH, -CONH2, -OCCl3, -OCF3, -OCBr3, -OCI3, -OCHCl2, -OCHBr2, -OCHI2, -OCHF2, -OCH2Cl, -OCH2Br, -OCH2I, -OCH2F, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, and R 4A and R 4B substituents may optionally be linked to form substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl, and R 5A and R 5BThe substituents may optionally be linked to form substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl compounds.

[0011] each X 4 and X 5 The first two integers are independently -F, -Cl, -Br, or -I. The second two integers are independently integers between 0 and 4. The third two integers are independently 1 or 2. The fourth two integers are independently 1 or 2. The fifth

[0012] In one embodiment, a pharmaceutical composition is provided comprising a compound described herein, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

[0013] In one embodiment, a method is provided for treating a protein aggregation disorder in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound described herein or a pharmaceutically acceptable salt thereof.

[0014] In one embodiment, a method is provided for reducing or interfering with the formation of protein aggregates, comprising contacting the protein aggregates with an effective amount of a compound described herein or a pharmaceutically acceptable salt thereof. [Brief explanation of the drawing]

[0015] [Figure 1A] These are atomic force microscope images of amyloid beta peptide 42 (Aβ42) protein aggregates and the effect of compound 8 thereon, which are described in more detail in Example 1. [Figure 1B] These are atomic force microscope images of amyloid beta peptide 42 (Aβ42) protein aggregates and the effect of compound 8 thereon, which are described in more detail in Example 1. [Figure 2]The following two ion mobility mass spectrographs of TAR DNA-binding protein 43 (TDP-43), which are further described in Example 2, are shown: one is in the absence of the protein aggregation-inhibiting compound (control), and the other is in the presence of compound 6. [Figure 3] Two ion mobility mass spectrographs and two mass / charge diagrams for a TAR DNA-binding protein 43 (TDP-43) co-incubation experiment are shown. One of each spectrograph and diagram represents the absence of a protein aggregation-interfering compound (control), and the other represents the presence of compound 4. The first row shows the raw mass / charge ratio diagram. The second row (peak arrival time) shows the protein size peak. [Figure 4] Two ion mobility mass spectrographs and two mass / charge diagrams for a TAR DNA-binding protein 43 (TDP-43) co-incubation experiment are shown. One of each spectrograph and diagram represents the absence of a protein aggregation-interfering compound (control), and the other represents the presence of compound 5. The first row shows the raw mass / charge ratio diagram. The second row (peak arrival time) shows the protein size peak. [Figure 5] Two ion mobility mass spectrographs and two mass / charge diagrams for a TAR DNA-binding protein 43 (TDP-43) co-incubation experiment are shown. One of each spectrograph and diagram represents the absence of a protein aggregation-interfering compound (control), and the other represents the presence of compound 6. The first row shows the raw mass / charge ratio diagram. The second row (peak arrival time) shows the protein size peak. [Figure 6]Two ion mobility mass spectrographs and two mass / charge diagrams for a TAR DNA-binding protein 43 (TDP-43) recovery experiment are shown. One of each spectrograph and diagram represents the absence of the protein aggregation-interfering compound (control), and the other represents the presence of compound 4. The first row shows the raw mass / charge ratio diagram. The second row (peak arrival time) shows the protein size peak. [Figure 7] Two ion mobility mass spectrographs and two mass / charge diagrams for a TAR DNA-binding protein 43 (TDP-43) recovery experiment are shown. One of each spectrograph and diagram represents the absence of the protein aggregation-interfering compound (control), and the other represents the presence of compound 8. The first row shows the raw mass / charge ratio diagram. The second row (peak arrival time) shows the protein size peak. [Figure 8] The results of the Aβ42 thioflavin T assay for compound 12, which are further described in Example 5, are shown below. [Figure 9] The results of the Aβ42 thioflavin T assay for compound 13, which are further described in Example 5, are shown below. [Figure 10] The TDP-43 thioflavin T assay results for compound 12, further described in Example 6, are shown below. [Figure 11] The TDP-43 thioflavin T assay results for compound 14, further described in Example 6, are shown below. [Modes for carrying out the invention]

[0016] I. Definition The abbreviations used herein have their conventional meanings within the fields of chemistry and biology. The chemical structures and formulas described herein are constructed according to the standard rules of chemical valence known in the field of chemistry.

[0017] Substituents, when specified by their conventional chemical formulas written from left to right, equally encompass chemically identical substituents resulting from writing the structure from right to left; for example, -CH2O- is equivalent to -OCH2-.

[0018] The term "alkyl," unless otherwise specified, means a linear (i.e., unbranched) or branched carbon chain (or carbon) or combination thereof, either by itself or as part of another substituent, which may be fully saturated, monounsaturated, or polyunsaturated, and may include monovalent, divalent, and polyvalent radicals. Alkyl may contain a specified number of carbons (e.g., C1-C1). 10 (where ∫ means 1 to 10 carbon atoms). In embodiments, the alkyl is fully saturated. In embodiments, the alkyl is monounsaturated. In embodiments, the alkyl is polyunsaturated. The alkyl is a non-cyclized chain. Examples of saturated hydrocarbon radicals include, but are not limited to, groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, t-butyl, isobutyl, sec-butyl, and methyl, and homologs and isomers such as n-pentyl, n-hexyl, n-heptyl, and n-octyl. Unsaturated alkyl groups have one or more double or triple bonds. Examples of unsaturated alkyl groups include, but are not limited to, vinyl, 2-propenyl, clotyl, 2-isopentenyl, 2-(butadienyl), 2,4-pentadienyl, 3-(1,4-pentadienyl), ethynyl, 1- and 3-propynyl, 3-butynyl, and higher homologs and isomers. An alkoxy is an alkyl group that is bonded to the rest of the molecule via an oxygen linker (-O-). The alkyl group can be an alkenyl group. The alkyl group can be an alkynyl group. An alkenyl contains one or more double bonds. An alkynyl contains one or more triple bonds.

[0019] The term "alkylene," unless otherwise specified, means a divalent radical derived from an alkyl group, either by itself or as part of another substituent, and is exemplified by, but is not limited to, -CH2CH2CH2CH2-. Typically, alkyl (or alkylene) groups have 1 to 24 carbon atoms, and groups having 10 or fewer carbon atoms are preferred herein. "Lower alkyl" or "lower alkylene" is generally a short-chain alkyl or alkylene group having 8 or fewer carbon atoms. The term "alkenylene," unless otherwise specified, means a divalent radical derived from an alkene, either by itself or as part of another substituent. The term "alkynylene," unless otherwise specified, means a divalent radical derived from an alkyne, either by itself or as part of another substituent. In embodiments, alkylenes are fully saturated. In embodiments, alkylenes are monounsaturated. In embodiments, alkylenes are polyunsaturated. Alkenylenes contain one or more double bonds. Alkynylenes contain one or more triple bonds.

[0020] The term "heteroalkyl," by itself or in combination with other terms, means, unless otherwise specified, a stable linear or branched chain, or combination thereof, comprising at least one carbon atom and at least one heteroatom (e.g., O, N, P, Si, and S), wherein the nitrogen and sulfur atoms may be optionally oxidized, and the nitrogen heteroatom may be optionally quaternized. The heteroatom (e.g., N, S, Si, or P) may be located at any internal position of the heteroalkyl group or at a position where the alkyl group is bonded to the rest of the molecule. Heteroalkyl groups are acyclic chains. Examples include, but are not limited to, -CH2-CH2-O-CH3, -CH2-CH2-NH-CH3, -CH2-CH2-N(CH3)-CH3, -CH2-S-CH2-CH3, -S-CH2-CH2, -S(O)-CH3, -CH2-CH2-S(O)2-CH3, -CH=CH-O-CH3, -Si(CH3)3, -CH2-CH=N-OCH3, -CH=CH-N(CH3)-CH3, -O-CH3, -O-CH2-CH3, and -CN. For example, up to two or three heteroatoms may be consecutive, such as -CH2-NH-OCH3 and -CH2-O-Si(CH3)3. The heteroalkyl portion may contain one heteroatom (e.g., O, N, S, Si, or P). The heteroalkyl moiety may contain two optionally different heteroatoms (e.g., O, N, S, Si, or P). The heteroalkyl moiety may contain three optionally different heteroatoms (e.g., O, N, S, Si, or P). The heteroalkyl moiety may contain four optionally different heteroatoms (e.g., O, N, S, Si, or P). The heteroalkyl moiety may contain five optionally different heteroatoms (e.g., O, N, S, Si, or P). The heteroalkyl moiety may contain up to eight optionally different heteroatoms (e.g., O, N, S, Si, or P). The term "heteroalkenyl," either by itself or in combination with another term, means a heteroalkyl containing at least one double bond unless otherwise specified. A heteroalkenyl may optionally contain one or more double bonds, plus one or more double bonds and / or one or more triple bonds.The term "heteroalkynyl," either by itself or in combination with another term, means a heteroalkyl group containing at least one triple bond unless otherwise specified. A heteroalkynyl may optionally contain one or more triple bonds, plus one or more triple bonds and / or one or more double bonds. In embodiments, the heteroalkyl group is fully saturated. In embodiments, the heteroalkyl group is monounsaturated. In embodiments, the heteroalkyl group is polyunsaturated.

[0021] Similarly, the term "heteroalkylene," unless otherwise specified, means a divalent radical derived from a heteroalkyl group, either by itself or as part of another substituent, and is exemplified, but not limited to, -CH2-CH2-S-CH2-CH2- and -CH2-S-CH2-CH2-NH-CH2-. For heteroalkylene groups, the heteroatom may also occupy either or both ends of the chain (e.g., alkyleneoxy, alkylenedioxy, alkyleneamino, alkylenediamino, etc.). Furthermore, in the case of alkylene and heteroalkylene linking groups, the orientation of the linking group is not implied by the direction in which the formula of the linking group is written. For example, the formula -C(O)2R'- represents both -C(O)2R'- and -R'C(O)2-. As described above, heteroalkyl groups as used herein include groups bonded to the rest of the molecule via a heteroatom, such as -C(O)R', -C(O)NR', ​​-NR'R'', -OR', -SR', and / or -SO2R'. When specific heteroalkyl groups, such as -NR'R'', are listed after "heteroalkyl groups," it will be understood that the terms heteroalkyl and -NR'R'' are neither redundant nor mutually exclusive. Rather, specific heteroalkyl groups are listed for clarity. Therefore, the term "heteroalkyl" herein should not be interpreted as excluding specific heteroalkyl groups such as -NR'R''. The term "heteroalkene" means a divalent radical derived from a heteroalkene, either by itself or as part of another substituent, unless otherwise specified. The term "heteroalkynylene" means a divalent radical derived from a heteroalkyne, either by itself or as part of another substituent, unless otherwise specified. In embodiments, the heteroalkylene is fully saturated. In embodiments, the heteroalkylene is monounsaturated. In the embodiment, the heteroalkylene is polyunsaturated. The heteroalkynylene contains one or more double bonds. The heteroalkynylene contains one or more triple bonds.

[0022] The terms "cycloalkyl" and "heterocycloalkyl," either by themselves or in combination with other terms, mean the cyclic versions of "alkyl" and "heteroalkyl," respectively, unless otherwise specified. Cycloalkyls and heterocycloalkyls are not aromatic. In addition, in the case of heterocycloalkyls, heteroatoms may occupy positions where the heterocycle is bonded to the rest of the molecule. Examples of cycloalkyls include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 1-cyclohexenyl, 3-cyclohexenyl, and cycloheptyl. Examples of heterocycloalkyls include, but are not limited to, 1-(1,2,5,6-tetrahydropyridyl), 1-piperidinyl, 2-piperidinyl, 3-piperidinyl, 4-morpholinyl, 3-morpholinyl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydrothien-2-yl, tetrahydrothien-3-yl, 1-piperazinyl, and 2-piperazinyl. "Cycloalkylene" and "heterocycloalkylene" refer to divalent radicals derived from cycloalkyl and heterocycloalkyl, respectively, either alone or as part of another substituent. In the embodiments, the cycloalkyl is fully saturated. In the embodiments, the cycloalkyl is monounsaturated. In the embodiments, the cycloalkyl is polyunsaturated. In the embodiments, the heterocycloalkyl is fully saturated. In the embodiments, the heterocycloalkyl is monounsaturated. In the embodiments, the heterocycloalkyl is polyunsaturated.

[0023] In the embodiments, the term "cycloalkyl" means a monocyclic, bicyclic, or polycyclic cycloalkyl ring system. In the embodiments, a monocyclic ring system is a cyclic hydrocarbon group containing 3 to 8 carbon atoms, such a group may be saturated or unsaturated but not aromatic. In the embodiments, the cycloalkyl group is fully saturated. A bicyclic or polycyclic cycloalkyl ring system refers to multiple rings fused together, at least one of the fused rings being a cycloalkyl ring, and the multiple rings are bonded to the parent molecule via any carbon atoms contained within the cycloalkyl rings of the multiple rings.

[0024] In embodiments, cycloalkyl is cycloalkenyl. The term "cycloalkenyl" is used according to its plain, ordinary meaning. In embodiments, cycloalkenyl is a monocyclic, bicyclic, or polycyclic cycloalkenyl ring system. A bicyclic or polycyclic cycloalkenyl ring system refers to a plurality of rings fused together, at least one of the fused rings being a cycloalkenyl ring, and the plurality of rings are bonded to the parent molecule via any carbon atoms contained within the cycloalkenyl rings of the plurality of rings.

[0025] In the embodiments, the term “heterocycloalkyl” means a monocyclic, bicyclic, or polycyclic heterocycloalkyl ring system. In the embodiments, the heterocycloalkyl group is fully saturated. A bicyclic or polycyclic heterocycloalkyl ring system refers to a group of rings fused together, at least one of the fused rings being a heterocycloalkyl ring, and the rings are bonded to the parent molecule via any atoms contained within the heterocycloalkyl rings of the rings.

[0026] The terms "halo" or "halogen" mean a fluorine, chlorine, bromine, or iodine atom, either by itself or as part of another substituent, unless otherwise specified. Furthermore, terms such as "haloalkyl" include monohaloalkyl and polyhaloalkyl. For example, the term "halo(C1-C4)alkyl" includes, but is not limited to, fluoromethyl, difluoromethyl, trifluoromethyl, 2,2,2-trifluoroethyl, 4-chlorobutyl, and 3-bromopropyl.

[0027] The term "acyl" means -C(O)R unless otherwise specified, where R is a substituted or unsubstituted alkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl.

[0028] The term "aryl," unless otherwise specified, means a polyunsaturated, aromatic, hydrocarbon substituent, which may be a single ring, or a polycyclic (preferably 1-3 rings) that is condensed together (i.e., a fused ring aryl), or covalently bonded. A fused ring aryl refers to multiple rings that are condensed together, at least one of which is an aryl ring, and the multiple rings are bonded to the parent molecule via any carbon atoms contained within the aryl rings of the multiple rings. The term "heteroaryl" refers to an aryl group (or ring) containing at least one heteroatom such as N, O, or S, where the nitrogen and sulfur atoms are optionally oxidized, and the nitrogen atom is optionally quaternized. Thus, the term "heteroaryl" includes a fused ring heteroaryl group (i.e., multiple rings that are condensed together, at least one of which is a heteroaromatic ring, and the multiple rings are bonded to the parent molecule via any atoms contained within the heteroaromatic rings of the multiple rings). A 5,6-fused heteroarylene refers to two rings fused together, one having 5 members and the other having 6 members, with at least one ring being a heteroaryl ring. Similarly, a 6,6-fused heteroarylene refers to two rings fused together, one having 6 members and the other having 6 members, with at least one ring being a heteroaryl ring. Furthermore, a 6,5-fused heteroarylene refers to two rings fused together, one having 6 members and the other having 5 members, with at least one ring being a heteroaryl ring. Heteroaryl groups can be bonded to the rest of the molecule via carbon atoms or heteroatoms.Non-limiting examples of aryl and heteroaryl groups include phenyl, naphthyl, pyrrolyl, pyrazolyl, pyridadinyl, triazinyl, pyrimidinyl, imidazolyl, pyrazinyl, prinyl, oxazolyl, isoxazolyl, thiazolyl, furyl, thienyl, pyridyl, pyrimidyl, benzothiazolyl, benzoxazolyl, benzimidazolyl, benzofuran, isobenzofuranyl, indolyl, isoindolyl, benzothiophenyl, isoquinolyl, quinoxalinyl, quinolyl, 1-naphthyl, 2-naphthyl, 4-biphenyl, 1-pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, 3-pyrzolyl, 3-pyrazolyl, 2-imidazolyl Examples include 4-imidazolyl, pyrazinyl, 2-oxazolyl, 4-oxazolyl, 2-phenyl-4-oxazolyl, 5-oxazolyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidyl, 4-pyrimidyl, 5-benzothiazolyl, purinyl, 2-benzimidazolyl, 5-indolyl, 1-isoquinolyl, 5-isoquinolyl, 2-quinoxalinyl, 5-quinoxalinyl, 3-quinolyl, and 6-quinolyl. The substituents for each of the above aryl ring systems and heteroaryl ring systems are selected from the group of permissible substituents listed below. "Arylene" and "heteroarylene" refer to divalent radicals derived from aryl and heteroaryl groups, respectively, either individually or as part of another substituent. The heteroaryl group substituent may be -O-bonded to the ring heteroatom nitrogen.

[0029] A spirocyclic ring is two or more rings that are bonded to each other via a single atom. The individual rings within a spirocyclic ring may be identical or different. The individual rings within a spirocyclic ring may be substituted or unsubstituted and may have different substituents than the other individual rings within a set of spirocyclic rings. Possible substituents of an individual ring within a spirocyclic ring are, if not part of the spirocyclic ring, possible substituents of the same ring (e.g., substituents of a cycloalkyl ring or a heterocycloalkyl ring). A spirocyclic ring may be a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted cycloalkylene, a substituted or unsubstituted heterocycloalkyl, or a substituted or unsubstituted heterocycloalkylene, and the individual rings within the spirocyclic ring group may be any of the preceding list, including having all of one type of ring (e.g., all rings are substituted heterocycloalkylenes, and each ring may be the same or different substituted heterocycloalkylene). When referring to a spirocyclic ring system, a heterocyclic spirocyclic ring means a spirocyclic ring in which at least one ring is heterocyclic and each ring may be different. When referring to a spirocyclic ring system, a substituted spirocyclic ring means that at least one ring is substituted and each substituent may be different at will.

[0030] symbol

[0031] [ka] The symbol indicates the bonding point of a chemical part to the rest of the molecule or chemical formula.

[0032] As used herein, the term "oxo" refers to oxygen that is double-bonded to a carbon atom.

[0033] The term "alkylarylene" refers to an arylene moiety covalently bonded to an alkylene moiety (also referred to herein as an alkylene linker). In embodiments, the alkylarylene group is defined by formula:

[0034] [ka] It holds.

[0035] The alkylarylene moiety may be substituted (for example, by substituents) in the alkylene moiety or arylene linker (for example, at carbon 2, 3, 4, or 6) with a halogen, oxo, -N3, -CF3, -CCl3, -CBr3, -CI3, -CN, -CHO, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO2CH3, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NHNH2, substituted or unsubstituted C1-C5 alkyl, or substituted or unsubstituted 2-5 member heteroalkyl. In the embodiment, the alkylarylene is unsubstituted.

[0036] Each of the above terms (e.g., "alkyl," "heteroalkyl," "cycloalkyl," "heterocycloalkyl," "aryl," and "heteroaryl") includes both substituted and unsubstituted forms of the radicals shown. Preferred substituents for each type of radical are provided below.

[0037] Substituents of alkyl radicals and heteroalkyl radicals (including groups often referred to as alkylene, alkenyl, heteroalkylene, heteroalkenyl, alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, and heterocycloalkenyl) range from zero to (2m'+1) (where m' is the total number of carbon atoms in such radicals), and include -OR', =O, =NR', =N-OR', -NR'R'', -SR', halogen, -SiR'R''R''', -OC(O)R', -C(O)R', -CO2R', -CONR'R'', and -OC(O)NR'. It can be one or more of various groups selected from, but not limited to, R'', -NR''C(O)R', -NR'C(O)NR''R''', -NR''C(O)2R', -NRC(NR'R''R''')=NR'''', -NRC(NR'R'')=NR''', -S(O)R', -S(O)2R', -S(O)2NR'R'', -NRSO2R', -NR'NR''R''', -ONR'R'', -NR'C(O)NR''NR'''R'''', -CN, -NO2, -NR'SO2R'', -NR'C(O)R'', -NR'C(O)OR'', and -NR'OR''. R, R', R'', R''', and R'''' each preferably independently represent hydrogen, a substituted or unsubstituted heteroalkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted heterocycloalkyl group, a substituted or unsubstituted aryl group (e.g., an aryl group substituted with 1 to 3 halogens), a substituted or unsubstituted heteroaryl group, a substituted or unsubstituted alkyl group, an alkoxy or thioalkoxy group, or an arylalkyl group. If the compounds described herein contain more than one R group, for example, each R group can be independently selected as each R', R'', R''', and R'''' group when more than one of these groups is present. If R' and R'' are bonded to the same nitrogen atom, they can be combined with the nitrogen atom to form a 4, 5, 6, or 7-membered ring. For example, -NR'R'' includes, but is not limited to, 1-pyrrolidinyl and 4-morpholinyl.From the above considerations regarding substituents, those skilled in the art will understand that the term "alkyl" includes groups containing carbon atoms bonded to groups other than hydrogen groups, such as haloalkyls (e.g., -CF3 and -CH2CF3) and acyls (e.g., -C(O)CH3, -C(O)CF3, -C(O)CH2OCH3, etc.).

[0038] Similar to the substituents described for alkyl radicals, substituents for aryl and heteroaryl groups vary, for example, in numbers ranging from 0 to the total number of open valencies on the aromatic ring system, such as -OR', -NR'R'', -SR', halogen, -SiR'R''R''', -OC(O)R', -C(O)R', -CO2R', -CONR'R'', -OC(O)NR'R'', -NR''C(O)R', -NR'C(O)NR''R''', -NR''C(O)2R', -NR-C(NR'R''R''')=NR'''', -NR-C(NR'R'')=NR''', -S(O)R', -S(O)2R', -S(O)2NR'R'', -NRSO2R', -NR'NR The R groups are selected from ''R''', -ONR'R'', -NR'C(O)NR''NR'''R'''', -CN, -NO2, -R', -N3, -CH(Ph)2, fluoro(C1~C4)alkoxy, and fluoro(C1~C4)alkyl, -NR'SO2R'', -NR'C(O)R'', -NR'C(O)OR'', and -NR'OR'', where R', R'', R''', and R'''' are preferably independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl. If the compounds described herein contain more than one R group, for example, each of the R groups is independently selected as each R', R'', R''', and R'''' group when more than one of these groups is present.

[0039] Substituents on a ring (e.g., cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkylene, heterocycloalkylene, arylene, or heteroarylene) may be shown as substituents on the ring (commonly referred to as floating substituents) rather than on specific atoms of the ring. In such cases, the substituent may be bonded to any of the ring atoms (according to the rules of chemical valency), and a substituent shown as bonded to one member of a fused or spirocyclic ring (a floating substituent on a monocyclic ring) may be a substituent on either the fused or spirocyclic ring (a floating substituent on a polycyclic ring). If the substituent is bonded to a ring rather than a specific atom (a floating substituent), and the subscript of the substituent is an integer greater than 1, multiple substituents may be on the same atom, the same ring, different atoms, different fused rings, or different spirocyclic rings, and each substituent may be of any choice different. If the bond site of a ring to the rest of the molecule is not limited to a single atom (a floating substituent), the bond site may be any atom of the ring, and in the case of a fused or spirocyclic ring, it may be any atom of either the fused or spirocyclic ring, according to the rules of valence. If a ring, fused or spirocyclic ring contains one or more ring heteroatoms, and the ring, fused or spirocyclic ring is shown together with another floating substituent (including, but not limited to, a bond site to the rest of the molecule), the floating substituent may be bonded to the heteroatom. If a ring heteroatom is shown to be bonded to one or more hydrogens in a structure or formula having a floating substituent (for example, a ring nitrogen having two bonds to a ring atom and a third bond to a hydrogen), when the heteroatom is bonded to the floating substituent, the substituent will be understood to replace the hydrogen according to the rules of valence.

[0040] Two or more substituents may optionally link together to form an aryl, heteroaryl, cycloalkyl, or heterocycloalkyl group. Such so-called ring-forming substituents are typically, though not always, found bonded to a cyclic base structure. In one embodiment, the ring-forming substituent is bonded to an adjacent member of the base structure. For example, two ring-forming substituents bonded to adjacent members of a cyclic base structure form a fused ring structure. In another embodiment, the ring-forming substituent is bonded to a single member of the base structure. For example, two ring-forming substituents bonded to a single member of a cyclic base structure form a spirocyclic structure. In yet another embodiment, the ring-forming substituent is bonded to a non-adjacent member of the base structure.

[0041] Two of the substituents on adjacent atoms of the aryl or heteroaryl ring are optionally of the formula -TC(O)-(CRR') q A ring of -U- may be formed, where T and U are independently -NR-, -O-, -CRR'-, or a single bond, and q is an integer from 0 to 3. Alternatively, two of the substituents on adjacent atoms of the aryl ring or heteroaryl ring may be of the formula -A-(CH2) r -B- (wherein A and B are independently -CRR'-, -O-, -NR-, -S-, -S(O)-, -S(O)2-, -S(O)2NR'-, or a single bond, and r is an integer from 1 to 4) substituents may be of any choice. One of the single bonds of the new ring thus formed may be of any choice replaced with a double bond. Alternatively, two of the substituents on adjacent atoms of the aryl ring or heteroaryl ring may be of any choice the substituent of formula -(CRR') s -X'-(C''R''R''') dSubstituents R, R', R'', and R'''' are preferably selected independently from hydrogen, substituted or unsubstituted alkyl groups, substituted or unsubstituted heteroalkyl groups, substituted or unsubstituted cycloalkyl groups, substituted or unsubstituted heterocycloalkyl groups, substituted or unsubstituted aryl groups, and substituted or unsubstituted heteroaryl groups.

[0042] As used herein, the terms “heteroatom” or “ring heteroatom” mean including oxygen (O), nitrogen (N), sulfur (S), phosphorus (P), and silicon (Si).

[0043] As used herein, “substituent” means a group selected from the following parts. (A) Oxo, halogen, -CCl3, -CBr3, -CF3, -CI3, -CHCl2, -CHBr2, -CHF2, -CHI2, -CH2Cl, -CH2Br, -CH2F, -CH2I, -OCCl3, -OCF3, -OCBr3, -OCI3, -OCHCl2, -OCHBr2, -OCHI2, -OCH F2, -OCH2Cl, -OCH2Br, -OCH2I, -OCH2F, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NHNH2, -NHC(O)NH2, -NHC(NH)NH2, - NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -N3, -SF5, unsubstituted alkyl (e.g., C1-C8 alkyl, C1-C6 alkyl, or C1-C4 alkyl), unsubstituted heteroalkyl (e.g., 2-8 membered heteroalkyl, 2-6 membered heteroalkyl, or 2-4 membered heteroalkyl), unsubstituted cycloalkyl (e.g., C3-C8 cycloalkyl, C3-C6 cycloalkyl, or C5-C6 cycloalkyl), unsubstituted heterocycloalkyl (e.g., 3-8 membered heterocycloalkyl, 3-6 membered heterocycloalkyl, or 5-6 membered heterocycloalkyl), unsubstituted aryl (e.g., C6-C10 Ariel, C 10 Aryl (or phenyl), or unsubstituted heteroaryl (e.g., 5-10 membered heteroaryl, 5-9 membered heteroaryl, or 5-6 membered heteroaryl), and (B) Alkyl (e.g., C1-C8 alkyl, C1-C6 alkyl, or C1-C4 alkyl), heteroalkyl (e.g., 2-8 membered heteroalkyl, 2-6 membered heteroalkyl, or 2-4 membered heteroalkyl), cycloalkyl (e.g., C3-C8 cycloalkyl, C3-C6 cycloalkyl, or C5-C6 cycloalkyl), heterocycloalkyl (e.g., 3-8 membered heterocycloalkyl, 3-6 membered heterocycloalkyl, or 5-6 membered heterocycloalkyl), aryl (e.g., C6-C 10 Ariel, C 10 Alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl (e.g., aryl or phenyl), heteroaryl (e.g., 5-10 membered heteroaryl, 5-9 membered heteroaryl, or 5-6 membered heteroaryl) substituted with at least one substituent selected from the following: (i) Oxo, halogen, -CCl3, -CBr3, -CF3, -CI3, -CHCl2, -CHBr2, -CHF2, -CHI2, -CH2Cl, -CH2Br, -CH2F, -CH2I, -OCCl3, -OCF3, -OCBr3, -OCI3, -OCHCl2, -OCHBr2, -OCHI2, -OCH F2, -OCH2Cl, -OCH2Br, -OCH2I, -OCH2F, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NHNH2, -NHC(O)NH2, -NHC(NH)NH2, - NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -N3, -SF5, unsubstituted alkyl (e.g., C1-C8 alkyl, C1-C6 alkyl, or C1-C4 alkyl), unsubstituted heteroalkyl (e.g., 2-8 membered heteroalkyl, 2-6 membered heteroalkyl, or 2-4 membered heteroalkyl), unsubstituted cycloalkyl (e.g., C3-C8 cycloalkyl, C3-C6 cycloalkyl, or C5-C6 cycloalkyl), unsubstituted heterocycloalkyl (e.g., 3-8 membered heterocycloalkyl, 3-6 membered heterocycloalkyl, or 5-6 membered heterocycloalkyl), unsubstituted aryl (e.g., C6-C 10 Ariel, C 10 Aryl (or phenyl), or unsubstituted heteroaryl (e.g., 5-10 membered heteroaryl, 5-9 membered heteroaryl, or 5-6 membered heteroaryl), and (ii) alkyl (e.g., C1-C8 alkyl, C1-C6 alkyl, or C1-C4 alkyl), heteroalkyl (e.g., 2-8 membered heteroalkyl, 2-6 membered heteroalkyl, or 2-4 membered heteroalkyl), cycloalkyl (e.g., C3-C8 cycloalkyl, C3-C6 cycloalkyl, or C5-C6 cycloalkyl), heterocycloalkyl (e.g., 3-8 membered heterocycloalkyl, 3-6 membered heterocycloalkyl, or 5-6 membered heterocycloalkyl), aryl (e.g., C6-C 10 Ariel, C 10Alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl (e.g., aryl or phenyl), heteroaryl (e.g., 5-10 membered heteroaryl, 5-9 membered heteroaryl, or 5-6 membered heteroaryl) substituted with at least one substituent selected from the following: (a) Oxo, halogen, -CCl3, -CBr3, -CF3, -CI3, -CHCl2, -CHBr2, -CHF2, -CHI2, -CH2Cl, -CH2Br, -CH2F, -CH2I, -OCCl3, -OCF3, -OCBr3, -OCI3, -OCHCl2, -OCHBr2, -OCHI2, -OCH F2, -OCH2Cl, -OCH2Br, -OCH2I, -OCH2F, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NHNH2, -NHC(O)NH2, -NHC(NH)NH2, - NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -N3, -SF5, unsubstituted alkyl (e.g., C1-C8 alkyl, C1-C6 alkyl, or C1-C4 alkyl), unsubstituted heteroalkyl (e.g., 2-8 membered heteroalkyl, 2-6 membered heteroalkyl, or 2-4 membered heteroalkyl), unsubstituted cycloalkyl (e.g., C3-C8 cycloalkyl, C3-C6 cycloalkyl, or C5-C6 cycloalkyl), unsubstituted heterocycloalkyl (e.g., 3-8 membered heterocycloalkyl, 3-6 membered heterocycloalkyl, or 5-6 membered heterocycloalkyl), unsubstituted aryl (e.g., C6-C 10 Ariel, C 10 Aryl (or phenyl), or unsubstituted heteroaryl (e.g., 5-10 membered heteroaryl, 5-9 membered heteroaryl, or 5-6 membered heteroaryl), and (b) alkyl (e.g., C1-C8 alkyl, C1-C6 alkyl, or C1-C4 alkyl), heteroalkyl (e.g., 2-8 membered heteroalkyl, 2-6 membered heteroalkyl, or 2-4 membered heteroalkyl), cycloalkyl (e.g., C3-C8 cycloalkyl, C3-C6 cycloalkyl, or C5-C6 cycloalkyl), heterocycloalkyl (e.g., 3-8 membered heterocycloalkyl, 3-6 membered heterocycloalkyl, or 5-6 membered heterocycloalkyl), aryl (e.g., C6-C 10 Ariel, C 10 aryl, heteroaryl (e.g., 5-10 membered heteroaryl, 5-9 membered heteroaryl, or 5-6 membered heteroaryl) substituted with at least one substituent selected from the following: alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl:oxo, halogen, -CCl3, -CBr3, -CF3, -CI3, -CHCl2, -CHBr2, -CHF2, -CHI2, -CH2Cl, -CH2Br, -CH2F, -CH2I, -OCCl3, -OCF3, -OCBr3, -OCI3, -OCHCl2, -OCHBr2, -OCHI2, -OCHF2, -OCH2Cl, -OCH2Br, -OCH2I, -OCH2F, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, - SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NHNH2, -NHC(O)NH2, -NHC(NH)NH2, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -N3, -SF5, unsubstituted alkyl (e.g., C1-C8 alkyl, C1-C6 alkyl, or C1-C4 alkyl), unsubstituted heteroalkyl (e.g., 2-8 membered heteroalkyl, 2-6 membered heteroalkyl, or 2-4 membered heteroalkyl), unsubstituted cycloalkyl (e.g., C3-C8 cycloalkyl, C3-C6 cycloalkyl, or C5-C6 cycloalkyl), unsubstituted heterocycloalkyl (e.g., 3-8 membered heterocycloalkyl, 3-6 membered heterocycloalkyl, or 5-6 membered heterocycloalkyl), unsubstituted aryl (e.g., C6-C 10 Ariel, C 10Aryl or phenyl, or unsubstituted heteroaryls (e.g., 5-10 membered heteroaryls, 5-9 membered heteroaryls, or 5-6 membered heteroaryls).

[0044] As used herein, "size-limited substituent" or "size-limited substituent group" means a group selected from all substituents described above for the substituent, and each substituted or unsubstituted alkyl is a substituted or unsubstituted C1-C 20 Each alkyl group is a substituted or unsubstituted heteroalkyl group, each substituted or unsubstituted 2-20 member heteroalkyl group, each substituted or unsubstituted cycloalkyl group is a substituted or unsubstituted C3-C8 cycloalkyl group, each substituted or unsubstituted heterocycloalkyl group is a substituted or unsubstituted 3-8 member heterocycloalkyl group, and each substituted or unsubstituted aryl group is a substituted or unsubstituted C6-C 10 Each heteroaryl is an aryl, and each substituted or unsubstituted heteroaryl is a substituted or unsubstituted 5- to 10-membered heteroaryl.

[0045] When used herein, "lower substituent" or "lower substituent group" means a group selected from all substituents described above for "substituent," where each substituted or unsubstituted alkyl is a substituted or unsubstituted C1-C8 alkyl, each substituted or unsubstituted heteroalkyl is a substituted or unsubstituted 2-8 member heteroalkyl, each substituted or unsubstituted cycloalkyl is a substituted or unsubstituted C3-C7 cycloalkyl, each substituted or unsubstituted heterocycloalkyl is a substituted or unsubstituted 3-7 member heterocycloalkyl, each substituted or unsubstituted aryl is a substituted or unsubstituted phenyl, and each substituted or unsubstituted heteroaryl is a substituted or unsubstituted 5-6 member heteroaryl.

[0046] In some embodiments, each substituent described in the compounds herein is substituted with at least one substituent. More specifically, in some embodiments, each substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, substituted heteroaryl, substituted alkylene, substituted heteroalkylene, substituted cycloalkylene, substituted heterocycloalkylene, substituted arylene, and / or substituted heteroarylene described in the compounds herein is substituted with at least one substituent. In other embodiments, at least one or all of these groups are substituted with at least one size-limiting substituent. In other embodiments, at least one or all of these groups are substituted with at least one lower substituent.

[0047] In other embodiments of the compounds described herein, each substituted or unsubstituted alkyl is a substituted or unsubstituted C1-C 20 It can be alkyl, each substituted or unsubstituted heteroalkyl is a substituted or unsubstituted 2-20 member heteroalkyl, each substituted or unsubstituted cycloalkyl is a substituted or unsubstituted C3-C8 cycloalkyl, each substituted or unsubstituted heterocycloalkyl is a substituted or unsubstituted 3-8 member heterocycloalkyl, and each substituted or unsubstituted aryl is a substituted or unsubstituted C6-C 10 The aryl and / or each substituted or unsubstituted heteroaryl is a substituted or unsubstituted 5- to 10-membered heteroaryl. In some embodiments of the compounds herein, each substituted or unsubstituted alkylene is a substituted or unsubstituted C1-C 20 Each alkylene is a substituted or unsubstituted heteroalkylene, each substituted or unsubstituted 2-20 member heteroalkylene, each substituted or unsubstituted cycloalkylene is a substituted or unsubstituted C3-C8 cycloalkylene, each substituted or unsubstituted heterocycloalkylene is a substituted or unsubstituted 3-8 member heterocycloalkylene, and each substituted or unsubstituted arylene is a substituted or unsubstituted C6-C 10 It is an arylene, and / or each substituted or unsubstituted heteroarylene is a substituted or unsubstituted 5- to 10-membered heteroarylene.

[0048] In some embodiments, each substituted or unsubstituted alkyl is a substituted or unsubstituted C1-C8 alkyl, each substituted or unsubstituted heteroalkyl is a substituted or unsubstituted 2-8 member heteroalkyl, each substituted or unsubstituted cycloalkyl is a substituted or unsubstituted C3-C7 cycloalkyl, each substituted or unsubstituted heterocycloalkyl is a substituted or unsubstituted 3-7 member heterocycloalkyl, and each substituted or unsubstituted aryl is a substituted or unsubstituted C6-C 10 Each aryl and / or each substituted or unsubstituted heteroaryl is a substituted or unsubstituted 5- to 9-membered heteroaryl. In some embodiments, each substituted or unsubstituted alkylene is a substituted or unsubstituted C1-C8 alkylene, each substituted or unsubstituted heteroalkylene is a substituted or unsubstituted 2- to 8-membered heteroalkylene, each substituted or unsubstituted cycloalkylene is a substituted or unsubstituted C3-C7 cycloalkylene, each substituted or unsubstituted heterocycloalkylene is a substituted or unsubstituted 3- to 7-membered heterocycloalkylene, and each substituted or unsubstituted arylene is a substituted or unsubstituted C6-C 10 The compound is an arylene, and / or each substituted or unsubstituted heteroarylene is a substituted or unsubstituted 5- to 9-membered heteroarylene. In some embodiments, the compound is the chemical species described in the following Examples section, figures, or tables.

[0049] In the embodiment, the substituted or unsubstituted portion (for example, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heterocycloalkylene, substituted or unsubstituted arylene, and / or substituted or unsubstituted heteroarylene) is unsubstituted (for example, unsubstituted alkyl, unsubstituted heteroalkyl, unsubstituted cycloalkyl, unsubstituted heterocycloalkyl, unsubstituted aryl, unsubstituted heteroaryl, unsubstituted alkylene, unsubstituted heteroalkylene, unsubstituted cycloalkylene, unsubstituted heterocycloalkylene, unsubstituted arylene, and / or unsubstituted heteroarylene). In this embodiment, the substituted or unsubstituted portion (for example, a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl, a substituted or unsubstituted alkylene, a substituted or unsubstituted heteroalkylene, a substituted or unsubstituted cycloalkylene, a substituted or unsubstituted heterocycloalkylene, a substituted or unsubstituted arylene, and / or a substituted or unsubstituted heteroarylene) is substituted (for example, a substituted alkyl, a substituted heteroalkyl, a substituted cycloalkyl, a substituted heterocycloalkyl, a substituted aryl, a substituted heteroaryl, a substituted alkylene, a substituted heteroalkylene, a substituted cycloalkylene, a substituted heterocycloalkylene, a substituted arylene, and / or a substituted heteroarylene).

[0050] In the embodiment, the substituted portion (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, substituted heteroaryl, substituted alkylene, substituted heteroalkylene, substituted cycloalkylene, substituted heterocycloalkylene, substituted arylene, and / or substituted heteroarylene) is substituted with at least one substituent, and if the substituted portion is substituted with multiple substituents, each substituent may be optionally different. In the embodiment, if the substituted portion is substituted with multiple substituents, each substituent is different.

[0051] In the embodiment, the substituted moiety (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, substituted heteroaryl, substituted alkylene, substituted heteroalkylene, substituted cycloalkylene, substituted heterocycloalkylene, substituted arylene, and / or substituted heteroarylene) is substituted with at least one size-limiting substituent, and if the substituted moiety is substituted with multiple size-limiting substituents, each size-limiting substituent may be of any choice different. In the embodiment, if the substituted moiety is substituted with multiple size-limiting substituents, each size-limiting substituent is different.

[0052] In the embodiment, the substituted portion (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, substituted heteroaryl, substituted alkylene, substituted heteroalkylene, substituted cycloalkylene, substituted heterocycloalkylene, substituted arylene, and / or substituted heteroarylene) is substituted with at least one lower substituent, and if the substituted portion is substituted with multiple lower substituents, each lower substituent may be of any choice different. In the embodiment, if the substituted portion is substituted with multiple lower substituents, each lower substituent is different.

