5,6-Condensed bicyclic amides and compositions for use as 15-prostaglandin dehydrogenase regulators

Abstract

This disclosure provides novel 15-hydroxy-prostaglandin dehydrogenase inhibitors, pharmaceutical compositions comprising such compounds, and methods for using such compounds and compositions in the treatment of 15-hydroxy-prostaglandin dehydrogenase-mediated diseases. Methods for producing such compounds and their intermediates are also provided. The compounds are of formula (I) It has the structure of TIFF2026517844000420.tif22170. Furthermore, this disclosure provides an intermediate useful for the synthesis of compounds of formula (I).

Description

[Technical Field]

[0001] Cross-reference of related applications This application claims priority to U.S. Provisional Patent Application No. 63 / 501,062 filed 9 May 2023, and this patent application is incorporated herein by reference in its entirety for any purpose as if it were fully described herein.

[0002] Novel compounds, pharmaceutical compositions containing such compounds, and methods for using such compounds and compositions in the treatment of 15-hydroxy-prostaglandin dehydrogenase-mediated diseases are provided herein. Methods for producing such compounds and their intermediates are also provided. [Background technology]

[0003] Short-chain dehydrogenases (SCDs) are a family of dehydrogenases involved in the synthesis and degradation of fatty acids, steroids, and several prostaglandins. Therefore, SCDs have been shown to be associated with various disorders, such as lipid storage disorders, muscle diseases, SCD deficiencies, and certain genetic disorders. SCD 15-hydroxy-prostaglandin dehydrogenase (15-PGDH) (also identified as 15-prostaglandin dehydrogenase or hydroxyprostaglandin dehydrogenase 15-(nicotinamide adenine dinucleotide)) represents a key enzyme in the inactivation of several active prostaglandins, leukotrienes, and hydroxyeicosatetraenoic acid (HETE). Recent studies have suggested that inhibitors and activators of 15-PGDH may have therapeutic value. 15-PGDH is responsible for the inactivation of prostaglandin E2 (PGE2), a downstream product of cyclooxygenase-2 (COX-2) metabolism. PGE2 has been shown to be beneficial in various biological processes, including hair density, skin wound healing, and bone formation. [Overview of the project] [Means for solving the problem]

[0004] Several embodiments disclosed herein provide novel compounds. In some embodiments, these compounds include a 5,6-condensed bicyclic thieno-aryl ring system, a 5,6-condensed bicyclic thieno-heteroaryl ring system, or a 5,6-condensed bicyclic thieno-heterocyclyl ring system as a core (see, for example, formula (I)). In some embodiments, the compounds disclosed herein are useful for modulating SCD, more specifically, for modulating and / or inhibiting the activity of 15-PDGH. In some embodiments, these 15-PGDH inhibitory compounds are useful for modulating tissue prostaglandin levels to treat diseases, disorders, or symptoms associated with 15-PGDH activity. In some embodiments, the compounds disclosed herein can be administered to a subject in an effective amount to inhibit 15-PGDH activity and / or treat 15-PGDH-mediated diseases, disorders, or symptoms.

[0005] Some embodiments disclosed herein are based on formula (I): [ka] With respect to the compound or its pharmaceutically acceptable salt, in the formula, [ka] teeth, [ka] And, a is N, -N + -O - or CH, b is N or CH, c is N, CH, or CR 3 And, d is N, CH, or CR 4 And, R 1a is -H, alkyl, haloalkyl, or heteroalkyl, R 1a These are either unsubstituted or each independently a halogen, -OH, and -N(R) b)2. It may be substituted with one or more substituents that are alkyl or alkoxy. R 1b is alkyl, haloalkyl, heteroalkyl, carbocyclic or heterocyclic. R 1b is unsubstituted or may be substituted with one or more substituents each independently being halogen, -OH, -N(R b )2, alkyl or alkoxy, or alternatively, R 1a and R 1b together form heterocyclic, R 1a and R 1b the heterocyclic formed by them is unsubstituted or may be substituted with one or more substituents each independently being halogen, -OH, -CN, -N(R b )2, alkyl, haloalkyl, alkoxy, heteroalkyl, cycloalkyl or heterocyclic. R 2 is heterocyclic, heteroaryl or alternatively, when a is -N + -O - then R 2 can be H. R 2 is unsubstituted or may be substituted with one or more examples of R 5 . Each example of R 5 is independently oxo, CN, alkyl, cycloalkyl, haloalkyl, alkoxy, C(O)N(R 6 )2, -N(R 6 )2, -N(R 6 )(alkylene - OH) or heterocyclic. Each example of R 5 is unsubstituted or may be substituted with one or more examples of R 6 . Each example of R 6 is independently -H, alkyl, C(O)alkyl, C(O)2alkyl, alkylene - OH or S(O) n alkyl, and n is 0, 1 or 2. R 6It may be unsubstituted or substituted with one or more substituents that are independently -F, -OH, and alkoxy. R 3 is -H, alkyl, cycloalkyl, aryl, heteroaryl, or heterocyclyl, R 3 These are either unsubstituted or each independently a halogen, -OH, oxo, and -N(R) b )2, may be substituted with one or more substituents that are alkyl, haloalkyl, alkoxy, alkylene-alkoxy or heteroalkyl, R 4 is -H, alkyl, CN, -F, -Cl- or N(R 7 )2, and if present, R 7 Each example is independently either -H or alkyl, or instead, two R 7 The substituents together form a heterocycline, R 7 It may be unsubstituted or substituted with one or more substituents, each independently being -F, -OH, alkyl, or alkoxy. If present, R b Each example is independently either -H or alkyl, or instead, two R b The substituents together form a heterocycline, R b It may be unsubstituted or substituted with one or more substituents, each independently of being -F, -OH, alkyl, or alkoxy.

[0006] In some embodiments, d is CH or CR 4 In some embodiments, d is CH.

[0007] In some embodiments, R 1a is -H, C 1~6 Alkyl, C 1~6 Haloalkyl or C 1~6 It is heteroalkyl. In some embodiments, R 1a These are either unsubstituted or each independently a halogen, -OH, and -N(R) b)2, C 1~3 Alkyl or C 1~3 It can be substituted with one or more substituents that are alkoxy.

[0008] In some embodiments, R 1b C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Heteroalkyl, C 3~10 It is a cycloalkyl or a heterocyclyl having 3 to 10 ring members. In some embodiments, R 1b These are either unsubstituted or each independently a halogen, -OH, and -N(R) b )2, C 1~3 Alkyl or C 1~3 It can be substituted with one or more substituents that are alkoxy.

[0009] In some embodiments, R 1a and R 1b These together form a heterocycline having 3 to 10 ring members. In some embodiments, R 1a and R 1b The heterocyclyls formed by this process are either unsubstituted or each independently contains a halogen, -OH, -CN, and -N(R) b )2, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 Heteroalkyl, C 3~6 It may be substituted with one or more substituents that are cycloalkyl or heterocyclyl having 3 to 6 ring members.

[0010] In some embodiments, R 2 is a heterocyclyl having 5 to 10 ring members, a heteroaryl having 5 to 10 ring members, or alternatively, a is -N + -O - If R 2 This can be H. In some embodiments, R 2 is either non-substitutive or R 5 It can be replaced with one or more examples of R 5Each example of is, independently, oxo, CN, C 1~6 alkyl, C 3~6 cycloalkyl, C 1~6 haloalkyl, C 1~6 alkoxy, C(O)N(R 6 )2, -N(R 6 )2, -N(R 6 )(C 1~6 alkylene-OH) or heterocyclyl having 3 to 10 members. In some embodiments, R 5 is unsubstituted or may be substituted with one or more examples of R 6 . In some embodiments, R 6 is unsubstituted or may be substituted with one or more substituents each independently being -F, -OH, C 1~3 alkoxy.

[0011] In some embodiments, R 3 is -H, C 1~6 alkyl, C 3~10 cycloalkyl, C 6~10 aryl, heteroaryl having 5 to 10 ring members or heterocyclyl having 3 to 10 ring members. In some embodiments, R 3 is unsubstituted or may be substituted with one or more substituents each independently being halogen, -OH, oxo, -N(R b )2, C 1~3 alkyl, C 1~3 haloalkyl, C 1~3 alkoxy, C 1~3 alkylene-C 1~3 alkoxy or C 1~6 heteroalkyl.

[0012] In some embodiments, R 4 is -H, alkyl or -N(R 7 )2. In some embodiments, R 4 is -H, C 1~6 alkyl or -N(R 7 )2 and, when present, each example of R 7 is independently -H or C 1~6It is alkyl, or instead, it has two R's. 7 The substituents together form a heterocyclyl having 3 to 6 ring members. In some embodiments, R 7 These are either unsubstituted or each is independently -F, -OH, C 1~3 Alkyl or C 1~3 It can be substituted with one or more substituents that are alkoxy. In some embodiments, R 7 These are either unsubstituted or each is independently -F, -OH, or C 1~3 It can be substituted with one or more substituents that are alkoxy.

[0013] In some embodiments, if R exists, b Each of these examples is independently -H or C 1~6 It is alkyl, or instead, it has two R's. b The substituents together form a heterocyclyl having 3 to 6 ring members. In some embodiments, R b These are either unsubstituted or each is independently -F, -OH, C 1~3 Alkyl or C 1~3 It can be substituted with one or more substituents that are alkoxy. In some embodiments, R b These are either unsubstituted or each is independently -F, -OH, or C 1~3 It can be substituted with one or more substituents that are alkoxy.

[0014] Some embodiments relate to pharmaceutical compositions comprising a compound or salt of formula (I) and pharmaceutically acceptable excipients.

[0015] Some embodiments relate to a compound or salt of formula (I) or a pharmaceutical composition comprising a compound of formula (I) for use as a pharmaceutical.

[0016] Some embodiments relate to pharmaceutical compositions comprising a compound or salt of formula (I) or a compound of formula (I) for use in the treatment of 15-PGDH-mediated diseases or disorders.

[0017] Some embodiments relate to pharmaceutical compositions comprising a compound or salt of formula (I) or a compound of formula (I) for use in the treatment of inflammatory bowel disease.

[0018] Some embodiments relate to pharmaceutical compositions comprising a compound or salt of formula (I) or a compound of formula (I) for use in the treatment of ulcerative colitis.

[0019] Some embodiments relate to pharmaceutical compositions comprising a compound or salt of formula (I) or a compound of formula (I) for use in the treatment of Crohn's disease.

[0020] Some embodiments relate to pharmaceutical compositions comprising a compound or salt of formula (I) or a compound of formula (I) for use in the treatment of fibrous diseases, disorders, or symptoms.

[0021] Some embodiments relate to a method for treating a 15-PGDH-mediated disease, disorder, or symptom in a subject requiring treatment of such disease, disorder, or symptom, comprising administering to the subject a therapeutically effective amount of a compound or salt of formula (I) or a pharmaceutical composition containing a compound of formula (I).

[0022] Some embodiments relate to a method for treating a disorder of the intestinal tract, gastrointestinal tract, or bowel in a subject requiring treatment of such disorder, comprising administering to the subject a therapeutically effective amount of a compound or salt of formula (I) or a pharmaceutical composition containing a compound of formula (I).

[0023] Further aspects and advantages will become apparent to those skilled in the art from a closer examination of the following detailed description. The following description includes specific examples, embodiments, and examples, with the understanding that this disclosure is exemplary and not intended to limit the embodiments of this disclosure to the specific examples, embodiments, and cases described herein. Rather, references to embodiments of this disclosure are intended to include alternative forms, modifications, and equivalents that may fall within the spirit and scope of the embodiments of this disclosure as defined by the appended claims. [Modes for carrying out the invention]

[0024] Several embodiments provide compounds and compositions, methods of use thereof, and methods of producing the same. In some embodiments, the compounds disclosed herein inhibit SCD and / or 15-PGDH and / or are useful for treating diseases, disorders, and symptoms of SCD and / or 15-PGDH. In some embodiments, the compounds disclosed herein have a 5,6-condensed bicyclic thieno-aryl ring system, a 5,6-condensed bicyclic thieno-heteroaryl ring system, or a 5,6-condensed bicyclic thieno-heterocyclyl ring system core structure. In some embodiments, the compounds disclosed herein have a 5,6-condensed bicyclic thieno-aryl ring system core structure. In some embodiments, the compounds disclosed herein have a 5,6-condensed bicyclic thieno-heteroaryl ring system core structure. In some embodiments, the compounds disclosed herein have a 5,6-condensed bicyclic thieno-heterocyclyl ring system core structure. In some embodiments, the compound comprises an alpha-positioned amide moiety at the 2-position of a 5,6-condensed bicyclic thieno-aryl ring system. In some embodiments, the compound comprises an alpha-positioned amide moiety at the 2-position of a 5,6-condensed bicyclic thieno-heteroaryl ring system. In some embodiments, the compound comprises an alpha-positioned amide moiety at the 2-position of a 5,6-condensed bicyclic thieno-heterocyclyl ring system. Elsewhere in this specification, these compounds may be referred to as 2-amide-5,6-condensed-thieno-aryl or 2-amide-5,6-condensed-thieno-heterocyclyl for brevity. These compounds and any other compounds disclosed herein may commonly be referred to as 15-PGDH inhibitors.

[0025] The following description provides background and examples, but should not be construed as limiting the scope of the invention as encompassed by the claims that follow in this specification or any other application claiming priority thereto. No single component or set of components is essential or indispensable. Section headings used herein are for structural purposes only and should not be construed as limiting the subject matter described. Features disclosed under one title (e.g., composition or combination) may be combined with features disclosed under a different title (e.g., treatment method).

[0026] definition Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those generally understood by those skilled in the art in which this disclosure pertains. If there are multiple definitions of a term herein, the definition in this section shall prevail unless otherwise noted.

[0027] The term "C" used herein a~b (or similar wording, e.g., C a ~C b )(where "a" and "b" are integers) refers to the number of carbon atoms in an alkyl, alkylene, alkenyl, alkenylene, alkynyl, alkynylene, haloalkyl, alkoxy, thioalkyl, heteroalkyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, or other group. That is, an alkyl, alkenyl, alkynyl, cycloalkyl ring, cycloalkenyl ring, cycloalkynyl ring, aryl ring, or heteroaryl ring can contain "a" to "b" (including the values ​​at both ends) carbon atoms. For example, "C 1~4 The "alkyl" group (or C1-C4 alkyl) refers to all alkyl groups having 1 to 4 carbon atoms (for example, 1, 2, 3, or 4), namely CH3-, CH3CH2-, CH3CH2CH2-, (CH3)2CH-, CH3CH2CH2CH2-, CH3CH2CH(CH3)-, and (CH3)3C-. 1~6The "alkyl" group refers to all alkyl groups having 1 to 6 carbon atoms (e.g., 1, 2, 3, 4, 5, or 6). If "a" and "b" are not specified for a group, the range described in those definitions is assumed. As can be recognized in light of prior disclosures, if a range is disclosed (for alkyl groups or other groups disclosed herein), each individual member within that disclosed range is also assumed and disclosed. Therefore, "C 1~6 When "alkyl" is disclosed, all alkyl groups having 1 to 6 carbon atoms and any alkyl group containing 1, 2, 3, 4, 5, or 6 carbon atoms or any combination thereof (e.g., 1, 2, 3, or 5 carbon atoms, 2, 3, 4, or 6 carbon atoms, etc.) are provided. Similarly, "C 1~3 When "alkyl" is disclosed, all alkyl groups having 1 to 3 carbon atoms and any alkyl groups containing 1 carbon, 2 carbon or 3 carbon atoms or any combination thereof (e.g., 1 or 3, 1 or 2, 2 or 3, etc.) are provided.

[0028] The term "alkyl" refers to a fully saturated (i.e., non-double or triple bond-free) linear or branched hydrocarbon chain. Examples of branched alkyl groups include, but are not limited to, isopropyl, sec-butyl, and t-butyl. Examples of linear alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, and n-heptyl. Alkyl groups can have 1 to 12 carbon atoms. An "alkyl" group can also be a lower alkyl group having 1 to 6 carbon atoms. 1~5 Alkyl includes C5 alkyl, C4 alkyl, C3 alkyl, C2 alkyl and C1 alkyl (i.e., methyl). 1~6 Alkyl is C 1~5 This includes all the parts of alkyl groups described above, but also C6 alkyl groups. 1~10 Alkyl is C 1~5 Alkyl and C 1~6 The alkyl group includes all the parts described above, but also C7, C8, C9 and C 10It also includes alkyl groups. Similarly, C 1~12 Alkyl includes all of the aforementioned parts, but C 11 and C 12 This also includes alkyl groups. Just as an example, "C 1~4 The term "alkyl" indicates the presence of 1 to 4 carbon atoms within the alkyl chain. Specifically, alkyl chains can be methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, or t-butyl. 1~12 Non-limiting examples of alkyl groups include, but are not limited to, methyl ("Me" or -CH3), ethyl, n-propyl, i-propyl, sec-propyl, n-butyl, i-butyl, sec-butyl, t-butyl, n-pentyl, neo-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, and n-dodecyl.

[0029] The term "alkylene" or "alkylene chain" refers to a fully saturated linear or branched divalent hydrocarbon chain radical having 1 to 12 carbon atoms. Examples of alkylene groups include, but are not limited to, methylene, ethylene, propylene, butylene, pentylene, hexylene, heptylene, and octylene. 1~12 Alkilen is C 12 Alkilen, C 11 Alkilen, C 10This includes alkylenes, C9 alkylenes, C8 alkylenes, C7 alkylenes, C6 alkylenes, C5 alkylenes, C4 alkylenes, C3 alkylenes, C2 alkylenes, and C1 alkylenes (i.e., methylene). Alkylenes can be lower alkylenes having 1 to 6 carbon atoms. Lower alkylenes include C6 alkylenes, C5 alkylenes, C4 alkylenes, C3 alkylenes, C2 alkylenes, and C1 alkylenes. It should also be understood that certain diradical naming conventions may include both monoradical and diradical naming conventions, depending on the context. For example, a substituent is understood to be a diradical if its position within the molecule requires two bonding sites to the rest of the molecule. Examples of substituents that are identified as alkyl but require two bonding sites include alkylenedi radicals such as -CH2-, -CH2CH2-, and -CH2CH(CH3)CH2-.

[0030] The term "alkenyl" or "alkenyl group" refers to a linear or branched hydrocarbon chain radical having 2 to 12 carbon atoms and one or more carbon-carbon double bonds. Alkenyl groups containing up to 12 carbon atoms are C 2~12 Alkenyls are alkenyls that contain up to 10 carbon atoms. 2~10 Alkenyls are alkenyl groups that contain up to six carbon atoms. 2~6 Alkenyls are alkenyls that contain up to five carbon atoms. 2~5 It is alkenil. 2~5 Alkenyls include C5 alkenyls, C4 alkenyls, C3 alkenyls, and C2 alkenyls. 2~6 Alkenil is C 2~5 This includes all the parts of the alkenyl described above, but also includes the C6 alkenyl. 2~10 Alkenil is C 2~5 Alkenyl and C 2~6 Regarding alkenyls, this includes all the parts described above, but C7, C8, C9 and C 10 Includes alkenyls. C 2~12 Alkenil includes all of the aforementioned parts, but C 11 and C 12Includes alkenyls. C 2~12 Non-limiting examples of alkenyls include ethenyl(vinyl), 1-propenyl, 2-propenyl(allyl), isopropenyl, 2-methyl-1-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 1-heptenyl, 2-heptenyl, 3-heptenyl, 4-heptenyl, 5-heptenyl, 6-heptenyl, 1-octenyl, 2-octenyl, 3-octenyl, 4-octenyl, 5-octenyl, 6-octenyl, 7-octenyl, 1-nonenyl, 2-nonenyl, 3-nonenyl Examples include 4-nonenyl, 5-nonenyl, 6-nonenyl, 7-nonenyl, 8-nonenyl, 1-decenyl, 2-decenyl, 3-decenyl, 4-decenyl, 5-decenyl, 6-decenyl, 7-decenyl, 8-decenyl, 9-decenyl, 1-undecenyl, 2-undecenyl, 3-undecenyl, 4-undecenyl, 5-undecenyl, 6-undecenyl, 7-undecenyl, 8-undecenyl, 9-undecenyl, 10-undecenyl, 1-dodecenyl, 2-dodecenyl, 3-dodecenyl, 4-dodecenyl, 5-dodecenyl, 6-dodecenyl, 7-dodecenyl, 8-dodecenyl, 9-dodecenyl, 10-dodecenyl, and 11-dodecenyl.

[0031] The term "alkynyl" or "alkynyl group" refers to a linear or branched hydrocarbon chain radical having 2 to 12 carbon atoms and one or more carbon-carbon triple bonds. An alkynyl group containing up to 12 carbon atoms is C 2~12 Alkynnyls are alkynyls that contain up to 10 carbon atoms. 2~10 Alkynnyl groups, which contain up to six carbon atoms, are C 2~6 Alkynnyls are alkynyls, and alkynyls containing up to 5 carbon atoms are C 2~5 It is alkinyl C 2~5 Alkynnyl includes C5 alkynyl, C4 alkynyl, C3 alkynyl, and C2 alkynyl. 2~6 Alkyl is C 2~5This includes all the parts of alkyl groups described above, but also C6 alkyl groups. 2~10 Alkinyl is C 2~5 Alkinyl and C 2~6 Regarding alkynyl, this includes all the parts described above, but C7, C8, C9 and C 10 Includes alkynyl. C 2~12 Alkinyl includes all of the aforementioned parts, but C 11 and C 12 Includes alkynyl. C 2~12 Non-limiting examples of alkenyls include ethynyl, propynyl, butynyl, and pentynyl.

[0032] The term "halogen" or "halo" refers to fluoro(-F), chloro(-Cl), bromo(-Br), or iodine(-I).

[0033] The term "haloalkyl" refers to a linear or branched alkyl group in which one or more or all hydrogen atoms are substituted with halogens. Examples of haloalkyl groups include, but are not limited to, -CF3, -CHF2, -CH2F, -CH2CF3, -CH2CHF2, -CH2CH2F, -CH2CH2Cl, -CH2CF2CF3, and other groups that are considered equivalent to any one of the aforementioned examples, taking into account the usual art and the teachings provided herein. Haloalkyl groups may be lower haloalkyl groups. Haloalkyl groups may be perhalated (e.g., perfluorinated).

[0034] The term "alkoxy" refers to the formula -OR, where R is an alkyl group as defined elsewhere herein. For illustrative purposes, "C 1~9 Examples of "alkoxys" include, but are not limited to, methoxy, ethoxy, n-propoxy, 1-methylethoxy (isopropoxy), n-butoxy, iso-butoxy, sec-butoxy, and tert-butoxy.

[0035] The term "heteroalkyl" refers to a linear or branched hydrocarbon chain (e.g., alkyl) containing one or more heteroatoms. Heteroatoms are given their obvious 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. Heteroalkyl groups can have 1 to 12 carbon atoms, but this definition also encompasses the existence of the term "heteroalkyl" unless a numerical range is specified. Heteroalkyl groups can also be lower heteroalkyl groups having 1 to 6 carbon atoms. In various embodiments, heteroalkyl groups may have 1 to 4 heteroatoms, 1 to 3 heteroatoms, 1 or 2 heteroatoms, or 1 heteroatom. The heteroalkyl group of a compound is "C 1~4 It may be designated as "heteroalkyl" or a similar name. A heteroalkyl group may contain one or more heteroatoms. For example, "C 1~4 "Heteroalkyl" indicates the presence of 1 to 4 carbon atoms in the heteroalkyl chain and, additionally, one or more heteroatoms in the chain's backbone. As can be understood from the above, in embodiments having one heteroatom, the heteroatom can be found at any point along the alkyl portion of the heteroalkyl, for example, at the first position (for example, the heteroatom of the heteroalkyl may act as the atom that directly bonds the alkyl to the rest of the molecule).

[0036] The term "aryl" refers to a hydrocarbon ring radical containing hydrogen and at least one aromatic ring. While aryl groups can have 6 to 18 carbon atoms, this definition also encompasses the presence of the term "aryl" unless a numerical range is specified. In some embodiments, aryl groups have 6 to 10 carbon atoms. The aryl group is "C 6~10 "Aryl", "C6 or C 10 It may be designated as "aryl" or a similar name. For example, the aryl group is C 6~14 Aryl group, C 6~10The aryl radical may be an aryl group or a C6 aryl group. For the purposes of the present invention, the aryl radical may be a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, which may include a condensed ring system or a bridged ring system, wherein at least one ring in the system is aromatic. Examples of aryl groups include, but are not limited to, phenyl, acetanslylenyl, acenaphtyrenyl, acephenanthrylenyl, anthracenyl, azlenyl, chrysenyl, fluoranthenyl, fluorenyl, as-indasenyl, s-indasenyl, indanyl, indenyl, naphthalenyl, phenalenyl, phenantrenyl, pleiadenyl, pyrenyl, and triphenylenyl.

[0037] The terms "carbocykrill," "carbocyclic," or "carbocyclic" refer to a ring system skeleton containing only carbon atoms and having 3 to 20 ring members (3 to 20 carbon atom ring members, C 3~20 This refers to a non-aromatic cyclic ring or cyclic system containing ). When a carbocyclyl is a cyclic system, two or more rings may be joined by condensation, bridging, or spiroconnection. Examples of carbocyclyls include cycloalkyl, cycloalkenyl, and cycloalkynyl. A carbocyclyl group can be a medium-sized carbocyclyl having 3 to 10 carbon atoms. A carbocyclyl group may have 3 to 6 carbon ring atoms. A carbocyclyl group is "C 3~6 It may be designated as "carbocykrill" or a similar name. Examples of carbocyclyl rings include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl, 2,3-dihydroindene, bisicle[2.2.2]octanyl, adamantyl, and spiro[4.4]nonanyl.

[0038] The term "cycloalkyl" refers to a non-aromatic monocyclic or polycyclic, fully saturated hydrocarbon radical consisting only of carbon and hydrogen atoms, which may include fused ring systems, bridged ring systems, or helical (spiro) ring systems having 3 to 20 carbon atom ring members (e.g., 3 to 10 ring atoms, 3 to 8 ring atoms, etc.), and which are bonded to the rest of the molecule by single bonds. The rings in the cycloalkyl ring or ring system are not aromatic. Examples of monocyclic cycloalkyl radicals include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Examples of polycyclic cycloalkyl radicals include adamantyl, norbornyl, dekalinyl, and 7,7-dimethyl-bicyclo[2.2.1]heptanyl.

[0039] The term "cycloalkenyl" refers to a monocyclic or polycyclic hydrocarbon radical consisting only of carbon and hydrogen atoms, having 3 to 20 carbon atom ring members (e.g., 3 to 10 ring atoms, 4 to 10 ring atoms, etc.), including fused ring systems, bridged ring systems, or helical (spiro) ring systems, and having one or more carbon-carbon double bonds linked to the rest of the molecule by single bonds. The rings in the cycloalkenyl ring or ring system are not aromatic. An example is cyclohexenyl. The cycloalkenyl group may contain 4 to 10 atoms in the ring. Examples of monocyclic cycloalkenyl radicals include cyclopentenyl, cyclohexenyl, cycloheptenyl, and cyclooctenyl. Examples of polycyclic cycloalkenyl radicals include bicyclo[2.2.1]hepta-2-enyl.

[0040] The term "cycloalkynyl" refers to a monocyclic or polycyclic hydrocarbon radical consisting only of carbon and hydrogen atoms, which may include a fused ring system, a bridged ring system, or a helical (e.g., spiro) ring system having 8 to 20 carbon atom ring members (e.g., 8 to 10 ring atoms), and which has one or more carbon-carbon triple bonds linked to the rest of the molecule by single bonds. The rings in the cycloalkynyl ring or ring system are not aromatic. Examples of monocyclic cycloalkynyl radicals include cycloheptynyl and cyclooctinyl.

[0041] The term “heterocyclyl” refers to monocyclic, bicyclic, and tricyclic ring systems with 3, 4, 5, 6, 7, 8, 9, 10, and up to 20 members, where a carbon atom, together with 1 to 5 heteroatoms (each independently being nitrogen (e.g., N, NH, NR, etc.), oxygen, or sulfur (e.g., S, S(O), S(O)2)) constitutes the ring system. Heterocyclyl or heterocyclic rings include non-heteroaryl ring systems (e.g., rings containing heteroatoms as ring members that do not fall under the definition of “heteroaryl”). Unless otherwise specifically specified herein, heterocyclyl radicals can be monocyclic, bicyclic, tricyclic, or tetracyclic ring systems, and may include fused, bridged, or spirocyclic ring systems; nitrogen, carbon, or sulfur atoms in heterocyclyl radicals may be optionally oxidized; nitrogen atoms may be optionally quaternized; and heterocyclyl radicals may be partially or completely saturated. Examples of such heterocyclyl radicals include azilidinyl, 1,3-dioxynyl, 1,3-dioxanyl, 1,4-dioxanyl, 1,3-oxathiolanyl, 1,3-oxathiolanyl, 1,3-dithiolyl, 1,3-dithiolanyl, 1,4-oxathionyl, tetrahydro-1,4-thiadinyl, dioxolanil, decahydroisoquinolyl, imidazolidinyl, isothiazolidinyl, isoxazolidinyl, maleimidyl, morpholinyl, and octahydroindodinyl. Examples include, but are not limited to, lyl, octahydroisoindolyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, piperidinyl, piperazinyl, 4-piperidonyl, pyrrolidinyl, pyrazolidinyl, quinuclidinyl, succinimidyl, thiazolidinyl, tetrahydrofuryl, trithianil, tetrahydropyranyl, thiomorpholinyl, thiamorpholinyl, 1-oxo-thiomorpholinyl, and 1,1-dioxo-thiomorpholinyl. The single bond sites of heterocyclyls, heterocyclic rings, or heterocycles to the rest of the molecule are mediated by ring member atoms that may be carbon or nitrogen. However, heterocycles may optionally contain one or more unsaturated bonds located in such a manner that no fully delocalized pi-electron system exists on any ring of the ring system.A heterocyclyl group can be an intermediate-sized heterocyclyl having 3 to 10 ring members. A heterocyclyl group can also be a heterocyclyl having 3 to 6 ring members. A heterocyclyl group may be designated as a "3-6 membered heterocyclyl" or a similar name.

[0042] The term "heteroaryl" refers to a 5-20 membered cyclic radical having 1-19 carbon atoms and 1-6 heteroatoms (each independently being nitrogen (e.g., N, NH, NR, etc.), oxygen, or sulfur) as ring members. Heteroaryl radicals can be monocyclic, bicyclic, tricyclic, or tetracyclic systems, including fused or bridged ring systems, with at least one ring being aromatic. Nitrogen, carbon, or sulfur atoms in heteroaryl radicals can be optionally oxidized, and nitrogen atoms can be optionally quaternized. Heteroaryl groups can contain 5-14 ring members (atoms within the ring), 5-10 ring members (atoms within the ring), 5-9 ring members (atoms within the ring), 5-7 ring members (atoms within the ring), or 5-6 ring members (atoms within the ring). Heteroaryl groups can be intermediate-sized heteroaryls with 5-10 ring members. Heteroaryl groups can also be heteroaryls with 5-6 ring members. A heteroaryl group can also be a heteroaryl having 6 to 9 ring members. A heteroaryl group may also have 6 ring members. A heteroaryl group may also have 9 ring members. In various embodiments, a heteroaryl contains 1 to 6 heteroatoms, 1 to 5 heteroatoms, 1 to 4 heteroatoms, 1 to 3 heteroatoms, 1 to 2 heteroatoms, or 1 heteroatom. For example, in various embodiments, a heteroaryl contains 1 to 5 nitrogen atoms, 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, 1 sulfur or oxygen atom, and so on.Examples include acridinil, benzimidazolyl, benzothiazolyl, benzindolyl, benzodioxolyl, benzofuranil, benzoxazolyl, benzothiazolyl, benzothiadiazolyl, benzo[b][1,4]dioxepinyl, 1,4-benzodioxanil, benzonaphthofuranil, benzoxazolyl, benzodioxolyl, benzodioxynil, benzopyranil, benzopyranonil, benzofuranil, benzothienyl (benzothiophenyl), benzotriazolyl, benzo[4,6]imidazo[1,2-a]pyridinil, carbazolyl, sinnolinil, dibenzofuranil, dibenzothiophenyl, furanil, isothiazolyl, imidazolyl, imidazo[1,2-a]pyridinil, indazolyl, indolyl, in Examples include, but are not limited to, dazolyl, isoindolyl, indolinyl, isoindolyl, indolidinyl, isoxazolyl, naphthilidinyl, oxadiazolyl, oxazolyl, 1-oxidepyridinyl, 1-oxidepyrimidinyl, 1-oxidepyradinyl, 1-oxidepyridazinyl, 1-oxidepyridazinyl, phenazinyl, phenothiazinyl, phenoxadinyl, phthalazinyl, pteridinyl, purinyl, pyrrolyl, pyrazolyl, pyridinyl, pyridinyl, pyrimidinyl, pyridadinyl, pyrazolopyridinyl, pyridinonyl, quinazolinyl, quinoxalinyl, quinolinyl, isoquinolinyl, tetrahydroquinolinyl, thiazolyl, thiadiazolyl, triazolyl, tetrazolyl, triazinyl, and thiophenyl (i.e., thienyl).

[0043] The term "polycyclic" refers to a ring system having multiple rings (e.g., bicyclic, tricyclic, or tetracyclic), which may include fused ring systems, bridged ring systems, and helical (e.g., spirocyclic) ring systems.

[0044] The term "hydroxy" (or "hydroxyl") refers to the -OH group.

[0045] The term "cyano" group refers to the "-CN" group.

[0046] The term "oxo" refers to an =O substituent.

[0047] The term "amino" refers to the NH2 group.

[0048] The term "alkylamino" is R A "-NR" is an alkyl group A This refers to the H group.

[0049] The term "dialkylamino" is R A and R B Each of them is an alkyl group "-NR" A R B It refers to the base. A and R B These, together with the nitrogen to which they are bound, can provide heteroaryl or heterocycline compounds.

[0050] The term "aminoalkyl" refers to amino groups linked via alkylene groups. Aminoalkyls can be unsubstituted or substituted.

[0051] Any "R" group used herein, for example, but not limited to, R 1 , R 2 , R 3 Etc. represents substituents that can be bonded to the indicated atom. R groups are either unsubstituted or substituted. When two “R” groups are described as “together” (or similar wording), these R groups and the atom to which they are bonded may form a ring (e.g., cycloalkyl, aryl, heteroaryl, heterocyclyl). When two R groups are said to form a ring (e.g., carbocykryl, heterocyclyl, aryl, or heteroaryl ring) “together with the atom to which they are bonded,” it means that the collective unit of the atom and the two R groups is the listed ring. A ring is not limited by the definition of each R group when taken individually. For example, the following substructure: [ka] If there exists and each example of R is defined independently as hydrogen or alkyl, or if each example of R together with the nitrogen to which R is bonded forms a heterocycline, then it means that each example of R can independently be hydrogen or alkyl, or instead, the underlying structure is structure: [ka] The formula has such that ring A is a nitrogen-containing heterocyclyl ring. Further illustrations, though not limited to, include NR. A R B Base R A and R B When it is indicated that they are "together", they are covalently bonded to each other, forming a ring. [ka] It means to form.

[0052] The following structures (or similar structures with different rings, heteroatoms, unsaturated bonds, etc.): [ka] A ring structure provided using [the specified method] may be shown.

[0053] When a cyclic structure is represented using this type of diagram, it means that an R group can be bonded to any position in the ring by substituting -H with -R. For example, the following ring: [ka] Regarding this, the following structure: [ka] This means that it includes any of the following, in the formula, [ka] This indicates the bond to the rest of the structure. Similarly, the following structure: [ka] (In the formula, [ka] The following structures are formed for each of the following (where n is 1-6): [ka] One of the above is assumed, or other variations (easily recognizable to those skilled in the art).

[0054] Additionally, if a nitrogen atom is present in the ring, a hydrogen atom may be removed from the nitrogen to achieve substitution. Therefore, the following structure: [ka] (In the formula, [ka] The following structures are formed for each of the following (where n is 1-6): [ka] One of the following is assumed, or other variations (easily recognizable to those skilled in the art). If specified, the nitrogen atom in the ring may provide a cation. Therefore, the following structure: [ka] (In the formula, [ka] The following structures are formed for each of the following (where n is 1-6): [ka] One of the above is assumed, or other variations (easily recognizable to those skilled in the art).

[0055] When two "adjacent" R groups are said to form a ring "together with the atom to which they are bonded," it means that the collective unit of the atom, the bond between them, and the two R groups is the enumerated ring. For example, the following substructure: [ka] There exists and R A and R B Each of them is independently hydrogen or alkyl, or R 1 and R 2 However, when these, together with the atom to which they are bonded, form an aryl or carbocykryl, R 1 and R 2 R can be selected from hydrogen or alkyl, or alternatively, the underlying structure is structure: [ka] The formula has the following characteristics, where A is an aryl ring or carbocyrill containing the represented double bond.

[0056] Whenever a substituent is represented as a diradical (i.e., has two bonding points to the rest of the molecule), it should be understood that the substituent can be bonded in any direction unless otherwise specified. For example, -AE- or [ka] The substituents represented as include substituents whose orientation is determined such that "A" is attached to the leftmost bond point of the molecule, and substituents whose orientation is determined such that "A" is attached to the rightmost bond point of the molecule.

[0057] As noted in the definition of alkylenes, it should be understood that certain radical naming conventions may include either monoradicals or diradicals, depending on the context. For example, a substituent is understood to be a diradical if it requires two bonding sites to the rest of the molecule. Diradical substituents identified as aminoalkyls that require two bonding sites include, for example, -NHCH2-, -NHCH2CH2-, and -NHCH2CH(CH3)CH2-. Other examples of substituents that may require two bonding sites include alkoxys, aryls, heteroaryls, carbocykries, and heterocyclines.

[0058] As used herein, radicals refer to species that possess a single unpaired electron, allowing the radical-containing species to covalently bond with another species. Therefore, in this context, radicals are not necessarily free radicals; rather, radicals represent specific parts of a larger molecule.

[0059] When a particular group (e.g., an R group) is indicated to be substituted, it is understood that such substitution occurs only if the bond valency allows it. Therefore, if the group is R and R is -H, or if an alkyl group containing R is indicated to be unsubstituted or substituted, it will be understood that the "-H" atom is unsubstituted because the bond valency does not allow it. On the other hand, if R is alkyl, R can be unsubstituted or substituted.

[0060] "Solvate" refers to a compound formed by the interaction of a solvent and a compound, metabolite, or salt thereof as described herein. A solvate means a solubilated form containing a stoichiometric or non-stoichiometric amount of solvent. When the solvent is water, the solvate formed is a hydrate; when the solvent is an alcohol, the solvate formed is an alcoholate. A hydrate is formed by a combination of one or more molecules of water with one of the substances in which water retains its molecular state as H2O. Such combinations can form one or more hydrates. Non-limiting examples of hydrates include monohydrates, dihydrates, etc. Non-limiting examples of solvates include ethanol solvate, acetone solvate, etc. It should be understood that the scope of this disclosure encompasses all solvents of the compounds disclosed herein and their stereoisomers, tautomers, and isotopically labeled forms or pharmaceutically acceptable salts of any of the foregoing.

[0061] The term "pharmaceutically acceptable excipients" includes all solvents, dispersions, coatings, antimicrobial and antifungal agents, as well as isotonic and absorption retardants. The use of such media and agents with pharmaceutically active substances is well known in the art. They are intended to be used in therapeutic compositions unless any conventional media or agent is incompatible with the active ingredient. In addition, various adjuvants commonly used in the art may be included, for example.

[0062] The term "pharmaceutically acceptable salt" refers to a salt that retains the biological efficacy and properties of a compound but is biologically or otherwise undesirable for medicinal use. In many cases, the compounds herein may form acid and / or base salts in the presence of amino and / or carboxyl groups or similar groups. Pharmaceutically acceptable acid addition salts may be prepared using and / or formed together with inorganic and organic acids. Examples of inorganic acids from which salts can be derived include hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, and phosphoric acid. Examples of organic acids from which salts can be derived include acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, camphosulfonic acid, maleic acid, malonic acid, succinic acid, fumaric acid, formic acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, and carbonic acid. Pharmaceutically acceptable base addition salts can be prepared using inorganic and organic bases, and / or formed together with inorganic and organic bases. Examples of inorganic bases from which salts can be derived include sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, and aluminum. Examples of organic bases from which salts can be derived include primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines, and basic ion exchange resins, specifically isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, and ethanolamine. Examples of organic bases from which salts can be derived include ethylenediamine, N-methylglucamine, lysine, arginine, ornithine, choline, N,N'-dibenzylethylenediamine, chloroprocaine, diethanolamine, procaine, N-benzylphenethylamine, piperazine, tris-(hydroxymethyl)-aminomethane, tetramethylammonium hydroxide, dibenzylamine, ephenamine, dehydroabiethylamine, N-ethylpiperidine, benzylamine, tetramethylammonium, tetraethylammonium, methylamine, dimethylamine, ethylamine, and basic amino acids.Other salts are known in the art, as described in International Publication No. 87 / 05297. In addition, salts of the compounds described herein may exist in hydrated or unhydrated (anhydrous) forms or as solvates with other solvent molecules.

[0063] The “intermediate” compounds used herein include structures produced from the described synthetic procedures before obtaining the final desired compound, whether isolated or generated in situ and not isolated. These intermediates are included within the scope of this disclosure. Exemplary embodiments of such intermediate compounds are described elsewhere in this specification.

[0064] Because the compounds of this disclosure may contain, for example, double bonds, one or more chiral carbon atoms, and rotationally hindered bonds, they may exist as stereoisomers such as double bond isomers (i.e., geometric isomers (E / Z)), enantiomers, diastereomers, and atropisomers. Therefore, it should be understood that the scope of this disclosure encompasses all possible stereoisomers of the exemplary compounds, including stereoisomerically pure forms (e.g., geometrically pure, enantiomerically pure (e.g., (R), (S), (R)(R), (S)(S)), diastereoisomerically pure, and atropisomerically pure) and mixtures of stereoisomers of any chemical structure (all or part) disclosed herein (e.g., both (R) and (S), diastereomers and atropisomers or mixtures of any of the aforementioned).

[0065] The term "mammal" is used in its usual biological sense. Specifically, it includes primates such as apes (chimpanzees, monkeys) and humans, as well as cattle, horses, sheep, goats, pigs, rabbits, dogs, cats, rats, and mice, but is not limited to these, and can include many other species.

[0066] Unless otherwise indicated, all figures used in this specification and the claims, representing amounts of components, reaction conditions, etc., should be understood in all cases as being modified by the term “approximately.” Therefore, unless otherwise specified, the numerical parameters shown in the following specification and the attached claims are approximations that may vary depending on the standard deviation found in their respective test measurements.

