Vanin-1 inhibitors

Abstract

This specification discloses bicyclic compounds, including pharmaceutical compositions containing one or more such compounds. This specification also discloses methods for producing bicyclic compounds having functional groups. This specification also discloses methods for treating diseases and / or conditions (e.g., inflammatory and / or cancer) using the bicyclic compounds disclosed herein.

Description

[Technical Field]

[0001] This specification discloses bicyclic compounds, including pharmaceutical compositions containing one or more such compounds. This specification also discloses methods for producing bicyclic compounds having functional groups. [Background technology]

[0002] The enzyme vascular non-inflammatory molecule-1 (vanin-1) is prominently present in many organs, including the liver, intestines, and kidneys. Its primary function is the metabolism of pantetheine to cysteamine and pantothenic acid. Vanin-1 plays a complex role in disease, exhibiting protective effects or acting as a sensitizer depending on the organ involved. [Overview of the Initiative]

[0003] Some embodiments disclosed herein relate to bicyclic compounds and their use as inhibitors of the enzymatic activity of vanin-1. Some embodiments relate to methods for producing bicyclic compounds and methods for using bicyclic compounds as therapeutic agents for treating inflammatory disease conditions. In some embodiments, the bicyclic compound comprises at least one aromatic ring substituted with at least one amine group. Some embodiments consist of or essentially consist of bicyclic compounds of formula (I) (or any other structure 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, one or more compounds of formula (I) (or any other structure disclosed herein) can be used to inhibit vanin-1 activity in a subject and treat a disease condition. In some embodiments, the disease condition is associated with inflammation. In some embodiments, the disease condition is associated with autoimmune diseases. In some embodiments, the disease condition is cancer mediated at least partially through vanin-1.

[0004] Some embodiments relate to a vanin-1 inhibitor. In some embodiments, the vanin-1 inhibitor comprises a compound having a structure represented by formula (I)

[0005]

Chemical formula

[0006] In some embodiments, A, B, U, V, W, X, Y, and Z are each independently selected from the group consisting of C, C(R 5 -R 3 ), N, N(R 5 -R 4 ), S, and S(R 5 -R 4 ), and at least one instance of A, B, U, V, W, X, Y, and Z is N, N(R 5 -R 4 ), S, or S(R 5 -R 4 ), and the remaining variables are C or C(R 5 -R 3 ); each instance of R 1 and R 2 is independently selected from the group consisting of -H, optionally substituted C 1-6 alkyl, optionally substituted C 1-20 alkylene, optionally substituted C 1-6 heteroalkyl, optionally substituted C 6-10 aryl, optionally substituted 3- to 10-membered arylalkyl, optionally substituted 5- to 10-membered heteroaryl, optionally substituted 3- to 10-membered heteroarylalkyl, optionally substituted 3- to 20-membered carbocyclic, optionally substituted 3- to 20-membered (carbocyclic)alkyl, optionally substituted 3- to 20-membered heterocyclic, and optionally substituted 3- to 20-membered (heterocyclic)alkyl, or does not exist; R 3 and R 4Each example, if present, independently includes -H, optionally substituted C1-6 alkyl, and optionally substituted C 1-20 Alkylene, substituted C as needed 1-6 Heteroalkyl, substituted C as needed 6-10 Selected from the group consisting of aryls, optionally substituted 5-10 member heteroaryls, optionally substituted 3-10 member arylalkyls, optionally substituted 3-20 member carbocyryls, optionally substituted 3-20 member (carbocyryl)alkyls, optionally substituted 3-20 member heterocyclyls, and optionally substituted 3-20 member (heterocyclyl)alkyls, or none; R 5 Each of these examples, if present, is independently replaced as needed with C. 1-20 Selected from the group consisting of alkylenes, or none at all; and n is 0, 1, or 2.

[0007] Some embodiments relate to compounds of formula (I) or pharmaceutically acceptable salts thereof.

[0008] [ka] In some embodiments, A, B, U, V, W, X, Y, and Z are independently C, C(R) 5 -R 3 ), N, N(R 5 -R 4 ), S, and S(R 5 -R 4 Selected from the group consisting of ), and at least one example of A, B, U, V, W, X, Y, and Z is N, N(R 5 -R 4 ), S, or S(R 5 -R 4 ) and the remaining variables are C or C(R 5 -R 3 ) and; R 1 and R 2Each of these examples is independent, -H, and C is substituted as needed. 1-6 Alkyl, substituted C as needed 1-20 Alkylene, substituted C as needed 1-6 Heteroalkyl, substituted C as needed 6-10 Selected from or absent from the group consisting of aryls, optionally substituted 3- to 10-membered arylalkyls, optionally substituted 5- to 10-membered heteroaryls, optionally substituted 3- to 10-membered heteroarylalkyls, optionally substituted 3- to 20-membered carbocyrills, optionally substituted 3- to 20-membered (carbocyrill)alkyls, optionally substituted 3- to 20-membered heterocyclines, and optionally substituted 3- to 20-membered (heterocyclyl)alkyls; R 3 and R 4 Each example, if present, independently includes -H, optionally substituted C1-6 alkyl, and optionally substituted C 1-20 Alkylene, substituted C as needed 1-6 Heteroalkyl, substituted C as needed 6-10 Selected from the group consisting of aryls, optionally substituted 5-10 member heteroaryls, optionally substituted 3-10 member arylalkyls, optionally substituted 3-20 member carbocyryls, optionally substituted 3-20 member (carbocyryl)alkyls, optionally substituted 3-20 member heterocyclyls, and optionally substituted 3-20 member (heterocyclyl)alkyls, or none; R 5 Each of these examples, if present, is independently replaced as needed with C. 1-20 Selected from the group consisting of alkylenes, or none at all; and n is 0, 1, or 2.

[0009] In some embodiments, Z is N. In some embodiments, V is N. In some embodiments, n is 0. In some embodiments, n is 1. In some embodiments, A is N(R5 -R 4 ) is. In some embodiments, R 5 It does not exist. In some embodiments, R 5 C is replaced as needed. 1-20 It is alkylene.

[0010] Some embodiments are compounds of formula (I) further represented by one or more of formula (Ia) or (Ib),

[0011] [ka] Or relating to its pharmaceutically acceptable salt.

[0012] In some embodiments, R 5 ha-(CH2) m - where m is an integer in the range of 0 to 20. In some embodiments, m is 0, 1, 2, 3, 4, 5, or 6. In some embodiments, m is 0, 1, 2, or 3. In some embodiments, m is 2.

[0013] In some embodiments, the structure of this formula (I) is:

[0014] [ka] Or further represented by a pharmaceutically acceptable salt thereof. In some embodiments, R 1 is -CH2-. In some embodiments, R 1 It does not exist. In some embodiments, R 2 R is a phenyl or 6-membered heterocycline, optionally substituted, where 1 to 3 heteroatoms are selected from N, O, and S. In some embodiments, R 2The group is pyridinyl, pyrimidinyl, or pyrazinyl. In some embodiments, this optionally substituted group is substituted with one to five groups selected from -F, -Cl, methyl, methoxy, -CN, and -CF3.

[0015] In some embodiments, R 4 teeth,

[0016] [ka] TIFF2026513524000006.tif236164TIFF2026513524000007.tif238162 Selected from the group consisting of .

[0017] In some embodiments, R 4 teeth,

[0018] [ka] Selected from the group consisting of TIFF2026513524000009.tif247164 and TIFF2026513524000010.tif222162.

[0019] In a specific embodiment, R 4 teeth,

[0020] [ka] Selected from the group consisting of .

[0021] In some embodiments, R 4 teeth,

[0022] [ka] Selected from the group consisting of .

[0023] In a particular embodiment, R4 is -H.

[0024] In a specific embodiment, R 4 teeth,

[0025] [ka] Selected from the group consisting of .

[0026] In a specific embodiment, R 4 teeth,

[0027] [ka] TIFF2026513524000015.tif49163 Selected from the group consisting of .

[0028] In a specific embodiment, R 4 teeth,

[0029] [ka] Selected from the group consisting of .

[0030] In a specific embodiment, R 4 teeth,

[0031] [ka] Selected from the group consisting of .

[0032] In a specific embodiment, R 4 teeth,

[0033] [ka] Selected from the group consisting of .

[0034] In certain embodiments, R 4 is

[0035]

Chemical formula

[0036] In some embodiments, R 1 is optionally substituted C 1-6 alkyl or optionally substituted C 1-20 alkylene. In further embodiments, R 1 is selected from the group consisting of -CH2-, -CH2CH2-, -CH(CH3)-, and -CHCH2(OH)-. In other embodiments, R 1 is -(CH2) p -, and p is an integer in the range from 0 to 20. In some embodiments, p is 0, 1, 2, 3, 4, 5, or 6

[0037] In some embodiments, R 2 is

[0038]

Chemical formula

[0039] In some embodiments, R 2 is

[0040]

Chemical formula

[0041] In certain embodiments, R 2 is

[0042]

Chem.

[0043] In certain embodiments, R 2 is

[0044]

Chem.

[0045] In some embodiments, R 2 is -H.

[0046] In some embodiments, R 2 is

[0047]

Chem.

[0048] In some embodiments, R 2 is

[0049]

Chem.

[0050] In some embodiments, R 2 is

[0051]

Chem.

[0052] In some embodiments, R 2 is

[0053]

Chem.

[0054] In some embodiments, R 2 is

[0055]

Chem.

[0056] In some embodiments, R 2 is

[0057]

Chem.

[0058] In some embodiments, R 2 is

[0059]

Chem.

[0060]

Chem.

[0061] In some embodiments, the structure of this formula (I) is further represented by a formula selected from any one of the following compounds:

[0062]

Chem.

[0063] Some embodiments relate to a compound of formula (I), or a pharmaceutically acceptable salt thereof, where the structure of formula (I) is:

[0064] [ka] It is further represented by the structure selected from.

[0065] Some embodiments relate to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein this compound is

[0066] [ka] TIFF2026513524000038.tif236162TIFF2026513524000039.tif240163TIFF2026513524000040.tif167163 Selected from.

[0067] Some embodiments relate to methods for treating VNN1-mediated conditions, the method comprising administering the compounds disclosed herein to a subject in need of treatment. Some embodiments relate to methods for inhibiting the enzymatic activity of vascular non-inflammatory molecule enzymes. In some embodiments, the method relates to inhibiting the enzymatic activity of vascular non-inflammatory molecule 1 (vanin 1) enzymes. In some embodiments, the method comprises administering the compounds disclosed herein to a patient in need of treatment, thereby treating the patient. In some embodiments, the method comprises administering an effective amount of the compounds disclosed herein to a patient in need of treatment. In some embodiments, in response to the presence of inflammatory and autoimmune diseases detected in a sample derived from the subject, the subject is administered an effective amount of the compound, thereby treating the inflammatory and autoimmune diseases of the subject. In some embodiments, the subject suffers from an autoimmune or inflammatory disease. In some embodiments, the subject suffers from a certain type of cancer. In some embodiments, the semi-maximal inhibitory concentration (IC) of the compounds disclosed herein is 50 The semi-maximal inhibitory concentration (IC) of the compound disclosed herein is less than approximately 5 μM. In some embodiments, the semi-maximal inhibitory concentration (IC) of the compound disclosed herein is less than approximately 5 μM. 50 The concentration is approximately less than 1 μM.

[0068] Some embodiments relate to methods for producing the compounds disclosed herein, which include functionalizing a bicyclic compound starting material with one or more substituents. Some embodiments relate to using the compounds disclosed herein to prepare therapeutic agents for treating autoimmune diseases, inflammatory diseases, or certain types of cancer. Some embodiments relate to using the compounds disclosed herein to treat autoimmune diseases, inflammatory diseases, or certain types of cancer. [Modes for carrying out the invention]

[0069] Detailed explanation In some embodiments disclosed herein, compounds useful for inhibiting the activity of vanin 1 in a subject are provided. In some embodiments, methods for treating diseases using these compounds or pharmaceutical compositions containing these compounds are also provided. In some embodiments, the compound is a bicyclic compound. In some embodiments, the bicyclic compound comprises at least one aromatic ring. In some embodiments, multiple functional groups are bonded to at least one aromatic ring. In some embodiments, the bicyclic compound comprises at least one aromatic ring substituted with at least one amine group. Some embodiments consist of, or are essentially derived from, the bicyclic compound of formula (I) (or any other structure disclosed herein), its pharmaceutically acceptable salts, enantiomers, methods for preparation, and / or methods for using it in the treatment of disease conditions mediated by VNN1.

[0070] The following descriptions are for context and examples only, and should not be construed as limiting the scope of the invention as contained in the claims following this specification or in any other application claiming priority to this specification. No single component or set of components is essential or indispensable. Any feature, structure, component, material, step, or method described and / or illustrated in any embodiment of this specification may be used together with or in place of any feature, structure, component, material, step, or method described and / or illustrated in any other embodiment of this specification.

[0071] definition Unless otherwise specified, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art of the field 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.

[0072] A “prodrug” refers to a drug that is converted to a parent drug in vivo. Prodrugs are often useful because, under certain circumstances, they may be easier to administer than the parent drug. For example, prodrugs may be bioavailable via oral administration where the parent drug is not. Prodrugs may also have better solubility in pharmaceutical compositions than the parent drug. Examples of prodrugs include, but are not limited to, compounds administered as esters ("prodrugs") to facilitate translocation across cell membranes where water solubility is detrimental to mobility, and then metabolically hydrolyzed to the active entity, a carboxylic acid, once inside the cell where water solubility is beneficial. Further examples of prodrugs include short peptides (polyamino acids) bound to acidic groups, where the peptide is metabolized to expose the active site. Conventional procedures for selecting and preparing 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.

[0073] The term “prodrug ester” refers to a derivative of the compounds disclosed herein formed by the addition of one of several esterifying groups that are hydrolyzed under physiological conditions. Examples of prodrug ester groups include pivoyloxymethyl, acetoxymethyl, phthalidyl, indanyl, and methoxymethyl, as well as other such groups known in the art, including the (5-R-2-oxo-1,3-dioxolene-4-yl)methyl group. Other examples of prodrug ester groups can be found, for example, in T. Higuchi and V. Stella, “Pro-drugs as Novel Delivery Systems,” Vol. 14, ACS Symposium Series, American Chemical Society (1975), and in “Bioreversible Carriers in Drug Design: Theory and Application,” edited by E.B. Roche, Pergamon Press: New York, pp. 14-21 (1987) (which presents examples of esters useful as prodrugs of compounds containing carboxyl groups). Each of the aforementioned references is incorporated herein by reference in its entirety.

[0074] The “metabolites” of the compounds disclosed herein include active species that are produced when the compounds are introduced into a biological environment.

[0075] A “solvate” refers to a compound formed by the interaction of a solvent with a compound, its metabolite, or a salt described herein. A suitable solvate is a pharmaceutically acceptable solvate, including a hydrate.

[0076] The term "pharmaceutically acceptable salt" refers to a salt of a compound that retains the biological efficacy and properties of the compound, which are desirable for use in pharmaceuticals, both biologically and otherwise. In many cases, the compounds herein can form acidic and / or basic salts due to the presence of an amino group and / or a carboxyl group or similar group. Pharmaceutically acceptable acid addition salts can be formed using inorganic and organic acids. Inorganic acids that can derivate salts include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, and phosphoric acid. Organic acids that can derivate salts include, for example, 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 using inorganic and organic bases. Inorganic bases that can derive salts include, for example, sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, and aluminum, with ammonium, potassium, sodium, calcium, and magnesium salts being particularly preferred. Organic bases that can derive salts include, for example, primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines, and basic ion exchange resins, particularly including, for example, isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, and ethanolamine. Many such salts are known in the art, as described in Johnston et al. WO87 / 05297, published September 11, 1987 (the whole of which is incorporated herein by reference).

[0077] When referring to numerical values, the phrase "or a range including and / or spanning the aforementioned values" (and its variations) means including any range including or spanning the aforementioned values. For example, if a reaction temperature is expressed as "20°C, 30°C, 40°C, 50°C, or a range including and / or spanning the aforementioned values," this includes the specific temperature given, or a temperature range spanning 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.

[0078] When used in this specification, "C a ~C b "C1-C4 alkyl" (where "a" and "b" are integers) 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. That is, an alkyl, alkenyl, alkynyl, cycloalkyl ring, cycloalkenyl ring, cycloalkynyl ring, aryl ring, or heteroaryl ring can contain "a" to "b" carbon atoms, including both ends. Therefore, for example, a "C1-C4 alkyl" group refers to 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, or 6). For alkyl, alkenyl, alkynyl, and cycloalkyl groups, if "a" and "b" are not specified, the range described in those definitions is included (including the broadest range).

[0079] As used herein, "alkyl" refers to a fully saturated (i.e., containing no double or triple bonds), straight-chain or branched hydrocarbon chain. The alkyl moiety may be branched or straight-chain. Examples of branched alkyl groups include, but are not limited to, iso-propyl, sec-butyl, t-butyl, etc. Examples of straight-chain alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl, etc. An alkyl group can have from 1 to 20 carbon atoms (as disclosed in another part of this specification, whenever an alkyl group appears in this specification, a numerical range such as "1 to 20" refers to each integer within the given range; for example, "1 to 20 carbon atoms" means that the alkyl group can 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, but the definition of the present invention also encompasses the appearance of the term "alkyl" where no numerical range is specified). The "alkyl" group may also be an intermediate-sized alkyl having from 1 to 12 carbon atoms. The "alkyl" group may also be a lower alkyl having from 1 to 6 carbon atoms. The alkyl group of a compound can also be designated as "C 1~6 alkyl" or a similar name. By way of mere example, "C 1~4"Alkyl" indicates that the alkyl chain contains 1 to 4 carbon atoms, i.e., the alkyl chain is selected from the group consisting of methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, and t-butyl. As just an example, "C1-C5 alkyl" indicates that the alkyl chain contains 1 to 5 carbon atoms, i.e., 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, tertiary butyl, pentyl, hexyl, etc. Alkyl groups may be substituted or unsubstituted.

[0080] As used herein, “alkenyl” refers to an alkyl group containing one or more double bonds in a linear or branched hydrocarbon chain. As defined in the definition of “alkyl,” the alkenyl group may be unsubstituted or substituted.

[0081] As used herein, "alkynyl" refers to an alkyl group containing one or more triple bonds in a linear or branched hydrocarbon chain. As defined in the definition of "alkyl," the alkynyl group may be unsubstituted or substituted.

[0082] As used herein, 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,

[0083] [ka] Then, a certain number of carbon atoms follow, and there is * This can be expressed by the following:

[0084] [ka] represents ethylene. An alkylene group can have 1 to 20 carbon atoms (wherever it appears 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 can consist of 1 carbon atom, 2 carbon atoms, 3 carbon atoms, etc., up to 20 carbon atoms, but the definition of this invention also covers appearances of the term "alkylene" where no numerical range is specified). An alkylene group may also be an intermediate-sized alkyl having 1 to 12 carbon atoms. An alkylene group may also be a lower alkyl having 1 to 6 carbon atoms. For example, a lower alkylene group can be formed by replacing one or more hydrogen atoms with a lower alkylene group and / or both hydrogen atoms on the same carbon with C 3~6 Monocyclic cycloalkyl groups (for example,

[0085] [ka] Substitution can be made by substitution with ). Furthermore, certain radical naming conventions should be understood to include either monoradicals or diradicals depending on the context. For example, if a substituent requires two bonding sites to the rest of the molecule, that substituent is understood to be a diradical. For example, substituents identified as alkyl requiring two bonding sites include diradicals such as -CH2-, -CH2CH2-, and -CH2CH(CH3)CH2-. Other radical naming conventions clearly indicate that the radical is a diradical such as "alkylene" or "alkenylene". The alkylene group may be substituted or unsubstituted.

[0086] As used herein, the term "halogen" or "halo" means any one of the radiostable atoms in the seventh column of the periodic table, for example, fluorine (-F), chlorine (-Cl), bromine (-Br), or iodine (-I).

[0087] As used herein, “haloalkyl” refers to 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 may be considered equivalent to any one of the above examples in light of the usual art and the teachings provided herein. Haloalkyl groups may be of intermediate size or lower haloalkyl groups. Haloalkyl groups may be substituted or unsubstituted.

[0088] As used herein, “alkoxy” includes, but is not limited to, “C” of the formula -OR (where R is alkyl as previously defined), such as methoxy, ethoxy, n-propoxy, 1-methylethoxy (isopropoxy), n-butoxy, iso-butoxy, sec-butoxy, and tert-butoxy. 1~9 This refers to "alkoxy." The alkoxy group may or may not be substituted.

[0089] As used herein, "polyethylene glycol" is defined as formula

[0090] [ka] The term refers to a repeating unit, where n is an integer greater than 1 and R is hydrogen or alkyl. The number of repeating units "n" can be indicated by referring to the member number. For example, "2-5 member polyethylene glycol" refers to a repeating unit where n is an integer selected from 2 to 5. In some embodiments, R is selected from methoxy, ethoxy, n-propoxy, 1-methylethoxy (isopropoxy), n-butoxy, iso-butoxy, sec-butoxy, and tert-butoxy.

[0091] As used herein, “heteroalkyl” refers to a linear or branched hydrocarbon chain (e.g., alkyl) containing one or more heteroatoms. Heteroatoms are given their plain and common meaning in organic chemistry and include, but are not limited to, elements other than carbon, such as nitrogen (e.g., aminos), oxygen (e.g., alkoxys, ethers, hydroxyls), sulfur, and halogens. A heteroalkyl group may have 1 to 20 carbon atoms, but the definition of this invention also covers occurrences of the term “heteroalkyl” without specifying a numerical range. A heteroalkyl group may also be an intermediate-sized heteroalkyl group having 1 to 12 carbon atoms. A heteroalkyl group may also be a lower heteroalkyl group having 1 to 6 carbon atoms. In various embodiments, a heteroalkyl group 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 can also be designated as "heteroalkyl" or a similar name. A heteroalkyl group may contain one or more heteroatoms. Just as an example, "C 1~4 The term "heteroalkyl" indicates that the heteroalkyl chain contains 1 to 4 carbon atoms, and in addition, one or more heteroatoms are present in the chain's backbone. Heteroalkyl groups may be substituted or unsubstituted.

[0092] The term "aromatic" refers to a ring or ring system having a conjugated π-electron system, including 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.

[0093] As used herein, “aryl” refers to an aromatic ring or ring system (i.e., two or more fused rings sharing two adjacent carbon atoms) whose ring skeleton contains only carbon atoms. If the aryl is a ring system, all rings in the system are aromatic. While an aryl group can have 6 to 18 carbon atoms, the definitions of this invention also cover occurrences of the term “aryl” where no numerical range is specified. In some embodiments, the aryl group has 6 to 10 carbon atoms. The aryl group is “C 6~10 "Aryl", "C6 or C 10 It can also be specified as "aryl" or a similar name. For example, an aryl group is C6~C 14 Aryl group, C6~C 10 The group may be an aryl group or a C6 aryl group. Examples of aryl groups include, but are not limited to, phenyl, naphthyl, azlenyl, and anthracenyl. The aryl group may be substituted or unsubstituted.

[0094] As used herein, "aryloxy" and "arylthio" refer to RO- and RS- (wherein R is aryl as previously defined), for example, "C 6~10 "aryloxy" or "C 6~10 This refers to, but is not limited to, "arylthio" groups, but phenyloxy groups are also included. The aryloxy or arylthio group may be substituted or unsubstituted.

[0095] "Aralkyl" or "arylalkyl" refers to an aryl group bonded as a substituent via an alkylene group, for example, "C 7~14 Examples include, but are not limited to, "aralkyl," benzyl, 2-phenylethyl, 3-phenylpropyl, and naphthylalkyl. In some examples, the alkylene group is a lower alkylene group (i.e., C 1~6 It is an alkylene group. The aralkyl or arylalkyl group may be substituted or unsubstituted.