[0053] In the embodiment, the substituted portion (e.g., substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, substituted heteroaryl, substituted alkylene, substituted heteroalkylene, substituted cycloalkylene, substituted heterocycloalkylene, substituted arylene, and / or substituted heteroarylene) is substituted with at least one substituent, size-limiting substituent, or lower substituent, and if the substituted portion is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may be different at will.

[0054] In the enumerated claims or descriptions of chemical formulas herein, each R substituent or L linker described as "substituted" without any reference to the identity of any chemical part constituting a "substituted" group (also referred herein as an "open substitution" or "openly substituted" R substituent or L linker for an "open" R substituent or L linker), the enumerated R substituent or L linker may, in embodiments, be substituted with one or more first substituents as defined below.

[0055] The first substituent is, for example, R 1 However, R 1.1 It may be substituted with one or more first substituents represented by R 2 However, R 2.1 It may be substituted with one or more first substituents represented by R 3 However, R 3.1 It may be substituted with one or more first substituents represented by R 4 However, R 4.1 It may be substituted with one or more first substituents represented by R 5 However, R 5.1 It may be substituted with one or more first substituents shown by, and similarly, the maximum or corresponding R 100 However, R 100.1As a further example, R 1A However, R 1A.1 It may be substituted with one or more first substituents represented by R 2A However, R 2A.1 It may be substituted with one or more first substituents represented by R 3A However, R 3A.1 It may be substituted with one or more first substituents represented by R 4A However, R 4A.1 It may be substituted with one or more first substituents represented by R 5A However, R 5A.1 It may be substituted with one or more first substituents shown by, and similarly, the maximum or corresponding R 100A However, R 100A.1 It can be substituted with one or more first substituents shown by . As a further example, L 1 However, R L1.1 It may be substituted with one or more first substituents represented by L 2 However, R L2.1 It may be substituted with one or more first substituents represented by L 3 However, R L3.1 It may be substituted with one or more first substituents represented by L 4 However, R L4.1 It may be substituted with one or more first substituents represented by L 5 However, R L5.1 It may be substituted with one or more first substituents shown by, and similarly, the maximum or corresponding L 100 However, R L100.1 It may be substituted with one or more first substituents indicated by . Thus, each numbered R group or L group described herein (alternatively, R WW or L WW (where "WW" represents the superscript number indicating the target R group or L group) are generally referred to as R in this specification. WW.1 or R LWW.1 It can be substituted with one or more first substituents called R. Then, each first substituent (e.g., R) 1.1 , R 2.1 , R 3.1 , R4.1 , R 5.1 ...R 100.1 ;R 1A.1 , R 2A.1 , R 3A.1 , R 4A.1 , R 5A.1 ...R 100A.1 R L1.1 , R L2.1 , R L3.1 , R L4.1 , R L5.1 ...R L100.1 ) has one or more second substituents (for example, each R 1.2 , R 2.2 , R 3.2 , R 4.2 , R 5.2 ...R 100.2 ;R 1A.2 , R 2A.2 , R 3A.2 , R 4A.2 , R 5A.2 ...R 100A.2 R L1.2 , R L2.2 , R L3.2 , R L4.2 , R L5.2 ...R L100.2 ) may be further substituted. Therefore, in this specification, R is used as described above. WW.1 Each first substituent that can be alternatively represented as is referred to herein as R WW.2 It may be further substituted with one or more second substituents that can be alternatively represented as follows.

[0056] Finally, each second substituent (e.g., R 1.2 , R 2.2 , R 3.2 , R 4.2 , R 5.2 ...R 100.2 ;R 1A.2 , R 2A.2 , R 3A.2 , R 4A.2 , R 5A.2 ...R 100A.2 R L1.2 , R L2.2 , R L3.2 , R L4.2 , R L5.2 ...R L100.2 ) has one or more third substituents (for example, R1.3 , R 2.3 , R 3.3 , R 4.3 , R 5.3 ...R 100.3 ;R 1A.3 , R 2A.3 , R 3A.3 , R 4A.3 , R 5A.3 ...R 100A.3 R L1.3 , R L2.3 , R L3.3 , R L4.3 , R L5.3 ...R L100.3 ) may be further substituted. Therefore, in this specification, R is used as described above. WW.2 Each second substituent that can be alternatively represented as is R in this specification. WW.3 It can be further substituted with one or more third substituents that can be alternatively represented as follows: Each of the first substituents may be of any choice different. Each of the second substituents may be of any choice different. Each of the third substituents may be of any choice different.

[0057] Therefore, when used herein, R WW represents an openly substituted substituent listed in the claims or the description of the chemical formula herein. "WW" represents the superscript number of the R group in question (e.g., 1, 2, 3, 1A, 2A, 3A, 1B, 2B, 3B). Similarly, L WW is an openly substituted linker as described in the claims or description of chemical formulas herein. Furthermore, "WW" represents the superscript number of the L group in question (1, 2, 3, 1A, 2A, 3A, 1B, 2B, 3B, etc.). As described above, in the embodiments, each R WW R may be unsubstituted, and in this specification, R WW.1 It may be independently substituted with one or more first substituents called R WW.1 R may be unsubstituted, and in this specification, R WW.2 They may be independently substituted with one or more second substituents referred to as R, each of which may be unsubstituted, and in this specification R WW.3They may be independently substituted with one or more third substituents referred to as . Similarly, each L WW The linker may be unsubstituted, and in this specification, R LWW.1 It may be independently substituted with one or more first substituents called R LWW.1 R may be unsubstituted, and in this specification, R LWW.2 They may be independently substituted with one or more second substituents referred to as R, each of which may be unsubstituted, and in this specification R LWW.3 It may be independently substituted with one or more third substituents referred to as . Each first substituent is optionally different. Each second substituent is optionally different. Each third substituent is optionally different. For example, R WW If the group is phenyl, the phenyl group is one or more R as defined below. WW.1 It is optionally replaced by the base, for example, R WW.1 R WW.2 In the case of substituted or unsubstituted alkyl groups, examples of such formed groups include one or more R groups. WW.2 This includes, but is not limited to, the R itself which has been optionally replaced by this R. WW.2 is one or more R WW.3 It is optionally replaced by R. WW R whose group is methyl WW.1 If the phenyl is substituted by, the methyl group may be further substituted, but is not limited to,

[0058] [ka] It can form a group that includes this.

[0059] R WW.1 These are independently oxo, halogen, and -CX. WW.1 3, -CHX WW.1 2, -CH2X WW.1 ,-OCX WW.1 3. -OCH2X WW.1 ,-OCHX WW.12, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NHNH2, -NHC(O)NH2, -NHC(NH)NH2, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -N3, R WW.2 Substituted or unsubstituted alkyl (e.g., C1-C8, C1-C6, C1-C4, or C1-C2), R WW.2 Substituted or unsubstituted heteroalkyls (e.g., 2-8 members, 2-6 members, 4-6 members, 2-3 members, or 4-5 members), R WW.2 Substituted or unsubstituted cycloalkyl groups (e.g., C3-C8, C3-C6, C4-C6, C5-C6), R WW.2 Substituted or unsubstituted heterocycloalkyls (e.g., 3-8 member, 3-6 member, 4-6 member, 4-5 member, or 5-6 member), R WW.2 Substitutable or unsubstituted aryls (e.g., C6~C) 12 , C6~C 10 , or phenyl), or R WW.2 The heteroaryl compounds are substituted or unsubstituted (e.g., 5-12 member, 5-10 member, 5-9 member, or 5-6 member). In the embodiment, R WW.1 These are independently oxo, halogen, and -CX. WW.1 3, -CHX WW.1 2, -CH2X WW.1 ,-OCX WW.1 3. -OCH2X WW.1 ,-OCHX WW.12, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NHNH2, -NHC(O)NH2, -NHC(NH)NH2, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -N3, unsubstituted alkyl (e.g., C1~C8, C 1-C6, C1-C4, C1-C2), unsubstituted heteroalkyl (e.g., 2-8 member, 2-6 member, 4-6 member, 2-3 member, or 4-5 member), unsubstituted cycloalkyl (e.g., C3-C8, C3-C6, C4-C6, C5-C6), unsubstituted heterocycloalkyl (e.g., 3-8 member, 3-6 member, 4-6 member, 4-5 member, or 5-6 member), unsubstituted aryl (e.g., C6-C) 12 , C6~C 10 X is a phenyl compound (or 5-12 member, 5-10 member, 5-9 member, or 5-6 member). WW.1 These are independently -F, -Cl, -Br, or -I.

[0060] R WW.2 These are independently oxo, halogen, and -CX. WW.2 3, -CHX WW.2 2, -CH2X WW.2 ,-OCX WW.2 3. -OCH2X WW.2 ,-OCHX WW.2 2, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NHNH2, -NHC(O)NH2, -NHC(NH)NH2, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -N3, R WW.3 Substituted or unsubstituted alkyl groups (e.g., C1-C8, C1-C6, C1-C4, C1-C2), R WW.3 Substituted or unsubstituted heteroalkyls (e.g., 2-8 members, 2-6 members, 4-6 members, 2-3 members, or 4-5 members), R WW.3 Substituted or unsubstituted cycloalkyl groups (e.g., C3-C8, C3-C6, C4-C6, C5-C6), R WW.3Substituted or unsubstituted heterocycloalkyls (e.g., 3-8 member, 3-6 member, 4-6 member, 4-5 member, or 5-6 member), R WW.3 Substitutable or unsubstituted aryls (e.g., C6~C) 12 , C6~C 10 , or phenyl), or R WW.3 The heteroaryl compounds are substituted or unsubstituted (e.g., 5-12 member, 5-10 member, 5-9 member, or 5-6 member). In the embodiment, R WW.2 These are independently oxo, halogen, and -CX. WW.2 3, -CHX WW.2 2, -CH2X WW.2 ,-OCX WW.2 3. -OCH2X WW.2 ,-OCHX WW.2 2, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NHNH2, -NHC(O)NH2, -NHC(NH)NH2, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -N3, unsubstituted alkyl (e.g., C1~C8, C 1-C6, C1-C4, C1-C2), unsubstituted heteroalkyl (e.g., 2-8 member, 2-6 member, 4-6 member, 2-3 member, or 4-5 member), unsubstituted cycloalkyl (e.g., C3-C8, C3-C6, C4-C6, C5-C6), unsubstituted heterocycloalkyl (e.g., 3-8 member, 3-6 member, 4-6 member, 4-5 member, or 5-6 member), unsubstituted aryl (e.g., C6-C) 12 , C6~C 10 X is a phenyl compound (or 5-12 member, 5-10 member, 5-9 member, or 5-6 member). WW.2 These are independently -F, -Cl, -Br, or -I.

[0061] R WW.3 These are independently oxo, halogen, and -CX. WW.3 3, -CHX WW.3 2, -CH2X WW.3 ,-OCX WW.3 3. -OCH2X WW.3 ,-OCHX WW.32, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NHNH2, -NHC(O)NH2, -NHC(NH)NH2, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -N3, unsubstituted alkyl (e.g., C1~C8, C 1-C6, C1-C4, C1-C2), unsubstituted heteroalkyl (e.g., 2-8 member, 2-6 member, 4-6 member, 2-3 member, or 4-5 member), unsubstituted cycloalkyl (e.g., C3-C8, C3-C6, C4-C6, C5-C6), unsubstituted heterocycloalkyl (e.g., 3-8 member, 3-6 member, 4-6 member, 4-5 member, or 5-6 member), unsubstituted aryl (e.g., C6-C) 12 , C6~C 10 X is a phenyl compound (or 5-12 member, 5-10 member, 5-9 member, or 5-6 member). WW.3 These are independently -F, -Cl, -Br, or -I.

[0062] Two different R WW When substituents are linked together to form an openly substituted ring (e.g., a substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, or substituted heteroaryl), in the embodiment, the openly substituted ring is referred to herein as R WW.1 It may be independently substituted with one or more first substituents called R WW.1 R may be unsubstituted, and in this specification, R WW.2 They may be independently substituted with one or more second substituents called R WW.2 R may be unsubstituted, and in this specification, R WW.3 It may be independently substituted with one or more third substituents called R WW.3 is unsubstituted. Each first substituent is optionally different. Each second substituent is optionally different. Each third substituent is optionally different. Two different R WW In the context where substituents are linked together to form an openly substituted ring, R WW.1 , RWW.2 , and R WW.3 The "WW" symbol in this context represents two different R WW Refers to a specified number of one of the substituents. For example, R 100A and R 100B In embodiments where the elements are optionally linked together to form an openly substituted ring, R WW.1 is R 100A.1 And R WW.2 is R 100A.2 And R WW.3 is R 100A.3 Alternatively, R 100A and R 100B In embodiments where the elements are optionally linked together to form an openly substituted ring, R WW.1 is R 100B.1 And R WW.2 is R 100B.2 And R WW.3 is R 100B.3 This is the case. WW.1 , R WW.2 , and R WW.3 This is as defined in the previous paragraph.

[0063] R LWW.1 These are independently oxo, halogen, and -CX. LWW.1 3, -CHX LWW.1 2, -CH2X LWW.1 ,-OCX LWW.1 3. -OCH2X LWW.1 ,-OCHX LWW.1 2, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NHNH2, -NHC(O)NH2, -NHC(NH)NH2, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -N3, R LWW.2 Substituted or unsubstituted alkyl (e.g., C1-C8, C1-C6, C1-C4, or C1-C2), R LWW.2 Substituted or unsubstituted heteroalkyls (e.g., 2-8 members, 2-6 members, 4-6 members, 2-3 members, or 4-5 members), R LWW.2 Substituted or unsubstituted cycloalkyl groups (e.g., C3-C8, C3-C6, C4-C6, C5-C6), RLWW.2 Substituted or unsubstituted heterocycloalkyls (e.g., 3-8 member, 3-6 member, 4-6 member, 4-5 member, or 5-6 member), R LWW.2 Substitutable or unsubstituted aryls (e.g., C6~C) 12 , C6~C 10 , or phenyl), or R LWW.2 The heteroaryl compounds are substituted or unsubstituted (e.g., 5-12 member, 5-10 member, 5-9 member, or 5-6 member). In the embodiment, R LWW.1 These are independently oxo, halogen, and -CX. LWW.1 3, -CHX LWW.1 2, -CH2X LWW.1 ,-OCX LWW.1 3. -OCH2X LWW.1 ,-OCHX LWW.1 2, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NHNH2, -NHC(O)NH2, -NHC(NH)NH2, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -N3, unsubstituted alkyl (e.g., C1~C8, C 1-C6, C1-C4, C1-C2), unsubstituted heteroalkyl (e.g., 2-8 member, 2-6 member, 4-6 member, 2-3 member, or 4-5 member), unsubstituted cycloalkyl (e.g., C3-C8, C3-C6, C4-C6, C5-C6), unsubstituted heterocycloalkyl (e.g., 3-8 member, 3-6 member, 4-6 member, 4-5 member, or 5-6 member), unsubstituted aryl (e.g., C6-C) 12 , C6~C 10 X is a phenyl compound (or 5-12 member, 5-10 member, 5-9 member, or 5-6 member). LWW.1 These are independently -F, -Cl, -Br, or -I.

[0064] R LWW.2 These are independently oxo, halogen, and -CX. LWW.2 3, -CHX LWW.2 2, -CH2X LWW.2 ,-OCX LWW.2 3. -OCH2X LWW.2 ,-OCHX LWW.22, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NHNH2, -NHC(O)NH2, -NHC(NH)NH2, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -N3, R LWW.3 Substituted or unsubstituted alkyl groups (e.g., C1-C8, C1-C6, C1-C4, C1-C2), R LWW.3 Substituted or unsubstituted heteroalkyls (e.g., 2-8 members, 2-6 members, 4-6 members, 2-3 members, or 4-5 members), R WW.3 Substituted or unsubstituted cycloalkyl groups (e.g., C3-C8, C3-C6, C4-C6, C5-C6), R LWW.3 Substituted or unsubstituted heterocycloalkyls (e.g., 3-8 member, 3-6 member, 4-6 member, 4-5 member, or 5-6 member), R LWW.3 Substitutable or unsubstituted aryls (e.g., C6~C) 12 , C6~C 10 , or phenyl), or R LWW.3 The heteroaryl compounds are substituted or unsubstituted (e.g., 5-12 member, 5-10 member, 5-9 member, or 5-6 member). In the embodiment, R LWW.2 These are independently oxo, halogen, and -CX. LWW.2 3, -CHX LWW.2 2, -CH2X LWW.2 ,-OCX LWW.2 3. -OCH2X LWW.2 ,-OCHX LWW.22, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NHNH2, -NHC(O)NH2, -NHC(NH)NH2, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -N3, unsubstituted alkyl (e.g., C1~C8, C 1-C6, C1-C4, C1-C2), unsubstituted heteroalkyl (e.g., 2-8 member, 2-6 member, 4-6 member, 2-3 member, or 4-5 member), unsubstituted cycloalkyl (e.g., C3-C8, C3-C6, C4-C6, C5-C6), unsubstituted heterocycloalkyl (e.g., 3-8 member, 3-6 member, 4-6 member, 4-5 member, or 5-6 member), unsubstituted aryl (e.g., C6-C) 12 , C6~C 10 X is a phenyl compound (or 5-12 member, 5-10 member, 5-9 member, or 5-6 member). LWW.2 These are independently -F, -Cl, -Br, or -I.

[0065] R LWW.3 These are independently oxo, halogen, and -CX. LWW.3 3, -CHX LWW.3 2, -CH2X LWW.3 ,-OCX LWW.3 3. -OCH2X LWW.3 ,-OCHX LWW.3 2, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NHNH2, -NHC(O)NH2, -NHC(NH)NH2, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -N3, unsubstituted alkyl (e.g., C1~C8, C 1-C6, C1-C4, C1-C2), unsubstituted heteroalkyl (e.g., 2-8 member, 2-6 member, 4-6 member, 2-3 member, or 4-5 member), unsubstituted cycloalkyl (e.g., C3-C8, C3-C6, C4-C6, C5-C6), unsubstituted heterocycloalkyl (e.g., 3-8 member, 3-6 member, 4-6 member, 4-5 member, or 5-6 member), unsubstituted aryl (e.g., C6-C) 12 , C6~C 10X is a phenyl compound (or 5-12 member, 5-10 member, 5-9 member, or 5-6 member). LWW.3 These are independently -F, -Cl, -Br, or -I.

[0066] Any R group (R) listed in the description of the chain or chemical formula described herein WW If the substituent is not specifically defined in this disclosure, then the R group (R WW The base is independently oxo, halogen, -CX WW 3, -CHX WW 2, -CH2X WW ,-OCX WW 3. -OCH2X WW ,-OCHX WW 2, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NHNH2, -NHC(O)NH2, -NHC(NH)NH2, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -N3, R WW.1 Substituted or unsubstituted alkyl groups (e.g., C1-C8, C1-C6, C1-C4, C1-C2), R WW.1 Substituted or unsubstituted heteroalkyls (e.g., 2-8 members, 2-6 members, 4-6 members, 2-3 members, or 4-5 members), R WW.1 Substituted or unsubstituted cycloalkyl groups (e.g., C3-C8, C3-C6, C4-C6, C5-C6), R WW.1 Substituted or unsubstituted heterocycloalkyls (e.g., 3-8 member, 3-6 member, 4-6 member, 4-5 member, or 5-6 member), R WW.1 Substitutable or unsubstituted aryls (e.g., C6~C) 12 , C6~C 10 , or phenyl), or R WW.1 As defined herein, substituted or unsubstituted heteroaryls (e.g., 5-12 member, 5-10 member, 5-9 member, or 5-6 member). WW These are independently -F, -Cl, -Br, and -I. Here again, "WW" represents the superscript number indicating the R group in question (e.g., 1, 2, 3, 1A, 2A, 3A, 1B, 2B, 3B, etc.).WW.1 , R WW.2 , and R WW.3 This is as defined above.

[0067] Any L linker group listed in the description of the chain or chemical formula described herein (i.e., L WW If the substituent is not clearly defined, then the L group (L WW groups) are independently a bond, -O-, -NH-, -C(O)-, -C(O)NH-, -NHC(O)-, -NHC(O)NH-, -NHC(NH)NH-, -C(O)O-, -OC(O)-, -S-, -SO2-, -SO2NH-, R LWW.1 Substituted or unsubstituted alkylenes (e.g., C1-C8, C1-C6, C1-C4, C1-C2), R LWW.1 Substituted or unsubstituted heteroalkylenes (e.g., 2-8 member, 2-6 member, 4-6 member, 2-3 member, or 4-5 member), R LWW.1 Substituted or unsubstituted cycloalkylenes (e.g., C3-C8, C3-C6, C4-C6, C5-C6), R LWW.1 Substituted or unsubstituted heterocycloalkylenes (e.g., 3-8 member, 3-6 member, 4-6 member, 4-5 member, or 5-6 member), R LWW.1 Substituted or unsubstituted arylenes (e.g., C6~C) 12 , C6~C 10 , or phenyl), or R LWW.1 As defined herein, substituted or unsubstituted heteroarylenes (e.g., 5-12 member, 5-10 member, 5-9 member, or 5-6 member). Furthermore, "WW" represents the superscript number indicating the L group in question (e.g., 1, 2, 3, 1A, 2A, 3A, 1B, 2B, 3B). LWW.1 , and R LWW.2 and R LWW.3 This is as defined above.

[0068] Certain compounds in this disclosure have an asymmetric carbon atom (optical or chiral center) or a double bond and, from the viewpoint of absolute stereochemistry, can be defined as (R)- or (S)- or (D)- or (L) for amino acids. Enantiomers, racemates, diastereomers, tautomers, geometric isomers, stereoisomers, and individual isomers are included within the scope of this disclosure. The compounds in this disclosure do not include compounds known in the art to be too unstable to synthesize and / or isolate. This disclosure is intended to include racemates and optically pure forms of compounds. Optically active (R)- and (S)- or (D)- and (L)- isomers may be prepared using chiral synthons or chiral reagents, or decomposed using conventional techniques. Where a compound described herein contains an olefin bond or other geometrically asymmetric center, unless otherwise specified, the compound is intended to include both E and Z geometric isomers.

[0069] As used herein, the term "isomer" refers to compounds that have the same number and types of atoms, and therefore the same molecular weight, but differ in terms of the structural or stereochemistry of their atoms.

[0070] As used herein, the term "tautomer" refers to one of two or more structural isomers that exist in equilibrium and are readily convertible from one isomeric form to another.

[0071] Certain compounds in this disclosure may exist in tautomer forms, and it will be apparent to those skilled in the art that all such tautomer forms of compounds are within the scope of the disclosure.

[0072] Unless otherwise specified, the structures shown herein also include all stereochemical forms of that structure, i.e., R and S configurations for each chiral center. Thus, single stereoisomers of the compound, as well as enantiomers and diastereomer mixtures, are within the scope of this disclosure.

[0073] Unless otherwise specified, the structures shown herein also mean that they may contain different compounds only in the presence of one or more isotopically enriched atoms. For example, substitution of hydrogen with deuterium or tritium, or 13 C or 14 Compounds having this structure, excluding those with carbon substitution by carbon-enriched carbon, are within the scope of this disclosure.

[0074] The compounds of this disclosure may also contain unnatural proportions of atomic isotopes in one or more of the atoms constituting such compounds. For example, the compounds may contain, for example, tritium ( 3 H), Iodine-125( 125 I), or carbon-14 ( 14 The compounds may be radiolabeled with radioactive isotopes such as C). All isotopic variations of the compounds of this disclosure, whether radioactive or not, are included within the scope of this disclosure.

[0075] Throughout this application, it should be noted that each amino acid position containing options, for example, more than one possible amino acid, is described in a Markush group. Each member of the Markush group should be considered separately, and it is particularly intended that the Markush group should not be read as a single unit, as it may include other embodiments.

[0076] As used herein, the terms “bioponjugate” and “bioponjugate linker” refer to the resulting association between atoms or molecules of a bioconjugate reactive group or bioconjugate reactive moiety. The association may be direct or indirect. For example, the conjugate between a first bioconjugate reactive group (e.g., -NH2, -COOH, -N-hydroxysuccinimide, or -maleimide) and a second bioconjugate reactive group (e.g., sulfhydryl, sulfur-containing amino acid, amine, amine side-chain-containing amino acid, or carboxylate) provided herein may be direct, for example, by a covalent bond or linker (e.g., the first linker of the second linker), or indirect, for example, by a non-covalent bond (e.g., electrostatic interactions (e.g., ionic bonds, hydrogen bonds, halogen bonds), van der Waals interactions (e.g., dipole-dipole, dipole-induced dipole, London dispersion), ring stacking (pi effect), hydrophobic interactions, etc.). In embodiments, bioconjugates or bioconjugate linkers are formed using bioconjugate chemistry (i.e., association of two bioconjugate reactive groups), including but not limited to nucleophilic substitution (e.g., reactions of amines and alcohols with acyl halides and active esters), electrophilic substitution (e.g., enamine reactions), and addition to multiple bonds of carbon-carbon and carbon-heteroatoms (e.g., Michael reactions, Diels-Alder additions). These and other useful reactions are discussed, for example, in March, ADVANCED ORGANIC CHEMISTRY, 3rd Ed., John Wiley & Sons, New York, 1985; Hermanson, BIOCONJUGATE TECHNIQUES, Academic Press, San Diego, 1996; and Feeney et al., MODIFICATION OF PROTEINS; Advances in Chemistry Series, Vol. 198, American Chemical Society, Washington, DC, 1982.In the embodiment, the first bioconjugate reactive group (e.g., maleimide moiety) is covalently bonded to the second bioconjugate reactive group (e.g., sulfhydryl). In the embodiment, the first bioconjugate reactive group (e.g., haloacetyl moiety) is covalently bonded to the second bioconjugate reactive group (e.g., sulfhydryl). In the embodiment, the first bioconjugate reactive group (e.g., pyridyl moiety) is covalently bonded to the second bioconjugate reactive group (e.g., sulfhydryl). In the embodiment, the first bioconjugate reactive group (e.g., -N-hydroxysuccinimide moiety) is covalently bonded to the second bioconjugate reactive group (e.g., amine). In the embodiment, the first bioconjugate reactive group (e.g., maleimide moiety) is covalently bonded to the second bioconjugate reactive group (e.g., sulfhydryl). In this embodiment, the first bioconjugate reactive group (e.g., a sulfo-N-hydroxysuccinimide moiety) is covalently bonded to the second bioconjugate reactive group (e.g., an amine).

[0077] Useful bioconjugate reactive groups used in the bioconjugate chemistry described herein include, for example, (a) carboxyl groups and various derivatives thereof, including but not limited to N-hydroxysuccinimide esters, N-hydroxybenzotriazole esters, acid halides, acylimidazoles, thioesters, p-nitrophenyl esters, alkyls, alkenyls, alkynyls, and aromatic esters; (b) hydroxyl groups that can be converted to esters, ethers, aldehydes, etc.; (c) haloalkyl groups in which halides can later be replaced by nucleophiles such as amines, carboxylic acid anions, thiol anions, carbanions, or alkoxide ions, thereby creating a covalent bond of a new group at the halogen atom site; (d) dienophile groups that can participate in the Diels-Alder reaction, such as maleimide or maleimide groups; and (e) subsequent derivation via the formation of carbonyl derivatives such as imines, hydrazones, semicarbazones, or oximes, or via mechanisms such as Grignard addition or alkyllithium addition. (f) Aldehydes or ketone groups that can be embolized, (g) Sulfonyl halogenated groups for subsequent reactions with amines to form sulfonamides, (h) Thiol groups that can be converted to disulfides, react with acyl halogenated groups, bond to metals such as gold, or react with maleimides, (i) Amines or sulfhydryl groups (e.g., those present in cysteine) that can be acylated, alkylated, or oxidized, (j) Alkenes that can undergo cycloaddition, acylation, Michael addition, etc., (g) Amines and Examples include epoxides that can react with hydroxyl compounds, (k) phosphoramidites and other standard functional groups useful for nucleic acid synthesis, (l) metal silicon oxide bonds, (m) metallic bonds to reactive phosphorus groups (e.g., phosphine) for forming, for example, phosphate diester bonds, (n) azides coupled to alkynes using copper-catalyzed cycloaddition click chemistry, and (o) biotin conjugates that can react with avidin or streptavidin to form avidin-biotin complexes or streptavidin-biotin complexes.

[0078] The reactive groups in the bioconjugate can be selected so as not to be involved in or interfere with the chemical stability of the conjugate described herein. Alternatively, the reactive functional groups can be protected from participation in the crosslinking reaction by the presence of a protecting group. In embodiments, the bioconjugate includes molecular entities obtained from the reaction of an unsaturated bond, such as maleimide, with a sulfhydryl group.

[0079] The terms "analog," "analogue," or "derivative" are used according to their plain, ordinary meanings in chemistry and biology to refer to compounds that are structurally similar to another compound (i.e., a so-called "reference" compound), but differ in composition, for example, by the substitution of one atom with an atom of a different element, or in the presence of a particular functional group, or by the substitution of one functional group with another functional group, or by the absolute stereochemistry of one or more chiral centers of the reference compound.

[0080] As used herein, the terms "a" or "an" mean one or more. In addition, as used herein, the phrase "substituted with a[n]" means that a given group may be substituted with one or more of any or all of the designated substituents. For example, a group such as an alkyl group or heteroaryl group may be "unsubstituted C1-C 20 If the group is "substituted with an alkyl or an unsubstituted 2-20 member heteroalkyl group", the group is one or more unsubstituted C1-C 20 It may contain alkyl and / or one or more unsubstituted 2-20 member heteroalkyl groups.

[0081] Furthermore, if a portion is substituted with an R substituent, that group may be referred to as "R-substituted." When a portion is R-substituted, that portion is substituted with at least one R substituent, and each R substituent is optionally distinct. When a particular R group is present in the description of a chemical species (e.g., formula (I)), Roman alphabet symbols may be used to distinguish each appearance of that particular R group. For example, multiple R 13 If substituents are present, each R 13 The substituent is R 13.A , R13.B , R 13.C , R 13.D It can be distinguished from, R 13.A , R 13.B , R 13.C , R 13.D Each of these is R 13 Within the scope of the definition, it may be defined differently at the discretion of the party. Where the R moiety, group, or substituent disclosed herein is bonded via a single bond, and the R moiety, group, or substituent is an oxo, a person skilled in the art will immediately recognize that the oxo is bonded via a double bond according to the usual rules of chemical valency.

[0082] The description of compounds in this disclosure is limited by the principles of chemical bonding known to those skilled in the art. Therefore, where a group can be substituted by one or more substituents, such substituents are selected such that they conform to the principles of chemical bonding and result in a compound that is not inherently unstable and / or likely to be unstable under ambient conditions such as aqueous, neutral, and certain known physiological conditions, as is known to those skilled in the art. For example, heterocycloalkyl or heteroaryl groups, conforming to the principles of chemical bonding known to those skilled in the art, bond to the rest of the molecule via a ring heteroatom, thereby avoiding an inherently unstable compound.

[0083] The term "pharmaceutically acceptable salt" means that, depending on the specific substituents found in the compounds described herein, salts of the active compound prepared using relatively non-toxic acids or bases may be obtained. If the compounds of this disclosure contain relatively acidic functional groups, base addition salts can be obtained by contacting such a compound in its neutral form with a sufficient amount of the desired base, either in its original form or in a suitable inert solvent. Examples of pharmaceutically acceptable base addition salts include sodium, potassium, calcium, ammonium, organic amino, or magnesium salts, or similar salts. If the compounds of this disclosure contain relatively basic functional groups, acid addition salts can be obtained by contacting such a compound in its neutral form with a sufficient amount of the desired acid, either in its original form or in a suitable inert solvent. Examples of pharmaceutically acceptable acid addition salts include salts derived from inorganic acids such as hydrochloric acid, hydrobromic acid, nitric acid, carbonic acid, monocarbonate, phosphoric acid, monohydrogen-phosphoric acid, dihydrogen-phosphoric acid, sulfuric acid, monohydrogen-sulfuric acid, hydroiodic acid, or phosphorous acid, as well as salts derived from relatively non-toxic organic acids such as acetic acid, propionic acid, isobutyric acid, maleic acid, malonic acid, benzoic acid, succinic acid, suberic acid, fumaric acid, lactic acid, mandelic acid, phthalic acid, benzenesulfonic acid, p-tolylsulfonic acid, citric acid, tartaric acid, oxalic acid, and methanesulfonic acid. Salts of amino acids such as arginates and salts of organic acids such as glucuronic acid or galactunoric acid are also included (see, for example, Berge et al., "Pharmaceutical Salts", Journal of Pharmaceutical Science, 1977, 66, 1-19). Certain compounds in this disclosure include both basic and acidic functional groups that enable the compound to be converted into either a base addition salt or an acid addition salt.

[0084] Therefore, the compounds of this disclosure may exist as salts with pharmaceutically acceptable acids, etc. This disclosure includes such salts. Non-limiting examples of such salts include hydrochlorides, hydrobroms, phosphates, sulfates, methanesulfons, nitrates, maleates, acetates, citrates, fumarates, propions, tartrates (e.g., (+)-tartrate, (-)-tartrate, or mixtures thereof including racemic mixtures), succinates, benzoates, and salts having amino acids, such as glutamic acid, and quaternary ammonium salts (e.g., methyl iodide, ethyl iodide, etc.). These salts can be prepared by methods known to those skilled in the art.

[0085] The neutral form of the compound is preferably regenerated by contacting the salt with a base or acid to isolate the parent compound in the conventional manner. The parent form of the compound may differ from the various salt forms in terms of certain physical properties, such as solubility in polar solvents.

[0086] In addition to salt forms, this disclosure provides compounds in prodrug forms. Prodrugs of the compounds described herein are compounds that readily undergo chemical transformation under physiological conditions to yield the compounds of this disclosure. Prodrugs of the compounds described herein can be converted in vivo after administration. Furthermore, prodrugs can be converted to the compounds of the present invention by chemical or biochemical methods in an ex vivo environment, for example, by contact with a suitable enzyme or chemical reagent.

[0087] Certain compounds in this disclosure may exist in solvated forms, including non-solvated and hydrated forms. Generally, the solvated forms are equivalent to the non-solvated forms and are included within the scope of this disclosure. Certain compounds in this disclosure may exist in polycrystalline or amorphous forms. Generally, all physical forms are equivalent for the uses envisioned by this disclosure and are intended to be within the scope of this disclosure.

[0088] A polypeptide or cell is "recombinant" if it is artificial or engineered, or if it is derived from or contains an artificial or engineered protein or nucleic acid (e.g., non-natural or non-wild type). For example, a polynucleotide that is inserted, for example, into a vector or any other heterologous position in the genome of a recombinant organism in such a way that it does not associate with nucleotide sequences normally adjacent to the polynucleotide as found in nature is a recombinant polynucleotide. A protein expressed in vitro or in vivo from a recombinant polynucleotide is an example of a recombinant polypeptide. Similarly, a polynucleotide sequence not found in nature, for example, a variant of a naturally occurring gene, is recombinant.

[0089] "Concurrent administration" means that the compositions described herein are administered simultaneously with, immediately before, or immediately after the administration of one or more additional therapeutic agents. The compounds disclosed herein may be administered to a patient alone or in combination. Concurrent administration means that the compounds (two or more compounds) may be administered simultaneously or sequentially, individually or in combination. For this reason, the preparations may also be combined with other active substances if desired (for example, to reduce metabolic degradation).

[0090] As used herein, “cell” means a cell that performs metabolic or other functions sufficient to store or replicate its genomic DNA. Cells can be identified by methods well known in the art, including, for example, the presence of an intact membrane, staining with a particular dye, the ability to produce offspring, or, in the case of gametes, the ability to produce viable offspring in combination with a second gamete. Cells may include prokaryotic cells and eukaryotic cells. Prokaryotic cells include, but are not limited to, bacteria. Eukaryotic cells include, but are not limited to, yeast cells and cells derived from plants and animals, such as mammalian cells, insect cells (e.g., Spodoptera), and human cells. Cells may be useful if they are naturally non-adherent or have been treated, for example, by trypsin treatment to prevent adhesion to a surface.

[0091] The terms “to treat” or “treatment” refer to any success in treatment or any sign of improvement of injury, disease, condition, or pathology, including any objective or subjective parameters such as reduction, remission, decrease in symptoms, or making the injury, condition, or pathology more tolerable to the patient, slowing the rate of degeneration or decline, reducing the debilitation at the end of degeneration, or improving the patient’s physical or mental health. Treatment or improvement of symptoms may be based on objective or subjective parameters, including the results of a physical examination, neuropsychiatric examination, and / or psychiatric evaluation. The terms “to treat” and their usage include the prevention of injury, condition, pathology, or disease. In embodiments, treating is prevention. In embodiments, treating does not include prevention. In embodiments, treating or treatment is not preventive treatment.

[0092] An “effective dose” is the amount of a compound sufficient to achieve a given purpose (e.g., to achieve an effect on the administered substance, to treat a disease, to reduce enzyme activity, to increase enzyme activity, to reduce a signaling pathway, or to reduce one or more symptoms of a disease or condition) compared to the absence of the compound. An example of an “effective dose” is an amount sufficient to contribute to the treatment, prevention, or reduction of one or more symptoms of a disease, which may also be referred to as a “therapeutic effective dose” in this context. “Reduction” (and its grammatical equivalent) of one or more symptoms means a reduction in the severity or frequency of symptoms, or the elimination of symptoms. The “preventive effective dose” of a drug is the amount of drug administered to a subject that, when administered, has the intended preventive effect, e.g., the amount of drug that prevents or delays the onset (or recurrence) of injury, disease, condition, or pathology, or reduces the likelihood of the onset (or recurrence) of injury, disease, condition, or pathology, or symptoms thereof. Complete preventive effect is not necessarily achieved by a single dose and may only occur after a series of doses. Therefore, a prophylactic effective dose may be administered in one or more doses. As used herein, “activity-reducing dose” refers to the amount of antagonist required to reduce the activity of an enzyme compared to the absence of the antagonist. As used herein, “function-inhibiting dose” refers to the amount of antagonist required to interfere with the function of an enzyme or protein compared to the absence of the antagonist. As used herein, “activity-increasing dose” refers to the amount of agonist required to increase the activity of an enzyme compared to the absence of the agonist. As used herein, “function-increasing dose” refers to the amount of agonist required to increase the function of an enzyme or protein compared to the absence of the agonist.The exact amount depends on the therapeutic purpose and can be determined by those skilled in the art using known techniques (see, for example, Lieberman, Pharmaceutical Dosage Forms (vols. 1-3, 1992), Lloyd, The Art, Science and Technology of Pharmaceutical Compounding (1999), Pickar, Dosage Calculations (1999), and Remington: The Science and Practice of Pharmacy, 20th Edition, 2003, Gennaro, Ed., Lippincott, Williams & Wilkins).

[0093] The terms "control" or "control experiment" are used in their plain, ordinary sense to refer to an experiment in which the subject or reagents of the experiment are treated similarly to a parallel experiment, except for the omission of experimental procedures, reagents, or variables. In some cases, a control is used as a criterion for comparison when evaluating the effect of an experiment. In some embodiments, the control is a measurement of protein activity (e.g., a signaling pathway) in the absence of a compound described herein (including embodiments, examples, figures, or tables).

[0094] "Contact" is used in its simple, ordinary sense and refers to a process that allows at least two distinct species (e.g., chemical compounds including biomolecules or cells) to become sufficiently proximal to react, interact, or physically touch. However, it should be understood that the resulting reaction products may be produced directly from the reaction between the added reagents, or from intermediates from one or more of the added reagents, or from the reaction mixture.

[0095] The term “contact” may also include enabling two species to react, interact, or come into physical contact, wherein the two species are the compounds described herein and cellular components (e.g., proteins, ions, lipids, nucleic acids, nucleotides, amino acids, proteins, particles, organelles, intracellular compartments, microorganisms, viruses, lipid droplets, vesicles, small molecules, protein complexes, protein aggregates, or macromolecules). In some embodiments, contact includes enabling the compounds described herein to interact with cellular components involved in signaling pathways (e.g., proteins, ions, lipids, nucleic acids, nucleotides, amino acids, proteins, particles, viruses, lipid droplets, organelles, intracellular compartments, microorganisms, vesicles, small molecules, protein complexes, protein aggregates, or macromolecules).

[0096] As defined herein, terms such as “activation,” “to activate,” and “to activate” in relation to proteins refer to the conversion of a protein from its initial inactive or inactivated state to a biologically active derivative. These terms refer to the activation, activation, sensitization, or upregulation of signal transduction, enzymatic activity, or the amount of a protein reduced in a particular disease.

[0097] Terms such as "agonist," "activator," and "upregulator" refer to substances capable of detecting an increase in the expression or activity of a given gene or protein. Agonists can increase expression or activity by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% compared to a control in the absence of the agonist. In certain cases, the expression or activity may be 1.5 times, 2 times, 3 times, 4 times, 5 times, 10 times, or more higher than the expression or activity in the absence of the agonist.