[0067] When referring to numerical values, the terms “or a range including and / or spanning the aforementioned values” (and variations thereof) mean including the aforementioned values ​​or any range spanning the aforementioned values. For example, when the 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 provided (e.g., 20°C, 30°C, 40°C, or 50°C) or a temperature range extending from 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 to 50°C.

[0068] compound One embodiment provided herein is formula (I) [ka] A compound of or a pharmaceutically acceptable salt of the said compound, in which, [ka] teeth, [ka] And, a is N, -N + -O - or CH, b is N or CH, c is N, CH, or CR 3 And, d is N, CH, or CR 4 And, R 1a is -H, C 1~6 Alkyl, C1~6 Haloalkyl or C 1~6 It is heteroalkyl, R 1a These are either unsubstituted or each independently a halogen, -OH, and -N(R) b )2, C 1~3 Alkyl or C 1~3 It may be substituted with one or more substituents that are alkoxy. R 1b C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Heteroalkyl, C 3~10 A cycloalkyl or heterocyclyl having 3 to 10 ring members, R 1b These are either unsubstituted or each independently a halogen, -OH, and -N(R) b )2, C 1~3 Alkyl or C 1~3 It may be substituted with one or more substituents that are alkoxy, or Instead, R 1a and R 1b They form heterocyclines together, each having 3 to 10 ring members. R 1a and R 1b The heterocyclyls formed by this process are either unsubstituted or each independently contains a halogen, -OH, -CN, and -N(R) b )2, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 Heteroalkyl, C 3~6 It may be substituted with one or more substituents that are cycloalkyl or heterocyclyl having 3 to 6 ring members. R 2 is a heterocyclyl having 5 to 20 ring members, a heteroaryl having 5 to 20 ring members, or alternatively, a is -N + -O - If R 2 It can be H, R 2 is either non-substitutive or R 5 It may be replaced with one or more examples of R 5Each example independently includes oxo, CN, halogen, -OH, and C. 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C(O)N(R) 6 )2, -N(R 6 )2, -N(R 6 )(C 1~6 It is an alkylene-OH or a heterocycline having 3 to 10 members. R 5 Each example is either non-substitution or R 6 It may be replaced with one or more examples of R 6 Each of these examples is independent of -H, C 1~6 Alkyl, C(O)C 1~6 Alkyl, C(O)2C 1~6 Alkyl, C 1~6 Alkylene-OH or S(O) n C 1~6 It is an alkyl group, and n is 0, 1, or 2. R 6 These are either unsubstituted or each is independently -F, -OH, C 1~3 It may be substituted with one or more substituents that are alkoxy. R 3 is -H, C 1~6 Alkyl, C 3~10 Cycloalkyl, C 6~10 The aryl, heteroaryl having 5 to 10 ring members, or heterocyclyl having 3 to 10 ring members, R 3 These are either unsubstituted or each independently a halogen, -OH, oxo, and -N(R) b )2, C 1~3 Alkyl, C 1~3 Haloalkyl, C 1~3 Alkoxy, C 1~3 Alkylene-C 1~3 Alkoxy or C 1~6 It may be substituted with one or more substituents that are heteroalkyl. R 4 is -H, C 1~6 Alkyl or -N(R) 7 )2, and if present, R7 Each of these examples is independently -H or C 1~6 It is alkyl, or instead, it has two R's. 7 The substituents together form a heterocyclyl having 3 to 6 ring members. R 7 These are either unsubstituted or each is independently -F, -OH, C 1~3 Alkyl or C 1~3 It may be substituted with one or more substituents that are alkoxy. If present, R b Each of these examples is independently -H or C 1~6 It is alkyl, or instead, it has two R's. b The substituents together form a heterocyclyl having 3 to 6 ring members. R b These are either unsubstituted or each is independently -F, -OH, C 1~3 Alkyl or C 1~3 It can be substituted with one or more substituents that are alkoxy. For example, a is -N + -O - If or only if R 2 This can be H. In some embodiments, R 2 It is not thiophenyl. In some embodiments, R 4 is -N(R 7 ) Not 2. In some embodiments, R 4 is -H or C 1~6 It is alkyl. In some embodiments, R 3 If R is phenyl, 4 is -H or C 1~6 It is alkyl. In some embodiments, R 3 If R is an unsubstituted phenyl, 4 is H or C 1~6 It is alkyl. In some embodiments, R 1a is -H, C 1~3 Alkyl, C 1~3 Heteroalkyl or C 1~3 In some embodiments, R 1a C 1~6 Alkyl, C 1~6Heteroalkyl or C 1~6 In some embodiments, R 1a C 1~3 Alkyl, C 1~3 Heteroalkyl or C 1~3 In some embodiments, R 1a C 1~6 Alkyl or C 1~6 In some embodiments, R 1a is -H or C 1~6 It is alkyl. In some embodiments, R 1a is -H or C 1~6 In some embodiments, R 1a is -H or C 1~6 It is heteroalkyl. In some embodiments, R 1a C 1~6 It is alkyl. In some embodiments, R 1a C 1~6 In some embodiments, R 1a C 1~6 It is heteroalkyl. In some embodiments, R 1a is -H. In some embodiments, R 1b C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Heteroalkyl, C 3~10 It is a cycloalkyl or a heterocyclyl having 3 to 10 ring members. In some embodiments, R 1b C 1~6 Alkyl, C 1~6 Haloalkyl or C 1~6 It is heteroalkyl. In some embodiments, R 1b is propyl. In some embodiments, R 1b C 3~10 It is a cycloalkyl or a heterocyclyl having 3 to 10 ring members. In some embodiments, R 1b is a haloalkyl. In some embodiments, R 1b It is a heterocyclyl having 3 to 10 ring members. In some embodiments, R1a and R 1b These together form a heterocycline having 5 to 12 ring members. In some embodiments, R 1a and R 1b These together form a heterocycline having 6 to 12 ring members. In some embodiments, R 1a and R 1b These together form a heterocycline having 5 to 12 ring members. In some embodiments, R 1a and R 1b These together form a heterocycline having 6 to 12 ring members. In some embodiments, R 1a and R 1b These together form a heterocycline having 3 to 10 ring members. In some embodiments, R 1a and R 1b These together form a heterocycline having 4 to 6 ring members. In some embodiments, R 2 is a heteroaryl having 5 to 10 ring members or a heterocyclyl having 3 to 10 ring members. In some embodiments, R 2 It is a heteroaryl having 5 to 10 ring members. In some embodiments, R 3 C 1~6 Alkyl, C 1~6 Haloalkyl, C 3~6 Cycloalkyl, C 6~10 The aryl, heteroaryl having 5 to 10 ring members, or heterocyclyl having 5 to 10 ring members. In some embodiments, R 3 C 1~6 Alkyl, C 1~6 It is a haloalkyl or a heterocyclyl having 5 to 10 ring members. In some embodiments, R 3 is C 3~6 It is cycloalkyl. In some embodiments, R 3This is a heteroaryl having 5 to 10 ring members. In some embodiments, the haloalkyl provided in Variable Embodiment 1 is perhaled, and each -H is replaced with a halogen. In some embodiments, the haloalkyl provided in Variable Embodiment 1 is not perhaled and has one or more CHs (e.g., 1, 2, 3, 4, 5, 6, 7, 8 or more). In some embodiments, the CHs present in the haloalkyl provided in Variable Embodiment 1 may be on the same carbon (e.g., providing CH2 or CH3). The haloalkyl provided in Variable Embodiment 1 includes at least one halogen and optionally more than that (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, more than that, or prehalo). In some embodiments, each halogen is independently -F, -Cl, -Br, or -I. In some embodiments, the heteroalkyl provided in Variable Embodiment 1 contains heteroatoms within the alkyl skeleton. In some embodiments, each heteroatom of the heteroalkyl provided in Variable Embodiment 1 is independently nitrogen, oxygen, or sulfur (e.g., S, SO, or SO2). In some embodiments, the heteroalkyl provided in Variable Embodiment 1 may have 1 to 4 heteroatoms (e.g., 1, 2, 3, or 4), 1 to 3 heteroatoms (e.g., 1, 2, or 3), 1 or 2 heteroatoms, or 1 heteroatom. In some embodiments, R 7 These are either unsubstituted or each is independently -F, -OH, or alkoxyC. 1~3 It can be substituted with one or more substituents. b These are either unsubstituted or each is independently -F, -OH, or C 1~3 It can be substituted with one or more substituents that are alkoxy.

[0069] Provided herein as Embodiment 2 is the compound or salt of Embodiment 1, R 1a If H, then a is CH, b is CH, and c is CR. 3 And d is CR 4 And R 2 is thienyl, and R3 is phenyl, and R 4 NH2 is R 1b is C 1~3 It is alkyl, R 1b is either non-substitutive or C 1~3 It can be replaced with alkoxy. In some embodiments, R 3 is not -H. In some embodiments, R 4 is not -H. In some embodiments, R 6 It is not -H.

[0070] Provided herein as Embodiment 3 is a compound or salt of Embodiment 1 or 2, and R 1a However, C 1~6 Alkyl, C 1~6 Haloalkyl or C 1~6 If it is a heteroalkyl group, then d is CH.

[0071] Provided herein as Embodiment 4 is a compound or salt from any one of Embodiments 1 to 3, and R 2 However, if it is triazolyl, tetrahydropyranil, or oxetanil, R 1b It is not an unsubstituted or substituted cross-linked [2.2.2] heterocyclyl having eight ring members.

[0072] Provided herein as Embodiment 5 is any one of the compounds or salts from Embodiments 1 to 4, and R 2 However, if it is a heteroaryl with 5 ring members or a heterocyclyl with 4 to 6 ring members, R 1b It is not an unsubstituted or substituted cross-linked [2.2.2] heterocyclyl having eight ring members.

[0073] Provided herein as Embodiment 6 is any one of the compounds or salts from Embodiments 1 to 5, and R 1b It is not an unsubstituted or substituted cross-linked [2.2.2] heterocyclyl having eight ring members.

[0074] Provided herein as Embodiment 7 is any one of the compounds or salts from Embodiments 1 to 6, and R 1a However, it is H or Me and R 1b However, C 1~3 Alkyl or C 1~3 If it is a haloalkyl, R 3 It is not an unsubstituted or substituted morpholinyl.

[0075] Provided herein as Embodiment 8 is any one of the compounds or salts from Embodiments 1 to 7, and R 1a If H, then R 3 It is not an unsubstituted or substituted morpholinyl.

[0076] Provided herein as Embodiment 9 is a compound or salt from any one of Embodiments 1 to 8, and R 1a and R 1b However, when providing unsubstituted or substituted piperidinyl together, R 3 It is not an unsubstituted or substituted morpholinyl.

[0077] Provided herein as Embodiment 10 is a compound or salt from any one of Embodiments 1 to 8, and R 3 It is not an unsubstituted or substituted morpholinyl.

[0078] Provided herein as Embodiment 11 is any one compound or salt from Embodiments 1 to 10, and R 2 It is a heteroaryl compound that does not contain sulfur as a ring member.

[0079] Provided herein as Embodiment 12 is a compound or salt from any one of Embodiments 1 to 11, and R 2 teeth, [ka] isn't it.

[0080] Provided herein as Embodiment 13 is a compound or salt from any one of Embodiments 1 to 12, and R 1a It is not -H.

[0081] Embodiment 14 provided herein is any one compound or salt from Embodiments 1 to 13, and R 1b It is not propyl.

[0082] Provided herein as Embodiment 15 is any one compound or salt from Embodiments 1 to 14, where d is CR 4 If R 4 N(R) 7 ) Not 2.

[0083] Provided herein as Embodiment 16 is any one compound or salt from Embodiments 1 to 15, where d is CR 4 If R 4 It is not NH2.

[0084] Provided herein as Embodiment 17 is any one compound or salt from Embodiments 1 to 16, and R 3 teeth, [ka] isn't it.

[0085] Provided herein as Embodiment 18 is a compound or salt of any one of Embodiments 1 to 17, wherein the compound of formula (I) is [ka] isn't it.

[0086] Provided herein as Embodiment 19 is any one compound or salt from Embodiments 1 to 18, and R 2 teeth, [ka] isn't it.

[0087] Provided herein as Embodiment 20 is a compound or salt from any one of Embodiments 1 to 19, wherein the compound of formula (I) is not 3-amino-N-methyl-6-(2-piperidinyl)thieno[2,3-b]pyridine-2-carboxamide.

[0088] Provided herein as Embodiment 21 is a compound or salt from any one of Embodiments 1 to 20, wherein the compound of formula (I) is neither 1-cyclopentyl-4-[[6-(2-furanyl)-4-(trifluoromethyl)thieno[2,3-b]pyridine-2-yl]carbonyl]-2-piperazinone nor 1-cyclopentyl-4-[[6-(2-thienyl)-4-(trifluoromethyl)thieno[2,3-b]pyridine-2-yl]carbonyl]-2-piperazinone. For example, in some embodiments, the compound of formula (I) is not 1-cyclopentyl-4-[[6-(2-furanyl)-4-(trifluoromethyl)thieno[2,3-b]pyridine-2-yl]carbonyl]-2-piperazinone. In some embodiments, the compound of formula (I) is not 1-cyclopentyl-4-[[6-(2-thienyl)-4-(trifluoromethyl)thieno[2,3-b]pyridine-2-yl]carbonyl]-2-piperazinone.

[0089] Provided herein as Embodiment 22 is a compound or salt of any one of Embodiments 1 to 21, wherein the compound of formula (I) is not: 2-(1H-indazole-4-yl)-N-methyl-4-(morpholine-4-yl)thieno[2,3-d]pyrimidine-6-carboxamide, N-methoxy-N-methyl-2-(4-morpholinyl)thieno[2,3-d]pyrimidine-6 -Carboxamide, N-ethyl-2-(1H-indazole-4-yl)-4-(morpholin-4-yl)thieno[2,3-d]pyrimidine-6-carboxamide, 2-(1H-indazole-4-yl)-N-(1-methylethyl)-4-(4-morpholinyl)thieno[2,3-d]pyrimidine-6-carboxamide, N-(2-hydroxyethyl)-2-(1H-indazole-4 -yl)-4-(morpholine-4-yl)thieno[2,3-d]pyrimidine-6-carboxamide, 2-(1H-indazole-4-yl)-4-(4-morpholinyl)-N-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidine-6-carboxamide, 2-(1H-indazole-4-yl)-N,N-dimethyl-4-(morpholine-4-yl)thieno[2,3-d ]pyrimidine-6-carboxamide, [2-(1H-indazole-4-yl)-4-(morpholine-4-yl)thieno[2,3-d]pyrimidine-6-yl](4-methylpiperazine-1-yl)methanone, or [2-(1H-indazole-4-yl)-4-(morpholine-4-yl)thieno[2,3-d]pyrimidine-6-yl](4-acetylpiperazine-1-yl)methanone. For example, in some embodiments, the compound of formula (I) is not 2-(1H-indazole-4-yl)-N-methyl-4-(morpholine-4-yl)thieno[2,3-d]pyrimidine-6-carboxamide. In some embodiments, the compound of formula (I) is not N-methoxy-N-methyl-2-(4-morpholinyl)thieno[2,3-d]pyrimidine-6-carboxamide. In some embodiments, the compound of formula (I) is not N-ethyl-2-(1H-indazole-4-yl)-4-(morpholin-4-yl)thieno[2,3-d]pyrimidine-6-carboxamide.In some embodiments, the compound of formula (I) is not 2-(1H-indazole-4-yl)-N-(1-methylethyl)-4-(4-morpholinyl)thieno[2,3-d]pyrimidine-6-carboxamide. In some embodiments, the compound of formula (I) is not N-(2-hydroxyethyl)-2-(1H-indazole-4-yl)-4-(morpholinyl)thieno[2,3-d]pyrimidine-6-carboxamide. In some embodiments, the compound of formula (I) is not 2-(1H-indazole-4-yl)-4-(4-morpholinyl)-N-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidine-6-carboxamide. In some embodiments, the compound of formula (I) is not 2-(1H-indazole-4-yl)-N,N-dimethyl-4-(morpholine-4-yl)thieno[2,3-d]pyrimidine-6-carboxamide. In some embodiments, the compound of formula (I) is not [2-(1H-indazole-4-yl)-4-(morpholine-4-yl)thieno[2,3-d]pyrimidine-6-yl](4-methylpiperazine-1-yl)methanone. In some embodiments, the compound of formula (I) is not [2-(1H-indazole-4-yl)-4-(morpholine-4-yl)thieno[2,3-d]pyrimidine-6-yl](4-acetylpiperazine-1-yl)methanone.

[0090] Embodiment 23 provided herein is any one compound or salt from Embodiments 1 to 22, and R 3 However, if it is a heterocyclyl containing an N ring member, R 3 It is not linked to the structure of formula (I) through the N-ring member of the heterocyclyl.

[0091] Provided herein as Embodiment 24 is a compound or salt of any one of Embodiments 1 to 23, wherein the compound of formula (I) is not: 2-(2-amino-5-pyrimidinyl)-N-methyl-4-(4-morpholinyl)thieno[3,2-d]pyrimidine-6-carboxamide, 2-(1H-indazole-4-yl)-N-methyl-4-(4-morpholinyl)thieno[3,2-d]pyrimidine-6-carboxamide, N-ethyl-2-(1H-indazole-4-yl)-4-(4-morpholinyl)thieno[3,2-d]pyrimidine Midine-6-carboxamide, 2-(1H-indole-4-yl)-N-(2-methoxyethyl)-4-(4-morpholinyl)thieno[3,2-d]pyrimidine-6-carboxamide, N-(2-hydroxyethyl)-2-(1H-indazole-4-yl)-4-(4-morpholinyl)thieno[3,2-d]pyrimidine-6-carboxamide, 2-(1H-indazole-4-yl)-N-(2-methylpropyl)-4-(4-morpholinyl)thieno[3,2-d]pyrimidine-6-carboxamide, N-(2-hydroxy-1-methylpropyl) (1H-indazole-4-yl)-4-(4-morpholinyl)thieno[3,2-d]pyrimidine-6-carboxamide, 2-(1H-indazole-4-yl)-N-(2-methoxyethyl)-4-(4-morpholinyl)thieno[3,2-d]pyrimidine-6-carboxamide, 2-(2-amino-5-pyrimidinyl)-4-(4-morpholinyl)-N-[2-(1-piperidinyl)ethyl]thieno[3,2-d]pyrimidine-6-carboxamide, 2-(1H-indazole-4-yl)-4-(4-morpholinyl) N-[2-(4-morpholinyl)ethyl]thieno[3,2-d]pyrimidine-6-carboxamide, 2-(1H-indazole-4-yl)-4-(4-morpholinyl)-N-[2-(1-piperidinyl)ethyl]thieno[3,2-d]pyrimidine-6-carboxamide, 2-(1H-indazole-4-yl)-4-(4-morpholinyl)-N-(2,2,2-trifluoroethyl)thieno[3,2-d]pyrimidine-6-carboxamide, [2-(2-amino-5-pyrimidinyl)-4-(4-morpholinyl)thieno[3,[2-d]pyrimidine-6-yl]-4-morpholinylmethanone, 2-(1H-indazole-4-yl)-N,N-dimethyl-4-(4-morpholinyl)thieno[3,2-d]pyrimidine-6-carboxamide, [2-(2-amino-5-pyrimidinyl)-4-(4-morpholinyl)thieno[3,2-d]pyrimidine-6-yl](4-methyl-1-piperazinyl)methanone, [2-(2-amino-5-pyrimidinyl)-4-(4-morpholinyl Linyl)thieno[3,2-d]pyrimidine-6-yl][4-(2-hydroxyethyl)-1-piperazinyl]methanone, [2-(1H-indazole-4-yl)-4-(4-morpholinyl)thieno[3,2-d]pyrimidine-6-yl]-4-morpholinylmethanone, N,N-bis(2-hydroxyethyl)-2-(1H-indazole-4-yl)-4-(4-morpholinyl)thieno[3,2-d]pyrimidine-6-carboxamide [2-(1H-indazole-4-yl)-4-(4-morpholinyl)thieno[3,2-d]pyrimidine-6-yl](4-methyl-1-piperazinyl)methanone, [2-(1H-indazole-4-yl)-4-(4-morpholinyl)thieno[3,2-d]pyrimidine-6-yl][3-(methylamino)-1-pyrrolidinyl]methanone, (4-hydroxy-1-piperidinyl)[2-(1H-indazole-4-yl)-4-(4- [Morpholinyl)thieno[3,2-d]pyrimidine-6-yl]methanone, [4-(2-hydroxyethyl)-1-piperazinyl][2-(1H-indazole-4-yl)-4-(4-morpholinyl)thieno[3,2-d]pyrimidine-6-yl]methanone or [2-(1H-indazole-4-yl)-4-(4-morpholinyl)thieno[3,2-d]pyrimidine-6-yl][4-(1-pyrrolidinyl)-1-piperidinyl]methanone. For example, in some embodiments, the compound of formula (I) is not 2-(2-amino-5-pyrimidinyl)-N-methyl-4-(4-morpholinyl)thieno[3,2-d]pyrimidine-6-carboxamide. In some embodiments, the compound of formula (I) is 2-(1H-indazole-4-yl)-N-methyl-4-(4-morpholinyl)thieno[3,It is not [2-d]pyrimidine-6-carboxamide. In some embodiments, the compound of formula (I) is not N-ethyl-2-(1H-indazole-4-yl)-4-(4-morpholinyl)thieno[3,2-d]pyrimidine-6-carboxamide. In some embodiments, the compound of formula (I) is not 2-(1H-indole-4-yl)-N-(2-methoxyethyl)-4-(4-morpholinyl)thieno[3,2-d]pyrimidine-6-carboxamide. In some embodiments, the compound of formula (I) is not N-(2-hydroxyethyl)-2-(1H-indazole-4-yl)-4-(4-morpholinyl)thieno[3,2-d]pyrimidine-6-carboxamide. In some embodiments, the compound of formula (I) is not 2-(1H-indazole-4-yl)-N-(2-methylpropyl)-4-(4-morpholinyl)thieno[3,2-d]pyrimidine-6-carboxamide. In some embodiments, the compound of formula (I) is not N-(2-hydroxy-1-methylethyl)-2-(1H-indazole-4-yl)-4-(4-morpholinyl)thieno[3,2-d]pyrimidine-6-carboxamide. In some embodiments, the compound of formula (I) is not 2-(1H-indazole-4-yl)-N-(2-methoxyethyl)-4-(4-morpholinyl)thieno[3,2-d]pyrimidine-6-carboxamide. In some embodiments, the compound of formula (I) is not 2-(2-amino-5-pyrimidinyl)-4-(4-morpholinyl)-N-[2-(1-piperidinyl)ethyl]thieno[3,2-d]pyrimidine-6-carboxamide. In some embodiments, the compound of formula (I) is not 2-(1H-indazole-4-yl)-4-(4-morpholinyl)-N-[2-(4-morpholinyl)ethyl]thieno[3,2-d]pyrimidine-6-carboxamide. In some embodiments, the compound of formula (I) is not 2-(1H-indazole-4-yl)-4-(4-morpholinyl)-N-[2-(1-piperidinyl)ethyl]thieno[3,2-d]pyrimidine-6-carboxamide. In some embodiments, the compound of formula (I) is 2-(1H-indazole-4-yl)-4-(4-morpholinyl)-N-(2,2,2-trifluoroethyl)thieno[3,It is not [2-d]pyrimidine-6-carboxamide. In some embodiments, the compound of formula (I) is not [2-(2-amino-5-pyrimidinyl)-4-(4-morpholinyl)thieno[3,2-d]pyrimidin-6-yl]-4-morpholinylmethanone. In some embodiments, the compound of formula (I) is not 2-(1H-indazole-4-yl)-N,N-dimethyl-4-(4-morpholinyl)thieno[3,2-d]pyrimidin-6-carboxamide. In some embodiments, the compound of formula (I) is not [2-(2-amino-5-pyrimidinyl)-4-(4-morpholinyl)thieno[3,2-d]pyrimidin-6-yl](4-methyl-1-piperazinyl)methanone. In some embodiments, the compound of formula (I) is not [2-(2-amino-5-pyrimidinyl)-4-(4-morpholinyl)thieno[3,2-d]pyrimidine-6-yl][4-(2-hydroxyethyl)-1-piperazinyl]methanone. In some embodiments, the compound of formula (I) is not [2-(1H-indazole-4-yl)-4-(4-morpholinyl)thieno[3,2-d]pyrimidine-6-yl]-4-morpholinylmethanone. In some embodiments, the compound of formula (I) is not N,N-bis(2-hydroxyethyl)-2-(1H-indazole-4-yl)-4-(4-morpholinyl)thieno[3,2-d]pyrimidine-6-carboxamide. In some embodiments, the compound of formula (I) is not [2-(1H-indazole-4-yl)-4-(4-morpholinyl)thieno[3,2-d]pyrimidine-6-yl](4-methyl-1-piperazinyl)methanone. In some embodiments, the compound of formula (I) is not [2-(1H-indazole-4-yl)-4-(4-morpholinyl)thieno[3,2-d]pyrimidine-6-yl][3-(methylamino)-1-pyrrolidinyl]methanone. In some embodiments, the compound of formula (I) is (4-hydroxy-1-piperidinyl)[2-(1H-indazole-4-yl)-4-(4-morpholinyl)thieno[3,It is not [2-d]pyrimidine-6-yl]methanone. In some embodiments, the compound of formula (I) is not [4-(2-hydroxyethyl)-1-piperazinyl][2-(1H-indazole-4-yl)-4-(4-morpholinyl)thieno[3,2-d]pyrimidine-6-yl]methanone. In some embodiments, the compound of formula (I) is not [2-(1H-indazole-4-yl)-4-(4-morpholinyl)thieno[3,2-d]pyrimidine-6-yl][4-(1-pyrrolidinyl)-1-piperidinyl]methanone.

[0092] Provided herein as Embodiment 25 is any one compound or salt from Embodiments 1 to 10, and R 1a H is and R 1b C 1~3 If it is alkyl, R 2 It is not a heteroaryl compound having 10 ring members and being substituted with NH2.

[0093] Provided herein as Embodiment 26 is any one compound or salt from Embodiments 1 to 25, and R 2 is pyrrolyl, and R 1b If R is methyl, 1a It is not H or methyl.

[0094] Embodiment 27 provided herein is any one of the compounds or salts from Embodiments 1 to 26. [ka] teeth, [ka] That is the case.

[0095] Embodiment 28 provided herein is any one of the compounds or salts from Embodiments 1 to 26. [ka] teeth, [ka] That is the case.

[0096] Embodiment 29 provided herein is a compound or salt from any one of Embodiments 1 to 28, where a is N.

[0097] Embodiment 30 provided herein is a compound or salt from any one of Embodiments 1 to 28, where a is CH.

[0098] Embodiment 31, as provided herein, is one of the compounds or salts from Embodiments 1 to 30, where b is N.

[0099] Embodiment 32, as provided herein, is a compound or salt from any one of Embodiments 1 to 30, where b is CH.

[0100] Embodiment 33, as provided herein, is a compound or salt from any one of Embodiments 1 to 32, where c is N.

[0101] Embodiment 34 provided herein is a compound or salt from any one of Embodiments 1 to 32, where c is CH.

[0102] Provided herein as Embodiment 35 is any one compound or salt from Embodiments 1 to 32, where c is CR 3 That is the case.

[0103] Embodiment 36, as provided herein, is a compound or salt from any one of Embodiments 1 to 35, where d is N.

[0104] Embodiment 37 provided herein is a compound or salt from any one of Embodiments 1 to 35, where d is CH.

[0105] Provided herein as Embodiment 38 is any one compound or salt from Embodiments 1 to 35, where d is CR 4 That is the case.

[0106] Provided herein as Embodiment 39 is any one of the compounds or salts from Embodiments 1 to 28. [ka] The basis is, [ka] For example, in some embodiments, [ka] The basis is, [ka] In some embodiments, [ka] The basis is, [ka] In some embodiments, [ka] The basis is, [ka] In some embodiments, [ka] The basis is, [ka] In some embodiments, [ka] The basis is, [ka] In some embodiments, [ka] The basis is, [ka] In some embodiments, [ka] The basis is, [ka] In some embodiments, [ka] The basis is, [ka] In some embodiments, [ka] The basis is, [ka] That is the case.

[0107] Provided herein as Embodiment 40 is one of the compounds or salts from Embodiments 1, 28, or 39. [ka] teeth, [ka] That is the case.

[0108] Provided herein as Embodiment 41 is one of the compounds or salts from Embodiments 1, 28, or 39. [ka] teeth, [ka] That is the case.

[0109] Provided herein as Embodiment 42 is one of the compounds or salts from Embodiments 1, 28, or 39. [ka] teeth, [ka] That is the case.

[0110] Provided herein as Embodiment 43 is one of the compounds or salts from Embodiments 1, 28, or 39. [ka] teeth, [ka] That is the case.

[0111] Provided herein as Embodiment 44 is one of the compounds or salts from Embodiments 1, 28, or 39. [ka] teeth, [ka] That is the case.

[0112] Provided herein as Embodiment 45 is one of the compounds or salts from Embodiments 1, 28, or 39. [ka] teeth, [ka] That is the case.

[0113] Embodiment 46 provided herein is one compound or salt from any of Embodiments 1 to 45, where two or fewer examples a, b, and c are N.

[0114] Embodiment 47 provided herein is one compound or salt from any of Embodiments 1 to 46, where two or fewer examples a, b, c, and d are N.

[0115] Embodiment 48 provided herein is one compound or salt from any of Embodiments 1 to 47, wherein only one of a, b, and c is N.

[0116] Embodiment 49 provided herein is one compound or salt from any of Embodiments 1 to 48, wherein only one of a, b, c, and d is N.

[0117] Provided herein as Embodiment 50 is any one compound or salt from Embodiments 1 to 49, and R 1a is -H, C 1~3 Alkyl or C 1~3 It is a haloalkyl. For example, in some embodiments, R 1a is -H or C 1~3 In some embodiments, R 1a C 1~3 Alkyl or C 1~3 In some embodiments, R 1a is -H or C 1~3 It is alkyl. In some embodiments, R 1a is C 1~2 It is alkyl. In some embodiments, R 1a is methyl. In some embodiments, R 1ais a C2 alkyl group. In some embodiments, R 1a is a C3 alkyl group. In some embodiments, R 1a is C 1~2 In some embodiments, R 1a is a C1 haloalkyl. In some embodiments, R 1a is a C2 haloalkyl. In some embodiments, R 1a It is a C3 haloalkyl.

[0118] Provided herein as Embodiment 51 is any one compound or salt from Embodiments 1 to 50, and R 1a is alkyl. For example, in some embodiments, R 1a is C 1~6 It is alkyl. In some embodiments, R 1a is C 1~5 It is alkyl. In some embodiments, R 1a is C 1~4 It is alkyl. In some embodiments, R 1a is C 1~3 It is alkyl. In some embodiments, R 1a is C 1~2 It is alkyl. In some embodiments, R 1a is C 2~3 It is alkyl. In some embodiments, R 1a is a C1 alkyl group. In some embodiments, R 1a is a C2 alkyl group. In some embodiments, R 1a It is a C3 alkyl group.

[0119] Provided herein as Embodiment 52 is any one compound or salt from Embodiments 1 to 50, R 1a is a haloalkyl. For example, in some embodiments, R 1a is C 1~6 In some embodiments, R 1a is C 1~5 In some embodiments, R 1a is C 1~4In some embodiments, R 1a is C 1~3 In some embodiments, R 1a is C 1~2 In some embodiments, R 1a is C 2~3 In some embodiments, R 1a is a C1 haloalkyl. In some embodiments, R 1a is a C2 haloalkyl. In some embodiments, R 1a It is a C3 haloalkyl.

[0120] Provided herein as Embodiment 53 is one of the compounds or salts from Embodiments 1 to 52, and R 1a R is substituted with 1, 2, 3, or 4 substituents. For example, in some embodiments, R 1a is substituted with 1 to 4 substituents. In some embodiments, R 1a is substituted with 1 to 3 substituents. In some embodiments, R 1a is substituted with one or two substituents. In some embodiments, R 1a is substituted with 2 to 4 substituents. In some embodiments, R 1a It is substituted with 3 to 4 substituents. In some embodiments, R 1a It is substituted with 2-3 substituents.

[0121] Provided herein as Embodiment 54 is any one compound or salt from Embodiments 1 to 53, and R 1a It is substituted with one, two, or three substituents.

[0122] Provided herein as Embodiment 55 is any one compound or salt from Embodiments 1 to 54, and R 1a It is substituted with one or two substituents.

[0123] Provided herein as Embodiment 56 is any one compound or salt from Embodiments 1 to 55, and R 1a It is substituted with one substituent.

[0124] Provided herein as Embodiment 57 is any one compound or salt from Embodiments 1 to 56, and R 1a If it is replaced, each R 1a The substituents are, independently, halogen, -OH, and C. 1~3 Alkyl or C 1~3 It is an alkoxy. For example, in some embodiments, R 1a is substituted with -F or -OH. In some embodiments, R 1a is -OH or C 1~3 It is replaced with alkoxy. In some embodiments, R 1a is -F or C 1~3 It is replaced with alkoxy. In some embodiments, R 1a R is substituted with -F, -OH, C1 alkyl, C2 alkyl, C3 alkyl, C1 alkoxy, C2 alkoxy and / or C3 alkoxy. In some embodiments, R 1a R is substituted with methyl, C2 alkyl and / or C3 alkyl. In some embodiments, R 1a is substituted with -C1 alkoxy, C2 alkoxy, or C3 alkoxy. In some embodiments, R 1a is substituted with -C1 alkoxy. In some embodiments, R 1a is replaced with C2 alkoxy. In some embodiments, R 1a It is replaced with C3 alkoxy. In some embodiments, R 1a is replaced with -F. In some embodiments, R 1a is substituted with -OH. In some embodiments, R 1a It is substituted with methyl.

[0125] Provided herein as Embodiment 58 is any one compound or salt from Embodiments 1 to 57, and R 1aIf it is replaced, each R 1a The substituents are independently -F, -OH, or C 1~3 It is an alkoxy.

[0126] Provided herein as Embodiment 59 is any one compound or salt from Embodiments 1 to 52, and R 1a This is a non-substitution.

[0127] Provided herein as Embodiment 60 is any one compound or salt from Embodiments 1 to 50, R 1a It is either -H or -CH3.

[0128] Provided herein as Embodiment 61 is one compound or salt from any of Embodiments 1-12 and 14-50, R 1a is -H.

[0129] Provided herein as Embodiment 62 is any one compound or salt from Embodiments 1 to 50, R 1a It is -CH3.

[0130] Provided herein as Embodiment 63 is any one compound or salt from Embodiments 1 to 62, and R 1b C 1~3 Alkyl, C 1~3 Haloalkyl, C 3~6 It is a cycloalkyl or a heterocyclyl having 3 to 6 ring members. For example, in some embodiments, R 1b C 1~3 Haloalkyl, C 3~6 It is a cycloalkyl or a heterocyclyl having 3 to 6 ring members. In some embodiments, R 1b C 1~3 Alkyl, C 3~6 It is a cycloalkyl or a heterocyclyl having 3 to 6 ring members. In some embodiments, R 1b C 1~3 Alkyl, C 1~3 Haloalkyl or C 3~6 It is cycloalkyl. In some embodiments, R1b C 1~3 Alkyl or C 3~6 It is cycloalkyl. In some embodiments, R 1b C 1~3 Alkyl or C 1~3 In some embodiments, R 1b C 3~6 It is a cycloalkyl or a heterocyclyl having 3 to 6 ring members. In some embodiments, R 1b C 1~3 It is a haloalkyl or a heterocyclyl having 3 to 6 ring members. In some embodiments, R 1b C 1~3 Haloalkyl or C 3~6 It is cycloalkyl. In some embodiments, R 1b If R is alkyl, 1b is C 1~2 It is alkyl. In some embodiments, R 1b If R is alkyl, 1b is C 2~3 It is alkyl. In some embodiments, R 1b If R is alkyl, 1b is a C1 alkyl group. In some embodiments, R 1b If R is alkyl, 1b is a C2 alkyl group. In some embodiments, R 1b If R is alkyl, 1b is a C3 alkyl group. In some embodiments, R 1b If R is a haloalkyl, 1b is C 1~2 In some embodiments, R 1b If R is a haloalkyl, 1b is C 2~3 In some embodiments, R 1b If R is a haloalkyl, 1b is a C1 haloalkyl. In some embodiments, R 1b If R is a haloalkyl, 1b is a C2 haloalkyl. In some embodiments, R 1bIf R is a haloalkyl, 1b R is a C3 haloalkyl. In some embodiments, R 1b If R is a cycloalkyl group, 1b is C 4~6 It is cycloalkyl. In some embodiments, R 1b If R is a cycloalkyl group, 1b is C 3~5 It is cycloalkyl. In some embodiments, R 1b If R is a cycloalkyl group, 1b R is a C3 cycloalkyl. In some embodiments, R 1b If R is a cycloalkyl group, 1b R is a C4 cycloalkyl. In some embodiments, R 1b If R is a cycloalkyl group, 1b R is a C5 cycloalkyl. In some embodiments, R 1b If R is a cycloalkyl group, 1b R is a C6 cycloalkyl. In some embodiments, R 1b If R is a heterocycline, 1b It is a heterocyclyl having 4 to 6 ring members. In some embodiments, R 1b If R is a heterocycline, 1b It is a heterocyclyl having 3 to 5 ring members. In some embodiments, R 1b If R is a heterocycline, 1b It is a heterocyclyl having three ring members. In some embodiments, R 1b If R is a heterocycline, 1b It is a heterocyclyl having four ring members. In some embodiments, R 1b If R is a heterocycline, 1b It is a heterocyclyl having five ring members. In some embodiments, R 1b If R is a heterocycline, 1b It is a heterocyclyl having six ring members.

[0131] Provided herein as Embodiment 64 is any one compound or salt from Embodiments 1 to 63, and R 1b It is a heterocycline.

[0132] Provided herein as Embodiment 65 is any one compound or salt from Embodiments 1 to 64, and R 1b It is a heterocycline, and each is independently nitrogen, oxygen, or -S(O) x - comprises 1, 2, 3, or 4 heteroatom ring members, where x is 0, 1, or 2. For example, in some embodiments, R 1b If R is a heterocycline, 1b A heterocyclyl comprises one or three heteroatom ring members. In some embodiments, R 1b If R is a heterocycline, 1b A heterocyclyl contains two or three heteroatom ring members.

[0133] Embodiment 66 provided herein is any one compound or salt from Embodiments 1 to 65, and R 1b It is a heterocyclyl and has one, two, or three heteroatom ring members.

[0134] Embodiment 67 provided herein is any one compound or salt from Embodiments 1 to 66, and R 1b It is a heterocyclyl and has one or two heteroatom ring members.

[0135] Provided herein as Embodiment 68 is any one compound or salt from Embodiments 1 to 67, and R 1b It is a heterocyclyl and has one heteroatom ring member.

[0136] Embodiment 69 provided herein is any one compound or salt from Embodiments 1 to 68, and R 1b It is a heterocycline, and has heteroatom ring members or R 1b The ring members contain or consist of nitrogen.

[0137] Provided herein as Embodiment 70 is any one compound or salt from Embodiments 1 to 69, and R 1b It is a heterocycline, and has heteroatom ring members or R 1b The heteroatom ring members contain or consist of oxygen.

[0138] Provided herein as Embodiment 71 is any one compound or salt from Embodiments 1 to 63, and R 1b It is alkyl.

[0139] Provided herein as Embodiment 72 is a compound or salt of any one of Embodiments 1 to 63, and R 1b It is a haloalkyl.

[0140] Provided herein as Embodiment 73 is a compound or salt of any one of Embodiments 1 to 63, and R 1b It is a cycloalkyl group.

[0141] Provided herein as Embodiment 74 is any one of the compounds or salts described in Embodiments 1 to 70, and R 1b It is a heterocyclyl with 3 to 6 ring members.

[0142] Provided herein as Embodiment 75 is any one compound or salt from Embodiments 1 to 74, and R 1b R is substituted with 1, 2, 3, or 4 substituents. For example, in some embodiments, R 1b is substituted with 1 to 4 substituents. In some embodiments, R 1b is substituted with 1 to 3 substituents. In some embodiments, R 1b is substituted with one or two substituents. In some embodiments, R 1b is substituted with 2 to 4 substituents. In some embodiments, R 1b It is substituted with 3 to 4 substituents. In some embodiments, R 1bIt is substituted with 2-3 substituents.

[0143] Provided herein as Embodiment 76 is any one compound or salt from Embodiments 1 to 75, and R 1b It is substituted with one, two, or three substituents.

[0144] Provided herein as Embodiment 77 is any one compound or salt from Embodiments 1 to 76, and R 1b It is substituted with one or two substituents.

[0145] Provided herein as Embodiment 78 is any one compound or salt from Embodiments 1 to 77, and R 1b It is substituted with one substituent.

[0146] Provided herein as Embodiment 79 is any one compound or salt from Embodiments 1 to 78, and R 1b If it is replaced, each R 1b The substituents are, independently, halogens, and C 1~3 Alkyl or C 1~3 It is an alkoxy. For example, in some embodiments, R 1b If it is replaced, each R 1b The substituents are independently halogens or C 1~3 It is an alkoxy. In some embodiments, R 1b If it is replaced, each R 1b The substituents are independently halogens or C 1~3 It is alkyl. In some embodiments, R 1b If it is replaced, each R 1b The substituents are, independently, C 1~3 Alkyl or C 1~3 It is an alkoxy. In some embodiments, the substituent is -F, -Cl, or -Br. In some embodiments, the substituent is -F, or -Cl. In some embodiments, the substituent is -F. In some embodiments, the substituent is C 1~2 It is alkyl. In some embodiments, the substituent is C2~3 It is alkyl. In some embodiments, the substituent is methyl. In some embodiments, the substituent is C2 alkyl. In some embodiments, the substituent is C3 alkyl. In some embodiments, the substituent is C 1~2 It is an alkoxy. In some embodiments, the substituent is C 2~3 It is an alkoxy. In some embodiments, the substituent is a C1 alkoxy. In some embodiments, the substituent is a C2 alkoxy. In some embodiments, the substituent is a C3 alkoxy.

[0147] Provided herein as Embodiment 80 is one compound or salt from any of Embodiments 1 to 78, each R 1b The substituents are independently -F, -OH, methyl, or -OMe. For example, in some embodiments, the substituent is -OH, methyl, or -OMe. In some embodiments, the substituent is -F, methyl, or -OMe. In some embodiments, the substituent is -F, -OH, or -OMe. In some embodiments, the substituent is -F, -OH, or methyl. In some embodiments, the substituent is -F or -OH. In some embodiments, the substituent is -F or methyl. In some embodiments, the substituent is -F or -OMe. In some embodiments, the substituent is -OH or methyl. In some embodiments, the substituent is -OH or -OMe. In some embodiments, the substituent is methyl or -OMe.