[0096] As used herein, “heteroaryl” refers to an aromatic ring or ring system (i.e., two or more fused rings sharing two adjacent atoms) whose ring skeleton contains one or more heteroatoms, i.e., elements other than carbon, including but not limited to nitrogen, oxygen, and sulfur. If the heteroaryl is a ring system, all rings in the system may be aromatic. A heteroaryl group can have 5 to 18 ring members (i.e., the number of atoms constituting the ring skeleton, including carbon atoms and heteroatoms), but the definition of the present invention also covers occurrences of the term “heteroaryl” without specifying a numerical range. For example, a heteroaryl group may have 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 also be designated as a “5-7 membered heteroaryl,” a “5-10 membered heteroaryl,” or a similar name. In various embodiments, the heteroaryl contains 1 to 4 heteroatoms, 1 to 3 heteroatoms, 1 to 2 heteroatoms, or 1 heteroatom. For example, in various embodiments, the heteroaryl contains 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., furazanil), 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, benzothiazole (e.g., benzothiazolyl), imidazole (e.g., imidazolyl), benzimidazole (e.g., benzimidazolyl), indole (e.g., indolyl), isoindole (e.g., isoindolyl) Examples include, but are not limited to, indazole, pyrazole (e.g., pyrazolyl), benzopyrazole, isoxazole (e.g., isoxazolyl), benzoisoxazole, isothiazole (e.g., isothiazolyl), triazole (e.g., triazolyl), benzotriazole, thiadiazole (e.g., thiadiazolyl), tetrazole, pyridine (e.g., pyridinyl), pyridazine (e.g., pyridazinyl), pyrimidine (e.g., pyrimidinyl), pyrazine (e.g., pyrazinyl), purine, pteridine, quinoline (e.g., quinolinyl), isoquinoline (e.g., isoquinolinyl), quinazoline, quinoxaline, cinnoline, and triazine (e.g., triazinyl). Heteroaryl rings may also contain a bridgehead nitrogen atom. Examples include, but are not limited to, pyrazolo[1,5-a]pyridine, imidazo[1,2-a]pyridine, and pyrazolo[1,5-a]pyrimidine. The heteroaryl group may be substituted or unsubstituted.

[0097] A "heteroaralkyl" or "heteroarylalkyl" is a heteroaryl group bonded as a substituent via an alkylene group. Examples include, but are not limited to, 2-thienylmethyl, 3-thienylmethyl, furylmethyl, thienylethyl, pyrrolylalkyl, pyridylalkyl, isoxazolylalkyl, and imidazolylalkyl. The heteroaralkyl group may be substituted or unsubstituted.

[0098] As used herein, “carbocyclyl” means a non-aromatic cyclic ring or cyclic system containing only carbon atoms in its cyclic framework. When a carbocyclyl is a cyclic system, two or more rings may be linked to each other by condensation, bridging, or spirobonding. Carbocyclyls can have any degree of saturation, provided that at least one ring in the ring is non-aromatic. Thus, carbocyclyls include cycloalkyls, cycloalkenyls, and cycloalkynyls. A carbocyclyl group can have 3 to 20 carbon atoms, but the definition of this invention also covers occurrences of the term “carbocyclyl” where no numerical range is specified. A carbocyclyl group may also be an intermediate-sized carbocyclyl having 3 to 10 carbon atoms. A carbocyclyl group may also be a carbocyclyl having 3 to 6 carbon atoms. A carbocyclyl group is “C 3~6 It may also be designated as "carbocyrill" or a similar name. Examples of carbocyrill 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 carbocyrill group may be substituted or unsubstituted.

[0099] As used herein, “cycloalkyl” refers to a monocyclic or polycyclic hydrocarbon ring system that is completely saturated (without double or triple bonds). If it consists of two or more rings, those rings may be bonded to each other in a condensation. A cycloalkyl group may contain 3 to 10 atoms in a ring(s) or 3 to 8 atoms in a ring(s), or as described in other parts thereof. A cycloalkyl group may be unsubstituted or substituted. Typical cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl.

[0100] "(Carbocyclyl)alkyl" refers to a carbocyryl group bonded as a substituent via an alkylene group, for example, "C 4~10 Examples include (carbocycryl)alkyl groups, but are not limited to these. Examples include cyclopropylmethyl, cyclobutylmethyl, cyclopropylethyl, cyclopropylbutyl, cyclobutylethyl, cyclopropylisopropyl, cyclopentylmethyl, cyclopentylethyl, cyclohexylmethyl, cyclohexylethyl, and cycloheptylmethyl. In some examples, the alkylene group is a lower alkylene group.

[0101] As used herein, "cycloalkenyl" means a carbocyclyl ring or ring system having at least one double bond, where none of the rings in the ring system are aromatic. Cyclohexenyl is an example. A cycloalkenyl group may contain 4 to 10 atoms in the ring(s). The cycloalkenyl group may be substituted or unsubstituted.

[0102] As used herein, “heterocyclyl” or “heteroalicyclyl” refers to monocyclic, bicyclic, and tricyclic ring systems with up to 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, and 20 members, where carbon atoms constitute these ring systems together with 1 to 5 heteroatoms. Heterocyclic rings may contain one or more unsaturated bonds as they may be, but the arrangement of these unsaturated bonds prevents a completely delocalized π-electron system from forming across all rings. Heteroatoms may be present in either the non-aromatic or aromatic ring of the ring system. Heteroatoms may be elements other than carbon, but are not limited to oxygen, sulfur, and nitrogen. A heterocycle may further contain one or more carbonyl or thiocarbonyl functional groups, thereby allowing its definition to include oxo and thio types, such as lactams, lactones, cyclic imides, cyclic thioimides, and cyclic carbamates. If composed of two or more rings, these rings may be bonded to each other in a condensation. In addition, any nitrogen in a heteroalicyclic can be quaternized. The heterocyclyl group or heteroalicyclic group may be substituted or unsubstituted.Examples of such "heterocyclyl" or "heteroalicyl" groups include 1,3-dioxine, 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-thiaidine, 2H-1,2-oxazine, maleimide, succinimide, barbituric acid, thiobarbituric acid, dioxopiperazine, hydantoin, dihydrouracil, trioxane, hexahydro-1,3,5-triazine, imidazoline, imidazolidin, isoox Examples include, but are not limited to, sazolin, isoxazolidine, oxazoline, oxazolidine, oxazolidinone, thiazoline, thiazolidinone, morpholine, oxirane, piperidine N-oxide, piperidine, piperazine, pyrrolidine, pyrrolidone, pyrrolidione, 4-piperidone, pyrazoline, pyrazolidine, 2-oxopyrrolidine, tetrahydropyran, 4H-pyran, tetrahydrothiopyran, thiamorpholine, thiamorpholine sulfoxide, thiamorpholine sulfone, and their benzo-condensed analogs (e.g., benzimidazolidinone, tetrahydroquinoline, 3,4-methylenedioxyphenyl). The heterocyclyl group may also be an intermediate-sized heterocyclyl having 3 to 10 ring members. The heterocyclyl group may also be a heterocyclyl having 3 to 6 ring members. A heterocyclyl group may be designated as a "3- to 6-membered heterocyclyl" or a similar name. The heterocyclyl group may be substituted or unsubstituted.

[0103] In various embodiments, the heterocyclil contains 1 to 4 heteroatoms, 1 to 3 heteroatoms, 1 to 2 heteroatoms, or 1 heteroatom. For example, in various embodiments, the heterocyclil contains 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 6-membered monocyclic heterocyclil, the heteroatom(s) are selected from 1 to 3 O, N, or S atoms, and in a preferred 5-membered monocyclic heterocyclil, the heteroatom(s) are selected from 1 or 2 heteroatoms selected from O, N, or S atoms. Examples of heterocyclyl rings include azepinyl, acridinyl, carbazolyl, cinnolinyl, 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, 1,4-oxathianyl, 2H-1,2-oxazinyl, trioxanil, hexa Examples include, but are not limited to, hydro-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-).

[0104] "(heterocyclyl)alkyl" refers to a heterocyclyl group bonded as a substituent via an alkylene group. Examples include, but are not limited to, imidazolinylmethyl and indolinylethyl.

[0105] "(heterocyclyl)alkynyl" is a heterocyclyl group that is bonded as a substituent via an alkynylene group.

[0106] As used herein, “acyl” refers to -C(=O)R, where R is hydrogen, C as defined herein. 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~7 These include carbocyclyls, aryls, 5- to 10-membered heteroaryls, and 5- to 10-membered heterocyclyls. Non-limiting examples include formyl, acetyl, propanoyl, benzoyl, and acrylic. The acyl group may be substituted or unsubstituted.

[0107] The "O-carboxyl" group refers to the "-OC(=O)R" group, where R is hydrogen and C as defined herein. 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~7 The compounds are selected from carbocyclyls, aryls, 5-10 membered heteroaryls, and 5-10 membered heterocyclyls. The O-carboxyl group may be substituted or unsubstituted.

[0108] The "C-carboxyl" group (or "ester") refers to the "-C(=O)OR" group, where R is hydrogen, -NH2, C as defined herein. 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~7The compounds are selected from carbocyclyls, aryls, 5- to 10-membered heteroaryls, and 5- to 10-membered heterocyclyls. A non-restrictive example is carboxyl (i.e., -C(=O)OH). The C-carboxyl may be substituted or unsubstituted.

[0109] As used herein, the term "hydroxy" refers to the -OH group.

[0110] The "cyano" group refers to the "-CN" group.

[0111] The "cyanate" group refers to the "-OCN" group.

[0112] The "isocyanate" group refers to the "-NCO" group.

[0113] The "thiocyanate" group refers to the "-SCN" group.

[0114] The "isothiocyanate" group refers to the "-NCS" group.

[0115] 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 groups, 5-10 membered heteroaryl groups, and 5-10 membered heterocyclines. The sulfinyl group may be substituted or unsubstituted.

[0116] 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 sulfonyl group is selected from aryl groups, 5-10 membered heteroaryl groups, and 5-10 membered heterocyclyl groups. The sulfonyl group can be provided in the form of a heterocyclyl ring. The sulfonyl group may be substituted or unsubstituted.

[0117] The "S-sulfonamide" group is "-SO2NR A R B This refers to the base, where R A and R B Each is independently defined as hydrogen, C as defined herein. 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~7 Carbocyclyl, C 6~10 Selected from aryls, 5-10 membered heteroaryls, and 5-10 membered heterocyclines. A and R B These can combine to form a heteroaryl or heterocyclic ring. The S-sulfonamide may be substituted or unsubstituted.

[0118] The "N-sulfonamide" group is "-N(R A )SO2R B This refers to the base, where R A and R B Each is independently defined as hydrogen, C as defined herein. 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~7 Carbocyclyl, C 6~10 The N-sulfonamide is selected from aryls, 5-10 membered heteroaryls, and 5-10 membered heterocyclines. The N-sulfonamide may be substituted or unsubstituted.

[0119] The "O-carbamyl" group is "-OC(=O)NR" A R B This refers to the base, where R A and R B Each is independently defined as hydrogen, C as defined herein. 1~6 Alkyl, C 2~6Alkenil, C 2~6 Alkinyl, C 3~7 Carbocyclyl, C 6~10 Selected from aryls, 5-10 membered heteroaryls, and 5-10 membered heterocyclines. A and R B These can combine to form a heteroaryl or heterocycle. The O-carbamyl may be substituted or unsubstituted.

[0120] The "N-carbamyl" group is "-N(R A )OC(=O)R B This refers to the base, where R A and R B Each is independently defined as hydrogen, C as defined herein. 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~7 Carbocyclyl, C 6~10 The N-carbamyl group is selected from aryl groups, 5-10 membered heteroaryl groups, and 5-10 membered heterocyclines. The N-carbamyl group may be substituted or unsubstituted.

[0121] The "O-thiocarbamyl" group is "-OC(=S)NR" A R B This refers to the base, where R A and R B Each is independently defined as hydrogen, C as defined herein. 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~7 Carbocyclyl, C 6~10 Selected from aryls, 5-10 membered heteroaryls, and 5-10 membered heterocyclines. A and R B These can combine to form a heteroaryl or heterocyclic ring. The O-thiocarbamyl may be substituted or unsubstituted.

[0122] The "N-thiocarbamyl" group is "-N(R A )OC(=S)R BThis refers to the base, where R A and R B Each is independently defined as hydrogen, C as defined herein. 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~7 Carbocyclyl, C 6~10 The N-thiocarbamyl group is selected from aryl groups, 5-10 membered heteroaryl groups, and 5-10 membered heterocyclyl groups. The N-thiocarbamyl group may be substituted or unsubstituted.

[0123] The "C-amide" group is "-C(=O)NR A R B This refers to the base, where R A and R B Each is independently defined as hydrogen, C as defined herein. 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~7 Carbocyclyl, C 6~10 Selected from aryls, 5-10 membered heteroaryls, and 5-10 membered heterocyclines. A and R B These can combine to form a heteroaryl or heterocyclic ring. The C-amide may be substituted or unsubstituted.

[0124] The "N-amide" group is "-N(R A )C(=O)R B This refers to the base, where R A and R B Each is independently defined as hydrogen, C as defined herein. 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~7 Carbocyclyl, C 6~10 Selected from aryls, 5-10 membered heteroaryls, and 5-10 membered heterocyclines. A and R B These can combine to form a heteroaryl or heterocyclic ring. The N-amide may be substituted or unsubstituted.

[0125] The "carbamide" or "carbamide" group refers to "(RARB)NC(=O)N(RC)", where RA, RB, and RC are independently hydrogen, alkyl, alkenyl, alkynyl, carbocykyl, aryl, heteroaryl, heterocyclyl, aralkyl, or heterocyclyl(alkyl) as defined herein. The carbamide may be substituted or unsubstituted.

[0126] The "amino" group is "-NR A R B This refers to the base, where R A and R B Each is independently defined as hydrogen, C as defined herein. 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~7 Carbocyclyl, C 6~10 Selected from aryls, 5-10 membered heteroaryls, and 5-10 membered heterocyclines. A and R B These can combine to form a heteroaryl or heterocyclic compound. The amino may be substituted or unsubstituted.

[0127] The "Alkamino" group is "-NR A R B This refers to the base, where R A is alkyl, R B Independently, as defined herein, hydrogen, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~7 Carbocyclyl, C 6~10 The algorithm is selected from aryl groups, 5-10 membered heteroaryl groups, and 5-10 membered heterocyclines. The alcamino may be substituted or unsubstituted.

[0128] The "aminoalkyl" group refers to an amino group bonded via an alkylene group. The aminoalkyl group may or may not be substituted.

[0129] The "alkoxyalkyl" group is an alkoxy group bonded via an alkylene group, for example, "C 2~8 This refers to "alkoxyalkyl" compounds, etc. The alkoxyalkyl compound may be substituted or unsubstituted.

[0130] As used herein, a substituted group is derived from an unsubstituted parent group, where one or more hydrogen atoms are replaced by another atom or group. Unless otherwise specified, when a group is considered "substituted", it is a C1-C6 alkyl (substituted as necessary with -OH or C-carboxy), C1-C6 alkenyl, C1-C6 alkynyl, C1-C6 heteroalkyl, C3-C7 carbocyrill (substituted as necessary with halo, -OH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), C3-C7-carbocyrill-C1-C6-alkyl (halo, C1-C6 5-10 member heterocyclyl (substituted as necessary with alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), 5-10 member heterocyclyl-C1-C6-alkyl (substituted as necessary 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 (substituted as necessary with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy) substituted as needed with aryl(halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), aryl(C1-C6)alkyl(halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), 5-10 member heteroaryl(halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy) (substituted with xy as needed), 5-10 member heteroaryl(C1-C6)alkyl (substituted with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy as needed), 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),This means that the molecule is substituted with one or more substituents independently selected from halo(C1-C6)alkoxy (e.g., -OCF3), C1-C6 alkylthio, arylthio, amino, amino(C1-C6)alkyl, monosubstituted amine groups, disubstituted amine groups, monosubstituted amine (alkyl), disubstituted amine (alkyl), nitro, thiocarbonyl, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C-amide, N-amide, S-sulfonamide, N-sulfonamide, C-carboxy, O-carboxy, acyl, cyanate, isocyanate, thiocyanate, isothiocyanate, sulfenyl, sulfinyl, sulfonyl, -O-NH2, oxo(=O), diamino group, polyamino, diether group, and polyether (e.g., diethylene glycol, triethylene glycol, oligoethylene glycol, polyethylene glycol, etc.). Whenever a group is described as “substituted as necessary” (or other similar wording), or as containing one or more “substituted as necessary,” that group may or may not be substituted with the aforementioned substituents.

[0131] In some embodiments, the substituted group(s) are substituted with one or more substituents individually and independently selected from C1-C4 alkyl, amino, hydroxy, and halogen groups.

[0132] The two substituents, together with the one or more atoms to which they are bonded, can form a spiro or a fused ring with the rest of the compound.

[0133] As used herein, any "R" group(s), for example, but not limited to these, 1 , R 2 , R 3Etc. represents substituents that can be bonded to the specified atom. The R group may be substituted or unsubstituted. When two "R" groups are described as "together" (or similar wording), the R groups and the atom to which they are bonded can form a cycloalkyl, aryl, heteroaryl, or heterocycle. When two R groups are described as "together with the atom to which they are bonded" forming a ring (e.g., a carbocykrill, heterocyclyl, aryl, or heteroaryl ring), it means that the collective unit of that atom and the two R groups is the described ring. Otherwise, the ring is not limited by the definition of each R group as it would be if considered individually. For example, the following substructures exist:

[0134] [ka]

[0135] R 1 and R 2 However, it is defined as being selected from the group consisting of hydrogen and alkyl, or R 1 and R 2 However, when they combine with the nitrogen to which they are bound, R 1 and R 2 This means that it can be selected from hydrogen or alkyl, or alternatively, this substructure has the following structure:

[0136] [ka]

[0137] Here, ring A is a heterocyclyl ring containing the nitrogen shown in the illustration. Further examples, though not limited to, include NR 1a R 1b Base R 1a and R 1b When it is specified that they "join together," it means that they are covalently bonded to each other, forming a ring.

[0138] [ka]

[0139] The cyclic structure can be represented using the following structures (or similar structures having different ring sizes, heteroatoms, etc.).

[0140] [ka] When a cyclic structure is shown using this type of structure, it means that the R group can be bonded to any position in the ring by replacing the -H with -R. For example, the following ring:

[0141] [ka] It includes any of the following ring structures:

[0142] [ka] Here,

[0143] [ka] The symbol indicates a connection with the rest of the structure. Similarly, in the following structure...

[0144] [ka] During the ceremony, ``

[0145] [ka] The symbol indicates a connection with the rest of the structure, and if n is between 1 and 5, one of the following structures or other variations thereof (as readily understood by those skilled in the art) is assumed.

[0146] [ka]

[0147] When it is stated that two "adjacent" R groups form a ring "together with the atom to which they are bonded," it means that the atom, the intervening bond, and the collective unit of the two R groups are the described ring. For example, the following substructure exists:

[0148] [ka] R 1 and R 2 However, it is defined as being selected from the group consisting of hydrogen and alkyl, or R 1 and R 2 However, if they combine with the atoms they are bonded to to form an aryl or carbocykrine, R 1 and R 2 This means that it can be selected from hydrogen or alkyl, or alternatively, that this substructure has the following structure:

[0149] [ka] Here, A is a carbocyclyl containing an aryl ring or the illustrated double bond.

[0150] Whenever a substituent is illustrated as a diradical (i.e., having two bonding points to the rest of the molecule), it should be understood that, unless otherwise specified, the substituent may be bonded in any orientation. For example, -AE- or

[0151] [ka] The substituents shown include substituents oriented such that "A" is bonded at the leftmost bond point of the molecule, and substituents where "A" is bonded at the rightmost bond point of the molecule.

[0152] As stated in the definition of alkylene, certain radical naming conventions should be understood to include either monoradicals or diradicals depending on the context. For example, a substituent (e.g., in the genus structure) is understood to be a diradical if it requires two bonding sites to the rest of the molecule. For example, substituents identified as aminoalkyls that require two bonding sites include diradicals such as -NHCH2-, -NHCH2CH2-, and -NHCH2CH(CH3)CH2-. Other examples of substituents that may require two bonding sites include alkoxys, aryls, heteroaryls, carbocykrills, and heterocyclyls.

[0153] As used herein, a radical refers to a species that possesses a single unpaired electron, enabling the species containing the radical to covalently bond with another species. Therefore, in this context, a radical is not necessarily a free radical; rather, a radical refers to a specific part of a larger molecule.

[0154] In any compound described herein having one or more chiral centers, unless the absolute stereochemistry is explicitly specified, each center is understood to be independently R-configuration, S-configuration, or a mixture thereof. Therefore, the compounds provided herein may be enantiomerically pure, enantiomerically enriched, racemic, diastereomerically pure, diastereomerically enriched, or a mixture of stereoisomers. In addition, in any compound described herein having one or more double bonds that produce geometric isomers that can be defined as E or Z, each double bond is understood to be independently E or Z, or a mixture thereof. In any compound described herein having one or more chiral centers, all possible diastereomers are also assumed. In any compound described herein, all tautomers are assumed. Furthermore, in any compound described herein, all isotopes of the atoms contained are assumed. For example, hydrogen may in any case contain hydrogen-1 (protium), hydrogen-2 (deuterium), hydrogen-3 (tritium), or other isotopes; carbon may in any case contain carbon-12, carbon-13, carbon-14, or other isotopes; oxygen may in any case contain oxygen-16, oxygen-17, oxygen-18, or other isotopes; fluorine may in any case contain fluorine-18, fluorine-19, or one or more other isotopes; and sulfur may in any case contain sulfur-32, sulfur-34, sulfur-35, sulfur-36, or one or more other isotopes.

[0155] As used herein, the term “inhibitor” means any compound, molecule, or composition that inhibits or reduces the activity of a target biomolecule. Inhibition can be achieved, for example, by blocking the phosphorylation of the target (e.g., by competing with adenosine triphosphate (ATP), the entity responsible for phosphorylation), by binding to a site outside the active site and influencing its activity through conformational changes, or by depriving kinases of the means to access molecular chaperone systems that rely on their intracellular stability, resulting in their ubiquitination and degradation.

[0156] As used herein, the term "vanin 1" is given its common meaning in the art and refers to an enzyme having pantetheinase activity that catalyzes the hydrolysis of pantetheine to pantothenic acid and cysteamine. Vanin 1 is part of the large vanin family, consisting of three human (VNN1, VNN2, and VNN3) and two mouse (Vnn1 and Vnn3) orthologue genes. Vanin functions in inflammation, oxidative stress, and cell migration, which are mediated by vanin-dependent cysteamine production.

[0157] As used herein, “subject,” “host,” “patient,” and “individual” are used interchangeably and given their usual meanings, and refer to organisms possessing the VNN1 protein. This includes mammals, such as humans, non-human primates, ungulates, dogs, cats, horses, mice, rats, etc. The term “mammal” includes both human and non-human mammals.

[0158] When used herein, “diagnosis” shall be given its ordinary meaning and shall include determining the subject’s susceptibility to a disease or disorder, determining whether the subject is currently affected by a disease or disorder, determining the prognosis of a subject affected by a disease or disorder (e.g., identifying cancer or a cancerous state, the stage of cancer, or the response of cancer to treatment), and using theametrics (e.g., monitoring the subject’s condition to provide information regarding the effectiveness or efficacy of treatment).

[0159] The terms “sample” or “biological sample” shall be given their usual meaning and shall encompass a variety of sample types obtained from living organisms that can be used in imaging, diagnostic, prognostic, or monitoring assays. This term includes blood, as well as other liquid samples of biological origin, solid tissue samples, such as biopsy specimens or tissue cultures, or cells and their progeny derived therefrom. This term includes samples that have been manipulated in any way after their procurement, for example, by treatment with reagents, solubilization, or concentration of certain components. This term encompasses clinical samples and also includes cells in cell cultures, cell supernatants, cell lysates, serum, plasma, biological fluids, and tissue samples.

[0160] As used herein, “natural amino acid side chain” refers to the side chain substituents of naturally occurring amino acids. Naturally occurring amino acids have substituents bonded to the α-carbon. Naturally occurring 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.

[0161] As used herein, "unnatural amino acid side chain" refers to a side chain substituent of an amino acid that does not exist in nature. Unnatural amino acids include β-amino acids (β 3 and β 2This includes homo-amino acids, proline and pyruvate derivatives, trisubstituted alanine derivatives, glycine derivatives, ring-substituted phenylalanine and tyrosine derivatives, linear core amino acids, and N-methyl amino acids. A non-limiting list of unnatural amino acids is available from Sigma-Aldridge's “Unnatural Amino Acids and Derivatives.” See also Travis S. Young and Peter G. Schultz, “Beyond the Canonical 20 Amino Acids: Expanding the Genetic Lexicon,” J. Biol. Chem., 2010;285:11039–11044, which is incorporated in its entirety by reference.