[0098] As defined herein, with respect to cellular component-inhibitor interactions, terms such as “inhibit,” “inhibit,” and “to inhibit” mean to adversely affect (e.g., reduce) the activity or function of a cellular component compared to the activity or function of the cellular component in the absence of the inhibitor (e.g., reduce signaling pathways stimulated by the cellular component (e.g., proteins, ions, lipids, viruses, lipid droplets, nucleic acids, nucleotides, amino acids, proteins, particles, organelles, intracellular compartments, microorganisms, vesicles, small molecules, protein complexes, protein aggregates, or macromolecules)). In embodiments, inhibition means to adversely affect (e.g., reduce) the concentration or level of a cellular component compared to the concentration or level of the cellular component in the absence of the inhibitor. In some embodiments, inhibition refers to the alleviation of a disease or disease symptoms. In some embodiments, inhibition refers to a decrease in the activity of a signal transduction pathway or signaling pathway (e.g., a reduction in pathways involving cellular components). Therefore, inhibition includes, at least partially, partially or completely blocking a stimulus, reducing, preventing, or delaying activation, or inactivating a signaling pathway, desensitizing enzyme-active cells, or downregulating the amount of a component.

[0099] The terms “inhibitor,” “suppressor,” “antagonist,” or “downregulator” are interchangeable and refer to substances capable of detecting a reduction in the expression or activity of a given gene or protein. An antagonist can reduce expression or activity by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, or 99% compared to a control in the absence of the antagonist. In certain cases, the expression or activity may be 1.5, 1 / 2, 1 / 3, 1 / 4, 1 / 5, 1 / 10, or less, compared to the expression or activity in the absence of the antagonist.

[0100] The term "regulatory factor" refers to a composition that increases or decreases the level of a target molecule, the function of a target molecule, or the physical state of a molecular target compared to when the composition is absent (for example, the target may be a cellular component (e.g., protein, ion, lipid, virus, lipid droplet, nucleic acid, nucleotide, amino acid, protein, particle, organelle, cell compartment, microorganism, vesicle, small molecule, protein complex, protein aggregate, or macromolecule)).

[0101] The term "expression" includes, but is not limited to, any stage involved in polypeptide production, including transcription, post-transcriptional modification, translation, post-translational modification, and secretion. Expression can be detected using conventional techniques for detecting proteins (e.g., ELISA, Western blotting, flow cytometry, immunofluorescence, immunohistochemistry, etc.).

[0102] The term "modulate" is used according to its simple, ordinary meaning and refers to the action of changing or altering one or more properties. "Modification" refers to the process of changing or altering one or more properties. For example, as applied to the effect of a modulator on a target protein, modulating means changing the properties or function of a target molecule, or the amount of a target molecule, by increasing or decreasing it.

[0103] "Patient," "patient in need," "subject," or "subject in need" refers to an organism that is suffering from or susceptible to a disease or condition that can be treated by administration of a pharmaceutical composition as provided herein. Non-limiting examples include humans, other mammals, Bovidae, rats, mice, dogs, monkeys, goats, sheep, cattle, deer, and other non-mammals. In embodiments, the patient is human. In embodiments, the patient in need is human. In embodiments, the subject is human. In embodiments, the subject in need is human.

[0104] "Disease" or "pathological condition" refers to a physical or health condition of a patient or subject that can be treated with the compounds or methods provided herein. In some embodiments, the disease is a disease relating to (e.g., resulting from) cellular components (e.g., proteins, ions, lipids, nucleic acids, nucleotides, amino acids, proteins, particles, organelles, intracellular compartments, microorganisms, vesicles, small molecules, protein complexes, protein aggregates, or macromolecules). In embodiments, the disease is a protein aggregation disorder. In embodiments, the disease is a neurodegenerative disease. In embodiments, the disease is diabetes mellitus. In embodiments, the disease is a p53 mutation cancer.

[0105] As used herein, the term “protein aggregation disorder” refers to a disease or condition characterized by protein aggregation. In embodiments, protein aggregation disorder includes non-neurological diseases such as primary systemic amyloidosis (AL amyloidosis), reactive systemic amyloidosis (AA amyloidosis), type II diabetes mellitus, injection-limited amyloidosis, beta-2 microglobulin amyloidosis, hereditary non-neuropathic amyloidosis, and Finnish-type hereditary systemic amyloidosis. In embodiments, protein aggregation disorder is a neurodegenerative disease. In embodiments, protein aggregation disorder is diabetes mellitus. In embodiments, protein aggregation disorder is p53 mutation cancer.

[0106] As used herein, the term “neurodegenerative disease” refers to a disease or condition in which the function of the nervous system in question is impaired. Examples of neurodegenerative diseases that can be treated with the compounds, pharmaceutical compositions, or methods described herein include, but are not limited to, Alexander disease, Alpers disease, Alzheimer’s disease, amyloidosis, amyotrophic lateral sclerosis (ALS), amyotrophic lateral sclerosis and frontotemporal lobar degeneration, antibody light chain amyloidosis, telangiectasia ataxia, Batten disease (also known as Spielmeyer-Vogt-Sjögren-Batten disease), and bovine spongiform encephalopathy. Encephalopathy (BSE), C9orf72 amyotrophic lateral sclerosis, Canavan disease, Cockayne syndrome, corticobasal degeneration, Creutzfeldt-Jakob disease, Lewy body dementia, diffuse Lewy body disease, facial sensorimotor neuropathy, familial amyloid polyneuropathy, frontotemporal dementia, frontotemporal lobar degeneration, tau-dominant frontotemporal lobar degeneration, TDP-43-dominant frontotemporal lobar degeneration, hereditary human prion disease, Gerstmann-Streussler-Scheinker syndrome, hereditary cerebral amyloid angiopathy, Huntington's disease, HIV-related dementia, Kennedy disease, Krabbe disease, Kuru disease, Lewy body dementia, Machado-Joseph disease (spinocerebellar ataxia type 3), multiple sclerosis, multiple system atrophy, multiple system thrombocytopenia These include plaque disease, myotonic disorder, narcolepsy, neuroborreliosis, Parkinson's disease, Parkinson's disease-associated dementia, Pelizaeus-Merzbacher disease, Perry syndrome, Pick's disease, Poli-Q disease, primary lateral sclerosis, primary progressive aphasia, prion disease, progressive supranuclear palsy, Refsum disease, Sandhoff disease, Schilder's disease, scrapie, semantic dementia, spinocerebellar ataxia and other Poli-Q diseases, sporadic amyotrophic lateral sclerosis, inclusion body myositis, subacute combined degeneration of the spinal cord secondary to pernicious anemia, schizophrenia, spinocerebellar ataxia (multiple types with various characteristics), spinal muscular atrophy, spinocerebellar ataxia, Steele-Richardson-Olzewski disease, spinal fistula, transthyretin amyloidosis, and variant Creutzfeldt-Jakob disease.

[0107] As used herein, the term “cancer” means all types of cancer, neoplasms, or malignant tumors found in mammals (e.g., humans), including leukemia, lymphoma, carcinoma, and sarcoma. Exemplary cancers that can be treated with the compounds or methods provided herein include thyroid cancer, endocrine cancer, brain cancer, breast cancer, cervical cancer, colon cancer, head and neck cancer, liver cancer, kidney cancer, lung cancer, non-small cell lung cancer, melanoma, mesothelioma, ovarian cancer, sarcoma, stomach cancer, uterine cancer, medulloblastoma, colorectal cancer, or pancreatic cancer. Further examples include Hodgkin's disease, non-Hodgkin lymphoma, multiple myeloma, neuroblastoma, glioma, glioblastoma multiforme, ovarian cancer, rhabdomyosarcoma, primary thrombocythemia, primary macroglobulinemia, primary brain tumor, malignant pancreatic insulinoma, malignant carcinoid, bladder cancer, pre-malignant skin lesions, testicular cancer, lymphoma, thyroid cancer, esophageal cancer, genitourinary cancer, malignant hypercalcemia, endometrial cancer, adrenocortical carcinoma, endocrine or exocrine pancreatic neoplasms, medullary thyroid carcinoma, medullary thyroid carcinoma, melanoma, colorectal cancer, papillary thyroid carcinoma, hepatocellular carcinoma, or prostate cancer.

[0108] The term "leukemia" broadly refers to a progressive malignant disease of the hematopoietic organs, generally characterized by the abnormal proliferation and development of white blood cells and their progenitor cells in the blood and bone marrow. Leukemia is generally clinically classified based on (1) the duration and characteristics of the disease—acute or chronic, (2) the type of cells involved—bone marrow (myeloid), lymphoid (lymphatic), or monocytes, and (3) an increase or absence of abnormal cell counts in the blood—leukemia or non-leukemia (subleukemia). Exemplary leukemias that can be treated with the compounds or methods provided herein include, for example, acute non-lymphocytic leukemia, chronic lymphocytic leukemia, acute granulocytic leukemia, chronic granulocytic leukemia, acute promyelocytic leukemia, adult T-cell leukemia, non-leukemia, leukocythemic leukemia, basophilic leukemia, blastocyte leukemia, bovine leukemia, chronic myelocytic leukemia, cutaneous leukemia, fetal leukemia, eosinophilic leukemia, Gross leukemia, hairy cell leukemia, hemoblastic leukemia, and hemocytoblastic leukemia. Examples include leukemia, histiocytic leukemia, stem cell leukemia, acute monocytic leukemia, leukopenic leukemia, lymphocytic leukemia, lymphoblastic leukemia, lymphoid leukemia, lymphoid leukemia, lymphosarcoma cell leukemia, mast cell leukemia, megakaryoblastic leukemia, monocytic leukemia, myeloblastic leukemia, myeloid leukemia, myelogranulocytic leukemia, myelomonocytic leukemia, Naegeli's leukemia, plasma cell leukemia, multiple myeloma, plasma cell leukemia, promyelocytic leukemia, Rieder cell leukemia, Schilling's leukemia, stem cell leukemia, subleukemia, or anaplastic cell leukemia.

[0109] As used herein, the term “lymphoma” refers to a group of cancers that affect hematopoietic and lymphoid tissues. These primarily develop in lymphocytes, which are blood cells found in the lymph nodes, spleen, thymus, and bone marrow. The two main types of lymphoma are non-Hodgkin lymphoma and Hodgkin's disease. Hodgkin's disease accounts for approximately 15% of all diagnosed lymphomas. It is a cancer associated with Reed-Sternberg malignant B lymphocytes. Non-Hodgkin's lymphoma (NHL) can be classified based on the rate at which the cancer grows and the types of cells involved. Types of NHL include invasive (high-grade) and slowly progressive (low-grade). Based on the types of cells involved, there are B-cell and T-cell NHL. Exemplary B-cell lymphomas that can be treated with the compounds or methods provided herein include, but are not limited to, small lymphocytic lymphoma, mantle cell lymphoma, follicular lymphoma, marginal zone lymphoma, extranodal (MALT) lymphoma, nodal (monocytic B-cell) lymphoma, splenic lymphoma, diffuse large cell B lymphoma, Burkitt lymphoma, lymphoblastic lymphoma, immunoblastic large cell lymphoma, or precursor B-lymphoblastic lymphoma. Exemplary T-cell lymphomas that can be treated with the compounds or methods provided herein include, but are not limited to, cutaneous T-cell lymphoma, peripheral T-cell lymphoma, anaplastic large cell lymphoma, mycosis fungoides, and precursor T-lymphoblastic lymphoma.

[0110] The term "sarcoma" generally refers to a tumor composed of a substance such as embryonic connective tissue, and generally consists of densely packed cells embedded in a fibrous or homogeneous substance. Sarcomas that can be treated with the compounds or methods provided herein include chondrosarcoma, fibrosarcoma, lymphosarcoma, melanosarcoma, myxosarcoma, osteosarcoma, Abemesy's sarcoma, liposarcoma, liposarcoma, hydatidiform soft tissue sarcoma, amelophyte fibrosarcoma, staphyloid sarcoma, green sarcoma, choriocarcinoma, embryonal sarcoma, Wilms' neoplastic sarcoma, endometrial sarcoma, stromal sarcoma, and Ewing's sarcoma. Examples include tumors, myofascial sarcomas, fibroblastic sarcomas, giant cell sarcomas, granulocytic sarcomas, Hodgkin's sarcoma, idiopathic multiple pigmented hemorrhagic sarcoma, B-cell immunoblastic sarcoma, lymphoma, T-cell immunoblastic sarcoma, Jensen's sarcoma, Kaposi's sarcoma, Kupffer cell sarcoma, angiosarcoma, leukemosarcoma, malignant mesenchymal sarcoma, paraosteal sarcoma, reticulocyte sarcoma, Rous sarcoma, serous cystic sarcoma, synovial sarcoma, or telangiectatic sarcoma.

[0111] The term "melanoma" is interpreted to mean a tumor arising from the melanocyte system of the skin and other organs. Examples of melanomas that can be treated with the compounds or methods provided herein include acral lentiginous melanoma, achromatic melanoma, benign juvenile melanoma, Cloudmann melanoma, S91 melanoma, Harding-Passé melanoma, juvenile melanoma, lentigo malignant melanoma, malignant melanoma, nodular melanoma, subungual melanoma, or superficial spreading melanoma.

[0112] The term "carcinoma" refers to a malignant neoplasm composed of epithelial cells that tend to invade surrounding tissues and metastasize. Exemplary carcinomas that can be treated with the compounds or methods provided herein include, for example, medullary thyroid carcinoma, familial medullary thyroid carcinoma, lobar cell carcinoma, acinar cell carcinoma, adenocellular carcinoma, adenoid cystic carcinoma, adenomatous carcinoma (carcinoma adenomatosum), adrenocortical carcinoma, alveolar carcinoma, alveolar cell carcinoma, basal cell carcinoma, basal cell carcinoma (carcinoma basocellulare), basal squamous cell carcinoma, bronchioloalveolar carcinoma, bronchiolar carcinoma, bronchogenic carcinoma, cerebriform carcinoma, cholangiocarcinoma, choriocarcinoma, colloidal carcinoma, comedo carcinoma, corpus carcinoma, cribriform carcinoma, armory carcinoma, skin carcinoma, cylindrical carcinoma, cylindrical cell carcinoma, tubular carcinoma, compact carcinoma Durum, fetal carcinoma, cerebral carcinoma, epidermoid carcinoma, pharyngeal tonsillar carcinoma, extrinsic carcinoma, ulcerative carcinoma, fibrous carcinoma, gelatinous carcinoma, colloidal adenocarcinoma, giant cell carcinoma, giant cell carcinoma, adenocarcinoma, granulosa cell carcinoma, piloma carcinoma, hematological carcinoma, hepatocellular carcinoma, Hürthle cell carcinoma, vitreous carcinoma, adrenal carcinoma, infant-fetal carcinoma, carcinoma in situ, carcinoma in epidermis, carcinoma in situ, Krompecher's carcinoma, Kulchitzky cell carcinoma, large cell carcinoma, lenticular carcinoma, lipomatous carcinoma, lymphoepithelial carcinoma, medullary carcinoma, medullary carcinoma, medullary carcinoma, black carcinoma, soft carcinoma (carcinoma molle), mucinous carcinoma, mucinous secretory carcinoma (carcinoma Muciparum, myxoid carcinoma, mucinous epidermoid carcinoma, mucinous carcinoma (carcinoma mucosum), mucosal carcinoma, myxomatous carcinoma, nasopharyngeal carcinoma, oat cell carcinoma, ossifying carcinoma, ossoidal carcinoma, papillary carcinoma, periportal carcinoma, pre-invasive carcinoma, squamous cell carcinoma, gelatinous carcinoma, renal cell carcinoma of the kidney, storage cell carcinoma, sarcomatoid carcinoma, Schneiderian carcinoma, scirrhous carcinoma, scrotal carcinoma, signet ring cell carcinoma, simple carcinoma, small cell carcinoma, solanoid carcinoma.Examples include carcinoma, spheroid cell carcinoma, spindle cell carcinoma, porous carcinoma, squamous cell carcinoma, string carcinoma, telangiectatic carcinoma, telangiectatic-like carcinoma, transitional cell carcinoma, tuberosum carcinoma, nodular carcinoma, verrucous carcinoma, and choriocarcinoma.

[0113] As used herein, the terms “metastasis,” “metastatic,” and “metastatic cancer” are interchangeable and refer to the spread of a proliferative disorder or disorder, such as cancer, from one organ or another non-adjacent organ or part of the body. “Metastatic cancer” is also called “stage IV cancer.” Cancer originates in a primary tumor, for example, in a site of origin called primary breast cancer, for example, the breast. Some cancer cells in a primary tumor or site of origin acquire the ability to penetrate and invade the surrounding normal tissue in the local area, and / or penetrate the walls of the lymphatic or vascular system and circulate through the system to other parts and tissues of the body. A clinically detectable secondary tumor formed from cancer cells of a primary tumor is called a metastatic or secondary tumor. When cancer cells metastasize, the metastatic tumor and its cells are presumed to be similar to those of the original tumor. Therefore, if lung cancer metastasizes to the breast, the secondary tumor in the breast site consists of abnormal lung cells, not abnormal breast cells. The secondary tumor of the breast is called metastatic lung cancer. Therefore, the term "metastatic cancer" refers to a disease in which the subject has or has had a primary tumor and has one or more secondary tumors. The term "non-metastatic cancer" or "subject with non-metastatic cancer" refers to a disease in which the subject has a primary tumor but does not have one or more secondary tumors. For example, metastatic lung cancer refers to a disease in a subject who has or has had a history of a primary lung tumor and has one or more secondary tumors in, for example, a second location or multiple locations in the breast.

[0114] The term "cutaneous metastasis" or "skin metastasis" refers to secondary malignant cell growth in the skin, where the malignant cells originate from the primary cancer site (e.g., breast). In cutaneous metastasis, cancer cells from the primary cancer site may migrate to the skin, where they divide and cause lesions. Skin metastasis can result from the migration of cancer cells from a breast cancer tumor to the skin.

[0115] The term "visceral metastasis" refers to secondary malignant cell growth in internal organs (e.g., heart, lungs, liver, pancreas, intestines) or body cavities (e.g., pleura, peritoneum), where the malignant cells originate from the primary cancer site (e.g., head and neck, liver, breast). In visceral metastasis, cancer cells from the primary cancer site may migrate to the internal organs, where they divide and cause lesions. Visceral metastasis may result from the migration of cancer cells from liver cancer tumors or head and neck tumors to the internal organs.

[0116] As used herein, the term “p53-mutated cancer” refers to cancer that expresses a mutated p53 protein. Examples of p53-mutated cancers include, but are not limited to, small cell lung cancer, squamous cell lung cancer, triple-negative breast cancer, and high-grade serous ovarian cancer.

[0117] The term "drug" is used according to its general meaning and refers to a substance that, when introduced into or into a subject (for example, into or onto the body of a subject or patient), has a physiological effect (e.g., a beneficial effect, useful in treating the subject). The drug part is the drug radical.

[0118] A “detectable drug,” “detectable compound,” “detectable label,” or “detectable portion” is a substance (e.g., an element), molecule, or composition that can be detected by spectroscopic, photochemical, biochemical, immunochemical, chemical, magnetic resonance imaging, or other physical means. For example, a detectable drug may include: 18 F, 32 P, 33 P, 45 Ti, 47 Sc, 52Fe 59 Fe 62 Cu、 64 Cu、 67 Cu、 67 Ga 68 Ga 77 As 86 Y、 90 Y、 89 Mr. 89 Zr、 94 Tc 94 Tc 99m Tc 99 For 105 pd 105 Rh、 111 Ag 111 in 123 I 124 I 125 I 131 I 142 Mr. 143 Mr. 149 PM 153 Sm、 154-1581 God 161 Tb 166 Dy 166 Ho 169 Err 175 sun 177 sun 186 Re 188 Re 189 Re 194 Ir 198 I 199 I 211 And 211 Pb、 212 Hello 212 Pb、 213 Hello 223 Ra 225 Ac、Cr、V、Mn、Fe、Co、Ni、Cu、La、Ce、Pr、Nd、Pm、Sm、Eu、Gd、Tb、Dy、Ho、Er、Tm、Yb、Lu、 32P, fluorophores (e.g., fluorescent dyes), modified oligonucleotides (e.g., portions described in international application PCT / US2015 / 022063, incorporated herein by reference), high electron density reagents, enzymes (e.g., commonly used in ELISA), biotin, digoxigenin, paramagnetic molecules, paramagnetic nanoparticles, ultrasmall superparamagnetic iron oxide ("USPIO") nanoparticles, USPIO nanoparticle aggregates, superparamagnetic iron oxide ("SPIO") nanoparticles, SPIO nanoparticle aggregates, single-crystal iron oxide nanoparticles, single-crystal iron oxide, nanoparticle contrast agents, liposomes, or gadolinium chelates. Other delivery vehicles containing chelate ("Gd-chelate") molecules, gadolinium, radioisotopes, radionuclides (e.g., carbon-11, nitrogen-13, oxygen-15, fluorine-18, rubidium-82), fluorodeoxyglucose (e.g., fluorine-18 labeled), any gamma-ray emitting nuclide, positron-emitting nuclide, radiolabeled glucose, radiolabeled water, radiolabeled ammonia, biocolloids, microbubbles (e.g., microbubble shells containing albumin, galactose, lipids, and / or polymers), air, heavy gases, perfluorocarbons, nitrogen, octafluoropropane, This includes perflexane lipid microspheres (microbubble gas cores including perflutren), iodine contrast agents (e.g., iohexol, iodixanol, iobersol, iopamidol, ioxiran, iopromide, diatrizoate, metrizoate, ioxagrate), barium sulfate, thorium dioxide, gold, gold nanoparticles, gold nanoparticle aggregates, fluorophores, two-photon fluorophores, or haptens, and proteins, or other entities that can be detected by incorporating a radiolabel into a peptide or an antibody that specifically reacts with a target peptide.

[0119] Radioactive materials (e.g., radioisotopes) that can be used as contrast agents and / or labeling agents according to embodiments of this disclosure include: 18 F, 32P, 33 P, 45 Ti, 47 Sc, 52 Fe, 59 Fe, 62 Cu, 64 Cu, 67 Cu, 67 Ga, 68 Ga, 77 As, 86 Y, 90 Y, 89 Sr, 89 Zr, 94 Tc, 94 Tc, 99m Tc, 99 Mo, 105 Pd, 105 Rh, 111 Ag, 111 In, 123 I, 124 I, 125 I, 131 I, 142 Pr, 143 Pr, 149 Pm, 153 Sm, 154-158 Gd, 161 Tb, 166 Dy, 166 Ho, 169 Er, 175 Lu, 177 Lu, 186 Re, 188 Re, 189 Re, 194 Ir, 198 Au, 199 Au, 211 At, 211 Pb, 212 Bi, 212 Pb, 213 Bi, 223 Ra, and 225Paramagnetic ions that can be used as additional contrast agents according to embodiments of this disclosure include, but are not limited to, ions of transition metals and lanthanide metals (e.g., metals with atomic numbers 21-29, 42, 43, 44, or 57-71). These metals include ions of Cr, V, Mn, Fe, Co, Ni, Cu, La, Ce, Pr, Nd, Pm, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, and Lu.

[0120] "Pharmacopoeia-acceptable excipients" and "pharmacopoeia-acceptable carriers" refer to substances that may be included in the compositions described herein without causing significant adverse toxicity to the patient, thereby assisting the administration and absorption of the activator to the target. Non-limiting examples of pharmacopoeia-acceptable excipients include water, NaCl, standard physiological saline, Ringer's lactate solution, standard sucrose, standard glucose, binders, fillers, disintegrants, lubricants, coatings, sweeteners, flavorings, salines (such as Ringer's solution), alcohols, oils, gelatin, carbohydrates (such as lactose, amylose, or starch), fatty acid esters, hydroxymethylcellulose, polyvinylpyrrolidine, and colorants. Such preparations may be sterilized and, if necessary, mixed with adjuvants such as lubricants, preservatives, stabilizers, wetting agents, emulsifiers, salts to affect osmotic pressure, buffers, colorants, and / or aromatics that do not react adversely with the compounds disclosed herein. Those skilled in the art will recognize that other pharmaceutical excipients are useful in the pharmaceutical compositions currently disclosed.

[0121] The term “preparation” is intended to include formulations of an active compound and an encapsulating material that serves as a carrier providing a capsule, in which the active ingredient, with or without other carriers, is surrounded by the carrier and therefore associated with the carrier. Similarly, cachets and lozenges are included. Tablets, powders, capsules, pills, cachets, and lozenges may be used as solid dosage forms suitable for oral administration.

[0122] As used herein, the term “about” means a range of values ​​that a person skilled in the art would reasonably consider to be similar to the specified value, including the specified value. In embodiments, “about” means within a standard deviation using measurements that are generally accepted in the art. In embodiments, “about” means a range of + / - 10% of the specified value. In embodiments, “about” includes the specified value.

[0123] As used herein, the term “administer” is used in its plain, ordinary sense and means to an object by oral administration, suppository administration, topical contact, intravenous, intraperitoneal, intramuscular, intrafocal, intrathecal, intranasal or subcutaneous administration, or implantation of a sustained-release device, such as a small osmotic pump. Administration is by any route, including parenteral and transmucosal (e.g., oral, sublingual, palatal, gingival, transnasal, vaginal, rectal, or transdermal). Parenteral administrations include, for example, intravenous, intramuscular, intraarteriole, intradermal, subcutaneous, intraperitoneal, intraventricular, and intracranial administration. Other modes of delivery include, but are not limited to, the use of liposomal formulations, intravenous infusion, and transdermal patches. “Concurrent administration” means that the compositions described herein are administered simultaneously with, immediately before, or immediately after the administration of one or more additional therapeutic agents. The compounds disclosed herein may be administered to a patient alone or in combination. Co-administration means administering compounds (two or more compounds) individually or in combination simultaneously or sequentially. Therefore, preparations may be combined with other active substances (for example, to reduce metabolic degradation) if desired. The compositions disclosed herein may be delivered transdermally, by topical routes, or formulated as applicators, solutions, suspensions, emulsions, gels, creams, ointments, pastes, jellies, topical applications, powders, and aerosols.

[0124] The compounds described herein can be used in combination with other activators known to be useful in treating diseases associated with cells expressing disease-related cellular components, or in combination with adjuvants that may not be effective on their own but may contribute to the effectiveness of the activators.

[0125] In some embodiments, simultaneous administration involves administering one activator within 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 20, or 24 hours of the second activator. Simultaneous administration involves administering two activators simultaneously, nearly simultaneously (e.g., within approximately 1, 5, 10, 15, 20, or 30 minutes of each other), or sequentially in any order. In some embodiments, simultaneous administration can be achieved by co-formulation, i.e., by preparing a single pharmaceutical composition containing both activators. In other embodiments, the activators may be formulated separately. In another embodiment, the activators and / or adjuvants may be linked or conjugated together.

[0126] In therapeutic use for the treatment of a disease, the compounds used in the pharmaceutical compositions disclosed herein may be administered at an initial dose of approximately 0.001 mg / kg to approximately 1000 mg / kg daily. Daily dose ranges of approximately 0.01 mg / kg to approximately 500 mg / kg, or approximately 0.1 mg / kg to approximately 200 mg / kg, or approximately 1 mg / kg to approximately 100 mg / kg, or approximately 10 mg / kg to approximately 50 mg / kg may be used. However, the dosage may vary depending on the patient's requirements, the severity of the condition being treated, and the compound or drug used. For example, the dosage can be determined empirically considering the type and stage of the disease diagnosed in a particular patient (e.g., cancer). In the context of the currently disclosed methods of therapeutic treatment, the dose administered to the patient should be sufficient to influence the patient's beneficial therapeutic response over time. The size of the dose will also be determined by the presence, nature, and extent of any adverse side effects associated with the administration of the compound in a particular patient. Determining the appropriate dosage for a particular situation is within the scope of a specialist's skill. Generally, treatment begins with a lower dose, below the optimal dose of the compound. The dosage is then gradually increased until the optimal effect is achieved under the given circumstances. For convenience, if desired, the total daily dose may be divided and administered in installments throughout the day.

[0127] In the context of a substance or the activity or function of a substance associated with a disease (e.g., a protein-related disease, a disease associated with a cellular component), the terms “associated” or “associated with” mean that the substance or the activity or function of a substance causes (all or part) the disease (e.g., cancer), or causes (all or part) the symptoms of the disease, or that the symptoms of the disease can be treated by modulating (e.g., inhibiting or activating) the substance (e.g., a cellular component). As used herein, if something is described as associated with a disease, it may be the causative agent and therefore a target for treatment of the disease.

[0128] As used herein, the term “abnormal” means different from normal. When used to describe enzyme activity, abnormal means activity that is greater or less than the average of a normal control or a normal non-disease control sample. Abnormal activity may refer to a disease-causing amount of activity, and a reduction in the disease or one or more disease symptoms is brought about by restoring the abnormal activity to a normal or non-disease-related amount (for example, by administering a compound or using the methods described herein).

[0129] As used herein, the term "electrophilic" refers to a chemical group that can accept electron density. An "electrophilic substituent," "electrophilic moiety," or "electrophilic moiety" refers to an electron-deficient chemical group, substituent, or moiety (monovalent chemical group) that can react with electron-donating groups such as nucleophiles by accepting an electron pair or electron density to form a bond.

[0130] As used herein, "nucleophile" refers to a chemical group that can provide electron density.

[0131] The term "isolated," when applied to nucleic acids or proteins, means that the nucleic acid or protein essentially does not contain other cellular components associated with it in its natural state. This can be, for example, homogeneous and may be either dry or aqueous solution. Purity and homogeneity are typically determined using analytical chemistry techniques such as polyacrylamide gel electrophoresis or high-performance liquid chromatography. The protein present as the dominant species in the formulation is substantially purified.

[0132] The term "amino acid" refers to naturally occurring and synthetic amino acids, as well as amino acid analogs and mimetic compounds that function similarly to naturally occurring amino acids. Naturally occurring amino acids are those encoded by the genetic code, as well as those that are later modified, such as hydroxyproline, γ-carboxyglutamate, and O-phosphoserine. Amino acid analogs are compounds that have the same basic chemical structure as naturally occurring amino acids, i.e., hydrogen, a carboxyl group, an amino group, and an α-carbon bonded to an R group, such as homoserine, norleucine, methionine sulfoxide, and methionine methylsulfonium. Such analogs may have a modified R group (e.g., norleucine) or a modified peptide skeleton, but retain the same basic chemical structure as naturally occurring amino acids. Amino acid mimetic compounds are compounds that have a different structure from the general chemical structure of amino acids but function similarly to naturally occurring amino acids. The terms "naturally occurring amino acids" and "non-natural amino acids" refer to amino acid analogs, synthetic amino acids, and amino acid mimetic compounds that are not found in nature.

[0133] Amino acids may be referred herein by either their commonly known three-letter symbols or the one-letter symbols recommended by the IUPAC-IUB Biochemical Nomenclature Committee. Similarly, nucleotides may be referred by their commonly accepted single-letter codes.

[0134] The terms “polypeptide,” “peptide,” and “protein” are used interchangeably herein to refer to polymers of amino acid residues, and the polymers may, in embodiments, be complexed with portions not composed of amino acids. The terms apply to amino acid polymers in which one or more amino acid residues are artificial chemical mimics of corresponding naturally occurring amino acids, as well as to naturally occurring and non-naturally occurring amino acid polymers.

[0135] The "position" of an amino acid or nucleotide base is indicated by a number that sequentially identifies each amino acid (or nucleotide base) in the reference sequence based on its position relative to the N-terminus (or 5'-terminus). Due to deletions, insertions, cleavages, and fusions that must be considered when determining the optimal alignment, the number of amino acid residues in a test sequence, generally determined by simply counting from the N-terminus, is not necessarily the same as the number of corresponding positions in the reference sequence. For example, if a variant has deletions compared to the aligned reference sequence, there will be no amino acid in the variant corresponding to the position in the reference sequence at the deletion site. If there are insertions in the aligned reference sequence, those insertions do not correspond to numbered amino acid positions in the reference sequence. In the case of cleavage or fusion, there may be a sequence of amino acids in either the reference sequence or the aligned sequence that does not correspond to any amino acid in the corresponding sequence.

[0136] When used in the context of numbering a given amino acid or polynucleotide sequence, the terms “numbered by reference” or “corresponding” refer to the numbering of residues in a particular reference sequence when the given amino acid or polynucleotide sequence is compared to that reference sequence.

[0137] The term "protein complex" is used according to its simple, ordinary meaning and refers to a protein associated with an additional substance (e.g., another protein, protein subunit, or compound). Protein complexes typically have a defined quaternary structure. The association between the protein and the additional substance may be covalent. In embodiments, the association between the protein and the additional substance (e.g., compound) is via non-covalent interactions. In embodiments, a protein complex refers to a group of two or more polypeptide chains. Proteins in a protein complex are linked by non-covalent protein-protein interactions. A non-limiting example of a protein complex is the proteasome.

[0138] The term “protein aggregate” is used according to its simple and common sense meaning and refers to the abnormal collection or accumulation of proteins (e.g., misfolded proteins). Protein aggregates are often associated with diseases (e.g., amyloidosis). In embodiments, unfolded / misfolded proteins can aggregate when they are misfolded as a result of changes in the amino acid sequence or changes in the natural environment that interfere with normal non-covalent interactions, and these misfolded proteins are not corrected or degraded. There are three main types of protein aggregates that can be formed: amorphous aggregates (also referred herein as amorphous protein aggregates), oligomers (also referred herein as protein oligomers), and amyloid fibrils.

[0139] As used herein, the terms “oligomer” and “protein oligomer” refer to protein aggregates having a size range from trimers to 20-mers. In embodiments, the oligomers have a size range of 40 kD to 500 kD.

[0140] As used herein, the term "reduces protein aggregate formation" means reducing the formation of protein aggregates compared to the absence of administration of the compounds provided herein.

[0141] As used herein, the term "inhibits protein aggregate formation" means reducing or preventing the formation of protein aggregates compared to the absence of administration of the compounds provided herein.

[0142] The terms "amyloid beta" or "beta-amyloid" are used according to their obvious and common meaning, referring to a mixture of peptides 36-43 amino acids long formed by the sequential cleavage of amyloid precursor protein (APP) by β- and γ-secretases. Amyloid beta is the main component of amyloid plaques found in the brains of people with Alzheimer's disease.

[0143] As used herein, the terms “amyloid beta peptide 42,” “Aβ42,” or “Aβ1-42” refer to the 42-amino acid isoform of amyloid beta.

[0144] As used herein, the terms “TAR DNA-binding protein 43” or “TDP-43” refer to the protein encoded by the TARDBP gene. In embodiments, TDP-43 has an amino acid sequence described in Entrez 23435, UniProt Q13148, or RefSeq(protein)NP_031401.1, or a corresponding amino acid sequence. In embodiments, the amino acid sequence is a sequence known at the time of filing of this application.

[0145] As used herein, the terms “alpha-synuclein” or “aSyn” refer to the protein encoded by the SNCA gene. In embodiments, aSyn has an amino acid sequence described in or corresponding to Entrez 6622, UniProt P37840, RefSeq(protein)NP_000336.1, RefSeq(protein)NP_001139526.1, RefSeq(protein)NP_001139527.1, RefSeq(protein)NP_009292.1, or RefSeq(protein)NP_001362214. In embodiments, the amino acid sequence is a sequence known at the time of filing of this application.

[0146] II. Compounds In one embodiment, the formula is:

[0147] [ka] A compound having, or a pharmaceutically acceptable salt thereof, is provided.

[0148] R 1 and R 2These are independently hydrogen, -CCl3, -CBr3, -CF3, -CI3, -CHCl2, -CHBr2, -CHF2, -CHI2, -CH2Cl, -CH2Br, -CH2F, -CH2I, -CN, -OH, -NH2, -COOH, -CONH2, -OCCl3, -OCF3, -OCBr3, -OCI3, -OCHCl2, -OCHBr2, -OCHI2, -OCHF2, -OCH2Cl, -OCH2Br, -OCH2I, -OCH2F, substituted or unsubstituted alkyl( For example, C1-C8, C1-C6, C1-C4, or C1-C2), substituted or unsubstituted heteroalkyls (for example, 2-8 members, 2-6 members, 4-6 members, 2-3 members, or 4-5 members), substituted or unsubstituted cycloalkyls (for example, C3-C8, C3-C6, C4-C6, or C5-C6), substituted or unsubstituted heterocycloalkyls (for example, 3-8 members, 3-6 members, 4-6 members, 4-5 members, or 5-6 members), substituted or unsubstituted aryls (for example, C6-C 10 R (or phenyl), or substituted or unsubstituted heteroaryl (e.g., 5-10 member, 5-9 member, or 5-6 member), bonded to the same nitrogen atom 1 and R 2 The substituents may optionally be linked to form substituted or unsubstituted heterocycloalkyl groups (e.g., 3-8 member, 3-6 member, 4-6 member, 4-5 member, or 5-6 member) or substituted or unsubstituted heteroaryl groups (e.g., 5-10 member, 5-9 member, or 5-6 member).

[0149] R 3These are independently oxo, halogen, -CCl3, -CBr3, -CF3, -CI3, -CH2Cl, -CH2Br, -CH2F, -CH2I, -CHCl2, -CHBr2, -CHF2, -CHI2, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NH2, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl3, -OCBr3, -OCF3, -OCI3, -OCH2Cl, -OCH2Br, -OCH2F, -OCH2I, -O CHCl2, -OCHBr2, -OCHF2, -OCHI2, -SF5, -N3, substituted or unsubstituted alkyl (e.g., C1-C8, C1-C6, C1-C4, or C1-C2), substituted or unsubstituted heteroalkyl (e.g., 2-8 member, 2-6 member, 4-6 member, 2-3 member, or 4-5 member), substituted or unsubstituted cycloalkyl (e.g., C3-C8, C3-C6, C4-C6, or C5-C6), substituted or unsubstituted heterocycloalkyl (e.g., 3-8 member, 3-6 member, 4-6 member, 4-5 member, or 5-6 member), substituted or unsubstituted aryl (e.g., C6-C 10 The compounds are phenyl, or substituted or unsubstituted heteroaryls (e.g., 5-10 member, 5-9 member, or 5-6 member).

[0150] R 4 These are, independently, halogen, -CX 4 3, -CHX 4 2, -CH2X 4 ,-OCX 4 3. -OCH2X 4 ,-OCHX 4 2, -CN, -SO n4 R 4D , -SO v4 NR 4A R 4B , -NR 4C NR 4A R 4B ,-ONR 4A R 4B , -NR 4C C(O)NR 4A R 4B , -N(O) m4, -NR 4A R 4B , -C(O)R 4C , -C(O)OR 4C ,-OC(O)R 4C -OC(O)OR 4C -C(O)NR 4A R 4B -OC(O)NR 4A R 4B , -OR 4D , -SR 4D , -NR 4A SO2R 4D , -NR 4A C(O)R 4C , -NR 4A C(O)OR 4C , -NR 4A Ure 4C -SF5, -N3, substituted or unsubstituted alkyl (e.g., C1-C8, C1-C6, C1-C4, or C1-C2), substituted or unsubstituted heteroalkyl (e.g., 2-8 member, 2-6 member, 4-6 member, 2-3 member, or 4-5 member), substituted or unsubstituted cycloalkyl (e.g., C3-C8, C3-C6, C4-C6, or C5-C6), substituted or unsubstituted heterocycloalkyl (e.g., 3-8 member, 3-6 member, 4-6 member, 4-5 member, or 5-6 member), substituted or unsubstituted aryl (e.g., C6-C 10 (or phenyl) or substituted or unsubstituted heteroaryl (e.g., 5-10 member, 5-9 member, or 5-6 member), with two R 4 The substituents can be optionally linked to substituted or unsubstituted cycloalkyl groups (e.g., C3-C8, C3-C6, C4-C6, or C5-C6), substituted or unsubstituted heterocycloalkyl groups (e.g., 3-8 member, 3-6 member, 4-6 member, 4-5 member, or 5-6 member), or substituted or unsubstituted aryl groups (e.g., C6-C6). 10 Alternatively, it may form a phenyl compound, or a substituted or unsubstituted heteroaryl compound (e.g., 5-10 member, 5-9 member, or 5-6 member).

[0151] R 5 These are, independently, halogen, -CX 5 3, -CHX 5 2, -CH2X 5,-OCX 5 3. -OCH2X 5 ,-OCHX 5 2, -CN, -SO n5 R 5D , -SO v5 NR 5A R 5B , -NR 5C NR 5A R 5B ,-ONR 5A R 5B , -NR 5C C(O)NR 5A R 5B , -N(O) m5 , -NR 5A R 5B , -C(O)R 5C , -C(O)OR 5C ,-OC(O)R 5C -OC(O)OR 5C -C(O)NR 5A R 5B -OC(O)NR 5A R 5B , -OR 5D , -SR 5D , -NR 5A SO2R 5D , -NR 5A C(O)R 5C , -NR 5A C(O)OR 5C , -NR 5A Ure 5C -SF5, -N3, substituted or unsubstituted alkyl (e.g., C1-C8, C1-C6, C1-C4, or C1-C2), substituted or unsubstituted heteroalkyl (e.g., 2-8 member, 2-6 member, 4-6 member, 2-3 member, or 4-5 member), substituted or unsubstituted cycloalkyl (e.g., C3-C8, C3-C6, C4-C6, or C5-C6), substituted or unsubstituted heterocycloalkyl (e.g., 3-8 member, 3-6 member, 4-6 member, 4-5 member, or 5-6 member), substituted or unsubstituted aryl (e.g., C6-C 10 The compounds are phenyl or substituted or unsubstituted heteroaryls (e.g., 5-10 member, 5-9 member, or 5-6 member).