[0148] Provided herein as Embodiment 81 is any one compound or salt from Embodiments 1 to 80, and R 1b It has been replaced with -OMe.

[0149] Provided herein as Embodiment 82 is any one compound or salt from Embodiments 1 to 74, and R 1b This is a non-substitution.

[0150] Provided herein as Embodiment 83 is one compound or salt from any one of Embodiments 1 to 63 or 82, and R 1b This is CH3, -CH2CH2-O-CH3, or unsubstituted cyclobutyl.

[0151] Provided herein as Embodiment 84 is one of the compounds or salts from Embodiments 1 to 49, [ka] teeth, [ka] It is represented by [this].

[0152] Provided herein as Embodiment 85 is one of the compounds or salts from Embodiments 1 to 49, [ka] teeth, [ka] It is represented by [this].

[0153] Provided herein as Embodiment 86 is one compound or salt from any of Embodiments 1 to 49, and R 1a and R 1b These together form a heterocycline with 3 to 10 members. For example, in some embodiments, R 1a and R 1b These together form a heterocycline having 3 to 6 ring members. In some embodiments, R 1a and R 1b These together form a heterocycline having 4 to 6 ring members. In some embodiments, R 1a and R 1b These together form a heterocycline having 5-6 ring members. In some embodiments, R 1a and R 1bThese together form a heterocycline having 3 to 5 ring members. In some embodiments, R 1a and R 1b These together form a heterocycline having 3-4 ring members. In some embodiments, R 1a and R 1b These together form a heterocycline having 4-5 ring members. In some embodiments, R 1a and R 1b These together form a heterocycline having 5 to 10 ring members. In some embodiments, R 1a and R 1b These together form a heterocycline having 6 to 10 ring members. In some embodiments, R 1a and R 1b These together form a heterocycline having 5 to 9 ring members. In some embodiments, R 1a and R 1b These together form a heterocycline having 6 to 9 ring members. In some embodiments, R 1a and R 1b This forms a heterocycline having three ring members. In some embodiments, R 1a and R 1b This forms a heterocycline having four ring members. In some embodiments, R 1a and R 1b This forms a heterocycline having five ring members. In some embodiments, R 1a and R 1b This forms a heterocycline having six ring members. In some embodiments, R 1a and R 1b This forms a heterocycline having seven ring members. In some embodiments, R 1a and R 1b They form a spiro-ring heterocycline together. In some embodiments, R 1a and R 1b They together form a heterocyclyl having a fused ring system. In some embodiments, R 1a and R 1bThey together form a heterocyclyl having a cross-linked ring system. In some embodiments, R 1a and R 1b It forms a heterocyclyl with two rings within the ring system.

[0154] Provided herein as Embodiment 87 is one compound or salt from any of Embodiments 1 to 49 and 86, and R 1a and R 1b They form heterocyclines together, R 1a and R 1b Each heteroatom ring member of a heterocycline is independently nitrogen, oxygen, or -S(O) x - and x is 0, 1, or 2.

[0155] Provided herein as Embodiment 88 is one compound or salt from any of Embodiments 1-49 and 86-87, and R 1a and R 1b This forms a heterocycline having one, two, or three heteroatom ring members. For example, in some embodiments, R 1a and R 1b This forms a heterocycline having one or three heteroatom ring members. In some embodiments, R 1a and R 1b These molecules together form heterocyclines, each having two or three heteroatom ring members.

[0156] Provided herein as Embodiment 89 is one compound or salt from any of Embodiments 1-49 and 86-88, and R 1a and R 1b These molecules together form heterocyclines, each having one or two heteroatom ring members.

[0157] Provided herein as Embodiment 90 is one compound or salt from any of Embodiments 1-49 and 86-89, R 1a and R 1b They form a heterocycline together, each having one heteroatom ring member.

[0158] Provided herein as Embodiment 91 is any one of the compounds or salts from Embodiments 87 to 90, R 1a and R 1b They form heterocyclines together, R 1a and R 1b The heteroatoms of heterocyclyls contain or consist of nitrogen.

[0159] Provided herein as Embodiment 92 is any one compound or salt from Embodiments 87 to 91, and R 1a and R 1b They form heterocyclines together, R 1a and R 1b The heteroatoms in heterocyclyl contain oxygen.

[0160] Provided herein as Embodiment 93 is one compound or salt from any of Embodiments 1 to 49 and 86 to 92, and R 1a and R 1b These together form heterocyclines substituted with 1, 2, 3, 4, or 5 substituents.

[0161] Provided herein as Embodiment 94 is one compound or salt from any of Embodiments 1 to 49 and 86 to 93, and R 1a and R 1b These combine to form heterocyclines substituted with 1, 2, 3, or 4 substituents.

[0162] Provided herein as Embodiment 95 is one compound or salt from any of Embodiments 1-49 and 86-94, and R 1a and R 1b These combine to form heterocyclines substituted with one, two, or three substituents.

[0163] Provided herein as Embodiment 96 is one compound or salt from any of Embodiments 1 to 49 and 86 to 95, and R 1a and R 1b These combine to form heterocyclines substituted with one or two substituents.

[0164] Provided herein as Embodiment 97 is one compound or salt from any of Embodiments 1 to 49 and 86 to 96, and R 1a and R 1b They form a heterocycline together, which is substituted with one substituent.

[0165] Provided herein as Embodiment 98 is one compound or salt from any of Embodiments 1 to 49 and 86 to 97, R 1a and R 1b However, when substituted heterocyclines are formed together, each substituent of the heterocycline is independently halogen, -CN, or C. 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 Heteroalkyl or C 3~6 It is a cycloalkyl group. For example, in some embodiments, R 1a and R 1b Each example of a substituent on a heterocyclyl is, independently, a halogen CN, C 1~6 Alkyl, C 1~6 Heteroalkyl, C 1~6 Alkoxy or C 1~6 In some embodiments, R 1a and R 1b An example of a substituent on a heterocyclyl is -OH. In some embodiments, R 1a and R 1b An example of a substituent on a heterocyclyl is -NH2. In some embodiments, R 1a and R 1b Examples of substituents on heterocyclines are halogens. In some embodiments, R 1a and R 1b Examples of substituents on heterocyclyls are -F, -Cl, or -Br. In some embodiments, R 1a and R 1b Examples of substituents on heterocyclyls are -F or -Cl. In some embodiments, R 1a and R 1bAn example of a substituent on a heterocyclyl is -F. In some embodiments, R 1a and R 1b Examples of substituents on heterocyclyls are C 1~3 It is alkyl. In some embodiments, R 1a and R 1b Examples of substituents on heterocyclyls are C 1~2 It is alkyl. In some embodiments, R 1a and R 1b Examples of substituents on heterocyclyls are C 2~3 It is alkyl. In some embodiments, R 1a and R 1b An example of a substituent on a heterocyclyl is methyl. In some embodiments, R 1a and R 1b Examples of substituents on heterocyclyls are C2 alkyl groups. In some embodiments, R 1a and R 1b Examples of substituents on heterocyclyls are C3 alkyl groups. In some embodiments, R 1a and R 1b Examples of substituents on heterocyclyls are C 1~3 In some embodiments, R 1a and R 1b Examples of substituents on heterocyclyls are C 1~2 In some embodiments, R 1a and R 1b Examples of substituents on heterocyclyls are C 2~3 In some embodiments, R 1a and R 1b Examples of substituents on heterocyclyls are C1-haloalkyls. In some embodiments, R 1a and R 1b Examples of substituents on heterocyclyls are C2 haloalkyls. In some embodiments, R 1a and R 1b Examples of substituents on heterocyclyls are C3 haloalkyls. In some embodiments, R 1a and R 1b Examples of substituents on heterocyclyls are C 1~3 It is heteroalkyl. In some embodiments, R1a and R 1b Examples of substituents on heterocyclyls are C 1~2 It is heteroalkyl. In some embodiments, R 1a and R 1b Examples of substituents on heterocyclyls are C 2~3 It is heteroalkyl. In some embodiments, R 1a and R 1b Examples of substituents on heterocyclyls are C1 heteroalkyls. In some embodiments, R 1a and R 1b Examples of substituents on heterocyclyls are C2 heteroalkyls. In some embodiments, R 1a and R 1b Examples of substituents on heterocyclyls are C3 heteroalkyls. In some embodiments, R 1a and R 1b Examples of substituents on heterocyclyls are C 1~2 It is an alkoxy. In some embodiments, R 1a and R 1b Examples of substituents on heterocyclyls are C 2~3 It is an alkoxy. In some embodiments, R 1a and R 1b An example of a substituent on a heterocyclyl is methoxy. In some embodiments, R 1a and R 1b Examples of substituents on heterocyclyls are C2 alkoxys. In some embodiments, R 1a and R 1b An example of a substituent on a heterocyclyl is a C3 alkoxy.

[0166] Provided herein as Embodiment 99 is one compound or salt from any of Embodiments 1 to 49 and 86 to 97, R 1a and R 1b However, when substituted heterocyclines are formed together, at least one substituent is -CF3, -CF2CF3, or -CF2CF2CF3.

[0167] Provided herein as Embodiment 100 is one compound or salt from any of Embodiments 1 to 49 and 86 to 97, and R 1a and R 1b However, when substituted heterocyclines are formed together, each substituent of the heterocycline is independently -F, -OH, oxo, -Me, -CF3, -CN, or methoxy. In some embodiments, R 1a and R 1b However, when a substituted heterocyclyl is formed together, the substituent of the heterocyclyl is -F. In some embodiments, R 1a and R 1b However, when a substituted heterocyclyl is formed together, the substituent of the heterocyclyl is -OH. In some embodiments, R 1a and R 1b However, when substituted heterocyclines are formed together, the substituents of the heterocyclines are oxo. In some embodiments, R 1a and R 1b However, when a substituted heterocyclyl is formed together, the substituent of the heterocyclyl is -Me. In some embodiments, R 1a and R 1b However, when a substituted heterocyclyl is formed together, the substituent of the heterocyclyl is -CF3. In some embodiments, R 1a and R 1b However, when a substituted heterocyclyl is formed together, the substituent of the heterocyclyl is -CN. In some embodiments, R 1a and R 1b However, when substituted together to form a heterocycline, the substituent on the heterocycline is methoxy.

[0168] Provided herein as Embodiment 101 is one compound or salt from any of Embodiments 1-49 and 86-92, and R 1a and R 1b They form unsubstituted heterocyclines together.

[0169] Provided herein as Embodiment 102 is one compound or salt from any of Embodiments 1-49 and 86-101, R 1a and R 1b When these molecules form a heterocyclyl, the heterocyclyl is a bicyclic fused ring system.

[0170] Provided herein as Embodiment 103 is one compound or salt from any of Embodiments 1-49 and 86-101, R 1a and R 1b When these molecules form a heterocyclil together, the heterocyclil is a bicyclic spirocycle system.

[0171] Provided herein as Embodiment 104 is one compound or salt from any of Embodiments 1-49 and 86-101, and R 1a and R 1b When these molecules form a heterocyclyl together, the heterocyclyl is a bridged ring system.

[0172] Provided herein as Embodiment 105 is one compound or salt from any of Embodiments 1-49 and 86-90, [ka] teeth, [ka] For example, in some embodiments, [ka] teeth, [ka] It is represented by. In some embodiments, [ka] teeth, [ka] It is represented by. In some embodiments, [ka] teeth, [ka] It is represented by. In some embodiments, [ka] teeth, [ka] It is represented by. In some embodiments, [ka] teeth, [ka] It is represented by. In some embodiments, [ka] teeth, [ka] It is represented by. In some embodiments, [ka] teeth, [ka] It is represented by. In some embodiments, [ka] teeth, [ka] It is represented by. In some embodiments, [ka] teeth, [ka] It is represented by. In some embodiments, [ka] teeth, [ka] It is represented by. In some embodiments, [ka] teeth, [ka] It is represented by. In some embodiments, [ka] teeth, [ka] It is represented by. In some embodiments, [ka] teeth, [ka] It is represented by. In some embodiments, [ka] teeth, [ka] It is represented by. In some embodiments, [ka] teeth, [ka] It is represented by. In some embodiments, [ka] teeth, [ka] It is represented by. In some embodiments, [ka] teeth, [ka] It is represented by. In some embodiments, [ka] teeth, [ka] It is represented by. In some embodiments, [ka] teeth, [ka] It is represented by. In some embodiments, [ka] teeth, [ka] It is represented by. In some embodiments, [ka] teeth, [ka] It is represented by. In some embodiments, [ka] teeth, [ka] It is represented by. In some embodiments, [ka] teeth, [ka] It is represented by. In some embodiments, [ka] teeth, [ka] It is represented by. In some embodiments, [ka] teeth, [ka] It is represented by. In some embodiments, [ka] teeth, [ka] It is represented by [this].

[0173] Provided herein as Embodiment 106 is one compound or salt from any of Embodiments 1-49 and 86-90, [ka] teeth, [ka] That is the case.

[0174] Provided herein as Embodiment 107 is one compound or salt from any of Embodiments 1-49 and 86-90, [ka] teeth, [ka] That is the case.

[0175] Provided herein as Embodiment 108 is one compound or salt from any of Embodiments 1 to 107, and R 2 It is a heterocycline.

[0176] Provided herein as Embodiment 109 is one compound or salt from any of Embodiments 1 to 107, and R 2 It is a heteroaryl compound.

[0177] Provided herein as Embodiment 110 is one compound or salt from any of Embodiments 1 to 109, and R 2 It has 1, 2, 3, 4, or 5 heteroatom ring members. For example, in some embodiments, R 2 It contains five heteroatom ring members. In some embodiments, R 2 It contains four heteroatom ring members. In some embodiments, R 2 It contains three heteroatom ring members. In some embodiments, R 2 It contains two heteroatom ring members. In some embodiments, R 2 It contains one heteroatom ring member. In some embodiments, R 2 It contains 1 to 5 heteroatom ring members. In some embodiments, R 2 It contains 1 to 4 heteroatom ring members. In some embodiments, R2 It contains 1 to 3 heteroatom ring members. In some embodiments, R 2 It contains 1-2 heteroatom ring members. In some embodiments, R 2 It contains 2 to 5 heteroatom ring members. In some embodiments, R 2 It contains 3 to 5 heteroatom ring members. In some embodiments, R 2 It contains 3 to 4 heteroatom ring members. In some embodiments, R 2 It contains a nitrogen atom as the sole ring heteroatom. In some embodiments, R 2 It contains one nitrogen atom as a ring heteroatom. In some embodiments, R 2 It contains two nitrogen atoms as a ring heteroatom. In some embodiments, R 2 It contains three nitrogen atoms as a ring heteroatom. In some embodiments, R 2 It contains four nitrogen atoms as a ring heteroatom. In some embodiments, R 2 It contains five nitrogen atoms as a ring heteroatom. In some embodiments, R 2 It contains one oxygen ring heteroatom, and the remaining ring heteroatoms are nitrogen atoms. In some embodiments, R 2 It contains an oxygen atom as the sole ring heteroatom.

[0178] Provided herein as Embodiment 111 is any one compound or salt from Embodiments 1 to 110, and R 2 It has 1, 2, 3, or 4 heteroatom ring members.

[0179] Provided herein as Embodiment 112 is any one compound or salt from Embodiments 1 to 111, and R 2 It has one, two, or three heteroatom ring members.

[0180] Provided herein as Embodiment 113 is one of the compounds or salts from Embodiments 1 to 112, and R 2 It has one or two heteroatom ring members.

[0181] Provided herein as Embodiment 114 is one of the compounds or salts from Embodiments 1 to 113, and R 2 It has one heteroatom ring member.

[0182] Provided herein as Embodiment 115 is any one compound or salt from Embodiments 1 to 114, and R 2 Each ring member heteroatom is independently nitrogen, oxygen, or -S(O) y - and y is 0, 1, or 2.

[0183] Provided herein as Embodiment 116 is one of the compounds or salts from Embodiments 1 to 115, and R 2 Each heteroatom in the ring is independently either nitrogen or oxygen.

[0184] Provided herein as Embodiment 117 is one of the compounds or salts from Embodiments 1 to 116, and R 2 Each ring heteroatom is nitrogen.

[0185] Provided herein as Embodiment 118 is any one compound or salt from Embodiments 1 to 116, and R 2 Each ring heteroatom is oxygen.

[0186] Provided herein as Embodiment 119 is any one compound or salt from Embodiments 1 to 118, and R 2 is a fused bicyclic group. In some embodiments, the fused bicyclic group R 2 It includes a 6-membered ring. In some embodiments, it is a condensed biringle R 2 It includes a 5-membered ring. In some embodiments, it is a condensed biringle R 2 It is a 5,6-membered condensed ring. In some embodiments, it is a condensed biringle R 2 It is a 6,6-membered condensed ring.

[0187] Provided herein as Embodiment 120 is any one compound or salt from Embodiments 1 to 119, and R 2 It contains 5 to 10 ring members.

[0188] Provided herein as Embodiment 121 is any one compound or salt from Embodiments 1 to 120, and R 2 It contains 5 to 9 ring members.

[0189] Provided herein as Embodiment 122 is any one compound or salt from Embodiments 1 to 120, R 2 It contains 10 ring members.

[0190] Provided herein as Embodiment 123 is any one compound or salt from Embodiments 1 to 121, and R 2 It contains nine ring members.

[0191] Provided herein as Embodiment 124 is one of the compounds or salts from Embodiments 1 to 118, and R 2 It contains six ring members.

[0192] Provided herein as Embodiment 125 is one compound or salt from any of Embodiments 1-109 and 111-118, and R 2 It includes five ring members.

[0193] Provided herein as Embodiment 126 is any one compound or salt from Embodiments 1 to 125, and R 2 R 5 It is replaced by one, two, three, four, or five examples of the above. For example, in some embodiments, R 2 This is 2 to 5 R's 5 It is substituted with a substituent. In some embodiments, R 2 This is 3-4 R 5 It is substituted with a substituent. In some embodiments, R 5 These are 3 to 5 R's 5 It is substituted with a substituent. In some embodiments, R2 It consists of 4-5 R's. 5 It is substituted with a substituent. In some embodiments, R 2 is 2, 3, 4 or 5 R 5 It is substituted with a substituent. In some embodiments, R 2 is 1, 2, or 4 R 5 It is substituted with a substituent. In some embodiments, R 2 is 1 or 3 R 5 It is substituted with a substituent.

[0194] Provided herein as Embodiment 127 is one of the compounds or salts from Embodiments 1 to 126, and R 2 R 5 It is replaced by one, two, three, or four of the following examples.

[0195] Provided herein as Embodiment 128 is one of the compounds or salts from Embodiments 1 to 127, and R 2 R 5 It is replaced by one, two, or three of the following examples.

[0196] Provided herein as Embodiment 129 is any one compound or salt from Embodiments 1 to 128, and R 2 R 5 It is replaced by one or two of the following examples.

[0197] Provided herein as Embodiment 130 is one of the compounds or salts from Embodiments 1 to 129, and R 2 R 5 It is replaced with one example.

[0198] Provided herein as Embodiment 131 is one of the compounds or salts from Embodiments 1 to 130, and R 5 R 6 It is replaced by one, two, or three of the following examples.

[0199] Provided herein as Embodiment 132 is any one compound or salt of Embodiments 1 to 129 and 145, wherein R 5 is substituted with one or two examples of R 6 .

[0200] Provided herein as Embodiment 133 is any one compound or salt of Embodiments 1 to 132, wherein R 5 is substituted with one example of R 6 .

[0201] Provided herein as Embodiment 134 is any one compound or salt of Embodiments 1 to 133, wherein each example of R 5 is independently oxo, halogen, -OH, CN, C 1~3 alkyl, C 3~6 cycloalkyl, C 1~3 haloalkyl, C 1~3 alkoxy, C(O)N(R 6 )2, -N(R 6 )2, -N(R 6 )(C 1~3 alkylene-OH) or heterocyclyl having 3 to 10 members. For example, in some embodiments, each R 5 is independently oxo, CN, C 1~3 alkyl, C 3~6 cycloalkyl, C 1~3 haloalkyl, C 1~3 alkoxy, C(O)N(R 6 )2, -N(R 6 )2, -N(R 6 )(C 1~3 alkylene-OH) or heterocyclyl having 3 to 10 members. In some embodiments, each R 5 is independently halogen, -OH, oxo or C 1~3 alkyl. In some embodiments, each R 5 is independently halogen, -OH, oxo, C 1~3 alkyl or C 1~3 alkoxy. In some embodiments, each R 5 is independently halogen, -OH, oxo or C1~3 It is an alkoxy. In some embodiments, each R 5 These are, independently, halogen, -OH, C 1~3 Alkyl or C 1~3 It is an alkoxy. In some embodiments, each R 5 These are, independently, halogen, oxo, and C 1~3 Alkyl or C 1~3 It is an alkoxy. In some embodiments, each R 5 These are independently -OH, oxo, and C. 1~3 Alkyl or C 1~3 It is an alkoxy. In some embodiments, each R 5 These are independently oxo and C 1~3 Alkyl or C 1~3 It is an alkoxy. In some embodiments, each R 5 These are, independently, halogen, C 1~3 Alkyl or C 1~3 It is an alkoxy. In some embodiments, each R 5 These are, independently, halogens, -OH, or C 1~3 It is an alkoxy. In some embodiments, each R 5 R is independently a halogen, -OH, or oxo. In some embodiments, each R 5 These are, independently, halogen, -OH, oxo, and C. 1~3 Alkyl or C 1~3 It is an alkoxy. In some embodiments, each R 5 These are independently -OH, oxo, and C. 1~3 Alkyl or C 1~3 In some embodiments, each R 5 These are independently oxo or C 1~3 It is alkyl. In some embodiments, each R 5 Independently, C 1~3 Alkoxy or C 1~3 It is alkyl. In some embodiments, each R 5 These are independently oxo or C 1~3 It is alkyl. In some embodiments, each R 5 R is independently a halogen or an oxo. In some embodiments, R5 An example of R is a halogen. In some embodiments, the halogen R 5 substituent (or independently one or more substituents) is -F, -Cl or -Br. In some embodiments, the halogen R 5 substituent (or independently one or more substituents) is -F or -Cl. In some embodiments, the halogen R 5 substituent (or independently one or more substituents) is -F. In some embodiments, R 5 An example of R is C 1~3 alkyl. In some embodiments, R 5 alkyl is C 1~2 alkyl. In some embodiments, R 5 alkyl is C 2~3 alkyl. In some embodiments, R 5 alkyl is methyl. In some embodiments, R 5 alkyl is C2 alkyl. In some embodiments, R 5 alkyl is C3 alkyl. In some embodiments, R 5 alkoxy is C 1~2 alkoxy. In some embodiments, R 5 alkoxy is C 2~3 alkoxy. In some embodiments, R 5 alkoxy is methoxy. In some embodiments, R 5 alkoxy is C2 alkoxy. In some embodiments, R 5 alkoxy is C3 alkoxy.

[0202] Provided herein as Embodiment 135 is any one compound or salt of Embodiments 1-133, wherein each example of R 5 is independently oxo, CN, C 1~3 alkyl, C 3~6 cycloalkyl, C 1~3 haloalkyl or C 1~3 alkoxy.

[0203] Provided herein as Embodiment 136 is one of the compounds or salts from Embodiments 1 to 133, and R 5 Each example is independent of -N(R 6 )2, -N(R 6 )(C 1~3 It is an alkylene-OH or a heterocycline having 3 to 10 members.

[0204] Provided herein as Embodiment 137 is one of the compounds or salts from Embodiments 1 to 136, and R 6 Each of these examples is independent of -H, C 1~3 Alkyl, C(O)C 1~3 Alkyl, C(O)2C 1~3 Alkyl, C 1~3 Alkylene-OH or S(O) n C 1~3 It is alkyl.

[0205] Provided herein as Embodiment 138 is one of the compounds or salts from Embodiments 1 to 136, and R 6 Each of these examples is independently -H, -Me, -C(O)OtBu, or -S(O)2C 1~6 It is alkyl.

[0206] Provided herein as Embodiment 139 is one of the compounds or salts from Embodiments 1 to 136, and R 6 Each example is independently -H or C 1~3 It is alkyl.

[0207] Provided herein as Embodiment 140 is any one compound or salt from Embodiments 1 to 136, and R 6 Each example is C 1~3 It is alkyl.

[0208] Provided herein as Embodiment 141 is one of the compounds or salts from Embodiments 1 to 136, and R 6 Each example is H.

[0209] Provided herein as Embodiment 142 is any one of the compounds or salts from Embodiments 1 to 130, and R 5 Each of these examples is independently -F, methyl, ethyl, or isopropyl.

[0210] Provided herein as Embodiment 143 is any one of the compounds or salts from Embodiments 1 to 130, R 5 Each example is methyl.

[0211] Provided herein as Embodiment 144 is one compound or salt from any of Embodiments 1-130 and 134-136, and R 5 Each of these examples is non-substitutional.

[0212] Provided herein as Embodiment 145 is one compound or salt from any of Embodiments 1 to 125, and R 2 This is a non-substitution.

[0213] Provided herein as Embodiment 146 is one of the compounds or salts from Embodiments 1 to 145, and R 2 teeth, [ka] And in the formula, [ka] This indicates that a double bond or a single bond may be present. X a Each of these examples is, independently, nitrogen, oxygen, or carbon. If present, each example of n is an integer selected from 1, 2, 3, 4, or 5. If present, each example of n' is an integer selected from 1, 2, 3, 4, or 5. If present, each example of p is an integer selected from 0, 1, 2, 3, or 4. If present, each example of s is an integer selected from 0, 1, 2, or 3. If present, each example of r is an integer independently selected from 0, 1, 2, 3, 4, or 5, and two examples of r are the same R 2 If present on the base, the sum of both combined r values ​​does not exceed 5. If it exists and is bonded to an N ring member, R 5 Each example is independent of C 1~6 Alkyl, C 1~6 Haloalkyl, C 3~6 A cycloalkyl or heterocyclyl having 3 to 10 members, If present and bonded to a C ring member, R 5 Each example is independently oxo, CN, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C(O)N(R) 6 )2, -N(R 6 )2, -N(R 6 )(C 1~6 It is a heterocycline having alkylene-OH, 3 to 10 members. If present, R 6 Each of these examples is independent of -H, C 1~3 Alkyl, C(O)C 1~3 Alkyl, C(O)2C 1~3 Alkyl, C 1~3 Alkylene-OH or S(O) n C 1~3 It is alkyl, -N=Ring nitrogen is R 5 It can bond to and provide a positive ion.

[0214] Provided herein as Embodiment 147 is one compound or salt from any of Embodiments 1 to 118 and 146, and R 2 teeth, [ka] And in the formula, [ka] This indicates that a double bond or a single bond may be present. X a Each of these examples is, independently, nitrogen, oxygen, or carbon. If present, each example of n is an integer selected from 1, 2, 3, 4, or 5. If present, each example of n' is an integer selected from 1, 2, 3, 4, or 5. If present, each example of s is an integer selected from 0, 1, 2, or 3. If it exists and is bonded to an N ring member, R 5 Each example is independent of C 1~6 Alkyl, C 1~6 Haloalkyl, C 3~6 A cycloalkyl or heterocyclyl having 3 to 10 members, If present and bonded to a C ring member, R 5 Each example is independently oxo, CN, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C(O)N(R) 6 )2, -N(R 6 )2, -N(R 6 )(C 1~6 It is a heterocycline having alkylene-OH, 3 to 10 members. If present, R 6 Each of these examples is independent of -H, C 1~3 Alkyl, C(O)C 1~3 Alkyl, C(O)2C 1~3 Alkyl, C 1~3 Alkylene-OH or S(O) n C 1~3 It is alkyl, -N=Ring nitrogen is R 5 It can bond to and provide a positive ion.

[0215] Provided herein as Embodiment 148 is one of the compounds or salts of 1-118, 127-133, and 146, and R 2 teeth, [ka] And in the formula, [ka] This indicates that a double bond or a single bond may be present. X a Each of these examples is, independently, nitrogen, oxygen, or carbon. If present, each example of p is an integer selected from 0, 1, 2, 3, or 4. If present, each example of s is an integer selected from 0, 1, 2, or 3. If it exists and is bonded to an N ring member, R 5 Each example is independent of C 1~6 Alkyl, C 1~6 Haloalkyl, C 3~6 A cycloalkyl or heterocyclyl having 3 to 10 members, If present and bonded to a C ring member, R 5 Each example is independently oxo, CN, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C(O)N(R) 6 )2, -N(R 6 )2, -N(R 6 )(C 1~6 It is a heterocycline having alkylene-OH, 3 to 10 members. If present, R 6 Each of these examples is independent of -H, C 1~3 Alkyl, C(O)C 1~3 Alkyl, C(O)2C 1~3 Alkyl, C 1~3 Alkylene-OH or S(O) n C 1~3 It is alkyl, -N=Ring nitrogen is R 5 It can bond to and provide a positive ion.

[0216] Provided herein as Embodiment 149 is one compound or salt from any of Embodiments 1 to 118 and 146, and R 2 teeth, [ka] And in the formula, [ka] This indicates that a double bond or a single bond may exist, X a Each example of r is independently nitrogen, oxygen, or carbon, and if present, each example of s is an integer selected from 0, 1, 2, or 3, and if present, each example of r is an integer selected independently from 0, 1, 2, 3, 4, or 5, and two examples of r are the same R 2 If present on the base, the sum of both combined r values ​​does not exceed 5, and if present and bonded to an N ring member, R 5 Each example is independent of C 1~6 Alkyl, C 1~6 Haloalkyl, C 3~6 If a cycloalkyl or heterocyclyl having 3 to 10 members is present and bonded to a C ring member, then R 5 Each example is independently oxo, CN, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C(O)N(R) 6 )2, -N(R 6 )2, -N(R 6 )(C 1~6 Alkylene-OH), a heterocyclyl having 3 to 10 members, if present, R 6 Each of these examples is independent of -H, C 1~3 Alkyl, C(O)C 1~3 Alkyl, C(O)2C 1~3 Alkyl, C 1~3 Alkylene-OH or S(O) n C 1~3 It is alkyl, and -N=ring nitrogen, R 5 It can be bonded to and provide a cation. In some embodiments, X a One example of this is N, and X a Five examples of these are C (for example, CH, CR). 5 (etc.) In some embodiments, X aThe two examples are N (independently N, NH, or NR). 5 ) and X a The four examples are C (for example, CH, CR). 5 (and so on).

[0217] Provided herein as Embodiment 150 is one compound or salt from any of Embodiments 1 to 118 and 146, and R 2 teeth, [ka] And in the formula, [ka] This indicates that a double bond or a single bond may be present. X a Each of these examples is, independently, nitrogen, oxygen, or carbon. If present, each example of s is an integer selected from 0, 1, 2, or 3. If present, each example of r is an integer independently selected from 0, 1, 2, 3, or 4, and two examples of r are the same R 2 If present on the base, the sum of both combined r values ​​does not exceed 5. If it exists and is bonded to an N ring member, R 5 Each example is independent of C 1~6 Alkyl, C 1~6 Haloalkyl, C 3~6 A cycloalkyl or heterocyclyl having 3 to 10 members, If present and bonded to a C ring member, R 5 Each example is independently oxo, CN, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C(O)N(R) 6 )2, -N(R 6 )2, -N(R 6 )(C 1~6 It is a heterocycline having alkylene-OH, 3 to 10 members. If present, R 6Each of these examples is independent of -H, C 1~3 Alkyl, C(O)C 1~3 Alkyl, C(O)2C 1-3 Alkyl, C 1~3 Alkylene-OH or S(O) n C 1~3 It is alkyl, -N=Ring nitrogen is R 5 It can bond to and provide a positive ion.

[0218] Provided herein as Embodiment 151 is one compound or salt from any of Embodiments 1 to 118 and 146, and R 2 teeth, [ka] And in the formula, [ka] This indicates that a double bond or a single bond may be present. X a Each of these examples is, independently, nitrogen, oxygen, or carbon. If present, each example of s is an integer selected from 0, 1, 2, or 3. If present, each example of r is an integer independently selected from 0, 1, 2, or 3, and two examples of r are the same R 2 If present on the base, the sum of both combined r values ​​does not exceed 5. If it exists and is bonded to an N ring member, R 5 Each example is independent of C 1~6 Alkyl, C 1~6 Haloalkyl, C 3~6 A cycloalkyl or heterocyclyl having 3 to 10 members, If present and bonded to a C ring member, R 5 Each example is independently oxo, CN, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C(O)N(R) 6 )2, -N(R 6)2, -N(R 6 )(C 1~6 It is a heterocycline having alkylene-OH, 3 to 10 members. If present, R 6 Each of these examples is independent of -H, C 1~3 Alkyl, C(O)C 1~3 Alkyl, C(O)2C 1~3 Alkyl, C 1~3 Alkylene-OH or S(O) n C 1~3 It is alkyl, -N=Ring nitrogen is R 5 It can bond to and provide a positive ion.

[0219] Provided herein as Embodiment 152 is one compound or salt from any of Embodiments 1 to 118 and 146, and R 2 teeth, [ka] And in the formula, [ka] This indicates that a double bond or a single bond may be present. X a Each of these examples is, independently, nitrogen, oxygen, or carbon. If present, each example of s is an integer selected from 0, 1, 2, or 3. If present, each example of r is an integer independently selected from 0, 1, 2, 3, or 4, and two examples of r are the same R 2 If present on the base, the sum of both combined r values ​​does not exceed 5. If it exists and is bonded to an N ring member, R 5 Each example is independent of C 1~6 Alkyl, C 1~6 Haloalkyl, C 3~6 A cycloalkyl or heterocyclyl having 3 to 10 members, If present and bonded to a C ring member, R 5 Each example is independently oxo, CN, C 1~6Alkyl, C 3~6 Cycloalkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C(O)N(R) 6 )2, -N(R 6 )2, -N(R 6 )(C 1~6 It is a heterocycline having alkylene-OH, 3 to 10 members. If present, R 6 Each of these examples is independent of -H, C 1~3 Alkyl, C(O)C 1~3 Alkyl, C(O)2C 1~3 Alkyl, C 1~3 Alkylene-OH or S(O) n C 1~3 It is alkyl, -N=Ring nitrogen is R 5 It can bond to and provide a positive ion.

[0220] Provided herein as Embodiment 153 is one compound or salt from any of Embodiments 1 to 109, and R 2 teeth, [ka] For example, in some embodiments, R 2 teeth, [ka] In some embodiments, R 2 teeth, [ka] In some embodiments, R 2 teeth, [ka] In some embodiments, R 2 teeth, [ka] In some embodiments, R2 teeth, [ka] In some embodiments, R 2 teeth, [ka] In some embodiments, R 2 teeth, [ka] In some embodiments, R 2 teeth, [ka] In some embodiments, R 2 teeth, [ka] In some embodiments, R 2 teeth, [ka] In some embodiments, R 2 teeth, [ka] In some embodiments, R 2 teeth, [ka] In some embodiments, R 2 teeth, [ka] In some embodiments, R 2 teeth, [ka] In some embodiments, R2 teeth, [ka] In some embodiments, R 2 teeth, [ka] In some embodiments, R 2 teeth, [ka] In some embodiments, R 2 teeth, [ka] In some embodiments, R 2 teeth, [ka] In some embodiments, R 2 teeth, [ka] In some embodiments, R 2 teeth, [ka] In some embodiments, R 2 teeth, [ka] In some embodiments, R 2 teeth, [ka] In some embodiments, R 2 teeth, [ka] In some embodiments, R2 teeth, [ka] In some embodiments, R 2 teeth, [ka] In some embodiments, R 2 teeth, [ka] In some embodiments, R 2 teeth, [ka] In some embodiments, R 2 teeth, [ka] In some embodiments, R 2 teeth, [ka] In some embodiments, R 2 teeth, [ka] In some embodiments, R 2 teeth, [ka] In some embodiments, R 2 teeth, [ka] In some embodiments, R 2 teeth, [ka] In some embodiments, R2 teeth, [ka] In some embodiments, R 2 teeth, [ka] In some embodiments, R 2 teeth, [ka] In some embodiments, R 2 teeth, [ka] In some embodiments, R 2 teeth, [ka] In some embodiments, R 2 teeth, [ka] That is the case.

[0221] Provided herein as Embodiment 154 is one compound or salt from any of Embodiments 1 to 107, and R 2 teeth, [ka] That is the case.

[0222] Provided herein as Embodiment 155 is one compound or salt from any of Embodiments 1 to 107, and R 2 teeth, [ka] That is the case.

[0223] Provided herein as Embodiment 156 is one compound or salt from any of Embodiments 1-130, 132 and 146-152, and R 5 Each example is independent of -N(R 6 )2, -OMe, -CF3, -CN, [ka] -NC(O)Me, [ka] That is the case.

[0224] Provided herein as Embodiment 157 is one compound or salt from any of Embodiments 1-130, 132 and 146-152, and R 5 Each of these examples is independently -OMe, -CF3, or -CH3.

[0225] Provided herein as Embodiment 158 ​​is any one compound or salt from Embodiments 1 to 157, and R 3 C 1~6 Alkyl, C 3~10 Cycloalkyl, C 6~10 These are aryls, heteroaryls having 5 to 10 ring members, and heterocyclyls having 3 to 10 ring members. For example, in some embodiments, R 3 C 1~6 Alkyl, C 3~6 Cycloalkyl, C 6~10 The aryl, heteroaryl having 5 to 10 ring members, or heterocyclyl having 5 to 10 ring members. In some embodiments, R 3 C 1~6 The alkyl group is a heteroaryl group having 5 to 10 ring members, or a heterocycline group having 5 to 10 ring members. In some embodiments, R 3 C 1~6 Alkyl, C 3~6 It is a cycloalkyl or a heteroaryl having 5 to 10 ring members. In some embodiments, R 3 It is a heteroaryl compound having 5 to 9 ring members.

[0226] Provided herein as Embodiment 159 is one of the compounds or salts from Embodiments 1 to 158, and R 3 C 3~6 These are cycloalkyls, heteroaryls having 5 to 10 ring members, or heterocyclyls having 3 to 10 ring members.

[0227] Provided herein as Embodiment 160 is any one compound or salt from Embodiments 1 to 159, and R 3 is a heteroaryl or heterocyclyl, and R 3 A heteroaryl or heterocyclyl comprises one, two, three, four, or five heteroatom ring members. For example, in some embodiments, R 3 It contains four heteroatom ring members. In some embodiments, R 3 It contains three heteroatom ring members. In some embodiments, R 3 It contains two heteroatom ring members. In some embodiments, R 3 It contains one heteroatom ring member. In some embodiments, R 3 It contains 1 to 4 heteroatom ring members. In some embodiments, R 3 It contains 1 to 3 heteroatom ring members. In some embodiments, R 3 It contains 1-2 heteroatom ring members. In some embodiments, R 3 It contains 3 to 4 heteroatom ring members. In some embodiments, R 3 It contains a nitrogen atom as the sole ring heteroatom. In some embodiments, R 3 It contains one nitrogen atom as a ring heteroatom. In some embodiments, R 3 It contains two nitrogen atoms as a ring heteroatom. In some embodiments, R 3 It contains three nitrogen atoms as a ring heteroatom. In some embodiments, R 3 It contains four nitrogen atoms as a ring heteroatom. In some embodiments, R 3It contains one oxygen ring heteroatom, and the remaining ring heteroatoms are nitrogen atoms. In some embodiments, R 3 It contains an oxygen atom as the sole ring heteroatom.

[0228] Provided herein as Embodiment 161 is any one compound or salt from Embodiments 1 to 160, and R 3 is a heteroaryl or heterocyclyl, and R 3 A heteroaryl or heterocyclyl contains one, two, three, or four heteroatom ring members.

[0229] Provided herein as Embodiment 162 is any one compound or salt from Embodiments 1 to 161, and R 3 is a heteroaryl or heterocyclyl, and R 3 A heteroaryl or heterocyclyl contains one, two, or three heteroatom ring members.

[0230] Provided herein as Embodiment 163 is any one compound or salt from Embodiments 1 to 162, and R 3 is a heteroaryl or heterocyclyl, and R 3 A heteroaryl or heterocyclyl contains one or two heteroatom ring members.

[0231] Provided herein as Embodiment 164 is any one compound or salt from Embodiments 1 to 163, and R 3 is a heteroaryl or heterocyclyl, and R 3 A heteroaryl or heterocyclyl contains one heteroatom ring member.

[0232] Provided herein as Embodiment 165 is any one compound or salt from Embodiments 1 to 164, and R 3 is a heteroaryl or heterocyclyl, and R 3 Each heteroatom in the ring is independently nitrogen, oxygen, or -S(O) z - and z is 0, 1, or 2.

[0233] Provided herein as Embodiment 166 is one compound or salt from any of Embodiments 1 to 165, and R 3 is a heteroaryl or heterocyclyl, and R 3 Each heteroatom in the ring is independently either nitrogen or oxygen.

[0234] Provided herein as Embodiment 167 is any one compound or salt from Embodiments 1 to 166, and R 3 is a heteroaryl or heterocyclyl, and R 3 Each heteroatom in the ring is nitrogen.

[0235] Provided herein as Embodiment 168 is one compound or salt from any of Embodiments 1-159 and 162-166, and R 3 is a heteroaryl or heterocyclyl, and R 3 Each heteroatom in the ring is oxygen.

[0236] Provided herein as Embodiment 169 is any one compound or salt from Embodiments 1 to 168, and R 3 These are fused bicyclic heteroaryl or fused bicyclic heterocyclic compounds.

[0237] Provided herein as Embodiment 170 is any one compound or salt from Embodiments 1 to 169, and R 3 It is a heteroaryl compound.

[0238] Provided herein as Embodiment 171 is one compound or salt from any of Embodiments 1 to 169, and R 3 It is a heterocyclic compound.

[0239] Provided herein as Embodiment 172 is any one compound or salt from Embodiments 1 to 171, and R 3 It contains 5 to 10 ring members.

[0240] Provided herein as Embodiment 173 is one of the compounds or salts from Embodiments 1 to 172, and R 3 It contains 5 to 9 ring members.

[0241] Provided herein as Embodiment 174 is one of the compounds or salts from Embodiments 1 to 173, and R 3 It has nine ring members.

[0242] Provided herein as Embodiment 175 is one compound or salt from any of Embodiments 1-159, 162-168 and 170-173, and R 3 It has six ring members.

[0243] Provided herein as Embodiment 176 is one compound or salt from any of Embodiments 1-159, 161-168 and 170-173, and R 3 It has five ring members.

