Small molecules for the treatment of autoimmune diseases

Abstract

This specification discloses bicyclic and tricyclic compounds, as well as pharmaceutical compositions containing one or more thereof. It also discloses methods for producing functionalized bicyclic and tricyclic compounds. Furthermore, it discloses methods for treating diseases and / or conditions (e.g., inflammatory and / or autoimmune diseases) using the bicyclic and tricyclic compounds disclosed herein.

Description

[Technical Field]

[0001] Cross-references to related applications This application claims priority to U.S. Provisional Patent Application No. 63 / 510,291, filed on 26 June 2023. That Provisional Application is incorporated herein by reference in its entirety for all purposes.

[0002] This specification discloses bicyclic and tricyclic compounds, as well as pharmaceutical compositions comprising one or more of these compounds. Methods for producing functionalized bicyclic and tricyclic compounds are also disclosed. [Background technology]

[0003] Autoimmune diseases, characterized by dysregulation of the immune response, place a significant burden on global healthcare systems and affect millions of patients worldwide. Current treatments for autoimmune diseases generally involve immunosuppressants, anti-inflammatory drugs, or combinations thereof. While these treatments help alleviate symptoms and manage the disease, they often have limitations, including adverse side effects, incomplete effectiveness, and the potential for long-term complications. Furthermore, some patients may develop resistance to conventional treatments or experience relapses, necessitating alternative treatment options. [Overview of the Initiative]

[0004] Some embodiments disclosed herein relate to bicyclic and tricyclic compounds, and their use in the treatment of autoimmune or inflammatory diseases. Some embodiments relate to methods for producing bicyclic and tricyclic compounds, and methods for using bicyclic and tricyclic compounds as therapeutic agents for the treatment of inflammatory disease conditions. Some embodiments include, consist of, or essentially consist of tricyclic compounds of formula (I) (or other structures disclosed herein), their pharmaceutically acceptable salts, enantiomers, methods for production, and / or methods for using them in the treatment of disease conditions. Some embodiments include, consist of, or essentially consist of bicyclic compounds of formula (II) (or other structures disclosed herein), their pharmaceutically acceptable salts, enantiomers, methods for production, and / or methods for using them in the treatment of disease conditions. In some embodiments, the disease condition is related to inflammation. In some embodiments, the disease condition is related to autoimmune diseases.

[0005] Some embodiments relate to compounds having the structure represented by formula I, or pharmaceutically acceptable salts thereof: [ka]

[0006] In some embodiments, R1 is selected from the group consisting of H, -OH, -CH3, or -OCH3; R2 is -H, -OH, or optionally substituted C 1-6 Alkyl, optionally substituted C 1-6 Alkoxy or optionally substituted C 1-6 Selected from the group consisting of haloalkyl groups; R3 is -CN, -OH, or optionally substituted C1-C 10 Alkyl, optionally substituted C1-C 10 Alkenyl, optionally replaced C1-C 10Selected from the group consisting of alkynyl, optionally substituted alkoxy, optionally substituted 3- to 10-membered carbocyclic, optionally substituted 6- to 10-membered aryl, optionally substituted 3- to 10-membered heterocyclic, optionally substituted 5- to 10-membered heteroaryl, and -NR5R6; R4 is -H, -(CO)CH3, optionally substituted C1-C 10 Selected from the group consisting of alkyl; and R5 and R6 are each optionally substituted C 1-6 Alkyl.

[0007] Some embodiments relate to a compound represented by formula (I), or a pharmaceutically acceptable salt thereof, and further to a compound represented by formula (Ia):

Chemical formula

[0008] In some embodiments, R7, R8, R9, R 10 , R 11 , and R 12 are each independently selected from the group consisting of -H, -OH, halogen, optionally substituted C 1-6 alkyl, optionally substituted C 1-6 alkoxy, optionally substituted C 1-6 alkyl, optionally substituted C 1-6 alkoxy, or optionally substituted C 1-6 haloalkyl; R 13 is selected from the group consisting of optionally substituted C 1-6 alkyl, optionally substituted C 1-20 alkylene, and absent; R 14 is selected from the group consisting of optionally substituted 3- to 20-membered heterocyclic, -NR 15 R 16 , and absent; and R 15 and R<第 16 are each optionally substituted C 1-6 alkyl.

[0009] In some embodiments, R7, R8, R 11 , and R 12 These are -H, and R9 and R 10 These are halogens. In a further embodiment, R9 and R 10 These are each -F. In some embodiments, R4 is -H. In other embodiments, R4 is -(CO)CH3. In some embodiments, R 13 This is C, which has been replaced by an optional substitution. 1-20 It is an alkylene. In a further embodiment, R 13 R is selected from the group consisting of ethylene and propylene. In some embodiments, R 14 R is a 5-membered heterocycline that has been optionally substituted. In some embodiments, R 14 teeth [ka] In another embodiment, R 14 -NR 15 R 16 In a further embodiment, R 15 and R 16 Each is independently selected from the group consisting of methyl, ethyl, and propyl. In some embodiments, R 13 This is C, which has been replaced by an optional substitution. 1-6 It is alkyl. In a further embodiment, R 13 It is -CH3.

[0010] In some embodiments, the structure of formula I, or a pharmaceutically acceptable salt thereof, is further represented by a formula selected from any one of the following compounds: [ka]

[0011] Some embodiments relate to compounds having the structure represented by formula II, or pharmaceutically acceptable salts thereof: [ka]

[0012] In some embodiments, R 17 R is selected from the group consisting of -H, -OH, and halogens; 18 This is C, which has been replaced by an optional substitution. 1-6 Alkyl, optionally substituted C 1-20 Selected from the group consisting of alkylenes and absence; R 19 This is a 3-20 member heterocycline that has been optionally replaced, -NR 21 R 22 Selected from the group consisting of , and non-existence; R 20 is selected from the group consisting of -H and 3-4 member heterocyclines substituted by optional choice; and R 21 and R 22 These are C, each replaced by an arbitrary choice. 1-6 It is alkyl.

[0013] In some embodiments, R 20 is a 4-membered heterocycline. In further embodiments, R 20 teeth [ka] In some embodiments, R 17 is a halogen. In a further embodiment, R 17 is -Cl. In some embodiments, R 18 C is replaced by an optional substitution. 1-20 It is an alkylene group. In further embodiments, R 18 R is selected from the group consisting of ethylene and propylene. In some embodiments, R 19 R is an optionally substituted 5-membered heterocycline. In further embodiments, R 19 teeth [ka] In another embodiment, R 19 -NR 21 R22 In a further embodiment, R 21 or R 22 Each is independently selected from the group consisting of methyl, ethyl, and propyl. In some embodiments, R 18 C is replaced by an optional substitution. 1-6 It is alkyl. In a further embodiment, R 18 It is -CH3.

[0014] In some embodiments, the structure of formula II, or a pharmaceutically acceptable salt thereof, is further represented by a formula selected from any one of the following compounds: [ka]

[0015] Some embodiments relate to methods for treating autoimmune or inflammatory diseases, comprising administering the compounds disclosed herein to subjects in need of treatment. In some embodiments, the subjects suffer from an autoimmune or inflammatory disease. In certain embodiments, the compounds disclosed herein do not substantially inhibit G9a.

[0016] Some embodiments relate to methods for producing the compounds disclosed herein, the methods comprising functionalizing a bicyclic compound starting material with one or more substituents. Some embodiments relate to the use of the compounds disclosed herein in the manufacture of pharmaceuticals for the treatment of autoimmune or inflammatory diseases. Some embodiments relate to the use of the compounds disclosed herein in the treatment of autoimmune or inflammatory diseases. [Brief explanation of the drawing]

[0017] Figure 1A is a graph showing the percentage change in body weight of mice with dextran sulfate sodium (DSS)-induced colitis after treatment with the selected compound.

[0018] Figure 1B is a chart showing the percentage change in body weight of mice with DSS-induced colitis after exposure to the selected conditions.

[0019] Figure 1C is a chart showing the colon length of mice with DSS-induced colitis after exposure to selected conditions.

[0020] Figure 2A is a graph showing the percentage change in body weight of mice with 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis after treatment with the selected compound.

[0021] Figure 2B is a chart showing the colonic length of mice with TNBS-induced colitis after exposure to selected conditions.

[0022] Figure 2C is a chart showing the histological scores of mice with TNBS-induced colitis after exposure to selected conditions.

[0023] Figure 2D is a chart showing the clinical scores of mice with TNBS-induced colitis after exposure to selected conditions. [Modes for carrying out the invention]

[0024] Detailed explanation Several embodiments disclosed herein provide compounds useful for treating autoimmune or inflammatory diseases in a subject. Several embodiments also provide methods for treating diseases utilizing these compounds or pharmaceutical compositions containing these compounds. In some embodiments, the compounds are bicyclic compounds. In other embodiments, the compounds are tricyclic compounds. In some embodiments, the bicyclic compounds include at least two aromatic rings. In some embodiments, the tricyclic compounds include at least two aromatic rings. In some embodiments, multiple functional groups are bonded to at least one aromatic ring. Several embodiments include, consist of, or are essentially derived from, the tricyclic compound of formula (I) (or other structures disclosed herein), its pharmaceutically acceptable salts, enantiomers, methods of preparation, and / or methods of use thereof in the treatment of autoimmune or inflammatory diseases. Several embodiments include, consist of, or are essentially derived from, the bicyclic compound of formula (II) (or other structures disclosed herein), its pharmaceutically acceptable salts, enantiomers, methods of preparation, and / or methods of use thereof in the treatment of autoimmune or inflammatory diseases.

[0025] The following description is for background and illustrative purposes only and should not be construed as limiting the scope of the inventions covered by the claims set forth herein or in other applications claiming priority thereto. No single component or set of components is essential or indispensable. Features, structures, components, materials, processes, or methods described and / or illustrated in any embodiment of this specification may be used in conjunction with, or in place of, features, structures, components, materials, processes, or methods described and / or illustrated in other embodiments of this specification.

[0026] definition Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those generally understood by those skilled in the art to which this disclosure pertains. All patents, applications, published applications, and other publications are incorporated by reference in their entirety. If there are multiple definitions of a term herein, the definition in this section shall prevail unless otherwise specified.

[0027] A "prodrug" refers to a drug that is converted to a parent drug in the body. Prodrugs are often useful because, in some situations, they are easier to administer than the parent drug. For example, even if the parent drug is not bioavailable when administered orally, the prodrug may be bioavailable when administered orally. Prodrugs may also have improved solubility in formulations compared to the parent drug. Examples of prodrugs, though not limited to them, include compounds administered as esters ("prodrugs") to promote cell membrane permeability where water solubility is unfavorable, and which are metabolically hydrolyzed into active carboxylic acids once inside the cell where water solubility is beneficial. Further examples of prodrugs include short peptides (polyamino acids) bound to an acidic group, which are metabolized to express an active site. Conventional procedures for the selection and preparation of appropriate prodrug derivatives are described, for example, in *Design of Prodrugs* (H. Bundgaard, ed., Elsevier, 1985), which is incorporated herein by reference in its entirety.

[0028] "Prodrug ester" refers to a derivative of a compound disclosed herein formed by adding one of several ester-forming groups that are hydrolyzed under physiological conditions. Examples of prodrug ester groups include pivoyloxymethyl, acetoxymethyl, phthalidyl, indanyl, methoxymethyl, and (5-R-2-oxo-1,3-dioxolene-4-yl)methyl, as well as other groups well known to those skilled in the art. Further examples of prodrug ester groups are described, for example, in T. Higuchi and V. Stella, *Pro-drugs as Novel Delivery Systems* (Vol. 14, ACS Symposium Series, American Chemical Society, 1975) and E.B. Roche, ed., *Bioreversible Carriers in Drug Design: Theory and Application* (Pergamon Press: New York, pp. 14-21, 1987) (which provides examples of esters useful as prodrugs for carboxyl-containing compounds). The above references are incorporated herein by reference in their entirety.

[0029] The “metabolites” of the compounds disclosed herein include active species that are generated when such compounds are introduced into the biological environment.

[0030] A "solvate" refers to a compound formed by the interaction of a solvent, a compound, a metabolite, or a salt thereof with a solvent as described herein. Suitable solvates include pharmaceutically acceptable solvates, including hydrates.

[0031] The term "pharmaceutically acceptable salt" refers to a salt that retains the biological efficacy and properties of a compound and is not biologically or otherwise undesirable for pharmaceutical use. In many cases, the compounds described herein can form acid salts and / or base salts in the presence of an amino group and / or a carboxyl group, or a similar group. Pharmaceutically acceptable acid addition salts can be formed with inorganic and organic acids. Examples of inorganic acids from which salts can be derived include hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, and phosphoric acid. Examples of organic acids that can produce salts include acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, and salicylic acid. Pharmaceutically acceptable base addition salts can be formed with inorganic and organic bases. Examples of inorganic bases that can produce salts include sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, and aluminum, with ammonium salts, potassium salts, sodium salts, calcium salts, and magnesium salts being particularly preferred. Examples of organic bases that can produce salts include primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines, and basic ion exchange resins, specifically isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, and ethanolamine. Many of these salts are well known to those skilled in the art, as described in WO87 / 05297, Johnston et al., published on September 11, 1987 (the whole of which is incorporated herein by reference).

[0032] When referring to numerical values, the term “range including and / or extending to the value” (and variations thereof) is intended to include any range including or extending to the value. For example, when a reaction temperature is expressed as “20°C, 30°C, 40°C, 50°C, or range including the value,” this includes a specific temperature value, or 20°C to 50°C, 20°C to 40°C, 20°C to 30°C, 30°C to 50°C, 30°C to 40°C, or 40°C or 50°C.

[0033] In this specification, "C a From C b "C1-C4 alkyl" refers to the number of carbon atoms in an alkyl, alkenyl, or alkynyl group, or the number of carbon atoms in a cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, or heteroaryl ring, where "a" and "b" are integers. That is, an alkyl, alkenyl, alkynyl, cycloalkyl ring, cycloalkenyl ring, cycloalkynyl ring, aryl ring, or heteroaryl ring can contain carbon atoms from "a" to "b". Therefore, for example, the "C1-C4 alkyl" group includes all alkyl groups having 1 to 4 carbon atoms (e.g., 1, 2, 3, or 4), i.e., CH3-, CH3CH2-, CH3CH2CH2-, (CH3)2CH-, CH3CH2CH2CH2-, CH3CH2CH(CH3)-, and (CH3)3C-. The "C1-C6 alkyl" group refers to all alkyl groups having 1 to 6 carbon atoms (e.g., 1, 2, 3, 4, 5, 6). If "a" and "b" are not specified for alkyl, alkenyl, alkynyl, cycloalkylcycloalkenyl, cycloalkynyl, aryl, or heteroaryl groups, the ranges described in those definitions (including the broadest range) are included.