[0152] R 6These are hydrogen, halogens, -CCl3, -CBr3, -CF3, -CI3, -CH2Cl, -CH2Br, -CH2F, -CH2I, -CHCl2, -CHBr2, -CHF2, -CHI2, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NH2, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl3, -OCBr3, -OCF3, -OCI3, -OCH2Cl, -OCH2Br, -OCH2F, -OCH2I, -OCHC l2, -OCHBr2, -OCHF2, -OCHI2, -SF5, -N3, substituted or unsubstituted alkyl (e.g., C1-C8, C1-C6, C1-C4, or C1-C2), substituted or unsubstituted heteroalkyl (e.g., 2-8 member, 2-6 member, 4-6 member, 2-3 member, or 4-5 member), substituted or unsubstituted cycloalkyl (e.g., C3-C8, C3-C6, C4-C6, or C5-C6), substituted or unsubstituted heterocycloalkyl (e.g., 3-8 member, 3-6 member, 4-6 member, 4-5 member, or 5-6 member), substituted or unsubstituted aryl (e.g., C6-C 10 The compounds are phenyl, or substituted or unsubstituted heteroaryls (e.g., 5-10 member, 5-9 member, or 5-6 member).

[0153] R 4A , R 4B , R 4C , R 4D , R 5A , R 5B , R 5C , and R 5DThese are independently hydrogen, -CCl3, -CBr3, -CF3, -CI3, -CHCl2, -CHBr2, -CHF2, -CHI2, -CH2Cl, -CH2Br, -CH2F, -CH2I, -CN, -OH, -NH2, -COOH, -CONH2, -OCCl3, -OCF3, -OCBr3, -OCI3, -OCHCl2, -OCHBr2, -OCHI2, -OCHF2, -OCH2Cl, -OCH2Br, -OCH2I, -OCH2F, substituted or unsubstituted alkyl( For example, C1-C8, C1-C6, C1-C4, or C1-C2), substituted or unsubstituted heteroalkyls (for example, 2-8 members, 2-6 members, 4-6 members, 2-3 members, or 4-5 members), substituted or unsubstituted cycloalkyls (for example, C3-C8, C3-C6, C4-C6, or C5-C6), substituted or unsubstituted heterocycloalkyls (for example, 3-8 members, 3-6 members, 4-6 members, 4-5 members, or 5-6 members), substituted or unsubstituted aryls (for example, C6-C 10 R (or phenyl), or substituted or unsubstituted heteroaryl (e.g., 5-10 member, 5-9 member, or 5-6 member), bonded to the same nitrogen atom 4A and R 4B The substituents may optionally link together to form substituted or unsubstituted heterocycloalkyl groups (e.g., 3-8 member, 3-6 member, 4-6 member, 4-5 member, or 5-6 member) or substituted or unsubstituted heteroaryl groups (e.g., 5-10 member, 5-9 member, or 5-6 member), with R bonded to the same nitrogen atom. 5A and R 5B The substituents may optionally be linked to form substituted or unsubstituted heterocycloalkyl groups (e.g., 3-8 member, 3-6 member, 4-6 member, 4-5 member, or 5-6 member) or substituted or unsubstituted heteroaryl groups (e.g., 5-10 member, 5-9 member, or 5-6 member).

[0154] each X 4 and X 5 These are independently -F, -Cl, -Br, or -I.

[0155] The symbols n4 and n5 are independent integers between 0 and 4.

[0156] The symbols m4, m5, v4, and v5 are independently either 1 or 2.

[0157] The symbol z3 is an integer between 0 and 8.

[0158] The symbol z4 is an integer between 0 and 5.

[0159] The symbol z5 represents an integer between 0 and 5.

[0160] In this embodiment, the compound is given by formula:

[0161] [ka] It has R 1 , R 2 , R 3 z3, R 4 z4, R 5 , and z5 are as described herein, including in embodiments.

[0162] In this embodiment, the compound is given by formula:

[0163] [ka] It has, in the formula, R 1 and R 2However, independently, hydrogen, -CCl3, -CBr3, -CF3, -CI3, -CHCl2, -CHBr2, -CHF2, -CHI2, -CH2Cl, -CH2Br, -CH2F, -CH2I, -CN, -OH, -NH2, -COOH, -CONH2, -OCCl3, -OCF3, -OCBr3, -OCI3, -OCHCl2, -OCHBr2, -OCHI2, -OCHF2, -OCH2Cl, -OCH2Br, -OCH2I, -OCH2F, substituted or unsubstituted alkyl (For example, C1C8, C1-C6, C1-C4, or C1-C2), substituted or unsubstituted heteroalkyls (for example, 2-8 members, 2-6 members, 4-6 members, 2-3 members, or 4-5 members), substituted or unsubstituted cycloalkyls (for example, C3-C8, C3-C6, C4-C6, or C5-C6), substituted or unsubstituted heterocycloalkyls (for example, 3-8 members, 3-6 members, 4-6 members, 4-5 members, or 5-6 members), substituted or unsubstituted aryls (for example, C6-C 10 R (or phenyl), or substituted or unsubstituted heteroaryl (e.g., 5-10 member, 5-9 member, or 5-6 member), bonded to the same nitrogen atom 1 and R 2 The substituents may optionally link together to form substituted or unsubstituted heterocycloalkyl groups (e.g., 3-8 members, 3-6 members, 4-6 members, 4-5 members, or 5-6 members), or substituted or unsubstituted heteroaryl groups (e.g., 5-10 members, 5-9 members, or 5-6 members), R 3However, independently, oxo, halogen, -CCl3, -CBr3, -CF3, -CI3, -CH2Cl, -CH2Br, -CH2F, -CH2I, -CHCl2, -CHBr2, -CHF2, -CHI2, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NH2, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl3, -OCBr3, -OCF3, -OCI3, -OCH2Cl, -OCH2Br, -OCH2F, -OCH2I, -O CHCl2, -OCHBr2, -OCHF2, -OCHI2, -SF5, -N3, substituted or unsubstituted alkyl (e.g., C1-C8, C1-C6, C1-C4, or C1-C2), substituted or unsubstituted heteroalkyl (e.g., 2-8 member, 2-6 member, 4-6 member, 2-3 member, or 4-5 member), substituted or unsubstituted cycloalkyl (e.g., C3-C8, C3-C6, C4-C6, or C5-C6), substituted or unsubstituted heterocycloalkyl (e.g., 3-8 member, 3-6 member, 4-6 member, 4-5 member, or 5-6 member), substituted or unsubstituted aryl (e.g., C6-C 10 R is either phenyl, or a substituted or unsubstituted heteroaryl (e.g., 5-10 member, 5-9 member, or 5-6 member), 4 However, independently, halogen, -CX 4 3, -CHX 4 2, -CH2X 4 ,-OCX 4 3. -OCH2X 4 ,-OCHX 4 2, -CN, -SO n4 R 4D , -SO v4 NR 4A R 4B , -NR 4C NR 4A R 4B ,-ONR 4A R 4B , -NR 4C C(O)NR 4A R 4B , -N(O) m4 , -NR 4A R 4B , -C(O)R4C , -C(O)OR 4C ,-OC(O)R 4C -OC(O)OR 4C -C(O)NR 4A R 4B -OC(O)NR 4A R 4B , -OR 4D , -SR 4D , -NR 4A SO2R 4D , -NR 4A C(O)R 4C , -NR 4A C(O)OR 4C , -NR 4A Ure 4C -SF5, -N3, substituted or unsubstituted alkyl (e.g., C1-C8, C1-C6, C1-C4, or C1-C2), substituted or unsubstituted heteroalkyl (e.g., 2-8 member, 2-6 member, 4-6 member, 2-3 member, or 4-5 member), substituted or unsubstituted cycloalkyl (e.g., C3-C8, C3-C6, C4-C6, or C5-C6), substituted or unsubstituted heterocycloalkyl (e.g., 3-8 member, 3-6 member, 4-6 member, 4-5 member, or 5-6 member), substituted or unsubstituted aryl (e.g., C6-C 10 R is either phenyl or a substituted or unsubstituted heteroaryl (e.g., 5-10 member, 5-9 member, or 5-6 member), 5 However, independently, halogen, -CX 5 3, -CHX 5 2, -CH2X 5 ,-OCX 5 3. -OCH2X 5 ,-OCHX 5 2, -CN, -SO n5 R 5D , -SO v5 NR 5A R 5B , -NR 5C NR 5A R 5B ,-ONR 5A R 5B , -NR 5C C(O)NR 5A R 5B , -N(O) m5 , -NR 5A R5B , -C(O)R 5C , -C(O)OR 5C ,-OC(O)R 5C -OC(O)OR 5C -C(O)NR 5A R 5B -OC(O)NR 5A R 5B , -OR 5D , -SR 5D , -NR 5A SO2R 5D , -NR 5A C(O)R 5C , -NR 5A C(O)OR 5C , -NR 5A Ure 5C -SF5, -N3, substituted or unsubstituted alkyl (e.g., C1-C8, C1-C6, C1-C4, or C1-C2), substituted or unsubstituted heteroalkyl (e.g., 2-8 member, 2-6 member, 4-6 member, 2-3 member, or 4-5 member), substituted or unsubstituted cycloalkyl (e.g., C3-C8, C3-C6, C4-C6, or C5-C6), substituted or unsubstituted heterocycloalkyl (e.g., 3-8 member, 3-6 member, 4-6 member, 4-5 member, or 5-6 member), substituted or unsubstituted aryl (e.g., C6-C 10 R is either phenyl or a substituted or unsubstituted heteroaryl (e.g., 5-10 member, 5-9 member, or 5-6 member), 4A , R 4B , R 4C , R 4D , R 5A , R 5B , R 5C , and R 5DHowever, independently, hydrogen, -CCl3, -CBr3, -CF3, -CI3, -CHCl2, -CHBr2, -CHF2, -CHI2, -CH2Cl, -CH2Br, -CH2F, -CH2I, -CN, -OH, -NH2, -COOH, -CONH2, -OCCl3, -OCF3, -OCBr3, -OCI3, -OCHCl2, -OCHBr2, -OCHI2, -OCHF2, -OCH2Cl, -OCH2Br, -OCH2I, -OCH2F, substituted or unsubstituted alkyl( For example, C1-C8, C1-C6, C1-C4, or C1-C2), substituted or unsubstituted heteroalkyls (for example, 2-8 members, 2-6 members, 4-6 members, 2-3 members, or 4-5 members), substituted or unsubstituted cycloalkyls (for example, C3-C8, C3-C6, C4-C6, or C5-C6), substituted or unsubstituted heterocycloalkyls (for example, 3-8 members, 3-6 members, 4-6 members, 4-5 members, or 5-6 members), substituted or unsubstituted aryls (for example, C6-C 10 R (or phenyl), or substituted or unsubstituted heteroaryl (e.g., 5-10 member, 5-9 member, or 5-6 member), bonded to the same nitrogen atom 4A and R 4B The substituents can optionally link together to form substituted or unsubstituted heterocycloalkyl groups (e.g., 3-8 member, 3-6 member, 4-6 member, 4-5 member, or 5-6 member) or substituted or unsubstituted heteroaryl groups (e.g., 5-10 member, 5-9 member, or 5-6 member), and R bonded to the same nitrogen atom 5A and R 5B The substituents may optionally link together to form substituted or unsubstituted heterocycloalkyl groups (e.g., 3-8 members, 3-6 members, 4-6 members, 4-5 members, or 5-6 members), or substituted or unsubstituted heteroaryl groups (e.g., 5-10 members, 5-9 members, or 5-6 members), each X 4 and X 5 However, independently, n4 and n5 are integers from 0 to 4, m4, m5, v4, and v5 are independently 1 or 2, z3 is an integer from 0 to 8, z4 is an integer from 0 to 5, and z5 is an integer from 0 to 5.

[0164] In this embodiment, the compound is

[0165] [ka] isn't it.

[0166] In this embodiment, the compound is given by formula:

[0167] [ka] It has R 1 , R 2 , R 3 z3, R 4 z4, R 5 , and z5 are as described herein, including in embodiments.

[0168] In this embodiment, the compound is given by formula:

[0169] [ka] It has R 1 , R 2 , R 3 z3, R 4 z4, R 5 , and z5 are as described herein, including in embodiments.

[0170] In this embodiment, the compound is given by formula:

[0171] [ka] It has R 1 , R 2 , R 3 z3, R 4 , R 5 , z5, and R 6 This, including embodiments, is as described herein.

[0172] In this embodiment, the compound is given by formula:

[0173] [ka] It has R 1 , R 2 , R 3 z3, R 4 , R 5 , and z5 are as described herein, including in embodiments.

[0174] In this embodiment, the compound is given by formula:

[0175] [ka] It has R 1 , R 2 , R 4 , R 5 , and z5 are as described herein, including in embodiments.

[0176] In this embodiment, the compound is given by formula:

[0177] [ka] It has R 1 , R 2 , R 4 , R 5 , and z5 are as described herein, including in embodiments.

[0178] In this embodiment, the compound is given by formula:

[0179] [ka] It has R 1 , R 2 , R 4 , R 5 , and z5 are as described herein, including in embodiments.

[0180] In this embodiment, the compound is given by formula:

[0181] [ka] It has R 1 , R 2 , R 5 , and z5 are as described herein, including in embodiments. 4.2 and R 4.3 This includes, independently, hydrogen, or R as described herein, including in embodiments. 4 It is any value.

[0182] In this embodiment, the compound is given by formula:

[0183] [ka] It has R 1 , R 2 , R 5 , and z5 are as described herein, including in embodiments. 4.2 , R 4.3 , and R 4.5 This includes, independently, hydrogen, or R as described herein, including in embodiments. 4 It is any value.

[0184] In this embodiment, the compound is given by formula:

[0185] [ka] It has R 1 , R 2 , R 5 , and z5 are as described herein, including in embodiments. 4.2 , R 4.3 , and R 4.4 This includes, independently, hydrogen, or R as described herein, including in embodiments. 4 It is any value.

[0186] R 4.2 , R 4.3 , R 4.4 , and R 4.5 These are independently hydrogen, halogen, and -CX 43, -CHX 4 2, -CH2X 4 ,-OCX 4 3. -OCH2X 4 ,-OCHX 4 2, -CN, -SO n4 R 4D , -SO v4 NR 4A R 4B , -NR 4C NR 4A R 4B ,-ONR 4A R 4B , -NR 4C C(O)NR 4A R 4B , -N(O) m4 , -NR 4A R 4B , -C(O)R 4C , -C(O)OR 4C ,-OC(O)R 4C -OC(O)OR 4C -C(O)NR 4A R 4B -OC(O)NR 4A R 4B , -OR 4D , -SR 4D , -NR 4A SO2R 4D , -NR 4A C(O)R 4C , -NR 4A C(O)OR 4C , -NR 4A Ure 4C -SF5, -N3, substituted or unsubstituted alkyl (e.g., C1-C8, C1-C6, C1-C4, or C1-C2), substituted or unsubstituted heteroalkyl (e.g., 2-8 member, 2-6 member, 4-6 member, 2-3 member, or 4-5 member), substituted or unsubstituted cycloalkyl (e.g., C3-C8, C3-C6, C4-C6, or C5-C6), substituted or unsubstituted heterocycloalkyl (e.g., 3-8 member, 3-6 member, 4-6 member, 4-5 member, or 5-6 member), substituted or unsubstituted aryl (e.g., C6-C 10 R is either phenyl or a substituted or unsubstituted heteroaryl (e.g., 5-10 member, 5-9 member, or 5-6 member), 4.2 and R4.3 The substituent may optionally be linked to form a substituted or unsubstituted cycloalkyl (e.g., C3-C8, C3-C6, C4-C6, or C5-C6), a substituted or unsubstituted heterocycloalkyl (e.g., 3- to 8-membered, 3- to 6-membered, 4- to 6-membered, 4- to 5-membered, or 5- to 6-membered), a substituted or unsubstituted aryl (e.g., C6-C 10 or phenyl), or a substituted or unsubstituted heteroaryl (e.g., 5- to 10-membered, 5- to 9-membered, or 5- to 6-membered), and R 4.3 and R 4.4 The substituent may optionally be linked to form a substituted or unsubstituted cycloalkyl (e.g., C3-C8, C3-C6, C4-C6, or C5-C6), a substituted or unsubstituted heterocycloalkyl (e.g., 3- to 8-membered, 3- to 6-membered, 4- to 6-membered, 4- to 5-membered, or 5- to 6-membered), a substituted or unsubstituted aryl (e.g., C6-C 10 or phenyl), or a substituted or unsubstituted heteroaryl (e.g., 5- to 10-membered, 5- to 9-membered, or 5- to 6-membered).

[0187] In an embodiment, the compound has the formula:

[0188]

Chemical formula

[0191] In this embodiment, the compound is given by formula:

[0192] [ka] The formula has such that z4 is an integer between 0 and 4. 1 , R 2 , R 3 , z3, R 4 , and R 5 This, including embodiments, is as described herein.

[0193] In this embodiment, the compound is given by formula:

[0194] [ka] The formula has such that z4 is an integer between 0 and 4. 1 , R 2 , R 3 , z3, R 4 , R 5 , and z5 are as described herein, including in embodiments.

[0195] In the embodiment, substitution R 1 (For example, substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and substituted R 1 However, if the group is substituted with multiple groups selected from substituents, size-restricting substituents, and lower substituents, each substituent, size-restricting substituent, and / or lower substituent may be optionally different. In the embodiment, R 1When it is substituted, it is substituted with at least one substituent. In the embodiment, R 1 When it is substituted, it is substituted with at least one size-limited substituent. In the embodiment, R 1 When it is substituted, it is substituted with at least one lower substituent.

[0196] In this embodiment, R 1 These are hydrogen, -CCl3, -CBr3, -CF3, -CI3, -CHCl2, -CHBr2, -CHF2, -CHI2, -CH2Cl, -CH2Br, -CH2F, -CH2I, -CN, -OH, -NH2, -COOH, -CONH2, -OCCl3, -OCF3, -OCBr3, -OCI3, -OCHCl2, -OCHBr2, -OCHI2, -OCHF2, -OCH2Cl, -OCH2Br, -OCH2I, -OCH2F, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0197] In this embodiment, R 1 These are hydrogen, substituted or unsubstituted C1-C4 alkyl groups, substituted or unsubstituted 2-6 member heteroalkyl groups, substituted or unsubstituted C3-C6 cycloalkyl groups, or substituted or unsubstituted 3-6 member heterocycloalkyl groups.

[0198] In this embodiment, R 1 is hydrogen. In this embodiment, R 1 is -CCl3. In the embodiment, R 1 is -CBr3. In the embodiment, R 1 is -CF3. In the embodiment, R 1 is -CI3. In the embodiment, R 1 is -CH2Cl. In the embodiment, R 1 is -CH2Br. In the embodiment, R 1 is -CH2F. In the embodiment, R 1 is -CH2I. In the embodiment, R1 is -CHCl2. In an embodiment, R 1 is -CHBr2. In an embodiment, R 1 is -CHF2. In an embodiment, R 1 is -CHI2. In an embodiment, R 1 is -CN. In an embodiment, R 1 is -OH. In an embodiment, R 1 is -NH2. In an embodiment, R 1 is -COOH. In an embodiment, R 1 is -CONH2. In an embodiment, R 1 is -OCCl3. In an embodiment, R 1 is -OCBr3. In an embodiment, R 1 is -OCF3. In an embodiment, R 1 is -OCI3. In an embodiment, R 1 is -OCH2Cl. In an embodiment, R 1 is -OCH2Br. In an embodiment, R 1 is -OCH2F. In an embodiment, R 1 is -OCH2I. In an embodiment, R 1 is -OCHCl2. In an embodiment, R 1 is -OCHBr2. In an embodiment, R 1 is -OCHF2. In an embodiment, R 1 is -OCHI2. In an embodiment, R 1 is unsubstituted C1 - C4 alkyl. In an embodiment, R 1 is unsubstituted methyl. In an embodiment, R 1 is unsubstituted ethyl. In an embodiment, R 1 is unsubstituted propyl. In an embodiment, R 1 is unsubstituted n - propyl. In an embodiment, R 1 is unsubstituted isopropyl. In an embodiment, R 1 is unsubstituted butyl. In an embodiment, R 1 is unsubstituted n - butyl. In an embodiment, R 1 is unsubstituted isobutyl. In an embodiment, R1 It is unsubstituted tert-butyl.

[0199] In the embodiment, substitution R 2 (For example, substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and substituted R 2 However, if the group is substituted with multiple groups selected from substituents, size-restricting substituents, and lower substituents, each substituent, size-restricting substituent, and / or lower substituent may be optionally different. In the embodiment, R 2 When it is substituted, it is substituted with at least one substituent. In the embodiment, R 2 When it is substituted, it is substituted with at least one size-limited substituent. In the embodiment, R 2 When it is substituted, it is substituted with at least one lower substituent.

[0200] In this embodiment, R 2 These are hydrogen, -CCl3, -CBr3, -CF3, -CI3, -CHCl2, -CHBr2, -CHF2, -CHI2, -CH2Cl, -CH2Br, -CH2F, -CH2I, -CN, -OH, -NH2, -COOH, -CONH2, -OCCl3, -OCF3, -OCBr3, -OCI3, -OCHCl2, -OCHBr2, -OCHI2, -OCHF2, -OCH2Cl, -OCH2Br, -OCH2I, -OCH2F, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0201] In this embodiment, R 2 These are hydrogen, substituted or unsubstituted C1-C4 alkyl groups, substituted or unsubstituted 2-6 member heteroalkyl groups, substituted or unsubstituted C3-C6 cycloalkyl groups, or substituted or unsubstituted 3-6 member heterocycloalkyl groups.

[0202] In this embodiment, R 2 is hydrogen. In this embodiment, R 2 is -CCl3. In the embodiment, R 2 is -CBr3. In the embodiment, R 2 is -CF3. In the embodiment, R 2 is -CI3. In the embodiment, R 2 is -CH2Cl. In the embodiment, R 2 is -CH2Br. In the embodiment, R 2 is -CH2F. In the embodiment, R 2 is -CH2I. In the embodiment, R 2 is -CHCl2. In the embodiment, R 2 is -CHBr2. In the embodiment, R 2 is -CHF2. In the embodiment, R 2 is -CHI2. In the embodiment, R 2 is -CN. In the embodiment, R 2 is -OH. In the embodiment, R 2 is -NH2. In the embodiment, R 2 is -COOH. In the embodiment, R 2 is -CONH2. In the embodiment, R 2 is -OCCl3. In the embodiment, R 2 is -OCBr3. In the embodiment, R 2 is -OCF3. In the embodiment, R 2 is -OCI3. In the embodiment, R 2 is -OCH2Cl. In the embodiment, R 2 is -OCH2Br. In the embodiment, R 2 is -OCH2F. In the embodiment, R 2 is -OCH2I. In the embodiment, R 2 is -OCHCl2. In the embodiment, R 2 is -OCHBr2. In the embodiment, R 2 is -OCHF2. In the embodiment, R 2 is -OCHI2. In the embodiment, R2 is an unsubstituted C1-C4 alkyl group. In the embodiment, R 2 is an unsubstituted methyl group. In this embodiment, R 2 is unsubstituted ethyl. In the embodiment, R 2 is unsubstituted propyl. In the embodiment, R 2 is unsubstituted n-propyl. In the embodiment, R 2 is an unsubstituted isopropyl. In the embodiment, R 2 is unsubstituted butyl. In the embodiment, R 2 is unsubstituted n-butyl. In the embodiment, R 2 is unsubstituted isobutyl. In this embodiment, R 2 It is unsubstituted tert-butyl.

[0203] In this embodiment, R 1 and R 2 It is an unsubstituted methyl group.

[0204] In this embodiment, R bonded to the same nitrogen atom 1 and R 2 The substituted ring formed when substituents are linked (e.g., substituted heterocycloalkyl and / or substituted heteroaryl) is substituted with at least one substituent, size-limited substituent, or lower substituent, and R is bonded to the same nitrogen atom. 1 and R 2 When the substituted ring formed by the linking of substituents is substituted with multiple groups selected from substituents, size-restricting substituents, and lower substituents, each substituent, size-restricting substituent, and / or lower substituent may be optionally different. In this embodiment, R bonded to the same nitrogen atom 1 and R 2 When a substituted ring formed by linking substituents is substituted, it is substituted with at least one substituent. In this embodiment, R bonded to the same nitrogen atom 1 and R 2 When a substituted ring formed by linking substituents is substituted, it is substituted with at least one size-limited substituent. In this embodiment, R bonded to the same nitrogen atom 1 and R2 When a substituted ring formed by linking substituents is substituted, it is substituted with at least one lower substituent.

[0205] In this embodiment, R 1 and R 2 The substituents, together with the nitrogen atom to which they are bonded, link together to form substituted or unsubstituted 3- to 8-membered heterocycloalkyl groups. In the embodiment, R 1 and R 2 The substituents, together with the nitrogen atom to which they are bonded, link together to form substituted or unsubstituted pyrrolidinyl molecules. In the embodiment, R 1 and R 2 The substituents, together with the nitrogen atom to which they are bonded, link together to form a methyl-substituted pyrrolidinyl. In the embodiment, R 1 and R 2 The substituents, together with the nitrogen atom to which they are bonded, are linked together.

[0206] [ka] It forms.

[0207] In the embodiment, substitution R 3 (For example, substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and substituted R 3 However, if the group is substituted with multiple groups selected from substituents, size-restricting substituents, and lower substituents, each substituent, size-restricting substituent, and / or lower substituent may be optionally different. In the embodiment, R 3 When it is substituted, it is substituted with at least one substituent. In the embodiment, R 3 When it is substituted, it is substituted with at least one size-limited substituent. In the embodiment, R 3 When it is substituted, it is substituted with at least one lower substituent.

[0208] In this embodiment, R 3 It is independently an oxo. In the embodiment, R 3 In this embodiment, R 3 Independently, is -F. In the embodiment, R 3 In this embodiment, R 3 Independently, is -Br. In the embodiment, R 3 Independently, is -I. In the embodiment, R 3 In this embodiment, R 3 Independently, is -CBr3. In the embodiment, R 3 In this embodiment, R 3 In this embodiment, R 3 Independently, is -CH2Cl. In the embodiment, R 3 Independently, is -CH2Br. In the embodiment, R 3 Independently, is -CH2F. In the embodiment, R 3 In this embodiment, R 3 is independently -CHCl2. In the embodiment, R 3 Independently, is -CHBr2. In the embodiment, R 3 In this embodiment, R 3 Independently, is -CHI2. In the embodiment, R 3 Independently, is -CN. In the embodiment, R 3 In this embodiment, R 3 In this embodiment, R 3 It is independently -COOH. In the embodiment, R 3 Independently, is -CONH2. In the embodiment, R 3 In this embodiment, R 3 In this embodiment, R 3 It is independently -SO3H. In the embodiment, R 3Independently, is -OSO3H. In the embodiment, R 3 Independently, is -SO2NH2. In the embodiment, R 3 Independently, is -NHNH2. In the embodiment, R 3 In this embodiment, R 3 This is independently -NHC(O)NH2. In the embodiment, R 3 This is independently -NHSO2H. In the embodiment, R 3 In this embodiment, R 3 This is independently -NHC(O)OH. In the embodiment, R 3 In this embodiment, R 3 Independently, is -OCCl3. In the embodiment, R 3 Independently, is -OCBr3. In the embodiment, R 3 Independently, is -OCF3. In the embodiment, R 3 In this embodiment, R 3 Independently, is -OCH2Cl. In the embodiment, R 3 Independently, is -OCH2Br. In the embodiment, R 3 Independently, is -OCH2F. In the embodiment, R 3 Independently, is -OCH2I. In the embodiment, R 3 is independently -OCHCl2. In the embodiment, R 3 Independently, is -OCHBr2. In the embodiment, R 3 Independently, is -OCHF2. In the embodiment, R 3 Independently, is -OCHI2. In the embodiment, R 3 In this embodiment, R 3 Independently, is -N3. In the embodiment, R 3 These are independently unsubstituted C1-C4 alkyl groups. In the embodiment, R 3 R is independently an unsubstituted methyl group. In this embodiment, R 3 R is independently unsubstituted ethyl. In the embodiment, R 3R is independently unsubstituted propyl. In the embodiment, R 3 R is independently unsubstituted n-propyl. In the embodiment, R 3 R is independently an unsubstituted isopropyl. In the embodiment, R 3 R is independently unsubstituted butyl. In this embodiment, R 3 R is independently unsubstituted n-butyl. In the embodiment, R 3 R is independently an unsubstituted isobutyl. In the embodiment, R 3 This is independently unsubstituted tert-butyl.

[0209] In this embodiment, z3 is 0. In this embodiment, z3 is 1. In this embodiment, z3 is 2. In this embodiment, z3 is 3. In this embodiment, z3 is 4. In this embodiment, z3 is 5. In this embodiment, z3 is 6. In this embodiment, z3 is 7. In this embodiment, z3 is 8.

[0210] In the embodiment, substitution R 4 (For example, substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and substituted R 4 However, if the group is substituted with multiple groups selected from substituents, size-restricting substituents, and lower substituents, each substituent, size-restricting substituent, and / or lower substituent may be optionally different. In the embodiment, R 4 When it is substituted, it is substituted with at least one substituent. In the embodiment, R 4 When it is substituted, it is substituted with at least one size-limited substituent. In the embodiment, R 4 When it is substituted, it is substituted with at least one lower substituent.

[0211] In the embodiment, substitution R 4A(For example, substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and substituted R 4A However, if the group is substituted with multiple groups selected from substituents, size-restricting substituents, and lower substituents, each substituent, size-restricting substituent, and / or lower substituent may be optionally different. In the embodiment, R 4A When it is substituted, it is substituted with at least one substituent. In the embodiment, R 4A When it is substituted, it is substituted with at least one size-limited substituent. In the embodiment, R 4A When it is substituted, it is substituted with at least one lower substituent.

[0212] In the embodiment, substitution R 4B (For example, substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and substituted R 4B However, if the group is substituted with multiple groups selected from substituents, size-restricting substituents, and lower substituents, each substituent, size-restricting substituent, and / or lower substituent may be optionally different. In the embodiment, R 4B When it is substituted, it is substituted with at least one substituent. In the embodiment, R 4B When it is substituted, it is substituted with at least one size-limited substituent. In the embodiment, R 4B When it is substituted, it is substituted with at least one lower substituent.

[0213] In this embodiment, R bonded to the same nitrogen atom 4A and R 4BThe substituted ring formed when substituents are linked (e.g., substituted heterocycloalkyl and / or substituted heteroaryl) is substituted with at least one substituent, size-limited substituent, or lower substituent, and R is bonded to the same nitrogen atom. 4A and R 4B When the substituted ring formed by the linking of substituents is substituted with multiple groups selected from substituents, size-restricting substituents, and lower substituents, each substituent, size-restricting substituent, and / or lower substituent may be optionally different. In this embodiment, R bonded to the same nitrogen atom 4A and R 4B When a substituted ring is formed when substituents are linked, it is substituted by at least one substituent. In this embodiment, R bonded to the same nitrogen atom 4A and R 4B When a substituted ring is formed when substituents are linked, it is substituted with at least one size-limited substituent. In this embodiment, R bonded to the same nitrogen atom 4A and R 4B When a substituted ring is formed by linking substituents, it is substituted with at least one lower substituent.

[0214] In the embodiment, substitution R 4C (For example, substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and substituted R 4C However, if the group is substituted with multiple groups selected from substituents, size-restricting substituents, and lower substituents, each substituent, size-restricting substituent, and / or lower substituent may be optionally different. In the embodiment, R 4C When it is substituted, it is substituted with at least one substituent. In the embodiment, R 4C When it is substituted, it is substituted with at least one size-limited substituent. In the embodiment, R 4C When it is substituted, it is substituted with at least one lower substituent.

[0215] In the embodiment, substitution R 4D (For example, substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and substituted R 4D However, if the group is substituted with multiple groups selected from substituents, size-restricting substituents, and lower substituents, each substituent, size-restricting substituent, and / or lower substituent may be optionally different. In the embodiment, R 4D When it is substituted, it is substituted with at least one substituent. In the embodiment, R 4D When it is substituted, it is substituted with at least one size-limited substituent. In the embodiment, R 4D When it is substituted, it is substituted with at least one lower substituent.

[0216] In this embodiment, R 4A R is independently hydrogen. In this embodiment, R 4A These are independently unsubstituted C1-C4 alkyl groups. In the embodiment, R 4A R is independently an unsubstituted methyl group. In this embodiment, R 4A R is independently unsubstituted ethyl. In the embodiment, R 4A R is independently unsubstituted propyl. In the embodiment, R 4A R is independently unsubstituted n-propyl. In the embodiment, R 4A R is independently an unsubstituted isopropyl. In the embodiment, R 4A R is independently unsubstituted butyl. In this embodiment, R 4A R is independently unsubstituted n-butyl. In the embodiment, R 4A R is independently an unsubstituted isobutyl. In the embodiment, R 4A This is independently unsubstituted tert-butyl.

[0217] In this embodiment, R 4B R is independently hydrogen. In this embodiment, R 4BThese are independently unsubstituted C1-C4 alkyl groups. In the embodiment, R 4B R is independently an unsubstituted methyl group. In this embodiment, R 4B R is independently unsubstituted ethyl. In the embodiment, R 4B R is independently unsubstituted propyl. In the embodiment, R 4B R is independently unsubstituted n-propyl. In the embodiment, R 4B R is independently an unsubstituted isopropyl. In the embodiment, R 4B R is independently unsubstituted butyl. In this embodiment, R 4B R is independently unsubstituted n-butyl. In the embodiment, R 4B R is independently an unsubstituted isobutyl. In the embodiment, R 4B This is independently unsubstituted tert-butyl.

[0218] In this embodiment, R 4C R is independently hydrogen. In this embodiment, R 4C These are independently unsubstituted C1-C4 alkyl groups. In the embodiment, R 4C R is independently an unsubstituted methyl group. In this embodiment, R 4C R is independently unsubstituted ethyl. In the embodiment, R 4C R is independently unsubstituted propyl. In the embodiment, R 4C R is independently unsubstituted n-propyl. In the embodiment, R 4C R is independently an unsubstituted isopropyl. In the embodiment, R 4C R is independently unsubstituted butyl. In this embodiment, R 4C R is independently unsubstituted n-butyl. In the embodiment, R 4C R is independently an unsubstituted isobutyl. In the embodiment, R 4C This is independently unsubstituted tert-butyl.

[0219] In this embodiment, R 4D R is independently hydrogen. In this embodiment, R 4D These are independently unsubstituted C1-C4 alkyl groups. In the embodiment, R 4DR is independently an unsubstituted methyl group. In this embodiment, R 4D R is independently unsubstituted ethyl. In the embodiment, R 4D R is independently unsubstituted propyl. In the embodiment, R 4D R is independently unsubstituted n-propyl. In the embodiment, R 4D R is independently an unsubstituted isopropyl. In the embodiment, R 4D R is independently unsubstituted butyl. In this embodiment, R 4D R is independently unsubstituted n-butyl. In the embodiment, R 4D R is independently an unsubstituted isobutyl. In the embodiment, R 4D R is independently unsubstituted tert-butyl. In the embodiment, R 4D These are independently substituted 3- to 8-membered heterocycloalkyl groups. In the embodiment, R 4D It is independently an unsubstituted oxetanyl.

[0220] In this embodiment, R 4 These are, independently, halogen, -CCl3, -CBr3, -CF3, -CI3, -CH2Cl, -CH2Br, -CH2F, -CH2I, -CHCl2, -CHBr2, -CHF2, -CHI2, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NH2, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -O CCl3, -OCBr3, -OCF3, -OCI3, -OCH2Cl, -OCH2Br, -OCH2F, -OCH2I, -OCHCl2, -OCHBr2, -OCHF2, -OCHI2, -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, with two R 4 The substituents may optionally be linked to form substituted or unsubstituted cycloalkyl groups, substituted or unsubstituted heterocycloalkyl groups, substituted or unsubstituted aryl groups, or substituted or unsubstituted heteroaryl groups.

[0221] In this embodiment, R 4 In this embodiment, R 4 Independently, is -F. In the embodiment, R 4 In this embodiment, R 4 Independently, is -Br. In the embodiment, R 4 Independently, is -I. In the embodiment, R 4 In this embodiment, R 4 Independently, is -CBr3. In the embodiment, R 4 In this embodiment, R 4 In this embodiment, R 4 Independently, is -CH2Cl. In the embodiment, R 4 Independently, is -CH2Br. In the embodiment, R 4 Independently, is -CH2F. In the embodiment, R 4 In this embodiment, R 4 is independently -CHCl2. In the embodiment, R 4 Independently, is -CHBr2. In the embodiment, R 4 In this embodiment, R 4 Independently, is -CHI2. In the embodiment, R 4 Independently, is -CN. In the embodiment, R 4 In this embodiment, R 4 In this embodiment, R 4 It is independently -COOH. In the embodiment, R 4 Independently, is -CONH2. In the embodiment, R 4 In this embodiment, R 4 In this embodiment, R 4 It is independently -SO3H. In the embodiment, R 4 Independently, is -OSO3H. In the embodiment, R4 Independently, is -SO2NH2. In the embodiment, R 4 Independently, is -NHNH2. In the embodiment, R 4 In this embodiment, R 4 This is independently -NHC(O)NH2. In the embodiment, R 4 This is independently -NHSO2H. In the embodiment, R 4 In this embodiment, R 4 This is independently -NHC(O)OH. In the embodiment, R 4 In this embodiment, R 4 Independently, is -OCCl3. In the embodiment, R 4 Independently, is -OCBr3. In the embodiment, R 4 Independently, is -OCF3. In the embodiment, R 4 In this embodiment, R 4 Independently, is -OCH2Cl. In the embodiment, R 4 Independently, is -OCH2Br. In the embodiment, R 4 Independently, is -OCH2F. In the embodiment, R 4 Independently, is -OCH2I. In the embodiment, R 4 is independently -OCHCl2. In the embodiment, R 4 Independently, is -OCHBr2. In the embodiment, R 4 Independently, is -OCHF2. In the embodiment, R 4 Independently, is -OCHI2. In the embodiment, R 4 In this embodiment, R 4 Independently, is -N3. In the embodiment, R 4 These are independently unsubstituted C1-C4 alkyl groups. In the embodiment, R 4 R is independently an unsubstituted methyl group. In this embodiment, R 4 R is independently unsubstituted ethyl. In the embodiment, R 4 R is independently unsubstituted propyl. In the embodiment, R4 R is independently unsubstituted n-propyl. In the embodiment, R 4 R is independently an unsubstituted isopropyl. In the embodiment, R 4 R is independently unsubstituted butyl. In this embodiment, R 4 R is independently unsubstituted n-butyl. In the embodiment, R 4 R is independently an unsubstituted isobutyl. In the embodiment, R 4 R is independently unsubstituted tert-butyl. In the embodiment, R 4 These are independently unsubstituted C2-C4 alkenyls. In the embodiment, R 4 Independently,

[0222] [ka] In this embodiment, R 4 These are independently unsubstituted 2-6 member heteroalkyl groups. In the embodiment, R 4 R is independently an unsubstituted methoxy compound. In this embodiment, R 4 R is independently an unsubstituted ethoxy. In this embodiment, R 4 R is independently an unsubstituted propoxy. In this embodiment, R 4 R is independently an unsubstituted n-propoxy. In this embodiment, R 4 R is independently an unsubstituted isopropoxy. In the embodiment, R 4 In this embodiment, R 4 Independently,

[0223] [ka] In this embodiment, R 4 Independently,

[0224] [ka] In this embodiment, R 4 These are independently substituted 2- to 6-membered heteroalkyl groups. In the embodiment, R4 Independently,

[0225] [ka] That is the case.

[0226] In this embodiment, R 4 These are independently halogens, -CCl3, -CBr3, -CF3, -CI3, -CH2Cl, -CH2Br, -CH2F, -CH2I, -CHCl2, -CHBr2, -CHF2, -CHI2, -CN, -OH, -NH2, -COOH, -CONH2, substituted or unsubstituted C1-C4 alkyls, or substituted or unsubstituted 2-6 member heteroalkyls. In embodiments, R 4 Independently, R is a halogen, -OH, -CN, unsubstituted C1-C4 alkyl, or unsubstituted 2-6 member heteroalkyl. In the embodiment, R 4 These are independently -F, -OH, -CN, -OC(O)CH3, -C(O)N(CH3)2, unsubstituted methyl, unsubstituted ethyl, or unsubstituted methoxy.

[0227] In this embodiment, R 4 These are, independently, halogen, -C(O)NR 4A R 4B , substituted or unsubstituted C1-C4 alkyl, or unsubstituted 2-6 member heteroalkyl, where R 4A and R 4B This is described herein, including embodiments. In embodiments, R 4 R is independently -Cl, -C(O)N(CH3)2, -CH2CN, unsubstituted methyl, unsubstituted ethyl, or unsubstituted methoxy. In embodiments, R 4 These are independently -CN, -OR 4D , or -OC(O)R 4C And in the formula, R 4C and R 4D This is described herein, including embodiments. In embodiments, R 4 These are independently -CN, -OH, or -OC(O)CH3. In the embodiment, R 4 Independently, -C(O)NR4A R 4B And in the formula, R 4A and R 4B This is described herein, including embodiments. In embodiments, R 4 Independently, is -C(O)N(CH3)2. In the embodiment, R 4 -OC(O)R 4C And in the formula, R 4C This is described herein, including embodiments. In embodiments, R 4 This is independently -OC(O)CH3. In the embodiment, R 4 Independently,

[0228] [ka] That is the case.