[0244] Provided herein as Embodiment 177 is one of the compounds or salts from Embodiments 1 to 158, and R 3 is C 3~4 It is a cycloalkyl group.

[0245] Provided herein as Embodiment 178 is any one compound or salt from Embodiments 1 to 158, and R 3 is C 1~6 It is alkyl.

[0246] Provided herein as Embodiment 179 is any one compound or salt from Embodiments 1 to 158, and R 3 is C 6~10 It is Ariel.

[0247] Provided herein as Embodiment 180 is any one compound or salt from Embodiments 1 to 158, and R 3 This is a C6 aryl compound.

[0248] Provided herein as Embodiment 181 is one of the compounds or salts from Embodiments 1 to 180, and R 3 R is substituted with 1, 2, 3, 4, or 5 substituents. For example, in some embodiments, R 3 It is substituted with 2 to 5 substituents. In some embodiments, R 3 It is substituted with 3 to 4 substituents. In some embodiments, R 3 It is substituted with 3 to 5 substituents. In some embodiments, R 3 is substituted with 4-5 substituents. In some embodiments, R 3 is substituted with 2, 3, 4, or 5 substituents. In some embodiments, R 3 is substituted with 1, 2, or 4 substituents. In some embodiments, R 3 It is substituted with one or three substituents.

[0249] Provided herein as Embodiment 182 is any one compound or salt from Embodiments 1 to 181, and R 3 It is substituted with 1, 2, 3, or 4 substituents.

[0250] Provided herein as Embodiment 183 is one of the compounds or salts from Embodiments 1 to 182, and R 3 It is substituted with one, two, or three substituents.

[0251] Provided herein as Embodiment 184 is one of the compounds or salts from Embodiments 1 to 183, and R 3 It is substituted with one or two substituents.

[0252] Provided herein as Embodiment 185 is one of the compounds or salts from Embodiments 1 to 184, and R 3 It is substituted with one substituent.

[0253] Provided herein as Embodiment 186 is one of the compounds or salts from Embodiments 1 to 185, and R 3 If it is replaced, each R 3 The substituents are, independently, halogen, -OH, and C. 1~3 Alkyl, C 1~3 Alkoxy or C 1~3 Alkylene-C 1~3 It is an alkoxy. For example, in some embodiments, R 3 Each substituent is independently C 1~3 Alkyl, C 1~3 Alkoxy or C 1~3 Alkylene-C 1~3 It is an alkoxy. In some embodiments, R 3 is substituted with -F or -OH. In some embodiments, R 3 is -OH or C 1~3 It is replaced with alkoxy. In some embodiments, R 3 is -F or C 1~3 It is replaced with alkoxy. In some embodiments, R 3 R is substituted with -F, -OH, C1 alkyl, C2 alkyl, C3 alkyl, C1 alkoxy, C2 alkoxy and / or C3 alkoxy. In some embodiments, R 3 R is substituted with methyl, C2 alkyl and / or C3 alkyl. In some embodiments, R 3 is substituted with -C1 alkoxy, C2 alkoxy, or C3 alkoxy. In some embodiments, R 3 is substituted with -C1 alkoxy. In some embodiments, R 3 is replaced with C2 alkoxy. In some embodiments, R 3 It is replaced with C3 alkoxy. In some embodiments, R 3 is replaced with -F. In some embodiments, R 3 is substituted with -OH. In some embodiments, R 3 It is substituted with methyl.

[0254] Provided herein as Embodiment 187 is one compound or salt from any of Embodiments 1 to 185, each R 3 The substituents are independently methyl, ethyl, or isopropyl.

[0255] Provided herein as Embodiment 188 is any one compound or salt from Embodiments 1 to 158, and R 3 teeth, [ka] And in the formula, [ka] This indicates that a double bond or a single bond may be present. X b Each of these examples is, independently, nitrogen, oxygen, or carbon. If present, each example of t is an integer selected from 1, 2, 3, 4, or 5. If present, each example of t' is an integer selected from 1, 2, 3, 4, or 5. If present, each example of u is an integer selected from 1, 2, 3, 4, or 5. If present, each example of v is an integer selected from 0, 1, 2, 3, 4, or 5, and two examples of v are the same R 3 If present on the base, the sum of both combined v values ​​does not exceed 5. If it exists and is bonded to an N ring member, R 13 Each example is independent of C 1~3 Alkyl, C 1~3 Haloalkyl or C 1~3 Alkylene-C 1~3 It is an alkoxy, If present and bonded to a C ring member, R 13 Each example independently includes halogen, -OH, oxo, and -N(R). b )2, C 1~3 Alkyl, C 1~3 Haloalkyl or C 1~3 Alkylene-OC 1~3 It is alkyl, -N=Ring nitrogen is R 13 It can bond to and provide a positive ion.

[0256] Provided herein as Embodiment 189 is one compound or salt from any of Embodiments 1-158 and 188, and R 3 teeth, [ka] And in the formula, If present, each example of t is an integer selected from 1, 2, 3, 4, or 5. If present, each example of t' is an integer selected from 1, 2, 3, 4, or 5. If present, each example of v is an integer selected from 0, 1, 2, 3, 4, or 5, and two examples of v are the same R 3 If present on the base, the sum of both combined v values ​​does not exceed 5. If it exists and is bonded to an N ring member, R 13 Each example is independent of C 1-3 Alkyl, C 1~3 Haloalkyl or C 1~3 Alkylene-C 1~3 It is an alkoxy, If present and bonded to a C ring member, R 13 Each example independently includes halogen, -OH, oxo, and C. 1~3 Alkyl, C 1~3 Haloalkyl or C 1~3 Alkylene-OC 1~3 Alkyl or Instead, R 13 The two examples are C 3~6 They form together cycloalkyl or heterocyclyl having 3 to 6 ring members, and these are R 3 If it has a ring structure, it can provide a fused ring system or a spiro ring system. -N=Ring nitrogen is R 13 It can bond to and provide a positive ion.

[0257] Provided herein as Embodiment 190 is any one compound or salt from Embodiments 1 to 158, and R 3 teeth, [ka] That is the case.

[0258] Provided herein as Embodiment 191 is any one compound or salt from Embodiments 1 to 158, and R 3 teeth, [ka] That is the case.

[0259] Provided herein as Embodiment 192 is any one compound or salt from Embodiments 1 to 158, and R 3 teeth, [ka] That is the case.

[0260] Provided herein as Embodiment 193 is one compound or salt from any of Embodiments 1 to 158, and R 3 teeth, [ka] That is the case.

[0261] Provided herein as Embodiment 194 is one compound or salt from any of Embodiments 1-16 and 17-158, and R 3 teeth, [ka] That is the case.

[0262] Provided herein as Embodiment 195 is one compound or salt from any of Embodiments 1 to 158, and R 3 teeth, [ka] That is the case.

[0263] Provided herein as Embodiment 196 is one compound or salt from any of Embodiments 1 to 157, and R 3 is -H.

[0264] Provided herein as Embodiment 197 is a compound or salt of any one of Embodiments 1 to 196, and R 4 is C 1~6 It is alkyl. For example, in some embodiments, R 4 is C 1~5 It is alkyl. In some embodiments, R 4 is C 1~4 It is alkyl. In some embodiments, R 4 is C 1~3 It is alkyl. In some embodiments, R 4 is C 1~2 It is alkyl. In some embodiments, R 4 is C 2~3 It is alkyl. In some embodiments, R 4 is a C1 alkyl group (e.g., methyl). In some embodiments, R 4 is a C2 alkyl group. In some embodiments, R 4 It is a C3 alkyl group.

[0265] Provided herein as Embodiment 198 is any one compound or salt from Embodiments 1 to 197, and R 4 is C 1~3 It is alkyl.

[0266] Provided herein as Embodiment 199 is one compound or salt from any of Embodiments 1-14 and 16-196, and R 4 is -N(R 7 )2.

[0267] Provided herein as Embodiment 200 is one of the compounds or salts from Embodiments 1-14, 16-196, and 199, and R7 At least one example of C 1~3 It is alkyl. For example, in some embodiments, R 7 At least one example of C 1~2 It is alkyl. In some embodiments, R 7 At least one example of C 2~3 It is alkyl. In some embodiments, R 7 At least one example of is a C1 alkyl group. In some embodiments, R 7 At least one example of is a C2 alkyl group. In some embodiments, R 7 At least one example of this is a C3 alkyl group. In some embodiments, R 7 Both examples are the same. In some embodiments, R 7 Each example is different.

[0268] Provided herein as Embodiment 201 is one of the compounds or salts from Embodiments 1-14, 16-196, and 199, and R 7 At least one example of this is -Me.

[0269] Provided herein as Embodiment 202 is one of the compounds or salts from Embodiments 1-14, 16-196, and 199, and R 7 H is at least one example of this.

[0270] Provided herein as Embodiment 203 is one compound or salt from any of Embodiments 1-14, 17-196 and 199, and R 7 Each example is H.

[0271] Provided herein as Embodiment 204 is one of the compounds or salts from Embodiments 1 to 196, and R 4 is -H.

[0272] Provided herein as Embodiment 205 is one of the compounds or salts of 1-27, 30, 32, 34, 38-40, 46, 47, 50-157, 197 and 198, wherein the compound of formula (I) is formula (Ia): [ka] It is a compound of [the compound].

[0273] Provided herein as Embodiment 206 is one of the compounds or salts of 1-14, 16-27, 29, 32, 34, 38, 39, 41, 46-196, 199, 202 and 203, wherein the compound of formula (I) is of formula (Ib): [ka] It is a compound of [the compound].

[0274] Provided herein as Embodiment 207 is one of the compounds or salts of 1-27, 29, 32, 34, 37, 39, 42, 46-157, 196 and 204, wherein the compound of formula (I) is of formula (Ic): [ka] It is a compound of [the compound].

[0275] Provided herein as Embodiment 208 is one of the compounds or salts of 1-27, 29, 32, 35, 37, 39, 41, 46-196 and 204, wherein the compound of formula (I) is of formula (Id): [ka] It is a compound of [the compound].

[0276] Provided herein as Embodiment 209 is one of the compounds or salts of 1-26, 28, 30, 32, 33, 37, 39, 43, 46-157 and 204, wherein the compound of formula (I) is of formula (Ie): [ka] It is a compound of [the compound].

[0277] Provided herein as Embodiment 210 is one of the compounds or salts of 1-27, 29, 31, 35, 37, 39, 44, 46, 47, 50-196 and 204, wherein the compound of formula (I) is of formula (If): [ka] It is a compound of [the compound].

[0278] Provided herein as Embodiment 211 is one of the compounds or salts of 1-27, 29, 32, 33, 37, 39, 45, 46, 47, 50-157 and 204, wherein the compound of formula (I) is formula (Ig): [ka] It is a compound of [the compound].

[0279] Provided herein as Embodiment 212 is one of the compounds or salts of 1-26, 28, 29, 32, 33, 37, 39, 45, 46, 47, 50-157 and 204, wherein the compound of formula (I) is of formula (Ih): [ka] It is a compound of [the compound].

[0280] Provided herein as Embodiment 213 is one of the compounds or salts of 1-26, 28, 29, 32, 34, 37, 39, 42, 46-157 and 204, wherein the compound of formula (I) is of formula (Ii): [ka] It is a compound of [the compound].

[0281] Provided herein as Embodiment 214 is one of the compounds or salts of 1-26, 28, 29, 32, 34, 38, 39, 42, 46-157 and 197-204, wherein the compound of formula (I) is of formula (Ij): [ka] It is a compound of [the compound].

[0282] Provided herein as Embodiment 215 is one of the compounds or salts of 1-26, 28, 29, 31, 35, 37, 39, 44, 46, 47, 50-196 and 204, wherein the compound of formula (I) is of formula (Ik): [ka] It is a compound of [the compound].

[0283] Provided herein as Embodiment 216 is one of the compounds or salts of 1-27, 29, 32, 34, 36, 39, 42, 46, 47, 48 and 50-157, wherein the compound of formula (I) is formula (Il): [ka] It is a compound of [the compound].

[0284] In some embodiments, a compound or salt of formula (I) (for example, as provided in Embodiment 1) may be further represented by one or more compounds of formulas (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), and / or (Il). For example, in some embodiments, a compound or salt of formula (I) (for example, as provided in Embodiment 1) may be further represented by all or any partial combination of formulas (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), and / or (Ik) (excluding formula (Il)). For example, in some embodiments, a compound or salt of formula (I) (for example, as provided in Embodiment 1) may be further represented by formulas (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), and / or (Il) (for example, excluding formula (Ik)). In some embodiments, a compound or salt of formula (I) (for example, as provided in Embodiment 1) may be further represented by formulas (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ih), and / or (Ii). In some embodiments, a compound or salt of formula (I) (for example, as provided in Embodiment 1) may be further represented by formulas (Ia), (Ib), (Ic), (Id), (Ie), (Ig), (Ih), and / or (Ii). In some embodiments, a compound or salt of formula (I) (for example, as provided in Embodiment 1) may be further represented by formulas (Ia), (Ib), (Ic), (Id), (If), (Ig), (Ih), and / or (Ii). In some embodiments, the compound or salt of formula (I) (for example, as provided in Embodiment 1) may be further represented by formulas (Ia), (Ib), (Ic), (Ie), (If), (Ig), (Ih), and / or (Ii).In some embodiments, a compound or salt of formula (I) (for example, as provided in Embodiment 1) may be further represented by formulas (Ia), (Ib), (Id), (Ie), (If), (Ig), (Ih), and / or (Ii). In some embodiments, a compound or salt of formula (I) (for example, as provided in Embodiment 1) may be further represented by formulas (Ia), (Ic), (Id), (Ie), (If), (Ig), (Ih), and / or (Ii). In some embodiments, a compound or salt of formula (I) (for example, as provided in Embodiment 1) may be further represented by formulas (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), and / or (Ii). In some embodiments, a compound or salt of formula (I) (for example, as provided in Embodiment 1) may be further represented by formulas (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), and / or (Ii). In some embodiments, a compound or salt of formula (I) (for example, as provided in Embodiment 1) may be further represented by formulas (Ia), (Ib), (Ic), (Id), (Ie), (If), and / or (Ig). In some embodiments, a compound or salt of formula (I) (for example, as provided in Embodiment 1) may be further represented by formulas (Ia), (Ib), (Ic), (Id), (Ie), (If), and / or (Ii). In some embodiments, a compound or salt of formula (I) (for example, as provided in Embodiment 1) may be further represented by formulas (Ia), (Ib), (Ic), (Id), (Ie), (Ih), and / or (Ii). In some embodiments, a compound or salt of formula (I) (for example, as provided in Embodiment 1) may be further represented by formulas (Ia), (Ib), (Ic), (Id), (Ig), (Ih), and / or (Ii). In some embodiments, a compound or salt of formula (I) (for example, as provided in Embodiment 1) may be further represented by formulas (Ia), (Ib), (Ic), (If), (Ig), (Ih), and / or (Ii).In some embodiments, a compound or salt of formula (I) (for example, as provided in Embodiment 1) may be further represented by formulas (Ia), (Ib), (Ie), (If), (Ig), (Ih), and / or (Ii). In some embodiments, a compound or salt of formula (I) (for example, as provided in Embodiment 1) may be further represented by formulas (Ia), (Id), (Ie), (If), (Ig), (Ih), and / or (Ii). In some embodiments, a compound or salt of formula (I) (for example, as provided in Embodiment 1) may be further represented by formulas (Ia), (Ic), (Id), (Ie), (If), (Ig), (Ih), and / or (Ii). In some embodiments, a compound or salt of formula (I) (for example, as provided in Embodiment 1) may be further represented by formulas (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), and / or (Ii). In some embodiments, a compound or salt of formula (I) (for example, as provided in Embodiment 1) may be further represented by formulas (Ia) and / or (Ib). In some embodiments, a compound or salt of formula (I) (for example, as provided in Embodiment 1) may be further represented by formulas (Ic), (Id), and / or (Ie). In some embodiments, a compound or salt of formula (I) (for example, as provided in Embodiment 1) may be further represented by formulas (If), (Ig), (Ih), and / or (Ii). In some embodiments, a compound or salt of formula (I) (for example, as provided in Embodiment 1) may be further represented by formulas (Ij), (Ik), and / or (Il). As recognized, any other combination of the formulas is also assumed. In some embodiments, provided herein are a compound or salt of any one or more of Embodiments 205 to 216 (including any partial combination of Embodiments 205 to 216), as further defined in any one or more of Embodiments 1 to 204.

[0285] Provided herein as Embodiment 217 is one compound or salt from any of Embodiments 1-27, 32, 34, 37 and 50-107, wherein the compound of formula (I) is of formula (Im): [ka] It is a compound of [the compound].

[0286] Provided herein as Embodiment 218 is one compound or salt from any of Embodiments 1-27, 32, 34, 37 and 50-107, where a is N + -O - If that is the case, [ka] The basis is, [ka] That is the case.

[0287] Provided herein as Embodiment 219 is a compound or salt of Embodiment 1, wherein the compound is [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] That is the case.

[0288] Provided herein as Embodiment 220 is a compound or salt of Embodiment 1, wherein the compound is [ka] [ka] [ka] [ka] [ka] That is the case.

[0289] Provided herein as Embodiment 221 is the compound or salt of Embodiment 1, wherein the compound is (3-methyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)-1-benzothiophen-2-yl)(3-methyl-4-morpholinyl)methanone, (3-methyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)-1-benzothiophen-2-yl)(4-morpholinyl)methanone, (4,4-difluoro-1-piperidinyl)(3-methyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)-1-benzothiophen-2-yl)methanone, (3-Methoxy-1-pyrrolidinyl)(3-methyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)-1-benzothiophen-2-yl)methanone, N-(2-methoxyethyl)-N,3-dimethyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)-1-benzothiophene-2-carboxamide, (2,2-dimethyl-4-morpholinyl)(3-methyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)-1-benzothiophen-2-yl)methanone, (3-Methoxy-1-piperidinyl)(3-methyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)-1-benzothiophen-2-yl)methanone, (3-methyl-6-(5-pyrimidinyl)-1-benzothiophen-2-yl)(4-morpholinyl)methanone, 1-Methyl-5-(3-methyl-2-(4-morpholinylcarbonyl)-1-benzothiophen-6-yl)-2(1H)-pyridinone, (6-(2-((2-hydroxyethyl)amino)-5-pyrimidinyl)-3-methyl-1-benzothiophen-2-yl)(4-morpholinyl)methanone, (3-methyl-6-(2-methyl-2H-indazole-5-yl)-1-benzothiophen-2-yl)(4-morpholinyl)methanone, (3-amino-4-cyclobutyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyridine-2-yl)(4-morpholinyl)methanone, (3-amino-4-cyclobutyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyridine-2-yl)(4,4-difluoro-1-piperidinyl)methanone, (3-amino-4-cyclobutyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyridine-2-yl)(1-piperidinyl)methanone, (3-amino-4-cyclobutyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)(3-methyl-4-morpholinyl)methanone, (7-oxide-4-(2-propanyl)thieno[2,3-b]pyridin-2-yl)(1-piperidinyl)methanone, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)(4-morpholinyl)methanone, (3-methyl-4-morpholinyl)(6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)methanone, (4-Cyclopropyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyridine-2-yl)(4-morpholinyl)methanone, (4-Cyclopropyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyridine-2-yl)(3,3-difluoro-1-piperidinyl)methanone, 4-Cyclopropyl-N-(2-methoxyethyl)-N-methyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyridine-2-carboxamide, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)-4-(1-methyl-1H-pyrazole-5-yl)thieno[2,3-b]pyridin-2-yl)(4-morpholinyl)methanone, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)-4-(1-methyl-1H-pyrazole-5-yl)thieno[2,3-b]pyridin-2-yl)(4-thiomorpholinyl)methanone, N-Cyclobutyl-4-Cyclopropyl-N-Methyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyridine-2-carboxamide, (5-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)(1-piperidinyl)methanone, (4-Cyclopropyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyridine-2-yl)(3-methyl-4-morpholinyl)methanone, 2-Methyl-2-propanyl 4-(5-(4-cyclopropyl-2-(1-piperidinylcarbonyl)thieno[2,3-b]pyridinyl-6-yl)-2-pyrimidinyl)-1-piperazine carboxylate, (4-Cyclopropyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyridine-2-yl)(4,4-difluoro-1-piperidinyl)methanone, (4-Cyclopropyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)(4-(trifluoromethyl)-1-piperidinyl)methanone, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)(4-(trifluoromethyl)-1-piperidinyl)methanone, (4-Cyclopropyl-6-(2-(1-piperazinyl)-5-pyrimidinyl)thieno[2,3-b]pyridinyl-2-yl)(1-piperidinyl)methanone, (4-Cyclopropyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyridine-2-yl)(1-piperidinyl)methanone, (4-Cyclopropyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyridine-2-yl)(1,4-oxazepan-4-yl)methanone, (4,4-difluoro-1-piperidinyl)(6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)methanone, (4,4-difluoro-2-methyl-1-piperidinyl)(6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)methanone, 2-methyl-6-(2-(1-piperidinylcarbonyl)thieno[2,3-b]pyridine-5-yl)-1(2H)-isoquinolinone, (3,3-dimethyl-4-morpholinyl)(6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)methanone, 4-((6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyridine-2-yl)carbonyl)-3-morpholine carbonate, (2-methyl-4-morpholinyl)(6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)methanone, 1-Methyl-5-(2-((3-methyl-4-morpholinyl)carbonyl)thieno[2,3-b]pyridin-6-yl)-2(1H)-pyridinone, (3-methyl-4-morpholinyl)(6-(1,3-thiazole-2-yl)thieno[2,3-b]pyridine-2-yl)methanone, 3-methyl-6-(2-((3-methyl-4-morpholinyl)carbonyl)thieno[2,3-b]pyridine-6-yl)-4(3H)-pyrimidinone, 1-Methyl-5-(2-(4-morpholinylcarbonyl)thieno[2,3-b]pyridin-6-yl)-2(1H)-pyridinone, (3-methyl-4-morpholinyl)(6-(1,3-thiazole-2-yl)thieno[2,3-b]pyridine-2-yl)methanone, 3-methyl-6-(2-((3-methyl-4-morpholinyl)carbonyl)thieno[2,3-b]pyridine-6-yl)-4(3H)-pyrimidinone, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyridine-2-yl)(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)methanone, 4-Molfolinyl(6-(1,3-thiazole-2-yl)thieno[2,3-b]pyridine-2-yl)methanone, 3-methyl-6-(2-(4-morpholinylcarbonyl)thieno[2,3-b]pyridin-6-yl)-4(3H)-pyrimidinone, (2,2-dimethyl-4-morpholinyl)(6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)methanone, 5-(2-(4-morpholinylcarbonyl)thieno[2,3-b]pyridin-6-yl)-2(1H)-pyridinone, (6-(2-methyl-2H-[1,2,3]triazolo[4,5-b]pyridine-6-yl)thieno[2,3-b]pyridine-2-yl)(4-morpholinyl)methanone, (3-methyl-4-morpholinyl)(6-(2-methyl-2H-[1,2,3]triazolo[4,5-b]pyridin-6-yl)thieno[2,3-b]pyridin-2-yl)methanone, (3-methyl-4-morpholinyl)(6-(3-methyl-3H-[1,2,3]triazolo[4,5-b]pyridine-6-yl)thieno[2,3-b]pyridine-2-yl)methanone, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)(7-oxa-4-azaspiro[2.5]octan-4-yl)methanone, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)(2-(trifluoromethyl)-4-morpholinyl)methanone, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)(4-oxa-7-azaspiro[2.5]octan-7-yl)methanone, 5-(2-(3-methyl-4-morpholinyl)carbonyl)thieno[2,3-b]pyridin-6-yl)-2(1H)-pyridinone, 4-Molfolinyl(6-(6-Quinolinyl)thieno[2,3-b]pyridin-2-yl)methanone, (6-(1-methyl-1H-imidazo[4,5-b]pyridine-6-yl)thieno[2,3-b]pyridine-2-yl)(4-morpholinyl)methanone, 2,8-Dioxa-5-azaspiro[3.5]nonan-5-yl(6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)methanone, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyridine-2-yl)(2-oxa-5-azabicyclo[2.2.2]octan-5-yl)methanone, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)(2-oxa-5-azabicyclo[4.1.0]heptan-5-yl)methanone, (6-(3-methyl-3H-[1,2,3]triazolo[4,5-b]pyridine-6-yl)thieno[2,3-b]pyridine-2-yl)(4-morpholinyl)methanone, (3-methyl-4-morpholinyl)(6-(6-quinolinyl)thieno[2,3-b]pyridin-2-yl)methanone, 4-Molfolinyl(6-(pyrido[2,3-b]pyrazine-7-yl)thieno[2,3-b]pyridine-2-yl)methanone, (3-methyl-4-morpholinyl)(6-(pyrido[2,3-b]pyrazine-7-yl)thieno[2,3-b]pyridine-2-yl)methanone, 7-methyl-3-(2-(4-morpholinylcarbonyl)thieno[2,3-b]pyridine-6-yl)-1,7-naphthyridine-8(7H)-one, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)(8-oxa-5-azaspiro[3.5]nonan-5-yl)methanone, 7-methyl-3-(2-((3-methyl-4-morpholinyl)carbonyl)thieno[2,3-b]pyridine-6-yl)-1,7-naphthyridine-8(7H)-one, (6-(1-methyl-1H-imidazo[4,5-b]pyridine-6-yl)thieno[2,3-b]pyridine-2-yl)(3-methyl-4-morpholinyl)methanone, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)(3-(trifluoromethyl)-4-morpholinyl)methanone, (4-Cyclopropyl-2-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-d]pyrimidine-6-yl)(4-morpholinyl)methanone, (4-Cyclopropyl-2-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-d]pyrimidine-6-yl)(1-pyrrolidinyl)methanone, (4-Cyclopropyl-2-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-d]pyrimidine-6-yl)(3,3-difluoro-1-piperidinyl)methanone, (4-Cyclopropyl-2-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-d]pyrimidine-6-yl)(1-piperidinyl)methanone, (4-Cyclopropyl-2-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-d]pyrimidine-6-yl)(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)methanone, (2-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)-4-(1-methyl-1H-pyrazole-5-yl)thieno[2,3-d]pyrimidine-6-yl)(4-morpholinyl)methanone, (2-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)-4-(1-methyl-1H-pyrazole-5-yl)thieno[2,3-d]pyrimidine-6-yl)(1-piperidinyl)methanone, (4,4-difluoro-1-piperidinyl)(2-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)-4-(1-methyl-1H-pyrazole-5-yl)thieno[2,3-d]pyrimidine-6-yl)methanone, (4,4-difluoro-1-piperidinyl)(4-(1-methyl-1H-pyrazole-5-yl)-2-(2-methyl-2H-[1,2,3]triazolo[4,5-b]pyridine-6-yl)thieno[2,3-d]pyrimidine-6-yl)methanone, 6-(6-((4,4-difluoro-1-piperidinyl)carbonyl)-4-(1-methyl-1H-pyrazole-5-yl)thieno[2,3-d]pyrimidine-2-yl)-3-methyl-4(3H)-pyrimidinone, (4,4-difluoro-1-piperidinyl)(4-(1-methyl-1H-pyrazole-5-yl)-2-(3-pyridinyl)thieno[2,3-d]pyrimidine-6-yl)methanone, (4,4-difluoro-1-piperidinyl)(4-(1-methyl-1H-pyrazole-5-yl)-2-(5-pyrimidinyl)thieno[2,3-d]pyrimidin-6-yl)methanone, (4,4-difluoro-1-piperidinyl)(2-(2-methoxy-5-pyrimidinyl)-4-(1-methyl-1H-pyrazole-5-yl)thieno[2,3-d]pyrimidine-6-yl)methanone, 5-(6-((4,4-difluoro-1-piperidinyl)carbonyl)-4-(1-methyl-1H-pyrazole-5-yl)thieno[2,3-d]pyrimidine-2-yl)-1-methyl-2(1H)-pyridinone, 5-(6-((4,4-difluoro-1-piperidinyl)carbonyl)-4-(1-methyl-1H-pyrazole-5-yl)thieno[2,3-d]pyrimidine-2-yl)-2-pyrimidinecarbonitrile, (4,4-difluoro-1-piperidinyl)(2-(2-(dimethylamino)-5-pyrimidinyl)-4-(1-methyl-1H-pyrazole-5-yl)thieno[2,3-d]pyrimidine-6-yl)methanone, (4,4-difluoro-1-piperidinyl)(4-(1-methyl-1H-pyrazole-5-yl)-2-(2-methyl-5-pyrimidinyl)thieno[2,3-d]pyrimidine-6-yl)methanone, (4,4-difluoro-1-piperidinyl)(4-(1-methyl-1H-pyrazole-5-yl)-2-(2-(trifluoromethyl)-5-pyrimidinyl)thieno[2,3-d]pyrimidine-6-yl)methanone, (2-(2-cyclopropyl-5-pyrimidinyl)-4-(1-methyl-1H-pyrazole-5-yl)thieno[2,3-d]pyrimidin-6-yl)(4,4-difluoro-1-piperidinyl)methanone, (4,4-difluoro-1-piperidinyl)(2-(1-methyl-1H-pyrazole-4-yl)-4-(1-methyl-1H-pyrazole-5-yl)thieno[2,3-d]pyrimidine-6-yl)methanone, (4,4-difluoro-1-piperidinyl)(4-(1-methyl-1H-pyrazole-5-yl)-2-(1-(trifluoromethyl)-1H-pyrazole-4-yl)thieno[2,3-d]pyrimidine-6-yl)methanone, (4,4-difluoro-1-piperidinyl)(2-(1-methyl-1H-pyrazole-3-yl)-4-(1-methyl-1H-pyrazole-5-yl)thieno[2,3-d]pyrimidine-6-yl)methanone, N-(5-(6-((4,4-difluoro-1-piperidinyl)carbonyl)-4-(1-methyl-1H-pyrazole-5-yl)thieno[2,3-d]pyrimidine-2-yl)-2-pyrimidinyl)acetamide, (4,4-difluoro-1-piperidinyl)(2-(1-methyl-1H-imidazole-5-yl)-4-(1-methyl-1H-pyrazole-5-yl)thieno[2,3-d]pyrimidine-6-yl)methanone, (4,4-difluoro-1-piperidinyl)(4-(1-methyl-1H-pyrazole-5-yl)-2-(1,3-thiazole-5-yl)thieno[2,3-d]pyrimidine-6-yl)methanone, (4,4-difluoro-1-piperidinyl)(4-(1-methyl-1H-pyrazole-5-yl)-2-(1,3-oxazole-5-yl)thieno[2,3-d]pyrimidine-6-yl)methanone, (4,4-difluoro-1-piperidinyl)(2-(2-(4-methyl-1-piperazinyl)-5-pyrimidinyl)-4-(1-methyl-1H-pyrazole-5-yl)thieno[2,3-d]pyrimidin-6-yl)methanone, (4,4-difluoro-1-piperidinyl)(4-(1-methyl-1H-pyrazole-5-yl)-2-(2-(4-morpholinyl)-5-pyrimidinyl)thieno[2,3-d]pyrimidine-6-yl)methanone, 5-(6-((4,4-difluoro-1-piperidinyl)carbonyl)-4-(1-methyl-1H-pyrazole-5-yl)thieno[2,3-d]pyrimidine-2-yl)-2(1H)-pyridinone, (4,4-difluoro-1-piperidinyl)(2-(3H-imidazo[4,5-b]pyridine-6-yl)-4-(1-methyl-1H-pyrazole-5-yl)thieno[2,3-d]pyrimidine-6-yl)methanone, (4,4-difluoro-1-piperidinyl)(2-(imidazo[1,2-a]pyridine-3-yl)-4-(1-methyl-1H-pyrazole-5-yl)thieno[2,3-d]pyrimidine-6-yl)methanone, (4,4-difluoro-1-piperidinyl)(4-(1-methyl-1H-pyrazole-5-yl)-2-(4-pyridazinyl)thieno[2,3-d]pyrimidine-6-yl)methanone, (4,4-difluoro-1-piperidinyl)(4-(1-methyl-1H-pyrazole-5-yl)-2-(2-pyrazinyl)thieno[2,3-d]pyrimidine-6-yl)methanone, 6-(6-((4,4-difluoro-1-piperidinyl)carbonyl)-4-(1-methyl-1H-pyrazole-5-yl)thieno[2,3-d]pyrimidine-2-yl)-2-methyl-1(2H)-isoquinolinone, (4,4-difluoro-1-piperidinyl)(4-(1-methyl-1H-pyrazole-5-yl)-2-(1,3-thiazole-2-yl)thieno[2,3-d]pyrimidine-6-yl)methanone, (4,4-difluoro-1-piperidinyl)(4-(1-methyl-1H-pyrazole-5-yl)-2-(1,3-oxazol-2-yl)thieno[2,3-d]pyrimidine-6-yl)methanone, N-(5-(6-((4,4-difluoro-1-piperidinyl)carbonyl)-4-(1-methyl-1H-pyrazole-5-yl)thieno[2,3-d]pyrimidine-2-yl)-2-pyrimidinyl)methanesulfonamide, 5-(6-((4,4-difluoro-1-piperidinyl)carbonyl)-4-(1-methyl-1H-pyrazole-5-yl)thieno[2,3-d]pyrimidine-2-yl)-2(1H)-pyrimidinone, (4,4-difluoro-1-piperidinyl)(3-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyrazine-6-yl)methanone, (4,4-difluoro-1-piperidinyl)(2-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyrazine-6-yl)methanone, (4,4-difluoro-1-piperidinyl)(5-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[3,2-b]pyridin-2-yl)methanone, (5-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[3,2-b]pyridin-2-yl)(1-piperidinyl)methanone, (3,3-difluoro-1-piperidinyl)(5-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[3,2-b]pyridin-2-yl)methanone, (5-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[3,2-b]pyridin-2-yl)(4-morpholinyl)methanone, (3-amino-5-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[3,2-b]pyridin-2-yl)(1-piperidinyl)methanone, (3-amino-5-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[3,2-b]pyridin-2-yl)(4-morpholinyl)methanone, (3-amino-5-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[3,2-b]pyridin-2-yl)(3,3-difluoro-1-piperidinyl)methanone, (3-amino-5-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[3,2-b]pyridin-2-yl)(4,4-difluoro-1-piperidinyl)methanone, (4-Cyclopropyl-2-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[3,2-d]pyrimidine-6-yl)(4-morpholinyl)methanone, 4-Molfolinyl(5-(4-Molfolinyl)[1,3]thiazolo[5,4-b]pyridin-2-yl)methanone, (5-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)[1,3]thiazolo[5,4-b]pyridin-2-yl)(4-morpholinyl)methanone, and (3-methyl-4-morpholinyl)(5-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)[1,3]thiazolo[5,4-b]pyridine-2-yl)methanone That is the case.

[0290] Provided herein as Embodiment 222 is a compound or salt of Embodiment 1, wherein the compound is (3-methyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)-1-benzothiophen-2-yl)((3S)-3-methyl-4-morpholinyl)methanone, (3-methyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)-1-benzothiophen-2-yl)((3R)-3-methyl-4-morpholinyl)methanone, ((3R)-3-methoxy-1-pyrrolidinyl)(3-methyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)-1-benzothiophen-2-yl)methanone, ((3S)-3-methoxy-1-pyrrolidinyl)(3-methyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)-1-benzothiophen-2-yl)methanone, ((3S)-3-methoxy-1-piperidinyl)(3-methyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)-1-benzothiophen-2-yl)methanone, ((3R)-3-methoxy-1-piperidinyl)(3-methyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)-1-benzothiophen-2-yl)methanone, (3-amino-4-cyclobutyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)((3S)-3-methyl-4-morpholinyl)methanone, (3-amino-4-cyclobutyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyridine-2-yl)((3R)-3-methyl-4-morpholinyl)methanone, ((3R)-3-methyl-4-morpholinyl)(6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)methanone, ((3S)-3-methyl-4-morpholinyl)(6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)methanone, (4-Cyclopropyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyridine-2-yl)((3S)-3-methyl-4-morpholinyl)methanone, (4-Cyclopropyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyridine-2-yl)((3R)-3-methyl-4-morpholinyl)methanone, ((2R)-4,4-difluoro-2-methyl-1-piperidinyl)(6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)methanone, ((2S)-4,4-difluoro-2-methyl-1-piperidinyl)(6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyridine-2-yl)methanone, ((2R)-4,4-difluoro-2-methyl-1-piperidinyl)(6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)methanone, ((2S)-4,4-difluoro-2-methyl-1-piperidinyl)(6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyridine-2-yl)methanone, (3R)-4-((6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyridine-2-yl)carbonyl)-3-morpholine carbonate, (3S)-4-((6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyridine-2-yl)carbonyl)-3-morpholine carbonate, ((2R)-2-methyl-4-morpholinyl)(6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)methanone, ((2S)-2-methyl-4-morpholinyl)(6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)methanone, 1-Methyl-5-(2-(((3S)-3-methyl-4-morpholinyl)carbonyl)thieno[2,3-b]pyridin-6-yl)-2(1H)-pyridinone, 1-Methyl-5-(2-(((3R)-3-methyl-4-morpholinyl)carbonyl)thieno[2,3-b]pyridin-6-yl)-2(1H)-pyridinone, ((3S)-3-methyl-4-morpholinyl)(6-(1,3-thiazole-2-yl)thieno[2,3-b]pyridine-2-yl)methanone, 3-methyl-6-(2-(((3S)-3-methyl-4-morpholinyl)carbonyl)thieno[2,3-b]pyridine-6-yl)-4(3H)-pyrimidinone, ((3R)-3-methyl-4-morpholinyl)(6-(1,3-thiazole-2-yl)thieno[2,3-b]pyridine-2-yl)methanone, 3-methyl-6-(2-(((3R)-3-methyl-4-morpholinyl)carbonyl)thieno[2,3-b]pyridine-6-yl)-4(3H)-pyrimidinone, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyridine-2-yl)((1R,5R)-8-oxa-3-azabicyclo[3.2.1]octan-3-yl)methanone, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyridine-2-yl)((1R,5S)-8-oxa-3-azabicyclo[3.2.1]octan-3-yl)methanone, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyridine-2-yl)((1S,5S)-8-oxa-3-azabicyclo[3.2.1]octan-3-yl)methanone, ((3S)-3-methyl-4-morpholinyl)(6-(2-methyl-2H-[1,2,3]triazolo[4,5-b]pyridin-6-yl)thieno[2,3-b]pyridin-2-yl)methanone, ((3R)-3-methyl-4-morpholinyl)(6-(2-methyl-2H-[1,2,3]triazolo[4,5-b]pyridine-6-yl)thieno[2,3-b]pyridine-2-yl)methanone, ((3R)-3-methyl-4-morpholinyl)(6-(3-methyl-3H-[1,2,3]triazolo[4,5-b]pyridin-6-yl)thieno[2,3-b]pyridin-2-yl)methanone, ((3S)-3-methyl-4-morpholinyl)(6-(3-methyl-3H-[1,2,3]triazolo[4,5-b]pyridine-6-yl)thieno[2,3-b]pyridine-2-yl)methanone, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)((2R)-2-(trifluoromethyl)-4-morpholinyl)methanone, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)((2S)-2-(trifluoromethyl)-4-morpholinyl)methanone, 5-(2-(((3S)-3-methyl-4-morpholinyl)carbonyl)thieno[2,3-b]pyridin-6-yl)-2(1H)-pyridinone, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyridine-2-yl)((1R,4R)-2-oxa-5-azabicyclo[2.2.2]octan-5-yl)methanone, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyridine-2-yl)((1R,4S)-2-oxa-5-azabicyclo[2.2.2]octan-5-yl)methanone, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyridine-2-yl)((1S,4R)-2-oxa-5-azabicyclo[2.2.2]octan-5-yl)methanone, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyridine-2-yl)((1S,4S)-2-oxa-5-azabicyclo[2.2.2]octan-5-yl)methanone, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)((1R,6R)-2-oxa-5-azabicyclo[4.1.0]heptan-5-yl)methanone, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)((1R,6S)-2-oxa-5-azabicyclo[4.1.0]heptan-5-yl)methanone, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)((1S,6R)-2-oxa-5-azabicyclo[4.1.0]heptan-5-yl)methanone, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)((1S,6S)-2-oxa-5-azabicyclo[4.1.0]heptan-5-yl)methanone, 5-(2-(((3R)-3-methyl-4-morpholinyl)carbonyl)thieno[2,3-b]pyridin-6-yl)-2(1H)-pyridinone, ((3S)-3-methyl-4-morpholinyl)(6-(6-quinolinyl)thieno[2,3-b]pyridine-2-yl)methanone, ((3S)-3-methyl-4-morpholinyl)(6-(pyrido[2,3-b]pyrazine-7-yl)thieno[2,3-b]pyridine-2-yl)methanone, ((3R)-3-methyl-4-morpholinyl)(6-(pyrido[2,3-b]pyrazine-7-yl)thieno[2,3-b]pyridine-2-yl)methanone, ((3R)-3-methyl-4-morpholinyl)(6-(6-quinolinyl)thieno[2,3-b]pyridine-2-yl)methanone, 7-methyl-3-(2-(((3S)-3-methyl-4-morpholinyl)carbonyl)thieno[2,3-b]pyridine-6-yl)-1,7-naphthyridine-8(7H)-one, (6-(1-methyl-1H-imidazo[4,5-b]pyridine-6-yl)thieno[2,3-b]pyridine-2-yl)((3S)-3-methyl-4-morpholinyl)methanone, (6-(1-methyl-1H-imidazo[4,5-b]pyridine-6-yl)thieno[2,3-b]pyridine-2-yl)((3R)-3-methyl-4-morpholinyl)methanone, 7-methyl-3-(2-(((3R)-3-methyl-4-morpholinyl)carbonyl)thieno[2,3-b]pyridine-6-yl)-1,7-naphthyridine-8(7H)-one, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)((3R)-3-(trifluoromethyl)-4-morpholinyl)methanone, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)((3S)-3-(trifluoromethyl)-4-morpholinyl)methanone, (4-Cyclopropyl-2-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-d]pyrimidine-6-yl)((1R,5S)-3-oxa-8-azabicyclo[3.2.1]octan-8-yl)methanone, ((3R)-3-methyl-4-morpholinyl)(5-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)[1,3]thiazolo[5,4-b]pyridin-2-yl)methanone, or ((3S)-3-methyl-4-morpholinyl)(5-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)[1,3]thiazolo[5,4-b]pyridin-2-yl)methanone That is the case.

[0291] Provided herein as Embodiment 223 is a compound or salt of Embodiment 1, wherein the compound is [ka] That is the case.

[0292] Provided herein as Embodiment 224 is a compound or salt of Embodiment 1, wherein the compound is [ka] That is the case.