[0034] In this specification, “alkyl” means a fully saturated (i.e., non-double or triple bonded) linear or branched hydrocarbon chain. Alkyl chains can be branched or linear. Examples of branched alkyl groups include, but are not limited to, isopropyl, sec-butyl, and t-butyl. Examples of linear alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, and n-heptyl. Alkyl groups may have 1 to 20 carbon atoms (as disclosed herein, numerical ranges such as “1 to 20” refer to each integer within a given range. For example, “1 to 20 carbon atoms” means that an alkyl group may consist of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 carbon atoms. However, the use of the term “alkyl” when no numerical range is specified is also included in this definition). The "alkyl" group may be a medium-chain alkyl group having 1 to 12 carbon atoms. The "alkyl" group may also be a lower alkyl group having 1 to 6 carbon atoms. The alkyl group of a compound is "C 1-6 It may be specified as "alkyl" or a similar notation. For illustrative purposes only, "C 1-4 "Alkyl" indicates that the alkyl chain has 1 to 4 carbon atoms, meaning the alkyl chain is selected from the group consisting of methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, and t-butyl. For illustrative purposes only, "C1-C5 alkyl" indicates that the alkyl chain has 1 to 5 carbon atoms, meaning the alkyl chain is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, pentyl (branched and linear), etc. Typical alkyl groups include, but are not limited to, methyl ("Me" or -CH3), ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, and hexyl. Alkyl groups may or may not have substituents.

[0035] In this specification, "alkenyl" refers to an alkyl group containing one or more double bonds in a linear or branched hydrocarbon chain. As stated in the definition of "alkyl," an alkenyl group may be unsubstituted or substituted.

[0036] In this specification, "alkynyl" refers to an alkyl group containing one or more triple bonds in a straight or branched hydrocarbon chain. As stated in the definition of "alkyl," an alkynyl group may or may not have substituents.

[0037] In this specification, the term "alkylene" refers to a divalent fully saturated linear aliphatic hydrocarbon group. Examples of alkylene groups include, but are not limited to, methylene, ethylene, propylene, butylene, pentylene, hexylene, heptylene, and octylene. Alkylene groups are defined by adding an asterisk (*) to the number of carbon atoms. [ka] It can be represented by, for example, [ka] represents ethylene. The alkylene group may have 1 to 20 carbon atoms (in this specification, numerical ranges such as "1 to 20" refer to each integer within that range; for example, "1 to 20 carbon atoms" means that the alkyl group is composed of 1 carbon atom, 2 carbon atoms, 3 carbon atoms, etc., and contains a maximum of 20 carbon atoms, but the use of the term "alkylene" without a specified numerical range is also included in this definition). The alkylene group may also be a medium-chain alkyl group having 1 to 12 carbon atoms. The alkylene group may also be a lower alkyl group having 1 to 6 carbon atoms. For example, a lower alkylene group may have one or more hydrogens on the lower alkylene group and / or both hydrogens on the same carbon atom C 3-6 Monocyclic cycloalkyl groups (for example) [ka] Substitution can be made by substitution with ). It should also be understood that certain radical naming conventions may include either single radicals or double radicals depending on the context. For example, if a substituent requires two bond sites to a molecular residue, that substituent is understood to be a double radical. For example, substituents that are identified as alkyl and require two bond sites include difunctional groups such as -CH2-, -CH2CH2-, and -CH2CH(CH3)CH2-. Other functional group naming conventions clearly indicate that the functional group is difunctional, such as "alkylene" or "alkenylene". Alkylene groups may or may not be substituted.

[0038] In this specification, the term "halogen" or "halo" means any of the radioactive stable elements belonging to Group 7 of the periodic table. Examples include fluorine (-F), chlorine (-Cl), bromine (-Br), or iodine (-I).

[0039] In this specification, “haloalkyl” means a linear or branched alkyl group in which one or more hydrogens are substituted with halogens. Examples of haloalkyl groups include, but are not limited to, -CF3, -CHF2, -CH2F, -CH2CF3, -CH2CHF2, -CH2CH2F, -CH2CH2Cl, -CH2CF2CF3, and other groups that are considered equivalent to any of the above examples in light of the ordinary art of those skilled in the art and the teachings described herein. Haloalkyl groups can be of medium size or low position. Haloalkyl groups may or may not have substituents.

[0040] In this specification, "alkoxy" refers to the formula -OR, where R is an alkyl group as defined above, for example, "C 1-9 The term "alkoxy" includes, but is not limited to, methoxy, ethoxy, n-propoxy, 1-methylethoxy (isopropoxy), n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, etc. The alkoxy group may or may not be substituted.

[0041] In this specification, "polyethylene glycol" means [ka] This refers to a compound represented by the formula , where n is an integer greater than 1 and R is a hydrogen atom or an alkyl group. The number of repeating units "n" may be indicated by the number of members. For example, "2-5 member polyethylene glycol" means that n is selected from an integer between 2 and 5. In some embodiments, R is selected from methoxy, ethoxy, n-propoxy, 1-methylethoxy (isopropoxy), n-butoxy, isobutoxy, sec-butoxy, and tert-butoxy.

[0042] In this specification, “heteroalkyl” refers to a linear or branched hydrocarbon chain (e.g., alkyl) containing one or more heteroatoms. Heteroatoms are given the simple and common sense meaning in organic chemistry and include elements other than carbon, including but not limited to nitrogen (e.g., aminos), oxygen (e.g., alkoxys, ethers, hydroxyls), sulfur, and halogens. Heteroalkyl groups may have 1 to 20 carbon atoms, but the use of the term “heteroalkyl” when no numerical range is specified is also included in this definition. Heteroalkyl groups may also be medium-sized heteroalkyl groups having 1 to 12 carbon atoms. Heteroalkyl groups may further be lower heteroalkyl groups having 1 to 6 carbon atoms. In various embodiments, heteroalkyl groups may have 1 to 4 heteroatoms, 1 to 3 heteroatoms, 1 or 2 heteroatoms, or 1 heteroatom. The heteroalkyl group of a compound is “C 1-4 It may be designated as "heteroalkyl" or a similar name. A heteroalkyl group may contain one or more heteroatoms. For example, "C 1-4 The term "heteroalkyl" indicates that the heteroalkyl chain contains 1 to 4 carbon atoms, and furthermore, the chain's backbone contains one or more heteroatoms. Heteroalkyl groups may or may not be substituted.

[0043] The term "aromatic" refers to a ring or ring system having a conjugated π-electron system, and includes both carbocyclic aromatics (e.g., phenyl) and heterocyclic aromatic groups (e.g., pyridine). The term includes monocyclic or fused polycyclic (i.e., rings sharing adjacent pairs of atoms) groups, provided that the entire ring system is aromatic.

[0044] In this specification, “aryl” refers to an aromatic ring or ring system (i.e., two or more fused rings sharing two adjacent carbon atoms) whose ring skeleton consists solely of carbon atoms. If an aryl is a ring system, all rings within the system are aromatic. While an aryl group may have 6 to 18 carbon atoms, this definition also includes the use of the term “aryl” when no numerical range is specified. In some embodiments, an aryl group has 6 to 10 carbon atoms. 6-10 "Aryl", "C6 or C 10 It may be designated as "aryl" or a similar name. For example, the aryl group is C6-C 14 Aryl group, C6-C 10 The group can be an aryl group or a C6 aryl group. Examples of aryl groups include, but are not limited to, phenyl, naphthyl, azuleniyl, and anthracenyl. The aryl group may or may not have substituents.

[0045] In this specification, "aryloxy" and "arylthio" refer to a group in which R is an aryl group as defined above (e.g., "C"). 6-10 "aryloxy" or "C 6-10 This refers to RO- and RS-, which are arylthio groups, and includes but is not limited to phenyloxy groups. The aryloxy or arylthio group may or may not be substituted.

[0046] "Aralkyl" or "arylalkyl" refers to an aryl group bonded via an alkylene group as a substituent, for example, "C 7-14These include "aralkyl," and are not limited to benzyl, 2-phenylethyl, 3-phenylpropyl, naphthylalkyl, etc. In some cases, the alkylene group is a lower alkylene group (i.e., C 1-6 It is an alkylene group. The aralkyl group or arylalkyl group may or may not be substituted.

[0047] In this specification, “heteroaryl” means an aromatic ring or ring system (i.e., two or more fused rings sharing two or more adjacent atoms) containing one or more heteroatoms, i.e., elements other than carbon, including but not limited to nitrogen, oxygen, and sulfur, within its ring skeleton. If the heteroaryl is a ring system, each ring in the system can be aromatic. A heteroaryl group may have 5 to 18 ring members (i.e., the number of atoms constituting the ring skeleton, including carbon atoms and heteroatoms), but this definition also includes the use of the term “heteroaryl” when no numerical range is specified. For example, a heteroaryl group may contain 4 to 14 ring members (atoms in the ring), 5 to 10 ring members (atoms in the ring), 5 to 7 ring members (atoms in the ring), or 5 to 6 ring members (atoms in the ring). A heteroaryl group may be designated as a “5-7 membered heteroaryl,” a “5-10 membered heteroaryl,” or a similar name. In various embodiments, the heteroaryl comprises 1 to 4 heteroatoms, 1 to 3 heteroatoms, 1 to 2 heteroatoms, or 1 heteroatom. For example, in various embodiments, the heteroaryl comprises 1 to 4 nitrogen atoms, 1 to 3 nitrogen atoms, 1 to 2 nitrogen atoms, 2 nitrogen atoms and 1 sulfur or oxygen atom, 1 nitrogen atom and 1 sulfur or oxygen atom, or 1 sulfur or oxygen atom.Examples of heteroaryl rings include furan (e.g., furyl), furazan (e.g., furazanyl group), thiophene (e.g., thienyl), benzothiophene (e.g., benzothienyl), phthalazine (e.g., phthalazinyl), pyrrole (e.g., pyrrolyl), oxazole (e.g., oxazolyl), benzoxazole (e.g., benzoxazolyl), 1,2,3-oxadiazole, 1,2,4-oxadiazole, thiazole (e.g., thiazolyl), 1,2,3-thiadiazole, 1,2,4-thiadiazole, and benzothiazole (e.g., benzothiazolyl). This includes, but is not limited to, imidazoles (e.g., imidazolyl), benzimidazoles (e.g., benzimidazolyl), indoles (e.g., indolyl), isoindoles (e.g., isoindolyl), indazoles, pyrazoles (e.g., pyrazolyl), benzopyrazoles, isoxazoles (e.g., isoxazolyl), benzoisoxazoles, isothiazoles (e.g., isothiazolyl), triazoles (e.g., triazolyl), benzotriazoles, thiadiazoles (e.g., thiadiazolyl), tetrazoles, pyridines (e.g., pyridinyl), pyridazines (e.g., pyridazinyl), pyrimidines (e.g., pyrimidinyl), pyrazines (e.g., pyrazinyl), purines, pteridines, quinolines (e.g., quinolinyl), isoquinolines (e.g., isoquinolinyl), quinazolines, quinoxalines, cinnolines, and triazines (e.g., triazinyl). The heteroaryl ring may contain a bridgehead nitrogen atom. For example, pyrazolo[1,5-a]pyridine, imidazo[1,2-a]pyridine, and pyrazolo[1,5-a]pyrimidine, but are not limited to these. The heteroaryl group may or may not have substituents.

[0048] A "heteroaralkyl" or "heteroarylalkyl" is a compound in which a heteroaryl group is bonded via an alkylene group as a substituent. Examples include, but are not limited to, 2-thienylmethyl, 3-thienylmethyl, furylmethyl, thienylethyl, pyrrolylalkyl, pyridylalkyl, isoxazolylalkyl, and imidazolylalkyl. The heteroaralkyl group may or may not have substituents.

[0049] In this specification, “carbocyclyl” means a non-aromatic cyclic ring or cyclic system containing only carbon atoms in its cyclic framework. If a carbocyclyl is a cyclic system, two or more rings may be linked by condensation, bridging, or spirobonding. A carbocyclyl can have any degree of saturation, as long as at least one ring in the cyclic system is aromatic. Therefore, carbocyclyls include cycloalkyls, cycloalkenyls, and cycloalkynyls. A carbocyclyl group may have 3 to 20 carbon atoms, but this definition also includes the use of the term “carbocyclyl” when no numerical range is specified. A carbocyclyl group may also be a medium-sized carbocyclyl with 3 to 10 carbon atoms. A carbocyclyl group may also be a carbocyclyl with 3 to 6 carbon atoms. A carbocyclyl group is “C 3-6 It may be designated as "carbocyrill" or a similar name. Examples of carbocyclyl rings include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl, 2,3-dihydroindene, bicyclo[2.2.2]octanyl, adamantyl, and spiro[4.4]nonanyl. The carbocyclyl group may or may not have substituents.

[0050] In this specification, "cycloalkyl" refers to a completely saturated (non-double or triple bonded) monocyclic or polycyclic hydrocarbon ring system. If composed of two or more rings, the rings may be linked by a condensed structure. A cycloalkyl group may contain 3 to 10 atoms or 3 to 8 atoms in the ring, or may be otherwise described herein. A cycloalkyl group may have substituents or not. Typical cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl.

[0051] "(Carbocyclyl)alkyl" refers to a carbocyclyl group bonded via an alkylene group as a substituent, for example, "C 4-10Examples include "(carbocykyl)alkyl," which includes, but is not limited to, cyclopropylmethyl, cyclobutylmethyl, cyclopropylethyl, cyclopropylbutyl, cyclobutylethyl, cyclopropylisopropyl, cyclopentylmethyl, cyclopentylethyl, cyclohexylmethyl, cyclohexylethyl, and cycloheptylmethyl. In some cases, the alkylene group is a lower alkylene group.

[0052] In this specification, "cycloalkenyl" means a carbocyclyl ring or ring system having at least one double bond, wherein none of the rings in the ring system are aromatic. An example is cyclohexenyl. A cycloalkenyl group may contain 4 to 10 atoms in the ring. A cycloalkenyl group may or may not have substituents.

[0053] In this specification, “heterocyclyl” or “hetero-alicyclyl” refers to monocyclic, bicyclic, and tricyclic ring systems with 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, and up to 20 members, where a carbon atom and 1 to 5 heteroatoms constitute the ring system. Heterocyclyls may optionally contain one or more unsaturated bonds, but their configuration does not result in a completely delocalized π-electron system throughout the entire ring system. Heteroatoms may be present in either a non-aromatic or aromatic ring within the ring system. Heteroatoms are elements other than carbon, including but not limited to oxygen, sulfur, and nitrogen. Heterocyclyls may further contain one or more carbonyl or thiocarbonyl functional groups, thereby expanding the definition to include oxo-based or thio-based systems such as lactams, lactones, cyclic imides, cyclic thioimides, and cyclic carbamates. When composed of two or more rings, the rings may be bonded in a condensed structure. Furthermore, the nitrogen within the heteroalicycline structure may be quaternized. The heterocyclyl or heteroalicycline group may or may not be substituted.Examples of such "heterocyclyl" or "hetero-allicyl" groups include 1,3-dioxin, 1,3-dioxane, 1,4-dioxane, 1,2-dioxolane, 1,3-dioxolane, 1,4-dioxolane, 1,3-oxatian, 1,4-oxathiolane, 1,3-dithiol, 1,3-dithiolane, 1,4-oxatian, tetrahydro-1,4-thiazine, 2H-1,2-oxazine, maleimide, succinimide, barbituric acid, thiobarbituric acid, dioxopiperazine, hydantoin, dihydrouracil, trioxane, hexahydro-1,3,5-triazine, imidazoline, imidazolidine, isoxazoline, This includes, but is not limited to, isoxazolidines, oxazolines, oxazolidines, oxazolidinones, thiazolines, thiazolidines, morpholines, oxirans, piperidine N-oxides, piperidines, piperazines, pyrrolidines, pyrrolidones, pyrrolidiones, 4-piperidones, pyrazolines, pyrazolidines, 2-oxopyrrolidines, tetrahydropyrans, 4H-pyrans, tetrahydrothiopyrans, thiamorpholins, thiamorpholin sulfoxides, thiamorpholin sulfones, and their benzo-condensed derivatives (e.g., benzimidazolidinones, tetrahydroquinolines, 3,4-methylenedioxyphenyls). The heterocyclyl group may be a moderately sized heterocyclyl having 3 to 10 ring members. The heterocyclyl group may be a heterocyclyl having 3 to 6 ring members. The heterocyclyl group may be designated as a "3-6 membered heterocyclyl" or a similar name. The heterocyclyl group may or may not have substituents.