[0229] In this embodiment, two R 4 The substituted ring formed when substituents are linked (e.g., substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) is substituted with at least one substituent, size-limited substituent, or lower substituent, and has two R 4 When the substituted ring formed by the linking of substituents is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may be optionally different. In this embodiment, two R 4 When a substituted ring formed by linking substituents is substituted, it is substituted with at least one substituent. In this embodiment, two R 4 When a substituted ring formed by linking substituents is substituted, it is substituted with at least one size-limited substituent. In the embodiment, two R 4 When a substituted ring formed by linking substituents is substituted, it is substituted with at least one lower substituent.

[0230] In this embodiment, two R 4The substituents link together to form substituted or unsubstituted 3- to 8-membered heterocycloalkyl groups. In the embodiment, two R 4 The substituents link together to form substituted or unsubstituted tetrahydrofuranils. In the embodiment, two R 4 The substituents link together to form substituted or unsubstituted pyrrolidinyl compounds. In the embodiment, two R 4 The substituents are linked together,

[0231] [ka] Forms. In this embodiment, two R 4 The substituents are linked together,

[0232] [ka] Forms. In this embodiment, two R 4 The substituents are linked together,

[0233] [ka] Forms. In this embodiment, two R 4 The substituents are linked together,

[0234] [ka] Forms. In this embodiment, two R 4 The substituents are linked together,

[0235] [ka] It forms.

[0236] In this embodiment, z4 is 0. In this embodiment, z4 is 1. In this embodiment, z4 is 2. In this embodiment, z4 is 3. In this embodiment, z4 is 4. In this embodiment, z4 is 5.

[0237] In the embodiment, substitution R4.2 (For example, substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and substituted R 4.2 However, if the group is substituted with multiple groups selected from substituents, size-restricting substituents, and lower substituents, each substituent, size-restricting substituent, and / or lower substituent may be optionally different. In the embodiment, R 4.2 When it is substituted, it is substituted with at least one substituent. In the embodiment, R 4.2 When it is substituted, it is substituted with at least one size-limited substituent. In the embodiment, R 4.2 When it is substituted, it is substituted with at least one lower substituent.

[0238] In the embodiment, substitution R 4.3 (For example, substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and substituted R 4.3 However, if the group is substituted with multiple groups selected from substituents, size-restricting substituents, and lower substituents, each substituent, size-restricting substituent, and / or lower substituent may be optionally different. In the embodiment, R 4.3 When it is substituted, it is substituted with at least one substituent. In the embodiment, R 4.3 When it is substituted, it is substituted with at least one size-limited substituent. In the embodiment, R 4.3 When it is substituted, it is substituted with at least one lower substituent.

[0239] In the embodiment, substitution R 4.4(For example, substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and substituted R 4.4 However, if the group is substituted with multiple groups selected from substituents, size-restricting substituents, and lower substituents, each substituent, size-restricting substituent, and / or lower substituent may be optionally different. In the embodiment, R 4.4 When it is substituted, it is substituted with at least one substituent. In the embodiment, R 4.4 When it is substituted, it is substituted with at least one size-limited substituent. In the embodiment, R 4.4 When it is substituted, it is substituted with at least one lower substituent.

[0240] In the embodiment, substitution R 4.5 (For example, substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and substituted R 4.5 However, if the group is substituted with multiple groups selected from substituents, size-restricting substituents, and lower substituents, each substituent, size-restricting substituent, and / or lower substituent may be optionally different. In the embodiment, R 4.5 When it is substituted, it is substituted with at least one substituent. In the embodiment, R 4.5 When it is substituted, it is substituted with at least one size-limited substituent. In the embodiment, R 4.5 When it is substituted, it is substituted with at least one lower substituent.

[0241] In this embodiment, R 4.2 , R 4.3 , R 4.4 , and R 4.5These are, independently, halogens, -CCl3, -CBr3, -CF3, -CI3, -CH2Cl, -CH2Br, -CH2F, -CH2I, -CHCl2, -CHBr2, -CHF2, -CHI2, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NH2, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl3, -OCBr3, -OCF3, -OCI3, -OCH2Cl, -OCH2Br, -OCH2F, -OCH2I, -OCHCl2, -OCHBr2, -OCHF2, -OCHI2, -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0242] In this embodiment, R 4.2 , R 4.3 , R 4.4 , and R 4.5 These are independently halogens, -CCl3, -CBr3, -CF3, -CI3, -CH2Cl, -CH2Br, -CH2F, -CH2I, -CHCl2, -CHBr2, -CHF2, -CHI2, -CN, -OH, -NH2, -COOH, -CONH2, substituted or unsubstituted C1-C4 alkyls, or substituted or unsubstituted 2-6 member heteroalkyls. In embodiments, R 4.2 , R 4.3 , R 4.4 , and R 4.5 Independently, R is a halogen, -OH, -CN, unsubstituted C1-C4 alkyl, or unsubstituted 2-6 member heteroalkyl. In the embodiment, R 4.2 , R 4.3 , R 4.4 , and R 4.5 These are independently -F, -OH, -CN, -C(O)N(CH3)2, unsubstituted methyl, unsubstituted ethyl, or unsubstituted methoxy.

[0243] In this embodiment, R 4.2 This is halogen, -C(O)NR 4A R4B , substituted or unsubstituted C1-C4 alkyl, or unsubstituted 2-6 member heteroalkyl, where R 4A and R 4B This is described herein, including embodiments. In embodiments, R 4.2 is -Cl, -C(O)N(CH3)2, -CH2CN, unsubstituted methyl, unsubstituted ethyl, or unsubstituted methoxy. In the embodiment, R 4.2 is -F. In this embodiment, R 4.2 is -Cl. In this embodiment, R 4.2 It is -CN.

[0244] In this embodiment, R 4.2 is -C(O)NR 4A R 4B And in the formula, R 4A and R 4B This is described herein, including embodiments. In embodiments, R 4.2 It is -C(O)N(CH3)2.

[0245] In this embodiment, R 4.3 -CN, -OR 4D , or -OC(O)R 4C And in the formula, R 4C and R 4D This is described herein, including embodiments. In embodiments, R 4.3 is -CN, -OH, or -OC(O)CH3. In the embodiment, R 4.3 It is -CN.

[0246] In this embodiment, R 4.4 is halogen, -OR 4D , an unsubstituted C1-C4 alkyl, or a substituted or unsubstituted 2-6 member heteroalkyl, where R 4D This is described herein, including embodiments. In embodiments, R 4.4 is -F. In this embodiment, R 4.4 is an unsubstituted methyl group. In this embodiment, R 4.4 is unsubstituted methoxy. In this embodiment, R 4.4is an unsubstituted ethoxy. In the embodiment, R 4.4 teeth,

[0247] [ka] In this embodiment, R 4.4 teeth,

[0248] [ka] In this embodiment, R 4.4 teeth,

[0249] [ka] That is the case.

[0250] In this embodiment, R 4.5 is a halogen, -OH, -OCHF2, unsubstituted C1-C4 alkyl, or substituted or unsubstituted 2-6 member heteroalkyl. In the embodiment, R 4.5 is -F. In this embodiment, R 4.5 is -OH. In the embodiment, R 4.5 is -OCHF2. In the embodiment, R 4.5 is an unsubstituted methyl group. In this embodiment, R 4.5 is unsubstituted methoxy. In this embodiment, R 4.5 teeth,

[0251] [ka] In this embodiment, R 4.5 teeth,

[0252] [ka] That is the case.

[0253] In the embodiment of formula (VI), R 4.2 is -C(O)N(CH3)2 or unsubstituted ethyl, where R 4.3It is -OH.

[0254] In the embodiment of formula (VII), R 4.2 It is -CH3, and R 4.3 is -CN, R 4.5 It is -OCH3.

[0255] In the embodiment of formula (VIII), R 4.2 It is -CH3, and R 4.3 is -CN, and R 4.4 It is -OCH3.

[0256] In this embodiment, R 4.2 and R 4.3 The substituted ring formed when substituents are linked (e.g., substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) is substituted with at least one substituent, size-limited substituent, or lower substituent, R 4.2 and R 4.3 When the substituted ring formed when substituents are linked is substituted with multiple groups selected from substituents, size-restricting substituents, and lower substituents, each substituent, size-restricting substituent, and / or lower substituent may be optionally different. In the embodiment, R 4.2 and R 4.3 When a substituted ring formed by linking substituents is substituted, it is substituted by at least one substituent. In the embodiment, R 4.2 and R 4.3 When a substituted ring formed by linking substituents is substituted, it is substituted with at least one size-limited substituent. In the embodiment, R 4.2 and R 4.3 When a substituted ring formed by linking substituents is substituted, it is substituted with at least one lower substituent.

[0257] In this embodiment, R 4.3 and R 4.4The substituted ring formed when substituents are linked (e.g., substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) is substituted with at least one substituent, size-limited substituent, or lower substituent, R 4.3 and R 4.4 When the substituted ring formed when substituents are linked is substituted with multiple groups selected from substituents, size-restricting substituents, and lower substituents, each substituent, size-restricting substituent, and / or lower substituent may be optionally different. In the embodiment, R 4.3 and R 4.4 When a substituted ring formed by linking substituents is substituted, it is substituted by at least one substituent. In the embodiment, R 4.3 and R 4.4 When a substituted ring formed by linking substituents is substituted, it is substituted with at least one size-limited substituent. In the embodiment, R 4.3 and R 4.4 When a substituted ring formed by linking substituents is substituted, it is substituted with at least one lower substituent.

[0258] In this embodiment, R 4.2 and R 4.3 The substituents link together to form substituted or unsubstituted 3- to 8-membered heterocycloalkyl groups. In the embodiment, R 4.2 and R 4.3 The substituents link together to form substituted or unsubstituted tetrahydrofuranils. In the embodiment, R 4.2 and R 4.3 The substituents link together to form substituted or unsubstituted pyrrolidinyl compounds. In the embodiment, R 4.2 and R 4.3 The substituents are linked together,

[0259] [ka] Forms R 4.2 and R 4.3 The substituents are linked together,

[0260] [ka] Forms R 4.2 and R 4.3 The substituents are linked together,

[0261] [ka] Forms R 4.2 and R 4.3 The substituents are linked together,

[0262] [ka] Forms R 4.2 and R 4.3 The substituents are linked together,

[0263] [ka] It forms.

[0264] In this embodiment, R 4.3 and R 4.4 The substituents link together to form substituted or unsubstituted 3- to 8-membered heterocycloalkyl groups. In the embodiment, R 4.3 and R 4.4 The substituents link together to form substituted or unsubstituted tetrahydrofuranils. In the embodiment, R 4.3 and R 4.4 The substituents link together to form substituted or unsubstituted pyrrolidinyl compounds. In the embodiment, R 4.3 and R 4.4 The substituents are linked together,

[0265] [ka] Forms R 4.3 and R 4.4 The substituents are linked together,

[0266] [ka] Forms R 4.3 and R 4.4 The substituents are linked together,

[0267] [ka] Forms R 4.3 and R 4.4 The substituents are linked together,

[0268] [ka] Forms R 4.3 and R 4.4 The substituents are linked together,

[0269] [ka] It forms.

[0270] In the embodiment, substitution R 5 (For example, substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and substituted R 5 However, if the group is substituted with multiple groups selected from substituents, size-restricting substituents, and lower substituents, each substituent, size-restricting substituent, and / or lower substituent may be optionally different. In the embodiment, R 5 When it is substituted, it is substituted with at least one substituent. In the embodiment, R 5 When it is substituted, it is substituted with at least one size-limited substituent. In the embodiment, R 5 When it is substituted, it is substituted with at least one lower substituent.

[0271] In the embodiment, substitution R 5A(For example, substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and substituted R 5A However, if the group is substituted with multiple groups selected from substituents, size-restricting substituents, and lower substituents, each substituent, size-restricting substituent, and / or lower substituent may be optionally different. In the embodiment, R 5A When it is substituted, it is substituted with at least one substituent. In the embodiment, R 5A When it is substituted, it is substituted with at least one size-limited substituent. In the embodiment, R 5A When it is substituted, it is substituted with at least one lower substituent.

[0272] In the embodiment, substitution R 5B (For example, substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and substituted R 5B However, if the group is substituted with multiple groups selected from substituents, size-restricting substituents, and lower substituents, each substituent, size-restricting substituent, and / or lower substituent may be optionally different. In the embodiment, R 5B When it is substituted, it is substituted with at least one substituent. In the embodiment, R 5B When it is substituted, it is substituted with at least one size-limited substituent. In the embodiment, R 5B When it is substituted, it is substituted with at least one lower substituent.

[0273] In this embodiment, R bonded to the same nitrogen atom 5A and R 5BThe substituted ring formed when substituents are linked (e.g., substituted heterocycloalkyl and / or substituted heteroaryl) is substituted with at least one substituent, size-limited substituent, or lower substituent, and R is bonded to the same nitrogen atom. 5A and R 5B When the substituted ring formed by the linking of substituents is substituted with multiple groups selected from substituents, size-limiting substituents, and lower substituents, each substituent, size-limiting substituent, and / or lower substituent may be optionally different. In this embodiment, R bonded to the same nitrogen atom 5A and R 5B When a substituted ring is formed when substituents are linked, it is substituted by at least one substituent. In this embodiment, R bonded to the same nitrogen atom 5A and R 5B When a substituted ring is formed when substituents are linked, it is substituted with at least one size-limited substituent. In the embodiment, R bonded to the same nitrogen atom 5A and R 5B When a substituted ring is formed by linking substituents, it is substituted with at least one lower substituent.

[0274] In the embodiment, substitution R 5C (For example, substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and substituted R 5C However, if the group is substituted with multiple groups selected from substituents, size-restricting substituents, and lower substituents, each substituent, size-restricting substituent, and / or lower substituent may be optionally different. In the embodiment, R 5C When it is substituted, it is substituted with at least one substituent. In the embodiment, R 5C When it is substituted, it is substituted with at least one size-limited substituent. In the embodiment, R 5C When it is substituted, it is substituted with at least one lower substituent.

[0275] In the embodiment, substitution R 5D (For example, substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and substituted R 5D However, if the group is substituted with multiple groups selected from substituents, size-restricting substituents, and lower substituents, each substituent, size-restricting substituent, and / or lower substituent may be optionally different. In the embodiment, R 5D When it is substituted, it is substituted with at least one substituent. In the embodiment, R 5D When it is substituted, it is substituted with at least one size-limited substituent. In the embodiment, R 5D When it is substituted, it is substituted with at least one lower substituent.

[0276] In this embodiment, R 5A R is independently hydrogen. In this embodiment, R 5A These are independently unsubstituted C1-C4 alkyl groups. In the embodiment, R 5A R is independently an unsubstituted methyl group. In this embodiment, R 5A R is independently unsubstituted ethyl. In the embodiment, R 5A R is independently unsubstituted propyl. In the embodiment, R 5A R is independently unsubstituted n-propyl. In the embodiment, R 5A R is independently an unsubstituted isopropyl. In the embodiment, R 5A R is independently unsubstituted butyl. In this embodiment, R 5A R is independently unsubstituted n-butyl. In the embodiment, R 5A R is independently an unsubstituted isobutyl. In the embodiment, R 5A This is independently unsubstituted tert-butyl.

[0277] In this embodiment, R 5B R is independently hydrogen. In this embodiment, R 5BThese are independently unsubstituted C1-C4 alkyl groups. In the embodiment, R 5B R is independently an unsubstituted methyl group. In this embodiment, R 5B R is independently unsubstituted ethyl. In the embodiment, R 5B R is independently unsubstituted propyl. In the embodiment, R 5B R is independently unsubstituted n-propyl. In the embodiment, R 5B R is independently an unsubstituted isopropyl. In the embodiment, R 5B R is independently unsubstituted butyl. In this embodiment, R 5B R is independently unsubstituted n-butyl. In the embodiment, R 5B R is independently an unsubstituted isobutyl. In the embodiment, R 5B This is independently unsubstituted tert-butyl.

[0278] In this embodiment, R 5C R is independently hydrogen. In this embodiment, R 5C These are independently unsubstituted C1-C4 alkyl groups. In the embodiment, R 5C R is independently an unsubstituted methyl group. In this embodiment, R 5C R is independently unsubstituted ethyl. In the embodiment, R 5C R is independently unsubstituted propyl. In the embodiment, R 5C R is independently unsubstituted n-propyl. In the embodiment, R 5C R is independently an unsubstituted isopropyl. In the embodiment, R 5C R is independently unsubstituted butyl. In this embodiment, R 5C R is independently unsubstituted n-butyl. In the embodiment, R 5C R is independently an unsubstituted isobutyl. In the embodiment, R 5C This is independently unsubstituted tert-butyl.

[0279] In this embodiment, R 5D R is independently hydrogen. In this embodiment, R 5D These are independently unsubstituted C1-C4 alkyl groups. In the embodiment, R 5DR is independently an unsubstituted methyl group. In this embodiment, R 5D R is independently unsubstituted ethyl. In the embodiment, R 5D R is independently unsubstituted propyl. In the embodiment, R 5D R is independently unsubstituted n-propyl. In the embodiment, R 5D R is independently an unsubstituted isopropyl. In the embodiment, R 5D R is independently unsubstituted butyl. In this embodiment, R 5D R is independently unsubstituted n-butyl. In the embodiment, R 5D R is independently an unsubstituted isobutyl. In the embodiment, R 5D This is independently unsubstituted tert-butyl.

[0280] In this embodiment, R 5 These are, independently, halogens, -CCl3, -CBr3, -CF3, -CI3, -CH2Cl, -CH2Br, -CH2F, -CH2I, -CHCl2, -CHBr2, -CHF2, -CHI2, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NH2, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl3, -OCBr3, -OCF3, -OCI3, -OCH2Cl, -OCH2Br, -OCH2F, -OCH2I, -OCHCl2, -OCHBr2, -OCHF2, -OCHI2, -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0281] In this embodiment, R 5These are independently halogens, -CCl3, -CBr3, -CF3, -CI3, -CH2Cl, -CH2Br, -CH2F, -CH2I, -CHCl2, -CHBr2, -CHF2, -CHI2, -CN, -OH, -NH2, -COOH, -CONH2, substituted or unsubstituted C1-C4 alkyls, or substituted or unsubstituted 2-6 member heteroalkyls.

[0282] In this embodiment, R 5 In this embodiment, R 5 Independently, is -F. In the embodiment, R 5 In this embodiment, R 5 Independently, is -Br. In the embodiment, R 5 Independently, is -I. In the embodiment, R 5 In this embodiment, R 5 Independently, is -CBr3. In the embodiment, R 5 In this embodiment, R 5 In this embodiment, R 5 Independently, is -CH2Cl. In the embodiment, R 5 Independently, is -CH2Br. In the embodiment, R 5 Independently, is -CH2F. In the embodiment, R 5 In this embodiment, R 5 is independently -CHCl2. In the embodiment, R 5 Independently, is -CHBr2. In the embodiment, R 5 In this embodiment, R 5 Independently, is -CHI2. In the embodiment, R 5 Independently, is -CN. In the embodiment, R 5 In this embodiment, R 5 In this embodiment, R 5 It is independently -COOH. In the embodiment, R 5Independently, is -CONH2. In the embodiment, R 5 In this embodiment, R 5 In this embodiment, R 5 It is independently -SO3H. In the embodiment, R 5 Independently, is -OSO3H. In the embodiment, R 5 Independently, is -SO2NH2. In the embodiment, R 5 Independently, is -NHNH2. In the embodiment, R 5 In this embodiment, R 5 This is independently -NHC(O)NH2. In the embodiment, R 5 This is independently -NHSO2H. In the embodiment, R 5 In this embodiment, R 5 This is independently -NHC(O)OH. In the embodiment, R 5 In this embodiment, R 5 Independently, is -OCCl3. In the embodiment, R 5 Independently, is -OCBr3. In the embodiment, R 5 Independently, is -OCF3. In the embodiment, R 5 In this embodiment, R 5 Independently, is -OCH2Cl. In the embodiment, R 5 Independently, is -OCH2Br. In the embodiment, R 5 Independently, is -OCH2F. In the embodiment, R 5 Independently, is -OCH2I. In the embodiment, R 5 is independently -OCHCl2. In the embodiment, R 5 Independently, is -OCHBr2. In the embodiment, R 5 Independently, is -OCHF2. In the embodiment, R 5 Independently, is -OCHI2. In the embodiment, R 5 In this embodiment, R 5Independently, is -N3. In the embodiment, R 5 These are independently unsubstituted C1-C4 alkyl groups. In the embodiment, R 5 R is independently an unsubstituted methyl group. In this embodiment, R 5 R is independently unsubstituted ethyl. In the embodiment, R 5 R is independently unsubstituted propyl. In the embodiment, R 5 R is independently unsubstituted n-propyl. In the embodiment, R 5 R is independently an unsubstituted isopropyl. In the embodiment, R 5 R is independently unsubstituted butyl. In this embodiment, R 5 R is independently unsubstituted n-butyl. In the embodiment, R 5 R is independently an unsubstituted isobutyl. In the embodiment, R 5 R is independently unsubstituted tert-butyl. In the embodiment, R 5 These are independently unsubstituted 2-6 member heteroalkyl groups. In the embodiment, R 5 R is independently an unsubstituted methoxy compound. In this embodiment, R 5 R is independently an unsubstituted ethoxy. In this embodiment, R 5 R is independently an unsubstituted propoxy. In this embodiment, R 5 R is independently an unsubstituted n-propoxy. In this embodiment, R 5 R is independently an unsubstituted isopropoxy. In the embodiment, R 5 It is independently an unsubstituted butoxy.

[0283] In this embodiment, z5 is 0. In this embodiment, z5 is 1. In this embodiment, z5 is 2. In this embodiment, z5 is 3. In this embodiment, z5 is 4. In this embodiment, z5 is 5.

[0284] In the embodiment, substitution R 6(For example, substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, and / or substituted heteroaryl) are substituted with at least one substituent, size-limited substituent, or lower substituent, and substituted R 6 However, if the group is substituted with multiple groups selected from substituents, size-restricting substituents, and lower substituents, each substituent, size-restricting substituent, and / or lower substituent may be optionally different. In the embodiment, R 6 When it is substituted, it is substituted with at least one substituent. In the embodiment, R 6 When it is substituted, it is substituted with at least one size-limited substituent. In the embodiment, R 6 When it is substituted, it is substituted with at least one lower substituent.

[0285] In this embodiment, R 6 These are halogens, -CCl3, -CBr3, -CF3, -CI3, -CH2Cl, -CH2Br, -CH2F, -CH2I, -CHCl2, -CHBr2, -CHF2, -CHI2, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NH2, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH -OCCl3, -OCBr3, -OCF3, -OCI3, -OCH2Cl, -OCH2Br, -OCH2F, -OCH2I, -OCHCl2, -OCHBr2, -OCHF2, -OCHI2, -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted aryl, or substituted or unsubstituted heteroaryl.

[0286] In this embodiment, R 6 is hydrogen. In this embodiment, R 6 is a halogen. In this embodiment, R 6 is -F. In this embodiment, R 6 is -Cl. In this embodiment, R6 is -Br. In the embodiment, R 6 is -I. In the embodiment, R 6 is -CCl3. In the embodiment, R 6 is -CBr3. In the embodiment, R 6 is -CF3. In the embodiment, R 6 is -CI3. In the embodiment, R 6 is -CH2Cl. In the embodiment, R 6 is -CH2Br. In the embodiment, R 6 is -CH2F. In the embodiment, R 6 is -CH2I. In the embodiment, R 6 is -CHCl2. In the embodiment, R 6 is -CHBr2. In the embodiment, R 6 is -CHF2. In the embodiment, R 6 is -CHI2. In the embodiment, R 6 is -CN. In the embodiment, R 6 is -OH. In the embodiment, R 6 is -NH2. In the embodiment, R 6 is -COOH. In the embodiment, R 6 is -CONH2. In the embodiment, R 6 is -NO2. In the embodiment, R 6 is -SH. In the embodiment, R 6 is -SO3H. In the embodiment, R 6 is -OSO3H. In the embodiment, R 6 is -SO2NH2. In the embodiment, R 6 is -NHNH2. In the embodiment, R 6 is -ONH2. In the embodiment, R 6 This is -NHC(O)NH2. In the embodiment, R 6 is -NHSO2H. In the embodiment, R 6 is -NHC(O)H. In the embodiment, R 6 is -NHC(O)OH. In the embodiment, R 6 is -NHOH. In the embodiment, R6 is -OCCl3. In the embodiment, R 6 is -OCBr3. In the embodiment, R 6 is -OCF3. In the embodiment, R 6 is -OCI3. In the embodiment, R 6 is -OCH2Cl. In the embodiment, R 6 is -OCH2Br. In the embodiment, R 6 is -OCH2F. In the embodiment, R 6 is -OCH2I. In the embodiment, R 6 is -OCHCl2. In the embodiment, R 6 is -OCHBr2. In the embodiment, R 6 is -OCHF2. In the embodiment, R 6 is -OCHI2. In the embodiment, R 6 is an unsubstituted C1-C4 alkyl group. In the embodiment, R 6 is an unsubstituted methyl group. In this embodiment, R 6 is unsubstituted ethyl. In the embodiment, R 6 is unsubstituted propyl. In the embodiment, R 6 is unsubstituted n-propyl. In the embodiment, R 6 is an unsubstituted isopropyl. In the embodiment, R 6 is unsubstituted butyl. In the embodiment, R 6 is unsubstituted n-butyl. In the embodiment, R 6 is unsubstituted isobutyl. In this embodiment, R 6 It is unsubstituted tert-butyl.

[0287] In this embodiment, R 1 When R is substituted, 1 As described in the definition section above under “first substituent”, R 1.1 It is substituted with one or more first substituents represented by R. In the embodiment, R 1.1 When a substituent is substituted, R 1.1 The substituents are as described in the section on “first substituents” in the definition section above, R1.2 It is substituted with one or more second substituents represented by R. In the embodiment, R 1.2 When a substituent is substituted, R 1.2 The substituents are as described in the section on “first substituents” in the definition section above, R 1.3 It is substituted with one or more third substituents represented by . In the above embodiment, R 1 , R 1.1 , R 1.2 , and R 1.3 As described in the definition section above under “First substituent”, each of them is R WW , R WW.1 , R WW.2 , and R WW.3 It has a value corresponding to the value of R WW , R WW.1 , R WW.2 , and R WW.3 These are, respectively, R 1 , R 1.1 , R 1.2 , and R 1.3 It corresponds to.

[0288] In this embodiment, R 2 When R is substituted, 2 As described in the definition section above under “first substituent”, R 2.1 It is substituted with one or more first substituents represented by R. In the embodiment, R 2.1 When a substituent is substituted, R 2.1 The substituents are as described in the section on “first substituents” in the definition section above, R 2.2 It is substituted with one or more second substituents represented by R. In the embodiment, R 2.2 When a substituent is substituted, R 2.2 The substituents are as described in the section on “first substituents” in the definition section above, R 2.3 It is substituted with one or more third substituents represented by . In the above embodiment, R 2 , R 2.1 , R 2.2 , and R 2.3As described in the definition section above under “First substituent”, each of them is R WW , R WW.1 , R WW.2 , and R WW.3 It has a value corresponding to the value of R WW , R WW.1 , R WW.2 , and R WW.3 These are, respectively, R 2 , R 2.1 , R 2.2 , and R 2.3 It corresponds to.

[0289] In this embodiment, R bonded to the same nitrogen atom 1 and R 2 When substituents are optionally linked to form a substituted moiety (e.g., a substituted heterocycloalkyl or substituted heteroaryl), that moiety is as described in the definition section above under “First substituent,” R 1.1 It is substituted with one or more first substituents represented by R. In the embodiment, R 1.1 When a substituent is substituted, R 1.1 The substituents are as described in the section on “first substituents” in the definition section above, R 1.2 It is substituted with one or more second substituents represented by R. In the embodiment, R 1.2 When a substituent is substituted, R 1.2 The substituents are as described in the section on “first substituents” in the definition section above, R 1.3 It is substituted with one or more third substituents represented by . In the above embodiment, R 1.1 , R 1.2 , and R 1.3 As described in the definition section above under “First substituent”, each of them is R WW.1 , R WW.2 , and R WW.3 It has a value corresponding to the value of R WW.1 , R WW.2 , and R WW.3 These are, respectively, R 1.1 , R 1.2 , and R1.3 It corresponds to.

[0290] In this embodiment, R bonded to the same nitrogen atom 1 and R 2 When substituents are optionally linked to form a substituted moiety (e.g., a substituted heterocycloalkyl or substituted heteroaryl), that moiety is as described in the definition section above under “First substituent,” R 2.1 It is substituted with one or more first substituents represented by R. In the embodiment, R 2.1 When a substituent is substituted, R 2.1 The substituents are as described in the section on “first substituents” in the definition section above, R 2.2 It is substituted with one or more second substituents represented by R. In the embodiment, R 2.2 When a substituent is substituted, R 2.2 The substituents are as described in the section on “first substituents” in the definition section above, R 2.3 It is substituted with one or more third substituents represented by . In the above embodiment, R 2.1 , R 2.2 , and R 2.3 As described in the definition section above under “First substituent”, each of them is R WW.1 , R WW.2 , and R WW.3 It has a value corresponding to the value of R WW.1 , R WW.2 , and R WW.3 These are, respectively, R 2.1 , R 2.2 , and R 2.3 It corresponds to.

[0291] In this embodiment, R 3 When R is substituted, 3 As described in the definition section above under “first substituent”, R 3.1 It is substituted with one or more first substituents represented by R. In the embodiment, R 3.1 When a substituent is substituted, R 3.1The substituents are as described in the section on “first substituents” in the definition section above, R 3.2 It is substituted with one or more second substituents represented by R. In the embodiment, R 3.2 When a substituent is substituted, R 3.2 The substituents are as described in the section on “first substituents” in the definition section above, R 3.3 It is substituted with one or more third substituents represented by . In the above embodiment, R 3 , R 3.1 , R 3.2 , and R 3.3 As described in the definition section above under “First substituent”, each of them is R WW , R WW.1 , R WW.2 , and R WW.3 It has a value corresponding to the value of R WW , R WW.1 , R WW.2 , and R WW.3 These are, respectively, R 3 , R 3.1 , R 3.2 , and R 3.3 It corresponds to.

[0292] In this embodiment, R 4 When R is substituted, 4 As described in the definition section above under “first substituent”, R 4.1 It is substituted with one or more first substituents represented by R. In the embodiment, R 4.1 When a substituent is substituted, R 4.1 The substituents are as described in the section on “first substituents” in the definition section above, R 4.2 It is substituted with one or more second substituents represented by R. In the embodiment, R 4.2 When a substituent is substituted, R 4.2 The substituents are as described in the section on “first substituents” in the definition section above, R 4.3 It is substituted with one or more third substituents represented by . In the above embodiment, R 4 , R4.1 , R 4.2 , and R 4.3 As described in the definition section above under “First substituent”, each of them is R WW , R WW.1 , R WW.2 , and R WW.3 It has a value corresponding to the value of R WW , R WW.1 , R WW.2 , and R WW.3 These are, respectively, R 4 , R 4.1 , R 4.2 , and R 4.3 It corresponds to.

[0293] In this embodiment, two R 4 When substituents are optionally linked to form a substituted moiety (e.g., a substituted cycloalkyl, a substituted heterocycloalkyl, a substituted aryl, or a substituted heteroaryl), that moiety is defined as R as described in the definition paragraph above in the description of “first substituent”. 4.1 It is substituted with one or more first substituents represented by R. In the embodiment, R 4.1 When a substituent is substituted, R 4.1 The substituents are as described in the section on “first substituents” in the definition section above, R 4.2 It is substituted with one or more second substituents represented by R. In the embodiment, R 4.2 When a substituent is substituted, R 4.2 The substituents are as described in the section on “first substituents” in the definition section above, R 4.3 It is substituted with one or more third substituents represented by . In the above embodiment, R 4 , R 4.1 , R 4.2 , and R 4.3 As described in the definition section above under “First substituent”, each of them is R WW , R WW.1 , R WW.2 , and R WW.3 It has a value corresponding to the value of R WW , R WW.1, R WW.2 , and R WW.3 These are, respectively, R 4 , R 4.1 , R 4.2 , and R 4.3 It corresponds to.

[0294] In this embodiment, R 4.2 When R is substituted, 4.2 As described in the definition section above under “first substituent”, R 4.2.1 It is substituted with one or more first substituents represented by R. In the embodiment, R 4.2.1 When a substituent is substituted, R 4.2.1 The substituents are as described in the section on “first substituents” in the definition section above, R 4.2.2 It is substituted with one or more second substituents represented by R. In the embodiment, R 4.2.2 When a substituent is substituted, R 4.2.2 The substituents are as described in the section on “first substituents” in the definition section above, R 4.2.3 It is substituted with one or more third substituents represented by . In the above embodiment, R 4.2 , R 4.2.1 , R 4.2.2 , and R 4.2.3 As described in the definition section above under “First substituent”, each of them is R WW , R WW.1 , R WW.2 , and R WW.3 It has a value corresponding to the value of R WW , R WW.1 , R WW.2 , and R WW.3 These are, respectively, R 4.2 , R 4.2.1 , R 4.2.2 , and R 4.2.3 It corresponds to.

[0295] In this embodiment, R 4.3 When R is substituted, 4.3 As described in the definition section above under “first substituent”, R 4.3.1It is substituted with one or more first substituents represented by R. In the embodiment, R 4.3.1 When a substituent is substituted, R 4.3.1 The substituents are as described in the section on “first substituents” in the definition section above, R 4.3.2 It is substituted with one or more second substituents represented by R. In the embodiment, R 4.3.2 When a substituent is substituted, R 4.3.2 The substituents are as described in the section on “first substituents” in the definition section above, R 4.3.3 It is substituted with one or more third substituents represented by . In the above embodiment, R 4.3 , R 4.3.1 , R 4.3.2 , and R 4.3.3 As described in the definition section above under “First substituent”, each of them is R WW , R WW.1 , R WW.2 , and R WW.3 It has a value corresponding to the value of R WW , R WW.1 , R WW.2 , and R WW.3 These are, respectively, R 4.3 , R 4.3.1 , R 4.3.2 , and R 4.3.3 It corresponds to.

[0296] In this embodiment, R 4.4 When R is substituted, 4.4 As described in the definition section above under “first substituent”, R 4.4.1 It is substituted with one or more first substituents represented by R. In the embodiment, R 4.4.1 When a substituent is substituted, R 4.4.1 The substituents are as described in the section on “first substituents” in the definition section above, R 4.4.2 It is substituted with one or more second substituents represented by R. In the embodiment, R 4.4.2 When a substituent is substituted, R 4.4.2The substituents are as described in the section on “first substituents” in the definition section above, R 4.4.3 It is substituted with one or more third substituents represented by . In the above embodiment, R 4.4 , R 4.4.1 , R 4.4.2 , and R 4.4.3 As described in the definition section above under “First substituent”, each of them is R WW , R WW.1 , R WW.2 , and R WW.3 It has a value corresponding to the value of R WW , R WW.1 , R WW.2 , and R WW.3 These are, respectively, R 4.4 , R 4.4.1 , R 4.4.2 , and R 4.4.3 It corresponds to.

[0297] In this embodiment, R 4.5 When R is substituted, 4.5 As described in the definition section above under “first substituent”, R 4.5.1 It is substituted with one or more first substituents represented by R. In the embodiment, R 4.5.1 When a substituent is substituted, R 4.5.1 The substituents are as described in the section on “first substituents” in the definition section above, R 4.5.2 It is substituted with one or more second substituents represented by R. In the embodiment, R 4.5.2 When a substituent is substituted, R 4.5.2 The substituents are as described in the section on “first substituents” in the definition section above, R 4.5.3 It is substituted with one or more third substituents represented by . In the above embodiment, R 4.5 , R 4.5.1 , R 4.5.2 , and R 4.5.3 As described in the definition section above under “First substituent”, each of them is R WW , R WW.1 , R WW.2, and R WW.3 It has a value corresponding to the value of R WW , R WW.1 , R WW.2 , and R WW.3 These are, respectively, R 4.5 , R 4.5.1 , R 4.5.2 , and R 4.5.3 It corresponds to.

[0298] In this embodiment, R 4.2 and R 4.3 When substituents are optionally linked to form a substituted moiety (e.g., a substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, or substituted heteroaryl), that moiety is as described in the "first substituent" section above, R 4.2.1 It is substituted with one or more first substituents represented by R. In the embodiment, R 4.2.1 When a substituent is substituted, R 4.2.1 The substituents are as described in the section on “first substituents” in the definition section above, R 4.2.2 It is substituted with one or more second substituents represented by R. In the embodiment, R 4.2.2 When a substituent is substituted, R 4.2.2 The substituents are as described in the section on “first substituents” in the definition section above, R 4.2.3 It is substituted with one or more third substituents represented by . In the above embodiment, R 4.2.1 , R 4.2.2 , and R 4.2.3 As described in the definition section above under “First substituent”, each of them is R WW.1 , R WW.2 , and R WW.3 It has a value corresponding to the value of R WW.1 , R WW.2 , and R WW.3 These are, respectively, R 4.2.1 , R 4.2.2 , and R 4.2.3 It corresponds to.

[0299] In this embodiment, R 4.2 and R4.3 When substituents are optionally linked to form a substituted moiety (e.g., a substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, or substituted heteroaryl), that moiety is as described in the "first substituent" section above, R 4.3.1 It is substituted with one or more first substituents represented by R. In the embodiment, R 4.3.1 When a substituent is substituted, R 4.3.1 The substituents are as described in the section on “first substituents” in the definition section above, R 4.3.2 It is substituted with one or more second substituents represented by R. In the embodiment, R 4.3.2 When a substituent is substituted, R 4.3.2 The substituents are as described in the section on “first substituents” in the definition section above, R 4.3.3 It is substituted with one or more third substituents represented by . In the above embodiment, R 4.3.1 , R 4.3.2 , and R 4.3.3 As described in the definition section above under “First substituent”, each of them is R WW.1 , R WW.2 , and R WW.3 It has a value corresponding to the value of R WW.1 , R WW.2 , and R WW.3 These are, respectively, R 4.3.1 , R 4.3.2 , and R 4.3.3 It corresponds to.

[0300] In this embodiment, R 4.3 and R 4.4 When substituents are optionally linked to form a substituted moiety (e.g., a substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, or substituted heteroaryl), that moiety is as described in the "first substituent" section above, R 4.3.1 It is substituted with one or more first substituents represented by R. In the embodiment, R 4.3.1 When a substituent is substituted, R 4.3.1The substituents are as described in the section on “first substituents” in the definition section above, R 4.3.2 It is substituted with one or more second substituents represented by R. In the embodiment, R 4.3.2 When a substituent is substituted, R 4.3.2 The substituents are as described in the section on “first substituents” in the definition section above, R 4.3.3 It is substituted with one or more third substituents represented by . In the above embodiment, R 4.3.1 , R 4.3.2 , and R 4.3.3 As described in the definition section above under “First substituent”, each of them is R WW.1 , R WW.2 , and R WW.3 It has a value corresponding to the value of R WW.1 , R WW.2 , and R WW.3 These are, respectively, R 4.3.1 , R 4.3.2 , and R 4.3.3 It corresponds to.

[0301] In this embodiment, R 4.3 and R 4.4 When substituents are optionally linked to form a substituted moiety (e.g., a substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, or substituted heteroaryl), that moiety is as described in the "first substituent" section above, R 4.4.1 It is substituted with one or more first substituents represented by R. In the embodiment, R 4.4.1 When a substituent is substituted, R 4.4.1 The substituents are as described in the section on “first substituents” in the definition section above, R 4.4.2 It is substituted with one or more second substituents represented by R. In the embodiment, R 4.4.2 When a substituent is substituted, R 4.4.2 The substituents are as described in the section on “first substituents” in the definition section above, R 4.4.3 It is substituted with one or more third substituents represented by . In the above embodiment, R4.4.1 , R 4.4.2 , and R 4.4.3 As described in the definition section above under “First substituent”, each of them is R WW.1 , R WW.2 , and R WW.3 It has a value corresponding to the value of R WW.1 , R WW.2 , and R WW.3 These are, respectively, R 4.4.1 , R 4.4.2 , and R 4.4.3 It corresponds to.

[0302] In this embodiment, R 4A When R is substituted, 4A As described in the definition section above under “first substituent”, R 4A.1 It is substituted with one or more first substituents represented by R. In the embodiment, R 4A.1 When a substituent is substituted, R 4A.1 The substituents are as described in the section on “first substituents” in the definition section above, R 4A.2 It is substituted with one or more second substituents represented by R. In the embodiment, R 4A.2 When a substituent is substituted, R 4A.2 The substituents are as described in the section on “first substituents” in the definition section above, R 4A.3 It is substituted with one or more third substituents represented by . In the above embodiment, R 4A , R 4A.1 , R 4A.2 , and R 4A.3 As described in the definition section above under “First substituent”, each of them is R WW , R WW.1 , R WW.2 , and R WW.3 It has a value corresponding to the value of R WW , R WW.1 , R WW.2 , and R WW.3 These are, respectively, R 4A , R 4A.1 , R 4A.2 , and R 4A.3It corresponds to.