[0162] The terms “drug” or “test drug” include any substance, molecule, element, compound, entity, or combination thereof. These terms include, but are not limited to, proteins, polypeptides, peptides or mimetic drugs, small organic molecules, polysaccharides, polynucleotides, etc. These terms may also include natural products, synthetic compounds or chemical compounds, or combinations of two or more substances. Unless otherwise specified, the terms “drug,” “substance,” and “compound” are used interchangeably herein.

[0163] The term "analog" is used herein to refer to a molecule that is structurally similar to a reference molecule but has been modified in a targeted and controlled manner by replacing specific substituents of the reference molecule with alternative substituents. Those skilled in the art can expect that the analog will exhibit the same, similar, or improved utility compared to the reference molecule. The synthesis and screening of analogs to identify variants of known compounds having improved characteristics (e.g., higher binding affinity to a target molecule) is a well-known technique in pharmaceutical chemistry.

[0164] While the “patient” or “subject” treated as disclosed herein is a human patient in some embodiments, the principles of the subject matter of this disclosure should be understood to indicate that the subject matter of this disclosure is valid for all vertebrate species, including mammals, that are intended to be included in the terms “subject” and “patient.” Appropriate subjects are generally mammalian subjects. The subject matter described herein is for use in research, as well as in veterinary and medical applications. The term “mammal” is used in its ordinary biological sense. Thus, this term includes, but is not limited to, primates, including monkeys (chimpanzees, apes, monkeys) and humans, cattle, horses, sheep, goats, pigs, rabbits, dogs, cats, rats and mice, as well as many other species.

[0165] The terms “pharmaceutically acceptable carrier” or “pharmaceutically acceptable excipient” include all kinds of solvents, dispersions, coatings, antimicrobial and antifungal agents, isotonic agents, and absorption retarders, etc. The use of such media and agents for pharmaceutically active substances is well known in the art. Unless any conventional media or agent is incompatible with the active ingredient, its use in a therapeutic composition is intended. In addition, various adjuvants, such as those commonly used in the art, may be included. Considerations for incorporating various components into a pharmaceutical composition are, for example, found in Gilman et al. (eds.) (1990), “Goodman and Gilman's: The Pharmacological Basis of Therapeutics,” 8th edition, Pergamon Press, which is incorporated herein by reference in its entirety.

[0166] "Effective dose" or "therapeutably effective dose," as used herein, means an amount of therapeutic agent that is effective in alleviating, to some extent, one or more of the symptoms of a disease or condition, or reducing the likelihood of such symptoms occurring, and including curing the disease or condition. "Curing" means that the symptoms of the disease or condition are eliminated, but effects may persist for a certain period of time or permanently after the cure has occurred (e.g., extensive tissue damage).

[0167] "To treat," "to treat," or "to treat" as used herein refers to administering a pharmaceutical composition for prophylactic and / or therapeutic purposes. The term "prophylactic treatment" refers to treating a subject who is not yet showing symptoms of a disease or condition but is susceptible to or otherwise at risk of developing a particular disease or condition, thereby reducing the likelihood that the patient will develop the disease or condition. The term "therapeutic treatment" refers to administering treatment to a subject.

[0168] As used herein, the term "weight percentage" refers to the weight of a component divided by the weight of the composition containing that component, multiplied by 100%. For example, if 5 grams of component A are added to 95 grams of component B, the weight percentage of component A is 5% (e.g., 5gA / (5gA+95gB)×100%).

[0169] The term “control” shall be given its usual meaning and shall include any sample or standard used for comparison with the sample being studied, processed, characterized, and analyzed. 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 historical control or a reference value or range of values ​​for a standard. In some embodiments, the control is a comparison with a wild-type VNN1 configuration or scenario.

[0170] The terms and phrases used in this application, and their variations thereof, should be interpreted as open-ended and not limiting unless otherwise explicitly stated, particularly in the appended claims. As such, the term “including” should be read as “including, without limitation,” “including but not limited to,” etc.; the term “comprising” as used herein is synonymous with “including,” “containing,” or “characterized by,” and is comprehensive or open-ended, not excluding further elements or method steps not described; the term “having” should be interpreted as “having at least”; and the term “includes” should be interpreted as “includes but is not limited to.” The term “example” is used to provide non-limiting examples of the item being discussed, rather than an exhaustive or limiting list of that item. The use of terms such as “preferred,” “desired,” “desired,” or “coveted,” and similar terms, should not be understood as implying that a particular feature is extremely important, essential, or even important to the structure or function of the present invention, but rather is intended simply to highlight alternative or further features that may or may not be utilized in particular embodiments of the present invention. In addition, the term “comprising” should be interpreted as synonymous with the phrase “having at least” or “including at least.” When used in the context of a method, “comprising” means that the method includes at least the steps described, but may include further steps.When used in the context of a compound, composition, or device, the term "comprising" means that the compound, composition, or device contains at least the listed features or components, but may also contain additional features or components. Similarly, a group of items related by the conjunction "and" should not be read as requiring each of those items to be present in the group, but rather as "and / or" unless otherwise explicitly stated. Likewise, a group of items related by the conjunction "or" should not be read as requiring mutual exclusivity among the items in the group, but rather as "and / or" unless otherwise explicitly stated.

[0171] Furthermore, it should be understood that the phrase "consisting essentially of" includes these elements specifically mentioned, as well as any further elements that do not substantially affect the fundamental and novel features of the claimed technology. The phrase "consisting of" excludes any unspecified elements.

[0172] With regard to substantially any use of plural and / or singular terms in this specification, a person skilled in the art can translate from plural to singular and / or singular to plural where appropriate to the context and / or application. For clarity, various singular / plural substitutions may be explicitly stated herein. The indefinite article “a” or “an” does not exclude the plural. A single processor or other unit may perform the functions of several items described in the claims. The mere fact that a particular strategy is described in different dependent claims does not indicate that a combination of these strategies cannot be used advantageously. No reference symbol in the claims should be construed as limiting its scope.

[0173] 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 a different heading (e.g., Method of Treatment).

[0174] Introduction The enzymatic activity of vanin-1 is associated with several inflammatory diseases, including ulcerative colitis, Crohn's disease, lupus, atherosclerosis, type 1 diabetes, atopic dermatitis, and psoriasis. Various small molecule inhibitors have been developed to modulate and / or inhibit vanin-1 activity. Small molecule inhibitors of the vascular non-inflammatory molecule 1 (vanin-1) enzyme have been used to treat inflammatory and autoimmune diseases. However, despite the existence of various vanin-1 inhibitors, there remains a demand for selective inhibitors that offer one or more advantages over current compounds and are used to treat diseases. Such advantages include improved activity and / or efficacy; a beneficial target selectivity profile tailored to each therapeutic objective; improved side effect profiles (such as reduced undesirable side effects or reduced side effect intensity); improved targeting of mutant receptors in diseased cells; improved physicochemical properties (such as solubility / stability in water, body fluids, and / or pharmaceutical formulations); improved pharmacokinetic properties (e.g., enabling reduced dosage or simpler administration); and ease of manufacture of the active pharmaceutical ingredient (e.g., by shortening the synthesis process) or ease of purification. Some embodiments disclosed herein relate to compounds that provide one or more of these (or other) advantages. Some embodiments disclosed herein relate to compounds that address one or more drawbacks of known active pharmaceutical ingredients.

[0175] Compound of formula (I) Some embodiments relate to bicyclic compounds. In some embodiments, the carboxypyrrole is a compound (or a pharmaceutically acceptable salt thereof) having the structure of formula (I).

[0176] [ka]

[0177] In some embodiments, A, B, U, V, W, X, Y, and Z are independently C, C(R 5 -R 3 ), N, N(R 5 -R 4 ), S, and S(R 5 -R 4 Selected from the group consisting of ), at least one of the examples of A, B, U, V, W, X, Y, and Z is N, N(R 5 -R 4 ), S, or S(R 5 -R 4 ) and the remaining variables are C or C(R 5 -R 3 ) is; R 1 and R 2 Each of these examples is independent, -H, and C is substituted as needed. 1-6 Alkyl, substituted C as needed 1-20 Alkylene, substituted C as needed 1-6 Heteroalkyl, substituted C as needed 6-10 Selected from the group consisting of aryl, optionally substituted 3- to 10-membered arylalkyl, optionally substituted 5- to 10-membered heteroaryl, optionally substituted 3- to 10-membered heteroarylalkyl, optionally substituted 3- to 20-membered carbocyrill, optionally substituted 3- to 20-membered (carbocyrill)alkyl, optionally substituted 3- to 20-membered heterocyclyl, or optionally substituted 3- to 20-membered (heterocyclyl)alkyl, or none at all; R 3 and R 4 Each example, if present, independently includes -H, optionally substituted C1-6 alkyl, and optionally substituted C 1-20 Alkylene, substituted C as needed 1-6 Heteroalkyl, substituted C as needed 6-10Selected from the group consisting of aryls, optionally substituted 3- to 10-membered arylalkyls, optionally substituted 3- to 20-membered carbocyclyls, optionally substituted 3- to 20-membered (carbocyclyl)alkyls, optionally substituted 3- to 20-membered heterocyclyls, and optionally substituted 3- to 20-membered (heterocyclyl)alkyls, or none at all; R 5 Each of these examples, if present, is independently replaced as needed with C. 1-20 Selected from the group consisting of alkylenes, or none at all; and n is 0, 1, or 2.

[0178] In some embodiments, A, B, U, V, W, X, Y, and Z are independently C, C(R 5 -R 3 ), N, N(R 5 -R 4 ), S, and S(R 5 -R 4 Selected from the group consisting of ). In some embodiments, A is N. In some embodiments, B is N. In some embodiments, U is N. In some embodiments, V is N. In some embodiments, W is N. In some embodiments, X is N. In some embodiments, Y is N. In some embodiments, Z is N. In some embodiments, A is N(R 5 -R 4 ) is. In some embodiments, B is N(R 5 -R 4 ) is. In some embodiments, V is N(R 5 -R 4 ) is. In some embodiments, W is N(R 5 -R 4 ) is. In some embodiments, Z is N(R 5 -R 4) is. In some embodiments, A is S. In some embodiments, B is S. In some embodiments, U is S. In some embodiments, V is S. In some embodiments, W is S. In some embodiments, X is S. In some embodiments, Y is S. In some embodiments, Z is S. In some embodiments, A is S(R 5 -R 4 ) is. In some embodiments, B is S(R 5 -R 4 ) is. In some embodiments, V is S(R 5 -R 4 ) is. In some embodiments, W is S(R 5 -R 4 ) is. In some embodiments, Z is S(R 5 -R 4 )

[0179] In some embodiments, R 1 -H, C which is substituted as needed. 1-6 Alkyl, substituted C as needed 1-20 Alkylene, substituted C as needed 1-6 Heteroalkyl, substituted C as needed 6-10 Selected from the group consisting of aryl, optionally substituted 3- to 10-membered arylalkyl, optionally substituted 5- to 10-membered heteroaryl, optionally substituted 3- to 10-membered heteroarylalkyl, optionally substituted 3- to 20-membered carbocyrill, optionally substituted 3- to 20-membered (carbocyrill)alkyl, optionally substituted 3- to 20-membered heterocyclyl, or optionally substituted 3- to 20-membered (heterocyclyl)alkyl, or none at all. In some embodiments, R 1 is -H. In some embodiments, R 1 C is replaced as needed. 1-6 It is alkyl. In some embodiments, R 1 C is replaced as needed. 1-20It is an alkylene. In some embodiments, R 1 C is replaced as needed. 1-6 It is heteroalkyl. In some embodiments, R 1 C is replaced as needed. 6-10 It is an arrow. In some embodiments, R 1 R is a 3- to 10-membered arylalkyl that is substituted as needed. In some embodiments, R 1 R is a 5- to 10-membered heteroaryl that is substituted as needed. In some embodiments, R 1 R is a 3- to 10-membered heteroarylalkyl that is substituted as needed. In some embodiments, R 1 R is a 3- to 20-membered carbocyclyl which is substituted as needed. In some embodiments, R 1 R is a 3- to 20-membered (carbocykyl)alkyl group which is substituted as needed. In some embodiments, R 1 R is a 3- to 20-membered heterocycline which is substituted as needed. In some embodiments, R 1 R is a 3- to 20-membered (heterocyclyl)alkyl group which is substituted as needed. In some embodiments, R 1 It does not exist.

[0180] In some embodiments, R 2 -H, C which is substituted as needed. 1-6 Alkyl, substituted C as needed 1-20 Alkylene, substituted C as needed 1-6 Heteroalkyl, substituted C as needed 6-10Selected from or absent from the group consisting of aryls, optionally substituted 3- to 10-membered arylalkyls, optionally substituted 5- to 10-membered heteroaryls, optionally substituted 3- to 10-membered heteroarylalkyls, optionally substituted 3- to 20-membered carbocyrills, optionally substituted 3- to 20-membered (carbocyrill)alkyls, optionally substituted 3- to 20-membered heterocyclines, and optionally substituted 3- to 20-membered (heterocyclyl)alkyls. In some embodiments, R 2 is -H. In some embodiments, R 2 C is replaced as needed. 1-6 It is alkyl. In some embodiments, R 2 C is replaced as needed. 1-20 It is an alkylene. In some embodiments, R 2 C is replaced as needed. 1-6 It is heteroalkyl. In some embodiments, R 2 C is replaced as needed. 6-10 It is an arrow. In some embodiments, R 2 R is a 3- to 10-membered arylalkyl that is substituted as needed. In some embodiments, R 2 R is a 5- to 10-membered heteroaryl that is substituted as needed. In some embodiments, R 2 R is a 3- to 10-membered heteroarylalkyl that is substituted as needed. In some embodiments, R 2 R is a 3- to 20-membered carbocyclyl which is substituted as needed. In some embodiments, R 2 R is a 3- to 20-membered (carbocykyl)alkyl group which is substituted as needed. In some embodiments, R 2 R is a 3- to 20-membered heterocycline which is substituted as needed. In some embodiments, R 2 R is a 3- to 20-membered (heterocyclyl)alkyl group which is substituted as needed. In some embodiments, R 2 It does not exist.

[0181] In some embodiments, R 3 If present, independently, -H, optionally substituted C1-6 alkyl, optionally substituted C 1-20 Alkylene, substituted C as needed 1-6 Heteroalkyl, substituted C as needed 6-10 Selected from or absent from the group consisting of aryls, optionally substituted 3- to 10-membered arylalkyls, optionally substituted 3- to 20-membered carbocyclyls, optionally substituted 3- to 20-membered (carbocyclyl)alkyls, optionally substituted 3- to 20-membered heterocyclyls, and optionally substituted 3- to 20-membered (heterocyclyl)alkyls. In some embodiments, R 3 is -H. In some embodiments, R 3 is a C1-6 alkyl which is substituted as needed. In some embodiments, R 3 C is replaced as needed. 1-20 It is an alkylene. In some embodiments, R 3 C is replaced as needed. 1-6 It is heteroalkyl. In some embodiments, R 3 C is replaced as needed. 6-10 It is an arrow. In some embodiments, R 3 R is a 3- to 10-membered arylalkyl that is substituted as needed. In some embodiments, R 3 R is a 3- to 20-membered carbocyclyl which is substituted as needed. In some embodiments, R 3 R is a 3- to 20-membered (carbocykyl)alkyl group which is substituted as needed. In some embodiments, R 3 R is a 3- to 20-membered heterocycline which is substituted as needed. In some embodiments, R 3 R is a 3- to 20-membered (heterocyclyl)alkyl group which is substituted as needed. In some embodiments, R 3 It does not exist.

[0182] In some embodiments, R 4 If present, independently, -H, optionally substituted C1-6 alkyl, optionally substituted C 1-20 Alkylene, substituted C as needed 1-6 Heteroalkyl, substituted C as needed 6-10 Selected from or absent from the group consisting of aryls, optionally substituted 3- to 10-membered arylalkyls, optionally substituted 3- to 20-membered carbocyclyls, optionally substituted 3- to 20-membered (carbocyclyl)alkyls, optionally substituted 3- to 20-membered heterocyclyls, and optionally substituted 3- to 20-membered (heterocyclyl)alkyls. In some embodiments, R 4 is -H. In some embodiments, R 4 is a C1-6 alkyl which is substituted as needed. In some embodiments, R 4 C is replaced as needed. 1-20 It is an alkylene. In some embodiments, R 4 C is replaced as needed. 1-6 It is heteroalkyl. In some embodiments, R 4 C is replaced as needed. 6-10 It is an arrow. In some embodiments, R 4 R is a 3- to 10-membered arylalkyl that is substituted as needed. In some embodiments, R 4 R is a 3- to 20-membered carbocyclyl which is substituted as needed. In some embodiments, R 4 R is a 3- to 20-membered (carbocykyl)alkyl group which is substituted as needed. In some embodiments, R 4 R is a 3- to 20-membered heterocycline which is substituted as needed. In some embodiments, R 4 R is a 3- to 20-membered (heterocyclyl)alkyl group which is substituted as needed. In some embodiments, R 4 It does not exist.

[0183] In some embodiments, R 5 If present, C is independently replaced as needed. 1-20 Selected from the group consisting of alkylenes, or absent. In some embodiments, R 5 C is replaced as needed. 1-20 It is an alkylene. In some embodiments, R 5 It does not exist. In some embodiments, R 5 ha-(CH2) m - and m is an integer in the range of 0 to 20. In some embodiments, m is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20. In some embodiments, m is 0. In some embodiments, m is 1. In some embodiments, m is 2. In some embodiments, m is 3. In some embodiments, m is 4. In some embodiments, m is 5. In some embodiments, m is 6. In some embodiments, m is 7. In some embodiments, m is 8. In some embodiments, m is 9. In some embodiments, m is 10. In some embodiments, m is 11. In some embodiments, m is 12. In some embodiments, m is 13. In some embodiments, m is 14. In some embodiments, m is 15. In some embodiments, m is 16. In some embodiments, m is 17. In some embodiments, m is 18. In some embodiments, m is 19. In some embodiments, m is 20.

[0184] In some embodiments, n is 0, 1, or 2. In some embodiments, n is 0. In some embodiments, n is 1. In some embodiments, n is 2.

[0185] In some embodiments, the structure of this formula (I) is further represented by a formula selected from either formula (Ia) or (Ib).

[0186] [ka]

[0187] In some embodiments, R 1 C is replaced as needed. 1-6 Alkyl or optionally substituted C 1-20 It is an alkylene. In further embodiments, R 1 R is selected from the group consisting of -CH2-, -CH2CH2-, -CH(CH3)-, and -CHCH2(OH)-. In some embodiments, R 1 is -CH2-. In some embodiments, R 1 is -CH2CH2-. In some embodiments, R 1 is -CH(CH3)-. In some embodiments, R 1 is -CHCH2(OH)-. In some embodiments, R 1 ha-(CH2) p- and p is an integer in the range of 0 to 20. In some embodiments, p is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20. In some embodiments, p is 0. In some embodiments, p is 1. In some embodiments, p is 2. In some embodiments, p is 3. In some embodiments, p is 4. In some embodiments, p is 5. In some embodiments, p is 6. In some embodiments, p is 7. In some embodiments, p is 8. In some embodiments, p is 9. In some embodiments, p is 10. In some embodiments, p is 11. In some embodiments, p is 12. In some embodiments, p is 13. In some embodiments, p is 14. In some embodiments, p is 15. In some embodiments, p is 16. In some embodiments, p is 17. In some embodiments, p is 18. In some embodiments, p is 19. In some embodiments, p is 20.

[0188] In a particular embodiment, R 1 and R 2 Each example is independently selected from a group consisting of the following structure:

[0189] [ka] TIFF2026513524000061.tif149163

[0190] In some embodiments, R 2 These are independently selected from the group consisting of the following structures:

[0191] [ka] In some embodiments, R 2 is -H. In some embodiments, R 2 teeth,

[0192] [ka] In some embodiments, R 2 teeth,

[0193] [ka] In some embodiments, R 2 teeth,

[0194] [ka] In some embodiments, R 2 teeth,

[0195] [ka] In some embodiments, R 2 teeth,

[0196] [ka] In some embodiments, R 2 teeth,

[0197] [ka] That is the case.

[0198] In a particular embodiment, R 3 and R 4 Each example, if present, is independently selected from a group consisting of the following structures:

[0199] [ka] TIFF2026513524000070.tif234163TIFF2026513524000071.tif238163

[0200] In some embodiments, for example, A is N(R 5 R 4 ) In further embodiments, R 4 The following structure is selected from the group:

[0201] [ka] In some embodiments, R 4 is -H. In some embodiments, R 4 teeth,

[0202] [ka] In some embodiments, R 4 teeth,

[0203] [ka] In some embodiments, R 4 teeth,

[0204] [ka] In some embodiments, R 4 teeth,

[0205] [ka] In some embodiments, R 4 teeth,

[0206] [ka] In some embodiments, R 4 teeth,

[0207] [ka] In some embodiments, R 4 teeth,

[0208] [ka] In some embodiments, R 4 teeth,

[0209] [ka] In some embodiments, R 4 teeth,

[0210] [ka] In some embodiments, R 4 teeth,

[0211] [ka] That is the case.

[0212] In some embodiments, the bicyclic compound includes at least one aromatic ring. In some embodiments, at least one aromatic ring is aryl. In some embodiments, at least one aromatic ring is heteroaryl. In some embodiments, at least one aromatic ring is optionally substituted. In further embodiments, at least one aromatic ring is substituted with at least one amine group.

[0213] In some embodiments, for example, at least one aromatic ring comprises a pyridine ring. In some embodiments, at least one aromatic ring is a pyridine ring. In some embodiments, the pyridine ring is substituted with at least one amine group. Without being bound by any particular theory, the at least one amine group bonded to at least one aromatic ring provides a strong binding ability to the compound of formula (I) disclosed herein and / or its pharmaceutically acceptable salts, thereby acting effectively as an enzyme activity inhibitor of vanin enzymes (e.g., vanin 1).

[0214] In some embodiments, formula (I) may be represented by one or more of the following (or other) compounds:

[0215] [ka]

[0216] In some embodiments, compounds having the structure of formula (I) are selected from one or more of the following structures: 2-((pyridine-3-ylmethyl)amino)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine-5-one; 2-((pyridine-3-ylmethyl)amino)-7,8-dihydro-1,6-naphthyridine-5(6H)-one; 6-(2-(dimethylamino)ethyl)-2-((pyrazine-2-ylmethyl)amino)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine-5-one; 6-(2-(dimethylamino)ethyl)-2-((pyridine-3-ylmethyl)amino)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine-5-one; 4-((5-oxo-2-((pyridine-3-ylmethyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)methyl)benzenesulfonamide; 6-(3,5-dimethylbenzyl)-2-((pyridine-3-ylmethyl)amino)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine-5-one; 6-benzyl-2-((pyridine-3-ylmethyl)amino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidine-5-one; 6-(2-(dimethylamino)ethyl)-2-((2-hydroxy-1-(pyridine-3-yl)ethyl)amino)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine-5-one; 6-(2-(dimethylamino)ethyl)-2-((1-(pyridine-3-yl)ethyl)amino)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine-5-one; 6-(3,5-dichlorobenzyl)-2-((pyridine-3-ylmethyl)amino)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine-5-one; 6-phenyl-2-((pyridine-3-ylmethyl)amino)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine-5-one; 6-(2-(dimethylamino)-2-methylpropyl)-2-((pyridine-3-ylmethyl)amino)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine-5-one; 6-(3-(dimethylamino)propyl)-2-((pyridine-3-ylmethyl)amino)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine-5-one; N-(2-(5-oxo-2-((pyridine-3-ylmethyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide; and N-(3-(5-oxo-2-((pyridine-3-ylmethyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)propyl)acetamide.