[0293] Provided herein as Embodiment 225 is a compound or salt of Embodiment 1, wherein the compound is [ka] That is the case.

[0294] Provided herein as Embodiment 226 is a compound or salt of Embodiment 1, wherein the compound is [ka] That is the case.

[0295] Provided herein as Embodiment 227 is a compound or salt of Embodiment 1, wherein the compound is [ka] That is the case.

[0296] Provided herein as Embodiment 228 is a compound or salt of Embodiment 1, wherein the compound is [ka] That is the case.

[0297] Provided herein as Embodiment 229 is a compound or salt of Embodiment 1, wherein the compound is [ka] That is the case.

[0298] Provided herein as Embodiment 230 is a compound or salt of Embodiment 1, wherein the compound is [ka] That is the case.

[0299] Provided herein as Embodiment 231 is a compound or salt of Embodiment 1, wherein the compound is [ka] That is the case.

[0300] Provided herein as Embodiment 232 is a compound or salt of Embodiment 1, wherein the compound is [ka] That is the case.

[0301] Provided herein as Embodiment 233 is a compound or salt of Embodiment 1, wherein the compound is [ka] That is the case.

[0302] Provided herein as Embodiment 234 is a compound or salt of Embodiment 1, wherein the compound is [ka] That is the case.

[0303] Provided herein as Embodiment 235 is a compound or salt of Embodiment 1, wherein the compound is [ka] That is the case.

[0304] Provided herein as Embodiment 236 is a compound or salt of Embodiment 1, wherein the compound is [ka] That is the case.

[0305] Provided herein as Embodiment 237 is a compound or salt of Embodiment 1, wherein the compound is [ka] That is the case.

[0306] Provided herein as Embodiment 238 is a compound or salt of Embodiment 1, wherein the compound is [ka] That is the case.

[0307] Provided herein as Embodiment 239 is a compound or salt of Embodiment 1, wherein the compound is [ka] That is the case.

[0308] Provided herein as Embodiment 240 is a compound or salt of Embodiment 1, wherein the compound is [ka] That is the case.

[0309] Provided herein as Embodiment 241 is a compound or salt of Embodiment 1, wherein the compound is [ka] That is the case.

[0310] Provided herein as Embodiment 242 is a compound or salt of Embodiment 1, wherein the compound is [ka] That is the case.

[0311] Provided herein as Embodiment 243 is a compound or salt of Embodiment 1, wherein the compound is [ka] That is the case.

[0312] Provided herein as Embodiment 244 is a compound or salt of Embodiment 1, wherein the compound is [ka] That is the case.

[0313] Provided herein as Embodiment 245 is a compound or salt of Embodiment 1, wherein the compound is [ka] That is the case.

[0314] Provided herein as Embodiment 246 is a compound or salt of Embodiment 1, wherein the compound is [ka] That is the case.

[0315] Provided herein as Embodiment 247 is a compound or salt of Embodiment 1, wherein the compound is [ka] That is the case.

[0316] Provided herein as Embodiment 248 is a compound or salt of Embodiment 1, wherein the compound is [ka] That is the case.

[0317] Provided herein as Embodiment 249 is a compound or salt of Embodiment 1, wherein the compound is [ka] That is the case.

[0318] Provided herein as Embodiment 250 is a compound or salt of Embodiment 1, wherein the compound is [ka] That is the case.

[0319] Provided herein as Embodiment 251 is a compound or salt of Embodiment 1, wherein the compound is [ka] That is the case.

[0320] Provided herein as Embodiment 252 is a compound or salt of Embodiment 1, wherein the compound is [ka] That is the case.

[0321] Provided herein as Embodiment 253 is a compound or salt of Embodiment 1, wherein the compound is [ka] That is the case.

[0322] Provided herein as Embodiment 254 is one of the compounds from Embodiments 1 to 253.

[0323] The compounds or salts disclosed in Embodiments 1 to 254 may be stereoisomerically pure or stereoisomerically enriched.

[0324] If the stereochemistry of a structure or part of a structure disclosed herein is not explicitly indicated (e.g., by dashed or thick lines), the structure or part of a structure shall be interpreted as either achiral or any possible stereoisomer of the structure or part of a structure. If the stereochemistry of a structure or part of a structure is explicitly indicated, a single stereoisomer of the structure or part of a structure shall be represented, with the understanding that the stereochemistry of the structure or part of a structure may have been arbitrarily assigned.

[0325] As used herein, the terms “stereoisomer” or “stereoisomerically pure” mean a single stereoisomer of a compound that substantially does not contain any other stereoisomers of that compound (e.g., geometric isomers, enantiomers, diastereomers, and atropisomers). For example, a stereoisomerically pure compound having one chiral center substantially does not contain any enantiomers of that compound, and a stereoisomerically pure compound having two chiral centers substantially does not contain any other enantiomers or diastereomers of that compound.

[0326] Typical stereoisomerically enriched compounds include: over 50% by weight of one stereoisomer and about 50% by weight or less of the other stereoisomer; over 60% by weight of one stereoisomer and about 40% by weight or less of the other stereoisomer; over 70% by weight of one stereoisomer and about 30% by weight or less of the other stereoisomer; over 80% by weight of one stereoisomer and about 20% by weight or less of the other stereoisomer; and over 90% by weight of one stereoisomer. This includes one stereoisomer and the other stereoisomer in an amount of about 10% by weight or less of the compound, one stereoisomer in an amount of more than 95% by weight of the compound and the other stereoisomer in an amount of about 5% by weight or less of the compound, one stereoisomer in an amount of more than 97% by weight of the compound and the other stereoisomer in an amount of about 3% by weight or less of the compound, one stereoisomer in an amount of more than 99% by weight of the compound and the other stereoisomer in an amount of about 1% by weight or less of the compound, or one stereoisomer in an amount of more than 99.9% by weight of the compound and the other stereoisomer in an amount of about 0.1% by weight or less of the compound.

[0327] This disclosure also includes pharmaceutical compositions comprising stereoisomerically pure forms (or enriched forms) and the use of stereoisomerically pure forms (or enriched forms) of any compound disclosed herein. Furthermore, this disclosure also includes pharmaceutical compositions comprising mixtures of stereoisomers of any compound disclosed herein and the use of such pharmaceutical compositions or mixtures of stereoisomers. These stereoisomers or mixtures thereof can be synthesized according to methods well known in the art and methods disclosed herein. Mixtures of stereoisomers can be resolved using standard techniques such as chiral columns or chiral resolving agents. For example, see Jacques et al., Enantiomers, Racemates and Resolutions (Wiley-Interscience, New York, 1981), Wilen et al., Tetrahedron 33:2725, Eliel, Stereochemistry of Carbon Compounds (McGraw-Hill, NY, 1962), and Wilen, Tables of Resolving Agents and Optical Resolutions, page 268 (Eliel, Ed., Univ. of Notre Dame Press, Notre Dame, IN, 1972).

[0328] As is known to those skilled in the art, certain compounds disclosed herein may exist in one or more tautomerized forms. Since one chemical structure may be used to represent only one tautomerized form, for convenience, a reference to a compound with a given structural formula will be understood to include other tautomers of that structural formula. Therefore, the scope of this disclosure should be understood to encompass all tautomerized forms of the compounds disclosed herein. Exemplary tautomers include enol and imine forms, keto and enamine forms, and their geometric isomers and mixtures. A tautomer is one of two or more structural isomers that exist in equilibrium and are readily convertible from one isomerized form to another. This reaction results in the formal transfer of hydrogen atoms, involving the switching of adjacent conjugated double bonds.

[0329] As discussed elsewhere in this Specification, the compounds disclosed herein, as well as their stereoisomers, tautomers, and isotopically labeled forms or pharmaceutically acceptable salts thereof, may exist in solvated or unsolvated forms.

[0330] In some embodiments, a compound of formula (I) (and / or any of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Il), (Im), 2-amide-5,6-condensed-thieno-aryl, 2-amide-5,6-condensed-thieno-heteroaryl, 2-amide-5,6-condensed-thieno-heterocyclyl, or any other compound disclosed herein) may be characterized by its ability to inhibit the enzymatic activity of 15-PGDH (e.g., recombinant 15-PGDH) in an assay. In some embodiments, the assay is a cell assay or a cell-free binding assay. In some embodiments, a compound of formula (I) (and / or any of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Il), (Im), 2-amide-5,6-condensed-thieno-aryl, 2-amide-5,6-condensed-thieno-heteroaryl, 2-amide-5,6-condensed-thieno-heterocyclyl, or any other compound disclosed herein) in an assay, the enzyme activity of 15-PGDH is reduced to approximately 1 μM, 250 nM, 50 nM, 20 nM, 10 nM, 5 nM, 2.5 nM, 1 nM, 0.1 nM, 0.01 nM, 1 pM or less, or including and / or ranging from the aforementioned values ​​to the aforementioned IC200 50Inhibits by a compound of formula (I) (and / or any of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Il), (Im), 2-amide-5,6-condensed-thieno-aryl, 2-amide-5,6-condensed-thieno-heteroaryl, 2-amide-5,6-condensed-thieno-heterocyclyl or disclosed herein) Any other compound can reduce the enzyme activity of recombinant 15-PGDH to approximately 20 nM to 0.01 pM, approximately 20 nM to 0.01 nM, approximately 20 nM to 0.1 nM, approximately 20 nM to 1 nM, approximately 10 nM to 0.01 pM, approximately 10 nM to 0.01 nM, approximately 10 nM to 0.1 nM, approximately 10 nM to 1 nM, approximately 5 nM to 0.01 pM, approximately 5 nM to 0.01 nM, approximately 5 nM to 0.1 nM, or approximately 5 nM to 1 nM IC 50 It inhibits it.

[0331] In some embodiments, IC 50 This is measured using assays such as those disclosed in the examples. In some embodiments, IC for 15-PGDH inhibition is measured. 50 The NADH signal is measured using a cell-free binding assay. In some embodiments, the assay with recombinant 15-PGDH enzyme is performed in a 384-well microtiter plate in 25 μL of reaction buffer containing 50 mM Tris, pH 7.5, 0.01% Tween-20, and 100 μM DTT. In some embodiments, concentration-response experiments with the test compound are performed at 22 concentrations derived from 2-fold serial dilutions in DMSO. In some embodiments, the test compound is pre-incubated with 15-PGDH at room temperature for 15 minutes. In some embodiments, PGE2 and β-NAD+ are then added to initiate the 15-PGDH reaction. After 60 minutes at room temperature, the reaction is quenched and the NADH signal is measured using a microtiter plate reader.

[0332] In some embodiments, compounds of formula (I) (and / or any of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Il), (Im), 2-amide-5,6-condensed-thieno-aryl, 2-amide-5,6-condensed-thieno-heteroaryl, 2-amide-5,6-condensed-thieno-heterocyclyl, or any other compound disclosed herein) can be characterized by low inhibition of acetylcholinesterase (ACHE). In some embodiments, ACHE inhibition can be measured using the method described in Ellman GL, et al., A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol. 1961;7:88-95. In some embodiments, ACHE inhibition is measured by colorimetric detection of the conversion of acetylthiocholine to thiocholine, using a compound concentration of 10 μM under Ellman conditions. In some embodiments, the substrate (acetylthiocholine, ATch) is provided at a concentration of 400 μM. In some embodiments, the ACHE enzyme is provided at a concentration of 1 mU. In some embodiments, dithiobisnitrobenzoate (DTNB) is provided at a concentration of 500 μM. In some embodiments, the reaction is carried out in a buffer of 8 mM NaH2PO4 / Na2HPO4, 20 mM NaCl, 0.06% Triton, 0.8 mM EDTA, and about 1 mU of enzyme (ACHE). In some embodiments, the test compound is added to the buffer containing the enzyme. In some embodiments, the enzymatic reaction is initiated by the addition of 400 μM substrate ATch and 500 μM DTNB. In this reaction, ATch is converted to thiocholine, which reacts with DTNB to form the yellow anion, 5-thio-2-nitrobenzoate. In some embodiments, absorbance is measured immediately (t=0) at λ=405 nm using a microplate reader. In some embodiments, the plate reader is an Envision or Perkin Elmer plate reader.In some embodiments, this measurement allows for confirmation of compound interference with spectrophotometric detection at this wavelength. After a 30-minute incubation, a second absorbance measurement is performed. Enzyme activity is determined by subtracting the signal measured at t=0 from the signal measured at t=30. In some embodiments, water is used as a control (in place of the experimental compound). In some embodiments, the compound of formula (I) (and / or any of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Il), (Im), 2-amide-5,6-condensed-thieno-aryl, 2-amide-5,6-condensed-thieno-heteroaryl, 2-amide-5,6-condensed-thieno-heterocyclyl, or any other compound disclosed herein) did not produce detectable inhibition of ACHE at a test compound concentration of 10 μM. In some embodiments, the compound of formula (I) (and / or any of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Il), (Im), 2-amide-5,6-condensed-thieno-aryl, 2-amide-5,6-condensed-thieno-heteroaryl, 2-amide-5,6-condensed-thieno-heterocyclyl, or any other compound disclosed herein) did not produce detectable inhibition of ACHE at a test compound concentration of 5 μM. In some embodiments, the compound of formula (I) (and / or any of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Il), (Im), 2-amide-5,6-condensed-thieno-aryl, 2-amide-5,6-condensed-thieno-heteroaryl, 2-amide-5,6-condensed-thieno-heterocyclyl, or any other compound disclosed herein) did not produce detectable inhibition of ACHE at a test compound concentration of 2.5 μM.In some embodiments, the compound of formula (I) (and / or any of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Il), (Im), 2-amide-5,6-condensed-thieno-aryl, 2-amide-5,6-condensed-thieno-heteroaryl, 2-amide-5,6-condensed-thieno-heterocyclyl, or any other compound disclosed herein) did not produce detectable inhibition of ACHE at a test compound concentration of 1.0 μM. In some embodiments, at a concentration of 10 μM of the test compound, the enzyme inhibition percentage is approximately 0% (undetectable), 0.05%, 0.1%, 0.5%, 0.75%, 1.0%, 2.0%, 5.0% or less, or includes and / or spans the aforementioned values.

[0333] isotope labeled compounds Furthermore, the scope of this disclosure includes all pharmaceutically acceptable isotope-labeled compounds of the compounds disclosed herein, such as compounds of formula (I) (and / or any of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Il), (Im), 2-amide-5,6-condensed-thieno-heteroaryl, 2-amide-5,6-condensed-thieno-heterocyclyl, or any other compound disclosed herein), in which one or more atoms are substituted by atoms having the same number of atoms but with atomic weights or mass numbers different from those commonly found in nature. Examples of isotopes suitable for inclusion in the compounds disclosed herein include: 2 H (deuterium) and 3 Hydrogen such as H (tritium), 11 C, 13 C and 14 Carbon such as C, 36 Chlorine such as Cl, 18 Fluorine such as F 123 I and 125 Iodine, such as I 13 N and 15 Nitrogen such as N 15 O, 17 O and 18 Oxygen such as O, 32Phosphorus such as P and 35 Examples include sulfur isotopes such as ₂S. Specific isotope-labeled compounds of formula (I) (e.g., those incorporating radioactive isotopes) are useful for studying the tissue distribution of drugs and / or substrates. Radioactive isotope tritium ( 3 H) and carbon-14 ( 14 C) is particularly useful for this purpose, given the ease of their incorporation and the ease of detection. Deuterium ( 2 Substitution with isotopes such as H or D may be advantageous in some situations because it can result in certain therapeutic benefits (e.g., extended in vivo half-life or reduced required dosage) arising from increased metabolic stability. In some embodiments, the compounds herein are deuterated at metabolic hotspots (e.g., a particular hydrogen atom in the structure is metabolically less stable than other hydrogens present in the molecule). 11 C, 18 F, 15 O and 13 Substitution with positron-emitting isotopes such as 1N may be useful, for example, in positron emission tomography (PET) studies to investigate target occupancy. The isotope-labeled compounds of the compounds disclosed herein can generally be prepared by conventional methods known to those skilled in the art or by processes similar to those described in the accompanying general synthesis schemes and examples, using appropriate isotope-labeling reagents instead of conventionally used unlabeled reagents.

[0334] solvate As discussed above, the compounds disclosed herein, as well as their stereoisomers and isotopically labeled forms or pharmaceutically acceptable salts thereof, may exist in solvated or unsolvated forms. As used herein, the term “solvate” refers to a molecular complex comprising a compound described herein or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable solvent molecules in stoichiometric or non-stoichiometric amounts. When the solvent is water, the solvate is referred to as a “hydrate.” Therefore, the scope of this disclosure should be understood to encompass all solvates of the compounds disclosed herein, as well as their stereoisomers, tautomers and isotopically labeled forms or pharmaceutically acceptable salts thereof.

[0335] Formulation and route of administration In the uses described herein, it may be possible to administer the compounds disclosed herein alone, but the compounds to be administered are typically present as active ingredients in a pharmaceutical composition. Therefore, in some embodiments, what is provided herein is a pharmaceutical composition comprising the compounds disclosed herein in combination with one or more pharmaceutically acceptable excipients, such as diluents, carriers, and adjuvants, and optionally other active ingredients. In some embodiments, the pharmaceutical composition contains a therapeutically effective amount of the compounds disclosed herein.

[0336] The compounds disclosed herein may be administered by any suitable route, in the form of a pharmaceutical composition adapted to such route, and in a dose effective for the intended treatment. The compounds and compositions presented herein may be administered, for example, orally, mucosally, topically, transdermally, rectally, pulmonaryly, parenterally, intranasally, intravascularly, intravenously, intra-arterially, intraperitoneally, intrathecally, subcutaneously, sublingually, intramuscularly, intrasternally, or vaginally, in drug units containing conventional pharmaceutically acceptable excipients, or by infusion techniques.

[0337] The pharmaceutical composition may be in the form of, for example, tablets, chewable tablets, minitablets, caplets, pills, beads, hard capsules, soft capsules, gelatin capsules, granules, powders, licks, patches, creams, gels, sachets, microneedle arrays, syrups, flavored syrups, juices, drops, injections, emulsions, microemulsions, ointments, aerosols, aqueous suspensions, or oily suspensions. The pharmaceutical composition is typically prepared in the form of a dosage unit containing a specific amount of the active ingredient.

[0338] Provided herein as Embodiment 255 is a pharmaceutical composition comprising one of the compounds or salts from Embodiments 1 to 254 and a pharmaceutically acceptable excipient.

[0339] Furthermore, this disclosure includes pharmaceutical compositions comprising a mixture of any of the compounds disclosed herein with one or more other activators disclosed herein.

[0340] Use of compounds and compositions, pharmaceuticals and treatment methods for their use As discussed herein, the compounds described herein should be understood to include all stereoisomers, tautomers, or pharmaceutically acceptable salts or solvates of any of the foregoing. Therefore, the scope of methods and uses provided herein should be understood to also include methods and uses employing all such forms. In addition to their usefulness in human treatment, the compounds provided herein may be useful in veterinary treatment of companion animals, exotic animals, and livestock, including mammals and rodents. For example, animals including horses, dogs, and cats may be treated with the compounds provided herein.

[0341] In some embodiments, methods for treating a patient are provided, as disclosed elsewhere in this specification. In some embodiments, the method involves administering a therapeutic dose of a 15-PGDH inhibitor compound (e.g., any one of the following compounds of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Il), (Im), 2-amide-5,6-condensed-thieno-aryl, 2-amide-5,6-condensed-thieno-heteroaryl, 2-amide-5,6-condensed-thieno-heterocyclyl, or any other compound disclosed herein) to the patient.

[0342] In some embodiments, the method includes selecting a patient. In some embodiments, the patient is a patient suffering from a 15-PGDH-mediated disease, disorder, or condition.

[0343] In some embodiments, the patient's response is measured after administration of a 15-PGDH inhibitor. In some embodiments, the beneficial effect of the 15-PGDH inhibitor may be evaluated by the reduction of one or more inflammatory biomarkers in a relevant sample derived from the subject. In some embodiments, the inflammatory biomarkers may include or consist of one or more cytokines or inflammatory cytokines (e.g., those associated with fibrosis). Examples of such cytokines include HHb, MIP2 (e.g., CCL3 or CCL4), IFN5, TGFP, TNFα, IL-6, MCP-1, IL2, and IL-10 in BAL fluid. Methods for measuring the amount of such biomarkers include, but are not limited to, ELISA. In some embodiments, the biomarker is an eicosanoid or PGE2 metabolite, such as prostaglandin E2 (PGE2), prostaglandin E metabolite (PGE-M, tetranor-PGEM), 15-ketoprostaglandin E2 (15-keto-PGE2), prostaglandin F2α (PGF2α), 6-ketoprostaglandin F1α (6-keto-PGF1α), prostaglandin D2 (PGD2), prostaglandin J2 (PGJ2), tetranor-PGE1 (TN-E), thromboxane B2 (TXB2), leukotriene B4 (LTB4), 15-H These include hydroxyeicosatetraenoic acid (15-HETE), 12-hydroxyeicosatetraenoic acid (12-HETE), 8-hydroxyeicosatetraenoic acid (8-HETE), 5-hydroxyeicosatetraenoic acid (5-HETE), 17-HDA, 12,13-dihydroxy-9Z-octadecenoic acid (12,13-DiHOME), 9,10-dihydroxy-9Z-octadecenoic acid (9,10-DiHOME), 14,15-dihydroxyeicosatrienoic acid (14,15-DHET), 11,12-dihydroxyeicosatrienoic acid (11,12-DHET), or combinations thereof. In some embodiments, the methods disclosed herein may include reducing the amount of one or more biomarkers in a sample derived from a subject compared to a control.In some embodiments, the methods disclosed herein may include reducing the amount of one or more biomarkers in a sample derived from a subject compared to a patient before treatment. In some embodiments, the methods disclosed herein may include increasing the amount of one or more biomarkers in a sample derived from a subject compared to a control. In some embodiments, the methods disclosed herein may include increasing the amount of one or more biomarkers in a sample derived from a subject compared to a patient before treatment. Therefore, the levels of these biomarkers may be measured before or after treatment with the 15-PDGH inhibitor disclosed herein.

[0344] In some embodiments, as disclosed elsewhere in this specification, the patient is a patient suffering from a 15-PGDH-mediated disease or disorder. In some embodiments, the 15-PGDH-mediated disease or disorder is inflammatory bowel disease, ulcerative colitis, Crohn's disease, fibrous disease, disorder, or condition. In some embodiments, the 15-PGDH-mediated disease or disorder is atherosclerosis. In some embodiments, the 15-PGDH-mediated disease or disorder is an autoimmune disease. In some embodiments, 15-PGDH-mediated diseases, disorders, or symptoms include systemic sclerosis, multifocal fibrosis, nephrogenic systemic fibrosis, renal fibrosis, glomerulosclerosis, renal tubulointerstitial fibrosis, progressive renal disease or diabetic nephropathy, myocardial fibrosis, pulmonary fibrosis, glomerulosclerotic pulmonary fibrosis, idiopathic pulmonary fibrosis, silicosis, asbestosis, interstitial lung disease, interstitial fibrotic lung disease, chemotherapy / radiation-induced pulmonary fibrosis, endocardial myocardial fibrosis, deltoid muscle fibrosis, pancreatitis, extraocular myofibrosis characterized by replacement of normal muscle tissue with fibrous tissue to varying degrees, retroperitoneal fibrosis, hepatic fibrosis, cirrhosis, chronic renal failure, myelofibrosis, myelofibrosis, acute fibrosis, or organ-specific fibrosis. In some embodiments, 15-PGDH-mediated diseases, disorders, or symptoms include intestinal ischemia, ischemia, ischemic brain disease, ischemic heart disease, ischemic peripheral vascular disease, ischemic placenta, ischemic kidney disease, ischemic vascular disease, ischemic reperfusion injury, limb ischemia, lower limb ischemia, myocardial ischemia, organ ischemia, peripheral ischemia, tissue ischemia, transient ischemic attack (TIA), and wounds to tissues or organs.

[0345] Provided herein as Embodiment 256 is any one compound or salt from Embodiments 1 to 254 or the pharmaceutical composition of Embodiment 255 for use as a pharmaceutical.

[0346] Provided herein as Embodiment 257 is a compound or salt from any one of Embodiments 1 to 254 or a pharmaceutical composition from Embodiment 255 for use in treating a 15-PGDH-mediated disease or disorder.

[0347] Provided herein as Embodiment 258 is a compound or salt from any one of Embodiments 1 to 254 or a pharmaceutical composition from Embodiment 255 for use in the treatment of inflammatory bowel disease.

[0348] Provided herein as Embodiment 259 is a compound or salt from any one of Embodiments 1 to 254 or a pharmaceutical composition from Embodiment 255 for use in the treatment of ulcerative colitis.

[0349] Provided herein as Embodiment 260 is a compound or salt from any one of Embodiments 1 to 254 or a pharmaceutical composition from Embodiment 255 for use in the treatment of Crohn's disease.

[0350] Provided herein as Embodiment 261 is a compound or salt from any one of Embodiments 1 to 254 or a pharmaceutical composition from Embodiment 255 for use in the treatment of fibrous diseases, disorders, or symptoms.

[0351] Provided herein as Embodiment 262 is a compound, salt, or composition of Embodiment 261, wherein fibrous diseases, disorders, or symptoms are characterized, in whole or in part, by the replacement of normal tissue elements due to the excessive production of fibrous material or the abnormal, non-functional, and / or excessive accumulation of matrix-related components, including the excessive production of fibrous material in the extracellular matrix.

[0352] Provided herein as Embodiment 263 is a compound, salt, or composition of Embodiment 261 or 262, wherein fibrotic diseases, disorders, or symptoms include systemic sclerosis, multifocal fibrosis, nephrogenic systemic fibrosis, renal fibrosis, glomerulosclerosis, renal tubulointerstitial fibrosis, progressive renal disease or diabetic nephropathy, myocardial fibrosis, pulmonary fibrosis, glomerulosclerosing pulmonary fibrosis, idiopathic pulmonary fibrosis, silicosis, asbestosis, interstitial lung disease, interstitial fibrotic lung disease, chemotherapy / radiation-induced pulmonary fibrosis, endocardial myocardial fibrosis, deltoid muscle fibrosis, pancreatitis, extraocular myofibrosis characterized by replacement of normal muscle tissue with fibrous tissue to varying degrees, retroperitoneal fibrosis, hepatic fibrosis, cirrhosis, chronic renal failure, myelofibrosis, myelofibrosis, acute fibrosis, or organ-specific fibrosis.

[0353] Provided herein as Embodiment 264 is a compound, salt, or composition of Embodiment 261 or 262, wherein the fibrotic disease, disorder, or symptom is idiopathic pulmonary fibrosis.

[0354] Provided herein as Embodiment 265 is a compound, salt, or composition of Embodiment 261 or 262, wherein the fibrotic disease, disorder, or symptom is renal fibrosis.

[0355] Provided herein as Embodiment 266 is a compound, salt, or composition of Embodiment 261 or 262, wherein the fibrotic disease, disorder, or condition is hepatic fibrosis.

[0356] Provided herein as Embodiment 267 is a compound or salt from any one of Embodiments 1 to 254 or a pharmaceutical composition from Embodiment 255 for use in the treatment of one or more of the following conditions: atherosclerotic cardiovascular disease, autoimmune disease, intestinal ischemia, ischemia, ischemic cerebrovascular disease, ischemic heart disease, ischemic peripheral vascular disease, ischemic placenta, ischemic kidney disease, ischemic vascular disease, ischemic reperfusion injury, limb ischemia, lower limb ischemia, myocardial ischemia, organ ischemia, peripheral ischemia, tissue ischemia, transient ischemic attack (TIA), and wounds to tissues or organs.

[0357] Provided herein as Embodiment 268 is a method for treating a 15-PGDH-mediated disease, disorder, or symptom in a subject requiring treatment of such disease, disorder, or symptom, comprising administering to the subject a therapeutically effective amount of any one compound or salt from Embodiments 1 to 254 or the pharmaceutical composition of Embodiment 255.

[0358] Embodiment 269 provided herein is a method for treating an intestinal, gastrointestinal, or bowel disorder in a subject requiring treatment of such disorder, comprising administering to the subject a therapeutically effective amount of any one compound or salt of Embodiments 1 to 254 or the pharmaceutical composition of Embodiment 255.

[0359] Provided herein as Embodiment 270 is the method of Embodiment 268 or 269, wherein the disease or disorder includes at least one of ulcerative colitis, inflammatory bowel disease, and Crohn's disease.

[0360] combination In some embodiments, the 15-PGDH inhibitor compounds disclosed herein (including compounds of formula (I) disclosed herein, compounds of other formulas, 2-amide-5,6-condensed-thieno-aryl, 2-amide-5,6-condensed-thieno-heterocyclyl, etc.) may be provided in combination with other therapeutic agents.

[0361] In some embodiments, the 15-PGDH inhibitors disclosed herein are used in combination with tumor necrosis factor (TNF) inhibitors (e.g., TNF-α inhibitors). In some embodiments, the TNF inhibitor may be an anti-TNF-α antibody (e.g., infliximab, adalimumab, certolizumab pegol, and golimumab), a receptor-constructor fusion protein (e.g., etanercept), or a small molecule, such as, but not limited to, pomalidomide, thalidomide, lenalidomide, and bupropion.

[0362] In some embodiments, the 15-PGDH inhibitors disclosed herein are used in combination with corticosteroids. In some embodiments, the corticosteroids include Acrobate, Alclomethasone dipropionate, Amsinafel, Amsinafid, Amcinonide, Aristocort A, Enhanced Betamethasone Dipropionate, Beclomethasone, Beclomethasone Dipropionate, Betamethasone, Betamethasone Benzoate, Betamethasone-17-Benzoate, Betamethasone Dipropionate, Betamethasone Sodium Phosphate, and Betamethasone Sodium Acetate, Betamethasone Valerate, and Betamethasone-17-Valerate. Acid esters, chloroprednisone, clobetasol propionate, clobetazone propionate, crocortolone, cordran, corticosterone, cortisol, cortisol acetate, cortisol cypionate, sodium cortisol phosphate, sodium cortisol succinate, cortisone, cortisone acetate, cortodoxone, cyclocoat, deflazacoat, difluprednate, desinolone, desonide, desowen, desoxymethasone, deoxycorticosterone acetate, deoxycorticosterone pivalate, 11- Deoxycortisol, dexamethasone, dexamethasone acetate, sodium dexamethasone phosphate, dichlorizone, diflorasone acetate, dihydroxycortisone, diprolene, diprolene, diprozone, betamethasone ester, floron, flucetonide, flulchloride, flucortron, fludrocortisone, fludrocortisone acetate, flumetalon, flumetazone, flumetazone pivarate, flunisolide, fluocinolone acetonide, fluocinolone acetonide acetate, fluocinonide, fl Orametholone, fluorocortisone, fluperolon, fluprednisolone, flurandrenolone acetonide, fluticasone propionate, fuprednisolone, halcinonide, halobetazole propionate, halog, hydrocortamate, hydrocortisone, hydrocortisone acetate, hydrocortisone butyrate, hydrocortisone valerate, hydrocortisone-17-valerate, kenalog, redex, locord, locorten, maxiflor, medrisone, meprednisone, methylprednisolone,6α-methylprednisolone, methylprednisolone acetate, sodium methylprednisolone succinate, methylprednisone, mometasone furoate, paramethasone, paramethasone acetate, prednidone, prednisone, prednisolone, prednisolone acetate, sodium prednisolone phosphate, sodium prednisolone succinate, prednisolone tebutate, prednisone, psolcon, cinal, temovert, tetrahydrocortisol, topicort, topicort LP, triamcinolone, triamcinolone acetonide, triamcinolone diacetate, triamcinolone hexacotonide, tridecylone, valison, westcolt, or a combination of the above.

[0363] In some embodiments, each component of a therapeutic combination may be administered using the same or different routes. For example, as disclosed elsewhere herein, the 15-PGDH inhibitor compounds disclosed herein may be administered by any suitable route, in the form of a pharmaceutical composition adapted to such route, and in a dose effective for the intended treatment. Each component of a therapeutic combination may be administered, for example, orally, mucosally, topically, transdermally, rectally, pulmonaryly, parenterally, intranasally, intravascularly, intravenously, intra-arterially, intraperitoneally, intrathecally, subcutaneously, sublingually, intramuscularly, intrasternally, or vaginally, in a dosage unit formulation containing conventional pharmaceutically acceptable excipients, or by infusion techniques.

[0364] Individual therapeutic agents containing this combination may be administered substantially simultaneously using any route disclosed for any disclosed treatment method (e.g., a method for treating IBD). Individual therapeutic agents containing this combination may be administered sequentially using any route disclosed for any disclosed treatment method (e.g., a method for treating IBD). Individual therapeutic agents containing this combination may be administered together as part of the same composition or as different compositions.

[0365] For certain biologics (e.g., antibody or protein-based therapeutics), it is understood that the therapeutic agent may be more appropriately administered by injection. Alternatively, small molecules (e.g., 15-PGDH inhibitors, 5,6-condensed bicyclic thieno-heterocyclines, compounds of any formula disclosed herein, etc.) may be suitable for injection or other methods of administration (e.g., via other routes, including oral administration).

[0366] Manufacturing method The compounds provided herein can be synthesized according to the procedures described in this section and the following sections. The synthetic methods described herein are illustrative only, and the compounds disclosed herein can also be synthesized by alternative routes utilizing alternative synthetic strategies, taking into account the teachings of this disclosure, as will be understood by those skilled in the art. It should be recognized that this general synthetic procedure and the specific examples provided herein are illustrative only and should not be construed as limiting the scope of this disclosure. See, for example, W. Friedrichsen, Furans, Thiophenes and Selenophenes with Fused Six-membered Heterocyclic Rings, in Comprehensive Heterocyclic Chemistry, 1984.

[0367] Typically, a compound of formula (I) (or, for example, any one of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Il), (Im), 2-amide-5,6-condensed-thieno-heteroaryl, 2-amide-5,6-condensed-thieno-heterocyclyl, or any other compound disclosed herein) can be synthesized using one or more steps according to the following scheme and / or using one or more of the following intermediates. Any variables used in the intermediates in the following scheme may be as defined elsewhere herein unless otherwise specified. For example, R 3 (or R 1a , R 1bIf R (or any other arbitrary variable) is defined in one way for expression (I) and in another way for expression (I-int-g), then R in expression (I) 3 (or R 1a , R 1b The definition for any other variable (or any other variable) is given by R in equation (I-int-g). 3 (or R 1a , R 1b The definitions of (or any other variable) may be substituted, and vice versa. Similarly, the definitions of variables in two different intermediates may be used interchangeably. Suitable reaction conditions (e.g., solvent, reaction temperature, and reagents) for the schemes considered in this section can be found in the examples provided herein.

[0368] Provided herein as Embodiment 271 is a method for producing the compound or salt of Embodiment 1, wherein the compound is of formula (I-int-c.1) [ka] The compound and formula (B a -R 2 ): [ka] This involves performing a Suzuki coupling with the compound, in formula, X H It is a halogen, B a This is a boronic acid group or a boronic acid ester group, [ka] This indicates that a double bond or a single bond may be present. X a Each of these examples is, independently, nitrogen, oxygen, or carbon. If present, each example of s is an integer selected from 0, 1, 2, or 3. If present, each example of r is an integer independently selected from 0, 1, 2, or 3, and two examples of r are the same R 2If present on the base, the sum of both r values ​​in the combination will not exceed 5. If it exists and is bonded to an N ring member, R 5 Each example is independent of C 1~6 Alkyl, C 1~6 Haloalkyl, C 3~6 A cycloalkyl or heterocyclyl having 3 to 10 members, If present and bonded to a C ring member, R 5 Each example is independently oxo, CN, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C(O)N(R) 6 )2, -N(R 6 )2, -N(R 6 )(C 1~6 It is a heterocycline having alkylene-OH, 3 to 10 members. If present, R 6 Each of these examples is independent of -H, C 1~3 Alkyl, C(O)C 1~3 Alkyl, C(O)2C 1~3 Alkyl, C 1~3 Alkylene-OH or S(O) n C 1~3 It is alkyl, -N=Ring nitrogen is R 5 It can bond to and provide a positive ion.

[0369] intermediate Some embodiments relate to intermediates useful for synthesizing any one compound of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Il), (Im), 2-amide-5,6-condensed-thieno-aryl, 2-amide-5,6-condensed-thieno-heteroaryl, 2-amide-5,6-condensed-thieno-heterocyclyl, or any other compound disclosed herein.

[0370] Equation (I-int-a) Some embodiments are given by formula (I-int-a): [ka] With respect to compounds or salts thereof, the variables are as defined elsewhere in this specification. In some embodiments, [ka] teeth, [ka] And, a is N or CH, b is N or CH, c is N, CH, or CR 3 And, d is N, CH, or CR 4 And, R 3 is -H, C 1~6 Alkyl, C 3~10 Cycloalkyl, C 6~10 The aryl, heteroaryl having 5 to 10 ring members, or heterocyclyl having 3 to 10 ring members, R 3 These are either unsubstituted or each independently a halogen, -OH, oxo, or C 1~3 Alkyl, C 1~3 Haloalkyl, C 1~3 Alkoxy, C 1~3 Alkylene-C 1~3 Alkoxy or C 1~6 It may be substituted with one or more substituents that are heteroalkyl. R 4 is -H or C 1~6 It is alkyl, R i1 C 1~6 It is an alkoxy, X H This represents a halogen atom.

[0371] In some embodiments, each X H In some embodiments, X represents -Cl or Br independently. H is -Cl. In some embodiments, Ri1 It is ethoxy.

[0372] Equation (I-int-b.1) Some embodiments are represented by formula (I-int-b.1): [ka] With respect to compounds or salts thereof, the variables are as defined elsewhere in this specification. In some embodiments, [ka] teeth, [ka] And, a is N or CH, b is N or CH, c is N, CH, or CR 3 And, d is N, CH, or CR 4 And, R 3 is -H, C 1~6 Alkyl, C 3~10 Cycloalkyl, C 6~10 The aryl, heteroaryl having 5 to 10 ring members, or heterocyclyl having 3 to 10 ring members, R 3 These are either unsubstituted or each independently a halogen, -OH, oxo, or C 1~3 Alkyl, C 1~3 Haloalkyl, C 1~3 Alkoxy, C 1~3 Alkylene-C 1~3 Alkoxy or C 1~6 It may be substituted with one or more substituents that are heteroalkyl. R 4 is -H or C 1~6 It is alkyl, X H It is a halogen.

[0373] In some embodiments, each X HIn some embodiments, X represents -Cl or -Br independently. H It is -Cl.

[0374] Expression (I-int-c.1) Some embodiments are represented by formula (I-int-c.1): [ka] With respect to compounds or salts thereof, the variables are as defined elsewhere in this specification. In some embodiments, [ka] teeth, [ka] And, a is N or CH, b is N or CH, c is N, CH, or CR 3 And, d is N, CH, or CR 4 And, R 1a is -H, C 1~6 Alkyl, C 1~6 Haloalkyl or C 1~6 It is heteroalkyl, R 1a These are either unsubstituted or each independently a halogen, -OH, and -N(R) b )2, C 1~3 Alkyl or C 1~3 It may be substituted with one or more substituents that are alkoxy. R 1b C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Heteroalkyl, C 3~10 A cycloalkyl or heterocyclyl having 3 to 10 ring members, R 1b These are either unsubstituted or each independently a halogen, -OH, and -N(R) b )2, C 1~3Alkyl or C 1~3 It may be substituted with one or more substituents that are alkoxy, or Instead, R 1a and R 1b They form heterocyclines together, each having 3 to 10 ring members. R 1a and R 1b The heterocyclyls formed by this process are either unsubstituted or each independently contains a halogen, -OH, -CN, and -N(R) b )2, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 Heteroalkyl, C 3~6 It may be substituted with one or more substituents that are cycloalkyl or heterocyclyl having 3 to 6 ring members. R 3 is -H, C 1~6 Alkyl, C 3~10 Cycloalkyl, C 6~10 The aryl, heteroaryl having 5 to 10 ring members, or heterocyclyl having 3 to 10 ring members, R 3 These are either unsubstituted or each independently a halogen, -OH, oxo, and -N(R) b )2, C 1~3 Alkyl, C 1~3 Haloalkyl, C 1~3 Alkoxy, C 1~3 Alkylene-C 1~3 Alkoxy or C 1~6 It may be substituted with one or more substituents that are heteroalkyl. R 4 is -H, C 1~6 Alkyl or N(R) 7 )2, If present, R 7 Each example is independently -H or C 1~6 Alkyl or Instead, two R's 7 The substituents together form a heterocyclyl having 3 to 6 ring members, R 7 These are either unsubstituted or each is independently -F, -OH, C1-3 It may be substituted with one or more substituents that are alkoxy. If present, R b Each of these examples is independently -H or C 1~6 It is alkyl, or instead, it has two R's. b The substituents together form a heterocyclyl having 3 to 6 ring members. R b These are either unsubstituted or each is independently -F, -OH, C 1~3 It can be substituted with one or more substituents that are alkoxy.

[0375] Equation (I-int-b.2) Some embodiments are represented by formula (I-int-b.2): [ka] With respect to compounds or salts thereof, the variables are as defined elsewhere in this specification. In some embodiments, [ka] teeth, [ka] And, a is N or CH, b is N or CH, c is N, CH, or CR 3 And, d is N, CH, or CR 4 And, R 2 These are heterocyclyls having 5 to 10 ring members, and heteroaryls having 5 to 10 ring members. R 2 is either non-substitutive or R 5 It can be replaced with one or more examples of R 5 Each example is independently oxo, CN, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C(O)N(R)6 )2, -N(R 6 )2, -N(R 6 )(C 1~6 It is an alkylene-OH or a heterocycline having 3 to 10 members. R 5 Each example is either non-substitution or R 6 It may be replaced with one or more examples of R 6 Each of these examples is independent of -H, C 1~6 Alkyl, C(O)C 1~6 Alkyl, C(O)2C 1~6 Alkyl, C 1~6 Alkylene-OH or S(O) n C 1~6 It is an alkyl group, and n is 0, 1, or 2. R 6 These are either unsubstituted or each is independently -F, -OH, C 1~3 It may be substituted with one or more substituents that are alkoxy. R 3 is -H, C 1~6 Alkyl, C 3~10 Cycloalkyl, C 6~10 The aryl, heteroaryl having 5 to 10 ring members, or heterocyclyl having 3 to 10 ring members, R 3 These are either unsubstituted or each independently a halogen, -OH, oxo, or C 1~3 Alkyl, C 1~3 Haloalkyl, C 1~3 Alkoxy, C 1~3 Alkylene-C 1~3 Alkoxy or C 1~6 It may be substituted with one or more substituents that are heteroalkyl, R 4 is -H or C 1~6 It is alkyl, If present, R b Each example is independently either -H or C 1~6 Alkyl or Instead, two R's b The substituents together form a heterocyclyl having 3 to 6 ring members. R bThese are either unsubstituted or each is independently -F, -OH, C 1~3 It may be substituted with one or more substituents that are alkoxy. R i1 C 1~6 It is an alkoxy.