[0303] In this embodiment, R 4B When R is substituted, 4B As described in the definition section above under “first substituent”, R 4B.1 It is substituted with one or more first substituents represented by R. In the embodiment, R 4B.1 When a substituent is substituted, R 4B.1 The substituents are as described in the section on “first substituents” in the definition section above, R 4B.2 It is substituted with one or more second substituents represented by R. In the embodiment, R 4B.2 When a substituent is substituted, R 4B.2 The substituents are as described in the section on “first substituents” in the definition section above, R 4B.3 It is substituted with one or more third substituents represented by . In the above embodiment, R 4B , R 4B.1 , R 4B.2 , and R 4B.3 As described in the definition section above under “First substituent”, each of them is R WW , R WW.1 , R WW.2 , and R WW.3 It has a value corresponding to the value of R WW , R WW.1 , R WW.2 , and R WW.3 These are, respectively, R 4B , R 4B.1 , R 4B.2 , and R 4B.3 It corresponds to.

[0304] In this embodiment, R bonded to the same nitrogen atom 4A and R 4B When substituents are optionally linked to form a substituted moiety (e.g., a substituted heterocycloalkyl or substituted heteroaryl), that moiety is as described in the definition section above under “First substituent,” R 4A.1 It is substituted with one or more first substituents represented by R. In the embodiment, R4A.1 When a substituent is substituted, R 4A.1 The substituents are as described in the section on “first substituents” in the definition section above, R 4A.2 It is substituted with one or more second substituents represented by R. In the embodiment, R 4A.2 When a substituent is substituted, R 4A.2 The substituents are as described in the section on “first substituents” in the definition section above, R 4A.3 It is substituted with one or more third substituents represented by . In the above embodiment, R 4A.1 , R 4A.2 , and R 4A.3 As described in the definition section above under “First substituent”, each of them is R WW.1 , R WW.2 , and R WW.3 It has a value corresponding to the value of R WW.1 , R WW.2 , and R WW.3 These are, respectively, R 4A.1 , R 4A.2 , and R 4A.3 It corresponds to.

[0305] In this embodiment, R bonded to the same nitrogen atom 4A and R 4B When substituents are optionally linked to form a substituted moiety (e.g., a substituted heterocycloalkyl or substituted heteroaryl), that moiety is as described in the definition section above under “First substituent,” R 4B.1 It is substituted with one or more first substituents represented by R. In the embodiment, R 4B.1 When a substituent is substituted, R 4B.1 The substituents are as described in the section on “first substituents” in the definition section above, R 4B.2 It is substituted with one or more second substituents represented by R. In the embodiment, R 4B.2 When a substituent is substituted, R 4B.2 The substituents are as described in the section on “first substituents” in the definition section above, R 4B.3It is substituted with one or more third substituents represented by . In the above embodiment, R 4B.1 , R 4B.2 , and R 4B.3 As described in the definition section above under “First substituent”, each of them is R WW.1 , R WW.2 , and R WW.3 It has a value corresponding to the value of R WW.1 , R WW.2 , and R WW.3 These are, respectively, R 4B.1 , R 4B.2 , and R 4B.3 It corresponds to.

[0306] In this embodiment, R 4C When R is substituted, 4C As described in the definition section above under “first substituent”, R 4C.1 It is substituted with one or more first substituents represented by R. In the embodiment, R 4C.1 When a substituent is substituted, R 4C.1 The substituents are as described in the section on “first substituents” in the definition section above, R 4C.2 It is substituted with one or more second substituents represented by R. In the embodiment, R 4C.2 When a substituent is substituted, R 4C.2 The substituents are as described in the section on “first substituents” in the definition section above, R 4C.3 It is substituted with one or more third substituents represented by . In the above embodiment, R 4C , R 4C.1 , R 4C.2 , and R 4C.3 As described in the definition section above under “First substituent”, each of them is R WW , R WW.1 , R WW.2 , and R WW.3 It has a value corresponding to the value of R WW , R WW.1 , R WW.2 , and R WW.3 These are, respectively, R 4C , R4C.1 , R 4C.2 , and R 4C.3 It corresponds to.

[0307] In this embodiment, R 4D When R is substituted, 4D As described in the definition section above under “first substituent”, R 4D.1 It is substituted with one or more first substituents represented by R. In the embodiment, R 4D.1 When a substituent is substituted, R 4D.1 The substituents are as described in the section on “first substituents” in the definition section above, R 4D.2 It is substituted with one or more second substituents represented by R. In the embodiment, R 4D.2 When a substituent is substituted, R 4D.2 The substituents are as described in the section on “first substituents” in the definition section above, R 4D.3 It is substituted with one or more third substituents represented by . In the above embodiment, R 4D , R 4D.1 , R 4D.2 , and R 4D.3 As described in the definition section above under “First substituent”, each of them is R WW , R WW.1 , R WW.2 , and R WW.3 It has a value corresponding to the value of R WW , R WW.1 , R WW.2 , and R WW.3 These are, respectively, R 4D , R 4D.1 , R 4D.2 , and R 4D.3 It corresponds to.

[0308] In this embodiment, R 5 When R is substituted, 5 As described in the definition section above under “first substituent”, R 5.1 It is substituted with one or more first substituents represented by R. In the embodiment, R 5.1When a substituent is substituted, R 5.1 The substituents are as described in the section on “first substituents” in the definition section above, R 5.2 It is substituted with one or more second substituents represented by R. In the embodiment, R 5.2 When a substituent is substituted, R 5.2 The substituents are as described in the section on “first substituents” in the definition section above, R 5.3 It is substituted with one or more third substituents represented by . In the above embodiment, R 5 , R 5.1 , R 5.2 , and R 5.3 As described in the definition section above under “First substituent”, each of them is R WW , R WW.1 , R WW.2 , and R WW.3 It has a value corresponding to the value of R WW , R WW.1 , R WW.2 , and R WW.3 These are, respectively, R 5 , R 5.1 , R 5.2 , and R 5.3 It corresponds to.

[0309] In this embodiment, R 5A When R is substituted, 5A As described in the definition section above under “first substituent”, R 5A.1 It is substituted with one or more first substituents represented by R. In the embodiment, R 5A.1 When a substituent is substituted, R 5A.1 The substituents are as described in the section on “first substituents” in the definition section above, R 5A.2 It is substituted with one or more second substituents represented by R. In the embodiment, R 5A.2 When a substituent is substituted, R 5A.2 The substituents are as described in the section on “first substituents” in the definition section above, R 5A.3It is substituted with one or more third substituents represented by . In the above embodiment, R 5A , R 5A.1 , R 5A.2 , and R 5A.3 As described in the definition section above under “First substituent”, each of them is R WW , R WW.1 , R WW.2 , and R WW.3 It has a value corresponding to the value of R WW , R WW.1 , R WW.2 , and R WW.3 These are, respectively, R 5A , R 5A.1 , R 5A.2 , and R 5A.3 It corresponds to.

[0310] In this embodiment, R 5B When R is substituted, 5B As described in the definition section above under “first substituent”, R 5B.1 It is substituted with one or more first substituents represented by R. In the embodiment, R 5B.1 When a substituent is substituted, R 5B.1 The substituents are as described in the section on “first substituents” in the definition section above, R 5B.2 It is substituted with one or more second substituents represented by R. In the embodiment, R 5B.2 When a substituent is substituted, R 5B.2 The substituents are as described in the section on “first substituents” in the definition section above, R 5B.3 It is substituted with one or more third substituents represented by . In the above embodiment, R 5B , R 5B.1 , R 5B.2 , and R 5B.3 As described in the definition section above under “First substituent”, each of them is R WW , R WW.1 , R WW.2 , and R WW.3 It has a value corresponding to the value of R WW , R WW.1, R WW.2 , and R WW.3 These are, respectively, R 5B , R 5B.1 , R 5B.2 , and R 5B.3 It corresponds to.

[0311] In this embodiment, R bonded to the same nitrogen atom 5A and R 5B When substituents are optionally linked to form a substituted moiety (e.g., a substituted heterocycloalkyl or substituted heteroaryl), that moiety is as described in the definition section above under “First substituent,” R 5A.1 It is substituted with one or more first substituents represented by R. In the embodiment, R 5A.1 When a substituent is substituted, R 5A.1 The substituents are as described in the section on “first substituents” in the definition section above, R 5A.2 It is substituted with one or more second substituents represented by R. In the embodiment, R 5A.2 When a substituent is substituted, R 5A.2 The substituents are as described in the section on “first substituents” in the definition section above, R 5A.3 It is substituted with one or more third substituents represented by . In the above embodiment, R 5A.1 , R 5A.2 , and R 5A.3 As described in the definition section above under “First substituent”, each of them is R WW.1 , R WW.2 , and R WW.3 It has a value corresponding to the value of R WW.1 , R WW.2 , and R WW.3 These are, respectively, R 5A.1 , R 5A.2 , and R 5A.3 It corresponds to.

[0312] In this embodiment, R bonded to the same nitrogen atom 5A and R 5BWhen substituents are optionally linked to form a substituted moiety (e.g., a substituted heterocycloalkyl or substituted heteroaryl), that moiety is as described in the definition section above under “First substituent,” R 5B.1 It is substituted with one or more first substituents represented by R. In the embodiment, R 5B.1 When a substituent is substituted, R 5B.1 The substituents are as described in the section on “first substituents” in the definition section above, R 5B.2 It is substituted with one or more second substituents represented by R. In the embodiment, R 5B.2 When a substituent is substituted, R 5B.2 The substituents are as described in the section on “first substituents” in the definition section above, R 5B.3 It is substituted with one or more third substituents represented by . In the above embodiment, R 5B.1 , R 5B.2 , and R 5B.3 As described in the definition section above under “First substituent”, each of them is R WW.1 , R WW.2 , and R WW.3 It has a value corresponding to the value of R WW.1 , R WW.2 , and R WW.3 These are, respectively, R 5B.1 , R 5B.2 , and R 5B.3 It corresponds to.

[0313] In this embodiment, R 5C When R is substituted, 5C As described in the definition section above under “first substituent”, R 5C.1 It is substituted with one or more first substituents represented by R. In the embodiment, R 5C.1 When a substituent is substituted, R 5C.1 The substituents are as described in the section on “first substituents” in the definition section above, R 5C.2 It is substituted with one or more second substituents represented by R. In the embodiment, R 5C.2When a substituent is substituted, R 5C.2 The substituents are as described in the section on “first substituents” in the definition section above, R 5C.3 It is substituted with one or more third substituents represented by . In the above embodiment, R 5C , R 5C.1 , R 5C.2 , and R 5C.3 As described in the definition section above under “First substituent”, each of them is R WW , R WW.1 , R WW.2 , and R WW.3 It has a value corresponding to the value of R WW , R WW.1 , R WW.2 , and R WW.3 These are, respectively, R 5C , R 5C.1 , R 5C.2 , and R 5C.3 It corresponds to.

[0314] In this embodiment, R 5D When R is substituted, 5D As described in the definition section above under “first substituent”, R 5D.1 It is substituted with one or more first substituents represented by R. In the embodiment, R 5D.1 When a substituent is substituted, R 5D.1 The substituents are as described in the section on “first substituents” in the definition section above, R 5D.2 It is substituted with one or more second substituents represented by R. In the embodiment, R 5D.2 When a substituent is substituted, R 5D.2 The substituents are as described in the section on “first substituents” in the definition section above, R 5D.3 It is substituted with one or more third substituents represented by . In the above embodiment, R 5D , R 5D.1 , R 5D.2 , and R 5D.3 As described in the definition section above under “First substituent”, each of them is R WW , RWW.1 , R WW.2 , and R WW.3 It has a value corresponding to the value of R WW , R WW.1 , R WW.2 , and R WW.3 These are, respectively, R 5D , R 5D.1 , R 5D.2 , and R 5D.3 It corresponds to.

[0315] In this embodiment, R 6 When R is substituted, 6 As described in the definition section above under “first substituent”, R 6.1 It is substituted with one or more first substituents represented by R. In the embodiment, R 6.1 When a substituent is substituted, R 6.1 The substituents are as described in the section on “first substituents” in the definition section above, R 6.2 It is substituted with one or more second substituents represented by R. In the embodiment, R 6.2 When a substituent is substituted, R 6.2 The substituents are as described in the section on “first substituents” in the definition section above, R 6.3 It is substituted with one or more third substituents represented by . In the above embodiment, R 6 , R 6.1 , R 6.2 , and R 6.3 As described in the definition section above under “First substituent”, each of them is R WW , R WW.1 , R WW.2 , and R WW.3 It has a value corresponding to the value of R WW , R WW.1 , R WW.2 , and R WW.3 These are, respectively, R 6 , R 6.1 , R 6.2 , and R 6.3 It corresponds to.

[0316] In this embodiment, the compound is given by formula:

[0317] [ka] It has. In this embodiment, the compound is of formula:

[0318] [ka] It has. In this embodiment, the compound is of formula:

[0319] [ka] It has. In this embodiment, the compound is of formula:

[0320] [ka] It has. In this embodiment, the compound is of formula:

[0321] [ka] It has. In this embodiment, the compound is of formula:

[0322] [ka] It has. In this embodiment, the compound is of formula:

[0323] [ka] It has. In this embodiment, the compound is of formula:

[0324] [ka] It has. In this embodiment, the compound is of formula:

[0325] [ka] It has. In this embodiment, the compound is of formula:

[0326] [ka] It has. In this embodiment, the compound is of formula:

[0327] [ka] It has. In this embodiment, the compound is of formula:

[0328] [ka] It has. In this embodiment, the compound is of formula:

[0329] [ka] It has. In this embodiment, the compound is of formula:

[0330] [ka] It has. In this embodiment, the compound is of formula:

[0331] [ka] It has. In this embodiment, the compound is of formula:

[0332] [ka] It has. In this embodiment, the compound is of formula:

[0333] [ka] It has. In this embodiment, the compound is of formula:

[0334] [ka] It has. In this embodiment, the compound is of formula:

[0335] [ka] It has. In this embodiment, the compound is of formula:

[0336] [ka] It has. In this embodiment, the compound is of formula:

[0337] [ka] It has. In this embodiment, the compound is of formula:

[0338] [ka] It has. In this embodiment, the compound is of formula:

[0339] [ka] It has. In this embodiment, the compound is of formula:

[0340] [ka] It has. In this embodiment, the compound is of formula:

[0341] [ka] It has. In this embodiment, the compound is of formula:

[0342] [ka] It has. In this embodiment, the compound is of formula:

[0343] [ka] It has. In this embodiment, the compound is of formula:

[0344] [ka] It has. In this embodiment, the compound is of formula:

[0345] [ka] It has. In this embodiment, the compound is of formula:

[0346] [ka] It has. In this embodiment, the compound is of formula:

[0347] [ka] It has. In this embodiment, the compound is of formula:

[0348] [ka] It has. In this embodiment, the compound is of formula:

[0349] [ka] It has. In this embodiment, the compound is of formula:

[0350] [ka] It has. In this embodiment, the compound is of formula:

[0351] [ka] It has. In this embodiment, the compound is of formula:

[0352] [ka] It has. In this embodiment, the compound is of formula:

[0353] [ka] It has. In this embodiment, the compound is of formula:

[0354] [ka] It has. In this embodiment, the compound is of formula:

[0355] [ka] It has. In this embodiment, the compound is of formula:

[0356] [ka] It has. In this embodiment, the compound is of formula:

[0357] [ka] It has. In this embodiment, the compound is of formula:

[0358] [ka] It has. In this embodiment, the compound is of formula:

[0359] [ka] It has. In this embodiment, the compound is of formula:

[0360] [ka] It has. In this embodiment, the compound is of formula:

[0361] [ka] It has. In this embodiment, the compound is of formula:

[0362] [ka] It has. In this embodiment, the compound is of formula:

[0363] [ka] It has. In this embodiment, the compound is of formula:

[0364] [ka] It has. In this embodiment, the compound is of formula:

[0365] [ka] It has. In this embodiment, the compound is of formula:

[0366] [ka] It has. In this embodiment, the compound is of formula:

[0367] [ka] It has. In this embodiment, the compound is of formula:

[0368] [ka] It has. In this embodiment, the compound is of formula:

[0369] [ka] It has. In this embodiment, the compound is of formula:

[0370] [ka] It has. In this embodiment, the compound is of formula:

[0371] [ka] It has. In this embodiment, the compound is of formula:

[0372] [ka] It has. In this embodiment, the compound is of formula:

[0373] [ka] It has. In this embodiment, the compound is of formula:

[0374] [ka] It has. In this embodiment, the compound is of formula:

[0375] [ka] It has. In this embodiment, the compound is of formula:

[0376] [ka] It has. In this embodiment, the compound is of formula:

[0377] [ka] It has. In this embodiment, the compound is of formula:

[0378] [ka] It has. In this embodiment, the compound is of formula:

[0379] [ka] It has. In this embodiment, the compound is of formula:

[0380] [ka] It holds.

[0381] In the embodiment, when the protein aggregation disease is a neurodegenerative disease, the compound is

[0382] [ka] isn't it.

[0383] In this embodiment, the compound is

[0384] [ka] No. In the embodiment, the compound is

[0385] [ka] isn't it.

[0386] In this embodiment, R 4 is -OR 4D No. In the embodiment, R 1 and R 2 is not an unsubstituted C1-C4 alkyl group. In the embodiment, R 1 and R 2 It is not hydrogen.

[0387] In this embodiment, the compound is

[0388] [ka] isn't it.

[0389] In this embodiment, R 6 It is not hydrogen. In the embodiment, R 6 is not an unsubstituted phenyl. In the embodiment, R 6 is not a substituted or unsubstituted phenyl. In the embodiment, R 6 is not an unsubstituted aryl. In the embodiment, R 6 It is neither a substituted nor a non-substituted aryl.

[0390] In the embodiments, the compound is useful as a comparative compound. In the embodiments, the comparative compound can be used to evaluate the activity of the test compound shown in the assay described herein (e.g., in the Examples section, figures, or tables).

[0391] In embodiments, the compound is a compound described herein, including in the embodiments. In embodiments, the compound is a compound described herein (for example, in the Examples section, figures, tables, or claims).

[0392] III. Pharmaceutical Compositions In one embodiment, a pharmaceutical composition is provided comprising a compound described herein, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

[0393] In the embodiment, the pharmaceutical composition contains an effective amount of the compound. In the embodiment, the pharmaceutical composition contains a therapeutically effective amount of the compound.

[0394] In the embodiments, the compound is a compound of formula (I), (Ia), (Ib), (II), (III), (IV), or (V), and all embodiments thereof are included. In the embodiments, the compound is a compound of formula (IA), (I), (II-A), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), or (XII), and all embodiments thereof are included. In the embodiments, the compound is a compound described herein, including the embodiments. In the embodiments, the compound is a compound described herein (for example, in the Examples section, figures, tables, or claims).

[0395] In the embodiment, the pharmaceutical composition is in oral dosage form. In the embodiment, the pharmaceutical composition is in tablet dosage form. In the embodiment, the pharmaceutical composition is in capsule dosage form. In the embodiment, the pharmaceutical composition is in intranasal dosage form. In the embodiment, the pharmaceutical composition is in intravenous dosage form. In the embodiment, the pharmaceutical composition is in injectable dosage form.

[0396] IV.Usage In one embodiment, a method is provided for treating a protein aggregation disorder in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound described herein or a pharmaceutically acceptable salt thereof.

[0397] In the embodiments, the compound is a compound of formula (I), (Ia), (Ib), (II), (III), (IV), or (V), and all embodiments thereof are included. In the embodiments, the compound is a compound of formula (IA), (I), (II-A), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), or (XII), and all embodiments thereof are included. In the embodiments, the compound is a compound described herein, including the embodiments. In the embodiments, the compound is a compound described herein (for example, in the Examples section, figures, tables, or claims).

[0398] In this embodiment, the protein aggregation disorder is a neurodegenerative disease. In this embodiment, the neurodegenerative disease is frontotemporal dementia. In this embodiment, the neurodegenerative disease is synucleinopathy. In this embodiment, the neurodegenerative disease is tauopathy. In this embodiment, the neurodegenerative disease is amyotrophic lateral sclerosis (ALS). In this embodiment, the neurodegenerative disease is sporadic amyotrophic lateral sclerosis. In this embodiment, the neurodegenerative disease is TDP-43 variant amyotrophic lateral sclerosis. In this embodiment, the neurodegenerative disease is amyotrophic lateral sclerosis and frontotemporal lobar degeneration. In this embodiment, the neurodegenerative disease is frontotemporal lobar degeneration. In this embodiment, the neurodegenerative disease is Pick's disease. In this embodiment, the neurodegenerative disease is frontotemporal lobar degeneration with a TDP-43 dominant pathology. In this embodiment, the neurodegenerative disease is frontotemporal lobar degeneration with a tau dominant pathology. In this embodiment, the neurodegenerative disease is semantic dementia. In this embodiment, the neurodegenerative disease is primary progressive aphasia. In this embodiment, the neurodegenerative disease is multiple system proteinosis. In this embodiment, the neurodegenerative disease is Perry syndrome. In this embodiment, the neurodegenerative disease is facial-onset sensorimotor neuropathy. In this embodiment, the neurodegenerative disease is valosin-containing protein (VCP) disease. In this embodiment, the neurodegenerative disease is inclusion body myositis. In this embodiment, the neurodegenerative disease is myotonic disorder. In this embodiment, the neurodegenerative disease is Alzheimer's disease. In this embodiment, the neurodegenerative disease is Parkinson's disease. In this embodiment, the neurodegenerative disease is Lewy body dementia. In this embodiment, the neurodegenerative disease is Parkinson's disease-associated dementia. In this embodiment, the neurodegenerative disease is multiple system atrophy. In this embodiment, the neurodegenerative disease is corticobasal degeneration. In this embodiment, the neurodegenerative disease is progressive supranuclear palsy. In this embodiment, the neurodegenerative disease is Huntington's disease. In this embodiment, the neurodegenerative disease is C9orf72 amyotrophic lateral sclerosis. In this embodiment, the neurodegenerative disease is amyloidosis. In this embodiment, the neurodegenerative disease is antibody light chain amyloidosis. In this embodiment, the neurodegenerative disease is transthyretin amyloidosis. In this embodiment, the neurodegenerative disease is prion disease.In this embodiment, the prion disease is Creutzfeldt-Jakob disease. In this embodiment, the prion disease is variant Creutzfeldt-Jakob disease. In this embodiment, the prion disease is hereditary human prion disease. In this embodiment, the prion disease is bovine spongiform encephalopathy. In this embodiment, the prion disease is scrapie. In this embodiment, the neurodegenerative disease is diffuse Lewy body disease. In this embodiment, the neurodegenerative disease is spinocerebellar ataxia. In this embodiment, the neurodegenerative disease is poly-Q disease. In this embodiment, the neurodegenerative disease is hereditary cerebral amyloid angiopathy. In this embodiment, the neurodegenerative disease is familial amyloid polyneuropathy. In this embodiment, the neurodegenerative disease is C9orf72 frontotemporal dementia. In this embodiment, the neurodegenerative disease is FUS ALS and FUS frontotemporal dementia. In this embodiment, the neurodegenerative disease is TMEM106b Parkinson's disease. In this embodiment, the neurodegenerative disease is TMEM106b Alzheimer's disease. In this embodiment, the neurodegenerative disease is TMEM106b ALS. In this embodiment, the neurodegenerative disease is TMEM175 Parkinson's disease. In this embodiment, the neurodegenerative disease is TMEM175 Alzheimer's disease. In this embodiment, the neurodegenerative disease is TMEM175 Alzheimer's disease.

[0399] In this embodiment, the protein aggregation disorder is diabetes mellitus. In this embodiment, the protein aggregation disorder is type II diabetes mellitus. In this embodiment, the protein aggregation disorder is type I diabetes mellitus. In this embodiment, the protein aggregation disorder is p53 mutation cancer. In this embodiment, the protein aggregation disorder is influenza A virus infection. In this embodiment, the protein aggregation disorder is herpesvirus infection. In this embodiment, the herpesvirus is M45 herpesvirus infection. In this embodiment, the protein aggregation disorder is primary systemic amyloidosis. In this embodiment, the protein aggregation disorder is reactive systemic amyloidosis. In this embodiment, the protein aggregation disorder is injection-limited amyloidosis. In this embodiment, the protein aggregation disorder is beta-2 microglobulin amyloidosis. In this embodiment, the protein aggregation disorder is hereditary nonneuropathic amyloidosis. In this embodiment, the protein aggregation disorder is Finnish-type hereditary systemic amyloidosis.

[0400] In the embodiments, the compound is administered orally. In the embodiments, the compound is administered intranasally. In the embodiments, the compound is administered intravenously. In the embodiments, the compound is administered by injection.

[0401] In one embodiment, a method is provided for reducing or interfering with the formation of protein aggregates, comprising contacting the protein aggregates with an effective amount of a compound described herein or a pharmaceutically acceptable salt thereof.

[0402] In the embodiments, the compound is a compound of formula (I), (Ia), (Ib), (II), (III), (IV), or (V), and all embodiments thereof are included. In the embodiments, the compound is a compound of formula (IA), (I), (II-A), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), or (XII), and all embodiments thereof are included. In the embodiments, the compound is a compound described herein, including the embodiments. In the embodiments, the compound is a compound described herein (for example, in the Examples section, figures, tables, or claims).

[0403] In this embodiment, the protein aggregate is a prion protein aggregate. In this embodiment, the protein aggregate is amyloid precursor protein aggregate. In this embodiment, the protein aggregate is beta-amyloid aggregate. In this embodiment, the protein aggregate is alpha-synuclein aggregate. In this embodiment, the protein aggregate is superoxide dismutase aggregate. In this embodiment, the protein aggregate is tau aggregate. In this embodiment, the protein aggregate is immunoglobulin aggregate. In this embodiment, the protein aggregate is amyloid-A aggregate. In this embodiment, the protein aggregate is transthyretin aggregate. In this embodiment, the protein aggregate is beta-2 microglobulin aggregate. In this embodiment, the protein aggregate is cystatin C aggregate. In this embodiment, the protein aggregate is apolipoprotein A1 aggregate. In this embodiment, the protein aggregate is TDP-43 aggregate. In this embodiment, the protein aggregate is islet amyloid polypeptide aggregate. In this embodiment, the protein aggregate is ANF aggregate. In the embodiment, the protein aggregate is a gelzoline aggregate. In the embodiment, the protein aggregate is an insulin aggregate. In the embodiment, the protein aggregate is a lysozyme aggregate. In the embodiment, the protein aggregate is a fibrinogen aggregate. In the embodiment, the protein aggregate is a huntingtin aggregate. In the embodiment, the protein aggregate is an ataxin aggregate. In the embodiment, the protein aggregate is an aggregate of a protein having poly-Q stretch. In the embodiment, the protein having poly-Q stretch is a protein having at least 36 consecutive glutamine residues.

[0404] In the embodiment, the protein aggregate is an oligomer. In the embodiment, the oligomer is a trimer. In the embodiment, the oligomer is a tetramer. In the embodiment, the oligomer is a pentamer. In the embodiment, the oligomer is a hexamer. In the embodiment, the oligomer is a heptamer. In the embodiment, the oligomer is an octamer. In the embodiment, the oligomer is a nonamer. In the embodiment, the oligomer is a decamer. In the embodiment, the oligomer is an 11-mer. In the embodiment, the oligomer is a 12-mer. In the embodiment, the oligomer is a 13-mer. In the embodiment, the oligomer is a 14-mer. In the embodiment, the oligomer is a 15-mer. In the embodiment, the oligomer is a 16-mer. In the embodiment, the oligomer is a 17-mer. In the embodiment, the oligomer is an 18-mer. In the embodiment, the oligomer is a 19-mer. In this embodiment, the oligomer is a 20-mer.

[0405] In the embodiment, the protein aggregate is an oligomer. In the embodiment, the oligomer has a size range of about 40kD to about 500kD. In the embodiment, the oligomer has a size range of about 50kD to about 400kD. In the embodiment, the oligomer has a size range of about 65kD to about 150kD. In the embodiment, the oligomer has a size range of about 100kD to about 300kD. In the embodiment, the oligomer has a size range of about 45kD to about 200kD. In the embodiment, the oligomer has a size range of about 80kD to about 500kD. In the embodiment, the oligomer is about 40kD. In the embodiment, the oligomer is about 50kD. In the embodiment, the oligomer is about 60kD. In the embodiment, the oligomer is about 70kD. In the embodiment, the oligomer is about 80kD. In the embodiment, the oligomer is approximately 90kD. In the embodiment, the oligomer is approximately 100kD. In the embodiment, the oligomer is approximately 120kD. In the embodiment, the oligomer is approximately 140kD. In the embodiment, the oligomer is approximately 160kD. In the embodiment, the oligomer is approximately 180kD. In the embodiment, the oligomer is approximately 200kD. In the embodiment, the oligomer is approximately 220kD. In the embodiment, the oligomer is approximately 240kD. In the embodiment, the oligomer is approximately 260kD. In the embodiment, the oligomer is approximately 280kD. In the embodiment, the oligomer is approximately 300kD. In the embodiment, the oligomer is approximately 320kD. In the embodiment, the oligomer is approximately 340kD. In the embodiment, the oligomer is approximately 360kD. In the embodiment, the oligomer is approximately 380 kD. In the embodiment, the oligomer is approximately 400 kD. In the embodiment, the oligomer is approximately 420 kD. In the embodiment, the oligomer is approximately 440 kD. In the embodiment, the oligomer is approximately 460 kD. In the embodiment, the oligomer is approximately 480 kD. In the embodiment, the oligomer is approximately 500 kD.

[0406] In the embodiment, the protein aggregate is an oligomer. In the embodiment, the oligomer has a size range of 40kD to 500kD. In the embodiment, the oligomer has a size range of 50kD to 400kD. In the embodiment, the oligomer has a size range of 65kD to 150kD. In the embodiment, the oligomer has a size range of 100kD to 300kD. In the embodiment, the oligomer has a size range of 45kD to 200kD. In the embodiment, the oligomer has a size range of 80kD to 500kD. In the embodiment, the oligomer is 40kD. In the embodiment, the oligomer is 50kD. In the embodiment, the oligomer is 60kD. In the embodiment, the oligomer is 70kD. In the embodiment, the oligomer is 80kD. In the embodiment, the oligomer is 90kD. In the embodiment, the oligomer is 100kD. In this embodiment, the oligomer is 120kD. In this embodiment, the oligomer is 140kD. In this embodiment, the oligomer is 160kD. In this embodiment, the oligomer is 180kD. In this embodiment, the oligomer is 200kD. In this embodiment, the oligomer is 220kD. In this embodiment, the oligomer is 240kD. In this embodiment, the oligomer is 260kD. In this embodiment, the oligomer is 280kD. In this embodiment, the oligomer is 300kD. In this embodiment, the oligomer is 320kD. In this embodiment, the oligomer is 340kD. In this embodiment, the oligomer is 360kD. In this embodiment, the oligomer is 380kD. In this embodiment, the oligomer is 400kD. In this embodiment, the oligomer is 420kD. In this embodiment, the oligomer is 440kD. In this embodiment, the oligomer is 460kD. In this embodiment, the oligomer is 480kD. In this embodiment, the oligomer is 500kD.

[0407] In the embodiments, contact occurs in vivo. In the embodiments, contact occurs in a subject and an effective amount of the compound is administered to the subject. In the embodiments, the subject has a protein aggregation disorder. In the embodiments, contact occurs in vitro. In the embodiments, contact occurs ex vivo.

[0408] In the embodiment, the amount of protein aggregates is reduced by approximately 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800, 900, or 1000 times compared to a control (e.g., when the compound is not present). In the embodiment, the amount of protein aggregates is reduced by approximately 1.5 times compared to a control (e.g., when the compound is not present). In the embodiment, the amount of protein aggregates is reduced by approximately 2 times compared to a control (e.g., when the compound is not present). In the embodiment, the amount of protein aggregates is reduced by approximately 5 times compared to a control (e.g., when the compound is not present). In the embodiment, the amount of protein aggregates is reduced by approximately 10 times compared to a control (e.g., when the compound is not present). In the embodiment, the amount of protein aggregates is reduced by approximately 25 times compared to the control (e.g., when the compound is not present). In the embodiment, the amount of protein aggregates is reduced by approximately 50 times compared to the control (e.g., when the compound is not present). In the embodiment, the amount of protein aggregates is reduced by approximately 100 times compared to the control (e.g., when the compound is not present). In the embodiment, the amount of protein aggregates is reduced by approximately 250 times compared to the control (e.g., when the compound is not present). In the embodiment, the amount of protein aggregates is reduced by approximately 500 times compared to the control (e.g., when the compound is not present). In the embodiment, the amount of protein aggregates is reduced by approximately 1000 times compared to the control (e.g., when the compound is not present).

[0409] In the embodiment, the amount of protein aggregates is reduced by at least 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800, 900, or 1000 times compared to a control (e.g., when the compound is not present). In the embodiment, the amount of protein aggregates is reduced by at least 1.5 times compared to a control (e.g., when the compound is not present). In the embodiment, the amount of protein aggregates is reduced by at least 2 times compared to a control (e.g., when the compound is not present). In the embodiment, the amount of protein aggregates is reduced by at least 5 times compared to a control (e.g., when the compound is not present). In the embodiment, the amount of protein aggregates is reduced by at least 10 times compared to a control (e.g., when the compound is not present). In the embodiment, the amount of protein aggregates is reduced by at least 25 times compared to a control (e.g., when the compound is not present). In the embodiment, the amount of protein aggregates is reduced by at least 50 times compared to a control (e.g., when the compound is not present). In the embodiment, the amount of protein aggregates is reduced by at least 100 times compared to a control (e.g., when the compound is not present). In the embodiment, the amount of protein aggregates is reduced by at least 250 times compared to a control (e.g., when the compound is not present). In the embodiment, the amount of protein aggregates is reduced by at least 500 times compared to a control (e.g., when the compound is not present). In the embodiment, the amount of protein aggregates is reduced by at least 1000 times compared to a control (e.g., when the compound is not present).

[0410] V. Embodiment Embodiment P1. A method for treating a protein aggregation disorder in a subject requiring such treatment, comprising administering to the subject a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt thereof, wherein the compound has the formula:

[0411] [ka] It has, in the formula, R 1 and R 2 However, independently, these are hydrogen, -CCl3, -CBr3, -CF3, -CI3, -CHCl2, -CHBr2, -CHF2, -CHI2, -CH2Cl, -CH2Br, -CH2F, -CH2I, -CN, -OH, -NH2, -COOH, -CONH2, -OCCl3, -OCF3, -OCBr3, -OCI3, -OCHCl2, -OCHBr2, -OCHI2, -OCHF2, -OCH2Cl, -OCH2Br, -OCH2I, -OCH2F, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, and R bonded to the same nitrogen atom 1 and R 2 The substituents may optionally link together to form substituted or unsubstituted heterocycloalkyl groups, or substituted or unsubstituted heteroaryl groups. R 3 However, independently, oxo, halogen, -CCl3, -CBr3, -CF3, -CI3, -CH2Cl, -CH2Br, -CH2F, -CH2I, -CHCl2, -CHBr2, -CHF2, -CHI2, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NH2, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHO H, -OCCl3, -OCBr3, -OCF3, -OCI3, -OCH2Cl, -OCH2Br, -OCH2F, -OCH2I, -OCHCl2, -OCHBr2, -OCHF2, -OCHI2, -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, R 4 However, independently, halogen, -CX 4 3, -CHX 4 2, -CH2X 4 ,-OCX 4 3. -OCH2X4 ,-OCHX 4 2, -CN, -SO n4 R 4D , -SO v4 NR 4A R 4B , -NR 4C NR 4A R 4B ,-ONR 4A R 4B , -NR 4C C(O)NR 4A R 4B , -N(O) m4 , -NR 4A R 4B , -C(O)R 4C , -C(O)OR 4C -OC(O)R 4C , -OC(O)OR 4C -C(O)NR 4A R 4B -OC(O)NR 4A R 4B , -OR 4D , -SR 4D , -NR 4A SO2R 4D , -NR 4A C(O)R 4C , -NR 4A C(O)OR 4C , -NR 4A Ure 4C -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, R 5 However, independently, halogen, -CX 5 3, -CHX 5 2, -CH2X 5 ,-OCX 5 3. -OCH2X 5 ,-OCHX 5 2, -CN, -SO n5 R 5D , -SO v5 NR 5A R 5B , -NR 5C NR 5A R5B ,-ONR 5A R 5B , -NR 5C C(O)NR 5A R 5B , -N(O) m5 , -NR 5A R 5B , -C(O)R 5C , -C(O)OR 5C -OC(O)R 5C , -OC(O)OR 5C -C(O)NR 5A R 5B -OC(O)NR 5A R 5B , -OR 5D , -SR 5D , -NR 5A SO2R 5D , -NR 5A C(O)R 5C , -NR 5A C(O)OR 5C , -NR 5A Ure 5C -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, R 4A , R 4B , R 4C , R 4D , R 5A , R 5B , R 5C , and R 5DHowever, independently, these are hydrogen, -CCl3, -CBr3, -CF3, -CI3, -CHCl2, -CHBr2, -CHF2, -CHI2, -CH2Cl, -CH2Br, -CH2F, -CH2I, -CN, -OH, -NH2, -COOH, -CONH2, -OCCl3, -OCF3, -OCBr3, -OCI3, -OCHCl2, -OCHBr2, -OCHI2, -OCHF2, -OCH2Cl, -OCH2Br, -OCH2I, -OCH2F, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, and R bonded to the same nitrogen atom 4A and R 4B The substituents can optionally link to form substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl atoms, and R bonded to the same nitrogen atom 5A and R 5B The substituents may optionally link together to form substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl groups. each X 4 and X 5 However, independently, they are -F, -Cl, -Br, or -I, n4 and n5 are independent integers between 0 and 4. m4, m5, v4, and v5 are independently 1 or 2. z3 is an integer between 0 and 8. z4 is an integer between 0 and 5. z5 is an integer between 0 and 5. The compound,

[0412] [ka] Not a method.

[0413] Embodiment P2. The method according to Embodiment P1, wherein the protein aggregation disorder is a neurodegenerative disease.

[0414] Embodiment P3. The method according to Embodiment P2, wherein the neurodegenerative disease is frontotemporal dementia, synucleinopathy, or tauopathy.

[0415] Embodiment P4. Neurodegenerative diseases include sporadic amyotrophic lateral sclerosis, amyotrophic lateral sclerosis and frontotemporal lobar degeneration, frontotemporal lobar degeneration, Pick's disease, frontotemporal lobar degeneration TDP-43 dominant condition, frontotemporal lobar degeneration tau dominant condition, semantic dementia, primary progressive aphasia, multiple system proteinosis, Perry syndrome, facial-onset sensorimotor neuropathy, sporadic inclusion body myositis, myotonic disorder, Alzheimer's disease, Parkinson's disease, and Lewy body dementia. The method of Embodiment P2, which is characterized by dementia, Parkinson's disease-related dementia, multiple system atrophy, corticobasal degeneration, progressive supranuclear palsy, Huntington's disease, C9orf72 amyotrophic lateral sclerosis, amyloidosis, antibody light chain amyloidosis, transthyretin amyloidosis, prion disease, diffuse Lewy body dementia, spinocerebellar ataxia, PolyQ disease, hereditary cerebral amyloid angiopathy, or familial amyloid polyneuropathy.

[0416] Embodiment P5. The method according to Embodiment P4, wherein the prion disease is Creutzfeldt-Jakob disease, variant Creutzfeldt-Jakob disease, hereditary human prion disease, bovine spongiform encephalopathy, or scrapie.

[0417] Embodiment P6. The method according to Embodiment P1, wherein the protein aggregation disorder is diabetes mellitus.

[0418] Embodiment P7. The method according to Embodiment P1, wherein the protein aggregation disorder is a p53 mutation cancer.

[0419] Embodiment P8. The method according to Embodiment P1, wherein the protein aggregation disorder is influenza A virus infection or herpes virus infection.

[0420] Embodiment P9. The method according to Embodiment P8, wherein the herpesvirus is M45 herpesvirus infection.

[0421] Embodiment P10. The method according to Embodiment P1, wherein the protein aggregation disorder is primary systemic amyloidosis, reactive systemic amyloidosis, type II diabetes mellitus, injection-limited amyloidosis, beta-2 microglobulin amyloidosis, hereditary nonneuropathic amyloidosis, or Finnish-type hereditary systemic amyloidosis.

[0422] Embodiment P11. The method according to any one of Embodiments P1 to P10, wherein the compound is administered orally, intranasally, intravenously, or by injection.

[0423] Embodiment P12. The compound is of formula:

[0424] [ka] The method according to any one of embodiments P1 to P11, having the characteristics of the method.

[0425] Embodiment P13.R 3 The method according to any one of embodiments P1 to P12, wherein the C1-C4 alkyl group is independently unsubstituted.

[0426] Embodiment P14.R 3 However, the method according to any one of embodiments P1 to P12, wherein the molecule is independently an unsubstituted methyl molecule.

[0427] The method according to any one of embodiments P1 to P12, wherein embodiment P15.z3 is 0.

[0428] The method according to any one of embodiments P1 to P14, wherein embodiment P16.z3 is 2.

[0429] Embodiment P17. The compound is of formula:

[0430] [ka] The method according to any one of embodiments P1 to P12, having the characteristics of the method.

[0431] Embodiment P18. The compound is of formula:

[0432] [ka] The method according to any one of embodiments P1 to P12, having the characteristics of the method.

[0433] Embodiment P19. The compound is of formula:

[0434] [ka] The method according to any one of embodiments P1 to P12, having the characteristics of the method.

[0435] Embodiment P20.R 1 The method according to any one of Embodiments P1 to P19, wherein the member is hydrogen, a substituted or unsubstituted C1-C4 alkyl group, a substituted or unsubstituted 2-6 member heteroalkyl group, a substituted or unsubstituted C3-C6 cycloalkyl group, or a substituted or unsubstituted 3-6 member heterocycloalkyl group.