[0054] In various embodiments, the heterocyclil comprises 1 to 4 heteroatoms, 1 to 3 heteroatoms, 1 to 2 heteroatoms, or 1 heteroatom. For example, in various embodiments, the heterocyclil comprises 1 to 4 nitrogen atoms, 1 to 3 nitrogen atoms, 1 to 2 nitrogen atoms, 2 nitrogen atoms and 1 sulfur or oxygen atom, 1 nitrogen atom and 1 sulfur or oxygen atom, or 1 sulfur or oxygen atom. In a preferred six-membered monocyclic heterocyclil, the heteroatoms(group) are selected from 1 to 3 from O, N, or S, and in a preferred five-membered monocyclic heterocyclil, the heteroatoms(group) are selected from 1 to 2 from O, N, or S. Examples of heterocyclyl rings include azepinyl, acridinyl, carbazolyl, cinolinyl, dioxolanil, imidazolinyl, imidazolidinyl, morpholinyl, oxylanil, oxepanil, thiepanil, piperidinyl, piperazinyl, dioxopiperazinyl, pyrrolidinyl, pyrrolidonyl, pyrrolidionyl, 4-piperidonyl, pyrazolinyl, pyrazolidinyl, 1,3-dioxynyl, 1,3-dioxanyl, 1,4-dioxynyl, 1,4-dioxanyl, 1,3-oxathianyl, 1,4-oxathianyl, This includes, but is not limited to, 1,4-oxathianyl, 2H-1,2-oxazinyl, trioxanyl, hexahydro-1,3,5-triazinyl, 1,3-dioxolyl, 1,3-dioxolanyl, 1,3-dithiolyl, 1,3-dithiolanyl, isoxazolinyl, isoxazolidinyl, oxazolinyl, oxazolidinyl, oxazolidinyl, oxazolidinyl, thiazolinyl, thiazolidinyl, 1,3-oxathiolanyl, indolinyl, isoindolinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothiophenyl, tetrahydrothiopyranyl, tetrahydro-1,4-thiadinyl, thiamorpholinyl, dihydrobenzofuranyl, benzimidazolidinyl, and tetrahydroquinoline. The sulfur of the heterocyclyl ring may be provided as a dioxide (e.g., -S(O)2-).

[0055] "(Heterocyclyl)alkyl" refers to a heterocyclyl group bonded via an alkylene group as a substituent. Examples include, but are not limited to, imidazolinylmethyl and indolinylethyl.

[0056] "(Heterocyclyl)alkynyl" refers to a heterocyclyl group bonded via an alkynylene group as a substituent.

[0057] In this specification, "acyl" refers to -C(=O)R, where R is hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 carbocyclic, aryl, 5- to 10-membered heteroaryl, and 5- to 10-membered heterocyclyl as defined herein. Non-limiting examples include formyl, acetyl, propanoyl, benzoyl, and acrylyl. The acyl group may or may not be substituted.

[0058] The "O-carboxy" group refers to the "-OC(=O)R" group, where R is selected from hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 carbocyclic, aryl, 5- to 10-membered heteroaryl, and 5- to 10-membered heterocyclyl (as defined herein). O-carboxy may or may not be substituted.

[0059] The "C-carboxy" group (or "ester") refers to the "-C(=O)OR" group, where R is hydrogen, -NH2, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7The group is selected from carbocyryl, aryl, 5-10 membered heteroaryl, and 5-10 membered heterocyclyl. A non-restrictive example is a carboxyl group (i.e., -C(=O)OH). The C-carboxyl group may be substituted or unsubstituted.

[0060] In this specification, "hydroxy" refers to the -OH group.

[0061] The "cyano" group refers to the "-CN" group.

[0062] The "cyanato" group refers to the "-OCN" group.

[0063] The "isocyanato" group refers to the "-NCO" group.

[0064] The "thiocyanate" group refers to the "-SCN" group.

[0065] The "isothiocyanate" group refers to the "-NCS" group.

[0066] The "sulfinyl" group refers to the "-S(=O)R" group, where R is hydrogen, C as defined herein. 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-7 Carbocyclyl, C 6-10 The group is selected from aryl, 5-10 membered heteroaryl, and 5-10 membered heterocyclyl. The sulfinyl group may or may not be substituted.

[0067] The "sulfonyl" group refers to the "-SO2R" or "-SO2-" group, where R is hydrogen, C as defined herein. 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-7 Carbocyclyl, C 6-10The group is selected from aryl, 5-10 membered heteroaryl, and 5-10 membered heterocyclyl. The sulfonyl group may be located within the heterocyclyl ring. The sulfonyl group may be substituted or unsubstituted.

[0068] The "S-sulfonamide" group is "-SO2NR A R B This refers to the base, where R A and R B As defined herein, hydrogen, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-7 Carbocyclyl, C 6-10 The following groups are independently selected from aryl, 5-10 membered heteroaryl, and 5-10 membered heterocyclo groups. A and R B These can bond to form heteroaryl or heterocyclyl groups. The S-sulfonamide group may or may not have substituents.

[0069] The "N-sulfonamide" group is defined as "-N(R A )SO2R B This refers to the base, where R A and R B As defined herein, hydrogen, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-7 Carbocyclyl, C 6-10 The N-sulfonamide is independently selected from aryl, 5-10 membered heteroaryl, and 5-10 membered heterocyclyl. The N-sulfonamide may be substituted or unsubstituted.

[0070] The "O-carbamyl" group is "-OC(=O)NR" A R B This refers to the base, where R A and R B As defined herein, hydrogen, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C3-7 Carbocyclyl, C 6-10 The following are independently selected from aryl, 5-10 membered heteroaryl, and 5-10 membered heterocyclyl. A and R B It can bind to form a heteroaryl or heterocycline. O-carbamyl may be substituted or unsubstituted.

[0071] The "N-carbamyl" group is "-N(R A )OC(=O)R B This refers to the base, where R A and R B As defined herein, hydrogen, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-7 Carbocyclyl, C 6-10 The compounds are independently selected from aryl, 5-10 membered heteroaryl, and 5-10 membered heterocyclyl. N-carbamyl may or may not be substituted.

[0072] The "O-thiocarbamyl" group is "-OC(=S)NR" A R B " refers to the base, R A and R B As defined herein, hydrogen, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-7 Carbocyclyl, C 6-10 The following are independently selected from aryl, 5-10 membered heteroaryl, and 5-10 membered heterocyclyl. A and R B It can bind to form a heteroaryl or heterocyclyl. O-thiocarbamyl may or may not have substituents.

[0073] The "N-thiocarbamyl" group is "-N(R A )OC(=S)R B This refers to the base, where R A and R BAs defined herein, hydrogen, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-7 Carbocyclyl, C 6-10 The compounds are independently selected from aryl, 5-10 membered heteroaryl, and 5-10 membered heterocyclyl. N-thiocarbamyl may or may not be substituted.

[0074] The "C-amide" group is called "C(=O)NR" A R B This refers to the base, where R A and R B However, as defined in this specification, hydrogen, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-7 Carbocyclyl, C 6-10 The following are independently selected from aryl, 5-10 membered heteroaryl, and 5-10 membered heterocyclyl. A and R B These can bind to form heteroaryl or heterocyclyl compounds. The C-amide may be substituted or unsubstituted.

[0075] The "N-amide" group is "-N(R A )C(=O)R B This refers to the base, where R A and R B As defined herein, hydrogen, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-7 Carbocyclyl, C 6-10 The following are independently selected from aryl, 5-10 membered heteroaryl, and 5-10 membered heterocyclyl. A and R B These can bond to form heteroaryl or heterocyclyl groups. The N-amide group may be substituted or unsubstituted.

[0076] The term "carbamide" or "carbamide" group refers to the "(RARB)NC(=O)N(RC)" group, where RA, RB, and RC can each be independently hydrogen, alkyl, alkenyl, alkynyl, carbocykyl, aryl, heteroaryl, heterocyclyl, aralkyl, or heterocyclyl(alkyl) as defined herein. The carbamide may be substituted or unsubstituted.

[0077] The "amino" group is "-NR" A R B This refers to the base, where R A and R B As defined herein, hydrogen, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-7 Carbocyclyl, C 6-10 The following are independently selected from aryl, 5-10 membered heteroaryl, and 5-10 membered heterocyclyl. A and R B These can bind to form heteroaryl or heterocyclyl groups. The amino group may or may not be substituted.

[0078] The "alcamino" group is "-NR" A R B " refers to the base, R A R is an alkyl group, B is hydrogen, C 1-6 Alkyl alkyl group, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-7 Carbocyclyl, C 6-10 The alkamino is independently selected from aryl, 5-10 membered heteroaryl, and 5-10 membered heterocyclyl. The alkamino may or may not be substituted.

[0079] An "aminoalkyl" group refers to an amino group bonded via an alkylene group. The aminoalkyl group may or may not have substituents.

[0080] An "alkoxyalkyl" group refers to an alkoxy group bonded via an alkylene group, such as "C2-8 alkoxyalkyl." Alkoxyalkyl groups may or may not have substituents.

[0081] In this specification, a substituent is derived from an unsubstituted parent group in which one or more hydrogen atoms are substituted with other atoms or groups. Unless otherwise specified, when a group is considered "substituted", it means that the group is a C1-C6 alkyl (optionally substituted with -OH or C-carboxy), a C1-C6 alkenyl, a C1-C6 alkynyl, a C1-C6 heteroalkyl, a C3-C7 carbocykyl (optionally substituted with halo, -OH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, or C1-C6 haloalkoxy), or a C3-C7-carbocykyl-C1-C 6-alkyl (optionally substituted with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), 5-10 member heterocyclyl (optionally substituted with N-amide, -OH, halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), 5-10 member heterocyclyl-C1-C6-alkyl (halo, C1-C6 alkyl, C1-C6 alkoxy, optionally substituted with C1-C6 haloalkyl, and C1-C6 haloalkoxy), aryl (optionally substituted with halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), aryl(C1-C6)alkyl (optionally substituted with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), 5-1 0-membered heteroaryl (optionally substituted with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), 5-10 membered heteroaryl (C1-C6)alkyl (optionally substituted with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), haloalkoxy, cycloalkenyl, halo, cyano, hydroxy, C1-C6 alkoxy,C1-C6 alkoxy(C1-C6)alkyl (i.e., ether), aryloxy, sulfhydryl (mercapto), halo(C1-C6)alkyl (e.g., -CF3), halo(C1-C6)alkoxy (e.g., -OCF3), C1-C6 alkylthio, arylthio, amino, amino(C1-C6)alkyl, monosubstituted amine group, disubstituted amine group, monosubstituted amine (alkyl), disubstituted amine (alkyl), nitro, thiocarbonyl, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C - This means that the group is substituted with one or more substituents independently selected from -amides, N-amides, S-sulfonamides, N-sulfonamides, C-carboxys, O-carboxys, acyls, cyanates, isocyanates, thiocyanates, isothiocyanates, sulfenyls, sulfinyls, sulfonyls, -O-NH2, oxo(=O), diamino groups, polyaminos, diether groups, and polyethers (e.g., diethylene glycol, triethylene glycol, oligoethylene glycol, polyethylene glycol, etc.). When it is described as "optionally substituted" (or similar expression), or as containing one or more "optional substituents," the group may or may not be substituted with any of the above substituents.

[0082] In some embodiments, the substituents are substituted with one or more substituents independently selected from C1-C4 alkyl, amino, hydroxy, and halogen.

[0083] Two substituents may form a ring with the atom or group of atoms to which they are bonded, and this ring may form a spiro structure or condense with the rest of the compound.

[0084] In this specification, R 1 , R 2 , R 3The following are examples of "R" groups, but are not limited to them. An "R" group represents a substituent that can bond to the indicated atom. The R group may be substituted or unsubstituted. When two "R" groups are described "as a whole" (or in a similar expression), those R groups and the atom to which they are bonded may form a cycloalkyl, aryl, heteroaryl, or heterocyclyl. When it is stated that two R groups "together with the bonded atom" form a ring (e.g., a carbocyclyl, heterocyclyl, aryl, or heteroaryl ring), it means that the assembly of the atom and the two R groups is the described ring. This ring, when considered individually, is not limited by the definition of each R group. For example, the following structure exists: [ka]

[0085] and R 1 and R 2 is selected from the group consisting of hydrogen and alkyl, or R 1 and R 2 If they form a heterocycline with the nitrogen to which they bind, R 1 and R 2 This means that it can be selected from hydrogen or alkyl, or that the substructure has the following structure: [ka]

[0086] Here, ring A is the nitrogen-containing heterocycline shown in the diagram. For example, NR 1a R 1b Base R 1a and R 1b When they are described as being "treated as a whole," it means they are covalently bonded to each other, forming a ring: [ka]

[0087] The cyclic structure can be represented using the following structural formula (or a similar structure having a different ring size, heteroatom, etc.):

Chem.

Chem.

Chem.

Chem.

Chem.

Chem.

Chem.

[0088] When two "adjacent" R groups are said to "form a ring together with the atoms to which they are attached", it means that the atoms, intervening bonds, and the aggregate of the two R groups constitute that ring structure. For example, when the following partial structure exists:

Chem.

[0089] When a substituent is shown as a diradical (i.e., having two binding points to the molecular residue), unless otherwise specified, it is understood that the substituent can be attached in any orientation. Thus, for example, -AE- or [Chemical formula] The depicted substituents include those oriented such that "A" is attached to the binding point at the left end of the molecule and those oriented such that "A" is attached to the binding point at the right end of the molecule.

[0090] As described in the definition of alkylene, it should also be understood that certain radical naming rules may include either a single radical or a double radical depending on the context. For example, when a substituent (e.g., within the substrate structure) requires two binding points to the rest of the molecule, the substituent is understood to be a diradical. For example, substituents identified as aminoalkyl and requiring two binding points include diradicals such as -NHCH2-, -NHCH2CH2-, -NHCH2CH(CH3)CH2-. Other examples of substituents requiring two binding points include alkoxy, aryl, heteroaryl, carbocyclic, heterocyclic, etc.

[0091] In this specification, a radical refers to a species having a single unpaired electron, and a species containing this radical can form covalent bonds with other species. Therefore, in this context, a radical is not necessarily a free radical. Rather, a radical represents a specific part of a larger molecule.