[0376] In some embodiments, R i1 It is ethoxy.

[0377] Expression (I-int-c.2) Some embodiments are represented by formula (I-int-c.1): [ka] With respect to the compounds or salts thereof, the variables are as disclosed elsewhere in this specification (for example, as disclosed for the compound of formula (I-int.b.2)).

[0378] Equation (I-int-d) Some embodiments are represented by formula (I-int-d): [ka] With respect to compounds or salts thereof, the variables are as defined elsewhere in this specification. In some embodiments, [ka] teeth, [ka] And, a is N or CH, b is N or CH, d is N, CH, or CR 4 And, R 4 is -H or C 1~6 It is alkyl, each X H This independently represents a suitable halogen atom or a similar reactive group.

[0379] In some embodiments, each X H In some embodiments, X represents -Cl or -Br independently. H It is -Cl.

[0380] Equation (I-int-e) Some embodiments are represented by formula (I-int-e): [ka] With respect to compounds or salts thereof, the variables are as defined elsewhere in this specification. In some embodiments, [ka] teeth, [ka] And, a is N or CH, b is N or CH, d is N, CH, or CR 4 And, R 3 C 1~6 Alkyl, C 3~10 Cycloalkyl, C 6~10 The aryl, heteroaryl having 5 to 10 ring members, or heterocyclyl having 3 to 10 ring members, R 3 These are either unsubstituted or each independently a halogen, -OH, oxo, and -N(R) b )2, C 1~3 Alkyl, C 1~3 Haloalkyl, C 1~3 Alkoxy, C 1~3 Alkylene-C 1~3 Alkoxy or C 1~6 It may be substituted with one or more substituents that are heteroalkyl. R 4 is -H or C 1~6 It is alkyl, If present, R b Each example is independently -H or C 1~6Alkyl or Instead, two R's b The substituents together form a heterocyclyl having 3 to 6 ring members. R b These are either unsubstituted or each is independently -F, -OH, C 1~3 It can be substituted with one or more substituents that are alkoxy.

[0381] Equation (I-int-f) Some embodiments are represented by formula (I-int-f): [ka] With respect to compounds or salts thereof, the variables are as defined elsewhere in this specification. In some embodiments, [ka] teeth, [ka] And, a is N or CH, b is N or CH, d is N, CH, or CR 4 And, R 3 C 1~6 Alkyl, C 3~10 Cycloalkyl, C 6~10 The aryl, heteroaryl having 5 to 10 ring members, or heterocyclyl having 3 to 10 ring members, R 3 These are either unsubstituted or each independently a halogen, -OH, oxo, and -N(R) b )2, C 1~3 Alkyl, C 1~3 Haloalkyl, C 1~3 Alkoxy, C 1~3 Alkylene-C 1~3 Alkoxy or C 1~6 It may be substituted with one or more substituents that are heteroalkyl. R 4 is -H or C1~6 It is alkyl, If present, R b Each example is independently -H or C 1~6 Alkyl or Instead, two R's b The substituents together form a heterocyclyl having 3 to 6 ring members. R b These are either unsubstituted or each is independently -F, -OH, C 1~3 It can be substituted with one or more substituents that are alkoxy.

[0382] Equation (I-int-g) Some embodiments are represented by the formula (I-int-g): [ka] With respect to compounds or salts thereof, the variables are as defined elsewhere in this specification. In some embodiments, [ka] teeth, [ka] And, a is N or CH, b is N or CH, d is N, CH, or CR 4 And, R 1a is -H, C 1~6 Alkyl, C 1~6 Haloalkyl or C 1~6 It is heteroalkyl, R 1a These are either unsubstituted or each independently a halogen, -OH, and -N(R) b )2, C 1~3 Alkyl or C 1~3 It may be substituted with one or more substituents that are alkoxy. R 1b C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6Heteroalkyl, C 3~10 A cycloalkyl or heterocyclyl having 3 to 10 ring members, R 1b These are either unsubstituted or each independently a halogen, -OH, and -N(R) b )2, C 1~3 Alkyl or C 1~3 It may be substituted with one or more substituents that are alkoxy, or Instead, R 1a and R 1b They form heterocyclines together, each having 3 to 10 ring members. R 1a and R 1b The heterocyclyls formed by this process are either unsubstituted or each independently contains a halogen, -OH, -CN, and -N(R) b )2, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 Heteroalkyl, C 3~6 It may be substituted with one or more substituents that are cycloalkyl or heterocyclyl having 3 to 6 ring members. R 3 is -H, C 1~6 Alkyl, C 3~10 Cycloalkyl, C 6~10 The aryl, heteroaryl having 5 to 10 ring members, or heterocyclyl having 3 to 10 ring members, R 3 These are either unsubstituted or each independently a halogen, -OH, oxo, and -N(R) b )2, C 1~3 Alkyl, C 1~3 Haloalkyl, C 1~3 Alkoxy, C 1~3 Alkylene-C 1~3 Alkoxy or C 1~6 It may be substituted with one or more substituents that are heteroalkyl. R 4 is -H, C 1~6 It is alkyl, If present, R b Each example is independently -H or C 1~6Is it alkyl? Or, instead, two R's b The substituents together form a heterocyclyl having 3 to 6 ring members. R b These are either unsubstituted or independently -F, -OH, and C. 1~3 It can be substituted with one or more substituents that are alkoxy.

[0383] Equations (I-int-h) and (I-int-h.1) Some embodiments are based on the formula (I-int-h): [ka] This relates to compounds or salts thereof. In some embodiments, R i1 C 1~6 It is an alkoxy. In some embodiments, R i1 (For example, equation (I-int-h.1) [ka] It is an ethoxy (as shown in [reference]).

[0384] Equations (I-int-i) and (I-int-i.1) Some embodiments of the formula (I-int-i) [ka] This relates to compounds or salts thereof. In some embodiments, R i1 C 1~6 It is an alkoxy. In some embodiments, R i1 (For example, the expression (I-int-i.1) [ka] It is an ethoxy (as shown in [reference]).

[0385] Equations (I-int-j) and (I-int-j.1) Some embodiments are given by formula (I-int-j): [ka] This relates to compounds or salts thereof. In some embodiments, the compound of formula (I-int-j) is prepared by oxidizing the compound of formula (I-int-i). In some embodiments, the compound of formula (I-int-i) is oxidized in the presence of manganese dioxide. In some embodiments, R i1 C 1~6 It is an alkoxy. In some embodiments, R i1 This is the formula (I-int-j.1) [ka] It is an ethoxy as shown in [image / diagram].

[0386] Equations (I-int-k), (I-int-k.1), and (I-int-k.2) Some embodiments use the formula (I-int-k): [ka] With respect to compounds or salts thereof, the variables are as defined elsewhere in this specification. In some embodiments, X H is a halogen. In some embodiments, X H is -Cl or -Br. In some embodiments, X H is -Cl. In some embodiments, R i1 C 1~6 It is an alkoxy. In some embodiments, R i1 This is the formula (I - int - k.1) [ka] The ethoxy is as shown, and the variables are as defined elsewhere in this specification. In some embodiments, X H This is -Cl and formula (I-int-k.2): [ka] R represented byi1 or a salt thereof. In some embodiments, the compound of formula (I-int-k.2) is prepared by chlorinating the compound of formula (I-int-j.1). In some embodiments, the compound of formula (I-int-j.1) is chlorinated in the presence of a chlorinating agent (e.g., phenylphosphonic acid dichloride). In some embodiments, the compound of formula (I-int-k.2) may be represented by the compound of formula (I-int-a).

[0387] Equation (I-int-l) Some embodiments are represented by the formula (I-int-l): [ka] This relates to compounds or salts thereof. In some embodiments, the compound of formula (I-int-l) is prepared by saponifying the compound of formula (I-int-k). In some embodiments, the compound of formula (I-int-k) is saponified in the presence of a strong base (e.g., NaOH). In some embodiments, the compound of formula (I-int-l) may be represented by the compound of formula (I-int-b). Some embodiments of formula (I-int-l.1): [ka] The present invention relates to compounds of the same or its salts. In some embodiments, the compound of formula (I-int-l.1) is prepared by saponifying the compound of formula (I-int-k.1). In some embodiments, the compound of formula (I-int-k.1) is saponified in the presence of a strong base (e.g., NaOH). In some embodiments, the compound of formula (I-int-l.1) may be represented by the compound of formula (I-int-b).

[0388] Equation (I-int-m) Some embodiments are represented by the formula (I-int-m): [ka] This relates to compounds or salts thereof. In some embodiments, R 2This is disclosed elsewhere in this specification.

[0389] Equation (I-int-n) Some embodiments are based on the formula (I-int-n): [ka] This relates to compounds or salts thereof.

[0390] Equation (I-int-o) Some embodiments are given by formula (I-int-o): [ka] With respect to the compounds or salts thereof, the variables are as defined elsewhere in this specification.

[0391] Preparation of the compound of formula (I) As illustrated in the following scheme, the compounds of formula (I) may be prepared using the disclosed intermediate compounds or any combination thereof.

[0392] Scheme 1.1 (Scheme 1a.1-1c.1) Scheme 1a.1: Saponification for providing equation (I-int-b.1) [ka] In some embodiments, the compound of formula (I-int-a) is saponified using a base (e.g., LiOH, NaOH, etc.). In some embodiments, the compound of formula (I-int-a) is saponified using LiOH. In some embodiments, the reaction is carried out in the presence of a suitable solvent. In some embodiments, the compound of formula (I-int-b.1) is provided. In some embodiments, the compound of formula (I-int-b.1) is subsequently subjected to coupling conditions that provide the compound of formula (I-int-c.1), as shown in scheme 1b.1.

[0393] Scheme 1b.1: Amide formation for providing the compound of formula (I-int-c.1) [ka] As illustrated in Scheme 1b.1, the compound of formula (I-int-c.1) is an intermediate of formula (I-int-b.1), formula HN(R 1a )(R 1b It can be prepared by reaction with an amine of formula (I-int-c.1). In some embodiments, the amide of formula (I-int-c.1) is prepared in the presence of a coupling reagent (e.g., TBTU, DCC, DIC, EDC HCl, etc.). In some embodiments, the amide of formula (I-int-c.1) is prepared in the presence of a base. In some embodiments, the base is an organic base. In some embodiments, the base is TEA, DIPEA, etc.

[0394] Scheme 1c.1: R to compound of formula (I) 2 Coupling [ka] As illustrated in Scheme 1c.1, the compound of formula (I) is an intermediate of formula (I-int-c.1) (where X H B represents a suitable halogen atom (e.g., -Cl, -Br, etc.) or a similar reactive group (e.g., -OTf, -OT, or -OM), a -R 2 It can be prepared by reaction with an intermediate of R. In some embodiments, 2 This is as defined elsewhere in this specification (for example, in formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Il), (Im), etc.). In some embodiments, B a This represents a reactive moiety suitable for cross-coupling reactions, such as the Suzuki or Still cross-coupling. In some embodiments, B aThis is a boronic acid or boronic acid ester (e.g., pinacol boronic acid) or a tributylstannyl group. In some embodiments, Suzuki coupling is performed using a palladium or similar transition metal catalyst with a suitable ligand, according to methods described in the literature and known to those skilled in the art.

[0395] Scheme 1.2 (Scheme 1a.2~1c.2) In an alternative embodiment of Scheme 1.1, R 2 The coupling can be performed on the compound of formula (I-int-a) before saponification. The intermediate is then obtained by saponification and amide formation. The conditions disclosed for Scheme 1.1 can be used for the simultaneous transformations in Scheme 1.2.

[0396] Scheme 1a.2: R to the compound of formula (I-int-b.2) 2 Coupling In some embodiments, the compound of formula (I-int-b.2) is R 2 It can be prepared by coupling to a compound of formula (I-int-a). Suzuki coupling or Still coupling conditions may be used, as disclosed elsewhere in this specification. [ka] In some embodiments, this transformation may be carried out using one or more conditions, such as those disclosed in Scheme 1c.1. In some embodiments, the variables are as disclosed elsewhere in this specification (see, for example, Scheme 1c.1).

[0397] Scheme 1b.2: Saponification to provide equation (I-int-c.2) In some embodiments, the compound of formula (I-int-c.2) can be prepared by saponification of the compound of formula (I-int-b.2) in the presence of a base. [ka] In some embodiments, this transformation may be carried out using one or more conditions, such as those disclosed in Scheme 1a.1.

[0398] Scheme 1c.2: Amide formation for providing the compound of formula (I) In some embodiments, the compound of formula (I) can be prepared by coupling an amine with the compound of formula (I-int-c.2) in the presence of a coupling reagent. [ka] In some embodiments, this transformation may be carried out using one or more conditions, such as those disclosed in Scheme 1b.1.

[0399] Scheme 2a: R to compound of formula (I-int-d) 3 Coupling [ka] As illustrated in Scheme 2a, the intermediate of formula (I-int-d) is B in a cross-coupling reaction (e.g., Suzuki). a -R 3 (Here, B a The Suzuki coupling is defined elsewhere in this specification and provides an intermediate of formula (I-int-e) immediately after coupling with a suitable reactive moiety, e.g., a boronic acid or boronic acid ester (e.g., pinacol boronic acid). In some embodiments, the Suzuki coupling is carried out using a palladium or similar transition metal catalyst with a suitable ligand, according to methods described in the literature and known to those skilled in the art.

[0400] Scheme 2b: Lithiation and carboxylation In some embodiments, the intermediate of formula (I-Int-e) is further subjected to coupling conditions that provide a compound of formula (I-Int-f), as shown in scheme 2b. [ka] As illustrated in Scheme 2b, the compound of formula (I-int-f) can be prepared by the reaction of the intermediate of formula (I-int-e) with a lithifying agent (e.g., n-Bu-Li). In some embodiments, the lithified compound of formula (I-int-e) is exposed to CO2 to provide the compound of formula (I-int-f).

[0401] Scheme 2c: Amide formation for providing a compound of formula (I-int-g) [ka] As illustrated in scheme 2c, the compound of formula (I-int-g) is an intermediate of formula (I-int-f), of formula HN(R 1a )(R 1b It can be prepared by the reaction of ) with an amine, R 1a and R 1b This is disclosed elsewhere in this specification. In some embodiments, the amide of formula (I-int-c) is carried out in the presence of a coupling reagent (e.g., TBTU, DCC, DIC, EDC HCl, etc.). In some embodiments, the amide of formula (I-int-c) is carried out in the presence of a base. In some embodiments, the base is an organic base. In some embodiments, the base is TEA, DIPEA, etc.

[0402] Scheme 2d: R to compound of formula (I-int-g) 2 Coupling [ka] As illustrated in Scheme 2d, the compound of formula (I) is involved in a cross-coupling reaction (e.g., Suzuki or Still) of formula (I-int-g) (where X H B represents an intermediate of a suitable halogen atom (e.g., -Cl, -Br, etc.) or a similar reactive group. a -R 2 (Here, B aIt can be prepared by reaction with an intermediate of a suitable reactive moiety, such as a boronic acid or boronic acid ester (e.g., pinacol boronic acid ester) or a tributylstannyl group. In some embodiments, R 2 This is defined elsewhere in this specification. In this embodiment, c is CR 3 And R 3 This is as defined elsewhere in this specification. In some embodiments, Suzuki coupling is performed using a palladium or similar transition metal catalyst with a suitable ligand, according to methods described in the literature and known to those skilled in the art.

[0403] Scheme 3 Scheme 3a: Preparation of the compound of formula (I-int-h) [ka] In some embodiments, methods for producing compounds of formula (I-int-h) are provided. In some embodiments, formula (I-int-h) is prepared by carrying out a SNAr reaction using ethyl glycinate (e.g., HCl salt of ethyl glycinate) and ethyl 5-chloro-4-nitro-4,5-dihydrothiophene-2-carboxylate. In some embodiments, the compounds of formula (I-int-h) are prepared in the presence of a base (e.g., potassium carbonate).

[0404] Scheme 3b: Cyclization to provide a compound of formula (I-int-i) [ka] In some embodiments, the compound of formula (I-int-i) is prepared by reducing the nitro group of formula (I-int-h) under appropriate reducing conditions. In some embodiments, the compound of formula (I-int-h) is reduced using Fe and AcOH.

[0405] Scheme 3c: Oxidation for providing a compound of formula (I-int-j) [ka] In some embodiments, the compound of formula (I-int-j) is prepared by oxidizing the compound of formula (I-int-j) under appropriate oxidation conditions. In some embodiments, the compound of formula (I-int-i) is oxidized in the presence of manganese dioxide.

[0406] Scheme 3d: Halogenation for providing a compound of formula (I-int-l) [ka] In some embodiments, the compound of formula (I-int-k) is prepared by halogenating the compound of formula (I-int-j). In some embodiments, the compound of formula (I-int-j) is halogenated in the presence of a halogenating agent (e.g., phenylphosphonic acid dichloride). In some embodiments, the compound of formula (I-int-k) may be represented by the compound of formula (I-int-a).

[0407] As will be recognized by those skilled in the art, compounds of formula I-int-k are also compounds of formula (I-int-a). Therefore, compounds of formula (I) can be prepared using one or more steps shown in formula (I-int-a) of the intermediate compound (e.g., one or more steps of scheme 1.1 and / or scheme 1.2). For example, in some embodiments, compounds of formula (I-int-k) or (I-int-k.1) can be saponified using conditions disclosed elsewhere in this specification to provide compounds of formula (I-int-l) or (I-int-l.1), respectively. In some embodiments, these compounds are subsequently saponified using conditions disclosed elsewhere in this specification. 2 When coupled, it can provide a compound of formula (I).

[0408] Scheme 4 Scheme 4a: R to 3,6-dihalo-picolinonitrile 2 Coupling In some embodiments, as shown below, the compound of formula (I-int-m) cross-couples 3,6-dichloropicolinonitrile with B in a cross-coupling reaction (e.g., Suzuki). a -R 2 (Here, B a The reaction is prepared by coupling with an intermediate of a suitable reactive moiety, for example, a boronic acid or boronic acid ester (e.g., pinacol boronic acid). In some embodiments, the Suzuki coupling is carried out using a palladium or similar transition metal catalyst with a suitable ligand, according to methods described in the literature and known to those skilled in the art. [ka]

[0409] Scheme 4b: Cyclization In some embodiments, the compound of formula (I-int-n) is, for example, ethyl acetate 2-mercapto(or C) 1~6 It is prepared by cyclizing the compound of formula (I-int-m) using mercaptoacetate. [ka]

[0410] Scheme 4c: Saponification [ka] In some embodiments, a compound of formula (I-int-n) may be saponified using conditions disclosed elsewhere in this specification to provide a compound of formula (I-int-o). As will be recognized by those skilled in the art, a compound of formula I-int-n is also a compound corresponding to formula (I-int-b.2). Therefore, a compound of formula (I) may be prepared using one or more steps shown in formula (I-int-b.2) of the intermediate compound (e.g., one or more steps in scheme 1.2). In some embodiments, a compound of formula (I-int-o) is prepared by saponifying a compound of formula (I-int-n). In some embodiments, a compound of formula (I-int-n) is saponified in the presence of a strong base (e.g., NaOH).

[0411] Scheme 4d: Amide formation for providing the compound of formula (I) [ka] In some embodiments, a compound of formula (I-int-o) (for example, of formula (I-int-c.2)) is then used under the conditions disclosed elsewhere in this specification to obtain HN(R 1a )(R 1b ) can be coupled to provide a compound of formula (I). In some embodiments, the preparation of the amide of formula (I) is carried out in the presence of a coupling reagent (e.g., TBTU, DCC, DIC, EDC HCl, etc.). In some embodiments, amide formation is carried out in the presence of a base. In some embodiments, the base is an organic base. In some embodiments, the base is TEA, DIPEA, etc. [Examples]

[0412] This section provides specific examples of compounds of formula I and methods for producing them.

[0413] [Table 1]

[0414] [Table 2]

[0415] [Table 3]

[0416] Section 1: Intermediates This section provides the synthesis of various intermediates used to prepare the compound of formula (I). Unless otherwise noted, all starting materials are commercially available from Fisher Scientific or similar vendors, or are known in the art and can be synthesized using known procedures employing ordinary techniques.

[0417] Intermediate 1: 2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-pyrazolo[3,4-b]pyridine [ka] Step 1: 5-Bromo-2-methyl-2H-pyrazolo[3,4-b]pyridine. NaHMDS (379 mL, 379 mmol) was added at 0°C to a mixture of 5-bromo-2H-pyrazolo[3,4-b]pyridine (50.0 g, 252 mmol) in THF (1600 mL). After stirring for 0.5 hours, MeI (47.4 mL, 757 mmol) was added at 0°C. The mixture was warmed to 25°C and stirred for 4 hours. The reaction mixture was quenched with H2O (300 mL) at 0°C, diluted with H2O (200 mL), extracted with siRNA (3 × 150 mL), washed with brine (150 mL), dried over Na2SO4, filtered, and concentrated under vacuum. A crude mixture of isomers was absorbed onto a silica gel plug and purified by column chromatography using a Redi-Sep packed silica gel column (12 g) eluting with a gradient of 0% to 70% siRNA in pet.ether to obtain 5-bromo-2-methyl-2H-pyrazolo[3,4-b]pyridine (8.00 g, 37.7 mmol, yield 74.7%) as a yellow solid. m / z(ESI): 212.0(M+H) + . 1 H NMR(400MHz,DMSO-d6)δ 8.59(d,J=2.38Hz,1H),8.42(s,1H)8.51(d,J=2.38Hz,1H),4.21(s,3H).

[0418] Step 2: 2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-pyrazolo[3,4-b]pyridine. 5-bromo-2-methyl-2H-pyrazolo[3,4-b]pyridine (20.0 g, 94 mmol) was dissolved in 1,4-dioxane (300 mL) and KOAc (13.86 g, 141 mmol), B2pin2 (28.7 g, 113 mmol), and Pd(dppf)Cl2-DCM adduct (3.85 g, 4.72 mmol) were added. The mixture was stirred at 100°C for 12 hours under an N2 atmosphere. The mixture was filtered through a Celite plug, and the filtrate was concentrated under vacuum. The reaction mixture was diluted with siRNA (50 mL) / pet. ether (300 mL) and stirred at 20°C for 15 minutes. The mixture was filtered, and the filter cake was washed with PET ether (3 × 300 mL). The filtrate was concentrated under vacuum, and the solid was further dried under reduced pressure to obtain intermediate 1 (24.0 g, 93 mmol, 98% yield) as a black solid. m / z(ESI): 178.1 (M-pinacol + 2OH) + . 1 H NMR(400MHz,DMSO-d6)δ 8.72(d,J=1.75Hz,1H),8.53(d,J=1.75Hz,1H),8.47(s,1H),4.21(s,3H),1.32(s,12H).

[0419] Intermediate 2: 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-[1,2,3]triazolo[4,5-b]pyridine [ka] Step 1: 6-Bromo-2H-[1,2,3]triazolo[4,5-b]pyridine. 5-Bromo-2,3-dihydropyridine-2,3-diamine (10.0 g, 52.6 mmol) was added to a solution of 1NH2SO4 (150 mL) in H2O (500 mL). The mixture was cooled to 0°C, and NaNO2 (4.25 g, 61.6 mmol) was added to H2O (120 mL). The mixture was then stirred at 25°C for 12 hours under an N2 atmosphere. The reaction mixture was poured into H2O (80 mL), extracted with 2Me-THF (3 × 60 mL), washed with brine (50 mL), dried over Na2SO4, filtered, and concentrated under vacuum to obtain the residue. The resulting residue was stirred in MTBE (50 mL) at 25°C for 0.5 hours. The suspension was filtered, and the filter cake was dried under reduced pressure to obtain 6-bromo-2H-[1,2,3]triazolo[4,5-b]pyridine (8.00 g, 40.2 mmol, 76% yield) as a brown solid. m / z(ESI): 198.9(M+H) + . 1 H NMR(400MHz,DMSO-d6)δ 8.78-8.79(m,2H).

[0420] Step 2: 6-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-[1,2,3]triazolo[4,5-b]pyridine. NaH (0.181 g, 7.54 mmol) was added to a solution of 6-bromo-1H-[1,2,3]triazolo[4,5-b]pyridine (1.000 g, 5.02 mmol) in THF (10 mL) at 0°C. The mixture was stirred at 0°C for 30 minutes. Then, (2-ethoxyethyl)trimethylsilyl chloride (1.103 g, 6.62 mmol) was added dropwise at 0°C, and stirring was continued for 1 hour. The reaction mixture was diluted with H2O (40 mL) and sat.NH4Cl solution (30 mL), extracted with HCl (3 × 30 mL), washed with brine (30 mL), dried over Na2SO4, filtered, and the filtrate was concentrated under vacuum. The crude substance was adsorbed onto a silica gel plug and purified by column chromatography using a SEPAFLASH® packed silica gel column (40 g) eluting with a gradient of 0% to 55% HCl in pet ether to obtain 6-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-[1,2,3]triazolo[4,5-b]pyridine (650 mg, 1.97 mmol, yield 39%) as oil. m / z(ESI): 328.9(M+H) + . 1 H NMR(400MHz,DMSO-d6)δ 9.02(d,J=2.0Hz,1H),8.92(d,J=2.0Hz,1H),6.04(s,2H),3.67(t,J=8.0Hz,2H),0.84(t,J=8.0Hz,2H),-0.11(s,9H).

[0421] Step 3: 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-[1,2,3]triazolo[4,5-b]pyridine. KOAc (44.7 mg, 0.456 mmol) and Pd(dppf)Cl2-DCM adduct (12.6 mg, 0.015 mmol) were added to a solution of 6-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-[1,2,3]triazolo[4,5-b]pyridine (100 mg, 0.304 mmol) in 1,4-dioxane (1 mL). The mixture was degassed with N2 and stirred at 80°C for 12 hours. The solvent was removed under vacuum, and the resulting crude boronic acid ester was used without further purification. m / z(ESI): 377.1(M+H) + .

[0422] Intermediate 3: 2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-[1,2,3]triazolo[4,5-b]pyridine [ka] Step 1: 6-bromo-2-methyl-2H-[1,2,3]triazolo[4,5-b]pyridine. 6-bromo-2-methyl-2H-[1,2,3]triazolo[4,5-b]pyridine was prepared according to the literature procedure (Journal of Organic Chemistry (2018), 83(12), 6334-6353).

[0423] Step 2: 2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-[1,2,3]triazolo[4,5-b]pyridine 6-bromo-2-methyl-2H-[1,2,3]triazolo[4,5-b]pyridine (1.50 g, 7.04 mmol) was dissolved in 1,4-dioxane (5 mL) and B2Pin2 (3.580 g, 14.08 mmol), KOAc (1.175 g, 11.97 mmol), and Pd(dppf)Cl2·DCM (0.575 g, 0.704 mmol) were added. The mixture was stirred at 110 °C for 12 hours. The reaction mixture was diluted with H2O (20 mL) and extracted with ELISA (3 × 10 mL). The combined organic layers were washed with brine (15 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure to obtain the residue. The residue was purified by column chromatography (SiO2, Pet ether / siRNA = 5 / 1~3 / 1) to obtain intermediate 3 as a yellow solid (1.60 g, 6.15 mmol, yield 87%). m / z(ESI): 261.0(M+H) +

[0424] Section 2 - General Procedure Group 1 Example 1-1: (3-methyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)-1-benzothiophen-2-yl)(4-morpholinyl)methanone A2 [ka] Step 1: (6-chloro-3-methylbenzo[b]thiophen-2-yl)(morpholino)methanone. This was performed on a stirred mixture of 6-chloro-3-methylbenzo[b]thiophen-2-carboxylic acid (400 mg, 1.77 mmol) and TBTU (850 mg, 2.65 mmol) in DMF (30 mL). The resulting solution was cooled to 0°C, and morpholine (184 mg, 2.12 mmol) and DIPEA (1.54 mL, 8.82 mmol) were added. The resulting mixture was stirred at 0°C for 1 hour. The reaction mixture was poured into H2O (40 mL). The mixture was then extracted with siRNA (3 × 30 mL). The combined organic layers were washed with brine (30 mL), dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure to obtain the residue. The residue was purified by column chromatography (40 g SiO2, eluent 0-28% siRNA / PET ether, flow rate 80 mL / min) to obtain the residue. (6-chloro-3-methylbenzo[b]thiophene-2-yl)(morpholino)methanone (500 mg, 1.690 mmol, yield 96%) was obtained as a white solid. 1 H NMR(400MHz,DMSO-d6)δ 8.17(d,J=1.6Hz,1H),7.84(d,J=8.4Hz,1H),7.48(dd,J=1.6,8.4Hz,1H),3.45-3.65(m,8H),2.36(s,3H).

[0425] Step 2: (3-methyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)benzo[b]thiophene-2-yl)(morpholino)methanone. A mixture of 2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-pyrazolo[3,4-b]pyridine (210 mg, 0.811 mmol), (6-chloro-3-methylbenzo[b]thiophene-2-yl)(morpholino)methanone (120 mg, 0.406 mmol), K3PO4 (172 mg, 0.811 mmol), and Pd(dppf)Cl2 (33.1 mg, 0.041 mmol) in THF (1 mL) and H2O (0.2 mL) was degassed three times with N2. The mixture was stirred at 80°C for 12 hours under an N2 atmosphere. The mixture was poured into H2O (20 ml). Subsequently, the mixture was extracted with siRNA (6 × 20 mL), the organic layer was washed with brine (30 mL), dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure. The residue was initially purified by flash silica gel chromatography (12 g SEPAFLASH® Silica Flash Column, eluent 0-60% siRNA / PET ether, flow rate 60 mL / min). The residue was further purified by preparative HPLC. Compound A2 (27.9 mg, 0.071 mmol, yield 18%) was obtained as a white solid. m / z (ESI): 393.1 (M + H) + . 1 H NMR(400MHz,DMSO-d6)δ 9.00(d,J=2.4Hz,1H),8.53(d,J=2.4Hz,1H),8.50(s,1H),8.41(d,J=1.6Hz,1H ),7.93(s,1H),7.86(d,J=6.1Hz,1H),4.235(s,3H),3.63-3.55(m,8H),2.55(br sJ=,3H)

[0426] The compounds in Table 1-1 were prepared according to the procedure described in Group A.1.

[0427] [Table 4]

[0428] Group 2 Example 2-1: (4,4-difluoro-1-piperidinyl)(3-methyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)-1-benzothiophen-2-yl)methanone A3 [ka] Step 1: 3-methyl-6-(2-methyl-2H-indazole-5-yl)benzo[b]thiophene-2-carboxylic acid. 3-methyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)benzo[b]thiophene-2-carboxylate ethyl (50 mg, 0.142 mmol) was added to a solution of tetrahydrofuran (1 mL), water (0.2 mL), and ethanol (0.1 mL) with LiOH·H2O (17.0 mg, 0.711 mmol) at 20°C. The mixture was stirred at 20°C for 12 hours. The reaction mixture was concentrated under reduced pressure. The resulting mixture was acidified to pH 2 with 0.1 N HCl. The aqueous phase was extracted with ELISA (3 × 10 mL). The combined organic matter was dried over MgSO4 and concentrated to obtain the product as a gray solid (40 mg, 0.124 mmol, yield 87%). 1 H NMR(400MHz,DMSO-d6)δ 8.98(d,J=1.9Hz,1H),8.44--8.52(m,2H),8.17(s,1H),7.66--7.80(m,2H),4.23(s,3H),2.67(s,3H).

[0429] Step 2: (4,4-difluoropiperidine-1-yl)(3-methyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)benzo[b]thiophene-2-yl)methanone. HATU (882 mg, 2.32 mmol) and DIPEA (0.405 mL, 2.32 mmol) were added to a solution of 3-methyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)benzo[b]thiophene-2-carboxylic acid (150 mg, 0.464 mmol) in DMF (2 mL) at 0°C. The mixture was stirred at 0°C for 2 min. Then, 4,4-difluoropiperidine (56.2 mg, 0.464 mmol) was added to the mixture. The mixture was stirred at 20°C for another hour. The reaction mixture was diluted with H2O (20 mL). The mixture was extracted with RINKAN (6 × 20 mL). The combined organic layer was washed with brine (30 mL), dried over Na₂SO₄, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by preparative HPLC (column: Waters Xbridge BEH C18 100 × 30 mm × 10 μm, mobile phase: [H₂O (10 mM NH₄HCO₃)-ACN], B%: 40%~80%, 8 min). Compound A3 (59.1 mg, 0.139 mmol, yield 30%) was obtained as a white solid. m / z (ESI): 427.2 (M + H) + , 1 H NMR(400MHz,DMSO-d6)δ 9.01(d,J=2.4Hz,1H),8.57(m,1H),8.55(s,1H),8.54(s,1H),7.97(d,J=4Hz,1H),7.94(s,1H),4.24(s,3H),3.67(br s,4H),2.42(s,3H),2.06(br s,4H). 19 F NMR(376MHz,DMSO-d6)δ -96.0(s,2F).

[0430] The compounds in Table 2-1 were prepared according to the procedure described in Group 2.

[0431] [Table 5]

[0432] [Table 6]

[0433] Group 3 Example 3-1: (3-amino-4-cyclobutyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)(4,4-difluoro-1-piperidinyl)methanone B4 [ka] Step 1: 4-Cyclobutyl-6-hydroxy-2-mercaptonicotinonitrile. To a solution of ethyl 3-cyclobutyl-3-oxopropionate (10.00 g, 58.75 mmol) in MeOH (100 mL), KOH (4.94 g, 88.1 mmol) and 2-cyanothioacetamide (8.83 g, 88.1 mmol) were added. The mixture was stirred at 60°C for 12 hours. The mixture was cooled to room temperature, and the product was collected by filtration. The solid was macerated with ELISA at 20°C for 30 min. The solid was collected and dried under reduced pressure. The crude product was used in the next step without further purification. 4-Cyclobutyl-6-hydroxy-2-mercaptonicotinonitrile (10.50 g, 49.38 mmol, yield 84%) was obtained as a white solid. 207.0(M+H) + . 1 H NMR(400MHz,DMSO-d6)δ 10.34-10.58(m,1H),5.36-5.44(m,1H),3.22-3.30(m,1H),2.17-2.26(m,2H),1.98-1.85(m,3H),1.67-1.76(m,1H).

[0434] Step 2: 3-amino-4-cyclobutyl-6-hydroxythieno[2,3-b]pyridine-2-carboxylate ethyl. 2-bromoethyl acetate (891 mg, 5.33 mmol, 0.590 mL) and NaOEt (990 mg, 14.54 mmol) were added to a solution of 4-cyclobutyl-6-hydroxy-2-sulfanylpyridine-3-carbonitride (1.00 g, 4.85 mmol) in EtOH (10 mL). The reaction mixture was stirred at 80°C for 2 hours. The reaction mixture was diluted with H2O (500 mL). The mixture was extracted with siRNA (3 × 300 mL). The combined organic layer was washed with brine (200 mL), dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure. The crude product was macerated with MTBE at 20°C for 20 min, and the solid was dried under reduced pressure. Ethyl 3-amino-4-cyclobutyl-6-hydroxythieno[2,3-b]pyridine-2-carboxylate (1.00 g, 3.18 mmol, 66% yield) was obtained as a white solid. m / z(ESI): 293.1(M+H) + . 1 H NMR(400MHz,DMSO-d6)δ 6.47(br s,2H),5.93(s,1H),4.13(q,J=7.1Hz,2H),3.88(br t,J=8.2Hz,1H),2.23-2.37(m,2H),1.88-2.06(m,3H),1.75(br d,J=8.4Hz,1H),1.22(t,J=7.1Hz,3H)

[0435] Step 3: 3-amino-4-cyclobutyl-6-(trifluoromethylsulfonyloxy)thieno[2,3-b]pyridine-2-carboxylate ethyl. 3-amino-4-cyclobutyl-6-hydroxythieno[2,3-b]pyridine-2-carboxylate ethyl (9.00 g, 30.8 mmol) was dissolved in DCM (100 mL) and DIPEA (7.96 g, 61.6 mmol, 10.72 mL) was added. The mixture was cooled to -78°C. Subsequently, Tf2O (9.55 g, 33.9 mmol, 5.59 mL) was added under N2 conditions at -78°C. The mixture was stirred at -78°C for 1 hour. The reaction mixture was diluted with H2O (500 mL) and allowed to reach room temperature. The mixture was extracted with ELISA (3 × 400 mL). The combined organic layers were washed with brine (300 mL), dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure. The residue was macerated with MTBE at 20°C for 20 min, and the solid was dried under reduced pressure. The residue was purified by flash silica gel chromatography (40 g SEPAFLASH® Silica Flash Column, eluent 0-15% siRNA / PET ether gradient, flow rate 100 mL / min). Ethyl 3-amino-4-cyclobutyl-6-(trifluoromethylsulfonyloxy)thieno[2,3-b]pyridine-2-carboxylate was obtained as a yellow solid. m / z(ESI): 425.0(M+H) + . 1 H NMR(400MHz,DMSO-d6)δ 7.45(s,1H),6.90(br s,2H),4.39(quin,J=8.4Hz,1H),4.29(q,J=7.0Hz,2H),2.41-2.48(m,2H),2.26( dt,J=2.3,9.0Hz,2H),2.00-2.13(m,1H),1.77-1.89(m,1H),1.29(t,J=7.1Hz,3H)

[0436] Step 4: 3-amino-4-cyclobutyl-6-(2-methylpyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-carboxylate ethyl. 3-amino-4-cyclobutyl-6-(trifluoromethylsulfonyloxy)thieno[2,3-b]pyridin-2-carboxylate ethyl (3.20 g, 7.54 mmol) and (2-methylpyrazolo[3,4-b]pyridin-5-yl)boronic acid (1.60 g, 9.05 mmol) were mixed in dioxane (30 mL) and H2O (6 mL). Pd(PPh3)4 (436 mg, 0.38 mmol) and K2CO3 (2.08 g, 15.08 mmol) were added under N2 conditions. The reaction mixture was stirred at 60°C for 12 hours and then diluted with H2O (200 mL). The mixture was extracted with ethyl acetate (3 × 300 mL). The combined organic layer was washed with brine (100 mL), dried over Na₂SO₄, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by flash silica gel chromatography (40 g SEPAFLASH® Silica Flash Column, eluent 0-100% ethyl acetate / pet ether gradient, flow rate 120 mL / min). Ethyl 3-amino-4-cyclobutyl-6-(2-methylpyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-carboxylate (2.00 g, 4.91 mmol, yield 65%) was obtained as a yellow solid. m / z(ESI): 408.1(M+H) + . 1 H NMR(400MHz,DMSO-d6)δ 9.42(d,J=2.3Hz,1H),9.05(d,J=2.3Hz,1H),8.57(s,1H),7.91(s,1H),6.86(s,2H),4.41-4.34(m,1H),4.2 7-4.32(m,2H),4.25(s,3H),2.35-2.47(m,4H),2.17-2.03(m,1H),1.83-1.94(m,1H),1.31(t,J=7.1Hz,3H).

[0437] Step 5: (3-amino-4-cyclobutyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyridine-2-yl)(4,4-difluoropiperidine-1-yl)methanone. A solution of ethyl 3-amino-4-cyclobutyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyridine-2-carboxylate (0.064 g, 0.157 mmol) and LiOH·H2O (0.066 g, 1.57 mmol) in THF (1 mL), H2O (0.5 mL), and MeOH (2 mL) was stirred at 60°C for 2 hours. The reaction mixture was concentrated under reduced pressure. The residue was taken in DMF (1 mL) and treated with 4,4-difluoropiperidine (0.029 g, 0.029 mL, 0.236 mmol), TBTU (0.076 g, 0.236 mmol), and TEA (0.064 g, 0.088 mL, 0.628 mmol). The resulting solution was stirred at RT for 5 hours, concentrated, and the residue was purified by automated flash chromatography using 0-10% MeOH in DCM (eluting the product at 4%) to obtain compound B4 (0.033 g, 0.068 mmol, yield: 44%). m / z(ESI): 483.1(M+H) + . 1 H NMR(400MHz,chloroform-d)δ 9.41(d,J=2.07Hz,1H)8.73(d,J=2.28Hz,1H)8.01(s,1H)7.65(s,1H)5.94(br s,2H)4.30(s,3H)4.19(t,J=8.40Hz,1H)3.85-3.93(m,4H)2.37-2.58(m,4H)1.97-2.23(m,6H). 19 F NMR (376 MHz, chloroform-d) δ -97.39 (s, 2F).

[0438] The compounds in Table 3-1 were prepared according to the procedure described for Group 3.