[0217] Method for producing the compound of formula (I) The compounds disclosed herein can be synthesized by the methods described below, or by modifications thereof. Modifications to these methods include, among other things, temperatures, solvents, reagents, etc., known to those skilled in the art. In general, it may be necessary and / or desirable to protect sensitive or reactive groups on any of the molecules involved during any process for preparing the compounds disclosed herein. This can be achieved by using conventional protecting groups, e.g., those described in "Protective Groups in Organic Chemistry" (JFWMcOmie, Plenum Press, 1973) and "Protecting Groups in Organic Synthesis" (3rd edition) by PGMGreen and TWWutts, Wiley, New York (1999), both of which are incorporated herein by reference in their entirety. Protecting groups can be removed at an appropriate subsequent step using methods known in the art. Synthetic chemical transformations useful for the synthesis of applicable compounds are known in the art, including, for example, those described in R. Larock's "Comprehensive Organic Transformations," VCH Publishers, 1989, or L. Paquette's "Encyclopedia of Reagents for Organic Synthesis," John Wiley and Sons, 1995, both of which are incorporated herein by reference in their entirety. The routes shown and described herein are merely illustrative and are not intended to, nor should be construed to, limit the scope of the claims in any way. Those skilled in the art will recognize modifications of the disclosed synthesis and devise alternative routes based on the disclosure herein. All such modifications and alternative routes are within the scope of the claims.

[0218] In the following scheme, protecting groups are selected in light of their compatibility with the essential synthetic steps, as well as their compatibility with the introduction and deprotection steps and the overall synthetic scheme (PGMGreen, TWWutts, Protecting Groups in Organic Synthesis (3rd edition), Wiley, New York (1999)).

[0219] If a compound of the present invention contains one or more chiral centers, such a compound can be prepared or isolated as a pure stereoisomer, i.e., as individual enantiomers or d(l) stereoisomers, or as a concentrated mixture of stereoisomers. All such stereoisomers (and concentrated mixtures) are included within the scope of the present invention unless otherwise specified. Pure stereoisomers (or concentrated mixtures) can be prepared, for example, using optically active starting materials or stereoselective reagents well known in the art. Alternatively, racemic mixtures of such compounds can be separated, for example, using chiral column chromatography, chiral resolving agents, etc.

[0220] The starting materials for the following reactions are generally known compounds or can be prepared by known procedures or obvious modifications thereof. For example, many of the 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 compounds can be prepared by following the procedures or obvious modifications described in standard reference books 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 Supplements (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).

[0221] Some non-limiting embodiments relate to methods for synthesizing compounds of formula (I) (e.g., compound 1, compound 2, etc.) and intermediates of compounds of formula (I).

[0222] Administration and pharmaceutical composition The compounds are administered in therapeutically effective doses. While the human dose levels of the compounds described herein have not yet been optimized, generally, daily doses may range from approximately 0.25 mg / kg to approximately 120 mg / kg or more per kg of body weight, from approximately 0.5 mg / kg or less to approximately 70 mg / kg, from approximately 1.0 mg / kg to approximately 50 mg / kg per kg of body weight, or from approximately 1.5 mg / kg to approximately 10 mg / kg per kg of body weight. Therefore, the dose range for administration to a 70 kg person would be approximately 17 mg to approximately 8000 mg per day, from approximately 35 mg or less to approximately 7000 mg or more per day, from approximately 70 mg to approximately 6000 mg per day, from approximately 100 mg to approximately 5000 mg per day, or from approximately 200 mg to approximately 3000 mg per day. The amount of active compound administered will naturally depend on the patient and their condition, the severity of the pain, the method and schedule of administration, and the judgment of the prescribing physician.

[0223] In some embodiments, compounds of formula (I), or pharmaceutically acceptable salts thereof, are 20 μM, 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 M, 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 of these values, approximately these, less than these, or approximately less than these, median inhibitory concentrations (IC 50 ) has activity. For example, in some embodiments, a compound of formula (I), or a pharmaceutically acceptable salt thereof, has a median inhibitory concentration (IC) that falls within or approximately within one of the following ranges: about 1 μM to about 10 μM, about 5 μM to about 15 μM, about 5 μM to about 10 μM, about 10 μM to about 20 μM, about 0.5 μM to about 1 μM, about 1 μM to about 5 μM, about 0.1 μM to about 1 μM, about 0.01 μM to about 0.9 μM, about 1 μM to about 2 μM, or about 0.8 μM to about 0.9 μM. 50 ) It has activity.

[0224] The compounds disclosed herein or pharmaceutically acceptable salts thereof may be administered by any of the accepted methods of administration of a drug that performs a similar utility, including but not limited to oral, subcutaneous, intravenous, intranasal, topical, transdermal, intraperitoneal, intramuscular, intrapulmonary, vaginal, rectal, or intraocular methods. Oral and parenteral administration is customary in the treatment of indications targeted by the preferred embodiments.

[0225] The useful compounds described above 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 edition, Lippincott Williams & Wilkins (2005), which are incorporated in whole by reference, are used. Accordingly, some embodiments include pharmaceutical compositions comprising (a) a safe and therapeutically effective amount of a compound described herein (including its enantiomers, diastereoisomers, tautomers, polymorphs, and solvates), or a pharmaceutically acceptable salt thereof, and (b) a pharmaceutically acceptable carrier, diluent, excipient, or combination thereof.

[0226] In addition to the selected useful compounds described above, some embodiments include compositions containing pharmaceutically acceptable carriers. The terms “pharmaceutically acceptable carrier” or “pharmaceutically acceptable excipient” include all kinds of solvents, dispersions, coatings, antimicrobial and antifungal agents, isotonic agents, and absorption retarders, etc. The use of such media and agents for pharmaceutically active substances is well known in the art. Unless any conventional media or agent is incompatible with the active ingredient, its use in therapeutic compositions is intended. In addition, various adjuvants, such as those commonly used in the art, may be included. Considerations for incorporating various components into pharmaceutical compositions are, for example, in Gilman et al. (eds.) (1990); Goodman and Gilman's: The Pharmacological Basis of Therapeutics, 8th edition, Pergamon Press, which is incorporated herein by reference in its entirety.

[0227] Some examples of substances that can serve as pharmaceutically acceptable carriers or components include sugars, e.g., lactose, glucose, and sucrose; starches, e.g., corn starch and potato starch; cellulose and its derivatives, e.g., sodium carboxymethylcellulose, ethylcellulose, and methylcellulose; powdered tragacanth; malt; gelatin; talc; solid lubricants, e.g., stearic acid and magnesium stearate; calcium sulfate; vegetable oils, e.g., peanut oil, cottonseed oil, sesame oil, olive oil, corn oil, and cocoa oil; polyols, e.g., propylene glycol, glycerin, sorbitol, mannitol, and polyethylene glycol; alginic acid; emulsifiers, e.g., TWEENs; humectants, e.g., sodium lauryl sulfate; colorants; flavorings; tableting agents, stabilizers; antioxidants; preservatives; pyrogen-free water; isotonic saline; and phosphate buffer solutions.

[0228] The selection of a pharmaceutically acceptable carrier to be used in combination with the target compound is essentially determined by the method of administering the compound.

[0229] The compositions described herein are preferably provided in unit dosage forms. As used herein, “unit dosage form” is a composition containing an amount of the compound suitable for administration in a single dose to an animal, preferably a mammalian, subject, in accordance with appropriate medical practice. However, the preparation of a single or unit dosage form does not imply that the dosage form is to be administered once daily or once in a course of treatment. Such dosage forms may be intended to be administered once, twice, three times, or more times daily, and may be administered as an infusion over a period of time (e.g., from about 30 minutes to about 2-6 hours) or as a continuous infusion, and may be given more than once in a course of treatment, but single doses are not specifically excluded. Those skilled in the art will understand that the formulation is not specifically intended for an entire course of treatment, and that such decisions are left to those skilled in the art of the field of treatment, not to the formulation.

[0230] As described above, useful compositions can be any of various suitable forms for various routes of administration, such as oral, nasal, rectal, topical (including percutaneous), ocular, intracerebral, intracranial, intrathecal, intra-arterial, intravenous, intramuscular, subcutaneous, or other parental 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 are manufactured by available methods. Depending on the desired specific route of administration, various pharmaceutically acceptable carriers known in the art may be used. Pharmaceutically acceptable carriers include, for example, solid or liquid fillers, diluents, diuretics (hydrotropies), surfactants, and encapsulating agents. Pharmaceutically active materials that do not substantially interfere with the inhibitory activity of the compound may be included as needed. The amount of carrier used with the compound is sufficient to provide a practical amount of substance for administering the compound per unit dose. Techniques and compositions useful in the methods described herein for the manufacture of dosage forms are described in the following references, all of which are incorporated herein by reference: "Modern Pharmaceutics," 4th edition, Chapters 9 and 10 (Banker and Rhodes, eds., 2002); Lieberman et al., "Pharmaceutical Dosage Forms: Tablets" (1989); and Ansel, "Introduction to Pharmaceutical Dosage Forms," ​​8th edition (2004).

[0231] Various oral dosage forms can be used, including solid forms such as tablets, capsules, granules, and active pharmaceutical ingredient powders. Tablets containing appropriate binders, lubricants, diluents, disintegrants, colorants, flavorings, fluidizers, and melting agents can be compressed, triturated, enterically coated, sugar-coated, film-coated, or multiple-compressed. Liquid oral dosage forms include aqueous solutions, emulsions, suspensions, solutions and / or suspensions reconstituted from non-foaming granules, and effervescent preparations reconstituted from effervescent granules, which contain appropriate solvents, preservatives, emulsifiers, suspending agents, diluents, sweeteners, melting agents, colorants, and flavorings.

[0232] Pharmaceutically acceptable carriers suitable for preparations of unit dosage forms for oral administration are well known in the art. Tablets typically contain conventional pharmaceutically acceptable adjuvants as inert diluents, e.g., calcium carbonate, sodium carbonate, mannitol, lactose, and cellulose; binders, e.g., starch, gelatin, and sucrose; disintegrants, e.g., starch, alginic acid, and croscarmelose; lubricants, e.g., magnesium stearate, stearic acid, and talc. Flow enhancers, e.g., silicon dioxide, can be used to improve the flowability characteristics of powder mixtures. Colorants, e.g., FD&C dyes, can be added for appearance. Sweeteners and flavorings, e.g., aspartame, saccharin, menthol, peppermint, and fruit flavors, are useful adjuvants for chewable tablets. Capsules typically contain one or more of the previously disclosed solid diluents. The selection of carrier components is made according to secondary considerations such as taste, cost, and storage stability, but these are not definitive and can be easily done by those skilled in the art.

[0233] Oral compositions also include liquid solutions, emulsions, suspensions, and the like. Pharmaceutically acceptable carriers suitable for the preparation of such compositions are well known 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 wetting agents include lecithin and polysorbate 80; and typical preservatives include methylparaben and sodium benzoate. Oral liquid compositions may also contain one or more components, such as sweeteners, flavorings, and colorants, as previously disclosed.

[0234] Such compositions may also be coated by conventional methods, typically using pH or time-dependent coatings, so that the compound of the subject is released in the gastrointestinal tract near the desired topical application, or released at various points in time to prolong the desired effect. Such dosage forms typically include, but are not limited to, one or more of the following: cellulose phthalate acetate, polyvinyl acetate phthalate, hydroxypropyl methylcellulose phthalate, ethylcellulose, Eudragit coating, wax, and shellac.

[0235] The compositions described herein may optionally contain other pharmacoactive substances.

[0236] Other compositions useful for systemic delivery of the subject compound include sublingual, intraoral buccal, and nasal dosage forms. Such compositions typically comprise soluble fillers, such as sucrose, sorbitol, and mannitol, as well as binders, such as one or more of acacia, microcrystalline cellulose, carboxymethylcellulose, and hydroxypropylmethylcellulose. Flow enhancers, lubricants, sweeteners, colorants, antioxidants, and flavoring agents previously disclosed may also be included.

[0237] Preservatives that may be used in the pharmaceutical compositions disclosed herein include, but are not limited to, benzalkonium chloride, PHMB, chlorobutanol, thimerosal, phenylmercury, acetate, and phenylmercury nitrate. A useful surfactant is, for example, Tween 80. Similarly, a variety of useful solvents may be used in the ophthalmic preparations disclosed herein. These solvents include, but are not limited to, polyvinyl alcohol, povidone, hydroxypropyl methylcellulose, poloxamer, carboxymethylcellulose, hydroxyethylcellulose, and purified water.

[0238] Osmotic regulators may be added if necessary or convenient. Examples of osmotic regulators include, but are not limited to, salts, particularly sodium chloride, potassium chloride, mannitol, and glycerin, or any other suitable ophthalmologically acceptable osmotic regulator.

[0239] Various buffers and methods can be used to adjust the pH, provided that the resulting preparation is ophthalmologically acceptable. For many compositions, the pH is between 4 and 9. Therefore, buffers include acetate buffers, citrate buffers, phosphate buffers, and borate buffers. Acids or bases may be used as needed to adjust the pH of these formulations.

[0240] For topical use, creams, ointments, gels, solutions, or suspensions 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 system, and a emollient.

[0241] For intravenous administration, the compounds and compositions described herein can be dissolved or dispersed in pharmaceutically acceptable diluents, such as saline or dextrose solutions. Suitable excipients, including but not limited to NaOH, sodium carbonate, sodium acetate, HCl, and citric acid, may be included to achieve a desired pH. In various embodiments, the pH of the final composition is in the range of 2 to 8, or preferably 4 to 7. Examples of antioxidant excipients include sodium bisulfite, sodium acetone bisulfite, sodium formaldehyde, sulfoxylates, thiourea, and EDTA. Other non-limiting examples of suitable excipients found in the final intravenous composition include sodium phosphate or potassium phosphate, citric acid, tartaric acid, gelatin, and carbohydrates, such as glucose, mannitol, and dextran. Further acceptable excipients are described in Powell et al., "Compendium of Excipients for Parenteral Formulations," PDA J Pharm Sci and Tech 1998, pp. 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, pp. 65, 287-332, both of which are incorporated herein by reference in their entirety. Antimicrobial agents, including but not limited to phenylmercury nitrate, thimerosal, benzethonium chloride, benzalkonium chloride, phenol, cresol, and chlorobutanol, may also be included to achieve bacteriostatic or fungiostatic solutions.

[0242] Compositions for intravenous administration may be provided to the caregiver in one or more solid forms, which are reconstituted immediately before administration with a suitable diluent, such as sterile water, saline solution, or glucose in water. In other embodiments, the composition is provided as a solution prepared for parenteral administration. In yet another embodiment, the composition is provided as a solution that is further diluted before administration. In embodiments comprising administering a combination of a compound described herein with another drug, the combination may be provided to the caregiver as a mixture, or the caregiver may mix the two drugs before administration, or the two drugs may be administered separately.

[0243] The actual doses of the active compounds described herein will depend on the specific compound and the condition being treated, and the selection of an appropriate dose is well within the knowledge of those skilled in the art.

[0244] The compounds and compositions described herein may, if desired, be presented as packs or dispenser devices containing one or more unit dosage forms with the active ingredient. Such packs or devices may include, for example, metal or plastic foil, such as blister packs, or glass, and rubber stoppers in vials, etc. The packs or dispenser devices may be accompanied by instructions for administration. Alternatively, the compounds and compositions described herein may be formulated on suitable pharmaceutical carriers, placed in appropriate containers, and labeled for the treatment of specified conditions.

[0245] The amount of compound in a formulation may vary depending on the general formulation used by those skilled in the art. Typically, a formulation contains, on a weight percentage (wt%) basis, about 0.01 to about 99.99 wt% of the total formulation of the compound according to the technology of the present invention, with the remainder being one or more suitable pharmaceutical excipients. Preferably, the compound is present at a level of about 1 to 80 wt%. Representative pharmaceutical formulations are described below.

[0246] Examples of formulations The following are representative examples of pharmaceutical preparations containing the compound of formula (I).

[0247] Formulation Example 1 - Tablet Formulation Thoroughly mix the following ingredients and compress them into a single, scored tablet.

[0248] [Table 1]

[0249] Formulation Example 2 - Capsule Formulation Thoroughly mix the following ingredients and fill them into hard gelatin capsule shells.

[0250] [Table 2]

[0251] Formulation Example 3 - Suspension Formulation The following ingredients are mixed to prepare a suspension for oral administration.

[0252] [Table 3]

[0253] Formulation Example 4 - Injectable Formulation The following components are mixed to prepare an injectable formulation.

[0254] [Table 4]

[0255] Formulation Example 5 - Suppository Formulation A suppository weighing 2.5 g was prepared by mixing the compound produced by the technology of the present invention with Witepsol (registered trademark) H-15 (saturated plant fatty acid triglyceride, Riches-Nelson, Inc., New York), and this suppository has the following composition.

[0256] [Table 5]

[0257] Treatment method Compounds of formula (I) disclosed herein, or their tautomers and / or pharmaceutically acceptable salts thereof, can effectively act as enzyme activity inhibitors of vanin enzymes (e.g., vanin 1). Several embodiments provide pharmaceutical compositions comprising one or more of the compounds disclosed herein and pharmaceutically acceptable excipients.

[0258] In some embodiments, methods are provided for preventing, treating, or relieving one or more inflammatory or autoimmune diseases in a subject. In some embodiments, the method comprises administering one or more of the compounds disclosed herein to a subject in need. In some embodiments, the method comprises administering one or more pharmaceutically acceptable salts thereof of the compounds disclosed herein to a subject in need.

[0259] In some embodiments, the compounds of the Disclosure are used to prevent, treat, or induce remission of 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 inducing remission of lupus, rheumatoid arthritis, atopic dermatitis, and psoriasis. In some embodiments, the method comprises administering one or more of the compounds disclosed herein to a subject in need. In some embodiments, the method comprises administering one or more pharmaceutically acceptable salts thereof of the compounds disclosed herein to a subject in need.

[0260] In some embodiments, the compounds of the Disclosure are used to treat cancer. In some embodiments, the cancer is selected from the group consisting of colorectal cancer, liver cancer, pancreatic cancer, gastric cancer, esophageal cancer, prostate cancer, breast cancer, cholangiocarcinoma, sarcoma, or acute myeloid leukemia. In some embodiments, the method comprises administering one or more of the compounds disclosed herein to a subject in need. In some embodiments, the method comprises administering one or more pharmaceutically acceptable salts thereof of the compounds disclosed herein to a subject in need.

[0261] In some embodiments, a method of administering one or more of the compounds disclosed herein results in the prevention, treatment, or remission of inflammatory or autoimmune diseases. In some embodiments, a method of administering one or more of the compounds disclosed herein results in the prevention, treatment, or remission of ulcerative colitis, Crohn's disease, atopic dermatitis, psoriasis, systemic lupus erythematosus, atherosclerosis, and type 1 diabetes. In some embodiments, the method comprises administering one or more pharmaceutically acceptable salts thereof of the compounds disclosed herein.

[0262] In some embodiments, a method of administering one or more of the compounds disclosed herein results in inhibition of vanin-1 activity in one or more organs of the subject. In some embodiments, inhibition of vanin-1 activity suppresses the expression and / or activity of pro-inflammatory signals. In some embodiments, the pro-inflammatory signals may be one or more cytokines. In some embodiments, cytokines include TNF-alpha (TNFA or TNF), interleukin-6 (IL-6), interleukin-1 beta (IL-1B), MCP1, and interleukin-8 (IL-8). In some embodiments, the method involves administering one or more pharmaceutically acceptable salts thereof of the compounds disclosed herein.

[0263] Some embodiments involve administering the compounds, compositions, and / or pharmaceutical compositions described herein in combination with other pharmaceuticals. “Combined administration” means that two or more drugs may be found simultaneously in the patient’s bloodstream, regardless of when or how they are actually administered. In one embodiment, these drugs are administered simultaneously. In such an embodiment, combined administration is achieved by combining multiple drugs into a single dosage form. In another embodiment, the drugs are administered over time. In one embodiment, the drugs are administered via the same route, for example, by oral administration. In another embodiment, the drugs are administered via different routes. For example, one is administered subcutaneously, another orally, and yet another by intravenous injection.

[0264] The following embodiments are provided for illustrative purposes of various embodiments of the Disclosure and are not intended to limit the Disclosure in any way. Those skilled in the art will readily see that the Disclosure is well suited to achieving the purposes, ultimate goals, and benefits of the Disclosure, as well as the purposes, ultimate goals, and benefits inherent in the Disclosure. Modifications and other uses of the Disclosure, as defined by the claims, will be obvious to those skilled in the art. [Examples]

[0265] Example 1: Synthesis of Bicyclic Compounds All reactions were carried out under an argon atmosphere. Reagents and solvents were commercially available and used without further purification. Hydrogenation reactions were performed using balloons. Microwave reactions were performed using a CEM Discover SP microwave synthesizer. Sample purification was performed using a Buchi Pureflash with an ELSD purification system, employing commercially available pre-packed silica gel columns. Thin-layer chromatography (TLC) was performed using aluminum plates and Merck Kiesegel 60 F254 (230-400 mesh) fluorescent-treated silica, visualized under ultraviolet light (254 nm) or by staining with potassium permanganate or ninhydrin solution as appropriate. Nuclear magnetic resonance (NMR) spectra were all acquired using a Bruker Advanced III HD 400 MHz NMR spectrometer. Chemical shifts were recorded in ppm(δ). HPLC / MS was performed using a Shimadzu 2020 single quadrupole mass spectrometer and a Shimadzu LC40B XR UHPLC, with a Shimadzu Nexcol C18 column (50 × 2.1 mm, particle size 1.8 μm) and the following method: Mobile phase A for the gradient was a 0.1% aqueous formic acid solution, and mobile phase B was a 0.1% acetonitrile formic acid solution; A / B (95:5) was run from 0 to 0.9 min; then A / B (5:95) from 0.9 to 2.2 min; A / B (5:95) from 2.2 to 4.14 min; then A / B (95:5) from 4.14 to 4.20 min; and finally A / B (95:5) from 4.2 to 6 min. The flow rate was 0.4 mL / min, the column temperature was maintained at 35°C, and the temperature of the automated preparator was maintained 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 a full scan. The purity of all compounds was analyzed using an Agilent 1260 Infinity II Lab LC series HPLC (1260 quaternary pump, 1260 vial autopreparator, ICC column oven, 1260 DAD WR detector).The sample was injected into a Phenomenex Synergi Polar-RP column (150 × 4.6 mm, 4 μm, 80 Å). A gradient was applied to the mobile phase (A: 0.1% trifluoroacetic acid aqueous solution, B: 0.1% trifluoroacetic acid acetonitrile solution; A / B (99:1) for 0 min; then 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), and the flow was pumped at a flow rate of 1 mL / min. The column oven was set to 35°C and the UV detector to 254 nm. Unless otherwise specified, the injection volume was 10 μL. For all compounds, those evaluated by biological assays had a purity of 90% or higher, and those evaluated by animal experiments had a purity of 95% or higher.

[0266] Example 2: Synthesis of 2-((pyridine-3-ylmethyl)amino)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine-5-one (compound 1)

[0267] [ka] To a solution of 2-chloro-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine-5-one (100 mg, 593.19 μmol) dissolved in 1-BuOH (2 mL) and DIPEA (0.52 mL, 2.99 mmol), pyridine-3-ylmethaneamine (128 mg, 1.18 mmol) was added at room temperature. This mixture was then heated to 140 °C overnight and subsequently cooled to room temperature. The reaction mixture was partitioned with water and ethyl acetate. The layers were separated, and the aqueous layer was further extracted with EA (2 × 25 mL). The organic layers were washed together with saturated brine, dried over anhydrous Na₂SO₄, filtered, and concentrated. The residue was purified by Büch's pure flash chromatography (silica, 40 g). Using 0-5% MeOH dissolved in DCM as the eluate, the desired product, 2-((pyridine-3-ylmethyl)amino)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine-5-one (compound 1) (103 mg, yield 72%), was obtained as a white solid. 1 H NMR (400MHz, DMSO)δ 8.57(dd, J=2.3, 0.9Hz, 1H), 8.45(dd,J=4.8, 1.7Hz, 1H), 8.03(s, 1H), 7.84(t, J=5.9Hz, 1H), 7.73(ddd,J=7.8, 2.3, 1.7Hz, 1H) , 7.60(d, J=8.6Hz, 1H), 7.35(ddd,J=7.8, 4.8, 0.9Hz, 1H), 6.56(d, J=8.6Hz, 1H), 4.58(d, J=5.9Hz, 2H), 4.15(d, J=1.1Hz, 2H). MS(ESI):C 13 H 12 Calculated value of N4O: 240, measured value: 241 (M+H) + .