[0092] In any compound having one or more chiral centers described herein, unless absolute stereochemistry is explicitly stated, it is understood that each center can independently be in an R configuration, an S configuration, or a mixture thereof. Therefore, the compounds provided herein may be pure as enantiomers, enantiomerically rich, racemic, pure as diastereomers, diastereomerically rich, or stereoisomerized. Furthermore, in any compound described herein, if it has one or more double bonds that produce geometric isomers definable as E or Z, it is understood that each double bond can independently be E, Z, or a mixture thereof. In any compound described herein, if it has one or more chiral centers, it is understood that all possible diastereomers are also assumed. In any compound described herein, all tautomers are assumed. Also, in any compound described herein, all isotopes of the atoms it contains are assumed. For example, any example of hydrogen may contain hydrogen-1 (protium), hydrogen-2 (deuterium), hydrogen-3 (tritium), or other isotopes; any example of carbon may contain carbon-12, carbon-13, carbon-14, or other isotopes; any example of oxygen may contain oxygen-16, oxygen-17, oxygen-18, or other isotopes; any example of fluorine may contain fluorine-18, fluorine-19, or one or more other isotopes; any example of sulfur may contain sulfur-32, sulfur-34, sulfur-35, sulfur-36, or one or more other isotopes.

[0093] In this specification, “inhibitor” means any compound, molecule, or composition that inhibits or reduces the activity of a target biomolecule. This inhibition may be achieved, for example, by inhibiting the phosphorylation of the target (e.g., by competition with adenosine triphosphate (ATP), a phosphorylation group donor), binding to a site other than the active site, influencing activity through structural changes, or inhibiting kinase access to a molecular chaperone system that depends on intracellular stability, thereby inducing ubiquitination and degradation.

[0094] In this specification, the term "banin-1" is given the common sense of those skilled in the art and refers to an enzyme having pantetheine-degrading activity that catalyzes the hydrolysis of pantetheine to pantothenic acid and cysteamine. Banin-1 is a member of the broader banin family and consists of three homologous genes of human origin (VNN1, VNN2, VNN3) and two homologous genes of mouse origin (Vnn1, Vnn3). Banins play a role in inflammation, oxidative stress, and cell migration processes mediated through banin-dependent cysteamine production.

[0095] In this specification, “subject,” “host,” “patient,” and “individual” are used interchangeably and are given their usual meanings, and refer to organisms possessing the VNN1 protein. This includes mammals, such as humans, non-human primates, ungulates, canids, felids, equids, mice, and rats. The term “mammal” includes both humans and non-human mammals.

[0096] As used herein, “diagnosis” is given in its ordinary sense and includes determining susceptibility to the disease or disorder of a subject, determining whether the subject is currently suffering from the disease or disorder, determining the prognosis of a subject suffering from the disease or disorder (e.g., identifying cancer or a cancerous condition, the stage of cancer, or the response to cancer treatment), and the use of serametics (e.g., monitoring the subject’s condition to provide information regarding the effectiveness or efficacy of the treatment).

[0097] The terms “sample” or “biological sample,” given their usual meaning, encompass a wide variety of samples obtained from living organisms that can be used in imaging, diagnostic, prognostic, or monitoring assays. This term includes blood and other liquid samples of biological origin, solid tissue samples such as biopsy specimens, or tissue cultures or cells and their offspring derived therefrom. It also includes samples that have been manipulated in any way after acquisition, such as through reagent treatment, solubilization, or concentration of specific components. In addition to clinical samples, it also includes cells in cell culture, cell supernatants, cell lysates, serum, plasma, body fluids, and tissue samples.

[0098] In this specification, "natural amino acid side chain" refers to the side chain substituent of a natural amino acid. Natural amino acids have substituents attached to the α-carbon. Natural amino acids include arginine, lysine, aspartic acid, glutamic acid, glutamine, asparagine, histidine, serine, threonine, tyrosine, cysteine, methionine, tryptophan, alanine, isoleucine, leucine, phenylalanine, valine, proline, and glycine.

[0099] In this specification, "non-natural amino acid side chain" refers to the side chain substituent of an amino acid other than a natural amino acid. Non-natural amino acids include β-amino acids (β 3 and β 2 This includes homoamino acids, proline and pyruvate derivatives, 3-substituted alanine derivatives, glycine derivatives, ring-substituted phenylalanine and tyrosine derivatives, linear core amino acids, and N-methyl amino acids. A non-exclusive list of unnatural amino acids is available from Sigma-Aldridge and is described in the section "Unnatural Amino Acids and Derivatives." See also "Beyond the Canonical 20 Amino Acids: Expanding the Genetic Lexicon" by Travis S. Young and Peter G. Schultz (J. Biol. Chem. 2010 285: 11039-11044), which is incorporated herein by reference in its entirety.

[0100] The terms “agent” or “test agent” include any substance, molecule, element, compound, entity, or combination thereof. This includes, but is not limited to, proteins, polypeptides, peptides or peptide mimetic compounds, low-molecular-weight organic compounds, polysaccharides, polynucleotides, etc. These may be natural products, synthetic compounds, chemical compounds, or combinations of two or more substances. Unless otherwise specified, the terms “agent,” “substance,” and “compound” are used interchangeably herein.

[0101] In this specification, "analog" refers to a molecule that is structurally similar to a reference molecule but has been modified in a targeted and controlled manner by substituting specific substituents of the reference molecule with other substituents. The analog is expected to exhibit identical, similar, or improved utility compared to the reference molecule, as would be expected by those skilled in the art. The synthesis and screening of analogs to identify variants of known compounds with improved properties (such as higher binding affinity to a target molecule) is a well-known approach in pharmaceutical chemistry.

[0102] The “patient” or “subject” treated as disclosed herein is a human patient in some embodiments, but the principles of the subject disclosed herein demonstrate that the subject disclosed herein is effective for all vertebrate species, including mammals, and these are intended to be included in the terms “subject” and “patient.” Suitable subjects are generally mammalian subjects. The subject described herein is useful for research purposes as well as veterinary and medical purposes. The term “mammal” is used in its ordinary biological sense. Thus, it includes, in particular, primates including monkeys (chimpanzees, apes, and monkeys) and humans, cattle, horses, sheep, goats, pigs, rabbits, dogs, cattle, rats, and mice, as well as many other species.

[0103] The terms “pharmaceutically acceptable carrier” or “pharmaceutically acceptable additive” include all solvents, dispersion media, coatings, antimicrobial and antifungal agents, isotonic agents and absorption retarders, etc. The use of such media and agents with pharmaceutically active substances is well known in this field. Their use in therapeutic compositions is conceivable unless conventional media or agents are incompatible with the active ingredient. Furthermore, various adjuvants commonly used in this field may be included. Considerations regarding the inclusion of various components in pharmaceutical compositions are, for example, described in Gilman et al. (Eds.) (1990); Goodman and Gilman's: The Pharmacological Basis of Therapeutics, 8th Ed., Pergamon Press, the entire contents of which are incorporated herein by reference.

[0104] In this specification, “effective dose” or “therapeutic dose” means an amount of therapeutic agent that is effective in alleviating, to some extent, one or more symptoms of a disease or condition, or reducing the likelihood of developing such symptoms, and includes cure of the disease or condition. “Cure” means the elimination of the symptoms of the disease or condition; however, certain long-term or permanent effects (e.g., extensive tissue damage) may remain after cure.

[0105] In this specification, “treatment,” “therapy,” or “to treat” means administering a pharmaceutical composition for preventive and / or therapeutic purposes. “Preventive treatment” means treating a subject who is not yet showing symptoms of a disease or condition but is susceptible to or at other risk of developing a particular disease or condition, thereby reducing the likelihood that the patient will develop the disease or condition. “Therapeutic treatment” means administering treatment to a subject.

[0106] As used herein, "percent by weight" of a component refers to the value obtained by dividing the weight of the component by the weight of the composition containing the component and multiplying by 100%. For example, when 5 grams of component A is added to 95 grams of component B, the percent by weight of component A is 5% (e.g., 5g A / (5g A + 95g B)×100%).

[0107] The term "control" is given its ordinary meaning and includes a sample or standard used for comparison with a sample being examined, treated, characterized, analyzed, etc. In some embodiments, the control is a sample obtained from a healthy patient, or a non-tumor tissue sample obtained from a patient diagnosed with a tumor. In some embodiments, the control is a past control or a reference value or range of values. In some embodiments, the control is a comparison with a wild-type VNN1 sequence or scenario.

[0108] The terms and expressions used herein, particularly in the appended claims, and their variations thereof, should be construed as open, not restrictive, unless otherwise specified. As an example, the term “including” should be construed as meaning “including but not limited to,” “including but not limited to,” etc. The term “constitutes” as used herein is synonymous with “including,” “contains,” and “characterized,” and is comprehensive or open, not excluding additional undescribed elements or method steps. The term “has” should be construed as “has at least.” The term “including” should be construed as “including but not limited to.” The term “example” is used to provide unrestricted examples of the item under discussion and is not an exhaustive or restrictive list. The use of terms such as “preferred,” “desirable,” or “desirable,” and similar words, should not be understood as suggesting that a particular feature is important, essential, or significant to the structure or function of the invention, but is merely intended. Terms such as “preferred,” “desirable,” or “desirable,” and similar phrases should not be understood as suggesting that a particular feature is important, essential, or significant to the structure or function of the invention, but rather should be interpreted as simply intended to highlight alternative or additional features that may or may not be utilized in a particular embodiment of the invention. Furthermore, the term “includes” should be interpreted as synonymous with the expression “have at least” or “include at least.” When used in reference to a process, “includes” means that the process includes at least the steps described, but may also include additional steps. When used in reference to a compound, composition, or apparatus, “contains” means that the compound, composition, or apparatus includes at least the features or components described, but may also include additional features or components. Similarly, a group of items linked by the conjunction “and” should not be interpreted as requiring all of those items to be present in the group, but should be interpreted as “and / or” unless explicitly stated otherwise.Similarly, a group of items linked by "or" should not be interpreted as requiring mutual exclusivity within that group, and should be interpreted as "and / or" unless explicitly specified otherwise.

[0109] Furthermore, the expression "essentially consists of" is understood to include the explicitly stated elements and additional elements that do not substantially affect the fundamental and novel characteristics of the claimed technology. The expression "essentially consists of" excludes elements that are not explicitly stated.

[0110] With regard to substantially any use of plural and / or singular terms herein, a person skilled in the art can appropriately interpret them from plural to singular and / or singular to plural, depending on the context and / or application. For clarity, various singular / plural combinations may be explicitly described herein. The indefinite articles "a" or "an" do not exclude the plural. A single processor or other unit may satisfy the functions of several items described in the claims. The mere fact that certain measures are described in different dependent claims does not indicate that a combination of these measures cannot be used advantageously. No reference symbol in the claims should be construed as limiting scope.

[0111] The section headings used herein are for structural purposes only and should not be construed as limiting the subject matter described. Features disclosed under one heading (e.g., Composition) may be used in combination with features disclosed under another heading (e.g., Method of Treatment). Compound of formula (I)

[0112] Some embodiments relate to tricyclic compounds. In some embodiments, the tricyclic compound is a compound having the structure of formula (I) (or a pharmaceutically acceptable salt thereof): [ka]

[0113] In some embodiments, R1 is selected from the group consisting of -H, -OH, -CH3, or -OCH3; R2 is -H, -OH, or optionally substituted C 1-6 Alkyl, optionally substituted C 1-6 Alkoxy or optionally substituted C 1-6 Selected from the group consisting of haloalkyl groups; R3 is -CN, -OH, or optionally substituted C1-C 10 Alkyl, optionally substituted C1-C 10 Alkenyl, optionally replaced C1-C 10 R4 is selected from the group consisting of alkynyl, optionally substituted alkoxy, optionally substituted 3-10 membered carbocyclyl, optionally substituted 6-10 membered aryl, optionally substituted 3-10 membered heterocyclyl, optionally substituted 5-10 membered heteroaryl, and -NR5R6; R4 is -H, -(CO)CH3, optionally substituted C1-C 10 Selected from the group consisting of alkyl groups; and R5 and R6 are optionally substituted with C 1-6 It is alkyl.

[0114] In some embodiments, R1 is selected from the group consisting of -H, -OH, -CH3, or -OCH3. In some embodiments, R1 is -H. In some embodiments, R1 is -OH. In some embodiments, R1 is -CH3. In some embodiments, R1 is -OCH3.

[0115] In some embodiments, R2 is replaced by -H, -OH, or C (optionally). 1-6 Alkyl, optionally substituted C 1-6 Alkoxy or optionally substituted C 1-6 Selected from the group of haloalkyls. In some embodiments, R2 is -H. In some embodiments, R2 is -OH. In some embodiments, R2 is optionally substituted with C 1-6It is alkyl. In some embodiments, R2 is optionally substituted with C 1-6 It is an alkoxy. In some embodiments, R2 is optionally substituted with C 1-6 It is a haloalkyl group.

[0116] In some embodiments, R3 is C1-C, which is optionally replaced with -CN, -OH, or C1-C 10 Alkyl, optionally substituted C1-C 10 Alkenyl, optionally replaced C1-C 10 The group is selected from alkynyl, optionally substituted alkoxy, optionally substituted 3-10 membered carbocyclyl, optionally substituted 6-10 membered aryl, optionally substituted 3-10 membered heterocyclyl, optionally substituted 5-10 membered heteroaryl, and -NR5R6. In some embodiments, R3 is -CN. In some embodiments, R3 is -OH. In some embodiments, R3 is optionally substituted C1-C 10 It is alkyl. In some embodiments, R3 is optionally substituted with C1-C 10 It is an alkenyl. In some embodiments, R3 is optionally replaced with C1-C 10 It is an alkynyl. In some embodiments, R3 is an optionally substituted alkoxy. In some embodiments, R3 is an optionally substituted 3-10 membered carbocyrill. In some embodiments, R3 is an optionally substituted 6-10 membered aryl. In some embodiments, R3 is an optionally substituted 3-10 membered heterocyclyl. In some embodiments, R3 is an optionally substituted 5-10 membered heteroaryl. In some embodiments, R3 is -NR5R6. In certain embodiments, R5 and R6 are optionally substituted C 1-6 It is alkyl. In some embodiments, R5 is optionally substituted with C 1-6 It is alkyl. In some embodiments, R6 is optionally substituted with C 1-6 It is alkyl.

[0117] In some embodiments, R4 is -H, -(CO)CH3, or C1-C which is optionally replaced. 10 Selected from the group consisting of alkyl groups. In some embodiments, R4 is -H. In some embodiments, R4 is -(CO)CH3. In some embodiments, R4 is optionally substituted C1-C 10 It is alkyl.

[0118] In some embodiments, the structure of formula (I), or a pharmaceutically acceptable salt thereof, is further represented by formula (Ia): [ka]

[0119] In some embodiments, R7, R8, R9, R 10 , R 11 and R 12 These are, independently, -H, -OH, halogen, and C, which is substituted by any choice. 1-6 Alkyl, optionally substituted C 1-6 Alkoxy, optionally substituted C 1-6 Alkyl, optionally substituted C 1-6 Alkoxy or optionally substituted C 1-6 Selected from the haloalkyl group; R 13 This is C, which has been replaced by an optional substitution. 1-6 Alkyl, optionally substituted C 1-20 Selected from the group consisting of alkylenes and absence; R 14 This is a 3-20 member heterocycline that has been optionally replaced, -NR 15 R 16 Selected from the group consisting of , and non-existence; and R 15 and R 16 These are C, each replaced by an arbitrary choice. 1-6 It is alkyl.