[0439] [Table 7]

[0440] [Table 8]

[0441] Group 4 Example 4-1: (5-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)(1-piperidinyl)methanone B16 [ka] Step 1: (5-bromothieno[2,3-b]pyridine-2-yl)(piperidine-1-yl)methanone. A mixture of 5-bromothieno[2,3-b]pyridine-2-carboxylic acid (258 mg, 1.00 mmol), TEA (303 mg, 0.421 mL, 3.00 mmol), and TBTU (353 mg, 1.10 mmol) in DMF (5 mL) was treated with piperidine (85 mg, 0.099 mL, 1.00 mmol). The reaction mixture was stirred at 25°C for 18 hours. The reaction mixture was diluted with H2O (5 mL). The resulting precipitate was collected by filtration, washed with H2O, and dried to obtain (5-bromothieno[2,3-b]pyridine-2-yl)(piperidine-1-yl)methanone (175.8 mg, 0.541 mmol, yield 54%) as a yellowish-brown solid. m / z(ESI):325.0 / 327.0(1:1)(M+H) + . 1 H NMR(400MHz,DMSO-d6)δ 8.74(d,J=2.1Hz,1H),8.61(d,J=2.3Hz,1H),7.62(s,1H),3.57-3.68(m,4H),1.63-1.72(m,2H),1.59(br d,J=4.8Hz,4H)

[0442] Step 2: (5-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyridine-2-yl)(1-piperidinyl)methanone. The vial was filled with (5-bromothieno[2,3-b]pyridine-2-yl)(piperidinyl)methanone (84 mg, 0.258 mmol), (2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)boronic acid (68.6 mg, 0.387 mmol), anhydrous K2CO3 (107 mg, 0.775 mmol), Pd(dppf)Cl2 (18.90 mg, 0.026 mmol), and 1,4-dioxane (1.2 mL) / H2O (0.3 mL). The vial was capped and stirred at 90°C for 1.5 hours. The reaction mixture was concentrated under reduced pressure, absorbed onto silica gel, and purified by chromatography using a Redi-Sep packed silica gel column (12 g) eluting with a gradient of 0% to 10% MeOH in DCM. Compound B16 (65.8 mg, 0.174 mmol, yield 68%) was obtained as a white solid. m / z(ESI): 378.0(M+H) + . 1 H NMR(400MHz,DMSO-d6)δ 9.03(d,J=2.3Hz,1H),9.01(d,J=2.5Hz,1H),8.68(d,J=2.3Hz,1H),8.61(d,J= 2.3Hz,1H),8.54(s,1H),7.71(s,1H),4.26(s,3H),3.62-3.70(m,4H),1.68(br d,J=5.4Hz,2H),1.54-1.64(m,4H)

[0443] Example 4-2: (4-Cyclopropyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)((3S)-3-methyl-4-morpholinyl)methanone B17S [ka] Step 1: 6-Chloro-4-cyclopropylthieno[2,3-b]pyridine. 4,6-dichlorothieno[2,3-b]pyridine (1.50 g, 7.35 mmol) and PEPPSI-iPr catalyst (0.501 g, 0.735 mmol) were stirred in 5 mL of THF at 0°C. A 0.5 M THF solution of cyclopropyl zinc(II) bromide (22 mL, 11 mmol) was added dropwise. The reaction mixture was stirred at 0°C for 30 min. The reaction mixture was diluted with saturated ammonium chloride solution and extracted with toluene (25 mL). The organic phase was concentrated, and the residue was purified by chromatography using a Redi-Sep packed silica gel column with 0-40% toluene in heptane to obtain 6-chloro-4-cyclopropylthieno[2,3-b]pyridine (0.571 g, 2.72 mmol, yield 37%). m / z(ESI):210.1(M+H) + . 1 ¹H NMR (400MHz, chloroform-d)δ: 7.68 (d, J=8.0Hz, 1H), 7.59 (d, J=8.0Hz, 1H), 6.81 (s, 1H), 2.30 (dt, J=5.0, 8.4Hz, 1H), 1.15-1.29 (m, 2H), 0.89-1.01 (m, 2H).

[0444] Step 2: 6-Chloro-4-cyclopropylthieno[2,3-b]pyridine-2-carboxylic acid. 6-Chloro-4-cyclopropylthieno[2,3-b]pyridine (0.57 g, 2.72 mmol) and tetrahydrofuran (3 mL) were added to a 50 mL pressure-relieving vial. The resulting solution was flushed with N2 and cooled to -78°C. A 2.5 M hexane (1.305 mL, 3.26 mmol) solution of n-butyllithium was added dropwise. The resulting mixture was stirred at -78°C for 5 minutes under an N2 atmosphere. Solid carbon dioxide (2.393 g, 54.4 mmol) was packed into a separate 50 mL pressure-relieving vial equipped with a cannula. The cannula was connected to the reaction vial, and the reaction mixture was foamed at -78°C for 20 minutes with the released CO2 gas. The reaction mixture was sparged with N2 for 5 minutes to flush out any dissolved CO2, and then warmed to 23°C for 30 minutes while sparging with N2. The reaction mixture was then quenched by the slow addition of sat. aq. NH4Cl (5 mL) and transferred to a separatory funnel containing Depositphotos (30 mL), H2O (10 mL), and 1N aq. HCl (10 mL). The aqueous layer was extracted with Depositphotos (30 mL), the combined organic matter was dried, and the residue was purified by automated flash column chromatography using 0-100% Depositphotos / EtOH (3:1) in heptane to obtain 6-chloro-4-cyclopropylthieno[2,3-b]pyridine-2-carboxylic acid (0.421 g, 1.659 mmol, yield: 61%) as a white solid. m / z(ESI): 254.1(M+H) + .

[0445] Step 3: (S)-(6-chloro-4-cyclopropylthieno[2,3-b]pyridine-2-yl)(3-methylmorpholino)methanone. A mixture of 6-chloro-4-cyclopropylthieno[2,3-b]pyridine-2-carboxylic acid (0.070 g, 0.276 mmol), (S)-3-methylmorpholine (0.033 g, 0.033 mL, 0.331 mmol), chloro-N,N,N',N'-tetramethylformamidinium hexafluorophosphate (0.093 g, 0.331 mmol), and 1-methylimidazole (0.068 g, 0.066 mL, 0.828 mmol) in ACN (1 mL) was stirred at rt for 12 hours. The reaction mixture was diluted with H2O (10 mL) and extracted with ELISA. The organic matter was concentrated to obtain crude (S)-(6-chloro-4-cyclopropylthieno[2,3-b]pyridine-2-yl)(3-methylmorpholino)methanone. m / z(ESI): 337.2(M+H) + .

[0446] Step 4: (S)-(4-cyclopropyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyridine-2-yl)(3-methylmorpholino)methanone. Crude (S)-(6-chloro-4-cyclopropylthieno[2,3-b]pyridine-2-yl)(3-methylmorpholino)methanone was dissolved in dioxane (3 mL) and H2O (1 mL) in a microwave vial and treated with [2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl]boronic acid (0.073 g, 0.414 mmol). Solid Pd(dppf)Cl2 (0.040 g, 0.055 mmol) and K2CO3 (0.114 g, 0.828 mmol) were added. The vial was sparged with argon, capped, and heated in a microwave oven at 110°C for 30 minutes. The reaction mixture was concentrated under reduced pressure, and the residue was purified by automated flash column chromatography using 0-100% siRNA / EtOH (3:1) in heptane to obtain compound B17S (0.082 g, 0.189 mmol, yield: 69%). m / z(ESI): 434.1(M+H) + . 1¹H NMR (400MHz, chloroform-d) δ 9.35 (d, J=2.30Hz, 1H) 8.71 (d, J=2.09Hz, 1H) 8.01 (s, 1H) 7.72 (s, 1H) 7.31 (s, 1H) 4.54 (br d,J=5.85Hz,1H)4.29(s,3H)4.15-4.24(m,1H)3.97(dd,J=11.50,3.34Hz,1H)3.68-3.78(m,2H)3.4 4-3.63(m,2H)2.33(tt,J=8.44,5.15Hz,1H)1.47-1.50(m,2H)1.19-1.32(m,3H)0.96-1.08(m,2H).

[0447] Alternative conditions for Group 4 (1) Instead of Pd(dppf)Cl2 and K2CO3, 0.2 equiv. cataCXium Pd G3 and K3PO4 were used as catalyst and base. Instead of 1,4-dioxane / H2O, toluene / H2O was used as the solvent.

[0448] (2) Instead of Pd(dppf)Cl2 and K2CO3, 5 mol% Pd(PPh3)4 and Na2CO3 were used as catalyst and base.

[0449] (3) Styl-cross coupling: 3-methyl-6-(tributylstannyl)pyrimidine-4(3H)-one (413 mg, 1.035 mmol) and Pd(PPh3)4 (100 mg, 0.086 mmol) were added to a stirred solution (1 equiv.) of the product from step 1 in 1,4-dioxane (1 mL). The mixture was stirred at 120°C for 12 hours under an N2 atmosphere. The reaction mixture was quenched by adding H2O (20 mL), extracted with SiO (5 × 20 mL), washed with brine (15 mL), dried over Na2SO4, filtered, and concentrated under vacuum. The crude substance was absorbed onto a silica gel plug and purified by column chromatography using a SEPAFLASH® packed silica gel column (4 g) eluting with a gradient of 0% to 100% SiO in pet ether to obtain the product.

[0450] The compounds in Table 4-1 were prepared according to the procedure described in Group 4.

[0451] [Table 9]

[0452] [Table 10]

[0453] [Table 11]

[0454] [Table 12]

[0455] [Table 13]

[0456] [Table 14]

[0457] [Table 15]

[0458] [Table 16]

[0459] [Table 17]

[0460] [Table 18]

[0461] [Table 19]

[0462] [Table 20]

[0463] [Table 21]

[0464] [Table 22]

[0465] [Table 23]

[0466] [Table 24]

[0467] [Table 25]

[0468] Group 5 Example 5-1: (7-oxide-4-(2-propanyl)thieno[2,3-b]pyridin-2-yl)(1-piperidinyl)methanone B7 [ka] Step 1: 4-Isopropyl-2-(methoxycarbonyl)thieno[2,3-b]pyridine. A round-bottom flask was packed with methyl 4-iodothieno[2,3-b]pyridine-2-carboxylate (0.500 g, 1.567 mmol), Pd(OAc)2 (0.018 g, 0.078 mmol), and 2'-(dicyclohexylphosphin)-N2,N2,N6,N6-tetramethyl-[1,1'-biphenyl]-2,6-diamine (0.068 g, 0.157 mmol). The flask was vacuumed three times and repacked with N2. THF (8 mL) was introduced under nitrogen. The mixture was cooled in an ice bath. 0.5 M tetrahydrofuran solution of 2-propyl zinc bromide (3.76 mL, 1.880 mmol) was slowly added via syringe under nitrogen. Upon completion of the addition, the ice bath was removed and the mixture was stirred overnight at ambient temperature. The mixture was cooled in an ice bath and then quenched with saturated ammonium chloride (0.3 mL) followed by MeOH (0.5 mL). The resulting mixture was stirred for 5 minutes and then concentrated under reduced pressure. The residue was loaded onto a silica gel pre-column (25 g) with MeOH / DCM and subjected to automated flash column chromatography using a 40-g REDISEP GOLD® column eluting with (MeOH / DCM, 11 min, 0-9%) to obtain methyl 4-isopropylthieno[2,3-b]pyridine-2-carboxylate (400 mg, 1.70 mmol, crude yield 108%) as a colorless oil. m / z(ESI):236.20(M+1) + . 1 H NMR (chloroform-d,400MHz)δ 8.50(d,1H,J=5.6Hz),8.27(d,1H,J=0.8Hz),7.62(dd,1H,J=0.8,5.6Hz),3.98(s,3H),3.6-3.7(m,1H),1.43(d,6H,J=6.9Hz).

[0469] Step 2: 4-Isopropyl-2-(methoxycarbonyl)thieno[2,3-b]pyridine-7-oxide. 3-chloroperoxybenzoic acid (277 mg, 1.606 mmol) was added as a solid all at once to a stirred solution of methyl 4-isopropylthieno[2,3-b]pyridine-2-carboxylate (270 mg, 1.147 mmol) in DCM (8 mL). The resulting mixture was stirred at ambient temperature for 48 hours. The DCM solution was directly loaded onto a silica gel pre-column (25 g) and subjected to automated flash column chromatography using a 40 g REDISEP GOLD® column, eluting for (Â / EtOH, 3 / 1.v / v) / heptane (1 min at 0%, 12 min at 0-60%, 2 min at 60-100%, and 6 min at 100%) to obtain 4-isopropyl-2-(methoxycarbonyl)thieno[2,3-b]pyridine 7-oxide (225 mg, 0.895 mmol, yield 78%) as an off-white solid. m / z(ESI): 252.20(M+1) + . 1 ¹H NMR (chloroform - d, 400 MHz): δ 8.2-8.3 (m, 2H), 7.55 (dd, 1H, J=0.7, 7.0 Hz), 4.2-4.4 (m, 1H), 3.98 (s, 3H), 1.55 (d, 6H, J=7.1 Hz).

[0470] Step 3: (7-oxide-4-(2-propanyl)thieno[2,3-b]pyridine-2-yl)(1-piperidinyl)methanone. A mixture of 4-isopropyl-2-(methoxycarbonyl)thieno[2,3-b]pyridine 7-oxide (20 mg, 0.080 mmol), bromotripyrrolidinophosphonium hexafluorophosphate (93 mg, 0.199 mmol), piperidine (172 mg, 0.20 mL, 2.020 mmol), and DIPEA (148 mg, 0.20 mL, 1.145 mmol) in THF (2 mL) in a 5 mL microwave reaction vessel was irradiated (15 h, 100 °C). The crude mixture was directly loaded onto a silica gel pre-column (25g) and subjected to automated flash column chromatography using a 24-g REDISEP GOLD® column eluted with MeOH / DCM (1 min at 0% and 11 min at 0-20%) to obtain an impure product. This was dissolved in MeOH and subjected to preparative reverse-phase HPLC (Gemini® Prep C18 10μm column, Phenomenex, Torrance, CA, gradient elution of 10-95% MeCN in H2O, both solvents containing 0.1% TFA, 15 min method for 15 min). After lyophilization, compound B7 (18 mg, 0.059 mmol, yield 74.3%) was obtained as an off-white solid. m / z(ESI): 305.0(M+H) + . 1 ¹H NMR (chloroform - d, 400 MHz): δ 8.49 (d, J=7.1 Hz, 1 H), 7.84 (d, J=7.1 Hz, 1 H), 7.79 (s, 1 H), 4.1-4.4 (m, 1 H), 3.69 (br s, 4 H), 1.60-1.80 (m, 6 H), 1.59 (d, J=6.9 Hz, 6 H).

[0471] Example 5-2: (4-Cyclopropyl-6-(2-(1-piperazinyl)-5-pyrimidinyl)thieno[2,3-b]pyridine-2-yl)(1-piperidinyl)methanone B22 [ka] A solution of 4-(5-(4-cyclopropyl-2-(piperidine-1-carbonyl)thieno[2,3-b]pyridin-6-yl)pyrimidine-2-yl)piperazine-1-carboxylate tert-butyl (63.8 mg, 0.116 mmol) in DCM (1 mL) was treated with 4N HCl solution in 1,4-dioxane (0.145 mL, 0.581 mmol). The reaction mixture was stirred at 25°C for 18 hours. The mixture was concentrated under vacuum to obtain compound B22 as a pale yellow solid, with hydrochloride salt (56.4 mg, 0.116 mmol, yield: 100%). m / z(ESI): 449.9(M+H) + . 1 H NMR(400MHz,DMSO-d6)δ 9.20(s,2H),9.17(br s,2H),7.92(s,1H),7.42(s,1H),4.03-4.10(m,4H),3.66(br d,J=5.4Hz,4H),3.21(br s,4H),2.53-2.60(m,1H),1.67(br d,J=4.4Hz,2H),1.60(br d,J=3.5Hz,4H),1.11-1.27(m,4H)

[0472] Group 6 Example 6-1: (4,4-difluoro-1-piperidinyl)(4-(1-methyl-1H-pyrazole-5-yl)-2-(2-methyl-2H-[1,2,3]triazolo[4,5-b]pyridin-6-yl)thieno[2,3-d]pyrimidine-6-yl)methanone C9 [ka] Step 1: 2-Chloro-4-(1-methyl-1H-pyrazole-5-yl)thieno[2,3-d]pyrimidine. 2,4-dichlorothieno[2,3-d]pyrimidine (300 mg, 1.463 mmol), 1-methyl-1H-pyrazole-5-boronic acid (184 mg, 1.46 mmol), potassium phosphate (621 mg, 2.93 mmol), and cataCXium A Pd G3 (53.3 mg, 0.073 mmol) were added to a 50-mL pressure-relieving vial. Then, THF (1.32 mL) and H2O (1.46 mL) were added, and the resulting mixture was gently sparged with N2 for 15 mins, and then heated to 70°C. After 16 hours, the mixture was cooled to 23°C. The mixture was concentrated to dryness. The resulting crude residue was purified by flash chromatography (0-50% in heptane, 3:1 Â:EtOH gradient) to obtain 2-chloro-4-(1-methyl-1Hpyrazole-5-yl)thieno[2,3-d]pyrimidine (138.6 mg, 0.553 mmol, yield: 38%) as an off-white solid. m / z(ESI): 250.9(M+H) + .

[0473] Step 2: 2-chloro-4-(1-methyl-1H-pyrazole-5-yl)thieno[2,3-d]pyrimidine-6-carboxylic acid. 2-chloro-4-(1-methyl-1H-pyrazole-5-yl)thieno[2,3-d]pyrimidine (138.6 mg, 0.553 mmol) and THF (5.5 mL) were added to a 50 mL pressure-relieving vial. The resulting solution was flushed with nitrogen and cooled to -78°C, and a 2.5 M hexane (0.243 mL, 0.608 mmol) solution of n-butyllithium was added dropwise. The resulting mixture was stirred at -78°C for 5 minutes under an N2 atmosphere. A separate 50 mL pressure-relieving vial was filled with CO2 solid (2.43 g, 55.3 mmol). The cannula was connected to two vials so that sublimated CO2 could bubble the reaction mixture at -78°C. After 20 mins, the cooling water bath was removed. The reaction mixture was sparged with N2 and heated to 23°C for 30 minutes, flushing out any dissolved CO2. The reaction mixture was quenched by the slow addition of sat. aq. NH4Cl (5 mL) and transferred to a separatory funnel containing siRNA (30 mL), H2O (10 mL) and 1N aq. HCl (10 mL). The aq. layer was extracted with siRNA (30 mL), the combined organic matter was dried over Na2SO4, filtered, and concentrated under vacuum to obtain 2-chloro-4-(1-methyl-1H-pyrazole-5-yl)thieno[2,3-d]pyrimidine-6-carboxylic acid (166.2 mg, 0.564 mmol, crude yield: 102%) as a black solid. m / z(ESI):294.85(M+H) + This substance was used in the next step without further purification.

[0474] Step 3: (2-chloro-4-(1-methyl-1H-pyrazole-5-yl)thieno[2,3-d]pyrimidine-6-yl)(4,4-difluoropiperidine-1-yl)methanone. 2-chloro-4-(1-methyl-1H-pyrazole-5-yl)thieno[2,3-d]pyrimidine-6-carboxylic acid (196.7 mg, 0.667 mmol), TBTU (321 mg, 1.001 mmol), and DMF (1.3 mL) were added to a 50 mL pressure-relieving vial. The resulting solution was cooled to 0°C, and 4,4-difluoropiperidine (129 mg, 0.120 mL, 1.068 mmol) and DIPEA (431 mg, 0.583 mL, 3.34 mmol) were added. The resulting mixture was stirred at 0°C. After 2 hours, the reaction mixture was transferred to a separatory funnel containing RINKAN (30 mL). The organic layer was washed with 1 M aq. LiCl (3 × 20 mL), dried over anhydrous Na₂SO₄, filtered, and concentrated to dryness. The resulting crude residue was purified by flash chromatography (0-100% RINKAN gradient in heptane) to obtain (2-chloro-4-(1-methyl-1H-pyrazole-5-yl)thieno[2,3-d]pyrimidine-6-yl)(4,4-difluoropiperidine-1-yl)methanone (133.1 mg, 0.335 mmol, yield: 50%) as a colorless foam. m / z(ESI): 398.05(M+H) + .

[0475] Step 4: (4,4-difluoropiperidine-1-yl)(4-(1-methyl-1H-pyrazole-5-yl)-2-(2-methyl-2H-[1,2,3]triazolo[4,5-b]pyridine-6-yl)thieno[2,3-d]pyrimidine-6-yl)methanone. (2-chloro-4-(1-methyl-1H-pyrazole-5-yl)thieno[2,3-d]pyrimidine-6-yl)(4,4-difluoropiperidine-1-yl)methanone (41 mg, 0.103 mmol), 2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-[1,2,3]triazolo[4,5-b]pyridine (28.1 mg, 0.108 mmol), K3PO4 (43.8 mg, 0.206 mmol), and cataCXium A Pd G3 (3.75 mg, 5.15 μmol) were added to a 10 mL pressure-relieving vial. Then, THF (0.9 mL) and H2O (0.1 mL) were added, and the resulting mixture was gently sparged with N2 for 10 mins before being heated to 70°C. After 16 hours, the mixture was cooled to 23°C and concentrated to dryness. The resulting crude residue was purified by reverse-phase preparative HPLC using a Phenomenex Luna column, 5 micron, C8(2), 100 Å, 150 × 21.2 mm (0.1% TFA / CAN in 0.1% TFA / H2O with a 10-60% gradient) to obtain compound C9 (24.9 mg, 0.041 mmol, yield: 40%) as an off-white solid after lyophilization. m / z(ESI): 496.2(M+H) + . 1 H NMR(400MHz,chloroform-d)δ 10.10(d,J=1.9Hz,1H),9.49(d,J=1.9Hz,1H),7.70-7.83(m,2H),6.92(d,J=2.1Hz,1H),4.67(s,3H),4.43(s,3H),3.92(br t,J=5.6Hz,4H),2.05-2.21(m,4H).

[0476] Alternative conditions for Group C: (1) K2HPO4 was used as the base instead of K3PO4.

[0477] (2) Instead of cataCXium A Pd G3, 5 mol% Pd(dtbf)Cl2 was used as the catalyst.

[0478] (3) Styl-cross coupling: 3-methyl-6-(tributylstannyl)pyrimidine-4(3H)-one (413 mg, 1.035 mmol) and cataCXium A Pd G3 (8.05 mg, 0.011 mmol) were added to a stirred solution (1 equiv.) of the product from step 1 in 1,4-dioxane (1 mL). The resulting mixture was sparged with N2 for 10 min and then heated to 90°C. After 15 hours, the mixture was cooled to 23°C and concentrated to dryness. The resulting crude residue was purified by reverse-phase preparative HPLC using a Phenomenex Luna column, 5 micron, C8(2), 100 Å, 150 × 21.2 mm (0.1% TFA / CAN gradient of 0.1% TFA / H2O) to obtain the product.

[0479] (4) Amide formation by TBTU: TBTU (46.3 mg, 0.144 mmol) and DMF (3 mL) were added to the stirred solution (1 equiv.) of the product from step 1. Pyrrolidine (15.39 mg, 18.07 μL, 0.216 mmol) and DIPEA (93 mg, 126 μL, 0.721 mmol) were added to the resulting solution. The resulting mixture was stirred at 23°C. After 30 minutes, the reaction mixture was transferred to a separatory funnel containing  (30 mL). The organic layer was washed with 1 M aq. LiCl (3 × 20 mL), dried on anhydrous Na₂SO₄, filtered, and concentrated to dryness. The resulting crude residue was purified by flash chromatography (0-100% in heptane, 3:1 Â:EtOH) to obtain the product.

[0480] The compounds in Table 6-1 were prepared according to the procedure described in Group 6.

[0481] [Table 26]

[0482] [Table 27]

[0483] [Table 28]

[0484] [Table 29]

[0485] [Table 30]

[0486] [Table 31]

[0487] [Table 32]

[0488] [Table 33]

[0489] [Table 34]

[0490] [Table 35]

[0491] [Table 36]

[0492] Group Hotel Example 7-1: (4,4-difluoro-1-piperidinyl)(2-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyrazine-6-yl)methanone C40 [ka] Step 1: 5-((2-ethoxy-2-oxoethyl)amino)-4-nitrothiophene-2-carboxylate ethyl. 5-chloro-4-nitrothiophene-2-carboxylate ethyl (500 mg, 2.12 mmol), glycine ethyl ester hydrochloride (444 mg, 3.18 mmol), anhydrous K2CO3 (880 mg, 6.37 mmol), and ACN (1.7 mL) were added to a 50 mL pressure-relieving vial. The resulting mixture was stirred at 70°C. After 2 hours, the reaction mixture was quenched by adding sat.aq.NH4Cl (10 mL), transferred to a separatory funnel containing H2O (10 mL) and siRNA (20 mL), and extracted with siRNA (20 mL). The combined organic phase was dried over Na2SO4 and concentrated to dryness. The resulting crude residue was purified by automated flash chromatography (0-50% ethyl ethyl heptane) to obtain 5-((2-ethoxy-2-oxoethyl)amino)-4-nitrothiophene-2-carboxylate ethyl (170.9 mg, 0.565 mmol, yield: 27%) as a yellow solid. m / z(ESI): 303.0(M+H) +

[0493] Step 2: 2-Oxo-1,2,3,4-tetrahydrothieno[2,3-b]pyrazine-6-carboxylate ethyl. 5-((2-ethoxy-2-oxoethyl)amino)-4-nitrothiophene-2-carboxylate ethyl (170.9 mg, 0.565 mmol), iron powder (95 mg, 1.70 mmol), acetic acid (3.88 mL), and H2O (0.65 mL) were added to a 50 mL pressure-relieving vial. The resulting mixture was stirred at 70°C. After 1 hour, the reaction mixture was filtered. The filtrate was frozen and directly freeze-dried to obtain crude 2-oxo-1,2,3,4-tetrahydrothieno[2,3-b]pyrazine-6-carboxylate ethyl as a brown solid. m / z(ESI): 226.9(M+H)+ This substance was used in the next step without further purification.

[0494] Step 3: 2-Oxo-1,2-dihydrothieno[2,3-b]pyrazine-6-carboxylate ethyl. 2-Oxo-1,2,3,4-tetrahydrothieno[2,3-b]pyrazine-6-carboxylate ethyl (128 mg, 0.566 mmol), manganese(IV) oxide (492 mg, 5.66 mmol), and THF (5.7 mL) were added to a 50 mL pressure-relieving vial. The resulting mixture was stirred at 50°C. After 30 minutes, the reaction mixture was filtered through a 1 cm Celite pad (20 mL siRNA eluent). The filtrate was concentrated to obtain 2-Oxo-1,2-dihydrothieno[2,3-b]pyrazine-6-carboxylate ethyl as a brown solid. m / z(ESI): 224.95(M+H) + This substance was used in the next step without further purification.

[0495] Step 4: 2-chlorothieno[2,3-b]pyrazine-6-carboxylate ethyl. 2-oxo-1,2-dihydrothieno[2,3-b]pyrazine-6-carboxylate ethyl (127 mg, 0.566 mmol) and phenylphosphonic acid dichloride (3.31 g, 17.0 mmol) were added to a 50 mL pressure-relieving vial. The resulting mixture was heated to 125°C. After 1.5 hours, the reaction mixture was cooled to 0°C and quenched by adding H2O (5 mL). The resulting mixture was transferred to a separatory funnel containing DCM (20 mL) and H2O (10 mL) and extracted with DCM (2 × 20 mL). The resulting crude residue was purified by flash chromatography (0-40% toluene in heptane) to obtain 2-chlorothieno[2,3-b]pyrazine-6-carboxylate ethyl (34.1 mg, 0.141 mmol, yield: 25%) as an off-white solid. m / z(ESI): 242.95(M+H) + .

[0496] Step 5: 2-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyrazine-6-carboxylate ethyl. 2-chlorothieno[2,3-b]pyrazine-6-carboxylate ethyl (34.1 mg, 0.141 mmol), (2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)boronic acid (27.4 mg, 0.155 mmol), anhydrous K3PO4 (59.7 mg, 0.281 mmol), and cataCXium A Pd G3 (10.23 mg, 0.014 mmol) were added to a 25-mL pressure-relieving vial. 1,4-dioxane (2.5 mL) and H2O (0.3 mL) were added. The resulting mixture was sparged with N2 for 10 mins and then heated to 70°C. After 17 hours, the mixture was cooled to 23°C and concentrated to dryness. The resulting crude residue was purified by flash chromatography (using a 10g Biotage column with 0-100% 3:1 siRNA:EtOH in heptane) to obtain 2-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyrazine-6-carboxylate ethyl (37.8 mg, 0.111 mmol, yield: 79%) as a pale yellow solid. m / z(ESI): 340.0(M+H) + .

[0497] Step 6: 2-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyrazine-6-carboxylic acid. Ethyl 2-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyrazine-6-carboxylic acid (37.8 mg, 0.111 mmol), 1,4-dioxane (0.56 mL), and MeOH (0.56 mL) were added to a 10 mL pressure-relieving vial. A 1 M NaOH aq. solution was added dropwise to the resulting suspension, which was vigorously stirred (0.200 mL, 0.200 mmol). The resulting mixture was stirred at 23°C. After 1 hour, the reaction was quenched by adding 1 N HCl (0.20 mL, 0.20 mmol). The resulting mixture was concentrated to dryness to obtain crude 2-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyrazine-6-carboxylic acid as an off-white solid. m / z(ESI):312.0(M+H) + This substance was used in the next step without further purification.

[0498] Step 7: (4,4-difluoropiperidine-1-yl)(2-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyrazine-6-yl)methanone 2,2,2-trifluoroacetate. 2-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyrazine-6-carboxylic acid (34.7 mg, 0.111 mmol), TBTU (64.4 mg, 0.201 mmol), and DMF (2.2 mL) were added to a 10 mL pressure-relieving vial. 4,4-difluoropiperidine (40.5 mg, 36.8 μL, 0.334 mmol) and DIPEA (144 mg, 195 μL, 1.12 mmol) were added to the resulting suspension. The resulting mixture was stirred at 23°C. After 15 minutes, the reaction mixture was filtered. The filtrate was directly purified by reverse-phase preparative HPLC using a Phenomenex Luna column, 5 micron, C8(2), 100 Å, 150 × 21.2 mm (0.1% TFA / CAN in 0.1% TFA / H2O with a 10-60% gradient) to obtain compound C40 (26.3 mg, 0.050 mmol, yield: 45%) as an off-white solid after lyophilization. m / z(ESI): 415.15(M+H) + . 1 H NMR(400MHz,chloroform-d)δ 9.54(d,J=2.1Hz,1H),9.11(s,1H),8.86(d,J=2.1Hz,1H),8.15(s,1H),7.70(s,1H),4.36(s,3H),3.94(br t,J=5.8Hz,4H),2.07-2.23(m,4H).

[0499] The compounds in Table 7-1 were prepared according to the procedure described in Group D.

[0500] [Table 37]

[0501] Group 8 Example 8-1: (3-amino-5-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[3,2-b]pyridin-2-yl)(1-piperidinyl)methanone C45 [ka] Step 1: 3-chloro-6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)picolinonitrile. A vial containing 3,6-dichloropicolinonitrile (0.500 g, 2.89 mmol), 2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-pyrazolo[3,4-b]pyridine (0.749 g, 2.89 mmol), anhydrous K2CO3 (0.799 g, 5.78 mmol), and Pd(dppf)Cl2 (0.211 g, 0.289 mmol) was vacuumed three times and refilled with N2. 1,4-dioxane (4 mL) and water (1 mL) were added via syringe. The mixture was stirred at 110°C for 12 hours under an N2 atmosphere. The reaction mixture was poured into H2O (10 mL) and extracted with siRNA (3 × 10 mL). The combined organic layer was washed with 15 mL of brine (15 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure to obtain 3-chloro-6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)picolinonitrile (1.10 g, 4.08 mmol, yield 71%) as a brown oil. m / z(ESI): 270.1

[0502] Step 2: 3-amino-5-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[3,2-b]pyridin-2-carboxylate ethyl. A mixture of 3-chloro-6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)picolinonitrile (1.00 g, 3.71 mmol), anhydrous K2CO3 (1.127 g, 8.16 mmol), and 2-mercaptoethyl acetate (0.668 g, 5.56 mmol) in EtOH (20 mL) was degassed with N2. The mixture was stirred at 80°C for 3 hours under an N2 atmosphere. The reaction mixture was concentrated under reduced pressure to remove the solvent. The mixture was poured into H2O (30 mL) and extracted with ELISA (3 × 25 mL). The combined organic layers were washed with 15 mL of brine (35 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure to obtain 3-amino-5-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[3,2-b]pyridine-2-carboxylate ethyl (0.67 g, 1.896 mmol, yield 51%) as a brown oil. m / z(ESI): 354.1

[0503] Step 3: 3-amino-5-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[3,2-b]pyridin-2-carboxylic acid. A mixture of ethyl 3-amino-5-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[3,2-b]pyridin-2-carboxylic acid (0.7 g, 1.981 mmol) and NaOH (0.119 g, 2.97 mmol) in EtOH (8 mL) and H2O (2 mL) was stirred at 80°C for 3 hours. The reaction mixture was concentrated under reduced pressure to obtain a residue. The residue was injected into 2O (5 mL) and the pH was adjusted to 4 by adding 1N HCl. Next, the mixture was filtered to obtain 3-amino-5-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[3,2-b]pyridine-2-carboxylic acid (0.62 g, 1.906 mmol, yield 84%) as a brown solid. m / z(ESI): 325.9.

[0504] Step 4: (3-amino-5-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[3,2-b]pyridin-2-yl)(piperidine-1-yl)methanone. Piperidine (31.4 mg, 0.369 mmol), HATU (140 mg, 0.369 mmol), and DIPEA (107 μL, 0.615 mmol) were added at 20°C to a solution of 3-amino-5-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[3,2-b]pyridin-2-carboxylic acid (100 mg, 0.307 mmol) in DMF (0.5 mL). The mixture was stirred at 20°C for 12 hours. The mixture was directly purified by preparative HPLC (column: Waters Xbridge BEH C18 100×30mm×10μm, mobile phase: H2O(NH4HCO3)-ACN, B%: 20%~50%, 8 min). Compound C45 (0.0043 g, 10.79 μmol, yield 3.5%) was obtained as an off-white solid. m / z(ESI): 393.1(M+H) + . 1 H NMR(400MHz,DMSO-d6)δ 9.62(d,J=2.0Hz,1H),9.05(d,J=2.0Hz,1H),8.56(s,1H),8.43(d,J=8.8Hz,1H),8.17 (d,J=8.4Hz,1H),6.25(s,2H),4.24(s,3H),3.60(t,J=4.8Hz,4H),1.57-1.64(m,6H).

[0505] Alternative conditions for Group E.1: (1) 5-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[3,2-b]pyridine-2-carbonyl chloride (0.080 g, 0.24 mmol)) and piperidine (0.021 g, 0.24 mmol) were dissolved in DCM (2 mL) and Et3N (0.068 mL, 0.49 mmol) was added at 20°C. The mixture was stirred at 20°C for 12 hours. The mixture was directly purified by preparative HPLC (column: Phenomenex C18 75 × 30 mm × 3 μm, mobile phase: H2O(NH3H2O+NH4HCO3)-ACN, B%: 25%~60%, 8 min) to obtain the product.

[0506] The compounds in Table 8-1 were prepared according to the procedure described in Group 8.

[0507] [Table 38]

[0508] [Table 39]

[0509] [Table 40]

[0510] Group 9 Example 9-1: (4-Cyclopropyl-2-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[3,2-d]pyrimidine-6-yl)(4-morpholinyl)methanone C49 [ka] Step 1: 2-Chloro-4-cyclopropylthieno[3,2-d]pyrimidine. 2,4-Dichlorothieno[3,2-d]pyrimidine (500 mg, 2.44 mmol) and PEPPSI-iPr catalyst (166 mg, 0.244 mmol) were stirred in 4 mL of THF at 23°C. A 0.5 M THF solution of cyclopropyl zinc(II) bromide (9.75 mL, 4.88 mmol) was added dropwise. The reaction mixture was stirred at 23°C. After 17 hours, the reaction mixture was diluted with sat.aq.NH4Cl (5 mL) and transferred to a separatory funnel containing H2O (20 mL) and HCl (40 mL). The aqueous phase was extracted with HCl (40 mL). The combined organic matter was dried over Na2SO4 and concentrated to dryness. The resulting crude residue was purified by flash chromatography (0-20% 3:1 Â:EtOH in heptane) to obtain 2-chloro-4-cyclopropylthieno[3,2-d]pyrimidine (133 mg, 0.632 mmol, yield, 26%) as an off-white solid. m / z(ESI):211.15(M+H)+ .

[0511] Step 2: 2-Chloro-4-cyclopropylthieno[3,2-d]pyrimidine-6-carboxylic acid. 2-Chloro-4-cyclopropylthieno[3,2-d]pyrimidine (133 mg, 0.632 mmol) and THF (6.3 mL) were added to a 50 mL pressure-relieving vial. The resulting solution was flushed with nitrogen and cooled to -78°C, after which a 2.5 M hexane solution of n-butyllithium (0.278 mL, 0.695 mmol) was added dropwise. The resulting mixture was stirred at -78°C for 5 minutes under an N2 atmosphere. A separate 50 mL pressure-relieving vial was filled with solid CO2 (2.78 g, 63.2 mmol), and a cannula was connected so that sublimation CO2 could aerate the reaction mixture at -78°C. After 20 minutes, the cooling water bath was removed. The reaction mixture was spurged with N2 and heated to 23°C for 30 minutes, flushing out any dissolved CO2. The reaction mixture was then quenched by the slow addition of sat. aq. NH4Cl (5 mL) and transferred to a separatory funnel containing siRNA (30 mL), H2O (10 mL), and 1N aq. HCl (10 mL). The aq. layer was extracted with siRNA (30 mL), the combined organic matter was dried over Na2SO4, filtered, and concentrated under vacuum to obtain 2-chloro-4-cyclopropylthieno[3,2-d]pyrimidine-6-carboxylic acid (160.6 mg, 0.631 mmol, yield: 100%) as an off-white solid. m / z(ESI): 254.95(M+H) + This substance was used in the next step without further purification.

[0512] Step 3: (2-chloro-4-cyclopropylthieno[3,2-d]pyrimidine-6-yl)(morpholino)methanone. 2-chloro-4-cyclopropylthieno[3,2-d]pyrimidine-6-carboxylic acid (51.8 mg, 0.203 mmol), TBTU (85 mg, 0.264 mmol), and DMF (4 mL) were added to a 50 mL pressure-relieving vial. The resulting solution was cooled to 0°C. Morpholine (28.4 mg, 28.5 μL, 0.325 mmol) and DIPEA (131 mg, 178 μL, 1.02 mmol) were added, and the resulting mixture was stirred at 0°C. After 3 hours, the reaction mixture was transferred to a separatory funnel containing RINKAN (30 mL). The organic layer was washed with 1 M aq. LiCl (3 × 20 mL), dried over anhydrous Na₂SO₄, filtered, and concentrated to dryness under reduced pressure. The resulting crude residue was purified by flash chromatography (0-100% RINKAN gradient in heptane) to obtain (2-chloro-4-cyclopropylthieno[3,2-d]pyrimidine-6-yl)(morpholino)methanone (48.2 mg, 0.149 mmol, yield: 73%) as a colorless foam. m / z(ESI): 324.1(M+H) + .

[0513] Step 4: (4-Cyclopropyl-2-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[3,2-d]pyrimidine-6-yl)(morpholino)methanone. (2-chloro-4-cyclopropylthieno[3,2-d]pyrimidine-6-yl)(morpholino)methanone (48.2 mg, 0.149 mmol), (2-methyl-2h-pyrazolo[3,4-b]pyridin-5-yl)boronic acid (31.6 mg, 0.179 mmol), anhydrous K3PO4 (95 mg, 0.447 mmol), and cataCXium A Pd G3 (5.42 mg, 7.44 μmol) were added to a 25-mL pressure-relieving vial. Next, THF (1.3 mL) and H2O (0.1 mL) were added, and the resulting mixture was sparged with N2 for 15 minutes. The mixture was heated to 70°C. After 17 hours, the mixture was cooled to 23°C and concentrated to dryness under reduced pressure. The resulting crude residue was purified by flash chromatography (0-100% 3:1 Â:EtOH in heptane) to obtain compound C49 (44.3 mg, 0.105 mmol, yield: 71%) as an off-white solid. m / z (ESI): 421.15 (M+H) + . 1 ¹H NMR (400MHz, chloroform-d) δ 9.85 (d, J=2.1Hz, 1H), 9.13 (d, J=2.1Hz, 1H), 8.04 (s, 1H), 7.64 (s, 1H), 4.31 (s, 3H), 3.83 (br s, 8H), 2.21-2.32 (m, 1H), 1.55-1.63 (m, 2H), 1.30-1.37 (m, 2H).

[0514] Group 10 Example 10-1: ((3R)-3-methyl-4-morpholinyl)(5-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)[1,3]thiazolo[5,4-b]pyridin-2-yl)methanone C52R [ka] Step 1: 5-Chlorothiazolo[5,4-b]pyridine-2-carboxylate lithium. LiOH·H2O (0.057 g, 1.36 mmol) was added to a solution of ethyl 5-chlorothiazolo[5,4-b]pyridine-2-carboxylate (0.300 g, 1.24 mmol) in THF (4 mL) and H2O (1 mL). The resulting mixture was stirred at rt for 4 hours. The reaction mixture was concentrated and freeze-dried to obtain crude 5-chlorothiazolo[5,4-b]pyridine-2-carboxylate lithium (0.275 g, 1.25 mmol, crude yield: 101%). m / z(ESI): 215.0(M+H) + The crude material was used without further purification.

[0515] Step 2: (R)-(5-chlorothiazolo[5,4-b]pyridine-2-yl)(3-methylmorpholino)methanone. A mixture of lithium 5-chlorothiazolo[5,4-b]pyridine-2-carboxylate (0.100 g, 0.453 mmol), (R)-3-methylmorpholine (0.055 g, 0.544 mmol), and PyBOP (0.283 g, 0.544 mmol) in N-methyl-2-pyrrolidinone (1 mL) was stirred at rt for 3 hours. The reaction mixture was diluted with H2O (10 mL) and extracted with ELISA (2 × 20 mL). The combined organic phase was concentrated, and the residue was purified by automated flash column chromatography using 0-80% toluene / etOH (3:1) in heptane (eluting the product at 35%) to obtain (R)-(5-chlorothiazolo[5,4-b]pyridine-2-yl)(3-methylmorpholino)methanone (0.048 g, 0.161 mmol, yield: 35.6%). m / z(ESI): 298.0(M+H) + .

[0516] Step 3: (R)-(5-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thiazolo[5,4-b]pyridin-2-yl)(3-methylmorpholino)methanone. The mixture of (R)-(5-chlorothiazolo[5,4-b]pyridine-2-yl)(3-methylmorpholino)methanone (0.048 g, 0.16 mmol, 129279-5-1), [2-methyl-2h-pyrazolo[3,4-b]pyridine-5-yl]boronic acid (0.057 g, 0.32 mmol), Pd(dppf)Cl2 (0.024 g, 0.032 mmol), and K2CO3 (0.067 g, 0.484 mmol, Oakwood) in 1,4-dioxane (2 mL) and H2O (0.5 mL) contained in a microwave vial was capped and heated in a microwave oven at 110°C for 30 minutes. The reaction mixture was concentrated, and the residue was purified by automated flash column chromatography using 0-100% Â / EtOH (3:1) in heptane (eluting the product at 95%) to obtain compound C52R (0.028 g, 0.071 mmol, yield: 44.0%). m / z(ESI): 395.0(M+H) + . 1 H NMR(400MHz,chloroform-d)δ 9.43(br s,1H)8.83(br s,1H)8.40(br d,J=7.11Hz,1H)7.94-8.13(m,2H)5.19-5.73(m,1H)4.39-4.94(m,1H)4.24-4.49(m,2H)3 .93-4.18(m,1H)3.75-3.90(m,2H)3.37-3.74(m,2H)1.59-2.28(m,1H)1.43-1.60(m,3H).

[0517] The compounds in Table 9 were prepared according to the procedure described in Group F.