[0268] Example 3: Synthesis of 2-((pyridine-3-ylmethyl)amino)-7,8-dihydro-1,6-naphthyridine-5(6H)-one (compound 2)

[0269] [ka] To a solution of 2-chloro-7,8-dihydro-1,6-naphthyrizin-5(6H)-one (300 mg, 1.64 mmol) dissolved in 1-BuOH (2 mL) and DIPEA (0.58 mL, 3.33 mmol), pyridine-3-ylmethaneamine (267 mg, 2.47 mmol) was added at room temperature. This mixture was then heated to 140°C overnight and subsequently cooled to room temperature. The reaction mixture was partitioned with water and ethyl acetate. The layers were separated, and the aqueous layer was further extracted with EA (2 × 25 mL). The organic layers were washed together with saturated brine, dried over anhydrous Na₂SO₄, filtered, and concentrated. The residue was purified by Büch's Pure Flash Chromatography (silica, 40 g). Using 0-5% MeOH dissolved in DCM as the eluate, the desired product, 2-((pyridine-3-ylmethyl)amino)-7,8-dihydro-1,6-naphthyridine-5(6H)-one (compound 2) (150 mg, yield 36%), was obtained as a light brown solid. 1 H NMR (400MHz, DMSO)δ 8.57(dd,J=2.3, 0.8Hz, 1H), 8.44(dd,J=4.8, 1.7Hz, 1H), 7.72(dd,J=8.3, 6.2Hz, 3H), 7.50(s, 1H), 7.34(ddd,J=7.8, 4.8, 0 .9Hz, 1H), 6.44(d, J=8.6Hz, 1H), 4.54(d, J=6.0Hz, 2H), 3.35(d, J=2.7Hz, 1H), 3.32(d, J=2.7Hz, 1H), 2.78(t, J=6.7Hz, 2H). MS(ESI):C 14 H 14 Calculated value of N4O:254, measured value 255(M+H) + .

[0270] Example 4: Synthesis of 2-chloro-6-(2-(dimethylamino)ethyl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine-5-one (compound 3A)

[0271] [ka] To 3 mL of THF, methyl 6-chloro-2-(chloromethyl)nicotinate (50 mg, 227.22 μmol) and N1,N1-dimethylethane-1,2-diamine (100 mg, 1.13 mmol) were added and stirred overnight at room temperature. Water was added, and the mixture was extracted with ethyl acetate (2 x 10 mL). The organic extracts were washed together with saturated brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by Büch's pure flash chromatography (silica, 24 g) using 0-60% ethyl acetate dissolved in hexane to obtain the desired product, 2-chloro-6-(2-(dimethylamino)ethyl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine-5-one (compound 3A) (50 mg, yield 93%), as a white solid. 1 H NMR (400MHz, DMSO) δ 8.11(d, J=8.0Hz, 1H), 7.63(d, J=8.0Hz, 1H), 4.58(s, 2H), 3.63(t, J=6.3Hz, 2H), 2.48(d, J=6.6Hz, 2H), 2.17(s, 6H). MS(ESI):C 11 H 14 The calculated value for ClN3O is 239, and the measured value is 240 (M+H). + .

[0272] Example 5: Synthesis of 6-(2-(dimethylamino)ethyl)-2-((pyridine-3-ylmethyl)amino)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine-5-one (compound 4)

[0273] [ka] To a solution of 2-chloro-6-(2-(dimethylamino)ethyl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine-5-one (70 mg, 292.03 μmol) dissolved in 1-BuOH (2 mL) and DIPEA (0.25 mL, 1.44 mmol), pyridine-3-ylmethaneamine (315 mg, 2.91 mmol) was added at room temperature. The mixture was then heated to 140 °C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's pure flash chromatography (silica, 24 g). Using 0-10% 0.7N NH3-MeOH dissolved in DCM as the eluent, the desired product, 6-(2-(dimethylamino)ethyl)-2-((pyridine-3-ylmethyl)amino)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine-5-one (compound 4) (33 mg, yield 47%), was obtained as a white solid. 1 H NMR (400MHz, DMSO)δ 8.56 (dd, J=2.2, 0.9Hz, 1H), 8.45 (dd, J=4.8, 1.7Hz, 1H), 7.86 (t, J=5.9Hz, 1H), 7.73 (dt, J=7.8, 2.0Hz, 1H), 7.59 (d, J=8.5Hz, 1H), 7.35 (ddd ,J=7.8, 4.8, 0.9Hz, 1H), 6.56(d, J=8.6Hz, 1H), 4.57(d, J=5.9Hz, 2H), 4.27(s, 2H), 3.51(t, J=6.4Hz, 2H), 2.42(t, J=6.4Hz, 2H), 2.15(s, 6H). MS(ESI):C 17 H 21 The calculated value for N5O is 311, and the measured value is 312 (M+H). + .

[0274] Example 6: Synthesis of 2-chloro-6-(3,5-dimethylbenzyl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine-5-one (compound 6A)

[0275] [ka] To a solution of 2-chloro-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine-5-one (100 mg, 593.19 μmol) dissolved in THF (8 mL), lithium bis(trimethylsilyl)amide (0.60 mL, 1 M THF solution, 600 μmol) was added dropwise at 0°C. After stirring for 10 minutes, 1-(bromomethyl)-3,5-dimethylbenzene (142 mg, 713.24 μmol) was added dropwise. The resulting reaction mixture was stirred at room temperature for 48 hours, and the reaction was stopped with saturated ammonium chloride aqueous solution. After extraction with ethyl acetate, the organic layer was washed with saturated brine, dried over anhydrous Na₂SO₄, filtered, and concentrated under reduced pressure to obtain the crude product. This was further purified by Büch's Pure Flash Chromatography (silica, 24 g) using 0-60% toluene dissolved in hexane to obtain the desired product, 2-chloro-6-(3,5-dimethylbenzyl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine-5-one (compound 6A) (70 mg, yield 41%), as a greenish solid. MS(ESI):C 16 H 15 The calculated value for ClN2O is 286, and the measured value is 287 (M+H). + .

[0276] Example 7: Synthesis of 6-(3,5-dimethylbenzyl)-2-((pyridine-3-ylmethyl)amino)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine-5-one (compound 6)

[0277] [ka] To a solution of 2-chloro-6-(3,5-dimethylbenzyl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine-5-one (70 mg, 244.11 μmol) dissolved in 1-BuOH (2 mL) and DIPEA (0.21 mL, 1.21 mmol), pyridine-3-ylmethaneamine (264 mg, 2.44 mmol) was added at room temperature. The mixture was then heated to 140 °C overnight and subsequently cooled to room temperature. The reaction mixture was partitioned with water and ethyl acetate. The layers were separated, and the aqueous layer was further extracted with EA (2 × 25 mL). The organic layers were washed together with saturated brine, dried over anhydrous Na₂SO₄, filtered, and concentrated. The residue was purified by Büch's Pure Flash Chromatography (silica, 24 g). Using 0-5% 0.7 NNH3-MeOH dissolved in DCM as the eluent, the desired product, 6-(3,5-dimethylbenzyl)-2-((pyridine-3-ylmethyl)amino)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine-5-one (compound 6) (41 mg, yield 47%), was obtained as a white solid. 1 H NMR (400MHz, DMSO)δ 8.69-8.52(m, 1H), 8.46(ddd,J=20.4, 4.8, 1.7Hz, 1H), 7.90(t, J=6.0Hz, 1H), 7.79-7.68(m, 1H), 7.64(d, J=8.6Hz, 1H), 7.36(ddd d, J=20.3, 7.8, 4.8, 1.0Hz, 1H), 6.91-6.81(m, 3H), 6.58(d, J=8.6Hz, 1H), 4.55(d, J=4.9Hz, 4H), 4.12(s, 2H), 2.25-2.17(m, 6H). MS(ESI):C 22 H 22 The calculated value for N4O is 358, and the measured value is 359 (M+H). + .

[0278] Example 8: Synthesis of 2-chloro-6-(2-(dimethylamino)-2-methylpropyl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine-5-one (compound 12A)

[0279] [ka] 5 mL of THF was mixed with methyl 6-chloro-2-(chloromethyl)nicotinate (150 mg, 681.67 μmol) and N1,N1-dimethylpropane-1,3-diamine (348 mg, 3.41 mmol) and stirred overnight at room temperature. The reaction mixture was concentrated, and the residue was purified by Büch's pure flash chromatography (silica, 24 g) using 0-5% 0.7N NH3-MeOH dissolved in DCM to obtain the desired product, 2-chloro-6-(2-(dimethylamino)-2-methylpropyl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine-5-one (compound 12A) (123 mg, yield 67%), as a white solid. 1 H NMR (400MHz, DMSO) δ 8.13 (d, J=8.1Hz, 1H), 7.62 (dd, J=8.1, 0.8Hz, 1H), 4.80 (s, 2H), 3.53 (s, 2H), 2.20 (s, 6H), 0.96 (s, 6H). MS(ESI):C 13 H 18 The calculated value for ClN3O is 267, and the measured value is 268 (M+H). + .

[0280] Example 9: Synthesis of 6-(2-(dimethylamino)-2-methylpropyl)-2-((pyridine-3-ylmethyl)amino)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine-5-one (compound 12)

[0281] [ka] To a solution of 2-chloro-6-(2-(dimethylamino)-2-methylpropyl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine-5-one (100 mg, 373.47 μmol) dissolved in 1-BuOH (4 mL) and DIPEA (0.32 mL, 1.84 mmol), pyridine-3-ylmethaneamine (202 mg, 1.87 mmol) was added at room temperature. This mixture was then heated to 140 °C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's pure flash chromatography (silica, 40 g) using 0-10% 0.7N NH3-MeOH dissolved in DCM to obtain the desired product, 6-(2-(dimethylamino)-2-methylpropyl)-2-((pyridine-3-ylmethyl)amino)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine-5-one (compound 12) (yield 63 mg, 50%), as a white solid. 1 H NMR (400MHz, DMSO)δ 8.56 (dd, J=2.3, 0.8Hz, 1H), 8.45 (dd, J=4.8, 1.7Hz, 1H), 7.86 (t, J=5.9Hz, 1H), 7.73 (dt, J=7.9, 2.0Hz, 1H), 7.60 (d, J=8.6Hz, 1H), 7.35(ddd,J=7.8, 4.8, 0.9Hz, 1H), 6.56(d, J=8.6Hz, 1H), 4.58(d, J=5.9Hz, 2H), 4.49(s, 2H), 3.42(s, 2H), 2.20(s, 6H), 0.94(s, 6H). MS(ESI):C 19 H 25 The calculated value for N5O is 339, and the measured value is 340 (M+H). + .

[0282] Example 10: Synthesis of 2-chloro-6-(3-(dimethylamino)propyl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine-5-one (compound 13A)

[0283] [ka] 5 mL of THF was mixed with methyl 6-chloro-2-(chloromethyl)nicotinate (150 mg, 681.67 μmol) and N2,N2,2-trimethylpropane-1,2-diamine (348 mg, 3.41 mmol) and stirred overnight at room temperature. The reaction mixture was concentrated, and the residue was purified by Büch's pure flash chromatography (silica, 24 g) using 0-5% 0.7N NH3-MeOH dissolved in DCM to obtain the desired product, 2-chloro-6-(3-(dimethylamino)propyl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine-5-one (compound 13A) (123 mg, yield 67%), as a white solid. 1 H NMR (400MHz, DMSO)δ 8.09 (d. MS(ESI):C 12 H 16 The calculated value for ClN3O is 253, and the measured value is 254 (M+H). + .

[0284] Example 11: Synthesis of 6-(3-(dimethylamino)propyl)-2-((pyridine-3-ylmethyl)amino)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine-5-one (compound 13)

[0285] [ka] To a solution of 2-chloro-6-(3-(dimethylamino)propyl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine-5-one (100 mg, 394.12 μmol) dissolved in 1-BuOH (4 mL) and DIPEA (0.34 mL, 1.97 mmol), pyridine-3-ylmethaneamine (213 mg, 1.97 mmol) was added at room temperature. This mixture was then heated to 140 °C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's pure flash chromatography (silica, 40 g) using 0-10% 0.7N NH3-MeOH dissolved in DCM to obtain the desired product, 6-(3-(dimethylamino)propyl)-2-((pyridine-3-ylmethyl)amino)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine-5-one (compound 13) (74 mg, yield 58%), as a white solid. 1 1H NMR (400 MHz, DMSO) δ 8.57(dd,J=2.3, 0.9Hz, 1H), 8.46(dd,J=4.8, 1.7Hz, 1H), 8.01(t, J=6.0Hz, 1H), 7.80-7.71(m, 1H), 7.60(d, J=8.5Hz, 1H), 7.36(ddd,J=7.8, 4.8, 0 .9Hz, 1H), 6.60(d, J=8.6Hz, 1H), 4.58(d, J=5.9Hz, 2H), 4.29(s, 2H), 3.5 1(t, J=6.5Hz, 2H), 2.99(t, J=8.2Hz, 2H), 2.70(s, 6H), 2.05-1.89(m, 2H). MS(ESI):C 18 H 23 The calculated value for N5O is 325, and the measured value is 326 (M+H). + .

[0286] Example 12: Synthesis of N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (Compound 14A)

[0287] [ka] To 5 mL of THF, methyl 6-chloro-2-(chloromethyl)nicotinate (150 mg, 681.67 μmol) and N-(2-aminoethyl)acetamide (348 mg, 3.41 mmol) were added and the mixture was stirred overnight at room temperature. The reaction mixture was concentrated, and the residue was purified by Büch's pure flash chromatography (silica, 24 g) using 0-5% 0.7N NH3-MeOH dissolved in DCM to obtain the desired product, N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (compound 14A) (169 mg, yield 98%), as a white solid. 1 H NMR (400MHz, DMSO)δ 8.12 (d. MS(ESI):C 11 H 12 The calculated value for ClN3O2 is 253, and the measured value is 254 (M+H). + .

[0288] Example 13: Synthesis of N-(2-(5-oxo-2-((pyridine-3-ylmethyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (compound 14)

[0289] [ka] To the solution product of N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (100 mg, 394.19 μmol) dissolved in 1-BuOH (4 mL) and DIPEA (0.34 mL, 1.97 mmol), pyridine-3-ylmethaneamine (213 mg, 1.97 mmol) was added at room temperature. This mixture was then heated to 140 °C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's Pure Flash Chromatography (silica, 40 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(5-oxo-2-((pyridine-3-ylmethyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (compound 14) (101 mg, yield 79%), as a white solid. 1 1H NMR (400 MHz, DMSO) δ 8.56 (dd, J=2.3, 0.8Hz, 1H), 8.45 (dd, J=4.8, 1.7Hz, 1H), 7.94 (t, J=5.9Hz, 1H), 7.87(t, J=5.9Hz, 1H), 7.73(dt, J=7.8, 2.0Hz, 1H), 7.59(d, J=8.6Hz, 1 H), 7.34(ddd,J=7.8, 4.8, 0.9Hz, 1H), 6.56(d, J=8.6Hz, 1H), 4.57(d, J=5.9 Hz, 2H), 4.27(s, 2H), 3.51-3.42(m, 2H), 3.25(q, J=6.0Hz, 2H), 1.74(s, 3H). MS(ESI):C 17 H 19 Calculated value of N5O2: 325, measured value: 326 (M+H) + .

[0290] Example 14: Synthesis of N-(3-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)propyl)acetamide (Compound 15A)

[0291] [ka] To 5 mL of THF, methyl 6-chloro-2-(chloromethyl)nicotinate (150 mg, 681.67 μmol) and N-(3-aminopropyl)acetamide (396 mg, 3.41 mmol) were added and stirred overnight at room temperature. The reaction mixture was concentrated, and the residue was purified by Büch's pure flash chromatography (silica, 24 g) using 0-5% 0.7N NH3-MeOH dissolved in DCM to obtain the desired product, N-(3-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)propyl)acetamide (compound 15A) (83 mg, yield 45%), as a white solid. MS(ESI):C 12 H 14 The calculated value for ClN3O2 is 267, and the measured value is 268 (M+H). + .

[0292] Example 15: Synthesis of N-(3-(5-oxo-2-((pyridine-3-ylmethyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)propyl)acetamide (Compound 15)

[0293] [ka] To the solution product of N-(3-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)propyl)acetamide (80 mg, 298.83 μmol) dissolved in 1-BuOH (3 mL) and DIPEA (0.26 mL, 1.49 mmol), pyridine-3-ylmethaneamine (162 mg, 1.50 mmol) was added at room temperature. This mixture was then heated to 140 °C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's Pure Flash Chromatography (silica, 40 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(3-(5-oxo-2-((pyridine-3-ylmethyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)propyl)acetamide (compound 15) (54 mg, yield 53%), as a white solid. 11H NMR (400 MHz, DMSO) δ 8.57(dd,J=2.3, 0.9Hz, 1H), 8.45(dd,J=4.8, 1.7Hz, 1H), 7.90-7.81(m, 2 H), 7.77-7.70(m, 1H), 7.59(d, J=8.6Hz, 1H), 7.35(ddd,J=7.8, 4.8, 0.9H z, 1H), 6.56(d, J=8.6Hz, 1H), 4.58(d, J=5.9Hz, 2H), 4.25(s, 2H), 3.42(t , J=7.1Hz, 2H), 3.01(q, J=6.7Hz, 2H), 1.79(s, 3H), 1.67(p, J=7.1Hz, 2H). MS(ESI):C 18 H 21 Calculated value of N5O2: 339, measured value: 340 (M+H) + .

[0294] Example 16: Synthesis of N-(2-(5-oxo-2-((pyridine-2-ylmethyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (compound 20)

[0295] [ka] 400 mg, 1.58 mmol) of N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (dissolved in 1-BuOH (10 mL)) and DIPEA (1.37 mL, 7.88 mmol) were mixed with 2-pyridinemethanamine (853 mg, 7.88 mmol) at room temperature. The mixture was then heated to 140 °C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(5-oxo-2-((pyridine-2-ylmethyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (120 mg, yield 24%), as a pale yellow solid. 1H NMR (400MHz, CDCl3)δ 8.56(ddd,J=5.0, 1.8, 1.0Hz, 1H), 7.75-7.63(m, 2H), 7.32(dt, J=7.8, 1.0Hz, 1H), 7.22(ddd,J=7.6, 4.9, 1.1Hz, 1H), 6.57(s, 1H), 6.49( d, J=8.6Hz, 1H), 6.33(t, J=5.1Hz, 1H), 4.72(d, J=5.0Hz, 2H), 4.30(s, 2H), 3.71(dd,J=6.8, 4.6Hz, 2H), 3.55-3.49(m, 2H), 1.93(s, 3H). MS(ESI):C 17 H 19 Calculated value of N5O2: 325, measured value: 326 (M+H) + .

[0296] Example 17: Synthesis of N-(2-(5-oxo-2-((pyridine-3-ylmethyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (compound 21)

[0297] [ka] To the solution product of N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (300 mg, 1.12 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (0.98 mL, 5.6 mmol), 3-pyridineethanamine (606 mg, 5.60 mmol) was added at room temperature. This mixture was then heated to 140 °C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Buch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(5-oxo-2-((pyridine-3-ylmethyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (90 mg, yield 23%), as a pale yellow solid. 1H NMR (400MHz, CDCl3)δ 8.62(d, J=2.2Hz, 1H), 8.52(dd,J=4.8, 1.6Hz, 1H), 7.79-7.64(m, 2H), 7.30-7.26(m, 1H), 6.41(d, J=8.6Hz, 2H), 5.45(t, J=5.9Hz, 1H) , 4.65(d, J=5.9Hz, 2H), 4.30(s, 2H), 3.71(dd,J=6.8, 4.6Hz, 2H), 3.51(q, J=5.3Hz, 2H), 2.16(q, J=7.6Hz, 2H), 1.07(t, J=7.6Hz, 3H). MS(ESI):C 18 H 21 Calculated value of N5O2: 339, measured value: 340 (M+H) + .

[0298] Example 18: Synthesis of (R)-N-(2-(5-oxo-2-((1-(pyridine-3-yl)ethyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (compound 22)

[0299] [ka] To the solution product of N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (400 mg, 1.58 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (1.37 mL, 7.88 mmol), (R)-methyl-3-pyridinemethanamine (578 mg, 4.73 mmol) was added at room temperature. The mixture was then heated to 140 °C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, (R)-N-(2-(5-oxo-2-((1-(pyridine-3-yl)ethyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (110 mg, yield 21%), as a yellow solid. 1H NMR (400MHz, CDCl3)δ 8.65 (d. J=6.8Hz, 1H), 5.06(q, J=6.8Hz, 1H), 4.36-4.18(m, 2H), 3.70(td, J=5.7, 1.9Hz, 2H), 3.50(p, J=5.3Hz, 2H), 1.92(s, 3H), 1.61(d, J=6.8Hz, 3H). MS(ESI):C 18 H 21 Calculated value of N5O2: 339, measured value: 340 (M+H) + .

[0300] Example 19: Synthesis of (S)-N-(2-(5-oxo-2-((1-(pyridine-3-yl)ethyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (compound 23)

[0301] [ka] To the solution product of N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (400 mg, 1.58 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (1.37 mL, 7.88 mmol), (S)-methyl-3-pyridinemethanamine (578 mg, 4.73 mmol) was added at room temperature. The mixture was then heated to 140 °C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, (S)-N-(2-(5-oxo-2-((1-(pyridine-3-yl)ethyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (120 mg, yield 22%), as a yellow solid. 1H NMR (400MHz, CDCl3)δ 8.65 (d. d. MS(ESI):C 18 H 21 Calculated value of N5O2: 339, measured value: 340 (M+H) + .

[0302] Example 20: Synthesis of N-(2-(2-(((6-methylpyridine3-yl)methyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (Compound 24)

[0303] [ka] To the solution product of N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (400 mg, 1.58 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (1.37 mL, 7.88 mmol), 6-methyl-3-pyridinemethanamine (771 mg, 6.31 mmol) was added at room temperature. This mixture was then heated to 140 °C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(2-(((6-methylpyridine3-yl)methyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (130 mg, yield 24%), as a white solid. 1H NMR (400MHz, DMSO)δ 8.39(s, 1H), 8.29(d, J=4.9Hz, 1H), 7.90(t, J=5.9Hz, 1H), 7.67(t, J=5.5Hz, 1H), 7.55(d, J=8.6Hz, 1H), 7.17(d, J=4.9Hz, 1H), 6 .53(d, J=8.6Hz, 1H), 4.51(d, J=5.5Hz, 2H), 4.25(s, 2H), 3.43(t, J=6.0Hz, 2H), 3.22(q, J=6.1Hz, 2H), 2.31(s, 3H), 1.71(s, 3H). MS(ESI):C 18 H 21 Calculated value of N5O2: 339, measured value: 340 (M+H) + .

[0304] Example 21: Synthesis of N-(2-(2-(((4-methylpyridine3-yl)methyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (Compound 25)

[0305] [ka] To the solution product of N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (400 mg, 1.58 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (1.37 mL, 7.88 mmol), 4-methyl-3-pyridinemethanamine (771 mg, 6.31 mmol) was added at room temperature. This mixture was then heated to 140 °C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(2-(((4-methylpyridine3-yl)methyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (90 mg, yield 17%), as a white solid. 1H NMR (400MHz, DMSO)δ 8.39(d, J=2.3Hz, 1H), 7.89(t, J=5.8Hz, 1H), 7.77(t, J=5.9Hz, 1H), 7.64-7.50(m, 2H), 7.16(d, J=7.9Hz, 1H), 6.50(d, J =8.5Hz, 1H), 4.48(d, J=5.8Hz, 2H), 4.23(s, 2H), 3.43(t, J=6.0Hz, 2H), 3.22(q, J=6.0Hz, 2H), 2.39(s, 3H), 1.71(s, 3H). MS(ESI):C 18 H 21 Calculated value of N5O2: 339, measured value: 340 (M+H) + .

[0306] Example 22: Synthesis of N-(2-(2-(((5-fluoropyridine-3-yl)methyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (Compound 26)

[0307] [ka] To the solution product of N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (300 mg, 1.18 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (1.03 mL, 5.91 mmol), 5-fluoro-3-pyridinemethanamine (597 mg, 4.73 mmol) was added at room temperature. This mixture was then heated to 140 °C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(2-(((5-fluoropyridine-3-yl)methyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (140 mg, yield 34%), as a white solid. 1H NMR (400MHz, DMSO)δ 8.42(d, J=2.5Hz, 2H), 7.87(dt, J=16.8, 5.9Hz, 2H), 7.69-7.53(m, 2H), 6.54(d, J=8.5Hz, 1H), 4.59(d, J=5.9Hz, 2H), 4.23(s, 2H), 3.43(t, J=6.0Hz, 2H), 3.21(q, J=6.1Hz, 2H), 1.71(s, 3H). MS(ESI):C 17 H 18 The calculated value for FN5O2 is 343, and the measured value is 344 (M+H). + .