[0120] In some embodiments, R4 is -H, -(CO)CH3, or C1-C which is optionally replaced. 10 Selected from the group consisting of alkyl groups. In some embodiments, R4 is -H. In some embodiments, R4 is -(CO)CH3. In some embodiments, R4 is optionally substituted C1-C 10 It is alkyl.

[0121] In some embodiments, R7, R8, R9, R 10 , R 11 , and R 12 These are, independently, -H, -OH, halogen, and C, which is substituted by any choice. 1-6 Alkyl, optionally substituted C 1-6 Alkoxy, optionally substituted C 1-6 Alkyl, optionally substituted C 1-6 Alkoxy or optionally substituted C 1-6 Selected from the haloalkyl group.

[0122] In some embodiments, R7 is -H, -OH, halogen, or optionally substituted with C 1-6 Alkyl, optionally substituted C 1-6 Alkoxy, optionally substituted C 1-6 Alkyl, optionally substituted C 1-6 Alkoxy or optionally substituted C 1-6 Selected from the group of haloalkyls. In some embodiments, R7 is -H. In some embodiments, R7 is -OH. In some embodiments, R7 is a halogen. In some embodiments, R7 is optionally substituted with C 1-6 It is alkyl. In some embodiments, R7 is optionally substituted with C 1-6 It is an alkoxy. In some embodiments, R7 is optionally substituted with C 1-6 It is alkyl. In some embodiments, R7 is optionally substituted with C 1-6It is an alkoxy. In some embodiments, R7 is optionally substituted with C 1-6 It is a haloalkyl group.

[0123] In some embodiments, R8 is replaced by -H, -OH, halogen, or optionally C 1-6 Alkyl, optionally substituted C 1-6 Alkoxy, optionally substituted C 1-6 Alkyl, optionally substituted C 1-6 Alkoxy or optionally substituted C 1-6 Selected from the group consisting of haloalkyls. In some embodiments, R8 is -H. In some embodiments, R8 is -OH. In some embodiments, R8 is a halogen. In some embodiments, R8 is optionally substituted with C 1-6 It is alkyl. In some embodiments, R8 is optionally substituted with C 1-6 It is an alkoxy. In some embodiments, R8 is optionally substituted with C 1-6 It is alkyl. In some embodiments, R8 is optionally substituted with C 1-6 It is an alkoxy. In some embodiments, R8 is optionally substituted with C 1-6 It is a haloalkyl group.

[0124] In some embodiments, R9 is replaced by -H, -OH, a halogen, or optionally C 1-6 Alkyl, optionally substituted C 1-6 Alkoxy, optionally substituted C 1-6 Alkyl, optionally substituted C 1-6 Alkoxy or optionally substituted C 1-6 Selected from the group consisting of haloalkyls. In some embodiments, R9 is -H. In some embodiments, R9 is -OH. In some embodiments, R9 is a halogen. In some embodiments, R9 is optionally substituted with C 1-6 It is alkyl. In some embodiments, R9 is optionally substituted with C1-6 It is an alkoxy. In some embodiments, R9 is optionally substituted with C 1-6 It is alkyl. In some embodiments, R9 is optionally substituted with C 1-6 It is an alkoxy. In some embodiments, R9 is optionally substituted with C 1-6 It is a haloalkyl group.

[0125] In some embodiments, R 10 C is substituted with -H, -OH, halogens, or optionally. 1-6 Alkyl, optionally substituted C 1-6 Alkoxy, optionally substituted C 1-6 Alkyl, optionally substituted C 1-6 Alkoxy or optionally substituted C 1-6 Selected from the group consisting of haloalkyls. In some embodiments, R 10 is -H. In some embodiments, R 10 is -OH. In some embodiments, R 10 is a halogen. In some embodiments, R 10 C is replaced by an optional substitution. 1-6 It is alkyl. In some embodiments, R 10 C is replaced by an optional substitution. 1-6 It is an alkoxy. In some embodiments, R 10 This is C, which has been replaced by an optional substitution. 1-6 It is alkyl. In some embodiments, R 10 This is C, which has been replaced by an optional substitution. 1-6 It is an alkoxy. In some embodiments, R 10 This is C, which has been replaced by an optional substitution. 1-6 It is a haloalkyl group.

[0126] In some embodiments, R 11 C is substituted with -H, -OH, halogens, or optionally. 1-6 Alkyl, optionally substituted C 1-6 Alkoxy, optionally substituted C 1-6Alkyl, optionally substituted C 1-6 Alkoxy or optionally substituted C 1-6 Selected from the group of haloalkyls. In some embodiments, R 11 is -H. In some embodiments, R 11 is -OH. In some embodiments, R 11 is a halogen. In some embodiments, R 11 C is replaced by an optional substitution. 1-6 It is alkyl. In some embodiments, R 11 C is replaced by an optional substitution. 1-6 It is an alkoxy. In some embodiments, R 11 C is replaced by an optional substitution. 1-6 It is alkyl. In some embodiments, R 11 C is replaced by an optional substitution. 1-6 It is an alkoxy. In some embodiments, R 11 C is replaced by an optional substitution. 1-6 It is a haloalkyl group.

[0127] In some embodiments, R 12 C is substituted with -H, -OH, halogens, or optionally. 1-6 Alkyl, optionally substituted C 1-6 Alkoxy, optionally substituted C 1-6 Alkyl, optionally substituted C 1-6 Alkoxy or optionally substituted C 1-6 Selected from the group consisting of haloalkyls. In some embodiments, R 12 is -H. In some embodiments, R 12 is -OH. In some embodiments, R 12 is a halogen. In some embodiments, R 12 C is replaced by an optional substitution. 1-6 It is alkyl. In some embodiments, R 12 C is replaced by an optional substitution. 1-6 It is an alkoxy. In some embodiments, R 12C is replaced by an optional substitution. 1-6 It is alkyl. In some embodiments, R 12 C is replaced by an optional substitution. 1-6 It is an alkoxy. In some embodiments, R 12 C is replaced by an optional substitution. 1-6 It is a haloalkyl group.

[0128] In some embodiments, R 13 This is C, which has been replaced by an optional substitution. 1-6 Alkyl, optionally substituted C 1-20 Selected from the group consisting of alkylenes and absence. In some embodiments, R 13 C is replaced by an optional substitution. 1-6 It is alkyl. In a further embodiment, R 13 is -CH3. In some embodiments, R 13 C is replaced by an optional substitution. 1-20 It is an alkylene. In a further embodiment, R 13 R is selected from the group consisting of ethylene and propylene. In some embodiments, R 13 R is ethylene. In some embodiments, R 13 R is propylene. In some embodiments, 13 It does not exist.

[0129] In some embodiments, R 14 These are 3-20 member heterocyclines that have been optionally replaced, -NR 15 R 16 Selected from the group consisting of , and non-existence. In some embodiments, R 14 R is a 3- to 20-membered heterocycline that is optionally substituted. In some embodiments, R 14 R is an optionally substituted 5-membered heterocycline. In further embodiments, R 14 teeth [ka] In some embodiments, R14 -NR 15 R 16 In some embodiments, R 14 It does not exist. In certain embodiments, R 15 and R 16 These are each C that have been replaced by arbitrary selection. 1-6 It is alkyl. In some embodiments, R 15 C is replaced by an optional substitution. 1-6 It is alkyl. In some embodiments, R 16 C is replaced by an optional substitution. 1-6 It is alkyl. In a further embodiment, R 15 and R 16 Each is independently selected from the group consisting of methyl, ethyl, and propyl. In some embodiments, R 15 R is selected from the group consisting of methyl, ethyl, and propyl. In some embodiments, R 15 is methyl. In some embodiments, R 15 is ethyl. In some embodiments, R 15 R is propyl. In some embodiments, R 16 R is selected from the group consisting of methyl, ethyl, and propyl. In some embodiments, R 16 is methyl. In some embodiments, R 16 is ethyl. In some embodiments, R 16 It is propyl.

[0130] In some embodiments, R7, R8, R 11 , and R 12 These are -H, and R9 and R 10 These are halogens. In a further embodiment, R9 and R 10 Each of these is -F. In some embodiments, R9 is -F. In some embodiments, R 10 It is -F.

[0131] In some embodiments, formula (I) may be represented by one or more of the following compounds (or other compounds): [ka]

[0132] In some embodiments, compounds having the structure of formula (I) are selected from one or more of the following: (5-(4,4-difluoropiperidine-1-yl)-9-methoxy-8-(3-(pyrrolidine-1-yl)propoxy)-2,3-dihydroimidazo[1,2-c]quinazolin-2-yl)methanol (also known as "Compound 2"); (5-(4,4-difluoropiperidine-1-yl)-9-methoxy-8-(2-(pyrrolidine-1-yl)ethoxy)-2,3-dihydroimidazo[1,2-c]quinazolin-2-yl)methanol (also known as "Compound 5"); (5-(4,4-difluoropiperidine-1-yl)-9-methoxy-8-(3-(pyrrolidine-1-yl)propoxy)-2,3-dihydroimidazo[1,2-c]quinazolin-2-yl)methylacetate (also known as "Compound 3"); (5-(4,4-difluoropiperidine-1-yl)-9-methoxy-8-(2-(pyrrolidine-1-yl)ethoxy)-2,3-dihydroimidazo[1,2-c]quinazolin-2-yl)methylacetate; and (5-(4,4-difluoropiperidine-1-yl)-8,9-dimethoxy-2,3-dihydroimidazo[1,2-c]quinazolin-2-yl)methanol (also known as "Compound 7"). Compound of formula (II)

[0133] Some embodiments relate to bicyclic compounds. In some embodiments, the bicyclic compound is a compound having the structure of formula (II) (or a pharmaceutically acceptable salt thereof): [ka]

[0134] In some embodiments, R 17 R is selected from the group consisting of -H, -OH, and halogens: 18 This is C, which has been replaced by an optional substitution. 1-6 Alkyl, optionally substituted C 1-20 Selected from the group consisting of alkylenes and absence: R 19 This is a 3-20 member heterocycline that has been optionally replaced, -NR 21 R 22 Selected from the group consisting of , and absence: R 20 R is selected from the group consisting of -H and 3-4 member heterocyclines that are optionally substituted: 21 and R 22 Each of these is replaced by C by any choice. 1-6 It is alkyl.

[0135] In some embodiments, R 17 R is selected from the group consisting of -H, -OH, and halogens. In some embodiments, R 17 is -H. In some embodiments, R 17 is -OH. In some embodiments, R 17 is a halogen. In a further embodiment, R 17 is -Cl. In some embodiments, R 17 is -F. In some embodiments, R 17 is -Br. In some embodiments, R 17 is -I.

[0136] In some embodiments, R 18 This is C, which has been replaced by an optional substitution. 1-6 Alkyl, optionally substituted C 1-20 Selected from the group consisting of alkylenes and those that are absent. In some embodiments, R 18 C is replaced by an optional substitution. 1-6 It is alkyl. Furthermore, R 18 It is -CH3.

[0137] In some embodiments, R 18 C is replaced by an optional substitution. 1-20 It is alkylene. Furthermore, R 18 R is selected from the group consisting of ethylene and propylene. In some embodiments, R 18 R is ethylene. In some embodiments, R 18 R is propylene. In some embodiments, 18 It does not exist.

[0138] In some embodiments, R 19 This is a 3-20 member heterocycline that has been optionally replaced, -NR 21 R 22 Selected from the group consisting of , and non-existence. In some embodiments, R 19 R is a 3-20 member heterocycline that has been optionally substituted. In some embodiments, R 19 is an optionally substituted 5-membered heterocycline. Furthermore, in some embodiments, R 19 teeth [ka] In some embodiments, R 19 It does not exist. In some embodiments, R 19 -NR 21 R 22 In a particular embodiment, R 21 and R 22 These are each C that have been replaced by arbitrary selection. 1-6 It is alkyl. In some embodiments, R 21 C is replaced by an optional substitution. 1-6 It is alkyl. In some embodiments, R 22 C is replaced by an optional substitution. 1-6 It is alkyl. In some embodiments, R 21 and R 22 Each is independently selected from the group consisting of methyl, ethyl, and propyl. In some embodiments, R 21R is selected from the group consisting of methyl, ethyl, and propyl. In some embodiments, R 21 is methyl. In some embodiments, R 21 is ethyl. In some embodiments, R 21 R is propyl. In some embodiments, R 22 R is selected from the group consisting of methyl, ethyl, and propyl. In some embodiments, R 22 is methyl. In some embodiments, R 22 is ethyl. In some embodiments, R 22 It is propyl.

[0139] In some embodiments, R 20 R is selected from the group consisting of -H and optionally substituted 3-4 member heterocyclines. In some embodiments, R 20 is -H. In some embodiments, R 20 R is a 3-4 member heterocycline that has been optionally substituted. In some embodiments, R 20 is a 4-membered heterocycline. In further embodiments, R 20 teeth [ka] That is the case.

[0140] In some embodiments, formula (II) may be represented by one or more of the following compounds (or others): [ka]

[0141] In some embodiments, the compound having the structure of formula (II) is selected from one or more of the following: 2-Chloro-6-methoxy-N-(oxetan-3-yl)-7-(3-(pyrrolidine-1-yl)propoxy)quinazoline-4-amine (also known as "Compound 1"); 2-Chloro-6-methoxy-N-(oxetan-3-yl)-7-(2-(pyrrolidine-1-yl)ethoxy)quinazoline-4-amine (also known as "compound 4"); and 2-Chloro-6,7-dimethoxy-N-(oxetan-3-yl)quinazoline-4-amine (also known as "Compound 6"). Methods for producing compounds of formulas I and II

[0142] The compounds disclosed herein can be synthesized by the methods described below, or by modifications thereof. Modifications to the methodology include, among many others, temperatures, solvents, reagents, etc., which are well known to those skilled in the art. Generally, in the preparation processes of the compounds disclosed herein, it may be necessary and / or desirable to protect sensitive or reactive groups on any of the relevant molecules. This can be achieved using conventional protecting groups, such as those described in *Protective Groups in Organic Chemistry* (edited by JFW McOmie, Plenum Press, 1973) and *Protecting Groups in Organic Synthesis* (3rd edition, Wiley, New York, 1999) by PGM Green and TW Wutts, which are incorporated herein by reference in their entirety. The protecting groups can be removed in appropriate subsequent steps using methods known in the art. Useful synthetic chemical transformations for the synthesis of applicable compounds are known in the art, such as those described in *Comprehensive Organic Transformations* (VCH Publishers, 1989) by R. Larock or *Encyclopedia of Reagents for Organic Synthesis* (John Wiley and Sons, edited by L. Paquette). This includes the works described in 1995, and these documents are incorporated herein by reference in their entirety. The synthetic routes shown and described herein are illustrative only and are not intended to limit the scope of the claims in any way, nor should they be construed as such. Those skilled in the art will recognize modifications of the disclosed synthetic methods and devise alternative routes based on the disclosure herein: all such modifications and alternative routes are within the scope of the claims.