[0436] Embodiment P21.R 1 The method according to any one of Embodiments P1 to P19, wherein the element is hydrogen or an unsubstituted C1-C4 alkyl group.

[0437] Embodiment P22.R 1 The method according to any one of embodiments P1 to P19, wherein the molecule is an unsubstituted methyl molecule.

[0438] Embodiment P23.R 2 The method according to any one of Embodiments P1 to P22, wherein the member is hydrogen, a substituted or unsubstituted C1-C4 alkyl group, a substituted or unsubstituted 2-6 member heteroalkyl group, a substituted or unsubstituted C3-C6 cycloalkyl group, or a substituted or unsubstituted 3-6 member heterocycloalkyl group.

[0439] Embodiment P24.R 2 The method according to any one of embodiments P1 to P22, wherein the element is hydrogen or an unsubstituted C1-C4 alkyl group.

[0440] Embodiment P25.R 2 The method according to any one of embodiments P1 to P22, wherein the molecule is an unsubstituted methyl molecule.

[0441] Embodiment P26.R 1 and R 2 The method according to any one of embodiments P1 to P19, wherein the substituents, together with the nitrogen atom to which they are bonded, link together to form a substituted or unsubstituted 3- to 8-membered heterocycloalkyl group.

[0442] Embodiment P27.R 1 and R 2 The method according to any one of embodiments P1 to P19, wherein the substituents, together with the nitrogen atom to which they are bonded, link together to form a substituted or unsubstituted pyrrolidinyl.

[0443] Embodiment P28.R 4 However, independently, halogens, -CCl3, -CBr3, -CF3, -CI3, -CH2Cl, -CH2Br, -CH2F, -CH2I, -CHCl2, -CHBr2, -CHF2, -CHI2, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NH2, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl3, -OCBr The method according to any one of Embodiments P1 to P27, wherein the member is -OCF3, -OCI3, -OCH2Cl, -OCH2Br, -OCH2F, -OCH2I, -OCHCl2, -OCHBr2, -OCHF2, -OCHI2, -SF5, -N3, a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl.

[0444] Embodiment P29.R 4The method according to any one of Embodiments P1 to P27, wherein the halogen is independently -CCl3, -CBr3, -CF3, -CI3, -CH2Cl, -CH2Br, -CH2F, -CH2I, -CHCl2, -CHBr2, -CHF2, -CHI2, -CN, -OH, -NH2, -COOH, -CONH2, substituted or unsubstituted C1-C4 alkyl, or substituted or unsubstituted 2-6 member heteroalkyl.

[0445] Embodiment P30.R 4 The method according to any one of embodiments P1 to P27, wherein the halogen is independently a halogen or an -OH.

[0446] Embodiment P31.R 4 The method according to any one of embodiments P1 to P27, wherein the molecule is independently -F or -OH.

[0447] Embodiment P32.R 5 However, independently, halogens, -CCl3, -CBr3, -CF3, -CI3, -CH2Cl, -CH2Br, -CH2F, -CH2I, -CHCl2, -CHBr2, -CHF2, -CHI2, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NH2, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl3, -OCBr The method according to any one of Embodiments P1 to P31, wherein 3, -OCF3, -OCI3, -OCH2Cl, -OCH2Br, -OCH2F, -OCH2I, -OCHCl2, -OCHBr2, -OCHF2, -OCHI2, -SF5, -N3, a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl.

[0448] Embodiment P33.R 5The method according to any one of Embodiments P1 to P31, wherein the halogen is independently -CCl3, -CBr3, -CF3, -CI3, -CH2Cl, -CH2Br, -CH2F, -CH2I, -CHCl2, -CHBr2, -CHF2, -CHI2, -CN, -OH, -NH2, -COOH, -CONH2, substituted or unsubstituted C1-C4 alkyl, or substituted or unsubstituted 2-6 member heteroalkyl.

[0449] Embodiment P34.R 5 However, the method according to any one of embodiments P1 to P31, wherein the halogen is independently present.

[0450] Embodiment P35.R 5 The method according to any one of embodiments P1 to P31, wherein the molecule is independently -F or -Cl.

[0451] The method according to any one of embodiments P1 to P31, wherein embodiment P36.z5 is 0.

[0452] The method according to any one of embodiments P1 to P35, wherein embodiment P37.z5 is 1.

[0453] Embodiment P38. Compound is of formula:

[0454] [ka] The method according to any one of embodiments P1 to P11, having the characteristics of the method.

[0455] Embodiment P39. A method for reducing or inhibiting the formation of protein aggregates, comprising contacting the protein aggregates with an effective amount of a compound or a pharmaceutically acceptable salt thereof, wherein the compound is of formula:

[0456] [ka] It has, in the formula, R 1 and R 2However, independently, these are hydrogen, -CCl3, -CBr3, -CF3, -CI3, -CHCl2, -CHBr2, -CHF2, -CHI2, -CH2Cl, -CH2Br, -CH2F, -CH2I, -CN, -OH, -NH2, -COOH, -CONH2, -OCCl3, -OCF3, -OCBr3, -OCI3, -OCHCl2, -OCHBr2, -OCHI2, -OCHF2, -OCH2Cl, -OCH2Br, -OCH2I, -OCH2F, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, and R bonded to the same nitrogen atom 1 and R 2 The substituents may optionally link together to form substituted or unsubstituted heterocycloalkyl groups, or substituted or unsubstituted heteroaryl groups. R 3 However, independently, oxo, halogen, -CCl3, -CBr3, -CF3, -CI3, -CH2Cl, -CH2Br, -CH2F, -CH2I, -CHCl2, -CHBr2, -CHF2, -CHI2, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NH2, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHO H, -OCCl3, -OCBr3, -OCF3, -OCI3, -OCH2Cl, -OCH2Br, -OCH2F, -OCH2I, -OCHCl2, -OCHBr2, -OCHF2, -OCHI2, -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, R 4 However, independently, halogen, -CX 4 3, -CHX 4 2, -CH2X 4 ,-OCX 4 3. -OCH2X 4 ,-OCHX 4 2, -CN, -SOn4 R 4D , -SO v4 NR 4A R 4B , -NR 4C NR 4A R 4B ,-ONR 4A R 4B , -NR 4C C(O)NR 4A R 4B , -N(O) m4 , -NR 4A R 4B , -C(O)R 4C , -C(O)OR 4C -OC(O)R 4C , -OC(O)OR 4C -C(O)NR 4A R 4B -OC(O)NR 4A R 4B , -OR 4D , -SR 4D , -NR 4A SO2R 4D , -NR 4A C(O)R 4C , -NR 4A C(O)OR 4C , -NR 4A Ure 4C -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, R 5 However, independently, halogen, -CX 5 3, -CHX 5 2, -CH2X 5 ,-OCX 5 3. -OCH2X 5 ,-OCHX 5 2, -CN, -SO n5 R 5D , -SO v5 NR 5A R 5B , -NR 5C NR 5A R 5B ,-ONR 5A R 5B, -NR 5C C(O)NR 5A R 5B , -N(O) m5 , -NR 5A R 5B , -C(O)R 5C , -C(O)OR 5C -OC(O)R 5C , -OC(O)OR 5C -C(O)NR 5A R 5B -OC(O)NR 5A R 5B , -OR 5D , -SR 5D , -NR 5A SO2R 5D , -NR 5A C(O)R 5C , -NR 5A C(O)OR 5C , -NR 5A Ure 5C -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, R 4A , R 4B , R 4C , R 4D , R 5A , R 5B , R 5C , and R 5D However, independently, these are hydrogen, -CCl3, -CBr3, -CF3, -CI3, -CHCl2, -CHBr2, -CHF2, -CHI2, -CH2Cl, -CH2Br, -CH2F, -CH2I, -CN, -OH, -NH2, -COOH, -CONH2, -OCCl3, -OCF3, -OCBr3, -OCI3, -OCHCl2, -OCHBr2, -OCHI2, -OCHF2, -OCH2Cl, -OCH2Br, -OCH2I, -OCH2F, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, and R bonded to the same nitrogen atom 4Aand R 4B The substituents can optionally link to form substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl atoms, and R bonded to the same nitrogen atom 5A and R 5B The substituents may optionally link together to form substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl groups. each X 4 and X 5 However, independently, they are -F, -Cl, -Br, or -I, n4 and n5 are independent integers between 0 and 4. m4, m5, v4, and v5 are independently 1 or 2. z3 is an integer between 0 and 8. z4 is an integer between 0 and 5. z5 is an integer between 0 and 5. The compound,

[0457] [ka] Not a method.

[0458] Embodiment P40. The method according to Embodiment P39, wherein the protein aggregate is a prion protein aggregate, amyloid precursor protein aggregate, beta-amyloid aggregate, alpha-synuclein aggregate, superoxide dismutase aggregate, tau aggregate, immunoglobulin aggregate, amyloid-A aggregate, transthyretin aggregate, beta-2 microglobulin aggregate, cystatin C aggregate, apolipoprotein A1 aggregate, TDP-43 aggregate, islet amyloid polypeptide aggregate, ANF aggregate, gelzolin aggregate, insulin aggregate, lysozyme aggregate, fibrinogen aggregate, huntingtin aggregate, or ataxin aggregate.

[0459] Embodiment P41. The method according to Embodiment P39, wherein the protein aggregate is a beta-amyloid aggregate.

[0460] Embodiment P42. The method of Embodiment P39, wherein the protein aggregates are tau aggregates.

[0461] Embodiment P43. The method according to Embodiment P39, wherein the protein aggregate is an alpha-synuclein aggregate.

[0462] Embodiment P44. The method according to Embodiment P39, wherein the protein aggregates are TDP-43 aggregates.

[0463] Embodiment P45. The method according to any one of Embodiments P39 to P44, wherein the protein aggregate is an oligomer.

[0464] Embodiment P46. The method according to any one of Embodiments P39 to P45, wherein contact occurs in vivo.

[0465] Embodiment P47. The method according to any one of Embodiments P39 to P45, wherein contact occurs in the subject and an effective amount of the compound is administered to the subject.

[0466] Embodiment P48. The compound of Embodiment P47, wherein the subject has a protein aggregation disorder.

[0467] Embodiment P49. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound, or a pharmaceutically acceptable salt thereof, wherein the compound has the formula:

[0468] [ka] It has, in the formula, R 1 and R 2However, independently, these are hydrogen, -CCl3, -CBr3, -CF3, -CI3, -CHCl2, -CHBr2, -CHF2, -CHI2, -CH2Cl, -CH2Br, -CH2F, -CH2I, -CN, -OH, -NH2, -COOH, -CONH2, -OCCl3, -OCF3, -OCBr3, -OCI3, -OCHCl2, -OCHBr2, -OCHI2, -OCHF2, -OCH2Cl, -OCH2Br, -OCH2I, -OCH2F, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, and R bonded to the same nitrogen atom 1 and R 2 The substituents may optionally link together to form substituted or unsubstituted heterocycloalkyl groups, or substituted or unsubstituted heteroaryl groups. R 3 However, independently, oxo, halogen, -CCl3, -CBr3, -CF3, -CI3, -CH2Cl, -CH2Br, -CH2F, -CH2I, -CHCl2, -CHBr2, -CHF2, -CHI2, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NH2, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHO H, -OCCl3, -OCBr3, -OCF3, -OCI3, -OCH2Cl, -OCH2Br, -OCH2F, -OCH2I, -OCHCl2, -OCHBr2, -OCHF2, -OCHI2, -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, R 4 However, independently, halogen, -CX 4 3, -CHX 4 2, -CH2X 4 ,-OCX 4 3. -OCH2X 4 ,-OCHX 4 2, -CN, -SOn4 R 4D , -SO v4 NR 4A R 4B , -NR 4C NR 4A R 4B ,-ONR 4A R 4B , -NR 4C C(O)NR 4A R 4B , -N(O) m4 , -NR 4A R 4B , -C(O)R 4C , -C(O)OR 4C -OC(O)R 4C , -OC(O)OR 4C -C(O)NR 4A R 4B -OC(O)NR 4A R 4B , -OR 4D , -SR 4D , -NR 4A SO2R 4D , -NR 4A C(O)R 4C , -NR 4A C(O)OR 4C , -NR 4A Ure 4C -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, R 5 However, independently, halogen, -CX 5 3, -CHX 5 2, -CH2X 5 ,-OCX 5 3. -OCH2X 5 ,-OCHX 5 2, -CN, -SO n5 R 5D , -SO v5 NR 5A R 5B , -NR 5C NR 5A R 5B ,-ONR 5A R 5B, -NR 5C C(O)NR 5A R 5B , -N(O) m5 , -NR 5A R 5B , -C(O)R 5C , -C(O)OR 5C -OC(O)R 5C , -OC(O)OR 5C -C(O)NR 5A R 5B -OC(O)NR 5A R 5B , -OR 5D , -SR 5D , -NR 5A SO2R 5D , -NR 5A C(O)R 5C , -NR 5A C(O)OR 5C , -NR 5A Ure 5C -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, R 4A , R 4B , R 4C , R 4D , R 5A , R 5B , R 5C , and R 5D However, independently, these are hydrogen, -CCl3, -CBr3, -CF3, -CI3, -CHCl2, -CHBr2, -CHF2, -CHI2, -CH2Cl, -CH2Br, -CH2F, -CH2I, -CN, -OH, -NH2, -COOH, -CONH2, -OCCl3, -OCF3, -OCBr3, -OCI3, -OCHCl2, -OCHBr2, -OCHI2, -OCHF2, -OCH2Cl, -OCH2Br, -OCH2I, -OCH2F, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, and R bonded to the same nitrogen atom 4Aand R 4B The substituents can optionally link to form substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl atoms, and R bonded to the same nitrogen atom 5A and R 5B The substituents may optionally link together to form substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl groups. each X 4 and X 5 However, independently, they are -F, -Cl, -Br, or -I, n4 and n5 are independent integers between 0 and 4. m4, m5, v4, and v5 are independently 1 or 2. z3 is an integer between 0 and 8. z4 is an integer between 0 and 5. z5 is an integer between 0 and 5. The compound,

[0469] [ka] It is not a pharmaceutical composition.

[0470] Embodiment P50. The pharmaceutical composition according to Embodiment P49, wherein the pharmaceutical composition is in oral dosage form, intranasal dosage form, intravenous dosage form, or injectable dosage form.

[0471] VI. Additional Embodiments Embodiment 1. A method for treating a protein aggregation disorder in a subject requiring such treatment, comprising administering to the subject a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt thereof, wherein the compound has the formula:

[0472] [ka] It has, in the formula, R 1 and R 2However, independently, these are hydrogen, -CCl3, -CBr3, -CF3, -CI3, -CHCl2, -CHBr2, -CHF2, -CHI2, -CH2Cl, -CH2Br, -CH2F, -CH2I, -CN, -OH, -NH2, -COOH, -CONH2, -OCCl3, -OCF3, -OCBr3, -OCI3, -OCHCl2, -OCHBr2, -OCHI2, -OCHF2, -OCH2Cl, -OCH2Br, -OCH2I, -OCH2F, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, and R bonded to the same nitrogen atom 1 and R 2 The substituents may optionally link together to form substituted or unsubstituted heterocycloalkyl groups, or substituted or unsubstituted heteroaryl groups. R 3 However, independently, oxo, halogen, -CCl3, -CBr3, -CF3, -CI3, -CH2Cl, -CH2Br, -CH2F, -CH2I, -CHCl2, -CHBr2, -CHF2, -CHI2, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NH2, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHO H, -OCCl3, -OCBr3, -OCF3, -OCI3, -OCH2Cl, -OCH2Br, -OCH2F, -OCH2I, -OCHCl2, -OCHBr2, -OCHF2, -OCHI2, -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, z3 is an integer between 0 and 8. R 4 However, independently, halogen, -CX 4 3, -CHX 4 2, -CH2X 4 ,-OCX 4 3. -OCH2X 4 ,-OCHX4 2, -CN, -SO n4 R 4D , -SO v4 NR 4A R 4B , -NR 4C NR 4A R 4B ,-ONR 4A R 4B , -NR 4C C(O)NR 4A R 4B , -N(O) m4 , -NR 4A R 4B , -C(O)R 4C , -C(O)OR 4C -OC(O)R 4C , -OC(O)OR 4C -C(O)NR 4A R 4B -OC(O)NR 4A R 4B , -OR 4D , -SR 4D , -NR 4A SO2R 4D , -NR 4A C(O)R 4C , -NR 4A C(O)OR 4C , -NR 4A Ure 4C -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, with two R 4 The substituents may optionally link together to form a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl. z4 is an integer between 0 and 5. R 5 However, independently, halogen, -CX 5 3, -CHX 5 2, -CH2X 5 ,-OCX 5 3. -OCH2X 5 ,-OCHX 52, -CN, -SO n5 R 5D , -SO v5 NR 5A R 5B , -NR 5C NR 5A R 5B ,-ONR 5A R 5B , -NR 5C C(O)NR 5A R 5B , -N(O) m5 , -NR 5A R 5B , -C(O)R 5C , -C(O)OR 5C -OC(O)R 5C , -OC(O)OR 5C -C(O)NR 5A R 5B -OC(O)NR 5A R 5B , -OR 5D , -SR 5D , -NR 5A SO2R 5D , -NR 5A C(O)R 5C , -NR 5A C(O)OR 5C , -NR 5A Ure 5C -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, z5 is an integer between 0 and 5. R 6However, hydrogen, halogen, -CCl3, -CBr3, -CF3, -CI3, -CH2Cl, -CH2Br, -CH2F, -CH2I, -CHCl2, -CHBr2, -CHF2, -CHI2, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SO3H, -OSO3H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NH2, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, - OCCl3, -OCBr3, -OCF3, -OCI3, -OCH2Cl, -OCH2Br, -OCH2F, -OCH2I, -OCHCl2, -OCHBr2, -OCHF2, -OCHI2, -SF5, -N3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, R 4A , R 4B , R 4C , R 4D , R 5A , R 5B , R 5C , and R 5D However, independently, these are hydrogen, -CCl3, -CBr3, -CF3, -CI3, -CHCl2, -CHBr2, -CHF2, -CHI2, -CH2Cl, -CH2Br, -CH2F, -CH2I, -CN, -OH, -NH2, -COOH, -CONH2, -OCCl3, -OCF3, -OCBr3, -OCI3, -OCHCl2, -OCHBr2, -OCHI2, -OCHF2, -OCH2Cl, -OCH2Br, -OCH2I, -OCH2F, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, and R bonded to the same nitrogen atom 4A and R 4B The substituents can optionally link to form substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl atoms, and R bonded to the same nitrogen atom 5A and R 5BThe substituents may optionally link together to form substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl groups. each X 4 and X 5 However, independently, they are -F, -Cl, -Br, or -I, n4 and n5 are independent integers between 0 and 4. m4, m5, v4, and v5 are independently 1 or 2. The compound,

[0473] [ka] Not a method.

[0474] Embodiment 2. The method according to Embodiment 1, wherein the protein aggregation disease is a neurodegenerative disease.

[0475] Embodiment 3. The method according to Embodiment 2, wherein the neurodegenerative disease is frontotemporal dementia, synucleinopathy, or tauopathy.

[0476] Embodiment 4. Neurodegenerative diseases include sporadic amyotrophic lateral sclerosis, TDP-43 variant amyotrophic lateral sclerosis, amyotrophic lateral sclerosis and frontotemporal lobar degeneration, frontotemporal lobar degeneration, Pick's disease, TDP-43 dominant state of frontotemporal lobar degeneration, tau dominant state of frontotemporal lobar degeneration, semantic dementia, primary progressive aphasia, multiple system proteinosis, Perry syndrome, facial-onset sensorimotor neuropathy, balocin-containing protein disease, inclusion body myositis, myotonic disorder, Alzheimer's disease, and parkinson's disease. The method according to Embodiment 2, wherein the condition is Parkinson's disease, dementia due to Lewy bodies, Parkinson's disease-related dementia, multiple system atrophy, corticobasal degeneration, progressive supranuclear palsy, Huntington's disease, C9orf72 amyotrophic lateral sclerosis, amyloidosis, antibody light chain amyloidosis, transthyretin amyloidosis, prion disease, diffuse Lewy body disease, spinocerebellar ataxia, PolyQ disease, hereditary cerebral amyloid angiopathy, familial amyloid polyneuropathy, C9orf72 frontotemporal dementia, FUS ALS and FUS frontotemporal dementia, TMEM106b Parkinson's disease, TMEM106b Alzheimer's disease, TMEM106b ALS, TMEM175 Parkinson's disease, TMEM175 Alzheimer's disease, or TMEM175 Alzheimer's disease.

[0477] Embodiment 5. The method according to Embodiment 4, wherein the prion disease is Creutzfeldt-Jakob disease, variant Creutzfeldt-Jakob disease, hereditary human prion disease, bovine spongiform encephalopathy, or scrapie.

[0478] Embodiment 6. The method according to Embodiment 1, wherein the protein aggregation disorder is diabetes mellitus.

[0479] Embodiment 7. The method according to Embodiment 1, wherein the protein aggregation disease is p53 mutation cancer.

[0480] Embodiment 8. The method according to Embodiment 1, wherein the protein aggregation disorder is influenza A virus infection or herpes virus infection.

[0481] Embodiment 9. The method according to Embodiment 8, wherein the herpesvirus is M45 herpesvirus infection.

[0482] Embodiment 10. The method according to Embodiment 1, wherein the protein aggregation disorder is primary systemic amyloidosis, reactive systemic amyloidosis, type II diabetes, type I diabetes, injection-limited amyloidosis, beta-2 microglobulin amyloidosis, hereditary nonneuropathic amyloidosis, or Finnish-type hereditary systemic amyloidosis.

[0483] Embodiment 11. The method according to any one of Emb...

Claims

1. A method for treating a protein aggregation disorder in a subject requiring such treatment, comprising administering to the subject a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt thereof, wherein the compound is of formula: 【Chemistry 1】 It has, in the formula, R ３ and R ２ are each, independently, hydrogen, -CCl ３ , -CBr ３ , -CF ３ , -CI ３ , -CHCl ２ , -CHBr ２ , -CHF ２ , -CHI ２ , -CH ２ Cl, -CH ２ Br, -CH ２ F, -CH ２ I, -CN, -OH, -NH ２ , -COOH, -CONH ２ , -OCl, -OCF ３ , -OCF ３ , -OCBr ３ , -OCI ３ , -OCHCl ２ , -OCHBr ２ , -OCHI ２ , -OCHF ２ , -OCH ２ Cl, -OCH ２ Br, -OCH ２ I, -OCH ２ F, a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl, and R １ and R ２ substituents may, optionally, be linked to form a substituted or unsubstituted heterocycloalkyl, or a substituted or unsubstituted heteroaryl, R ３ However, independently, oxo, halogen, -CCl ３ , - CBr ３ , -CF ３ , -CI ３ ien-CH ２ Cl, -CH ２ Br, -CH ２ F, -CH ２ I, -CHCl ２ , -CHBr ２ ,-CHF ２ , -CHI ２ , -CN, -OH, -NH ２ , -COOH, -CONH ２ , -NO ２ , -SH, -SO ３ H, -OSO ３ H, -SO ２ NH ２ , -NHNH ２ , -ONH ２ , -NHC(O)NH ２ , - NHSO ２ H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl ３ , -OCBr ３ , -OCF ３ , -OCI ３ , -OCH ２ Cl, -OCH ２ Br, -OCH ２ F, -OCH ２ I, -OCHCl ２ , -OCHBr ２ , -OCHF ２ , -OCHI ２ , -SF ５ , -N ３ , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, z3 is an integer from 0 to 8, R ４ is independently halogen, -CX ４ ３ , -CHX ４ ２ , -CH ２ X ４ , -OCX ４ ３ , -OCH ２ X ４ , -OCHX ４ ２ , -CN, -SO ｎ４ R ４Ｄ , -SO ｖ４ NR ４Ａ R ４Ｂ , -NR ４Ｃ NR ４Ａ R ４Ｂ , -ONR ４Ａ R ４Ｂ , -NR ４Ｃ C(O)NR ４Ａ R ４Ｂ , -N(O) ｍ４ , -NR ４Ａ R ４Ｂ , -C(O)R ４Ｃ , -C(O)OR ４Ｃ , -OC(O)R ４Ｃ , -OC(O)OR ４Ｃ , -C(O)NR ４Ａ R ４Ｂ , -OC(O)NR ４Ａ R ４Ｂ , -OR ４Ｄ , -SR ４Ｄ , -NR ４Ａ SO ２ R ４Ｄ , -NR ４Ａ C(O)R ４Ｃ , -NR ４Ａ C(O)OR ４Ｃ , -NR ４Ａ OR ４Ｃ , -SF ５ , -N ３ , a substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, and two Rs ４ The substituents may optionally link together to form a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl. z4 is an integer between 0 and 5. R ５ However, independently, halogen, -CX ５ ３ EN-CHX ５ ２ ien-CH ２ X ５ , -OCX ５ ３ , -OCH ２ X ５ , -OCHX ５ ２ -CN, -SO ｎ５ R ５Ｄ , -SO ｖ５ NR ５Ａ R ５Ｂ , -NR ５Ｃ NR ５Ａ R ５Ｂ , -ONR ５Ａ R ５Ｂ , -NR ５Ｃ C(O)NR ５Ａ R ５Ｂ , -N(O) ｍ５ , -NR ５Ａ R ５Ｂ , -C(O)R ５Ｃ , -C(O)OR ５Ｃ , -OC(O)R ５Ｃ , -OC(O)OR ５Ｃ , -C(O)NR ５Ａ R ５Ｂ , -OC(O)NR ５Ａ R ５Ｂ , -OR ５Ｄ , -SR ５Ｄ , -NR ５Ａ SO ２ R ５Ｄ , -NR ５Ａ C(O)R ５Ｃ , -NR ５Ａ C(O)OR ５Ｃ , -NR ５Ａ OR ５Ｃ , -SF ５ , -N ３ , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, z5 is an integer between 0 and 5. R ６ However, hydrogen, halogens, -CCl ３ , - CBr ３ , -CF ３ , -CI ３ ien-CH ２ Cl, -CH ２ Br, -CH ２ F, -CH ２ I, -CHCl ２ , -CHBr ２ ,-CHF ２ , -CHI ２ , -CN, -OH, -NH ２ , -COOH, -CONH ２ , -NO ２ , -SH, -SO ３ H, -OSO ３ H, -SO ２ NH ２ , -NHNH ２ , -ONH ２ , -NHC(O)NH ２ , - NHSO ２ H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl ３ , -OCBr ３ , -OCF ３ , -OCI ３ , -OCH ２ Cl, -OCH ２ Br, -OCH ２ F, -OCH ２ I, -OCHCl ２ , -OCHBr ２ , -OCHF ２ , -OCHI ２ , -SF ５ , -N ３ , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, R ４Ａ , R ４Ｂ , R ４Ｃ , R ４Ｄ , R ５Ａ , R ５Ｂ , R ５Ｃ , and R ５Ｄ However, independently, hydrogen, -CCl ３ , - CBr ３ , -CF ３ , -CI ３ -CHCl ２ , -CHBr ２ ,-CHF ２ , -CHI ２ ien-CH ２ Cl, -CH ２ Br, -CH ２ F, -CH ２ I, -CN, -OH, -NH ２ , -COOH, -CONH ２ -OCCl ３ , -OCF ３ , -OCBr ３ , -OCI ３ , -OChCl ２ , -OCHBr ２ , -OCHI ２ , -OCHF ２ , -OCH ２ Cl, -OCH ２ Br, -OCH ２ I, -OCH ２ F, a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl, with R bonded to the same nitrogen atom. ４Ａ and R ４Ｂ The substituents can optionally link to form substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl atoms, and R bonded to the same nitrogen atom ５Ａ and R ５Ｂ The substituents may optionally link together to form substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl groups. Each X ４ and X ５ However, independently, they are -F, -Cl, -Br, or -I. n4 and n5 are independent integers between 0 and 4. m4, m5, v4, and v5 are independently 1 or 2. The aforementioned compound, 【Chemistry 2】 Not a method.

2. The method according to claim 1, wherein the protein aggregation disorder is a neurodegenerative disease.

3. The method according to claim 2, wherein the neurodegenerative disease is frontotemporal dementia, synucleinopathy, or tauopathy.

4. The aforementioned neurodegenerative diseases include sporadic amyotrophic lateral sclerosis, TDP-43 variant amyotrophic lateral sclerosis, amyotrophic lateral sclerosis and frontotemporal lobar degeneration, frontotemporal lobar degeneration, Pick's disease, TDP-43 dominant frontotemporal lobar degeneration, tau dominant frontotemporal lobar degeneration, semantic dementia, primary progressive aphasia, multiple system proteinosis, Perry syndrome, facial-onset sensorimotor neuropathy, balocin-containing protein disorders, inclusion body myositis, myotonic disorder, Alzheimer's disease, and Parkinson's disease. The method according to claim 2, wherein the condition is dementia caused by Lewy bodies, Parkinson's disease-related dementia, multiple system atrophy, corticobasal degeneration, progressive supranuclear palsy, Huntington's disease, C9orf72 amyotrophic lateral sclerosis, amyloidosis, antibody light chain amyloidosis, transthyretin amyloidosis, prion disease, diffuse Lewy body disease, spinocerebellar ataxia, PolyQ disease, hereditary cerebral amyloid angiopathy, familial amyloid polyneuropathy, C9orf72 frontotemporal dementia, FUS ALS and FUS frontotemporal dementia, TMEM106b Parkinson's disease, TMEM106b Alzheimer's disease, TMEM106b ALS, TMEM175 Parkinson's disease, TMEM175 Alzheimer's disease, or TMEM175 Alzheimer's disease.

5. The method according to claim 4, wherein the prion disease is Creutzfeldt-Jakob disease, variant Creutzfeldt-Jakob disease, hereditary human prion disease, bovine spongiform encephalopathy, or scrapie.

6. The method according to claim 1, wherein the protein aggregation disorder is diabetes mellitus.

7. The method according to claim 1, wherein the protein aggregation disorder is a p53 mutation cancer.

8. The method according to claim 1, wherein the protein aggregation disorder is an influenza A virus infection or a herpes virus infection.

9. The method according to claim 8, wherein the herpesvirus is M45 herpesvirus infection.

10. The method according to claim 1, wherein the protein aggregation disorder is primary systemic amyloidosis, reactive systemic amyloidosis, type II diabetes, type I diabetes, injection-limited amyloidosis, beta-2 microglobulin amyloidosis, hereditary nonneuropathic amyloidosis, or Finnish-type hereditary systemic amyloidosis.

11. The method according to claim 1, wherein the compound is administered orally, intranasally, intravenously, or by injection.

12. R ６ However, hydrogen or unsubstituted C １ ~C ４ The method according to any one of claims 1 to 11, wherein the alkyl group is used.

13. R ６ The method according to any one of claims 1 to 11, wherein the molecule is hydrogen or an unsubstituted methyl molecule.

14. The aforementioned compound has the formula: 【Transformation 3】 The method according to any one of claims 1 to 11, comprising:

15. The aforementioned compound has the formula: 【Chemistry 4】 The method according to any one of claims 1 to 11, comprising:

16. R ３ However, independently, non-substituted C １ ~C ４ The method according to any one of claims 1 to 11, wherein the alkyl group is used.

17. R ３ The method according to any one of claims 1 to 11, wherein the molecule is independently an unsubstituted methyl molecule.

18. The method according to any one of claims 1 to 11, wherein z3 is 0.

19. The method according to any one of claims 1 to 11, wherein z3 is 2.

20. The aforementioned compound has the formula: 【Transformation 5】 The method according to any one of claims 1 to 11, comprising:

21. The aforementioned compound has the formula: 【Transformation 6】 The method according to any one of claims 1 to 11, comprising:

22. The aforementioned compound has the formula: 【Transformation 7】 The method according to any one of claims 1 to 11, comprising:

23. R ４ However, independently, halogen, -CCl ３ , - CBr ３ , -CF ３ , -CI ３ ien-CH ２ Cl, -CH ２ Br, -CH ２ F, -CH ２ I, -CHCl ２ , -CHBr ２ ,-CHF ２ , -CHI ２ , -CN, -OH, -NH ２ , -COOH, -CONH ２ , -NO ２ , -SH, -SO ３ H, -OSO ３ H, -SO ２ NH ２ , -NHNH ２ , -ONH ２ , -NHC(O)NH ２ , - NHSO ２ H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl ３ , -OCBr ３ , -OCF ３ , -OCI ３ , -OCH ２ Cl, -OCH ２ Br, -OCH ２ F, -OCH ２ I, -OCHCl ２ , -OCHBr ２ , -OCHF ２ , -OCHI ２ , -SF ５ , -N ３ , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, and two R ４ The method according to any one of claims 1 to 11, wherein the substituents can optionally be linked to form a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl.

24. R ４ However, independently, halogen, -CCl ３ , - CBr ３ , -CF ３ , -CI ３ ien-CH ２ Cl, -CH ２ Br, -CH ２ F, -CH ２ I, -CHCl ２ , -CHBr ２ ,-CHF ２ , -CHI ２ , -CN, -OH, -NH ２ , -COOH, -CONH ２ , substitution or non-substitution C １ ~C ４ The method according to any one of claims 1 to 11, wherein the alkyl is or a substituted or unsubstituted 2 to 6-membered heteroalkyl.

25. R ４ However, independently, halogen, -OH, -CN, and unsubstituted C １ ~C ４ The method according to any one of claims 1 to 11, wherein the alkyl is or an unsubstituted 2- to 6-membered heteroalkyl.

26. R ４ However, independently, -F, -OH, -CN, -OC(O)CH ３ , -C(O)N(CH ３ ) ２ The method according to any one of claims 1 to 11, wherein the unsubstituted methyl, unsubstituted ethyl, or unsubstituted methoxy.

27. The aforementioned compound has the formula: 【Transformation 8】 It has, in the formula, R ４．２ , R ４．３ , R ４．４ , and R ４．５ However, independently, hydrogen, halogen, -CX ４ ３ EN-CHX ４ ２ ien-CH ２ X ４ , -OCX ４ ３ , -OCH ２ X ４ , -OCHX ４ ２ -CN, -SO ｎ４ R ４Ｄ , -SO ｖ４ NR ４Ａ R ４Ｂ , -NR ４Ｃ NR ４Ａ R ４Ｂ , -ONR ４Ａ R ４Ｂ , -NR ４Ｃ C(O)NR ４Ａ R ４Ｂ , -N(O) ｍ４ , -NR ４Ａ R ４Ｂ , -C(O)R ４Ｃ , -C(O)OR ４Ｃ , -OC(O)R ４Ｃ , -OC(O)OR ４Ｃ , -C(O)NR ４Ａ R ４Ｂ , -OC(O)NR ４Ａ R ４Ｂ , -OR ４Ｄ , -SR ４Ｄ , -NR ４Ａ SO ２ R ４Ｄ , -NR ４Ａ C(O)R ４Ｃ , -NR ４Ａ C(O)OR ４Ｃ , -NR ４Ａ OR ４Ｃ , -SF ５ , -N ３ , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, R ４．２ and R ４．３ The substituents may optionally link together to form a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl, R ４．３ and R ４．４ The method according to any one of claims 1 to 11, wherein the substituents can optionally be linked to form a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl.

28. R ４．２ , R ４．３ , R ４．４ , and R ４．５ However, independently, hydrogen, halogen, -CCl ３ , - CBr ３ , -CF ３ , -CI ３ ien-CH ２ Cl, -CH ２ Br, -CH ２ F, -CH ２ I, -CHCl ２ , -CHBr ２ ,-CHF ２ , -CHI ２ , -CN, -OH, -NH ２ , -COOH, -CONH ２ , -NO ２ , -SH, -SO ３ H, -OSO ３ H, -SO ２ NH ２ , -NHNH ２ , -ONH ２ , -NHC(O)NH ２ , - NHSO ２ H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl ３ , -OCBr ３ , -OCF ３ , -OCI ３ , -OCH ２ Cl, -OCH ２ Br, -OCH ２ F, -OCH ２ I, -OCHCl ２ , -OCHBr ２ , -OCHF ２ , -OCHI ２ , -SF ５ , -N ３ , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, R ４．２ and R ４．３ The substituents may optionally link together to form a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl, R ４．３ and R ４．４ The method according to claim 27, wherein the substituents can optionally be linked to form a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl.

29. R ４．２ , R ４．３ , R ４．４ , and R ４．５ However, independently, hydrogen, halogen, -CCl ３ , - CBr ３ , -CF ３ , -CI ３ ien-CH ２ Cl, -CH ２ Br, -CH ２ F, -CH ２ I, -CHCl ２ , -CHBr ２ ,-CHF ２ , -CHI ２ , -CN, -OH, -NH ２ , -COOH, -CONH ２ , substitution or non-substitution C １ ~C ４ The method according to claim 27, wherein the alkyl is, or a substituted or unsubstituted 2-6 member heteroalkyl.

30. R １ However, hydrogen, substituted or unsubstituted C １ ~C ４ Alkyl, substituted or unsubstituted 2-6 member heteroalkyl, substituted or unsubstituted C ３ ~C ６ The method according to any one of claims 1 to 11, wherein the cycloalkyl or substituted or unsubstituted 3 to 6-membered heterocycloalkyl.

31. R １ However, hydrogen or unsubstituted C １ ~C ４ The method according to any one of claims 1 to 11, wherein the alkyl group is used.

32. R １ The method according to any one of claims 1 to 11, wherein the molecule is an unsubstituted methyl molecule.

33. R ２ However, hydrogen, substituted or unsubstituted C １ ~C ４ Alkyl, substituted or unsubstituted 2-6 member heteroalkyl, substituted or unsubstituted C ３ ~C ６ The method according to any one of claims 1 to 11, wherein the cycloalkyl or substituted or unsubstituted 3 to 6-membered heterocycloalkyl.

34. R ２ However, hydrogen or unsubstituted C １ ~C ４ The method according to any one of claims 1 to 11, wherein the alkyl group is used.

35. R ２ The method according to any one of claims 1 to 11, wherein the molecule is an unsubstituted methyl molecule.

36. R １ and R ２ The method according to any one of claims 1 to 11, wherein the substituents, together with the nitrogen atom to which they are bonded, link together to form a substituted or unsubstituted 3 to 8-membered heterocycloalkyl group.

37. R １ and R ２ The method according to any one of claims 1 to 11, wherein the substituents, together with the nitrogen atom to which they are bonded, link together to form a substituted or unsubstituted pyrrolidinyl.

38. R ５ However, independently, halogen, -CCl ３ , - CBr ３ , -CF ３ , -CI ３ ien-CH ２ Cl, -CH ２ Br, -CH ２ F, -CH ２ I, -CHCl ２ , -CHBr ２ ,-CHF ２ , -CHI ２ , -CN, -OH, -NH ２ , -COOH, -CONH ２ , -NO ２ , -SH, -SO ３ H, -OSO ３ H, -SO ２ NH ２ , -NHNH ２ , -ONH ２ , -NHC(O)NH ２ , - NHSO ２ H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl ３ , -OCBr ３ , -OCF ３ , -OCI ３ , -OCH ２ Cl, -OCH ２ Br, -OCH ２ F, -OCH ２ I, -OCHCl ２ , -OCHBr ２ , -OCHF ２ , -OCHI ２ , -SF ５ , -N ３ The method according to any one of claims 1 to 11, wherein the alkyl is substituted or unsubstituted, the heteroalkyl is substituted or unsubstituted, the cycloalkyl is substituted or unsubstituted, the heterocycloalkyl is substituted or unsubstituted, the aryl is substituted or unsubstituted, or the heteroaryl is substituted or unsubstituted.

39. R ５ However, independently, halogen, -CCl ３ , - CBr ３ , -CF ３ , -CI ３ ien-CH ２ Cl, -CH ２ Br, -CH ２ F, -CH ２ I, -CHCl ２ , -CHBr ２ ,-CHF ２ , -CHI ２ , -CN, -OH, -NH ２ , -COOH, -CONH ２ , substitution or non-substitution C １ ~C ４ The method according to any one of claims 1 to 11, wherein the alkyl is or a substituted or unsubstituted 2 to 6-membered heteroalkyl.