[0308] Example 23: Synthesis of N-(2-(5-oxo-2-((pyridine-4-ylmethyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (compound 27)

[0309] [ka] To the solution product of N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (300 mg, 1.18 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (1.03 mL, 5.91 mmol), 4-pyridinemethanamine (639 mg, 5.91 mmol) was added at room temperature. This mixture was then heated to 140 °C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Buch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(5-oxo-2-((pyridine-4-ylmethyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (145 mg, yield 38%), as a pale yellow solid. 1H NMR (400MHz, CDCl3)δ 8.64-8.48(m, 2H), 7.75(d, J=8.5Hz, 1H), 7.37-7.18(m, 2H), 6.41(d, J=8.5Hz, 2H), 5.46(t, J=6.2Hz, 1 H), 4.67(d, J=6.1Hz, 2H), 4.29(s, 2H), 3.71(dd,J=6.8, 4.5Hz, 2H), 3.51(q, J=5.3Hz, 2H), 1.92(s, 3H). MS(ESI):C 17 H 19 Calculated value of N5O2: 325, measured value: 326 (M+H) + .

[0310] Example 24: Synthesis of N-(2-(2-((2-methoxybenzyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (Compound 28)

[0311] [ka] To the solution product of N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (400 mg, 1.58 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (1.37 mL, 7.88 mmol), 2-methoxybenzylamine (1.08 g, 7.88 mmol) was added at room temperature. This mixture was then heated to 140 °C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(2-((2-methoxybenzyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (160 mg, yield 29%), as a white solid. 1H NMR (400MHz, DMSO)δ 7.89(d, J=6.6Hz, 1H), 7.65-7.48(m, 2H), 7.19(q, J=7.4Hz, 2H), 6.96(dd, J=8.2, 1.9Hz, 1H), 6.85(td, J=7.4, 1.9Hz, 1H), 6.53(d, J=8.6 Hz, 1H), 4.47(d, J=5.2Hz, 2H), 4.21(d, J=2.1Hz, 2H), 3.79(d, J=2.1Hz, 3H), 3.51-3.40(m, 2H), 3.23-3.16(m, 2H), 1.71(d, J=2.2Hz, 3H). MS(ESI):C 19 H 22 Calculated value of N4O3: 354, measured value: 355 (M+H) + .

[0312] Example 25: Synthesis of N-(2-(2-((5-fluoro-2-methoxybenzyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (Compound 29)

[0313] [ka] To the solution product of N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (400 mg, 1.58 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (1.37 mL, 7.88 mmol), 5-fluoro-2-methoxybenzenemethaneamine (734 mg, 4.73 mmol) was added at room temperature. This mixture was then heated to 140 °C overnight and subsequently cooled to room temperature. This reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(2-((5-fluoro-2-methoxybenzyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (130 mg, yield 22%), as a white solid. 1H NMR (400MHz, DMSO)δ 7.89(t, J=5.9Hz, 1H), 7.64(t, J=6.0Hz, 1H), 7.56(dd,J=8.4, 1.0Hz, 1H), 7.13-6.90(m, 3H), 6.55(d, J=8.6Hz, 1H), 4.47 (d, J=5.9Hz, 2H), 4.22(s, 2H), 3.78(d, J=1.1Hz, 3H), 3.42(t, J=6.0Hz, 2H), 3.21(q, J=6.0Hz, 2H), 1.71(d, J=1.2Hz, 3H). MS(ESI):C 19 H 21 The calculated value for FN4O3 is 372, and the measured value is 373 (M+H). + .

[0314] Example 26: Synthesis of N-(2-(2-((2-fluoro-6-methoxybenzyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (compound 30)

[0315] [ka] To the solution product of N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (400 mg, 1.58 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (1.37 mL, 7.88 mmol), 2-fluoro-6-methoxybenzenemethaneamine (734 mg, 4.73 mmol) was added at room temperature. This mixture was then heated to 140 °C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(2-((2-fluoro-6-methoxybenzyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (150 mg, yield 26%), as a white solid. 1H NMR (400MHz, DMSO)δ 7.92(d, J=6.1Hz, 1H), 7.51(dd,J=8.5, 2.0Hz, 1H), 7.39-7.24(m, 2H), 6.95-6.72(m, 2H), 6.51(dd,J=8.7, 2.0Hz, 1H), 4.45(d, J=4.6Hz, 2H), 4.27(d, J=2.0Hz, 2H), 3.80(d, J=2.0Hz, 3H), 3.44(t, J=6.1Hz, 2H), 3.23(d, J=6.8Hz, 2H), 1.73(d, J=2.0Hz, 3H). MS(ESI):C 19 H 21 The calculated value for FN4O3 is 372, and the measured value is 373 (M+H). + .

[0316] Example 27: Synthesis of N-(2-(2-((4-fluoro-2-methoxybenzyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (Compound 31)

[0317] [ka] To the solution product of N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (400 mg, 1.58 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (1.37 mL, 7.88 mmol), 4-fluoro-2-methoxybenzenemethaneamine (734 mg, 4.73 mmol) was added at room temperature. This mixture was then heated to 140 °C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Buch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(2-((4-fluoro-2-methoxybenzyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (164 mg, yield 28%), as a white solid. 1H NMR (400MHz, DMSO)δ 7.89(t, J=5.8Hz, 1H), 7.55(ddd,J=10.8, 7.8, 3.6Hz, 2H), 7.27-7.12(m, 1H), 6.87(dt, J=11.3, 2.6Hz, 1H), 6.67(tt, J=8.5, 2.6Hz, 1H), 6.52(d , J=8.6Hz, 1H), 4.42(d, J=5.7Hz, 2H), 4.22(d, J=2.3Hz, 2H), 3.80(d, J= 2.3Hz, 3H), 3.53-3.40(m, 2H), 3.26-3.15(m, 2H), 1.71(d, J=2.3Hz, 3H). MS(ESI):C 19 H 21 The calculated value for FN4O3 is 372, and the measured value is 373 (M+H). + .

[0318] Example 28: Synthesis of N-(2-(2-(((4-methoxypyridine-3-yl)methyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (Compound 32)

[0319] [ka] To the solution product of N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (400 mg, 1.58 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (1.37 mL, 7.88 mmol), 4-methoxy-3-pyridinemethanamine (654 mg, 4.73 mmol) was added at room temperature. This mixture was then heated to 140 °C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(2-(((4-methoxypyridine-3-yl)methyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (98 mg, yield 18%), as a white solid. 1H NMR (400MHz, DMSO)δ 8.33(d, J=5.6Hz, 1H), 8.25(s, 1H), 7.90(t, J=5.8Hz, 1H), 7.61(t, J=5.7Hz, 1H), 7.55(d, J=8.6Hz, 1H), 7.01(d, J=5.6Hz, 1H), 6 .54(d, J=8.5Hz, 1H), 4.46(d, J=5.6Hz, 2H), 4.23(s, 2H), 3.85(s, 3H), 3.43(t, J=6.0Hz, 2H), 3.20(d, J=6.0Hz, 2H), 1.71(s, 3H). MS(ESI):C 18 H 21 Calculated value of N5O3: 355, measured value: 356 (M+H) + .

[0320] Example 29: Synthesis of N-(2-(2-((5-fluoro-2-methoxybenzyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (Compound 33)

[0321] [ka] To the solution product of N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (300 mg, 1.12 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (0.98 mL, 5.60 mmol), 5-fluoro-2-methoxybenzenemethaneamine (522 mg, 3.36 mmol) was added at room temperature. This mixture was then heated to 140 °C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Buch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(2-((5-fluoro-2-methoxybenzyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (165 mg, yield 38%), as a white solid. 1H NMR (400MHz, DMSO)δ 8.33(d, J=5.6Hz, 1H), 8.25(s, 1H), 7.90(t, J=5.8Hz, 1H), 7.61(t, J=5.7Hz, 1H), 7.55(d, J=8.6Hz, 1H), 7.01(d, J=5.6Hz, 1H), 6 .54(d, J=8.5Hz, 1H), 4.46(d, J=5.6Hz, 2H), 4.23(s, 2H), 3.85(s, 3H), 3.43(t, J=6.0Hz, 2H), 3.20(d, J=6.0Hz, 2H), 1.71(s, 3H). MS(ESI):C 20 H 23 The calculated value for FN4O3 is 386, and the measured value is 387 (M+H). + .

[0322] Example 30: Synthesis of N-(2-(2-(((6-methylpyridine3-yl)methyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (Compound 34)

[0323] [ka] To the solution product of N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (200 mg, 0.75 mmol) dissolved in 1-BuOH (8 mL) and DIPEA (0.65 mL, 3.74 mmol), 6-methyl-3-pyridinemethanamine (274 mg, 2.24 mmol) was added at room temperature. This mixture was then heated to 140°C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(2-(((6-methylpyridine3-yl)methyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (85 mg, yield 32%), as a white solid. 1H NMR (400MHz, DMSO)δ 8.38 (d. d, J=5.9Hz, 2H), 4.23(s, 2H), 3.43(t, J=6.2Hz, 2H), 3.22(q, J=5.9Hz, 2H), 2.39(s, 3H), 1.97(q, J=7.6Hz, 2H), 0.89(td, J=7.6, 1.1Hz, 3H). MS(ESI):C 19 H 23 Calculated value of N5O2: 353, measured value: 354 (M+H) + .

[0324] Example 31: Synthesis of N-(2-(2-((4-methylbenzyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (Compound 35)

[0325] [ka] To the solution product of N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (300 mg, 1.18 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (1.03 mL, 5.91 mmol), 4-methylbenzylamine (430 mg, 3.55 mmol) was added at room temperature. This mixture was then heated to 140 °C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(2-((4-methylbenzyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (110 mg, yield 28%), as a white solid. 1H NMR (400MHz, DMSO)δ 7.89(t, J=5.9Hz, 1H), 7.71(t, J=5.9Hz, 1H), 7.53(d, J=8.6Hz, 1H), 7.28-7.15(m, 2H), 7.15-6.99(m, 2H), 6.49(d, J =8.6Hz, 1H), 4.46(d, J=5.9Hz, 2H), 4.22(s, 2H), 3.47-3.35(m, 2H), 3.21(q, J=6.0Hz, 2H), 2.23(s, 3H), 1.71(s, 3H). MS(ESI):C 19 H 22 Calculated value of N4O2: 338, measured value: 339 (M+H) + .

[0326] Example 32: Synthesis of N-(2-(2-((2,4-dimethylbenzyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (compound 36)

[0327] [ka] To the solution product of N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (300 mg, 1.18 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (1.03 mL, 5.91 mmol), 2,4-dimethylbenzenemethaneamine (480 mg, 3.55 mmol) was added at room temperature. This mixture was then heated to 140 °C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(2-((2,4-dimethylbenzyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (110 mg, yield 26%), as a white solid. 1H NMR (400MHz, DMSO)δ 7.90(t, J=6.0Hz, 1H), 7.63-7.48(m, 2H), 7.10(d, J=7.7Hz, 1H), 6.96(d, J=1.7Hz, 1H), 6.91(dd, J=7.7, 1.9Hz, 1H), 6.51(d, J=8 .6Hz, 1H), 4.42(d, J=5.5Hz, 2H), 4.23(s, 2H), 3.52-3.37(m, 2H), 3.22(q, J=6.0Hz, 2H), 2.24(s, 3H), 2.20(s, 3H), 1.72(s, 3H). MS(ESI):C 20 H 24 Calculated value of N4O2: 352, measured value: 353 (M+H) + .

[0328] Example 33: Synthesis of N-(2-(5-oxo-2-((2,4,6-trifluorobenzyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (compound 37)

[0329] [ka] To the solution product of N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (300 mg, 1.18 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (1.03 mL, 5.91 mmol), 2,4,6-trifluorobenzenemethaneamine (572 mg, 3.55 mmol) was added at room temperature. This mixture was then heated to 140°C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Buch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(5-oxo-2-((2,4,6-trifluorobenzyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (95 mg, yield 21%), as a pale yellow solid. 1H NMR (400MHz, DMSO)δ 7.90(t, J=5.9Hz, 1H), 7.62(t, J=5.2Hz, 1H), 7.54(d, J=8.6Hz, 1H), 7.25-7.10(m, 2H), 6.49(d, J=8. 6Hz, 1H), 4.49(d, J=5.1Hz, 2H), 4.25(s, 2H), 3.51-3.41(m, 2H), 3.23(q, J=6.2Hz, 2H), 1.72(s, 3H). MS(ESI):C 18 H 17 The calculated value for F3N4O2 is 378, and the measured value is 379 (M+H). + .

[0330] Example 34: Synthesis of N-(2-methyl-1-(5-oxo-2-((pyridine-3-ylmethyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)propan-2-yl)acetamide (compound 38)

[0331] [ka] To the solution product of N-(1-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)-2-methylpropan-2-yl)acetamide (300 mg, 1.06 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (0.93 mL, 5.32 mmol), 3-pyridinemethanamine (576 mg, 5.32 mmol) was added at room temperature. This mixture was then heated to 140 °C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-methyl-1-(5-oxo-2-((pyridine-3-ylmethyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)propan-2-yl)acetamide (115 mg, yield 31%), as a white solid. 1H NMR (400MHz, DMSO)δ 8.67-8.50(m, 1H), 8.41(dd, J=4.8, 1.7Hz, 1H), 7.84(t, J=5.9Hz, 1H), 7.80-7.66(m, 1H), 7.58(d, J=8.6Hz, 1H), 7.50(s, 1H), 7.3 1(ddd,J=7.8, 4.8, 0.9Hz, 1H), 6.54(d, J=8.6Hz, 1H), 4.55(d, J=5.9Hz, 2H), 4.25(s, 2H), 3.63(s, 2H), 1.77(s, 3H), 1.17(s, 6H). MS(ESI):C 19 H 23 Calculated value of N5O2: 353, measured value: 354 (M+H) + .

[0332] Example 35: Synthesis of N-(2-(5-oxo-2-((pyrimidine-2-ylmethyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (compound 39)

[0333] [ka] To the solution product of N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (300 mg, 1.18 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (0.82 mL, 4.73 mmol), 2-pyrimidinemethanamine (258 mg, 2.37 mmol) was added at room temperature. This mixture was then heated to 140 °C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(5-oxo-2-((pyrimidine-2-ylmethyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (120 mg, yield 31%), as a yellow solid. 1H NMR (400MHz, DMSO)δ 8.73(d, J=4.9Hz, 2H), 7.88(t, J=5.9Hz, 1H), 7.80(t, J=5.9Hz, 1H), 7.55(d, J=8.6Hz, 1H), 7.35(t, J=4.9Hz, 1H), 6.63(d, J=8.6Hz, 1H), 4.73(d, J=5.9Hz, 2H), 4.18(s, 2H), 3.51-3.36(m, 2H), 3.20(q, J=6.0Hz, 2H), 1.70(s, 3H). MS(ESI):C 16 H 18 Calculated value of N6O2: 326, measured value: 327 (M+H) + .

[0334] Example 36: Synthesis of N-(2-(2-(((6-cyanopyridine-3-yl)methyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (Compound 40)

[0335] [ka] To the solution product of N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (300 mg, 1.18 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (0.82 mL, 4.73 mmol), 5-(aminomethyl)-2-pyridinecarbonitride (315 mg, 2.37 mmol) was added at room temperature. This mixture was then heated to 140°C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Buch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(2-(((6-cyanopyridine-3-yl)methyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (98 mg, yield 24%), as a pale yellow solid. 1H NMR (400MHz, DMSO)δ 8.69(dd, J=2.1, 0.9Hz, 1H), 8.08-7.81(m, 4H), 7.59(d, J=8.6Hz, 1H), 6.56(d, J=8.6Hz, 1H), 4.64(d, J=6.0Hz, 2H), 4.21(s, 2H), 3.42(t, J=6.1Hz, 2H), 3.21(p, J=6.6Hz, 2H), 1.71(s, 3H). MS(ESI):C 18 H 18 Calculated value of N6O2: 350, measured value: 351 (M+H) + .

[0336] Example 37: Synthesis of N-(2-(2-(((6-cyanopyridine-3-yl)methyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (Compound 41)

[0337] [ka] To the solution product of N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (300 mg, 1.18 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (0.82 mL, 4.73 mmol), 5-(aminomethyl)-3-pyridinecarbonitride (315 mg, 2.37 mmol) was added at room temperature. This mixture was then heated to 140°C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Buch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(2-(((6-cyanopyridine-3-yl)methyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (105 mg, yield 25%), as a pale yellow solid. 1H NMR (400MHz, DMSO)δ 8.87(d, J=2.0Hz, 1H), 8.80(d, J=2.2Hz, 1H), 8.20(t, J=2.1Hz, 1H), 7.88(dd, J=9.7, 4.1Hz, 2H), 7.59(d, J=8.5Hz, 1 H), 6.55(d, J=8.5Hz, 1H), 4.60(d, J=5.9Hz, 2H), 4.23(s, 2H), 3.51-3.39(m, 2H), 3.21(q, J=6.0Hz, 2H), 1.71(s, 3H). MS(ESI):C 18 H 18 Calculated value of N6O2: 350, measured value: 351 (M+H) + .

[0338] Example 38: Synthesis of N-(2-(5-oxo-2-((pyridine-3-ylmethyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)cyclopropanecarboxamide (Compound 42)

[0339] [ka] To the solution product of N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)cyclopropanecarboxamide (300 mg, 1.07 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (0.75 mL, 4.29 mmol), 3-pyridinemethanamine (232 mg, 2.14 mmol) was added at room temperature. This mixture was then heated to 140°C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(5-oxo-2-((pyridine-3-ylmethyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)cyclopropanecarboxamide (114 mg, yield 30%), as a pale yellow solid. 1H NMR (400MHz, DMSO)δ 8.53 (dd, J=2.3, 0.9Hz, 1H), 8.41 (dd, J=4.8, 1.7Hz, 1H), 8.11 (t, J=5.9Hz, 1H), 7. 82(t, J=6.0Hz, 1H), 7.78-7.67(m, 1H), 7.56(d, J=8.5Hz, 1H), 7.31(ddd,J=7.8, 4. 8, 0.9Hz, 1H), 6.53(d, J=8.6Hz, 1H), 4.54(d, J=5.9Hz, 2H), 4.23(s, 2H), 3.44(t, J =6.1Hz, 2H), 3.25(d, J=6.0Hz, 2H), 1.43(tt, J=7.2, 5.6Hz, 1H), 0.67-0.48(m, 4H). MS(ESI):C 19 H 21 Calculated value of N5O2: 351, measured value: 352 (M+H) + .

[0340] Example 39: Synthesis of N-(2-(2-(((5-cyanopyridine-3-yl)methyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)cyclopropanecarboxamide (Compound 43)

[0341] [ka] To the solution product of N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)cyclopropanecarboxamide (300 mg, 1.07 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (0.75 mL, 4.29 mmol), 5-(aminomethyl)-3-pyridinecarbonitride (286 mg, 2.14 mmol) was added at room temperature. This mixture was then heated to 140°C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(2-(((5-cyanopyridine-3-yl)methyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)cyclopropanecarboxamide (95 mg, yield 24%), as a white solid. 1 H NMR (400MHz, DMSO)δ 8.87(d, J=2.0Hz, 1H), 8.80(d, J=2.2Hz, 1H), 8.19(t, J=2.1Hz, 1H), 8.10(t, J=5.9Hz, 1H), 7.87(t, J=5.9Hz, 1H), 7.59(d, J=8.5Hz, 1H), 6.55( d, J=8.5Hz, 1H), 4.60(d, J=5.9Hz, 2H), 4.23(s, 2H), 3.44(t, J=6.1Hz, 2H), 3.25(q, J=5.9Hz, 2H), 1.42(p, J=6.3Hz, 1H), 0.55(d, J=5.7Hz, 4H). MS(ESI):C 20 H 20 Calculated value of N6O2: 376, measured value: 377 (M+H) + .

[0342] Example 40: Synthesis of 2,2,2-trifluoro-N-(2-(5-oxo-2-((pyridine-3-ylmethyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (compound 44)

[0343] [ka] To the solution product of N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)-2,2,2-trifluoroacetamide (300 mg, 0.98 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (0.68 mL, 3.90 mmol), 3-pyridinemethanamine (316 mg, 2.93 mmol) was added at room temperature. This mixture was then heated to 140 °C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Buch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, 2,2,2-trifluoro-N-(2-(5-oxo-2-((pyridine-3-ylmethyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (80 mg, yield 22%), as a yellow solid. 1 H NMR (400MHz, DMSO)δ 9.46(t, J=5.8Hz, 1H), 8.53(dd,J=2.4, 0.8Hz, 1H), 8.41(dd,J=4.8, 1.7Hz, 1H), 7.85(t, J=5.9Hz, 1H), 7.79-7.66(m, 1H), 7.57(d, J=8.6Hz, 1H), 7.31(ddd,J=7.8, 4.8, 0.9Hz, 1H), 6.53(d, J=8.6Hz, 1H), 4.54(d, J=5.9Hz, 2H), 4.23(s, 2H), 3.55(dd,J=6.6, 5.0Hz, 2H), 3.38(t, J=5.8Hz, 2H). MS(ESI):C 17 H 16 The calculated value for F3N5O2 is 379, and the measured value is 380 (M+H). + .

[0344] Example 41: Synthesis of N-(2-(2-(((4-methylpyridine3-yl)methyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (Compound 45)

[0345] [ka] To the solution product of N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (300 mg, 1.12 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (0.98 mL, 5.60 mmol), 4-methyl-3-pyridinemethanamine (274 mg, 2.24 mmol) was added at room temperature. This mixture was then heated to 140°C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(2-(((4-methylpyridine3-yl)methyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (133 mg, yield 34%), as a white solid. 1 1H NMR (400 MHz, DMSO) δ 8.39(s, 1H), 8.29(d, J=4.9Hz, 1H), 7.82(t, J=5.8Hz, 1H), 7.67(t, J=5.5Hz , 1H), 7.55(d, J=8.6Hz, 1H), 7.17(dt, J=4.9, 0.7Hz, 1H), 6.53(d, J=8.6Hz, 1H), 4.51(d, J=5.4Hz, 2H), 4.24(s, 2H), 3.43(q, J=6.4Hz, 2H), 3.23(q, J=6 .1Hz, 2H), 2.39-2.22(m, 3H), 1.97(q, J=7.6Hz, 2H), 0.89(t, J=7.6Hz, 3H). MS(ESI):C 19 H 23 Calculated value of N5O2: 353, measured value: 354 (M+H) + .

[0346] Example 42: Synthesis of N-(2-(5-oxo-2-((pyrazine-2-ylmethyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (compound 46)

[0347] [ka] To the solution product of N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (300 mg, 1.12 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (0.98 mL, 5.60 mmol), 2-aminomethylpyrazine (245 mg, 2.24 mmol) was added at room temperature. This mixture was then heated to 140°C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(5-oxo-2-((pyrazine-2-ylmethyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (120 mg, yield 31%), as a yellow solid. 1 H NMR (400MHz, DMSO)δ 8.65-8.54(m, 2H), 8.49(d, J=2.6Hz, 1H), 7.92(t, J=5.9Hz, 1H), 7.80(t, J=5.9Hz, 1H), 7.58(d, J=8.6Hz, 1H), 6.59(d, J=8.6Hz, 1 H), 4.67(d, J=5.9Hz, 2H), 4.20(s, 2H), 3.42(t, J=6.0Hz, 2H), 3.21(q, J=6.0Hz, 2H), 1.96(q, J=7.6Hz, 2H), 0.88(t, J=7.6Hz, 3H). MS(ESI):C 17 H 20 Calculated value of N6O2: 340, measured value: 341 (M+H) + .