[0143] In the scheme below, protecting groups are selected based on their compatibility with the required synthetic steps, as well as their compatibility with the introduction and deprotection steps and the overall synthetic scheme (PGM Green, TW Wutts, *Protecting Groups in Organic Synthesis* (3rd ed.), Wiley, New York (1999)).

[0144] If a compound produced by this technique contains one or more chiral centers, the compound can be prepared or isolated as a pure stereoisomer, i.e., individual enantiomers or d(l) stereoisomers, or as a stereoisomer-enriched mixture. Unless otherwise specified, all of these stereoisomers (and enriched mixtures) are included in the scope of this technique. Pure stereoisomers (or enriched mixtures) can be prepared, for example, using optically active starting materials or stereoselective reagents well known in this art. Alternatively, racemic mixtures of such compounds can be separated, for example, using chiral column chromatography, chiral separation agents, etc.

[0145] The starting materials for the following reactions are generally known compounds or can be prepared by known procedures or obvious variations thereof. For example, many starting materials are available from commercial suppliers such as Aldrich Chemical Co. (Milwaukee, Wisconsin, USA), Bachem (Torrance, California, USA), Emka-Chemce, or Sigma (St. Louis, Missouri, USA). Other starting materials may be prepared based on procedures described in standard references, such as Fieser and Fieser's Reagents for Organic Synthesis, Volumes 1–15 (John Wiley, and Sons, 1991), Rodd's Chemistry of Carbon Compounds, Volumes 1–5, and Supplementals (Elsevier Science Publishers, 1989), Organic Reactions, Volumes 1–40 (John Wiley and Sons, 1991), March's Advanced Organic Chemistry (John Wiley and Sons, 5th edition, 2001), and Larock's Comprehensive Organic Transformations (VCH Publishers Inc., 1989), or obvious variations thereof.

[0146] Some non-limiting embodiments relate to methods for synthesizing compounds of formula (I) and formula (II), as well as intermediates of compounds of formula (I) and formula (II). Administration and pharmaceutical composition

[0147] The compounds are administered in therapeutically effective doses. While human doses for the compounds described herein have not been optimized, generally, daily doses range from approximately 0.25 mg / kg to over 120 mg / kg per body weight, from approximately 0.5 mg / kg to approximately 70 mg / kg, from approximately 1.0 mg / kg to approximately 50 mg / kg per body weight, or from approximately 1.5 mg / kg to approximately 10 mg / kg per body weight. Therefore, for a person weighing 70 kg, the dose range would be approximately 17 mg / day to approximately 8000 mg / day, from approximately 35 mg / day to approximately 7000 mg / day or more, from approximately 70 mg / day to approximately 6000 mg / day, from approximately 100 mg / day to approximately 5000 mg / day, or from approximately 200 mg to approximately 3000 mg / day. The amount of active ingredient administered naturally depends on the subject, the state of the disease being treated, the severity of the condition, the method and schedule of administration, and the judgment of the prescribing physician.

[0148] In some embodiments, the compound of formula (I), or a pharmaceutically acceptable salt thereof, is a median inhibitory concentration (IC) of about, less than, about less than 20 μM, less than 15 μM, 10 μM, 5 μM, 4 μM, 3 μM, 2 μM, 1.9 μM, 1.8 μM, 1.7 μM, 1.6 μM, 1.5 μM, 1.4 μM, 1.3 μM, 1.2 μM, 1.1 μM, 1 μM, 0.9 μM, 0.8 μM, 0.7 μM, 0.6 μM, 0.5 μM, 0.4 μM, 0.3 μM, 0.2 μM, 0.1 μM, 0.09 μM, 0.08 μM, 0.07 μM, 0.06 μM, 0.05 μM, 0.04 μM, 0.03 μM, 0.02 μM, or 0.01 μM, or any range in between. 50 ) has activity. For example, in some embodiments, the compound of formula (I), or a pharmaceutically acceptable salt thereof, has a half-number inhibitory concentration (IC) within any of the following ranges. 50 ) Active concentrations: approximately 1 μM to 10 μM, approximately 5 μM to 15 μM, approximately 5 μM to 10 μM, approximately 10 μM to 20 μM, approximately 0.5 μM to 1 μM, approximately 1 μM to 5 μM, approximately 0.1 μM to 1 μM, approximately 0.01 μM to 0.9 μM, approximately 1 μM to 2 μM, or approximately 0.8 μM to 0.9 μM.

[0149] The compounds disclosed herein or pharmaceutically acceptable salts thereof may be administered by any route of administration accepted for drugs with similar efficacy, including but not limited to oral, subcutaneous, intravenous, nasal, topical, transdermal, intraperitoneal, intramuscular, intrapulmonary, vaginal, rectal, or intraocular administration. Oral and parenteral administration are common in the treatment of indications targeted by the preferred embodiments.

[0150] As described above, useful compounds can be formulated into pharmaceutical compositions for use in the treatment of these conditions. Standard pharmaceutical formulation techniques, such as those disclosed in Remington's The Science and Practice of Pharmacy, 21st Ed., Lippincott Williams & Wilkins (2005), are used, and this literature is incorporated in its entirety by reference. Accordingly, some embodiments include pharmaceutical compositions comprising: (a) a safe and therapeutically effective amount of a compound described herein (including its enantiomers, diastereomers, tauteromers, polymorphs, and solvates) or a pharmaceutically acceptable salt thereof; and (b) a pharmaceutically acceptable carrier, diluent, excipient, or combination thereof.

[0151] In addition to the useful selected compounds described above, some embodiments include compositions containing pharmaceutically acceptable carriers. The term “pharmaceutically acceptable carrier” or “pharmaceutically acceptable excipient” includes any solvent, dispersion medium, coating agent, antimicrobial and antifungal agent, isotonic agent and absorption retarder, etc. The use of such media and agents with pharmacologically active substances is well known in the art. Their use in therapeutic compositions is envisioned unless conventional media or agents are incompatible with the active ingredient. Furthermore, various adjuvants commonly used in the art may be included. Considerations regarding the inclusion of various components in pharmaceutical compositions are described, for example, in Gilman et al. (Eds.) (1990) Goodman and Gilman's: The Pharmacological Basis of Therapeutics, 8th edition, Pergamon Press, and are incorporated in their entirety by reference.

[0152] Examples of pharmaceutically acceptable carriers or substances that function as components include sugars such as lactose, glucose, and sucrose; starches such as corn starch and potato starch; cellulose and its derivatives, such as sodium carboxymethylcellulose, ethylcellulose, and methylcellulose; tragacanth powder; malt; gelatin; talc; solid lubricants such as stearic acid and magnesium stearate; calcium sulfate; vegetable oils such as peanut oil, cottonseed oil, sesame oil, olive oil, corn oil, and theobroma oil; polyols such as propylene glycol, glycerin, sorbitol, mannitol, and polyethylene glycol; alginic acid; emulsifiers such as TWEEN® S; wetting agents such as sodium lauryl sulfate; colorants; fragrances; tableting agents and stabilizers; antioxidants; preservatives; water that does not contain pyrogens; isotonic saline; and phosphate buffer.

[0153] The selection of a pharmaceutically acceptable carrier to be used in combination with the compound of the present invention is basically determined by the method of administration of the compound.

[0154] The compositions described herein are preferably provided in unit dosage forms. In this specification, “unit dosage form” means a composition containing an amount of the compound suitable for a single dose to an animal, preferably a mammalian, subject, in accordance with the principles of quality medicine. However, the preparation of a single dose or unit dosage form does not mean that the dosage form is administered once daily or once per course of treatment. Such dosage forms are intended to be administered once, twice, three or more times daily, and may be administered by intravenous infusion over a set period of time (e.g., about 30 minutes to about 2-6 hours) or by continuous intravenous infusion, and may be administered multiple times during the course of treatment, but single doses are not specifically excluded. Those skilled in the art will recognize that this formulation does not specifically envision the entire course of treatment, and such decisions are left to experts in the therapeutic art rather than the prescriber.

[0155] As described above, useful compositions can be in any of various forms suitable for various routes of administration, e.g., oral, intranasal, intrarectal, topical (including transdermal), intraocular, intracerebral, intracranial, intrathecal, intraarterial, intravenous, intramuscular, subcutaneous, or other parenteral routes of administration. In some embodiments, the composition may be in a form suitable for subcutaneous administration. Those skilled in the art will understand that oral and nasal compositions include compositions administered by inhalation and manufactured using available methods. Depending on the desired specific route of administration, a variety of pharmaceutically acceptable carriers well known among those skilled in the art can be used. Pharmaceutically acceptable carriers include, for example, solid or liquid fillers, diluents, hydration enhancers, surfactants, and encapsulating materials. Any pharmacologically active substance that does not substantially interfere with the inhibitory activity of the compound may be included. The amount of carrier used in combination with the compound is sufficient to provide a practical amount of the substance per unit dose of the compound. The techniques and compositions for producing dosage forms useful for the methods described herein are described in the following references, all of which are incorporated herein by reference: Modern Pharmaceutics, 4th Ed., Chapters 9 and 10 (Banker & Rhodes, editors, 2002); Lieberman et al., Pharmaceutical Dosage Forms: Tablets (1989); and Ansel, Introduction to Pharmaceutical Dosage Forms 8th Edition (2004).

[0156] Various oral dosage forms are available, including solid dosage forms such as tablets, capsules, granules, and bulk powders. Tablets can be compressed tablets, finely ground tablets, enteric coated tablets, sugar-coated tablets, film-coated tablets, or multi-compressed tablets, and contain appropriate binders, lubricants, diluents, disintegrants, colorants, flavorings, flow enhancers, and solvents. Liquid oral dosage forms include aqueous solutions, emulsions, suspensions, solutions and / or suspensions reconstituted from non-foaming granules, and effervescent formulations reconstituted from effervescent granules, which contain appropriate solvents, preservatives, emulsifiers, suspending agents, diluents, sweeteners, solvents, colorants, and flavorings.

[0157] Pharmaceutically acceptable carriers suitable for the preparation of oral dosage forms are well known in the art. Tablets typically contain conventionally pharmaceutically acceptable excipients such as inert diluents (e.g., calcium carbonate, sodium carbonate, mannitol, lactose, cellulose), binders (e.g., starch, gelatin, sucrose), disintegrants (e.g., starch, alginic acid, croscarmellose), and lubricants (e.g., magnesium stearate, stearic acid, talc). Fluidity enhancers such as silicon dioxide are used to improve the fluidity of powder mixtures. Colorants such as FD&C dyes are added to adjust appearance. Sweeteners and flavorings such as aspartame, saccharin, menthol, peppermint, and fruit flavors are suitable excipients for chewable tablets. Capsules typically contain one or more of the aforementioned solid excipients. The selection of carrier components depends on secondary considerations such as taste, cost, and storage stability, which are not critical and can be easily performed by those skilled in the art.

[0158] Oral compositions also include liquid solutions, emulsions, and suspensions. pharmaceutically acceptable carriers suitable for the preparation of such compositions are well known to those skilled in the art. Typical components of carriers for syrups, elixirs, emulsions, and suspensions include ethanol, glycerol, propylene glycol, polyethylene glycol, liquid sucrose, sorbitol, and water. For suspensions, typical suspending agents include methylcellulose, sodium carboxymethylcellulose, AVICEL RC-591, tragacanth, and sodium alginate; typical humectants include lecithin and polysorbate 80; and typical preservatives include methylparaben and sodium benzoate. Oral liquid compositions may also contain one or more of the sweeteners, flavorings, colorants, etc., disclosed above.

[0159] Such compositions can be coated by conventional methods, typically pH-dependent or time-dependent coatings, thereby releasing the target compound near the desired local application site in the gastrointestinal tract or at various timings to extend the desired effect. Such dosage forms typically include, but are not limited to, cellulose acetate phthalate, polyvinyl acetate phthalate, hydroxypropyl methylcellulose phthalate, ethylcellulose, eudarite coatings, waxes, and shellac.

[0160] The compositions described herein may optionally contain other active pharmaceutical ingredients.

[0161] Other compositions useful for achieving systemic delivery of the compounds of the present invention include dosage forms for sublingual, oral, and nasal administration. Such compositions typically contain one or more soluble fillers such as sucrose, sorbitol, and mannitol, and binders such as acacia, microcrystalline cellulose, carboxymethylcellulose, and hydroxypropylmethylcellulose. Lubricants, sweeteners, colorants, antioxidants, and fragrances disclosed above may also be included.

[0162] Preservatives usable in the pharmaceutical compositions disclosed herein include, but are not limited to, benzalkonium chloride, PHMB, chlorobutanol, thimerosal, acetic acid, and phenylmercury nitrate. An example of a useful surfactant is Tween® 80. Similarly, a variety of useful bases may be used in the ophthalmic formulations disclosed herein. These bases include, but are not limited to, polyvinyl alcohol, povidone, hydroxypropyl methylcellulose, poloxamer, carboxymethylcellulose, hydroxyethylcellulose, and purified water.

[0163] Osmotic regulators may be added as needed or for convenience. These include, but are not limited to, salts, particularly sodium chloride, potassium chloride, mannitol, glycerin, or other ophthalmologically acceptable osmotic regulators.

[0164] Various buffers and pH-adjusting methods can be used, provided that the resulting formulation is ophthalmologically acceptable. In many compositions, the pH ranges from 4 to 9. Therefore, buffers include acetate buffer, citrate buffer, phosphate buffer, borate buffer, and the like. Acids or bases can be used to adjust the pH of these formulations as needed.

[0165] For topical use, creams, ointments, gels, solutions, suspensions, etc., containing the compounds disclosed herein are used. Topical formulations may generally consist of a pharmaceutical carrier, a co-solvent, an emulsifier, a penetration enhancer, a preservative, and a emollient.

[0166] For intravenous administration, the compounds and compositions described herein can be dissolved or dispersed in a pharmaceutically acceptable diluent such as physiological saline or glucose solution. To achieve the desired pH, suitable excipients, including but not limited to NaOH, sodium carbonate, sodium acetate, HCl, and citric acid, may be included. In various embodiments, the pH of the final composition is in the range of 2 to 8, preferably 4 to 7. Antioxidant excipients include sodium bisulfite, sodium acetone bisulfite, sodium formaldehyde, sulfoxylates, thiourea, and EDTA. Other non-limiting examples of suitable additives to be included in the final intravenous composition include sodium phosphate or potassium phosphate, citric acid, tartaric acid, gelatin, and carbohydrates such as dextrose, mannitol, and dextran. Further permissible additives are described in Powell et al., Compendium of Excipients for Parenteral Formulations, PDA J Pharm Sci and Tech 1998, 52 238-311, and Nema et al., Excipients and Their Role in Approved Injectable Products: Current Usage and Future Directions, PDA J Pharm Sci and Tech 2011, 65 287-332, both of which are incorporated herein by reference in their entirety. Bacteriostatic or antifungal solutions can also be formed, including but not limited to phenylmercury nitrate, thimerosal, benzethonium chloride, benzalkonium chloride, phenol, cresol, and chlorobutanol.