40. R ５ The method according to any one of claims 1 to 11, wherein the halogen is independently...

41. R ５ The method according to any one of claims 1 to 11, wherein the element is independently -F or -Cl.

42. The method according to any one of claims 1 to 11, wherein z5 is 0.

43. The method according to any one of claims 1 to 11, wherein z5 is 1.

44. The aforementioned compound has the formula: 【Chemistry 9】 【Chemistry 10】 The method according to any one of claims 1 to 11, comprising:

45. A method for reducing or inhibiting the formation of protein aggregates, comprising contacting the protein aggregates with an effective amount of a compound or a pharmaceutically acceptable salt thereof, wherein the compound is of formula: 【Chemistry 11】 It has, in the formula, R １ and R ２ However, independently, hydrogen, -CCl ３ , - CBr ３ , -CF ３ , -CI ３ -CHCl ２ , -CHBr ２ ,-CHF ２ , -CHI ２ ien-CH ２ Cl, -CH ２ Br, -CH ２ F, -CH ２ I, -CN, -OH, -NH ２ , -COOH, -CONH ２ -OCCl ３ , -OCF ３ , -OCBr ３ , -OCI ３ , -OChCl ２ , -OCHBr ２ , -OCHI ２ , -OCHF ２ , -OCH ２ Cl, -OCH ２ Br, -OCH ２ I, -OCH ２ F, a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl, with R bonded to the same nitrogen atom. １ and R ２ The substituents may optionally link together to form substituted or unsubstituted heterocycloalkyl groups, or substituted or unsubstituted heteroaryl groups. R ３ However, independently, oxo, halogen, -CCl ３ , - CBr ３ , -CF ３ , -CI ３ ien-CH ２ Cl, -CH ２ Br, -CH ２ F, -CH ２ I, -CHCl ２ , -CHBr ２ ,-CHF ２ , -CHI ２ , -CN, -OH, -NH ２ , -COOH, -CONH ２ , -NO ２ , -SH, -SO ３ H, -OSO ３ H, -SO ２ NH ２ , -NHNH ２ , -ONH ２ , -NHC(O)NH ２ , - NHSO ２ H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl ３ , -OCBr ３ , -OCF ３ , -OCI ３ , -OCH ２ Cl, -OCH ２ Br, -OCH ２ F, -OCH ２ I, -OCHCl ２ , -OCHBr ２ , -OCHF ２ , -OCHI ２ , -SF ５ , -N ３ , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, z3 is an integer from 0 to 8, R ４ However, independently, halogen, -CX ４ ３ EN-CHX ４ ２ ien-CH ２ X ４ , -OCX ４ ３ , -OCH ２ X ４ , -OCHX ４ ２ -CN, -SO ｎ４ R ４Ｄ , -SO ｖ４ NR ４Ａ R ４Ｂ , -NR ４Ｃ NR ４Ａ R ４Ｂ , -ONR ４Ａ R ４Ｂ , -NR ４Ｃ C(O)NR ４Ａ R ４Ｂ , -N(O) ｍ４ , -NR ４Ａ R ４Ｂ , -C(O)R ４Ｃ , -C(O)OR ４Ｃ , -OC(O)R ４Ｃ , -OC(O)OR ４Ｃ , -C(O)NR ４Ａ R ４Ｂ , -OC(O)NR ４Ａ R ４Ｂ , -OR ４Ｄ , -SR ４Ｄ , -NR ４Ａ SO ２ R ４Ｄ , -NR ４Ａ C(O)R ４Ｃ , -NR ４Ａ C(O)OR ４Ｃ , -NR ４Ａ OR ４Ｃ , -SF ５ , -N ３ , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, and two R ４ The substituents may optionally link together to form a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl. z4 is an integer between 0 and 5. R ５ However, independently, halogen, -CX ５ ３ EN-CHX ５ ２ ien-CH ２ X ５ , -OCX ５ ３ , -OCH ２ X ５ , -OCHX ５ ２ -CN, -SO ｎ５ R ５Ｄ , -SO ｖ５ NR ５Ａ R ５Ｂ , -NR ５Ｃ NR ５Ａ R ５Ｂ , -ONR ５Ａ R ５Ｂ , -NR ５Ｃ C(O)NR ５Ａ R ５Ｂ , -N(O) ｍ５ , -NR ５Ａ R ５Ｂ , -C(O)R ５Ｃ , -C(O)OR ５Ｃ , -OC(O)R ５Ｃ , -OC(O)OR ５Ｃ , -C(O)NR ５Ａ R ５Ｂ , -OC(O)NR ５Ａ R ５Ｂ , -OR ５Ｄ , -SR ５Ｄ , -NR ５Ａ SO ２ R ５Ｄ , -NR ５Ａ C(O)R ５Ｃ , -NR ５Ａ C(O)OR ５Ｃ , -NR ５Ａ OR ５Ｃ , -SF ５ , -N ３ , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, z5 is an integer between 0 and 5. R ６ However, hydrogen, halogens, -CCl ３ , - CBr ３ , -CF ３ , -CI ３ ien-CH ２ Cl, -CH ２ Br, -CH ２ F, -CH ２ I, -CHCl ２ , -CHBr ２ ,-CHF ２ , -CHI ２ , -CN, -OH, -NH ２ , -COOH, -CONH ２ , -NO ２ , -SH, -SO ３ H, -OSO ３ H, -SO ２ NH ２ , -NHNH ２ , -ONH ２ , -NHC(O)NH ２ , - NHSO ２ H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl ３ , -OCBr ３ , -OCF ３ , -OCI ３ , -OCH ２ Cl, -OCH ２ Br, -OCH ２ F, -OCH ２ I, -OCHCl ２ , -OCHBr ２ , -OCHF ２ , -OCHI ２ , -SF ５ , -N ３ , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, R ４Ａ , R ４Ｂ , R ４Ｃ , R ４Ｄ , R ５Ａ , R ５Ｂ , R ５Ｃ , and R ５Ｄ However, independently, hydrogen, -CCl ３ , - CBr ３ , -CF ３ , -CI ３ -CHCl ２ , -CHBr ２ ,-CHF ２ , -CHI ２ ien-CH ２ Cl, -CH ２ Br, -CH ２ F, -CH ２ I, -CN, -OH, -NH ２ , -COOH, -CONH ２ -OCCl ３ , -OCF ３ , -OCBr ３ , -OCI ３ , -OChCl ２ , -OCHBr ２ , -OCHI ２ , -OCHF ２ , -OCH ２ Cl, -OCH ２ Br, -OCH ２ I, -OCH ２ F, a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl, with R bonded to the same nitrogen atom. ４Ａ and R ４Ｂ The substituents can optionally link to form substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl atoms, and R bonded to the same nitrogen atom ５Ａ and R ５Ｂ The substituents may optionally link together to form substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl groups. Each X ４ and X ５ However, independently, they are -F, -Cl, -Br, or -I. n4 and n5 are independent integers between 0 and 4. m4, m5, v4, and v5 are independently 1 or 2. The aforementioned compound, 【Chemistry 12】 Not a method.

46. The method according to claim 45, wherein the protein aggregate is a prion protein aggregate, amyloid precursor protein aggregate, beta-amyloid aggregate, alpha-synuclein aggregate, superoxide dismutase aggregate, tau aggregate, immunoglobulin aggregate, amyloid-A aggregate, transthyretin aggregate, beta-2 microglobulin aggregate, cystatin C aggregate, apolipoprotein A1 aggregate, TDP-43 aggregate, islet amyloid polypeptide aggregate, ANF aggregate, gelzolin aggregate, insulin aggregate, lysozyme aggregate, fibrinogen aggregate, huntingtin aggregate, or ataxin aggregate.

47. The method according to claim 45, wherein the protein aggregate is a beta-amyloid aggregate.

48. The method according to claim 45, wherein the protein aggregate is a tau aggregate.

49. The method according to claim 45, wherein the protein aggregate is an alpha-synuclein aggregate.

50. The method according to claim 45, wherein the protein aggregate is a TDP-43 aggregate.

51. The method according to claim 45, wherein the protein aggregate is an oligomer.

52. The method according to any one of claims 45 to 51, wherein the contact occurs in vivo.

53. The method according to any one of claims 45 to 51, wherein the contact occurs in the subject and an effective amount of the compound is administered to the subject.

54. The method according to claim 53, wherein the subject has a protein aggregation disorder.

55. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound, or a pharmaceutically acceptable salt thereof, wherein the compound is of formula: 【Chemistry 13】 It has, in the formula, R １ and R ２ However, independently, hydrogen, -CCl ３ , - CBr ３ , -CF ３ , -CI ３ -CHCl ２ , -CHBr ２ ,-CHF ２ , -CHI ２ ien-CH ２ Cl, -CH ２ Br, -CH ２ F, -CH ２ I, -CN, -OH, -NH ２ , -COOH, -CONH ２ -OCCl ３ , -OCF ３ , -OCBr ３ , -OCI ３ , -OChCl ２ , -OCHBr ２ , -OCHI ２ , -OCHF ２ , -OCH ２ Cl, -OCH ２ Br, -OCH ２ I, -OCH ２ F, a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl, with R bonded to the same nitrogen atom. １ and R ２ The substituents may optionally link together to form substituted or unsubstituted heterocycloalkyl groups, or substituted or unsubstituted heteroaryl groups. R ３ However, independently, oxo, halogen, -CCl ３ , - CBr ３ , -CF ３ , -CI ３ ien-CH ２ Cl, -CH ２ Br, -CH ２ F, -CH ２ I, -CHCl ２ , -CHBr ２ ,-CHF ２ , -CHI ２ , -CN, -OH, -NH ２ , -COOH, -CONH ２ , -NO ２ , -SH, -SO ３ H, -OSO ３ H, -SO ２ NH ２ , -NHNH ２ , -ONH ２ , -NHC(O)NH ２ , - NHSO ２ H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl ３ , -OCBr ３ , -OCF ３ , -OCI ３ , -OCH ２ Cl, -OCH ２ Br, -OCH ２ F, -OCH ２ I, -OCHCl ２ , -OCHBr ２ , -OCHF ２ , -OCHI ２ , -SF ５ , -N ３ , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, z3 is an integer from 0 to 8, R ４ However, independently, halogen, -CX ４ ３ EN-CHX ４ ２ ien-CH ２ X ４ , -OCX ４ ３ , -OCH ２ X ４ , -OCHX ４ ２ -CN, -SO ｎ４ R ４Ｄ , -SO ｖ４ NR ４Ａ R ４Ｂ , -NR ４Ｃ NR ４Ａ R ４Ｂ , -ONR ４Ａ R ４Ｂ , -NR ４Ｃ C(O)NR ４Ａ R ４Ｂ , -N(O) ｍ４ , -NR ４Ａ R ４Ｂ , -C(O)R ４Ｃ , -C(O)OR ４Ｃ , -OC(O)R ４Ｃ , -OC(O)OR ４Ｃ , -C(O)NR ４Ａ R ４Ｂ , -OC(O)NR ４Ａ R ４Ｂ , -OR ４Ｄ , -SR ４Ｄ , -NR ４Ａ SO ２ R ４Ｄ , -NR ４Ａ C(O)R ４Ｃ , -NR ４Ａ C(O)OR ４Ｃ , -NR ４Ａ OR ４Ｃ , -SF ５ , -N ３ , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, and two R ４ The substituents may optionally link together to form a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl. z4 is an integer between 0 and 5. R ５ is independently halogen, -CX ５ ３ -, -CHX ５ ２ -, -CH ２ X ５ -, -OCX ５ ３ -, -OCH ２ X ５ -, -OCHX ５ ２ -, -CN, -SO ｎ５ R ５Ｄ -, -SO ｖ５ NR ５Ａ R ５Ｂ -, -NR ５Ｃ NR ５Ａ R ５Ｂ -, -ONR ５Ａ R ５Ｂ -, -NR ５Ｃ C(O)NR ５Ａ R ５Ｂ -, -N(O) ｍ５ -, -NR ５Ａ R ５Ｂ -, -C(O)R ５Ｃ -, -C(O)OR ５Ｃ -, -OC(O)R ５Ｃ -, -OC(O)OR ５Ｃ -, -C(O)NR ５Ａ R ５Ｂ -, -OC(O)NR ５Ａ R ５Ｂ -, -OR ５Ｄ -, -SR ５Ｄ -, -NR ５Ａ SO ２ R ５Ｄ -, -NR ５Ａ C(O)R ５Ｃ -, -NR ５Ａ C(O)OR ５Ｃ -, -NR ５Ａ OR ５Ｃ -, -SF ５ -, -N ３ a substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, z5 is an integer between 0 and 5. R ６ is hydrogen, halogen, -CCl ３ , -CBr ３ , -CF ３ , -CI ３ , -CH ２ Cl, -CH ２ Br, -CH ２ F, -CH ２ I, -CHCl ２ , -CHBr ２ , -CHF ２ , -CHI ２ , -CN, -OH, -NH ２ , -COOH, -CONH ２ , -NO ２ , -SH, -SO ３ H, -OSO ３ H, -SO ２ NH ２ , -NHNH ２ , -ONH ２ , -NH C(O)NH ２ , -NHSO ２ H, -NH C(O)H, -NH C(O)OH, -NHOH, -OCl ３ , -OBr ３ , -OF ３ , -OI ３ , -OCH ２ Cl, -OCH ２ Br, -OCH ２ F, -OCH ２ I, -OCHCl ２ , -OCHBr ２ , -OCHF ２ , -OCHI ２ , -SF ５ , -N ３ is a substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, R ４Ａ , R ４Ｂ , R ４Ｃ , R ４Ｄ , R ５Ａ , R ５Ｂ , R ５Ｃ , and R ５Ｄ However, independently, hydrogen, -CCl ３ , - CBr ３ , -CF ３ , -CI ３ -CHCl ２ , -CHBr ２ ,-CHF ２ , -CHI ２ ien-CH ２ Cl, -CH ２ Br, -CH ２ F, -CH ２ I, -CN, -OH, -NH ２ , -COOH, -CONH ２ -OCCl ３ , -OCF ３ , -OCBr ３ , -OCI ３ , -OChCl ２ , -OCHBr ２ , -OCHI ２ , -OCHF ２ , -OCH ２ Cl, -OCH ２ Br, -OCH ２ I, -OCH ２ F, a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl, with R bonded to the same nitrogen atom. ４Ａ and R ４Ｂ The substituents can optionally link to form substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl atoms, and R bonded to the same nitrogen atom ５Ａ and R ５Ｂ The substituents may optionally link together to form substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl groups. Each X ４ and X ５ However, independently, they are -F, -Cl, -Br, or -I. n4 and n5 are independent integers between 0 and 4. m4, m5, v4, and v5 are independently 1 or 2. The aforementioned compound, 【Chemistry 14】 It is not a pharmaceutical composition.

56. The pharmaceutical composition according to claim 55, wherein the pharmaceutical composition is in the form of an oral dosage form, an intranasal dosage form, an intravenous dosage form, or an injectable dosage form.

57. A compound, or a pharmaceutically acceptable salt thereof, of the formula: 【Chemistry 15】 It has, in the formula, R １ and R ２ However, independently, non-substituted C １ ~C ４ It is alkyl, R ３ However, independently, oxo, halogen, -CCl ３ , - CBr ３ , -CF ３ , -CI ３ ien-CH ２ Cl, -CH ２ Br, -CH ２ F, -CH ２ I, -CHCl ２ , -CHBr ２ ,-CHF ２ , -CHI ２ , -CN, -OH, -NH ２ , -COOH, -CONH ２ , -NO ２ , -SH, -SO ３ H, -OSO ３ H, -SO ２ NH ２ , -NHNH ２ , -ONH ２ , -NHC(O)NH ２ , - NHSO ２ H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl ３ , -OCBr ３ , -OCF ３ , -OCI ３ , -OCH ２ Cl, -OCH ２ Br, -OCH ２ F, -OCH ２ I, -OCHCl ２ , -OCHBr ２ , -OCHF ２ , -OCHI ２ , -SF ５ , -N ３ , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, z3 is an integer from 0 to 8, R ４ , R ４．２ , and R ４．３ However, independently, halogen, -CX ４ ３ EN-CHX ４ ２ ien-CH ２ X ４ , -OCX ４ ３ , -OCH ２ X ４ , -OCHX ４ ２ -CN, -SO ｎ４ R ４Ｄ , -SO ｖ４ NR ４Ａ R ４Ｂ , -NR ４Ｃ NR ４Ａ R ４Ｂ , -ONR ４Ａ R ４Ｂ , -NR ４Ｃ C(O)NR ４Ａ R ４Ｂ , -N(O) ｍ４ , -NR ４Ａ R ４Ｂ , -C(O)R ４Ｃ , -C(O)OR ４Ｃ , -OC(O)R ４Ｃ , -OC(O)OR ４Ｃ , -C(O)NR ４Ａ R ４Ｂ , -OC(O)NR ４Ａ R ４Ｂ , -OR ４Ｄ , -SR ４Ｄ , -NR ４Ａ SO ２ R ４Ｄ , -NR ４Ａ C(O)R ４Ｃ , -NR ４Ａ C(O)OR ４Ｃ , -NR ４Ａ OR ４Ｃ , -SF ５ , -N ３ , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, and two R ４ The substituents may optionally link together to form a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl, R ４．２ and R ４．３ The substituents may optionally link together to form a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl. z4 is an integer between 0 and 3, R ５ However, independently, halogen, -CX ５ ３ EN-CHX ５ ２ ien-CH ２ X ５ , -OCX ５ ３ , -OCH ２ X ５ , -OCHX ５ ２ -CN, -SO ｎ５ R ５Ｄ , -SO ｖ５ NR ５Ａ R ５Ｂ , -NR ５Ｃ NR ５Ａ R ５Ｂ , -ONR ５Ａ R ５Ｂ , -NR ５Ｃ C(O)NR ５Ａ R ５Ｂ , -N(O) ｍ５ , -NR ５Ａ R ５Ｂ , -C(O)R ５Ｃ , -C(O)OR ５Ｃ , -OC(O)R ５Ｃ , -OC(O)OR ５Ｃ , -C(O)NR ５Ａ R ５Ｂ , -OC(O)NR ５Ａ R ５Ｂ , -OR ５Ｄ , -SR ５Ｄ , -NR ５Ａ SO ２ R ５Ｄ , -NR ５Ａ C(O)R ５Ｃ , -NR ５Ａ C(O)OR ５Ｃ , -NR ５Ａ OR ５Ｃ , -SF ５ , -N ３ , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, z5 is an integer between 0 and 5. R ４Ａ , R ４Ｂ , R ４Ｃ , R ４Ｄ , R ５Ａ , R ５Ｂ , R ５Ｃ , and R ５Ｄ However, independently, hydrogen, -CCl ３ , - CBr ３ , -CF ３ , -CI ３ -CHCl ２ , -CHBr ２ ,-CHF ２ , -CHI ２ ien-CH ２ Cl, -CH ２ Br, -CH ２ F, -CH ２ I, -CN, -OH, -NH ２ , -COOH, -CONH ２ -OCCl ３ , -OCF ３ , -OCBr ３ , -OCI ３ , -OChCl ２ , -OCHBr ２ , -OCHI ２ , -OCHF ２ , -OCH ２ Cl, -OCH ２ Br, -OCH ２ I, -OCH ２ F, a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl, with R bonded to the same nitrogen atom. ４Ａ and R ４Ｂ The substituents can optionally link to form substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl atoms, and R bonded to the same nitrogen atom ５Ａ and R ５Ｂ The substituents may optionally link together to form substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl groups. Each X ４ and X ５ However, independently, they are -F, -Cl, -Br, or -I. n4 and n5 are independent integers between 0 and 4. m4, m5, v4, and v5 are independently 1 or 2. R ４．３ However, -NR ４Ａ C(O)R ４Ｃ Not a compound, or a pharmaceutically acceptable salt thereof.

58. R １ The compound according to claim 57, wherein the methyl group is unsubstituted.

59. R ２ The compound according to claim 57, wherein the methyl group is unsubstituted.

60. R ３ However, independently, non-substituted C １ ~C ４ The compound according to claim 57, wherein it is alkyl.

61. R ３ The compound according to claim 57, wherein the compound is independently an unsubstituted methyl group.

62. The compound according to claim 57, wherein z3 is 2.

63. The compound according to claim 57, wherein z3 is 0.

64. R ４．２ However, halogen, -C(O)NR ４Ａ R ４Ｂ , substitution or non-substitution C １ ~C ４ The compound according to claim 57, which is alkyl or an unsubstituted 2-6 member heteroalkyl.

65. R ４Ａ and R ４Ｂ However, independently, hydrogen or unsubstituted C １ ~C ４ The compound according to claim 64, wherein it is alkyl.

66. R ４．２ However, -Cl, -C(O)N(CH ３ ) ２ ien-CH ２ The compound according to claim 57, wherein the compound is -CN, unsubstituted methyl, unsubstituted ethyl, or unsubstituted methoxy.

67. R ４．３ However, -CN, -OR ４Ｄ , or -OC(O)R ４Ｃ The compound according to claim 57.

68. R ４Ｃ and R ４Ｄ However, independently, hydrogen or unsubstituted C １ ~C ４ The compound according to claim 67, wherein it is alkyl.

69. R ４．３ However, -CN, -OH, or -OC(O)CH ３ The compound according to claim 57.

70. R ４．２ and R ４．３ The compound according to claim 57, wherein the substituents link together to form a substituted or unsubstituted 3- to 8-membered heterocycloalkyl group.

71. R ４．２ and R ４．３ The compound according to claim 57, wherein the substituents link together to form a substituted or unsubstituted tetrahydrofuranil or a substituted or unsubstituted pyrrolidinyl.

72. R ４．２ and R ４．３ The substituents are linked together, 【Chemistry 16】 The compound according to claim 57, which forms a compound.

73. R ４ However, independently, halogen, -CCl ３ , - CBr ３ , -CF ３ , -CI ３ ien-CH ２ Cl, -CH ２ Br, -CH ２ F, -CH ２ I, -CHCl ２ , -CHBr ２ ,-CHF ２ , -CHI ２ , -CN, -OH, -NH ２ , -COOH, -CONH ２ , -NO ２ , -SH, -SO ３ H, -OSO ３ H, -SO ２ NH ２ , -NHNH ２ , -ONH ２ , -NHC(O)NH ２ , - NHSO ２ H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl ３ , -OCBr ３ , -OCF ３ , -OCI ３ , -OCH ２ Cl, -OCH ２ Br, -OCH ２ F, -OCH ２ I, -OCHCl ２ , -OCHBr ２ , -OCHF ２ , -OCHI ２ , -SF ５ , -N ３ , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, and two R ４ The compound according to claim 57, wherein the substituents can optionally link to form a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl.

74. R ４ However, independently, halogen, unsubstituted C １ ~C ４ The compound according to claim 57, which is alkyl or an unsubstituted 2-6 member heteroalkyl.

75. R ４ The compound according to claim 57, which is independently an unsubstituted methoxy compound.

76. The compound according to claim 57, wherein z4 is 1.

77. The compound according to claim 57, wherein z4 is 0.

78. R ５ However, independently, halogen, -CCl ３ , - CBr ３ , -CF ３ , -CI ３ ien-CH ２ Cl, -CH ２ Br, -CH ２ F, -CH ２ I, -CHCl ２ , -CHBr ２ ,-CHF ２ , -CHI ２ , -CN, -OH, -NH ２ , -COOH, -CONH ２ , -NO ２ , -SH, -SO ３ H, -OSO ３ H, -SO ２ NH ２ , -NHNH ２ , -ONH ２ , -NHC(O)NH ２ , - NHSO ２ H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl ３ , -OCBr ３ , -OCF ３ , -OCI ３ , -OCH ２ Cl, -OCH ２ Br, -OCH ２ F, -OCH ２ I, -OCHCl ２ , -OCHBr ２ , -OCHF ２ , -OCHI ２ , -SF ５ , -N ３ The compound according to any one of claims 57 to 77, wherein it is a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl.

79. R ５ However, independently, halogen, -CCl ３ , - CBr ３ , -CF ３ , -CI ３ ien-CH ２ Cl, -CH ２ Br, -CH ２ F, -CH ２ I, -CHCl ２ , -CHBr ２ ,-CHF ２ , -CHI ２ , -CN, -OH, -NH ２ , -COOH, -CONH ２ , substitution or non-substitution C １ ~C ４ The compound according to any one of claims 57 to 77, wherein it is alkyl, or a substituted or unsubstituted 2 to 6-membered heteroalkyl.

80. The compound according to any one of claims 57 to 77, wherein z5 is 0.

81. formula: 【Chemistry 17】 The compound according to claim 57, having the following characteristics.

82. A compound, or a pharmaceutically acceptable salt thereof, of the formula: [Chemistry 18] It has, in the formula, R １ and R ２ However, independently, hydrogen, -CCl ３ , - CBr ３ , -CF ３ , -CI ３ -CHCl ２ , -CHBr ２ ,-CHF ２ , -CHI ２ ien-CH ２ Cl, -CH ２ Br, -CH ２ F, -CH ２ I, -CN, -OH, -NH ２ , -COOH, -CONH ２ -OCCl ３ , -OCF ３ , -OCBr ３ , -OCI ３ , -OChCl ２ , -OCHBr ２ , -OCHI ２ , -OCHF ２ , -OCH ２ Cl, -OCH ２ Br, -OCH ２ I, -OCH ２ F, a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl, with R bonded to the same nitrogen atom. １ and R ２ The substituents may optionally link together to form substituted or unsubstituted heterocycloalkyl groups, or substituted or unsubstituted heteroaryl groups. R ３ However, independently, oxo, halogen, -CCl ３ , - CBr ３ , -CF ３ , -CI ３ ien-CH ２ Cl, -CH ２ Br, -CH ２ F, -CH ２ I, -CHCl ２ , -CHBr ２ ,-CHF ２ , -CHI ２ , -CN, -OH, -NH ２ , -COOH, -CONH ２ , -NO ２ , -SH, -SO ３ H, -OSO ３ H, -SO ２ NH ２ , -NHNH ２ , -ONH ２ , -NHC(O)NH ２ , - NHSO ２ H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl ３ , -OCBr ３ , -OCF ３ , -OCI ３ , -OCH ２ Cl, -OCH ２ Br, -OCH ２ F, -OCH ２ I, -OCHCl ２ , -OCHBr ２ , -OCHF ２ , -OCHI ２ , -SF ５ , -N ３ , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, z3 is an integer from 0 to 8, R ４ However, independently, halogen, -CX ４ ３ EN-CHX ４ ２ ien-CH ２ X ４ , -OCX ４ ３ , -OCH ２ X ４ , -OCHX ４ ２ -CN, -SO ｎ４ R ４Ｄ , -SO ｖ４ NR ４Ａ R ４Ｂ , -NR ４Ｃ NR ４Ａ R ４Ｂ , -ONR ４Ａ R ４Ｂ , -NR ４Ｃ C(O)NR ４Ａ R ４Ｂ , -N(O) ｍ４ , -NR ４Ａ R ４Ｂ , -C(O)R ４Ｃ , -C(O)OR ４Ｃ , -OC(O)R ４Ｃ , -OC(O)OR ４Ｃ , -C(O)NR ４Ａ R ４Ｂ , -OC(O)NR ４Ａ R ４Ｂ , -OR ４Ｄ , -SR ４Ｄ , -NR ４Ａ SO ２ R ４Ｄ , -NR ４Ａ C(O)R ４Ｃ , -NR ４Ａ C(O)OR ４Ｃ , -NR ４Ａ OR ４Ｃ , -SF ５ , -N ３ , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, and two R ４ The substituents may optionally link together to form a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl. z4 is an integer between 0 and 4, R ５ However, halogen, -CX ５ ３ EN-CHX ５ ２ ien-CH ２ X ５ , -OCX ５ ３ , -OCH ２ X ５ , -OCHX ５ ２ -CN, -SO ｎ５ R ５Ｄ , -SO ｖ５ NR ５Ａ R ５Ｂ , -NR ５Ｃ NR ５Ａ R ５Ｂ , -ONR ５Ａ R ５Ｂ , -NR ５Ｃ C(O)NR ５Ａ R ５Ｂ , -N(O) ｍ５ , -NR ５Ａ R ５Ｂ , -C(O)R ５Ｃ , -C(O)OR ５Ｃ , -OC(O)R ５Ｃ , -OC(O)OR ５Ｃ , -C(O)NR ５Ａ R ５Ｂ , -OC(O)NR ５Ａ R ５Ｂ , -OR ５Ｄ , -SR ５Ｄ , -NR ５Ａ SO ２ R ５Ｄ , -NR ５Ａ C(O)R ５Ｃ , -NR ５Ａ C(O)OR ５Ｃ , -NR ５Ａ OR ５Ｃ , -SF ５ , -N ３ , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, z5 is an integer between 0 and 5. R ４Ａ , R ４Ｂ , R ４Ｃ , R ４Ｄ , R ５Ａ , R ５Ｂ , R ５Ｃ , and R ５Ｄ However, independently, hydrogen, -CCl ３ , - CBr ３ , -CF ３ , -CI ３ -CHCl ２ , -CHBr ２ ,-CHF ２ , -CHI ２ ien-CH ２ Cl, -CH ２ Br, -CH ２ F, -CH ２ I, -CN, -OH, -NH ２ , -COOH, -CONH ２ -OCCl ３ , -OCF ３ , -OCBr ３ , -OCI ３ , -OChCl ２ , -OCHBr ２ , -OCHI ２ , -OCHF ２ , -OCH ２ Cl, -OCH ２ Br, -OCH ２ I, -OCH ２ F, a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl, with R bonded to the same nitrogen atom. ４Ａ and R ４Ｂ The substituents can optionally link to form substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl atoms, and R bonded to the same nitrogen atom ５Ａ and R ５Ｂ The substituents may optionally link together to form substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl groups. Each X ４ and X ５ However, independently, they are -F, -Cl, -Br, or -I. n4 and n5 are independent integers between 0 and 4. m4, m5, v4, and v5 are independently 1 or 2. The aforementioned compound, 【Chemistry 19】 Not a compound, or a pharmaceutically acceptable salt thereof.

83. R １ However, hydrogen or unsubstituted C １ ~C ４ The compound according to claim 82, wherein it is alkyl.

84. R １ The compound according to claim 82, wherein the methyl group is unsubstituted.

85. R ２ However, hydrogen or unsubstituted C １ ~C ４ The compound according to claim 82, wherein it is alkyl.

86. R ２ The compound according to claim 82, wherein the methyl group is unsubstituted.

87. R ３ However, independently, non-substituted C １ ~C ４ The compound according to claim 82, wherein it is alkyl.

88. R ３ The compound according to claim 82, wherein the compound is independently an unsubstituted methyl group.

89. The compound according to claim 82, wherein z3 is 2.

90. The compound according to claim 82, wherein z3 is 0.

91. R ４ However, independently, halogen, -CCl ３ , - CBr ３ , -CF ３ , -CI ３ ien-CH ２ Cl, -CH ２ Br, -CH ２ F, -CH ２ I, -CHCl ２ , -CHBr ２ ,-CHF ２ , -CHI ２ , -CN, -OH, -NH ２ , -COOH, -CONH ２ , -NO ２ , -SH, -SO ３ H, -OSO ３ H, -SO ２ NH ２ , -NHNH ２ , -ONH ２ , -NHC(O)NH ２ , - NHSO ２ H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl ３ , -OCBr ３ , -OCF ３ , -OCI ３ , -OCH ２ Cl, -OCH ２ Br, -OCH ２ F, -OCH ２ I, -OCHCl ２ , -OCHBr ２ , -OCHF ２ , -OCHI ２ , -SF ５ , -N ３ , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, and two R ４ The compound according to claim 82, wherein the substituents can optionally link to form a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl.

92. R ４ However, independently, halogen, unsubstituted C １ ~C ４ The compound according to claim 82, which is alkyl or an unsubstituted 2-6 member heteroalkyl.

93. The compound according to claim 82, wherein z4 is 0.

94. R ５ However, independently, halogen, -CCl ３ , - CBr ３ , -CF ３ , -CI ３ ien-CH ２ Cl, -CH ２ Br, -CH ２ F, -CH ２ I, -CHCl ２ , -CHBr ２ ,-CHF ２ , -CHI ２ , -CN, -OH, -NH ２ , -COOH, -CONH ２ , -NO ２ , -SH, -SO ３ H, -OSO ３ H, -SO ２ NH ２ , -NHNH ２ , -ONH ２ , -NHC(O)NH ２ , - NHSO ２ H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl ３ , -OCBr ３ , -OCF ３ , -OCI ３ , -OCH ２ Cl, -OCH ２ Br, -OCH ２ F, -OCH ２ I, -OCHCl ２ , -OCHBr ２ , -OCHF ２ , -OCHI ２ , -SF ５ , -N ３ The compound according to any one of claims 82 to 93, wherein it is a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl.

95. R ５ However, independently, halogen, -CCl ３ , - CBr ３ , -CF ３ , -CI ３ ien-CH ２ Cl, -CH ２ Br, -CH ２ F, -CH ２ I, -CHCl ２ , -CHBr ２ ,-CHF ２ , -CHI ２ , -CN, -OH, -NH ２ , -COOH, -CONH ２ , substitution or non-substitution C １ ~C ４ The compound according to any one of claims 82 to 93, wherein it is an alkyl group, or a substituted or unsubstituted 2 to 6-membered heteroalkyl group.

96. R ５ The compound according to any one of claims 82 to 93, wherein the compound is independently a halogen.

97. R ５ The compound according to any one of claims 82 to 93, wherein independently, it is -Cl.

98. The compound according to any one of claims 82 to 93, wherein z5 is 0.

99. formula: 【Chemistry 20】 The compound according to claim 82, having the following characteristics.

100. A compound, or a pharmaceutically acceptable salt thereof, of the formula: 【Chemistry 21】 It has, in the formula, R １ and R ２ However, independently, hydrogen, -CCl ３ , - CBr ３ , -CF ３ , -CI ３ -CHCl ２ , -CHBr ２ ,-CHF ２ , -CHI ２ ien-CH ２ Cl, -CH ２ Br, -CH ２ F, -CH ２ I, -CN, -OH, -NH ２ , -COOH, -CONH ２ -OCCl ３ , -OCF ３ , -OCBr ３ , -OCI ３ , -OChCl ２ , -OCHBr ２ , -OCHI ２ , -OCHF ２ , -OCH ２ Cl, -OCH ２ Br, -OCH ２ I, -OCH ２ F, a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl, with R bonded to the same nitrogen atom. １ and R ２ The substituents may optionally link together to form substituted or unsubstituted heterocycloalkyl groups, or substituted or unsubstituted heteroaryl groups. R ３ However, independently, oxo, halogen, -CCl ３ , - CBr ３ , -CF ３ , -CI ３ ien-CH ２ Cl, -CH ２ Br, -CH ２ F, -CH ２ I, -CHCl ２ , -CHBr ２ ,-CHF ２ , -CHI ２ , -CN, -OH, -NH ２ , -COOH, -CONH ２ , -NO ２ , -SH, -SO ３ H, -OSO ３ H, -SO ２ NH ２ , -NHNH ２ , -ONH ２ , -NHC(O)NH ２ , - NHSO ２ H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl ３ , -OCBr ３ , -OCF ３ , -OCI ３ , -OCH ２ Cl, -OCH ２ Br, -OCH ２ F, -OCH ２ I, -OCHCl ２ , -OCHBr ２ , -OCHF ２ , -OCHI ２ , -SF ５ , -N ３ , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, z3 is an integer from 0 to 8, R ４ However, independently, halogen, -CX ４ ３ EN-CHX ４ ２ ien-CH ２ X ４ , -OCX ４ ３ , -OCH ２ X ４ , -OCHX ４ ２ -CN, -SO ｎ４ R ４Ｄ , -SO ｖ４ NR ４Ａ R ４Ｂ , -NR ４Ｃ NR ４Ａ R ４Ｂ , -ONR ４Ａ R ４Ｂ , -NR ４Ｃ C(O)NR ４Ａ R ４Ｂ , -N(O) ｍ４ , -NR ４Ａ R ４Ｂ , -C(O)R ４Ｃ , -C(O)OR ４Ｃ , -OC(O)R ４Ｃ , -OC(O)OR ４Ｃ , -C(O)NR ４Ａ R ４Ｂ , -OC(O)NR ４Ａ R ４Ｂ , -OR ４Ｄ , -SR ４Ｄ , -NR ４Ａ SO ２ R ４Ｄ , -NR ４Ａ C(O)R ４Ｃ , -NR ４Ａ C(O)OR ４Ｃ , -NR ４Ａ OR ４Ｃ , -SF ５ , -N ３ , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, and two R ４ The substituents may optionally link together to form a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl. z4 is an integer between 0 and 5. R ５ However, halogen, -CX ５ ３ EN-CHX ５ ２ ien-CH ２ X ５ , -OCX ５ ３ , -OCH ２ X ５ , -OCHX ５ ２ -CN, -SO ｎ５ R ５Ｄ , -SO ｖ５ NR ５Ａ R ５Ｂ , -NR ５Ｃ NR ５Ａ R ５Ｂ , -ONR ５Ａ R ５Ｂ , -NR ５Ｃ C(O)NR ５Ａ R ５Ｂ , -N(O) ｍ５ , -NR ５Ａ R ５Ｂ , -C(O)R ５Ｃ , -C(O)OR ５Ｃ , -OC(O)R ５Ｃ , -OC(O)OR ５Ｃ , -C(O)NR ５Ａ R ５Ｂ , -OC(O)NR ５Ａ R ５Ｂ , -OR ５Ｄ , -SR ５Ｄ , -NR ５Ａ SO ２ R ５Ｄ , -NR ５Ａ C(O)R ５Ｃ , -NR ５Ａ C(O)OR ５Ｃ , -NR ５Ａ OR ５Ｃ , -SF ５ , -N ３ , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, z5 is an integer between 0 and 5. R ６ However, halogen, -CCl ３ , - CBr ３ , -CF ３ , -CI ３ ien-CH ２ Cl, -CH ２ Br, -CH ２ F, -CH ２ I, -CHCl ２ , -CHBr ２ ,-CHF ２ , -CHI ２ , -CN, -OH, -NH ２ , -COOH, -CONH ２ , -NO ２ , -SH, -SO ３ H, -OSO ３ H, -SO ２ NH ２ , -NHNH ２ , -ONH ２ , -NHC(O)NH ２ , - NHSO ２ H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl ３ , -OCBr ３ , -OCF ３ , -OCI ３ , -OCH ２ Cl, -OCH ２ Br, -OCH ２ F, -OCH ２ I, -OCHCl ２ , -OCHBr ２ , -OCHF ２ , -OCHI ２ , -SF ５ , -N ３ , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted aryl, or substituted or unsubstituted heteroaryl, R ４Ａ , R ４Ｂ , R ４Ｃ , R ４Ｄ , R ５Ａ , R ５Ｂ , R ５Ｃ , and R ５Ｄ However, independently, hydrogen, -CCl ３ , - CBr ３ , -CF ３ , -CI ３ -CHCl ２ , -CHBr ２ ,-CHF ２ , -CHI ２ ien-CH ２ Cl, -CH ２ Br, -CH ２ F, -CH ２ I, -CN, -OH, -NH ２ , -COOH, -CONH ２ -OCCl ３ , -OCF ３ , -OCBr ３ , -OCI ３ , -OChCl ２ , -OCHBr ２ , -OCHI ２ , -OCHF ２ , -OCH ２ Cl, -OCH ２ Br, -OCH ２ I, -OCH ２ F, a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl, with R bonded to the same nitrogen atom. ４Ａ and R ４Ｂ The substituents can optionally link to form substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl atoms, and R bonded to the same nitrogen atom ５Ａ and R ５Ｂ The substituents may optionally link together to form substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl groups. Each X ４ and X ５ However, independently, they are -F, -Cl, -Br, or -I. n4 and n5 are independent integers between 0 and 4. A compound, or a pharmaceutically acceptable salt thereof, wherein m4, m5, v4, and v5 are independently 1 or 2.

101. formula: 【Chemistry 22】 The compound according to claim 100, having the following characteristics.

102. R １ However, hydrogen or unsubstituted C １ ~C ４ The compound according to claim 100, wherein it is alkyl.

103. R １ The compound according to claim 100, wherein the compound is an unsubstituted methyl group.

104. R ２ However, hydrogen or unsubstituted C １ ~C ４ The compound according to claim 100, wherein it is alkyl.

105. R ２ The compound according to claim 100, wherein the compound is an unsubstituted methyl group.

106. The compound according to claim 100, wherein z3 is 0.

107. R ４ However, independently, halogen, -CCl ３ , - CBr ３ , -CF ３ , -CI ３ ien-CH ２ Cl, -CH ２ Br, -CH ２ F, -CH ２ I, -CHCl ２ , -CHBr ２ ,-CHF ２ , -CHI ２ , -CN, -OH, -NH ２ , -COOH, -CONH ２ , -NO ２ , -SH, -SO ３ H, -OSO ３ H, -SO ２ NH ２ , -NHNH ２ , -ONH ２ , -NHC(O)NH ２ , - NHSO ２ H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl ３ , -OCBr ３ , -OCF ３ , -OCI ３ , -OCH ２ Cl, -OCH ２ Br, -OCH ２ F, -OCH ２ I, -OCHCl ２ , -OCHBr ２ , -OCHF ２ , -OCHI ２ , -SF ５ , -N ３ , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, and two R ４ The compound according to claim 100, wherein the substituents can optionally be linked to form a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl.

108. R ４ However, independently, halogen, -OH, and unsubstituted C １ ~C ４ The compound according to claim 100, which is alkyl or an unsubstituted 2-6 member heteroalkyl.

109. R ４ The compound according to claim 100, wherein the -OH group is independent.

110. R ５ However, independently, halogen, -CCl ３ , - CBr ３ , -CF ３ , -CI ３ ien-CH ２ Cl, -CH ２ Br, -CH ２ F, -CH ２ I, -CHCl ２ , -CHBr ２ ,-CHF ２ , -CHI ２ , -CN, -OH, -NH ２ , -COOH, -CONH ２ , -NO ２ , -SH, -SO ３ H, -OSO ３ H, -SO ２ NH ２ , -NHNH ２ , -ONH ２ , -NHC(O)NH ２ , - NHSO ２ H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCCl ３ , -OCBr ３ , -OCF ３ , -OCI ３ , -OCH ２ Cl, -OCH ２ Br, -OCH ２ F, -OCH ２ I, -OCHCl ２ , -OCHBr ２ , -OCHF ２ , -OCHI ２ , -SF ５ , -N ３ The compound according to any one of claims 100 to 109, wherein it is a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl.

111. The compound according to any one of claims 100 to 109, wherein z5 is 0.

112. formula: 【Chemistry 23】 The compound according to claim 100, having the following characteristics.

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