[0518] [Table 41]

[0519] Section 3: Biochemistry and Cell Assays Example 11: Inhibition Study The dose-response of the inhibition of 15-PGDH activity by compounds was determined using human recombinant 15-PGDH enzymatic assays. These assays measured 15-PGDH enzyme activity by quantifying the amount of NADH produced during a 60-minute reaction initiated by the addition of PGE2 and NAD+. Under the conditions of these experiments, the increase in the NADH signal immediately following the oxidation of PGE2 and reduction of NAD+ was linearly proportional to the 15-PGDH enzyme activity. Recombinant human, mouse, rat, and canine 15-PGDH enzymatic assays were performed in 384-well microtiter plates in 25 μL of reaction buffer containing 50 mM Tris, pH 7.5, 0.01% Tween-20, and 100 μM DTT. In concentration-response experiments with the compounds tested, 22 concentrates derived from 2-fold serial dilutions in DMSO were pre-incubated with 15-PGDH at room temperature for 15 minutes. Subsequently, PGE2 and β-NAD+ were added to initiate the 15-PGDH reaction. After 60 minutes at room temperature, the reaction was quenched, and the NADH signal was measured using a microtiter plate reader.

[0520] The following data (Table 11-1) shows the IC50 values ​​of each compound used to inhibit the enzyme activity of recombinant 15-PGDH in the assay described above.

[0521] [Table 42]

[0522] [Table 43]

[0523] [Table 44]

[0524] [Table 45]

[0525] [Table 46]

[0526] [Table 47]

[0527] Example 12: Cellular 15-PGDH Inhibition Study This assay was used to quantify IL-1β-induced native prostaglandin E2 (PGE2) produced by A549 cells (epithelial cells derived from lung cancer) in cell culture supernatant. Inhibition of 15-PGDH blocked PGE2 degradation, resulting in PGE2 accumulation above baseline levels. In short, A549 cells were subjected to 2.5 ng / mL IL-1β(EC2) 80 The samples were treated with ) and a 15-PGDH inhibitor for 24 hours. PGE2 was detected by a competitive HTRF assay using an anti-PGE2 antibody labeled with Europium cryptate and deuterium-labeled PGE2. PGE2 present in the sample prevents FRET from occurring by competing for binding between the two HTRF detection solutions (reagents). The specific signal is inversely proportional to the PGE2 concentration. The IC50 value was calculated from this binding data.

[0528] The following data (Table 12-1) lists the IC50 values ​​of each compound used to inhibit enzyme activity in the assay described above.

[0529] [Table 48]

[0530] [Table 49]

[0531] [Table 50]

Claims

1. Equation (I) 【Chemistry 1】 (In the formula, 【Chemistry 2】 teeth, 【Transformation 3】 And, a is N, -N ＋ -O － or CH, b is N or CH, c is N, CH, or C-R ３ And, d is N, CH, or C-R ４ And, R １ａ is -H, C １～６ Alkyl, C １～６ Haloalkyl or C １～６ It is heteroalkyl, R １ａ is unsubstituted or is independently substituted with one or more substituents each of which is halogen, -OH, -N(R ｂ ), ２ C １～３ alkyl or C １～３ alkoxy; R １ｂ C １～６ Alkyl, C １～６ Haloalkyl, C １～６ Heteroalkyl, C ３～１０ A cycloalkyl or heterocyclyl having 3 to 10 ring members, R １ｂ These are either unsubstituted or each independently a halogen, -OH, and -N(R) ｂ ) ２ , C １～３ Alkyl or C １～３ It may be substituted with one or more substituents that are alkoxy, or Instead, R １ａ and R １ｂ It forms a heterocycline with 3 to 10 ring members together, R １ａ and R １ｂ The heterocyclyl formed by the above is either unsubstituted or each independently contains a halogen, -OH, -CN, and -N(R) ｂ ) ２ , C １～６ Alkyl, C １～６ Haloalkyl, C １～６ Alkoxy, C １～６ Heteroalkyl, C ３～６ It may be substituted with one or more substituents that are cycloalkyl or heterocyclyl having 3 to 6 ring members. R ２ is a heterocyclyl or heteroaryl having 5 to 20 ring members, or alternatively, a is -N ＋ -O － If R ２ H is, R ２ is either unsubstituted or R ５ It may be replaced with one or more examples of R ５ Each example independently includes oxo, CN, halogen, -OH, and C. １～６ Alkyl, C ３～６ Cycloalkyl, C １～６ Haloalkyl, C １～６ Alkoxy, C(O)N(R) ６ ) ２ , -N(R ６ ) ２ , -N(R ６ ) (C １～６ It is an alkylene-OH or a heterocycline having 3 to 10 members. R ５ Each example is either non-substitutable or R ６ It may be replaced with one or more examples of R ６ Each example is independently -H, C １～６ Alkyl, C(O)C １～６ Alkyl, C(O) ２ C １～６ Alkyl, C １～６ Alkylene-OH or S(O) ｎ C １～６ It is an alkyl group, and n is 0, 1, or 2. R ６ These are either unsubstituted or each is independently -F, -OH, C １～３ It may be substituted with one or more substituents that are alkoxy. R ３ is -H, C １～６ Alkyl, C ３～１０ Cycloalkyl, C ６～１０ The aryl, heteroaryl having 5 to 10 ring members, or heterocyclyl having 3 to 10 ring members, R ３ These are either unsubstituted or each independently a halogen, -OH, oxo, and -N(R) ｂ ) ２ , C １～３ Alkyl, C １～３ Haloalkyl, C １～３ Alkoxy, C １～３ Alkylene-C １～３ Alkoxy or C １～６ It may be substituted with one or more substituents that are heteroalkyl. R ４ is -H, C １～６ Alkyl or -N(R) ７ ) ２ And if it exists, R ７ Each example is independently -H or C １～６ It is alkyl, or instead, it has two R's. ７ The substituents together form a heterocyclyl having 3 to 6 ring members. R ７ These are either unsubstituted or each is independently -F, -OH, C １～３ Alkyl or C １～３ It may be substituted with one or more substituents that are alkoxy. If present, R ｂ Each example is independently -H or C １～６ It is alkyl, or instead, it has two R's. ｂ The substituents together form a heterocyclyl having 3 to 6 ring members. R ｂ is unsubstituted or is substituted with one or more substituents each independently being -F, -OH, C １～３ alkyl or C １～３ alkoxy; R １ａ When R is H, a is CH, b is CH, c is C-R ３ and d is C-R ４ where R ２ is thienyl, R ３ is phenyl, R ４ is NH ２ and R １ｂ is C １～３ alkyl, and R １ｂ is unsubstituted or may be substituted with C １～３ alkoxy, R １ａ C １～６ Alkyl, C １～６ Haloalkyl or C １～６ If it is a heteroalkyl group, then d is CH, R ２ If R is triazolyl, tetrahydropyranil, or oxetanil, １ｂ This is not an unsubstituted or substituted cross-linked [2.2.2] heterocyclyl having eight ring members, R ２ However, if it is a heteroaryl having five ring members or a heterocyclyl having four to six ring members, R １ｂ This is not an unsubstituted or substituted cross-linked [2.2.2] heterocyclyl having eight ring members, R １ａ is H or Me, and R １ｂ C １～３ Alkyl or C １～３ If R is a haloalkyl, ３ This is not unsubstituted or substituted morpholinyl, R １ａ If H, then R ３ This is not unsubstituted or substituted morpholinyl, R １ａ and R １ｂ However, if unsubstituted or substituted piperidinil or unsubstituted or substituted piperidinil is provided together, R ３ (This is not unsubstituted or substituted morpholinyl.) A compound of the said compound or a pharmaceutically acceptable salt of the said compound.

2. R ２ The compound or salt according to claim 1, wherein is a heteroaryl that does not contain S as a ring member. 【Request Item 3】 【Chemistry 4】 teeth, 【Transformation 5】 The compound or salt according to claim 1 or 2. 【Request Item 4】 【Chemistry 6】 teeth, 【Transformation 7】 The compound or salt according to claim 1 or 2. 【Request Item 5】 【Chemistry 8】 The basis is, 【Chemistry 9】 The compound or salt according to any one of claims 1 to 4.

6. R １ａ -H, unsubstituted or substituted C １～３ Alkyl or unsubstituted or substituted C １～３ A compound or salt according to any one of claims 1 to 5, which is a haloalkyl compound.

7. R １ａ The compound or salt according to any one of claims 1 to 6, wherein is substituted with one substituent.

8. R １ａ If it is replaced, each R １ａ The substituents are, independently, halogen, -OH, and C. １～３ Alkyl or C １～３ A compound or salt according to any one of claims 1 to 7, which is an alkoxy.

9. R １ａ The compound or salt according to any one of claims 1 to 8, wherein the compound is unsubstituted.

10. R １ａ is -H or -CH ３ The compound or salt according to any one of claims 1 to 5.

11. R １ｂ C is either unsubstituted or substituted. １～３ Alkyl, unsubstituted, or substituted C １～３ Haloalkyl, unsubstituted or substituted C ３～６ The compound or salt according to any one of claims 1 to 10, which is a cycloalkyl or an unsubstituted or substituted heterocyclyl having 3 to 6 ring members.

12. R １ｂ The compound or salt according to any one of claims 1 to 11, wherein is an unsubstituted or substituted heterocyclyl.

13. R １ｂ These are unsubstituted or substituted heterocyclyls, each independently comprising nitrogen, oxygen, or -S(O) ｘ A compound or salt according to any one of claims 1 to 12, comprising 1, 2, 3 or 4 heteroatom ring members, wherein x is 0, 1 or 2.

14. R １ｂ The compound or salt according to any one of claims 1 to 13, wherein is an unsubstituted or substituted heterocyclyl having one, two, or three heteroatom ring members.

15. R １ｂ The compound or salt according to any one of claims 1 to 14, wherein is an unsubstituted or substituted heterocyclyl having one or two heteroatom ring members.

16. R １ｂ The compound or salt according to any one of claims 1 to 11, wherein is an unsubstituted or substituted alkyl group.

17. R １ｂ The compound or salt according to any one of claims 1 to 11, wherein is an unsubstituted or substituted haloalkyl.

18. R １ｂ The compound or salt according to any one of claims 1 to 11, wherein is an unsubstituted or substituted cycloalkyl group.

19. R １ｂ The compound or salt according to any one of claims 1 to 12, wherein is an unsubstituted or substituted 3- to 6-membered heterocyclyl.

20. R １ｂ The compound or salt according to any one of claims 1 to 19, wherein is substituted with one or two substituents.

21. R １ｂ The compound or salt according to any one of claims 1 to 20, wherein is substituted with one substituent.

22. R １ｂ If it is replaced, each R １ｂ The substituents are, independently, halogens, and C １～３ Alkyl or C １～３ A compound or salt according to any one of claims 1 to 21, which is an alkoxy.

23. Each R １ｂ The compound or salt according to any one of claims 1 to 21, wherein the substituent is independently -F, -OH, methyl, or -OMe.

24. R １ｂ The compound or salt according to any one of claims 1 to 23, wherein -OMe is substituted.

25. R １ｂ The compound or salt according to any one of claims 1 to 19, wherein the compound is unsubstituted.

26. R １ｂ is, -CH ３ ien-CH ２ CH ２ -O-CH ３ The compound or salt according to any one of claims 1 to 11 or 25, or an unsubstituted cyclobutyl.

27. R １ａ and R １ｂ The compound or salt according to any one of claims 1 to 6, wherein the compound or salt together forms a heterocycline with 3 to 10 members.

28. R １ａ and R １ｂ It forms a heterocycline together, and the R １ａ and R １ｂ Each heteroatom ring member of a heterocycline is independently nitrogen, oxygen, or -S(O) ｘ The compound or salt according to any one of claims 1 to 6 or 27, wherein x is 0, 1 or 2.

29. R １ａ and R １ｂ The compound or salt according to any one of claims 1 to 6 or 27 or 28, wherein the compound or salt together forms a heterocyclil having one or two heteroatom ring members.

30. R １ａ and R １ｂ The compound or salt according to any one of claims 1 to 6 or 27 to 29, wherein the compound or salt together forms a heterocyclyl substituted with one or two substituents.

31. R １ａ and R １ｂ The compound or salt according to any one of claims 1 to 6 or 27 to 29, wherein the compound or salt together forms a heterocyclyl substituted with one substituent.

32. R １ａ and R １ｂ However, when substituted heterocyclines are formed together, each substituent of the heterocycline is independently halogen, -CN, C １～６ Alkyl, C １～６ Haloalkyl, C １～６ Alkoxy, C １～６ Heteroalkyl or C ３～６ A compound or salt according to any one of claims 1 to 6 or 27 to 30, which is a cycloalkyl compound.

33. R １ａ and R １ｂ The compound or salt according to any one of claims 1 to 6 or 27 to 29, wherein it together forms an unsubstituted heterocycline.

34. R １ａ and R １ｂ The compound or salt according to any one of claims 1 to 6 or 27 to 33, wherein when the compounds together form a heterocyclil, the heterocyclil is a bicyclic condensed ring system. 【Request Item 35】 【Chemistry 10】 teeth, 【Chemistry 11】 The compound or salt according to any one of claims 1 to 6 or 27 to 34.

36. R ２ The compound or salt according to any one of claims 1 to 35, wherein the compound is a heteroaryl compound.

37. R ２ The compound or salt according to any one of claims 1 to 36, having one, two, three, or four heteroatom ring members.

38. R ２ Each ring member heteroatom is independently nitrogen, oxygen, or -S(O) ｙ The compound or salt according to any one of claims 1 to 37, wherein y is 0, 1, or 2.

39. R ２ The compound or salt according to any one of claims 1 to 38, wherein is a condensed bicyclic group.

40. R ２ R ５ A compound or salt according to any one of claims 1 to 39, substituted with one or two examples of the above.

41. R ５ Each example independently represents oxo, CN, and C. １～３ Alkyl, C ３～６ Cycloalkyl, C １～３ Haloalkyl, C １～３ Alkoxy, C(O)N(R) ６ ) ２ , -N(R ６ ) ２ , -N(R ６ ) (C １～３ The compound or salt according to any one of claims 1 to 40, which is an alkylene-OH or a heterocyclyl having 3 to 10 members.

42. R ５ Each example is independently -F, methyl, ethyl, or isopropyl, the compound or salt according to any one of claims 1 to 41.

43. R ３ C １～６ Alkyl, C ３～１０ Cycloalkyl, C ６～１０ A compound or salt according to any one of claims 1 to 42, wherein the compound is an aryl, a heteroaryl having 5 to 10 ring members, or a heterocyclyl having 3 to 10 ring members.

44. R ４ The compound or salt according to any one of claims 1 to 43, wherein is -H.

45. The aforementioned compound, 【Chemistry 12】 【Chemistry 13】 【Chemistry 14】 【Chemistry 15】 【Chemistry 16】 【Chemistry 17】 [Chemistry 18] 【Chemistry 19】 【Chemistry 20】 【Chemistry 21】 【Chemistry 22】 【Chemistry 23】 【Chemistry 24】 【Chemistry 25】 The compound or salt according to claim 1.

46. The aforementioned compound, 【Chemistry 26】 【Chemistry 27】 【Chemistry 28】 【Chemistry 29】 【Transformation 30】 The compound or salt according to claim 1.

47. The aforementioned compound, (3-methyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)-1-benzothiophen-2-yl)(3-methyl-4-morpholinyl)methanone, (3-methyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)-1-benzothiophen-2-yl)(4-morpholinyl)methanone, (4,4-difluoro-1-piperidinyl)(3-methyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)-1-benzothiophen-2-yl)methanone, (3-Methoxy-1-pyrrolidinyl)(3-methyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)-1-benzothiophen-2-yl)methanone, N-(2-methoxyethyl)-N,3-dimethyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)-1-benzothiophene-2-carboxamide, (2,2-dimethyl-4-morpholinyl)(3-methyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)-1-benzothiophen-2-yl)methanone, (3-Methoxy-1-piperidinyl)(3-methyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)-1-benzothiophen-2-yl)methanone, (3-methyl-6-(5-pyrimidinyl)-1-benzothiophen-2-yl)(4-morpholinyl)methanone, 1-methyl-5-(3-methyl-2-(4-morpholinylcarbonyl)-1-benzothiophen-6-yl)-2(1H)-pyridinone, (6-(2-((2-hydroxyethyl)amino)-5-pyrimidinyl)-3-methyl-1-benzothiophen-2-yl)(4-morpholinyl)methanone, (3-methyl-6-(2-methyl-2H-indazole-5-yl)-1-benzothiophen-2-yl)(4-morpholinyl)methanone, (3-amino-4-cyclobutyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)(4-morpholinyl)methanone, (3-amino-4-cyclobutyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)(4,4-difluoro-1-piperidinyl)methanone, (3-amino-4-cyclobutyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)(1-piperidinyl)methanone, (3-amino-4-cyclobutyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)(3-methyl-4-morpholinyl)methanone, (7-oxide-4-(2-propanyl)thieno[2,3-b]pyridin-2-yl)(1-piperidinyl)methanone, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)(4-morpholinyl)methanone, (3-methyl-4-morpholinyl)(6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)methanone, (4-Cyclopropyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)(4-morpholinyl)methanone, (4-Cyclopropyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)(3,3-difluoro-1-piperidinyl)methanone, 4-Cyclopropyl-N-(2-methoxyethyl)-N-methyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyridine-2-carboxamide, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)-4-(1-methyl-1H-pyrazole-5-yl)thieno[2,3-b]pyridine-2-yl)(4-morpholinyl)methanone, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)-4-(1-methyl-1H-pyrazole-5-yl)thieno[2,3-b]pyridine-2-yl)(4-thiomorpholinyl)methanone, N-cyclobutyl-4-cyclopropyl-N-methyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyridine-2-carboxamide, (5-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)(1-piperidinyl)methanone, (4-Cyclopropyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)(3-methyl-4-morpholinyl)methanone, 2-Methyl-2-propanyl 4-(5-(4-cyclopropyl-2-(1-piperidinylcarbonyl)thieno[2,3-b]pyridinyl-6-yl)-2-pyrimidinyl)-1-piperazine carboxylate, (4-Cyclopropyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)(4,4-difluoro-1-piperidinyl)methanone, (4-Cyclopropyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)(4-(trifluoromethyl)-1-piperidinyl)methanone, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)(4-(trifluoromethyl)-1-piperidinyl)methanone, (4-Cyclopropyl-6-(2-(1-piperazinyl)-5-pyrimidinyl)thieno[2,3-b]pyridine-2-yl)(1-piperidinyl)methanone, (4-Cyclopropyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)(1-piperidinyl)methanone, (4-Cyclopropyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyridine-2-yl)(1,4-oxazepan-4-yl)methanone, (4,4-difluoro-1-piperidinyl)(6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)methanone, (4,4-difluoro-2-methyl-1-piperidinyl)(6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)methanone, 2-methyl-6-(2-(1-piperidinylcarbonyl)thieno[2,3-b]pyridine-5-yl)-1(2H)-isoquinolinone, (3,3-dimethyl-4-morpholinyl)(6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)methanone, 4-((6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyridine-2-yl)carbonyl)-3-morpholine carbonate, (2-methyl-4-morpholinyl)(6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)methanone, 1-Methyl-5-(2-((3-methyl-4-morpholinyl)carbonyl)thieno[2,3-b]pyridin-6-yl)-2(1H)-pyridinone, (3-methyl-4-morpholinyl)(6-(1,3-thiazole-2-yl)thieno[2,3-b]pyridine-2-yl)methanone, 3-methyl-6-(2-((3-methyl-4-morpholinyl)carbonyl)thieno[2,3-b]pyridine-6-yl)-4(3H)-pyrimidinone, 1-Methyl-5-(2-(4-morpholinylcarbonyl)thieno[2,3-b]pyridin-6-yl)-2(1H)-pyridinone, (3-methyl-4-morpholinyl)(6-(1,3-thiazole-2-yl)thieno[2,3-b]pyridine-2-yl)methanone, 3-methyl-6-(2-((3-methyl-4-morpholinyl)carbonyl)thieno[2,3-b]pyridine-6-yl)-4(3H)-pyrimidinone, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyridine-2-yl)(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)methanone, 4-Molfolinyl(6-(1,3-thiazole-2-yl)thieno[2,3-b]pyridine-2-yl)methanone, 3-methyl-6-(2-(4-morpholinylcarbonyl)thieno[2,3-b]pyridin-6-yl)-4(3H)-pyrimidinone, (2,2-dimethyl-4-morpholinyl)(6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)methanone, 5-(2-(4-morpholinylcarbonyl)thieno[2,3-b]pyridin-6-yl)-2(1H)-pyridinone, (6-(2-methyl-2H-[1,2,3]triazolo[4,5-b]pyridine-6-yl)thieno[2,3-b]pyridine-2-yl)(4-morpholinyl)methanone, (3-methyl-4-morpholinyl)(6-(2-methyl-2H-[1,2,3]triazolo[4,5-b]pyridine-6-yl)thieno[2,3-b]pyridine-2-yl)methanone, (3-methyl-4-morpholinyl)(6-(3-methyl-3H-[1,2,3]triazolo[4,5-b]pyridine-6-yl)thieno[2,3-b]pyridine-2-yl)methanone, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)(7-oxa-4-azaspiro[2.5]octan-4-yl)methanone, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)(2-(trifluoromethyl)-4-morpholinyl)methanone, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)(4-oxa-7-azaspiro[2.5]octan-7-yl)methanone, 5-(2-(3-methyl-4-morpholinyl)carbonyl)thieno[2,3-b]pyridin-6-yl)-2(1H)-pyridinone, 4-Molfolinyl (6-(6-Quinolinyl)thieno[2,3-b]pyridine-2-yl)methanone, (6-(1-methyl-1H-imidazo[4,5-b]pyridine-6-yl)thieno[2,3-b]pyridine-2-yl)(4-morpholinyl)methanone, 2,8-dioxa-5-azaspiro[3.5]nonan-5-yl(6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)methanone, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)(2-oxa-5-azabicyclo[2.2.2]octan-5-yl)methanone, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)(2-oxa-5-azabicyclo[4.1.0]heptan-5-yl)methanone, (6-(3-methyl-3H-[1,2,3]triazolo[4,5-b]pyridine-6-yl)thieno[2,3-b]pyridine-2-yl)(4-morpholinyl)methanone, (3-methyl-4-morpholinyl)(6-(6-quinolinyl)thieno[2,3-b]pyridine-2-yl)methanone, 4-Molfolinyl (6-(pyrido[2,3-b]pyrazine-7-yl)thieno[2,3-b]pyridine-2-yl)methanone, (3-methyl-4-morpholinyl)(6-(pyrido[2,3-b]pyrazine-7-yl)thieno[2,3-b]pyridine-2-yl)methanone, 7-methyl-3-(2-(4-morpholinylcarbonyl)thieno[2,3-b]pyridine-6-yl)-1,7-naphthyridine-8(7H)-one, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)(8-oxa-5-azaspiro[3.5]nonan-5-yl)methanone, 7-methyl-3-(2-((3-methyl-4-morpholinyl)carbonyl)thieno[2,3-b]pyridine-6-yl)-1,7-naphthyridine-8(7H)-one, (6-(1-methyl-1H-imidazo[4,5-b]pyridine-6-yl)thieno[2,3-b]pyridine-2-yl)(3-methyl-4-morpholinyl)methanone, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)(3-(trifluoromethyl)-4-morpholinyl)methanone, (4-Cyclopropyl-2-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-d]pyrimidine-6-yl)(4-morpholinyl)methanone, (4-cyclopropyl-2-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-d]pyrimidine-6-yl)(1-pyrrolidinyl)methanone, (4-Cyclopropyl-2-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-d]pyrimidine-6-yl)(3,3-difluoro-1-piperidinyl)methanone, (4-Cyclopropyl-2-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-d]pyrimidine-6-yl)(1-piperidinyl)methanone, (4-Cyclopropyl-2-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-d]pyrimidine-6-yl)(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)methanone, (2-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)-4-(1-methyl-1H-pyrazole-5-yl)thieno[2,3-d]pyrimidine-6-yl)(4-morpholinyl)methanone, (2-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)-4-(1-methyl-1H-pyrazole-5-yl)thieno[2,3-d]pyrimidine-6-yl)(1-piperidinyl)methanone, (4,4-difluoro-1-piperidinyl)(2-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)-4-(1-methyl-1H-pyrazole-5-yl)thieno[2,3-d]pyrimidine-6-yl)methanone, (4,4-difluoro-1-piperidinyl)(4-(1-methyl-1H-pyrazole-5-yl)-2-(2-methyl-2H-[1,2,3]triazolo[4,5-b]pyridine-6-yl)thieno[2,3-d]pyrimidine-6-yl)methanone, 6-(6-((4,4-difluoro-1-piperidinyl)carbonyl)-4-(1-methyl-1H-pyrazole-5-yl)thieno[2,3-d]pyrimidine-2-yl)-3-methyl-4(3H)-pyrimidinone, (4,4-difluoro-1-piperidinyl)(4-(1-methyl-1H-pyrazole-5-yl)-2-(3-pyridinyl)thieno[2,3-d]pyrimidine-6-yl)methanone, (4,4-difluoro-1-piperidinyl)(4-(1-methyl-1H-pyrazole-5-yl)-2-(5-pyrimidinyl)thieno[2,3-d]pyrimidine-6-yl)methanone, (4,4-difluoro-1-piperidinyl)(2-(2-methoxy-5-pyrimidinyl)-4-(1-methyl-1H-pyrazole-5-yl)thieno[2,3-d]pyrimidine-6-yl)methanone, 5-(6-((4,4-difluoro-1-piperidinyl)carbonyl)-4-(1-methyl-1H-pyrazole-5-yl)thieno[2,3-d]pyrimidine-2-yl)-1-methyl-2(1H)-pyridinone, 5-(6-((4,4-difluoro-1-piperidinyl)carbonyl)-4-(1-methyl-1H-pyrazole-5-yl)thieno[2,3-d]pyrimidine-2-yl)-2-pyrimidinecarbonitrile, (4,4-difluoro-1-piperidinyl)(2-(2-(dimethylamino)-5-pyrimidinyl)-4-(1-methyl-1H-pyrazole-5-yl)thieno[2,3-d]pyrimidine-6-yl)methanone, (4,4-difluoro-1-piperidinyl)(4-(1-methyl-1H-pyrazole-5-yl)-2-(2-methyl-5-pyrimidinyl)thieno[2,3-d]pyrimidine-6-yl)methanone, (4,4-difluoro-1-piperidinyl)(4-(1-methyl-1H-pyrazole-5-yl)-2-(2-(trifluoromethyl)-5-pyrimidinyl)thieno[2,3-d]pyrimidine-6-yl)methanone, (2-(2-cyclopropyl-5-pyrimidinyl)-4-(1-methyl-1H-pyrazole-5-yl)thieno[2,3-d]pyrimidin-6-yl)(4,4-difluoro-1-piperidinyl)methanone, (4,4-difluoro-1-piperidinyl)(2-(1-methyl-1H-pyrazole-4-yl)-4-(1-methyl-1H-pyrazole-5-yl)thieno[2,3-d]pyrimidine-6-yl)methanone, (4,4-difluoro-1-piperidinyl)(4-(1-methyl-1H-pyrazole-5-yl)-2-(1-(trifluoromethyl)-1H-pyrazole-4-yl)thieno[2,3-d]pyrimidine-6-yl)methanone, (4,4-difluoro-1-piperidinyl)(2-(1-methyl-1H-pyrazole-3-yl)-4-(1-methyl-1H-pyrazole-5-yl)thieno[2,3-d]pyrimidine-6-yl)methanone, N-(5-(6-((4,4-difluoro-1-piperidinyl)carbonyl)-4-(1-methyl-1H-pyrazole-5-yl)thieno[2,3-d]pyrimidine-2-yl)-2-pyrimidinyl)acetamide, (4,4-difluoro-1-piperidinyl)(2-(1-methyl-1H-imidazole-5-yl)-4-(1-methyl-1H-pyrazole-5-yl)thieno[2,3-d]pyrimidine-6-yl)methanone, (4,4-difluoro-1-piperidinyl)(4-(1-methyl-1H-pyrazole-5-yl)-2-(1,3-thiazole-5-yl)thieno[2,3-d]pyrimidine-6-yl)methanone, (4,4-difluoro-1-piperidinyl)(4-(1-methyl-1H-pyrazole-5-yl)-2-(1,3-oxazole-5-yl)thieno[2,3-d]pyrimidine-6-yl)methanone, (4,4-difluoro-1-piperidinyl)(2-(2-(4-methyl-1-piperazinyl)-5-pyrimidinyl)-4-(1-methyl-1H-pyrazole-5-yl)thieno[2,3-d]pyrimidin-6-yl)methanone, (4,4-difluoro-1-piperidinyl)(4-(1-methyl-1H-pyrazole-5-yl)-2-(2-(4-morpholinyl)-5-pyrimidinyl)thieno[2,3-d]pyrimidine-6-yl)methanone, 5-(6-((4,4-difluoro-1-piperidinyl)carbonyl)-4-(1-methyl-1H-pyrazole-5-yl)thieno[2,3-d]pyrimidine-2-yl)-2(1H)-pyridinone, (4,4-difluoro-1-piperidinyl)(2-(3H-imidazo[4,5-b]pyridine-6-yl)-4-(1-methyl-1H-pyrazole-5-yl)thieno[2,3-d]pyrimidine-6-yl)methanone, (4,4-difluoro-1-piperidinyl)(2-(imidazo[1,2-a]pyridine-3-yl)-4-(1-methyl-1H-pyrazole-5-yl)thieno[2,3-d]pyrimidine-6-yl)methanone, (4,4-difluoro-1-piperidinyl)(4-(1-methyl-1H-pyrazole-5-yl)-2-(4-pyridazinyl)thieno[2,3-d]pyrimidine-6-yl)methanone, (4,4-difluoro-1-piperidinyl)(4-(1-methyl-1H-pyrazole-5-yl)-2-(2-pyrazinyl)thieno[2,3-d]pyrimidine-6-yl)methanone, 6-(6-((4,4-difluoro-1-piperidinyl)carbonyl)-4-(1-methyl-1H-pyrazole-5-yl)thieno[2,3-d]pyrimidine-2-yl)-2-methyl-1(2H)-isoquinolinone, (4,4-difluoro-1-piperidinyl)(4-(1-methyl-1H-pyrazole-5-yl)-2-(1,3-thiazole-2-yl)thieno[2,3-d]pyrimidine-6-yl)methanone, (4,4-difluoro-1-piperidinyl)(4-(1-methyl-1H-pyrazole-5-yl)-2-(1,3-oxazole-2-yl)thieno[2,3-d]pyrimidine-6-yl)methanone, N-(5-(6-((4,4-difluoro-1-piperidinyl)carbonyl)-4-(1-methyl-1H-pyrazole-5-yl)thieno[2,3-d]pyrimidine-2-yl)-2-pyrimidinyl)methanesulfonamide, 5-(6-((4,4-difluoro-1-piperidinyl)carbonyl)-4-(1-methyl-1H-pyrazole-5-yl)thieno[2,3-d]pyrimidine-2-yl)-2(1H)-pyrimidinone, (4,4-difluoro-1-piperidinyl)(3-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyrazine-6-yl)methanone, (4,4-difluoro-1-piperidinyl)(2-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyrazine-6-yl)methanone, (4,4-difluoro-1-piperidinyl)(5-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[3,2-b]pyridin-2-yl)methanone, (5-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[3,2-b]pyridin-2-yl)(1-piperidinyl)methanone, (3,3-difluoro-1-piperidinyl)(5-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[3,2-b]pyridin-2-yl)methanone, (5-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[3,2-b]pyridin-2-yl)(4-morpholinyl)methanone, (3-amino-5-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[3,2-b]pyridin-2-yl)(1-piperidinyl)methanone, (3-amino-5-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[3,2-b]pyridin-2-yl)(4-morpholinyl)methanone, (3-amino-5-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[3,2-b]pyridin-2-yl)(3,3-difluoro-1-piperidinyl)methanone, (3-amino-5-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[3,2-b]pyridin-2-yl)(4,4-difluoro-1-piperidinyl)methanone, (4-Cyclopropyl-2-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[3,2-d]pyrimidine-6-yl)(4-morpholinyl)methanone, 4-Morpholinyl (5-(4-Morpholinyl)[1,3]thiazolo[5,4-b]pyridine-2-yl)methanone, (5-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)[1,3]thiazolo[5,4-b]pyridin-2-yl)(4-morpholinyl)methanone, or (3-methyl-4-morpholinyl)(5-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)[1,3]thiazolo[5,4-b]pyridin-2-yl)methanone The compound or salt according to claim 1.

48. The aforementioned compound, (3-methyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)-1-benzothiophen-2-yl)((3S)-3-methyl-4-morpholinyl)methanone, (3-methyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)-1-benzothiophen-2-yl)((3R)-3-methyl-4-morpholinyl)methanone, ((3R)-3-methoxy-1-pyrrolidinyl)(3-methyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)-1-benzothiophen-2-yl)methanone, ((3S)-3-methoxy-1-pyrrolidinyl)(3-methyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)-1-benzothiophen-2-yl)methanone, ((3S)-3-methoxy-1-piperidinyl)(3-methyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)-1-benzothiophen-2-yl)methanone, ((3R)-3-methoxy-1-piperidinyl)(3-methyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)-1-benzothiophen-2-yl)methanone, (3-amino-4-cyclobutyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyridine-2-yl)((3S)-3-methyl-4-morpholinyl)methanone, (3-amino-4-cyclobutyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)((3R)-3-methyl-4-morpholinyl)methanone, ((3R)-3-methyl-4-morpholinyl)(6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)methanone, ((3S)-3-methyl-4-morpholinyl)(6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)methanone, (4-Cyclopropyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)((3S)-3-methyl-4-morpholinyl)methanone, (4-Cyclopropyl-6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)((3R)-3-methyl-4-morpholinyl)methanone, ((2R)-4,4-difluoro-2-methyl-1-piperidinyl)(6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyridine-2-yl)methanone, ((2S)-4,4-difluoro-2-methyl-1-piperidinyl)(6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyridine-2-yl)methanone, ((2R)-4,4-difluoro-2-methyl-1-piperidinyl)(6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyridine-2-yl)methanone, ((2S)-4,4-difluoro-2-methyl-1-piperidinyl)(6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyridine-2-yl)methanone, (3R)-4-((6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyridine-2-yl)carbonyl)-3-morpholine carbonate, (3S)-4-((6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyridine-2-yl)carbonyl)-3-morpholine carbonate, ((2R)-2-methyl-4-morpholinyl)(6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)methanone, ((2S)-2-methyl-4-morpholinyl)(6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)methanone, 1-Methyl-5-(2-(((3S)-3-methyl-4-morpholinyl)carbonyl)thieno[2,3-b]pyridinyl-6-yl)-2(1H)-pyridinone, 1-Methyl-5-(2-(((3R)-3-methyl-4-morpholinyl)carbonyl)thieno[2,3-b]pyridinyl)-2(1H)-pyridinone, ((3S)-3-methyl-4-morpholinyl)(6-(1,3-thiazole-2-yl)thieno[2,3-b]pyridine-2-yl)methanone, 3-methyl-6-(2-(((3S)-3-methyl-4-morpholinyl)carbonyl)thieno[2,3-b]pyridine-6-yl)-4(3H)-pyrimidinone, ((3R)-3-methyl-4-morpholinyl)(6-(1,3-thiazole-2-yl)thieno[2,3-b]pyridine-2-yl)methanone, 3-methyl-6-(2-(((3R)-3-methyl-4-morpholinyl)carbonyl)thieno[2,3-b]pyridine-6-yl)-4(3H)-pyrimidinone, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)((1R,5R)-8-oxa-3-azabicyclo[3.2.1]octan-3-yl)methanone, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyridine-2-yl)((1R,5S)-8-oxa-3-azabicyclo[3.2.1]octan-3-yl)methanone, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyridine-2-yl)((1S,5S)-8-oxa-3-azabicyclo[3.2.1]octan-3-yl)methanone, ((3S)-3-methyl-4-morpholinyl)(6-(2-methyl-2H-[1,2,3]triazolo[4,5-b]pyridine-6-yl)thieno[2,3-b]pyridine-2-yl)methanone, ((3R)-3-methyl-4-morpholinyl)(6-(2-methyl-2H-[1,2,3]triazolo[4,5-b]pyridine-6-yl)thieno[2,3-b]pyridine-2-yl)methanone, ((3R)-3-methyl-4-morpholinyl)(6-(3-methyl-3H-[1,2,3]triazolo[4,5-b]pyridine-6-yl)thieno[2,3-b]pyridine-2-yl)methanone, ((3S)-3-methyl-4-morpholinyl)(6-(3-methyl-3H-[1,2,3]triazolo[4,5-b]pyridine-6-yl)thieno[2,3-b]pyridine-2-yl)methanone, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)((2R)-2-(trifluoromethyl)-4-morpholinyl)methanone, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)((2S)-2-(trifluoromethyl)-4-morpholinyl)methanone, 5-(2-(((3S)-3-methyl-4-morpholinyl)carbonyl)thieno[2,3-b]pyridin-6-yl)-2(1H)-pyridinone, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)((1R,4R)-2-oxa-5-azabicyclo[2.2.2]octan-5-yl)methanone, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridine-5-yl)thieno[2,3-b]pyridine-2-yl)((1R,4S)-2-oxa-5-azabicyclo[2.2.2]octan-5-yl)methanone, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)((1S,4R)-2-oxa-5-azabicyclo[2.2.2]octan-5-yl)methanone, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)((1S,4S)-2-oxa-5-azabicyclo[2.2.2]octan-5-yl)methanone, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)((1R,6R)-2-oxa-5-azabicyclo[4.1.0]heptan-5-yl)methanone, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)((1R,6S)-2-oxa-5-azabicyclo[4.1.0]heptan-5-yl)methanone, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)((1S,6R)-2-oxa-5-azabicyclo[4.1.0]heptan-5-yl)methanone, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)((1S,6S)-2-oxa-5-azabicyclo[4.1.0]heptan-5-yl)methanone, 5-(2-(((3R)-3-methyl-4-morpholinyl)carbonyl)thieno[2,3-b]pyridin-6-yl)-2(1H)-pyridinone, ((3S)-3-methyl-4-morpholinyl)(6-(6-quinolinyl)thieno[2,3-b]pyridine-2-yl)methanone, ((3S)-3-methyl-4-morpholinyl)(6-(pyrido[2,3-b]pyrazine-7-yl)thieno[2,3-b]pyridine-2-yl)methanone, ((3R)-3-methyl-4-morpholinyl)(6-(pyrido[2,3-b]pyrazine-7-yl)thieno[2,3-b]pyridine-2-yl)methanone, ((3R)-3-methyl-4-morpholinyl)(6-(6-quinolinyl)thieno[2,3-b]pyridine-2-yl)methanone, 7-methyl-3-(2-(((3S)-3-methyl-4-morpholinyl)carbonyl)thieno[2,3-b]pyridine-6-yl)-1,7-naphthyridine-8(7H)-one, (6-(1-methyl-1H-imidazo[4,5-b]pyridine-6-yl)thieno[2,3-b]pyridine-2-yl)((3S)-3-methyl-4-morpholinyl)methanone, (6-(1-methyl-1H-imidazo[4,5-b]pyridine-6-yl)thieno[2,3-b]pyridine-2-yl)((3R)-3-methyl-4-morpholinyl)methanone, 7-methyl-3-(2-(((3R)-3-methyl-4-morpholinyl)carbonyl)thieno[2,3-b]pyridine-6-yl)-1,7-naphthyridine-8(7H)-one, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)((3R)-3-(trifluoromethyl)-4-morpholinyl)methanone, (6-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-b]pyridin-2-yl)((3S)-3-(trifluoromethyl)-4-morpholinyl)methanone, (4-Cyclopropyl-2-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)thieno[2,3-d]pyrimidine-6-yl)((1R,5S)-3-oxa-8-azabicyclo[3.2.1]octan-8-yl)methanone, ((3R)-3-methyl-4-morpholinyl)(5-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)[1,3]thiazolo[5,4-b]pyridin-2-yl)methanone, or ((3S)-3-methyl-4-morpholinyl)(5-(2-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)[1,3]thiazolo[5,4-b]pyridin-2-yl)methanone The compound or salt according to claim 1.

49. The compound according to any one of claims 1 to 48.

50. A pharmaceutical composition comprising a compound or salt according to any one of claims 1 to 49 and a pharmaceutically acceptable excipient.

51. A compound or salt according to any one of claims 1 to 49 or a pharmaceutical composition according to claim 50, for use in the treatment of 15-PGDH-mediated diseases or disorders.

52. A compound or salt according to any one of claims 1 to 49, or a pharmaceutical composition according to claim 50, for use in the treatment of inflammatory bowel disease.

53. A compound or salt according to any one of claims 1 to 49, or a pharmaceutical composition according to claim 50, for use in the treatment of ulcerative colitis.

54. A compound or salt according to any one of claims 1 to 49, or a pharmaceutical composition according to claim 50, for use in the treatment of Crohn's disease.

55. A compound or salt according to any one of claims 1 to 49, or a pharmaceutical composition according to claim 50, for use in the treatment of fibrous diseases.

56. A method for producing the compound or salt described in claim 1, wherein the formula (I-int-c.1) 【Chemistry 31】 The compound of formula (B ａ -R ２ ): 【Chemistry 32】 Reacting with the compound (In the formula, X Ｈ It is a halogen, B ａ This is a boronic acid group or a boronic acid ester group, 【Transformation 33】 This indicates that a double bond or a single bond may be present. X ａ Each of these examples is, independently, nitrogen, oxygen, or carbon. If present, each example of s is an integer selected from 0, 1, 2, or 3. If present, each example of r is an integer independently selected from 0, 1, 2, or 3, and two examples of r are the same R ２ If present on the base, the sum of both combined r values ​​does not exceed 5. If it exists and is bonded to an N ring member, R ５ Each example is independent of C １～６ Alkyl, C １～６ Haloalkyl, C ３～６ A cycloalkyl or a heterocyclyl having 3 to 10 members, and If present and bonded to a C ring member, R ５ Each example independently represents oxo, CN, and C. １～６ Alkyl, C ３～６ Cycloalkyl, C １～６ Haloalkyl, C １～６ Alkoxy, C(O)N(R) ６ ) ２ , -N(R ６ ) ２ , -N(R ６ ) (C １～６ It is a heterocycline having 3 to 10 members (alkylene-OH). If present, R ６ Each example is independently -H, C １～３ Alkyl, C(O)C １～３ Alkyl, C(O) ２ C １～３ Alkyl, C １～３ Alkylene-OH or S(O) ｎ C １～３ It is an alkyl group, and n is 0, 1, or 2. -N = cyclic nitrogen is R ５ (It can be bonded to and provide a cation.) A method that includes this.

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