[0167] Compositions for intravenous administration may be provided to the caregiver in one or more solid forms that are reconstituted immediately before administration with a suitable diluent such as sterile water, saline solution, or dextrose aqueous solution. In other embodiments, the composition is provided in a parenterally administerable solution. In yet another embodiment, the composition is provided as a solution that is further diluted before administration. In embodiments of the combined administration of the compounds described herein with other agents, the combination may be provided to the caregiver as a mixture, the caregiver may mix the two agents before administration, or the two agents may be administered separately.

[0168] The actual dosage of the active compounds described herein depends on the specific compound and the condition being treated: the selection of an appropriate dosage is within the scope of the knowledge of those skilled in the art.

[0169] The compounds and compositions described herein may, as necessary, be provided in packaging or dispenser devices containing one or more unit dosage forms comprising the active ingredient. Such packaging or devices may consist of, for example, metal or plastic foil such as blister packs, or glass and rubber stoppers such as vials. Dosage instructions may be attached to the packaging or dispenser devices. The compounds and compositions described herein may be formulated in suitable pharmaceutical carriers, placed in appropriate containers, and prepared for the treatment of indications.

[0170] The amount of compound in the formulation can vary within the range used by those skilled in the art. Typically, the formulation contains approximately 0.01 to 99.99 wt% of the compound according to this technology, based on the total formulation, with the remainder being one or more suitable pharmaceutical excipients. Preferably, the compound is present at a concentration of approximately 1 to 80% by weight. Representative formulation examples are shown below. Examples of formulations

[0171] The following are representative examples of formulations containing the compound of formula I. Formulation Example 1 - Tablet Formulation

[0172] Thoroughly mix the following ingredients and compress them into a single, scored tablet. Table 0.1 [Table 1] Formulation Example 2 - Capsule Formulation

[0173] The following ingredients are mixed uniformly and filled into hard-shell gelatin capsules. [Table 2] Formulation Example 3 - Suspension Formulation

[0174] Mix the following ingredients to prepare a suspension for oral administration. [Table 3] Formulation Example 4 - Injectable Formulation

[0175] The following components are mixed to prepare an injectable formulation. [Table 4] Formulation Example 5 - Suppository Formulation

[0176] A suppository weighing 2.5 g in total is prepared by mixing the compound of this technology with Witepsol® H-15 (saturated vegetable fatty acid triglyceride; Riches-Nelson, Inc., New York) and has the following composition: [Table 5] Treatment method

[0177] Compounds of formulas (I) and (II) disclosed herein, or their tautomers and / or pharmaceutically acceptable salts, can effectively treat autoimmune or inflammatory diseases. Some embodiments provide pharmaceutical compositions comprising one or more compounds disclosed herein and pharmaceutically acceptable excipients.

[0178] Some embodiments provide methods for preventing, treating, or improving one or more inflammatory or autoimmune diseases in a subject. In some embodiments, the method comprises administering one or more compounds disclosed herein to a subject in need. In some embodiments, the method comprises administering pharmaceutically acceptable salts of one or more compounds disclosed herein to a subject in need. In some embodiments, the subject suffers from an autoimmune disease. In some embodiments, the subject suffers from an inflammatory disease.

[0179] In some embodiments, the disclosed compounds are used to prevent, treat, or improve ulcerative colitis, Crohn's disease, rheumatoid arthritis, atopic dermatitis, psoriasis, lupus (e.g., systemic lupus erythematosus), atherosclerosis, and type 1 diabetes. Some embodiments provide methods for preventing, treating, or improving lupus, rheumatoid arthritis, atopic dermatitis, and psoriasis. In some embodiments, the method comprises administering one or more of the disclosed compounds to a subject of interest. In some embodiments, the method comprises administering pharmaceutically acceptable salts of one or more of the disclosed compounds to a subject of interest.

[0180] In some embodiments, the disclosed compounds are used to treat cancer. In some embodiments, the cancer is selected from the group consisting of colon cancer, liver cancer, pancreatic cancer, gastric cancer, esophageal cancer, prostate cancer, breast cancer, bile duct cancer, sarcoma, or acute myeloid leukemia. In some embodiments, the method comprises administering one or more of the compounds disclosed herein to a subject of interest. In some embodiments, the method comprises administering pharmaceutically acceptable salts of one or more of the compounds disclosed herein to a subject of interest.

[0181] In some embodiments, a method of administering one or more compounds disclosed herein results in the prevention, treatment, or improvement of inflammatory or autoimmune diseases. In some embodiments, a method of administering one or more compounds disclosed herein results in the prevention, treatment, or improvement of ulcerative colitis, Crohn's disease, atopic dermatitis, psoriasis, systemic lupus erythematosus, atherosclerosis, and type 1 diabetes. In some embodiments, the method comprises administering pharmaceutically acceptable salts of one or more compounds disclosed herein.

[0182] In some embodiments, the method of administering one or more compounds disclosed herein does not substantially inhibit G9a (also known as "euchromatin histone lysine N-methyltransferase 2" or "EHMT2").

[0183] Some embodiments provide the use of the compounds disclosed herein in the preparation of pharmaceuticals for the treatment of autoimmune or inflammatory diseases. Some embodiments provide the use of the compounds disclosed herein in the treatment of autoimmune or inflammatory diseases. In some embodiments, such use includes the treatment of autoimmune diseases. In some embodiments, such use includes the treatment of inflammatory diseases.

[0184] Some embodiments involve administering the compounds, compositions, and / or pharmaceutical compositions described herein in combination with additional pharmaceuticals. "Combined administration" means that two or more drugs are present in the patient's bloodstream at the same time, regardless of when or how they are actually administered. In one embodiment, the drugs are administered simultaneously. In one such embodiment, combined administration is achieved by formulating the drugs into a single dosage form. In another embodiment, the drugs are administered sequentially. In one embodiment, the drugs are administered via the same route, such as orally. In another embodiment, the drugs are administered via different routes, for example, one drug by subcutaneous administration, another by oral administration, and yet another by intravenous injection.

[0185] The following embodiments are provided to illustrate various embodiments of the Disclosure and are not intended to limit the Disclosure in any way. Those skilled in the art will readily understand that the Disclosure is adequately suited to achieving the purposes described and obtaining the effects and benefits described, as well as to achieving the purposes, effects and benefits inherent in the Disclosure. Those skilled in the art will readily understand, within the spirit of this Specified, the modifications and other uses defined by the claims. Examples Example 1: Compound Synthesis

[0186] All reactions were carried out under an argon atmosphere. Commercial reagents and solvents were used, and no further purification was performed. Hydrogenation reactions were carried out under balloon conditions. Microwave reactions were performed using a CEM Discover SP microwave synthesizer. Sample purification was performed using a Buchi Pureflash equipped with a commercially available pre-packed silica gel column ELSD purification system. Thin-layer chromatography (TLC) was performed on aluminum plates using Merck Kieselgel 60 F254 (230-400 mesh) fluorescent silica, visualized under ultraviolet light (254 nm), or stained with potassium permanganate solution or ninhydrin solution as needed. All nuclear magnetic resonance (NMR) spectra were acquired using a Bruker Avance III HD 400 MHz NMR spectrometer; chemical shifts were reported in ppm(δ). HPLC / MS was performed using a Shimadzu Nexera X2 UHPLC system with a Sciex 5500 Qtrap mass spectrometer and a Phenomenex Luna C18 column (50 x 2.0 mm, particle size 3 μm), following the procedure below: Gradient mobile phase A contained 0.1% formic acid in water, and mobile phase B contained 0.1% formic acid in acetonitrile. 0-0.9 min: A / B (95:5); 0.9-2.2 min: A / B (5:95); 2.2-4.14 min: A / B (5:95); 4.14-4.20 min: A / B (95:5); 4.2-6 min: A / B (95:5). The flow rate was maintained at 0.4 mL / min, the column temperature at 35°C, and the autosampler temperature at 4°C. The ion spray voltage, dry gas temperature, ion source gas 1, and ion source gas 2 were set to 4500V, 500°C, 35V, and 45V, respectively, and ESI was set to positive mode using full scan. The purity of all compounds was analyzed using an Agilent 1260 Infinity II Lab LC series HPLC (1260Quat pump, 1260 vial autosampler, ICC column oven, 1260 DAD WR detector). Samples were injected into a Phenomenex Synergi Polar RP column (150×4.6mm, 4μm, 80Å).A gradient mobile phase (A: 0.1% trifluoroacetic acid aqueous solution, B: 0.1% trifluoroacetic acid acetonitrile solution; A / B (99:1) from 0 min; A / B (1:99) from 0 to 15 min; A / B (1:99) from 15 to 18 min; A / B (99:1) from 18 to 18.1 min; A / B (99:1) from 18.1 to 20 min) was injected at a flow rate of 1 mL / min. The UV detector was set to 254 nm and the column oven was set to 35°C. Unless otherwise specified, the injection volume was 10 μL. All compounds evaluated in biological tests had a purity of ≥90%, and in animal tests, the purity was ≥95%. Example 2: Synthesis of 2-chloro-6-methoxy-N-(oxetan-3-yl)-7-(3-(pyrrolidine-1-yl)propoxy)quinazoline-4-amine (compound 1) [ka]

[0187] Commercially available 2,4-dichloro-6-methoxy-7-(3-(pyrroridine-1-yl)propoxy)quinazoline (2.00 g, 5.61 mmol) and 3-oxetanamine (0.62 g, 8.42 mmol) were dissolved in anhydrous DMF (15 mL), and DIPEA (2.93 mL, 16.84 mmol) was added. The sealed reaction tube was heated at 50°C for 3 days under an argon atmosphere. The cooled reaction was quenched with saturated NaHCO3, extracted with an 8:2 dichloromethane / isopropanol mixed solvent (3 times × 50 mL), and then washed once with brine. The combined organic layer was dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by Buchi Pureflash chromatography on a silica gel cartridge (80g) using 95:5CH2Cl2:MeOHw / 2%7N ammonia to obtain 2-chloro-6-methoxy-N-(oxetan-3-yl)-7-(3-(pyrrolidine-1-yl)propoxy)quinazoline-4-amine (1.37g, 62%) as a beige solid. 1H NMR(400MHz, CDCl3-d):δ 7.10(s, 1H), 6.92(s, 1H), 6.25(d, 1H, J = 8.0 Hz), 5.38(m, 1H), 5.10(t, 2H, J = 8.0 Hz), 4.65(t, 2H, J = 4.0 Hz), 4.14(t, 2H, J = 4.0 Hz), 3.95(s, 3H), 2.61(dd, 2H, J = 8.0 Hz), 2.50(m, 4H), 2.08(m, 2H), 1.76(m, 4H). MS(ESI):C 19 H 25 Calculated value for ClN4O3: 392, measured value: 393 (M+H) + . Example 3: Synthesis of (5-(4,4-difluoropiperidine-1-yl)-9-methoxy-8-(3-(pyrrolidine-1-yl)propoxy)-2,3-dihydroimidazo[1,2-c]quinazolin-2-yl)methanol (Compound 2) [ka]

[0188] DIPEA (0.06 g, 0.51 mmol) was added to a solution of 2-chloro-6-methoxy-N-(octan-3-yl)-7-(3-(pyrrolidine-1-yl)propoxy)quinazoline-4-amine (0.20 g, 0.51 mmol) and 4,4-difluoropiperidine hydrochloride (0.40 g, 2.55 mmol) in anhydrous 2-butanol (4 mL). The sealed tubes were subjected to 90°C under an argon atmosphere. oThe mixture was heated in 1C for 5 days. Then, one drop of concentrated hydrochloric acid was added, and heating was continued overnight. After confirming the completion of the reaction by TLC, the cooled mixture was quenched with saturated NaHCO3 solution, extracted with a dichloromethane / isopropanol mixed solvent (8:2) (3 times × 50 mL), and washed once with brine. The combined organic layer was dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by Buchi Pureflash chromatography on a silica gel cartridge (24 g) using 8:2CH2Cl2:MeOHw / 2% 7N ammonia to obtain (5-(4,4-difluoropiperidine-1-yl)-9-methoxy-8-(3-(pyrrolidine-1-yl)propoxy)-2,3-dihydroimidazo[1,2-c]quinazolin-2-yl)methanol (0.21 g, 87%) as an orange solid. 1 H NMR (400 MHz, CDCl3): δ 7.29 (s, 1H), 6.72 (s, 1H), 4.35 (m, 1H), 4.13 (m, 1H), 4.04 (m, 1H), 3.87 (s, 3H), 3.63 (dd, 1H, J = 12.0, MS (ESI): Calculated value C 24 H 33 Calculated value for F2N5O3: 477, Measured value: 478 (M+H) + . Example 4: Synthesis of (5-(4,4-difluoropiperidine-1-yl)-9-methoxy-8-(3-(pyrrolidine-1-yl)propoxy)-2,3-dihydroimidazo[1,2-c]quinazolin-2-yl)methylacetate (compound 3) [ka]

[0189] (5-(4,4-difluoropyrrolinidine-1-yl)-9-methoxy-8-(3-(pyrrolinidine-1-yl)propoxy)-2,3-dihydroimidazo[1,2-c]quinazolin-2-yl)methanol (0.015 g, 0.031 mmol) and DIPEA (0.008 g, 0.063 mmol) were dissolved in anhydrous THF (1 mL), to which acetyl chloride (0.004 g, 0.047 mmol) was added under an argon atmosphere in an ice bath. The sealed tube was then stirred overnight at room temperature. After confirming the completion of the reaction by TLC, the cooled mixture was quenched with saturated NaHCO3 and extracted with an 8:2 dichloromethane / isopropanol mixed solvent (3 times × 50 mL), followed by one wash with brine. The combined organic layer was dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by Buchi Pureflash chromatography on a silica gel cartridge (12 g) using 95:5CH2Cl2:MeOHw / 2%7N ammonia to obtain (5-(4,4-difluoropiperidine-1-yl)-9-methoxy-8-(3-(pyrrolidine-1-yl)propoxy)-2,3-dihydroimidazo[1,2-c]quinazolin-2-yl)methyl acetate (0.013 g, 79%) as a red solid. 1 H NMR (400 MHz, CDCl3): δ 7.28 (s, 1H), 6.84 (s, 1H), 4.49 (m, 1H), 4.27 (dd, 2H, J = 8.0, 4.0 Hz), 4.18 (dd, 2H, J = 12.0, 8.0 Hz), 4.13 (t, 2H, J = 4.0 Hz) 4.07 (t, 1H, J = 8.0 Hz), 3.88 (s, 3H), 3.80 (dd, 1H, J = 12.0, 8.0 Hz), 3.31 (m, 4H), 2.61 (t, 2H, J = 4.0 Hz), 2.51 (m, 4H), 2.10 (m, 6H), 2.05 (s, 3H), 1.76 (m, 4H). MS (ESI): C 26 H 35 Calculated value for F2N5O4: 519, Measured value: 520 (M+H) + . Example 5: Synthesis of 2-chloro-6-methoxy-N-(oxetan-3-yl)-7-(2-(pyrrolidine-1-yl)ethoxy)quinazoline-4-amine (compound 4) [ka]