[0348] Example 43: Synthesis of N-(2-(5-oxo-2-((pyridine-3-ylmethyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)butylamide (compound 47)

[0349] [ka] To the solution product of N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)butylamide (300 mg, 1.06 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (0.93 mL, 5.32 mmol), 3-pyridinemethanamine (230 mg, 2.13 mmol) was added at room temperature. This mixture was then heated to 140 °C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(5-oxo-2-((pyridine-3-ylmethyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)butylamide (125 mg, yield 33%), as a white solid. 1 H NMR (400MHz, DMSO)δ 8.53 (dd, J=2.3, 0.9Hz, 1H), 8.41 (dd, J=4.8, 1.7Hz, 1H), 7.83 (dt, J=9.0, 5.9Hz, 2H), 7.69(dt, J=7.9, 1.9Hz, 1H), 7.56(d, J=8.6Hz, 1H), 7.31(ddd,J=7.8, 4.8, 0.9Hz, 1H), 6.52(d, J=8.6Hz, 1H), 4.54(d, J=5.9Hz, 2H), 4.23(s, 2H), 3.43(t, J=6.0Hz, 2H), 3.23 (q, J=5.7Hz, 2H), 1.93(t, J=7.3Hz, 2H), 1.40(h, J=7.4Hz, 2H), 0.73(t, J=7.4Hz, 3H). MS(ESI):C 19 H 23 Calculated value of N5O2: 353, measured value: 354 (M+H) + .

[0350] Example 44: Synthesis of N-(2-(5-oxo-2-((pyrazine-2-ylmethyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)butylamide (compound 48)

[0351] [ka] To the solution product of N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)butylamide (300 mg, 1.06 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (0.93 mL, 5.32 mmol), 2-aminomethylpyrazine (232 mg, 2.13 mmol) was added at room temperature. This mixture was then heated to 140 °C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Buch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(5-oxo-2-((pyrazine-2-ylmethyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)butylamide (95 mg, yield 25%), as a yellow solid. 1 H NMR (400MHz, DMSO)δ 8.65-8.45(m, 3H), 7.92(t, J=5.9Hz, 1H), 7.83(t, J=5.8Hz, 1H), 7.57(d, J=8.6Hz, 1H), 6.59(d, J=8.6Hz, 1H), 4.67(d, J=5.9Hz, 2H), 4.20(s, 2H), 3.43(t, J=5.9Hz, 2H), 3.24-3.14(m, 2H), 1.93(t, J=7.3Hz, 2H), 1.39(h, J=7.3Hz, 2H), 0.72(t, J=7.4Hz, 3H). MS(ESI):C 18 H 22 Calculated value of N6O2: 354, measured value: 355 (M+H) + .

[0352] Example 45: Synthesis of N-(2-(5-oxo-2-((pyrazine-2-ylmethyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)cyclopropanecarboxamide (compound 49)

[0353] [ka] To the solution product of N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)cyclopropanecarboxamide (300 mg, 1.07 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (0.93 mL, 5.36 mmol), 2-aminomethylpyrazine (234 mg, 2.14 mmol) was added at room temperature. This mixture was then heated to 140 °C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(5-oxo-2-((pyrazine-2-ylmethyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)cyclopropanecarboxamide (125 mg, yield 33%), as a yellow solid. 1 H NMR (400MHz, DMSO)δ 8.67-8.54(m, 2H), 8.49(d, J=2.6Hz, 1H), 8.10(t, J=5.8Hz, 1H), 7.93(t, J=5.9Hz, 1H), 7.58(d, J=8.6Hz, 1H), 6.60(d, J=8.6 Hz, 1H), 4.67(d, J=5.9Hz, 2H), 4.20(s, 2H), 3.47-3.38(m, 2H), 3.26-3.15(m, 2H), 1.42(p, J=6.3Hz, 1H), 0.63-0.46(m, 4H). MS(ESI):C 18 H 20 Calculated value of N6O2: 352, measured value: 353 (M+H) + .

[0354] Example 46: N-(2-(2-((4-fluorobenzyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (compound 51)

[0355] [ka] Preparation: N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (300 mg, 1.18 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (1.03 mL, 5.91 mmol) were mixed with (4-fluorophenyl)methanamine (296 mg, 2.37 mmol) at room temperature. The mixture was then heated to 140 °C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(2-((4-fluorobenzyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (134 mg, yield 33%), as a white solid. 1 H NMR (400MHz, DMSO)δ 7.90(t, J=5.8Hz, 1H), 7.77(t, J=6.0Hz, 1H), 7.55(d, J=8.6Hz, 1H), 7.33(ddt, J=8.8, 5.4, 2.6Hz, 2H), 7.19-7.05(m, 2H), 6.50(d, J=8.5Hz, 1H), 4.50(d, J=5.9Hz, 2H), 4.23(s, 2H), 3.52-3.37(m, 2H), 3.21(q, J=6.0Hz, 2H), 1.71(s, 3H). MS(ESI):C 18 H 19 The calculated value for FN4O2 is 342, and the measured value is 343 (M+H). + .

[0356] Example 47: N-(2-(2-((2,4-difluorobenzyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (compound 52)

[0357] [ka] Preparation: To a solution of N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (300 mg, 1.18 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (1.03 mL, 5.91 mmol), (2,4-difluorophenyl)methanamine (339 mg, 2.37 mmol) was added at room temperature. This mixture was then heated to 140 °C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(2-((2,4-difluorobenzyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (140 mg, yield 33%), as a white solid. 1 H NMR (400MHz, DMSO)δ 7.90(t, J=5.8Hz, 1H), 7.74(t, J=5.8Hz, 1H), 7.56(d, J=8.6Hz, 1H), 7.39(td, J=8.7, 6.7Hz, 1H), 7.19(ddd,J=10.6, 9.3, 2.6Hz, 1H), 7.01(tdd , J=8.5, 2.6, 1.0Hz, 1H), 6.53(d, J=8.6Hz, 1H), 4.52(d, J=5.7Hz, 2H), 4.23(s, 2H), 3.43(t, J=6.0Hz, 2H), 3.21(q, J=6.0Hz, 2H), 1.71(s, 3H). MS(ESI):C 18 H 18 The calculated value for F2N4O2 is 360, and the measured value is 361 (M+H). + .

[0358] Example 48: N-(2-(5-oxo-2-((2,4,5-trifluorobenzyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (compound 53)

[0359] [ka] Preparation: To a solution of N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (300 mg, 1.18 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (1.03 mL, 5.91 mmol), (2,4,5-trifluorophenyl)methanamine (381 mg, 2.37 mmol) was added at room temperature. This mixture was then heated to 140 °C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(5-oxo-2-((2,4,5-trifluorobenzyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (116 mg, yield 26%), as a white solid. 1 H NMR (400MHz, DMSO)δ 7.89(t, J=5.8Hz, 1H), 7.77(t, J=5.9Hz, 1H), 7.62-7.45(m, 2H), 7.39(ddd,J=11.2, 9.1, 6.8Hz, 1H), 6.54(d, J=8.6Hz, 1H), 4.51(d, J=5.8Hz, 2H), 4.23(s, 2H), 3.43(t, J=6.0Hz, 2H), 3.21(q, J=6.0Hz, 2H), 1.71(s, 3H). MS(ESI):C 18 H 17 The calculated value for F3N4O2 is 378, and the measured value is 379 (M+H). + .

[0360] Example 49: N-(2-(2-((5-chloro-2,4-difluorobenzyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (compound 54)

[0361] [ka] Preparation: To a solution of N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (300 mg, 1.18 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (1.03 mL, 5.91 mmol), (5-chloro-2,4-difluorophenyl)methanamine (420 mg, 2.37 mmol) was added at room temperature. This mixture was then heated to 140 °C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(2-((5-chloro-2,4-difluorobenzyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (95 mg, yield 20%), as a white solid. 1 H NMR (400MHz, DMSO)δ 7.90(t, J=5.9Hz, 1H), 7.77(t, J=5.8Hz, 1H), 7.64-7.46(m, 3H), 6.55(d, J=8.5Hz, 1H), 4 .52(d, J=5.7Hz, 2H), 4.23(s, 2H), 3.53-3.39(m, 2H), 3.22(q, J=6.0Hz, 2H), 1.71(s, 3H). MS(ESI):C 18 H 17 The calculated value for F2ClN4O2 is 395, and the measured value is 396 (M+H). + .

[0362] Example 50: N-(2-(2-((2,4-difluorobenzyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (Compound 55)

[0363] [ka] Preparation: N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (300 mg, 1.12 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (0.98 mL, 5.60 mmol) were mixed with (2,4-difluorophenyl)methanamine (321 mg, 2.24 mmol) at room temperature. The mixture was then heated to 140°C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(2-((2,4-difluorobenzyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (140 mg, yield 33%), as a white solid. 1 H NMR (400MHz, DMSO)δ 7.81(t, J=5.9Hz, 1H), 7.74(t, J=5.8Hz, 1H), 7.56(d, J=8.5Hz, 1H), 7.39(td, J=8.7, 6.6Hz, 1H), 7.19(ddd,J=10.5, 9.3, 2.6Hz, 1H), 7.01(tdd,J=8.5, 2.6, 1 .0Hz, 1H), 6.52(d, J=8.6Hz, 1H), 4.52(d, J=5.7Hz, 2H), 4.23(s, 2H), 3.58-3. 38(m, 2H), 3.22(q, J=6.0Hz, 2H), 1.97(q, J=7.6Hz, 2H), 0.89(t, J=7.6Hz, 3H). MS(ESI):C 19 H 20 The calculated value for F2N4O2 is 374, and the measured value is 375 (M+H). + .

[0364] Example 51: N-(2-(5-oxo-2-((2,4,5-trifluorobenzyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (compound 56)

[0365] [ka] Preparation: N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (300 mg, 1.12 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (0.98 mL, 5.60 mmol) were mixed with (2,4,5-trifluorophenyl)methanamine (361 mg, 2.24 mmol) at room temperature. The mixture was then heated to 140°C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(5-oxo-2-((2,4,5-trifluorobenzyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (113 mg, yield 26%), as a white solid. 1 H NMR (400MHz, DMSO)δ 7.78(dt, J=19.9, 5.9Hz, 2H), 7.65-7.46(m, 2H), 7.39(ddd,J=11.1, 9.1, 6.8Hz, 1H), 6.54(d, J=8.5Hz, 1H), 4.51(d, J= 5.8Hz, 2H), 4.23(s, 2H), 3.53-3.35(m, 2H), 3.23(dt, J=11.7, 5.1Hz, 2H), 1.96(q, J=7.6Hz, 2H), 0.89(t, J=7.6Hz, 3H). MS(ESI):C 19 H 19 The calculated value for F3N4O2 is 392, and the measured value is 393 (M+H). + .

[0366] Example 52: N-(2-(2-(((5-methylpyridine3-yl)methyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (Compound 57)

[0367] [ka] Preparation: N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (300 mg, 1.12 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (0.98 mL, 5.60 mmol) were mixed with (5-methylpyridine3-yl)methanamine (361 mg, 2.24 mmol) at room temperature. The mixture was then heated to 140°C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(2-(((5-methylpyridine3-yl)methyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (123 mg, yield 31%), as a white solid. 1 H NMR (400MHz, DMSO)δ 8.39-8.30(m, 1H), 8.25(dd, J=2.2, 0.9Hz, 1H), 7.80(dt, J=15.0, 5.9Hz, 2H), 7.64-7.43(m, 2H), 6.51(d, J=8.6Hz, 1H), 4.50(d, J=5. 8Hz, 2H), 4.23(s, 2H), 3.50-3.37(m, 2H), 3.22(q, J=6.0Hz, 2H), 2.24(t, J=0.7Hz, 3H), 1.97(q, J=7.6Hz, 2H), 0.89(t, J=7.6Hz, 3H). MS(ESI):C 19 H 23 Calculated value of N5O2: 353, measured value: 354 (M+H) + .

[0368] Example 53: N-(2-(2-(((5-methylpyridine3-yl)methyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (Compound 58)

[0369] [ka] Preparation: To a solution of N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (300 mg, 1.18 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (1.03 mL, 5.91 mmol), (5-methylpyridine3-yl)methanamine (381 mg, 2.37 mmol) was added at room temperature. This mixture was then heated to 140°C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(2-(((5-methylpyridine3-yl)methyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (119 mg, yield 30%), as a white solid. 1 H NMR (400MHz, DMSO)δ 8.33(d, J=2.1Hz, 1H), 8.26(d, J=2.1Hz, 1H), 7.90(t, J=5.9Hz, 1H), 7.78(t, J=5.9Hz, 1H), 7.63-7.45(m, 2H), 6.52(d, J=8. 6Hz, 1H), 4.51(d, J=5.8Hz, 2H), 4.23(s, 2H), 3.55-3.37(m, 2H), 3.22(q, J=6.1Hz, 2H), 2.24(d, J=0.8Hz, 3H), 1.71(s, 3H). MS(ESI):C 18 H 21 Calculated value of N5O2: 339, measured value: 340 (M+H) + .

[0370] Example 54: N-(2-(2-(((2-methylpyridine3-yl)methyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (Compound 59)

[0371] [ka] Preparation: N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (300 mg, 1.12 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (0.98 mL, 5.60 mmol) were mixed with (2-methylpyridine3-yl)methanamine (361 mg, 2.24 mmol) at room temperature. The mixture was then heated to 140°C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(2-(((2-methylpyridine3-yl)methyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (97 mg, yield 24%), as a white solid. 1 H NMR (400MHz, DMSO)δ 8.29 (dd, J=4.8, 1.7Hz, 1H), 7.81 (t, J=5.9Hz, 1H), 7.72 (t, J=5.7Hz, 1H), 7.55 (dd, J=8.9, 1.7Hz, 2H), 7.25-7.09 (m, 1H), 6.54 (d, J=8.6Hz, 1H), 4.50(d, J=5.6Hz, 2H), 4.22(s, 2H), 3.54-3.38(m, 2H), 3.22(q, J=6.0Hz, 2H), 2.48(s, 3H), 1.97(q, J=7.6Hz, 2H), 0.89(t, J=7.6Hz, 3H). MS(ESI):C 19 H 23 Calculated value of N5O2: 353, measured value: 354 (M+H) + .

[0372] Example 55: N-(2-(2-(((2-methylpyridine3-yl)methyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (compound 60)

[0373] [ka] Preparation: N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (300 mg, 1.18 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (1.03 mL, 5.91 mmol) were mixed with (2-methylpyridine3-yl)methanamine (381 mg, 2.37 mmol) at room temperature. The mixture was then heated to 140°C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(2-(((2-methylpyridine3-yl)methyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (103 mg, yield 26%), as a white solid. 1 H NMR (400MHz, DMSO)δ 8.29(dd,J=4.8, 1.7Hz, 1H), 7.89(t, J=5.8Hz, 1H), 7.73(t, J=5.7Hz, 1H), 7.62-7.50(m, 2H), 7.14(dd,J=7.6, 4.8Hz, 1H), 6. 54(d, J=8.5Hz, 1H), 4.50(d, J=5.6Hz, 2H), 4.23(s, 2H), 3.43(t, J=6.0Hz, 2H), 3.23-3.16(m, 2H), 2.48(s, 3H), 1.71(s, 3H). MS(ESI):C 18 H 21 Calculated value of N5O2: 339, measured value: 340 (M+H) + .

[0374] Example 56: N-(2-(5-oxo-2-((3,4,5-trifluorobenzyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (compound 71)

[0375] [ka] Preparation: To a solution of N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (300 mg, 1.18 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (1.03 mL, 5.91 mmol), (3,4,5-trifluorophenyl)methanamine (381 mg, 2.37 mmol) was added at room temperature. This mixture was then heated to 140 °C overnight and subsequently cooled to room temperature. This reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(5-oxo-2-((3,4,5-trifluorobenzyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (138 mg, yield 31%), as a white solid. 1 H NMR (400MHz, DMSO)δ 7.86(dt, J=25.8, 6.0Hz, 2H), 7.58(d, J=8.6Hz, 1H), 7.31-7.17(m, 2H), 6.54(d, J=8.6Hz, 1H) ), 4.51(d, J=6.0Hz, 2H), 4.22(s, 2H), 3.55-3.37(m, 2H), 3.21(q, J=6.1Hz, 2H), 1.71(s, 3H). MS(ESI):C 18 H 17 The calculated value for F3N4O2 is 378, and the measured value is 379 (M+H). + .

[0376] Example 56: N-(2-(5-oxo-2-((3,4,5-trifluorobenzyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (compound 72)

[0377] [ka] Preparation: N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (300 mg, 1.12 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (0.98 mL, 5.60 mmol) were mixed with (3,4,5-trifluorophenyl)methanamine (361 mg, 2.24 mmol) at room temperature. The mixture was then heated to 140°C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(5-oxo-2-((3,4,5-trifluorobenzyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (145 mg, yield 33%), as a white solid. 1 H NMR (400MHz, DMSO)δ 7.82(q, J=5.8Hz, 2H), 7.58(d, J=8.5Hz, 1H), 7.33-7.14(m, 2H), 6.53(d, J=8.5Hz, 1H), 4.51(d, J=6.0Hz, 2H), 4.22(s, 2H), 3.53-3.37(m, 2H), 3.22(q, J=6.0Hz, 2H), 1.96(q, J=7.6Hz, 2H), 0.88(t, J=7.6Hz, 3H). MS(ESI):C 19 H 19 The calculated value for F3N4O2 is 392, and the measured value is 393 (M+H). + .

[0378] Example 57: N-(2-(5-oxo-2-((2,4,6-trifluorobenzyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (compound 73)

[0379] [ka] Preparation: N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (300 mg, 1.12 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (0.98 mL, 5.60 mmol) were mixed with (2,4,6-trifluorophenyl)methanamine (361 mg, 2.24 mmol) at room temperature. The mixture was then heated to 140°C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(5-oxo-2-((2,4,6-trifluorobenzyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (108 mg, yield 25%), as a white solid. 1 H NMR (400MHz, DMSO)δ 7.83(t, J=5.9Hz, 1H), 7.62(t, J=5.2Hz, 1H), 7.53(d, J=8.6Hz, 1H), 7.24-7.07(m, 2H), 6.48(d, J=8.6Hz, 1H), 4.48 (d, J=5.1Hz, 2H), 4.25(s, 2H), 3.53-3.40(m, 2H), 3.24-3.13(m, 2H), 1.97(q, J=7.6Hz, 2H), 0.89(t, J=7.6Hz, 3H). MS(ESI):C 19 H 19 The calculated value for F3N4O2 is 392, and the measured value is 393 (M+H). + .

[0380] Example 58: N-(2-(5-oxo-2-(((4-(trifluoromethyl)pyridine-3-yl)methyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (compound 62)

[0381] [ka] Preparation: To a solution of N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (300 mg, 1.18 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (1.03 mL, 5.91 mmol), (4-(trifluoromethyl)pyridine-3-yl)methanamine (381 mg, 2.37 mmol) was added at room temperature. This mixture was then heated to 140°C overnight and subsequently cooled to room temperature. This reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(5-oxo-2-(((4-(trifluoromethyl)pyridine-3-yl)methyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (95 mg, yield 20%), as a white solid. 1 H NMR (400MHz, DMSO)δ 8.77(s, 1H), 8.76-8.65(m, 1H), 7.88(q, J=5.5Hz, 2H), 7.70(d, J=5.1Hz, 1H), 7.60(d, J=8.6Hz, 1H), 6.59( d, J=8.6Hz, 1H), 4.73(d, J=5.6Hz, 2H), 4.22(s, 2H), 3.51-3.37(m, 2H), 3.21(q, J=6.0Hz, 2H), 1.70(s, 3H). MS(ESI):C 18 H 18 The calculated value for F3N5O2 is 393, and the measured value is 394 (M+H). + .

[0382] Example 59: N-(2-(5-oxo-2-(((4-(trifluoromethyl)pyridine-3-yl)methyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (compound 74)

[0383] [ka] Preparation: To a solution of N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (300 mg, 1.12 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (0.98 mL, 5.60 mmol), (4-(trifluoromethyl)pyridine-3-yl)methanamine (361 mg, 2.24 mmol) was added at room temperature. This mixture was then heated to 140°C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(5-oxo-2-(((4-(trifluoromethyl)pyridine-3-yl)methyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (102 mg, yield 22%), as a white solid. 1 H NMR (400MHz, DMSO)δ 8.77(s, 1H), 8.77-8.66(m, 1H), 7.88(t, J=5.7Hz, 1H), 7.81(t, J=5.9Hz, 1H), 7.70(d, J=5.1Hz, 1H), 7.60(d, J=8.5Hz, 1H), 6.59(d, J= 8.5Hz, 1H), 4.73(d, J=5.5Hz, 2H), 4.22(s, 2H), 3.53-3.37(m, 2H), 3.21(q, J=6.0Hz, 2H), 1.96(q, J=7.6Hz, 2H), 0.88(t, J=7.6Hz, 3H). MS(ESI):C 19 H 20 The calculated value for F3N5O2 is 407, and the measured value is 408 (M+H). + .

[0384] Example 60: N-(2-(5-oxo-2-((2,3,4-trifluorobenzyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (compound 75)

[0385] [ka] Preparation: To a solution of N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (300 mg, 1.18 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (1.03 mL, 5.91 mmol), (2,3,4-trifluorophenyl)methanamine (381 mg, 2.37 mmol) was added at room temperature. This mixture was then heated to 140 °C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(5-oxo-2-((2,3,4-trifluorobenzyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (120 mg, yield 27%), as a white solid. 1 H NMR (400MHz, DMSO)δ 7.90(t, J=5.9Hz, 1H), 7.81(t, J=5.9Hz, 1H), 7.57(d, J=8.6Hz, 1H), 7.32-7.12(m, 2H), 6.54(d, J=8. 5Hz, 1H), 4.56(d, J=5.8Hz, 2H), 4.23(s, 2H), 3.50-3.39(m, 2H), 3.21(q, J=6.0Hz, 2H), 1.71(s, 3H). MS(ESI):C 18 H 17 The calculated value for F3N4O2 is 378, and the measured value is 379 (M+H). + .

[0386] Example 61: N-(2-(5-oxo-2-((2,3,4-trifluorobenzyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (compound 76)

[0387] [ka] Preparation: N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (300 mg, 1.12 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (0.98 mL, 5.60 mmol) were mixed with (2,3,4-trifluorophenyl)methanamine (361 mg, 2.24 mmol) at room temperature. The mixture was then heated to 140°C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(5-oxo-2-((2,3,4-trifluorobenzyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (117 mg, yield 27%), as a white solid. 1 H NMR (400MHz, DMSO)δ 7.81(td, J=5.7, 2.3Hz, 2H), 7.57(d, J=8.6Hz, 1H), 7.35-7.12(m, 2H), 6.53(d, J=8.6Hz, 1H), 4.56(d, J=5.8 Hz, 2H), 4.22(s, 2H), 3.54-3.37(m, 2H), 3.22(q, J=6.0Hz, 2H), 1.96(q, J=7.6Hz, 2H), 0.89(t, J=7.6Hz, 3H). MS(ESI):C 19 H 19 The calculated value for F3N4O2 is 392, and the measured value is 393 (M+H). + .

[0388] Example 62: N-(2-(2-((4-fluoro-2-methylbenzyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (compound 77)

[0389] [ka] Preparation: To a solution of N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (300 mg, 1.18 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (1.03 mL, 5.91 mmol), (4-fluoro-2-methiphenyl)methanamine (329 mg, 2.37 mmol) was added at room temperature. This mixture was then heated to 140 °C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Buch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(2-((4-fluoro-2-methylbenzyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (145 mg, yield 34%), as a white solid. 1 H NMR (400MHz, DMSO)δ 7.90(t, J=5.8Hz, 1H), 7.62(t, J=5.5Hz, 1H), 7.54(d, J=8.6Hz, 1H), 7.24(dd, J=8.5, 6.1Hz, 1H), 7.12-6.98(m, 1H), 6.92(tt, J=8.7, 3. 1Hz, 1H), 6.52(d, J=8.6Hz, 1H), 4.44(d, J=5.5Hz, 2H), 4.23(s, 2H), 3.47-3.36(m, 2H), 3.22(q, J=6.0Hz, 2H), 2.29(s, 3H), 1.72(s, 3H). MS(ESI):C 19 H 21 The calculated value for FN4O2 is 356, and the measured value is 357 (M+H). + .