[0190] DIPEA (3.40 g, 26.30 mmol) was added to a solution of commercially available 2,4-dichloro-6-methoxy-7-(2-(pyrroridine-1-yl)ethoxy)quinazoline (3.00 g, 8.77 mmol) and 3-oxetanamine (0.96 g, 13.15 mmol) in anhydrous DMF (20 mL). The sealed reaction tube was heated at 50 °C for 3 days under an argon atmosphere. The cooled reaction was quenched with saturated NaHCO₃, extracted with an 8:2 dichloromethane / isopropanol mixed solvent (3 times × 50 mL), and then washed once with brine. The combined organic layer was dried over anhydrous Na₂SO₄, filtered, and concentrated under reduced pressure. The residue was purified by Buchi Pureflash chromatography on a silica gel cartridge (80g) using 95:5CH2Cl2:methyl alcohol w / 2% 7N ammonia to obtain 2-chloro-6-methoxy-N-(oxetan-3-yl)-7-(2-(pyrrolidine-1-yl)ethoxy)quinazoline-4-amine (1.37g, 62%) as a beige solid. 1 H NMR (400 MHz, DMSO-d): δ 8.83 (d, 1H, J = 5.2 Hz), 7.70 (s, 1H), 7.10 (s, 1H), 5.16(m,1H), 4.89(t, 2H, J=6.4Hz), 4.65 (t, 2H, J = 6.0 MS (ESI): C 18 H 23 Calculated value of ClN4O3: 378, Measured value: 379 (M+H) + . Example 6: Synthesis of (5-(4,4-difluoropiperidine-1-yl)-9-methoxy-8-(2-(pyrrolidine-1-yl)ethoxy)-2,3-dihydroimidazo[1,2-c]quinazolin-2-yl)methanol (Compound 5) [ka]

[0191] In 10 mL of anhydrous 2-butanol, 2-chloro-6-methoxy-N-(oxetan-3-yl)-7-(2-(pyrrolidine-1-yl)ethoxy)quinazoline-4-amine (0.20 g, 0.51 mmol) and 4,4-difluoropiperidine hydrochloride (0.58 g, 3.70 mmol) were dissolved in 10 mL of anhydrous 2-butanol, to which DIPEA (0.82 g, 6.33 mmol) was added. The sealed tube was heated at 90°C for 5 days under an argon atmosphere. After confirming the completion of the reaction by TLC, the cooled mixture was quenched with saturated NaHCO3 and extracted with an 8:2 dichloromethane / isopropanol mixed solvent (3 times × 50 mL), followed by one wash with brine. The combined organic layer was dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by Buchi Pureflash chromatography on a silica gel cartridge (24 g) using 8:2CH2Cl2:MeOHw / 2%7N ammonia to obtain (5-(4,4-difluoropiperidine-1-yl)-9-methoxy-8-(2-(pyrrolidine-1-yl)ethoxy)-2,3-dihydroimidazo[1,2-c]quinazolin-2-yl)methanol (0.12 g, 24%) as a beige solid. 1 H NMR (400 MHz, CDCl3): δ 7.29 (s, 1H), 6.64 (a, 1H), 4.34 (tt, 1H, J = 9.4, 2.9 Hz), 4.18 (m,, 2H), 4.12-3.97 (m, 3H), 3.65 (dd, 1H, J = MS (ESI): C 23 H 31 Calculated value for F2N5O3: 463, Measured value: 464 (M+H) + . Example 7: Synthesis of 2-chloro-6,7-dimethoxy-N-(oxetan-3-yl)quinazoline-4-amine (compound 6) [ka]

[0192] DIPEA (3.40 g, 26.30 mmol) was added to a solution of commercially available 2,4-dichloro-6,7-dimethoxyquinazoline (3.00 g, 8.77 mmol) and 3-oxetanamine (0.96 g, 13.15 mmol) in anhydrous DMF (20 mL). The sealed tube was heated at 50°C for 3 days under an argon atmosphere. The cooled reaction was quenched with saturated NaHCO3, extracted with an 8:2 dichloromethane / isopropanol mixed solvent (3 × 50 mL), and washed once with brine. The combined organic layer was dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by Buchi Pureflash chromatography on a silica gel cartridge (80 g) using 95:5CH2Cl2:MeOHw / 2%7N ammonia, and 2-chloro-6,7-dimethoxy-N-(oxetan-3-yl)quinazoline-4-amine (4.80 g, 84%) was obtained as a white solid. 1 H NMR (400 MHz, CDCl3-d): δ 8.82 (d, 1H, J = 5.6 Hz), 7.69 (s, 1H), 7.09 (s, 1H), 5.16 (m, 1H), 4.89 (t, 2H, J = 6.8 Hz), 4.65 (t, 2H, J = 6.4 Hz), 3.91 (s, 3H), 3.89 (s, 3H). MS (ESI): C 13 H 14 Calculated value of ClN3O3: 295, Measured value: 296 (M+H) + . Example 8: Synthesis of (5-(4,4-difluoropiperidine-1-yl)-8,9-dimethoxy-2,3-dihydroimidazo[1,2-c]quinazolin-2-yl)methanol (compound 7) [ka]

[0193] 2-Chloro-6,7-dimethoxy-N-(oxetan-3-yl)quinazoline-4-amine (0.40 g, 1.35 mmol) and 4,4-difluoropiperidine hydrochloride (0.75 g, 4.73 mmol) were dissolved in an 8:2 mixed solvent of anhydrous 2-butanol / THF (10 mL), and DIPEA (1.05 g, 8.12 mmol) was added. The sealed reaction tube was heated at 90°C for 5 days under an argon atmosphere. After confirming the completion of the reaction by TLC, the cooled mixture was quenched with saturated NaHCO3, extracted with an 8:2 mixed solvent of dichloromethane / isopropanol (3 × 50 mL), and washed once with brine. The combined organic layer was dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by Buchi Pureflash chromatography on a silica gel cartridge (24 g) using 8:2CH2Cl2:MeOHw / 2%7N ammonia to obtain (5-(4,4-difluoropiperidine-1-yl)-8,9-dimethoxy-2,3-dihydroimidazo[1,2-c]quinazolin-2-yl)methanol (0.21 g, 42%) as a beige solid. 1 H NMR (400 MHz, CDCl3): 7.34 (s, 1H), 6.70 (s, 1H), 4.39 (tt, 1H, J = 9.4, 2.9 Hz), 4.13 - 4.03 (m, 3H), 3.94 (s, 3H), 3.91 (s, 3H), 3.66 (dd,1H, J = 11.9, 3.1 Hz), 3.33 (t, 4H, J = 5.7 Hz), 2.14 (m, 5H). MS (ESI): C 18 H 22 Calculated value for F2N4O3: 380, Measured value: 381 (M+H) + . Example 9: Test using DSS-induced colitis mice

[0194] The effects of compound 2 in mice with dextran sulfate sodium (DSS)-induced colitis were evaluated. C57BL / 6 mice (body weight 20-22 grams) were ad libitum and assigned to four different groups (n=8 in each group). After a 72-hour acclimatization period, the test group received the test compound orally at a dose of 25 mg / kg per day with vehicle. The control group received vehicle alone ("vehicle"). After 24 hours, the mice's body weight was measured, and DSS was added to their drinking water. Subsequently, the mice were treated with the test compound, compound 2 (also known as "Cpd002"), and their body weight was measured daily. DSS water was replenished every 72 hours for 5 consecutive days, after which the DSS water was replaced with drinking water. On day 12, the mice were sacrificed, and clinical scores were assessed.

[0195] Figure 1A is a graph comparing the percentage change in body weight after administration of compound 2 in mice with DSS-induced colitis with a control group administered only with vehicle. The results show that the compound 2 group showed increased body weight compared to the vehicle-only group. Furthermore, Figure 1B shows the percentage change in body weight after exposure to compound 2 in mice with DSS-induced colitis, compared with mice administered only with vehicle. In addition, when the mice were sacrificed 12 days after DSS induction, as shown in Figure 1C, the colon length was prolonged in the mice administered with compound 2, but not in the mice administered only with vehicle (control group). Example 10: Test using mice with TNBS-induced colitis

[0196] The effect of compound 2 was evaluated against outcomes in mice with 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis. C57BL / 6 mice (body weight 20-22 grams) were ad libitum and assigned to four different groups (n=8 in each group). After a 72-hour acclimatization period, the test group received 25 mg / kg of the test compound daily via PO (oral administration). The control group received only the vehicle ("vehicle"). After 24 hours, the mice's body weight was measured, and TNBS was administered rectally using a 5 cm polyethylene tube (1 / 4 inch). Subsequently, the mice were treated with the test compound, compound 2 (also known as "Cpd002"), and their body weight was measured daily for 4 days. On day 4, the mice were sacrificed, and clinical scores were evaluated.

[0197] Figure 2A is a graph showing the percentage change in body weight in mice with TNBS-induced colitis after administration of compound 2. Figure 2B is a chart showing colon length in mice with TNBS-induced colitis after exposure to compound 2. As shown in Figure 2B, colon length increased in the compound 2 administration group compared to the control group that received the vehicle alone. Figure 2C is a chart showing the histological scores in mice with TNBS-induced colitis after exposure to compound 2, and Figure 2D is a chart showing the clinical scores in mice with TNBS-induced colitis after exposure to compound 2.

Claims

1. Compounds having the structure represented by formula I, or pharmaceutically acceptable salts thereof: 【Chemistry 1】 Here: R １ These are -H, -OH, and -CH ３ , or -OCH ３ Selected from the group consisting of; R ２ C is replaced by -H, -OH, or any other element. １－６ Alkyl, optionally substituted C １－６ Alkoxy or optionally substituted C １－６ Selected from the group consisting of haloalkyls; R ３ is selected from the group consisting of -CN, -OH, optionally substituted C １ -C １０ alkyl, optionally substituted C １ -C １０ alkenyl, optionally substituted C １ -C １０ alkynyl, optionally substituted alkoxy, optionally substituted 3- to 10-membered carbocyclic ring, optionally substituted 6- to 10-membered aryl, optionally substituted 3- to 10-membered heterocyclic ring, optionally substituted 5- to 10-membered heteroaryl, and -NR ５ R ６ ; and is selected from the group consisting of R ４ is -H, -(CO)CH ３ , C replaced by arbitrary selection １ -C １０ Selected from the group consisting of alkyl groups; and R ５ and R ６ These are C, each replaced by an arbitrary choice. １－６ It is alkyl.

2. The structure of equation (I) is further expressed by equation (Ia): 【Chemistry 2】 Here: R ７ , R ８ , R ９ , R １０ , R １１ , and R １２ These are, independently, -H, -OH, halogen, and C, which is substituted by any choice. １－６ Alkyl, optionally substituted C １－６ Alkoxy, optionally substituted C １－６ Alkyl, optionally substituted C １－６ Alkoxy or optionally substituted C １－６ Selected from the group consisting of haloalkyls; R １３ C is replaced by an optional substitution. １－６ Alkyl, optionally substituted C １－２０ Selected from the group consisting of alkylenes and their absence; R １４ This is a 3-20 member heterocycline, -NR, which is optionally substituted. １５ R １６ Selected from the group consisting of , and non-existence; and R １５ and R １６ These are C, each replaced by an arbitrary choice. １－６ The compound according to claim 1, wherein it is alkyl.

3. R ７ , R ８ , R １１ and R １２ Each of these is -H, and R ９ and R １０ The compound according to claim 2, wherein each of the elements is a halogen.

4. R ９ and R １０ The compound according to claim 2 or 3, wherein each of the two is -F.

5. R ４ The compound according to any one of claims 2 to 4, wherein is -H.

6. R ４ ha-(CO)CH ３ The compound according to any one of claims 2 to 4.

7. R １３ C is replaced by an optional substitution. １－２０ The compound according to any one of claims 2 to 6, which is an alkylene.

8. R １３ The compound according to any one of claims 2 to 7, wherein is selected from the group consisting of ethylene and propylene.

9. R １４ The compound according to any one of claims 2 to 8, wherein is a five-membered heterocycline to which is optionally substituted.

10. R １４ but 【Transformation 3】 The compound according to any one of claims 2 to 9.

11. R １４ ga-NR １５ R １６ The compound according to any one of claims 2 to 8.

12. R １５ and R １６ The compound according to claim 11, wherein each is independently selected from the group consisting of methyl, ethyl, and propyl.

13. R １３ C is replaced by an optional substitution. １－６ A compound according to any one of claims 2 to 6, wherein it is alkyl.

14. R １３ ha-CH ３ The compound according to claim 12.

15. The structure of equation I is further structured as follows 【Chemistry 4】 A compound according to claim 1, or a pharmaceutically acceptable salt thereof, represented by a structure selected from the above.

16. Compounds having the structure represented by formula II, or pharmaceutically acceptable salts thereof: 【Transformation 5】 Here: R １７ It is selected from the group consisting of -H, -OH, and halogens; R １８ C is replaced by an optional substitution. １－６ Alkyl, optionally substituted C １－２０ Selected from the group consisting of alkylenes and their absence; R １９ This is a 3-20 member heterocycline, -NR, which is optionally substituted. ２１ R ２２ Selected from the group consisting of , and non-existence; R ２０ is selected from the group consisting of -H and optionally substituted 3-4 member heterocyclines; and R ２１ and R ２２ These are C, each replaced by an arbitrary choice. １－６ It is alkyl.

17. R ２０ The compound according to claim 16, wherein is a four-membered heterocycline.

18. R ２０ teeth 【Transformation 6】 The compound according to claim 16 or 17.

19. R １７ The compound according to any one of claims 16 to 18, wherein is a halogen.

20. R １７ The compound according to any one of claims 16 to 19, wherein is -Cl.

21. R １８ C is replaced by an optional substitution. １－２０ The compound according to any one of claims 16 to 20, which is an alkylene.

22. R １８ The compound according to any one of claims 16 to 21, wherein is selected from the group consisting of ethylene and propylene.

23. R １９ The compound according to any one of claims 16 to 22, wherein is an optionally substituted five-membered heterocycline.

24. R １９ teeth 【Transformation 7】 The compound according to any one of claims 16 to 23.

25. R １９ is -NR ２１ R ２２ and is a compound according to any one of claims 16 to 22.

26. R ２１ and R ２２ The compound according to claim 25, wherein each is independently selected from the group consisting of methyl, ethyl, and propyl.

27. R １８ C is replaced by an optional substitution. １－６ The compound according to any one of claims 16 to 20, wherein it is alkyl.

28. R １８ is -CH ３ and is the compound according to claim 25.

29. The structure of equation II is further structured as follows: 【Transformation 8】 The compound according to claim 16, or a pharmaceutically acceptable salt thereof, represented by a structure selected from the above.

30. A method for treating an autoimmune disease or inflammatory disease, comprising administering a compound according to any one of claims 1 to 29 to a subject in need of treatment.

31. The method according to claim 30, wherein the subject is suffering from an autoimmune disease or an inflammatory disease.

32. A method according to claim 30 or 31, wherein the compound according to any one of claims 1 to 31 does not substantially inhibit G9a.

33. Use of the compound according to any one of claims 1 to 29 for the manufacture of a pharmaceutical product for treating an autoimmune disease or an inflammatory disease.

34. Use of the compound according to any one of claims 1 to 29 for the treatment of an autoimmune disease or an inflammatory disease.

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