[0390] Example 63: N-(2-(2-((4-fluoro-2-methylbenzyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (Compound 78)

[0391] [ka] Preparation: N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (300 mg, 1.12 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (0.98 mL, 5.60 mmol) were mixed with (4-fluoro-2-methiphenyl)methanamine (312 mg, 2.24 mmol) at room temperature. The mixture was then heated to 140 °C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(2-((4-fluoro-2-methylbenzyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (113 mg, yield 27%), as a white solid. 1 H NMR (400MHz, DMSO)δ 7.82(t, J=5.9Hz, 1H), 7.61(t, J=5.6Hz, 1H), 7.54(d, J=8.6Hz, 1H), 7.24(dd,J= 8.5, 6.1Hz, 1H), 7.01 (ddd, J=10.0, 2.8, 0.8Hz, 1H), 6.92 (td, J=8.8, 2.8Hz, 1H) , 6.51(d, J=8.6Hz, 1H), 4.44(d, J=5.5Hz, 2H), 4.23(s, 2H), 3.49-3.37(m, 2H), 3 .22(q, J=6.0Hz, 2H), 2.29(s, 3H), 1.97(q, J=7.6Hz, 2H), 0.89(t, J=7.6Hz, 3H). MS(ESI):C 20 H 23 The calculated value for FN4O2 is 370, and the measured value is 371 (M+H). + .

[0392] Example 64: N-(2-(2-((2-chloro-4-fluorobenzyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (compound 79)

[0393] [ka] Preparation: To a solution of N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (300 mg, 1.18 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (1.03 mL, 5.91 mmol), (2-chloro-4-fluorophenyl)methanamine (377 mg, 2.37 mmol) was added at room temperature. This mixture was then heated to 140 °C overnight and subsequently cooled to room temperature. This reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(2-((2-chloro-4-fluorobenzyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (133 mg, yield 30%), as a white solid. 1 H NMR (400MHz, DMSO)δ 7.90(t, J=5.9Hz, 1H), 7.78(t, J=5.8Hz, 1H), 7.58(d, J=8.5Hz, 1H), 7.47-7.30(m, 2H), 7.16(td, J=8.5, 2.6Hz, 1H) , 6.56(d, J=8.5Hz, 1H), 4.55(d, J=5.8Hz, 2H), 4.22(s, 2H), 3.53-3.38(m, 2H), 3.21(q, J=6.0Hz, 2H), 1.71(s, 3H). MS(ESI):C 18 H 18 The calculated value for ClFN4O2 is 377, and the measured value is 378 (M+H). + .

[0394] Example 65: N-(2-(2-((2-chloro-4-fluorobenzyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (Compound 80)

[0395] [ka] Preparation: N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (300 mg, 1.12 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (0.98 mL, 5.60 mmol) were mixed with (2-chloro-4-fluorophenyl)methanamine (358 mg, 2.24 mmol) at room temperature. The mixture was then heated to 140°C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Buch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(2-((2-chloro-4-fluorobenzyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (145 mg, yield 33%), as a white solid. 1 H NMR (400MHz, DMSO)δ 7.79(dt, J=15.2, 5.8Hz, 2H), 7.57(d, J=8.6Hz, 1H), 7.46-7.30(m, 2H), 7.16(td, J=8.5, 2.7Hz, 1H), 6.56(d, J=8.6Hz, 1H), 4 .55(d, J=5.7Hz, 2H), 4.22(s, 2H), 3.43(t, J=6.0Hz, 2H), 3.21(q, J=6.0Hz, 2H), 1.96(q, J=7.6Hz, 2H), 0.89(t, J=7.6Hz, 3H). MS(ESI):C 19 H 20 Calculated value for ClFN4O2: 391, measured value: 392 (M+H) + .

[0396] Example 66: N-(2-(2-((5-fluoro-2-methylbenzyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (Compound 81)

[0397] [ka] Preparation: N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (300 mg, 1.18 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (1.03 mL, 5.91 mmol) were mixed with (5-fluoro-2-methiphenyl)methanamine (329 mg, 2.37 mmol) at room temperature. The mixture was then heated to 140 °C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(2-((5-fluoro-2-methylbenzyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (139 mg, yield 33%), as a white solid. 1 H NMR (400MHz, DMSO)δ 7.90(t, J=5.8Hz, 1H), 7.70(t, J=5.8Hz, 1H), 7.57(d, J=8.6Hz, 1H), 7.30-7.13(m, 1H), 7.09-6.90(m, 2H), 6.55(d, J =8.5Hz, 1H), 4.47(d, J=5.7Hz, 2H), 4.23(s, 2H), 3.52-3.37(m, 2H), 3.21(q, J=6.0Hz, 2H), 2.25(s, 3H), 1.71(s, 3H). MS(ESI):C 19 H 21 The calculated value for FN4O2 is 356, and the measured value is 357 (M+H). + .

[0398] Example 67: N-(2-(2-((5-fluoro-2-methylbenzyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (Compound 82)

[0399] [ka] Preparation: N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (300 mg, 1.12 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (0.98 mL, 5.60 mmol) were mixed with (5-fluoro-2-methiphenyl)methanamine (312 mg, 2.24 mmol) at room temperature. The mixture was then heated to 140 °C overnight and subsequently cooled to room temperature. This reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(2-((5-fluoro-2-methylbenzyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (105 mg, yield 25%), as a white solid. 1 H NMR (400MHz, DMSO)δ 7.81(t, J=5.9Hz, 1H), 7.69(t, J=5.8Hz, 1H), 7.56(d, J=8.6Hz, 1H), 7.17(ddd,J=8.4, 5.9, 0.8Hz, 1H), 7.06-6.88(m, 2H), 6.54(d, J=8.6Hz, 1H), 4.47(d, J=5.7Hz, 2H), 4.22(s, 2H), 3.53-3.37(m, 2H), 3.22(q, J=6.0Hz, 2H), 2.25(s, 3H), 1.97(q, J=7.6Hz, 2H), 0.89(t, J=7.6Hz, 3H). MS(ESI):C 20 H 23 The calculated value for FN4O2 is 370, and the measured value is 371 (M+H). + .

[0400] Example 68: N-(2-(2-((2-methylbenzyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (compound 83)

[0401] [ka] Preparation: N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (300 mg, 1.18 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (1.03 mL, 5.60 mmol) were mixed with (2-methiphenyl)methanamine (287 mg, 2.37 mmol) at room temperature. The mixture was then heated to 140 °C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(2-((2-methylbenzyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (113 mg, yield 28%), as a white solid. 1 H NMR (400MHz, DMSO)δ 7.90 (t, J=5.9Hz, 1H), 7.62 (t, J=5.6Hz, 1H), 7.54 (d, J=8.6Hz, 1H), 7.22 (dd, J=6.3, 2.3Hz, 1H), 7.17-7.06 (m, 3H), 6.53 (d, J=8.6Hz, 1H), 4.47(d, J=5.5Hz, 2H), 4.23(s, 2H), 3.50-3.38(m, 2H), 3.22(q, J=6.0Hz, 2H), 2.28(s, 3H), 1.72(s, 3H). MS(ESI):C 19 H 22 Calculated value of N4O2: 338, measured value: 339 (M+H) + .

[0402] Example 69: N-(2-(2-((2-methylbenzyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (Compound 84)

[0403] [ka] Preparation: N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (200 mg, 0.75 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (0.65 mL, 3.74 mmol) were mixed with (2-methiphenyl)methanamine (181 mg, 1.49 mmol) at room temperature. The mixture was then heated to 140 °C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Buch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(2-((2-methylbenzyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (101 mg, yield 38%), as a white solid. 1 H NMR (400MHz, DMSO)δ 7.82(t, J=5.8Hz, 1H), 7.61(t, J=5.5Hz, 1H), 7.54(d, J=8.6Hz, 1H), 7.31-7.18(m, 1H), 7.16-7.02(m, 3H), 6.52(d, J=8.6Hz, 1H), 4.4 7(d, J=5.5Hz, 2H), 4.23(s, 2H), 3.52-3.37(m, 2H), 3.22(q, J=7.0Hz, 2H), 2.28(s, 3H), 1.97(q, J=7.6Hz, 2H), 0.89(t, J=7.6Hz, 3H). MS(ESI):C 20 H 24 Calculated value of N4O2: 352, measured value: 353 (M+H) + .

[0404] Example 70: N-(2-(2-((3-fluorobenzyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (compound 85)

[0405] [ka] Preparation: N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (300 mg, 1.18 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (1.03 mL, 5.91 mmol) were mixed with (3-fluorophenyl)methanamine (296 mg, 2.37 mmol) at room temperature. The mixture was then heated to 140 °C overnight and subsequently cooled to room temperature. This reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(2-((3-fluorobenzyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)acetamide (149 mg, yield 37%), as a white solid. 1 H NMR (400MHz, DMSO)δ 7.90(t, J=6.0Hz, 1H), 7.81(t, J=6.1Hz, 1H), 7.56(d, J=8.5Hz, 1H), 7.33(td, J=7.9, 6.1Hz, 1H), 7.23-6.95(m, 3H) , 6.52(d, J=8.6Hz, 1H), 4.54(d, J=6.0Hz, 2H), 4.22(s, 2H), 3.53-3.36(m, 2H), 3.21(q, J=6.0Hz, 2H), 1.71(s, 3H). MS(ESI):C 18 H 19 The calculated value for FN4O2 is 342, and the measured value is 343 (M+H). + .

[0406] Example 71: N-(2-(2-((3-fluorobenzyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (compound 86)

[0407] [ka] Preparation: N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (200 mg, 0.75 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (0.65 mL, 3.74 mmol) were mixed with (3-fluorophenyl)methanamine (187 mg, 1.49 mmol) at room temperature. The mixture was then heated to 140°C overnight and subsequently cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(2-((3-fluorobenzyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)propionamide (104 mg, yield 39%), as a white solid. 1 H NMR (400MHz, DMSO)δ 7.81(dt, J=5.9, 3.0Hz, 2H), 7.56(d, J=8.6Hz, 1H), 7.33(td, J=8.0, 6.1Hz, 1H), 7.21-6.97(m, 3H), 6.52(d, J=8.6Hz, 1H), 4.54(d, J=6.0Hz, 2H), 4.22(s, 2H), 3.54-3.38(m, 2H), 3.22(q, J=6.0Hz, 2H), 1.96(q, J=7.6Hz, 2H), 0.89(t, J=7.6Hz, 3H). MS(ESI):C 19 H 21 The calculated value for FN4O2 is 356, and the measured value is 357 (M+H). + .

[0408] Example 72: N-(2-(2-(((6-methylpyridine3-yl)methyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)cyclopropanecarboxamide (Compound 87)

[0409] [ka] Preparation: N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)cyclopropanecarboxamide (300 mg, 1.07 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (0.93 mL, 5.36 mmol) were mixed with (6-methylpyridine3-yl)methanamine (262 mg, 2.14 mmol) at room temperature. The mixture was then heated to 140°C overnight and subsequently cooled to room temperature. This reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(2-(((6-methylpyridine3-yl)methyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)cyclopropanecarboxamide (109 mg, yield 28%), as a white solid. 1 H NMR (400MHz, DMSO)δ 8.39(dd, J=2.4, 0.8Hz, 1H), 8.11(t, J=5.9Hz, 1H), 7.77(t, J=5.9Hz, 1H), 7.66-7.47(m, 2H), 7.23-7.08(m, 1H), 6.50(d, J=8.6Hz, 1H), 4 .48(d, J=5.9Hz, 2H), 4.23(s, 2H), 3.44(t, J=6.3Hz, 2H), 3.27-3.20(m, 2H), 2.39(s, 3H), 1.43(tt, J=7.2, 5.7Hz, 1H), 0.66-0.43(m, 4H). MS(ESI):C 20 H 23 Calculated value of N5O2: 365, measured value: 366 (M+H) + .

[0410] Example 73: N-(2-(2-(((4-methylpyridine3-yl)methyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)cyclopropanecarboxamide (Compound 88)

[0411] [ka] Preparation: N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)cyclopropanecarboxamide (300 mg, 1.07 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (0.93 mL, 5.36 mmol) were mixed with (4-methylpyridine3-yl)methanamine (262 mg, 2.14 mmol) at room temperature. The mixture was then heated to 140°C overnight and subsequently cooled to room temperature. This reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(2-(((4-methylpyridine3-yl)methyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)cyclopropanecarboxamide (89 mg, yield 23%), as a white solid. 1 1H NMR (400 MHz, DMSO) δ 8.39(s, 1H), 8.29(d, J=4.9Hz, 1H), 8.11(t, J=5.8Hz, 1H), 7.67(t, J=5.5Hz , 1H), 7.56(d, J=8.6Hz, 1H), 7.17(dt, J=4.8, 0.8Hz, 1H), 6.53(d, J=8.6Hz, 1 H), 4.51(d, J=5.5Hz, 2H), 4.25(s, 2H), 3.44(t, J=6.1Hz, 2H), 3.27-3.23(m , 2H), 2.31(d, J=0.6Hz, 3H), 1.43(tt, J=7.1, 5.7Hz, 1H), 0.65-0.48(m, 4H). MS(ESI):C 20 H 23 Calculated value of N5O2: 365, measured value: 366 (M+H) + .

[0412] Example 74: N-(2-(2-(((2-methylpyridine3-yl)methyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)cyclopropanecarboxamide (Compound 89)

[0413] [ka] Preparation: To a solution of N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)cyclopropanecarboxamide (300 mg, 1.07 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (0.93 mL, 5.36 mmol), (2-methylpyridine3-yl)methanamine (262 mg, 2.14 mmol) was added at room temperature. This mixture was then heated to 140°C overnight and subsequently cooled to room temperature. This reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(2-(((2-methylpyridine3-yl)methyl)amino)-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)cyclopropanecarboxamide (96 mg, yield 25%), as a white solid. 1 H NMR (400MHz, DMSO)δ 8.28 (dd, J=4.9, 1.8Hz, 1H), 8.10 (t, J=5.9Hz, 1H), 7.73 (t, J=5.7Hz, 1H), 7.56 (dd, J=8.2, 4.2Hz, 2H), 7.23-7.06 (m, 1H), 6.54 (d, J=8.6Hz, 1H) , 4.50(d, J=5.6Hz, 2H), 4.23(s, 2H), 3.44(t, J=6.1Hz, 2H), 3.23(d, J=6 .2Hz, 2H), 2.48(s, 3H), 1.43(tt, J=7.2, 5.7Hz, 1H), 0.66-0.47(m, 4H). MS(ESI):C 20 H 23 Calculated value of N5O2: 365, measured value: 366 (M+H) + .

[0414] Example 75: N-(2-(5-oxo-2-((2,4,6-trifluorobenzyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)cyclopropanecarboxamide (Compound 90)

[0415] [ka] Preparation: N-(2-(2-chloro-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)cyclopropanecarboxamide (300 mg, 1.07 mmol) dissolved in 1-BuOH (10 mL) and DIPEA (0.93 mL, 5.36 mmol) were mixed with (2,4,6-trifluorophenyl)methanamine (346 mg, 2.14 mmol) at room temperature. The mixture was then heated to 140 °C overnight and subsequently cooled to room temperature. This reaction mixture was concentrated under reduced pressure, and the residue was purified by Büch's Pure Flash Chromatography (silica, 80 g) using 0-10% MeOH dissolved in DCM as the eluent to obtain the desired product, N-(2-(5-oxo-2-((2,4,6-trifluorobenzyl)amino)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-yl)ethyl)cyclopropanecarboxamide (115 mg, yield 27%), as a white solid. 1 H NMR (400MHz, DMSO)δ 8.11(t, J=5.9Hz, 1H), 7.62(t, J=5.2Hz, 1H), 7.54(d, J=8.6Hz, 1H), 7.29-7.05(m, 2H), 6.49(d, J=8.6Hz, 1H), 4.49(d , J=5.1Hz, 2H), 4.25(s, 2H), 3.45(t, J=6.0Hz, 2H), 3.27-3.17(m, 2H), 1.43(tt, J=7.1, 5.7Hz, 1H), 0.66-0.48(m, 4H). MS(ESI):C 20 H 19 The calculated value for F3N4O2 is 404, and the measured value is 405 (M+H). + .

[0416] Example 76: VNN1 inhibitory binding assay A vanin-1 inhibitory binding assay was performed on the selected compounds described herein and the reference compound RR6 (also known as "(R)-2,4-dihydroxy-3,3-dimethyl-N-(3-oxo-4-phenylbutyl)butanamide"), and IC was obtained. 50 The value was determined.

[0417] To a 384-well assay plate, 5 μL of 3×(45 μM) pantothenic acid-AMC was added to a final concentration of 15 μM (ultimately a 0.25% DMSO solution). Then, 5 μL of 3× desired concentrations of the test compounds (compound 1; compound 2; and RR6) dissolved in 0.75% DMSO were added to the designated wells (ultimately a 0.25% DMSO solution). The concentration ranges of the tested compounds were 10, 3.33, 1.11, 0.37, 0.12, 0.04, 0.01, 0.0046, 0.001, and 0.0005 μM. 5 μL of 0.75% DMSO was also added to the positive and negative control wells.

[0418] 5 μL of 1.4 ng / μL vanin-1 was added to the assay plate to a final volume of 7 ng per well, and the plate was sealed with a plate sealer. An additional 5 μL of assay buffer was added to the negative control, and the assay plate was then centrifuged briefly (30 seconds at 1000 rpm) in a plate centrifuge. The assay plate was incubated in the dark at room temperature for 20 minutes, and then immediately measured using a PerkinElmer Envision 2105 multimode plate reader.

[0419] Fluorescence measurements were performed at excitation wavelengths of 355 nm and emission wavelengths of 460 nm. The inhibition rate of the test compound was calculated using the following formula:

[0420] [ka]

[0421] In the above equation, "A" is the relative fluorescence units of the test compound (test compound + pantothenic acid-AMC + vanin-1); "B" is the relative fluorescence units of the lowest mean (DMSO + pantothenic acid-AMC + assay buffer); and "C" is the relative fluorescence units of the highest mean (DMSO + pantothenic acid-AMC + vanin-1). Vanin-1 inhibitory IC of the tested compounds (compound 1, compound 2, and reference compound RR6) 50 This is summarized in Table 6.

[0422] [Table 6] TIFF2026513524000166.tif157164

[0423] As shown in Table 6, the median inhibitory concentration of compound 2 was equivalent to that of RR6, a widely known and extremely potent and selective vanin 1 inhibitor. Furthermore, compound 1 showed up to two orders of magnitude higher potency than RR6.

[0424] Example 77: Logical example of treatment for IBD patients This embodiment is a logical embodiment. The VNN1 inhibitor disclosed herein is used to treat patients with disease-active ulcerative colitis and Crohn's disease who have been sensitive to or resistant to previous anti-TNFA treatments. The inhibitor is administered orally daily for 12 weeks in capsules at doses of 50-200 mg. After completion of treatment, patients show both clinical and histological improvement, as assessed by Mayo or CDAI clinical scores, endoscopic observations, and histological indicators.

[0425] Example 78: Logical implementation in the treatment of cancer patients This embodiment is a logical example. The VNN1 inhibitor disclosed herein is used to treat patients with colorectal cancer, liver cancer, pancreatic cancer, gastric cancer, esophageal cancer, prostate cancer, breast cancer, cholangiocarcinoma, sarcoma, or acute myeloid leukemia. The inhibitor is administered orally daily in capsules at doses of 50-200 mg to patients who are receiving or not receiving chemotherapy. After completion of treatment, patients show clinical improvement characterized by improved prognosis and survival.

Claims

1. Equation (I): 【Chemistry 1】 [In the formula, W, X, and Y are each independently C, C(R) ５ -R ３ ), N, S, and S(R ５ -R ４ Selected from the group consisting of; A is N(R5 - R4); B is CH2; U is a carbon atom; V is either N or CH; Z is N, N(R ５ -R ４ ), S, and S(R ５ -R ４ Selected from the group consisting of; Each example of R1 is independently C, optionally substituted １－２０ selected from the group consisting of alkylene, optionally substituted 3- to 10-member arylalkyl, optionally substituted 3- to 20-member (carbocyclic)alkyl, and optionally substituted 3- to 20-member (heterocyclic)alkyl; Each example of R2 is independently substituted as needed. ６－１０ Selected from the group consisting of aryls, optionally substituted 3- to 10-membered arylalkyls, optionally substituted 5- to 10-membered heteroaryls, optionally substituted 3- to 10-membered heteroarylalkyls, optionally substituted 3- to 20-membered carbocyrills, and optionally substituted 3- to 20-membered (carbocyrill)alkyls; Each example of R 3, if present, is independently selected from the group consisting of -H, optionally substituted C1-6 alkyl, optionally substituted C1-6 heteroalkyl, optionally substituted C6-10 aryl, optionally substituted 3- to 10-membered arylalkyl, optionally substituted 3- to 20-membered carbocyryl, optionally substituted 3- to 20-membered (carbocyryl)alkyl, or optionally substituted 3- to 20-membered (heterocyclyl)alkyl; or is absent; Each example of R 4, if present, is independently -H, and C is substituted as needed. １－６ Alkyl, substituted C as needed １－６ Heteroalkyl, substituted C as needed ６－１０ Selected from the group consisting of aryls, optionally substituted 5- to 10-membered heteroaryls, optionally substituted 3- to 10-membered arylalkyls, optionally substituted 3- to 20-membered carbocyclyls, optionally substituted 3- to 20-membered (carbocyclyl)alkyls, and optionally substituted 3- to 20-membered (heterocyclyl)alkyls, or none at all; R ５ Each of these examples, if present, is independently replaced as necessary with C. １－２０ Selected from the group consisting of alkylenes, or absent; and, n is 0. A compound having the structure represented by , or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1, wherein Z is N.

3. R ５ The compound according to claim 1 or 2, wherein the compound is not present.

4. R ５ Replace C as needed １－２０ The compound according to claim 1 or 2, wherein the compound is alkylene.

5. The structure of the above formula (I) is, formula (Ia): 【Chemistry 2】 The compound according to claim 1, or a pharmaceutically acceptable salt thereof, as further represented by.

6. R ５ ga- (CH ２ ) ｍ The compound according to claim 5, wherein m is an integer in the range of 0 to 20.

7. The compound according to claim 6, wherein m is 0, 1, 2, 3, 4, 5, or 6.

8. The compound according to claim 6, wherein m is 0, 1, 2, or 3.

9. The compound according to claim 6, wherein m is 2.

10. R ４ but, 【Transformation 3】 【change】 【change】 A compound according to any one of claims 1 to 9, selected from the group consisting of the following.

11. R ４ but, 【Chemistry 4】 A compound according to claim 10, selected from the group consisting of the following.

12. R ４ The compound according to claim 11, wherein is H.

13. R １ Replace C as needed １－２０ The compound according to any one of claims 1 to 12, wherein it is an alkylene.

14. R １ ga-CH ２ -ien-CH ２ CH ２ -, -CH(CH ３ ) -, and -CHCH ２ A compound according to any one of claims 1 to 12, selected from the group consisting of (OH)-.

15. R １ ga- (CH ２ ) ｐ The compound according to any one of claims 1 to 12, wherein p is an integer in the range of 1 to 20.

16. The compound according to claim 15, wherein p is 1, 2, 3, 4, 5, or 6.

17. The structure of the above formula (I) is, formula (Ic): 【Transformation 5】 The compound according to claim 1, or a pharmaceutically acceptable salt thereof, as further represented by.

18. R １ ga-CH ２ - The compound according to claim 17.

19. R ２ The compound according to claim 17, wherein the phenyl is substituted as needed.

20. R ２ The compound according to claim 17, wherein is pyridinyl, pyrimidinyl, or pyrazinyl.

21. The phenyl that is substituted as needed is -F, -Cl, methyl, methoxy, -CN, and -CF ３ The compound according to claim 19, which is substituted with one to five groups selected from the above.

22. The aforementioned compound, 【Transformation 6】 【change】 【change】 【change】 A compound according to claim 1, or a pharmaceutically acceptable salt thereof, selected from the above.

23. A method for treating a VNN1-mediated condition, comprising administering a compound according to any one of claims 1 to 22 to a subject in need of treatment.

24. The method according to claim 23, wherein the subject is suffering from an autoimmune disease, an inflammatory disease, or a certain type of cancer.

25. The compound according to any one of claims 1 to 22 has a half-inhibitory concentration (IC) of less than about 5 μM. ５０ The method according to claim 24, having ).

26. The compound according to any one of claims 1 to 22 has a half-inhibitory concentration (IC) of less than about 1 μM. ５０ The method according to claim 25, having ).

27. A method for producing a compound according to any one of claims 1 to 22, comprising functionalizing a starting material of a bicyclic compound with one or more substituents.

28. Use of the compound according to any one of claims 1 to 22 for preparing a therapeutic agent for treating an autoimmune disease, an inflammatory disease, or certain types of cancer.

29. Use of the compound according to any one of claims 1 to 22 for the treatment of autoimmune diseases, inflammatory diseases, or certain types of cancer.

Images